[Hepatotoxicity by tamsulosin / dutasteride: report of a probable case]. / Hepatotoxicidad por tamsulosina / dutasterida: reporte de un caso probable.

Tamsulosin and dutasteride are drugs widely used to treat benign prostatic hypertrophy. having a good safety profile. There are few reports of liver injury associated with the use of tamsulosin; however, there are no reports of hepatic toxicity from the use of dutasteride and the combined use of tamsulosin/dutasteride. We present the case of a 64-year-old man who developed liver injury after the combined use of tamsulosin/dutasteride, developing a pattern of hepatocellular damage and acute hepatitis symptoms. Viral, autoimmune, and metabolic storage diseases of the liver were ruled out, as well as biliary pathology by means of abdominal ultrasound and resonance cholangiography. In the causality evaluation, CIOMS-RUCAM presented: 6 points (probable) and Naranjo: 4 points (possible). The patient presented a clinical and laboratory response after discontinuing the drug.

Herbal and Dietary Supplements-Induced Liver Injury in Latin America: Experience From the LATINDILI Network.

BACKGROUND: Herbal and dietary supplements (HDS) consumption, a growing cause of hepatotoxicity, is a common practice among Latin-American populations. OBJECTIVES: To evaluate clinical, laboratory features and outcome in HDS-hepatotoxicity included in the Latin America-Drug Induced Liver Injury (LATINDILI) Network. METHODS: A total of 29 adjudicated cases of HDS hepatotoxicity reported to the LATINDILI Network from October 2011 through December 2019 were compared with 322 DILI cases due to conventional drugs and 16 due to anabolic steroids as well as with other series of HDS-hepatotoxicity. RESULTS: From 367 DILI cases, 8% were attributed to HDS. An increasing trend in HDS-hepatotoxicity was noted over time (p = .04). Camellia sinensis, Herbalife® products, and Garcinia cambogia, mostly used for weight loss, were the most frequently adjudicated causative agents. Mean age was 45 years (66% female). Median time to onset was 31 days. Patients presented typically with hepatocellular injury (83%) and jaundice (66%). Five cases (17%) developed acute liver failure. Compared to conventional medications and anabolic steroids, HDS hepatotoxicity cases had the highest levels of aspartate and alanine transaminase (p = .008 and p = .021, respectively), had more re-exposure events to the culprit HDS (14% vs 3% vs 0%; p = .026), and had more severe and fatal/liver transplantation outcomes (21% vs 12% vs 13%; p = .005). Compared to other DILI cohorts, less HDS hepatotoxicity cases in Latin America were hospitalized (41%). CONCLUSIONS: HDS-hepatotoxicity in Latin-America affects mainly young women, manifests mostly with hepatocellular injury and is associated with higher frequency of accidental re-exposure. HDS hepatotoxicity is more serious with a higher chance of death/liver transplantation than DILI related to conventional drugs.

SARS-CoV-2 vaccination and risk of severe COVID-19 outcomes in patients with autoimmune hepatitis.

BACKGROUND: Data regarding outcome of Coronavirus disease 2019 (COVID-19) in vaccinated patients with autoimmune hepatitis (AIH) are lacking. We evaluated the outcome of COVID-19 in AIH patients who received at least one dose of Pfizer- BioNTech (BNT162b2), Moderna (mRNA-1273) or AstraZeneca (ChAdOx1-S) vaccine. PATIENTS AND METHODS: We performed a retrospective study on AIH patients with COVID-19. The outcomes of AIH patients who had acute respiratory syndrome coronavirus 2 (SARS-CoV-2) breakthrough infection after at least one dose of COVID-19 vaccine were compared to unvaccinated patients with AIH. COVID-19 outcome was classified according to clinical state during the disease course as: (i) no hospitalization, (ii) hospitalization without oxygen supplementation, (iii) hospitalization with oxygen supplementation by nasal cannula or mask, (iv) intensive care unit (ICU) admission with non-invasive mechanical ventilation, (v) ICU admission with invasive mechanical ventilation or (vi) death, and data was analyzed using ordinal logistic regression. RESULTS: We included 413 (258 unvaccinated and 155 vaccinated) patients (81%, female) with a median age of 52 (range: 17-85) years at COVID-19 diagnosis. The rates of hospitalization were (36.4% vs. 14.2%), need for any supplemental oxygen (29.5% vs. 9%) and mortality (7% vs. 0.6%) in unvaccinated and vaccinated AIH patients with COVID-19. Having received at least one dose of SARS-CoV-2 vaccine was associated with a significantly lower risk of worse COVID-19 severity, after adjusting for age, sex, comorbidities and presence of cirrhosis (adjusted odds ratio [aOR] 0.18, 95% confidence interval [CI], 0.10-0.31). Overall, vaccination against SARS-CoV-2 was associated with a significantly lower risk of mortality from COVID-19 (aOR 0.20, 95% CI 0.11-0.35). CONCLUSIONS: SARS-CoV-2 vaccination significantly reduced the risk of COVID-19 severity and mortality in patients with AIH.

