Immune modulation via dendritic cells by the effect of Thymosin-alpha-1 on immune synapse in HCMV infection.

Tα1 (Thymosin-alpha-1) is a thymus-derived hormone that has been demonstrated to be effective on diverse immune cell subsets. The objective of this study was to determine the in vitro immunomodulatory effect of Tα1 in human cytomegalovirus (HCMV) infection. Dendritic cells (DCs) were isolated from peripheral blood mononuclear cells (PBMCs) by negative selection and cultured in the presence or absence of Tα1. The immunophenotyping of DCs was characterised by multiparametric flow cytometry assessing CD40, CD80, TIM-3 and PDL-1 markers, as well as intracellular TNFα production. Then, autologous CD4+ or CD8+ T-Lymphocytes (TLs) isolated by negative selection from PBMCs were co-cultured with DCs previously treated with Tα1 in the presence or absence of HCMV. Intracellular TNFα, IFNγ, IL-2 production, CD40-L and PD-1 expression were assessed through immunophenotyping, and polyfunctionality in total TLs and memory subsets were evaluated. The results showed that Tα1 increased CD40, CD80, TIM-3 and TNFα intracellular production while decreasing PDL-1 expression, particularly on plasmacytoid dendritic cells (pDCs). Therefore, Tα1 modulated the production of TNFα, IFNγ and IL-2 in both total and memory subsets of CD4+ and CD8+ TLs by upregulating CD40/CD40-L and downregulating PDL-1/PD-1 expression. Our study concludes that Tα1 enhances antigen-presenting capacity of DCs, improves TLs responses to HCMV infection, and enhances the polyfunctionality of CD8+ TLs. Consequently, Tα1 could be an alternative adjuvant for use in therapeutic cell therapy for immunocompromised patients.

Sincronismo muscular en patrones de movimiento de miembros superiores descritos por Kabat: latencia al inicio del pico de la máxima activación electromiográfica / Muscle timing in upper limb movement patterns described by Kabat: Latency at the beginning of the peak of maximum electromyographic activation

Introducción El método Kabat sostiene que el sincronismo normal se produce de distal a proximal, lo cual requiere evidencia electromiográfica. Objetivo Describir el sincronismo muscular de patrones motores de miembros superiores descritos por Kabat, en posiciones sedente y supina, a partir de la medición de la latencia al inicio del pico de la máxima activación electromiográfica (IPMA-EMG) de músculos seleccionados. Material y métodos Se realizó un estudio analítico comparativo. Se evaluó a 20 hombres y 20 mujeres entre 19 y 26 años. Cada participante realizó 3repeticiones activas sin resistencia externa de cada uno de los patrones de movimiento (flexor y extensor) de las 2diagonales. Se registró la latencia del IPMA-EMG para cada uno de los 8músculos evaluados en los 4patrones de movimiento, tanto en supino como en sedente. Estos se promediaron y se ordenaron de menor a mayor para obtener la secuencia de contracciones musculares en cada patrón de movimiento. Se compararon las secuencias obtenidas para cada patrón en sedente y supino y se valoró la existencia de correlaciones entre ellas. Resultados Se observó correlación significativa en las secuencias del IPMA-EMG entre posiciones supina y sedente, en todos los patrones de movimiento (p<0,05), excepto en el patrón extensor de la primera diagonal (p=0,139). No hubo diferencias estadísticamente significativas entre posiciones en ninguno de los patrones (p>0,05). Conclusiones Aunque con variaciones en la IPMA-EMG, se halló, en general, un sincronismo muscular de proximal a distal, más evidenciado en la posición sedente y en los patrones flexores (AU)

Introduction The Kabat method argues that normal synchronism occurs from distal to proximal, which requires electromyographic evidence. Objective To describe the muscular timing of motor patterns of the upper limbs described by Kabat, in seated and supine positions, from the measurement of the latency at the beginning of the peak of the maximum electromyographic activation (BPM-EMG-A) of selected muscles. Material and methods A comparative analytical study was carried out. Twenty men and 20 women between 19 and 26 years old were evaluated. Each participant performed 3active repetitions without external resistance of each of the movement patterns (flexor and extensor) of the 2diagonals. BPM-EMG-A latency was recorded for each of the 8muscles tested in the 4movement patterns, both supine and seated. These were averaged and ordered from lowest to highest to obtain the sequence of muscle contractions in each movement pattern. The sequences obtained for each pattern in seated and supine were compared and the existence of correlations between them was assessed. Results Significant correlation was observed in the BPM-EMG-A sequences between supine and seated positions, in all movement patterns (P<0.05), except in the extensor pattern of the first diagonal (P=0.139). There were no statistically significant differences between positions in any of the patterns (P>0.05). Conclusion Although with variations in BPM-EMG-A, muscle timing was generally found from proximal to distal, more evident in the sitting position and in flexor patterns (AU)

The use of alpha 1 thymosin as an immunomodulator of the response against SARS-Cov2.

BACKGROUND: Since the beginning of SARS-CoV2 pandemic, the mortality rate among elderly patients (60-90 years) has been around 50%, so age has been a determining factor of a worse COVID-19 prognosis. Associated with age, the thymic function involution and depletion plays an important role, that could be related to a dysregulated and ineffective innate and adaptive immune response against SARS-CoV2. Our study aims to further in vitro effect of human Thymosin-alpha-1 (α1Thy) treatment on the immune system in population groups with different thymic function levels in the scenario of SARS-CoV2 infection. RESULTS: Activation markers such as CD40, CD80 and TIM-3 were upregulated in α1Thy presence, especially in plasmacytoid dendritic cells (pDCs) and, with increased TNFα production was observed compared to untreated condition. Co-cultures of CD4 + and CD8 + T cells with DCs treated with α1Thy in response to SARS-CoV2 peptides showed a decrease in the cytokine production compared to the condition without α1Thy pre-treated. A decrease in CD40L activation co-receptor expression in CD8 + LTs was also observed, as well as an increase in PD1 in CD4 + TLs expression in both age groups. In fact, there are no age-related differences in the immunomodulatory effect of the hormone, and it seems that effector memory and terminally differentiated memory T lymphocyte subsets were the most actively influenced by the immunomodulatory α1Thy effect. Finally, the polyfunctionality measured in SARS-CoV2 Specific-T cells response was maintained in α1Thy presence in total and memory subpopulations CD4 + and CD8 + T-cells, despite decreased proinflammatory cytokines production. CONCLUSION: The hormone α1Thy could reduce, through the modulation of DCs, the amount of proinflammatory cytokines produced by T cells. Moreover, α1Thy improve lymphocyte functionality and could become a beneficial therapeutic alternative as an adjuvant in SARS-CoV2 treatment either in the acute phase after infection or reinfection. In addition, the effect on the T immune response means that α1Thy can be incorporated into the vaccination regimen, especially in the most immunologically vulnerable individuals such as the elderly. SUBJECTS: Thymosin alpha 1, Dendritic cells, SARS-CoV2-specific T cells response, Immunomodulation.

