bluuebunny/crossref_metadata_2025 huggingface dataset:
Factors influencing women’s sex work in a Lebanese sample: results of a case-control study
Authors: Slim Maria , Haddad Chadia , Sfeir Elsa , Rahme Clara , Hallit Souheil , Obeid Sahar
Published: September 2020

Background

Many constituents contribute to the rise of sex work in Lebanon such as the socio-economic situation in the country (poverty, increased unemployment rates, and religious divisions), as well as the political and social instability. Several emotional and psychological factors such as depression, stress, anxiety, low self-esteem, emotional abuse, may force some people to rely on trading sex as a coping strategy for persevering. Therefore, it was deemed interesting to explore and understand factors that are correlated with sex work in Lebanon where no study, to our knowledge, has been written on this critical point. The objective of the study was to assess factors (such as trauma, child abuse, partner abuse, depression, anxiety, and stress) associated with women joining sex work among a sample of the Lebanese population.

Methods

A case-control study was conducted on a group of women (60 sex workers recruited from a prison for women) involved in sex work matched for age and sex with a control group (60 non-sex workers). Controls were chosen from the same prison population as the sex workers.

Results

A logistic regression was conducted, taking being a sex worker vs not as the dependent variable; independent factors were sociodemographic characteristics, child (psychological, neglect, physical and verbal) and inter partner violence (physical and non-physical), depression, anxiety and stress. Higher anxiety (aOR = 1.08) and higher inter partner physical violence (aOR = 1.02) were altogether related with higher chances of being a sex worker.

Conclusion

This study proposes an association between child abuse, inter partner violence, alcohol consumption, anxiety, and sex work. Future research may also need to contemplate other factors not examined here, including parental substance use, personality traits, and many others.
UKCAT and medical student selection in the UK – what has changed since 2006?
Authors: Greatrix Rachel , Dowell Jonathan
Published: September 2020

Background

The United Kingdom Clinical Aptitude Test (UKCAT) is an aptitude test used since 2006 within selection processes of a consortium of UK medical and dental schools.

Since 2006, student numbers have increased in medical training and schools now have an increased focus on widening access. A growing evidence base has emerged around medical student selection (Patterson et al., Med Educ 50:36–60, 2016) leading to changes in practice. However, whilst some papers describe local selection processes, there has been no overview of trends in selection processes over time across Universities.

This study reports on how the use of the UKCAT in medical student selection has changed and comments on other changes in selection processes.

Methods

Telephone interviews were conducted annually with UKCAT Consortium medical schools. Use of the UKCAT was categorised and data analysed to identify trends over time.

Results

The number of schools using the UKCAT to select applicants for interview has risen, with cognitive test results contributing significantly to outcomes at this stage at many universities. Where schools use different weighted criteria (Factor Method), the UKCAT has largely replaced the use of personal statements. Use of the test at offer stage has also increased; the most significant use being to discriminate between applicants at a decision borderline. A growing number of schools are using the UKCAT Situational Judgement Test (SJT) in selection.

In 2018, all but seven (out of 26) schools made some adjustment to selection processes for widening access applicants. Multiple Mini Interviews (MMIs) are now used by the majority of schools.

Whilst medical student numbers have increased over this time, the ratio of applicants to places has fallen. The probability of applicants being invited to interview or receiving an offer has increased.

Conclusions

More medical schools are using the UKCAT in undergraduate selection processes in an increasing number of ways and with increasing weight compared with 2007. It has replaced the use of personal statements in all but a few Consortium medical schools.

An increased focus on academic attainment and the UKCAT across medical schools may be leading to the need for schools to interview and make offers to more applicants.
Barriers and facilitators for transitioning of young people from adolescent clinics to adult ART clinics in Uganda: unintended consequences of successful adolescent ART clinics
Authors: Mbalinda Scovia Nalugo , Bakeera-Kitaka Sabrina , Lusota Derrick Amooti , Magongo Eleanor Namusoke , Musoke Philippa , Kaye Dan Kabonge
Published: September 2020

Background

There is a growing number of adolescents and young adults living with HIV (YPLHIV) who require the transfer of care from pediatric/ adolescent clinics to adult Antiretroviral therapy (ART) clinics. A successful transition is critical for optimum health outcomes, yet facilities may lack infrastructure, human resources (with appropriate knowledge and skills), and a supportive environment, as only 3% of clinics in Uganda caring for YPLHIV have a process for supporting this critical transition from pediatric to adult care, and, facilitators and barriers of a successful transition are not well documented. The purpose of this study was to explore the facilitators and barriers of transitioning among adolescents from adolescent clinics to adult ART clinics.

Method

Eighteen focus group discussions were held in nine health facilities with 174 adolescents and YPLHIV to assess barriers and facilitators regarding transitioning to adult clinics. The focus group discussions were audio-recorded and transcribed. The Silences Framework using a thematic approach guided the analysis.

Results

The key emerging issues were: Unfriendly adults in adult clinics, Care provided in the adolescent clinics, fear of stigma from health care providers, Congestion and long waiting time, fear to lose friends were barriers to transitioning. Transitioning preparation is key to a successful transition, moving as a cohort facilitates transition, and care in adult clinics offers new opportunities, could facilitate readiness and transition.

