Journal articles on the topic 'GBV screening'
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Watanabe, Maria Angelica Ehara, Ana Karina Melim Benthien Miquelão, Carlos Eduardo Coral de Oliveira, Karen Brajão de Oliveira, Thiago Franco Nasser, Mateus Nóbrega Aoki, Patrícia Sayuri Suzuki, Marla Karine Amarante, Emerson José Venâncio, and Elbens Marcos Minoreli de Azevedo. "Detection of GBV-C/HGV RNA in cervico-vaginal smears from healthy individuals." Brazilian Archives of Biology and Technology 51, no. 5 (October 2008): 917–22. http://dx.doi.org/10.1590/s1516-89132008000500007.
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The purpose of the present study was to evaluate the sexual transmission of GBV-C/HGV, through RNA detection in cervicovaginal smears. Therefore the GBV-C/HGV RNA in cervicovaginal smears from apparently healthy women was investigated using routine proceedings for prophylactic screening to cervical cancer. GBV-C/HGV RNA was detected by reverse transcriptase and polymerase chain reaction (RT-PCR). Only one woman presented co-infection with human papilloma virus (HPV). The GBV-C/HGV RNA was detected in 13/73 (17.57%) healthy women and it's prevalence in participating women between 28-43 years old was 53.85%. No association was found with GBV-C/HGV for the age of first sexual intercourse and number of pregnancies. In GBV-C/HGV RNA positive women, 69.23% were married. In conclusion, the present findings show that cervical and vaginal specimens could contain the GBV-C/HGV RNA.
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Bally, Cyrus Ashivira, Proscovia Adema, Kennedy Situma, Samuel Musau, Roberts Osangale, and Grace Kibet. "ENORMITY AND PATTERNS OF GENDER BASED VIOLENCE AT KENYA MEDICAL TRAINING COLLEGE CAMPUSES." International Journal of Health Sciences 5, no. 1 (July 19, 2022): 33–51. http://dx.doi.org/10.47941/ijhs.933.
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Purpose: To unravel the socio-demographic factors, assess knowledge, awareness and institutional factors that are associated with gender based violence at KMTC campuses.
Methodology: A semi structured questionnaire was utilized to conduct a cross-sectional descriptive study of 302 participants, yielding to 300 responses.
Findings: The study findings divulged that (81) 27% of 302 participants had experienced Gender Based Violence (GBV) at the institution and its community. Majority of the respondents were aged 31 years and above. The predictors of GBV at KMTC among staff with statistically significance were: Level of education (χ2 (df=4) =72.54, p=0.01), the type of GBV especially sexual and economic abuse (χ2 (df=4) =72.57, p=0.00), lack of GBV policy in place and lack of GBV recovery centres p=0.00 respectively. In conclusion level of education, the type of GBV, lack of GBV policy in place and lack of GBV recovery centres were pin pointed as the most imperative prognosticators that were associated with GBV.
Unique contribution of theory, practice and policy: The study recommends KMTC as a government institution to strengthen the policies already in use about GBV at the college, to health educate its staff about GBV especially sexual and physical abuse via workshops and seminars, to set up GBV recovery centres in every region of Kenya in the respective major campuses and employ qualified staff who can be able to provide GBV services such as counselling, screening and treatment to its staff, students and community at large.
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Aryal, Shreyashi, Sagun B. Pant, and Sebina Baniya. "Gender-based Violence in Women attending Gynecology Outpatient Department in a Hospital of Western Nepal: An Issue of Endurance and Invisibility." Journal of South Asian Federation of Obstetrics and Gynaecology 9, no. 3 (August 2017): 225–29. http://dx.doi.org/10.5005/jp-journals-10006-1500.
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ABSTRACT Introduction Gender-based violence (GBV) is faced by many women in Nepal but health-seeking behavior is rare. A reproductive health facility may be the only place where a woman comes for a health visit. So, health care providers, especially gynecologists, play an important role to identify women suffering from GBV as they see clients suffering from the reproductive health effects of GBV on a daily basis. The purpose of this study was to find the prevalence and severity of GBV in women attending the outpatient department (OPD) and to compare their clinical diagnosis with those not facing GBV. Materials and methods This is a prospective study conducted at Lumbini Medical College Teaching Hospital for a period of 3 months enrolling 741 nonpregnant women attending the OPD. A structured questionnaire was used for interview to identify women facing abuse and to assess their gynecological problems. Results Out of 741 women, 172 faced GBV, so the prevalence was 23.21%. Emotional and physical abuse was the most common type of abuse faced by 56 (32.56%), but the severity was reported more in sexual abuse [8 (57.14%)]. Pain abdomen was the most common symptom [69 (40.12%)], and chronic pelvic pain (CPP) [60 (34.89%)] was the commonest clinical diagnosis made in these women. Chronic pelvic pain was diagnosed more in women facing abuse (p < 0.001). Conclusion In this study, about one in four women in reproductive age group had experienced GBV. Gynecology OPD of a tertiary hospital could be used as a screening setting that can assist in early detection and prevention of GBV in Nepal. How to cite this article Aryal S, Pant SB, Baniya S. Gender-based Violence in Women attending Gynecology Outpatient Department in a Hospital of Western Nepal: An Issue of Endurance and Invisibility. J South Asian Feder Obst Gynae 2017;9(3):225-229.
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Yalcinoz-Ucan, Busra, Laura Zilney, Agnes Zientarska-Kayko, Timothy Ireland, and Dillon Thomas Browne. "Examining the effectiveness of psychological interventions for marginalised and disadvantaged women and individuals who have experienced gender-based violence: protocol for a scoping review." BMJ Open 12, no. 7 (July 2022): e060479. http://dx.doi.org/10.1136/bmjopen-2021-060479.
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IntroductionExposure to gender-based violence (GBV) has devastating psychological outcomes for victims/survivors. Particularly in conditions where GBV intersects with multiple forms of oppression, the negative impacts of violence are more challenging to overcome and potential pathways for recovery become less accessible. However, evidence regarding the availability and effectiveness of mental health interventions for GBV survivors from marginalised and disadvantaged communities has yet to be systematically integrated and synthesised. The proposed scoping review will examine the relevant literature regarding the availability and effectiveness of psychological interventions for survivors of GBV from marginalised and disadvantaged backgrounds. This review will (i) document what psychological interventions have been available and empirically established for marginalised and disadvantaged women and individuals with experiences of GBV, (ii) provide a narrative examination of the treatment outcomes of identified interventions regarding their effectiveness and (iii) examine the degree to which GBV interventions in selected sources are designed and applied with a recognition of the social determinants of mental health.Methods and analysisThe search for the proposed scoping review will include five electronic databases: PsycINFO, Scopus, Web of Science, Ovid Medline, and CINAHL. The database search will be completed in June 2022. An additional search will be conducted before the completion of the study in December 2022. The search will target research studies published after 2010. The primary eligibility criterion for study selection is having a focus on psychological interventions for GBV survivors from marginalised and disadvantaged groups. Two reviewers will conduct screening and data extraction. The data will be evaluated to map the treatment outcomes of interventions and their effectiveness. Implications for clinical services will be discussed.Ethics and disseminationNo ethical consideration is foreseen for this scoping review. The dissemination will be done through a publication in a top-tier open access journal and conference presentations.
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Decker, Michele R., Carrie Lyons, Kathleen Guan, Vanessa Mosenge, Ghislane Fouda, Daniel Levitt, Anna Abelson, et al. "A Systematic Review of Gender-Based Violence Prevention and Response Interventions for HIV Key Populations: Female Sex Workers, Men Who Have Sex With Men, and People Who Inject Drugs." Trauma, Violence, & Abuse 23, no. 2 (February 11, 2022): 676–94. http://dx.doi.org/10.1177/15248380211029405.
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Gender-based violence (GBV) is that perpetrated based on sex, gender identity, or perceived adherence to socially defined gender norms. This human rights violation is disproportionately experienced by HIV key populations including female sex workers (FSW), people who inject drugs (PWID), and men who have sex with men (MSM). Consequently, addressing GBV is a global priority in HIV response. There is limited consensus about optimal interventions and little known about effectiveness. Our systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was registered in International Prospective Register of Systematic Reviews. Peer-reviewed and non-peer-reviewed literature were searched for articles that described a GBV prevention or response intervention specifically for key populations including FSW, PWID, and MSM. Results were organized by level(s) of implementation and pillars of a comprehensive GBV response: prevention, survivor support, and accountability/justice. Of 4,287 articles following removal of duplicates, 32 unique interventions (21 FSW, seven PWID, and nine MSM, not mutually exclusive) met inclusion criteria, representing 13 countries. Multisectoral interventions blended empowerment, advocacy, and crisis response with reductions in violence. Individual-level interventions included violence screening and response services. Violence-related safety promotion and risk reduction counseling within HIV risk reduction programming reduced violence. Quantitative evaluations were limited. Violence prevention and response interventions for FSW, PWID, and MSM span individual, community, and multisectoral levels with evidence of promising practices at each level. The strongest evidence supported addressing violence in the context of sexually transmitted infection/HIV risk reduction. As interventions continue to emerge, the rigor of accompanying evaluations must simultaneously advance to enable clarity on the health and safety impact of GBV prevention and response programming.
