Infective Endocarditis of a Rare Etiology of Streptococcus alactolyticus: A Case Report and Literature Review.

Streptococcus alactolyticus is a non-motile Gram-positive, catalase-negative cocci, a part of group D Streptococci. In the literature, S. alactolyticus is documented as a causative agent of infective endocarditis, demonstrated by blood cultures in only four other cases, representing an extremely rare circumstance. Here, we describe a case of infective endocarditis due to S. alactolyticus in a young patient known with a bicuspid aortic valve and associated with a sigmoid precancerous polyp. The patient was also known to have blood hypertension and type II diabetes. Symptoms at the debut appeared insidiously and were non-specific: fatigue, loss of appetite, weight loss, night sweats, and fever. They lasted for the entire period of the illness with transient improvement during the courses of antibiotics. He followed more antibiotic courses prescribed for various clinical diagnoses. Each round of antibiotic treatment transitorily alleviated the symptoms, which reappeared each time after the cessation. The correct diagnosis was made only about three months after the appearance of the first clinical manifestations. This was based on ultrasound criteria (presence of vegetation and lesions of aortic cusps) and microbiological criteria (isolation of S. alactolyticus in blood cultures). A course of six weeks of ceftriaxone was considered the opportune antibiotic therapy. Similar to all other cases described in the literature, our patient presented important damage to the valvular tissue and required cardiac surgery to re-establish the normal function of the valve. The surgery consisted of the excision of the severely affected natural aortic valve and her replacement with a mechanical prosthetic valve. Following medical and surgical treatment, the patient is completely healed and has a normal life. Our case is noteworthy because of the scarcity of the involvement of S. alactolyticus in the pathogeny of infective endocarditis. This is the fifth published case with this etiology, and an overview of all five cases is provided in the article.

Timing of treatment shapes the path to androgen receptor signaling inhibitor resistance in prostate cancer.

There is optimism that cancer drug resistance can be addressed through appropriate combination therapy, but success requires understanding the growing complexity of resistance mechanisms, including the evolution and population dynamics of drug-sensitive and drug-resistant clones over time. Using DNA barcoding to trace individual prostate tumor cells in vivo , we find that the evolutionary path to acquired resistance to androgen receptor signaling inhibition (ARSI) is dependent on the timing of treatment. In established tumors, resistance occurs through polyclonal adaptation of drug-sensitive clones, despite the presence of rare subclones with known, pre-existing ARSI resistance. Conversely, in an experimental setting designed to mimic minimal residual disease, resistance occurs through outgrowth of pre-existing resistant clones and not by adaptation. Despite these different evolutionary paths, the underlying mechanisms responsible for resistance are shared across the two evolutionary paths. Furthermore, mixing experiments reveal that the evolutionary path to adaptive resistance requires cooperativity between subclones. Thus, despite the presence of pre-existing ARSI-resistant subclones, acquired resistance in established tumors occurs primarily through cooperative, polyclonal adaptation of drug-sensitive cells. This tumor ecosystem model of resistance has new implications for developing effective combination therapy.

Assessing the spatial distribution of elemental concentrations in surface sediments of Lake Victoria, Kenya: implications for ecological health and management.

Lacustrine sediment quality indicates the effects of both natural and anthropogenic activities on the ecosystem and communities. Despite its ecological importance, myriad complexities, and potential contaminant sources, the spatial distribution of surficial sediments in Lake Victoria's Winam Gulf has never been comprehensively documented. The purpose of this study was to assess the spatial distribution, pathways, and ecological risk of metal elements in the lake using a sediment matrix. Sediment samples were collected throughout the gulf in November 2022. The concentrations of Al, As, Cd, Co, Cr, Cu, Fe, K, Mn, Mo, Ni, P, Pb, Sb, Sn, Ti, Tl, U, and Zn were compared to different contamination metrics and ecological risk assessment indices. The average concentrations were in the following decreasing order: Zn > > > Cr > > Cu > Ni > Pb > Co > As > Cd with mean (± SD) of 185 ± 45 mg kg-1, 56 ± 15 mg kg-1, 45 ± 16 mg kg-1, 37 ± 11 mg kg-1, 24 ± 5 mg kg-1, 20 ± 7 mg kg-1, 3.9 ± 1.3 mg kg-1, 0.30 ± 0.09 mg kg-1, respectively, with strong indications of anthropogenic sources. Average concentrations were in the following decreasing order: Zn > > > Cr, Cu, Ni, Pb, Co, As, and Cd levels (mean ± SD) were 185 ± 45 mg kg-1, 56 ± 15 mg kg-1, 45 ± 16 mg kg-1, 37 ± 11 mg kg-1, 24 ± 5 mg kg-1, 20 ± 7 mg kg-1, 3.9 ± 1.3 mg kg-1 and 0.30 ± 0.09 mg kg-1 with strong indications of anthropogenic sources. The geo-accumulation index (Igeo) and enrichment factor categorisation schemes, respectively, classified these as uncontaminated (level 0) and depletion to minimal enrichment (level 1), while the ecological risk analysis classified them as "low risk". The mouth of the Nyando River, as well as Kisumu, Kendu, and Homa bays, were the most element-enriched and should be prioritised for focused monitoring and remediation. As a result, targeted land management of urban, industrial, transportation, and agricultural areas offers the opportunity to reduce sediment inputs into the lake ecosystem.

