[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.

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.

Parkinson's disease: an update on preclinical studies of induced pluripotent stem cells.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease among adults worldwide. It is characterised by the death of dopaminergic neurons in the substantia nigra pars compacta and, in some cases, presence of intracytoplasmic inclusions of α-synuclein, called Lewy bodies, a pathognomonic sign of the disease. Clinical diagnosis of PD is based on the presence of motor alterations. The treatments currently available have no neuroprotective effect. The exact causes of PD are poorly understood. Therefore, more precise preclinical models have been developed in recent years that use induced pluripotent stem cells (iPSC). In vitro studies can provide new information on PD pathogenesis and may help to identify new therapeutic targets or to develop new drugs.

Preoperative oral practices and incidence of postoperative complications in hospital medical-surgical procedures: A meta-analysis.

BACKGROUND:  Oral decay prior to a hospital medical-surgical procedure is a risk factor for the development of postoperative complications. However, perioperative oral practices as a protective factor have not been studied. This review aims to evaluate the effectiveness of perioperative oral practices in the reduction of risk of developing postoperative complications in in-hospital medical surgical procedures. MATERIAL AND METHODS: This review and meta-analysis was conducted according to Cochrane guidelines. Medline, Scopus, Scielo, and Cochrane were consulted. Articles of the previous 10 years concerning adult patients undergoing perioperative oral practices prior to hospital medical-surgical procedures, were included. Data of the type of perioperative oral practice, type of postoperative complication and measures of effect on the development of complications were extracted. RESULTS: Of a pool of 1470 articles, 13 were included for systematic review and 10 for meta-analysis. The most common perioperative oral procedures were focalized approach (FA), referred to only the elimination of infectious foci in the oral cavity and comprehensive approach (CA), referred to a integral approach of the patient's oral health, both of which were mainly performed in oncologic surgeries, both were effective in the reduction of postoperative complications (RR=0.48, [95% CI 0.36 - 0.63]). The most reported postoperative complication was postoperative pneumonia. CONCLUSIONS: Perioperative oral management proved to be a protective factor against the development of postoperative complications.

Spanish validation of the Stigma of Occupational Stress Scale for Doctors (SOSS-D) and factors associated with physician burnout.

OBJECTIVES: The aim of this study was to investigate the psychometric properties of the Spanish version of the Stigma of Occupational Stress Scale for Doctors (SOSS-D) and the factors associated with Physician Burnout in Paraguay. METHODS: Participants included 747 Paraguayan healthcare workers, aged 24-77 years old, of both sexes. SOSS-D was translated into Spanish and validated through an exploratory and confirmatory factor analysis. Participants were also scored with the Oldenburg Burnout Inventory (OLBI), the CAGE questionnaire, and the stigma subscale of the Perceived Barriers to Psychological Treatment (PBPT) measure. RESULTS: Three factors had a raw eigenvalue greater than 1, and explained 61.7% of total variance. The confirmatory analysis confirmed that the scale is three-dimensional. The model adjustment was good, according to all fit indices. OLBI results indicate clinically significant disengagement in 85.9% and clinically significant exhaustion in 91.6% of participants. Of the 747 participants, 57.6% reported alcoholic beverage consumption and among those, 19.3% had problematic alcohol consumption according to the CAGE questionnaire. The correlation between SOSS-D and the stigma subscale of the PBPT was statistically significant (r = 0.245, p < 0.001). CONCLUSIONS: The Spanish version of the SOSS-D was found to have good psychometric properties and adequately reproduces the three-dimensional model of the original English version.

Psychometric properties of the Spanish version of the Fear of COVID-19 scale in Paraguayan population.

OBJECTIVE: The aim of this study is to test the psychometric properties of the Spanish validation of the Fear of COVID-19 Scale (FCV-19S) in a Paraguayan population. METHODS: Participants were recruited through an Internet-based survey. All participants whose scores in the Hospital Anxiety and Depression Scale (HADS) and The Fear Questionnaire (FQ) were greater than zero were included. 1245 subjects responded voluntarily: 1077 subjects, scoring >0, were considered. RESULTS: To establish construct validity of the FCV-19S, an exploratory factor analysis was performed using the KMO test, which was adequate, and the Bartlett sphericity test, which was significant (p <.0001). The CFI, NFI, GFI, TLI and RMSEA indices were used to evaluate the model and showed good adjustment. Cronbach's α showed valid internal consistency (α = 0.86). This validation was supported by significant correlation (p <.001) with the HADS scale for anxiety and depression and with the FQ scale for specific phobia. CONCLUSIONS: The Spanish version of the FCV-19S is a 7-item scale with two dimensions, psychological symptoms and physiological symptoms, which demonstrated robust psychometric properties in a Paraguayan population.

