Finishing lambs using an integral feed under a restricted-feeding program in an intensive production system in Northern Mexico

The objective of this study was to compare the productive performance of finishing lambs using an integral diet under a restricted-feeding program. Ten Dorper lambs were assigned to two homogenous groups according to live weight and age under a complete randomised block design. Group 1 was fed a traditional diet commonly used by the producer and group 2 was fed an integral feed restricted to 75% of dry matter requirement of lambs. The evaluated variables were: dry matter intake, initial and final live weight, daily weight gain, feed efficiency and body growth expressed in height, body length, thoracic diameter, cane length and cane width. A partial cost analysis was carried out to evaluate the economic viability. Lambs fed with the integral feed had better feed efficiency, higher dry matter intake, daily weight gain, height, body length and thoracic diameter when compared with the lambs fed the traditional diet. The use of an integral feed under a restricted-feeding program reduced the cost of finishing lambs by 2.46 dollars per head and finishing length by 120 days. Overall, providing an integral feed under a restricted-feeding program is a viable alternative for improving finishing lambs under intensive conditions in the Northern Mexico

Complicaciones y evaluación terapéutica de la meningoencefalitis bacteriana / Complications and therapeutic assessment of the bacterial meningoencephalitis

Se realizó un estudio descriptivo, longitudinal y prospectivo a los pacientes con el diagnóstico de meningoencefalitis bacteriana en el Hospital General Docente Abel Santamaría de Pinar del Río, durante 2 años. Se pesquisaron las complicaciones, los exámenes paraclínicos, el tratamiento y respuesta al mismo. Se aplicaron las pruebas para la comparación de proporciones de un mismo grupo, test para la comparación de proporciones de grupos independientes y técnicas estadísticas descriptivas para la estimación porcentual de parámetros. Se encontraron el mayor número de casos en el grupo de edades entre 30 y 59 años, seguido del grupo entre 60 y 79 años. Las convulsiones y el edema cerebral fueron las complicaciones neurológicas más frecuentes mientras que la neumonía fue la complicación sistémica más frecuente. La tinción de Gram del líquido cefalorraquídeo identificó diplococos Gram positivos mayoritariamente y su cultivo constató que el Streptococcus pneumoniae fue el germen más periódico. Las cefalosporinas de tercera generación siguen siendo los medicamentos de elección para iniciar tratamiento empírico de las meningoencefalitis bacteriana extrahospitalarias.Palabras Clave: MENINGOENCEFALITIS/complicaciones, EDEMA CEREBRAL/líquido cefalorraquídeo, NEUMONÍA/diagnóstico.ABSTRACTA descriptive, longitudinal and prospective study was conducted with patients suffering from bacterial meningoencephalitis at "Abel Santamaria Cuadrado" University Hospital, Pinar del Rio during two years. Complications, paraclinical examinations, treatment and response were screened and tests were applied to assess the comparison of proportions to the same group, independent groups and descriptive statistical techniques to estimate the percentage of the parameters. The majority of the cases were found in the age-bracket between 30-59 years old, followed by the group of ages from 60 to 79. The seizures and brain edema were the most usual neurological complications while pneumonia was the most frequent systemic complication. Finding in the stain of the spinal fluid a Gram-positive diplococcus and in the culture a Streptococcus pneumoniae was verified as the most periodic germen. Cephalosporin of third generation is still the elective medications to start the empiric treatment of the extrahospital bacterial meningoencephalitis.Key words: bacterial meningoencephalitis, brain edema, pneumoni

The role of the muscarinic system in regulating estradiol secretion varies during the estrous cycle: the hemiovariectomized rat model

There is evidence that one gonad has functional predominance. The present study analyzed the acute effects of unilateral ovariectomy (ULO) and blocking the cholinergic system, by injecting atropine sulfate (ATR), on estradiol (E(2)) serum concentrations during the estrous cycle. The results indicate that ULO effects on E(2 )concentrations are asymmetric, vary during the estrous cycle, and partially depend on the cholinergic innervation. Perforation of the left peritoneum resulted in lower E(2 )serum concentrations in the three stages of the estrous cycle. At proestrus, unilateral or bilateral perforation of the peritoneum resulted in lower E(2 )serum concentrations. ULO of the right ovary (left ovary in situ) resulted in significantly higher E(2 )concentrations than animals with ULO of the left ovary (right ovary in situ). ATR treatment to ULO rats on D1 resulted in a significant drop of E(2 )serum concentrations. ULO rats treated with ATR on D2 or P, resulted in an asymmetrical E(2) secretion response; when the right ovary remained in situ an increase in E(2) was observed, and a decrease when the left ovary remained in situ. The results obtained in the present study suggest that each ovary's ability to compensate the secretion of E(2 )from the missing ovary is different and varies during the estrous cycle. The results also suggest that the cholinergic system participates in regulating ovarian E(2 )secretion. Such participation varies according to the ovary remaining in situ and the stage of the estrous cycle of the animal. The results agree with previously stated hypothesis of a neural pathway arising from the peritoneum that participates in regulating E(2 )secretion, and also supports the idea of cross-talk between the ovaries, via a neural communication, that modulates E(2 )secretion

