bluuebunny/crossref_metadata_2025 huggingface dataset:
Activated protein C modulates T-cell metabolism and epigenetic FOXP3 induction via α-ketoglutarate
Authors: Gupta Dheerendra , Elwakiel Ahmed , Ranjan Satish , Pandey Manish Kumar , Krishnan Shruthi , Ambreen Saira , Henschler Reinhard , Rana Rajiv , Keller Maria , Ceglarek Uta , Shahzad Khurrum , Kohli Shrey , Isermann Berend
Published: June 2023

A direct regulation of adaptive immunity by the coagulation protease activated protein C (aPC) has recently been established. Preincubation of T cells with aPC for 1 hour before transplantation increases FOXP3+ regulatory T cells (Tregs) and reduces acute graft-versus-host disease (aGVHD) in mice, but the underlying mechanism remains unknown. Because cellular metabolism modulates epigenetic gene regulation and plasticity in T cells, we hypothesized that aPC promotes FOXP3+ expression by altering T-cell metabolism. To this end, T-cell differentiation was assessed in vitro using mixed lymphocyte reaction or plate-bound α-CD3/CD28 stimulation, and ex vivo using T cells isolated from mice with aGVHD without and with aPC preincubation, or analyses of mice with high plasma aPC levels. In stimulated CD4+CD25− cells, aPC induces FOXP3 expression while reducing expression of T helper type 1 cell markers. Increased FOXP3 expression is associated with altered epigenetic markers (reduced 5-methylcytosine and H3K27me3) and reduced Foxp3 promoter methylation and activity. These changes are linked to metabolic quiescence, decreased glucose and glutamine uptake, decreased mitochondrial metabolism (reduced tricarboxylic acid metabolites and mitochondrial membrane potential), and decreased intracellular glutamine and α-ketoglutarate levels. In mice with high aPC plasma levels, T-cell subpopulations in the thymus are not altered, reflecting normal T-cell development, whereas FOXP3 expression in splenic T cells is reduced. Glutamine and α-ketoglutarate substitution reverse aPC-mediated FOXP3+ induction and abolish aPC-mediated suppression of allogeneic T-cell stimulation. These findings show that aPC modulates cellular metabolism in T cells, reducing glutamine and α-ketoglutarate levels, which results in altered epigenetic markers, Foxp3 promoter demethylation and induction of FOXP3 expression, thus favoring a Treg-like phenotype.
Theranostic RGD@Fe3O4-Au/Gd NPs for the targeted radiotherapy and MR imaging of breast cancer
Authors: Amraee Azadeh , Alamzadeh Zahra , Irajirad Rasoul , Sarikhani Abolfazl , Ghaznavi Habib , Ghadiri Harvani Hossein , Mahdavi Seied Rabi , Shirvalilou Sakine , Khoei Samideh
Published: June 2023

Background

As a radiosensitizing agent in magnetic resonance imaging (MRI), gadolinium is disadvantageous in that it confers a rather high toxicity and low longitudinal comfort time (r1). We hypothesized that gadolinium when combined with gold-coated iron oxide nanoparticles (NPs), might deliver better radiosensitization in MRI-based cancer theranostics. After being synthesized ligand/receptor RGD@Fe3O4-Au/Gd nanoparticles, they were characterized via some methods, such as visible–ultraviolet spectroscopy (UV–VIS), Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), and transmission electron microscope (TEM). Using relaxometry, the parameters of contrast change in T1-weighted MRI and the rate of radiation sensitivity on cancerous (MCF-7, SK-BR-3 and MDA-MB-231 (and reference (MCF-10a) breast cell lines were investigated.

Results

The presence of ultra-small iron oxide, gold, gadolinium, and RGD peptide as components of the RGD@Fe3O4-Au/Gd nanocomplex was confirmed by UV–visible, FTIR, EDX and XRD tests. With a size ranging from 4.124 nm (DLS) to 15 nm (TEM), these NPs exhibited a surface charge of –45.7 mV and a magnetic saturation of 3 emu/g. The concentrations of iron, gadolinium and gold samples in the nanocomplex were 1000, 1171 and 400 parts per million (ppm), respectively. In the relaxometry test, the rates of r2/r1 and r1 NPs were 1.56 and 23.5 mM−1 s−1. The dose increase factor for targeted (RGD@Fe3O4-Au/Gd) and non-targeted (Fe3O4-Au/Gd) NPs at 6 MV and 2 Gy was 89.1 and 59.1, respectively.

Conclusion

Owing to an enhanced signal-to-noise ratio (SNR), as confirmed by the MRI of RGD receptor-expressing MDA-MB-231 cells, RGD@Fe3O4-Au/Gd NPs were found to confer higher radiosensitization and an overall better performance as a novel radiosensitizer for MRI-based breast cancer theranostics than Fe3O4-Au/Gd nanocomplex.

Graphical Abstract
Disease burden of tuberculosis and post-tuberculosis in Inner Mongolia, China, 2016–2018 — based on the disease burden of post-TB caused by COPD
Authors: Jing Caimei , Zheng Huiqiu , Wang Xuemei , Wang Yanling , Zhao Yifan , Liu Sijia , Zhao Jing , Du Qianqian
Published: June 2023

Background

Tuberculosis (TB) remains one of the most serious infectious diseases worldwide. China has the second highest TB burden globally, but existing studies have mostly neglected the post-tuberculosis (post-TB) disease burden. This study estimated the disease burden of TB and post-TB in Inner Mongolia, China, from 2016 to 2018.

