The midgut epithelium of mosquitoes adjusts cell proliferation and endoreplication to respond to physiological challenges.

BACKGROUND: Hematophagous mosquitoes transmit many pathogens that cause human diseases. Pathogen acquisition and transmission occur when female mosquitoes blood feed to acquire nutrients for reproduction. The midgut epithelium of mosquitoes serves as the point of entry for transmissible viruses and parasites. RESULTS: We studied midgut epithelial dynamics in five major mosquito vector species by quantifying PH3-positive cells (indicative of mitotic proliferation), the incorporation of nucleotide analogs (indicative of DNA synthesis accompanying proliferation and/or endoreplication), and the ploidy (by flow cytometry) of cell populations in the posterior midgut epithelium of adult females. Our results show that the epithelial dynamics of post-emergence maturation and of mature sugar-fed guts were similar in members of the Aedes, Culex, and Anopheles genera. In the first three days post-emergence, ~ 20% of cells in the posterior midgut region of interest incorporated nucleotide analogs, concurrent with both proliferative activity and a broad shift toward higher ploidy. In mature mosquitoes maintained on sugar, an average of 3.5% of cells in the posterior midgut region of interest incorporated nucleotide analogs from five to eight days post-emergence, with a consistent presence of mitotic cells indicating constant cell turnover. Oral bacterial infection triggered a sharp increase in mitosis and nucleotide analog incorporation, suggesting that the mosquito midgut undergoes accelerated cellular turnover in response to damage. Finally, blood feeding resulted in an increase in cell proliferation, but the nature and intensity of the response varied by mosquito species and by blood source (human, bovine, avian or artificial). In An. gambiae, enterocytes appeared to reenter the cell cycle to increase ploidy after consuming blood from all sources except avian. CONCLUSIONS: We saw that epithelial proliferation, differentiation, and endoreplication reshape the blood-fed gut to increase ploidy, possibly to facilitate increased metabolic activity. Our results highlight the plasticity of the midgut epithelium in mosquitoes' physiological responses to distinct challenges.

Antitumoral photoinduced effects of crude extract, fractions, and naphthoquinones from Sinningia magnifica (Otto & A. Dietr.) Wiehler (Gesneriaceae) in a bioguided study.

Photodynamic therapy (PDT) has been used for various purposes, including as an antitumor resource in a noninvasive therapy with minimal side effects. Sinningia magnifica (Otto & A. Dietr.) Wiehler is a rupicolous plant found in rock crevices in Brazilian tropical forests. Initial studies indicate the presence of phenolic glycosides and anthraquinones in species of the genus Sinningia (Generiaceae family). It is known that anthraquinones are natural photosensitizers with potential PDT applications. This led us to investigate the potential compounds of S. magnifica for use as a natural photosensitizer against the melanoma (SK-MEL-103) and the prostate cancer (PC-3) cell lines in a bioguided study. Our results showed that singlet oxygen production by the 1,3-DPBF photodegradation assay greatly increased in the presence of crude extract and fractions. The biological activity evaluation showed photodynamic action against melanoma cell line SK-MEL-103 and prostate cell line PC-3. These results suggest the presence of potential photosensitizing substances, as demonstrated in this in vitro antitumor PDT study by the naphthoquinones Dunniol and 7-hydroxy-6-methoxy-α-dunnione for the first time. Naphthoquinones, anthraquinones and phenolic compounds were identified in the crude extract by UHPLC-MS/MS analysis, motivating us to continue with the bioguided phytochemical study aiming to discover more photochemically bioactive substances in Gesneriaceae plants.

Genomic Analysis and Development of Infectious Clone of a Novel Carlavirus Infecting Blueberry.

A new blueberry virus was discovered using high-throughput sequencing. Using sequence identity values, phylogenetics, and serological and biological properties, we propose the virus, putatively named blueberry virus S (BluVS), to be a distinct species within the genus Carlavirus (family Betaflexiviridae). The genome was analyzed in depth, and an infectious clone was developed to initiate studies on virus pathogenicity. Agroinfiltration of the binary vector construct produced severe systemic symptoms in Nicotiana occidentalis. Back-inoculation using sap from agroinfiltrated N. occidentalis produced identical symptoms to the recipient plants (N. occidentalis), and virus purification yielded flexuous carlavirus-like particles. However, unlike blueberry scorch virus (BlScV), BluVS caused symptomless infection in Chenopodium quinoa and reacted weakly to BlScV antibodies in an enzyme-linked immunosorbent assay. Collectively, the results provide evidence for the distinct speciation of BluVS. The availability of an infectious clone provides tools for future studies on the biology of the virus.

