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Heterotopic and orthotopic ovarian tissue autotransplantation techniques, currently used in humans, will become promising alternative methods for fertility preservation in domestic and wild animals. Thus, this study describes for the first time the efficiency of a heterotopic ovarian tissue autotransplantation technique in a large livestock species (i.e., horses) after ovarian fragments were exposed or not to a cooling process (4°C/24 h) and/or VEGF before grafting. Ovarian fragments were collected in vivo via an ultrasound-guided biopsy pick-up method and surgically autografted in a subcutaneous site in both sides of the neck in each mare. The blood flow perfusion at the transplantation site was monitored at days 2, 4, 6, and 7 post-grafting using color-Doppler ultrasonography. Ovarian grafts were recovered 7 days post-transplantation and subjected to histological analyses. The exposure of the ovarian fragments to VEGF before grafting was not beneficial to the quality of the tissue; however, the cooling process of the fragments reduced the acute hyperemia post-grafting. Cooled grafts compared with non-cooled grafts contained similar values for normal and developing preantral follicles, vessel density, and stromal cell apoptosis; lower collagen type III fibers and follicular density; and higher stromal cell density, AgNOR, and collagen type I fibers. In conclusion, VEGF exposure before autotransplantation did not improve the quality of grafted tissues. However, cooling ovarian tissue for at least 24 h before grafting can be beneficial because satisfactory rates of follicle survival and development, stromal cell survival and proliferation, as well as vessel density, were obtained.

