Effect of adding PCSK9 inhibitors to lipid-lowering interventions on arterial stiffness: A systematic review and meta-analysis.

BACKGROUND: Atherosclerosis, a leading cause of mortality, necessitates effective management of hypercholesterolemia, specifically elevated low-density lipoprotein cholesterol (LDL-C). The emergence of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) has revolutionised lipid-lowering. PCSK9i demonstrates substantial LDL-C reduction and cardiovascular benefits, particularly in statin-intolerant or nonresponsive individuals. However, the potential pleiotropic effects of PCSK9i, especially on arterial stiffness, remain a subject of investigation. This systematic review and meta-analysis seek to provide a nuanced understanding of the potential pleiotropic effects of PCSK9i, specifically on arterial health. The primary objective was to analyse the influence of PCSK9i on arterial stiffness, extending beyond traditional lipid-lowering metrics and contributing to a more comprehensive approach to cardiovascular risk reduction. METHODS: A systematic search was conducted across major databases, clinical trial registries and grey literature. Inclusion criteria comprised adults in prospective cohort studies undergoing PCSK9i augmentation in lipid-lowering therapy, with a focus on arterial stiffness measured by pulse wave velocity (PWv). Random-effects meta-analyses, sensitivity analyses and meta-regression models were employed to assess the pooled effect of adding PCSK9i to lipid-lowering interventions on arterial stiffness. RESULTS: Five studies (158 participants) met the inclusion criteria, demonstrating a significant reduction in PWv (mean difference: -2.61 m/s [95% CI: -3.70, -1.52]; ES: -1.62 [95% CI: -2.53, -.71]) upon adding PCSK9i to lipid-lowering interventions. Subgroup analysis and meta-regression models suggested potential sex-based and baseline PWv-dependent variations, emphasising patient-specific characteristics. CONCLUSION: The meta-analysis provides robust evidence that adding PCSK9i to lipid-lowering interventions significantly improves arterial stiffness, indicating broader vascular benefits beyond LDL-C reduction.

Overall survival for early and locally advanced non-small-cell lung cancer from one institution: 2000–2017

Purpose Lung cancer is the leading cause of cancer death in Spain. The objective of our study was to evaluate the characteristics of patients diagnosed with stages I–III non-small-cell lung cancer, as well as the impact that epidemiological changes, diagnostic improvements and surgical therapeutic innovations have had on survival in the past 20 years. Methods Retrospective analysis of patients diagnosed with early and locally advanced non-small-cell lung cancer between years 2000 and 2017 in our institution. Results A total of 859 patients were included. An increase in the percentage of women diagnosed over time was observed. Statistically significant differences were observed in the mean age at diagnosis, with a progressive increase in the different periods. The percentage of current or former smokers was similar in all periods. Adenocarcinoma was the most frequent histologic type with a progressive increase in its frequency. The percentage of patients diagnosed in early stages has been increasing over the years. In stages I–II, there was a significant increase in the median survival (29.7 months: 2000–2004, 68.73 months: 2010–2014) that could be seen in stage III as well (14.7 months: 2000–2004, 30.63 months: 2015–2017). Conclusions A variation of clinical characteristics of lung cancer in Spain has been observed in recent years, as well as an improvement in survival in early and locally advanced stages, due not only to the treatments, but also to a more accurate detection of these tumors. Little progress has been made in tobacco habit with high stable percentages over the years (AU)

Overall survival for early and locally advanced non-small-cell lung cancer from one institution: 2000-2017.

PURPOSE: Lung cancer is the leading cause of cancer death in Spain. The objective of our study was to evaluate the characteristics of patients diagnosed with stages I-III non-small-cell lung cancer, as well as the impact that epidemiological changes, diagnostic improvements and surgical therapeutic innovations have had on survival in the past 20 years. METHODS: Retrospective analysis of patients diagnosed with early and locally advanced non-small-cell lung cancer between years 2000 and 2017 in our institution. RESULTS: A total of 859 patients were included. An increase in the percentage of women diagnosed over time was observed. Statistically significant differences were observed in the mean age at diagnosis, with a progressive increase in the different periods. The percentage of current or former smokers was similar in all periods. Adenocarcinoma was the most frequent histologic type with a progressive increase in its frequency. The percentage of patients diagnosed in early stages has been increasing over the years. In stages I-II, there was a significant increase in the median survival (29.7 months: 2000-2004, 68.73 months: 2010-2014) that could be seen in stage III as well (14.7 months: 2000-2004, 30.63 months: 2015-2017). CONCLUSIONS: A variation of clinical characteristics of lung cancer in Spain has been observed in recent years, as well as an improvement in survival in early and locally advanced stages, due not only to the treatments, but also to a more accurate detection of these tumors. Little progress has been made in tobacco habit with high stable percentages over the years.