Attempts to use breeding approaches in Aedes aegypti to create lines with distinct and stable relative Wolbachia densities.

Wolbachia is an insect endosymbiont being used for biological control in the mosquito Aedes aegypti because it causes cytoplasmic incompatibility (CI) and limits viral replication of dengue, chikungunya, and Zika viruses. While the genetic mechanism of pathogen blocking (PB) is not fully understood, the strength of both CI and PB are positively correlated with Wolbachia densities in the host. Wolbachia densities are determined by a combination of Wolbachia strain and insect genotype, as well as interactions with the environment. We employed both artificial selection and inbreeding with the goal of creating lines of Ae. aegypti with heritable and distinct Wolbachia densities so that we might better dissect the mechanism underlying PB. We were unable to shift the mean relative Wolbachia density in Ae. aegypti lines by either strategy, with relative densities instead tending to cycle over a narrow range. In lieu of this, we used Wolbachia densities in mosquito legs as predictors of relative densities in the remaining individual's carcass. Because we worked with outbred mosquitoes, our findings indicate either a lack of genetic variation in the mosquito for controlling relative density, natural selection against extreme densities, or a predominance of environmental factors affecting densities. Our study reveals that there are moderating forces acting on relative Wolbachia densities that may help to stabilize density phenotypes post field release. We also show a means to accurately bin vector carcasses into high and low categories for non-DNA omics-based studies of Wolbachia-mediated traits.

Empiema necessitatis por Mycobacterium tuberculosis en Pediatría: Reporte de caso / Empyema necessitatis due to mycobacterium tuberculosis in pediatrics: case report

El empiema necessitatis es una entidad clínica poco frecuente en la población pediátrica, la principal etiología está asociada a infección por Mycobacterium tuberculosis, en pacientes inmunocompetentes o inmunosuprimidos, el diagnóstico principal debe realizarse de manera oportuna, buscando evitar complicaciones o lesiones permanentes en los pacientes que la padecen.(AU)

Empyema necessitatis is a rare clinical entity in the pediatric population, the main etiology is associated with infection by Mycobacterium tuberculosis, in immunocompetent or immunosuppressed patients, the main diagnosis must be made in a timely manner, seeking to avoid complications or permanent injuries in the patients who suffer from it.(AU)

Characteristics of fingertip injuries and proposal of a treatment algorithm from a hand surgery referral center in Mexico City.

BACKGROUND: Fingertips are the most commonly injured anatomical structures in the upper extremity. The aim of this work is to present our experience in the management of fingertip injuries. METHODS: All patients with fingertip injuries managed by Plastic and Reconstructive Surgery Division of Hospital General “Dr Manuel Gea Gonzalez” in Mexico from July 2010 to June 2015 were included; their demographic characteristics were described, as well as patterns of injury and management. RESULTS: A total of 1,265 patients were included in the study, 75% were males. The mean age of presentation was 20.5 ± 16.46 years; the age group most commonly affected was younger than 15 years (46.7%). Right and left-sided injuries were almost equally prevalent (51 vs. 49%). The most commonly injured fingers were the third (27.2%), and second (25.8%). Eighty-seven percent of the patients presented with single-digit injuries. Fingertip amputations were the most common type of injury with 620 cases (49%), followed by simple fingertip lacerations (574 cases, 45%), and nail bed injuries in 71 cases (5.6%). Surgical management was necessary in 95.8% of the cases. CONCLUSIONS: Fingertip injuries remain the most common reason for consultation in hand emergencies. A structured approach for their treatment is necessary to obtain the best clinical outcomes.

