Miracle-dz/UniFAR-FTUs huggingface dataset:
Porcine sperm vitrification I: cryoloops method

The aims of this study were to evaluate porcine sperm vitrification in cryoloops, with and without two different cryoprotectants and assess two warming procedures. Extended (n = 3; r = 4) and raw (n = 5; r = 2) semen was diluted in media without and with cryoprotectants (4% dimethylformamide and 4% glycerol) to a final concentration of 20 × 106 spermatozoa ml−1 and vitrified using the cryoloops method. Two warming procedures were evaluated: rapid method (30 s at 37°C) and an ultra‐rapid method (7 s at 75°C, followed by 30 s at 37°C). Total motility (phase contrast), sperm viability (6‐carboxifluorescein diacetate and propidium iodide stain), membrane function (hypo‐osmotic swelling test), acrosome integrity (phase contrast), chromatin condensation (toluidine blue stain) and chromatin susceptibility to acid denaturation (acridine orange stain) were evaluated before and after vitrification and analysed using Friedman's test. In all media, the only seminal parameters that were maintained after vitrification were chromatin condensation and integrity. Vitrification of porcine spermatozoon using cryoloops, both in the presence or absence of cryoprotectants and independent of the warming procedure used, permits conservation of sperm chromatin condensation and integrity. It would be interesting to further verify this by producing porcine embryos using vitrified spermatozoon with intracytoplasmic sperm injection.
Gossypol Induces Apoptosis by Activating p53 in Prostate Cancer Cells and Prostate Tumor–Initiating Cells

Prostate cancer continues to represent a burgeoning medical problem in the United States. Recent studies suggest that gossypol, a bioactive phytochemical produced by cotton plants, is a promising agent against prostate cancer. The current studies were undertaken to examine the chemotherapeutic efficacy of gossypol on human prostate cancer cell lines and prostate tumor–initiating cells. Gossypol reduced the viability of three prostate cancer cell lines (LAPC4, PC3, and DU145) with an IC50 between 3 and 5 μmol/L. Additionally, gossypol was effective at inhibiting prostate tumor–initiating cell-driven tumor growth in a nonobese diabetic/severe combined immunodeficient xenograft model. Our integrated molecular profiling approach encompassing proteomics, activated transcription factors, and genomics suggests that the decrease in viability was associated with increased DNA damage and the induction of apoptosis. Exposure of DU145 cells to gossypol (1–10 μmol/L) resulted in the activation of 13 proteins and 7 transcription factors, and the expression of 17 genes involved in the mitochondrial pathway of apoptosis. These studies show for the first time that gossypol treatment induces DNA damage and activates p53. Collectively, these data support the use of gossypol as a novel agent for prostate cancer. Mol Cancer Ther; 9(2); 461–70
From One Syndrome to Many: Incorporating Geriatric Consultation Into HIV Care

Antiretroviral therapy has enabled people to live long lives with human immunodeficiency virus (HIV). As a result, most HIV-infected adults in the United States are >50 years of age. In light of this changing epidemiology, HIV providers must recognize and manage multiple comorbidities and aging-related syndromes. Geriatric principles can help meet this new challenge, as preservation of function and optimization of social and psychological health are relevant to the care of aging HIV-infected adults, even those who are not yet old. Nonetheless, the field is still in its infancy. Although other subspecialties have started to explore the role of geriatricians, little is known about their role in HIV care, and few clinics have incorporated geriatricians. This article introduces basic geriatric nomenclature and principles, examines several geriatric consultation models from other subspecialties, and describes our HIV and Aging clinical program to encourage investigation of best practices for the care of this population.
Strigolactones cross the kingdoms: plants, fungi, and bacteria in the arbuscular mycorrhizal symbiosis