Methods

Population data were collected from TB Information Management System. Post-TB disease burden was defined as the burden caused by Chronic Obstructive Pulmonary Disease (COPD) occurring after patients with TB were cured. To estimate the incidence rate of TB, standardized mortality rate, life expectancy, and cause eliminated life expectancy, using descriptive epidemiological, abridged life table and cause eliminated life table. On this basis, the Disability-Adjusted Life Years (DALY), Years Lived with Disability (YLD) and Years of Life Lost (YLL) due to TB were further be estimated. The data were analyzed using Excel 2016 and SPSS 26.0. Joinpoint regression models were used to estimate the time and age trends of the disease burden of TB and post-TB.

Results

The TB incidence in 2016, 2017, and 2018 was 41.65, 44.30, and 55.63/100,000, respectively. The standardized mortality in the same period was 0.58, 0.65, and 1.08/100,000, respectively. From 2016 to 2018, the total DALYs of TB and post-TB were 5923.33, 6258.03, and 8194.38 person-years, and the DALYs of post-TB from 2016 to 2018 were 1555.89, 1663.33, and 2042.43 person-years. Joinpoint regression showed that the DALYs rate increased yearly from 2016 to 2018, and the rate of males was higher than that of females. TB and post-TB DALYs rates showed a rising tendency with increasing age (AAPC values were 149.6% and 157.0%, respectively, P < 0.05), which was higher in the working-age population and elderly.

Conclusion

The disease burden of TB and post-TB was heavy and increased year by year in Inner Mongolia from 2016 to 2018. Compared with the youngster and females, working-age population and the elderly and males had a higher disease burden. Policymakers should be paid more attention to the patients’ sustained lung injury after TB cured. There is a pressing need to identify more effective measures for reducing the burden of TB and post-TB of people, to improve their health and well-being.
Piperacillin-tazobactam induced immune hemolytic anemia led to increased renal impairment and eventual death from multiple organ failure in a patient with hypertensive nephropathy: case report and literature review
Authors: Wu Yong , Wu Yuanjun , Guo Ganping , Zeng Jiajun , Liu Yan , Wu Yueqin
Published: June 2023

Background

Piperacillin is one of the most common drugs that cause drug-induced immune hemolytic anemia, but a complete description of the serological features and course of the disease is rare. This study completely describes the serological characteristics and course of a patient with hypertensive nephropathy who developed drug-induced immune hemolytic anemia and worsened renal function during repeated administration of piperacillin-tazobactam.

Case presentation

A 79-year-old male patient with hypertensive nephropathy who developed severe hemolytic anemia and worsened renal function during intravenous piperacillin-tazobactam anti-infective treatment due to lung infection. Serological tests showed that the result of the direct antiglobulin test for anti-IgG was positive (4 +) and anti-C3d was negative, and the irregular red blood cell antibody screening test was negative. Plasma samples collected at different times from 2 days before to 12 days after the discontinuation of piperacillin-tazobactam administration were incubated with piperacillin solution and red blood cells of O-type healthy blood donors at 37 °C, IgG piperacillin-dependent antibodies were detected, and the highest titer was 128. However, no tazobactam-dependent antibody was detected in any plasma samples. Therefore, the patient was diagnosed with piperacillin-induced immune hemolytic anemia. Although blood transfusion and continuous renal replacement therapy were given, the patient died of multiple organ failure 15 days after the administration of piperacillin-tazobactam was stopped.

Conclusion

This is the first complete description of the disease course and serological changes of piperacillin-induced immune hemolytic anemia, which is bound to help deepen the understanding of drug-induced immune hemolytic anemia and draw profound lessons from it.
Pontine stroke in a patient with Chronic Progressive External Ophthalmoplegia (CPEO): a case report
Authors: Eliyan Yazan , Rezania Kourosh , Gomez Christopher M. , Seibert Kaitlin
Published: June 2023

Background

Chronic progressive external ophthalmoplegia (CPEO) is a mitochondrial disease with slowly progressive bilateral ptosis and symmetric ophthalmoplegia due to a genetic mutation that results in defective oxidative phosphorylation. Common genes that are implicated in CPEO include POLG, RRM2B, ANT1 and PEO1/TWNK. Here, we report a case of a patient diagnosed with CPEO caused by a novel mutation in PEO/TWNK after suffering a right pontine stroke.

Case presentation

A 70-year-old man with history of chronic progressive bilateral ptosis and ophthalmoplegia, as well as similar ocular symptoms in his father and grandfather, presented with acute onset of right hemifacial weakness and dysarthria. Brain MRI revealed an acute ischemic stroke in the right dorsal pons. The patient did not experience diplopia due to severe baseline ophthalmoplegia. Creatine kinase was elevated to 6,080 U/L upon admission and normalized over the course of one week; electromyography revealed a myopathic process. Genetic testing revealed a novel mutation c.1510G > A (p. Ala504Thr) in a pathogenic “hot spot” of the C10ORF2 gene (TWNK/PEO1), which is associated with CPEO. The mutation appears to be deleterious using several pathogenicity prediction tools.

