Clinical and Histopathologic Features of Subungual Melanoma in 57 Mexican Patients: A 5-Year Cohort Study. / Características clínicas e histopatológicas de melanoma subungueal en 57 pacientes mexicanos: una cohorte de 5 años.

Although subungual melanoma is uncommon, it is associated with worse outcomes than melanomas in other locations and accounts for 1% to 23% of all melanomas, depending on the population. The aim of this study was to describe the clinical and histopathologic features of subungual melanoma in a Mexican population. We identified 303 patients with melanoma, and of these, 19% (57 patients with a median age of 71 years) had subungual melanoma. The main sites affected were the lower limbs (52.6%) and the toe (75.4%). The most common histologic subtype was acral lentiginous melanoma (50.9%). Median Breslow thickness was 3 mm, and stage IA tumors were the most common (in 28.1% of patients). Recurrence and metastasis occurred in 19.3% and 8.8% of patients, respectively. The clinical and histopathologic features identified are similar to those described in the literature. Early diagnosis and treatment are crucial for improving prognosis.

[Translated article] Clinical and Histopathologic Features of Subungual Melanoma in 57 Mexican Patients: A 5-Year Cohort Study.

Although subungual melanoma is uncommon, it is associated with worse outcomes than melanomas in other locations and accounts for 1% to 23% of all melanomas, depending on the population. The aim of this study was to describe the clinical and histopathologic features of subungual melanoma in a Mexican population. We identified 303 patients with melanoma, and of these, 19% (57 patients with a median age of 71 years) had subungual melanoma. The main sites affected were the lower limbs (52.6%) and the toe (75.4%). The most common histologic subtype was acral lentiginous melanoma (50.9%). Median Breslow thickness was 3 mm, and stage IA tumors were the most common (in 28.1% of patients). Recurrence and metastasis occurred in 19.3% and 8.8% of patients, respectively. The clinical and histopathologic features identified are similar to those described in the literature. Early diagnosis and treatment are crucial for improving prognosis.

Gender, hormone therapy, and HIV: what should cardiologists know?

Transgender individuals represent the fastest growing minority in the United States and are disproportionately affected by HIV. Hormone therapy is the most common treatment for gender dysphoria in transgender individuals. As HIV is an independent risk factor for coronary artery disease, it is critical to further research the influence masculinising and feminising hormone therapies have on cardiovascular disease. There is a clinical need for evidence-based guidelines for cardiologists to follow to effectively care for and treat transgender patients. For this to be done, the interplay between HIV, hormone therapy, and cardiovascular disease must be better understood through collaboration between researchers and clinicians to achieve maximum benefit from recent advancements.

Importance of oil overlay for production of porcine embryos in vitro.

Technologies to edit the zygote genome have revolutionized biomedical research not only for the creation of animal models for the study of human disease but also for the generation of functional human cells and tissues through interspecies blastocyst complementation technology. The pig is the ideal species for these purposes due to its great similarity in anatomy and physiology to humans. Emerging biotechnologies require the use of oocytes and/or embryos of good quality, which might be obtained using in vitro production (IVP) techniques. However, the current porcine embryo IVP systems are still suboptimal and result in low monospermic fertilization and blastocyst formation rates and poor embryo quality. During recent years, intensive investigations have been performed to evaluate the influence of specific compounds on gametes and embryos and to avoid the use of undefined supplements (serum and serum derivate) in the incubation media. However, little consideration has been given to the use of the mineral oil (MO) to overlay incubation droplets, which, albeit being a routine component of the IVP systems, is a totally undefined and thus problematic product for the safety of gametes and embryos. In this review, we provide an overview on the advantages and disadvantages of using MO to cover the incubation media. We also review one important concern in IVP laboratories: the use of oils containing undetected contamination. Finally, we discuss the effects of different types of oils on the in vitro embryo production outcomes and the transfer of compounds from oil into the culture media.

BIBI: Bayesian inference of breed composition.

