Статті в журналах з теми "NVH reduction control"
Щоб переглянути інші типи публікацій з цієї теми, перейдіть за посиланням: NVH reduction control.
Оформте джерело за APA, MLA, Chicago, Harvard та іншими стилями
Ознайомтеся з топ-50 статей у журналах для дослідження на тему "NVH reduction control".
Біля кожної праці в переліку літератури доступна кнопка «Додати до бібліографії». Скористайтеся нею – і ми автоматично оформимо бібліографічне посилання на обрану працю в потрібному вам стилі цитування: APA, MLA, «Гарвард», «Чикаго», «Ванкувер» тощо.
Також ви можете завантажити повний текст наукової публікації у форматі «.pdf» та прочитати онлайн анотацію до роботи, якщо відповідні параметри наявні в метаданих.
Переглядайте статті в журналах для різних дисциплін та оформлюйте правильно вашу бібліографію.
1
Guo, Han, Jianwu Zhang, and Haisheng Yu. "Robust optimisation of dynamic and NVH characteristics for compound power-split hybrid transmission." Proceedings of the Institution of Mechanical Engineers, Part K: Journal of Multi-body Dynamics 233, no. 4 (June 25, 2019): 817–26. http://dx.doi.org/10.1177/1464419319856774.
Повний текст джерелаАнотація:
In this paper, vibro-acoustic characteristics of a power-split hybrid transmission including a compound planetary gear set are investigated by numerical procedure and refined system dynamics modelling. For validation of the numerical predictions, bench tests are performed for dynamic and acoustic responses of the hybrid transmission, contribution rates of acoustic radiation power induced due to the planetary gears, support bearings, transmission shafts and the gearbox housing are estimated. In improving the noise, vibration and harshness (NVH) performance of the transmission during hybrid vehicle acceleration, traction torques of the motors against the planetary gear parametric resonance are formulated and an optimal control strategy is proposed. By real road NVH test results acquired on board of the midsize hybrid car, it is demonstrated that a significant reduction of the planetary gear whine noise is achieved. As a result, numerical approaches applied to establish relationships between torques of the two traction motors and parametric excitations of the compound planetary gear train are experimentally validated.
2
Jiang, Tao, Jiang Liu, Cheng Peng, and Shuliang Wang. "Laboratory Test of a Vehicle Active Noise-Control System Based on an Adaptive Step Size Algorithm." Applied Sciences 13, no. 1 (December 24, 2022): 225. http://dx.doi.org/10.3390/app13010225.
Повний текст джерелаАнотація:
NVH (noise, vibration, and harshness) is a key factor affecting vehicle comfort. Compared with traditional sound absorption and isolation methods, active noise control (ANC) offers a significant advantage in solving the problem of low- and medium-frequency noise from road surfaces. However, the classic filtered-x least mean squares (FxLMS) algorithm is ineffective in terms of adapting to different road noises to ensure a stable noise reduction effect when facing the complex and changeable noise environment of moving vehicles. Therefore, an adaptive step size algorithm (ASSFxLMS) is proposed in this paper, which can adjust the step size according to the size of the reference signal to ensure the stability of the adaptive process. In order to improve the performance of the algorithm, a particle swarm optimization algorithm is also used to automatically adjust the parameters, so that the step size of the adaptive algorithm always maintains a relatively ideal size. The simulated pulse noise of standard SαS distribution was used as the reference signal for the simulation. The simulation results show that compared with other algorithms, the proposed algorithm under different degrees of pulse noise conditions, noise reduction stability, and noise reduction amplitude are improved. In order to further verify the feasibility of the algorithm in vehicle road noise reduction, this paper also conducted a hardware-in-the-loop noise reduction experiment in the laboratory, employing the road noise data collected by the real vehicle. Under different interior noise conditions, the proposed active noise-control system has a maximum noise reduction effect of 12 dB for low-frequency noise below 100 Hz.
3
Shin, Hyunki, Donghyuk Jung, Manbae Han, Seungwoo Hong, and Donghee Han. "Minimization of Torque Deviation of Cylinder Deactivation Engine through 48V Mild-Hybrid Starter-Generator Control." Sensors 21, no. 4 (February 18, 2021): 1432. http://dx.doi.org/10.3390/s21041432.
Повний текст джерелаАнотація:
Cylinder deactivation (CDA) is an effective technique to improve fuel economy in spark ignition (SI) engines. This technique enhances volumetric efficiency and reduces throttling loss. However, practical implementation is restricted due to torque fluctuations between individual cylinders that cause noise, vibration, and harshness (NVH) issues. To ease torque deviation of the CDA, we propose an in-cylinder pressure based 48V mild-hybrid starter-generator (MHSG) control strategy. The target engine realizes CDA with a specialized engine configuration of separated intake manifolds to independently control the airflow into the cylinders. To handle the complexity of the combined CDA and mild-hybrid system, GT-POWER simulation environment was integrated with a SI turbulent combustion model and 48V MHSG model with actual part specifications. The combustion model is essential for in-cylinder pressure-based control; thus, it is calibrated with actual engine experimental data. The modeling results demonstrate the precise accuracy of the engine cylinder pressures and of quantities such as MAF, MAP, BMEP, and IMEP. The proposed control algorithm also showed remarkable control performance, achieved by instantaneous torque calculation and dynamic compensation, with a 99% maximum reduction rate of engine torque deviation under target CDA operations.
4
Mayer, Dirk, Thilo Bein, Hendrik Buff, Benedict Götz, Oliver Schwarzhaupt, and Dominik Spancken. "Enhanced lightweight design by composites – Results of the EU project ENLIGHT." Journal of Reinforced Plastics and Composites 37, no. 19 (March 22, 2018): 1217–24. http://dx.doi.org/10.1177/0731684418762321.
Повний текст джерелаАнотація:
Over recent decades, cars have become larger and heavier with every new generation. The main drivers of such a weight increase have been the improved safety and comfort requirements. Decades of R&D investments to tackle this tendency have resulted in a substantial increase in the weight-specific performance of components and assemblies in terms of cost, strength and stiffness. However, the need for weight reduction in future electric vehicles, without unduly compromising performance and safety, is even stronger since additional weight translates into either reduced driving range or in larger, heavier and more expensive batteries. Within this context, the European Green Vehicle project ENLIGHT developed highly innovative lightweight material technologies for application in structural vehicle parts of future volume produced electric vehicles. Among others, ENLIGHT developed thermoplastic matrix composite and associated manufacturing technologies to a stage that they were applicable at least in medium volume production. The material development was complemented by investigating the required manufacturing and assembly technologies as well. In this paper, a summary of the major results obtained during the four-year project year is presented. A special focus is given to a semi-active composite control arm with significant reduced weight but enhanced NVH properties.
5
LØVDAL, IRENE STRANDEN, MARIA BEFRING HOVDA, PER EINAR GRANUM, and JAN THOMAS ROSNES. "Promoting Bacillus cereus Spore Germination for Subsequent Inactivation by Mild Heat Treatment." Journal of Food Protection 74, no. 12 (December 1, 2011): 2079–89. http://dx.doi.org/10.4315/0362-028x.jfp-11-292.
Повний текст джерелаАнотація:
Sublethal heat treatment may activate dormant spores and thereby potentiate the conversion of spores to vegetative cells. As the germinated spore is known to possess lower heat resistance than its dormant counterpart, it has been postulated that double heat treatment, i.e., spore heat activation followed by germination and then by heat inactivation, can be used to control spores in foods. Production of refrigerated processed foods of extended durability often includes more than one heat treatment of the food components. This work simulates conventional heat treatment procedures and evaluates double heat treatment as a method to improve spore control in model food matrixes of meat broth and cream sauce. Bacillus cereus NVH 1230-88 spores were supplemented in food model matrixes and heat activated at 70°C and then heat inactivated at 80 or 90°C. The samples were held at 29 to 30°C for 1 h between primary and secondary heat treatments, to allow spore germination. Nutrients naturally present in the food matrixes, e.g., amino acids and inosine, could act as germinants that induce germination. The levels of germinants could be too low to produce effective germination within 1 h. Following primary heat treatment, some samples were therefore supplemented with a combination of L-alanine and inosine, a germinant mixture known to be effective for B. cereus spores. In both matrixes, a combination of double heat treatment (heat activation, germination, and inactivation) and addition of germinants gave a reduction in spore counts equivalent to or greater than that obtained with a single heat treatment for 12 min at 90°C. Addition of germinants was essential to induce effective germination in cream sauce during 1 h at 29 to 30°C, and germinants were therefore a crucial supplement to obtain an effect of double heat treatment in this matrix. These data will be valuable when setting up temperature-time-germinant combinations for an optimized spore reduction in mild-heat–treated foods.
6
Qiu, Yang, Dongwoo Hong, and Byeongil Kim. "Active Mitigation Strategy of Structure-Borne Vibration with Complex Frequency Spectra from Asymmetric Plate-like Mounting Systems in Next Generation Mobilities." Symmetry 15, no. 1 (January 7, 2023): 178. http://dx.doi.org/10.3390/sym15010178.
Повний текст джерелаАнотація:
The complicated spectrum produced by electric and hybrid car engines is particularly sensitive to the mid-frequency range. Furthermore, sensor placement in future mobility is crucial because when the positions and orientations of sensors are altered by excessive vehicle vibration, it results in the malfunctioning of autonomous driving systems. Smart structure-based active mounting approaches have been developed to reduce engine-induced vibration. These are made to continually adjust the mounts’ dynamic properties and enhance their performances in terms of noise, vibration, and harshness (NVH) under diverse operating circumstances. It can take the place of the engine support system’s current mount technique. The performance of the source part for reducing vibration when the structure is triggered by a sinusoidal and multi-frequency signal is the main subject of this study. The overall structure, which has two active mounts based on the source-paths-receiver structure, was modeled using a lumped parameter model. In the source section, sinusoidal, amplitude modulation (AM), and frequency modulation (FM) signals were used in order to assess the effectiveness of vibration reduction in the mid-frequency band. The normalized least mean-square (NLMS) technique was utilized to assess the effectiveness of an active mounting system, and a tracking signal was employed as a control signal. The algorithm was further expanded to the multi-NLMS algorithm to monitor the complex spectral signal. This demonstrates how an active mounting system can successfully reduce vibrations when the structure is activated by many mid-frequency complex signals.
7
Courteille, E., and F. Mortier. "Idle shake vibration optimization of an engine mounting system through the practical application of transfer path analysis." Noise Control Engineering Journal 68, no. 6 (November 1, 2020): 459–69. http://dx.doi.org/10.3397/1/376838.
Повний текст джерелаАнотація:
This article presents a practical application of experimental transfer path analysis (TPA) for optimizing idle shake vibrations of a front-wheel-drive car with a transversely mounted four-cylinder diesel engine. Performance control of the vehicle engine mounting system must take into account the multiple dynamic interactions between the engine mounting system, subframe modes and the vehicle suspension. Experimental methods can be used in conjunction with simulations to design and optimize the engine mounting system. TPA is a powerful tool for the diagnosis of vibration and noise transmission via multiple solid paths. TPA allows a quick diagnosis of the engine mounting system performances on vehicle comfort. A strong synergy between numerical model and experimental data finally makes it possible to find better design alternatives, not necessarily obvious to the designer. This study is the guideline for an optimization of the engine mount noise vibration and harshness (NVH) performances by using a hybrid approach, combining an analytical approach and measurement data. First, a diagnosis of the transmission of structure-borne vibrations via the engine mounting system to the seat floor is done at constant idle speed. This method is used to rank individual engine mount contributions in the low-frequency vibration level inside the vehicle. Then, an original approach allows the optimization of the vibration level at idle speed by offsetting contributions of the engine mount paths by adding damping in the right engine mount. This approach has led to the design and validation of an original double inertia-track hydroelastic mount prototype which allows a 5-dB reduction on the seat floor vibration level. The future development of a new version is planned to confirm and optimized the obtained results. The length of the second inertia track will be increased to reach the targeted characteristics, and the adjustment system will be removed to respect the overall dimension constraints of the mount.
8
Robinson, L., and K. Kimpinski. "P.004 Neurogenic orthostatic hypotension results in impaired information processing speed." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 45, s2 (June 2018): S17. http://dx.doi.org/10.1017/cjn.2018.106.