Características y factores asociados a trastornos de la esfera mental en estudiantes de medicina de la costa, sierra y selva peruana / Characteristics and factors associated with disorders of the mental sphere in medical students of the coast, mountains and Peruvian jungle

Resumen Introducción: Los trastornos de la esfera mental son cada vez más frecuentes, estos deben ser medidos en los estudiantes que están sometidos a gran presión y según el lugar de influencia. Objetivos: Determinar las características y factores asociados a trastornos de la esfera mental en estudiantes de medicina de la costa, sierra y selva peruana. Metodología: Se realizó un estudio transversal analítico preliminar, a través de la aplicación del Inventario Clínico Multiaxial de Millon (MCMI-II), a 105 estudiantes, dicha encuesta midió los distintos trastornos de la esfera mental; a los cuales se les asoció con variables socio-educativas. Resultados: Grandes porcentajes de encuestados tuvieron compulsividad (29%) y narcisismo elevado (28%). En el análisis multivariado se encontró que las mujeres tuvieron menor frecuencia de trastorno esquizoide (p=0,027); conforme aumentó la edad también hubo mayor frecuencia de trastornos evitativo (p=0,049) y ansiedad (p= 0,043); a mayor año académico se encontró menor frecuencia de trastorno dilusional (p=0,010); los estudiantes de la universidad de la sierra tuvieron más narcisismo (p=0,011), compulsividad (p=0,018) y paranoide (p=0,041); los estudiantes de la universidad de la selva tuvieron más agresividad-sádica (p=0,021), narcisismo (p=0,020) y compulsividad (p=0,005); estas dos últimas fueron comparados versus los que estudiaban en la costa. Conclusión: Se encontró gran frecuencia de algunos trastornos, así como algunos factores asociados, lo que puede ser útil como análisis situacional, lo que debería generar mayores trabajos en la materia.

Introduction: The disorders of the mental sphere are increasingly frequent, these should be measured in students who are under great pressure and according to the place of influence. Objectives: To determine the characteristics and factors associated with disorders of the mental sphere in medical students of the coast, mountains and Peruvian jungle. Methodology: A preliminary analytical cross-sectional study was carried out, through the application of the Millon Multiaxial Clinical Inventory (MCMI-II), to 105 students, said survey measured the different disorders of the mental sphere; to which they were associated with socio-educational variables. Results: Large percentages of respondents had compulsivity (29%) and high narcissism (28%). In the multivariate analysis it was found that women had a lower frequency of schizoid disorder (p = 0.027); as age increased there was also a higher frequency of avoidance disorders (p = 0.049) and anxiety (p = 0.043); the higher the academic year, the lower the frequency of dilution disorder (p = 0.010); the students of the Universidad de la Sierra had more narcissism (p = 0.011), compulsivity (p = 0.018) and paranoid (p = 0.041); the students of the jungle university had more aggressive-sadistic (p = 0.021), narcissism (p = 0.020) and compulsivity (p = 0.005); These last two were compared versus those studying on the coast. Conclussion: We found a high frequency of some disorders, as well as some associated factors, which can be useful as a situational analysis, which should generate more work in the field.

Pregnancy rates in hair sheep after Ovsynch synchronization and a combined intracervical fixed-time artificial insemination and 10-day mating period.

AIM: This study aimed to evaluate the pregnancy rates in hair ewes using an Ovsynch synchronization protocol under a breeding system that combines fixed-time insemination plus a 10-day mating period as an alternative. MATERIALS AND METHODS: Through an experimental study (n=27), ewes were randomly located into one of three treatments: (1) Pre-synch (n=9): Prostaglandin F2α (PGF2α)+Gonadotropin-releasing hormone (GnRH)+PGF2α+GnRH; (2) Ovsynch (n=9): GnRH+PGF2α+GnRH; and (3) control: Ewes bred by natural mating (NM) (n=9). Ewes were fixed-time inseminated (fixed-time artificial insemination [FTAI]) with fresh semen, collected just before the insemination time through vaginoscopy at 16 h after the second GnRH (gonadorelin) injection. Each experimental group was placed separately during 15 days and, after this time, fertile rams were allowed back with ewes for a 10-day mating period. Control group ewes remained with the rest of the herd suitable for breeding and were bred under NM. Pregnancy diagnosis was performed by ultrasound at 28-, 56-, and 84-day post-breeding to differentiate between FTAI and NM pregnancies. Total (FTAI±NM) pregnancy rates at 56-day post-breeding were used to compared Pre-synch, Ovsynch, and control. For this purpose, two-tailed proportions comparison z-test was used with a 95% confidence level, for testing as the null hypothesis whether two proportions were equal. RESULTS: Pregnancy rates were higher in control ewes (66.4%) than FTAI (46.6%). When pregnancy rates after a 10-day mating period (40%) were added, the final rate (86.6%) was significantly (p<0.05) higher in Ovsynch-based protocols. The pregnancy rate was significantly lower in FTAI ewes compared to FTAI +10-day mating group (p<0.05). The overall pregnancy rate was 88.0, 85.7, and 67.0 (p>0.05) for Pre-synch, Ovsynch, and control ewes, respectively. CONCLUSION: These results provide evidence on the benefits of combined FTAI protocols for improving the reproductive efficiency of sheep.

