Novel risk loci for COVID-19 hospitalization among admixed American populations.

The genetic basis of severe COVID-19 has been thoroughly studied, and many genetic risk factors shared between populations have been identified. However, reduced sample sizes from non-European groups have limited the discovery of population-specific common risk loci. In this second study nested in the SCOURGE consortium, we conducted a genome-wide association study (GWAS) for COVID-19 hospitalization in admixed Americans, comprising a total of 4702 hospitalized cases recruited by SCOURGE and seven other participating studies in the COVID-19 Host Genetic Initiative. We identified four genome-wide significant associations, two of which constitute novel loci and were first discovered in Latin American populations (BAZ2B and DDIAS). A trans-ethnic meta-analysis revealed another novel cross-population risk locus in CREBBP. Finally, we assessed the performance of a cross-ancestry polygenic risk score in the SCOURGE admixed American cohort. This study constitutes the largest GWAS for COVID-19 hospitalization in admixed Latin Americans conducted to date. This allowed to reveal novel risk loci and emphasize the need of considering the diversity of populations in genomic research.

Effectiveness of different percutaneous electrolysis protocols in the endogenous modulation of pain: A Double-Blinded Randomized Clinical Trial.

OBJECTIVE: This randomized clinical trial investigated if the application of percutaneous electrolysis (PE) enhances endogenous pain mechanisms (EPM) when compared with a simple needle application (acting as sham). METHODS: Forty-six asymptomatic subjects, aged 18-40 years, were randomized into three groups receiving a single ultrasound-guided PE intervention consisting of a needle insertion on the lateral epicondyle: sham (without electrical current), low-intensity (0.3 mA, 90s), or high-intensity (three pulses of 3 mA, 3s) PE. Widespread pressure pain thresholds (PPT), conditioned pain modulation (CPM), and temporal summation (TS) were bilaterally assessed in the lateral epicondyle, bicipital groove, transverse process of C5 and tibialis anterior muscle. Outcomes were obtained by an assessor blinded to the treatment allocation of the subjects. RESULTS: No significant changes in CPM were observed in either group (omnibus ANOVA all, P > .05). A significant bilateral increase in PPT in the lateral epicondyle in the high intensity group as compared with the sham group was observed (P < .01). A significant decrease of TS in both low (P = .002) and high (P = .049) intensity groups on the right, but not on the left, tibialis anterior was also observed when compared with the sham group. CONCLUSIONS: One session of PE is able to slightly stimulate modulatory pathways related to nociceptive gain, particularly pressure pain sensitivity and temporal summation but not conditioning pain modulation, when compared with a sham needle intervention, with changes even contralaterally. No significant differences were found between low- and high-intensity doses of percutaneous electrolysis.

Seroprevalence as an Indicator of Undercounting of COVID-19 Cases in a Large Well-Described Cohort.

Introduction: Reported confirmed cases represent a small portion of overall true cases for many infectious diseases. The undercounting of true cases can be considerable when a significant portion of infected individuals are asymptomatic or minimally symptomatic, as is the case with COVID-19. Seroprevalence studies are an efficient way to assess the extent to which true cases are undercounted during a large-scale outbreak and can inform efforts to improve case identification and reporting. Methods: A longitudinal seroprevalence study of active duty U.S. military members was conducted from May 2020 through June 2021. A random selection of service member serum samples submitted to the Department of Defense Serum Repository was analyzed for the presence of antibodies reactive to SARS-CoV-2. The monthly seroprevalence rates were compared with those of cumulative confirmed cases reported during the study period. Results: Seroprevalence was 2.3% in May 2020 and increased to 74.0% by June 2021. The estimated true case count based on seroprevalence was 9.3 times greater than monthly reported cases at the beginning of the study period and fell to 1.7 by the end of the study. Conclusions: In our sample, confirmed case counts significantly underestimated true cases of COVID-19. The increased availability of testing over the study period and enhanced efforts to detect asymptomatic and minimally symptomatic cases likely contributed to the fall in the seroprevalence to reported case ratio.

