Auswahl der wissenschaftlichen Literatur zum Thema „320.5/5/0917671“

Bacteria and archaea use the CRISPR–Cas system as an adaptive response against infection by foreign nucleic acids. Owing to its remarkable flexibility, this mechanism has been harnessed and adopted as a powerful tool for genome editing. The CRISPR–Cas system includes two classes that are subdivided into six types and 19 subtypes according to conservation of thecasgene and loci organization. Recently, a new protein with endonuclease activity belonging to class 2 type V has been identified. This endonuclease, termed Cpf1, in complex with a single CRISPR RNA (crRNA) is able to recognize and cleave a target DNA preceded by a 5′-TTN-3′ protospacer-adjacent motif (PAM) complementary to the RNA guide. To obtain structural insight into the inner workings of Cpf1, the crystallization of an active complex containing the full extent of the crRNA and a 31-nucleotide dsDNA target was attempted. The gene encoding Cpf1 fromFrancisella novicidawas cloned, overexpressed and purified. The crRNA was transcribed and purifiedin vitro. Finally, the ternary FnCpf1–crRNA–DNA complex was assembled and purified by preparative electrophoresis before crystallization. Crystals belonging to space groupC2221, with unit-cell parametersa= 85.2,b= 137.6,c= 320.5 Å, were obtained and subjected to preliminary diffraction experiments.

17012 Background: We previously reported that carboplatin pleurodesis in patients with advanced lung adenocarcinoma with MPE, renal insufficiency, and poor performance status (PS) was an effective palliative therapy. However, the efficacy and toxicity profile of carboplatin pleurodesis in patients with NSCLC with MPE in comparison with those of cisplatin pleurodesis have not been reported. Methods: Thirty patients with stage IIIB/IV NSCLC accompanied with MPE who did not have an indication for systemic chemotherapy because of poor PS more than 2 were randomized to carboplatin pleurodesis (target area under the curve as 5 μg-min/ml using Calvert’s formula) and cisplatin pleurodesis (80 mg/m2) in a single-blind and controlled trial. Enrollment took place between Oct 2004 and Dec 2005. Primary efficacy endpoints were the best confirmed response rate, time to progression (TTP) in controlling MPE and adverse effects. Results: Fifteen of 30 patients were treated by carboplatin pleurodesis, and resting 15 of 30 patients were treated by cisplatin pleurodesis to control MPE. The response rate in carboplatin pleurodesis was not statistically different from that for patients in cisplatin pleurodesis (P = .226). The use of anticancer drugs for pleurodesis was not significantly associated with response rate in logistic regression analysis (relative risk = 14.2, 95% CI: 0.6–320.5, P = .095). Median TTP in carboplatin pleurodesis was not different from that in cisplatin pleurodesis (96 days vs 83 days). The use of carboplatin for pleurodesis (P = .016) and gender (P = .005) were associated with prolongation of TTP in the Cox regression method. Kaplan-Meier analysis showed that the progression free probability curve in carboplatin pleurodesis was not different from that in cisplatin pleurodesis (P = .275). The rate of Grade 3 thrombocytopenia in carboplatin pleurodesis (25%) was higher than that in cisplatin pleurodesis (0%), but there was no statistical significance (P = .096). Conclusions: Carboplatin pleurodesis and cisplatin pleurodesis may be feasible and acceptable toxicity profiles. No significant financial relationships to disclose.

