Restricted dispersal in a sea of gene flow.

How far do marine larvae disperse in the ocean? Decades of population genetic studies have revealed generally low levels of genetic structure at large spatial scales (hundreds of kilometres). Yet this result, typically based on discrete sampling designs, does not necessarily imply extensive dispersal. Here, we adopt a continuous sampling strategy along 950 km of coast in the northwestern Mediterranean Sea to address this question in four species. In line with expectations, we observe weak genetic structure at a large spatial scale. Nevertheless, our continuous sampling strategy uncovers a pattern of isolation by distance at small spatial scales (few tens of kilometres) in two species. Individual-based simulations indicate that this signal is an expected signature of restricted dispersal. At the other extreme of the connectivity spectrum, two pairs of individuals that are closely related genetically were found more than 290 km apart, indicating long-distance dispersal. Such a combination of restricted dispersal with rare long-distance dispersal events is supported by a high-resolution biophysical model of larval dispersal in the study area, and we posit that it may be common in marine species. Our results bridge population genetic studies with direct dispersal studies and have implications for the design of marine reserve networks.

Subtropical goats ovulate in response to the male effect after a prolonged treatment of artificial long days to stimulate their milk yield.

The objectives of this study were to determine (i) if in subtropical goats that gave birth during mid-December, the exposition to an artificial long-day photoperiod consisting in only 14 hr of light per day can increase the milk yield and (ii) to test whether these females can respond to the male effect at the end of the prolonged photoperiodic treatment. In experiment 1, 17 lactating goats were maintained under natural short days (control group), while another 22 goats were maintained under artificial long days (treated group) consisting in 14 hr light and 10 hr darkness starting at day 10 of lactation. The continuous exposition to an artificial long-day photoperiod produced an increase in the milk yield level during the first 110 days of lactation (time × treatment interaction; p = .01), while none of the milk components were modified due to the photoperiodic treatment (p > .05). In experiment 2, all control and treated anovulatory goats were submitted to the male effect using photostimulated males. All females showed oestrous behaviour within the first 10 days that were in contact with males (100% in both groups; p > .05). Thus, the latency to onset of oestrus did not differ between females from control (58.2 ± 3.0 hr) and treated (62 ± 4.6 hr) groups. Male exposition provoked ovulation independently if females were previously under long days or natural photoperiod (96 vs 100%, respectively; p = .79). It was concluded that exposure to 14 hr of light per day in subtropical goats that gave birth in late autumn stimulates milk yield without preventing the ovulation in response to the male effect at the end of the prolonged photoperiodic treatment.

[Troponin-T and n-terminal pro-brain type natriuretic peptide plasma levels and its relationship with mortality in COVID-19]. / Niveles plasmáticos de troponina T y de la fracción aminoterminal del propéptido natriurético cerebral y su relación con mortalidad en COVID-19.

INTRODUCTION: Cardiovascular compromise in coronavirus disease 2019 (COVID-19) does not necessarily present with the classic symptoms described in myocarditis. There is growing evidence demonstrating subclinical cardiovascular compromise in the context of the intense inflammation unleashed, the cytokine storm involved, the baseline prothrombotic state, and the consequent endothelial dysfunction. We set out to analyse whether Troponin-T (TT) and the amino-terminal fraction of pro-brain natriuretic peptide (NT-proBNP) determined at hospital admission, are related to mortality during the hospitalization of these patients. MATERIAL AND METHODS: Analytical, observational, retrospective cohort and cross-sectional study. It included subjects with COVID-19 hospitalized for moderate-severe illness, from 20/03/20 to 15/11/20. The TT and NT-proBNP obtained in the first 24 hours from admission were analysed. Altered TT was considered if ≥.014 ng/dl and altered NT-proBNP if ≥300 pg/ml. RESULTS: One hundred and eight subjects were included, 63.2% men, age 51.5 years (59-43), 28% were admitted to the Critical Unit and 25% died. The group with elevated TT presented higher mortality (OR = 3.1; 95%CI = 1.10-8.85; p = .02). The group with elevated NT-proBNP also show higher mortality (OR = 3.47; 95%CI = 1.21-9.97; p = .01). On multivariate analysis, only NT-proBNP ≥300 pg/ml remained an independent risk factor. CONCLUSIONS: NT-proBNP levels ≥300 pg/ml at admission in patients with moderate-severe COVID-19 were associated with higher mortality.