Strigolactones (SLs) first evolved as regulators of simple developmental processes in very ancient plant lineages, and then assumed new roles to sustain the increasing biological complexity of land plants. Their versatility is also shown by the fact that during evolution they have been exploited, once released in the rhizosphere, as a communication system towards plant-interacting organisms even belonging to different kingdoms. Here, we reviewed the impact of SLs on soil microbes, paying particular attention to arbuscular mycorrhizal fungi (AMF). SLs induce several responses in AMF, including spore germination, hyphal branching, mitochondrial metabolism, transcriptional reprogramming, and production of chitin oligosaccharides which, in turn, stimulate early symbiotic responses in the host plant. In the specific case study of the AMF Gigaspora margarita, SLs are also perceived, directly or indirectly, by the well-characterized population of endobacteria, with an increase of bacterial divisions and the activation of specific transcriptional responses. The dynamics of SLs during AM root colonization were also surveyed. Although not essential for the establishment of this mutualistic association, SLs act as positive regulators as they are relevant to achieve the full extent of colonization. This possibly occurs through a complex crosstalk with other hormones such as auxin, abscisic acid, and gibberellins.
Immunology of lymphatic filariasis

The immune responses to filarial parasites encompass a complex network of innate and adaptive cells whose interaction with the parasite underlies a spectrum of clinical manifestations. The predominant immunological feature of lymphatic filariasis is an antigen‐specific Th2 response and an expansion of IL‐10 producing CD4+ T cells that is accompanied by a muted Th1 response. This antigen‐specific T‐cell hyporesponsiveness appears to be crucial for the maintenance of the sustained, long‐standing infection often with high parasite densities. While the correlates of protective immunity to lymphatic filariasis are still incompletely understood, primarily due to the lack of suitable animal models to study susceptibility, it is clear that T cells and to a certain extent B cells are required for protective immunity. Host immune responses, especially CD4+ T‐cell responses clearly play a role in mediating pathological manifestations of LF, including lymphedema, hydrocele and elephantiasis. The main underlying defect in the development of clinical pathology appears to be a failure to induce T‐cell hyporesponsiveness in the face of antigenic stimulation. Finally, another intriguing feature of filarial infections is their propensity to induce bystander effects on a variety of immune responses, including responses to vaccinations, allergens and to other infectious agents. The complexity of the immune response to filarial infection therefore provides an important gateway to understanding the regulation of immune responses to chronic infections, in general.
Genetic analysis of uterine adenosarcomas and phyllodes tumors of the breast

Uterine adenosarcomas and breast phyllodes tumors (PTs) are morphologically similar, being composed of stromal projections in a leaf‐like fashion lined by epithelial cells. Here, we investigated whether their histologic similarities would be mirrored at the genetic level. The previously reported repertoires of somatic genetic alterations found in 19 adenosarcomas and 22 PTs (six benign, six borderline, and 10 malignant) were compared. PTs significantly more frequently displayed mutations affecting MED12, the TERT gene promoter and bona fide cancer genes, whereas adenosarcomas harbored a higher rate of MDM2/CDK4 and TERT gene amplifications. Pathway analyses based on the genes affected by somatic genetic alterations in these tumors indicated that Wnt signaling likely plays a role in the biology of adenosarcomas and benign/borderline PTs. In conclusion, despite the differences at the gene level, PTs and adenosarcomas share remarkable morphologic similarities and enrichment for somatic genetic alterations affecting Wnt pathway‐related genes.
Factors associated with self-reported adherence among adolescents on antiretroviral therapy in Zimbabwe

Nonadherence to medication is the key obstacle to human immunodeficiency virus (HIV) treatment success. The group at highest risk of nonadherence is adolescents, but relatively little is known about risk factors for and protective factors against poor adherence in this age group. We undertook a cross-sectional study of 262 HIV-infected adolescents aged 10–19 years on antiretroviral therapy at two clinics in Harare, Zimbabwe, to investigate personal and system-level factors associated with optimal self-reported adherence. Suboptimal adherence was common with only 101 (39%) reporting “excellent” adherence. Having the guardian present at each clinical encounter, comfort with asking questions to the health provider and participating in group sessions led by a professional facilitator were all significantly associated with excellent adherence (p < 0.05). Strengthening the parent–child dyad and professional-led groups as strategies to improve adherence should be evaluated.
Risk of Kaposi sarcoma during the first months on combination antiretroviral therapy

