Field experience with the 8-HPV-type oncoprotein test for cervical cancer screening among HPV-positive women living with and without HIV in LMICs.

Overexpression of HPV-oncoproteins E6 and E7 is necessary for HPV-driven cervical carcinogenesis. Hence, these oncoproteins are promising disease-specific biomarkers. We assessed the technical and operational characteristics of the 8-HPV-type OncoE6/E7 Cervical Test in different laboratories using cervical samples from HPV-positive women living with (WLWH) and without HIV. The 8-HPV-type OncoE6/E7 Test (for short: "OncoE6/E7 test") was performed in 2833 HIV-negative women and 241 WLWH attending multicentric studies in Latin America (ESTAMPA study), and in Africa (CESTA study). Oncoprotein positivity were evaluated at each testing site, according to HIV status as well as type-specific agreement with HPV-DNA results. A feedback questionnaire was given to the operators performing the oncoprotein test to evaluate their impression and acceptability regarding the test. The OncoE6/E7 test revealed a high positivity rate heterogeneity across all testing sites (I2: 95.8%, p < .01) with significant lower positivity in WLWH compared to HIV-negative women (12% vs 25%, p < .01). A similar HPV-type distribution was found between HPV DNA genotyping and oncoprotein testing except for HPV31 and 33 (moderate agreement, k = 0.57). Twenty-one laboratory technicians were trained on oncoprotein testing. Despite operators' concerns about the time-consuming procedure and perceived need for moderate laboratory experience, they reported the OncoE6/E7 test as easy to perform and user-friendly for deployment in resource-limited settings. The high positivity rate variability found across studies and subjectivity in test outcome interpretation could potentially results in oncoprotein false positive/negative, and thus the need for further refinements before implementation of the oncoprotein testing in screen-triage-and-treat approaches is warranted.

Bathymetric origin shapes the physiological responses of Pterygophora californica (Laminariales, Phaeophyceae) to deep marine heatwaves.

Kelp communities are experiencing exacerbated heat-related impacts from more intense, frequent, and deeper marine heatwaves (MHWs), imperiling the long-term survival of kelp forests in the climate change scenario. The occurrence of deep thermal anomalies is of critical importance, as elevated temperatures can impact kelp populations across their entire bathymetric range. This study evaluates the impact of MHWs on mature sporophytes of Pterygophora californica (walking kelp) from the bathymetric extremes (8-10 vs. 25-27 m) of a population situated in Baja California (Mexico). The location is near the southernmost point of the species's broad distribution (from Alaska to Mexico). The study investigated the ecophysiological responses (e.g., photobiology, nitrate uptake, oxidative stress) and growth of adult sporophytes through a two-phase experiment: warming simulating a MHW and a post-MHW phase without warming. Generally, the effects of warming differed depending on the bathymetric origin of the sporophytes. The MHW facilitated essential metabolic functions of deep-water sporophytes, including photosynthesis, and promoted their growth. In contrast, shallow-water sporophytes displayed metabolic stress, reduced growth, and oxidative damage. Upon the cessation of warming, certain responses, such as a decline in nitrate uptake and net productivity, became evident in shallow-water sporophytes, implying a delay in heat-stress response. This indicates that variation in temperatures can result in more prominent effects than warming alone. The greater heat tolerance of sporophytes in deeper waters shows convincing evidence that deep portions of P. californica populations have the potential to serve as refuges from the harmful impacts of MHWs on shallow reefs.

Performance of visual inspection of the cervix with acetic acid (VIA) for triage of HPV screen-positive women: results from the ESTAMPA study.