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Keys, Jessica R., Peter A. Leone, Joseph J. Eron, Kelcie Alexander, Myra Brinson, and Ronald Swanstrom. "Large scale screening of human sera for HCV RNA and GBV-C RNA." Journal of Medical Virology 86, no. 3 (October 31, 2013): 473–77. http://dx.doi.org/10.1002/jmv.23829.
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Wijegunasekara, JLHR, and KDP Wijesinghe. "Health Sector Interventions to address Gender Based Violence: in Sri Lanka." Journal of Medical Research 6, no. 5 (October 28, 2020): 246–48. http://dx.doi.org/10.31254/jmr.2020.6515.
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Gender Based Violence (GBV) is a common form of violence globally and includes physical, sexual, emotional and economic violence. GBV has serious consequences for women’s health and well-being and takes a high national cost for the treatment and rehabilitation. Prevalence of GBV is usually underestimated. GBV is addressed globally using good practices in justice, health, education and multi- sector. Health sector is in a valuable position to support survivors and change social attitudes. Interventions taken in the health sector should be targeted at all three levels; primary prevention, secondary prevention and tertiary prevention. There are different models used in health care settings in different countries. “Mithuru Piyasa (in Sinhalese) / Natpu Nilayam (in Tamil)” which is staffed with a medical officer and a nursing officer was introduced in Sri Lanka as a “One Stop Crisis Centre/One Stop Service Centre” for survivors within the health institutions. Its main functions are screening, medical care, befriending services, risk assessment and safety planning, referral to legal, social, counseling and rehabilitation services, advocacy and community mobilization. Services are provided adhering to its guiding principles of safety, confidentiality, respect, non - discrimination, responsibility, competence and compassion. Documentation, Information management, progress review and evaluation are carried out for the sustainability of the service. Still this opportunity is not fully utilized. Service provision is not uniform in quality, coverage, equity, efficiency and effectiveness. Administrators are expected to develop their interest and pay their attention with priority, in supporting the functioning of these centres established under outpatient department by proper operation, expanding country wide and marketing.
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Valentine Chidi Obidile, Antor Odu Ndep, Onyeka Chukwudalu Ekwebene, Chidozie Precious Azubike, Lois Ezinne Obidile-Ikwegbu, Ray-Desmond Umechinedu, and Charles Nnamdi Ezeaka. "Post gender-based violence care, support services and health outcomes among victims of gender-based violence in Akwa Ibom and Cross-River States Nigeria." International Journal of Science and Research Archive 6, no. 2 (July 30, 2022): 006–15. http://dx.doi.org/10.30574/ijsra.2022.6.2.0138.
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Background: Gender-based violence has a negative impact on the physical and mental health of the victim, especially younger adults. Methodology: This cross-sectional descriptive study was carried out in Cross River and Akwa Ibom States of Nigeria using both qualitative and quantitative approaches. The study population comprised young adults aged 15-39 years in Cross River and Akwa Ibom States. The principal researcher and three field assistants administered 426 copies of the questionnaire to respondents. The data were analyzed using Statistical Packages for the Social Sciences software (SPSS) version 22. Thematic analysis was used for the qualitative data. Results: The majority of respondents 346(83.8%) knew that gender-based violence affects the health and wellbeing of victims; there were 267(64.6%) young adults who identified that gender-based violence poses both long-term and short-term effects on the health of the victims with 198(47.9%) who have suffered at least, one form of gender-based violence. Shame, (32.7%), anger, (27.8%), Bruises/injuries (25.2%) and low self-esteem (22.5) were the most frequently reported physical and emotional health effects of GBV. Many do not seek care due to shame. For those who sought care, counseling 97(49%), HIV/AIDS counselling and screening 66 (33.3%), STI screening 52(26.2%), and oral pills 24(12.2%) were some of the services accessed by victims. Discussion: This finding is consistent with reports from other GBV studies whose respondents suffered depression (48.8%), fear and anxiety (31.0%), which they argued were more serious conditions than the physical health impact of gender-based violence. Mental and emotional health outcomes of GBV are mostly invisible to others, making it harder for victims to seek help. Conclusion: Gender-based violence has negative impact on the physical and mental health of the victim, especially younger adults.
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Nordbø, Svein Arne, Sidsel Krokstad, Per Winge, Finn Egil Skjeldestad, and Are B. Dalen. "Prevalence of GB Virus C (Also Called Hepatitis G Virus) Markers in Norwegian Blood Donors." Journal of Clinical Microbiology 38, no. 7 (2000): 2584–90. http://dx.doi.org/10.1128/jcm.38.7.2584-2590.2000.
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GB virus C (GBV-C), also called hepatitis G virus (HGV), occurs worldwide, but the clinical significance of this virus is still unclear. Plasma samples from 1,001 blood donors were tested by reverse transcription PCR using primers from the NS5 region and by a commercial enzyme-linked immunosorbent assay (ELISA) for the detection of immunoglobulin G antibodies against the putative envelope of HGV (anti-HGV E2). GBV-C/HGV RNA was present in the plasma from 2.5% of the blood donors, and anti-HGV E2 antibodies could be detected in 10.5% of the samples. Only one of the blood donors with viremia had elevated levels of alanine aminotransferase. Among ELISA-positive donors, there was a significantly higher percentage (16.5%) of individuals who had been treated by acupuncture than individuals who had not been given this treatment (9.4%). No other variables showed significant differences. Screening of medical records from 401 recipients of blood from PCR-positive donors revealed no association with liver disease. Four of 12 partners (33%) were HGV RNA positive, and sequence analyses of the strains showed that four of the couples probably were infected with the same strains, while strains from different couples were not identical. Anti-HGV E2 antibodies were detected in serum samples from four other partners. The prevalence of GBV-C/HGV among blood donors in our region is dramatically higher than the prevalence of hepatitis C virus (0.03%).
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Schuler, Sidney Ruth, Quach Thu Trang, Vu Song Ha, and Hoang Tu Anh. "Qualitative Study of an Operations Research Project to Engage Abused Women, Health Providers, and Communities in Responding to Gender-Based Violence in Vietnam." Violence Against Women 17, no. 11 (November 2011): 1421–41. http://dx.doi.org/10.1177/1077801211433990.
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This article describes an action research project designed to engage women, health providers, and communities to respond to gender-based violence (GBV) in Vietnam. Based on results from in-depth interviews and group discussions, it considers the extent to which the project approaches were empowering for abused women. The results underscore the problems entailed in introducing systematic screening for gender-based violence into government health facilities in the low-resource setting of Vietnam, the importance of combining ideational change and rights components with support for abused women, and the difficulty of engaging male perpetrators.
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KHARRAT, IMEN, DHIA BOUKTILA, MAHA MEZGHANI-KHEMAKHEM, HANEM MAKNI, and MOHAMED MAKNI. "Biotype characterization and genetic diversity of the greenbug, Schizaphis graminum (Hemiptera: Aphididae), in north Tunisia." Revista Colombiana de Entomología 38, no. 1 (June 30, 2012): 87–90. http://dx.doi.org/10.25100/socolen.v38i1.8926.
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The greenbug Schizaphis graminum, is a major pest of wheat worldwide. Biotype screening of this pest is essential to develop pest management programs. In this research, eight greenbug clones, collected on wheat in the cereal-growing region of Béja (north Tunisia), were used to determine their damage on six reference wheat cultivars. All tested clones shared a unique biotypic profile, similar to biotype C. Moreover, DNA from the tested clones and that from seven reference clones of biotypes C, E, F, G, H, I and K, was analyzed, using 5 RAPD-PCR primers. The UPGMA method clustered samples into two distinct clades: a first one (I) included clones from north Tunisia, which were clearly associated to agricultural biotypes C, E, I and K, while a second clade (II) included non agricultural biotypes F, G and H. Results reported in this paper suggest that resistance genes Gb2, Gb3, Gb4, Gb5 and Gb6 in wheat would be the most efficient if used in wheat improvement programs for resistance against greenbug in Tunisia.
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Logie, Carmen H., Angela Kaida, Alexandra de Pokomandy, Nadia O’Brien, Pat O’Campo, Jay MacGillivray, Uzma Ahmed, et al. "Prevalence and Correlates of Forced Sex as a Self-Reported Mode of HIV Acquisition Among a Cohort of Women Living With HIV in Canada." Journal of Interpersonal Violence 35, no. 21-22 (July 12, 2017): 5028–63. http://dx.doi.org/10.1177/0886260517718832.