Considerations for environmental biogeochemistry and food security for aquaculture around Lake Victoria, Kenya.

The impact of population expansion through economic growth and development has been identified as one of the key drivers of both water and sediment contamination from potentially harmful elements (PHEs). This presents a major hazard not only to aquatic ecosystems but local riparian communities and beyond who rely heavily on this natural resource for drinking water and fish-a valuable source of dietary micronutrients and protein. The present study measured biogeochemical concentration of PHEs in water, sediment and fish from locations pooled into four zones within Winam Gulf and Lake Victoria area of Kenya. Captured fish were used as a sentinel receptor of lake health to evaluate potential risks to fisheries and aquaculture food security. In water, concentrations of arsenic (As), cadmium (Cd), chromium (Cr), copper (Cu) and lead (Pb) were observed above the United States Environmental Protection Agency (US EPA) maximum contamination level drinking water guidelines (MCL), with aluminium (Al) observed above the Aquatic Life Criteria in all four zones. Similarly, sediment concentrations in all four zones exceeded the US EPA Effects range low (ERL) threshold guidelines for Cu, nickel (Ni), zinc (Zn) and Pb, with Cu, Zn and Pb classed at moderate contamination levels using the contamination factor. Fish tissue concentrations from the four zones were calculated using recommended daily intakes (RDI) and for PHEs as provisional maximum tolerable intakes (PMTIs) and indicated most macro- and micronutrients were at or below 10% RDI from aquaculture and wild fish, with Se indicating a greater RDI (16-29%) in all the zones. Contributions of PHEs to PMTIs were below threshold guidelines for both aquaculture and wild fish with only Cd, Cr and Pb levels being above the PMTI thresholds. There is a need to assess the long-term effects of persistent anthropogenic PHE input into Winam Gulf and the wider Lake Victoria basin. Continued monitoring of PHEs using both historical and more recent data will enable future management policies to be implemented through improved mitigation strategies to reduce their impact on water quality, fish health and subsequent human health.

Barriers to a healthy diet and physical activity in Mexican adults: results from the Mexican Health and Nutrition Survey.

This study aims to (1) identify the most prevalent perceived barriers for healthy eating and performing physical activity among adults in Mexico; and (2) determine the association between perceived barriers, with body mass index (BMI) categories, geo-demographic and socio-economic characteristics. We carried out a cross-sectional, secondary analysis of publicly available data from the Mexican Health and Nutrition Survey 2016. We extracted data from 6406 adults, aged 20-65 years, including: perceived barriers for healthy eating and for performing physical activity, BMI, residence area, region of Mexico, sex, age and socio-economic status. Logistic regression models were used to evaluate the association between perceived barriers with the categories of obesity, geographic and socio-demographic variables. Seventy-four point nine percent of the respondents were categorised as having either overweight or obesity, 80.5% reported at least one barrier to healthy eating and 78.3% at least one barrier to performing physical activity. Of the listed barriers, the most reported barriers were 'lack of affordability' (58.6%) for healthy eating and 'lack of time' (51.2%) for performing physical activity. Females (OR 1.27, 95% CI 1.11 to 1.46) and people with obesity (OR 1.19, 95% CI 1.01 to 1.41) were more likely to report barriers to a healthy diet; and females (OR 1.39, 95% CI 1.41 to 1.59), people with obesity (OR 1.41, 95% CI 1.19 to 1.69) and those living in rural areas (OR 1.49, 95% CI 1.30 to 1.72) were more likely to report barriers to performing physical activity. There was a high prevalence of reported barriers for healthy eating and performing physical activity. Females, people with obesity, and those living in rural areas are more likely to report barriers for healthy eating and for performing physical activity. Targeted health programmes and tailored interventions that address the barriers to a healthy lifestyle that these groups experience may encourage healthier lifestyle behaviours in a greater proportion of Mexican adults.