VIA is recommended for triage of HPV-positive women attending cervical screening. In the multicentric ESTAMPA study, VIA performance for detection of cervical intraepithelial neoplasia grade 3 or worse (CIN3+) among HPV-positive women was evaluated. Women aged 30-64 years were screened with HPV testing and cytology and referred to colposcopy if either test was positive. At colposcopy visit, study-trained midwives/nurses/GPs performed VIA ahead of colposcopy. VIA was considered positive if acetowhite lesions were observed in or close to the transformation zone. Ablative treatment eligibility was assessed for VIA positives. Performance indicators were estimated. Three thousand one hundred and forty-two HPV-positive women were included. Sensitivity for CIN3+ was 85.9% (95% CI 81.2-89.5) among women <50 years and, although not significant, slightly lower in women 50+ (78.0%, 95% CI 65.9-86.6). Overall specificity was 58.6% (95% CI 56.7-60.5) and was significantly higher among women 50+ (70.3%, 95% CI 66.8-73.5) compared to women <50 (54.3%, 95% CI 52.1-56.5). VIA positivity was lower among women 50+ (35.2%, 95% CI 31.9-38.6) compared to women <50 (53.2, 95% CI 51.1-55.2). Overall eligibility for ablative treatment was 74.5% and did not differ by age. VIA sensitivity, specificity, and positivity, and ablative treatment eligibility varied highly by provider (ranges: 25%-95.4%, 44.9%-94.4%, 8.2%-65.3%, 0%-98.7%, respectively). VIA sensitivity for cervical precancer detection among HPV-positive women performed by trained providers was high with an important reduction in referral rates. However, scaling-up HPV screening triaged by VIA will be challenging due to the high variability of VIA performance and providers' need for training and supervision.

Dyspnea Severity Assessment Based on Vocalization Behavior with Deep Learning on the Telephone.

In this paper, a system to assess dyspnea with the mMRC scale, on the phone, via deep learning, is proposed. The method is based on modeling the spontaneous behavior of subjects while pronouncing controlled phonetization. These vocalizations were designed, or chosen, to deal with the stationary noise suppression of cellular handsets, to provoke different rates of exhaled air, and to stimulate different levels of fluency. Time-independent and time-dependent engineered features were proposed and selected, and a k-fold scheme with double validation was adopted to select the models with the greatest potential for generalization. Moreover, score fusion methods were also investigated to optimize the complementarity of the controlled phonetizations and features that were engineered and selected. The results reported here were obtained from 104 participants, where 34 corresponded to healthy individuals and 70 were patients with respiratory conditions. The subjects' vocalizations were recorded with a telephone call (i.e., with an IVR server). The system provided an accuracy of 59% (i.e., estimating the correct mMRC), a root mean square error equal to 0.98, false positive rate of 6%, false negative rate of 11%, and an area under the ROC curve equal to 0.97. Finally, a prototype was developed and implemented, with an ASR-based automatic segmentation scheme, to estimate dyspnea on line.

Automatic Detection of Dyspnea in Real Human-Robot Interaction Scenarios.

A respiratory distress estimation technique for telephony previously proposed by the authors is adapted and evaluated in real static and dynamic HRI scenarios. The system is evaluated with a telephone dataset re-recorded using the robotic platform designed and implemented for this study. In addition, the original telephone training data are modified using an environmental model that incorporates natural robot-generated and external noise sources and reverberant effects using room impulse responses (RIRs). The results indicate that the average accuracy and AUC are just 0.4% less than those obtained with matched training/testing conditions with simulated data. Quite surprisingly, there is not much difference in accuracy and AUC between static and dynamic HRI conditions. Moreover, the beamforming methods delay-and-sum and MVDR lead to average improvement in accuracy and AUC equal to 8% and 2%, respectively, when applied to training and testing data. Regarding the complementarity of time-dependent and time-independent features, the combination of both types of classifiers provides the best joint accuracy and AUC score.