Conclusion

YPLHIV expressed fear to transition to adult clinics mainly because of the perceived better care provided in the adolescent clinic, thus constituting a barrier to smooth transition A range of individual, social and health system and services-related factors hindered transitioning. The expectation of transitioning as a group, assurance of similar care as in the adolescent clinic, and guarantees of confidentiality, privacy, and autonomy in decision-making for care was perceived as facilitators. Understanding barriers and facilitators can enable the Ministry of Health to improve the quality of life of YPLHIV through linkage to care, adherence, retention, and viral suppression. There is a need to better planning and preparation for clinical providers and YPLHIV with a focus on age-appropriate and individualized case management transition as well as focus on improving both clinical and psychosocial support throughout the process.
Type 2 diabetes and reduced exercise tolerance: a review of the literature through an integrated physiology approach
Authors: Nesti Lorenzo , Pugliese Nicola Riccardo , Sciuto Paolo , Natali Andrea
Published: September 2020

The association between type 2 diabetes mellitus (T2DM) and heart failure (HF) is well established. Early in the course of the diabetic disease, some degree of impaired exercise capacity (a powerful marker of health status with prognostic value) can be frequently highlighted in otherwise asymptomatic T2DM subjects. However, the literature is quite heterogeneous, and the underlying pathophysiologic mechanisms are far from clear. Imaging-cardiopulmonary exercise testing (CPET) is a non-invasive, provocative test providing a multi-variable assessment of pulmonary, cardiovascular, muscular, and cellular oxidative systems during exercise, capable of offering unique integrated pathophysiological information. With this review we aimed at defying the cardiorespiratory alterations revealed through imaging-CPET that appear specific of T2DM subjects without overt cardiovascular or pulmonary disease. In synthesis, there is compelling evidence indicating a reduction of peak workload, peak oxygen assumption, oxygen pulse, as well as ventilatory efficiency. On the contrary, evidence remains inconclusive about reduced peripheral oxygen extraction, impaired heart rate adjustment, and lower anaerobic threshold, compared to non-diabetic subjects. Based on the multiparametric evaluation provided by imaging-CPET, a dissection and a hierarchy of the underlying mechanisms can be obtained. Here we propose four possible integrated pathophysiological mechanisms, namely myocardiogenic, myogenic, vasculogenic and neurogenic. While each hypothesis alone can potentially explain the majority of the CPET alterations observed, seemingly different combinations exist in any given subject. Finally, a discussion on the effects -and on the physiological mechanisms-of physical activity and exercise training on oxygen uptake in T2DM subjects is also offered. The understanding of the early alterations in the cardiopulmonary response that are specific of T2DM would allow the early identification of those at a higher risk of developing HF and possibly help to understand the pathophysiological link between T2DM and HF.
The SNPs rs429358 and rs7412 of APOE gene are association with cerebral infarction but not SNPs rs2306283 and rs4149056 of SLCO1B1 gene in southern Chinese Hakka population
Authors: Wu Heming , Huang Qingyan , Yu Zhikang , Wu Hailing , Zhong Zhixiong
Published: September 2020

Background

Apolipoprotein E (ApoE) and solute carrier organic anion transporter family member 1B1 (SLCO1B1) regulate lipid metabolism. However, the relationship between genetic polymorphisms of APOE and SLCO1B1 and cerebral infarction (CI) remains unclear.

Methods

A total of 938 CI patients and 1028 control participants were included in the study. The rs429358 and rs7412 single nucleotide polymorphisms (SNPs) in the APOE gene and rs2306283 and rs4149056 SNPs in the SLCO1B1 gene were analyzed by fluorescence polymerase chain reaction (PCR).

Results

The genotype ɛ3/ɛ3 was the most common APOE genotype, with ɛ3 being the allele with the highest frequency, followed by ɛ4 and ɛ2. Statistically significant differences of genotype ɛ2/ɛ2 (χ2 = 3.866, P = 0.049), ɛ2/ɛ3 (χ2 = 20.030, P < 0.001), ɛ3/ɛ4 (χ2 = 16.960, P < 0.001), and ɛ4/ɛ4 (χ2 = 4.786, P = 0.029) between CI patients and controls were detected. The SLCO1B1 genotype *1b/*1b and haplotype *1b showed the highest frequency in the study sample. There was no statistically significant difference in the frequencies of SLCO1B1 genotypes and haplotypes among CI patients comparing with controls. Moreover, ε4 carriers had significantly higher low-density lipoprotein-cholesterol (LDL-C) and apolipoprotein B (Apo-B) and lower apolipoprotein A1 (Apo-A1)/Apo-B levels than ε2 and ε3 carriers, but ε2 carriers showed lower LDL-C and Apo-B and higher Apo-A1/Apo-B than ε3 and ε4 carriers. Further, logistic regression analysis revealed that high LDL-C, high ApoB, smoking, hypertension and the ε4 allele were risks for the presence of CI.

Conclusions

This study indicated that the APOE SNPs rs429358 and rs7412 may be associated with susceptibility to cerebral infarction in southern Chinese Hakka population.
How can nanotechnology help to combat COVID-19? Opportunities and urgent need
Authors: Campos Estefânia V. R. , Pereira Anderson E. S. , de Oliveira Jhones Luiz , Carvalho Lucas Bragança , Guilger-Casagrande Mariana , de Lima Renata , Fraceto Leonardo Fernandes
Published: September 2020