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Gender-based violence (GBV) is a global epidemic associated with increased HIV exposure. We assessed the prevalence and correlates of HIV acquisition via forced sex among women living with HIV (WLWH) in Canada. Baseline questionnaire data were analyzed for WLWH (≥16 years) with data on self-reported mode of HIV acquisition, enrolled in a community-based cohort study in British Columbia, Ontario, and Québec. We assessed forced sex (childhood, adulthood) as a self-reported mode of HIV acquisition. Of 1,330 participants, the median age was 42 (interquartile range [IQR] = 35-50) years; 23.5% were Indigenous, 26.3% African/Caribbean/Black, 43% White, and 7.2% of Other ethnicities. Forced sex was the third dominant mode of HIV transmission at 16.5% ( n = 219; vs. 51.6% consensual sex, 19.7% sharing needles, 5.3% blood transfusion, 3.8% perinatal, 1.3% contaminated needles, 0.4% other, 1.6% do not know/prefer not to answer). In multivariable analyses, significant correlates of HIV acquisition from forced versus consensual sex included legal status as a landed immigrant (adjusted odds ratio [aOR] = 1.99; 95% confidence interval [CI] = [1.12, 3.54]) or refugee (aOR = 3.62; 95% CI = [1.63, 8.04]) versus Canadian citizen; African/Caribbean/Black ethnicity versus Caucasian (aOR = 2.49; 95% CI = [1.43, 4.35]), posttraumatic stress disorder symptoms (aOR = 3.00; 95% CI = [1.68, 5.38]), histories of group home residence (aOR = 2.40; 95% CI = [1.10, 5.23]), foster care (aOR = 2.18; 95% CI = [1.10, 4.34]), and having one child relative to having three or more children (aOR = 0.52; 95% CI = [0.31, 0.89]). GBV must be considered a distinct HIV risk factor; forced sex is a significant underrecognized risk factor and mode of women’s HIV acquistion. Public health reporting systems can separate consensual and forced sex in reporting modes of HIV acquisition. Practitioners can engage in screening practices to meet client needs.
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Liu, Xiuying, Yibing Huang, Min Cheng, Ling Pan, Youhui Si, Guirong Li, Yuqiang Niu, et al. "Screening and Rational Design of Hepatitis C Virus Entry Inhibitory Peptides Derived from GB Virus A NS5A." Journal of Virology 87, no. 3 (November 21, 2012): 1649–57. http://dx.doi.org/10.1128/jvi.02201-12.
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ABSTRACTChronic infection by hepatitis C virus (HCV) is a cause of the global burden of liver diseases. HCV entry into hepatocytes is a complicated and multistep process that represents a promising target for antiviral intervention. The recently reported amphipathic α-helical virucidal peptide (C5A) from the HCV NS5A protein suggests a new category of antiviral drug candidates. In this study, to identify C5A-like HCV inhibitors, synthetic peptides derived from the C5A-corresponding NS5 protein region of selectedFlaviviridaeviruses were evaluated for their anti-HCV activities. A peptide from GB virus A (GBV-A), but not other flaviviruses, demonstrated an inhibitory effect on HCV infection. Through a series of sequence optimizations and modifications of the peptide helicity and hydrophobicity, we obtained a peptide designated GBVA10-9 with highly potent anti-HCV activity. GBVA10-9 suppressed infection with both cell culture-derived and pseudotyped HCVin vitro, and the 50% cell culture inhibitory concentration ranged from 20 nM to 160 nM, depending on the genotypic origin of the envelope proteins. GBVA10-9 had no detectable effects on either HCV attachment to Huh7.5.1 cells or viral RNA replication. No virucidal activity was found with GBVA10-9, suggesting an action mechanism distinct from that of C5A. The inhibitory effect of GBVA10-9 appeared to occur at the postbinding step during viral entry. Taken together, the results with GBVA10-9 demonstrated a potent activity for blocking HCV entry that might be used in combination with other antivirals directly targeting virus-encoded enzymes. Furthermore, GBVA10-9 also provides a novel tool to dissect the detailed mechanisms of HCV entry.
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Lefrère, Jean-Jacques, Françoise Roudot-Thoraval, François Lefrère, Alain Kanfer, Martine Mariotti, Joelle Lerable, Micheline Thauvin, Guillaume Lefèvre, Philippe Rouger, and Robert Girot. "Natural history of the TT virus infection through follow-up of TTV DNA–positive multiple-transfused patients." Blood 95, no. 1 (January 1, 2000): 347–51. http://dx.doi.org/10.1182/blood.v95.1.347.
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Abstract Little is known about the natural history and the pathogenicity of the TT virus (TTV). We present our findings of a cross-sectional study based on the TTV DNA screening of 173 multiple-transfused patients and a longitudinal study based on the follow-up of TTV DNA–positive patients. Overall, 48 patients (27.7%) tested positive for TTV DNA. The influence of the number of blood donor exposures on the prevalence of blood-borne viral infection indicates that TTV, hepatitis C virus (HCV), and an RNA virus known as GB virus C/hepatitis G virus (GBV-C/HGV) share a parenteral transmission, but that TTV, in contrast to the 2 other viruses, is also transmitted by at least another efficient means. The patients having a well-defined date of TTV infection were positive for TTV DNA during a mean period of 3.1 years. A chronic infection was observed in 31 cases (86%). TTV carriage appeared clinically benign in all patients. No clinical evidence of a disease potentially linked to the TTV infection was observed in patients with TTV DNA carriage over several years. The majority of TTV carriers had no biochemical evidence of liver disease. The prevalence of elevated serum alanine aminotransferase (ALT) level was higher in the TTV DNA–positive group, even in the absence of HCV infection, but the observed peaks of ALT level were most often transient and very mild. The prevalence of TTV DNA observed in blood recipients is consistent with that of TTV infection observed in blood donors. TTV infection frequently tends to persist. (Blood. 2000;95:347-351)
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Lefrère, Jean-Jacques, Françoise Roudot-Thoraval, François Lefrère, Alain Kanfer, Martine Mariotti, Joelle Lerable, Micheline Thauvin, Guillaume Lefèvre, Philippe Rouger, and Robert Girot. "Natural history of the TT virus infection through follow-up of TTV DNA–positive multiple-transfused patients." Blood 95, no. 1 (January 1, 2000): 347–51. http://dx.doi.org/10.1182/blood.v95.1.347.001k42_347_351.
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Little is known about the natural history and the pathogenicity of the TT virus (TTV). We present our findings of a cross-sectional study based on the TTV DNA screening of 173 multiple-transfused patients and a longitudinal study based on the follow-up of TTV DNA–positive patients. Overall, 48 patients (27.7%) tested positive for TTV DNA. The influence of the number of blood donor exposures on the prevalence of blood-borne viral infection indicates that TTV, hepatitis C virus (HCV), and an RNA virus known as GB virus C/hepatitis G virus (GBV-C/HGV) share a parenteral transmission, but that TTV, in contrast to the 2 other viruses, is also transmitted by at least another efficient means. The patients having a well-defined date of TTV infection were positive for TTV DNA during a mean period of 3.1 years. A chronic infection was observed in 31 cases (86%). TTV carriage appeared clinically benign in all patients. No clinical evidence of a disease potentially linked to the TTV infection was observed in patients with TTV DNA carriage over several years. The majority of TTV carriers had no biochemical evidence of liver disease. The prevalence of elevated serum alanine aminotransferase (ALT) level was higher in the TTV DNA–positive group, even in the absence of HCV infection, but the observed peaks of ALT level were most often transient and very mild. The prevalence of TTV DNA observed in blood recipients is consistent with that of TTV infection observed in blood donors. TTV infection frequently tends to persist. (Blood. 2000;95:347-351)
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Manietta, Christina, Mike Rommerskirch-Manietta, Daniel Purwins, and Martina Roes. "Consulting concepts and structures for people with dementia in Germany: a protocol for a ‘grey-shaded’ scoping review." BMJ Open 12, no. 4 (April 2022): e059771. http://dx.doi.org/10.1136/bmjopen-2021-059771.
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IntroductionLiterature reviews represent an important type of study for the various professions in healthcare. The consideration and inclusion of grey literature is gaining importance in all types of reviews. However, searching for grey literature is challenging for different reasons and the search is often insufficiently transparently reported in reviews. The aim of this protocol is to describe our planned methodical approach for a scoping review with a specific focus on grey literature related to the topic of consulting according to §7a of the German Social Law, Book XI (SGB XI) for people with dementia and their relatives in Germany.Methods and analysisWe will use the following search strategies: (1) search in the German electronic databases, for example, Livivo and GeroLit (via GBV), (2) google search engines, (3) targeted websites, for example, Alzheimer’s association and (4) contact experts, for example, stakeholders of private care insurance companies who provide consulting according to §7a SGB XI. Additionally, we will conduct a search in the academic electronic databases MEDLINE (via PubMed) and CINAHL (via EBSCO). For included grey literature, we will conduct a backward citation tracking via reference lists. For included scientific articles, we will conduct a backward (via reference lists) and forward (via Google scholar) citation tracking. Each strategy will be conducted by one reviewer. Screening of the identified potentially relevant records will be conducted in Covidence by two reviewers independently. Results will be charted in a table and illustrated descriptively.Ethics and disseminationThere are no ethical concerns with conducting a scoping review. We will discuss our results regarding consulting according to §7a SGB XI for people with dementia and their relatives with a variety of stakeholders in Germany. We will disseminate the thematic results and the methodological reflection of our search approach in the form of articles in peer-reviewed and non-peer-reviewed journals.
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Kitagawa, Yosuke, Shota Tanaka, Yugo Kuriki, Kyoko Yamamoto, Takahide Nejo, Satoshi Takahashi, Masashi Nomura, et al. "DDIS-02. DEVELOPMENT OF NOVEL SPRAY-TYPE FLUORESCENT PROBES FOR GLIOBLASTOMA DETECTION." Neuro-Oncology 21, Supplement_6 (November 2019): vi65. http://dx.doi.org/10.1093/neuonc/noz175.262.