Повний текст джерелаАнотація:
Background: Neurogenic orthostatic hypotension (NOH) is characterized by a reduction in systolic blood pressure of ≥20 mmHg or diastolic blood pressure of ≥10 mmHg within three minutes of upright posture. NOH is prevalent in the elderly population who is at increased risk for cognitive decline, therefore it is imperative to investigate if there is a relationship between NOH and impaired cognition. Methods: Currently, 9 control subjects and 4 NOH patients have been recruited. Cognitive function is assessed using the symbol digit modalities test (SDMT) which assesses information processing speed and the Stroop test which measures response inhibition. SDMT and Stroop test are administered when the table is supine and during tilt. Results: NOH patients scored significantly worse on SDMT when lying (p=0.018) and standing (p=0.004) compared to the control group. Control subjects performed significantly better when standing for both SDMT (p=0.008) and Stroop (p=0.026), whereas NOH patients had similar scores when lying and standing for SDMT and Stroop. Conclusions: Preliminary results show that information processing speed is slower in NOH patients than controls in both the supine and standing positions. NOH patients have a more difficult time inhibiting unwanted responses compared to controls when standing, which is represented by a greater interference score in NOH patients.
9
Rockswold, Sarah B., Gaylan L. Rockswold, David A. Zaun, and Jiannong Liu. "A prospective, randomized Phase II clinical trial to evaluate the effect of combined hyperbaric and normobaric hyperoxia on cerebral metabolism, intracranial pressure, oxygen toxicity, and clinical outcome in severe traumatic brain injury." Journal of Neurosurgery 118, no. 6 (June 2013): 1317–28. http://dx.doi.org/10.3171/2013.2.jns121468.
Повний текст джерелаАнотація:
Object Preclinical and clinical investigations indicate that the positive effect of hyperbaric oxygen (HBO2) for severe traumatic brain injury (TBI) occurs after rather than during treatment. The brain appears better able to use baseline O2 levels following HBO2 treatments. In this study, the authors evaluate the combination of HBO2 and normobaric hyperoxia (NBH) as a single treatment. Methods Forty-two patients who sustained severe TBI (mean Glasgow Coma Scale [GCS] score 5.7) were prospectively randomized within 24 hours of injury to either: 1) combined HBO2/NBH (60 minutes of HBO2 at 1.5 atmospheres absolute [ATA] followed by NBH, 3 hours of 100% fraction of inspired oxygen [FiO2] at 1.0 ATA) or 2) control, standard care. Treatments occurred once every 24 hours for 3 consecutive days. Intracranial pressure, surrogate markers for cerebral metabolism, and O2 toxicity were monitored. Clinical outcome was assessed at 6 months using the sliding dichotomized Glasgow Outcome Scale (GOS) score. Mixed-effects linear modeling was used to statistically test differences between the treatment and control groups. Functional outcome and mortality rates were compared using chi-square tests. Results There were no significant differences in demographic characteristics between the 2 groups. In comparison with values in the control group, brain tissue partial pressure of O2 (PO2) levels were significantly increased during and following combined HBO2/NBH treatments in both the noninjured and pericontusional brain (p < 0.0001). Microdialysate lactate/pyruvate ratios were significantly decreased in the noninjured brain in the combined HBO2/NBH group as compared with controls (p < 0.0078). The combined HBO2/NBH group's intracranial pressure values were significantly lower than those of the control group during treatment, and the improvement continued until the next treatment session (p < 0.0006). The combined HBO2/NBH group's levels of microdialysate glycerol were significantly lower than those of the control group in both noninjured and pericontusional brain (p < 0.001). The combined HBO2/NBH group's level of CSF F2-isoprostane was decreased at 6 hours after treatment as compared with that of controls, but the difference did not quite reach statistical significance (p = 0.0692). There was an absolute 26% reduction in mortality for the combined HBO2/NBH group (p = 0.048) and an absolute 36% improvement in favorable outcome using the sliding dichotomized GOS (p = 0.024) as compared with the control group. Conclusions In this Phase II clinical trial, in comparison with standard care (control treatment) combined HBO2/NBH treatments significantly improved markers of oxidative metabolism in relatively uninjured brain as well as pericontusional tissue, reduced intracranial hypertension, and demonstrated improvement in markers of cerebral toxicity. There was significant reduction in mortality and improved favorable outcome as measured by GOS. The combination of HBO2 and NBH therapy appears to have potential therapeutic efficacy as compared with the 2 treatments in isolation. Clinical trial registration no.: NCT00170352 (ClinicalTrials.gov).
10
Chang, Chia-Cheng, Nobumasa Kuwana, Susumu Ito, and Tadashi Ikegami. "Response of cerebral blood flow and cerebrovascular reactivity to acetazolamide in patients with dementia and idiopathic normal-pressure hydrocephalus." Neurosurgical Focus 7, no. 4 (October 1999): E11. http://dx.doi.org/10.3171/foc.1999.7.4.12.
Повний текст джерелаАнотація:
The responses of cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to administration of acetazolamide were investigated in 16 patients with dementia and ventriculomegaly to clarify the cerebral hemodynamics in patients with idiopathic normal-pressure hydrocephalus (NPH). The mean CBF velocity in the whole brain was measured by the Patlak plot method by using technetium-99m hexamethylpropyleneamine oxime single-photon emission computerized tomography. The CVR values were obtained from the response to administration of 500 mg of acetazolamide and calculated as the percentage of change from the baseline mean CBF value. The mean CBF value was significantly reduced (p < 0.01) in six patients with (35.2 ± 5 ml/100 g/minute) and 10 patients without (33.5 ± 2.8 ml/100 g/minute) NPH compared with the age-matched normal controls (40.8 ± 3.2 ml/100 g/minute), showing no significant difference. The CVR was significantly impaired in patients with NPH (0.8 ± 1.7%; p < 0.001), whereas in patients without NPH preserved CVR (11.3 ± 3%) was demonstrated compared with the normal controls (14.7 ± 1.1%). In patients with NPH a significantly lower CVR (p < 0.001) was shown than in those without NPH. The CVR significantly increased (p < 0.001) after placement of a shunt in patients with NPH. Reductions in both CBF and CVR may be diagnostic indicators of NPH in patients with dementia in whom ventriculomegaly is present. In patients with dementia and idiopathic NPH both reduced CBF and extremely impaired CVR are shown. The results of the present study suggest that ischemia due to the process of NPH is responsible for the reduction of CBF and manifestation of symptoms in patients with idiopathic NPH.
11
Taqui, Ather, Russell Cerejo, Ahmed Itrat, Farren B. S. Briggs, Andrew P. Reimer, Stacey Winners, Natalie Organek, et al. "Reduction in time to treatment in prehospital telemedicine evaluation and thrombolysis." Neurology 88, no. 14 (March 8, 2017): 1305–12. http://dx.doi.org/10.1212/wnl.0000000000003786.
Повний текст джерелаАнотація:
Objective:To compare the times to evaluation and thrombolytic treatment of patients treated with a telemedicine-enabled mobile stroke treatment unit (MSTU) vs those among patients brought to the emergency department (ED) via a traditional ambulance.Methods:We implemented a MSTU with telemedicine at our institution starting July 18, 2014. A vascular neurologist evaluated each patient via telemedicine and a neuroradiologist and vascular neurologist remotely assessed images obtained by the MSTU CT. Data were entered in a prospective registry. The evaluation and treatment of the first 100 MSTU patients (July 18, 2014–November 1, 2014) was compared to a control group of 53 patients brought to the ED via a traditional ambulance in 2014. Times were expressed as medians with their interquartile ranges.Results:Patient and stroke severity characteristics were similar between 100 MSTU and 53 ED control patients (initial NIH Stroke Scale score 6 vs 7, p = 0.679). There was a significant reduction of median alarm-to-CT scan completion times (33 minutes MSTU vs 56 minutes controls, p < 0.0001), median alarm-to-thrombolysis times (55.5 minutes MSTU vs 94 minutes controls, p < 0.0001), median door-to-thrombolysis times (31.5 minutes MSTU vs 58 minutes controls, p = 0.0012), and symptom-onset-to-thrombolysis times (97 minutes MSTU vs 122.5 minutes controls, p = 0.0485). Sixteen patients evaluated on MSTU received thrombolysis, 25% of whom received it within 60 minutes of symptom onset.Conclusion:Compared with the traditional ambulance model, telemedicine-enabled ambulance-based thrombolysis resulted in significantly decreased time to imaging and treatment.
12
Lin, A. H., V. E. Groppi, and R. R. Gorman. "Platelet-derived growth factor does not induce c-fos in NIH 3T3 cells expressing the EJ-ras oncogene." Molecular and Cellular Biology 8, no. 11 (November 1988): 5052–55. http://dx.doi.org/10.1128/mcb.8.11.5052-5055.1988.
Повний текст джерелаАнотація:
Platelet-derived growth factor (PDGF), the calcium ionophore A23187, and the tumor promoter phorbol myristate acetate stimulated c-fos mRNA levels in control NIH 3T3 cells. However, NIH 3T3 cells transformed by EJ-ras DNA transfection, which have diminished PDGF-stimulated phospholipase C activity, showed a 95% reduction in PDGF-stimulated c-fos mRNA levels. The responses to A23187 and phorbol myristate acetate were also attenuated, but not as severely as the PDGF-mediated induction. The reduction in PDGF-stimulated c-fos induction did not appear to be a general result of cellular transformation, since src-transformed NIH 3T3 cells displayed a strong PDGF-stimulated c-fos induction. Despite the reduction in PDGF-stimulated c-fos induction, EJ-ras-transformed cells still responded mitogenically to PDGF. These data suggest that the magnitude of c-fos induction cannot be directly correlated with PDGF-stimulated mitogenesis in EJ-ras-transformed NIH 3T3 cells.
13
Lin, A. H., V. E. Groppi, and R. R. Gorman. "Platelet-derived growth factor does not induce c-fos in NIH 3T3 cells expressing the EJ-ras oncogene." Molecular and Cellular Biology 8, no. 11 (November 1988): 5052–55. http://dx.doi.org/10.1128/mcb.8.11.5052.
Повний текст джерелаАнотація:
Platelet-derived growth factor (PDGF), the calcium ionophore A23187, and the tumor promoter phorbol myristate acetate stimulated c-fos mRNA levels in control NIH 3T3 cells. However, NIH 3T3 cells transformed by EJ-ras DNA transfection, which have diminished PDGF-stimulated phospholipase C activity, showed a 95% reduction in PDGF-stimulated c-fos mRNA levels. The responses to A23187 and phorbol myristate acetate were also attenuated, but not as severely as the PDGF-mediated induction. The reduction in PDGF-stimulated c-fos induction did not appear to be a general result of cellular transformation, since src-transformed NIH 3T3 cells displayed a strong PDGF-stimulated c-fos induction. Despite the reduction in PDGF-stimulated c-fos induction, EJ-ras-transformed cells still responded mitogenically to PDGF. These data suggest that the magnitude of c-fos induction cannot be directly correlated with PDGF-stimulated mitogenesis in EJ-ras-transformed NIH 3T3 cells.
14
Garg, Bhawan Deep, Anju Bansal, and Nandkishor S. Kabra. "Role of Kangaroo Mother Care in the Management of Neonatal Hyperbilirubinemia in Both Term and Preterm Neonates: A Systematic Review." Journal of Perinatal Education 29, no. 3 (June 29, 2020): 123–33. http://dx.doi.org/10.1891/j-pe-d-18-00043.
Повний текст джерелаАнотація:
BackgroundNeonatal hyperbilirubinemia (NNH) is the most common clinical sign seen in neonatal practice. Kangaroo mother care (KMC), a new strategy has been tried for the management of hyperbilirubinemia.AimsTo evaluate the role of KMC for reduction of bilirubin and duration of phototherapy in term and preterm neonates.MethodThe literature search was done for various randomized control trials by searching the Cochrane Central Register of Controlled Trials, PubMed, EMBASE, ongoing clinical trials and abstracts of conferences.ResultsThis review included five RCTs that fulfilled inclusion criteria. Out of five trials, two trials reported a significant reduction in bilirubin and three trials reported a significant reduction in duration of phototherapy.ConclusionKMC may be a novel strategy in the management of NNH. However, due to small sample size and heterogeneity between the trials, the current evidence is not sufficient. Hence, large trials with adequate sample sizes are needed.
15
Jeon, Hye Jun, Hyeonwook Park, Salh Alhammadi, Jae Hak Jung, and Woo Kyoung Kim. "Optimal Magnetic Graphite Heater Design for Impurity Control in Single-Crystal Si Grower Using Crystal Growth Simulation." Processes 10, no. 1 (December 30, 2021): 70. http://dx.doi.org/10.3390/pr10010070.
