Butyrate supplementation in the liquid diet of dairy calves leads to a rapid recovery from diarrhea and reduces its occurrence and relapses in the preweaning period.

The present study aimed to evaluate the effect of continuous butyrate administration in dairy calves' liquid diet considering diarrhea, metabolic profile, gastrointestinal development, and corporal growth. Immediately after birth, calves were randomly allocated into 2 groups of 62 calves (50 females and 12 males), with access to water and a solid feed ad libitum. The butyrate group (BG) received 4 g/d of sodium butyrate (Admix Easy, Adisseo) diluted in the whole milk, and the control group (CG) received whole milk with no supplementation. Sodium butyrate was administered from d 1 of life until the weaning at 90 d. Feces consistency was assessed daily for the first 30 d of life and characterized by scores from 0 to 4 (0 and 1 for normal, and 2, 3, and 4 for abnormal feces). Diarrhea was diagnosed when the animals had abnormal feces and fever. Morbidity, recurrence, mortality, and lethality data were recorded and compared between the groups. Average daily gain (ADG) and corporal growth (body weight, thoracic perimeter, height at the withers, and croup width) were evaluated weekly, from the first day to d 30, and later at 45, 60, and 90 d of life. Blood samples were taken weekly for up to 30 d to determine the circulating levels of total calcium, phosphorus, chloride, bicarbonate, glucose, ß-hydroxybutyrate, and nonesterified fatty acids. The males were euthanized at 15 (n = 6 per group) and 30 d (n = 6 per group) for morphometric, histological, and gene expression analysis of the gastrointestinal tract. The results showed that the BG had a lower rate of morbidity (BG = 30% vs. CG = 50%) and recurrence (BG = 26.7% vs. CG = 60%) of diarrhea than the CG. In addition, the BG had abnormal feces for a shorter period (BG = 4.64 ± 0.47 d vs. CG = 8.6 ± 0.65 d). The ADG tended to be higher in BG than CG up to 30 and 60 d. Metabolic evaluations showed the lowest levels of glucose and highest levels of nonesterified fatty acids in BG. On d 30 of life, rumen papillae length, papilla area, duodenum villus length, and crypt depth were higher in BG than in CG. The duodenal gene expression at 30 d showed that animals with diarrhea episodes that did not receive butyrate had the highest levels of transcripts for the LCT and GLP2 genes. In addition, in different ways, both butyrate and neonatal diarrhea affected the gene expression of IGF1, SLC5A1, and AQP3. These results allow us to conclude that continuous supplementation with sodium butyrate improves gastrointestinal development, reduces the occurrence of diarrhea, and makes clinical conditions milder with faster recovery, favoring a higher ADG in the first 30 and 60 d of life. Based on these results, we conclude that sodium butyrate can be indicated for liquid diet supplementation to accelerate gastrointestinal tract development and prevent severe cases of neonatal diarrhea, tending to improve average daily gain until weaning.

The posterior insular cortex is necessary for the consolidation of tone fear conditioning.

The insular cortex (IC) is notably implicated in emotional and cognitive processing; however, little is known regarding to what extent its two main subregions play functionally distinct roles on memory consolidation of conditioned fear tasks. Here we verified the effects of temporary functional inactivation of the anterior (aIC) and posterior IC (pIC) on contextual and tone fear memory. Rats received post-training bilateral infusions of the GABAA receptor agonist muscimol into either the aIC or pIC and were tested 48 and 72 h after the delay tone fear conditioning session to assess the background contextual (CFC) and tone (TFC) fear conditioning, respectively. Inactivation of the aIC during memory consolidation did not affect fear memory for CFC or TFC. On the other hand, post-training inactivation of the pIC impaired TFC but not CFC. Our findings indicate that the pIC is a necessary part of the neural circuitry related to the consolidation of cued-fear memories.

Identification of bacteriophages in the vagina of pregnant women: a descriptive study.

OBJECTIVE: To determine the presence and identity of extracellular bacteriophage (phage) families, genera and species in the vagina of pregnant women. DESIGN: Descriptive, observational cohort study. SETTING: São Paulo, Brazil. POPULATION: Pregnant women at 21-24 weeks' gestation. METHODS: Vaginal samples from 107 women whose vaginal microbiome and pregnancy outcomes were previously determined were analysed for phages by metagenomic sequencing. MAIN OUTCOME MEASURES: Identification of phage families, genera and species. RESULTS: Phages were detected in 96 (89.7%) of the samples. Six different phage families were identified: Siphoviridae in 69.2%, Myoviridae in 49.5%, Microviridae in 37.4%, Podoviridae in 20.6%, Herelleviridae in 10.3% and Inviridae in 1.9% of the women. Four different phage families were present in 14 women (13.1%), three families in 20 women (18.7%), two families in 31 women (29.1%) and one family in 31 women (29.1%). The most common phage species detected were Bacillus phages in 48 (43.6%), Escherichia phages in 45 (40.9%), Staphylococcus phages in 40 (36.4%), Gokushovirus in 33 (30.0%) and Lactobacillus phages in 29 (26.4%) women. In a preliminary exploratory analysis, there were no associations between a particular phage family, the number of phage families present in the vagina or any particular phage species and either gestational age at delivery or the bacterial community state type present in the vagina. CONCLUSIONS: Multiple phages are present in the vagina of most mid-trimester pregnant women. TWEETABLE ABSTRACT: Bacteriophages are present in the vagina of most pregnant women.

