Sperm melatonin receptors, seminal plasma melatonin and semen freezability in goats.

Goat bucks are seasonal breeders that show variation in sperm quality, endogenous melatonin (MLT), and presumably in the expression of MLT receptors on the sperm throughout the year, which may modify sperm freezability. The aim of this study was to determine whether sperm freezability is associated with (i) endogenous melatonin levels in seminal plasma and (ii) the expression of sperm plasma membrane melatonin receptors (MT1, MT2). To evaluate this, spermatozoa from seven Saanen goat bucks were cryopreserved throughout the year in Mexico using a standard freezing protocol. Seminal plasma MLT concentrations were determined by ELISA and the expression and localization of MT1 and MT2 were detected by immunocytochemistry and confirmed by western blotting. The recovery rate of progressive motility after thawing was higher in spring than autumn and winter; in contrast, the F pattern (CTC assay) was higher in winter than in the other seasons. A proportional increase in the AR pattern (CTC assay) was smaller in winter than in the other seasons and the proportion of sperm showing high plasma membrane fluidity was higher in spring than in summer and autumn. The seminal plasma MLT concentrations showed no significant interseasonal differences. The MT1 receptor was immunolocalised at the apical region of the sperm head, while MT2 was mainly localised in the neck. The relative expression of MLT receptors showed significant differences between summer and winter for all bands, except at 75 kDa of MT2. In conclusion, there was an association between the relative expression of MT1 and MT2 receptors throughout the year and sperm freezability in goat bucks in México. Post-thaw sperm quality is enhanced in semen samples collected during breeding season.

Passive Membrane Permeability of Sizable Acyclic ß-Hairpin Peptides.

The recent shift toward increasingly larger drug modalities has created a significant demand for novel classes of compounds with high membrane permeability that can inhibit intracellular protein-protein interactions (PPIs). While major advances have been made in the design of cell-permeable helices, stapled ß-sheets, and cyclic peptides, the development of large acyclic ß-hairpins lags far behind. Therefore, we investigated a series of 26 ß-hairpins (MW > 1.6 kDa) belonging to a chemical space far beyond the Lipinski "rule of five" (fbRo5) and showed that, in addition to their innate plasticity, the lipophilicity of these peptides (log D 7.4 ≈ 0 ± 0.7) can be tuned to drastically improve the balance between aqueous solubility and passive membrane permeability.

Conus venom fractions inhibit the adhesion of Plasmodium falciparum erythrocyte membrane protein 1 domains to the host vascular receptors.

Using high-throughput BioPlex assays, we determined that six fractions from the venom of Conus nux inhibit the adhesion of various recombinant PfEMP-1 protein domains (PF08_0106 CIDR1α3.1, PF11_0521 DBL2ß3, and PFL0030c DBL3X and DBL5e) to their corresponding receptors (CD36, ICAM-1, and CSA, respectively). The protein domain-receptor interactions permit P. falciparum-infected erythrocytes (IE) to evade elimination in the spleen by adhering to the microvasculature in various organs including the placenta. The sequences for the main components of the fractions, determined by tandem mass spectrometry, yielded four T-superfamily conotoxins, one (CC-Loop-CC) with I-IV, II-III connectivity and three (CC-Loop-CXaaC) with a I-III, II-IV connectivity. The 3D structure for one of the latter, NuxVA = GCCPAPLTCHCVIY, revealed a novel scaffold defined by double turns forming a hairpin-like structure stabilized by the two disulfide bonds. Two other main fraction components were a miniM conotoxin, and a O2-superfamily conotoxin with cysteine framework VI/VII. This study is the first one of its kind suggesting the use of conotoxins for developing pharmacological tools for anti-adhesion adjunct therapy against malaria. Similarly, mitigation of emerging diseases like AIDS and COVID-19, can also benefit from conotoxins as inhibitors of protein-protein interactions as treatment. BIOLOGICAL SIGNIFICANCE: Among the 850+ species of cone snail species there are hundreds of thousands of diverse venom exopeptides that have been selected throughout several million years of evolution to capture prey and deter predators. They do so by targeting several surface proteins present in target excitable cells. This immense biomolecular library of conopeptides can be explored for potential use as therapeutic leads against persistent and emerging diseases affecting non-excitable systems. We aim to expand the pharmacological reach of conotoxins/conopeptides by revealing their in vitro capacity to disrupt protein-protein and protein-polysaccharide interactions that directly contribute to pathology of Plasmodium falciparum malaria. This is significant for severe forms of malaria, which might be deadly even after treated with current parasite-killing drugs because of persistent cytoadhesion of P. falciparum infected erythrocytes even when parasites within red blood cells are dead. Anti-adhesion adjunct drugs would de-sequester or prevent additional sequestration of infected erythrocytes and may significantly improve survival of malaria patients. These results provide a lead for further investigations into conotoxins and other venom peptides as potential candidates for anti-adhesion or blockade-therapies. This study is the first of its kind and it suggests that conotoxins can be developed as pharmacological tools for anti-adhesion adjunct therapy against malaria. Similarly, mitigation of emerging diseases like AIDS and COVID-19, can also benefit from conotoxins as potential inhibitors of protein-protein interactions as treatment.