Socioeconomic and demographic predictors of resident knowledge, attitude, and practice regarding arthropod-borne viruses in Panama.

BACKGROUND: We sought to identify if socioeconomic and demographic factors play a role in resident knowledge, attitude, and practice regarding Dengue, Chikungunya, and Zika in order to inform effective management procedures for disease prevention in Panama, a middle-income tropical country in Central America. All three are arthropod-borne viruses transmitted by Aedes mosquito vectors present in the focal region of Panama City, the largest city in Central America and an urban region of extreme socioeconomic polarization. METHODS: Between November 2017 and February 2018, we administered standardized, anonymous knowledge, attitude, and practice surveys to 263 residents split between two neighborhoods of high socioeconomic status (SES) and two neighborhoods of low SES. We then summed the knowledge, attitude, and practice scores respectively, and used linear and logistic regressions to quantify relationships with socioeconomic and demographic factors. RESULTS: Low-SES neighborhoods with high proportions of low income residents, residents over 70 years old had lower mean knowledge scores compared to other groups. Furthermore, residents in neighborhoods of low SES reported more mosquito biting relative to residents in neighborhoods of high SES, yet comparably lower level of concerns for disease transmission. Additionally, knowledge was lower for the more novel emergent threats of Chikungunya and Zika, compared to the endemic Dengue. CONCLUSION: Findings suggest that low-SES neighborhoods with high proportions of low income, low education, and elderly residents should be targeted for outreach programs designed to prevent DENV, CHIKV, or ZIKV in Panama City. These outcomes support our initial hypotheses as lower relative knowledge and fewer practices related to the prevention of Dengue, Chikungunya, and Zika were found in low-SES neighborhoods. There is also a widespread lack of adequate knowledge regarding these diseases as well as low levels of concern in areas of highly reported mosquito biting. We provide suggestions for taking neighborhood socioeconomic status and specific aspects resident health literacy and attitude into account for creating more effective outreach campaigns as both endemic and novel arthropod-borne disease rates continue to increase throughout Latin America.

Relationship between cyberbullying and health-related quality of life in a sample of children and adolescents.

PURPOSE: Health-related quality of life (HRQoL) is a well-known construct that refers to a state of complete physical, mental, and social well-being. Its relationship with multiple forms of violence, including bullying, has been widely explored, but this is not the case for cyberbullying. The main objective is to analyze how HRQoL varies depending on the role played in cyberbullying, its temporal stability, and gender and age differences. METHOD: An analytical and longitudinal study was conducted at two temporal moments. At Time 1 (December 2015), 920 Spanish students aged between 11 and 18 years participated (Mage = 13.36, SD = 1.83: 48.9% boys and 51.1% girls). At Time 2 (April 2016), there were 313 participants (Mage 12.81 years, SD = 1.59: 53.4% boys and 46.6% girls). We used the Cyberbullying Test (technological scale) and the Spanish version of the KIDSCREEN-52. RESULTS: Cybervictims and cyberbully-victims present worse scores in all dimensions of the KIDSCREEN-52 (p < .001), compared to cyberbystanders or uninvolved individuals. There are gender differences only in cyberaggression and cyberbystanding. There are significant inverse correlations between all the dimensions of the KIDSCREEN-52 and cybervictimization, with Bullying (r = - .603, p < .001), Mood (r = - .329, p < .001), and School environment (r = - .327, p < .001) being particularly relevant. There were statistically significant differences between T1 and T2 for cyberbystanding (lower scores at T2). CONCLUSION: Cybervictims and cyberbully-victims have worse quality of life in all the dimensions than uninvolved individuals, especially in Psychological well-being, School environment, and Bullying.