Background: Transcranial direct current stimulation (tDCS) might modulate neural activity and promote neural plasticity in patients with fibromyalgia (FM). This multi-group randomized clinical trial compared home-based active tDCS (HB-a-tDCS) on the left dorsolateral prefrontal cortex (l-DLPFC) or home-based sham tDCS (HB-s-tDCS), and HB-a-tDCS or HB-s-tDCS on the primary motor cortex (M1) in the connectivity analyses in eight regions of interest (ROIs) across eight resting-state electroencephalography (EEG) frequencies., Methods: We included 48 women with FM, aged 30 to 65, randomly assigned to 2:1:2:1 to receive 20 sessions during 20 minutes of HB-a-tDCS 2mA or HB-s-tDCS, over l-DLPFC or M1, respectively. EEG recordings were obtained before and after treatment with eyes open (EO) and eyes closed (EC)., Results: In the EC condition, comparing pre to post-treatment, the HB-a-tDCS on l-DLPFC decreased the lagged coherence connectivity in the delta frequency band between the right insula and left anterior cingulate cortex (ACC) (t = -3.542, p = .048). The l-DLPFC HB-a-tDCS compared to HB-s-tDCS decreased the lagged coherence connectivity in the delta frequency band between the right insula and left ACC (t = -4.000, p = .017). In the EO condition, the l-DLPFC HB-a-tDCS compared to M1 HB-s-tDCS increased the lagged coherence connectivity between the l-DLPFC and left ACC in the theta band (t = -4.059, p = .048). Regression analysis demonstrated that the HB-a-tDCS effect on the l-DLPFC was positively correlated with sleep quality. On the other hand, the HB-a-tDCS on l-DLPFC and HB-s-tDCS on M1 were positively correlated with pain catastrophizing., Conclusions: These results show that HB-a-tDCS affects the neural connectivity between parts of the brain that control pain's emotional and attentional aspects, which are most noticeable at lower EEG frequencies in a rest state. This effect on neural oscillations could serve as a neural marker associated with its efficacy in alleviating fibromyalgia symptoms., Clinical Trial Registration: identifier [NCT03843203]., Competing Interests: WC, National Council for Scientific and Technological Development - (CNPq), Brazil, ILST reported grants from National Council for Scientific and Technological Development, and Fundación de Amparo à Pesquisa do Estado do Rio Grande do Sul during the conduct of the study and PRSS grants from National Council for Scientific and Technological Development during the conduct of the study. PRSS reported grants from Financiadora de Estudos e Projetos during the conduct of the study; in addition, WC, ILST, PRSS had a patent for BR 20 2015 016450 0 licensed to Quark Medical. The tDCS device used in this study was developed and patented by PRSS, DPSJ, ILST, and WC, and these authors received royalties from Quark Medical (patent for BR 20 2015 016450 0 licensed to Quark Medical). DPSJ reported grants from Financiadora de Estudos e Projetos during the conduct of the study. No other competing interests were reported. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Lopes Alves et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Autophagy and the ubiquitin-proteasome system (UPS) are important cellular mechanisms that coordinate protein degradation essential for proteostasis. P62/SQSTM1 is a receptor cargo protein able to deliver ubiquitinated targets to the proteasome proteolytic complex and/or to the autophagosome. In the insect vector of Chagas disease, Rhodnius prolixus, previous works have shown that the knockdown of different autophagy-related genes (ATGs) and ubiquitin-conjugating enzymes resulted in abnormal oogenesis phenotypes and embryo lethality. Here, we investigate the role of the autophagy/UPS adaptor protein p62 during the oogenesis and reproduction of this vector. We found that R. prolixus presents one isoform of p62 encoded by a non-annotated gene. The predicted protein presents the domain architecture anticipated for p62: PB1 (N-term), ZZ-finger, and UBA (C-term) domains, and phylogenetic analysis showed that this pattern is highly conserved within insects. Using parental RNAi, we found that although p62 is expressed in the ovary, midgut, and fat body of adult females, systemic silencing of this gene did not result in any apparent phenotypes under in-house conditions. The insects' overall levels of blood meal digestion, lifespan, yolk protein production, oviposition, and embryo viability were not altered when compared to controls. Because it is known that autophagy and UPS can undergo compensatory mechanisms, we asked whether the silencing of p62 was triggering adaptative changes in the expression of genes of the autophagy, UPS, and the unfolded protein response (UPR) and found that only ATG1 was slightly up regulated in the ovaries of silenced females. In addition, experiments to further investigate the role of p62 in insects previously silenced for the E1-conjugating enzyme (a condition known to trigger the upregulation of p62), also did not result in any apparent phenotypes in vitellogenic females., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Pereira et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: People who use drugs (PWUD) frequent emergency departments at a higher rate than the general population, and experience a greater frequency of soft tissue infections, pneumonia, and chronic conditions such as, HIV/AIDs and hepatitis C. This population has distinct health care considerations (e.g. withdrawal management) and are also more likely to leave or be discharged from hospital against medical advice., Methods: This study examines the experiences of PWUD who have left or been discharged from hospital against medical advice to understand the structural vulnerabilities that shape experiences with emergency departments. Semi-structured qualitative interviews were conducted with 30 PWUD who have left or been discharged from hospital against medical advice within the past two years as part of a larger study on hospital care and drug use in Vancouver, Canada., Results: Findings characterize the experiences and perceptions of PWUD in emergency department settings, and include: (1) stigmatization of PWUD and compounding experiences of discrimination; (2) perceptions of overall neglect; (3) inadequate pain and withdrawal management; and (4) leaving ED against medical advice and a lack of willingness to engage in future care., Conclusions: Structural vulnerabilities in ED can negatively impact the care received among PWUD. Findings demonstrate the need to consider how structural factors impact care for PWUD and to leverage existing infrastructure to incorporate harm reduction and a structural competency focused care. Findings also point to the need to consider how withdrawal and pain are managed in emergency department settings., Competing Interests: The authors have declared no competing interests., (Copyright: © 2023 Mayer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