MASCC/ISOO clinical practice guidelines for the management of mucositis: sub-analysis of current interventions for the management of oral mucositis in pediatric cancer patients.

OBJECTIVE: The aim of this sub-analysis was to highlight the MASCC/ISOO clinical practice guidelines for the management of oral mucositis (OM) in pediatric patients and to present unique considerations in this patient population. METHODS: This sub-analysis of the pediatric patient population is based on the systematic review conducted by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISSO) published in 2019/2020. Studies were scored and assigned a level of evidence based on previously published criteria. Data regarding adverse effects and compliance was collected from the original publications. RESULTS: A total of 45 papers were included and assessed in this sub-analysis, including 21 randomized controlled trials (RCTs). Chewing gum was demonstrated to be not effective in preventing OM in pediatric cancer patients in 2 RCTs. The efficacy of all other interventions could not be determined based on the available literature. CONCLUSION: There is limited or conflicting evidence about interventions for the management of OM in pediatric cancer patients, except for chewing gum which was ineffective for prevention. Therefore, currently, data from adult studies may need to be extrapolated for the management of pediatric patients. Honey and photobiomodulation therapy in this patient population had encouraging potential. Implementation of a basic oral care protocol is advised amid lack of high level of evidence studies.

Oral shedding of CMV and HSV-1 in hematopoietic stem cell transplantation patients.

OBJECTIVES: To evaluate the oral shedding of herpesviruses in patients undergoing hematopoietic stem cell transplantation (HSCT) and correlate it with oral mucositis (OM). METHODS: Saliva samples were collected before the HSCT and on day D + 8. Multiplex Polymerse Chain Reaction (PCR) was performed to detect herpes simplex virus (HSV)-1 and HSV-2, Epstein-Barr virus (EBV), Cytomegalovirus (CMV), Variella-zoster virus (VZV), and human herpesvirus (HHV)-6, HHV-7, and HHV-8. OM was assessed according to WHO criteria. RESULTS: Thirty one patients were enrolled, in which 20 of 31 (64.5%) were males; median age was 50 (21-70) years; 16 of 31 (51.6%) underwent allo-HSCT; and 15 of 31 (48.4%) underwent auto-HSCT. On D + 8, OM grades III and IV were observed in 8 of 31 (25.8%) patients. In the first salivary collection, EBV was found in 24 of 31 (77.4%), followed by HHV-6 (7/31, 22.6%) and HHV-7 (8/31 25.8%). In the second collection, EBV was found in 24 of 27(89%), followed by HSV-1 (8/27, 30%) and CMV, HHV-6, and HHV-7 (5/27, 18.5%, each one). On D + 8, OM grades II and IV were associated with the presence of HSV-1. HSV-1 was also associated with worsening degrees of OM on D + 15. CONCLUSION: The presence of HSV-1 and CMV in oral samples was more frequent on day D + 8 after HSCT. HSV-1 detection was associated with severity and worsening of OM. HSV-1 and CMV seem to be associated with oral dysbiosis due to HSCT.

Maternal supplementation with cobalt sources, folic acid, and rumen-protected methionine and its effects on molecular and functional correlates of the immune system in neonatal Holstein calves.