Effects of eccentric, concentric and eccentric/concentric training on muscle function and mass, functional performance, cardiometabolic health, quality of life and molecular adaptations of skeletal muscle in COPD patients: a multicentre randomised trial.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third cause of death worldwide. COPD is characterised by dyspnoea, limited exercise tolerance, and muscle dysfunction. Muscle dysfunction has been linked to dysregulation between muscle protein synthesis, myogenesis and degradation mechanisms. Conventional concentric cycling has been shown to improve several clinical outcomes and reduce muscle wasting in COPD patients. Eccentric cycling is a less explored exercise modality that allows higher training workloads imposing lower cardio-metabolic demand during exercise, which has shown to induce greater muscle mass and strength gains after training. Interestingly, the combination of eccentric and concentric cycling training has scarcely been explored. The molecular adaptations of skeletal muscle after exercise interventions in COPD have shown equivocal results. The mechanisms of muscle wasting in COPD and whether it can be reversed by exercise training are unclear. Therefore, this study aims two-fold: (1) to compare the effects of 12 weeks of eccentric (ECC), concentric (CONC), and combined eccentric/concentric (ECC/CONC) cycling training on muscle mass and function, cardiometabolic health, physical activity levels and quality of life in severe COPD patients; and (2) to examine the molecular adaptations regulating muscle growth after training, and whether they occur similarly in specific muscle fibres (i.e., I, IIa and IIx). METHODS: Study 1 will compare the effects of 12 weeks of CONC, ECC, versus ECC/CONC training on muscle mass and function, cardiometabolic health, levels of physical activity and quality of life of severe COPD patients using a multicentre randomised trial. Study 2 will investigate the effects of these training modalities on the molecular adaptations regulating muscle protein synthesis, myogenesis and muscle degradation in a subgroup of patients from Study 1. Changes in muscle fibres morphology, protein content, genes, and microRNA expression involved in skeletal muscle growth will be analysed in specific fibre-type pools. DISCUSSION: We aim to demonstrate that a combination of eccentric and concentric exercise could maximise the improvements in clinical outcomes and may be ideal for COPD patients. We also expect to unravel the molecular mechanisms underpinning muscle mass regulation after training in severe COPD patients. TRIAL REGISTRY: Deutshches Register Klinischer Studien; Trial registration: DRKS00027331; Date of registration: 12 January 2022. https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00027331 .

Exacerbación de las inequidades educativas en tiempos de Covid-19.

No disponible.

Tracing Lung Cancer Risk Factors Through Mutational Signatures in Never-Smokers.

Epidemiologic studies often rely on questionnaire data, exposure measurement tools, and/or biomarkers to identify risk factors and the underlying carcinogenic processes. An emerging and promising complementary approach to investigate cancer etiology is the study of somatic "mutational signatures" that endogenous and exogenous processes imprint on the cellular genome. These signatures can be identified from a complex web of somatic mutations thanks to advances in DNA sequencing technology and analytical algorithms. This approach is at the core of the Sherlock-Lung study (2018-ongoing), a retrospective case-only study of over 2,000 lung cancers in never-smokers (LCINS), using different patterns of mutations observed within LCINS tumors to trace back possible exposures or endogenous processes. Whole genome and transcriptome sequencing, genome-wide methylation, microbiome, and other analyses are integrated with data from histological and radiological imaging, lifestyle, demographic characteristics, environmental and occupational exposures, and medical records to classify LCINS into subtypes that could reveal distinct risk factors. To date, we have received samples and data from 1,370 LCINS cases from 17 study sites worldwide and whole-genome sequencing has been completed on 1,257 samples. Here, we present the Sherlock-Lung study design and analytical strategy, also illustrating some empirical challenges and the potential for this approach in future epidemiologic studies.

Revisiting the dengue epidemic of 2011 in Paraguay: molecular epidemiology of dengue virus in the Asuncion metropolitan area.