To address the need for simple, safe, sensitive, and scalable SARS-CoV-2 tests, we validated and implemented a PCR test that uses a saliva collection kit use at home. Individuals self-collected 300 μl saliva in vials containing Darnell Rockefeller University Laboratory (DRUL) buffer and extracted RNA was assayed by RT-PCR (the DRUL saliva assay). The limit of detection was confirmed to be 1 viral copy/μl in 20 of 20 replicate extractions. Viral RNA was stable in DRUL buffer at room temperature up to seven days after sample collection, and safety studies demonstrated that DRUL buffer immediately inactivated virus at concentrations up to 2.75x106 PFU/ml. Results from SARS-CoV-2 positive nasopharyngeal (NP) swab samples collected in viral transport media and assayed with a standard FDA Emergency Use Authorization (EUA) test were highly correlated with samples placed in DRUL buffer. Direct comparison of results from 162 individuals tested by FDA EUA oropharyngeal (OP) or NP swabs with co-collected saliva samples identified four otherwise unidentified positive cases in DRUL buffer. Over six months, we collected 3,724 samples from individuals ranging from 3 months to 92 years of age. This included collecting weekly samples over 10 weeks from teachers, children, and parents from a pre-school program, which allowed its safe reopening while at-risk pods were quarantined. In sum, we validated a simple, sensitive, stable, and safe PCR-based test using a self-collected saliva sample as a valuable tool for clinical diagnosis and screening at workplaces and schools., Competing Interests: T.P.S. wishes to thank the Richard Lounsbery Foundation, the Elinor Schwartz Charitable Trust and the Danica Foundation for support. DEO is an inventor on a provisional unlicensed patent entitled “Method and System for RNA Isolation from Self-Collected and Small Volume Samples”, US 63/050,155. C.M.R acknowledges the generous support of the G. Harold and Leila Y. Mathers Charitable Foundation, the BAWD Foundation, and The Rockefeller University. R.B.D. discloses that he receives consulting fees as a Senior Visiting Fellow at MITRE Corporation, that he has started a charitable LLC, D4S Testing, to offer free DRUL saliva testing to NYC school children, and that he is an Investigator of the Howard Hughes Medical Institute. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

Background: Trauma is a leading cause of death and disability worldwide. In low- and middle-income countries (LMICs), trauma patients have a higher risk of experiencing delays to care due to limited hospital resources and difficulties in reaching a health facility. Reducing delays to care is an effective method for improving trauma outcomes. However, few studies have investigated the variety of care delays experienced by trauma patients in LMICs. The objective of this study was to describe the prevalence of pre- and in-hospital delays to care, and their association with poor outcomes among trauma patients in a low-income setting., Methods: We used a prospective traumatic brain injury (TBI) registry from Kilimanjaro Christian Medical Center in Moshi, Tanzania to model nine unique delays to care. Multiple regression was used to identify delays significantly associated with poor in-hospital outcomes., Results: Our analysis included 3209 TBI patients. The most common delay from injury occurrence to hospital arrival was 1.1 to 4.0 hours (31.9%). Most patients were evaluated by a physician within 15.0 minutes of arrival (69.2%). Nearly all severely injured patients needed and did not receive a brain computed tomography scan (95.0%). A majority of severely injured patients needed and did not receive oxygen (80.8%). Predictors of a poor outcome included delays to lab tests, fluids, oxygen, and non-TBI surgery., Conclusions: Time to care data is informative, easy to collect, and available in any setting. Our time to care data revealed significant constraints to non-personnel related hospital resources. Severely injured patients with the greatest need for care lacked access to medical imaging, oxygen, and surgery. Insights from our study and future studies will help optimize resource allocation in low-income hospitals thereby reducing delays to care and improving trauma outcomes in LMICs., Competing Interests: The authors have declared that no competing interests exist.

To disseminate research, scholars once relied on university media services or journal press releases, but today any academic can turn to Twitter to share their published work with a broader audience. The possibility that scholars can push their research out, rather than hope that it is pulled in, holds the potential for scholars to draw wide attention to their research. In this manuscript, we examine whether there are systematic differences in the types of scholars who most benefit from this push model. Specifically, we investigate the extent to which there are gender differences in the dissemination of research via Twitter. We carry out our analyses by tracking tweet patterns for articles published in six journals across two fields (political science and communication), and we pair this Twitter data with demographic and educational data about the authors of the published articles, as well as article citation rates. We find considerable evidence that, overall, article citations are positively correlated with tweets about the article, and we find little evidence to suggest that author gender affects the transmission of research in this new media., Competing Interests: The authors have declared that no competing interests exist.