Calves born to multiparous Holstein cows fed during the last 30 d of pregnancy 2 different cobalt sources [cobalt glucoheptonate (CoPro) or cobalt pectin (CoPectin)], folic acid (FOA), and rumen-protected methionine (RPM) were used to study neonatal immune responses after ex vivo lipopolysaccharide (LPS) challenge. Groups were (n = 12 calves/group) CoPro, FOA+CoPro, FOA+CoPectin, and FOA+CoPectin+RPM. Calves were weighed at birth and blood collected at birth (before colostrum), 21 d of age, and 42 d of age (at weaning). Growth performance was recorded once a week during the first 6 wk of age. Energy metabolism, inflammation, and antioxidant status were assessed at birth through various plasma biomarkers. Whole blood was challenged with 3 µg/mL of LPS or used for phagocytosis and oxidative burst assays. Target genes evaluated by real-time quantitative PCR in whole blood samples were associated with immune response, antioxidant function, and 1-carbon metabolism. The response in mRNA abundance in LPS challenged versus nonchallenged samples was assessed via Δ = LPS challenged - LPS nonchallenged samples. Phagocytosis capacity and oxidative burst activity were measured in neutrophils and monocytes, with data reported as ratio (percentage) of CD14 to CH138A-positive cells. Data including all time points were subjected to ANOVA using PROC MIXED in SAS 9.4 (SAS Institute Inc.), with Treatment, Sex, Age, and Treatment × Age as fixed effects. A 1-way ANOVA was used to determine differences at birth, with Treatment and Sex as fixed effects. Calf birth body weight and other growth parameters did not differ between groups. At birth, plasma haptoglobin concentration was lower in FOA+CoPro compared with CoPro calves. We detected no effect for other plasma biomarkers or immune function due to maternal treatments at birth. Compared with CoPro, in response to LPS challenge, whole blood from FOA+CoPectin and FOA+CoPectin+RPM calves had greater mRNA abundance of intercellular adhesion molecule 1 (ICAM1). No effect for other genes was detectable. Regardless of maternal treatments, sex-specific responses were observed due to greater plasma concentrations of haptoglobin, paraoxonase, total reactive oxygen metabolites, nitrite, and ß-carotene in female versus male calves at birth. In contrast, whole blood from male calves had greater mRNA abundance of IRAK1, CADM1, and ITGAM in response to LPS challenge at birth. The longitudinal analysis of d 0, 21, and 42 data revealed greater bactericidal permeability-increasing protein (BPI) mRNA abundance in whole blood from FOA+CoPectin versus FOA+CoPro calves, coupled with greater abundance in FOA+CoPro compared with CoPro calves. Regardless of maternal treatments, most genes related to cytokines and cytokine receptors (IL1B, IL10, TNF, IRAK1, CXCR1), toll-like receptor pathway (TLR4, NFKB1), adhesion and migration (ICAM1, ITGAM), antimicrobial function (MPO), and antioxidant function (GPX1) were downregulated over time. Phagocytosis capacity and oxidative burst activity in both neutrophils and monocytes did not differ due to maternal treatment. Regardless of maternal treatments, we observed an increase in the percentage of neutrophils capable of phagocytosis and oxidative burst activity over time. Overall, these preliminary assessments suggested that maternal supplementation with FOA and Co combined with RPM had effects on a few plasma biomarkers of inflammation at birth and molecular responses associated with inflammatory mechanisms during the neonatal period.

Maternal body condition influences neonatal calf whole-blood innate immune molecular responses to ex vivo lipopolysaccharide challenge.

Managing body condition in dairy cows during the close-up period could alter the availability of nutrients to the fetus during the final growth stages in utero. We investigated how maternal body condition score (BCS) in late pregnancy affected calf whole-blood mRNA abundance and IL-1ß concentrations after ex vivo lipopolysaccharide (LPS) challenge. Thirty-eight multiparous Holstein cows and their calves from a larger cohort were retrospectively grouped by prepartal BCS as normal BCS (≤3.25; n = 22; NormBCS) and high BCS (≥3.75; n = 16; HighBCS). Calf blood samples collected at birth (before receiving colostrum, d 0) and at ages 21 and 42 d (at weaning) were used for ex vivo whole-blood challenge with 3 µg/mL of LPS before mRNA isolation. Target genes evaluated by real-time quantitative PCR were associated with immune response, antioxidant function, and 1-carbon metabolism. Plasma IL-1ß concentrations were also measured. Responses in plasma IL-1ß and mRNA abundance were compared between LPS-challenged and nonchallenged samples. Statistical analyses were performed at all time points using a MIXED model in SAS 9.4. Neither birth body weight (NormBCS = 43.8 ± 1.01 kg; HighBCS = 43.9 ± 1.2 kg) nor colostrum IgG concentration (NormBCS = 70 ± 5.4 mg/mL; HighBCS = 62 ± 6.5 mg/mL) differed between groups. At birth, whole blood from calves born to HighBCS cows had greater mRNA abundance of IL1B, NFKB1, and GSR and lower GPX1 and CBS abundance after LPS challenge. The longitudinal analysis of d 0, 21, and 42 data revealed a BCS × age effect for SOD2 and NOS2 due to lower mRNA abundance at 42 d in the HighBCS calves. Regardless of maternal BCS, mRNA abundance decreased over time for genes encoding cytokines (IL1B, IL6, IL10, TNF), cytokine receptors (IRAK1, CXCR1), toll-like receptor pathway (TLR4, NFKB1), adhesion and migration (CADM1, ICAM1, ITGAM), and antimicrobial function (MPO). Concentration of IL-1ß after LPS challenge was also markedly lower at 21 d regardless of maternal BCS. Overall, results suggested that maternal BCS in late prepartum influences the calf immune system response to an inflammation challenge after birth. Although few genes among those studied were altered due to maternal BCS, the fact that genes related to oxidative stress and 1-carbon metabolism responded to LPS challenge in HighBCS calves underscores the potential role of methyl donors (e.g., methionine, choline, and folic acid) in the early-life innate immune response.