Incidents of viral outbreaks have increased at an alarming rate over the past decades. The most recent human coronavirus known as COVID-19 (SARS-CoV-2) has already spread around the world and shown R0values from 2.2 to 2.68. However, the ratio between mortality and number of infections seems to be lower in this case in comparison to other human coronaviruses (such as severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV)). These outbreaks have tested the limits of healthcare systems and have posed serious questions about management using conventional therapies and diagnostic tools. In this regard, the use of nanotechnology offers new opportunities for the development of novel strategies in terms of prevention, diagnosis and treatment of COVID-19 and other viral infections. In this review, we discuss the use of nanotechnology for COVID-19 virus management by the development of nano-based materials, such as disinfectants, personal protective equipment, diagnostic systems and nanocarrier systems, for treatments and vaccine development, as well as the challenges and drawbacks that need addressing.
Topically applicated curcumin/gelatin-blended nanofibrous mat inhibits pancreatic adenocarcinoma by increasing ROS production and endoplasmic reticulum stress mediated apoptosis
Authors: Cheng Tao , Zhang Zhiheng , Shen Hua , Jian Ziying , Li Junsheng , Chen Yujun , Shen Yi , Dai Xinyi
Published: September 2020

Background

Pancreatic adenocarcinoma (PDAC) is one of the most fatal malignancies. Surgical resection supplemented by chemotherapy remains the major therapeutic regimen, but with unavoidable resistance and systemic toxic reaction. Curcumin is a known safe natural compound that can effectively eliminate pancreatic adenocarcinoma cells in vitro, making it a promising candidate for substitution in subsequent chemotherapy. However, due to its extremely low bioavailability caused by its insolubility and circular elimination, curcumin had an unexpectedly modest therapeutic effect in clinical trials.

Results

Here, we electrospun curcumin/gelatin-blended nanofibrous mat to largely improve curcumin’s bioavailability by local controlled-release. With characterization by scanning electron microscopy, fluorescence microscopy, Fourier transform infrared spectroscopy, X-ray diffraction and high-performance liquid chromatography, it was revealed that curcumin was uniformly dispersed in the fiber of the mats with nanoscopic dimensions and could be continuously released into the surrounding medium for days. The cancer inhibitory effects of nano-curcumin and underlying mechanisms were further explored by assays using pancreatic adenocarcinoma cell and experiments using xenograft model. The results showed the released nano-curcumin could effectively inhibit pancreatic adenocarcinoma cell proliferation not only in vitro, but more importantly in vivo. This cytotoxic effect of nano-curcumin against pancreatic adenocarcinoma was achieved through provoking the production of intracellular reactive oxygen species and activating endoplasmic reticulum stress, which leads to enhanced cell apoptosis via decreased phosphorylation of signal transducer and activator of transcription 3.

Conclusions

Clinically, curcumin/gelatin-blended nanofibrous mat could be a promising, secure, efficient and affordable substitutional agent for the elimination of residual cancer cells after tumor resection. Moreover, our strategy to obtain curcumin released from nanofibrous mat may provide a universally applicable approach for the study of the therapeutic effects and molecular mechanisms of other potential medicines with low bioavailability.
Excessive daytime sleepiness and its predictors among medical and health science students of University of Gondar, Northwest Ethiopia: institution-based cross-sectional study
Authors: Dagnew Baye , Andualem Zewudu , Dagne Henok
Published: September 2020

Background

Excessive daytime sleepiness (EDS) is a condition of sleepiness when a person would not be expected to sleep. University students are prone to EDS due to the competitive learning environment and fragmented night sleep. No study was conducted in Ethiopia on EDS. Therefore, this study aimed to determine EDS and its predictors among University of Gondar (UoG) Medical and Health Science students.

Methods

Institution-based cross-sectional study was carried out on 383 Medical and Health Science students of UoG who were recruited using a computer-generated simple random sampling technique. We used a validated Epworth daytime sleepiness tool to collect data. Epi-Info™ 7 and Stata 14 were used for data entry and analysis, respectively. Bivariable and multivariable binary logistic regression analyses were performed to find out predictors. Odds ratio with 95% uncertainty interval were computed. In the final model, a variable with a p < 0.05 was declared as a predictor of EDS.

Results

Three hundred and eighty-three students completed the questionnaire. Males were 69.97% and the mean age of participants was 20.79 (±1.83) years. In the current study, the prevalence of EDS was 31.07% (95% UI: 26.62–35.91). The odds of getting EDS was 1.83 (AOR = 1.83, 95% UI: 1.14–2.96) and 1.84 (AOR = 1.84, 95% UI: 1.13–3.00) higher among students who reported night sleep behaviour disorders and depression, respectively.

Conclusion

This study revealed that EDS is high and predicted by depression and night sleep behaviour disorders. These findings suggest the need to set preventive strategies such as counselling of students to reduce depression and night sleep behaviour disorders. Further studies particularly qualitative studies are required to find out more factors affecting EDS.
Pancreatic acinar cell carcinoma with a ductal adenocarcinoma component: a case report and analysis of the histogenesis of the tumor
Authors: Kimura Toshihisa , Tabata Shinsuke , Togawa Tamotsu , Onchi Hidetoshi , Iida Atsushi , Sato Yasunori , Goi Takanori
Published: September 2020

Background

Pancreatic cancer composed of acinar cell carcinoma (ACC) and ductal adenocarcinoma (DAC) is rare, and the clinicopathological characteristics of ACC with DAC have yet to be elucidated. Herein, we report a case of ACC with a DAC component of the pancreas and examined the histogenesis of this tumor.