Impact of Public Health Policies on Alcohol-Associated Liver Disease in Latin America: An Ecological Multinational Study.

BACKGROUND AND AIMS: Alcohol-associated liver disease (ALD) is the leading cause of liver-related mortality in Latin America, yet the impact of public health policies (PHP) on liver disease is unknown. We aimed to assess the association between alcohol PHP and deaths due to ALD in Latin American countries. APPROACH AND RESULTS: We performed an ecological multinational study including 20 countries in Latin America (628,466,088 inhabitants). We obtained country-level sociodemographic information from the World Bank Open Data source. Alcohol-related PHP data for countries were obtained from the World Health Organization Global Information System of Alcohol and Health. We constructed generalized linear models to assess the association between the number of PHP (in 2010) and health outcomes (in 2016). In Latin America, the prevalence of obesity was 27% and 26.1% among male and female populations, respectively. The estimated alcohol per capita consumption among the population at 15 years old or older was 6.8 L of pure alcohol (5.6 recorded and 1.2 unrecorded). The overall prevalence of alcohol use disorders (AUD) was 4.9%. ALD was the main cause of cirrhosis in 64.7% of male and 40.0% of female populations. A total of 19 (95%) countries have at least one alcohol-related PHP on alcohol. The most frequent PHP were limiting drinking age (95%), tax regulations (90%), drunk-driving policies and countermeasures (90%), and government monitoring systems and community support (90%). A higher number of PHP was associated with a lower ALD mortality (PR, 0.76; 95% CI, 0.61-0.93; P = 0.009), lower AUD prevalence (PR, 0.80; 95% CI, 0.65-0.99; P = 0.045), and lower alcohol-attributable road traffic deaths (PR, 0.81; 95% CI, 0.65-1.00; P = 0.051). CONCLUSIONS: Our study indicates that in Latin America, countries with higher number of PHP have lower mortality due to ALD, lower prevalence of AUD, and lower alcohol-attributable road traffic mortality.

Immunohistochemical detection of chlamydia trachomatis in sexually transmitted infectious proctitis.

INTRODUCTION: Since 2003, a progressive increase in sexually transmitted infections (STI), presented as proctitis, has been described in homosexual men. In 2013 Arnold et al. described microscopic features that enable pathologists to formulate a histological diagnosis of STI related proctitis. The aim of this study is to identify the presence of Chlamydia trachomatis by immunohistochemistry in a group of patients with male to male sexual activity and pathology compatible with STI proctitis. METHODS: Cross-sectional study. The study included 54 patients with risky sexual activity and histopathology compatible with STI-proctitis according to Arnold´s recommendations. The Chlamydia trachomatis identification was carried out retrospectively on paraffin blocks using mouse monoclonal antibodies from Santa Cruz biotechnology. RESULTS: all patients were young men with male to male sexual activity, 69% were positive for HIV. The most common endoscopic presentation was rectal ulcer (61%). Basal lymphoplasmacytic inflammation and mild crypt distortion were the most common histological findings. The immunohistochemical study identified positivity for Chlamydia trachomatis in 40% (18 of 45 tested) of STI proctitis cases. DISCUSSION: The epidemiological and endoscopic characteristics of the patients studied are similar to those previously reported. In accordance with Arnold et al., the most common histological findings were (a) mild distortion of the crypts; (b) dense and basal lymphoplasmacytic infiltrate and (c) scarcity of eosinophils. The positivity of chlamydia trachomatis in immunohistochemistry was lower than others studies that used PCR for this purpose. We did not find similar published studies to compare our results. CONCLUSIONS: In summary, 54 cases of patients with STI related proctitis are presented, all of them with distinctive histological characteristics and third of the cases tested positive by IHC for Chlamydia trachomatis.