Entorno laboral saludable en Asia y América del Norte revisión de alcance

Objetivos Realizar una revisión de alcance sobre entorno laboral saludable (ELS) en países de Asia y América del Norte. Métodos Revisión de documentos de diversos diseños metodológicos resultantes de la matriz PRISMA obtenidos en bases de datos como Scopus, PubMed, Biblioteca Virtual de la Salud (BVS) y otros motores de búsqueda entre los años 2015 y 2020 empleando los descriptores Healthy, Workplace, Enviroment Work y conectores AND y OR. Resultados Se obtuvo un total de 36 documentos finales. El 66,7% de los estudios encontrados fueron en países de América del Norte. El 44,4% de las publicaciones se realizaron en el año 2019 y 2020. Se halló que la base de datos que más arrojó publicaciones acerca de ELS fue Scopus y la revista que más publicó fue BVS; igualmente los temas más relevantes para alcanzar ELS fueron la promoción de la salud en el lugar de trabajo mediante la intervención de estrategias encaminadas a los estilos de vida saludables y el impacto de la productividad. Conclusiones Las estrategias de ELS permiten que los programas de promoción de la salud sean implementados en las empresas con el fin de mejorar los estilos de vida y las condiciones laborales de los trabajadores, incentivando la actividad física, la alimentación balanceada, disminuyendo la ingesta de bebidas alcohólicas y el tabaquismo. Los ELS se relaciona con la mejora continua debido a que favorece el aumento de la productividad y por ende es importante que se puedan implementar en el contexto de la educación, negocios, comercio y desarrollo económico.

Objectives Conduct a scope review on Healthy Working Environment (ELS, by its initials in Spanish) in Asian and North American countries. Methods Review of documents of various methodological designs resulting from the PRISMA matrix obtained in databases such as Scopus, PubMed, Virtual Health Library (VHL) and other search engines from the years 2015 to 2020 using the following descriptors: Healthy, Workplace, Enviroment Work and the connectors AND and OR. Results A total of 36 final documents were obtained. 66.7% of the studies found were in North American countries. 44.4% of publications were made between 2019 and 2020. It was found that the database that yielded the most publications about ELS was Scopus and the magazine that published the most was VHL; also, the most relevant issues to achieve ELS were the promotion of health in the workplace through the intervention of strategies aimed at healthy lifestyles, and the impact of productivity. Conclusions ELS strategies allow health promotion programs to be implemented in companies in order to improve the lifestyles and working conditions of workers, encou-raging physical activity, balanced eating, and reducing alcohol intake and smoking. The ELS are related to the continuous improvement because it favors the increase of productivity and therefore it is important that they can be implemented in the context of education, business, trade, and economic development.

Prenatal exposure to valproic acid and treatment with intranasal oxytocin have sex-specific effects on behavior in Long Evans rats.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social behaviors and communication. In rodents and humans, prenatal exposure to antiepileptic valproic acid is associated with an increased risk for autistic-like characteristics. One potential treatment is oxytocin, a prosocial neuropeptide that can be delivered intranasally. However, the sex-specific effects of valproic acid exposure and intranasal oxytocin treatment on behavior have not been fully explored. Pregnant Long Evans rats were administered valproic acid (500 mg/kg) or saline midday on gestational day 12, and after weaning, male and female pups were assigned to control (saline-saline), valproic acid-saline, or valproic acid-oxytocin groups. Oxytocin (0.8 IU/kg) or saline was delivered intranasally 30-60 min before tests for anxiety-like behaviors (elevated plus maze), social interactions (sociability) and sociosexual behaviors (partner preference, 50 kHz vocalizations and scent marking). Prenatal exposure to valproic acid resulted in sex-specific differences in behavior. When compared to controls, valproic acid males showed enhanced anxiety-like behaviors in adolescence and fewer scent marks in adulthood, while valproic acid females showed reduced sexual (partner) preference as adults. Intranasal oxytocin was anxiolytic for valproic acid males, but moderately anxiogenic for valproic acid females, and in both sexes it surprisingly impaired social interactions in the sociability test. Furthermore, intranasal oxytocin failed to improve sociosexual deficits in valproic acid rats. These findings highlight the importance of conducting preclinical studies in both sexes, and suggest that oxytocin may be an effective treatment in animal models with heightened anxiety-like behaviors.