BACKGROUND: Dengue is one of the most important re-emerging viral diseases and the most common human arthropod-borne viral infection worldwide. Any of the four Dengue virus serotypes (DENV-1 to 4) can cause asymptomatic infections or clinical manifestations that range in severity from a mild, self-limited illness, to a severe disease characterized by a shock syndrome that can lead to death. Paraguay suffers periodic epidemic outbreaks of dengue since 1988 when the DENV-1 was introduced in the country. Epidemics caused by all four serotypes have been reported and the country. Although dengue is endemic in Paraguay, few studies have described the molecular epidemiology of DENV in the country, which is important to understand the local and global spread, as well as the evolution of this pathogen. METHODS: This was a cross-sectional study of a convenience sample. Suspected dengue patients of any age were recruited from the Emergency Laboratory of the Central Hospital of the Institute of Social Welfare, Asuncion, Paraguay, from February to June of 2011. A DENV antigen test was used to confirm the infection. The protein E gene sequences of isolated viruses were sequenced for phylogenetic analysis. RESULTS: Dengue was confirmed in 55.1% of the participants (n = 98/178). The most frequent clinical findings were fever, headache, and myalgia. Identity analyses of the protein E gene sequence of 56 viruses isolated showed the circulation of DENV-1 (n = 45) and DENV-2 (n = 11) in the Asuncion metropolitan area in 2011. Molecular epidemiology analyses suggest that DENV-1 was introduced into Paraguay from Argentina, while the DENV-2 from Brazil, replacing previous virus lineages. CONCLUSIONS: We have analyzed the molecular epidemiology of DENV-1 and DENV-2 isolated in Paraguay in 2011. We found strong evidence that DENV-1 was introduced into Paraguay from Argentina, while the DENV-2 from Brazil, replacing previous virus lineages. Molecular epidemiology studies are of great interest to analyze the dynamic of DENV spread, which are useful for early implementation of containment measures to reduce the risk of explosive epidemics caused by this virus.

Patients with schizophrenia have decreased COVID-19 prevalence among hospitalised patients with psychiatric and neurological diseases: A retrospective analysis in Mexican population.

BACKGROUND: Increased coronavirus disease 2019 (COVID-19) incidence and mortality in hospitalised patients with psychiatric and neurologic disorders have been reported. METHODS: The clinical records of 198 patients with psychiatric and neurological disorders hospitalised in the Dr Rafael Serrano Psychiatric Hospital in Puebla during the peak of the first wave of the COVID-19 pandemic in Mexico were analysed for psychiatric or neurologic diagnosis, gender, age, medical diagnosis, and COVID-19 prevalence. For patients with COVID-19, the effects of gender, and medical diagnosis were explored. RESULTS: There was an increased COVID-19 prevalence in the studied population (43.94%), compared with the national Mexican (~0.21% to 0.63%) and worldwide average in the general population (~0.13% to 4.28%). However, the mortality rate (5.75%) was lower than that reported in Mexico (11.28%-13.55%), which was higher than the worldwide average (2.95%-4.98%). We detected increased COVID-19 prevalence in patients with comorbidities (odds ratios [OR] 0.4; 95% CI: 0.2-1, P = .0447). Moreover, patients with schizophrenia spectrum disorders have a decreased predisposition to COVID-19 (OR 0.4, 95% CI: 0.2-0.8; P = .0250), as opposed to patients with intellectual disability that are predisposed to COVID-19 (OR 2.2, 95% CI: 0.2-0.8; P = .0434), in comparison with the rest of the hospital population. CONCLUSION: The prevalence of COVID-19 in hospitalised patients with psychiatric disorders is increased compared with that of the general population; however, a lower mortality rate was detected. Also, an increased risk of COVID-19 was detected in patients with comorbidities. Interestingly, the observed variation in COVID-19 prevalence in patients with schizophrenia and intellectual disability was not associated with age or other specific medical diagnoses.

Physical Activity Levels and Associated Factors in a Latin American COPD Population of Patients. The LASSYC Study.