Effects of Mating and Social Exposure on Cell Proliferation in the Adult Male Prairie Vole (Microtus ochrogaster).

Microtus ochrogaster is a rodent with a monogamous reproductive strategy characterized by strong pair bond formation after 6 h of mating. Here, we determine whether mating-induced pair bonding increases cell proliferation in the subventricular zone (SVZ), rostral migratory stream (RMS), and dentate gyrus (DG) of the hippocampus in male voles. Males were assigned to one of the four groups: (1) control: males were placed alone in a clean cage; (2) social exposure to a female (SE m/f): males that could see, hear, and smell a sexually receptive female but where physical contact was not possible, because the animals were separated by an acrylic screen with small holes; (3) social exposure to a male (SE m/m): same as group 2 but males were exposed to another male without physical contact; and (4) social cohabitation with mating (SCM): males that mated freely with a receptive female for 6 h. This procedure leads to pair bond formation. Groups 2 and 3 were controls for social interaction. Male prairie voles were injected with 5-bromo-2'-deoxyuridine (BrdU) during the behavioral tests and were sacrificed 48 h later. Brains were processed to identify the new cells (BrdU-positive) and neuron precursor cells (neuroblasts). Our principal findings are that in the dorsal region of the SVZ, SCM and SE m/f and m/m increase the percentage of neuron precursor cells. In the anterior region of the RMS, SE m/f decreases the percentage of neuron precursor cells, and in the medial region SE m/f and m/m decrease the number of new cells and neuron precursor cells. In the infrapyramidal blade of the subgranular zone of the DG, SE m/m and SCM increase the number of new neuron precursor cells and SE m/m increases the percentage of these neurons. Our data suggests that social interaction, as well as sexual stimulation, leads to pair bonding in male voles modulating cell proliferation and differentiation to neuronal precursor cells at the SVZ, RMS, and DG.

Real-world data on the efficacy and safety of weekly oral vinorelbine in breast cancer patients previously treated with anthracycline or taxane-based regimens.

PURPOSE: To evaluate the efficacy and safety of oral weekly vinorelbine 60 mg/m2 for metastatic breast cancer (MBC) in patients previously treated with anthracyclines or taxanes in routine clinical practice. MATERIALS AND METHODS: Fifty-five patients were enrolled in a prospective multicentre study conducted in Spain. Women ≥ 18 years of age with locally advanced breast cancer who were not candidates for surgical treatment with a radical intention or patients with stage IV disease, and who had received a prior taxane or anthracycline regimen were eligible for participation. RESULTS: Median age was 67 years. Median progression-free survival was 3.7 months (95% CI 2.5-4.9), median overall survival 10 months (95% CI 6.6-13.5), and overall response rate and clinical benefit rate were 29.1% and 49.1%, respectively. Main grade 3 and 4 toxicities were neutropenia 9.1%, febrile neutropenia 3.6% and constipation 3.6%. In total, 86% of the patients received complete treatment without delays or dose reduction. Moreover, HER2-positive patients who received oral vinorelbine concomitantly with trastuzumab showed better response (complete response: HER2-positive 14.3% vs. HER2-negative 0%; partial response: HER2-positive 42.9% vs. HER2-negative 25.6%; p = 0.008), better disease control rate (HER2-positive 100% vs. HER2-negative 46.2%; p = 0.011), and better values for the remaining analysed variables than HER2-negative patients. CONCLUSION: Our study provides real-world data on the use of oral weekly vinorelbine, which proves an effective and well-tolerated regimen for MBC patients previously treated with taxanes or anthracyclines. Patients with HER2-positive disease could also benefit from this treatment in combination with trastuzumab.

Decanethiol functionalized silver nanoparticles are new powerful leishmanicidals in vitro.