Amyloid ß, Lipid Metabolism, Basal Cholinergic System, and Therapeutics in Alzheimer's Disease.

The presence of insoluble aggregates of amyloid ß (Aß) in the form of neuritic plaques (NPs) is one of the main features that define Alzheimer's disease. Studies have suggested that the accumulation of these peptides in the brain significantly contributes to extensive neuronal loss. Furthermore, the content and distribution of cholesterol in the membrane have been shown to have an important effect on the production and subsequent accumulation of Aß peptides in the plasma membrane, contributing to dysfunction and neuronal death. The monomeric forms of these membrane-bound peptides undergo several conformational changes, ranging from oligomeric forms to beta-sheet structures, each presenting different levels of toxicity. Aß peptides can be internalized by particular receptors and trigger changes from Tau phosphorylation to alterations in cognitive function, through dysfunction of the cholinergic system. The goal of this review is to summarize the current knowledge on the role of lipids in Alzheimer's disease and their relationship with the basal cholinergic system, as well as potential disease-modifying therapies.

Giant gastric lipoma as an uncommon cause of upper gastrointestinal bleeding.

A 52-year-old male patient presented to the Emergency Room due to melena. A gastroscopy was performed, which revealed a submucosal lesion in the antrum of the stomach. The lesion was lined with regular smooth mucosa except for an apical ulceration. Histology showed gastric mucosa with foveolar hyperplasia. Abdominal computed tomography (CT) showed a homogeneous, well-delimited fat-density mass measuring 5.9 x 4.3 cm. Laparoscopic surgery then found a solid tumor involving the whole thickness of the anterior wall at the prepyloric area, which was resected. Microscopic examination revealed a homogeneous, soft, ulcerated submucosal mass of yellowish adipose tissue that was 5 x 5 x 2 cm in size. Microscopically, the tumor was composed of mature fatty tissue with fibrous septa, and was partially encapsulated and circumscribed. It was reported as a submucosal lipoma. The patient had a favorable outcome.

Prospective Latin American cohort evaluating outcomes of patients with COVID-19 and abnormal liver tests on admission.

INTRODUCTION & OBJECTIVES: The independent effect of liver biochemistries as a prognostic factor in patients with COVID-19 has not been completely addressed. We aimed to evaluate the prognostic value of abnormal liver tests on admission of hospitalized patients with COVID-19. MATERIALS & METHODS: We performed a prospective cohort study including 1611 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through July 31, 2020 in 38 different Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters, including liver function tests, on admission and during hospitalization. All patients were followed until discharge or death. We fit multivariable logistic regression models, further post-estimation effect through margins and inverse probability weighting. RESULTS: Overall, 57.8% of the patients were male with a mean age of 52.3 years, 8.5% had chronic liver disease and 3.4% had cirrhosis. Abnormal liver tests on admission were present on 45.2% (CI 42.7-47.7) of the cohort (n = 726). Overall, 15.1% (CI 13.4-16.9) of patients died (n = 244). Patients with abnormal liver tests on admission presented higher mortality 18.7% (CI 15.9-21.7), compared to those with normal liver biochemistries 12.2% (CI 10.1-14.6); P < .0001). After excluding patients with history of chronic liver disease, abnormal liver tests on admission were independently associated with death [OR 1.5 (CI 1.1-2.0); P = 0.01], and severe COVID-19 (2.6 [2.0-3.3], P < .0001), both adjusted by age, gender, diabetes, pneumonia and body mass index >30. CONCLUSIONS: The presence of abnormal liver tests on admission is independently associated with mortality and severe COVID-19 in hospitalized patients with COVID-19 infection and may be used as surrogate marker of inflammation. CLINICALTRIALS.GOV: NCT04358380.