Management of adverse events from the treatment of encorafenib plus cetuximab for patients with BRAF V600E-mutant metastatic colorectal cancer: insights from the BEACON CRC study.

Colorectal cancer is the second leading cause of cancer deaths worldwide, with a 5-year relative survival of 14% in patients with metastatic colorectal cancer (mCRC). Patients with BRAF V600E mutations, which occur in ∼10%-15% of patients with mCRC, have a poorer prognosis compared with those with wild-type BRAF tumours. The combination of the BRAF inhibitor encorafenib with the epidermal growth factor receptor inhibitor cetuximab currently represents the only chemotherapy-free targeted therapy approved in the USA and Europe for previously treated patients with BRAF V600E-mutated mCRC. As a class, BRAF inhibitors are associated with dermatologic, gastrointestinal, and renal events, as well as pyrexia and secondary skin malignancies. Adverse event (AE) profiles of specific BRAF inhibitors vary, however, and are affected by the specific agents given in combination. In patients with mCRC, commonly reported AEs of cetuximab monotherapy include infusion reactions and dermatologic toxicities. Data from the phase III BEACON CRC study indicate that the combination of encorafenib with cetuximab has a distinct safety profile. Here we review the most frequently reported AEs that occurred with this combination in BEACON CRC and best practices for managing and mitigating AEs that require more than standard supportive care.

Stimulation of bile duct epithelial secretion by glybenclamide in normal and cholestatic rat liver.

Cholestasis is a cardinal complication of liver disease, but most treatments are merely supportive. Here we report that the sulfonylurea glybenclamide potently stimulates bile flow and bicarbonate excretion in the isolated perfused rat liver. Video-microscopic studies of isolated hepatocyte couplets and isolated bile duct segments show that this stimulatory effect occurs at the level of the bile duct epithelium, rather than through hepatocytes. Measurements of cAMP, cytosolic pH, and Ca2+ in isolated bile duct cells suggest that glybenclamide directly activates Na+-K+-2Cl- cotransport, rather than other transporters or conventional second-messenger systems that link to secretory pathways in these cells. Finally, studies in livers from rats with endotoxin- or estrogen-induced cholestasis show that glybenclamide retains its stimulatory effects on bile flow and bicarbonate excretion even under these conditions. These findings suggest that bile duct epithelia may represent an important new therapeutic target for treatment of cholestatic disorders.

Physiological expression of pancreatic somatostatin receptors in 99mTc-HYNIC-TOC scintigraphy.

PURPOSE: To describe the frequency of head and/or pancreas uncinate process uptake of 99mTc-HYNIC-TOC, to study its nature, and analyze its diagnostic value. MATERIALS AND METHODS: Retrospective evaluation of 47 consecutive 99mTc-HYNIC-TOC examinations was conducted. Head and/or pancreas uncinate process uptake was considered to be physiological in patients with normal CT at the same episode and in follow-up. It was analyzed if age or diabetes mellitus was justifying the existence or not of uptake. RESULTS: 32.5% patients showed uptake; 73% of them were mild. 84.6% patients with uptake have no pathology and 4% had neuroendocrine pancreatic disease at CT. Neither the age nor the diabetes mellitus established differences in patients without lesion. CONCLUSIONS: Near one-third of patients show physiological uptake by head and/or pancreas uncinate process at 99mTc-HYNIC-TOC scintigraphy. It seems that neither the diabetes nor the ages are factors that determine this physiological uptake.

Continuous light after a long-day treatment is equivalent to melatonin implants to stimulate testosterone secretion in Alpine male goats.