A hybrid artificial intelligence model leverages multi-centric clinical data to improve fetal heart rate pregnancy prediction across time-lapse systems.

STUDY QUESTION: Can artificial intelligence (AI) algorithms developed to assist embryologists in evaluating embryo morphokinetics be enriched with multi-centric clinical data to better predict clinical pregnancy outcome? SUMMARY ANSWER: Training algorithms on multi-centric clinical data significantly increased AUC compared to algorithms that only analyzed the time-lapse system (TLS) videos. WHAT IS KNOWN ALREADY: Several AI-based algorithms have been developed to predict pregnancy, most of them based only on analysis of the time-lapse recording of embryo development. It remains unclear, however, whether considering numerous clinical features can improve the predictive performances of time-lapse based embryo evaluation. STUDY DESIGN, SIZE, DURATION: A dataset of 9986 embryos (95.60% known clinical pregnancy outcome, 32.47% frozen transfers) from 5226 patients from 14 European fertility centers (in two countries) recorded with three different TLS was used to train and validate the algorithms. A total of 31 clinical factors were collected. A separate test set (447 videos) was used to compare performances between embryologists and the algorithm. PARTICIPANTS/MATERIALS, SETTING, METHODS: Clinical pregnancy (defined as a pregnancy leading to a fetal heartbeat) outcome was first predicted using a 3D convolutional neural network that analyzed videos of the embryonic development up to 2 or 3 days of development (33% of the database) or up to 5 or 6 days of development (67% of the database). The output video score was then fed as input alongside clinical features to a gradient boosting algorithm that generated a second score corresponding to the hybrid model. AUC was computed across 7-fold of the validation dataset for both models. These predictions were compared to those of 13 senior embryologists made on the test dataset. MAIN RESULTS AND THE ROLE OF CHANCE: The average AUC of the hybrid model across all 7-fold was significantly higher than that of the video model (0.727 versus 0.684, respectively, P = 0.015; Wilcoxon test). A SHapley Additive exPlanations (SHAP) analysis of the hybrid model showed that the six first most important features to predict pregnancy were morphokinetics of the embryo (video score), oocyte age, total gonadotrophin dose intake, number of embryos generated, number of oocytes retrieved, and endometrium thickness. The hybrid model was shown to be superior to embryologists with respect to different metrics, including the balanced accuracy (P ≤ 0.003; Wilcoxon test). The likelihood of pregnancy was linearly linked to the hybrid score, with increasing odds ratio (maximum P-value = 0.001), demonstrating the ranking capacity of the model. Training individual hybrid models did not improve predictive performance. A clinic hold-out experiment was conducted and resulted in AUCs ranging between 0.63 and 0.73. Performance of the hybrid model did not vary between TLS or between subgroups of embryos transferred at different days of embryonic development. The hybrid model did fare better for patients older than 35 years (P < 0.001; Mann-Whitney test), and for fresh transfers (P < 0.001; Mann-Whitney test). LIMITATIONS, REASONS FOR CAUTION: Participant centers were located in two countries, thus limiting the generalization of our conclusion to wider subpopulations of patients. Not all clinical features were available for all embryos, thus limiting the performances of the hybrid model in some instances. WIDER IMPLICATIONS OF THE FINDINGS: Our study suggests that considering clinical data improves pregnancy predictive performances and that there is no need to retrain algorithms at the clinic level unless they follow strikingly different practices. This study characterizes a versatile AI algorithm with similar performance on different time-lapse microscopes and on embryos transferred at different development stages. It can also help with patients of different ages and protocols used but with varying performances, presumably because the task of predicting fetal heartbeat becomes more or less hard depending on the clinical context. This AI model can be made widely available and can help embryologists in a wide range of clinical scenarios to standardize their practices. STUDY FUNDING/COMPETING INTEREST(S): Funding for the study was provided by ImVitro with grant funding received in part from BPIFrance (Bourse French Tech Emergence (DOS0106572/00), Paris Innovation Amorçage (DOS0132841/00), and Aide au Développement DeepTech (DOS0152872/00)). A.B.-C. is a co-owner of, and holds stocks in, ImVitro SAS. A.B.-C. and F.D.M. hold a patent for 'Devices and processes for machine learning prediction of in vitro fertilization' (EP20305914.2). A.D., N.D., M.M.F., and F.D.M. are or have been employees of ImVitro and have been granted stock options. X.P.-V. has been paid as a consultant to ImVitro and has been granted stocks options of ImVitro. L.C.-D. and C.G.-S. have undertaken paid consultancy for ImVitro SAS. The remaining authors have no conflicts to declare. TRIAL REGISTRATION NUMBER: N/A.

Infección urinaria de presentación atípica: caso clínico y revisión de literatura

Introducción: el síndrome de orina púrpura es una presentación clínica poco frecuente en el ámbito de urgencias, caracterizado por coloración anormal de la orina secundaria a una reacción química de algunos patógenos que producen infección de vías urinarias, siendo más frecuente en pacientes con múltiples comorbilidades y diferentes factores de riesgo. Objetivo: el objetivo de este manuscrito es presentar el caso de un paciente con síntomas atípicos de infección de vías urinarias. Presentación del caso: varón de 88 años de edad, con antecedente de diabetes mellitus no insulino-requiriente, con hiperplasia prostática benigna que ingresó al servicio de urgencias por síntomas irritativos urinarios asociados a uso de sonda vesical, con orina de coloración violeta en bolsa recolectora. El urocultivo reportó la presencia de Proteus vulgaris multisensible, por lo que se decidió dar manejo con cefepima de 1 gr cada ocho horas, con lo cual se obtuvo una adecuada evolución clínica. Discusión y conclusión: el síndrome de la bolsa de orina púrpura es una presentación clínica atípica, pero muy llamativa de la infección urinaria. Esta se genera como resultado de la conversión del triptófano en la dieta en indoxil sulfato que, una vez se elimina por la orina, se transforma en índigo (color violeta) e indirrubina (color rojo), dando este aspecto clínico.