Повний текст джерелаАнотація:
In this paper, we report a successfully modified single-crystal Si growth furnace for impurity control. Four types of arbitrary magnetic heater (AMGH) systems with 3, 4, 5, and poly parts were designed in a coil shape and analyzed using crystal growth simulation. The concentration of oxygen impurities in single-crystal Si ingots was compared among the designed AMGHs and a normal graphite heater (NGH). The designed AMGHs were confirmed to be able to control turbulence and convection in a molten state, which created a vortex that influenced the oxygen direction near the melt–crystal interface. It was confirmed that replacing NGH with AMGHs resulted in a reduction in the average oxygen concentration at the Si melt–crystal interface by approximately 4.8%.
16
Li, Shuling, Jiannong Liu, Tingting Gong, Haifeng Guo, Prasad L. Gawade, Michael Anthony Kelsh, Brian D. Bradbury, Rajesh Belani, and Gary H. Lyman. "Risk of neutropenia-related hospitalization (NRH) related to duration of short-acting granulocyte colony stimulating factor (sG-CSF) for primary prophylaxis." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e18181-e18181. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e18181.
Повний текст джерелаАнотація:
e18181 Background: In clinical trials, efficacy of 1011 days of primary prophylactic (PP) sG-CSF is similar to a single dose of pegfilgrastim for preventing febrile neutropenia (FN). However, most patients receive < 10 days of PP sG-CSF in clinical practice. This study assessed the effect of PP sG-CSF duration on the risk of NRH. Methods: Using Medicare 20% sample data, we conducted a nested case-control study within a cohort of patients aged ≥66 y with breast, colorectal, lung, ovarian, or prostate cancer or NHL who initiated first cycle of chemotherapy 1/1/20089/30/2016, had ≥1 y continuous coverage in Medicare parts A and B before cycle day 1 (baseline), and received PP sG-CSF. We identified NRH cases (ICD-9, 288.0X; ICD-10, D70.X) from cycle day 5 to end of cycle 1. We matched each case to up to 4 controls based on age (± 1 y), tumor type, regimen risk for FN (intermediate/high [ > 10%], other), and year using incidence density sampling. Duration of sG-CSF (days of use from cycle day 1 to the day before case date) was categorized as < 5 and ≥5 days. We used conditional logistic regression adjusted for race, sex, and Charlson comorbidity index (CCI) at baseline to estimate relative risk of NRH related to duration of sG-CSF. Results: Of 1431 patients receiving PP sG-CSF, 68 cases matched 231 controls. Cases were similar to controls in age (76 vs 75 y), tumor type (NHL, 62% vs 62%; lung cancer, 25% vs 25%), intermediate-/high-risk regimen (65% vs 67%), and male sex (50% vs 48%) but had slightly higher CCI (3.9 vs 3.3). The percentage of patients with ≥5 days of PP sG-CSF use was 26% in cases and 41% in controls. The adjusted OR (95% CI) for NRH was 0.48 (0.250.93) for ≥5 vs < 5 days of PP sG-CSF; results were consistent across sensitivity analyses (Table). Conclusions: Among elderly cancer patients receiving PP sG-CSF, ≥5 days of sG-CSF use was associated with substantial reduction in the risk of NRH.[Table: see text]
17
Wakley, Alexa A., and Ling Cao. "Contribution of CD137-CD137L pathway in sciatic nerve crush-induced behavioral hypersensitivity and functional reduction." Journal of Immunology 204, no. 1_Supplement (May 1, 2020): 64.13. http://dx.doi.org/10.4049/jimmunol.204.supp.64.13.
Повний текст джерелаАнотація:
Abstract The T cell costimulatory molecule CD137L is involved in the development of neuropathic pain following peripheral nerve injury. Previously, our work has shown that absence or neutralization of CD137L reduces hypersensitivity, sensory and functional impairment following a sciatic nerve crush (SNC). CD137L activation utilizes both a CD137-dependent and a CD137-independent pathway. To further determine the contribution of these pathways, we examined pain-like and functional recovery-related behavioral responses following intrathecal injection (IT) of a CD137 neutralizing antibody (αCD137; daily days 3–10) after SNC in male and female B6 mice. Mice were randomly assigned to 1 of 4 groups: PBS, 0.5μg isotype control, 0.1 or 0.5μg of αCD137, and then were evaluated for sensitivity (von Frey, Hargreaves, & cold plantar test), sensory (pin prick assay) and motor (hind limb grip strength, toe spread reflex and toe spacing score) functions before surgery and on post-surgery days 1–77. On post-SNC day 1, all groups showed changes in sensitivity and decreased sensory and motor functions. αCD137 treatment did not alter mechanical, heat or hypersensitivity compared to PBS- or isotype-treated controls. αCD137-treated groups showed faster sensory (pin prick score) and motor functional recovery (toe spread reflex, toe spacing), as well as slightly greater improvement in grip strength test compared to controls. Together, our results indicate partial involvement of the CD137-dependent pathway in SNC-induced sensory and motor function changes following peripheral nerve injury. (Supported by NIH/NINDS R01NS098426 (Cao))
18
Cacuci, Dan Gabriel. "Overview of Arbitrarily High-Order Adjoint Sensitivity and Uncertainty Quantification Methodology for Large-Scale Systems." Energies 15, no. 18 (September 8, 2022): 6590. http://dx.doi.org/10.3390/en15186590.
Повний текст джерелаАнотація:
This work reviews from a unified viewpoint the concepts underlying the “nth-Order Comprehensive Adjoint Sensitivity Analysis Methodology for Response-Coupled Forward/Adjoint Linear Systems” (nth-CASAM-L) and the “nth-Order Comprehensive Adjoint Sensitivity Analysis Methodology for Nonlinear Systems” (nth-CASAM-N) methodologies. The practical application of the nth-CASAM-L methodology is illustrated for an OECD/NEA reactor physics benchmark, while the practical application of the nth-CASAM-N methodology is illustrated for a nonlinear model of reactor dynamics that exhibits periodic and chaotic oscillations. As illustrated both by the general theory and by the examples reviewed in this work, both the nth-CASAM-L and nth-CASAM-N methodologies overcome the curse of dimensionality in sensitivity analysis. The availability of efficiently and exactly computed sensitivities of arbitrarily high order can lead to major advances in all areas that need such high-order sensitivities, including data assimilation, model calibration, uncertainty reduction, and predictive modeling.
19
Kabakov, Anna, and Andrew Merker. "The Comparative Dosing and Glycemic Control of Intermediate and Long-Acting Insulins in Adult Patients With Type 1 and 2 Diabetes Mellitus." Journal of Pharmacy Technology 38, no. 1 (November 10, 2021): 46–53. http://dx.doi.org/10.1177/87551225211055700.
Повний текст джерелаАнотація:
Objective: The various basal insulin products possess differences in pharmacokinetics that can significantly impact glycemic control and total daily basal insulin dosing. In addition, there will be instances where transitions between the different long-acting insulins will need to be made. Because every basal insulin product is not interchangeable on a 1:1 unit-to-unit basis, it is important for health care providers to understand the expected dose adjustments necessary to maintain a similar level of glycemic control. Data Sources: A Medline and Web of Science search was conducted in September 2021 using the following keywords and medical subjecting headings: NPH, glargine, detemir, type 1 diabetes mellitus, and type 2 diabetes mellitus. Study Selection and Data Extraction: Included articles were those that followed adult patients with type 1 diabetes mellitus and/or type 2 diabetes mellitus and compared the following types of insulin: “NPH and glargine,” “NPH and detemir,” and “glargine and detemir” for at least 4 weeks, had documented basal insulin (BI) doses, and excluded pregnant patients. Data synthesis: Twenty-five articles were found that include adult type 1 and/or type 2 diabetes mellitus patients. Once daily NPH can be converted unit-to-unit to glargine or detemir. Twice daily NPH converted to glargine or detemir requires an initial 20% reduction in BI dose. An increase in dose of BI is recommended when transitioning from glargine to detemir. Glargine and detemir consistently resulted in improved glycemic control with lower incidence of hypoglycemic events compared with NPH. Conclusions: When transitioning between long-acting insulins, the doses are not always interchangeable on a 1:1 basis. Unit dose adjustments are likely if transitioning between BIs and can influence short-term parameters in the acute care setting and long-term parameters in the outpatient setting.
20
Broks, K., A. Geenen, F. Nelen, and P. Jacobsen. "The Potential of Real Time Control to reduce Combined Sewer Overflow." Hydrology Research 26, no. 3 (June 1, 1995): 223–36. http://dx.doi.org/10.2166/nh.1995.0013.
Повний текст джерелаАнотація:
The potential of Real Time Control (RTC) to reduce the overflow volume from a combined sewer system has been investigated for a catchment in Copenhagen, named Strandvaenget. The results have been compared with the alternative of increasing the storage volume of the system. The RTC strategy has been derived using a mathematical optimization and a rule based method. As the only objective is to reduce the Combined Sewer Overflow (CSO), the developed rule based control algorithm can achieve almost the same results as the optimization method. From the results of time series calculations, it can be concluded that the introduction of RTC appears very promising when the mean yearly CSO volume has to be reduced. In this research, the potential of RTC is investigated for an increasing amount of storage volume and for an increasing demand for reduction of CSO volume.
21
Kamber, Harth Mohamed, Tawfiq Jasim Mohammed Al-Marzooq, Malath Anwar Hussein, Qays Ahmed Hassan, and Ahmed Abid Marzouq. "The use of Cinnamon (Cinnamomum Bark) for Patients with Chronic Prostatitis/Chronic Pelvic Pain Syndrome: A Randomized Controlled Trial." Open Access Macedonian Journal of Medical Sciences 8, B (August 5, 2020): 439–45. http://dx.doi.org/10.3889/oamjms.2020.3311.
Повний текст джерелаАнотація:
BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is common, yet no curative treatment identified. Cinnamon is a herbal substance, which has many applications in medicine.
AIM: The aim of the study was to study the effect of cinnamon on patients with chronic pelvic pain syndrome.
METHODS: Sixty patients with documented CP/CPPS randomized into two groups during 2018 and 2019 in Baghdad. The first group received 60 capsules each contained 1 g of cinnamon. The other group received 60 capsules each contained 1 g of sugar powder (placebo). All the patients instructed to take one capsule twice daily for 1 month. National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) was reported for both groups at baseline and after 1 month of treatment. The primary outcome was a patient perceivable improvement defined as a reduction of the NIH-CPSI by 6 or more points after 1 month, whereas improvement of sub-scores of NIH-CPSI (pain, urinary symptoms, and quality of life) considered as a secondary outcome, and adverse reactions reported.
RESULTS: Thirteen patients (43.3%) of the cinnamon group have 6 or more points of reduction in the total NIH-CPSI compared to four patients (13.3%) of the control groups (p = 0.01). The improvement in total NIH-CPSI score was mainly due to improvement in pain sub-score, whereas in urinary symptoms, there was marginal change with no significant change in the quality of life score. The only reported side effect was gastric upset in one patient.
CONCLUSION: The study concluded that cinnamon improves NIH-CPSI in patients with CP/CPPS.
REGISTRATION: The study was registered on ClinicalTrials.gov with the ID: NCT03946163.
22
Marra, Lays Pires, Daniel da Silva Pereira, and Gustavo Laine Araújo de Oliveira. "VP53 Long-Acting Insulin Analogues In Brazil: Clinical And Economic Impact." International Journal of Technology Assessment in Health Care 35, S1 (2019): 88. http://dx.doi.org/10.1017/s0266462319003179.
Повний текст джерелаАнотація:
IntroductionThe aim was to evaluate the effectiveness, safety and economic impact of long-acting insulin analogues (LAIA) compared to NPH for type 1 diabetes mellitus (DM1).MethodsA search was performed in five electronic databases to find systematic reviews (SR) comparing at least a LAIA to NPH insulin for DM1. Budget impact analysis was performed from the perspective of Brazilian public health system (SUS), with NPH insulin as the base scenario. The costs were extracted from the Integrated System of Administration of General Services (SIASG). The market share was calculated per month, using a logarithmic function with maximum diffusion of 50% at the end of the time horizon - five years.ResultsA total of 160 studies were identified and seven SR of low to uncertain risk of bias were selected. LAIA have shown modest clinical benefit and its effect is more prominent for the control of severe and nocturnal hypoglycaemia. Insulins glargine and detemir compared to NPH were associated with reduction in HbA1c levels between 0.16% and 0.40% and associated with lower risk of episodes of severe hypoglycemia. Insulin degludec compared to NPH showed no statistically significant difference in the reduction of HbA1c levels and in the episodes of severe hypoglycemia. The budget impact ranges from USD 210 million (detemir) to USD 670 million (degludec) over five years.ConclusionsThe use of LAIA as a basal insulin regimen for DM1 may benefit more patients with recurrent episodes of hypoglycemia. However, the fragility of the outcomes considered to evaluate the clinical impact of LAIA and the high budget impact with its use should be considered, and may compromise SUS sustainability. In view of these aspects, CONITEC recommended the incorporation of one of the LAIA, if the treatment is equal to or less than that of NPH insulin and according to the criteria established by a guideline.