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Abstract PURPOSE: ALA is commonly used as an intraoperative tool in malignant glioma surgery, which has been proven effective for radical tumor resection and extended progression-free survival. However, there are some limitations in its use, such as false positivity, false negativity, and inability of re-administration. We aim to develop a novel fluorescent labeling system which can be repeatedly administered by spray during surgery, using hydroxymethyl rhodamine green (HMRG) as fluorescent scaffold originally designed at our university for cancer detection. [Methods]Primary probe screening was performed using the homogenized glioblastoma (GBM) samples with the fluorescent probe library comprised of more than 320 kinds of HMRG fluorescent scaffold combined with various types of dipeptides. Second probe screening was performed using fresh GBM specimens and the selected probes in primary screening. To identify the responsible enzymes, diced electrophoresis gel (DEG) assay was performed. This method utilizes the combination of two dimensional electrophoresis (isoelectric point and molecular weight) and a multiwell-plate-based fluorometric assay to find protein spots with the specified activities. [Results] The prominent probes were selected based upon the above two-step screenings. We identified two enzymes by proteome analysis and experiments using inhibitors, which was further confirmed with real-time PCR and western blotting. [Discussion] This screening methodology is innovative in that it is based on selecting probes from the probe library that respond to clinical samples rather than creating probes from the responsible enzymes. Practical fluorescent probes can be established even for low-grade gliomas, which would be a breakthrough for rapid intraoperative diagnosis in glioma surgery. [Conclusion] HMRG-based aminopeptidase fluorescent probes may be effective for GBM detection.
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Kitagawa, Yosuke, Shota Tanaka, Yugo Kuriki, Kyoko Yamamoto, Taijun Hana, Tsukasa Koike, Yoshinori Kushihara, et al. "BOT-03 INVESTIGATION OF NOVEL SPRAY TYPE FLUORESCENT PROBE FOR GLIOBLASTOMA DETECTION." Neuro-Oncology Advances 1, Supplement_2 (December 2019): ii12. http://dx.doi.org/10.1093/noajnl/vdz039.055.
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Abstract PURPOSE 5-ALA is commonly used as an intraoperative tool in malignant glioma surgery, which has been proven effective for radical tumor resection and extended progression-free survival. However, there are some limitations in its use, such as false positivity, false negativity, and inability of re-administration. We aim to develop a novel fluorescent labeling system which can be repeatedly administered by spray during surgery, using hydroxymethyl rhodamine green (HMRG) as fluorescent scaffold originally designed at our university for cancer detection. METHODS Primary probe screening was performed using the homogenized glioblastoma (GBM) samples with the fluorescent probe library comprised of more than 320 kinds of HMRG fluorescent scaffold combined with various types of dipeptides. Second probe screening was performed using fresh GBM specimens and the selected probes in primary screening. To identify the responsible enzymes, diced electrophoresis gel (DEG) assay was performed. This method utilizes the combination of two dimensional electrophoresis (isoelectric point and molecular weight) and a multiwell-plate-based fluorometric assay to find protein spots with the specified activities. RESULTS The prominent probes were selected based upon the above two-step screenings. We identified two enzymes by proteome analysis and experiments using inhibitors, which was further confirmed with real-time PCR and western blotting. DISCUSSION This screening methodology is innovative in that it is based on selecting probes from the probe library that respond to clinical samples rather than creating probes from the responsible enzymes. Practical fluorescent probes can be established even for low-grade gliomas, which would be a breakthrough for rapid intraoperative diagnosis in glioma surgery. CONCLUSION HMRG-based aminopeptidase fluorescent probes may be effective for GBM detection.
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Davies, H. Dele, Carol E. Adair, Eric S. Partlow, Reginald Sauve, Don E. Low, and Allison McGeer. "Two-year survey of Alberta laboratories processing of antenatal group B streptococcal (GBS) screening specimens: implications for GBS screening programs." Diagnostic Microbiology and Infectious Disease 35, no. 3 (November 1999): 169–76. http://dx.doi.org/10.1016/s0732-8893(99)00076-0.
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Wilson, Kelli M., Lesley A. Mathews-Griner, Tara Williamson, Rajarshi Guha, Lu Chen, Paul Shinn, Crystal McKnight, et al. "Mutation Profiles in Glioblastoma 3D Oncospheres Modulate Drug Efficacy." SLAS TECHNOLOGY: Translating Life Sciences Innovation 24, no. 1 (October 5, 2018): 28–40. http://dx.doi.org/10.1177/2472630318803749.
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Glioblastoma (GBM) is a lethal brain cancer with a median survival time of approximately 15 months following treatment. Common in vitro GBM models for drug screening are adherent and do not recapitulate the features of human GBM in vivo. Here we report the genomic characterization of nine patient-derived, spheroid GBM cell lines that recapitulate human GBM characteristics in orthotopic xenograft models. Genomic sequencing revealed that the spheroid lines contain alterations in GBM driver genes such as PTEN, CDKN2A, and NF1. Two spheroid cell lines, JHH-136 and JHH-520, were utilized in a high-throughput drug screen for cell viability using a 1912-member compound library. Drug mechanisms that were cytotoxic in both cell lines were Hsp90 and proteasome inhibitors. JHH-136 was uniquely sensitive to topoisomerase 1 inhibitors, while JHH-520 was uniquely sensitive to Mek inhibitors. Drug combination screening revealed that PI3 kinase inhibitors combined with Mek or proteasome inhibitors were synergistic. However, animal studies to test these drug combinations in vivo revealed that Mek inhibition alone was superior to the combination treatments. These data show that these GBM spheroid lines are amenable to high-throughput drug screening and that this dataset may deliver promising therapeutic leads for future GBM preclinical studies.
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Ntafoulis, Ioannis, Anne Kleijn, Cassandra Posthoorn-Verheul, Stijn L. W. Koolen, Trisha Kers, Chelsea W. J. den Hollander, Jie Ju, et al. "DDDR-27. A PATIENT-DERIVED DRUG SCREENING PLATFORM PREDICTS RESPONSE TO TEMOZOLOMIDE AND IDENTIFIES POTENTIAL NEW TREATMENTS FOR GLIOBLASTOMA." Neuro-Oncology 24, Supplement_7 (November 1, 2022): vii104—vii105. http://dx.doi.org/10.1093/neuonc/noac209.392.
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Abstract BACKGROUND Major obstacles that have impeded the development of effective new therapies for GBM include inter- and intratumoral heterogeneity, the blood-brain-barrier and use of sub-optimal cell line-based preclinical models. Taking these hurdles into account, we have set up a patient-derived GBM drug-screening platform. We optimized protocols to improve cell culture success rate and retrospectively assessed the predictive power of our assay for patient response to TMZ. A large panel of GBM cells was screened for sensitivity to available oncological agents. Drugs of interest were selected based on favorable physicochemical properties for BBB crossing and potent activity in (a subset of) GBM cultures. Finally, we determined the success rate of performing a small-scale screen with 20 selected agents within 4 weeks of receiving tumor tissue. RESULTS By combining both CUSA and tissue piece-derived dissociation protocols, culture success increased to 95%, ensuring representation of the near-complete spectrum of GBM subtypes. Single-cell sequencing studies confirmed heterogeneity in our low-passage cell cultures. In vitro screening of TMZ on a large cohort (n = 55) identified 3 response categories (responders/intermediates/non-responders) for which Cox regression analysis revealed significantly different overall survival curves of corresponding patients. Screening of 107 FDA-approved anticancer agents on 45 GBM cultures underscored the tremendous intertumoral heterogeneity in drug sensitivities. We identified 20 potent agents each effective at clinically-achievable concentrations in (a subset of) GBM cultures and having favorable BBB penetration properties (CNS-MPO score). Screening of these agents on a per patient basis within 4 weeks of receiving tissue was successful in 18 out of 24 (75%) tested tumors. In the remaining cases the tumor cells grew very slowly and longer culture times were required. CONCLUSION Our drug screening platform offers a tool to predict TMZ response and assess sensitivity to candidate treatments, either for GBM subsets or on a per patient basis.
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Tucker, Miriam E. "Prenatal GBS Screening: Less Likely in Hispanic Women, Others." Pediatric News 39, no. 9 (September 2005): 20. http://dx.doi.org/10.1016/s0031-398x(05)70565-8.
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Tucker, Miriam E. "Early-Onset GBS Down 31% Since Universal Screening Began." Pediatric News 40, no. 2 (February 2006): 6. http://dx.doi.org/10.1016/s0031-398x(06)70853-0.
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Nguyen, Nancy, Teresa Worstell, Emily Griffin, Richard Beigi, Leonardo Pereira, and Aaron Caughey. "489: Repeat antepartum GBS screening: a cost-effectiveness analysis." American Journal of Obstetrics and Gynecology 210, no. 1 (January 2014): S244. http://dx.doi.org/10.1016/j.ajog.2013.10.522.
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Nienow Birch, Mary Nicole, Alyssa R. Hersh, Karen J. Scrivner, and Aaron B. Caughey. "853: The cost effectiveness of multiple GBS screening intervals." American Journal of Obstetrics and Gynecology 218, no. 1 (January 2018): S509. http://dx.doi.org/10.1016/j.ajog.2017.11.390.
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Brown, Andrew P., and Fiona C. Denison. "Selective or universal screening for GBS in pregnancy (review)." Early Human Development 126 (November 2018): 18–22. http://dx.doi.org/10.1016/j.earlhumdev.2018.09.002.