Cadaveric and Ultrasound Validation of Percutaneous Electrolysis Approach at the Distal Biceps Tendon: A Potential Treatment for Biceps Tendinopathy.

Distal biceps brachii tendinopathy is a musculoskeletal pain condition-comprising chronic intrasubstance degeneration with alterations of the tendon structure-that is difficult to treat. Preliminary evidence suggests a positive effect for pain and related disability of percutaneous electrolysis treatment in patients with tendinopathy. Ultrasound is an excellent diagnostic tool to identify tendon injuries, such as tendinopathy, and to guide treatment approaches. Different approaches using ultrasound evaluation of the biceps tendon have been described. Our aim was to determine the validity and safety of a percutaneous electrolysis approach, targeting insertion of the distal tendon of biceps brachii, in both human (ultrasound-guided) and Thiel-embalmed cadaver (not ultrasound-guided) models. There were two approaches evaluated: an anterior approach with the elbow in extension and the forearm in supination and a posterior approach with the elbow in flexion and the forearm in pronation. A needle was inserted following the tendon up to its insertion into the radial tuberosity. The anterior approach, both in cadaveric study and US-guided intervention, revealed a close relationship between the distal biceps tendon and the brachial artery. The mean distance of the depth of the biceps tendon distal to the brachial artery was 0.21 ± 0.021 cm in the cadavers and 0.51 ± 0.024 cm in subjects. It was also found that the anterior approach has a potential technical difficulty due to the anatomical location of the brachial artery. With the posterior approach, it was possible to safely identify the tendon insertion and the needle approach, since no important vascular and nervous structures were visualized in the window of insertion of the needle. The clinician rated the posterior approach as low difficulty in all subjects. Current results would support a posterior approach with US guidance as a safe approach for applying the percutaneous electrolysis technique for insertional tendinopathies of the distal biceps brachii tendon. The current study did not assess the effectiveness of the proposed intervention; accordingly, future studies investigating the clinical effectiveness of the proposed intervention are needed.

Analytical and computational properties of the variable symmetric division deg index.

The aim of this work is to obtain new inequalities for the variable symmetric division deg index $ SDD_\alpha(G) = \sum_{uv \in E(G)} (d_u^\alpha/d_v^\alpha+d_v^\alpha/d_u^\alpha) $, and to characterize graphs extremal with respect to them. Here, by $ uv $ we mean the edge of a graph $ G $ joining the vertices $ u $ and $ v $, and $ d_u $ denotes the degree of $ u $, and $ \alpha \in \mathbb{R} $. Some of these inequalities generalize and improve previous results for the symmetric division deg index. In addition, we computationally apply the $ SDD_\alpha(G) $ index on random graphs and we demonstrate that the ratio $ \langle SDD_\alpha(G) \rangle/n $ ($ n $ is the order of the graph) depends only on the average degree $ \langle d \rangle $.

Characterizing Diagnostic Inertia in Arterial Hypertension With a Gender Perspective in Primary Care.