In rams, artificial long days followed by continuous light stimulate testosterone secretion during the non-breeding season. The objective of this study was to determine whether artificial long days followed by continuous light could stimulate testosterone secretion in Alpine bucks as well as in those exposed to long days followed by a melatonin treatment. All bucks were kept in shaded open pens. Control males were exposed to natural photoperiod conditions (n=5). Males of the two experimental groups were exposed to 2.5 months of long days from 1 December (n=5 each). On 16 February, one group of males was exposed to 24 h of light per day until 30 June; the other group was exposed to natural variations of photoperiod and received two s.c. melatonin implants. Testicular weight was determined every 2 weeks, and the plasma testosterone concentrations once a week. In the control and the two photoperiodic-treated groups, a treatment×time interaction was detected for testicular weight and plasma testosterone concentrations (P<0.001). In control bucks, testicular weight increased from January and peaked in June, whereas in both photoperiodic-treated groups, this variable increased from January, but peaked in April, when the values were higher than in controls (P<0.05). In the control group, plasma testosterone concentrations remained low from January to June, whereas in both photoperiodic-treated groups, this variable remained low from January to March; thereafter, these levels increased in both photoperiodic-treated groups, and were higher than controls in April and May (P<0.05). We conclude that continuous light after a long-day treatment stimulate testosterone secretion in Alpine male goats during the non-breeding season as well as the long days followed by a melatonin treatment. Therefore, continuous light could replace the implants of melatonin.

Early ovarian follicular development in prepubertal Wistar rats acutely exposed to androgens.

Androgens may directly modulate early ovarian follicular development in preantral stages and androgen excess before puberty may disrupt this physiological process. Therefore, the aim of this study was to investigate the dynamics of follicular morphology and circulating androgen and estradiol levels in prepubertal Wistar rats acutely exposed to androgens. Prepubertal female Wistar rats were distributed into three groups: control, equine chorionic gonadotropin (eCG) intervention and eCG plus dehydroepiandrosterone (DHEA) intervention (eCG+DHEA). Serum DHEA, testosterone and estradiol levels were determined, and ovarian morphology and morphometry were assessed. The eCG+DHEA group presented increased serum estradiol and testosterone levels as compared with the control group (P<0.01), and higher serum DHEA concentration v. the eCG-only and control groups (P<0.01). In addition, the eCG+DHEA group had a higher number of, and larger-sized, primary and secondary follicles as compared with the control group (P<0.05). The eCG group presented intermediate values for number and size of primary and secondary follicles, without significant differences as compared with the other two groups. The number of antral follicles was higher in the eCG+DHEA and eCG groups v. controls (P<0.05). The number of primordial, atretic and cystic follicles were similar in all groups. In conclusion, the present experimental model using an acute eCG+DHEA intervention was useful to investigate events involved in initial follicular development under hyperandrogenic conditions, and could provide a reliable tool to study defective follicular development with possible deleterious reproductive consequences later in life.

Apoptosis as a mechanism of natural resistance to HIV-1 infection in an exposed but uninfected population.

BACKGROUND: Apoptosis, also known as programmed cell death, has been reported not only as a pathogenic mechanism, but also as a mechanism of resistance and control of a variety of infections. Particularly during HIV-1 infection, apoptosis is the main mechanism by which infected and uninfected CD4+ lymphocytes are eliminated. However, apoptosis as a mechanism of natural resistance to HIV infection has this far not been explored. OBJECTIVE: To determine whether apoptosis could explain, at least in part, the natural resistance to HIV infection observed in some exposed but uninfected individuals (ESN). RESULTS: Our data shows that peripheral blood monocytes in the ESN group has a predisposition to undergo spontaneous apoptosis, as well as apoptosis induced by HIV infection in vitro, compared with monocyte population from the control group at low risk of HIV infection. CONCLUSIONS: These findings suggest that, in some ESN individuals, monocytes could play an important role in the control of HIV infection by undergoing apoptosis. However, since the variability among individuals is large, studies with larger cohorts focusing in monocyte apoptosis as pathogenic mechanisms are required.

Characteristics related to poor glycemic control in NIDDM patients in community practice.