23
Kim, Youngjung, Robyn Sysko, Andreas Michaeledes, Tatiana Ramos, and Tom Hildebrandt. "92 Effects of Smartphone Coaching Intervention on Dietary Intake for Bariatric Surgery Candidates: A Pilot Randomized Controlled Trial." CNS Spectrums 24, no. 1 (February 2019): 220–21. http://dx.doi.org/10.1017/s1092852919000683.
Повний текст джерелаАнотація:
AbstractIntroductionBariatric surgery outcomes are variable, often with suboptimal weight loss and/or weight relapse. Smartphone coaching applications offer a potential window of affecting behavioral change to improve outcomes in a widespread and cost-effective way, but clinical efficacy is unknown. In phase I of this pilot study, we investigated effects of pre-surgical treatment with a mobile coaching platform Noom Coach for Bariatric Health.MethodsForty adult candidates (82.5% female) for bariatric surgery were recruited for pilot randomized controlled trial (Noom Bariatric Health vs. Standard Care). All participants’ dietary intake was assessed initially and after 8weeks of intervention, with the 24-hour dietary recall (ASA24) to analyze food intake. Paired t-tests were used to compare within group changes in dietary parameters. Independent t-tests were used to assess inter-group differences at the end of treatment.ResultsPost intervention, both Noom and Control groups consumed numerically less total calories, empty calories, fat, and carbohydrates compared to their baseline. Reduction in empty calorie consumption was significant only in Noom (t=2.39, p=0.04, Cohen’s d=0.96) and not in Control (t=0.89, p=0.40, Cohen’s d=0.30). Both total kcal and total fat intake showed larger numerical reductions within Noom (kcal,fat: t=1.94,2.07; p=0.08,0.07; Cohen’s d=1.03,1.06) compared to reductions seen within Control (kcal,fat; t=0.41,0.48; p=0.69,0.64; Cohen’s d=0.14,0.16). There were no other significant changes in macronutrients and micronutrients within groups. At the end of treatment, Noom compared to Control groups had significantly lower percentage fat intake (t=3.02, p=0.008, Cohen’s d=1.42) without initial difference at screening (t=1.12, p=0.27, Cohen’s d=0.36).DiscussionThough limited due to small sample size, preliminary results appear promising that mobile coachingintervention may have beneficial effects on diet pre-bariatric surgery. We will discuss the impact of these findings on potential post-surgery outcomes.Funding Acknowledgements: NIH R44DK116370, Mount Sinai Hospital
24
Martínez-Gac, Lorena, Miriam Marqués, Zaira García, Miguel R. Campanero, and Ana C. Carrera. "Control of Cyclin G2 mRNA Expression by Forkhead Transcription Factors: Novel Mechanism for Cell Cycle Control by Phosphoinositide 3-Kinase and Forkhead." Molecular and Cellular Biology 24, no. 5 (March 1, 2004): 2181–89. http://dx.doi.org/10.1128/mcb.24.5.2181-2189.2004.
Повний текст джерелаАнотація:
ABSTRACT Cyclin G2 is an unconventional cyclin highly expressed in postmitotic cells. Unlike classical cyclins that promote cell cycle progression, cyclin G2 blocks cell cycle entry. Here we studied the mechanisms that regulate cyclin G2 mRNA expression during the cell cycle. Analysis of synchronized NIH 3T3 cell cultures showed elevated cyclin G2 mRNA expression levels at G0, with a considerable reduction as cells enter cell cycle. Downregulation of cyclin G2 mRNA levels requires activation of phosphoinositide 3-kinase, suggesting that this enzyme controls cyclin G2 mRNA expression. Because the phosphoinositide 3-kinase pathway inhibits the FoxO family of forkhead transcription factors, we examined the involvement of these factors in the regulation of cyclin G2 expression. We show that active forms of the forkhead transcription factor FoxO3a (FKHRL1) increase cyclin G2 mRNA levels. Cyclin G2 has forkhead consensus motifs in its promoter, which are transactivated by constitutive active FoxO3a forms. Finally, interference with forkhead-mediated transcription by overexpression of an inactive form decreases cyclin G2 mRNA expression levels. These results show that FoxO genes regulate cyclin G2 expression, illustrating a new role for phosphoinositide 3-kinase and FoxO transcription factors in the control of cell cycle entry.
25
Selge, Charlotte, Florian Schoeberl, Andreas Zwergal, Georg Nuebling, Thomas Brandt, Marianne Dieterich, Roman Schniepp, and Klaus Jahn. "Gait analysis in PSP and NPH." Neurology 90, no. 12 (February 21, 2018): e1021-e1028. http://dx.doi.org/10.1212/wnl.0000000000005168.
Повний текст джерелаАнотація:
ObjectiveTo test whether quantitative gait analysis of gait under single- and dual-task conditions can be used for a differential diagnosis of progressive supranuclear palsy (PSP) and idiopathic normal-pressure hydrocephalus (iNPH).MethodsIn this cross-sectional study, temporal and spatial gait parameters were analyzed in 38 patients with PSP (Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy diagnostic criteria), 27 patients with iNPH (international iNPH guidelines), and 38 healthy controls. A pressure-sensitive carpet was used to examine gait under 5 conditions: single task (preferred, slow, and maximal speed), cognitive dual task (walking with serial 7 subtractions), and motor dual task (walking while carrying a tray).ResultsThe main results were as follows. First, both patients with PSP and those with iNPH exhibited significant gait dysfunction, which was worse in patients with iNPH with a more broad-based gait (p < 0.001). Second, stride time variability was increased in both patient groups, more pronounced in PSP (p = 0.009). Third, cognitive dual task led to a greater reduction of gait velocity in PSP (PSP 34.4% vs iNPH 16.9%, p = 0.002). Motor dual task revealed a dissociation of gait performance: patients with PSP considerably worsened, but patients with iNPH tended to improve.ConclusionPatients with PSP seem to be more sensitive to dual-task perturbations than patients with iNPH. An increased step width and anisotropy of the effect of dual-task conditions (cognitive vs motor) seem to be good diagnostic tools for iNPH.
26
Zhang, Lei, Zahid Hussain, and Zhuanqin Ren. "Recent Advances in Rational Diagnosis and Treatment of Normal Pressure Hydrocephalus: A Critical Appraisal on Novel Diagnostic, Therapy Monitoring and Treatment Modalities." Current Drug Targets 20, no. 10 (July 12, 2019): 1041–57. http://dx.doi.org/10.2174/1389450120666190214121342.
Повний текст джерелаАнотація:
Background:Normal pressure hydrocephalus (NPH) is a critical brain disorder in which excess Cerebrospinal Fluid (CSF) is accumulated in the brain’s ventricles causing damage or disruption of the brain tissues. Amongst various signs and symptoms, difficulty in walking, slurred speech, impaired decision making and critical thinking, and loss of bladder and bowl control are considered the hallmark features of NPH.Objective:The current review was aimed to present a comprehensive overview and critical appraisal of majorly employed neuroimaging techniques for rational diagnosis and effective monitoring of the effectiveness of the employed therapeutic intervention for NPH. Moreover, a critical overview of recent developments and utilization of pharmacological agents for the treatment of hydrocephalus has also been appraised.Results:Considering the complications associated with the shunt-based surgical operations, consistent monitoring of shunting via neuroimaging techniques hold greater clinical significance. Despite having extensive applicability of MRI and CT scan, these conventional neuroimaging techniques are associated with misdiagnosis or several health risks to patients. Recent advances in MRI (i.e., Sagittal-MRI, coronal-MRI, Time-SLIP (time-spatial-labeling-inversion-pulse), PC-MRI and diffusion-tensor-imaging (DTI)) have shown promising applicability in the diagnosis of NPH. Having associated with several adverse effects with surgical interventions, non-invasive approaches (pharmacological agents) have earned greater interest of scientists, medical professional, and healthcare providers. Amongst pharmacological agents, diuretics, isosorbide, osmotic agents, carbonic anhydrase inhibitors, glucocorticoids, NSAIDs, digoxin, and gold-198 have been employed for the management of NPH and prevention of secondary sensory/intellectual complications.Conclusion:Employment of rational diagnostic tool and therapeutic modalities avoids misleading diagnosis and sophisticated management of hydrocephalus by efficient reduction of Cerebrospinal Fluid (CSF) production, reduction of fibrotic and inflammatory cascades secondary to meningitis and hemorrhage, and protection of brain from further deterioration.
27
Khan, Ismailkhan Enayathulla, and Rajendran Paramasivam. "Reduction in Waiting Time in an M/M/1/N Encouraged Arrival Queue with Feedback, Balking and Maintaining of Reneged Customers." Symmetry 14, no. 8 (August 22, 2022): 1743. http://dx.doi.org/10.3390/sym14081743.
Повний текст джерелаАнотація:
In this research, we look at the work associated with the encouraged arrival line with feedback, balking and maintaining reneged clients. We analyse the quality control policy for the Markovian model using an iterative method to the nth customer in the system. We derive performance measures for the expected number of units in the system, as well as in the queue and the average number of occupied services and the expected waiting time in the system, as well as in the queue. To show the effectiveness, we provide numerical examples for the average default rate and average retention rate. The developed formula also satisfies Little’s formula.
28
Liang, Zhijian, Jinsheng Zeng, Cuimei Zhang, Sirun Liu, Xueying Ling, Fang Wang, Li Ling, Qinghua Hou, Shihui Xing, and Zhong Pei. "Progression of Pathological Changes in the Middle Cerebellar Peduncle by Diffusion Tensor Imaging Correlates With Lesser Motor Gains After Pontine Infarction." Neurorehabilitation and Neural Repair 23, no. 7 (February 25, 2009): 692–98. http://dx.doi.org/10.1177/1545968308331142.
Повний текст джерелаАнотація:
Background. Wallerian degeneration in pyramidal tract following supratentorial stroke has been detected by some studies using diffusion tensor imaging (DTI), but the Wallerian degeneration in middle cerebellar peduncle after pontine infarction and its potential clinical significance remain to be confirmed. Methods. Seventeen patients with a recent focal pontine infarct underwent 3 DTIs at week 1 (W1), week 4 (W4), and week 12 (W12) after onset. Seventeen age-matched and gender-matched controls underwent DTI one time. Mean diffusivity and fractional anisotropy (FA) were measured in the basis pontis and bilateral middle cerebellar peduncles. Neurological deficit, motor deficit, functional independence, and limbs ataxia were assessed with the National Institutes of Health (NIH) Stroke Scale, Fugl-Meyer scale, Barthel Index, and the second part of International Cooperative Ataxia Rating Scale. Results. FA values at the bilateral middle cerebellar peduncles decreased significantly from W1 to W12 progressively ( P < .01). The patients improved on the NIH Stroke Scale, Fugl-Meyer scale, and Barthel Index over time ( P < .01). Greater absolute value of percentage reduction of FA at the bilateral middle peduncles, however, was associated with the less absolute value of percentage reduction of the NIH Stroke Scale and less increase in the Fugl-Meyer scale, as well as greater ataxia over time. Conclusions. Wallerian degeneration in the middle cerebellar peduncle revealed by DTI may hinder the process of neurological recovery following a focal pontine infarct.
29
de Vasconcellos, Jaira F., Colleen Byrnes, Y. Terry Lee, Megha Kaushal, Joshua M. Allwardt, Antoinette Rabel, and Jeffery L. Miller. "Targeted Reduction of Let-7a miRNA Increases Fetal Hemoglobin in Human Adult Erythroblasts." Blood 124, no. 21 (December 6, 2014): 451. http://dx.doi.org/10.1182/blood.v124.21.451.451.