Background and Objectives: Substantial evidence shows that diagnostic inertia leads to failure to achieve screening and diagnosis objectives for arterial hypertension (AHT). In addition, different studies suggest that the results may differ between men and women. This study aimed to evaluate the differences in diagnostic inertia in women and men attending public primary care centers, to identify potential gender biases in the clinical management of AHT. Study Design/Materials and Methods: Cross-sectional descriptive and analytical estimates were obtained nested on an epidemiological ambispective cohort study of patients aged ≥30 years who attended public primary care centers in a Spanish region in the period 2008-2012, belonging to the ESCARVAL-RISK cohort. We applied a consistent operational definition of diagnostic inertia to a registry- reflected population group of 44,221 patients with diagnosed hypertension or meeting the criteria for diagnosis (51.2% women), with a mean age of 63.4 years (62.4 years in men and 64.4 years in women). Results: Of the total population, 95.5% had a diagnosis of hypertension registered in their electronic health record. Another 1,968 patients met the inclusion criteria for diagnostic inertia of hypertension, representing 4.5% of the total population (5% of men and 3.9% of women). The factors significantly associated with inertia were younger age, normal body mass index, elevated total cholesterol, coexistence of diabetes and dyslipidemia, and treatment with oral antidiabetic drugs. Lower inertia was associated with age over 50 years, higher body mass index, normal total cholesterol, no diabetes or dyslipidemia, and treatment with lipid-lowering, antiplatelet, and anticoagulant drugs. The only gender difference in the association of factors with diagnostic inertia was found in waist circumference. Conclusion: In the ESCARVAL-RISK study population presenting registered AHT or meeting the functional diagnostic criteria for AHT, diagnostic inertia appears to be greater in men than in women.

Novel genes and sex differences in COVID-19 severity.

Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10-22 and P = 8.1 × 10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10-8) and ARHGAP33 (P = 1.3 × 10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.

Synergistic effect of compounds directed to triosephosphate isomerase, a combination to develop drug against trichomoniasis.

The development of new drugs is continuous in the world; currently, saving resources (both economic ones and time) and preventing secondary effects have become a necessity for drug developers. Trichomoniasis is the most common nonviral sexually transmitted infection affecting more than 270 million people around the world. In our research group, we focussed on developing a selective and more effective drug against Trichomonas vaginalis, and we previously reported on a compound, called A4, which had a trichomonacidal effect. Later, we determined another compound, called D4, which also had a trichomonacidal effect together with favorable toxicity results. Both A4 and D4 are directed at the enzyme triosephosphate isomerase. Thus, we made combinations between the two compounds, in which we determined a synergistic effect against T. vaginalis, determining the IC50 and the toxicity of the best relationship to obtain the trichomonacidal effect. With these results, we can propose a combination of compounds that represents a promising alternative for the development of a new therapeutic strategy against trichomoniasis.

Mating-induced analgesia is dependent of copulatory male pattern in high- and low- yawning male rats.

Mating behavior in rodents can modulate pain sensations in both sexes. In males, the execution of mounts, intromissions, and ejaculations induced a progressive increase in their vocalization thresholds induced by tail shocks and other types of noxious stimuli. We selectively inbred two sublines from Sprague-Dawley (SD) rats that differed in their spontaneous yawning frequency. The high-yawning (HY) subline had a mean of 20 yawns/h and a different pattern of sexual behavior characterized by longer interintromission intervals and more sexual bouts that delayed ejaculation. The low-yawning (LY) subline and SD rats yawned as a mean 2 and 1 yawns/h, respectively. So, we determine mating-induced analgesia in HY, LY, and SD male rats by measuring vocalization thresholds in response to noxious electric tail shocks. Our results showed that the magnitude of mating-induced analgesia was lower in HY and LY rats with respect to SD rats. When the rats performed different components of male sexual pattern, both sublines exhibited a significantly lower increase in their vocalization thresholds with respect to SD rats-being sublines less responsive regarding mating-induced analgesia. Pain modulation mechanisms depend on responses to stress, so the low levels of analgesia obtained in the yawning sublines may be due either to differences in their response to stress in other paradigms, or to atypical performance of male sexual behavior during mating, an event which as a stressful event in rats. Therefore, the yawning sublines are a suitable model for analyzing how a different temporal pattern in the display of male sexual behavior affects analgesia mechanisms. Our results concur with Wistar rats with different endophenotypes that could apply to humans as well.

Gender Differences in the Diagnosis of Dyslipidemia: ESCARVAL-GENERO.