Reduced physical activity (PA) is an independent risk factor for lung function decline, hospitalization and mortality in chronic obstructive pulmonary disease (COPD) and affects a large proportion of patients from Europe and the United States. However, little is known of the level of PA of COPD patients in Latin America. The aim of this study was to provide information of the level of PA and its determinants in COPD patients in Latin America. This is an observational, cross-sectional study on patients with COPD in seven Latin American countries. PA level was evaluated with the short version of the International Physical Activity Questionnaire (IPAQ) and the association between PA and other variables was investigated. Complete information of PA level was obtained in 734 COPD patients consecutively recruited from specialized outpatient clinics; 448 (61%) were men, with a mean age of 69.6 years (standard deviation [SD] = 8.7) and a mean FEV1 (% predicted) = 49.1% (17.5%). In 37.9% the level of PA was low, and the average sitting time was 36.1 h per week. Patients with low levels of PA were older, with higher levels of dyspnea and higher CAT scores. Additionally, we found that patients with low level of PA presented more symptoms during the day. Low levels of PA have been observed in a large proportion of COPD patients of Latin America, which is higher in women and older patients and it is related with worse functional and clinical characteristics.

Increased Endocytosis of Cadmium-Metallothionein through the 24p3 Receptor in an In Vivo Model with Reduced Proximal Tubular Activity.

BACKGROUND: The proximal tubule (PT) is the major target of cadmium (Cd2+) nephrotoxicity. Current dogma postulates that Cd2+ complexed to metallothionein (MT) (CdMT) is taken up through receptor-mediated endocytosis (RME) via the PT receptor megalin:cubilin, which is the predominant pathway for reuptake of filtered proteins in the kidney. Nevertheless, there is evidence that the distal parts of the nephron are also sensitive to damage induced by Cd2+. In rodent kidneys, another receptor for protein endocytosis, the 24p3 receptor (24p3R), is exclusively expressed in the apical membranes of distal tubules (DT) and collecting ducts (CD). Cell culture studies have demonstrated that RME and toxicity of CdMT and other (metal ion)-protein complexes in DT and CD cells is mediated by 24p3R. In this study, we evaluated the uptake of labeled CdMT complex through 24p3R after acute kidney injury (AKI) induced by gentamicin (GM) administration that disrupts PT function. Subcutaneous administration of GM at 10 mg/kg/day for seven days did not alter the structural and functional integrity of the kidney's filtration barrier. However, because of PT injury, the concentration of the renal biomarker Kim-1 increased. When CdMT complex coupled to FITC was administered intravenously, both uptake of the CdMT complex and 24p3R expression in DT increased and also colocalized after PT injury induced by GM. Although megalin decreased in PT after GM administration, urinary protein excretion was not changed, which suggests that the increased levels of 24p3R in the distal nephron could be acting as a compensatory mechanism for protein uptake. Altogether, these results suggest that PT damage increases the uptake of the CdMT complex through 24p3R in DT (and possibly CD) and compensate for protein losses associated with AKI.

Natriuretic peptides and echocardiographic parameters in Mexican children environmentally exposed to arsenic.

BACKGROUND: Arsenic exposure is associated with cardiovascular risk in adults; however, few epidemiologic studies have evaluated biomarkers of cardiovascular risk in children who are environmentally exposed to arsenic. OBJECTIVE: The aim of this study was to assess the associations between urinary arsenic, plasma natriuretic peptides and echocardiographic parameters in Mexican children exposed to arsenic through the drinking water. METHODS: We conducted a cross-sectional study with 192 children (3-8 years old) from Zimapan, Hidalgo, Mexico. B-type natriuretic peptide (BNP), NT-proBNP and atrial natriuretic peptide (ANP) were measured by ELISA, urinary arsenic concentration (UAs) were measured via by hydride generation-cryotrapping-atomic absorption spectrometry, and cardiac parameters were measured by echocardiography. RESULTS: The median plasma concentrations of ANP, BNP and NT-proBNP were 36.9 ng/mL, 49.7 pg/mL, and 226.1 pg/mL, respectively. Using multivariable models, a dose-response relationship was observed between BNP concentrations and UAs tertiles (<47 ng/mL: reference, 47-72 ng/mL: 48.7 pg/mL, >72 ng/mL: 52.2 pg/mL, P-trend = 0.020). BNP concentrations also increased with increasing U-tAs as continuous variables (0.43 pg/mL increase per 1 ng/mL increase of U-tAs; P-Value = 0.008). Additionally, BNP was positively associated with arsenic methylated metabolites (U-MAs and U-DMAs). On the other hand, BNP was inversely related to relative wall thickness (RWT). No associations were found for other cardiac parameters. Finally, neither ANP nor NT-proBNP were significantly related to arsenic exposure or echocardiographic parameters. CONCLUSIONS: In this study, we showed associations between plasma BNP and arsenic exposure. Our results support the importance of reducing childhood arsenic exposure, which may have cardiovascular effects early in life.