High-rate algal pond for removal of pharmaceutical compounds from urban domestic wastewater under tropical conditions. Case study: Santiago de Cali, Colombia.

This study evaluated the capacity of a pilot-scale high-rate algal pond (HRAP) to remove pharmaceutical compounds (PCs) from domestic wastewater in the city of Santiago de Cali, Colombia. The compounds analyzed included antiepileptics, hypolipidemic drugs, tranquilizers and analgesics, and anti-inflammatory drugs. The HRAP operated under a continuous water flow of 0.2 m3d-1 and a 3-day hydraulic retention time (HRT). Removal efficiencies were high (>70%) for fenofibric acid, ibuprofen, and paracetamol; medium (30-70%) for gabapentin, lamotrigine, fenofibrate, gemfibrozil, diclofenac, ketoprofen, naproxen, and pentoxifylline; and low (<30%) for carbamazepine and its metabolite 10,11-Dihidro-10,11-dihidroxicarbamazepine (CBZ-Diol). The findings herein are similar to other studies, but were obtained with a shorter HRT. These results show that tropical environmental conditions favor photodegradation and contribute to the development of microalgae and the biodegradation process. Twenty microalgae species were identified, with the phylum Chlorophyta as the most abundant, particularly due to its natural introduction. The removal of the PCs also reflected a percentage reduction (>50%) in the ecological hazard posed by most of the compounds, although it is important to note that the hazard from gemfibrozil and ibuprofen remained high even after treatment, indicating the need for complementary treatment.

Uso de la crioterapia en la fatiga muscular post esfuerzo en individuos que realizan práctica deportiva: revisión sistemática / Use of cryotherapy in post-effort muscle fatigue in individuals who practice sports: systematic review / Uso da crioterapia na fadiga muscular pós-esforço em indivíduos que realizam prática esportiva: revisão sistemática

Introducción. En la práctica deportiva, la fatiga muscular es un factor de riesgo para lesión muscular, constituyéndose en un problema que aparece cuando la carga mecánica a la cual se somete un músculo o grupo muscular es superior a la resistencia de este. Objetivo. Describir las intervenciones con crioterapia en Fatiga Muscular post esfuerzo, en individuos que realizan práctica deportiva, a través de una Revisión Sistemática. Método. Se realizó la búsqueda en bases de datos PUBMED/MEDLINE, EMBASE, LILACS, SCIELO, SCIENCE DIRECT, Registro Cochrane Central de Ensayos Controlados con la estrategia de búsqueda: Sports Medicine, Cryotherapy, Muscle Fatigue, Recovery of Function, Physical Exertion, Muscle Damage. La identificación y detección de las referencias fueron exportadas al gestor de referencias MENDELEY. La evaluación del Riesgo de Sesgo se realizó con el uso del software Review Manager y la calidad metodológica con lo reportado por la Base de Datos PEDro. Resultados. Se evaluaron 19 ensayos clínicos aleatorizados en los cuales se evidencia que la crioterapia reporta cambios en la fatiga muscular desde la disminución del dolor y biomarcadores. La inmersión en agua fría fue la modalidad más efectiva para acelerar la cinética de recuperación 72 horas después del ejercicio; demostró menor dolor y mayores niveles de recuperación, percibidos a lo largo de 24 a 48 horas después del ejercicio. Conclusión. De la totalidad de modalidades de crioterapia, la inmersión en agua fría es la que reporta mejores resultados en el proceso de recuperación de la fatiga muscular.