Evidence shows that objectives for detecting and controlling dyslipidemia are not being effectively met, and outcomes differ between men and women. This study aimed to assess gender-related differences in diagnostic inertia around dyslipidemia. This ambispective, epidemiological, cohort registry study included adults who presented to public primary health care centers in a Spanish region from 2008 to 2012, with dyslipidemia and without cardiovascular disease. Diagnostic inertia was defined as the registry of abnormal diagnostic parameters-but no diagnosis-on the person's health record in a window of six months from inclusion. A total of 58,970 patients were included (53.7% women) with a mean age of 58.4 years in women and 57.9 years in men. The 6358 (20.1%) women and 4312 (15.8%) men presenting diagnostic inertia had a similar profile, although in women the magnitude of the association with younger age was larger. Hypertension showed a larger association with diagnostic inertia in women than in men (prevalence ratio 1.81 vs. 1.56). The overall prevalence of diagnostic inertia in dyslipidemia is high, especially in women. Both men and women have a higher risk of cardiovascular morbidity and mortality.

Expression Analyses of Genes Related to Multixenobiotic Resistance in Mytilus galloprovincialis after Exposure to Okadaic Acid-Producing Dinophysis acuminata.

The mussel Mytilus galloprovincialis is one of the most important aquaculture species in Europe. Its main production problem is the accumulation of toxins during coastal blooms, which prevents mussel commercialization. P-glycoprotein (ABCB1/MDR1/P-gp) is part of the multixenobiotic resistance system in aquatic organisms, and okadaic acid, the main DSP toxin, is probably a substrate of the P-gp-mediated efflux. In this study, the presence and possible role of P-gp in the okadaic acid detoxification process was studied in M. galloprovincialis. We identified, cloned, and characterized two complete cDNAs of mdr1 and mdr2 genes. MgMDR1 and MgMDR2 predicted proteins had the structure organization of ABCB full transporters, and were identified as P-gp/MDR/ABCB proteins. Furthermore, the expression of mdr genes was monitored in gills, digestive gland, and mantle during a cycle of accumulation-elimination of okadaic acid. Mdr1 significantly increased its expression in the digestive gland and gills, supporting the idea of an important role of the MDR1 protein in okadaic acid efflux out of cells in these tissues. The expression of M. galloprovincialismrp2, a multidrug associated protein (MRP/ABCC), was also monitored. As in the case of mdr1, there was a significant induction in the expression of mrp2 in the digestive gland, as the content of okadaic acid increased. Thus, P-gp and MRP might constitute a functional defense network against xenobiotics, and might be involved in the resistance mechanisms to DSP toxins.

Triosephosphate isomerase as a therapeutic target against trichomoniasis.

Trichomoniasis is the most common non-viral sexually transmitted infection, caused by the protozoan parasite Trichomonas vaginalis, affecting millions of people worldwide. The main treatment against trichomoniasis is metronidazole and other nitroimidazole derivatives, but up to twenty percent of clinical cases of trichomoniasis are resistant to these drugs. In this study, we used high-performance virtual screening to search for molecules that specifically bind to the protein, triosephosphate isomerase from T. vaginalis (TvTIM). By in silico molecular docking analysis, we selected six compounds from a chemical library of almost 500,000 compounds. While none of the six inhibited the enzymatic activity of recombinant triosephosphate isomerase isoforms, one compound (A4; 3,3'-{[4-(4-morpholinyl)phenyl]methylene}bis(4- hydroxy-2H-chromen-2-one) altered their fluorescence emission spectra, suggesting that this chemical might interfere in an important non-glycolytic function of TvTIM. In vitro assays demonstrate that A4 is not cytotoxic but does have trichomonacidal impact on T. vaginalis cultures. With these results, we propose this compound as a potential drug with a new therapeutic target against Trichomonas vaginalis.

The Potential Link between Episodes of Diverticulitis or Hemorrhoidal Proctitis and Diets with Selected Plant Foods: A Case-Control Study.