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Pudelko, Linda, Steven Edwards, Mirela Balan, Daniel Nyqvist, Jonathan Al-Saadi, Johannes Dittmer, Ingrid Almlöf, Thomas Helleday, and Lars Bräutigam. "An orthotopic glioblastoma animal model suitable for high-throughput screenings." Neuro-Oncology 20, no. 11 (May 10, 2018): 1475–84. http://dx.doi.org/10.1093/neuonc/noy071.
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Abstract Background Glioblastoma (GBM) is an aggressive form of brain cancer with poor prognosis. Although murine animal models have given valuable insights into the GBM disease biology, they cannot be used in high-throughput screens to identify and profile novel therapies. The only vertebrate model suitable for large-scale screens, the zebrafish, has proven to faithfully recapitulate biology and pathology of human malignancies, and clinically relevant orthotopic zebrafish models have been developed. However, currently available GBM orthotopic zebrafish models do not support high-throughput drug discovery screens. Methods We transplanted both GBM cell lines as well as patient-derived material into zebrafish blastulas. We followed the behavior of the transplants with time-lapse microscopy and real-time in vivo light-sheet microscopy. Results We found that GBM material transplanted into zebrafish blastomeres robustly migrated into the developing nervous system, establishing an orthotopic intracranial tumor already 24 hours after transplantation. Detailed analysis revealed that our model faithfully recapitulates the human disease. Conclusion We have developed a robust, fast, and automatable transplantation assay to establish orthotopic GBM tumors in zebrafish. In contrast to currently available orthotopic zebrafish models, our approach does not require technically challenging intracranial transplantation of single embryos. Our improved zebrafish model enables transplantation of thousands of embryos per hour, thus providing an orthotopic vertebrate GBM model for direct application in drug discovery screens.
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Stackhouse, Christian T., James R. Rowland, Rachael S. Shevin, Raj Singh, G. Yancey Gillespie, and Christopher D. Willey. "A Novel Assay for Profiling GBM Cancer Model Heterogeneity and Drug Screening." Cells 8, no. 7 (July 11, 2019): 702. http://dx.doi.org/10.3390/cells8070702.
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Accurate patient-derived models of cancer are needed for profiling the disease and for testing therapeutics. These models must not only be accurate, but also suitable for high-throughput screening and analysis. Here we compare two derivative cancer models, microtumors and spheroids, to the gold standard model of patient-derived orthotopic xenografts (PDX) in glioblastoma multiforme (GBM). To compare these models, we constructed a custom NanoString panel of 350 genes relevant to GBM biology. This custom assay includes 16 GBM-specific gene signatures including a novel GBM subtyping signature. We profiled 11 GBM-PDX with matched orthotopic cells, derived microtumors, and derived spheroids using the custom NanoString assay. In parallel, these derivative models underwent drug sensitivity screening. We found that expression of certain genes were dependent on the cancer model while others were model-independent. These model-independent genes can be used in profiling tumor-specific biology and in gauging therapeutic response. It remains to be seen whether or not cancer model-specific genes may be directly or indirectly, through changes to tumor microenvironment, manipulated to improve the concordance of in vitro derivative models with in vivo models yielding better prediction of therapeutic response.
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Di Renzo, G. C., P. Melin, A. Berardi, M. Blennow, X. Carbonell-Estrany, G. P. Donzelli, S. Hakansson, et al. "Intrapartum GBS screening and antibiotic prophylaxis: a European consensus conference." Journal of Maternal-Fetal & Neonatal Medicine 28, no. 7 (August 27, 2014): 766–82. http://dx.doi.org/10.3109/14767058.2014.934804.
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Zhao, Wenting, Eleonora Spinazzi, Athanassios Dovas, Pavan Upadhyayula, Tamara Marie, Michael Sisti, Jeff Bruce, Peter D. Canoll, and Peter Sims. "COMP-12. SINGLE-CELL TRANSCRIPTOME PROFILING OF GBM TISSUE ACUTE SLICE CULTURES FOR PERSONALIZED DRUG SCREENING." Neuro-Oncology 21, Supplement_6 (November 2019): vi63. http://dx.doi.org/10.1093/neuonc/noz175.255.
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Abstract Glioblastoma (GBM) is the most common and malignant type of primary brain tumor, and more effective treatment options are needed. Both inter- and intratumoral heterogeneity present major challenges to the application of targeted therapies in GBM. Therefore, precision medicine approaches to GBM would benefit significantly from the ability to predict drugs or drug combinations that target specific subpopulations of tumor cells. Model systems, such as adherent cell lines, neurospheres, patient-derived xenografts (PDXs), and patient-derived organoids, have been reported as platforms for drug screening and accessing drug responses. However, these models do not recapitulate the full heterogeneity of GBM tissue, lack key components of the tumor microenvironment or take weeks to months to establish, which limits the predictive power of drug response assays or delays clinical decision-making. To address these limitations, we are combining ex vivo slices of intact, patient-derived GBM tissue with single-cell RNA-seq (scRNA-seq) for small-scale drug screening and assessment of patient- and cell type-specific drug responses. We generated slices from both preclinical mouse glioma models and surgical specimens from GBM patients and showed that acute slices preserved both the tumor heterogeneity and tumor microenvironment observed in scRNA-seq of cells directly isolated from tumor tissue. To test drug responses, we treated tissue slices from GBM mouse models and five different patients with six drugs for 18hr. By performing scRNA-Seq and analyzing transcriptional profiles of treated and untreated control slices, we identified drug-induced transcriptional responses in specific subpopulations of tumor cells, patient-specific drug sensitivities, and drug effects conserved in both mouse and human tumors. The GBM tissue slices were generated immediately following surgical resection, and experiments were completed within 24 hours. With these features, our method is attractive for rapidly accessing cell type- and patient-specific drug responses and has potential for preclinical drug screening and guiding personalized treatment for GBM.
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Parmaksız, Ergün, and Meral Meşe. "Fabry disease: A single-center experience." Ukrainian Journal of Nephrology and Dialysis, no. 2(70) (June 30, 2021): 13–18. http://dx.doi.org/10.31450/ukrjnd.2(70).2021.02.
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Fabry disease (FD) is an inborn X-linked lysosomal storage disorder resulting from α–galactosidase A (α-Gal) activity deficiency in lysosomes. This results in the accumulation of particularly globotriaosylceramide (Gb3) within lysosomes in a wide variety of cells. This study aimed to analyze the clinical presentation, findings and family screenings of index cases, management and outcomes of FD patients in our center.
Methods. Data including demographic characteristics, personal history of comorbidities, laboratory findings at the time of diagnosis were recorded. α – Gal activity was measured in all males and females as initial analysis. The cut-off trigger was determined as 1.2 mmol/L per hour. Mutation analysis was performed in males and females with decreased α – Gal activity as a diagnostic assay. In addition, mutation analysis was performed change in females with normal α – Gal providing they have clinical signs or family history for FD.
Results. The individuals from nine FD families were presented.
Conclusion. Screening for genetic diseases such as FD has crucial conclusions. The detection of FD in an index case leads to appropriate therapy for that patient. Family screening can be started and additional undiagnosed individuals can be detected.
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Koskan, Alexis M., and Madeline Fernandez-Pineda. "Anal Cancer Prevention Perspectives Among Foreign-Born Latino HIV-Infected Gay and Bisexual Men." Cancer Control 25, no. 1 (January 1, 2018): 107327481878036. http://dx.doi.org/10.1177/1073274818780368.
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This study explores understanding of primary and secondary prevention of anal cancer among human immunodeficiency virus (HIV)-infected foreign-born Latino gay and bisexual men (GBM). Between August 2015 and December 2016, researchers conducted 33 in-depth, semi-structured interviews with HIV-infected foreign-born Latino GBM. Interview questions sought to determine participants’ knowledge and perceived barriers and facilitators to primary and secondary prevention of anal cancer. Researchers analyzed interview transcripts using a qualitative content analysis approach. For primary prevention, men reported a lack of knowledge about the human papillomavirus (HPV) vaccine. However, for secondary prevention, roughly 60% of participants had previously screened for anal dysplasia via anal Papanicolaou (Pap) smear. However, participants reported willingness to screen, and provider recommendation was the most common screening facilitator. Men reported stigma related to their HIV status, sexual orientation, and anal Pap smear procedures as anal cancer screening barriers. Participants reported willingness to use a self-screening anal Pap smear test if it was commercially available. Health providers continue to be the leading source of health information. Therefore, provider recommendation for HPV vaccination and anal cancer screening among age-eligible foreign-born Latino HIV-infected GBM is critical. More work is needed to destigmatize HIV and sexual orientation to influence positive health behaviors among this population. Future intervention research could test the effects of provider-led interventions and also media campaigns aimed at influencing HPV vaccine uptake and anal cancer screening among this population.
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Shapovalov, Vladimir, Liliya Kopanitsa, Lavinia-Lorena Pruteanu, Graham Ladds, and David S. Bailey. "Transcriptomics-Based Phenotypic Screening Supports Drug Discovery in Human Glioblastoma Cells." Cancers 13, no. 15 (July 27, 2021): 3780. http://dx.doi.org/10.3390/cancers13153780.