Background: Purple urine syndrome is a rare clinical presentation in the emergency room, characterized by abnormal colouration of the urine secondary to a chemical reaction of some pathogens that cause urinary tract infection, being more frequent in patients with multiple comorbidities and different risk factor's. Purpose: The objective of the article is present the case of a patient with atypical symptoms of urinary tract infection. Clinical case: An 88-year-old male, with a history of non-insulin diabetes mellitus, benign prostatic hyperplasia, who was admitted to the emergency room due to irritative urinary symptoms associated with the use of a urinary catheter, with purple urine in a collection bag. Urine culture reported the presence of multisensitive Proteus vulgaris, for which it was decided to give treatment with Cefepime 1 g every 8 hours, with which it was obtained with adequate clinical evolution. Conclusions: Purple urine bag syndrome is an atypical but very striking clinical presentation of urinary tract infection. This is generated as a result of the conversion of tryptophan in the diet into indoxyl sulfate, which, once it is eliminated in the urine, transforms into indigo (purple color) and indirubin (red color), giving this clinical appearance.

Nanotechnology against human cytomegalovirus in vitro: polyanionic carbosilane dendrimers as antiviral agents.

BACKGROUND: Human cytomegalovirus (HCMV) is a worldwide infection, causing different troublesome in immunosupressed patients and very related to Human Immunodeficiency Virus 1 (HIV-1) infection, mainly in developing countries, with a co-infection rate of 80% in Africa. The high cost of present treatments and the lack of routinely tests in these countries urge the necessity to develop new molecules or strategies against HCMV. The new treatments should be low-cost and capable of avoiding the emerging problem of resistant virus. Nanoparticles play an important role in several viral infections. Our main focus is to study the potential activity of polyanionic carbosilane dendrimers (PDC), which are hyperbranched molecules with several sulfonate or sulfate groups in their periphery, against different viruses. RESULTS: We studied the activity of G1-S4, G2-S16 and G2-S24P PDCs in MRC-5 cell line against HCMV infection by several plaque reduction assays. Our results show that dendrimers present good biocompatibility at the concentrations tested (1-50 µM) for 6 days in cell culture. Interestingly, both G2-S16 and G2-S24P showed a remarked inhibition at 10 µM against HCMV infection. Results on attachment and virucidal assays indicated that the inhibition was not directed to the virus or the virus-cell attachment. However, results of time of addition, showed a longer lasting activity of these dendrimers in comparison to ganciclovir, and the combination of G2-S16 or G2-S24P with ganciclovir increases the HCMV inhibition around 90 %. CONCLUSIONS: Nanotechnology, in particular polyanionic carbosilane dendrimers, have proved their potential application against HCMV, being capable of inhibiting the infection by themselves or enhancing the activity of ganciclovir, the actual treatment. These compounds represent a low-cost approach to fight HCMV infections.

Body mass data set for 1,317 bird and 270 mammal species from Colombia.

Body mass is one of the most important phenotypic attributes in animal ecology and life history. This trait is widely used in the fields of ecology and macroevolution, since it influences physiology, morphological functions, and a myriad of ecological and social interactions. In this data set, our aim was to gather a comprehensive bird and mammal body mass data set from northern South America. We report body mass, discriminated by sex, for 42,022 individual birds and 7,441 mammals representing 1,317 bird species (69% of Colombia's avifauna) and 270 mammal species (51% of Colombian mammals) from the Neotropics. The data were sourced from vouchers collected between 1942 and 2020 and from individuals captured and released at banding stations over the last two decades for birds (2000-2020) and the last decade for mammals (2010-2020), by 10 research groups and institutions in Colombia. This data set fills gaps identified in other similar databases, as it focuses on northern South America, a highly diverse Neotropical region often underrepresented in morphological data sets. We provide wide taxonomic coverage for studies interested in information both at regional and local scales. There are no copyright restrictions; the present data paper should be appropriately cited when data are used for publication. The authors would appreciate learning about research projects, teaching exercises, and other uses given to this data set and are open to contribute in further collaborations using these data.

Comparative study of preimplantation development following distinct assisted oocyte activation protocols in a PLC-zeta knockout mouse model.

Mammalian fertilization encompasses a series of Ca2+ oscillations initiated by the sperm factor phospholipase C zeta (PLCζ). Some studies have shown that altering the Ca2+ oscillatory regime at fertilization affects preimplantation blastocyst development. However, assisted oocyte activation (AOA) protocols can induce oocyte activation in a manner that diverges profoundly from the physiological Ca2+ profiling. In our study, we used the newly developed PLCζ-null sperm to investigate the independent effect of AOA on mouse preimplantation embryogenesis. Based on previous findings, we hypothesized that AOA protocols with Ca2+ oscillatory responses might improve blastocyst formation rates and differing Ca2+ profiles might alter blastocyst transcriptomes. A total of 326 MII B6D2F1-oocytes were used to describe Ca2+ profiles and to compare embryonic development and individual blastocyst transcriptomes between four control conditions: C1 (in-vivo fertilization), C2 (ICSI control sperm), C3 (parthenogenesis) and C4 (ICSI-PLCζ-KO sperm) and four AOA groups: AOA1 (human recombinant PLCζ), AOA2 (Sr2+), AOA3 (ionomycin) and AOA4 (TPEN). All groups revealed remarkable variations in their Ca2+ profiles; however, oocyte activation rates were comparable between the controls (91.1% ± 13.8%) and AOA (86.9% ± 11.1%) groups. AOA methods which enable Ca2+ oscillatory responses (AOA1: 41% and AOA2: 75%) or single Ca2+ transients (AOA3: 50%) showed no significantly different blastocyst rates compared to ICSI control group (C2: 70%). In contrast, we observed a significant decrease in compaction (53% vs. 83%) and blastocyst rates (41% vs. 70%) in the absence of an initial Ca2+ trigger (AOA4) compared with the C2 group. Transcription profiles did not identify significant differences in gene expression levels between the ICSI control group (C2) and the four AOA groups.