Conclusions

This case report describes a patient with late-onset CPEO caused by a novel, likely pathogenic, mutation in the TWNK gene. Although the patient presented with a pontine stroke, it manifested with solely new onset facial palsy, as he had a severe underlying ophthalmoplegia secondary to his CPEO.
Comment on: “Do maternal albumin levels affect post-operative complications after cesarean delivery?”
Authors: Zhou Shuangqiong , Cao Xiuhong , Liu Zhiqiang
Published: June 2023

Hypoalbuminemia is often considered an independent risk factor for surgical site infections. This study first demonstrated that albumin level ≥ 3.3 g/dL was independently associated with adverse maternal outcomes. In this letter to the editor, we would like to raise some concerns about the study and clarify the interpretation of the results.
Women’s perspectives on disrespect and abuse during facility-based childbirth in Ethiopia: a qualitative study
Authors: Adinew Yohannes Mehretie , Kelly Janet , Smith Morgan , Marshall Amy
Published: June 2023

Background

Disrespect and abuse violates women’s basic human rights and autonomy and can traumatize women who are already in a vulnerable position during childbirth and deter them from utilizing skilled care for future childbirth. This study explored women’s perspectives on the acceptability of disrespect and abuse during facility-based childbirth in Ethiopia.

Methods

A qualitative descriptive design using five focus group discussions and fifteen in-depth, semi-structured, interviews was conducted with women between October 2019 to January 2020 in north Showa zone of Oromia region, central Ethiopia. Using purposive sampling, women who had given birth at public health facilities of North Showa zone during the twelve months preceding data collection were recruited, regardless of birth outcome. Inductive thematic analysis using Open Code software was used to explore the perspectives of participants.

Results

While women reject disrespectful and abusive acts during childbirth generally, they may consider some disrespectful acts as acceptable and or necessary under certain circumstances. Four emerging themes were identified. (1) Disrespect and abuse is not acceptable, (2) Disrespectful and abusive actions are acceptable only if intended to save lives, (3) Disrespectful and abusive actions are an accepted part of everyday practice to prevent complications and adverse outcomes, (4) Disrespectful and abusive actions are necessary to discipline disobedient women.

Conclusion

Women’s perceptions of disrespectful and abusive acts of care providers is deeply rooted within the context of violence in Ethiopia and the societal hierarchies that have systematically disempowered women. Given the pervasiveness of disrespect and abusive actions during childbirth, policymakers, clinical managers and care providers must take these essential contextual and societal norms into account and devise comprehensive clinical interventions that addresses the root causes.
Collection of smartphone and internet addiction
Authors: Lin Chung-Ying , Ratan Zubair Ahmed , Pakpour Amir H
Published: June 2023

The enigma of smartphone and internet addiction has plagued academics for the last decade, now scholars believe this behavior might have a substantial effect on human health and social issues. However, there are literature gaps. Thus, BMC Psychiatry works with us to launch the special collection “Smartphone and Internet Addiction”.
Shift work is associated with an increased risk of type 2 diabetes and elevated RBP4 level: cross sectional analysis from the OHSPIW cohort study
Authors: Wang Li , Ma Qi , Fang BinBin , Su YinXia , Lu Wanxian , Liu Mengdi , Li Xue , Liu Jiwen , He LiJuan
Published: June 2023

Background

Shift work, with its growing prevalence globally, disrupts the body's inherent circadian rhythm. This disruption may escalate the risk of chronic diseasesxacerbate chronic disease risk by dysregulating physiological, behavioral, and psychosocial pathways. This study aimed to evaluate the effect of shift work on type 2 diabetes (T2DM) and Retinol binding protein 4 (RBP4) level.

Methods

The current study employed a multi-stage stratified cluster sampling technique, examining 1499 oilfield workers from the OHSPIW cohort who participated in occupational health assessments between March 2017 and June 2018.The evaluation involved shift work, sleep quality, T2DM status with questionnaires and plasma RBP4 levels in blood samples. Statistical analysis includes, Chi-square tests, t-tests, multivariate logistic regression analyses, and multivariate linear mixed models.

Results

The prevalence rate of T2DM in shift workers (6.56%) was significantly higher than in day workers (4.21%) (OR = 1.60, 95% CI: 1.01–2.53), with no significant difference found in the family history of diabetes, hypertension, or other chronic heart diseases (P = 0.378). The shift worker (6.89 ± 3.35) also exhibited distinctly higher PSQI scores than day workers (5.99 ± 2.87) (P < 0.001). Adjusting the age, gender, BMI, family income, tobacco smoking, alcohol drinking and PSQI, hailed shift work as a risk factor for T2DM (OR = 1.91, 95% CI: 1.17–3.14). The pairwise comparison revealed significant differences in RBP4 levels across different groups: shift and non-shift workers both with and without T2DM (P < 0.001). The RBP4 level of the shift group without T2DM was higher than the non-shift group without T2DM (P < 0.05). The levels of RBP4 level in shift and non-shift groups with T2DM was higher than those without T2DM (P < 0.05). The multivariate linear mixed model showed that when age, gender, BMI, diabetes, PSQI, family income, smoking and drinking remained unchanged, the RBP4 level of the shift workers increased by an average of 9.51 μg/mL compared with the day workers.

Conclusions

Shift work is associated with an increased risk of T2DM and high levels of RBP4. Follow-up of RBP4 could facilitateearly detection of T2DM among shift workers.
Efficacy and safety of EGFR-TKIs in combination with angiogenesis inhibitors as first-line therapy for advanced EGFR-mutant non-small-cell lung cancer: a systematic review and meta-analysis
Authors: Hu Di , Zhou Yan-Yan , Ma Hong-Bo , Tao Miao-Miao , Huang Qun-Zhen , Yang Zhen-Zhou , Zhou Qi
Published: June 2023

Background

For patients with advanced non-small-cell lung cancer (NSCLC) with EGFR mutations, the suggested course of action is epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs). Even with a high disease control rate, a majority of patients develop acquired EGFR-TKIs resistance and eventually advance. To increase the benefits of treatment, clinical trials are increasingly exploring the value of EGFR-TKIs combined with angiogenesis inhibitors as a first-line treatment in advanced NSCLC carrying EGFR mutations.