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We have used three established human glioblastoma (GBM) cell lines—U87MG, A172, and T98G—as cellular systems to examine the plasticity of the drug-induced GBM cell phenotype, focusing on two clinical drugs, the phosphodiesterase PDE10A inhibitor Mardepodect and the multi-kinase inhibitor Regorafenib, using genome-wide drug-induced gene expression (DIGEX) to examine the drug response. Both drugs upregulate genes encoding specific growth factors, transcription factors, cellular signaling molecules, and cell surface proteins, while downregulating a broad range of targetable cell cycle and apoptosis-associated genes. A few upregulated genes encode therapeutic targets already addressed by FDA approved drugs, but the majority encode targets for which there are no approved drugs. Amongst the latter, we identify many novel druggable targets that could qualify for chemistry-led drug discovery campaigns. We also observe several highly upregulated transmembrane proteins suitable for combined drug, immunotherapy, and RNA vaccine approaches. DIGEX is a powerful way of visualizing the complex drug response networks emerging during GBM drug treatment, defining a phenotypic landscape which offers many new diagnostic and therapeutic opportunities. Nevertheless, the extreme heterogeneity we observe within drug-treated cells using this technique suggests that effective pan-GBM drug treatment will remain a significant challenge for many years to come.
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Thaker, Nikhil G., Fang Zhang, Peter R. McDonald, Tong Ying Shun, John S. Lazo, and Ian F. Pollack. "Functional genomic analysis of glioblastoma multiforme through short interfering RNA screening: a paradigm for therapeutic development." Neurosurgical Focus 28, no. 1 (January 2010): E4. http://dx.doi.org/10.3171/2009.10.focus09210.
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Glioblastoma multiforme (GBM) is a high-grade brain malignancy arising from astrocytes. Despite aggressive surgical approaches, optimized radiation therapy regimens, and the application of cytotoxic chemotherapies, the median survival of patients with GBM from time of diagnosis remains less than 15 months, having changed little in decades. Approaches that target genes and biological pathways responsible for tumorigenesis or potentiate the activity of current therapeutic modalities could improve treatment efficacy. In this regard, several genomic and proteomic strategies promise to impact significantly on the drug discovery process. High-throughput genome-wide screening with short interfering RNA (siRNA) is one strategy for systematically exploring possible therapeutically relevant targets in GBM. Statistical methods and protein-protein interaction network databases can also be applied to the screening data to explore the genes and pathways that underlie the pathological basis and development of GBM. In this study, we highlight several genome-wide siRNA screens and implement these experimental concepts in the T98G GBM cell line to uncover the genes and pathways that regulate GBM cell death and survival. These studies will ultimately influence the development of a new avenue of neurosurgical therapy by placing the drug discovery process in the context of the entire biological system.
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Gragnaniello, Vincenza, Alessandro P. Burlina, Giulia Polo, Antonella Giuliani, Leonardo Salviati, Giovanni Duro, Chiara Cazzorla, et al. "Newborn Screening for Fabry Disease in Northeastern Italy: Results of Five Years of Experience." Biomolecules 11, no. 7 (June 27, 2021): 951. http://dx.doi.org/10.3390/biom11070951.
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Fabry disease (FD) is a progressive multisystemic lysosomal storage disease. Early diagnosis by newborn screening (NBS) may allow for timely treatment, thus preventing future irreversible organ damage. We present the results of 5.5 years of NBS for FD by α-galactosidase A activity and globotriaosylsphingosine (lyso-Gb3) assays in dried blood spot through a multiplexed MS/MS assay. Furthermore, we report our experience with long-term follow-up of positive subjects. We screened more than 170,000 newborns and 22 males were confirmed to have a GLA gene variant, with an incidence of 1:7879 newborns. All patients were diagnosed with a variant previously associated with the later-onset phenotype of FD or carried an unclassified variant (four patients) or the likely benign p.Ala143Thr variant. All were asymptomatic at the last visit. Although lyso-Gb3 is not considered a reliable second tier test for newborn screening, it can simplify the screening algorithm when its levels are elevated at birth. After birth, plasma lyso-Gb3 is a useful marker for non-invasive monitoring of all positive patients. Our study is the largest reported to date in Europe, and presents data from long-term NBS for FD that reveals the current incidence of FD in northeastern Italy. Our follow-up data describe the early disease course and the trend of plasma lyso-Gb3 during early childhood.
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Parra-Cantu, Carolina, Wanlu Li, Alfredo Quiñones-Hinojosa, and Yu Shrike Zhang. "3D bioprinting of glioblastoma models." Journal of 3D Printing in Medicine 4, no. 2 (June 2020): 113–25. http://dx.doi.org/10.2217/3dp-2019-0027.
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The most common and malignant primary brain tumor in adults is glioblastoma (GBM). In vitro 3D brain models are needed to better understand the pathological processes underlying GBM and ultimately develop more efficient antineoplastic agents. Here, we describe the bioprinting methods that have been used to fabricate volumetric GBM models. We explain several factors that should be considered for 3D bioprinting, including bioinks, cells and construct designs, in relation to GBM modeling. Although 3D-bioprinted brain models are still to be improved, they have the potential to become a powerful tool for drug screening.
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Jiang, Xiaoqing, Bin Li, Zhiquan Qiu, Yong Yu, Zhishuai Li, Jingjing Zheng, Chenyang Wang, et al. "Use of DNA methylation to distinguish gallbladder carcinoma." Journal of Clinical Oncology 37, no. 15_suppl (May 20, 2019): e15605-e15605. http://dx.doi.org/10.1200/jco.2019.37.15_suppl.e15605.
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e15605 Background: Gallbladder cancer (GBC), an uncommon malignancy with a high mortality rate, is often diagnosed late due to lack of early symptoms and the relative hidden nature of the gallbladder. Despite the advancements in imaging technologies, there is no reliable screening test for GBC. The role of aberrant DNA methylation in the process of tumorigenesis both at individual genes and a genome-wide scale has been well elucidated. It occurs very early in cancer development, thus capable of serving as a screening marker. Methods: Panel Design: Methylation data of tumor samples (12 types, n = 4,772), adjacent normal (8 types, n = 411), and normal white blood cells (n = 656) from TCGA and GSE were compared. Differentially methylated sites were derived using a Bayesian hierarchical model-DSS with an adjusted p-value < 0.05. Our panel covers 80,672 CpG sites, spanning 1.05Mb of human genome. This panel contains 12,196 GBC relevant CpG sites. We performed targeted bisulfite sequencing on 23 GBC patients (6 stage II-III, 17 stage IV) and 13 patients with non-malignant gallbladder diseases (cholecystitis and gallstones). Of the 23 GBC patients, we obtained adjacent normal tissue from 7 of them. Basic clinical features such as age, gender, of patients with GBC and patients with non-malignant gallbladder diseases were comparable. Results: Among the 12,196 GBC relevant CpG sites, 10,216 sites were statistically significantly hypermethylated and 275 sites were statistically significantly hypomethylated comparing to patients with non-malignant gallbladder disease as well as adjacent normal gallbladder tissues. Subsequently, we used the derived differentially methylated CpG sites to construct a linear regression model, achieving an area under curve of 99%. Collectively, the methylation levels were comparable between tissues with non-malignant disease and adjacent normal. Interestingly, when considering the 275 hypomethylated markers alone, we observed that the methylation level of adjacent normal tissues is significantly higher than tissues with non-malignant disease. Conclusions: Collectively, our panel can effectively distinguish GBC samples from non-cancerous samples, demonstrating the potential of DNA methylation in GBC screening. Furthermore, hypomethylation markers can be used to distinguish non-malignant disease from the healthy.
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Tsung, Kathleen, Jane Han, Kristie Liu, Eddie Loh, and Frank Attenello. "CNSC-31. CRISPR FUNCTIONAL SCREEN IDENTIFIES A NOVEL LONG NONCODING RNA MODULATING GLIOBLASTOMA INVASION." Neuro-Oncology 24, Supplement_7 (November 1, 2022): vii29. http://dx.doi.org/10.1093/neuonc/noac209.112.
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Abstract INTRODUCTION Glioblastoma(GBM) invasion studies traditionally target coding genes. Long noncoding RNAs (lncRNAs), are transcripts without coding potential, with limited data regarding function. We leveraged CRISPR-interference, repressing lncRNA transcription via Cas9-KRAB, to evaluate invasive function of GBM-associated lncRNAs in a CRISPRi functional screen. METHODS 2,307 candidate lncRNAs were assembled from GBM differential gene expression. Guide RNAs targeting candidates were lentivirally incorporated into GBM screening populations. Screen populations were evaluated via Matrigel invasion, comparing sgRNA populations before/after a 24-hour invasion period. ASO treatment evaluated pharmacologic targeting of candidate lncRNAs. Top screening candidates were evaluated in a patient derived glioma stem cell (GSC) line, USC02, as well as U87 and U251 commercial lines. Differential gene expression was assessed in multiple cell lines following lncRNA knockdown via RNA-seq followed by GSEA and pathway analysis was evaluated to assess downstream mechanistic candidates affected by lncRNA KD. RESULTS Forty-eight lncRNAs were significantly associated with GBM invasion, with lncRNA repression associated with decreased invasion of 31-85%(p< 0.01). Individual validation of a candidate lncRNA KD, LH02236, confirmed 85% decrease in tumor cell invasion versus control. Evaluation of gene expression across normal cortex and tumor samples from GSEA/TCGA datasets revealed LH02236 is significantly more expressed in GBM versus low grade glioma, and in low grade glioma versus normal cortex. Expression of LH02236 was significantly associated with patient survival (p< 0.0001). Gene expression analysis of LH02236 knockdown revealed Sox10 to be highly correlated with lncRNA expression across multiple cell lines. CONCLUSION Large scale CRISPRi screening identified LH02236, a previously unannotated lncRNA, as essential to invasion in patient lines. Gene expression is significantly associated with tumor grade and patient survival. Analysis of knockdown across multiple cell lines suggests Sox 10, commonly associated with GSC function, is modulated by this novel lncRNA.