Proteinuria persistente en pacientes pediátricos, caracterización histopatológica y su influencia en la progresión de la enfermedad renal crónica / Persistent proteinuria in pediatric patients, histopathological characterization and its influence on chronic kidney disease progression / Proteinúria persistente em pacientes pediátricos, caracterização histopatológica e sua influência na progressão da doença renal crónica

Objetivo: describir los hallazgos histopatológicos y la progresión a enfermedad renal crónica de los pacientes sometidos a biopsia renal en un hospital de referencia de la ciudad de Medellín entre 2005 y 2014. Metodología: estudio descriptivo retrospectivo. Se revisaron historias clínicas de pacientes menores de 18 años con diagnóstico de proteinuria persistente, a quienes se les realizó biopsia renal durante el período 2005-2014 en el Hospital Pablo Tobón Uribe. Se analizaron variables sociodemográficas, clínicas, histológicas y de laboratorio. Resultados: se incluyeron 71 pacientes. La edad promedio del diagnóstico de proteinuria persistente fue 10.07 años. El 69.1% y 20.6% de los pacientes presentaron hematuria e hipertensión arterial respectivamente. La glomerulonefritis por IgA fue el hallazgo histológico más frecuente (21.13%), seguido de la nefropatía lúpica (18.31%). Del total de pacientes, 69.0% recibieron inhibidores de la enzima convertidora de angiotensina y el 15.9% presentaron deterioro de la función renal al cuarto año de seguimiento. Conclusiones: la prevalencia de glomerulopatías en niños con proteinuria persistente fue alta. Se sugiere la realización de la biopsia renal con el fin de detectar tempranamente glomerulopatías primarias o secundarias asociadas para así instaurar un tratamiento oportuno que controle o retarde el deterioro de la función renal.

Objective: To describe the histopathological findings and their progression of chronic kidney disease in pediatric patients who underwent kidney biopsy due to persistent proteinuria during 2005-2015 at a high-complexity hospital in Medellin, Colombia. Methods: A retrospective, cohort study was carried out; the medical records of children under 18 with diagnosis of persistent proteinuria were reviewed. Sociodemographic, clinical, and histopathological variables were analyzed. Results: A total of 71 patients were included. The mean age at the diagnosis of persistent proteinuria was 10.07 years old. 69.1% and 20.6% of the patients had hematuria and hypertension, respectively. Overall, the predominant pathological diagnosis in the current study was IgA nephropathy (21.13%) followed by lupus nephropathy (18.31%). 69.0% of the patients received angiotensin-converting enzyme inhibitors. At the last follow-up, 15.9% presented impaired renal function. Conclusion: In our cohort, the prevalence of glomerulopathies in children with persistent proteinuria was high. We recommended performing kidney biopsy in children with persistent proteinuria. This allows early detection of primary or secondary glomerulopathies to retard progression of renal damage.

Objetivo: descrever os descobrimentos histopatológicos e a progressão a doença renal crónica dos pacientes submetidos a biopsia renal num hospital de referência da cidade de Medellín entre 2005 e 2014. Metodologia: estudo descritivo retrospectivo. Se revisaram histórias clínicas de pacientes menores de 18 anos com diagnóstico de proteinuria persistente, a quem se lhes realizou biopsia renal durante o período 2005-2014 no Hospital Pablo Tobón Uribe. Se analisaram variáveis sócio-demográficas, clínicas, histológicas e de laboratório. Resultados: se incluíram 71 pacientes. A idade média do diagnóstico de proteinúria persistente foi de 10.07 anos. 69.1% e 20.6% dos pacientes apresentaram hematúria e hipertensão arterial respectivamente. A glomerulonefrite por IgA foi a descoberta histológico mais frequente (21.13%), seguido da nefropatia lúpico (18.31%). Do total de pacientes, 69.0% receberam inibidores da enzima convertedora de angiotensina e 15.9% apresentaram deterioro da função renal ao quarto ano de seguimento. Conclusões: a prevalência de glomerulopatias em crianças com proteinúria persistente foi alta. Se sugere a realização da biopsia renal com o fim de detectar precocemente glomerulopatias primárias ou secundárias associadas para assim instaurar um tratamento oportuno que controle ou retarde o deterioro da função renal.

Facial reanimation surgery in Möbius syndrome: Experience from 76 cases from a tertiary referral hospital in Latin America.