A systematic review of the indirect and social costs studies in fragility fractures.

Fragility fractures (FF) are the main clinical consequence of osteoporosis. FF lead to a loss in quality of life (QL), increased dependency and higher costs due to loss of productivity. Despite this, very few studies have been performed about the indirect or social costs of FF. The objective of this review was to systematically synthesize published evidence regarding indirect costs of FF. We conducted a systematic literature review of empirical studies published as peer review papers between 1998 and 2019. A total of 295 papers were found about costs and osteoporosis. After an iterative process, only 16 papers fit the criteria of selection. Despite the important consequences for QL, only seven studies have included research of the issue and only one about dependency. Treatments are cost-effective, but adherence is low. Multiple fractures, older age and low socioeconomic profile imply higher costs. Most studies are performed using the human capital methodology. The main two variables are loss of productivity and absenteeism. Most of the people included in the samples are out of the active population. Those studies that include a follow-up period vary in a range between 3 months and 2 years. Depending on sample and methodology, the indirect costs (IC) are between 2 and 50%. The direct costs associated with FF generally far outweigh the IC. There is a lack of studies about the effects of treatments and adherence and about the dependency system. The changing role of women in coming generations will increase indirect costs.

Systematic review of oral cryotherapy for the management of oral mucositis in cancer patients and clinical practice guidelines.

PURPOSE: To update the 2013 Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology (MASCC/ISOO) clinical practice guidelines on oral cryotherapy for the management of oral mucositis (OM) caused by cancer therapies. METHODS: A systematic review was conducted by the Mucositis Study Group of MASCC/ISOO. The evidence for each intervention for specific cancer treatment modalities was assigned a level of evidence (LoE). The findings were added to the database used to develop the 2013 MASCC/ISOO clinical practice guidelines. Based on the LoE, the guidelines were set as: recommendation, suggestion, or no guideline possible. RESULTS: A total of 114 papers were identified: 44 from PubMed and 70 from Web of Science. After abstract triage and merging with the 2013 database, 36 papers were reviewed. The LoE for prevention of OM with oral cryotherapy in patients undergoing autologous hematopoietic stem cell transplant using high-dose melphalan conditioning protocols was upgraded, and the guideline changed to recommendation. Additionally, the recommendation for prevention of OM with oral cryotherapy in patients receiving bolus 5-fluorouracil for the treatment of solid tumors was confirmed. No guidelines were possible for other clinical settings. CONCLUSIONS: The evidence supports recommendations for the use of oral cryotherapy for the prevention of OM for either (i) patients undergoing autologous hematopoietic stem cell transplant with high-dose melphalan conditioning protocols or (ii) patients receiving bolus 5-fluorouracil chemotherapy.

Potential paths for the introduction of risk analysis to improve the veterinary epidemiology curriculum in Ukraine.

The main purpose of veterinary education institutions is to prepare qualified, well-trained and knowledgeable professionals ready to serve local and global communities. Veterinary programmes vary within and among countries, creating a disparity in competencies. In less-developed economies, adhering to the World Organisation for Animal Health (OIE) â€ËœDay 1 competencies' and following its â€ËœGuidelines for a Model Core Veterinary Curriculum' may decrease this discrepancy. The authors offer a comparison of Ukraine's veterinary epidemiology curriculum with the OIE suggested â€ËœCore Veterinary Curriculum', particularly for infectious disease pathology in which epidemiology is taught, and propose different paths to structure advanced educational programmes in epidemiology. This course is relevant for the development of international animal trade and expansion of markets for animal products in Ukraine.