Effects of α-conotoxin ImI on TNF-α, IL-8 and TGF-ß expression by human macrophage-like cells derived from THP-1 pre-monocytic leukemic cells.

α7 nicotinic acetylcholine receptors (nAChRs) are ubiquitous in the nervous system and ensure important neurophysiological functionality for many processes. However, they are also found in cells of the immune system, where their role has been less studied. Here we report the pro-inflammatory effect of ImI, a well characterized conotoxin that inhibits α7 nAChRs, on differentiated THP-1 pre-monocyte macrophages (MDM) obtained by phorbol 12-myristate 13 acetate (PMA) treatment. Enzyme-linked immunosorbent assay (ELISA) performed on supernatant fluids of LPS challenged MDM showed ImI-mediated upregulation of pro-inflammatory cytokine TNF-α in an ImI concentration-dependent manner from 0.5 to 5.0 µmol/L and for IL-8 up to 1.0 µmol/L. Levels of anti-inflammatory cytokine TGF-ß remained practically unaffected in ImI treated MDMs. Nicotine at 10 µmol/L significantly downregulated the release of TNF-α, but showed a lesser effect on IL-8 secretion and no effect on TGF-ß. Fluorescent competitive assays involving ImI, α-bungarotoxin and nicotine using MDM and the murine macrophage RAW 264.7 suggest a common binding site in the α7 receptor. This work extends the application of conotoxins as molecular probes to non-excitatory cells, such as macrophages and supports the involvement of the α7 nAChR in regulating the inflammatory response via the cholinergic anti-inflammatory pathway (CAP).

Seroprevalence and risk factors for Trypanosoma cruzi infection in the Amazon region of Ecuador.

Trypanosoma cruzi infection in the Ecuadorian Amazon region has recently been reported. A seroepidemiologic survey conducted in four provinces in this region indicates a seroprevalence rate of 2.4% among the 6,866 samples collected in 162 communities. Among children < OR = 10 years of age, 1.2% were seropositive. Risk factors for T. cruzi seropositivity were having been born and remaining in the Ecuadorian Amazon provinces, age, living in a house with a thatch roof and open or mixed wall construction, recognizing the vector insects, and reporting being bitten by a triatomine bug. These data suggest active transmission of Chagas' disease in the Ecuadorian Amazon region is associated with poor housing conditions, and highlight the need for further studies aimed at understanding the biology of the insect vectors, reservoir species, and the clinical impact of T. cruzi infection as the basis for future educational and control programs in this region.