Case presentation

A 69-year-old man was admitted to our hospital complaining of appetite loss, constipation, epigastric dull pain, and jaundice. Abdominal computed tomography and magnetic resonance cholangiopancreatography revealed a pancreatic head tumor with dilatation of the bile duct and the distal main pancreatic duct. Under the diagnosis of pancreatic head cancer, a pancreatoduodenectomy was performed. The histology of the resected tumor consisted of mainly ACC with a focus of DAC, which was confirmed by mucin staining and immunohistochemistry for antigens such as BCL10, trypsin, Smad4, p16, p53, and MUC1. There was histological transition between the components of ACC and DAC, and immunostaining of the transitional zone showed equivocal results for the antigens. KRAS was wild-type in both ACC and DAC. The patient was treated with adjuvant chemotherapy with S-1 for 1 year. No evidence of recurrence or metastasis was observed after 9 years of follow-up.

Conclusions

A rare case of pancreatic ACC with a DAC component in a patient with long-term survival after surgery was reported. Immunohistochemical and molecular analysis indicated that DAC might have arisen from ACC through transdifferentiation in this case.
Growth hormone alleviates oxidative stress and improves the IVF outcomes of poor ovarian responders: a randomized controlled trial
Authors: Gong Yan , Zhang Kun , Xiong Dongsheng , Wei Jiajing , Tan Hao , Qin Shengfang
Published: September 2020

Background

Oxidative stress (OS), defined as an imbalance between excessive reactive oxygen species (ROS) and/or reactive nitrogen species (RNS) production and antioxidant insufficiency, has been suggested to be involved in the pathogenesis of poor ovarian response (POR). Growth hormone (GH) can reduce OS in some cell types. This study investigated whether GH can improve OS and the in vitro fertilization and embryo transfer (IVF-ET) outcomes of poor ovarian responders.

Methods

This study enrolled 105 patients with POR and 58 patients without POR (controls) who were diagnosed according to the Bologna criteria and underwent conventional IVF-ET. Poor ovarian responders were randomly assigned to two groups: the POR-GH group, which received pretreatment with GH 4 IU/d on day 2 of the previous menstrual cycle before IVF until the trigger day, and the POR-C group, which received no pretreatment. OS markers in follicular fluid (FF), ROS levels in granulosa cells (GCs), and the IVF outcomes of the groups were compared.

Results

Endometrial thickness on trigger day, the number of cleaved embryos, the number of higher-quality embryos, and the rates of embryo formation, higher-quality embryo formation, implantation and clinical pregnancy were significantly increased in the POR-GH group compared with the POR-C group (P < 0.05). Moreover, compared to those in the non-POR group, FF malondialdehyde (MDA), total oxidant status (TOS), oxidative stress index (OSI) and ROS levels in GCs were significantly higher, whereas superoxide dismutase (SOD) and the total antioxidant capacity (TAC) were significantly lower in the POR-C group (P < 0.05). Furthermore, compared with those in the POR-C group, the FF TAC was significantly increased in the POR-GH group, and TOS, OSI and intracellular ROS levels were significantly reduced (P < 0.05).

Conclusions

Pretreatment with GH alleviates OS and improves oocyte quality and IVF outcomes of poor ovarian responders.

Trial registration

Chinese Clinical Trial Registry. ChiCTR1900021269. Registered 8 February 2019, http://www.chictr.org.cn/edit.aspx?pid=35837&htm=4.
Sugar-sweetened beverages increases the risk of hypertension among children and adolescence: a systematic review and dose–response meta-analysis
Authors: Farhangi Mahdieh Abbasalizad , Nikniaz Leila , Khodarahmi Mahdieh
Published: September 2020

Background

In the current systematic review and meta-analysis, we summarized the studies that evaluated the effects of sugar-sweetened beverages (SSBs) intake on blood pressure among children and adolescents.

Methods

In a systematic search from PubMed, Scopus, Embase and Cochrane electronic databases up to 20 April 2020, the observational studies that evaluated the association between sugar-sweetened beverages intake and hypertension, systolic or diastolic blood pressure (SBP, DBP) were retrieved.

Results

A total of 14 studies with 93873 participants were included in the current meta-analysis. High SSB consumption was associated with 1.67 mmHg increase in SBP in children and adolescents (WMD: 1.67; CI 1.021–2.321; P < 0.001). The difference in DBP was not significant (WMD: 0.313; CI −0.131– 0.757; P = 0.108). High SSB consumers were 1.36 times more likely to develop hypertension compared with low SSB consumers (OR: 1.365; CI 1.145–1.626; P = 0.001). In dose–response meta-analysis, no departure from linearity was observed between SSB intake and change in SBP (P-nonlinearity = 0.707) or DBP (P-nonlinearity = 0.180).

Conclusions

According to our finding, high SSB consumption increases SBP and hypertension in children and adolescents.
Mathematical models for devising the optimal SARS-CoV-2 strategy for eradication in China, South Korea, and Italy
Authors: Jiang Shuo , Li Qiuyue , Li Chaoqun , Liu Shanshan , He Xiaomeng , Wang Tao , Li Hua , Corpe Christopher , Zhang Xiaoyan , Xu Jianqing , Wang Jin
Published: September 2020

Background

Coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), spreads rapidly and has attracted worldwide attention.

Methods

To improve the forecast accuracy and investigate the spread of SARS-CoV-2, we constructed four mathematical models to numerically estimate the spread of SARS-CoV-2 and the efficacy of eradication strategies.