The aim of this paper was to develop statistical models to estimate individual breed composition based on the previously proposed idea of regressing discrete random variables corresponding to counts of reference alleles of biallelic molecular markers located across the genome on the allele frequencies of each marker in the pure (base) breeds. Some of the existing regression-based methods do not guarantee that estimators of breed composition will lie in the appropriate parameter space, and none of them account for uncertainty about allele frequencies in the pure breeds, that is, uncertainty about the design matrix. To overcome these limitations, we proposed two Bayesian generalized linear models. For each individual, both models assume that the counts of the reference allele at each marker locus follow independent Binomial distributions, use the logit link and pose a Dirichlet prior over the vector of regression coefficients (which corresponds to breed composition). This prior guarantees that point estimators of breed composition such as the posterior mean pertain to the appropriate space. The difference between these models is that model termed BIBI does not account for uncertainty about the design matrix, while model termed BIBI2 accounts for such an uncertainty by assigning independent Beta priors to the entries of this matrix. We implemented these models in a data set from the University of Florida's multibreed Angus-Brahman population. Posterior means were used as point estimators of breed composition. In addition, the ordinary least squares estimator proposed by Kuehn et al. () (OLSK) was also computed. BIBI and BIBI2 estimated breed composition more accurately than OLSK, and BIBI2 had a 7.69% improvement in accuracy as compared to BIBI.

Tspan33 is Expressed in Transitional and Memory B Cells, but is not Responsible for High ADAM10 Expression.

Tetraspanins are a family of transmembrane proteins that form membrane microdomains. They play important roles in migration, adhesion and other cellular processes. TspanC8, a subfamily of tetraspanins, was found to associate and promote ADAM10 trafficking and cell surface localization. One of its members, Tspan33, is expressed in activated B cells. Using RT-PCR and flow cytometry, we analysed the pattern of expression of Tspan33 in B cells from healthy donors. We found Tspan33 expression in early and late stages of B cell development. However, Tspan33 expression did not correlate with ADAM10 surface expression. We also found expression of Tspan33 early in the activation process. Given its predominant expression in activated B cells and in several lymphomas, but not in naive B cells, we hypothesize that Tspan33 could be a potential target for therapeutic purposes.

Effects of meiotic inhibitors and gonadotrophins on porcine oocytes in vitro maturation, fertilization and development.

This study evaluated the effect of three reversible meiotic inhibitors (MINs) and their interaction with gonadotrophins (Gns) on the meiotic maturation and developmental competence of porcine oocytes. In experiment 1, the oocytes were matured for 22 hr in the presence or absence of dbcAMP (1 mM), cycloheximide (7 µM) or cilostamide (20 µM) with or without Gns, and for an additional 22 hr in the absence of MINs and Gns. At 22 hr of maturation, regardless of the presence of Gns, a higher proportion (p < .001) of oocytes cultured in the presence of MINs were effectively arrested at the germinal vesicle stage compared with the oocytes cultured without MINs. At 44 hr of maturation, the proportion of oocytes that reached MII was higher (p < .05) in groups with Gns compared with groups without Gns. In experiment 2, oocytes that were matured as in experiment 1 were inseminated and cultured for 7 days to evaluate fertilization parameters and blastocyst formation. Only oocytes from the dbcAMP + Gns group had higher (p < .05) efficiency of fertilization compared with the other treatment groups. The presence of dbcAMP during maturation also increased (p < .05) blastocyst formation and efficiency of blastocyst formation in both the presence and absence of Gns. These results indicate that the interaction of Gns with the tested MINs improved meiotic progression. In addition, regardless of supplementation with Gns, the presence of dbcAMP during the first maturation period increased and even doubled the capacity of oocytes to develop to the blastocyst stage.

Gaussian covariance graph models accounting for correlated marker effects in genome-wide prediction.

Several statistical models used in genome-wide prediction assume uncorrelated marker allele substitution effects, but it is known that these effects may be correlated. In statistics, graphical models have been identified as a useful tool for covariance estimation in high-dimensional problems and it is an area that has recently experienced a great expansion. In Gaussian covariance graph models (GCovGM), the joint distribution of a set of random variables is assumed to be Gaussian and the pattern of zeros of the covariance matrix is encoded in terms of an undirected graph G. In this study, methods adapting the theory of GCovGM to genome-wide prediction were developed (Bayes GCov, Bayes GCov-KR and Bayes GCov-H). In simulated data sets, improvements in correlation between phenotypes and predicted breeding values and accuracies of predicted breeding values were found. Our models account for correlation of marker effects and permit to accommodate general structures as opposed to models proposed in previous studies, which consider spatial correlation only. In addition, they allow incorporation of biological information in the prediction process through its use when constructing graph G, and their extension to the multi-allelic loci case is straightforward.