Roles of the multiplex real-time PCR assay and ß-D-glucan in a high-risk population for intra-abdominal candidiasis (IAC).

Multiplex quantitative real-time PCR (MRT-PCR) using blood can improve the diagnosis of intra-abdominal candidiasis (IAC). We prospectively studied 39 patients with suspected IAC in the absence of previous antifungal therapy. Blood cultures, MRT-PCR, and ß-D-glucan (BDG) in serum were performed in all patients. IAC was defined according to the 2013 European Consensus criteria. For MRT-PCR, the probes targeted the ITS1 or ITS2 regions of ribosomal DNA. Candidaemia was confirmed only in four patients (10%), and IAC criteria were present in 17 patients (43.6%). The sensitivity of MRT-PCR was 25% but increased to 63.6% (P = .06) in plasma obtained prior to volume overload and transfusion; specificity was above 85% in all cases. BDG performance was improved using a cutoff > 260 pg/ml, and improvement was not observed in samples obtained before transfusion. In this cohort of high risk of IAC and low rate of bloodstream infection, the performance of non-culture-based methods (MRT-PCR or BDG) was moderate but may be a complementary tool given the limitations of diagnostic methods available in clinical practice. Volume overload requirements, in combination with other factors, decrease the accuracy of MRT-PCR in patients with IAC.

Metastatic involvement of skeletal muscle from gastric adenocarcinoma.

Gastric cancer represents the fifth most common cancer diagnosis worldwide and the third leading cause of cancer-related mortality. In the USA, the overall 5-year survival rate is 31%, with distant disease nearing 5%. The most common sites of metastasis are the liver and peritoneum. Skeletal muscle involvement has been rarely reported. Since clinical and imaging findings overlap with primary sarcomas, a confirmatory biopsy is required for diagnosis. Prognosis remains poor with treatment options including palliative chemotherapy, radiotherapy and surgical resection. We report the case of a 57-year-old female presenting with extensive involvement of skeletal muscle 10 years after achieving remission. In addition to illustrating the refractoriness and poor outcomes associated with muscle involvement, this case and comprehensive review of the literature highlights important characteristics of disease biology and tumor genomics that warrant detailed discussion and exposition to a wider audience.

Comparative analysis of different nuclear transfer techniques to prevent the transmission of mitochondrial DNA variants.

Prevention of mitochondrial DNA (mtDNA) diseases may currently be possible using germline nuclear transfer (NT). However, scientific evidence to compare efficiency of different NT techniques to overcome mtDNA diseases is lacking. Here, we performed four types of NT, including first or second polar body transfer (PB1/2T), maternal spindle transfer (ST) and pronuclear transfer (PNT), using NZB/OlaHsd and B6D2F1 mouse models. Embryo development was assessed following NT, and mtDNA carry-over levels were measured by next generation sequencing (NGS). Moreover, we explored two novel protocols (PB2T-a and PB2T-b) to optimize PB2T using mouse and human oocytes. Chromosomal profiles of NT-generated blastocysts were evaluated using NGS. In mouse, our findings reveal that only PB2T-b successfully leads to blastocysts. There were comparable blastocyst rates among PB1T, PB2T-b, ST and PNT embryos. Furthermore, PB1T and PB2T-b had lower mtDNA carry-over levels than ST and PNT. After extrapolation of novel PB2T-b to human in vitro matured (IVM) oocytes and in vivo matured oocytes with smooth endoplasmic reticulum aggregate (SERa) oocytes, the reconstituted embryos successfully developed to blastocysts at a comparable rate to ICSI controls. PB2T-b embryos generated from IVM oocytes showed a similar euploidy rate to ICSI controls. Nevertheless, our mouse model with non-mutated mtDNAs is different from a mixture of pathogenic and non-pathogenic mtDNAs in a human scenario. Novel PB2T-b requires further optimization to improve blastocyst rates in human. Although more work is required to elucidate efficiency and safety of NT, our study suggests that PBT may have the potential to prevent mtDNA disease transmission.

Efectividad del modelo de reaprendizaje motor para la recuperación de la mano espástica del adulto con hemiplejía. Revisión sistemática y metaanálisis / Effectiveness of a motor relearning programme for recovery of the spastic hand in adults with hemiplegia. Systematic review and meta-analysis

Introducción: En la hemiplejía, la afectación de la función manual está asociada con dificultad en la ejecución de patrones selectivos de movimiento de tipo individual y bilateral, y aunque no está claro el potencial de recuperación, existen métodos de intervención que pueden disminuir los niveles de discapacidad, como el modelo de reaprendizaje motor. Objetivo: Determinar la efectividad del modelo de reaprendizaje motor en la función de la mano espástica del adulto con hemiplejía. Materiales y métodos: Se realizó una búsqueda sistemática de literatura científica en PubMed, registro Central Cochrane de Ensayos Clínicos Controlados, LILACS, Scielo, así como en diferentes bibliotecas virtuales desde julio de 2015 hasta febrero de 2016. Para determinar la calidad de los estudios se usó la lista de chequeo de la estrategia CONSORT (Consolidated Standars of Reporting Trials) y se evaluó la calidad metodológica mediante la escala de PEDro. Resultados: Se incluyeron 8 estudios, 4 de los cuales fueron seleccionados para metaanálisis e incluían entrenamiento orientado a tareas y de la fuerza muscular. Se encontró que los efectos del modelo no fueron estadísticamente significativos con relación a otro tipo de intervenciones, aunque hubo una tendencia a la mejoría. Conclusión: Los estudios muestran efectividad del modelo de reaprendizaje motor para el tratamiento de la mano espástica del adulto con hemiplejía, aunque no se evidencian estudios que muestren gran poder estadístico con suficiente calidad metodológica para determinar su efectividad frente a la terapia convencional

Introduction: In hemiplegia, the involvement of manual function is associated with difficulty in executing selective patterns of individual and bilateral movement. Although the potential for recovery is not clear, there are interventions that can reduce disability, such as the motor relearning model. Objective: To determine the effectiveness of the motor relearning model in improving the function of the spastic hand in adults with hemiplegia. Materials and methods: A systematic search of scientific literature was performed in PubMed, Cochrane Central Register of Controlled Trials, LILACS, and Scielo, as well as in different virtual libraries from July 2015 to February 2016. To determine the quality of the studies, the CONSORT strategy (Consolidated Standards of Reporting Trials) was used and the methodological quality was evaluated using the PEDro scale. Results: Eight studies were included, and 4 were selected for a meta-analysis. The selected studies included task-oriented and muscular strength training and found that the effects of the model were not statistically significant in relation to other types of interventions, although there was a tendency to improvement. Conclusion: The studies show the effectiveness of the motor relearning model for the treatment of spastic hand in adults with hemiplegia, although there are no studies showing strong statistical power and with sufficient methodological quality to determine their effectiveness compared with that of conventional therapy

Platelet-activating factor acetylhydrolase 1B3 (PAFAH1B3) is required for the formation of the meiotic spindle during in vitro oocyte maturation.