OBJECTIVE: To identify clinical characteristics related to poor glycemic control in patients with NIDDM cared for by Michigan primary care physicians. RESEARCH DESIGN AND METHODS: This study was a cross-sectional secondary analysis of data from 393 NIDDM patients (mean age, 63 +/- 11 years; 54% female; 92% white) in the 1990-1991 Michigan Diabetes in Communities II Study. We evaluated patient demographic, clinical, and physiological characteristics, attitudes toward diabetes, and self-care ability. Logistic regression was used for multivariate evaluation of the characteristics of those patients whose glycosylated hemoglobin (normal GHb 4-8%) was in the upper 25% of the study sample (GHb > 11.6%). RESULTS: A high meal-stimulated plasma C-peptide was associated with a lower likelihood of poor control (odds ratio [OR] for highest quartile vs. all others = 0.37; 95% CI 0.23-0.58). Longer time since diagnosis (OR for each 5 years duration = 1.28; 95% CI 1.07-1.53), poor self-care ability (OR = 1.85; 95% CI 1.27-2.71), and perceived absence of dietary recommendations (OR = 2.37; 95% CI 1.11-5.08) were also independently associated with presence in the highest GHb quartile. Characteristics that were not significantly related to poor glycemic control included sex, age, obesity, educational level, exercise, self-rated health status, and pharmacological treatment. CONCLUSIONS: 1) Poor glycemic control may reflect progressive failure of islet function, although the independent relationships of C-peptide level and time since diagnosis are consistent with concepts of heterogeneous mechanisms underlying NIDDM. 2) Despite the important relationships of biological characteristics of NIDDM to glycemic control, patient attitudes and self-care ability may be useful targets for designing management strategies for certain poorly controlled patients.

Sorption of lead in soil as a function of pH: a study case in México.

Reactions of lead sorption onto soil are largely affected by properties and composition of soil and its solution. In this study, the lead sorption onto regosol eutric soil from Francisco I. Madero, Zacatecas, Mexico is evaluated at different pH values. Soil samples were suspended in lead solutions of 10, 25, 50, 100, 150, 200, 300, and 400 mg/l (as Pb(NO3)2). The pH was adjusted at 2, 3, 4, and 5.5 with nitric acid for each of the lead solution concentrations. In all the cases the ionic strength was I=0.09 M with calcium nitrate. The solid-liquid-ratios were fixed in 1:100 and 1:200 g/ml. The results show that lead sorption increases when pH increases. Experimental isotherms were adjusted by both Langmuir and Freundlich models. The Langmuir affinity parameter, K, indicates that the lead sorption capacity of Francisco I. Madero soils is largely perceptible to pH changes.

Estimating cancer screening indicators in the primary care setting.

The software "Profile: A Cancer Risk Profile of Your Patient Practice" was used to estimate cancer screening activities in a primary care practice. "Profile" is a public health tool that does not track the screening histories of individual patients, but rather, using a sampling strategy, provides estimates for the entire practice of the age and sex specific number of screening eligible patients, the number screened, and the number that should have been screened, based on National Cancer Institute/American Cancer Society (NCI/A CS) guidelines. This report describes "Profile," and the results it generated from a sample of medical records. Primary care providers who seek to integrate primary and secondary cancer prevention activities into their routine practices will find it useful to have an objective estimate of their current level of such activities.

Reverse transcriptase PCR and staging prostate cancer.

OBJECTIVE: To present a brief review of the diagnostic dilemma of staging prostate cancer and how a novel diagnostic technique, the reverse transcriptase polymerase chain reaction, is being used as an aid to better stage and manage the disease. DATA SOURCE: Research articles about prostate cancer and the reverse transcriptase polymerase chain reaction published in the last 5 years, as well as data gathered by the authors. STUDY SELECTION: Performed by the authors. DATA EXTRACTION: Performed by the authors. DATA SYNTHESIS: Prostate cancer is the most common cancer among men in the U.S. A wide variety of methods are used for the diagnosis; however, accurate staging of the disease to determine the most effective treatment is a problem. Because metastatic prostate cancer is routinely understaged, the reverse transcriptase polymerase chain reaction to identify prostate cancer cells in the circulatory system is becoming an important diagnostic aid for staging and monitoring the disease. It is analytically and clinically sensitive as well as specific. CONCLUSION: The reverse transcriptase polymerase chain reaction is a highly accurate aid in staging and monitoring prostate cancer. Its prognostic value, particularly when a small number of prostate cancer cells are detected in the circulatory system requires further long-term follow-up studies.

Bacterial infections in a hematology and oncology inpatient unit. Changing spectrum of bacteremias.