Results

Using the Susceptible-Exposed-Infected-Removed (SEIR) model, and including measures such as city closures and extended leave policies implemented by the Chinese government that effectively reduced the β value, we estimated that the β value and basic transmission number, R0, of SARS-CoV-2 was 0.476/6.66 in Wuhan, 0.359/5.03 in Korea, and 0.400/5.60 in Italy. Considering medicine and vaccines, an advanced model demonstrated that the emergence of vaccines would greatly slow the spread of the virus. Our model predicted that 100,000 people would become infected assuming that the isolation rate α in Wuhan was 0.30. If quarantine measures were taken from March 10, 2020, and the quarantine rate of α was also 0.3, then the final number of infected people was predicted to be 11,426 in South Korea and 147,142 in Italy.

Conclusions

Our mathematical models indicate that SARS-CoV-2 eradication depends on systematic planning, effective hospital isolation, and SARS-CoV-2 vaccination, and some measures including city closures and leave policies should be implemented to ensure SARS-CoV-2 eradication.
Deficiency of the microglial Hv1 proton channel attenuates neuronal pyroptosis and inhibits inflammatory reaction after spinal cord injury
Authors: Li Xuefei , Yu Zhiyuan , Zong Weifeng , Chen Peng , Li Jia , Wang Minghuan , Ding Fengfei , Xie Minjie , Wang Wei , Luo Xiang
Published: September 2020

Background

Spinal cord injury (SCI) causes neurological dysfunction with devastating consequences. SCI pathogenesis is accompanied by inflammasome activation and neuronal damage. But the spatial pattern and the time course of neuronal pyroptosis and apoptosis after SCI should be further elucidated. The microglial voltage-gated proton channel (Hv1) is implicated in reactive oxygen species (ROS)-induced neuronal damage following ischemic stroke. However, there is a lack of quantification on the neuronal pyroptosis and apoptosis associated with microglial Hv1 after SCI.

Methods

We analyzed spatial and temporal characteristics of neuronal pyroptosis and apoptosis following SCI and investigated the effects of Hv1 deficiency on neuronal pyroptosis and the nod-like receptor 3 (NLRP3) inflammasome pathway by using a mouse model of SCI. We tested the effects of Hv1-deficient microglia on ROS production in vivo and examined the relationship between ROS and neuronal pyroptosis in vitro.

Results

We observed that apoptosis was detected closer to the injury core than pyroptosis. The incidence of neuronal apoptosis peaked on day 1 after SCI and occurred before pyroptosis. Hv1 deficiency reduced neuronal apoptosis and NLRP3-inflammasome-mediated pyroptosis, improved axonal regeneration, and reduced motor deficits. SCI led to elevated ROS levels, whereas Hv1 deficiency downregulated microglial ROS generation. In vitro, ROS upregulated neuronal pyroptosis and activated the NLRP3 inflammasome pathway, both of which were reversed by addition of a ROS scavenger. Our results suggested that microglial Hv1 regulated neuronal apoptosis and NLRP3-induced neuronal pyroptosis after SCI by mediating ROS production.

Conclusion

Following SCI, neuronal pyroptosis lasted longer and occurred farther away from the injury core compared with that of neuronal apoptosis. Microglial Hv1 deficiency downregulated microglial ROS generation and reduced apoptosis and NLRP3-induced neuronal pyroptosis. Our findings may provide novel insights into Hv1-associated mechanisms underlying neuronal damage after SCI.
Programmed death-1 expression and regulatory T cells increase in the Intestinal mucosa of cytomegalovirus colitis in patients with HIV/AIDS
Authors: Sun Lei , Yang Kun , Zhang Liang , Qi Li-ming , Chen Jia-min , Li Ping , Xiao Jiang , Zhao Hong-xin , Wang Peng
Published: September 2020

Background

Cytomegalovirus (CMV) is among the most common opportunistic infections identified in patients with HIV/AIDS. CMV often targets the colon in such patients. However, the role of regulatory T cells (Tregs) and Programmed death-1 (PD-1) in intestinal CMV infection is unclear. In this study, we evaluate the expression of programmed death -1 (PD-1) and its association with regulatory T cells (Tregs) in patients with HIV/AIDS having CMV colitis.

Methods

CMV was detected in the intestinal mucosal biopsy samples via nucleic acid in situ hybridization. PD-1, CD4, CD8, and Treg-specific marker as well as the winged-helix transcription factor and forkhead box P3 (FoxP3) were detected by immunohistochemical methods.

Results

Intestinal CMV diease was identified in 20 out of 195 patients with HIV/AIDS enrolled in our study. CMV was diagnosed microscopically by the presence of giant cell inclusion bodies in epithelial cells, histiocytes, and fibroblasts. Levels of immunoreactive PD-1 detected in mucosal biopsies from patients with HIV/AIDS having CMV colitis were significantly higher than CMV-negative control group (p = 0.023). FoxP3+ cells were detected in the CMV colitis group slight more than that in the control group. CD4+ T lymphocyte counts in the peripheral blood and intestinal mucosal biopsies from CMV colitis group were all notably decreased compared with those with control group (p < 0.001 for both). PD-1 had a significant negative correlation with CD4 counts in intestinal mucosa (p = 0.016). CD8+T lymphocyte counts in peripheral blood and intestinal mucosa were slightly lower than those in the control group, although the differences were not statistically significant.

Conclusions

CMV colitis with HIV/AIDS is associated with significant changes in T lymphocyte populations. These findings may have important implications for disease pathogenesis and progression.
S-Adenosylmethionine (SAMe) in major depressive disorder (MDD): a clinician-oriented systematic review
Authors: Cuomo Alessandro , Beccarini Crescenzi Bruno , Bolognesi Simone , Goracci Arianna , Koukouna Despoina , Rossi Rodolfo , Fagiolini Andrea
Published: September 2020

Background

Major depressive disorder (MDD) is a recurrent illness with high rates of chronicity, treatment-resistance, and significant economic impact. S-Adenosylmethionine (SAMe), a molecule that is formed naturally in the human body, has shown antidepressant effects and may expand the available options for treating MDD. This systematic review examines the evidence concerning the efficacy of SAMe as monotherapy or in combination with antidepressants.