Introduction. In sports practice, muscle fatigue is a risk factor for muscle injury becoming a problem that appears when the mechanical load to which a muscle or muscle group is subjected is greater than its resistance. Objective. Describe post-effort Muscular Fatigue in active Men and Women who perform sports practice against interventions with cryotherapy, through a Systematic Review. Method. PUBMED / MEDLINE, EMBASE, LILACS, SCIELO, SCIENCE DIRECT, Central Cochrane Registry of Controlled Trials with the search strategy were searched: Sports Medicine, Cryotherapy, Muscle Fatigue, Recovery of Function, Physical Exertion, Muscle Damage The identification and detection of references were exported to the MENDELEY reference manager. The Bias Risk assessment was performed with the use of Review Manager software and methodological quality as reported by the PEDro Database. Results. 19 randomized clinical trials were evaluated in which it is evident that cryotherapy reports changes in muscle fatigue since the decrease in pain, and biomarkers. Cold water immersion was the most effective modality to accelerate recovery kinetics 72 hours after exercise; showed less pain and higher levels of recovery perceived over 24 to 48 hours after exercise. Conclusion. Of all the cryotherapy modalities, the immersion in cold water is the one that reports the best results in the process of recovery of muscular fatigue.

Introdução. Na prática esportiva, a fadiga muscular é um fator de risco para a lesão muscular, tornando- se um problema que ocorre quando a carga mecânica à qual um músculo ou grupo muscular é submetido é superior à resistência do músculo. Objetivo. Descrever as intervenções com crioterapia na fadiga muscular pós-esforço, em indivíduos que realizam prática esportiva, por meio de uma revisão sistemática. Método. Foi realizada uma busca nas bases de dados PUBMED/MEDLINE, EMBASE, LILACS, SCIELO, SCIENCE DIRECT, Registro Central Cochrane de Ensaios Controlados com a estratégia de busca: Medicina Esportiva, Crioterapia, Fadiga Muscular, Recuperação da Função, Esforço Físico, Dano Muscular. A identificação e detecção das referências foram exportadas para o gerenciador de referência do MENDELEY. A avaliação do risco de viés foi realizada com o uso do software Review Manager de revisão e qualidade metodológica com a relatada pelo banco de dados PEDro. Resultados. Dezenove ensaios clínicos randomizados foram avaliados nos quais se evidencia que a crioterapia relata alterações na fadiga muscular desde a diminuição da dor e dos biomarcadores. A imersão em água fria foi a modalidade mais eficaz para acelerar a cinética de recuperação 72 horas após o exercício; demonstrou menos dor e níveis mais altos de recuperação, percebidos entre 24 e 48 horas após o exercício. Conclusão. De todas as modalidades de crioterapia, a imersão em água fria é a que proporciona os melhores resultados no processo de recuperação da fadiga muscular.

Vitamin D supplementation in cutaneous malignant melanoma outcome (ViDMe): a randomized controlled trial.

BACKGROUND: Previous studies have investigated the protective effect of vitamin D serum levels, at diagnosis and during the follow-up period after treatment, on melanoma outcome. In the present study we assess whether vitamin D supplementation, in the follow-up period after diagnosis and surgical resection of the primary tumor, has a protective effect on relapse of cutaneous malignant melanoma and whether this protective effect correlates with vitamin D levels in serum and Vitamin D Receptor immunoreactivity in the primary tumor. METHODS/DESIGN: This study is a multicenter randomized double blind placebo- controlled phase III trial. Patients between the age of 18 and 80 years diagnosed and treated surgically for a melanoma stage IB-III are eligible for randomization in a 1:1 ratio to active treatment or placebo. The study drug is taken each month and consists of either 100,000 International Unit cholecalciferol or arachidis oleum raffinatum used as a placebo. The primary endpoint is relapse free survival. The secondary endpoints are 25 hydroxyvitamin D3 serum levels at diagnosis and at 6 month intervals, melanoma subtype, melanoma site and stage of melanoma at diagnosis according to the 2009 American Joint Committee on Cancer melanoma staging and classification. At randomization a bloodsample is taken for DNA analysis. The study is approved by the local Ethics Committees. DISCUSSION: If we can confirm our hypothesis that vitamin D supplementation after removal of the tumor has a protective effect on relapse of cutaneous malignant melanoma we may reduce the burden of CMM at several levels. Patients, diagnosed with melanoma may have a better clinical outcome and improved quality of life. There will be a decrease in health care costs related to treatment of metastatic disease and there will be a decrease in loss of professional years, which will markedly reduce the economic burden of the disease. TRIAL REGISTRATION: Clinical Trial.gov, NCT01748448 , 05/12/2012.