INTRODUCTION: Möbius syndrome is defined as a combined congenital bilateral facial and abducens nerve palsies. The main goal of treatment is to provide facial reanimation by means of a dynamic surgical procedure. The microneurovascular transfer of a free muscle transplant is the procedure of choice for facial animation in a child with facial paralysis. OBSERVATION: Between January 2008 and January 2017, 124 patients with the syndrome have been approached at our institution. Distribution according to Möbius Syndrome classification presents as follows: Complete Möbius syndrome (n=88), Incomplete Möbius syndrome (n=28), Möbius-Like syndrome (n=8). Seventy-nine female and 45 male patients. Sixty-one percent have undergone a microsurgical procedure (n=76), in all of them, a free gracilis flap transfer was performed. DISCUSSION: Our proposed treatment protocol for complete Möbius syndrome is determined by the available donor nerves. We prefer to use the masseteric nerve as first choice, however, if this nerve is not available, then our second choice is the spinal accesory nerve. For this purpose, all patients have an electromyography performed preoperatively. Overall, dynamic facial reanimation obtained through the microvascular transfer of the gracilis muscle have proved to improve notoriously oral comissure excursion and speech intelligibility. CONCLUSION: The free gracilis flap transfer is a reproducible procedure for patients with Möbius syndrome. It is of utmost importance to select the best motor nerve possible, based on an individualized preoperative clinical and electromyographic evaluation. To our best knowledge, this is the largest series of patients with Möbius syndrome globally, treated at a single-institution.

Omega-3 versus isoflavones in the control of vasomotor symptoms in postmenopausal women.

Determine the efficacy and tolerability of omega-3 fatty acids versus soybean isoflavones in reducing the vasomotor symptoms (VMSs) frequency in postmenopausal women. A randomized, prospective, two-arm study was performed in healthy postmenopausal women aged 45-65. The two arms were: two capsules/day of omega-3 (425 mg of omega-3/capsule) administered orally (n = 38) and two tablets/day of soybean isoflavones (54.4 mg of isoflavones/tablet) (n = 30), over 16 weeks. The mean baseline frequency of moderate and severe VMSs per week in the omega-3 group was 24.56 and 23.90, respectively, and 19.65 and 19.51 in the isoflavone group. After 4 months, the reduction in moderate and severe hot flashes with omega-3 was significant (p < .001), whereas in the case of isoflavones, there was a significant difference in severe (p = .02) hot flashes after 4 months, but not in moderate hot flashes (p = .077). Omega-3 did not demonstrate significant efficacy differences versus isoflavones over time. The use of omega-3 has a beneficial effect on hot flash reduction after 4 months of treatment. This is comparable to the benefits found with soybean isoflavones after 3-4 weeks and after 4 months in severe hot flash women, but higher than those found with soybean isoflavones in moderate symptom women.

Antimicrobial Resistance Genes in Pigeons from Public Parks in Costa Rica.

Antimicrobial resistance is known to be an emerging problem, but the extent of the issue remains incomplete. The aim of this study was to determine the presence or absence of nine resistance genes (blaTEM , catI, mecA, qnrS, sulI, sulII, tet(A), tet(Q), vanA) in the faeces of 141 pigeons from four urban parks in Alajuela, Guadalupe, Tres Ríos and San José in Costa Rica. The genes were identified by real-time PCR directly from enema samples. About 30% of the samples were positive for genes catI and sulI; between 13% and 17% were positive for qnrS, sulII, tet(A) and tet(Q); and 4% were positive for blaTEM . The mecA and vanA genes were not detected. The average of antimicrobial resistance genes detected per pigeon was 2. Eight different patterns of resistance were identified, without differences in the sampling areas, being the most common pattern 2 (sulII positive samples). During rainy season, the genes more frequently found were sulI and tet(A). In conclusion, the urban inhabiting pigeons tested are currently carrying antimicrobial resistance genes, potentially acting as reservoirs of resistant bacteria and vectors to humans. To the authors' knowledge, this is the first study carried out on direct detection of resistance genes in the digestive metagenomes of pigeons.

p53-independent ibrutinib responses in an Eµ-TCL1 mouse model demonstrates efficacy in high-risk CLL.