Objective:To determine whether incident AIDS-defining Kaposi sarcoma or Pneumocystis jiroveci pneumonia (PJP) is associated with combination antiretroviral therapy (cART) initiation. Design:Compare risk for Kaposi sarcoma and PJP by time on cART and CD4 reconstitution. Methods:In the FHDH-ANRS CO4 cohort (N = 66 369), Kaposi sarcoma (N = 1811) and PJP (N = 1718) incidence rates were computed by demographic and HIV strata. Crude and adjusted relative risk (RR) with 95% confidence intervals (CIs) following cART initiation were calculated by Poisson regression with untreated patients during 1996–2009 as reference. CD4 cell counts were compared by Wilcoxon rank sum tests. Results:The risk of Kaposi sarcoma was very high during months 1–3 on cART (N = 160, RRCrude 3.94, 95% CI 3.26–4.76), which was incompletely attenuated by adjustment for demographics and contemporaneous CD4 cell count (RRAdj 1.25, 95% CI 1.02–1.53). Corresponding PJP risk was minimally elevated (N = 84, RRCrude 1.80, 95% CI 1.42–2.30) and markedly reduced with adjustment on the same variables and PJP prophylaxis (RRAdj 0.52, CI 0.41–0.67). HIV load had no added effect. Median CD4 cell count at cART initiation was much lower in patients with incident Kaposi sarcoma (82 cells/&mgr;l) or PJP (61 cells/&mgr;l) within 3 months than in those who did not develop these conditions (>250 cells/&mgr;l). Notably, median CD4 cell count change was +44 cells/&mgr;l per month with incident Kaposi sarcoma within 3 months of cART initiation versus 0 cells/&mgr;l per month with incident PJP (P = 0.0003). Conclusion:Failure of CD4 cell count reconstitution during months 1–3 on cART fully accounted for incident PJP. In contrast, there were 1.6 additional Kaposi sarcoma cases per 1000 person-years during months 1–3 on cART, suggesting that immune reconstitution may contribute to the risk for AIDS-defining Kaposi sarcoma.
Yawning and locomotor behavior induced by dopamine receptor agonists in mice and rats

Dopaminergic (DA) agonist-induced yawning in rats seems to be mediated by DA D3 receptors, and low doses of several DA agonists decrease locomotor activity, an effect attributed to presynaptic D2 receptors. Effects of several DA agonists on yawning and locomotor activity were examined in rats and mice. Yawning was reliably produced in rats, and by the cholinergic agonist, physostigmine, in both the species. However, DA agonists were ineffective in producing yawning in Swiss–Webster or DA D2R and DA D3R knockout or wild-type mice. The drugs significantly decreased locomotor activity in rats at one or two low doses, with activity returning to control levels at higher doses. In mice, the drugs decreased locomotion across a 1000–10 000-fold range of doses, with activity at control levels (U-91356A) or above control levels [(±)-7-hydroxy-2-dipropylaminotetralin HBr, quinpirole] at the highest doses. Low doses of agonists decreased locomotion in all mice except the DA D2R knockout mice, but were not antagonized by DA D2R or D3R antagonists (L-741 626, BP 897, or PG01037). Yawning does not provide a selective in-vivo indicator of DA D3R agonist activity in mice. Decreases in mouse locomotor activity by the DA agonists seem to be mediated by D2 DA receptors.
Identifying genes required for respiratory growth of fission yeast

We have used both auxotroph and prototroph versions of the latest deletion-mutant library to identify genes required for respiratory growth on solid glycerol medium in fission yeast. This data set complements and enhances our recent study on functional and regulatory aspects of energy metabolism by providing additional proteins that are involved in respiration. Most proteins identified in this mutant screen have not been implicated in respiration in budding yeast. We also provide a protocol to generate a prototrophic mutant library, and data on technical and biological reproducibility of colony-based high-throughput screens.
The connotations of botho philosophy and its potential contribution towards environmental conservation: the case of Tlokoeng community in Lesotho

This paper explores innovative environmental education strategies to conserve biodiversity in a rural-based context, in Lesotho. A case study approach was employed to investigate the community’s conception of botho philosophy and how it might promote nature conservation. Focus Group Interviews were conducted with 105 participants. The responses were analyzed to determine the community’s emerging definition and conception of botho. The findings indicate features of botho that parallel the ones that are found in the literature. In addition, botho was described metaphysically as a holistic spiritualised worldview that is concerned with a harmonious co-existence with others, nature and the Creator and empirically, in terms of moral attributes that foster co-existence within the socio-economic and natural systems. It is illustrated that botho can contribute towards environmental education discourse and nature conservation and thus diversify the pre-dominantly Euro-centric knowledge landscape in Lesotho.
Sustaining guideline implementation: A multisite perspective on activities, challenges and supports.