Identification of functional candidate variants and genes for feed efficiency in Holstein and Jersey cattle breeds using RNA-sequencing.

The identification of functional genetic variants and associated candidate genes linked to feed efficiency may help improve selection for feed efficiency in dairy cattle, providing economic and environmental benefits for the dairy industry. This study used RNA-sequencing data obtained from liver tissue from 9 Holstein cows [n = 5 low residual feed intake (RFI), n = 4 high RFI] and 10 Jersey cows (n = 5 low RFI, n = 5 high RFI), which were selected from a single population of 200 animals. Using RNA-sequencing, 3 analyses were performed to identify: (1) variants within low or high RFI Holstein cattle; (2) variants within low or high RFI Jersey cattle; and (3) variants within low or high RFI groups, which are common across both Holstein and Jersey cattle breeds. From each analysis, all variants were filtered for moderate, modifier, or high functional effect, and co-localized quantitative trait loci (QTL) classes, enriched biological processes, and co-localized genes related to these variants, were identified. The overlapping of the resulting genes co-localized with functional SNP from each analysis in both breeds for low or high RFI groups were compared. For the first two analyses, the total number of candidate genes associated with moderate, modifier, or high functional effect variants fixed within low or high RFI groups were 2,810 and 3,390 for Holstein and Jersey breeds, respectively. The major QTL classes co-localized with these variants included milk and reproduction QTL for the Holstein breed, and milk, production, and reproduction QTL for the Jersey breed. For the third analysis, the common variants across both Holstein and Jersey breeds, uniquely fixed within low or high RFI groups were identified, revealing a total of 86,209 and 111,126 functional variants in low and high RFI groups, respectively. Across all 3 analyses for low and high RFI cattle, 12 and 31 co-localized genes were overlapping, respectively. Among the overlapping genes across breeds, 9 were commonly detected in both the low and high RFI groups (INSRR, CSK, DYNC1H1, GAB1, KAT2B, RXRA, SHC1, TRRAP, PIK3CB), which are known to play a key role in the regulation of biological processes that have high metabolic demand and are related to cell growth and regeneration, metabolism, and immune function. The genes identified and their associated functional variants may serve as candidate genetic markers and can be implemented into breeding programs to help improve the selection for feed efficiency in dairy cattle.

Development and comparison of RNA-sequencing pipelines for more accurate SNP identification: practical example of functional SNP detection associated with feed efficiency in Nellore beef cattle.

BACKGROUND: Optimization of an RNA-Sequencing (RNA-Seq) pipeline is critical to maximize power and accuracy to identify genetic variants, including SNPs, which may serve as genetic markers to select for feed efficiency, leading to economic benefits for beef production. This study used RNA-Seq data (GEO Accession ID: PRJEB7696 and PRJEB15314) from muscle and liver tissue, respectively, from 12 Nellore beef steers selected from 585 steers with residual feed intake measures (RFI; n = 6 low-RFI, n = 6 high-RFI). Three RNA-Seq pipelines were compared including multi-sample calling from i) non-merged samples; ii) merged samples by RFI group, iii) merged samples by RFI and tissue group. The RNA-Seq reads were aligned against the UMD3.1 bovine reference genome (release 94) assembly using STAR aligner. Variants were called using BCFtools and variant effect prediction (VeP) and functional annotation (ToppGene) analyses were performed. RESULTS: On average, total reads detected for Approach i) non-merged samples for liver and muscle, were 18,362,086.3 and 35,645,898.7, respectively. For Approach ii), merging samples by RFI group, total reads detected for each merged group was 162,030,705, and for Approach iii), merging samples by RFI group and tissues, was 324,061,410, revealing the highest read depth for Approach iii). Additionally, Approach iii) merging samples by RFI group and tissues, revealed the highest read depth per variant coverage (572.59 ± 3993.11) and encompassed the majority of localized positional genes detected by each approach. This suggests Approach iii) had optimized detection power, read depth, and accuracy of SNP calling, therefore increasing confidence of variant detection and reducing false positive detection. Approach iii) was then used to detect unique SNPs fixed within low- (12,145) and high-RFI (14,663) groups. Functional annotation of SNPs revealed positional candidate genes, for each RFI group (2886 for low-RFI, 3075 for high-RFI), which were significantly (P < 0.05) associated with immune and metabolic pathways. CONCLUSION: The most optimized RNA-Seq pipeline allowed for more accurate identification of SNPs, associated positional candidate genes, and significantly associated metabolic pathways in muscle and liver tissues, providing insight on the underlying genetic architecture of feed efficiency in beef cattle.