Повний текст джерелаАнотація:
Abstract MicroRNAs (miRNAs) are a class of small, noncoding RNAs that bind and regulate target messenger RNAs (mRNAs). The let-7 family consists of twelve genes encoding nine highly conserved miRNAs that are involved in developmental timing events in multicellular organisms. Previous studies showed regulation during the fetal-to-adult transition in the erythroid lineage with significant increases in let-7 miRNAs from adult compared to umbilical cord blood reticulocytes (1). Further studies indicated that reduced expression of let-7 in adult CD34+ cells by “sponge” targeting the miRNA family seed region caused increased fetal hemoglobin (HbF), but the mean level of HbF remained less than 20% of the total hemoglobin (2). Increased expression of LIN28A (a major regulator of all let-7 miRNAs) caused greater increases in HbF (greater than 30% of the total) in cultured erythrocytes from pediatric patients with HbSS genotype (3). However, these studies did not address the potential for targeting an individual let-7 miRNA family member to regulate HbF expression. For this purpose, we initially determined the expression levels of mature let-7 family members in purified cell populations sorted from peripheral blood. The total levels of let-7 miRNAs in peripheral blood cells were as follows: reticulocytes: 1.7E+08 ± 1.0E+08 copies/ng; neutrophils: 2.0E+07 ± 1.1E+07 copies/ng; lymphocytes: 1.1E+07 ± 6.2E+06 copies/ng and monocytes: 3.5E+06 ± 2.7E+06 copies/ng. Among the individual species, let-7a was identified as a predominantly expressed let-7 family member in reticulocytes. As such, we hypothesized that specifically targeting let-7a may be sufficient to regulate HbF levels. To study the effects of let-7a miRNAs upon erythropoiesis and globin expression, a lentiviral construct that incorporated the tough decoy (TuD) design to target let-7a was compared with empty vector controls. Transductions were performed in CD34+ cells from five adult healthy volunteers cultivated ex vivo in erythropoietin-supplemented serum-free media for 21 days. Down-regulation of let-7a was confirmed by Q-RT-PCR at day 14 (control: 1.4E+07 ± 2.4E+06 copies/ng; let-7a-TuD: 1.6E+06 ± 4.6E+05 copies/ng; p=0.0003). Cell proliferation and differentiation were comparable in let-7a-TuD versus control transductions. Expression levels of globin genes were evaluated upon let-7a-TuD by Q-RT-PCR. Let-7a-TuD transductions caused significantly increased gamma-globin mRNA expression levels compared to control transductions (control: 1.2E+06 ± 6.8E+05 copies/ng; let-7a-TuD: 1.1E+07 ± 4.5E+06 copies/ng; p=0.004). HPLC analyses at the end of the culture period demonstrated robust increases in HbF levels after let-7a-TuD transduction (HbF control: 4.7 ± 0.6%; let-7a-TuD: 38.2 ± 3.8%; p=0.00003). In addition, the expression patterns of the erythroid transcription factors BCL11A, KLF1 and SOX6 were investigated. Let-7a-TuD decreased BCL11A mRNA expression levels (control: 1.7E+03 ± 4.5E+02 copies/ng; let-7a-TuD: 4.3E+02 ± 1.8E+02 copies/ng; p=0.003), but major changes in KLF1 or SOX6 were not detected. In summary, we report here that the let-7 miRNA family is differentially expressed in purified cell populations from adult human blood, and that let-7a is a predominantly expressed species in reticulocytes. Further, targeted reduction of let-7a in erythroblasts is sufficient to cause robust increases in gamma-globin mRNA expression and HbF to mean levels around 35-40% of the total hemoglobin produced. Targeting of individual let-7 genes or RNA transcripts may be useful for therapeutic induction of HbF expression in patients with sickle cell disease or other beta-hemoglobinopathies. 1) Noh SJ et al. J Transl Med. 7:98 (2009). 2) Lee YT et al. Blood. 122:1034-41 (2013). 3) Vasconcellos JF et al. Blood. 122: Abstract 313 (2013). Disclosures No relevant conflicts of interest to declare.
30
Richardson, Shakyra S., Courtnee Bell, Leandra Jones, FNU Medhavi, Tayhlor Tanner, Stephanie Lundy, Yusuf Omosun, and Francis O. Eko. "Evaluation of the protective efficacy of a novel rVCG-based Chlamydia abortus vaccine in a pregnant mouse model." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 181.06. http://dx.doi.org/10.4049/jimmunol.208.supp.181.06.
Повний текст джерелаАнотація:
Abstract Chlamydia abortus (Cab) is the cause of ovine enzootic abortion (OEA) in small ruminants and poses a zoonotic risk to pregnant women, which may result in spontaneous abortion. Although antibiotics are effective against Cab infection, most infections are asymptomatic, suggesting alternative strategies may be required for controlling these infections. We tested the ability of a recombinant Vibrio cholerae ghost (rVCG)-based Cab subunit vaccine expressing the truncated Cab polymorphic membrane protein 18D (rVCG-Pmp18.3) to protect against Cab-induced abortion in a pregnant mouse model. Thus, groups of female C57bl/6J mice were immunized intranasally (IN) with rVCG-Pmp18.3 and mated with males 3 weeks post immunization. Immunized and control mice were infected IN or transcervically (TC) at day 10 of pregnancy and the number of pups per mouse was enumerated 7 days postpartum. Mice were sacrificed on day 8 and Cab burden in the lungs and spleens was determined. The results showed IN immunization protected mice against abortion and neonatal death while IN infected control mice lost 20% of their litter and 60% of TC infected controls lost their entire litter 7 days post-parturition. Immunized mice completely cleared the infection in the lungs and showed a significant reduction (p ≤0.0001) in bacterial burden in the spleen compared to non-immunized, infected controls. Furthermore, immunized mice were protected from uterine dilation compared to 60% of non-immunized controls that developed tubal pathology. These results demonstrate the ability of rVCG-Pmp18.3 to prevent respiratory/systemic infection and protect against Cab-induced abortion and tubal pathologies in mice, suggesting its potential development as a vaccine for ruminants. Supported by PHS grant R01AI41231 and NIH R01AI26897
31
Lee, Lena J., Robert Shamburek, Hyojin Son, Gwenyth R. Wallen, Robert Cox, Sharon Flynn, Li Yang, Margaret Bevans, Leslie Wehrlen, and Alyson Ross. "Effects of a yoga-based stress reduction intervention on stress, psychological outcomes and cardiometabolic biomarkers in cancer caregivers: A randomized controlled trial." PLOS ONE 17, no. 11 (November 10, 2022): e0277009. http://dx.doi.org/10.1371/journal.pone.0277009.
Повний текст джерелаАнотація:
Caregiving stress is a risk factor for cardiometabolic disease. Therefore, integrating cardiometabolic biomarkers into caregiving research provides a more comprehensive assessment of an individual’s health and response to an intervention. The objective of this study was to examine the effects of a yoga-based stress reduction intervention on stress, psychological outcomes, and cardiometabolic biomarkers in cancer caregivers. This prospective randomized controlled trial enrolled family caregivers of adult patients who underwent an allogeneic HSCT at the National Institutes of Health (NIH) Clinical Center. All subjects received usual care education. Participants in the intervention group received an Iyengar yoga intervention self-administered over six weeks using an audio recording file. The primary outcome was perceived stress (measured using the NIH toolbox Perceived Stress). The secondary outcomes were psychological factors (depression and anxiety measured using PROMIS® Depression and Anxiety), and cardiometabolic biomarkers measured by nuclear magnetic resonance spectroscopy. A total of 50 family caregivers (mean [SD] age, 44.9 [15.2] years; 42 [84.0%] women) were randomized, 25 to the intervention group and 25 to the control group. No group differences were noted in stress, depression, and anxiety. Significant interaction effects between group and time were found in large TRL-P (F(1,43) = 10.16, p = 0.003) and LP-IR (F(1,42) = 4.28, p = 0.045). Post-hoc analyses revealed that the levels of large TRL-P (mean difference = 1.68, CI = [0.86, 2.51], p< .001) and LP-IR (mean difference = 5.67, CI = [1.15, 10.18], p = 0.015) significantly increased over time in the control group but while remained stable in the intervention group (mean difference = -0.15, CI = [-0.96, 0.66], p = 0.718; mean difference = -0.81, CI = [-5.22, 3.61], p = 0.714, respectively). Even when perceptions of psychological distress remain unchanged, incorporating gentle yoga poses and breathing exercises may reduce the risk of cardiometabolic disease in caregivers by inhibiting the development of insulin resistance. Standard lipids of cardiometabolic risk do not appear to be robust enough to detect short-term early changes of cardiometabolic risk in caregivers. Trial registration: ClinicalTrials.gov Identifier: NCT02257853.
32
Kiradzhiyska, Denitsa, Nikolina Milcheva, Rositsa Mancheva, Tsvetelina Batsalova, Balik Dzhambazov, and Nikolay Zahariev. "Preparation and Preliminary Evaluation of Silver-Modified Anodic Alumina for Biomedical Applications." Metals 12, no. 1 (December 27, 2021): 51. http://dx.doi.org/10.3390/met12010051.
Повний текст джерелаАнотація:
The present study reports a specific method for preparation of silver-modified anodic alumina substrates intended for biomaterial applications. Al2O3 coatings were obtained by anodization of technically pure aluminum alloy in sulfuric acid electrolyte. Silver deposition into the pores of the anodic structures was carried out employing in situ thermal reduction for different time periods. The obtained coatings were characterized using scanning electron microscopy (SEM), potentiodynamic scanning after 168 h in 3.5% NaCl solution and bioassays with human fibroblast and NIH/3T3 cell lines. The modified alumina substrates demonstrated better biocompatibility compared to the control anodic Al2O3 pads indicated by increased percent cell survival following in vitro culture with human and mouse fibroblasts. The Ag-deposition time did not affect considerably the biocompatibility of the investigated anodic layers. SEM analyses indicated that mouse NIH/3T3 cells and human fibroblasts adhere to the silver-coated alumina substrates retaining normal morphology and ability to form cell monolayer. Therefore, the present studies demonstrate that silver coating of anodic alumina substrates improves their biocompatibility and their eventual biomedical application.
33
Luna, Nenuel Angelo B., and Leilani B. Mercado-Asis. "Giving Insulin Is Not a Guessing Game: Insulin Replacement Therapy in Type 2 Diabetes Mellitus." Journal of Medicine, University of Santo Tomas 6, no. 1 (April 30, 2022): 868–80. http://dx.doi.org/10.35460/2546-1621.2022-0032.
Повний текст джерелаАнотація:
In 2021, 537 million adults were living with diabetes. Being a progressive disease, there would eventually be failure of oral hypoglycemic agents (OHA) to maintain good glycemic control and a majority will require insulin. However, optimal glycemic control has not been satisfactory in a significant proportion of patients who were on insulin therapy. Patient factors (eg, awareness, compliance, socioeconomic) have been identified but physician-related factors are as important. These include incorrect choice and inappropriate combination of insulin therapy which could be corrected by making the treatment physiologic. The purpose of this article is to improve management decisions in type 2 diabetes by reviewing its pathophysiology and identifying the optimum insulin regimen that could mimic such. Since eventual beta cell failure is central to its pathophysiology, it is but reasonable to replace insulin by mimicking its physiologic secretion. Hence, the term Insulin Replacement Therapy (IRT) should be utilized. This could be provided by the combination of premix insulin (ie, NPH + regular insulin) and rapid-acting insulin which has been reported to provide an initial 17.5% HbA1c reduction and even 18% reduction on 5-year follow-up providing sustainable control. A stepwise approach is an effective tool for insulin intensification. Hypoglycemia in insulin therapy could be prevented with an appropriate dietary regimen through automatic snacking. Keywords: Insulin replacement therapy, type 2 diabetes mellitus, pathophysiology
34
Cao, Liang, Eva Morgun, Samantha Genardi, Lavanya Visvabharathy, Haochu Huang, and Chyung-Ru Wang. "Mettl14-dependent m6A modification controls iNKT cells development and function." Journal of Immunology 208, no. 1_Supplement (May 1, 2022): 55.01. http://dx.doi.org/10.4049/jimmunol.208.supp.55.01.
Повний текст джерелаАнотація:
Abstract N6-Methyladenosine (m6A), the most common form of RNA modification, controls CD4+ T cell homeostasis by targeting the IL-7/STAT5/SOCS signaling pathways. The role of m6A modification in unconventional T cell development remains unknown. Using mice with T cell-specific deletion of RNA methyltransferase METTL14 (T-Mettl14 −/−), we demonstrated that m6A modification was indispensable for iNKT cell homeostasis. Loss of METTL14-dependent m6A modification led to the upregulation of p53-mediated apoptosis in double positive thymocytes, which in turn decreased distal Va-Ja gene rearrangements, including the invariant Va14-Ja18 TCR, resulting in a drastic reduction of iNKT numbers in the thymus and periphery. Residual T-Mettl14−/− iNKT cells exhibited increased apoptosis, impaired maturation, and decreased responsiveness to IL-2/IL-15 and TCR stimulation. Furthermore, METTL14 knockdown in mature iNKT cells diminished their cytokine production, correlating with increased Cish expression and decreased TCR signaling. Collectively, our study highlights a critical role for METTL14-dependent-m6A modification in iNKT cell development and function. This work was supported by NIH grants R01 AI41083 and R01 AI057460 to C.-R.W.