Platelet-activating factor (PAF) is a well-described autocrine growth factor involved in several reproductive processes and is tightly regulated by its hydrolysing enzyme, PAF acetylhydrolase 1B (PAFAH1B). This intracellular enzyme consists of three subunits: one regulatory, 1B1, and two catalytic, 1B2 and 1B3. PAFAH1B3 has remained uncharacterised until now. Here, we report that PAFAH1B3 is present during the different stages of the first meiotic division in bovine, murine and human oocytes. In these species, the PAFAH1B3 subunit was clearly present in the germinal vesicle, while at metaphase I and II, it localised primarily at the meiotic spindle structure. In cattle, manipulation of the microtubules of the spindle by nocodazole, taxol or cryopreservation revealed a close association with PAFAH1B3. On the other hand, disruption of the enzyme activity either by P11, a selective inhibitor of PAFAH1B3, or by PAFAH1B3 antibody microinjection, caused arrest at the MI stage with defective spindle morphology and consequent failure of first polar body extrusion. In conclusion, our results show that one of the catalytic subunits of PAFAH1B, namely PAFAH1B3, is present in bovine, murine and human oocytes and that it plays a functional role in spindle formation and meiotic progression during bovine oocyte maturation.

Human oocyte calcium analysis predicts the response to assisted oocyte activation in patients experiencing fertilization failure after ICSI.

STUDY QUESTION: Can human oocyte calcium analysis predict fertilization success after assisted oocyte activation (AOA) in patients experiencing fertilization failure after ICSI? SUMMARY ANSWER: ICSI-AOA restores the fertilization rate only in patients displaying abnormal Ca2+ oscillations during human oocyte activation. WHAT IS KNOWN ALREADY: Patients capable of activating mouse oocytes and who showed abnormal Ca2+ profiles after mouse oocyte Ca2+ analysis (M-OCA), have variable responses to ICSI-AOA. It remains unsettled whether human oocyte Ca2+ analysis (H-OCA) would yield an improved accuracy to predict fertilization success after ICSI-AOA. STUDY DESIGN, SIZE, DURATION: Sperm activation potential was first evaluated by MOAT. Subsequently, Ca2+ oscillatory patterns were determined with sperm from patients showing moderate to normal activation potential based on the capacity of human sperm to generate Ca2+ responses upon microinjection in mouse and human oocytes. Altogether, this study includes a total of 255 mouse and 122 human oocytes. M-OCA was performed with 16 different sperm samples before undergoing ICSI-AOA treatment. H-OCA was performed for 11 patients who finally underwent ICSI-AOA treatment. The diagnostic accuracy to predict fertilization success was calculated based on the response to ICSI-AOA. PARTICIPANTS/MATERIALS, SETTING, METHODS: Patients experiencing low or total failed fertilization after conventional ICSI were included in the study. All participants showed moderate to high rates of activation after MOAT. Metaphase II (MII) oocytes from B6D2F1 mice were used for M-OCA. Control fertile sperm samples were used to obtain a reference Ca2+ oscillation profile elicited in human oocytes. Donated human oocytes, non-suitable for IVF treatments, were collected and vitrified at MII stage for further analysis by H-OCA. MAIN RESULTS AND THE ROLE OF CHANCE: M-OCA and H-OCA predicted the response to ICSI-AOA in 8 out of 11 (73%) patients. Compared to M-OCA, H-OCA detected the presence of sperm activation deficiencies with greater sensitivity (75 vs 100%, respectively). ICSI-AOA never showed benefit to overcome fertilization failure in patients showing normal capacity to generate Ca2+ oscillations in H-OCA and was likely to be beneficial in cases displaying abnormal H-OCA Ca2+ oscillations patterns. LIMITATIONS, REASONS FOR CAUTION: The scarce availability of human oocytes donated for research purposes is a limiting factor to perform H-OCA. Ca2+ imaging requires specific equipment to monitor fluorescence changes over time. WIDER IMPLICATIONS OF THE FINDINGS: H-OCA is a sensitive test to diagnose gamete-linked fertilization failure. H-OCA allows treatment counseling for couples experiencing ICSI failures to either undergo ICSI-AOA or to participate in gamete donation programs. The present data provide an important template of the Ca2+ signature observed during human fertilization in cases with normal, low and failed fertilization after conventional ICSI. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the Flemish fund for scientific research (FWO-Vlaanderen, G060615N). The authors have no conflict of interest to declare.

Strontium fails to induce Ca2+ release and activation in human oocytes despite the presence of functional TRPV3 channels.