The incidence of infection is increased in patients with cancer and certain hematologic disorders. We retrospectively reviewed all the patients evaluated for infection in our Hematology-Oncology unit during a six month period. The purpose of this study was to identify the most common organisms causing infection, evaluate the usefulness of tests performed as well as to determine the outcome and complications of therapy. Contrary to earlier experience the most common organisms causing bacteremia were gram-positive. Despite this finding, gram-negative organisms remained important pathogens specially of the respiratory and urine tract judging by their predominance in urine and sputum cultures. Of the commonly ordered tests, the chest X-ray was the most frequently positive test for infection and the complication rate of antibiotic therapy was 15%. We conclude that in addition to the traditional antibiotics effective against gram-negative organisms, institution of antibiotics effective against gram-positive organisms including Staphylococcus epidermides, should be considered early in the management of these patients.

Improving oral hygiene for the seriously ill patient: implementing research-based practice.

A research-based policy and procedure to improve the oral hygiene care of intubated and other seriously ill patients was developed, implemented, and evaluated. The project resulted in (a) improved oral hygiene for patients, (b) standardization and simplification of nursing practice, and (c) a reduction in supply costs. The project has implications for nursing practice and evidence-based practice protocol development.

[Hepatocellular carcinoma: clinical and epidemiological characteristics]. / Carcinoma hepatocelular: características clinicoepidemiológicas.

We present 12 patients with CHC, 11 men and one woman, median age, 59.9 +/- 10.1 cared for in two hospitals from La Plata city. The median age, the predominance of men and presence of cirrhosis in the 75% are similar findings to European 41% of the patients, consulted of the CHC has increased in our environment. The fact that all the patients have been symptomatic at the moment of the consultation, that one of them had normal liver function tests and that only two of them had nodule of less than 5 cm of diameter, suggest advanced stage of the disease. At the same time, the median of survival of 8.3 +/- 9 (DS) months post-diagnosis and of 3.6 +/- 8 (DS) months post surgery. 90.9% had a risk factor to undergo CHC (alcohol, HBC, HCV). Because of one patient, the risk of hemodyalizer patients to have CHC is emphasized. Therefore, it is important to prevent and treat viral infections. In this study, the diagnosis of the echography was of 100% and the histologic corroboration was done by percutaneous biopsy with ultrasound or TC assessment. We observed that the levels of alpha-fetoprotein had a weak, negative correlation, not significative, with the diameters of the nodules. Although it is true that the size of the sample and the retrospective character of the investigation inhibits us to draw definitive conclusions, the behaviour of alfafetoprotein creates doubts about its value in the diagnosis and screening of the CHC.

[Sexual transmission of Hepatitis C virus]. / Transmisiòn sexual del virus de Hepatitis C.

Fifty heterosexual partners out of 50 patients (index cases) without confirmed or probable risk factors of parenteral transmission by HCV were studied from 1/1997 to 1/2001. The index cases were HCV Ab (+) (EIA 3rd Abbott and PCR + by RT-nested PCR). The couples with probable or confirmed risk factors of parenteral transmission were strictly excluded. No case of HCV infection was found, suggesting that sexual via wouldn't be a direct transmission of HCV.

Hepatotoxicidad: patrón colestásico inducido por fármacos / Hepatotoxicity: A Drug-Induced Cholestatic Pattern

La enfermedad hepática inducida por fármacos (DILI) es una condición poco frecuente; sin embargo, explica el 40%-50% de las insuficiencias hepáticas agudas. Su patrón es colestásico en un 20%-40%, causado por la inhibición de los transportadores que regulan la síntesis biliar; esta reducción en la actividad es mediada directa o indirectamente por los medicamentos y sus metabolitos, por polimorfismos genéticos y otros factores de riesgo del paciente. Sus manifestaciones van desde las alteraciones bioquímicas en ausencia de síntomas, hasta la insuficiencia hepática aguda y el daño hepático crónico. Aunque no existe un examen o marcador que indique el diagnóstico absoluto de la enfermedad, se han desarrollado escalas y algoritmos que permiten valorar la probabilidad de DILI colestásica, y otras pruebas que por su complejidad y costo no son de uso rutinario. Por lo anterior, es principalmente un diagnóstico de exclusión basado en evidencia circunstancial. El patrón colestásico de DILI presenta una mejor tasa de supervivencia general pero un mayor riesgo de desarrollo de enfermedad hepática crónica. En la mayoría de los casos, el cuadro del paciente mejora con el retiro del medicamento responsable del daño; la hemodiálisis y el trasplante deben considerarse solo para casos selectos. No se ha probado la eficacia de otras terapias. En este artículo se profundizará en la fisiopatología, la presentación clínica, bioquímica e histopatológica, además del diagnóstico, manejo y pronóstico de este tipo de colestasis.