35
Nash, William T., Shinji Tanaka та Mark D. Okusa. "Vagus nerve stimulation leads to contraction of the spleen and dampened IFNγ production in response to TLR stimulation". Journal of Immunology 208, № 1_Supplement (1 травня 2022): 111.31. http://dx.doi.org/10.4049/jimmunol.208.supp.111.31.
Повний текст джерелаАнотація:
Abstract Vagus nerve stimulation (VNS) generates an anti-inflammatory state and limits the pathology of inflammatory diseases, such as sepsis and acute kidney injury. Interestingly, splenectomy prior to stimulation results in a loss of this protection. Thus, the spleen is a central organ for converting VNS signals into protective anti-inflammation. To better understand the interplay between VNS and the spleen and gain insight into the mechanisms of anti-inflammation, we performed a broad query of the spleen post-VNS. Mice received either electrical stimulation of the left-cervical vagus nerve or sham surgery. Spleens were harvested and assessed for mass, immune cell populations, and splenocyte in vitro cytokine production in response to TLR4, 3, and 9 agonists (LPS, poly I:C, and CpG, respectively). We discovered that by 48 hours post-VNS, spleen mass was reduced and the number of CD45+ cells was significantly decreased compared to sham mice. Analysis of CD45+ cells revealed that many individual immune cell populations were diminished. B cells, T cells, NK cells, dendritic cells, and basophils were all significantly reduced and eosinophils and monocytes showed strong trends towards reduction, nearing significance. In response to TLR agonists, our Luminex analysis revealed a strong impact on TLR4 stimulation, with 12 of the 32 measured cytokines showing a significant reduction in supernatants from VNS samples. TLR3 and TLR9 stimulation also exhibited significant reductions in a subset of the measured cytokines, but only IFNγ exhibited strong signs of reduced production in all TLR stimulation conditions. Thus, VNS has profound impacts in the spleen and some of the observed protection could be due to tighter control of immune cell IFNγ secretion. Supported by grants from the NIH (R01 DK123248)
36
Chang, Chia-Cheng, Hiroyuki Asada, Toshiro Mimura, and Shinichi Suzuki. "A prospective study of cerebral blood flow and cerebrovascular reactivity to acetazolamide in 162 patients with idiopathic normal-pressure hydrocephalus." Journal of Neurosurgery 111, no. 3 (September 2009): 610–17. http://dx.doi.org/10.3171/2008.10.17676.
Повний текст джерелаАнотація:
Object Cerebral blood flow (CBF) and cerebrovascular reactivity (CVR) to acetazolamide were investigated prospectively in 162 patients with a proposed diagnosis of idiopathic normal-pressure hydrocephalus (NPH). The aim of this study was to assess the usefulness of the measurement of CBF and CVR in determining which patients would be likely to benefit from shunt placement. Methods The mean CBF of the whole brain was measured according to the Patlak plot method by using technetium-99m hexamethylpropyleneamine oxime. The CVR value was obtained from the response to administration of 500 mg acetazolamide and calculated as the percentage change from the baseline mean CBF value. Results One hundred forty-six patients (90.1%) responded to shunt placement (“responders”), but 16 patients (9.9%) did not (“nonresponders”). No significant difference in preoperative CBF was observed between responders and nonresponders. Preoperative CVR was significantly impaired (p < 0.0025) in responders compared with healthy controls, but not in nonresponders. Responders with the incomplete triad had a significant reduction (p < 0.001) in preoperative CVR, but not in preoperative CBF, compared with healthy controls. Responders with the complete triad had significantly lower preoperative CBF and CVR than those with the incomplete triad (p < 0.01 and p < 0.05, respectively). Postoperative CBF and CVR increased significantly (p < 0.025 and p < 0.001, respectively) in responders. Conclusions Both CBF and CVR decrease with the development of NPH, suggesting that hemodynamic ischemia may be responsible for manifestation of the symptoms. Impaired CVR and reduced CBF with the development of symptoms can be proposed as diagnostic criteria for idiopathic NPH.
37
Zielinski, Mark, Robert Strecker, James McKenna, James McNally, Brian Cade, and Susan Redline. "0033 Dysregulated sleep and NREM sleep electroencephalogram delta power induced by intermittent hypoxia exposure are attenuated in NLRP3 knockout mice." Sleep 45, Supplement_1 (May 25, 2022): A15—A16. http://dx.doi.org/10.1093/sleep/zsac079.032.
Повний текст джерелаАнотація:
Abstract Introduction The nucleotide-binding domain leucine rich family pyrin containing 3 (NLRP3) inflammasome protein complex activates caspase-1 to convert the pro-forms of IL-18 and IL-1 beta (IL-1β) into their active forms and is involved in homeostatic sleep and sleep responses to pathogenic stimuli. Intermittent hypoxia (IH) is a hallmark of sleep disordered breathing (SDB) and both IL-18 receptors are associated with SDB in humans. Thus, we hypothesized that NLRP3 inflammasomes are involved in SDB-related sleep disturbances. Methods Sleep architecture was assessed by polysomnography in NLRP3 knockout (KO) and wild-type (WT) mice (N = 8 per group). A gas exchange mixer delivered house air serving as a control or chronic IH that involved 90 second episodic oxygen reductions that consisted of ambient oxygen (21%) with brief hypoxic conditions (~10%) that lasted for 3 seconds for the first 10 h of the light period for 5 consecutive days. Gene expression and protein levels in the brain and lungs were assayed using real-time polymerase chain reaction and enzyme-linked immunosorbent assays, respectively. Results In WT mice, significant increased non-rapid-eye movement (NREM) sleep amounts and NREM sleep electroencephalogram delta power (0.5-4 Hz) were found after 1 day of IH compared to control conditions (p < 0.001). After 5 days of IH, WT mice showed a significant attenuation in NREM sleep amounts and NREM sleep delta power (p < 0.001) and increased wake bout frequency (p = 0.006) when compared to control conditions. However, the IH-induced NREM sleep and NREM sleep delta power enhancements and reductions were attenuated (21-35%) in NLRP3 KO mice compared to WT mice. In WT mice, NLRP3, IL-1β, IL-18 and caspase-1 gene expression, IL-1β and IL-18 protein levels, and caspase-1 activity were significantly increased in the somatosensory cortices, NTS, and lungs after both 1 and 5 days of IH when compared to control conditions (p < 0.05 for all), although NLRP3 KO mice did not exhibit significant differences in molecules downstream of NLRP3 inflammasome activation. Conclusion Our findings indicate that altered NLRP3 inflammasome activation contributes to dysregulated sleep occurring from IH and likely is involved in sleep disturbances in SDB. Support (If Any) VA Career Development Aware IBX002823, VA Merit BX004500, NIH/NIMH 1R21MH125242, NIH/NHLBI R03 HL154284, and NIH/NHLBI R35 HL135818. JTM received partial salary compensation and funding from Merck Investigator Sponsored Programs but has no conflict of interest with this work.
38
Xu, Shitian, Yuanfang Chai, Yao Yue, Xia Yan, and Xiaofeng Zhang. "Seasonal changes of sediment fluxes in the Yangtze River: roles of precipitation change, human conservation measures in sub-basins, and large dams." Hydrology Research 52, no. 2 (February 26, 2021): 461–77. http://dx.doi.org/10.2166/nh.2021.157.
Повний текст джерелаАнотація:
Abstract Seasonal sediment flux change is a key issue in riverbed evolution and flood control. This paper analyzed variations in sediment fluxes of the Yangtze River in dry and flood seasons during 1961–2014 and the impacts of precipitation change and human interference. Sediment fluxes in both dry and flood seasons decreased by 6.8–74.6 and 14.6–38.7%, respectively, based on daily sediment observations at six mainstream stations. However, precipitation increased sediment yields in both dry and flood seasons by 0.72–4.22 t/km2 (3.5–17.8%) and 4.95–73.32 t/km2 (1.9–25.5%), respectively, based on the reconstructed sediment series without anthropogenic interference. Therefore, sediment reduction due to human conservation measures and dam construction was up to 0.07–20.74 t/km2 (0.9–64.6%) in dry seasons and 27.47–85.35 t/km2 (6.5–23.7%) in flood seasons during 1980–2002, and further reduced 3.61–41.31 t/km2 (46.0–102.9%) in dry seasons and 175.63–471.52 t/km2 (59.6–126.2%) in flood seasons after the Three Gorges Reservoir (TGR) became operational in 2003. Contributions of human activities in six subregions to the reduction of the seaward sediment fluxes were calculated. Therein, the TGR only took up 3.2 and 23.9% in dry and flood seasons, respectively, which is below expectation.
39
Vizcaíno, Gilberto, Juan Paul Montalvo Herdoiza, Aline Siteneski, and Wendy Tauriz Navarro. "Secondary prevention in minor ischemic stroke with antiplatelet treatment. Systematic review and meta-analysis of comparative studies with aspirin under non-inferiority criteria." Investigación Clínica 61, no. 3 (September 2020): 265–82. http://dx.doi.org/10.22209/ic.v61n3a06.
Повний текст джерелаАнотація:
Minor ischemic stroke is the most frequent presentation of cerebral vascular disease and treatment with antiplatelet drugs can be used for the prevention of its recurrence. This systematic review and meta-analysis was aimed to assess non-inferiority criteria about the effect in the comparison of different antiplatelet schemes using aspirin as active control. Twelve randomized studies with a total of 52204 patients were chosen. All met the inclusion criteria with minor recurrent ischemic stroke as end point and any extracranial bleeding as safety event. The results showed a significant risk reduction of 22% [RR (95% CI) = 0.78 (0.72-0.84), p<0.0001, NNT: 67] in the recurrence of ischemic events with any antiplatelet drug (combined or not with aspirin) versus aspirin alone and there were no differences in the bleeding risk [RR (95% CI) = 1.02 (0.74- 1.41), p= 0.899, NNH: 500]. Dual antiplatelet therapy (DAPT) and cilostazol were more effective compared with aspirin alone (22% and 32% risk reduction respectively) but only cilostazol showed a higher reduction (52%) of bleeding events. In conclusion, although in some instances equivalence was demonstrated, a clinical superiority in the risk reduction for recurrent ischemic stroke of any antiplatelet treatment versus aspirin alone was observed. With the sole exception of the cilostazol trials there was an increase of the bleeding risk when the antiplatelet drugs treatments were compared with aspirin alone.
40
Huang, Mei-Chuan, Susan R. Watson, Jia-Jun Liao, and Edward J. Goetzl. "TH17 Augmentation in OTII TCR plus T Cell-Selective Type 1 Sphingosine 1-Phosphate Receptor Double Transgenic Mice (95.9)." Journal of Immunology 178, no. 1_Supplement (April 1, 2007): S178. http://dx.doi.org/10.4049/jimmunol.178.supp.95.9.
Повний текст джерелаАнотація:
Abstract Sphingosine 1-phosphate (S1P) in blood and lymph controls lymphoid traffic and tissue migration of T cells through signals from the type 1 S1P receptor (S1P1), but less is known of effects of the S1P-S1P1 axis on non-migration functions of T cells. CD4 T cells from a double transgenic (DTG) mouse express OTII TCRs specific for ovalbumin peptide 323–339 (OVA) and a high level of TG S1P1, resistant to suppression by T cell activation. Activated DTG CD4 T cells respond as expected to S1P by chemotactic migration and reduction of OVA-evoked secretion of IFN-gamma. In addition, DTG CD4 T cells stimulated by OVA secrete a mean of 2.5-fold more IL-17 than those from OTII single TG mice with concomitantly higher levels of mRNA encoding IL-17 by real-time PCR and intracellular IL-17 detected by ELISpot assays. OVA challenge of subcutaneous air-pockets elicited influx of more OTII-TCR-positive T cells producing a higher level of IL-17 in DTG mice than OTII control mice. Augmentation of the number and activity of Th17 cells by the S1P-S1P1 axis may enhance host defense against microbes and in other settings increase host susceptibility to autoimmune diseases. (supported by NIH HL31809)
41
Huang, F., S. L. Patel, D. Combs, and S. Parthasarathy. "0656 Mortality and Hospitalization in Patients With Heart Failure and Sleep Apnea: A Retrospective Study of Positive Airway Pressure Therapy in Medicare Beneficiaries." Sleep 43, Supplement_1 (April 2020): A250—A251. http://dx.doi.org/10.1093/sleep/zsaa056.652.