Methods

A systematic search in Medline, Psychinfo, AMED, and Cochrane Controlled Trials Register was conducted for any reference recorded up to March 2020. Double-blind, randomised controlled trials, comparing the antidepressant efficacy of SAMe to placebo or/and to other antidepressants, were selected. Two authors evaluated each study independently and then, reconciled findings.

Results

Eight trials, with a total of 11 arms and 1011 subjects, evaluating the efficacy of SAMe used as monotherapy or as adjunctive therapy (512 individuals), were included in this review. The study duration ranged between 2 and 12 weeks and the daily dose of SAMe varied from 200 to 3200 mg. Five comparisons evaluated the differences between SAMe and placebo and SAMe resulted significantly better than placebo in three of these studies. Four comparisons evaluated the differences between SAMe and other antidepressants (imipramine or escitalopram) and showed no significant difference. One study showed that SAMe was significantly better than placebo in accelerating the response to imipramine from day 4 to day 12, but the mean scores were not statistically different at the day 14 endpoint. One study showed that SAMe combined with serotonin reuptake inhibitors (SSRI) was better than PBO combined with SSRI. The studies reported only mild, transient or non-clinically relevant side effects.

Conclusions

The existing trials of SAMe, used as monotherapy or add on to another antidepressants, have shown encouraging and generally positive results. However, more evidence is necessary before definitive conclusions can be drawn. Larger, double-blind randomised controlled studies are warranted to confirm the antidepressant effectiveness of SAMe.
Severe fatigue due to valproate-induced hypothyroidism in a case of bipolar disorder
Authors: Kanamori Tadashi , Suzuki Masahiro , Kaneko Yoshiyuki , Yamada Kouju , Kubo Hideyuki , Uchiyama Makoto
Published: September 2020

Background

Valproate-induced hypothyroidism is a rare condition and has been considered asymptomatic. Here, we report a case of bipolar I disorder who developed symptomatic valproate-induced hypothyroidism.

Case presentation

A 44-year-old woman with bipolar I disorder complained of severe fatigue after starting valproate. She showed a hormonal pattern of central hypothyroidism. Thyroid autoantibodies were negative, and no pituitary abnormality was seen on magnetic resonance imaging. After stopping valproate, her severe fatigue rapidly improved with normalizing thyroid function.

Conclusions

Our case suggests that valproate-induced hypothyroidism should be considered when patients complain of excessive fatigue under treatment with valproate.
Ramifications of untreated hypothyroidism: case report of cognitive impairment and acute psychosis in an elderly female
Authors: Leal Janette C. , Beito Allison H.
Published: September 2020

Hypothyroidism is a common condition in the general population. While myxedema is a known complication, we present a case highlighting a late-onset presentation of psychosis with confounding cognitive impairment in a patient who believed she no longer needed thyroid replacement medication because of her advanced age.
Analysing the potential of hydrophilic adhesive systems to optimise orthodontic bracket rebonding
Authors: Knaup Isabel , Böddeker Antonia , Tempel Katrin , Weber Eva , Bartz Jenny Rosa , Rückbeil Marcia Viviane , Craveiro Rogério Bastos , Wagner Yvonne , Wolf Michael
Published: September 2020

Introduction

Bond failure during fixed orthodontic treatment is a frequently occurring problem. As bracket rebonding is associated with reduced shear bond strength, the aim of the present investigation is to analyse the effect of different innovative rebonding systems to identify optimised rebonding protocols for orthodontic patient care.

Methods

Metallic brackets were bonded to the frontal enamel surfaces of 240 bovine lower incisors embedded in resin bases. Teeth were randomly divided into two major experimental groups: in group 1 a hydrophilic primer (Assure™ PLUS) was compared to commonly used orthodontic adhesives (Transbond XT™, BrackFix®, Grengloo™) and a zero control. In group 2 different rebonding systems were analysed using a hydrophilic primer (Assure™ PLUS), a methyl methacrylate-consisting primer (Plastic Conditioner) and a conventional adhesive (Transbond XT™). All teeth were tested for shear bond strength according to the DIN-13990 standard, the Adhesive Remnant Index and enamel fracture rate.

Results

The hydrophilic primer enhanced shear bond strength at first bonding (Assure™ PLUS 20.29 ± 4.95 MPa vs. Transbond XT™ 18.45 ± 2.57 MPa; BrackFix® 17 ± 5.2 MPa; Grengloo™ 19.08 ± 3.19 MPa; Meron 8.7 ± 3.9 MPa) and second bonding (Assure™ PLUS 16.76 ± 3.71 MPa vs. Transbond XT™ 13.06 ± 3.19 MPa). Using Plastic Conditioner did not seem to improve shear bond strength at rebonding (13.57 ± 2.94). When enamel etching was left out, required shear bond strength could not be achieved (Plastic Conditioner + Assure™ PLUS 8.12 ± 3.34 MPa; Plastic Conditioner: 3.7 ± 1.95 MPa). Hydrophilic priming systems showed decreased ARI-scores (second bonding: 2.63) and increased enamel fracture rates (first bonding: 55%; second bonding 21,05%).