Custodiol cardioplegia solution compared to cold blood cardioplegia in pediatric cardiac surgery: a single-institution experience.

OBJECTIVE: Custodiol is an intracellular, crystalloid cardioplegia solution that is a single-dose alternative to multi-dose cold blood cardioplegia; however, there is scarce data regarding its use in infants and children. The objective of this study was to compare its impact on myocardial function in infants. METHODS: Single-center retrospective review including 132 patients <12 months old undergoing biventricular repair. There were 106 patients who received single-dose Custodiol and 27 patients who received multi-dose blood cardioplegia. Demographic and echocardiographic data were compared between the two groups. RESULTS: Patients receiving Custodiol were slightly younger (100 ± 62 days) and lower weight (4.7 ± 1.3 kg) compared to 152 ± 86 days and 5.2 ± 1.3 kg for blood cardioplegia (p < 0.05). The Society of Thoracic Surgeons/European Association for Cardio-Thoracic Surgery Congenital Heart Surgery score was similar between both groups. Average cardiopulmonary bypass time was similar between both groups (Custodiol 93 ± 54 minutes vs. blood 81 ± 44 minutes, p = 0.46) as was aortic cross-clamp time (Custodiol 58 ± 33 minutes vs. cold blood 53 ± 33 minutes, p = 0.62). Pre-operative left ventricular ejection fraction was similar for blood 73 ± 8% versus Custodiol 70 ± 9%, p = 0.21. There was also no intergroup difference in left ventricular ejection fraction 24 hours post op (blood 64 ± 9% vs. Custodiol 65 ± 12%, p = 0.53) or at discharge (blood 66 ± 10% vs. Custodiol 66 ± 11%, p = 0.95). The pre-operative right ventricle function by fractional area change was also similar in blood cardioplegia (46 ± 13%) versus Custodiol (48 ± 9%, p = 0.38) and showed similar drops in parameters in the two groups 24 hours after surgery and at discharge. CONCLUSION: Single-dose Custodiol is as safe as blood cardioplegia for myocardial protection in congenital cardiac surgery for the cross-clamp times evaluated in this study. Evaluation at longer cross-clamp times would be helpful to determine if there is a greater benefit to single-dose Custodiol versus more repeated doses of blood cardioplegia for longer cross-clamp times.

Evaluation of the neuropharmacological effects of Gardenin A in mice.

This work describes the neuropharmacological (sedative, anxiolytic, antidepressant, and anticonvulsant) actions of Gardenin A (GA) (0.1-25 mg/kg p.o.), a flavonoid found in medicinal plants. The sedative effects of GA were assessed with the pentobarbital-induced sleep test. The anxiolytic actions of GA were evaluated with the elevated plus-maze, the light-dark box test, the exploratory cylinder assay, and the open field test. Motor coordination was evaluated with the rotarod test and the open field test. The antidepressant-like actions of GA were evaluated with the tail suspension test and forced swimming test. The mechanisms of the anxiolytic-like and antidepressant-like effects of GA were assessed using inhibitors of neurotransmission pathways. The anticonvulsant activity of GA was evaluated with the strychnine-induced seizure test. The sedative effects of GA were evident only at a dose of 25 mg/kg, which increased the duration of sleep but did not alter sleep onset. GA showed anxiolytic-like actions with activity comparable to that of clonazepam in all experimental tests. The GABAA receptor antagonist bicuculline reversed the anxiolytic-like effects of GA. Furthermore, GA showed significant antidepressant-like actions in both models with activity comparable to that of fluoxetine. Yohimbine, an α2-adrenoceptor blocker, inhibited the antidepressant-like actions of GA. In addition, GA (1-10 mg/kg) did not affect locomotor coordination in mice and delayed the onset of convulsions. These findings suggest that GA induces anxiolytic-like effects and has anticonvulsant actions by the possible involvement of the GABAergic system. The antidepressant-like actions of GA may be mediated by noradrenergic neurotransmission.