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Jones, Matthew, Ralph K. Akyea, Katherine Payne, Steve E. Humphries, Hasidah Abdul-Hamid, Stephen Weng, and Nadeem Qureshi. "Cost-Effectiveness of Screening Algorithms for Familial Hypercholesterolaemia in Primary Care." Journal of Personalized Medicine 12, no. 3 (February 22, 2022): 330. http://dx.doi.org/10.3390/jpm12030330.
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Although familial hypercholesterolemia (FH) screening within primary care is considered cost-effective, which screening approach is cost-effective has not been established. This study determines the cost-effectiveness of six case-finding strategies for screening of electronic health records to identify index patients who have genetically confirmed monogenic FH in English primary care. A decision tree was constructed to represent pathways of care for each approach (FH Case Identification Tool (FAMCAT) versions 1 and 2, cholesterol screening, Dutch Lipid Clinic Network (DLCN), Simon Broome criteria, no active screening). Clinical effectiveness was measured as the number of monogenic FH cases identified. Healthcare costs for each algorithm were evaluated from an NHS England perspective over a 12 week time horizon. The primary outcome was the incremental cost per additional monogenic FH case identified (ICER). FAMCAT2 was found to dominate (cheaper and more effective) cholesterol and FAMCAT1 algorithms, and extendedly dominate DLCN. The ICER for FAMCAT2 vs. no active screening was 8111 GBP (95% CI: 4088 to 14,865), and for Simon Broome vs. FAMCAT2 was 74,059 GBP (95% CI: −1,113,172 to 1,697,142). Simon Broome found the largest number of FH cases yet required 102 genetic tests to identify one FH patient. FAMCAT2 identified fewer, but only required 23 genetic tests.
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Nguyen, Trang, Enyuan Shang, Consuelo Torrini, Chang Shu, Mike-Andrew Westhoff, Georg Karpel-Massler, and Markus Siegelin. "TMET-39. INHIBITION OF THE TCA-CYCLE IS SYNTHETICALLY LETHAL WITH LOSS OF FUNCTION OF BCL-XL IN GLIOBLASTOMA." Neuro-Oncology 24, Supplement_7 (November 1, 2022): vii270. http://dx.doi.org/10.1093/neuonc/noac209.1044.
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Abstract Glioblastoma (GBM) remains an incurable disease, requiring more effective therapies. Through CRISPR and RNAi library screening interrogation we identified several TCA-cycle enzymes as essential for GBM growth. By combining a transcriptome and metabolite screening analyses we discovered that inhibition of the TCA-cycle by the clinically validated drug compound, CPI-613, is synthetically lethal with Bcl-xL loss of function (genetically and through the clinically validated BH3-mimetic, ABT263) in patient-derived xenograft as well neurosphere GBM cultures. Carbon tracing experiments (U-13 C-glucose and U-13 C-glutamine) and extracellular flux analysis showed that CPI-613 interferes with mitochondrial respiration. In turn, CPI-613 mediated energy deprivation drives an integrated stress response with an up-regulation of the BH3-only domain protein, Noxa in an ATF4 dependent manner as demonstrated by genetic loss of function experiments. Consistently, silencing of Noxa rescued from cell death induced by CPI-613 as well as by the combination treatment of ABT263 and CPI-613 in model systems of GBM. In patient-derived xenograft models of GBM in mice, the combination treatment of ABT263 and CPI613 suppressed tumor growth more potently than each compound on its own. Therefore, combined inhibition of Bcl-xL along with interference of the TCA-cycle might be a novel treatment strategy for GBM.
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Ntafoulis, I., T. Kers, M. van der Kaaij, R. Balvers, J. Hayes, J. van Rij, R. Tching, et al. "P11.27 Drug screening of available anti-cancer drugs on patient-derived GBM cultures identifies candidate treatments for a subpopulation of GBM patients." Neuro-Oncology 21, Supplement_3 (August 2019): iii48—iii49. http://dx.doi.org/10.1093/neuonc/noz126.173.
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Abstract BACKGROUND The development of new therapeutic agents generally takes many years to translate to clinically-effective new treatments. Among the strategies to reduce this time frame, efforts are now being undertaken to investigate drug repurposing. With this approach, compounds available for a specific disease are evaluated for their therapeutic efficacy in other diseases. We have set up a patient-derived cell culture model to apply this strategy for glioblastoma (GBM). MATERIAL AND METHODS Fresh patient-derived tumour tissue was dissociated and cultured in serum-free medium supplemented with EGF and bFGF. MGMT status was determined by methylation-specific PCR.Drug screening was performed using the NIH anti-cancer collection containing 114 approved oncology drugs. Compounds include chemotherapeutic agents as well as small molecule targeted agents. Readout for drug effects is based on ATP-based viability assay. Using systems modelling approaches, integrated analysis of both mutational and expression data of each tumour is applied to identify key pathways involved in response to specific compounds. RESULTS Molecular analysis demonstrated that copy number variations are preserved under serum-free culture conditions and that the MGMT methylation status is retained in over 75% of cases. Screening of the NIH anti-cancer collection on 55 GBM cell cultures revealed high intertumoral variation in response to most drugs. This included subsets of GBM revealing exceptionally high sensitivity to specific agents at clinically-feasible concentrations. Further ranking of the compounds was made based on the therapeutic index (IC50 tumour versus normal human astrocytes) and predicted blood-brain-barrier crossing capability. Currently, integrated analysis of molecular profiles of the tumour in relation to the drug response data is ongoing with the aim of identifying response predictors to these clinically-approved anti-cancer agents. CONCLUSION Our patient-derived in vitro drug screening assay may offer a tool to identify available anti-cancer agents that are effective in a subpopulation of GBM patients and that may be implemented in future stratified clinical trials for this patient group.
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Potez, Marine, Jongmyung Kim, Chunhua She, Neelkamal Chaudhary, and James Liu. "STEM-02. IN VIVO PHAGE DISPLAY IDENTIFIES PEPTIDE TARGETING N-CADHERIN ON GLIOMA STEM CELLS." Neuro-Oncology 22, Supplement_2 (November 2020): ii196. http://dx.doi.org/10.1093/neuonc/noaa215.819.
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Abstract Glioblastoma (GBM) is the most aggressive primary brain tumor with high mortality rates and resistance to conventional therapy. Glioma stem cells (GSCs) comprise a sub-population of glioma tumor cells with the ability of self-renewal and tumor recapitulation, and may be responsible for GBM’s treatment resistant properties. Identification of surface receptors that are novel and specific to GSCs may be the key to the development of effective therapeutic strategies. We have selected a GSC specific targeting peptide isolated through in vitro and in vivo phage display biopanning. This screening technique allowed us to determine a peptide (GBM-IC2) which binds specifically to GSCs in vitro, and to GBM tissue in vivo. Although this screening process allows for isolation of cell specific targeting peptides, it does so without identification of the cellular binding partner. Given the specificity of the peptide, identification of the cellular receptor may allow for discovery of novel markers to identify GSCs. To identify the peptide binding partner of GBM-IC2, the biotinylated peptide was incubated with GSC protein lysate. The peptide, along with its binding partner, was isolated using streptavidin agarose resin. The binding partner protein was then identified using mass spectroscopy. This revealed N-cadherin (CDH2) as a potential binding partner for the GBM-IC2 peptide. GBM-IC2 demonstrated specificity for targeting CDH2 compared to control peptide using ELISA. Lentiviral induced overexpression of CDH2 in HEK293 cells allowed for GBM-IC2 peptide binding. Competition assay was performed by applying anti-CDH2 antibody to GBM-IC2 peptide and GSCs in culture. Application of anti-CDH2 antibody decreased peptide binding to GSCs, confirming CDH2 as the binding partner for GBM-IC2. These results demonstrate that cell specific targeting peptides isolated through phage display may lead to the isolation of novel cell specific proteins through immunoprecipitation isolation and mass spectroscopy analysis.
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Kwon, Youngihn, Juyeon Lee, Joo Hee Park, Yoo Mee Kim, Se Hwa Kim, Young Jun Won, and Hyung-Yong Kim. "Osteoporosis Pre-Screening Using Ensemble Machine Learning in Postmenopausal Korean Women." Healthcare 10, no. 6 (June 14, 2022): 1107. http://dx.doi.org/10.3390/healthcare10061107.
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As osteoporosis is a degenerative disease related to postmenopausal aging, early diagnosis is vital. This study used data from the Korea National Health and Nutrition Examination Surveys to predict a patient’s risk of osteoporosis using machine learning algorithms. Data from 1431 postmenopausal women aged 40–69 years were used, including 20 features affecting osteoporosis, chosen by feature importance and recursive feature elimination. Random Forest (RF), AdaBoost, and Gradient Boosting (GBM) machine learning algorithms were each used to train three models: A, checkup features; B, survey features; and C, both checkup and survey features, respectively. Of the three models, Model C generated the best outcomes with an accuracy of 0.832 for RF, 0.849 for AdaBoost, and 0.829 for GBM. Its area under the receiver operating characteristic curve (AUROC) was 0.919 for RF, 0.921 for AdaBoost, and 0.908 for GBM. By utilizing multiple feature selection methods, the ensemble models of this study achieved excellent results with an AUROC score of 0.921 with AdaBoost, which is 0.1–0.2 higher than those of the best performing models from recent studies. Our model can be further improved as a practical medical tool for the early diagnosis of osteoporosis after menopause.