We evaluated, for the first time, the leishmanicidal potential of decanethiol functionalized silver nanoparticles (AgNps-SCH) on promastigotes and amastigotes of different strains and species of Leishmania: L. mexicana and L. major isolated from different patients suffering from localized cutaneous leishmaniasis (CL) and L. mexicana isolated from a patient suffering from diffuse cutaneous leishmaniasis (DCL). We recorded the kinetics of promastigote growth by daily parasite counting for 5 days, promastigote mobility, parasite reproduction by CFSE staining's protocol and promastigote killing using the propidium iodide assay. We also recorded IC50's of promastigotes and amastigotes, therapeutic index, and cytotoxicity by co-culturing macrophages with AgNps-SCH or sodium stibogluconate (Sb) used as reference drug. We used Sb as a reference drug since it is used as the first line treatment for all different types of leishmaniasis. At concentrations 10,000 times lower than those used with Sb, AgNps-SCH had a remarkable leishmanicidal effect in all tested strains of parasites and there was no toxicity to J774A.1 macrophages since > 85% were viable at the concentrations used. Therapeutic index was about 20,000 fold greater than the corresponding one for Sb treated cells. AgNps-SCH inhibited > 80% promastigote proliferation in all tested parasites. These results demonstrate there is a high leishmanicidal potential of AgNps-SCH at concentrations of 0.04 µM. Although more studies are needed, including in vivo testing of AgNps-SCH against different types of leishmaniasis, they can be considered a potential new treatment alternative.

Mating and social exposure induces an opioid-dependent conditioned place preference in male but not in female prairie voles (Microtus ochrogaster).

In rodents, sexual stimulation induces a positive affective state that is evaluated by the conditioned place preference (CPP) test. Opioids are released during sexual behavior and modulate the rewarding properties of this behavior. Prairie voles (Microtus ochrogaster) are a socially monogamous species, in which copulation with cohabitation for 6h induces a pair bond. However, the mating-induced reward state that could contribute to the establishment of the long-term pair bond has not been evaluated in this species. The present study aimed to determine whether one ejaculation or cohabitation with mating for 6h is rewarding for voles. We also evaluated whether this state is opioid dependent. Our results demonstrate that mating with one ejaculation and social cohabitation with mating for 6h induce a CPP in males, while exposure to a sexually receptive female without mating did not induce CPP. In the female vole, mating until one ejaculation, social cohabitation with mating, or exposure to a male without physical interaction for 6h did not induce CPP. To evaluate whether the rewarding state in males is opioid dependent, the antagonist naloxone was injected i.p. The administration of naloxone blocked the rewarding state induced by one ejaculation and by social cohabitation with mating. Our results demonstrate that in the prairie vole, on the basis of the CPP in the testing conditions used here, the stimulation received with one ejaculation and the mating conditions that lead to pair bonding formation may be rewarding for males, and this reward state is opioid dependent.

Central nervous system development-related microRNAs levels increase in the serum of gestational diabetic women during the first trimester of pregnancy.

MicroRNAs are heterochronic molecules important during brain development, which could be altered by gestational diabetes mellitus (GDM). To explore these molecules in maternal serum, we performed an RT-qPCR analysis. Our results revealed the heterochronic character of some neural development-related microRNA in serum samples of pregnant women. In relation to the first trimester, higher levels of miR-183-5p, -200b-3p, and -125-5p in the second trimester, and higher levels of miR-137 in the third trimester, were found. Furthermore, an insult such as GDM led to higher levels of miR-183-5p, -200b-3p, -125-5p, and -1290 relative to the control in the first trimester, which might be related to changes in neurogenesis and cell proliferation. An in silico analysis suggested that increased microRNAs in the second trimester in the control contributed to cell proliferation and neuron differentiation and that the rise in miR-137 in the third trimester led to neuron maturation. In the diabetic, higher levels of the microRNAs in the first trimester suggested alterations in cell proliferation and neuron differentiation. In conclusion, we showed that fetal-related microRNAs can be detected in the serum of pregnant woman and exhibit temporary regulation during pregnancy and that microRNAs involved in cell proliferation and neuron differentiation are upregulated under GDM.

Generic framework for mining cellular automata models on protein-folding simulations.

Cellular automata model identification is an important way of building simplified simulation models. In this study, we describe a generic architectural framework to ease the development process of new metaheuristic-based algorithms for cellular automata model identification in protein-folding trajectories. Our framework was developed by a methodology based on design patterns that allow an improved experience for new algorithms development. The usefulness of the proposed framework is demonstrated by the implementation of four algorithms, able to obtain extremely precise cellular automata models of the protein-folding process with a protein contact map representation. Dynamic rules obtained by the proposed approach are discussed, and future use for the new tool is outlined.

Association between two polymorphisms of histamine-metabolising enzymes and the severity of allergic rhinitis in a group of Mexican children.