Plant-parasitic nematodes of the genus Meloidogyne, known as root-knot nematodes (RKN), have an important economic impact on golf course turfgrasses. The most prevalent RKN species associated with grasses are M. chitwoodi, M. graminicola, M. graminis, M. incognita, M. marylandi, M. microtyla, M. minor, M. naasi and M. sasseri. In 2010, slight thickening of the roots and RKN females with unusual features were observed in turfgrass roots on golf courses in Araras, São Paulo state, Brazil. This population (MgARA) was maintained in the lab and studied including morphological, morphometrical, biochemical and molecular markers. Morphology and morphometry were variable and not useful for identification, although perineal pattern morphology showed highly similarity with M. graminis description. Concerning to biochemical characterisation, the esterase phenotype Mg1, characterised by a very slow and fainter band, was detected in some protein homogenates. Regarding to molecular analysis, D2-D3 region of 28S rDNA gene and cytochrome oxidase subunit II region from mitochondrial DNA were amplified by PCR and sequenced. Phylogenetic analysis revealed that the Brazilian isolate, found associated with turfgrass, grouped with M. graminis isolates (98-99% bootstrap; variation of 8-11 and 0-24 bp, respectively), close to M. marylandi, supporting its identification as M. graminis. This is the first report of M. graminis on golf courses in Brazil.

Background: Misiones Province in northeastern Argentina is considered to be a region with a high prevalence of HPV infection and a high mortality rate due to cervical cancer. The reasons for this epidemiological trend are not completely understood. To gain insight into this problem, we explored the relationship between mitochondrial DNA (mtDNA) ancestry, HPV infection, and development of cervical lesions/cancer in women from the city of Posadas in Misiones Province., Methods: Two hundred and sixty-one women, including 92 cases of patients diagnosed with cervical lesions and 169 controls, were analyzed. mtDNA ancestry was assessed through HVS1 sequencing, while the detection and typing of HPV infection was conducted through nested multiplex PCR analysis. Multivariate logistic regression was conducted with the resulting data to estimate the odds ratios (ORs) adjusted by socio-demographic variables., Results: The study participants showed 68.6% Amerindian, 26.1% European and 5.3% African mtDNA ancestry, respectively. Multiple regression analysis showed that women with African mtDNAs were three times more likely to develop a cervical lesion than those with Native American or European mtDNAs [OR of 3.8 (1.2-11.5) for ancestry and OR of 3.5 (1.0-12.0) for L haplogroups], although the associated p values were not significant when tested under more complex multivariate models. HPV infection and the development of cervical lesions/cancer were significant for all tested models, with the highest OR values for HPV16 [OR of 24.2 (9.3-62.7)] and HPV-58 [OR of 19.0 (2.4-147.7)]., Conclusion: HPV infection remains a central risk factor for cervical cancer in the Posadas population. The potential role of African mtDNA ancestry opens a new avenue for future medical association studies in multiethnic populations, and will require further confirmation in large-scale studies.