Повний текст джерелаАнотація:
Abstract Introduction Sleep apnea is common in patients with heart failure (HF) and can be treated with positive airway pressure (PAP) therapy. In patients with both HF and sleep apnea, whether treatment of PAP therapy is associated with reduction in hospitalization or mortality is unclear. Methods We used 5% Medicare limited-dataset (LDS) from 2013-2015 to perform a retrospective study of hospitalizations and mortality in HF patients with sleep apnea who received or did not receive PAP therapy over an 18-month time period. All-cause mortality during post-treatment period, any and HF-related hospitalizations in baseline, pre-treatment and post-treatment periods were measured and compared. Propensity score matching, generalized estimating equations (GEE) model for repeated measures analysis and COX-survival analysis adjusted by multiple covariates were used for longitudinal comparisons and mortality. Results We have identified 281,161 patients with at least two distinct HF onsets and 62,800 of them had sleep apnea diagnosis (22%). Of these patients, 5,540 of them had initiated their PAP therapy while 12,129 of them only had their sleep apnea diagnosis during the selection time frame from Jan 1st, 2014 to June 30th, 2015 without PAP treatment (control group). After adjusting for various confounders and propensity score matching, bilevel PAP was strongly associated with lower hospitalization and HF-associated hospitalization (Bilevel-PAP vs. Control: Any hospitalization, OR=0.62, 95%CI=0.53-0.74, p<0.0001; HF-associated hospitalization, OR=0.65, 95%CI=0.55-0.78, p<0.0001). Cox proportional hazards survival analysis revealed that all of the PAP-treated groups had a better 6-month survival after treatment initiation when compared to controls (any PAP therapy vs. Control: HR=0.32, 95%CI=0.28-0.37, p<0.0001). Conclusion In a retrospective analysis, PAP therapy was associated with lower 6-month all-cause mortality among Medicare beneficiaries with HF and sleep apnea. Bilevel-PAP therapy was consistently associated with significant reduction in hospitalization among these patients. Our observational findings warrant confirmation by future prospective intervention trials. Support NIH (HL126140; MD011600; HL138377; HL140144; IPA-014264-00001), PCORI (PPRND-1507-31666; PCS-1504-30430), American Academy of Sleep Medicine Foundation (169-SR-17), and Philips Healthcare/ Philips-Respironics Inc.
42
AlHareky, Muhanad, Jehan AlHumaid, Sumit Bedi, Maha El Tantawi, Mazin AlGahtani, and Yousef AlYousef. "Effect of a Vibration System on Pain Reduction during Injection of Dental Anesthesia in Children: A Randomized Clinical Trial." International Journal of Dentistry 2021 (January 30, 2021): 1–8. http://dx.doi.org/10.1155/2021/8896408.
Повний текст джерелаАнотація:
Background. The ‘‘gate control’’ theory suggests pain can be reduced by simultaneous activation of larger diameter nerve fibers using appropriate coldness, warmth, rubbing, pressure, or vibration. This study investigated the efficacy of a device combining cold and vibration, for needle-related procedural pain in children. Methodology. A total of 51 children aged 5–12 years participated in this randomized controlled clinical trial. Half of the children were in the control group and received maxillary buccal infiltration, by injecting 1.8 ml of 2% lidocaine with 1 : 100,000 adrenaline using topical anesthesia 20% benzocaine gel for 15 seconds, while the other half were in the test group and received the same anesthesia using a commercially available external cold and a vibrating device. A face version of Visual Analogue Scale (VAS) was used as a subjective measure to assess the child’s pain experience. The parents were requested to evaluate the child’s ability to tolerate pain using a behavioral/observational pain scale. Sound, Eyes, and Motor (SEM) scale and Faces, Legs, Activity, Cry, and Consolability (FLACC) scale were used to record the child’s pain as perceived by the external evaluator. T-test or Mann–Whitney U-test was used for scale variables, paired sample T-test or Wilcoxon rank t-test was used for before and after data, and chi-square was used for categorical variable, based on the results of normality test. Results. The results showed a statistically significant reduction in pain after the injection for the test group compared with control using VAS scale (mean = 6.68 (1.09) and 8.42 (0.50); p = 0.001 ) and FLACC scale (mean = 5.92 (1.05) and 8.16 (0.54); p = 0.002 ), but not when using SEM scale (mean 3.22 (0.42) and 4.24 (2.74); p = 0.08 ). Conclusions. Combined external cold and vibrating devices can be an effective alternative in reducing experienced pain and fear in children undergoing infiltration dental anesthesia. This study was registered with clinical trial registry of the United States National Institutes of Health (NIH) at ClinicalTrials.gov (NCT03953001).
43
Benoun, Joseph M., Jasmine C. Labuda, Zachary N. Fogassy, Oanh Pham, Quynh-Mai Pham, Lynn Puddington, and Stephen J. McSorley. "Antibiotic treatment causes a reduction in antigen-specific T cell memory and increased susceptibility to secondary infection." Journal of Immunology 198, no. 1_Supplement (May 1, 2017): 216.8. http://dx.doi.org/10.4049/jimmunol.198.supp.216.8.
Повний текст джерелаАнотація:
Abstract Salmonella enterica serovar Typhi causes recurrent and relapsing infection in antibiotic-treated individuals, suggesting that rapid bacterial clearance hinders the development of adaptive immunity. We have developed an antibiotic-treatment model in mice to examine this issue. This model demonstrates poor secondary protection after antibiotic treatment and allows the use of antigen-specific reagents to examine this issue in detail. Infection with Salmonella Typhimurium (BRD509-2W1S) caused expansion of Salmonella-specific CD4 T cells that were detected in peripheral blood, lymphoid tissues, and various non-lymphoid tissues. In contrast, antibiotic-treated mice had lower CD4 clonal expansion that persisted for months after infection. This reduced clonal frequency of Salmonella-specific CD4 T cells correlated with diminished protective immunity to secondary infection. In order to examine the protective contribution of circulating and non-circulating CD4 T cells, parabiosis experiments were performed whereby mice previously infected with BRD509-2W1S were paired with naïve mice for 30 days. Previously infected mice were more capable of controlling secondary infection compared to naïve parabionts or naïve control mice, however naïve parabionts were partially protected, indicating the requirement of both tissue resident and circulating cellular populations. Current experiments are underway to restore full protection during antibiotic intervention. Greater understanding of how antibiotics hinder CD4 memory development may allow for therapeutics to boost protective immunity to secondary or relapsing Salmonella infections. (Funding: NIH 5P01AI056172-09)
44
Violet, Pierre-Christian, Ifechukwude Ebenuwa, Stacey Chung, Jeffrey Atkinson, Danny Manor, and Mark Levine. "Sequestration of Vitamin E by Liver Fat in vivo, in vitro and in Women with Hepato-steatosis." Current Developments in Nutrition 4, Supplement_2 (May 29, 2020): 1696. http://dx.doi.org/10.1093/cdn/nzaa063_094.
Повний текст джерелаАнотація:
Abstract Objectives Hepato-steatosis (HS) due to obesity is now the most common cause of chronic liver disease in the Americas and Western Europe. The only means to prevent disease is avoidance of obesity. α-Tocopherol at doses of 800 I.U. daily was reported to have partial treatment effects for NASH. Because alpha tocopherol is a fat-soluble vitamin, we hypothesized that excess fat in liver, as found in HS, could act unintentionally sequester vitamin E, thereby altering its normal physiology and contributing to development of NASH. Using oral and intravenous deuterated tocopherols, evidence showing HS altered a-tocopherol physiology was reported based on pharmacokinetics studies in obese women with HS. Here we further tested the sequestration hypothesis in vitro, and in vivo. Methods In vitro, we investigated effects of fat on intracellular vitamin E localization. Control human and mouse hepatocytes and hepatocytes pre-loaded with fat were incubated with fluorescent α-tocopherol (BDP-α-tocopherol). In vivo experiments were performed using mice fed a high fat diet with different vitamin E doses. Results Compared to controls, fat- loaded cells contained more a-tocopherol, and BDP-a-tocopherol was specifically localized into intracellular fat droplets. In cells incubated with BDP a-tocopherol, we found that fat loading decreased a-tocopherol release. Induced expression of TPP, which mediates vitamin E intracellular disposition under normal conditions, was not observed in fat loaded cells, further confirming vitamin E was trapped in fat. Livers of mice fed high fat diet had more vitamin E compared to controls. By further increasing vitamin E content of the high fat diet, we observed a reduction in liver size and liver fat in the high vitamin E group. Using a mouse metabolic chamber, we observed a slight reduction of oxygen consumption rate in the high vitamin E group compared to controls. Conclusions Considered together, these findings imply that fat in the liver may produce unrecognized hepatic vitamin E sequestration, which could drive liver disease. These results are consistent with the possibility that increased vitamin E intake might, if begun at an early stage, restore vitamin E physiology, potentially decreasing or preventing progression of HS to NASH. Funding Sources NIH intramural program (DK053213–14).
45
Kaplan, Michael L., Ramesh K. Vellore, Phillip J. Marzette, and John M. Lewis. "The Role of Windward-Side Diabatic Heating in Sierra Nevada Spillover Precipitation." Journal of Hydrometeorology 13, no. 4 (August 1, 2012): 1172–94. http://dx.doi.org/10.1175/jhm-d-11-06.1.
Повний текст джерелаАнотація:
Abstract This study focuses on the meso-α- and meso-β-scale manifestations of the latent-heat-induced reduction of windward-side blocking to two flood-producing precipitation events on the leeside of the Sierra Nevada. Two simulations were performed—one employing full microphysics [control (CTRL)] and a second in which the latent heating terms are turned off in the microphysics [no latent heating (NLH)]. The differences between the CTRL and NLH are consistent with upstream latent heating—the moist, divergent, and ascending flow dominates the leeside of the mountain range in the CTRL producing copious spillover precipitation while dry high-momentum/downslope-descending flow dominates the NLH simulation on the leeside. A comprehensive sequence of events for spillover precipitation is formulated as follows: 1) Ascent within the exit region of a polar jet streak develops in response to velocity divergence aloft. 2) This ascent phases with ascent from the windward-side flow to create a mesoscale region of heavy upslope precipitation. 3) The latent heat release from the upslope precipitation reduces the upstream static stability and blocking. 4) A mesoscale ridge in the thickness field builds in the upper troposphere and induces subgeostrophic flow in the jet’s exit region above the mountain range. 5) Adjustments to this ridge result in a cross-mountain midlevel jet that facilitates a river of midlevel moisture advected over to the leeside. 6) Stretching of moist isentropic surfaces in proximity to the plume of moisture fluxes causes destabilization on the leeside and formation of a leeside mesolow. 7) Boundary layer air accelerates into the leeside mesolow to form a mountain-parallel low-level flow.
46
Khaskhachikh, D. A., and V. O. Potapov. "Molecular mechanisms of resistance of endometrial hyperplasia to progestogen therapy based on the study of the expression of estrogen and progesterone receptors and paracrine cellular markers of cellular interaction." Medicni perspektivi 27, no. 4 (December 29, 2022): 123–35. http://dx.doi.org/10.26641/2307-0404.2022.4.271185.