Comparison of different prognostic scores for patients with cirrhosis hospitalized with SARS-CoV-2 infection.

INTRODUCTION AND OBJECTIVES: Viral infections have been described to increase the risk of decompensation in patients with cirrhosis. We aimed to determine the effect of SARS-CoV-2 infection on outcome of hospitalized patients with cirrhosis and to compare the performance of different prognostic models for predicting mortality. PATIENTS: We performed a prospective cohort study including 2211 hospitalized patients with confirmed SARS-CoV-2 infection from April 15, 2020 through October 1, 2020 in 38 Hospitals from 11 Latin American countries. We registered clinical and laboratory parameters of patients with and without cirrhosis. All patients were followed until discharge or death. We evaluated the prognostic performance of different scoring systems to predict mortality in patients with cirrhosis using ROC curves. RESULTS: Overall, 4.6% (CI 3.7-5.6) subjects had cirrhosis (n = 96). Baseline Child-Turcotte-Pugh (CTP) class was assessed: CTP-A (23%), CTP-B (45%) and CTP-C (32%); median MELD-Na score was 19 (IQR 14-25). Mortality was 47% in patients with cirrhosis and 16% in patients without cirrhosis (P < .0001). Cirrhosis was independently associated with death [OR 3.1 (CI 1.9-4.8); P < .0001], adjusted by age, gender, and body mass index >30. The areas under the ROC curves for performance evaluation in predicting 28-days mortality for Chronic Liver Failure Consortium (CLIF-C), North American Consortium for the Study of End-Stage Liver Disease (NACSELD), CTP score and MELD-Na were 0.85, 0.75, 0.69, 0.67; respectively (P < .0001). CONCLUSIONS: SARS-CoV-2 infection is associated with elevated mortality in patients with cirrhosis. CLIF-C had better performance in predicting mortality than NACSELD, CTP and MELD-Na in patients with cirrhosis and SARS-CoV-2 infection. Clinicaltrials.gov:NCT04358380.

A Latin American survey on demographic aspects of hospitalized, decompensated cirrhotic patients and the resources for their management.

INTRODUCTION & OBJECTIVES: Liver cirrhosis is a major cause of mortality worldwide. Adequate diagnosis and treatment of decompensating events requires of both medical skills and updated technical resources. The objectives of this study were to search the demographic profile of hospitalized cirrhotic patients in a group of Latin American hospitals and the availability of expertise/facilities for the diagnosis and therapy of decompensation episodes. METHODS: A cross sectional, multicenter survey of hospitalized cirrhotic patients. RESULTS: 377 patients, (62% males; 58±11 years) (BMI>25, 57%; diabetes 32%) were hospitalized at 65 centers (63 urbans; 57 academically affiliated) in 13 countries on the survey date. Main admission causes were ascites, gastrointestinal bleeding, hepatic encephalopathy and spontaneous bacterial peritonitis/other infections. Most prevalent etiologies were alcohol-related (AR) (40%); non-alcoholic-steatohepatitis (NASH) (23%), hepatitis C virus infection (HCV) (7%) and autoimmune hepatitis (AIH) (6%). The most frequent concurrent etiologies were AR+NASH. Expertise and resources in every analyzed issue were highly available among participating centers, mostly accomplishing valid guidelines. However, availability of these facilities was significantly higher at institutions located in areas with population>500,000 (n=45) and in those having a higher complexity level (Gastrointestinal, Liver and Internal Medicine Departments at the same hospital (n=22). CONCLUSIONS: The epidemiological etiologic profile in hospitalized, decompensated cirrhotic patients in Latin America is similar to main contemporary emergent agents worldwide. Medical and technical resources are highly available, mostly at great population urban areas and high complexity medical centers. Main diagnostic and therapeutic approaches accomplish current guidelines recommendations.

[Localization and size of colon adenomas as factors related to high gradedysplasia]. / Localización y tamaño de los adenomas del colon como factoresasociados a displasia de alto grado.