BackgroundRheumatoid arthritis (RA) is the most common chronic inflammatory rheumatic disease affecting small and medium-sized joints symmetrically, leading to poor functional outcomes and structural damages with time. The RA elementary inflammatory lesions, synovitis and tenosynovitis, have been associated with the development and worsening of bone erosions leading to loss of joint function and pain. The median age at diagnosis of RA patients, ranged between 50-60 years old, age at which degenerative and inflammation lesions relative to osteoarthritis (OA) damages may be present and interfere to establish a diagnosis of inflamed and/or structural RA disease.ObjectivesTo assess prevalence, topography and severity of inflammation and erosion on ultrasound (US) in RA and OA patients and to propose US thresholds to classify RA patients.MethodsPatients fulfilling ACR 1987 and/or ACR/EULAR 2010 criteria for RA or ACR criteria for hand OA were reprospectively included. Synovitis and tenosynovitis (TS) in B and Power Doppler (PD) modes on seven bilateral joints (carpus, MCP2, 3, 5, MTP2, 3, 5) were scored according to a four-grade scale of severity. Erosive disease was defined by the presence of at least one erosion >2 mm confirmed in 2 perpendicular plans on 30 targeted facet joints. Sensitivity, specificity and OR for the diagnosis of RA were calculated for each elementary (inflammatory and erosive) US lesion.Results153 patients were included: 107 (31 early <2 years) RA and 46 OA patients. Synovitis (B and PD modes) was observed in 92 (85.9%) RA and 12 (26%) OA patients, respectively (p <0.0001). TS (B and PD modes) was depicted in 61(57%) RA and 4 (8.7%) OA patients, respectively (p <0.0001). 71 (66%) RA and 5 (11%) OA patients responded to the definition of erosive disease (p<0.001). The combination of US erosion and PD+ synovitis provided the best compromise to classify RA patients: sensitivity 49.1% (39.7-58.4)), specificity 97.8% (87.4-99.5) and OR= 43.8 (CI95: 8.2-230.2). For early RA, PD+ TS provided the best compromise: sensitivity 54.8% (37.8-58.4), specificity 97.8% (87.4 -100) and OR= 54.6 (CI95: 9.3- 320.5).ConclusionThe combination of PD+ synovitis and erosion in RA and PD+ tenosynovitis alone in early RA offered the best compromise to classify RA versus OA patients.References[1]Scott DL et al. Rheumatoid arthritis. The Lancet.[2]Funck-Brentano et al. Prediction of Radiographic Damage in Early Arthritis by Sonographic Erosions and Power Doppler Signal: A Longitudinal Observational Study. Arthritis Care & Research.[3]Vlychou et al. Ultrasonographic evidence of inflammation is frequent in hands of patients with erosive osteoarthritis. Osteoarthritis and Cartilage.[4]Roux et al. Ultrasonographic criteria for the diagnosis of erosive rheumatoid arthritis using osteoarthritic patients as controls compared to validated radiographic criteria. Joint Bone Spine.[5]Sahbudin et al. The role of ultrasound-defined tenosynovitis and synovitis in the prediction of rheumatoid arthritis development.Disclosure of InterestsNone declared.