Luminescence and Nonlinear Optical Properties in Copper(I) Halide Extended Networks.

The syntheses, structures, and luminescence properties of a series of copper(I) halide coordination polymers, prepared with mono- and bidentate N-heteroaromatic ligands, are reported. These metal-organic coordination networks form [Cu2I2L]n for bidentate ligands (where L = pyrazine (1), quinazoline (2)) and [CuIL]n for monodentate ligands (where L = 3-benzoylpyridine (3) and 4-benzoylpyridine(4)). Both sets of compounds exhibit a double-stranded stair-Cu2I2-polymer, or "ladder" structure with the ligand coordinating to the metal in a bidentate (bridging two stairs) or monodentate mode. The copper bromide analogues for the bidentate ligands were also targeted, [Cu2Br2L]n for L = pyrazine (5) with the same stair structure, as well as compositions of [CuBr(L)]n for L = pyrazine (6) and quinazoline (7), which have a different structure type, where the -Cu-Br- forms a single-stranded "zigzag" chain. These copper halide polymers were found to be luminescent at room temperature, with emission peaks ranging from ∼550 to 680 nm with small shifts at low temperature. The structure (stair or chain), the halide (I or Br), as well as the ligand play an important role in determining the position and intensity of emission. Lifetime measurements at room and low temperatures confirm the presence of thermally activated delayed fluorescence, or singlet harvesting for compounds 1, 2, and 7. We also investigated the nonlinear optical properties and found that, of this series, [CuBr(quinazoline)]n shows a very strong second harmonic generating response that is ∼150 times greater than that of α-SiO2.

Mice Lacking GPR88 Show Motor Deficit, Improved Spatial Learning, and Low Anxiety Reversed by Delta Opioid Antagonist.

BACKGROUND: GPR88 is an orphan G protein coupled receptor highly enriched in the striatum, and previous studies have focused on GPR88 function in striatal physiology. The receptor is also expressed in other brain areas, and here we examined whether GPR88 function extends beyond striatal-mediated responses. METHODS: We created Gpr88 knockout mice and examined both striatal and extrastriatal regions at molecular and cellular levels. We also tested striatum-, hippocampus-, and amygdala-dependent behaviors in Gpr88(-/-) mice using extensive behavioral testing. RESULTS: We found increased G protein coupling for delta opioid receptor (DOR) and mu opioid, but not other Gi/o coupled receptors, in the striatum of Gpr88 knockout mice. We also found modifications in gene transcription, dopamine and serotonin contents, and dendritic morphology inside and outside the striatum. Behavioral testing confirmed striatal deficits (hyperactivity, stereotypies, motor impairment in rotarod). In addition, mutant mice performed better in spatial tasks dependent on hippocampus (Y-maze, novel object recognition, dual solution cross-maze) and also showed markedly reduced levels of anxiety (elevated plus maze, marble burying, novelty suppressed feeding). Strikingly, chronic blockade of DOR using naltrindole partially improved motor coordination and normalized spatial navigation and anxiety of Gpr88(-/-) mice. CONCLUSIONS: We demonstrate that GPR88 is implicated in a large repertoire of behavioral responses that engage motor activity, spatial learning, and emotional processing. Our data also reveal functional antagonism between GPR88 and DOR activities in vivo. The therapeutic potential of GPR88 therefore extends to cognitive and anxiety disorders, possibly in interaction with other receptor systems.

Benefit to neoadjuvant anti-human epidermal growth factor receptor 2 (HER2)-targeted therapies in HER2-positive primary breast cancer is independent of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) status.