The Recipients' Parity Does Not Influence Their Reproductive Performance Following Non-Surgical Deep Uterine Porcine Embryo Transfer.

With the development of the non-surgical deep uterine (NsDU) embryo transfer (ET) technology, the commercial applicability of ET in pigs is now possible. There are, nevertheless, many factors that influence NsDU-ET effectiveness that need to be addressed. The aim of this study was to evaluate the effects of the weaned recipients' parity on fertility and prolificacy following NsDU-ET. The recipients (n = 120) were selected based on their reproductive history and body condition and grouped into three categories according to their parity: primiparous sows, sows of parity 2 and sows of parities from 3 to 5. Thirty fresh embryos (morulae and unhatched blastocysts) were non-surgically transferred into one uterine horn of each recipient. It was possible to insert the NsDU-ET catheter through the cervix along a uterine horn in 98.3% of the recipients. The parity had no influence on the difficulty grade of the insertions or on the percentage of correct insertions. The cervix and uterine wall were not perforated during the insertions, and vaginal discharge was not observed after transfer in any of the recipients. There were no differences in the pregnancy rates (74.8%), farrowing rates (71.2%) or litter sizes (9.6 ± 3.3) between groups. Also, there were no differences between groups regarding to the piglets' birthweights or piglet production efficiency. In conclusion, these results demonstrate that weaned sows from parity 1 to 5 are appropriate to be used as recipients in NsDU-ET programs, which increase the possibilities for the utilization of ET in the recipient farms.

Generation of human organs in pigs via interspecies blastocyst complementation.

More than eighteen years have passed since the first derivation of human embryonic stem cells (ESCs), but their clinical use is still met with several challenges, such as ethical concerns regarding the need of human embryos, tissue rejection after transplantation and tumour formation. The generation of human induced pluripotent stem cells (iPSCs) enables the access to patient-derived pluripotent stem cells (PSCs) and opens the door for personalized medicine as tissues/organs can potentially be generated from the same genetic background as the patient recipients, thus avoiding immune rejections or complication of immunosuppression strategies. In this regard, successful replacement, or augmentation, of the function of damaged tissue by patient-derived differentiated stem cells provides a promising cell replacement therapy for many devastating human diseases. Although human iPSCs can proliferate unlimitedly in culture and harbour the potential to generate all cell types in the adult body, currently, the functionality of differentiated cells is limited. An alternative strategy to realize the full potential of human iPSC for regenerative medicine is the in vivo tissue generation in large animal species via interspecies blastocyst complementation. As this technology is still in its infancy and there remains more questions than answers, thus in this review, we mainly focus the discussion on the conceptual framework, the emerging technologies and recent advances involved with interspecies blastocyst complementation, and will refer the readers to other more in-depth reviews on dynamic pluripotent stem cell states, genome editing and interspecies chimeras. Likewise, other emerging alternatives to combat the growing shortage of human organs, such as xenotransplantation or tissue engineering, topics that has been extensively reviewed, will not be covered here.

Vaccine-associated varicella and rubella infections in severe combined immunodeficiency with isolated CD4 lymphocytopenia and mutations in IL7R detected by tandem whole exome sequencing and chromosomal microarray.