Metformin induces a fasting- and antifolate-mimicking modification of systemic host metabolism in breast cancer patients

Certain dietary interventions might improve the therapeutic index of cancer treatments. An alternative to the "drug plus diet" approach is the pharmacological reproduction of the metabolic traits of such diets. Here we explored the impact of adding metformin to an established therapeutic regimen on the systemic host metabolism of cancer patients. A panel of 11 serum metabolites including markers of mitochondria! function and intermediates/products of folate-dependent one-carbon metabolism were measured in paired baseline and post-treatment sera obtained from HER2-positive breast cancer patients randomized to receive either metformin combined with neoadjuvant chemotherapy and trastuzumab or an equivalent regimen without metformin. Metabolite profiles revealed a significant increase of the ketone body beta-hydroxybutyrate and of the TCA intermediate alpha-ketoglutarate in the metformin-containing arm. A significant relationship was found between the follow-up levels of homocysteine and the ability of treatment arms to achieve a pathological complete response (pCR). In the metformin-containing arm, patients with significant elevations of homocysteine tended to have a higher probability of pCR. The addition of metformin to an established anticancer therapeutic regimen causes a fasting-mimicking modification of systemic host metabolism. Circulating homocysteine could be explored as a clinical pharmacodynamic biomarker linking the antifolate-like activity of metformin and biological tumor response

Neoadjuvant Metformin Added to Systemic Therapy Decreases the Proliferative Capacity of Residual Breast Cancer

The proliferative capacity of residual breast cancer (BC) disease indicates the existence of partial treatment resistance and higher probability of tumor recurrence. We explored the therapeutic potential of adding neoadjuvant metformin as an innovative strategy to decrease the proliferative potential of residual BC cells in patients failing to achieve pathological complete response (pCR) after pre-operative therapy. We performed a prospective analysis involving the intention-to-treat population of the (Metformin and Trastuzumab in Neoadjuvancy) METTEN study, a randomized multicenter phase II trial of women with primary, non-metastatic (human epidermal growth factor receptor 2) HER2-positive BC evaluating the efficacy, tolerability, and safety of oral metformin (850 mg twice-daily) for 24 weeks combined with anthracycline/taxane-based chemotherapy and trastuzumab (arm A) or equivalent regimen without metformin (arm B), before surgery. We centrally evaluated the proliferation marker Ki67 on sequential core biopsies using visual assessment (VA) and an (Food and Drug Administration) FDA-cleared automated digital image analysis (ADIA) algorithm. ADIA-based pre-operative values of high Ki67 (>= 20%), but not those from VA, significantly predicted the occurrence of pCR in both arms irrespective of the hormone receptor status (p = 0.024 and 0.120, respectively). Changes in Ki67 in residual tumors of non-pCR patients were significantly higher in the metformin-containing arm (p = 0.025), with half of all patients exhibiting high Ki67 at baseline moving into the low-Ki67 (<20%) category after neoadjuvant treatment. By contrast, no statistically significant changes in Ki67 occurred in residual tumors of the control treatment arm (p = 0.293). There is an urgent need for innovative therapeutic strategies aiming to provide the protective effects of decreasing Ki67 after neoadjuvant treatment even if pCR is not achieved. Metformin would be evaluated as a safe candidate to decrease the aggressiveness of residual disease after neoadjuvant (pre-operative) systemic therapy of BC patients

The C Allele of ATM rs11212617 Associates With Higher Pathological Complete Remission Rate in Breast Cancer Patients Treated With Neoadjuvant Metformin