Le principal objectif des établissements d'enseignement vétérinaire consiste à préparer des professionnels qualifiés, bien formés et compétents prêts à se mettre au service de leur communauté locale et, plus largement, de la communauté mondiale. Les programmes d'enseignement de la médecine vétérinaire varient d'un pays à l'autre et parfois même à l'échelle nationale, aboutissant ainsi à des compétences disparates. Dans les pays en développement, l'adhésion aux recommandations de l'Organisation mondiale de la santé animale (OIE) sur les compétences minimales attendues des jeunes diplômés en médecine vétérinaire (compétences dites « au premier jour ¼) et aux lignes directrices de l'OIE relatives au Cursus de formation initiale vétérinaire permet de réduire ces disparités. Les auteurs procèdent à une comparaison entre le cursus d'épidémiologie vétérinaire en Ukraine et le cursus de formation initiale vétérinaire recommandé par l'OIE, en particulier en ce qui concerne les cours de pathologie des maladies infectieuses qui intègrent une composante épidémiologique ; ils proposent ensuite différentes voies permettant de structurer des programmes d'enseignement de haut niveau en épidémiologie. Ces formations sont nécessaires pour soutenir les échanges internationaux d'animaux et améliorer l'accès aux marchés des produits d'origine animale ukrainiens. L'épidémiologie est une discipline essentielle pour le Secteur de l'évaluation des risques, récemment créés au sein des Services nationaux ukrainiens chargés de la sécurité sanitaire des aliments et la protection des consommateurs. La formation professionnelle est d'une importance cruciale et les vétérinaires diplômés issus des institutions ukrainiennes seront dotés des compétences de base essentielles pour commencer à travailler à l'appui des échanges internationaux d'animaux et de produits d'origine animale et rejoindre la fonction publique. Les objectifs à long terme visent à améliorer les programmes d'enseignement vétérinaire en Ukraine, en réformant l'enseignement de l'épidémiologie, et à concevoir et diffuser un modèle d'évaluation du contenu des cours d'épidémiologie dans les écoles vétérinaires dans l'ensemble du pays.

Los establecimientos de enseñanza veterinaria tienen por principal cometido preparar a profesionales cualificados, bien formados e informados y prestos para servir a la población local y mundial. Dado que los programas de enseñanza veterinaria varían entre países y dentro de ellos, también difieren las competencias adquiridas. En economías poco desarrolladas, el hecho de guiarse por las «competencias mínimas¼ del recién titulado, según las define la Organización Mundial de Sanidad Animal (OIE), y de seguir las pautas del «Modelo de plan de estudios básico de formación veterinaria¼ de la OIE puede ayudar a reducir estas disparidades. Los autores comparan el plan de estudios ucraniano en materia de epidemiología veterinaria con el «Plan de estudios básico de formación veterinaria¼ recomendado por la OIE, sobre todo en lo tocante a las enfermedades infecciosas, pues en esta materia se inscribe la enseñanza de la epidemiología, y proponen diferentes fórmulas para estructurar programas de formación avanzada al respecto. Esta formación reviste interés para el desarrollo del comercio internacional de animales y la expansión de los mercados de productos animales en Ucrania. La epidemiología es esencial para el Sector de la evaluación de riesgos recién creados en el Servicio Estatal Ucraniano de Higiene de los Alimentos y Protección del Consumidor. La formación de profesionales reviste máxima importancia. Los veterinarios titulados por establecimientos ucranianos contarán con los conocimientos básicos necesarios para empezar a trabajar en el comercio de animales y productos de origen animal o para administraciones públicas. El objetivo a largo plazo se cifra en mejorar el plan de estudios veterinarios de Ucrania introduciendo cambios en las clases de epidemiología y en elaborar una plantilla común para evaluar los contenidos de epidemiología impartidos en las facultades de veterinaria de cualquier parte del país.

Age-Related Changes in Ang II Receptor Localization and Expression in the Developing Auditory Pathway.

We studied Ang II receptor localization in different nuclei of the auditory system, by means of binding autoradiography, during brain development. The inferior colliculus (IC), a large midbrain structure which serves as an obligatory synaptic station in both the ascending and descending auditory pathways, exhibited high Ang II AT2 binding at all ages (P0, P8, P15, P30), being maximal at P15. These observations were confirmed by in situ hybridization and immunofluorescence at P15, demonstrating that AT2 receptor mRNA localized at the same area recognized by AT2 antibodies and anti ß III-tubulin suggesting the neuronal nature of the reactive cells. Ang II AT1 receptors were absent at early developmental ages (P0) in all nuclei of the auditory system and a low level was observed in the IC at the age P8. AT2 receptors were present at ventral cochlear nucleus and superior olivary complex, being higher at P15 and P8, respectively. We also explored the effect of prenatal administration of Ang II or PD123319 (AT2 antagonist) on binding of Ang II receptors at P0, P8, P15. Both treatments increased significantly the level of AT2 receptors at P0 and P8 in the IC. Although total binding in the whole IC from P15 animals showed no difference between treatments, the central nucleus of the IC exhibited higher binding. Our results supports a correlation between the timing of the higher expression of Ang II AT2 receptors in different nuclei, the onset of audition and the establishment of neuronal circuits of the auditory pathway.

Changes in the total ozone content over the period 2006 to 2100 and the effects on the erythemal and vitamin D effective UV doses for South America and Antarctica.