In areas without newborn screening for severe combined immunodeficiency (SCID), disease-defining infections may lead to diagnosis, and in some cases, may not be identified prior to the first year of life. We describe a female infant who presented with disseminated vaccine-acquired varicella (VZV) and vaccine-acquired rubella infections at 13 months of age. Immunological evaluations demonstrated neutropenia, isolated CD4 lymphocytopenia, the presence of CD8(+) T cells, poor lymphocyte proliferation, hypergammaglobulinaemia and poor specific antibody production to VZV infection and routine immunizations. A combination of whole exome sequencing and custom-designed chromosomal microarray with exon coverage of primary immunodeficiency genes detected compound heterozygous mutations (one single nucleotide variant and one intragenic copy number variant involving one exon) within the IL7R gene. Mosaicism for wild-type allele (20-30%) was detected in pretransplant blood and buccal DNA and maternal engraftment (5-10%) demonstrated in pretransplant blood DNA. This may be responsible for the patient's unusual immunological phenotype compared to classical interleukin (IL)-7Rα deficiency. Disseminated VZV was controlled with anti-viral and immune-based therapy, and umbilical cord blood stem cell transplantation was successful. Retrospectively performed T cell receptor excision circle (TREC) analyses completed on neonatal Guthrie cards identified absent TREC. This case emphasizes the danger of live viral vaccination in severe combined immunodeficiency (SCID) patients and the importance of newborn screening to identify patients prior to high-risk exposures. It also illustrates the value of aggressive pathogen identification and treatment, the influence newborn screening can have on morbidity and mortality and the significant impact of newer genomic diagnostic tools in identifying the underlying genetic aetiology for SCID patients.

Robust T cell responses to aspergillosis in chronic granulomatous disease: implications for immunotherapy.

Chronic granulomatous disease (CGD) patients are highly susceptible to invasive aspergillosis and might benefit from aspergillus-specific T cell immunotherapy, which has shown promise in treating those with known T cell defects such as haematopoietic stem cell transplant (HSCT) recipients. But whether such T cell defects contribute to increased risks for aspergillus infection in CGD is unclear. Hence, we set out to characterize the aspergillus-specific T cell response in CGD. In murine CGD models and in patients with CGD we showed that the CD4(+) T cell responses to aspergillus were unimpaired: aspergillus-specific T cell frequencies were even elevated in CGD mice (P < 0·01) and humans (P = 0·02), compared to their healthy counterparts. CD4-depleted murine models suggested that the role of T cells might be redundant because resistance to aspergillus infection was conserved in CD4(+) T cell-depleted mice, similar to wild-type animals. In contrast, mice depleted of neutrophils alone or neutrophils and CD4(+) T cells developed clinical and pathological evidence of pulmonary aspergillosis and increased mortality (P < 0·05 compared to non-depleted animals). Our findings that T cells in CGD have a robust aspergillus CD4(+) T cell response suggest that CD4(+) T cell-based immunotherapy for this disease is unlikely to be beneficial.

Organic π-conjugated copolymers as molecular charge qubits.

We propose a design for molecular charge qubits based on π-conjugated block copolymers and determine their electronic structure as well as their vibrational active modes. By tuning the length of the oligomers, the tunnel coupling in the charge qubit and its decoherence properties due to molecular vibrations can be chemically engineered. Coherent oscillations result with quality factors of up to 10(4) at room temperature. In turn, the molecular vibrational spectrum induces strong non-Markovian electronic effects which support the survival of quantum coherence.

Genetic diversity and mating system of Copaifera langsdorffii (Leguminosae/Caesalpinioideae).

Copaifera langsdorffii, locally known as copaíba, is a valuable tropical tree with medicinal properties of its oil. We studied the genetic variation, genetic structure, and the mating system of trees in stands of C. langsdorffii (Leguminosae/Caesalpinioideae) located in an extensive area between the Pardo and Mogi-Guaçu basins in São Paulo State, Brazil, and their offspring, conserved in an ex situ germplasm bank at the University of São Paulo in Ribeirão Preto, SP, Brazil, using six microsatellite loci. Leaves were collected from 80 seed trees and from 259 offspring and their DNA extracted. A total of 140 and 175 alleles were found in the seed trees and their offspring, respectively. Low genetic differentiation was observed between stands, indicating intense gene flow due to efficient pollen dispersion vectors. An estimation of the outcrossing rate showed that these stands are outcrossed (tm = 0.98, P > 0.05). The mean variance of the effective population size of each family in two of the stands was 3.69 and 3.43, while the total effective population size retained in the germplasm bank was between 81 and 96. The paternity correlation was low, ranging from 0.052 to 0.148, demonstrating that the families implanted in this germplasm bank are composed predominantly of half-sibs.

A decreased expression of interferon stimulated genes in peri-implantation endometrium of embryo transfer recipient sows could contribute to embryo death.