Method

Using PubMed, EMBASE and Cochrane Library, to locate published full-text articles in print or online, a thorough literature search was done from the database's inception to February 2021. Additionally, oral presentation RCTs from ESMO and ASCO were obtained. We sifted out RCTs that used EGFR-TKIs along with angiogenesis inhibitors as first-line therapy for advanced EGFR-mutant NSCLC. ORR, AEs, OS, and PFS were the endpoints. Review Manager version 5.4.1 was used for data analysis.

Results

One thousand eight hundred twenty-one patients were involved in 9 RCTs. According to the results, combining EGFR-TKIs with angiogenesis inhibitors therapy prolonged PFS of advanced EGFR-mutation NSCLC patients on the whole [HR:0.65 (95%CI: 0.59~0.73, P<0.00001)]. No significant statistical difference was identified between the combination group and single drug group in OS(P=0.20) and ORR (P=0.11). There are more adverse effects when EGFR-TKIs are used in combination with angiogenesis inhibitors than when used alone.

Conclusion

The combination of EGFR-TKIs and angiogenesis inhibitors prolonged PFS in patients with EGFR-mutant advanced NSCLC, but the OS and ORR benefit was not significant, and the risk of adverse events was higher, more pronounced with hypertension and proteinuria; PFS in subgroups suggested that the combination was associated with better PFS in the smoking, liver metastasis, and no brain metastasis groups, and the included studies suggested that the smoking group , liver metastasis group, and brain metastasis group may have a potential OS benefit.
Assessment of oral health knowledge, literacy, and attitude among schoolteachers towards oral health - A cross-sectional study
Authors: Aldowah Omir , Assiry Ali A , Mujallid Nizar F , Ashi Farid N , Abduljawad Faisal , Al-Zahrani Minna M. , Ezzaddin Rawam , Karobari Mohmed Isaqali
Published: June 2023

Background

To accomplish the purpose of health education and health promotion programs, schools are the most effective place for delivering health information to children. The main purpose of our research was to inform, gather evidence and contribute to developing knowledge regarding the OHL, knowledge, and attitude among school teachers towards oral health in Najran region of Saudi Arabia.

Methods

A questionnaire-based cross-sectional study was conducted in Najran region of Saudi Arabia for 6 months. A stratified cluster random sampling of 252 teachers was taken to represent all the teachers of Najran region of Saudi Arabia. The questionnaire contains 2 parts, sociodemographic part that include age, gender, education, teaching level, and income of the participants. The second part contains 25 items that assess the OHL (HelD-14 questions), knowledge (6 questions), and attitude (5 questions) of the participants. SPSS software version 26 was used to enter and analyze the data (IBM SPSS, Chicago, IL, USA software version 26.0). Multiple Logistic regression was applied to check the relationship between OHL and the associated factors. The Chi-square test was applied to evaluate knowledge of study participants. The level of significance was set up at p < 0.05.

Results

A total of 252 school teachers with a Mean age of school teachers 32.25 ± 8.46 participated in the study. The multiple logistic regression model shows the association between age, education, and OHL level of school teachers. After adjustment for sociodemographic factors age (OR = 0.219, 95% CI: 0.058–0.834), education (OR = 9.053, 95% CI: 1.135–72,023) were significantly associated with OHL of school teachers. Female participants showed better performance with respect to all the knowledge questions, a significantly higher level of knowledge (p-value < 0.05) was reported with all the questions except the second question (dental plaques causes). 94.8% of teachers agreed that children’s teeth should be checked by a dentist on a regular basis, while 96.8% agreed that dental health education should be included in the primary school curriculum and that all teachers should receive dental health education training.

Conclusion

Overall, school teachers have high oral health literacy, adequate knowledge, and a positive attitude toward oral health. The female teachers had more knowledge about dentistry than their male counterparts.
General practice undergraduate and vocational training: ambulatory teaching and trainers’ curriculum and remuneration – a cross-sectional study among 30 member countries of WONCA Europe
Authors: Devillers Louise , Friesse Sébastien , Caranta Mette , Tarazona Vincent , Bourrion Bastien , Saint-Lary Olivier
Published: June 2023

Background

After a long phase without any propositions for real ambulatory training inside general practitioners’ offices, general practice (GP) vocational training has begun to appear progressively and has been integrated into undergraduate medical programmes. The aim of this study was to provide an overview of GP vocational training and GP trainers in member countries of the World Organization of National Colleges, Academies and Academic Associations of General Practitioners/Family Physicians (WONCA) Europe.

Method

We carried out this cross-sectional study between September 2018 and March 2020. The participants responded to a questionnaire in real-life conversations, video conferences or e-mail exchanges. The respondents included GP trainers, teachers and general practitioners involved in the GP curriculum recruited during European GP congresses.

Results

Representatives from 30 out of 45 WONCA Europe member countries responded to the questionnaire. Based on their responses, there is a well-established period for GP internships in undergraduate medical programmes, but with varying lengths. The programmes for some countries offer an internship after students graduate from medical school but before GP specialisation to ensure the career choice of the trainees. After specialisation, private practice GP internships are offered; however, in-hospital GP internships are more common. GP trainees no longer have a passive role during their internships. GP trainers are selected based on specific criteria and in countries, they have to follow some teacher training programmes. In addition to income from medical appointments carried out by GP trainees, GP trainers from some countries receive additional remuneration from various organisations.