Spontaneus subscapular abscess. A clinical case / Absceso subescapular espontáneo. Caso clínico

Infections of the subscapular space are very infrequent entities, which is why their diagnosis (for which it is crucial to carry out magnetic resonance imaging or, failing that, computerized tomography) can prove complicated. This difficulty in making the diagnosis conditions the speed of treatment (surgical draining that can be accompanied by antibiotherapy), which is crucial for the medium and long-term prognosis. We present the case of a patient who developed a spontaneous subscapular abscess that was drained using a delto-pectoral approach, with the subscapular space accessed via a medial route to the coracoids. The relevance of this case lies in its singular character and in the description of an approach that has only been used in two prior cases in the literature

Las infecciones del espacio subescapular son entidades muy poco frecuentes y, por ello, su diagnóstico (para el que resulta clave la realización de una resonancia magnética o, en su defecto, una tomografía computarizada) puede resultar complicado. Esta dificultad en el diagnóstico condiciona la rapidez en el tratamiento (drenaje quirúrgico acompañado o no de antibioterapia), que resulta clave para el pronóstico a medio y largo plazo. Presentamos el caso de un paciente que desarrolló un absceso subescapular espontáneo que se drenó mediante un abordaje delto-pectoral, accediendo al espacio subescapular por vía medial a la coracoides. La relevancia del caso presentado radica en su singularidad y en la descripción de una vía de abordaje que solo ha sido empleada en dos casos previos en la literatura

Spontaneus subscapular abscess. A clinical case.

Infections of the subscapular space are very infrequent entities, which is why their diagnosis (for which it is crucial to carry out magnetic resonance imaging or, failing that, computerized tomography) can prove complicated. This difficulty in making the diagnosis conditions the speed of treatment (surgical draining that can be accompanied by antibiotherapy), which is crucial for the medium and long-term prognosis. We present the case of a patient who developed a spontaneous subscapular abscess that was drained using a delto-pectoral approach, with the subscapular space accessed via a medial route to the coracoids. The relevance of this case lies in its singular character and in the description of an approach that has only been used in two prior cases in the literature.

Low Golimumab Trough Levels at Week 6 Are Associated With Poor Clinical, Endoscopic and Histological Outcomes in Ulcerative Colitis Patients: Pharmacokinetic and Pharmacodynamic Sub-analysis of the Evolution Study.

BACKGROUND AND AIMS: Golimumab has an established exposure-response relationship in patients with ulcerative colitis [UC]. However, the association of serum golimumab trough levels [TL] with objective markers of disease activity, such as endoscopic and histological activity scores and concentrations of biomarkers, remains less understood. This report describes the relationship of serum golimumab TL at the end of the induction period [Week 6] with clinical, endoscopic, histological, and biomarker parameters. METHODS: This was an open-label, uncontrolled, prospective and interventional study. Moderate to severely active UC patients naïve to biologic therapy were treated with golimumab. Serum golimumab TL and faecal calprotectin levels were measured at baseline [Week 0 of induction] and Week 6. RESULTS: A total of 34 patients completed the induction phase [Week 6] and were included in this analysis. Overall, 47.1% and 14.7% of patients achieved clinical response and remission with significantly higher serum golimumab TL in patients with early response or remission [3.7 µg/mL vs 1.3 µg/mL, p = 0.0013; and 3.1 µg/mL vs 1.7 µg/mL, p = 0.0164, respectively]. In addition, golimumab TL were significantly higher in patients achieving histological remission [4.2 µg/mL vs 1.7 µg/mL, p = 0.0049]. Week 6 golimumab TL were inversely correlated with the total Mayo score [rs = -0.546; p = 0.0008], the Mayo endoscopic subscore [rs = -0.381; p = 0.0262], the Geboes histological activity score [rs = -0.464; p = 0.0057], and faecal calprotectin levels [rs = -0.497; p = 0.0044]. CONCLUSIONS: A higher early exposure to golimumab is associated with a better objective response in active UC patients and appears to drive the outcome at Week 6.

Cardiorespiratory fitness and site-specific risk of cancer in men: A systematic review and meta-analysis.

BACKGROUND: Cardiorespiratory fitness is a strong predictor of all-cause morbidity and mortality; nevertheless, the association between cardiorespiratory fitness and the risk of cancer remains unclear. Thus, the aim of this study was to synthetize the evidence on the relationship between cardiorespiratory fitness and the risk of several sites of cancer in men. METHODS: A computerised search in MEDLINE, EMBASE and Web of Science databases from their inception to 13th February 2019 was performed. Both fixed and random-effects models were used to calculate the pooled hazard ratio (HR) estimates and their 95% confidence intervals (CIs) to examine the effect of high and moderate versus low cardiorespiratory fitness on site-specific cancer (lung, colon/rectum, prostate) and all-sites cancer. RESULTS: Ten studies were included in the qualitative review, and seven of them were included in the meta-analysis. Using low cardiorespiratory fitness as the reference group, moderate and high levels of cardiorespiratory fitness were associated with a lower risk (HRs) of lung cancer, 0.53 (95% confidence interval [CI], 0.39 to 0.68) and 0.52 (95% CI, 0.42 to 0.61); colorectal cancer, 0.74 (95% CI, 0.55 to 0.93) and 0.77 (95% CI, 0.62 to 0.92) and all cancer sites, 0.86 (95% CI, 0.79 to 0.93) and 0.81 (95% CI, 0.75 to 0.87), respectively. CONCLUSIONS: Among men, cardiorespiratory fitness plays an important role in protecting against the risk of lung and colorectal cancer. Additionally, this protective effect was observed for all-sites cancer risk. These results show the importance of good cardiorespiratory fitness as a potential factor in cancer prevention.