STUDY QUESTION: Are the transient receptor potential cation channels vanilloid 3 (TRPV3) present and able to mediate strontium (Sr2+) induced artificial activation in human oocytes? SUMMARY ANSWER: Sr2+ did not induce Ca2+ rises or provoke activation in human oocytes, however, mRNA for the TRPV3 channel was present in metaphase II (MII) human oocytes after IVM and TRPV3 agonists induced Ca2+ rises and oocyte activation, demonstrating the channels were functional. WHAT IS KNOWN ALREADY: Selective activation of TRPV3 by agonists induces Ca2+ entry and promotes mouse oocyte activation, and the absence of TRPV3 channels in mouse oocytes prevents Sr2+ mediated artificial activation. Sr2+ is sometimes used to overcome fertilization failure after ICSI in the clinic, but its efficiency is still controversial and the mechanism(s) of how it mediates the Ca2+ flux has not been studied yet in human. STUDY DESIGN SIZE DURATION: The protein distribution (n = 10) and mRNA expression level (n = 19) of the TRPV3 channels was investigated in human MII oocytes after IVM. The Sr2+ (10 mM) and TRPV3 agonists (200 µM 2-aminoethoxydiphenyl borate [2-APB] and 200 µM carvacrol)-induced Ca2+ response was analyzed in human (n = 15, n = 16 and n = 16, respectively) and mouse oocytes (n = 15, n = 19 and n = 26, respectively). The subsequent embryonic developmental potential following the parthenogenetic activation using these three agents was recorded in human (n = 10, n = 9 and n = 9, respectively) and mouse (n = 20 per agent) oocytes, by determining pronucleus, or 2-cell and blastocyst formation rates. PARTICIPANTS/MATERIALS SETTING METHODS: MII oocytes from B6D2F1 mice (6-10 weeks old) as well as human IVM oocytes and IVO oocytes (from patients aged 25-38 years old) with aggregates of smooth endoplasmic reticulum clusters were used. The expression of TRPV3 channels was determined by immunofluorescence staining with confocal microscopy and RT-PCR, and the temporal evolution of intracellular Ca2+ concentration was measured by time-lapse imaging after exposure to Sr2+ and TRPV3 agonists (2-APB and carvacrol). Artificial activation efficiency was assessed using these agents. MAIN RESULTS AND THE ROLE OF CHANCE: Sr2+ did not promote Ca2+ oscillations or provoke activation in human oocytes. Transcripts of TRPV3 channels were present in IVM MII human oocytes. TRPV3 protein was expressed and distributed throughout the ooplasm of human oocytes, rather than particularly concentrated in plasma membrane as observed in mouse MII oocytes. Both agonists of TRPV3 (2-APB and carvacrol), promoted a single Ca2+ transient and activated a comparable percentage of more than half of the exposed human oocytes (P > 0.05). The agonist 2-APB was also efficient in activating mouse oocytes, however, significantly fewer mouse oocytes responded to carvacrol than 2-APB in both the Ca2+ analysis and activation test (P < 0.001). LIMITATIONS REASONS FOR CAUTION: The availability of fresh IVO matured oocytes in human was limited. Data from TRPV3 knockout model are not included. WIDER IMPLICATIONS OF THE FINDINGS: The benefit of clinical application using Sr2+ to overcome fertilization failure after ICSI requires further validation. STUDY FUNDING/COMPETING INTERESTS: This study was supported by FWO-Vlaanderen, China Scholarship Council and Special Research Fund from Ghent University (Bijzonder Onderzoeksfonds, BOF). No competing interests are declared.

African histoplasmosis: new clinical and microbiological insights.

African histoplasmosis is defined as the fungal infection caused by Histoplasma capsulatum var. duboisii (Hcd). Studies focused on distinguishing Hcd and H. capsulatum var. capsulatum (Hcc), which coexist in Africa, are scarce or outdated, and African strains are continuously underrepresented. In this work, 13 cases of African patients with histoplasmosis diagnosed in the Spanish Mycology Reference Laboratory have been reviewed showing that 77% had disseminated disease and AIDS as underlying disease although Hcd infection has been classically considered a rare presentation in AIDS patients. Strains isolated from these patients and other clinical and reference strains were studied by assessing classical identification methods and performing a three-loci multi-locus sequence analysis (MLSA). Classical identification methods based on biochemical tests and measurement of yeast size proved to be useless in distinguishing both varieties. The MLSA defined an African cluster, with a strong statistical support, that included all strains with African origin. Finally, mating type was also determined by using molecular methods revealing an unequal mating type distribution in African strains. In conclusion, historical statements and classical identification methods were useless to distinguish between varieties, whereas molecular analyses revealed that all strains with African origin grouped together suggesting that traditional classification should be revised. Further investigation is required in order to unravel traditional concepts about Hcd infection and support results obtained in this work.

Caracterización clínica del loxoscelismo dermonecrótico en equinos de córdoba, colombia / Clinical characterization of dermonecrotic loxoscelism in equine of Córdoba, Colombia / Caracterização clínica da loxoscelismo dermonecrótica em equinos de Córdoba, Colômbia

Resumen El objetivo de este estudio fue evaluar las características clínicas del loxoscelismo dermonecrótico (LDN) en equinos del departamento de Córdoba, Colombia. El estudio, fue de tipo descriptivo, no probabilístico, las muestra fueron seleccionadas por conveniencia. Se utilizaron nueve caballos criollos (Equus ferus caballus) y dos burros (Equus asinus africanus) con LDN diagnosticados clínica e histopatológicamente en diferentes producciones del Departamento. Al describir las lesiones cutáneas, éstas se caracterizaron por la presencia de una severa dermatitis necrótica, con edema y un área eritematosa focal, al detallar el área lesionada, se observó un punto necrótico central y dos halos alrededor (un halo blanco medial y un halo violáceo más externo) en la mayoría de los casos estudiados; así como ausencia de signos neurológicos y sistémicos. Las lesiones se ubicaron en la mayoría de los casos a nivel dorsal, seguido de la región rostral, pecho y pene. Histopatológicamente en la coloración de Hematoxilina Eosina (H&E), se observó severa dermatitis piogranulomatosa, con marcada infiltración de polimorfonucleares especialmente neutrófilos, con vacuolización de la capa basal de la epidermis y edema en la unión dermo-epidérmica. El diagnóstico definitivo de LDN en los 11 animales estudiados, se fundamentó en las manifestaciones clínicas observadas, las características anatomopatológicas de las lesiones y los resultados histopatológicos. El presente informe constituye el primer reporte de LDN en el Departamento de Córdoba, ya que no se encontraron reportes en la literatura consultada.

Abstract The aim of this study was to characterize the clinical aspects of dermonecrotic loxoscelism (LDN) in horses department of Cordoba, Colombia. This study was descriptive, not probabilistic, in animals of convenience. Nine horses (Equus ferus caballus) and 2 donkeys (Equus asinus africanus) were used with LDN diagnosed clinically and histopathologically in different productions of the Department. When describing the skin lesions, these were characterized by the presence of severe necrotic dermatitis, with edema and a focal erythematous area, when detailing the injured area, a central necrotic spot and two halos around it (a medial white halo and a halo Violet) in most of the cases studied; As well as absence of neurological and systemic signs. The lesions were located in most cases at the dorsal level, followed by the rostral region, chest and penis. Histopathologically in the staining of Hematoxylin Eosin (H & E), severe piogranulomatous dermatitis was observed, with marked infiltration of polymorphonuclear cells especially neutrophils, with vacuolization of the basal layer of the epidermis and edema in the dermo-epidermal junction. The definitive diagnosis of LDN in the 11 animals studied was based on the clinical manifestations observed, the anatomopathological characteristics of the lesions and the histopathological results. The present report constitutes the first LDN report in the Department of Córdoba, since no reports were found in the consulted literature.