Background: Safety champions are effective in a variety of safety initiatives; however, there are no reports of their role in hospital-acquired infections prevention., Objective: We aimed to describe the association of the presence of a physician safety champion with our urinary catheter device utilization ratios (DUR) in the Pediatric Intensive Care Unit (PICU)., Methods: Our PICU has incidence rates of catheter-associated urinary tract infections (CAUTI) and urinary catheter DUR above the 90th percentile. Using a quasi-experimental design, we compared our DUR when the PICU team was exposed and unexposed (champion's maternity leaves) to a physician safety champion. Hospital acquired infection (HAI) surveillance of all PICU admissions between April 1st 2009 and June 29th 2013 was done prospectively. To ensure stable acuity of the patient population over time, we used the central venous catheter (CVC) DUR as a control., Results: The urinary catheter DUR was 0.44 (95% confidence interval [CI] 0.42-0.45) during the unexposed period versus 0.39 (95%CI 0.38-0.40) during the exposed period, for an absolute difference of 0.05 (95%CI 0.03-0.06; p<0.0001). The overall CVC DUR increased from 0.57 (95%CI 0.55-0.58) during the unexposed period to 0.63 (95%CI 0.61-0.64) during the exposed period, an absolute increase of 0.06 (95%CI 0.04-0.08; p<0.0001). Comparing the exposed and unexposed periods, adjusting for time trend, we observed a 17% decrease in the urinary catheter DUR when the safety champion was present (odds ratio [OR] 0.83; 95%CI 0.77-0.90). The rate of catheter-associated urinary tract infections did not change., Conclusions: The presence of a unit-based safety champion can have a positive impact on urinary catheter DUR in a PICU.

How do student-athletes form opinions? This is a particularly important question given ongoing debates about whether student-athletes should be paid and/or allowed to unionize. These debates concern the rights and benefits accrued directly to student-athletes, and thus, understanding their attitudes is of obvious import. Yet, virtually no recent work has delved into how student-athletes form opinions on these issues. We fill this gap with a theoretical framework that predicts changes in social context alter opinions. This leads to the hypothesis that opinions will change once a student-athlete completes his/her career and finds him/herself in a distinct social network. We test the prediction with a survey, implemented in 2012, of one of the most notable athletic conferences in the National Collegiate Athletic Association (NCAA): the Big Ten. We find that post-career student-athletes demonstrate higher levels of support for pay for play and unionization. Our results suggest that student-athletes' opinions seem to depend on their extant social contexts. While our data, from 2012, neither speak to current opinions - given the quickly evolving landscape of college athletics - nor demonstrate what reforms may be "best," they do accentuate the power of social context in shaping student-athletes' attitudes.

Background and Purpose: In this study, we demonstrate the use of Molecular topology (MT) in an Alzheimer's disease (AD) drug discovery program. MT uses and expands upon the principles governing the molecular connectivity theory of numerically characterizing molecular structures, in the present case, active anti-AD drugs/agents, using topological descriptors to build models. Topological characterization has been shown to embody sufficient molecular information to provide strong correlation to therapeutic efficacy., Experimental Approach: We used MT to include multiple bioactive properties that allows for the identification of multi-functional single agent compounds, in this case, the dual functions of β-amyloid (Aβ) -lowering and anti-oligomerization. Using this technology, we identified and designed novel compounds in chemical classes unrelated to current anti-AD agents that exert dual Aβ lowering and anti-Aβ oligomerization activities in animal models of AD. AD is a multifaceted disease with different pathological features., Conclusion and Implications: Our study, for the first time, demonstrated that MT can provide novel strategy for discovering drugs with Aβ lowering and anti-aggregation dual activities for AD.

Next-generation sequencing (NGS) studies in cancer are limited by the amount, quality and purity of tissue samples. In this situation, primary xenografts have proven useful preclinical models. However, the presence of mouse-derived stromal cells represents a technical challenge to their use in NGS studies. We examined this problem in an established primary xenograft model of small cell lung cancer (SCLC), a malignancy often diagnosed from small biopsy or needle aspirate samples. Using an in silico strategy that assign reads according to species-of-origin, we prospectively compared NGS data from primary xenograft models with matched cell lines and with published datasets. We show here that low-coverage whole-genome analysis demonstrated remarkable concordance between published genome data and internal controls, despite the presence of mouse genomic DNA. Exome capture sequencing revealed that this enrichment procedure was highly species-specific, with less than 4% of reads aligning to the mouse genome. Human-specific expression profiling with RNA-Seq replicated array-based gene expression experiments, whereas mouse-specific transcript profiles correlated with published datasets from human cancer stroma. We conclude that primary xenografts represent a useful platform for complex NGS analysis in cancer research for tumours with limited sample resources, or those with prominent stromal cell populations.