Background Cutaneous leishmaniasis (CL) is endemic in Yemen. About 4440 cases were reported in 2019. On July 23, 2018, a Hajjah governorate surveillance officer notified the Ministry of Public Health and Population about an increase in the number of CL cases in Bani-Oshb, Kuhlan district, Hajjah governorate. On July 24, 2018, Yemen Field Epidemiology Training Program sent a team to perform an investigation. Objective We aimed to describe a CL outbreak in Hajjah governorate and determine its risk factors. Methods A descriptive study and case-control study (1:1 ratio) were conducted. Cases included people who met the suspected or confirmed case definition of the World Health Organization and lived in Bani-Oshb subdistrict during the period from August 2017 to July 2018. Controls included people living for at least 1 year in Bani-Oshb without new or old skin lesions. Crude odds ratios (cORs) and adjusted odds ratios (aORs) with 95% CI were used to test the significance of associations. Results We identified 30 CL cases. Among the 30 patients, 7 (23%) were younger than 5 years, 17 (57%) were 5 to 14 years, 17 (57%) were females, and 23 (77%) had one lesion. The attack rate was 7 per 1000 population in the age group <15 years and 1 per 1000 population in the age group ≥15 years. On bivariate analysis, the following factors were significantly associated with CL: female gender (cOR 5.2, 95% CI 1.7-16.5), malnutrition (cOR 5.2, 95% CI 1.7-16.5), not using a bed net (cOR 14.5, 95% CI 1.7-122.4), poor house lighting (cOR 6.4, 95% CI 2.1-19.7), poor house hygiene (cOR 11.2, 95% CI 3.1-40.7), poor sanitation (cOR 14.5, 95% CI 1.7-122.4), living in houses without window nets (cOR 5.2, 95% CI 1.3-21.2), plantation around the house (cOR 6.5, 95% CI 2.1-20.5), animal barn inside or close to the house (cOR 9.3, 95% CI 1.9-46.7), raising animals (cOR 8.1, 95% CI 1.6-40.7), and having animal dung in or near the house (cOR 6.8, 95% CI 1.7-27.7). The following risk factors remained significant on multivariate stepwise analysis: female gender (aOR 22.7, 95% CI 1.6-320.5), malnutrition (aOR 17.2, 95% CI 1.3-225.8), poor house hygiene (aOR 45.6, 95% CI 2.5-846.4), plantation around the house (aOR 43.8, 95% CI 1.9-1009.9), and raising animals (aOR 287.1, 95% CI 5.4-15205.6). Conclusions CL was endemic in Hajjah governorate, and an increase in cases was confirmed. Many individual, housing, and animal related factors were shown to contribute to CL endemicity. Implementation of control measures directed toward altering the factors favoring contact among vectors, reservoirs, and susceptible humans is strongly recommended to control future outbreaks.

Stereophotogrammetry as a method for the surface scanning can be used to capture some properties of the human body parts. The objective of this study is to quantify the foot stress distribution in 3D during its quasi-static stand using a footprint into an imprinting material when knowing its mechanical properties. One foot of a female, having the mass of 65kg, was chosen for the FEM foot model construction. After obtaining her foot imprint to the dental imprinting material, its positive plaster cast was created, whose surface was possible to scan using stereophotogrammetry. The imprint surface digital model was prepared with the help of the Konica-Minolta Vivid 9i triangulation scanner. This procedure provides the measured object models in a high resolution. The resulting surface mesh of the foot imprint involved 9.600 nodes and 14.000 triangles, approximately, after reduction due to the FEM analysis. Simulation of foot imprint was solved as the 3D time dependent nonlinear mechanical problem in the ADINA software. The sum of vertical reactions calculated at the contact area nodes was 320.5 N, which corresponds to the mass of 32.67 kg. This value is in a good agreement with the subject half weight – the load of one foot during its quasi-static stand. The partial pressures resulting from this mathematical model match the real pressures on the interface of the foot and imprinting material quite closely. Principally, these simulations can be used to assess the contact pressures in practical cases, e.g., between a foot and its footwear.

Stereophotogrammetry as a method for the surface scanning can be used to capture some properties of the human body parts. The objective of this study is to quantify the foot stress distribution in 3D during its quasi-static stand using a footprint into an imprinting material when knowing its mechanical properties. One foot of a female, having the mass of 65kg, was chosen for the FEM foot model construction. After obtaining her foot imprint to the dental imprinting material, its positive plaster cast was created, whose surface was possible to scan using stereophotogrammetry. The imprint surface digital model was prepared with the help of the Konica-Minolta Vivid 9i triangulation scanner. This procedure provides the measured object models in a high resolution. The resulting surface mesh of the foot imprint involved 9.600 nodes and 14.000 triangles, approximately, after reduction due to the FEM analysis. Simulation of foot imprint was solved as the 3D time dependent nonlinear mechanical problem in the ADINA software. The sum of vertical reactions calculated at the contact area nodes was 320.5 N, which corresponds to the mass of 32.67 kg. This value is in a good agreement with the subject half weight – the load of one foot during its quasi-static stand. The partial pressures resulting from this mathematical model match the real pressures on the interface of the foot and imprinting material quite closely. Principally, these simulations can be used to assess the contact pressures in practical cases, e.g., between a foot and its footwear.