Background: The minor allele (C) of the single-nucleotide polymorphism (SNP) rs11212617, located near the ataxia telangiectasia mutated (ATM) gene, has been associated with an increased likelihood of treatment success with metformin in type 2 diabetes. We herein investigated whether the same SNP would predict clinical response to neoadjuvant metformin in women with early breast cancer (BC). Methods: DNA was collected from 79 patients included in the intention-to-treat population of the METTEN study, a phase 2 clinical trial of HER2-positive BC patients randomized to receive either metformin combined with anthracycline/taxane-based chemotherapy and trastuzumab or equivalent regimen without metformin, before surgery. SNP rs11212617 genotyping was assessed using allelic discrimination by quantitative polymerase chain reaction. Results: Logistic regression analyses revealed a significant relationship between the rs11212617 genotype and the ability of treatment arms to achieve a pathological complete response (pCR) in patients (odds ratio [OR](genotypexarm) = 10.33, 95% confidence interval [CI]: 1.29-82.89, p = 0.028). In the metformin-containing arm, patients bearing the rs11212617 C allele had a significantly higher probability of pCR (ORA/C,C/C = 7.94, 95% CI: 1.60-39.42, p = 0.011). Conversely, no association was found between rs11212617 and clinical response in the reference arm (ORA/C,C/C = 0.77, 95% CI: 0.20-2.92, p = 0.700). After controlling for tumor size and hormone receptor status, the rs11212617 C allele remained a significant predictor of pCR solely in the metformin-containing arm. Conclusions: If reproducible, the rs11212617 C allele might warrant consideration as a predictive clinical biomarker to inform the personalized use of metformin in BC patients

Cuban scientific production in Medicine and Public Health: Scopus 2003-2011

El objetivo de este trabajo fue analizar la evolución del volumen y la visibilidad de la producción científica cubana en Salud Pública y en Medicina para determinar si siguen los mismos patrones de comunicación, y recomendar buenas prácticas de publicación. Se aplicaron indicadores bibliométricos de volumen, visibilidad y colaboración extraídos del portal SCImago Institutions Rankings a partir de datos de Scopus, para el área temática Medicine y la categoría Public Health, Environmental and Occupational Health, período 2003-2011. Cuba tiene una posición relativamente alta en los rankings de volumen de producción científica tanto en Medicina como en Salud Pública en los contextos internacionales y regionales, mientras que en impacto está entre los últimos países. La tendencia de la producción es al crecimiento, aunque en Salud Pública es más acelerado. El liderazgo es alto, pero la colaboración internacional está por debajo de lo esperado. La publicación en revistas de alto impacto (primer cuartil) y los artículos en el 10% más citado (excelencia) son escasos. Se concluye que el volumen y el impacto de la publicación no están acorde al potencial científico de salud cubana. Se recomienda incrementar la colaboración científica, la publicación de artículos en revistas de alto impacto, la preparación de los recursos humanos y seguir las recomendaciones internacionales sobre las buenas prácticas de edición y publicación científica.The aim of this study was to analyze the evolution of the quantity and visibility of Cuban scientific production in Public Health and Medicine to determine if they follow the same patterns of scientific communication and the recommended best practices for publication. Bibliometric indicators of quantity, visibility and cooperation were extracted from the SCImago Institutions Rankings website, which is based on Scopus data, in the field of Medicine and category of Public Health, Environmental and Occupational Health from 2003 to 2011.Cubahas a relatively high position in the rankings of scientific production in both Medicine and Public Health within the international and regional contexts, but its impact is ranked among the last countries. The production trend of both fields has increased, but public health is increasing faster. Leadership is high, but international collaboration is below expectations. Publication in high impact journals (first quartile) and articles in the set 10% most cited documents (excellence) are scarce. Thus, it may be concluded that the volume and impact of publication are not in accordance with the scientific potential of Cuban health. We recommend increasing scientific cooperation, publishing articles in high impact journals, training human resources and following the international recommendations for good editorial and scientific publication practices

A Fungal Versatile GH10 Endoxylanase and Its Glycosynthase Variant: Synthesis of Xylooligosaccharides and Glycosides of Bioactive Phenolic Compounds