Recent studies show that the ozone layer will recover by the middle part of this century. This is a significant result arising from the Montreal Protocol, and highlights the success of this environmental protection agreement. Climate change projections show that Total Ozone Content (TOC) levels will increase significantly by the end of this century, mainly at higher latitudes. This increase may result in a reduction of the adverse effects of UV radiation overexposure. By contrast, reduced UV radiation levels at the surface of the Earth can result in reduced levels of vitamin D synthesis among the inhabitants of these regions. In this study we provide estimates for the UVI, erythemal, and vitamin-D weighted daily doses for ten different locations in South America and Antarctica. Our calculations were based on ozone projections provided by climate models set forth in the last IPCC report. Results show that the increase of TOC levels in middle and high latitude regions may result in decreased UVI and UV doses throughout the century. In high latitudes, erythemal doses and vitamin D synthesis doses may be reduced by up to 22 and 39%, respectively, if anthropogenic emissions continue to rise throughout the century. Furthermore, there may be reductions of up to 9 and 12%, respectively, in mid-latitudes (20°S to 35°S). Significant variations at Equatorial sites were not observed. In most of South America, the attenuation in UVR caused by increases in TOC during the 21st century is neither enough to promote protective effects from this radiation, nor for the lack of UVR for vitamin D synthesis. The incidence of UVR in tropical and sub-tropical areas of the continent will continue to be a public health risk for the entire 21st century during all seasons, regardless of the climatic scenarios. Our results can be used as an important tool for health studies focusing on the excess and/or lack of sun exposure.

The pathogenesis of mucositis: updated perspectives and emerging targets.

Mucositis research and treatment are a rapidly evolving field providing constant new avenues of research and potential therapies. The MASCC/ISOO Mucositis Study Group regularly assesses available literature relating to pathogenesis, mechanisms, and novel therapeutic approaches and distils this to summary perspectives and recommendations. Reviewers assessed 164 articles published between January 2011 and June 2016 to identify progress made since the last review and highlight new targets for further investigation. Findings were organized into sections including established and emerging mediators of toxicity, potential insights from technological advances in mucositis research, and perspective. Research momentum is accelerating for mucositis pathogenesis, and with this has come utilization of new models and interventions that target specific mechanisms of injury. Technological advances have the potential to revolutionize the field of mucositis research, although focused effort is needed to move rationally targeted interventions to the clinical setting.

Saliva versus serum cortisol to identify subclinical hypercortisolism in adrenal incidentalomas: simplicity versus accuracy.

PURPOSE: Subclinical hypercortisolism (SCH) leads to metabolic derangements and increased cardiovascular risk. Cortisol autonomy is defined by the overnight 1 mg dexamethasone suppression test (DST). Saliva cortisol is an easier, stress-free, and cost-effective alternative to serum cortisol. We compared 23 h and post-1 mg DST saliva with serum cortisol to identify SCH in adrenal incidentalomas (AI). METHODS: We analyzed 359 DST obtained retrospectively from 226 AI subjects (173F/53 M; 19-83 years) for saliva and serum cortisol. We used three post-DST serum cortisol cutoffs to uncover SCH: 1.8, 2.5, and 5.0 µg/dL. We determined post-DST and 23 h saliva cortisol cutoffs by ROC curve analysis and calculated their sensitivities (S) and specificities (E). RESULTS: The sensitive 1.8 µg/dL cutoff defined 137 SCH and 180 non-functioning adenomas (NFA): post-DST and 23 h saliva cortisol S/E were: 75.2%/74.4% and 59.5%/65.9%, respectively. Using the specific 5.0 µg/dL cortisol cutoff (22 SCH/295 NFA), post-DST and 23 h saliva cortisol S/E were 86.4%/83.4% and 66.7%/80.4%, respectively. Using the intermediate 2.5 µg/dL cutoff (89 SCH/228 NFA), post-DST and 23 h saliva cortisol S/E were 80.9%/68.9% and 65.5%/62.8%, respectively. CONCLUSION: Saliva cortisol showed acceptable performance only with the 5.0 µg/dL cortisol cutoff, as in overt Cushing's syndrome. Lower cutoffs (1.8 and 2.5 µg/dL) that identify larger samples of patients with poor metabolic outcomes are less accurate for screening. These results may be attributed to pre-analytical factors and inherent patient conditions. Thus, saliva cortisol cannot replace serum cortisol to identify SCH among patients with AI for screening DST.

Hematological and biochemical parameters of dairy calves submitted to pegbovigrastim administration.