Повний текст джерелаАнотація:
The problem of resistance of non atypical endometrial hyperplasia (NEH) to traditionally accepted, pathogenetically sound therapy with different types of progestins is currently an unsolved problem. In about 17-20% of cases there is a recurrence or even progression of atypical forms of endometrial hyperplasia (AEH), which required the use of surgical treatments. The aim of the study was to investigate the results of hormone therapy with different types of progestins for the treatment of endometrial hyperplasia in women with different types of expression of estrogen and progesterone receptors in combination with the expression of intercellular adhesion molecules E-cadherin and β-catenin to determine the cause of hormonal resistance, formation of groups of women with progestogen-sensitive endometrial hyperplasia (EH) non atypical type NEH (+), which can use progestogens for treatment, and progestogen-resistant forms of endometrial hyperplasia with non atypical NEH (-), which should be offered alternative therapy. The study was performed on the morphological material of the endometrium obtained by diagnostic biopsy in women with abnormal uterine bleeding who were diagnosed with NEH by histological examination. For immunohistochemical study, 80 endometrial samples were taken from women with abnormal uterine bleeding (AUВ) and in the same women after treatment of endometrial hyperplasia without atypia in 3 and 6 months of therapy. The control group (CG) consisted of a group of 20 women who were followed-up without treatment tactics. All women were divided into 3 groups in which different types of progestins were used for treatment: group I – continuous intake of 100 mg of micronized progesterone per os twice a day for 6 months, group II – 20 mg of dihydrogesterone per os twice a day for 6 months, group III – in which LNG-IUD was used. The state of proliferation and differentiation in the studied tissues was assessed by the expression of their key molecular participants – estrogen receptors (ERα) and progesterone (PGR), transmembrane glycoproteins of E-cadherin and β-catenin. ERα and PGR expression were determined by immunohistochemistry and calculated by the semi-quantitative H-index method. Evaluation of the expression of E-cadherin and β-catenin was performed by determining the percentage of IHH-positive cells to these antigens depending on the degree of their color. The criterion for the effectiveness of NEH treatment was considered to be a biopsy in 3 and 6 months of treatment in the absence of pathological changes in the endometrium. The results showed that after the use of progestogens in group I there was a change in the endometrium to the secretory type in 45% of cases, in group II with dydrogesterone therapy – in 55% there was a reduction of EH to normal histological picture. The intrauterine system with levonorgestrel (LNG-IUD) showed the greatest efficiency, with the use of which in 75% of cases normalization of the endometrial structure was observed. In the control group in 32% of cases the structure of the endometrium normalized. After 6 months of treatment with gestagens, both oral forms (micronized progesterone, dydrogesterone) and the use of LNG-IUDs showed a positive effect from their use; the therapeutic form of gestagens for therapy is not significant in reducing excessive endometrial proliferation. In the control group of patients who did not receive therapy or discontinued therapy for various reasons, it was shown that 47% of patients had spontaneous regression of EH. The overall percentage of no effect from treatment was 20% in groups I, II and III. Determination of ERα expression in all groups showed a pronounced expression in glands and stroma, which did not differ significantly in the group with NEH (+) and in NEH (-). Analysis of PGR expression of NEH in endometrium (-) showed that in glandular cells (50.82±0.73) and in the stroma (47.34±0.82) it was lower than in the endometrium of women with NEH (+) (gland 187±3.1; stroma 166.4±2.3; p<0.05), as well as in the unchanged endometrium in the proliferative phase (glands 193.2±8.5; stroma 178.7±6.3; p<0.05) and the secretory phase (glands 140.2±4.4; stroma 116.6±3.1; p<0.05). A study of E-cadherin expression in women with EH (-) showed that in 86.4% of cases the expression was absent and in 13.6% it decreased. In NEH (+) women, 49.2% of E-cadherin expression was weak, in 34.4% – moderate, and in 16.4% – negative, indicating an association between PGR and E-cadherin expression. In women with NEH (-) there was marked cytoplasmic expression of β-catenin up to 80%, which can be interpreted as potentially threatening the progression of NEH in atypical forms and relapses. Thus, the study of molecular mechanisms of resistance of endometrial hyperplasia to progestogen therapy will help to develop a differential approach to its diagnosis and treatment.
47
Wolnik, B., D. Wiza, T. Szczepanik, A. Syta, and T. Klupa. "Switching from Neutral Protamine Hagedorn Insulin to Insulin Glargine 300 U/mL Improves Glycaemic Control and Reduces Hypoglycaemia Risk: Results of a Multicentre, Prospective, Observational Study." Journal of Diabetes Research 2020 (April 8, 2020): 1–8. http://dx.doi.org/10.1155/2020/8751348.
Повний текст джерелаАнотація:
Type 2 diabetes mellitus (T2DM) is a major cause of morbidity and mortality worldwide and is an important public health issue. A significant proportion of insulin-treated patients with T2DM do not reach target glycated haemoglobin (HbA1c) values, which ultimately increases their risk of long-term microvascular and macrovascular complications. One potential option to improve diabetes control in these patients may be the use of new insulin formulations including second-generation basal insulin analogues such as insulin glargine 300 U/mL (Gla-300). Several published randomised controlled trials have assessed the clinical effectiveness of Gla-300, mostly versus insulin glargine 100 U/mL as well as insulin degludec. However, there is limited information about the real-world effectiveness of Gla-300 when patients are transitioned directly from neutral protamine Hagedorn (NPH) human basal insulin. The primary objective of this study was to evaluate the effectiveness of Gla-300, defined as the percentage of participants with an HbA1c reduction of ≥0.5%, 6 months after switching from NPH insulin, in participants with T2DM. Secondary objectives included the safety assessment based on the percentage of patients experiencing ≥1 episodes and the number of hypoglycaemic episodes by category: severe, symptomatic, symptomatic confirmed, diurnal or nocturnal, change in body weight, and insulin dose. A total of 469 participants completed the 6-month observation period. Mean baseline HbA1c was 9.19%. The percentage of participants with a ≥0.5% improvement in HbA1c from baseline was 71.7% at 6 months. Mean HbA1c decreased at 3 and 6 months by 0.77% (±0.98) and 1.01% (±1.12), respectively (p<0.00001 versus baseline), while fasting glycaemia decreased by 32 mg/dL and 37 mg/dL, respectively (p<0.00001 versus baseline). There were moderate increases in the doses of both Gla-300 and, if used, short-acting insulins during the 6 months of observation. The percentage of participants with ≥1 hypoglycaemia event during the preceding 4 weeks decreased significantly from baseline to 3 and 6 months, as did the proportion with symptomatic hypoglycaemia at night (p<0.00001 versus baseline). No participants had severe hypoglycaemia after a switch to Gla-300. Body mass, waist and hip circumferences, and waist : hip ratio did not change significantly. In conclusion, this large, prospective, observational study demonstrated that switching from NPH insulin to Gla-300 resulted in a significant improvement in HbA1c, with only a moderate increase in insulin dose, a decreased risk of hypoglycaemia, and no increase in body weight.
48
Machado, Natalia, William Todd, and Clifford Saper. "029 Median preoptic dual control over sleep regulation." Sleep 44, Supplement_2 (May 1, 2021): A13—A14. http://dx.doi.org/10.1093/sleep/zsab072.028.
Повний текст джерелаАнотація:
Abstract Introduction Previous studies suggest that the median preoptic nucleus (MnPO) plays an important role in regulating the wake-sleep cycle and in particular homeostatic sleep drive. However, the precise cellular phenotypes, targets and central mechanisms by which the MnPO neurons regulate the wake-sleep cycle remain unknown. Both glutamatergic (Vglut2+) and GABAergic (Vgat+) MnPO neurons innervate brain regions implicated in sleep promotion and maintenance, suggesting that both cell types may participate on sleep control. Methods In this study, we used two genetically-targeted approaches associated with electroencephalographic (EEG) and electromyographic (EMG) recordings in Vgat-IRES-cre and Vglut2-IRES-cre mice to investigate the role of the MnPOVgat and MnPOVglut2 neurons in modulating wake-sleep behavior. Results First, using a chemogenetic approach, we found that activation of MnPOVgat neurons reduced the latency for the first NREM sleep episode, produced an increase in NREM sleep and reduced wakefulness. Then, to test the role of MnPOVgat and MnPOVglut2 neurons in regulating sleep homeostasis, we recorded EEG and EMG responses in mice that had the Vgat+ or Vglut2+ neurons deleted from the MnPO. After deletion of MnPOVgat neurons, mice showed a reduction of NREM sleep and an increase in wakefulness during the light phase. Deletion of MnPOVgat neurons also reduced sleep recovery after 4 hours of sleep deprivation (SD). On the other hand, deletion of the MnPOVglut2 neurons did not change the wake-sleep cycle during the 24h baseline condition, but prevented the sleep recovery immediately after SD. To understand the underlying mechanism in preventing sleep recovery in both MnPOVglut2- and MnPOVgat-deleted mice groups, we exposed these animals to a psychological stress protocol. In response to a psychological stressor, mice with deletion of glutamatergic, but not GABAergic MnPO neurons, had an exacerbation of the stress-induced insomnia. Conclusion Our results suggest that both neuron populations differentially participate in wake-sleep control, with MnPOVgat neurons being critically involved in sleep homeostasis, and MnPOVglut2 neurons promoting sleep during allostatic (stressful) challenges. Support (if any) NIH Grants NS085477, NS072337, HL095491 and Sleep Research Society Foundation (Award 026-JP-20).
49
Li, Lijia, Xiaosen Li, Yi Wang, Chaozhong Qin, Bo Li, Yongjiang Luo, and Jingchun Feng. "Investigating the Interaction Effects between Reservoir Deformation and Hydrate Dissociation in Hydrate-Bearing Sediment by Depressurization Method." Energies 14, no. 3 (January 21, 2021): 548. http://dx.doi.org/10.3390/en14030548.
Повний текст джерелаАнотація:
Natural gas hydrate (NGH) has been widely focused on having great potential for alternative energy. Numerous studies on gas production from hydrate-bearing sediments have been conducted in both laboratory and field. Since the strength of hydrate-bearing sediments depends on the saturation of NGH, the decomposition of NGH may cause the failure of sediments, then leading to reservoir deformation and other geological hazards. Plenty of research has shown that the reservoir deformation caused by hydrate decomposition is considerable. In order to investigate this, the influence of sediment deformation on the production of NGH, a fully coupled thermo-hydro-chemo-mechanical (THMC) model is established in this study. The interaction effects between reservoir deformation and hydrate dissociation are discussed by comparing the simulation results of the mechanical coupling and uncoupled models on the laboratory scale. Results show that obvious differences in behaviors between gas and water production are observed among these two models. Compared to the mechanical uncoupled model, the mechanical coupling model shows a significant compaction process when given a load equal to the initial pore pressure, which leads to a remarkable decrease of effective porosity and reservoir permeability, then delays the pore pressure drop rate and reduces the maximum gas production rate. It takes a longer time for gas production in the mechanical coupling model. Since the reservoir temperature is impacted by the comprehensive effects of the heat transfer from the boundary and the heat consumption of hydrate decomposition, the reduced maximum gas production rate and extended gas production process for the mechanical coupling model lead to the minimum reservoir temperature in the mechanical coupling model larger than that of the mechanical uncoupled model. The reduction of the effective porosity for the mechanical coupling model causes a larger cumulative water production. The results of this paper indicate that the reservoir deformation in the gas production process should be taken into account by laboratory and numerical methods to accurately predict the behaviors of gas production on the field scale.
50
Wang, Lu, Barbara Belisle, Mansour Bassiri, Ping Xu, Dmitri Debabov, Chris Celeri, Nichole Alvarez, et al. "Chemical Characterization and Biological Properties of NVC-422, a Novel, StableN-Chlorotaurine Analog." Antimicrobial Agents and Chemotherapy 55, no. 6 (March 21, 2011): 2688–92. http://dx.doi.org/10.1128/aac.00158-11.
Повний текст джерелаАнотація:
ABSTRACTDuring oxidative burst, neutrophils selectively generate HOCl to destroy invading microbial pathogens. Excess HOCl reacts with taurine, a semi-essential amino acid, resulting in the formation of the longer-lived biogenerated broad-spectrum antimicrobial agent,N-chlorotaurine (NCT). In the presence of an excess of HOCl or under moderately acidic conditions, NCT can be further chlorinated, or it can disproportionate to produceN,N-dichlorotaurine (NNDCT). In the present study, 2,2-dimethyltaurine was used to prepare a more stableN-chlorotaurine, namely,N,N-dichloro-2,2-dimethyltaurine (NVC-422). In addition, we report on the chemical characterization,in vitroantimicrobial properties, and cytotoxicity of this compound. NVC-422 was shown effectively to kill all 17 microbial strains tested, including antibiotic-resistantStaphylococcus aureusandEnterococcus faecium. The minimum bactericidal concentration of NVC-422 against Gram-negative and Gram-positive bacteria ranged from 0.12 to 4 μg/ml. The minimum fungicidal concentrations againstCandida albicansandCandida glabratawere 32 and 16 μg/ml, respectively. NVC-422 has anin vitrocytotoxicity (50% cytotoxicity = 1,440 μg/ml) similar to that of NNDCT. Moreover, our data showed that this agent possesses rapid, pH-dependent antimicrobial activity. At pH 4, NVC-422 completely killed bothEscherichia coliandS. aureuswithin 5 min at a concentration of 32 μg/ml. Finally, the effect of NVC-422 in the treatment of anE. coli-infected granulating wound rat model was evaluated. Treatment of the infected granulating wound with NVC-422 resulted in significant reduction of the bacterial tissue burden and faster wound healing compared to a saline-treated control. These findings suggest that NVC-422 could have potential application as a topical antimicrobial.