BACKGROUND: It has been suggested that polymorphisms of histamine metabolising enzymes can be a risk factor for developing histamine-involving diseases. The aim of the present study is to research the possible association between two functional single nucleotide polymorphisms (SNPs): C314T in the Histamine-N-Methyl Transferase gene and C2029G in the Diamine Oxidase gene, with the severity of allergic rhinitis and the number of allergic diseases, in a group of allergic Mexican children. METHODS: We studied 154 unrelated allergic children. SNPs were analysed by RT-PCR. The total serum IgE was measured by chemiluminescence and the serum histamine by ELISA. We used logistic regression analysis to determine OR. RESULTS: Patients carrying the mutant allele for any SNP had more risk to develop higher rhinitis severity or a bigger number of allergic diseases. Haplotype analysis revealed that this effect is synergistic. In patients carrying one or two mutant alleles, serum histamine levels were higher than those of patients carrying only wild alleles. Serum IgE levels were not associated with the presence of mutant alleles. CONCLUSION: The presence of these SNPs in patients with allergic rhinitis can lead to higher serum histamine, therefore to a higher risk of developing more severe symptoms or more associated allergic diseases, even if the serum IgE remains low.

Escherichia coli-induced temporal and differential secretion of heat-shock protein 70 and interleukin-1ß by human fetal membranes in a two-compartment culture system.

INTRODUCTION: Escherichia coli is recognized as an etiological bacteria associated with chorioamnionitis and the preterm premature rupture of fetal membranes. This pathological condition induces pro-inflammatory cytokines and degradative metalloproteinases, which are considered biological markers secreted in an acute stage of infection. Heat-shock proteins (HSPs) are an important component of the innate immunity response and are found in different pathological conditions. They have not been previously measured in human fetal membranes in response to infectious conditions. We hypothesized that the choriodecidual tissue and amniotic epithelium secreted temporal and differential Hsp-60, Hsp-70, and interleukin (IL)-1ß mediated by E. coli infection. METHODS: Fetal membranes were mounted in a two-compartment culture system and infected with two passes of live E. coli at different doses (10², 104, 105, and 106 colony-forming units (CFU)/mL) and intervals of incubation (3, 6, and 24 h). The culture medium was collected, and Hsp-60, Hsp-70, and IL-1ß were assessed using the enzyme-linked immunosorbent assay (ELISA) method. RESULTS: After 3 and 6 h of infection, E. coli induced an increase in Hsp-70 secretion in the choriodecidual tissue. However, after 24 h of incubation, Hsp-70 was downregulated and we observed an increase in IL-1ß secretion. By contrast, E. coli induced a lower Hsp-60 secretion in the amnion compared to Hsp-70. DISCUSSION: Human fetal membranes responded actively to E. coli infection, with an increase in Hsp-70 during the first hours of infection. After 24 h, there was an increase in the liberation of IL-1ß.

Cultivo de cepas de levaduras de suelo trumao en ®vinaza¼ / Cultivation of yeast strains of the trumao soil in ®vinasse¼

30 cepas de levaduras aisladas desde un suelo trumao (Hapludans) usado como pradera en rotación, se cultivaron individualmente (100 µl = a 102 ufc delevaduras/mL) en matraces con 50 mL de ®vinaza¼, estos fueron incubados en un agitador orbital a 150 rpm, 23 °C por 5 días, luego de la incubación el contenido de cada matraz se centrifugo a 3.500 rpm por 20 min., a los pellet obtenidos se les determino: el peso seco (PS); fosforo total (FT) por digestión ácida y posterior lectura a 400 nm; proteínas totales (PT) por colorimetría Biuret a 595 nm y lípidos totales (LT) mediante el método colorimétrico de la sulfo-fosfo vainillina a 520 nm. Las 30 cepas de levaduras crecieron en la vinaza. El mayor PS lo registro la cepa 25 (331 g de levadura L-1 de ®vinaza¼). FT lo registro la cepa 28 (4,8 mg g-1 de levadura seca). PT lo registro la cepa 24 (25,90 mg g-1 de levadura seca) y LT lo registro la cepa 18 (287,4 mg g-1 de levadura seca).