This study was designed to evaluate the response of hematological and biochemical parameters submitted to pegbovigrastim administration and postchallenge with lipopolysaccharide (LPS). In experiment 1, 20 newborn Holstein calves were divided into 2 groups: the Imrestor (Elanco Saúde Animal, São Paulo, Brazil) group (IMR, n = 10), which received a 25 µg/kg of body weight (BW) subcutaneous administration of pegbovigrastim, and the control group (CTR, n = 10), which received a subcutaneous administration of 0.9% saline solution. Blood samples were collected on d 0, 10, 12, and 14 relative to birth to analyze the biochemical and hematological parameters. Moreover, growth measurements were taken on d 0, 7, 14, 21, and 60 relative to birth. The number of total leukocytes in the IMR group increased on d 12 and 14 in comparison to the CTR group, as well as the counts of segmented neutrophils, band cells, and monocytes. No differences were observed in the other hematological, biochemical, and growth parameters. In experiment 2, 20 Holstein calves from 30 to 60 d old were divided into 4 groups: group 1 (LPS, n = 5) received a 0.25 µg/kg of BW single intravenous dose of Escherichia coli LPS at d 0; group 2 (IMR, n = 5) received a 25 µg/kg of BW subcutaneous dose of pegbovigrastim at d 1; group 3 (IMR + LPS, n = 5) received a 0.25 µg/kg of BW intravenous LPS dose at d 0 and a 25 µg/kg of BW subcutaneous dose of pegbovigrastim at d 1; and group 4 (CTR, n = 5) received an intravenous dose of 0.9% sodium chloride at d 0 and a subcutaneous dose of 0.9% sodium chloride at d 1. For the analysis of biochemical and hematological parameters, blood samples were collected on d -1, 0, 1, 2, 3, 4, 8, 14, and 21 relative to LPS administration. An increase in the number of total leukocytes was observed in the IMR, IMR + LPS, and LPS groups, and the IMR group remained as the highest from d 2 to 21. The levels of paraoxonase 1 were higher in the IMR group compared with all the others. The administration of pegbovigrastim in the dairy calves increased the number of circulating leukocytes, especially neutrophils, with an increase in paraoxonase 1, without altering the metabolites for the hepatic function.

Serological and molecular markers of hepatitis E virus infection in HIV-infected patients in Brazil.

In Brazil, the circulation of hepatitis E virus (HEV) has been demonstrated in distinct groups of individuals and some animals, but its prevalence among individuals with human immunodeficiency virus (HIV) infection is unknown. This study aimed to assess the frequency of serological and molecular HEV markers in individuals infected with HIV from São Paulo, Brazil. Serum and plasma samples of 354 HIV-infected patients collected between 2007 and 2013 were included. All samples were tested for anti-HEV IgG and IgM antibodies and HEV RNA. Anti-HEV IgG and IgM antibodies were detected in 10.7% (38/354) and 1.4% (5/354) of the samples, respectively. Both antibodies were detected simultaneously in only two samples. HEV RNA was not detected in any sample. There was no significant correlation of anti-HEV serological status (positivity to anti-HEV IgG and/or IgM) with sex, age, CD4+ T cell count, HIV viral load, antiretroviral therapy, liver enzyme levels, or coinfection with hepatitis B virus and/or hepatitis C virus. Our study provides serological evidence of past and recent HEV infections in HIV-infected patients from São Paulo, Brazil. However, the occurrence of ongoing HEV infection appears be a rare event in this population.

Stillbirth rates in 20 countries of Latin America: an ecological study.

OBJECTIVE: To describe country-level stillbirth rates and their change over time in Latin America, and to measure the association of stillbirth rates with socio-economic and health coverage indicators in the region. DESIGN: Ecological study. SETTING: 20 countries of Latin America. POPULATION OR SAMPLE: Aggregated data from pregnant women with countries as units of analysis. METHODS: We used stillbirth estimates, and socio-economic and healthcare coverage indicators reported from 2006 to 2016 from UNICEF, United Nations Development Programme and World Bank datasets. We calculated Spearman's correlation coefficients between stillbirths rates and socioeconomic and health coverage indicators. MAIN OUTCOME MEASURES: National estimates of stillbirth rates in each country. RESULTS: The estimated stillbirth rate for Latin America for 2015 was 8.1 per 1000 births (range 3.1-24.9). Seven Latin America countries had rates higher than 10 stillbirths per 1000 births. The average annual reduction rate for the region was 2% (range 0.1-3.8%), with the majority of Latin America countries ranging between 1.5 and 2.5%. National stillbirth rates were correlated to: women's schooling (rS = -0.7910), gross domestic product per capita (rS = -0.8226), fertility rate (rS = 0.6055), urban population (rS = -0.6316), and deliveries at health facilities (rS = -0.6454). CONCLUSIONS: Country-level estimated stillbirth rates in Latin America varied widely in 2015. The trend and magnitude of reduction in stillbirth rates between 2000 and 2015 was similar to the world average. Socio-economic and health coverage indicators were correlated to stillbirth rates in Latin America. TWEETABLE ABSTRACT: Stillbirth rates decreased in Latin America but remain relatively high, with wide variations among countries.

Methionine and choline supply during the peripartal period alter polymorphonuclear leukocyte immune response and immunometabolic gene expression in Holstein cows.