Conclusions

Based on the present study we found that rebonding strength could be compensated by the use of hydrophilic priming systems. The additional use of a methyl methacrylate-consisting primer does not seem to enhance shear bond strength. No etching approaches resulted in non-sufficient bond strength.
Alexithymia, aggressive behavior and depression among Lebanese adolescents: A cross-sectional study
Authors: Sfeir Elsa , Geara Claudine , Hallit Souheil , Obeid Sahar
Published: September 2020

Background

For a long time, Lebanon has been considered an unstable country. This can have a negative impact on Lebanese adolescents that consequently face secondary emotional stress, leading to more mental health problems such as anxiety, depression, and alexithymia. The objective of this study was to assess the association between alexithymia, depression and aggressive behavior in a sample of Lebanese adolescents.

Methods

This is a cross-sectional study, conducted between September 2018 and February 2019, which enrolled 568 young adolescents aged between 15 and 18 years using a proportionate sample from two Lebanese governorates. Out of 750 questionnaires distributed, 568 (75.73%) were completed and collected back.

Results

The mean age was 15.87 ± 0.82 years, with 302 (53.2%) females; 180 (31.7%) were alexithymic, 193 (34.0%) and 181 (31.9%) had moderate (scores between (89 and 111) and high (scores ≥ 112) aggression respectively, whereas 176 (31.0%) and 149 (26.2%) had moderate (scores between 3 and 4) and high (scores ≥ 5) depression respectively. Higher levels of alexithymia were significantly associated with higher depression (Beta = 0.44), higher total aggression (Beta = 0.78), higher physical aggression (Beta = 0.24), higher verbal aggression (Beta = 0.14), higher anger (Beta = 0.22), and higher hostility (Beta = 0.19).

Conclusion

The prevalence of alexithymic behaviors, as well as aggression and depression in Lebanese students appears to be very high in comparison with students worldwide. Alexithymia was significantly associated with higher depression, physical and verbal aggression, anger and hostility among adolescents. Factors underlying the high level of alexithymia remain not fully elucidated.
Safety measures for COVID-19: a review of surgical preparedness at four major medical centres in Saudi Arabia
Authors: Alsofyani Mohammad A. , Malaekah Haifaa M. , Bashawyah Ahmed , Bawazeer Mohammed , Akkour Khalid , Alsalmi Sultan , Alkhairy Abdu , Dajim Nayef Bin , Khalifah Salahaddeen , Almalki Ibrahim A. , Kassab Farid , Barnawi Mohammad , Almalki Mosfer , Alharthi Mohammed , Alharthi Majed , Almalki Abdulaziz , Almalki Abdullah H. , Bourghli Anouar , Obeid Ibrahim
Published: September 2020

In view of the worldwide coronavirus disease 2019 (COVID-19) pandemic, hospitals need contingency planning. This planning should include preparation for an unexpected patient surge. This measure is evolving concomitantly with the implementation of the needed infection control rules. Here, we present our experience in contingency planning at four large tertiary hospitals in Saudi Arabia during this global pandemic, with a focus on dealing with COVID-19 patients who need to undergo surgery. The planning covers response measures required in the operating room and supporting units, including the administrative department, intensive care unit, and different sections of the surgical department. Furthermore, it covers the role of education and simulation in preparing health care providers and ensuring smooth workflow between all sections. We additionally discuss the guidelines and policies implemented in different surgical specialties. These measures are necessary to prevent the transmission of COVID-19 within healthcare facilities. Throughout the COVID-19 pandemic, the healthcare system should develop a comprehensive pandemic plan and set guidelines addressing the management of urgent and malignant cases. The guidelines should be in concordance with internal guidelines.
D1 receptors in the anterior cingulate cortex modulate basal mechanical sensitivity threshold and glutamatergic synaptic transmission
Authors: Darvish-Ghane Soroush , Quintana Clémentine , Beaulieu Jean-Martin , Martin Loren J.
Published: September 2020

The release of dopamine (DA) into target brain areas is considered an essential event for the modulation of many physiological effects. While the anterior cingulate cortex (ACC) has been implicated in pain related behavioral processes, DA modulation of synaptic transmission within the ACC and pain related phenotypes remains unclear. Here we characterized a Crispr/Cas9 mediated somatic knockout of the D1 receptor (D1R) in all neuronal subtypes of the ACC and find reduced mechanical thresholds, without affecting locomotion and anxiety. Further, the D1R high-efficacy agonist SKF 81297 and low efficacy agonist (±)-SKF-38393 inhibit α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor (AMPAR) currents in the ACC. Paradoxically, the D1R antagonists SCH-23390 and SCH 33961 when co-applied with D1R agonists produced a robust short-term synergistic depression of AMPAR currents in the ACC, demonstrating an overall inhibitory role for D1R ligands. Overall, our data indicate that absence of D1Rs in the ACC enhanced peripheral sensitivity to mechanical stimuli and D1R activation decreased glutamatergic synaptic transmission in ACC neurons.
LncRNA PSMB8-AS1 contributes to pancreatic cancer progression via modulating miR-382-3p/STAT1/PD-L1 axis
Authors: Zhang Hao , Zhu Changhao , He Zhiwei , Chen Shiyu , Li Lin , Sun Chengyi
Published: September 2020

Background

Accumulating evidence demonstrates the essential role of long non-coding RNA (lncRNA) in various types of cancers, including pancreatic cancer. However, the functions and regulation mechanism of lncRNA PMSB8-AS1 in pancreatic cancer are largely unclear.