Thirty strains of yeast isolated from a volcanic ash soil (Hapludans), used as pasture rotation, were individually cultured (100 µl = 102 cfu of yeast cells mL-1) in flasks with 50 mL of ®vinasse¼, these were incubated at 23 °C for 5 day, after incubation the contents of each flask was centrifuged at 3500 rpm for 20 min, the pellet obtained was determined: dry weight (DW); total phosphorus (FT) by acid digestion and later reading at 400 nm; total protein (TP) by Biuret at 595 nm and total lipid (TL) by the colorimetric method of the sulfo-phospho-vanillin at 520 nm. The Thirty strains of yeast grown on vinasse. The best DW, was determined for strain 25 (331 g yeast L-1 ®vinasse¼). FT was determined for strain 28 (4,8 mg g-1 dry yeast). TP was determined for strain 24 (25, 90 mg g-1 dry yeast) and TL was determined for strain18 (287, 4 mg g-1 dry yeast).

Frecuencia de consumo de alimentos cariogénicos y prevalencia de caries dental en escolares venezolanos de estrato socioeconómico bajo / Frequency of consumption of cariogenic and prevalence of dental caries in low socioeconomic income venezuelan schoolchildren

El objetivo de este estudio fue relacionar la frecuencia del consumo de alimentos cariogénicos con la prevalencia de caries dental en 95 escolares entre 5 a 14 años de edad, del género masculino y femenino, de una zona urbana de estrato bajo de Valencia, Venezuela. Se utilizó cuestionario de frecuencia de consumo e índices ceo-d y CPO-D. Se aplicó t-student, Kruskal-Wallis, correlación de Spearman y análisis de regresión lineal múltiple. Los alimentos fueron consumidos en forma diaria, semanal y a cualquier hora. El promedio del ceo-d fue 3,88±3,2 y CPO-D, 1,7±2,6 con diferencia significativa según edad, en ambos índices. No hubo diferencia significativa según género en ambas variables. El ceo presentó correlación significativa negativa con edad y consumo de gaseosas y el CPO-D positiva con edad y golosinas dulces. El análisis de regresión lineal múltiple mostró posibles factores de riesgo de caries en la dentición temprana: edad y gaseosas, con relación lineal significativa (r2: 0,378; p: 0,000) y en la dentición permanente, edad y consumo de golosinas dulces, evidenciándose también una relación lineal significativa (r2: 0,225; 0,207; p: 0,000). Los resultados muestran un elevado consumo de alimentos cariogénicos en los niños, lo que pudo influenciar en la aparición de caries dental. Deben implementarse estrategias de educación nutricional a nivel escolar para el control del consumo de golosinas y dulces y orientar a los padres sobre una dieta saludable a los niños

The aim of this study was to relate the frequency of consumption of cariogenic foods with dental caries prevalence in 95 school children between 5 -14 years old, male and female, from a low socioeconomic urban area from Valencia, Venezuela. A food frequency questionnaire and dmft and DMFT caries indices were used. It was applied student t-test, Kruskal-Wallis, Spearman correlation and multiple linear regression analysis. Foods were consumed daily, weekly and anytime. Dmft index (3,88±3,2) and DMFT (1,79±2,6) with a significant difference by age in both indices. There was no significant difference by gender both variables. Dmft had a statistically significant negative correlation with age and soft drinks and positive DMFT, age and sweet candies. Multiple linear regression analysis showed possible risk factors of caries in the early dentition: age and soft drinks with significant linear relationship (r2: 0,378; p: 0,000) and permanent dentition, age and consumption sweet candies (r2: 0,225; p: 0,000), demonstrating also a significant linear relationship. Results show a high cariogenic food intake in children, which could influence the development of dental caries. Strategies should be implemented nutritional education at school level for to control of consumption of sweets and candies and guide parents about a healthy diet for children

Histamine is required during neural stem cell proliferation to increase neuron differentiation.

Histamine in the adult central nervous system (CNS) acts as a neurotransmitter. This amine is one of the first neurotransmitters to appear during development reaching its maximum concentration simultaneously with neuron differentiation peak. This suggests that HA plays an important role in neurogenesis. We have previously shown that HA is able to increase neuronal differentiation of neural stem cells (NSCs) in vitro, by activating the histamine type 1 receptor. However the mechanism(s) by which HA has a neurogenic effect on NSCs has not been explored. Here we explore how HA is able to increase neuron phenotype. Cortex neuroepithelium progenitors were cultured and at passage two treatments with 100 µM HA were given during cell proliferation and differentiation or only during differentiation. Immunocytochemistry was performed on differentiated cultures to detect mature neurons. To explore the expression of certain important transcriptional factors involved on asymmetric cell division and commitment, RT-PCR and qRT-PCR were performed. Results indicate that HA is required during cell proliferation in order to increase neuron differentiation and suggest that this amine increases neuron commitment during the proliferative phase probably by rising prospero1 and neurogenin1 expression.