Evaluation of vascular and kidney injury biomarkers in Mexican children exposed to inorganic fluoride.

Exposure to inorganic fluoride (F) has been implicated in cardiovascular and kidney dysfunction mainly in adult populations. However, limited epidemiological information from susceptible populations, such as children, is available. In this study we evaluated the relationship of F exposure with some vascular and kidney injury biomarkers in children. A cross-sectional study was conducted in 374 Mexican schoolchildren. Dental fluorosis and F concentrations in the water and urine were evaluated. The glomerular filtration rate (eGFR) and the urinary concentrations of kidney injury molecule 1 (KIM-1) and cystatin-C (uCys-C) were examined to assess kidney injury. The carotid intima media thickness (cIMT) and serum concentrations of vascular adhesion molecule 1 (VCAM-1), intracellular adhesion molecule 1 (ICAM-1), endothelin 1(ET-1) and cystatin-C (sCys-C) were measured to assess vascular alterations. High proportions of children exposed to F were observed (79.7% above 1.2 ppm F in urine) even in the low water F exposure regions, which suggested additional sources of F exposure. In robust multiple linear regression models, urinary F was positively associated with eGFR (ß = 1.3, p = 0.015), uCys-C (ß = -8.5, p = 0.043), VCAM-1 (ß = 111.1, p = 0.019), ICAM-1 (ß = 57, p = 0.032) and cIMT (ß = 0.01, p = 0.032). An inverse association was observed with uCys-C (ß = -8.5, p = 0.043) and sCys-C (ß = -9.6, p = 0.021), and no significant associations with ET-1 (ß = 0.069, p = 0.074) and KIM-1 (ß = 29.1, p = 0.212) were found. Our findings revealed inconclusive results regarding F exposure and kidney injury. However, these results suggest that F exposure is related to early vascular alterations, which may increase the susceptibility of cardiovascular diseases in adult life.

HUMAN PARAINFLUENZA 2 RELATED ILLNESS AND A DEATH IN A GROUP OF CAPTIVE WESTERN LOWLAND GORILLAS (GORILLA GORILLA GORILLA).

An onset of respiratory disease in a captive bachelor group (n = 3) of western lowland gorillas (Gorilla gorilla gorilla) was concomitant with peak attendance of visitors at the institution and with unwanted occurrences of food items being thrown in the gorillas' enclosure. While the condition of two individuals improved with supportive therapy and antibiotics, the third gorilla died three days following initiation of treatment. A fatal bacterial pneumonia, secondary to an infection by a human parainfluenza virus 2 (HIPV-2), was considered to be the cause of death based on histopathology, lung cultures, and reverse transcription PCR. HPIV-2 activity in the human population of the province was detected for that period, including the same viral strain. This report confirms a HPIV-2 respiratory illness and associated death in a gorilla. Clinical presentation and context suggest conspecifics were also affected and that contaminated food thrown by visitors may have been the source of infection.

Bisphenol A alters oocyte maturation by prematurely closing gap junctions in the cumulus cell-oocyte complex.