OBJECTIVE: To determine whether localization and size are related to the presence of high-grade dysplasia of colon adenomas in patients of a Peruvian hospital. MATERIALS AND METHODS: This is a descriptive transversal study. We checked colonoscopyreports of 2014-2015 years of Hospital Daniel Alcides Carrion, we included the polyps found in patients older than 18 years old, and excluded reports from patients with colorectal cancer, an antecedent of oncological surgery, inflammatory bowel disease and polyposis (6 or more). We used data based on localization (proximal and distal colon, based on the splenic angle), size (less than 10 mm and 10 mm or more), shape (pediculate and sessile) and grade of dysplasia (low and high-grade). We calculated the strength of association by OR, and we determined whether there was association by Chi-square test with a significance value less than 0.05. RESULTS: We reviewed a total of 1710 of colonoscopy reports, 378 patients had polyps, so the adenoma detection rate was 22.1%. There were 458 polyps, from which 254 were adenomas. From these adenomas, we found an association between distal colon localization and high-grade dysplasia (OR 2.68 IC 1.12-6.42, p < 0.05); likewise, there was an association between the size of the adenomas and high-grade dysplasia (OR 7.75 IC 3.05-19.69, p<0.05). We did not find any association between the shape and grade of dysplasia. CONCLUSION: This study concludes that there is an association between the size of 10 mm or more and localization in the distal colon with high-grade dysplasia of adenomas.

Active coping of prenatally stressed rats in the forced swimming test: involvement of the Nurr1 gene.

Depending on genetic predisposition, prenatal stress may result in vulnerability or resilience to develop psychiatric disorders in adulthood. Nurr1 is an immediate early gene, important in the brain for the stress response. We tested the hypothesis that prenatal stress and the decrease of hippocampal Nurr1 alter offspring behavioral responses in the forced swimming test (FST). Pregnant Wistar rats were exposed to restraint stress (45 min, thrice daily) from gestation day 14. Prenatally stressed (PS) and non-prenatally stressed (NPS) male offspring were treated bilaterally with a Nurr1 antisense oligodeoxynucleotide (ODN; or control) into the hippocampus at 97 d of age. After 1 h, the rats were exposed to the FST (acute stressor) to analyze their behavioral responses. Thirty minutes after the FST, we analyzed the gene expression of Nurr1, Bdnf and Nr3c1 (genes for Nurr1, brain-derived neurotrophic factor (BDNF) and glucocorticoid receptor (GR), respectively) in the hippocampus, prefrontal cortex (PFC) and hypothalamus. Results showed that the decrease of hippocampal Nurr1 after the antisense ODN in adult NPS rats induces immobility (indicating depressive-like behavior). The PS adult rats, including the group with decreased hippocampal Nurr1, presented low immobility in the FST. This low immobility was concordant with maintenance of Nurr1 and Bdnf expression levels in the three analyzed brain regions; Nr3c1 gene expression was also maintained in the PFC and hypothalamus. These findings suggest that Nurr1 and associated genes could participate in the brain modifications induced by prenatal stress, allowing active coping (resilience) with acute stress in adulthood.

[Celiac disease and negative serology villous atrophy: histological comparison and immunohistochemical study of CD3, CD4, CD8 and CD56 lymphocytes]. / Enfermedad celíaca vs. atrofia villositaria serológicamente negativa: similitudes y diferencias histológicas y en el perfil inmunohistoquímico de linfocitos CD3, CD4, CD8 y CD56.

UNLABELLED: There is a group of enteropathies recently known as seronegative villous atrophy (SNVA), which can simulate celiac disease. OBJECTIVE: The aim of this study was to describe histological and immunohistochemical differences between a group of Celiac disease and SNVA patients. MATERIAL AND METHODS: Microscopy reexamination and Immunohistochemistry study were performed for a group of 15 celiac patients and 19 SNVA patients. Histological features as severe atrophy, crypt hyperplasia, plasma cells number, eosinophils number, neutrophils presence were studied; CD4, CD8, CD3, and CD56 markers were studied through immunohistochemistry. RESULTS: There was a significant difference between the frequency of observation of crypt hyperplasia (p=0.0348) and plasma cells (p=0.0348) in celiac disease patients than SNVA patients. In celiac disease was bigger. The number and distribution of CD 8, CD4 and CD56 lymphocytes was similar in both groups. The percentage of CD3 positive intraepithelial lymphocytes (p=0.0144) was higher in SNVA. CONCLUSION: Histological and immunohistochemical evaluation shows more similarities than differences. The differences found in this study suggest more humoral immune response in celiac disease than in SNVA.