Prevalencia y factores asociados a conducta suicida en estudiantes de la Universidad Nacional Mayor de San Marcos, Lima-Perú / Prevalence and associated factors of suicidal behavior in students of the Universidad Nacional Mayor de San Marcos, Lima-Peru

Introducción. La Organización Mundial de la Salud ha señalado el incremento de riesgo suicida en personas de 15 a 44 años, grupo etario en el que se ubican los estudiantes universitarios. Objetivo. Determinar prevalencias de conducta suicida y variables asociadas en estudiantes de pregrado de la Universidad Nacional Mayor de San Marcos (UNMSM), Lima-Perú. Métodos. Estudio analítico, transversal. La población objetivo fue de 24 118 estudiantes matriculados en 2015. Se aplicaron los instrumentos de conducta suicida de la Encuesta Nacional de Salud Mental en el Perú 2002 y 2012, las escalas de ansiedad y depresión de Zung y el cuestionario CAGE para problemas de alcohol, a una muestra de 1819 estudiantes obtenida mediante muestreo bietápico. Se estimaron prevalencias y se empleó regresión logística para determinar factores asociados. Resultados. Las prevalencias de vida, último año, últimos seis meses y último mes de los componentes de la conducta suicida fueron: deseos de morir (35%; 13,9%; 11% y 5,6%); ideación suicida (22,4%; 8,2%; 6% y 3,3%); plan suicida (17,7%; 4,4%; 3,5% y 1,6%); e intento suicida (11,1%; 3,7%; 2,8% y 1,4%). Los factores de riesgo en términos de odds ratio (OR) ajustados y sus IC 95% fueron: condición de mujer 1,48 (IC 95%: 1,03-2,12), depresión 2,46 (IC 95%: 1,49-4,06), angustia 2,5 (IC 95%: 1,38-4,6), y vivir en hogar no nuclear 2,51 (IC 95%: 1,70-3,72). De los estudiantes que intentaron suicidarse sólo 16% buscó ayuda profesional y 21% pensó repetir el intento. Conclusiones. Los estudiantes de la UNMSM tienen mayor riesgo de conducta suicida que los de la población en general, tanto por razones científicas como por responsabilidad moral se recomienda implementar estrategias de intervención para revertir esta tendencia y proteger a este valioso recurso humano.

Introduction. World Health Organization has pointed out the increasing suicidal risk in the 115 - 44 years of age. University students are inmerse in that age group risk. Objective. To estimate the prevalence of suicidal behavior and associated variables in undergraduate students of Universidad Nacional Mayor de San Marcos (UNMSM). Methodos. Transversal and analytic study. Target population: 24 118 students registered in 2015. The Suicide Behavior Questionnaire of the 2002, 2012 Mental Health National Survey, the Zung self-rated anxiety and depression scales, and the CAGE questionnaire for potential alcohol-related problems were applied to a sample of 1819 students obtained by a bietapic with probabililty proportional to size sampling procedure. Results. Life, last year, last 6 months, and last month prevalences of suicide behavior`s components of were, in that order: (i) death wish (35%; 13,9%; 11%; 5,6%); (ii) suicidal ideation (22,4%; 8,2%; 6%;3,3%); (iii) suicidal planning (17,7%; 4,4%; 3,5%; 1,6%); and (iv) suicidal attempt (11,1%; 3,7%; 2,8%; 1,4%), and higher than the prevalences of metropolitan Lima general population. Risk factors, in terms of OR and 95% CI were: being female 1,48 (1,03-2,12), depression 2,46 (1,49-4,06), anxiety 2,5 (1,38-4,6), and living in a non nuclear home 2,51 (1,70-3,72). Only 16% of the students who attempted suicide sought professional help and 21% considered repeating the attempt. Conclusions. UNMSM undergraduate students show a riskier suicide behavior tan the general population. Both for scientific reasons and moral responsibility it is highly recommended to implement intervention strategies in order to revert this trend and protect this valuable human resource.