Deletion of the short-arm of chromosome 17 (17p-) is one of the most critical genetic alterations used in chronic lymphocytic leukemia (CLL) risk stratification. The tumor suppressor TP53 maps to this region, and its loss or mutation accelerates CLL progression, hampers response to chemotherapy and shortens survival. Although florescent in situ hybridization analyses for 17p deletions are routinely performed during clinical diagnoses, p53 mutational status is often unexamined. Given the limited clinical data that exists for frontline treatment of patients with CLL harboring TP53 mutations, there is a need to understand the biology of CLL with TP53 mutations and identify treatment strategies for this subset of patients. Herein, we used a CLL mouse model (Eµ-TCL1) harboring one of the most common TP53 hot-spot mutations observed in CLL (p53(R172H), corresponding to p53(R175H) in humans) to evaluate its impact on disease progression, survival, response to therapy and loss of the remaining wild-type Trp53 allele following ibrutinib treatment. We show that ibrutinib was effective in increasing survival, activating cellular programs outside the p53 pathway and did not place selective pressure on the remaining wild-type Trp53 allele. These data provide evidence that ibrutinib acts as an effective treatment for aggressive forms of CLL with TP53 mutations.

Genetic variation among 82 pharmacogenes: The PGRNseq data from the eMERGE network.

Genetic variation can affect drug response in multiple ways, although it remains unclear how rare genetic variants affect drug response. The electronic Medical Records and Genomics (eMERGE) Network, collaborating with the Pharmacogenomics Research Network, began eMERGE-PGx, a targeted sequencing study to assess genetic variation in 82 pharmacogenes critical for implementation of "precision medicine." The February 2015 eMERGE-PGx data release includes sequence-derived data from ∼5,000 clinical subjects. We present the variant frequency spectrum categorized by variant type, ancestry, and predicted function. We found 95.12% of genes have variants with a scaled Combined Annotation-Dependent Depletion score above 20, and 96.19% of all samples had one or more Clinical Pharmacogenetics Implementation Consortium Level A actionable variants. These data highlight the distribution and scope of genetic variation in relevant pharmacogenes, identifying challenges associated with implementing clinical sequencing for drug treatment at a broader level, underscoring the importance for multifaceted research in the execution of precision medicine.

Effects of seasonal ambient heat stress (spring vs. summer) on physiological and metabolic variables in hair sheep located in an arid region.

Twenty Dorper × Pelibuey primiparous ewes were used to evaluate effects of seasonal ambient heat stress (i.e., spring vs. summer) on physiological and metabolic responses under production conditions in an arid region. Ten ewes experiencing summer heat stress (i.e., temperature = 34.8 ± 4.6 °C; THI = 81.6 ± 3.2 units) and 10 under spring thermoneutral conditions (temperature = 24.2 ± 5.4 °C; THI = 68.0 ± 4.8 units) were corralled together to measure rectal temperature, respiratory frequency, and skin temperatures at 0600, 1200, 1800, and 2400 h on four occasions over 40 days. Blood metabolite and electrolyte concentrations were also measured at 0600 and 1800 hours. Data were analyzed with a completely randomized design using repeated measurements in time. Rectal and skin temperatures, as well as respiratory frequency, were higher (P < 0.01) in summer than spring at all measured days. Blood serum glucose, cholesterol, triglycerides, and chlorine concentrations were lower (P < 0.01) in summer than spring at 0800 and 1800 hours. In contrast, summer heat stress increased (P < 0.01) blood urea and potassium concentrations at 0800 and 1800 hours. Compared with spring thermoneutral conditions, summer heat stress affected the physiological and metabolic status of hair breed ewes in an arid region, which included blood metabolite and electrolyte adjustments to efficiently cope with summer heat stress.

Agua potable y saneamiento en la nueva ruralidad de América Latina / Drinking water and sanitation in the new rurality of Latin America

Los países de América Latina y El Caribe avanzan hacia una mayor urbanización, pero la población rural no desaparecerá. Se estima que, en 2030, algunos países tendrán una población rural superior al 30%. A su vez, el conjunto de cambios sociales, económicos y políticos están diseñando lo que se ha denominado "la nueva ruralidad".El acceso a agua y saneamiento es un derecho humano. Pese a los avances logrados en las dos últimas décadas, se mantienen las brechas de cobertura entre áreas rurales y urbanas y entre acceso a agua y a saneamiento. Sin embargo, se tienen experiencias exitosas validadas en programas con un amplio componente de participación comunitaria, tales como los de Ecuador, Bolivia, Honduras, Nicaragua y Perú; en varios casos, se cuenta con estrategias de intervención en las que las comunidades rurales implementan la contratación de servicios de los proveedores para acceder a la rehabilitación o construcción de sus sistemas de agua potable y saneamiento básico