[Eosinophilic and lymphocytic colitis: different histological manifestations of a same process in patients with chronic diarrhea]. / Colitis eosinofílica y colitis linfocítica: ¿diferentes manifestaciones histológicas de un mismo proceso en pacientescon diarrea crónica?

OBJECTIVES: 1) To determine the prevalence of increased number of eosinophils in colonic mucosa of patients with lymphocytic colitis (LC). 2) To determine the coexistence of eosinophilic colitis (EC) in patients with lymphocytic colitis. MATERIALS AND METHODS: slides of adult patients with cronic diarrhea with diagnosis of LC were reviewed between October 2009 and March 2012. The number of eosinophils was quantified. RESULTS: Sixty eight patients with LC were included. Elevated eosinophils were found in 76.5 and in 51.4% a diagnosis of EC was established. CONCLUSION: 3 out of 4 patients with LC had elevated eosinophils and 1 of 2 patients with LC had criteria for EC.

Neuroprotective-Neurorestorative Effects Induced by Progesterone on Global Cerebral Ischemia: A Narrative Review.

Progesterone (P4) is a neuroactive hormone having pleiotropic effects, supporting its pharmacological potential to treat global (cardiac-arrest-related) cerebral ischemia, a condition associated with an elevated risk of dementia. This review examines the current biochemical, morphological, and functional evidence showing the neuroprotective/neurorestorative effects of P4 against global cerebral ischemia (GCI). Experimental findings show that P4 may counteract pathophysiological mechanisms and/or regulate endogenous mechanisms of plasticity induced by GCI. According to this, P4 treatment consistently improves the performance of cognitive functions, such as learning and memory, impaired by GCI. This functional recovery is related to the significant morphological preservation of brain structures vulnerable to ischemia when the hormone is administered before and/or after a moderate ischemic episode; and with long-term adaptive plastic restoration processes of altered brain morphology when treatment is given after an episode of severe ischemia. The insights presented here may be a guide for future basic research, including the study of P4 administration schemes that focus on promoting its post-ischemia neurorestorative effect. Furthermore, considering that functional recovery is a desired endpoint of pharmacological strategies in the clinic, they could support the study of P4 treatment for decreasing dementia in patients who have suffered an episode of GCI.

Synthesis and evaluation of molecular rotors with large and bulky tert-butyldiphenylsilyloxy-substituted trityl stators.

The search for voluminous stators that may accommodate large rotator units and speed rotational dynamics in the solid state led us to investigate a simple and efficient method for the synthesis of molecular rotors with tert-butyldiphenylsilyl-protected (TBDPS) triphenylmethyl stators. Additionally, solid state characterization of these systems with two-, four-, and six-TBDPS groups provided us with a description of their crystallinity and thermal stability. Among them, molecular rotor 7c with the largest and most symmetric stator resulting from six peripheral silyl groups showed the best tendency to crystallize, and the study of its isotopologue 7c-d(4) by solid state (2)H NMR revealed a 2-fold motion of the 1,4-diethynylphenylene-d(4) rotator in the kHz regime.

[Probiotic supplement (Lactobacillus acidophilus and bulgaricus) utility in the treatment of irritable bowel syndrome]. / Utilidad del suplemento de probioticos (Lactobacillus acidophilus y bulgaricus) en el tratamiento del sindrome de intestino irritable.