Salud mental en estudiantes de pregrado de la Facultad de Medicina de la Universidad Nacional Mayor de San Marcos / Mental health in undergraduate students from Universidad Nacional Mayor de San Marcos School of Medicine

Introducción. Estudios previos evidencian problemas de salud mental en estudiantes de pre-grado de la Facultad de Medicina de la Universidad Nacional Mayor de San Marcos (UNMSM). Objetivo. Evaluar si existen diferencias entre la frecuencia de problemas de salud mental entre los estudiantes de primer año, y el resto de años de estudio, en alumnos de las cinco escuelas profesionales de la Facultad de Medicina de la UNMSM. Métodos. Estudio transversal. Se utilizaron instrumentos validados para evaluar problemas de salud mental: intento suicida, pensamiento homicida, conducta disocial, problemas con el alcohol, depresión y angustia. Adicionalmente, se midieron niveles de resiliencia. Se incluyeron estudiantes de todas las escuelas profesionales de la Facultad de Medicina, en dos grupos de análisis: estudiantes de primer año y estudiantes de los otros años. Resultados. Se evidenció que en alumnos de primer año se encontró un 7,5% de intento suicida, 18,9% de conducta disocial y 21,9% de pensamiento homicida de prevalencia de vida. Asimismo, se encontró un 4,8% de problemas con el alcohol, 8,5% de depresión y 3,2% de angustia de prevalencia periódica. La frecuencia de problemas de salud mental fue mayor según transcurrieron los años de estudio, aunque con diferencias estadísticamente significativas sólo en depresión, angustia y problemas con el alcohol. El 29,3% de encuestados tuvo bajo nivel de resiliencia. Conclusión. Se encontraron frecuencias preocupantes de problemas de salud mental en los estudiantes de pregrado de la Facultad de Medicina de la UNMSM, aunque un porcentaje de alumnos ya ingresa a la universidad afectado por ellos. El entorno universitario sería factor agravante en depresión, ansiedad y problemas con el alcohol.

Introduction. Previous studies pointed out mental health problems in undergraduate health students of school of medicine from Universidad Nacional Mayor de San Marcos (UNMSM). Objective. To assess if there are differences between the frequency of mental health problems between first-year students and other years’ students from five professional schools of the UNMSM school of medicine. Methods. A cross-sectional study. Validated instruments were used to assess mental health problems: suicidal intent, homicidal thinking, disocial behavior, alcoholism, depression and anguish. In addition, levels of resilience were evaluated. Students from all professional schools of the Faculty of Medicine were included in two analysis groups: first-year students and other years’ students. Results. 7,5% of suicide attempts, 18,9% of disocial behavior and 21,9% of homicidal thinking lifetime prevalence were found in first-year students. Similarly, 4,8% of alcoholism, 8,5% of depression and 3,2% of anxiety point prevalence were found on same group of study. The frequency of mental health problems was higher according to the years of study, with statistically significant differences only in depression, anxiety and alcoholism. 29,3% of respondents have a low level of resilience Conclusion. Concerning frequencies of mental health problems were found in undergraduate students of UNMSM School of Medicine, although a percentage of students were admitted in university with mental health problems. The university environment would be an aggravating factor in depression, anxiety and alcohol problems.

[Stress, anxiety and depression in magistrates from Lima, Peru]. / Estrés, ansiedad y depresión en magistrados de Lima, Perú

OBJECTIVE: To measure the general and work related stress, depression and anxiety in Magistrates (Judges and District Attorneys) of Lima Judicial District. MATERIAL AND METHODS: We carried out a transversal and descriptive study. A population of 1137 magistrates from the Lima Jurisdictional District of the Judicial System, was randomly sampled by a strata representing every agency of the Judicial System. The final sample included 287 magistrates: 138 District Attorneys and 149 Judges. After informed consent, a questionnaire composed by four previously validated instruments was applied to measure general and work related stress, anxiety and depression. RESULTS: General stress was present in 18.5 % of the participants; work related stress 33.7 %; anxiety 12.5 %, and depression 15 %. All three conditions were present in 6.6 % of the participants and at least one in 25.9 %. General stress was associated to depression (OR: 4.9; IC95 % 1.6-15.1) and anxiety (OR: 8.5; IC95 % 2.5-28.6) by logistic regression. CONCLUSION: Lima Judicial District's Magistrates present a triad composed by high levels of labor stress, anxiety and depression. A quarter of the participants present at least one of those conditions. In that perspective, it is recommended that intervention and preventive programs address stress, anxiety and depression simultaneously, given their strong association.