Conclusion

This study collected information on how undergraduate and postgraduate medical students are exposed to GP, how GP training is organised and the actual status of GP trainers among WONCA Europe member countries. Our exploration of GP training provides an update of the data collected by Isabel Santos and Vitor Ramos in the 1990s and describes some specificities that can inspire other organisations to prepare young, highly qualified general practitioners.
Models of social prescribing to address non-medical needs in adults: a scoping review
Authors: Oster Candice , Skelton Claire , Leibbrandt Richard , Hines Sonia , Bonevski Billie
Published: June 2023

Background

The health and wellbeing consequences of social determinants of health and health behaviours are well established. This has led to a growing interest in social prescribing, which involves linking people to services and supports in the community and voluntary sectors to address non-medical needs. However, there is considerable variability in approaches to social prescribing with little guidance on how social prescribing could be developed to reflect local health systems and needs. The purpose of this scoping review was to describe the types of social prescribing models used to address non-medical needs to inform co-design and decision-making for social prescribing program developers.

Methods

We searched Ovid MEDLINE(R), CINAHL, Web of Science, Scopus, National Institute for Health Research Clinical Research Network, Cochrane Central Register of Controlled Trials, WHO International Clinical Trial Registry Platform, and ProQuest – Dissertations and Theses for articles and grey literature describing social prescribing programs. Reference lists of literature reviews were also searched. The searches were conducted on 2 August 2021 and yielded 5383 results following removal of duplicates.

Results

148 documents describing 159 social prescribing programs were included in the review. We describe the contexts in which the programs were delivered, the program target groups and services/supports to which participants were referred, the staff involved in the programs, program funding, and the use of digital systems.

Conclusions

There is significant variability in social prescribing approaches internationally. Social prescribing programs can be summarised as including six planning stages and six program processes. We provide guidance for decision-makers regarding what to consider when designing social prescribing programs.
Community-based HIV prevention services for transgender people in Ukraine: current situation and potential for improvement
Authors: Neduzhko Oleksandr , Saliuk Tetiana , Kovtun Oksana , Semchuk Nadiia , Varetska Olga
Published: June 2023

Background

Community-based HIV-prevention services are a key approach to prevent HIV transmission among key population representatives. Transgender people have multiple specific needs and it is crucial to use prevention approaches that effectively respond to those needs and facilitate barriers on the way to use HIV prevention and related services. This study is aimed to explore the current state of community-based HIV prevention services among transgender people in Ukraine, its limitations and potential for improvement based on the experience and perceptions of transgender people, physicians, and community social workers providing services to transgender people.

Methods

Semi-structured in-depth interviews were conducted among physicians providing services to transgender people (N = 10), community social workers (N = 6), and transgender people (N = 30). The objectives of the interviews were to explore: the relevance of the community-based HIV prevention services to the needs of transgender people; the key components of the most preferred (“ideal”) HIV-prevention package for transgender people; ways to optimize the existing HIV prevention package for transgender people including enrollment and retention. Systematically collected data were analyzed and coded into the main domains, thematic categories and subcategories using thematic analysis.

Results

The current HIV prevention programs were well-evaluated by the majority of respondents. Gender-affirming care was found to be the key need of transgender people. Integration of HIV prevention services and gender-affirming care was perceived as the main way to address the needs of transgender people. Internet-based and peer word-of-mouth recruitment may improve enrollment in services. Optimization of existing HIV prevention package may include: psychological counseling, referral and navigation to medical services, legal services, pre- and post-exposure prevention, dissemination of tube lubricants, femidoms and latex wipes, use of oral fluid test systems for HIV self-testing.

Conclusions

The findings of this study suggest potential solutions to improve community-based HIV prevention services for transgender people by introducing a transgender people -oriented package, which integrates gender transition, HIV prevention and other services. Provision of prevention services based on assessed risk and referral/navigation to related services are the key options for optimization of the existing HIV prevention package.

Trial registration

Not applicable.
Associations between smoking and vaping prevalence, product use characteristics, and mental health diagnoses in Great Britain: a population survey
Authors: Taylor Eve , Brose Leonie S , McNeill Ann , Brown Jamie , Kock Loren , Robson Debbie
Published: June 2023

Background

Rates of diseases and death from tobacco smoking are substantially higher among those with a mental health condition (MHC). Vaping can help some people quit smoking, but little is known about vaping among people with MHCs or psychological distress. We assessed the prevalence and characteristics (heaviness, product type) of smoking and/or vaping among those with and without a history of single or multiple MHC diagnoses and with no, moderate or serious psychological distress.

Methods

Data from 27,437 adults in Great Britain surveyed between 2020 and 2022. Multinomial regressions analysed associations between smoking, vaping and dual use prevalence, smoking/vaping characteristics and (a) history of a single or multiple MHC and (b) moderate or serious psychological distress, adjusted for age, gender, and socioeconomic status.

Results

Compared with people who had never smoked, those who currently smoked were more likely to report a history of a single (12.5% vs 15.0%, AOR=1.62, 95% CI=1.46–1.81,p<.001) or multiple MHCs (12.8% vs 29.3%, AOR=2.51, 95% CI=2.28–2.75,p<.001).