AIMS AND OBJECTIVES To examine activities conducted, challenges encountered and supports used when sustaining nursing practice guideline implementation in multiple healthcare organisations over 3 years. BACKGROUND Numerous models and frameworks exist to guide the implementation of guidelines, yet very few focus on sustaining improved practice changes. It is not known if one intervention or multiple interventions are required, nor the long-term activities, challenges and supports for sustaining improved practices. DESIGN Qualitative descriptive study. METHODS We conducted focus group interviews with steering committee members and individual interviews with leaders and direct care providers at the end of a 3-year guideline implementation study. The National Health Service Sustainability Model was used to guide data collection and analysis. RESULTS The eight sites included three teaching hospitals, a community hospital, a long-term care facility, two community health agencies and a community health centre. Individual interviews were conducted with 36 leaders and 26 direct care providers. Focus group interviews were conducted with steering committee members (n = 70) at each site. Guideline implementation activities (n = 45) included developing new outcome monitoring systems, conducting chart audits, communicating progress to internal stakeholders, appointing interprofessional staff to steering committees, developing educational sessions and resources for staff and patients, revising policies and procedures, and developing partnerships with external organisations. Supports included lessons learned from previous and concurrent change initiatives, and commitment, involvement and positive attitudes of staff and leaders. CONCLUSION Activities identified by the participants addressed all 10 factors in the Sustainability Model in the three areas of process, staff and organisation. The challenges and supports encountered provide insights into the process of guideline implementation and sustainability. RELEVANCE TO CLINICAL PRACTICE A multilevel action plan for staff, leaders and the organisation is recommended when introducing and sustaining practice changes.
Efficacy of Local Antimicrobials in the Non-Surgical Treatment of Patients With Periodontitis and Diabetes: A Systematic Review.

BACKGROUND Patients with diabetes present a worse response to periodontal treatment. Local antimicrobials as an adjunct to scaling and root planing (SRP) provide additional benefits in the treatment of periodontitis in healthy patients. This review aims to evaluate the effects of local antimicrobials as an adjunct to SRP, compared with SRP alone, on periodontal clinical parameters of patients with chronic periodontitis (CP) and diabetes mellitus (DM). METHODS Only randomized controlled trials with: 1) at least 6 months of follow-up; 2) SRP, in combination with local antimicrobials; and 3) patients with periodontitis and DM were considered eligible. MEDLINE, EMBASE, and LILACS databases were searched for articles published up to January 2016. Random-effects meta-analyses were conducted for clinical attachment level (CAL), probing depth (PD), bleeding on probing, and gingival index change after treatment. RESULTS Of 153 papers potentially relevant to this review, six were included. The majority of trials showed a significant PD reduction and CAL gain associated with use of local antimicrobials in patients with type 1 and type 2 DM. Only studies that included well-controlled patients and applied antimicrobials at the deepest sites or sites with baseline PD ≥5 mm presented significant PD reduction and CAL gain. CONCLUSION In patients with DM and CP, use of local antimicrobials as an adjunct to SRP may result in additional benefits compared with SRP alone in PD reduction and CAL gain, especially in well-controlled individuals and deep sites.
Diagnostic performance of combined noninvasive coronary angiography and myocardial perfusion imaging using 320-MDCT: the CT angiography and perfusion methods of the CORE320 multicenter multinational diagnostic study.

OBJECTIVE Coronary MDCT angiography has been shown to be an accurate noninvasive tool for the diagnosis of obstructive coronary artery disease (CAD). Its sensitivity and negative predictive value for diagnosing percentage of stenosis are unsurpassed compared with those of other noninvasive testing methods. However, in its current form, it provides no information regarding the physiologic impact of CAD and is a poor predictor of myocardial ischemia. CORE320 is a multicenter multinational diagnostic study with the primary objective to evaluate the diagnostic accuracy of 320-MDCT for detecting coronary artery luminal stenosis and corresponding myocardial perfusion deficits in patients with suspected CAD compared with the reference standard of conventional coronary angiography and SPECT myocardial perfusion imaging. CONCLUSION We aim to describe the CT acquisition, reconstruction, and analysis methods of the CORE320 study.
Treatment of Heart Failure by a Methanocarba Derivative of Adenosine Monophosphate: Implication for a Role of Cardiac Purinergic P2X Receptors