The study of endoxylanases as catalysts to valorize hemicellulosic residues and to obtain glycosides with improved properties is a topic of great industrial interest. In this work, a GH10 β-1,4-endoxylanase (XynSOS), from the ascomycetous fungus Talaromyces amestolkiae, has been het- erologously produced in Pichia pastoris, purified, and characterized. rXynSOS is a highly glycosylated monomeric enzyme of 53 kDa that contains a functional CBM1 domain and shows its optimal activity on azurine cross-linked (AZCL)–beechwood xylan at 70 ◦C and pH 5. Substrate specificity and kinetic studies confirmed its versatility and high affinity for beechwood xylan and wheat arabi- noxylan. Moreover, rXynSOS was capable of transglycosylating phenolic compounds, although with low efficiencies. For expanding its synthetic capacity, a glycosynthase variant of rXynSOS was developed by directed mutagenesis, replacing its nucleophile catalytic residue E236 by a glycine (rXynSOS-E236G). This novel glycosynthase was able to synthesize β-1,4-xylooligosaccharides (XOS) of different lengths (four, six, eight, and ten xylose units), which are known to be emerging prebiotics. rXynSOS-E236G was also much more active than the native enzyme in the glycosylation of a broad range of phenolic compounds with antioxidant properties. The interesting capabilities of rXynSOS and its glycosynthase variant make them promising tools for biotechnological application.This research was funded by the MICIU/AEI/FEDER [RTI2018-093683-B-I00, RTI2018- 094751-B-C22, PID2019-107476GB-I00], Comunidad de Madrid [RETOPROSOST-2-CM P2018/EMT- 4459], and CIBERES (an initiative from the Spanish Institute of Health Carlos IPeer reviewe

A phase 2 trial of neoadjuvant metformin in combination with trastuzumab and chemotherapy in women with early HER2-positive breast cancer: the METTEN study

The METTEN study assessed the efficacy, tolerability, and safety of adding metformin to neoadjuvant chemotherapy plus trastuzumab in early HER2-positive breast cancer (BC). Women with primary, non-metastatic HER2-positive BC were randomized (1:1) to receive metformin (850 mg twice-daily) for 24 weeks concurrently with 12 cycles of weekly paclitaxel plus trastuzumab, followed by four cycles of 3-weekly FE75C plus trastuzumab (arm A), or equivalent regimen without metformin (arm B), followed by surgery. Primary endpoint was the rate of pathological complete response (pCR) in the per-protocol efficacy population. pCR rate was numerically higher in the metformin-containing arm A (19 of 29 patients [65.5%, 95% CI: 47.3-80.1]) than in arm B (17 of 29 patients [58.6%, 95% CI: 40.7-74.5]; OR 1.34 [95% CI: 0.46-3.89], P = 0.589). The rate of breast-conserving surgery was 79.3% and 58.6% in arm A and B (P = 0.089), respectively. Blood metformin concentrations (6.2 μmol/L, 95% CI: 3.6-8.8) were within the therapeutic range. Seventy-six percent of patients completed the metformin-containing regimen; 13% of patients in arm A dropped out because of metformin-related gastrointestinal symptoms. The most common adverse events (AEs) of grade ≥3 were neutropenia in both arms and diarrhea in arm A. None of the serious AEs was deemed to be metformin-related. Addition of anti-diabetic doses of metformin to a complex neoadjuvant regimen was well tolerated and safe. Because the study was underpowered relative to its primary endpoint, the efficacy data should be interpreted with caution

Impact of FLT3–ITD Mutation Status and Its Ratio in a Cohort of 2901 Patients Undergoing Upfront Intensive Chemotherapy: A PETHEMA Registry Study

FLT3–ITD results in a poor prognosis in terms of overall survival (OS) and relapse-free survival (RFS) in acute myeloid leukemia (AML). However, the prognostic usefulness of the allelic ratio (AR) to select post-remission therapy remains controversial. Our study focuses on the prognostic impact of FLT3–ITD and its ratio in a series of 2901 adult patients treated intensively in the pre-FLT3 inhibitor era and reported in the PETHEMA registry. A total of 579 of these patients (20%) harbored FLT3–ITD mutations. In multivariate analyses, patients with an FLT3–ITD allele ratio (AR) of >0.5 showed a lower complete remission (CR rate) and OS (HR 1.47, p = 0.009), while AR > 0.8 was associated with poorer RFS (HR 2.1; p 0.5). Using the maximally selected log-rank statistics, we established an optimal cutoff of FLT3–ITD AR of 0.44 for OS, and 0.8 for RFS. We analyzed the OS and RFS according to FLT3–ITD status in all patients, and we found that the group of FLT3–ITD-positive patients with AR 0.44, allo-HSCT was superior to auto-HSCT in terms of OS and RFS. This study provides more evidence for a better characterization of patients with AML harboring FLT3–ITD mutations.Depto. de MedicinaFac. de MedicinaTRUEInstituto de Salud Carlos IIIFundación CRIS Contra el CáncerInstituto de Investigación Hospital 12 de OctubreUnión Europeapu