Compared with non-vapers, current vapers were more likely to report a history of a single (13.5% vs 15.5%, AOR=1.28, 95% CI=1.11–1.48,p<.001) or multiple MHCs (15.5% vs 33.4%, AOR=1.66, 95% CI=1.47–1.87,p<.001). Dual users were more likely to report a history of multiple MHCs (36.8%), but not a single MHC than exclusive smokers (27.2%) and exclusive vapers (30.4%) (allp<.05). Similar associations were reported for those with moderate or serious psychological distress.

Smoking roll-your-own cigarettes and smoking more heavily, were associated with a history of single or multiple MHCs. There were no associations between vaping characteristics and a history of MHCs. Frequency of vaping, device type and nicotine concentration differed by psychological distress.

Conclusions

Smoking, vaping and dual use were substantially higher among those with a history of MHC, especially multiple MHC, and experiencing past month distress than those not having a history of MHC or experiencing past month distress respectively. Analysis used descriptive epidemiology and causation cannot be determined.
Metal-enriched HSP90 nanoinhibitor overcomes heat resistance in hyperthermic intraperitoneal chemotherapy used for peritoneal metastases
Authors: Wang Qiang , Liu Peng , Wen Yingfei , Li Kuan , Bi Bo , Li Bin-bin , Qiu Miaojuan , Zhang Shiqiang , Li You , Li Jia , Chen Hengxing , Yin Yuan , Zeng Leli , Zhang Changhua , He Yulong , Zhao Jing
Published: June 2023

Clinical hyperthermic intraperitoneal chemotherapy (HIPEC) is regarded as a potential treatment that can prolong survival of patients with peritoneal metastases after cytoreductive surgery. However, treated tumor cells are prone to becoming heat resistant to HIPEC therapy through high expression of heat shock proteins (HSPs). Here, a carrier-free bifunctional nanoinhibitor was developed for HIPEC therapy in the management of peritoneal metastases. Self-assembly of the nanoinhibitor was formed by mixing Mn ion and epigallocatechin gallate (EGCG) in a controllable manner. Such nanoinhibitor directly inhibited HSP90 and impaired the HSP90 chaperone cycle by reduced intracellular ATP level. Additionally, heat and Mn ion synergistically induced oxidative stress and expression of caspase 1, which activated GSDMD by proteolysis and caused pyroptosis in tumor cells, triggering immunogenic inflammatory cell death and induced maturation of dendritic cells through the release of tumor antigens. This strategy to inhibit heat resistance in HIPEC presented an unprecedented paradigm for converting “cold” tumors into “hot” ones, thus significantly eradicating disseminated tumors located deep in the abdominal cavity and stimulating immune response in peritoneal metastases of a mouse model. Collectively, the nanoinhibitor effectively induced pyroptosis of colon tumor cells under heat conditions by inhibiting heat stress resistance and increasing oxidative stress, which may provide a new strategy for treatment of colorectal peritoneal metastases.
Spontaneous formation of MXene-oxidized sono/chemo-dynamic sonosensitizer/nanocatalyst for antibacteria and bone-tissue regeneration
Authors: Yu Yang , Sun Houyi , Lu Qunshan , Sun Junyuan , Zhang Pengfei , Zeng Linran , Vasilev Krasimir , Zhao Yunpeng , Chen Yu , Liu Peilai
Published: June 2023

Prolonged and incurable bacterial infections in soft tissue and bone are currently causing large challenges in the clinic. Two-dimensional (2D) materials have been designed to address these issues, but materials with satisfying therapeutic effects are still needed. Herein, CaO2-loaded 2D titanium carbide nanosheets (CaO2-TiOx@Ti3C2, C-T@Ti3C2) were developed. Surprisingly, this nanosheet exhibited sonodynamic ability, in which CaO2caused the in situ oxidation of Ti3C2MXene to produce acoustic sensitiser TiO2on its surface. In addition, this nanosheet displayed chemodynamic features, which promoted a Fenton reaction triggered by self-supplied H2O2. We detected that C-T@Ti3C2nanosheets increased reactive oxygen species (ROS) production in response to sonodynamic therapy, which displayed an ideal antibacterial effect. Furthermore, these nanoreactors facilitated the deposition of Ca2+, which promoted osteogenic transformation and enhanced bone quality in osteomyelitis models. Herein, a wound healing model and prosthetic joint infection (PJI) model were established, and the C-T@Ti3C2nanosheets played a protective role in these models. Taken together, the results indicated that the C-T@Ti3C2nanosheets function as a multifunctional instrument with sonodynamic features, which might reveal information regarding the treatment of bacterial infections during wound healing.

Graphical Abstract
“I don’t want to die”: a qualitative study of coping strategies to prevent fentanyl-related overdose deaths among people who inject drugs and its implications for harm reduction policies
Authors: Abadie R.
Published: June 2023

Background

Fentanyl and fentanyl-related analogues are the main drivers of overdose death in the USA, particularly among people who inject drugs (PWID). Despite the fact that non-Hispanic whites exhibit higher population rates of synthetic opioid mortality, overdose deaths have increased among African American and Latinos in urban areas. Yet little attention has been paid to the introduction of fentanyl among rural PWID in Puerto Rico.

Methods

We conducted N = 38 in-depth interviews with PWID in rural Puerto Rico to document participants’ experiences of injection drug use after the arrival of fentanyl and the strategies they implemented to manage overdose death risks.