Pig pregnancy succeeds thanks to a well-coordinated system ruling both maternal immune activation and embryonic antigen tolerance. In physiological pregnancies, the maternal immune system should tolerate the presence of hemi-allogeneic conceptuses from the pre-implantation phase to term, while maintaining maternal defence against pathogens. Allogeneic pregnancies, as after embryo transfer (ET), depict high embryo mortality during the attachment phase, calling for studies of the dynamic modifications in immune processes occurring at the maternal-foetal interface, for instance, of interferon (IFN)-stimulated genes (ISGs). These ISGs are generally activated by IFN secreted by the conceptus during the process of maternal recognition of pregnancy (MRP) and responsible for recruiting immune cells to the site of embryo attachment, thus facilitating cell-antigen presentation and angiogenesis. We performed RNA-Seq analysis in peri-implantation (days 18 and 24) endometrial samples retrieved from artificially inseminated sows (hemi-allogeneic embryos (HAL) group) or sows subjected to ET (allogeneic embryos (AL) group) to monitor alterations of gene expression that could be jeopardising early pregnancy. Our results showed that endometrial gene expression patterns related to immune responses differed between hemi- or allogeneic embryo presence, with allogeneic embryos apparently inducing conspicuous modifications of immune-related genes and pathways. A decreased expression (P < 0.05; FC < -2) of several interferon ISGs, such as CXCL8, CXCL10, IRF1, IRF9, STAT1, and B2M, among others was detected in the endometrium of sows carrying allogeneic embryos on day 24 of pregnancy. This severe downregulation of ISGs in allogeneic pregnancies could represent a failure of ET-embryos to signal IFN to the endometrium to warrant the development of adequate immunotolerance mechanisms to facilitate embryo development, thus contributing to elevated embryo death.

Aspects Towards the Anastomotic Healing in Crohn's Disease: Clinical Approach and Current Gaps in Research.

Anastomotic leakage is a major complication in gastrointestinal and colorectal surgery and its occurrence increases morbidity and mortality. Its incidence is even higher in Crohn's disease surgeries. Several authors have identified factors involved in the pathophysiology of anastomotic leak in the literature, aiming to reduce its occurrence and, therefore, improve its surgical treatment. Surgical technique is the most discussed topic in studies on guiding the performance of side-to-side stapled anastomosis. Preoperative nutritional therapy also has been shown to reduce the risk of anastomotic leakage. Other factors remain controversial - immunomodulator use and biologic therapy, antibiotics, and gut microbiota - with studies showing a reduction in the risk of complication while other studies show no correlation. Although mesenteric adipose tissue has been related to disease recurrence, there is no evidence in the literature that it is related to a higher risk of anastomotic leakage. Further exploration on this topic is necessary, including prospective research, to support the development of techniques to prevent anastomotic leakage, in this way benefiting the inflammatory bowel disease patients who have to undergo a surgical procedure.

Metagenomics analysis reveals universal signatures of the intestinal microbiota in colorectal cancer, regardless of regional differences.

The human gut microbiota is a complex and dynamic community of microorganisms living in our intestines and has emerged as an important factor for colorectal adenocarcinoma (CRC). The purpose of our study was to investigate the microbiota composition in Brazilian CRC patients compared with a local control population (CTL) to find out which changes could be considered universal or regional features in CRC microbiota. Fecal samples were obtained from 28 CRC and 23 CTL individuals. The 16S rRNA gene was used for metagenomic analysis. In addition to the anthropometric variables, the clinical stage (TNM 2018) was considered. Patients with CRC had a significant increase in alpha diversity and a higher percentage of genus Prevotella and a decreased proportion of Megamonas and Ruminococcus. Additionally, the proportion of Faecalibacterium prausnitzii was associated with a better prognosis in the first stages of CRC, and Fusobacterium nucleatum proved to be an important marker of colorectal carcinogenesis and tumor aggressiveness. Although regional differences influence the composition of the microbiota, in the case of CRC, the microhabitat created by the tumor seems to be a major factor. Our results contribute to a better understanding of the carcinogenic process, and even in different environments, some factors appear to be characteristic of the microbiota of patients with CRC.