In ovarian follicles, cumulus cells communicate with the oocyte through gap junction intercellular communication (GJIC), to nurture the oocyte and control its meiosis arrest and division. Bisphenol A (BPA) is a monomer found in polycarbonate-made containers that can induce functional alterations, including impaired oocyte meiotic division and reduced molecule transfer in GJIC. However, how BPA alters oocyte meiotic division is unclear. We investigated whether BPA effects on oocyte meiotic division were correlated with reduced transfer in GJIC. Cumulus cell-oocyte complexes (COCs) isolated from mouse preovulatory follicles were cultured with 0, 0.22, 2.2, 22, 220, and 2200 nM BPA for 2 h. An additional 16-h incubation with epidermal growth factor (EGF) was performed to promote the occurrence of meiotic resumption and progression to metaphase II. Without EGF stimulus, BPA treatment increased the percentage of oocytes undergoing meiotic resumption, decreased GJIC in the COCs, and did not modify GJIC gene (Cx43 and Cx37) and protein (CX43) expression. Following EGF stimulus, BPA increased the percentage of oocytes that remained at the anaphase and telophase stages, and decreased the percentage of oocytes reaching the metaphase II stage. Concomitantly, BPA reduced the expansion of cumulus cells. Carbenoxolone (a GJIC inhibitor) and 6-diazo-5-oxo-l-norleucine (a cumulus cell-expansion inhibitor) exerted effects on meiotic division similar to those exerted by BPA. These data suggest that BPA accelerates meiotic progression, leading to impaired prophase I-to-metaphase II transition, and that this adverse effect is correlated with reduced bidirectional communication in the COC.

The shift in GH3 cell shape and cell motility is dependent on MLCK and ROCK.

Cytoskeletal organization, actin-myosin contractility and the cell membrane together regulate cell morphology in response to the cell environment, wherein the extracellular matrix (ECM) is an indispensable component. Plasticity in cell shape enables cells to adapt their migration mode to their surroundings. GH3 endocrine cells respond to different ECM proteins, acquiring different morphologies: a rounded on collagen I-III (C I-III) and an elongated on collagen IV (C IV). However, the identities of the molecules that participate in these responses remain unknown. Considering that actin-myosin contractility is crucial to maintaining cell shape, we analyzed the participation of MLCK and ROCK in the acquisition of cell shape, the generation of cellular tension and the cell motility mode. We found that a rounded shape with high cortical tension depends on MLCK and ROCK, whereas in cells with an elongated shape, MLCK is the primary protein responsible for cell spreading. Further, in cells with a slow and directionally persistent motility, MLCK predominates, while rapid and erratic movement is ROCK-dependent. This behavior also correlates with GTPase activation. Cells on C I-III exhibited higher Rho-GTPase activity than cells on C IV and vice versa with Rac-GTPase activity, showing a plastic response of GH3 cells to their environment, leading to the generation of different cytoskeleton and membrane organizations and resulting in two movement strategies, rounded and fibroblastoid-like.

Mercury levels in human population from a mining district in Western Colombia.

A biomonitoring study was carried out to examine the adverse impacts of total mercury in the blood (HgB), urine (HgU) and human scalp hair (HgH) on the residents of a mining district in Colombia. Representative biological samples (scalp hair, urine and blood) were collected from volunteered participants (n=63) to estimate the exposure levels of THg using a Direct mercury analyzer. The geometric mean of THg concentrations in the hair, urine and blood of males were 15.98µg/g, 23.89µg/L and 11.29µg/L respectively, whereas the females presented values of 8.55µg/g, 5.37µg/L and 8.80µg/L. Chronic urinary Hg (HgU) levels observed in male workers (32.53µg/L) are attributed to their long termed exposures to inorganic and metallic mercury from gold panning activities. On an average, the levels of THg are increasing from blood (10.05µg/L) to hair (12.27µg/g) to urine (14.63µg/L). Significant positive correlation was found between hair and blood urinary levels in both male and female individuals. Thus the present biomonitoring investigation to evaluate the Hg levels and associated health issues would positively form a framework for further developmental plans and policies in building an ecofriendly ecosystem.