BACKGROUND: Assessment of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) might be an important tool in identifying human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients unlikely to derive benefit from anti-HER2 therapies. However, studies to date have failed to demonstrate its predictive role in any treatment setting. PATIENTS AND METHODS: Prospectively collected baseline core biopsies from 429 early-stage HER2-positive breast cancer patients treated with trastuzumab, lapatinib, or their combination in the Neo-ALTTO study were stained using two anti-PTEN monoclonal antibodies (CST and DAKO). The association of PTEN status and PI3K pathway activation (defined as either PTEN loss and/or PIK3CA mutation) with total pathological complete response (tpCR) at surgery, event-free survival (EFS), and overall survival (OS) was evaluated. RESULTS: PTEN loss was observed in 27% and 29% of patients (all arms, n = 361 and n = 363) for CST and DAKO, respectively. PTEN loss was more frequently observed in hormone receptor (HR)-negative (33% and 36% with CST and DAKO, respectively) compared with HR-positive tumours (20% and 22% with CST and DAKO, respectively). No significant differences in tpCR rates were observed according to PTEN status. PI3K pathway activation was found in 47% and 48% of patients (all arms, n = 302 and n = 301) for CST and DAKO, respectively. Similarly, tpCR rates were not significantly different for those with or without PI3K pathway activation. Neither PTEN status nor PI3K pathway activation were predictive of tpCR, EFS, or OS, independently of treatment arm or HR status. High inter-antibody and inter-observer agreements were found (>90%). Modification of scoring variables significantly affected the correlation between PTEN and HR status but not with tpCR. CONCLUSION: These data show that PTEN status determination is not a useful biomarker to predict resistance to trastuzumab and lapatinib-based therapies. The lack of standardization of PTEN status determination may influence correlations between expression and relevant clinical end points. CLINICAL TRIALS: This trial is registered with ClinicalTrials.gov: NCT00553358.

Desarrollo motor en niños con desnutrición en Tunja, Boyacá / Motor development in children with malnutrition in Tunja, Boyacá

OBJETIVO: caracterizar el desempeño motor grueso y fino y el estado nutricional en niños de cero a tres años de un Centro de Recuperación Nutricional (CRN) de Tunja. MATERIALES Y MÉTODOS: estudio observacional descriptivo de corte transversal en niños menores de 36 meses, hospitalizados en el CRN en el período comprendido entre enero y junio de 2011, se realizó la revisión de 46 historias clínicas y de los datos antropométricos del programa ANTHRO, sumado a la aplicación de la Escala Abreviada del Desarrollo (EAD). RESULTADOS : se evidenció asociación significativa entre motricidad gruesa, fina y la desnutrición aguda (p>0,05).Con los demás grados de desnutrición no se encontró relación (p>0,05). DISCUSION:el niño con desnutrición aguda tiene un desarrollo medio de la motricidad fina, los estados de desnutrición aguda son menos influyentes para el estado de desarrollo alerta en la motricidad fina que en la motricidad gruesa, sin embargo, es interesante el hallazgo concerniente al estado de desarrollo medio en las variables motricidad gruesa y fina donde el comportamiento es similar en torno al estado de desnutrición aguda con elevados porcentajes de compromiso.

OBJECTIVE:to characterize the gross and fine motor performance and nutritional status of children from nutritional rehabilitation center (nrc) of Tunja aged 0-3 years. METHODOLOGY: an observational, cross-sectional descriptive study conducted on children under 36 months who were hospitalized at the nrc between January and June 2011. A total of 46 medical records were reviewed. Likewise, the anthropometric data of the anthro program were analyzed, and the Abbreviated Development Scale (ade) was applied. RESULTS:a significant association was observed between motor dexterity (both gross and fine) and acute malnutrition (p 0.05). No association was found with other grades of malnutrition (p 0.05). DISCUSSION:children with acute malnutrition have a medium development of fine motor skills. Acute malnutrition states have less influence on the development of the alert status in fine motor dexterity than in that of gross motor dexterity. Despite this, the finding concerning the medium state of development for gross and fine motor dexterity is interesting because the behavior is similar for the state of acute malnutrition with high rates of damage.

Capturing intra-tumor genetic heterogeneity by de novo mutation profiling of circulating cell-free tumor DNA: a proof-of-principle.