Diverticulitis and hemorrhoidal proctitis in the population are significant public health problems. We studied the potential association between the intake of certain plant foods and diverticulitis or hemorrhoidal episodes through a case-control study including 410 cases and 401 controls. We used a semiquantitative food frequency questionnaire. The intake was additionally quantified according to a 24 h recall. The plant foods or derived food products were categorized by their main chemical components into ethanol, caffeine/theine/theobromine, capsaicin, alliin, acids, eugenol, and miscellaneous foods such as curcumin. The mean score for overall intake of plant foods under consideration was 6.3 points, and this was significantly higher in cases (8.5) than in controls (4.1). Overall intake was similar in cases presenting with diverticulitis or hemorrhoidal proctitis. Cases had 13 times the odds of being in the upper quartile for overall intake (>7 points), compared to controls. Explanatory logistic regression models showed that the strongest association with diverticulitis and hemorrhoidal proctitis was shown by the chemical food group of capsaicin, followed by ethanol, eugenol, caffeine/theine/theobromine, and acids. Neither alliin nor miscellaneous food groups showed any association. High, frequent consumption of capsaicin, followed by ethanol, eugenol, caffeine/theine/theobromine, and acids increase the risk of diverticulitis and hemorrhoidal proctitis.

Transcriptional Response in the Digestive Gland of the King Scallop (Pecten maximus) After the Injection of Domoic Acid.

Some diatom species of the genus Pseudo-nitzschia produce the toxin domoic acid. The depuration rate of domoic acid in Pecten maximus is very low; for this reason, king scallops generally contain high levels of domoic acid in their tissues. A transcriptomic approach was used to identify the genes differentially expressed in the P. maximus digestive gland after the injection of domoic acid. The differential expression analysis found 535 differentially expressed genes (226 up-regulated and 309 down-regulated). Protein-protein interaction networks obtained with the up-regulated genes were enriched in gene ontology terms, such as vesicle-mediated transport, response to stress, signal transduction, immune system process, RNA metabolic process, and autophagy, while networks obtained with the down-regulated genes were enriched in gene ontology terms, such as response to stress, immune system process, ribosome biogenesis, signal transduction, and mRNA processing. Genes that code for cytochrome P450 enzymes, glutathione S-transferase theta-1, glutamine synthase, pyrroline-5-carboxylate reductase 2, and sodium- and chloride-dependent glycine transporter 1 were among the up-regulated genes. Therefore, a stress response at the level of gene expression, that could be caused by the domoic acid injection, was evidenced by the alteration of several biological, cellular, and molecular processes.

COVID-SCORE Spain: public perceptions of key government COVID-19 control measures.

BACKGROUND: Spain was initially one of the countries most affected by the coronavirus disease 2019 (COVID-19) pandemic. In June 2020, the COVID-SCORE-10 study reported that the Spanish public's perception of their government's response to the pandemic was low. This study examines these perceptions in greater detail. METHODS: We employed an ordered logistic regression analysis using COVID-SCORE-10 data to examine the Spanish public's perception of 10 key aspects of their government's COVID-19 control measures. These included support for daily needs, mental and general health services, communication, information and coordination, which were examined by gender, age, education level, having been affected by COVID-19 and trust in government's success in addressing unexpected health threats. RESULTS: 'Trust in the government' showed the greatest odds of positive perception for the 10 measures studied. Odds of positive perception of communication significantly varied by gender, education level and having been affected by COVID-19, whereas for information and coordination of disease control, odds significantly varied by gender and having been affected by COVID-19. Odds of positive perception for access to mental health services significantly varied by gender and education level. Age was not significant. CONCLUSION: Public perception of the government's pandemic response in Spain varied by socio-demographic and individual variables, particularly by reported trust in the government. Fostering public trust during health threats may improve perception of response efforts. Future efforts should tailor interventions that consider gender, education level and whether people have been affected by COVID-19.

Gender Inequalities in Diagnostic Inertia around the Three Most Prevalent Cardiovascular Risk Studies: Protocol for a Population-Based Cohort Study.