Results

Participants suggest that the arrival of fentanyl in large scale happened after Hurricane Maria in 2017; this coincided with a dramatic increase in overdose episodes and deaths. Fear of overdose deaths motivated some participants to substitute intravenous drug use for other forms of substance use or to seek MOUD. PWID that continued injection use resorted to conducting “hit tests,” avoiding injecting alone, using naloxone, and employing fentanyl testing strips.

Conclusions

While overdose deaths would have been higher without participants’ willingness to adopt harm-reduction strategies, this paper illustrates the limits of these policies to address the current epidemic of fentanyl-related overdose deaths among this population. More studies are needed to understand how health disparities shape overdose risks for minority populations. However, major policy changes, in particular the revision of the harmful role of the War on Drugs and the termination of failed neoliberal economic policies that contribute to deaths of despair, should be addressed if we are to make a dent in this epidemic.
Microglial cell response to experimental periodontal disease
Authors: Almarhoumi Rawan , Alvarez Carla , Harris Theodore , Tognoni Christina M. , Paster Bruce J. , Carreras Isabel , Dedeoglu Alpaslan , Kantarci Alpdogan
Published: June 2023

Objectives

Microglial activation is critical for modulating the neuroinflammatory process and the pathological progression of neurodegenerative diseases, such as Alzheimer's disease (AD). Microglia are involved in forming barriers around extracellular neuritic plaques and the phagocytosis of β-amyloid peptide (Aβ). In this study, we tested the hypothesis that periodontal disease (PD) as a source of infection alters inflammatory activation and Aβ phagocytosis by the microglial cells.

Methods

Experimental PD was induced using ligatures in C57BL/6 mice for 1, 10, 20, and 30 days to assess the progression of PD. Animals without ligatures were used as controls. Maxillary bone loss and local periodontal tissue inflammation associated with the development of PD were confirmed by morphometric bone analysis and cytokine expression, respectively. The frequency and the total number of activated microglia (CD45+ CD11b+ MHCII+) in the brain were analyzed by flow cytometry. Mouse microglial cells (1 × 105) were incubated with heat-inactivated bacterial biofilm isolated from the ligatures retrieved from the teeth or with Klebsiella variicola, a relevant PD-associated bacteria in mice. Expression of pro-inflammatory cytokines, toll-like receptors (TLR), and receptors for phagocytosis was measured by quantitative PCR. The phagocytic capacity of microglia to uptake β-amyloid was analyzed by flow cytometry.

Results

Ligature placement caused progressive periodontal disease and bone resorption that was already significant on day 1 post-ligation (p < 0.05) and continued to increase until day 30 (p < 0.0001). The severity of periodontal disease increased the frequency of activated microglia in the brains on day 30 by 36%. In parallel, heat-inactivated PD-associated total bacteria and Klebsiella variicola increased the expression of TNFα, IL-1β, IL-6, TLR2, and TLR9 in microglial cells (1.6-, 83-, 3.2-, 1.5-, 1.5-fold, respectively p < 0.01). Incubation of microglia with Klebsiella variicola increased the Aβ-phagocytosis by 394% and the expression of the phagocytic receptor MSR1 by 33-fold compared to the non-activated cells (p < 0.0001).

Conclusions

We showed that inducing PD in mice results in microglia activation in vivo and that PD-associated bacteria directly promote a pro-inflammatory and phagocytic phenotype in microglia. These results support a direct role of PD-associated pathogens in neuroinflammation.
Measuring social norms of intimate partner violence to exert control over wife agency, sexuality, and reproductive autonomy: an item response modelling of the IPV-ASRA scale
Authors: Boyce Sabrina C. , Minnis Alexandra M. , Deardorff Julianna , McCoy Sandra I. , Challa Sneha , Johns Nicole , Aliou Sani , Brooks Mohamad , Nouhou Abdoul-Moumouni , Gochyyev Perman , Wilson Mark , Baker Holly , Silverman Jay G.
Published: June 2023

Background

The field of violence prevention research is unequivocal that interventions must target contextual factors, like social norms, to reduce gender-based violence. Limited research, however, on the social norms contributing to intimate partner violence or reproductive coercion exists. One of the driving factors is lack of measurement tools to accurately assess social norms.

Methods

Using an item response modelling approach, this study psychometrically assesses the reliability and validity of a social norms measure of the acceptability of intimate partner violence to exert control over wife agency, sexuality, and reproductive autonomy with data from a population-based sample of married adolescent girls (ages 13–18) and their husbands in rural Niger (n = 559 husband-wife dyads) collected in 2019.

Results

A two-dimensional Partial Credit Model for polytomous items was fit, showing evidence of reliability and validity. Higher scores on the “challenging husband authority” dimension were statistically associated with husband perpetration of intimate partner violence.

Conclusions

This brief scale is a short (5 items), practical measure with strong reliability and validity evidence. This scale can help identify populations with high-need for social norms-focused IPV prevention and to help measure the impact of such efforts.
Leveraging CD16 fusion receptors to remodel the immune response for enhancing anti-tumor immunotherapy in iPSC-derived NK cells
Authors: Meng Fanyi , Zhang Siqi , Xie Juan , Zhou Yuan , Wu Qingling , Lu Binyan , Zhou Shixin , Zhao Xiangyu , Li Yang
Published: June 2023

Background

The cytotoxicity of NK cells is largely dependent on IgG Fc receptor CD16a, which mediates antibody-dependent cell-mediated cytotoxicity (ADCC). The high-affinity and non-cleavable CD16 (hnCD16) is developed and demonstrated a multi-tumor killing potential. However, the hnCD16 receptor activates a single CD16 signal and provides limited tumor suppression. How to exploit the properties of hnCD16 and incorporate NK cell-specific activation domains is a promising development direction to further improve the anti-tumor activity of NK cells.