BACKGROUND: Plasma-derived cell-free tumor DNA (ctDNA) constitutes a potential surrogate for tumor DNA obtained from tissue biopsies. We posit that massively parallel sequencing (MPS) analysis of ctDNA may help define the repertoire of mutations in breast cancer and monitor tumor somatic alterations during the course of targeted therapy. PATIENT AND METHODS: A 66-year-old patient presented with synchronous estrogen receptor-positive/HER2-negative, highly proliferative, grade 2, mixed invasive ductal-lobular carcinoma with bone and liver metastases at diagnosis. DNA extracted from archival tumor material, plasma and peripheral blood leukocytes was subjected to targeted MPS using a platform comprising 300 cancer genes known to harbor actionable mutations. Multiple plasma samples were collected during the fourth line of treatment with an AKT inhibitor. RESULTS: Average read depths of 287x were obtained from the archival primary tumor, 139x from the liver metastasis and between 200x and 900x from ctDNA samples. Sixteen somatic non-synonymous mutations were detected in the liver metastasis, of which 9 (CDKN2A, AKT1, TP53, JAK3, TSC1, NF1, CDH1, MML3 and CTNNB1) were also detected in >5% of the alleles found in the primary tumor sample. Not all mutations identified in the metastasis were reliably identified in the primary tumor (e.g. FLT4). Analysis of ctDNA, nevertheless, captured all mutations present in the primary tumor and/or liver metastasis. In the longitudinal monitoring of the patient, the mutant allele fractions identified in ctDNA samples varied over time and mirrored the pharmacodynamic response to the targeted therapy as assessed by positron emission tomography-computed tomography. CONCLUSIONS: This proof-of-principle study is one of the first to demonstrate that high-depth targeted MPS of plasma-derived ctDNA constitutes a potential tool for de novo mutation identification and monitoring of somatic genetic alterations during the course of targeted therapy, and may be employed to overcome the challenges posed by intra-tumor genetic heterogeneity. REGISTERED CLINICAL TRIAL: www.clinicaltrials.gov, NCT01090960.

Factores de riesgo cardiovascular y su relación con la composición corporal en estudiantes universitarios / University students’ cardiovascular risk factors and their relationship with body composition

Objetivo Evaluar la prevalencia de factores de riesgo cardiovascular en una población de jóvenes universitarios y su relación con la composición corporal. Materiales y Métodos Se realizó un estudio de prevalencia, con muestreo aleatorio en 193 jóvenes (94 mujeres y 99 hombres) entre 16 y 26 años. Se midió: colesterol total, lipoproteínas de baja y alta densidad (LDL-C y HDL-C), triglicéridos (TG) y glucosa, presión arterial en reposo, perímetro abdominal, talla, peso, porcentaje de grasa y masa muscular, se aplicó una encuesta para evaluar hábitos nutricionales, de vida y estrés. Resultados Los factores de riesgo cardiovascular más relevantes encontrados en hombres fueron: valores de LDL-C ≥100 mg/dl (60,6 %), porcentaje de grasa >20% (50,0 %) y valores de HDL-C <40 mg/dl (39,4 %); en mujeres: porcentaje de grasa >33% (63,0 %), LDL-C ≥100 mg/dl (39,4 %) y HDL-C <50 mg/dl (91,5 %). 12,1 % de los hombres y 21,3 % de las mujeres reunieron criterios de síndrome metabólico, 19,2 % de los hombres y 27,7 % de las mujeres tienen riesgo aterogénico alto. Se encontraron correlaciones significativas con la composición corporal. Conclusión Existe una alta prevalencia de factores de riesgo cardiovascular en jóvenes universitarios, dados por alteraciones del perfil lipídico y cambios antropométricos relacionados, esto sugiere la necesidad de modificaciones en sus hábitos de vida y la composición corporal.(AU)

Objective Assessing the prevalence of major risk factors for cardiovascular disease in a sample population of university students and their relationship with body composition. Methods A prevalence study was carried out on a random sample of 193 16 to 26 year-old university students (94 females and 99 males). Total cholesterol, high density lipoproteins (HDL), low density lipoproteins (LDL), triglycerides (TG) and glucose, resting blood pressure, waist circumference, height, weight and body fat and muscle mass percentages were measured. The participants answered a survey to assess their nutritional habits, lifestyle and stress. Results The major cardiovascular risk factors for males were ≥100 mg/dl (60.6%) LDL-C, >20% (50.0%) body fat percentage (BF%) and <40 mg/dl (39.4%) HDL-C; female risk factors were >33% (63.0%) BF%, ≥100 mg/dl (39.4%) LDL-C and <50 mg/dl (91.5%) HDL-C. Both male (12.1%) and female students (21.3 %) had criteria for metabolic syndrome and males (19.2%) and females (27.7%) had a high atherogenic index of plasma (AIP). Significant correlations with body composition were found. Conclusion Cardiovascular risk factors had high prevalence in this sample of undergraduate students due to alterations in their blood, lipid profile and anthropometric changes, suggesting that modifications must be made regarding their lifestyles and body composition.(AU)