Resumo O objetivo deste estudo foi caracterizar os aspectos clínicos da loxoscelismo dermonecrótica (LDN) em equinos de Córdoba, Colômbia. Este estudo foi descritivo, não probabilístico, em animais de conveniência. Foram usados 9 cavalos (Equus ferus caballus) e 2 jumentos (Equus asinus africanus) com LDN clinicamente e histologicamente diagnosticado no Departamento diferentes produções. Ao descrever as lesões da pele, que foram caracterizados pela presença de dermatite necrotizante grave, edema e focal área eritematosa, detalhando a área lesionada, um ponto necrótico central e dois halos foram observados em torno de (halo branco medial e halo mais exterior) violáceo, na maioria dos casos estudados; e ausência de sinais neurológicos e sistémicas. As lesões foram localizados na maioria dos casos ao nível dorsal, seguida da rostral, peito e do pénis. Foi observada histologicamente em hematoxilina-eosina (H & E), dermatite piogranulomatosa grave, com infiltração acentuada de neutrófilos polimorfonucleares especialmente com vacuolização da camada basal da epiderme e edema na junção dermo-epidérmica. O diagnóstico definitivo da LDN nos 11 animais estudados foi baseado nas manifestações clínicas observadas, características histopatológicas de lesões e os resultados histopatológicos. O presente relatório constitui o primeiro relatório LDN no Departamento de Córdoba, uma vez que não foram encontrados relatórios na literatura consultada.

Syndrome of Inappropriate Anti-Diuretic Hormone Secretion Secondary to Strongyloides stercoralis Infection in an Allogeneic Stem Cell Transplant Patient: A Case Report and Literature Review.

Syndrome of inappropriate anti-diuretic hormone (SIADH) has been reported to be associated with systemic Strongyloides stercoralis. Here, we report a case of a stem cell transplant (SCT) recipient who developed severe SIADH secondary to systemic S Stercoralis. The SIADH resolved quickly after treating the systemic S Stercoralis with ivermectin. A systematic review of the literature was performed by PubMed, Scopus, and Cochrane database search. Only eight cases of S Stercoralis in allogeneic SCT recipients have been previously reported. To our knowledge, ours is the first reported case of SIADH secondary to S Stercoralis infection in an allogeneic SCT recipient. Prior to transplantation, even if asymptomatic, patients from endemic regions should be screened with strongyloides immunoglobulin (Ig)G serology. Pretransplantation eosinophilia should be evaluated by screening multiple stool samples for ova and parasites. Transplant candidates with positive serology or stool tests can be treated pretransplantation to eradicate infection. Patients at risk for S Stercoralis who develop nonspecific gastrointestinal complaints, rash, pulmonary infiltrates, or gram-negative bacteremia or meningitis may have S Stercoralis hyperinfection syndrome. Our case indicates that the development of SIADH may be an additional clue to this diagnosis. Appropriate diagnostic studies, including repeat stool and other body fluid sampling, should be expedited and ivermectin therapy initiated rapidly to prevent significant morbidity and mortality.

Glycemia levels in Colombian creole foals during their first hours of life / Niveles de glicemia en potros criollo colombiano durante sus primeras horas de vida / Glicemia potros Crioulos colombianos durante seu primeiras horas de vida

The blood glucose level is an important parameter for clinical dedicated to equine neonatology, especially in neonatal care units, where is critical as a prognostic indicator parameter, so you need to have parameters precise reference to assist the decision making. In the race Criollo Colombiano we have not found reference values, so in clinical practice are used values for different races and backgrounds, and this is the first report in this race in Colombia. The study was conducted in the municipality of Bolivar City; where blood glucose levels were assessed in peripheral blood sample using a portable glucometer. They were evaluated 29 infants children foals stabled mares, measurements were made before the first lactation (T0) and three measurements at intervals of three hours. (T3, T6 and T9). Confidence intervals for the population mean were determined, and a comparison was made between the sexes, a regression equation for predicting glucose was also determined by the measurement time. T0 was determined that an average of 81.76 ± 9.25 mg / dL, was presented to the T3 was 88.97 ± 11.73 mg / dL, for the T6 112.31 ± 16.52 mg / dL and T9 118.52 ± 13.59 was mg / dL. Polynomial regression equation was Glucose = 80.27 + 1.617 tiempo2-0,127tiempo3 (R2 = 0.58). No statistically significant difference (p> 0.05) was found between the sexes.

El nivel de glicemia es un parámetro importante para el clínico dedicado a la neonatología equina, especialmente en las unidades de cuidados neonatales, en las cuales es un parámetro crítico como indicador pronóstico, por lo que es necesario tener parámetros de referencia precisos que ayuden a la toma de decisiones. En la raza Criollo Colombiano no se han encontrado valores de referencia, por lo que en la práctica clínica son usados valores establecidos para razas y ambientes diferentes, siendo este el primer reporte en esta raza en Colombia. El estudio se desarrolló en el municipio de Ciudad Bolívar; en donde se evaluaron los niveles de glicemia en muestra de sangre periférica mediante un glucómetro portátil. Fueron evaluados 29 potros neonatos hijos de yeguas estabuladas, se realizaron mediciones antes de la primera lactancia (T0) y tres mediciones más con intervalos de tres horas. (T3, T6 y T9). Se determinaron los intervalos de confianza para la media poblacional, y se realizó una comparación entre sexos, también se determinó una ecuación de regresión para la predicción de la glucosa según el tiempo de medición. Se determinó que al T0 se presentó una media de 81,76 ± 9,25 mg/dL, para el T3 fue de 88,97 ± 11,73 mg/dL, para el T6 de 112,31 ± 16,52 mg/dL y para el T9 fue de 118,52 ± 13,59 mg/dL. La ecuación de regresión polinómica fue Glucosa = 80,27+1,617 tiempo2- 0,127tiempo3 (R2 =0,58). No se encontró diferencia estadísticamente significativa (p>0,05) entre los sexos.