Methods

Quantitative reverse transcription PCR (qRT-PCR) is used to examine the expression of PMSB8-AS1 in PC tissues and PC cell lines. The effect of PMSB8-AS1 on the proliferation of PC cells was detected using CCK8 assay, colony assay, and flow cytometry. The effect of PMSB8-AS1 on the migration and invasion of pancreatic cancer cells was detected using a wound-healing assay and transwell migration assay. Bioinformatic analysis, double luciferase reporting assay, western blot, and rescue experiments were used to detect the regulatory relationship between PMSB8-AS1, miR-382–3p, STAT1, and PD-L1.

Results

PMSB8-AS1 expression was upregulated in PC tissues and cell lines and positively associated with the worst survival in patients with PC. The in vitro and in vivo assays demonstrated that overexpression of PMSB8-AS1 significantly promoted pancreatic cancer cell proliferation, migration, and invasion, whereas knockdown of PMSB8-AS1 suppressed cell proliferation, migration, invasion, and EMT, and decreased apoptosis of PC cells. Besides, PMSB8-AS1 directly bound to miR-382–3p downregulated its expression. Besides, PMSB8-AS1 reversed the effect of miR-382–3p on the growth and metastasis of PC cells, which might be targeted on STAT1. Furthermore, STAT1 is the transcriptional factor that activates the expression of PD-L1.

Conclusion

lncRNA PMSB8-AS1 promotes pancreatic cancer progression via STAT1 by sponging miR-382–3p involving regulation PD-L1.
(1,3)-β-d-Glucan-based empirical antifungal interruption in suspected invasive candidiasis: a randomized trial
Authors: De Pascale Gennaro , Posteraro Brunella , D’Arrigo Sonia , Spinazzola Giorgia , Gaspari Rita , Bello Giuseppe , Montini Luca Maria , Cutuli Salvatore Lucio , Grieco Domenico Luca , Di Gravio Valentina , De Angelis Giulia , Torelli Riccardo , De Carolis Elena , Tumbarello Mario , Sanguinetti Maurizio , Antonelli Massimo
Published: September 2020

Background

(1,3)-β-d-Glucan has been widely used in clinical practice for the diagnosis of invasive Candida infections. However, such serum biomarker showed potential to guide antimicrobial therapy in order to reduce the duration of empirical antifungal treatment in critically ill septic patients with suspected invasive candidiasis.

Methods

This was a single-centre, randomized, open-label clinical trial in which critically ill patients were enrolled during the admission to the intensive care unit (ICU). All septic patients who presented invasive Candida infection risk factors and for whom an empirical antifungal therapy was commenced were randomly assigned (1:1) in those stopping antifungal therapy if (1,3)-β-d-glucan was negative ((1,3)-β-d-glucan group) or those continuing the antifungal therapy based on clinical rules (control group). Serum 1,3-β-d-glucan was measured at the enrolment and every 48/72 h over 14 days afterwards. The primary endpoint was the duration of antifungal treatment in the first 30 days after enrolment.

Results

We randomized 108 patients into the (1,3)-β-d-glucan (n = 53) and control (n = 55) groups. Median [IQR] duration of antifungal treatment was 2 days [1–3] in the (1,3)-β-d-glucan group vs. 10 days [6–13] in the control group (between-group absolute difference in means, 6.29 days [95% CI 3.94–8.65], p < 0.001). Thirty-day mortality was similar (28.3% [(1,3)-β-d-glucan group] vs. 27.3% [control group], p = 0.92) as well as the overall rate of documented candidiasis (11.3% [(1,3)-β-d-glucan group] vs. 12.7% [control group], p = 0.94), the length of mechanical ventilation (p = 0.97) and ICU stay (p = 0.23).

Conclusions

In critically ill septic patients admitted to the ICU at risk of invasive candidiasis, a (1,3)-β-d-glucan-guided strategy could reduce the duration of empirical antifungal therapy. However, the safety of this algorithm needs to be confirmed in future, multicentre clinical trial with a larger population.

Trial registration

ClinicalTrials.gov, NCT03117439, retrospectively registered on 18 April 2017
How to deal with a temporary suspension and restarting your trial: our experiences and lessons learnt
Authors: Constable Lynda , Davidson Tracey , Breeman Suzanne , Cotton Seonaidh , McDonald Alison , Wileman Samantha , Norrie John
Published: September 2020

Whilst the issues around early termination of randomised controlled trials (RCTs) are well documented in the literature, trials can also be temporarily suspended with the real prospect that they may subsequently restart. There is little guidance in the literature as to how to manage such a temporary suspension. In this paper, we describe the temporary suspension of a trial within our clinical trials unit because of concerns over the safety of transvaginal synthetic mesh implants. We also describe the challenges, considerations, and lessons learnt during the suspension that we are now applying in the current COVID-19 pandemic which has led to activities in many RCTs across the world undergoing a temporary suspension.

There were three key phases within the temporary suspension: the decision to suspend, implementation of the suspension, and restarting. Each of these phases presented individual challenges which are discussed within this paper, along with the lessons learnt. There were obvious challenges around recruitment, delivery of the intervention, and follow-up. Additional challenges included communication between stakeholders, evolving risk assessment, updates to trial protocol and associated paperwork, maintaining site engagement, data-analysis, and workload within the trial team and Sponsor organisation.

Based on our experience of managing a temporary suspension, we developed an action plan and guidance (see Additional File 1) for managing a significant trial event, such as a temporary suspension. We have used this document to help us manage the suspension of activities within our portfolio of trials during the current COVID-19 pandemic.