Diagnostic agreement between video capsule endoscopy and single and double balloon enteroscopy for small bowel bleeding at a tertiary care hospital in Bogota, Colombia. / Concordancia diagnóstica entre la videocápsula endoscópica y enteroscopia mono y de doble balón en la hemorragia de intestino delgado en un hospital de alta complejidad en Bogotá, Colombia.

INTRODUCTION: Video capsule endoscopy and balloon-assisted enteroscopy are complementary diagnostic methods in the study of small bowel bleeding, and different factors can affect their diagnostic yield. AIMS: To define the level of agreement between video capsule endoscopy and enteroscopy in small bowel bleeding, according to the type of lesion, in a cohort of patients at a tertiary care referral center. MATERIALS AND METHODS: A retrospective study was conducted that included 428 capsule endoscopies performed within the time frame of 2011 and 2019 at our healthcare institution. Seventy-four video capsule endoscopies, followed by enteroscopy, in 71 patients suspected of presenting with small bowel bleeding, were analyzed. RESULTS: Mean patient age was 63.9 ± 13.5 years and 42 patients were women. The two diagnostic procedures were performed. Overall diagnostic yield of positive findings between video capsule endoscopy and enteroscopy was 86.5% vs. 58.1%, respectively (p = 0.0527). Agreement between video capsule endoscopy and enteroscopy for positive pathologic findings was weak (Ik = 0.17, 95% CI: -0.0097-0.3543), but according to lesion type, it was good for inflammatory lesions (Ik = 0.71, 95% CI: 0.5182-0.9119) and moderate for angiectasias (Ik = 0.45, 95% CI: 0.2469-0.6538) and tumors (Ik = 0.40, 95% CI: 0.1217-0.6794). The results between the two methods differed in 38 patients (51.3%). There was complete intestinal capsule retention in one patient (1.4%) and active bleeding in 13 (17.6%). CONCLUSIONS: The present study showed that the two techniques had a similar overall detection rate for small bowel lesions, but the type of lesion was the main factor that could modify diagnostic agreement.

The most highly cited articles of the Revista de Gastroenterología de México over a 22-year period (1996-2018). / Los artículos más citados en la Revista de Gastroenterología de México en un período de 22 años (1996-2018).

INTRODUCTION AND AIM: The Revista de Gastroenterología de México (RGM), founded in 1935, is one of the most influential journals of scientific dissemination in Mexico and Latin America. The aim of the present review was to characterize the RGM's most frequently cited original articles, review articles, and consensuses. METHODS: The most cited original articles, review articles, and consensuses of the RGM were identified using the Scopus, PubMed, and Google Scholar databases. Their designs and topics, as well as their authors and participating institutions, were analyzed. RESULTS: The most highly cited articles of the RGM corresponded to the period from 1996 to 2018, with a mean of 16.5 citations per article. Fifty-eight percent (n = 29) of the articles belonged to the area of gastroenterology and 20% (n = 10) to surgery. The most frequent topics were functional gastrointestinal disorders, hepatitis virus, and gastric cancer. Thirty-six percent of the articles had a nonrandomized prospective design, followed by cross-sectional studies (26%) and randomized prospective studies (18%). CONCLUSION: The 50 most-cited articles included a total of 826 citations and the 10 most-cited consensuses and review articles had a total of 208 citations. Those studies encompass a diversity of disciplines related to gastroenterology that have impacted the scientific community and correspond to the work of different active research groups in Mexico and other countries.

Rotated balance in humans due to repetitive rotational movement.

We show how asymmetries in the movement patterns during the process of regaining balance after perturbation from quiet stance can be modeled by a set of coupled vector fields for the derivative with respect to time of the angles between the resultant ground reaction forces and the vertical in the anteroposterior and mediolateral directions. In our model, which is an adaption of the model of Stirling and Zakynthinaki (2004), the critical curve, defining the set of maximum angles one can lean to and still correct to regain balance, can be rotated and skewed so as to model the effects of a repetitive training of a rotational movement pattern. For the purposes of our study a rotation and a skew matrix is applied to the critical curve of the model. We present here a linear stability analysis of the modified model, as well as a fit of the model to experimental data of two characteristic "asymmetric" elite athletes and to a "symmetric" elite athlete for comparison. The new adapted model has many uses not just in sport but also in rehabilitation, as many work place injuries are caused by excessive repetition of unaligned and rotational movement patterns.