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Weitzman, Jonathan B. "Barcode screening." Genome Biology 2 (2001): spotlight—20011112–01. http://dx.doi.org/10.1186/gb-spotlight-20011112-01.
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Nahar, Limon Khatun, Kevin G. Murphy, and Sue Paterson. "Misuse and Mortality Related to Gabapentin and Pregabalin are Being Under-Estimated: A Two-Year Post-Mortem Population Study." Journal of Analytical Toxicology 43, no. 7 (May 7, 2019): 564–70. http://dx.doi.org/10.1093/jat/bkz036.
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Abstract Due to the rise in their misuse and associated mortality, the UK government is reclassifying gabapentin (GBP) and pregabalin (PGL) to Class C controlled drugs from April 2019. However, it is impossible to gauge the extent of their use with current post-mortem toxicological screening, where GBP and PGL are only screened for if they are mentioned in the case documents. This study determines the prevalence of GBP and PGL, the potential extent of their under-reporting and poly-drug use in a post-mortem population. Between 1 January 2016 and 31 December 2017, 3,750 deceased from Coroners’ cases in London and South East England underwent a routine drugs screen and a specific screen for GBP and PGL. The prevalence of both drugs was determined in the cohort and the subcategories of heroin users and non-heroin-users. The prevalence of both drugs was compared to tramadol (Class C drug). Case documents were reviewed to investigate the under-reporting of GBP and PGL and poly-drug use. Of 3,750 samples analyzed, 118 (3.1%) were positive for GBP, 229 (6.1%) for PGL and 120 (3.2%) were positive for tramadol. If routine analysis without additional screening of GBP and PGL had been performed in this cohort, GBP would have been under-reported by 57.6% (P < 0.0001) and PGL by 53.7% (P < 0.0001) in deaths. The most common drug group observed with GBP and PGL was non-heroin-related opioids at 60.2% and 64.6%, respectively. In total 354 deceased (9.4%) were heroin users. GBP was positive in 23 (6.5%) of these cases and PGL was positive in 69 (19.5%). The prevalence of PGL in heroin users (19.5%) was 4.1 times greater than in non-heroin users (4.7%) (P < 0.0001). GBP and PGL are being significantly under reported in fatalities. Both drugs are extensively used with opioids. The prevalence of PGL in heroin users is highly significant.
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Alexander, Brian Michael, Lorenzo Trippa, Sarah C. Gaffey, Isabel Arrillaga, Eudocia Quant Lee, Shyam Kumar Tanguturi, Manmeet Singh Ahluwalia, et al. "Individualized screening trial of innovative glioblastoma therapy (INSIGhT)." Journal of Clinical Oncology 35, no. 15_suppl (May 20, 2017): TPS2079. http://dx.doi.org/10.1200/jco.2017.35.15_suppl.tps2079.
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TPS2079 Background: Patient with glioblastoma (GBM) with unmethylated MGMT promoters derive limited benefit from temozolomide (TMZ) and have dismal outcome. Prioritizing the numerous available therapies and biomarkers for late stage testing requires an efficient clinical testing platform. INSIGhT (NCT02977780) is a biomarker-based, Bayesian adaptively randomized, multi-arm phase II platform screening trial for patients with newly diagnosed GBM and unmethylated MGMT promoters. Methods: INSIGhT compares experimental arms to a common control of standard concurrent TMZ and radiation therapy (RT) followed by adjuvant TMZ. The primary endpoint is overall survival (OS). Patients with newly diagnosed, unmethylated GBM that are IDH R132H mutation negative, and with genomic data available or who consent to whole exome sequencing through the ALLELE companion study for biomarker grouping are eligible. Two experimental arms consist of concurrent RT/TMZ followed by adjuvant neratinib (EGFR, HER2, and HER4 inhibitor) or abemaciclib CDK 4/6 inhibitor), respectively, in place of TMZ. The other experimental arm is CC-115 (TORC1/2 and DNA PK inhibitor), which replaces TMZ in both the concurrent and adjuvant phases. Biomarker groups include: EGFR + patients with EGFR amplification/mutation; PI3K + patients with PIK3CA mutation/amplification, PIK3R1 mutation, AKT3amplification, PIK3C2B > 1 copy gain, or PTEN dual loss; CDK: + patients with wild-type RB1 and CDK4 amplification, CDK6 amplification, or CDKN2A > 1 copy loss. Given the lack of pretrial biomarker data and the anticipated overlap of the groups, randomization will initially be equal. As the trial progresses, randomization probabilities will be adapted based on the Bayesian estimation of the probability of treatment impact on progression-free survival (PFS). These randomization probabilities can vary among the biomarker groups so predictive biomarkers will be identified and utilized if present. Treatment arms may drop due to low probability of treatment impact on OS, and new arms may be added. Experimental arms are compared only with control and should be thought of as discrete experimental questions, with INSIGhT being open to new investigators with proposed therapeutic hypotheses. Clinical trial information: NCT02977780.
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Volmar, Marie, Bernhard Nagl, Alisha Haug, Sven Richter, Haithanm Alenezi, Christel Herold-Mende, Katrin Lamszus, et al. "DDIS-35. RelA-ACTIVITY IS ESSENTIAL FOR CANNABIDIOL-MEDIATED CYTOTOXICITY IN AN IDENTIFIED SUBSET OF GLIOBLASTOMA." Neuro-Oncology 21, Supplement_6 (November 2019): vi70—vi71. http://dx.doi.org/10.1093/neuonc/noz175.286.
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Abstract Glioblastoma (GBM) therapy could strongly profit from simplified procedures for personalized medicine. Cannabidiol (CBD) is explored for GBM-patients, but the mode of drug-action is largely unknown and stratification markers are missing. We investigated CBD-induced cytotoxicity in a panel of human primary GBM cells as well as transgenic mouse gliomas and in different orthotopic or transgenic in vivo models. We observed therapeutic efficiency of CBD in a subset of GBM, obtained genetic markers indicating CBD-sensitive GBM and found that the p53 status segregated cell-death modes. Genome wide loss of function screening, transcription factor binding studies and knockout-models indicated a central for role for NFkB (RelA) in CBD-initiated GBM-death. CBD mediated nuclear import of RelA lacking an essential post-translational modification and reduced RelA-activity. CBD altered redox levels specifically in drug-sensitive GBM and ROS-levels in unstimulated GBM predicted therapeutic response. Hence, quantifying ROS in GBM represents a simple bioassay to identify individuals potentially profiting from CBD-application in neurooncology.
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Dinevska, Marija, Natalia Gazibegovic, Andrew P. Morokoff, Andrew H. Kaye, Katharine J. Drummond, Theo Mantamadiotis, and Stanley S. Stylli. "Inhibition of Radiation and Temozolomide-Induced Glioblastoma Invadopodia Activity Using Ion Channel Drugs." Cancers 12, no. 10 (October 8, 2020): 2888. http://dx.doi.org/10.3390/cancers12102888.
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Glioblastoma (GBM) is the most prevalent and malignant type of primary brain cancer. The rapid invasion and dissemination of tumor cells into the surrounding normal brain is a major driver of tumor recurrence, and long-term survival of GBM patients is extremely rare. Actin-rich cell membrane protrusions known as invadopodia can facilitate the highly invasive properties of GBM cells. Ion channels have been proposed to contribute to a pro-invasive phenotype in cancer cells and may also be involved in the invadopodia activity of GBM cells. GBM cell cytotoxicity screening of several ion channel drugs identified three drugs with potent cell killing efficacy: flunarizine dihydrochloride, econazole nitrate, and quinine hydrochloride dihydrate. These drugs demonstrated a reduction in GBM cell invadopodia activity and matrix metalloproteinase-2 (MMP-2) secretion. Importantly, the treatment of GBM cells with these drugs led to a significant reduction in radiation/temozolomide-induced invadopodia activity. The dual cytotoxic and anti-invasive efficacy of these agents merits further research into targeting ion channels to reduce GBM malignancy, with a potential for future clinical translation in combination with the standard therapy.
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Milanowski, Lukasz M., Olajumoke Oshinaike, Ronald L. Walton, Alexandra I. Soto‐Beasley, Rana Hanna Al‐Shaikh, Audrey J. Strongosky, Owen A. Ross, Zbigniew K. Wszolek, and Shamsideen Abayomi Ogun. "Screening of GBA Mutations in Nigerian Patients with Parkinson's Disease." Movement Disorders 36, no. 12 (September 29, 2021): 2971–73. http://dx.doi.org/10.1002/mds.28803.
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abduhameed, Wasanadnan. "IMPROVING RATE OF GBS SCREENING IN ANTENATAL PATIENT TO IMPROVE NEONATAL OUTCOME." International Journal of Advanced Research 5, no. 12 (December 31, 2017): 1163–70. http://dx.doi.org/10.21474/ijar01/6070.
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