O nível de açúcar no sangue é um parâmetro importante para clínico dedicado a neonatologia equino, especialmente em unidades de cuidados neonatais, onde é crítica como um parâmetro indicador de prognóstico, por isso você precisa ter parâmetros de referência precisos para ajudar o tomada de decisã o. Na corrida Criollo Colombiano nã o foram encontrados valores de referência, de modo que na prática clínica sã o os valores usados para diferentes raças e origens, e este é o primeiro relatório nesta corrida na Colô mbia. O estudo foi realizado no municipalidades de Ciudad Bolívar; onde os níveis de glicose no sangue foram avaliados em amostra de sangue periférico usando um glicosímetro portátil. Foram avaliadas 29 crianças crianças potros éguas estabulados, as medidas foram feitas antes da primeira lactaçã o (T0) e três medições em intervalos de três horas. (T3, T6 e T9). foram determinados intervalos de confiança para a média da populaçã o, e foi feita uma comparaçã o entre os sexos, uma equaçã o de regressã o para a previsã o de glicose também foi determinada pelo tempo de mediçã o. T0 foi determinado que uma média de 81,76 ± 9,25 mg / dL, foi apresentada para a T3 era 88,97 ± 11,73 mg / dL, para a T6 112,31 ± 16,52 mg / dL e T9 118,52 ± 13,59 era mg / dL. equaçã o de regressã o polinomial foi Glucose = 80,27 + 1.617 tempo 2-0,127 tempo 3 (R2 = 0,58). Nã o foi encontrada diferença estatisticamente significativa (p> 0,05) entre os sexos..

Clinical, histological and histochemical description of equine pemphigus foliaceus: a case report / Descripción clínica, histológica e histoquímica del pénfigo foliáceo equino: un reporte de caso / Descriçã o clínica, histológica e histoquímica pênfigo foliáceo eqüinos: relato do caso

The aim of this study was to describe the clinical, gross and microscopic lesions as diagnostic methods pemphigus foliaceus (PF) in an imported horse Silla Argentino, castrated male, 9 years old from the municipality of Montería (Córdoba, Colombia). In describing the clinical case, the presence of scabs generalized mainly at the level of the chest and abdomen, initially presented ventral edema and some areas had pustules and vesicles, as well as fever and marked pruritus was observed. The lesions were located bilaterally at the level of face, thoracic region, abdominal, gluteal and limbs. Histopathological in the HE stain, was observed the presence of acantholytic keratinocytes and areas acantholytic sloughing in the granular layer, hyperplasia and epidermal desquamation; areas subepidermal spongiosis and various subcorneal pustules characterized by the presence of intact neutrophils and degenerate and dermal edema hyalinization moderate collagen, likewise in TG staining, poor dermal collagen proliferation disorganized with little presence of diffuse connective tissue was observed, while in the PR/P staining, areas of red birefringence was observed, indicating moderate presence of mature type I collagen (red bright polarization). The diagnosis was based on clinical signs, histopathological findings, differential diagnosis and response to medical treatment. In the literature there are no reports of PF in the Department, so it is the first report of this disease in horses of Córdoba.

El objetivo de este estudio fue describir las manifestaciones clínicas, lesiones macro y microscópicas como métodos de diagnóstico del pénfigo foliáceo (PF) en un caballo importado Silla Argentino, macho entero, de 9 años de edad, procedente del municipio de Montería (Córdoba, Colombia). Al describir el caso clínico, se observó presencia de costras generalizadas principalmente a nivel de tórax y abdomen, inicialmente presentó edema ventral y algunas zonas presentaron pústulas y vesículas, así como fiebre y prurito marcado. Las lesiones se ubicaron en forma bilateral, a nivel de rostro, región torácica, abdominal, glútea y extremidades. Histopatológicamente en la coloración de HE, se observó la presencia de queratinocitos acantolíticos y áreas de esfacelación acantolítica en la capa granulosa, Hiperplasia y descamación epidérmica, áreas de espongiosis subepidérmica y diversas pústulas subcórneas caracterizadas por la presencia de neutrófilos íntegros y degenerados y edema dérmico con moderada hialinización del colágeno, así mismo en la tinción de T-G, se observó escasa proliferación dérmica de colágeno desorganizados con escasa presencia de tejido conjuntivo difuso, mientras que en la tinción de P-R/P, se observó áreas de birrefringencia rojiza, indicando moderada presencia de colágeno maduro tipo I (color rojo brillante en la polarización). El diagnóstico se fundamentó en los signos clínicos, hallazgos histopatológicos, diagnóstico diferencial y respuesta al tratamiento médico. En la literatura consultada no existen reportes de PF en el Departamento, por lo que es el primer reporte de esta enfermedad en caballos de Córdoba.

O objetivo deste estudo foi descrever as lesões clínicas, macroscópicas e microscópicas como métodos de diagnóstico do pénfigo foliaceo (PF) num cavalo importado Argentino, macho, de 9 anos de idade do município de Montería (Córdoba, Colô mbia). Ao descrever o caso clínico, observou-se a presença de crostas generalizadas, principalmente ao nível do tórax e do abdómen, inicialmente apresentaram edema ventral e algumas áreas tinham pústulas e vesículas, bem como febre e prurido marcado. As lesões eram localizadas bilateralmente, a altura da face, regiã o torácica, abdominal, glúteos e membros. Foi observada na histopatologia na coloraçã o de HE, a presença de queratinócitos acantolíticos e áreas de descamaçã o acantolíticas na camada granular, hiperplasia e descamaçã o da epiderme, áreas de espongiose subepidermal e várias pústulas subcórneas caracterizados pela presença de neutrófilos intactos e degenerados, edema dérmico moderado e hialinizaçã o de colágeno, também na coloraçã o T-G, observou-se pobre proliferaçã o de colágeno dérmico desorganizado com pouca presença de tecido conjuntivo difuso, enquanto na coloraçã o de PR/P, observou-se a presença de áreas de birrefringência avermelhada, indicando presença moderada de colágeno tipo I maduro (vermelho brilhante na polarizaçã o). O diagnóstico foi baseado nos sinais clínicos, achados histopatológicos, diagnóstico diferencial e resposta ao tratamento médico. Na literatura nã o há relatos de PF no Departamento, por isso é o primeiro relato da doença em cavalos de Córdoba.