Evidence is accumulating to support a potentially important role for purinergic (P2X) receptors in heart failure (HF). We tested the hypothesis that a hydrolysis-resistant nucleotide analog with agonist activity at myocardial P2X receptors (P2XRs) improves the systolic HF phenotype in mouse and dog models. We developed a hydrolysis-resistant adenosine monophosphate derivative, (1′S,2R,3S,4′R,5′S)-4-(6-amino-2-chloro-9H-purin-9-yl)-1-[phosphoryloxymethyl] bicycle[3.1. 0]hexane-2,3-diol) (MRS2339), with agonist activity at native cardiac P2XRs. Chronic MRS2339 infusion in postinfarct and calsequestrin (CSQ) mice with HF resulted in higher rates of pressure change (+dP/dt), left ventricle (LV)-developed pressure, and cardiac output in an in vitro working heart model. Heart function in vivo, as determined by echocardiography-derived fractional shortening, was also improved in MRS2339-infused mice. The beneficial effect of MRS2339 was dose-dependent and was identical to that produced by cardiac myocyte-specific overexpression of the P2X4 receptor. The HF improvement was associated with the preservation of LV wall thickness in both systole and diastole in postinfarct and CSQ mice. In dogs with pacing-induced HF, MRS2339 infusion reduced left ventricular end-diastolic pressure, improved arterial oxygenation, and increased +dP/dt. MRS2339 treatment also decreased LV chamber size in mice and dogs with HF. In murine and canine models of systolic HF, in vivo administration of a P2X nucleotide agonist improved contractile function and cardiac performance. These actions were associated with preserved LV wall thickness and decreased LV remodeling. The data are consistent with a role of cardiac P2XRs in mediating the beneficial effect of this agonist.
BURNOUT E FATORES ASSOCIADOS EM DOCENTES DA UNIVERSIDADE FEDERAL DO RIO DE JANEIRO

As Universidades, nas ultimas decadas, tem vivenciado problemas de recursos e condicoes precarias de trabalho. A partir dos anos 90, se institucionalizou uma nova forma de gestao administrativa e academica que acabou impactando nos processos de trabalho e no adoecimento dos docentes do nivel superior, em particular. Este artigo tem por objetivo apresentar os indices de Burnout em docentes da Universidade Federal do Rio de Janeiro-UFRJ em 2014, e investigar a correlacao entre ela e caracteristicas demograficas, laborais e condicoes de saude e lazer. Foram entrevistados 155 docentes das areas da saude, exatas e humanas. Utilizou-se um instrumento auto aplicado composto por variaveis demograficas, laborais e pela escala Maslach Burnout Inventory (MBI). Os resultados apontaram que a dimensao da exaustao emocional foi a que mais apresentou fatores associados e que as mulheres mais jovens foram as mais vulneraveis nesta dimensao, evidenciando a sobrecarga de trabalho como fator de risco. Conclui-se, entao, que a sobrecarga de trabalho tem funcionado como fator de risco na vida dos docentes da UFRJ, tornando-os vulneraveis ao desenvolvimento de Burnout, principalmente, no tocante a dimensao da exaustao emocional.
Amyloid-β1–42 Slows Clearance of Synaptically Released Glutamate by Mislocalizing Astrocytic GLT-1

GLT-1, the major glutamate transporter in the adult brain, is abundantly expressed in astrocytic processes enveloping synapses. By limiting glutamate escape into the surrounding neuropil, GLT-1 preserves the spatial specificity of synaptic signaling. Here we show that the amyloid-β peptide Aβ1–42 markedly prolongs the extracellular lifetime of synaptically released glutamate by reducing GLT-1 surface expression in mouse astrocytes and that this effect is prevented by the vitamin E derivative Trolox. These findings indicate that astrocytic glutamate transporter dysfunction may play an important role in the pathogenesis of Alzheimer's disease and suggest possible mechanisms by which several current treatment strategies could protect against the disease.