Although drug induced liver disease is a rare condition, it explains 40% to 50% of all cases of acute liver failure. In 20% to 40% of the cases, the pattern is cholestatic and is caused by inhibition of the transporters that regulate bile synthesis. This reduction in activity is directly or indirectly mediated by drugs and their metabolites and/or by genetic polymorphisms and other risk factors of the patient. Its manifestations range from biochemical alterations in the absence of symptoms to acute liver failure and chronic liver damage. Although there is no absolute test or marker for diagnosis of this disease, scales and algorithms have been developed to assess the likelihood of cholestatic drug induced liver disease. Other types of evidence are not routinely used because of their complexity and cost. Diagnosis is primarily based on exclusion using circumstantial evidence. Cholestatic drug induced liver disease has better overall survival rates than other patters, but there are higher risks of developing chronic liver disease. In most cases, the patient’s condition improves when the drug responsible for the damage is removed. Hemodialysis and transplantation should be considered only for selected cases. The effectiveness of other therapies is unproven. This article will delve into the pathophysiology, biochemistry, and histopathology and the clinical presentation of the disease and will discuss diagnosis, management and prognosis of this type of cholestasis.

Stimulation of reproductive activity in anovulatory Alpine goats exposed to bucks treated only with artificially long days.

Two experiments were conducted in a subtropical latitude to determine the response of Alpine male goats to a treatment with artificially long days (experiment 1), and the response of anovulatory lactating Alpine does exposed to males treated only with artificially long days (experiment 2). In experiment 1, one group of males was kept under natural photoperiod (n = 4) while another was exposed to 2.5 months of artificially long days (16 h of light/day) from 1 December (n = 4). Plasma testosterone concentrations were determined weekly. Intensity of odor of males was determined every 2 weeks. Sexual behavior of bucks was observed during 3 days about 90 days after the end of the long day treatment. A treatment-by-time interaction was detected for testosterone secretion (P < 0.001). In control males, low plasma concentrations of testosterone were observed from March to June. In contrast, in long-day treated males, high levels of testosterone were observed from March to June (P < 0.05). A treatment-by-time interaction was detected for the intensity of male odor (P < 0.01). The male odor was stronger in long-day treated bucks than in untreated ones from March to June (P < 0.05). The number of ano-genital sniffing, nudging and flehmen was greater in long-day treated males than in untreated ones when exposed to anestrous does (P < 0.05). In experiment 2, one group of males was left under natural photoperiod variations (n = 5) and the other (n = 5) was submitted to the same photoperiodic treatment described in experiment 1. On 3 May, three untreated and three long-day treated males were put in contact with anestrous Alpine does left under natural photoperiod. Fertility was higher in does exposed to light-treated males (36/45, 80%) than those in contact with untreated ones (3/45, 7%; P < 0.05). Prolificacy was similar (P > 0.05) in does exposed to treated (1.8 ± 0.1) and untreated males (1.7 ± 0.3). These results indicate that the sexual activity of Alpine male goats raised in subtropical latitudes can be induced using only artificially long days and that such males are effective in stimulating reproductive activity in anovulatory females in late spring.

Meningitis de Mollaret: reporte de caso / Mollaret´s meningitis: A case report

La meningitis de Mollaret es una enfermedad rara caracterizada por episodios recurrentes y autolimitados de meningitis linfocítica. Se presenta un caso de meningitis de Mollaret asociado a la infección por herpes simple tipo 2 en una mujer de 27 años con confirmación por reacción en cadena de la polimerasa (PCR) del líquido cefalorraquídeo y se hace una revisión del tema.

Mollaret´s meningitis is a rare disease characterized by recurrent and self-limited episodes of lymphocytic meningitis. We present a case of a 27-year-old woman with Mollaret´s meningitis related to viral infection with herpes simplex virus type 2 confirmed by cerebrospinal fluid polymerase chain reaction ( PCR ).