Evidence shows that objectives for detecting and controlling cardiovascular risk factors are not being effectively met, and moreover, outcomes differ between men and women. This study will assess the gender-related differences in diagnostic inertia around the three most prevalent cardiovascular risk factors: dyslipidemia, arterial hypertension, and diabetes mellitus, and to evaluate the consequences on cardiovascular disease incidence. This is an epidemiological and cohort study. Eligible patients will be adults who presented to public primary health care centers in a Spanish region from 2008 to 2011, with hypertension, dyslipidemia, or/and diabetes and without cardiovascular disease. Participants' electronic health records will be used to collect the study variables in a window of six months from inclusion. Diagnostic inertia of hypertension, dyslipidemia, and/or diabetes is defined as the registry of abnormal diagnostic parameters-but no diagnosis-on the person's health record. The cohort will be followed from the date of inclusion until the end of 2019. Outcomes will be cardiovascular events, defined as hospital admission due to ischemic cardiopathy, stroke, and death from any cause. The results of this study could inform actions to rectify the structure, organization and training of health care teams in order to correct the inequality.

Military Participation in Health Security: Analysis of Joint External Evaluation Reports and National Action Plans for Health Security.

Militaries around the world play an important but at times poorly defined and underappreciated role in global health security. They are often called upon to support civilian authorities in humanitarian crises and to provide routine healthcare for civilians. Military personnel are a unique population in a health security context, as they are highly mobile and often deploy to austere settings domestically and internationally, which may increase exposure to endemic and emerging infectious diseases. Despite the role of militaries, few studies have systematically evaluated their involvement in global health security activities including the Global Health Security Agenda. We analyzed Joint External Evaluation (JEE) mission reports (n = 94) and National Action Plan for Health Security plans (n = 12), published as of July 2020, to determine the extent to which military organizations were involved in the evaluation process, military involvement in health security activities were described, and specific recommendations were provided for the country's military. For JEE reports, descriptions of military involvement were highest in 3 of the 4 core areas: Respond (76%), Prevent (39%), and Detect (32%). Similarly, National Action Plan for Health Security plans mentioned military involvement in the same 3 core areas: Respond (58%), Prevent (33%), and Detect (33%). Only 28% of JEE reports provided recommendations for the military in any of the core areas. Our results indicate that military roles and contributions are incorporated into some aspects of country-level health security activities, but that more extensive involvement may be warranted to improve national capabilities to prevent, detect, and respond to infectious disease threats.

Parameterizing a tumor humeral prosthesis and development of a set.

BACKGROUND: The reconstruction of the proximal humerus is possible from the resection of the tumor and the placement of a prosthesis. In some cases, they do not meet the anthropometric aspects of the patients. OBJECTIVE: To determine the parameters to size the components of a humeral prosthesis and the development of a set, using design software. METHOD: Forty patients were selected for prostheses, radiographs and CT scans were analyzed and statistical tests were applied to the measurements. RESULTS: The length of the tumors was 8-20 cm. The minimum length of the humerus was 28 cm and 33 cm the maximum. Correlation was observed between the humerus and the tumor and the height of the patient with p = 0.93088 and p = 0.904564, respectively; humerus diameter, p = 0.2345. The set will include three components, diameter 6-10 mm, and length of 24, 26 and 28 cm. Three modular spacers with lengths of 6, 8.5 and 13 cm. Crowns 6.5 and 8.5 cm long, 1.3 cm in diameter and 5 mm nut. CONCLUSION: With the development of the set, poorly calculated resections and adaptation to any humerus size can be resolved.