Polymorphonuclear leukocytes (PMNL) are the first responders upon pathogen invasion and hence play an important role in inflammatory and immune responses. Rumen-protected methionine (MET) and choline (CHOL) during the peripartal period affect the immune response and inflammatory status in dairy cows to different extents. We aimed to examine the effect of MET and CHOL supply on expression of genes regulating key PMNL functions and associations with whole-blood immune challenge. Thirty multiparous Holstein cows from a larger cohort randomly assigned from -21 to 30 d relative to parturition to a basal control (CON) diet, CON plus MET at a rate of 0.08% of dry matter, or CON plus CHOL at 60 g/d were used. Blood was sampled at -10, 7, and 30 d relative to parturition for inflammatory biomarker analyses and PMNL isolation. Neutrophil and monocyte phagocytosis and oxidative burst in vitro were assessed in whole blood at 1, 7, and 28 d. Although neutrophil and monocyte phagocytosis did not differ, oxidative burst in neutrophils and monocytes was greater in MET-supplemented cows relative to CON cows. Compared with CON, PMNL adhesion and migration-related genes (ITGAM, ITGB2, ITGA4) were downregulated in response to MET and CHOL. Expression of CADM1 and SELL was also lower in MET-supplemented cows compared with CON cows but not in CHOL cows. In contrast, compared with CON cows, the expression of ICAM1 was lower in CHOL but not MET cows. Similar to adhesion and migration-related genes, cows receiving MET- or CHOL-supplemented diets had lower expression of inflammation-related genes (IL1ß, IL10RA, NFKB1, STAT3, TLR2). However, expression of IRAK1 and TLR4 was lower in MET- but not CHOL-supplemented cows. Plasma taurine concentration was greater in MET cows compared with CHOL and CON cows, suggesting a better redox status in plasma. In agreement with plasma taurine, oxidative stress-related genes (CBS, CTH, GPX1, GSS, SOD2) in PMNL were lower in response to MET and to CHOL supply. Overall, immunometabolic gene expression profile and blood biomarker analyses suggest an overall better redox status in PMNL during the transition period in response to MET and CHOL supply. These adaptations in PMNL might be beneficial for mounting a better bactericidal response upon challenge.

Effect of oestrous synchrony between embryo donors and recipients, embryo quality and state on the pregnancy rate in beef cattle.

This study aimed to evaluate the effect of oestrous synchrony between donors and recipients and the embryo quality on the pregnancy rate in beef cow recipients. The experiment was performed over two years at an embryo transfer (ET) centre in Southern Brazil. Ninety Aberdeen Angus cows were subjected to superovulation (SOV) protocols, resulting in the recovery of 1,048 transferable embryos. Eleven groups were formed with intervals of 6 hr, from -30 to +30 hr, with respect to recipient versus donor oestrous detection. Evaluation of embryo quality was according to the IETS guidelines. The overall pregnancy rate was 52%. Effects related to donor and recipient oestrous synchronization on pregnancy rate were observed (p = .01), ranging from 36% to 50%. The embryo quality rate affected the pregnancy rate, where Grade I resulted in 57% and Grade III in 43% of pregnancy (p < .001). The embryonic state (frozen or fresh) showed no (p > .05) effect on pregnancy rate: 53% for fresh embryos and 44% for frozen embryos. The odds ratio for explanatory variables causing pregnancy indicated that Grade III embryos had 31% less chance of conception compared to Grade I. Thus, oestrous synchrony between donor and recipient, considering ±30 hr apart, can affect the pregnancy rate along with embryo quality.

Posterior tibial nerve stimulation in the treatment of fecal incontinence: a systematic review.

Fecal incontinence severely impacts on quality of life, causing stigmatization and social exclusion. Posterior tibial nerve stimulation (PTNS) is one technique used for treatment. This systematic review aims to assess the effectiveness of PTNS for the treatment of fecal incontinence. A literature review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) declaration. Pubmed, Scopus, Web of Knowledge and PEDro databases were searched for both randomized clinical trials and cases series. The outcome variables were treatment effectiveness, severity of incontinence and quality of life; all were measured in the short, mid and long-term after performing both percutaneous and transcutaneous PTNS. Twenty-three studies met the selection criteria. Two clinical trials found significant differences in treatment effectiveness compared to the placebo response. Fifteen cases series observed significant differences in terms of effectiveness, severity and quality of life. All clinical trials achieved a reduction in the number of incontinence episodes and an increase in the deferral time for defecation. Optimal results were achieved by interventions consisting of one or two weekly sessions of a 30-60 minutes duration and the use of pulse widths of 200 µs and frequencies of 10-20 Hz. Percutaneous stimulation did not demonstrate better results compared to transcutaneous application. PTNS is an effective technique for the treatment of fecal incontinence, although long-term interventions are required in order to prolong its effects in the long-term.