Methods

To expand the applications of hnCD16-mediated ADCC for NK cell-based immunotherapy in cancer, we designed the hnCD16 Fusion Receptor (FR) constructs with the ectodomain of hnCD16 fused with NK cell-specific activating domains in the cytoplasm. FR constructs were transduced into CD16-negative NK cell line and human iPSC-derived NK (iNK) cells and effective FR constructs were screened. The up-regulation of immune activation- and cytokine-releasing-related pathways in FR-transduced NK cells was screened and validated by RNA sequencing and multiplex cytokines release assay, respectively. The tumor-killing efficiency was tested in vitro and in vivo via co-culture with tumor cell lines and xenograft mice-bearing human B-cell lymphoma, respectively.

Results

We screened the most effective combination to kill B cell lymphoma, which was fused with the ectodomain of hnCD16a, NK-specific co-stimulators (2B4 and DAP10) and CD3ζ in cytoplasmic domains. The screened construct showed excellent cytotoxicity effects and sharp multiple cytokines releasing both in the NK cell line and iNK cells. The transcriptomic analysis and validation assays of hnCD16- and hnCD16FR-transduced NK cells showed that hnCD16FR transduction remodeled immune-related transcriptome in NK cells, where significant upregulation of genes related to cytotoxicity, high cytokines releasing, induced tumor cell apoptosis, and ADCC in comparison with hnCD16 transduction were highlighted. In vivo xenograft studies demonstrated that a single low-dose regimen of engineered hnCD16FR iPSC-derived NK cells co-administered with anti-CD20 mAb treatment mediated potent activity and significantly improved survival.

Conclusion

We developed a novel hnCD16FR construct that exhibits more potent cytotoxicity than reported hnCD16, which is a promising approach to treat malignancies with improved ADCC properties. We also offer a rationale for NK activation domains that remodel immune response to enhance CD16 signaling in NK cells.
Serum vascular endothelial growth factor associated with the progression of granulosa cell tumor: a report of two cases
Authors: Takasaki Kazuki , Ichinose Takayuki , Miyagawa Yuko , Fukui Shiho , Hashimoto Kei , Nishida Haruka , Takahashi Yuko , Hiraike Haruko , Saito Koji , Sasajima Yuko , Nagasaka Kazunori
Published: June 2023

Background

Granulosa cell tumors (GCTs) account for approximately 2% of ovarian malignancies and are considered a rare type of ovarian cancer. GCTs are characterized by irregular genital bleeding after menopause due to female hormone production as well as late recurrence around 5–10 years after initial treatment. In this study, we investigated two cases of GCTs to find a biomarker that can be used to evaluate the treatment and predict recurrence.

Case presentation

Case 1 was a 56-year-old woman who presented to our hospital with abdominal pain and distention. An abdominal tumor was found, and GCTs were diagnosed. Serum vascular endothelial growth factor (VEGF) levels decreased after surgery. Case 2 involved a 51-year-old woman with refractory GCTs. Carboplatin–paclitaxel combination therapy and bevacizumab were administered after the tumor resection. After chemotherapy, a decline in VEGF levels was observed, but serum VEGF levels increased again with disease progression.

Conclusions

VEGF expression may be of clinical importance in GCTs as a clinical biomarker for disease progression, which may be used to determine the efficacy of bevacizumab against GCTs.
Epidemiology, clinical aspects, and management of pediatric drowning
Authors: Pellegrino Francesco , Raffaldi Irene , Rossi Roberta , De Vito Barbara , Pagano Manuela , Garelli Davide , Bondone Claudia
Published: June 2023

Drowning is the third leading cause of injury death in the pediatric population worldwide, with incidence peaking among those aged 1–4 years and again in adolescence.

The purpose of this commentary is to review the basic pathophysiology of drowninginjury and factors that affect the outcome, such as submersion and hypothermia. We also discuss principles of prehospital and in-hospital management, comprising resuscitation and stabilization, administration of oxygen and intravenous liquids, and central reheating.

Even though the mortality rate has decreased in recent years, further investments and safety measures are needed to prevent child drowning deaths.
The role of the pediatrician in the management of the child and adolescent with gender dysphoria
Authors: Micangeli Ginevra , Profeta Giovanni , Colloridi Fiorenza , Pirro Federica , Tarani Francesca , Ferraguti Giampiero , Spaziani Matteo , Isidori Andrea M. , Menghi Michela , Fiore Marco , Tarani Luigi
Published: June 2023

Gender dysphoria is a clinical condition characterized by significant distress due to the discordance between biological sex and gender identity. Currently, gender dysphoria is also found more frequently in children and adolescents, thanks to greater social sensibleness and new therapeutic possibilities. In fact, it is estimated that the prevalence of gender dysphoria in pediatric age is between 0.5% and 2% based on the statistics of the various countries. Therefore, the pediatrician cannot fail to update himself on these issues and above all should be the reference figure in the management of these patients. Even if the patient must be directed to a referral center and be followed up by a multidisciplinary team, the treating pediatrician will care to coordinate the clinical and therapeutic framework. The aim of the present report is therefore to integrate literature data with our clinical experience to propose a new clinical approach in which the pediatrician should be the reference in the care of these patients, directing them towards the best therapeutic approach and staying in contact with the specialists of the referral center.