ANTECEDENTES: La reconstrucción del húmero proximal es posible a partir de la resección del tumor y la colocación de una prótesis. En algunos casos, las prótesis no cumplen con los aspectos antropométricos de los pacientes. OBJETIVO: Determinar los parámetros para dimensionar los componentes de una prótesis de húmero y el desarrollo de un set, mediante software de diseño. MÉTODO: Se seleccionaron 40 pacientes para prótesis, se analizaron radiografías y tomografías computarizadas, y se aplicaron pruebas estadísticas a las mediciones. RESULTADOS: La longitud de los tumores fue de 8-20 cm. La longitud mínima del húmero fue de 28 cm y la máxima fue de 33 cm. Se observó correlación entre el húmero y el tumor y la altura del paciente, con p = 0.93088 y p = 0.904564, respectivamente; para el diámetro del húmero, p = 0.2345. El set incluye tres componentes, con diámetro de 6-10 mm y longitud de 24, 26 y 28 cm; tres espaciadores modulares con longitudes de 6, 8,5 y 13 cm; coronas de 6,5 y 8,5 cm de largo, 1,3 cm de diámetro y tuerca de 5 mm. CONCLUSIÓN: Con el desarrollo del set se pueden resolver resecciones mal calculadas y la adaptación a cualquier tamaño de húmero.

Hyperglycemic levels in early stage of diabetic nephropathy affect differentially renal expression of claudins-2 and -5 by oxidative stress.

AIMS: This study attempts to elicit whether the level of hyperglycemia in an early stage of diabetic nephropathy changes the renal expression of claudins-2 and -5 and to determine the involvement of glucose-induced oxidative stress. MAIN METHODS: Streptozotocin-induced type-1 and type-2 diabetic (DM1, DM2)-rat models were used. At 14-week old, the rats were placed in metabolic cages to evaluate proteinuria, creatinine clearance, and electrolyte excretion. Proximal tubules and glomeruli were isolated and analyzed by Western blot and immunofluorescence. Renal oxidative stress and metalloproteinase activities were evaluated. KEY FINDINGS: We found that claudin-5 expression in glomeruli and claudin-2 expression in proximal tubules were significantly reduced in DM1 versus DM2 model, paralleling with higher proteinuria and loss of sodium and potassium reabsorption, increased malondialdehyde levels, but lower antioxidant capacity in both models. Enzymatic activity of MMP-2 and-9 was increased in both diabetic groups versus control being higher in DM1 than DM2, suggesting higher claudin's degradation. SIGNIFICANCE: The level of hyperglycemia determines the time-dependent progression to diabetic nephropathy; hyperglycemia-induced oxidative stress parallels an increase in metalloproteinases (MMPs) activities consequently affecting the integrity of claudin-2 and -5 in glomerulus and proximal tubule. Our results suggest that chronic high-glycemia levels in early stages of diabetic nephropathy decrease expression of claudins-2 and -5, increase oxidative stress, and induce MMP-activity faster than chronic middle-glycemia levels.

Amoebicidal effect of 5,5'-[(4-nitrophenyl)methylene]bis-6-hydroxy-2-mercapto-3-methyl-4(3H)-pyrimidinone), a new drug against Entamoeba histolytica.

Entamoeba histolytica is a cosmopolitan protozoan parasite that can produce infections in the intestine and some organs (liver, lungs, and brain), with worldwide prevalence. There are treatments against E. histolytica (antiparasitics), but as the drugs used in these treatments have presented some type of resistance and/or side effects, there are cases with complications of this disease. Therefore, it is necessary to develop new drugs aimed at a specific therapeutic target against this parasite. Here, we used the compound 5,5'-[(4-nitrophenyl)methylene]bis(6-hydroxy-2-mercapto-3-methyl-4(3H)-pyrimidinone) in the patenting process (called D4). D4 has a reported specific use against a glycolytic enzyme, the triosephosphate isomerase of Trichomonas vaginalis (TvTIM). We determined that D4 has an amoebicidal effect in in vitro cultures, with an IC50 value of 18.5 µM, and we proposed a specific site of interaction (Lys77, His110, Gln115, and Glu118) in the triosephosphate isomerase of E. histolytica (EhTIM). Furthermore, compound D4 has favorable experimental and theoretical toxicity results. Therefore, D4 should be further investigated as a potential drug against E. histolytica.