BACKGROUND: Irritable bowel syndrome (IBS) is a very common functional condition and a frequent cause of consultation in gastroenterology. With a multifactorial pathophysiology IBS is characterized by abdominal pain, distension and altered bowel habits. Loperamide, antispasmodics and antidepressants are symptomatic relievers of this disorder. Recently probiotics were incorporated to therapy, and could improve the symptomatology. METHODS: multicenter randomized placebo-controlled trial that included IBS patients, diagnosed with Rome III criteria. The patients were given pinaverium bromure and placebo or pinaverium bromure and probiotics for 3 weeks. The intensity of symptoms and the effect of therapy were evaluated with the Francis Score, before and after the treatment. Statistics were done with SPSS 12.0 (C.I 95%). RESULTS: 51 patients were evaluated, with an average age of 43 years old, mostly mestizo, 75% (38) married and 55% (28) female. There were statistical differences in four variables: abdominal pain, intensity of pain, days of pain and total score at the end of therapy. CONCLUSIONS: Probiotics used as supplement are effective in improving symptomatology of IBS.

Progesterone treatment in rats after severe global cerebral ischemia promotes hippocampal dentate gyrus neurogenesis and functional recovery.

OBJECTIVE: Rats treated with progesterone (P4) after ischemia show an adequate functional performance despite a significant loss of hippocampal pyramidal neurons, suggesting that P4 could favour a permissive microenvironment for cerebral plasticity mechanisms. The possibility of P4 treatment promoting the survival of newly generated hippocampal neurons, in relation to the performance of ischemic rats in a spatial learning task, was assessed in this study. METHODS: Adult male rats were subjected to a severe global cerebral ischemia episode (30 min) and treated with P4 or its vehicle at 15 min, 2, 6, 24, 48 and 72 h of reperfusion. From day 4 to 8 post-ischemia 5-bromo-2-deoxyuridine (BrdU) was administered to label proliferating cells. Twenty-one days post-ischemia, the rats were exposed to the Morris water maze to assess behavioral parameters of spatial learning and memory. Subsequently, the brain was perfusion-fixed and immunofluorescence procedures were performed to quantify the number of new mature neurons (BrdU+/NeuN+) in the dentate gyrus (DG) of the hippocampus. RESULTS: Rats subjected to severe global cerebral ischemia and treated with P4 had a significantly better performance in spatial learning-memory tests, than those treated with vehicle, and a significantly higher number of new mature neurons (BrdU+/NeuN+) in the DG. CONCLUSION: These findings show that post-ischemia P4 treatment, following an episode of severe global cerebral ischemia, promotes the survival of newly generated hippocampal neurons in the DG, which may be one of the mechanisms of cerebral plasticity induced by the hormone, that underlie a successful functional performance in learning and memory tests.

Lessons Learned From Hurricane Maria in Puerto Rico: Practical Measures to Mitigate the Impact of a Catastrophic Natural Disaster on Radiation Oncology Patients.

PURPOSE: Although the wind, rain, and flooding of Hurricane Maria in Puerto Rico abated shortly after its landfall on September 20, 2017, the disruption of the electrical, communications, transportation, and medical infrastructure of the island was unprecedented in scope and caused lasting harm for many months afterward. A compilation of recommendations from radiation oncologists who were in Puerto Rico during the disaster, and from a panel of American Society for Radiation Oncology (ASTRO) cancer experts was created. METHODS AND MATERIALS: Radiation oncologists throughout Puerto Rico collaborated and improvised to continue treating patients in the immediate aftermath of the storm and as routine clinical operations were restored gradually. Empirical lessons from the experience of radiation therapy administration in this profoundly altered context of limited resources, impaired communication, and inadequate transportation were organized into a recommended template, applicable to any radiation oncology practice. ASTRO disease-site experts provided evidence-guidelines for mitigating the impact of a 2- to 3-week interruption in radiation therapy. RESULTS: Practical measures to mitigate the medical impact of a disaster are summarized within the framework of "Prepare, Communicate, Operate, Compensate." Specific measures include the development of an emergency operations plan tailored to specific circumstances, prospective coordination with other radiation oncology clinics before a disaster, ongoing communications with emergency management organizations, and routine practice of alternate methods to disseminate information among providers and patients. CONCLUSIONS: These recommendations serve as a starting point to assist any radiation oncology practice in becoming more resiliently prepared for a local or regional disruption from any cause. Disease-site experts provide evidence-based guidelines on how to mitigate the impact of a 2- to 3-week interruption in radiation therapy for lung, head and neck, uterine cervix, breast, and prostate cancers through altered fractionation or dose escalation.