Estrés, ansiedad y depresión en magistrados de Lima, Perú / Stress, anxiety and depression in magistrates from Lima, Peru

Objetivos. Determinar los niveles de estrés general y laboral, depresión y ansiedad en magistrados (jueces y fiscales) del Distrito Judicial de Lima, Perú. Materiales y métodos. Estudio transversal y descriptivo. De una población de 1137 magistrados del Poder Judicial y del Ministerio Público del Distrito Jurisdiccional de Lima se tomó una muestra aleatoria estratificada donde cada institución constituyó un estrato. La muestra estuvo conformada por 287 magistrados: 138 fiscales y 149 jueces. Se aplicó un cuestionario compuesto por cuatro instrumentos para determinar los niveles de estrés general y laboral, ansiedad y depresión, previo consentimiento informado. Resultados. El estrés general estuvo presente en el 18,5 por ciento de los magistrados, el estrés laboral en 33,7 por ciento, ansiedad en 12,5 por ciento y depresión en 15,0 por ciento. Estas tres condiciones estuvieron presentes en el 6,6 por ciento de los magistrados, y al menos una estuvo presente en el 25,9 por ciento. El estrés general estaba asociado con la depresión (OR: 4,9; IC95 por ciento 1,6-15,1) y ansiedad (OR: 8,5; IC95 por ciento 2,5-28,6) en el modelo de regresión logística. Conclusiones. Un porcentaje significativo de magistrados del Distrito Judicial de Lima presentan altos niveles de estrés, ansiedad y depresión; un cuarto de los encuestados presentan, al menos, una de estas condiciones. Se recomienda que los programas de intervención y prevención se dirijan al manejo del estrés, ansiedad y depresión en conjunto, dada su alta asociación.

Objective. To measure the general and work related stress, depression and anxiety in Magistrates (Judges and District Attorneys) of Lima Judicial District. Material and methods. We carried out a transversal and descriptive study. A population of 1137 magistrates from the Lima Jurisdictional District of the Judicial System, was randomly sampled by a strata representing every agency of the Judicial System. The final sample included 287 magistrates: 138 District Attorneys and 149 Judges. After informed consent, a questionnaire composed by four previously validated instruments was applied to measure general and work related stress, anxiety and depression. Results. General stress was present in 18.5 percent of the participants; work related stress 33.7 percent; anxiety 12.5 percent, and depression 15 percent. All three conditions were present in 6.6 percent of the participants and at least one in 25.9 percent. General stress was associated to depression (OR: 4.9; IC95 percent 1.6-15.1) and anxiety (OR: 8.5; IC95 percent 2.5-28.6) by logistic regression. Conclusion. Lima Judicial District’s Magistrates present a triad composed by high levels of labor stress, anxiety and depression. A quarter of the participants present at least one of those conditions. In that perspective, it is recommended that intervention and preventive programs address stress, anxiety and depression simultaneously, given their strong association.

Estudios de la cobertura de vacunación en cuatro distritos de Lima Metropolitana / Study of the inmunization cover at four districts of Lima Metropolitana

Trata de la medición del impacto que ha tenido el Programa de Movilización de la Mujer y Supervivencia del Niño (PMMS), que desarrolla el Gobierno Peruano y UNICEF, sobre la cobertura y oportunidad de la vacunación de los niños menores de tres años de edad, en cuatro distritos de Lima Metropolitana: Carabayllo, Puente Piedra, San Martín de Porres y Lince. En los dos primeros, se estima que el PMMS tiene alta actividad y en los dos últimos, que su presencia es muy baja o no existe