Glycated haemoglobin A1c as a predictor of preeclampsia in type 1 diabetic pregnant women: A systematic review and meta-analysis.

OBJECTIVE: To examine the relationship between the increase of glycated haemoglobin A1c (HbA1c) levels and the risk of preeclampsia in pregnant with type 1 diabetes mellitus; and to determine from which trimester the increase of HbA1c levels better predicts the risk of suffering preeclampsia in type 1 diabetic pregnant women. METHODS: We systematically searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews and Web of Science databases, from inception to May 2017, for observational studies addressing the association of HbA1c levels with preeclampsia. Fixed effects models were used to compute pooled estimates of odds ratio (OR) and respective 95% confidence intervals (95% CI) for preeclampsia in type 1 diabetic pregnant women. Additionally, subgroup analyses were performed based on pregnancy trimester. RESULTS: Five published studies were included in the systematic review and meta-analysis. There was an increase in the risk of preeclampsia with a 1% increase of HbA1c during pregnancy (OR = 1.38; 95% CI 1.26-1.52, I2=0.0%). When analyses were performed based on pregnancy trimester to estimate the risk of preeclampsia with a 1% increase of HbA1c, pooled OR estimates were 1.37 (95% CI 1.24-1.51, I2=0.0%) for the first trimester and 1.67 (95% CI 1.44-1.93, I2=0.0%) for the second/third trimester. CONCLUSION: HbA1c is a reliable predictor of preeclampsia in type 1 diabetic pregnant women. Our findings highlight the importance of including HbA1c measurements in the first antenatal visit to control the risk of preeclampsia in pregnant women. Systematic review registration: PROSPERO: CRD42017058394.

Handgrip and knee extension strength as predictors of cancer mortality: A systematic review and meta-analysis.

The specific role of different strength measures on mortality risk needs to be clarified to gain a better understanding of the clinical importance of different muscle groups, as well as to inform intervention protocols in relation to reducing early mortality. The aim of the systematic review and meta-analysis was to determine the relationship between muscular strength and risk of cancer mortality. Eligible cohort studies were those that examined the association between muscular strength, as assessed using validated tests, and cancer mortality in healthy youth and adults. The hazard ratio (HR) estimates obtained were pooled using random effects meta-analysis models. The outcome was cancer mortality assessed using the HR (Cox proportional hazards model). Eleven prospective studies with 1 309 413 participants were included, and 9787 cancer-specific deaths were reported. Overall, greater handgrip (HR = 0.97, 95% CI, 0.92-1.02; P = .055; I2  = 18.9%) and knee extension strength (HR = 0.98, 95% CI, 0.95-1.00; P = .051; I2  = 60.6%) were barely significant associated with reduced risk of cancer mortality. Our study suggests that higher level of muscular strength is not statistically associated with lower risk of cancer mortality.

Pregnancy leisure physical activity and children's neurodevelopment: a narrative review.

In recent years, interest in the relation between maternal physical activity during pregnancy and children's neurocognitive development has been growing. Several observational studies and clinical trials have analysed this relation and they differ in the findings, especially for children's language-related skills and IQ. Physical activity assessment, amount of physical activity and the test used for measuring children's cognition could affect this relation, as well as other factors that should be considered. This article will review the evidence on the effects of physical activity during pregnancy on children's different cognitive domains. TWEETABLE ABSTRACT: Leisure physical during pregnancy positively affects offspring's general intelligence and language skills.

The effects of physical activity interventions on glycated haemoglobin A1c in non-diabetic populations: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Epidemiological evidence suggests that physical activity has a positive effect on reducing glycated haemoglobin A1c (HbA1c) levels not only in diabetics, but also in healthy subjects. Moreover, a positive association of HbA1c levels with cardiovascular disease and mortality in non-diabetic populations has recently been reported. This is a protocol for a systematic review and meta-analysis aiming to estimate the effects of physical activity on glycaemic control measured by HbA1c levels in non-diabetic populations; and to determine which type of physical activity has a greater influence on glycaemic control. METHODS AND ANALYSIS: The search will be conducted using MEDLINE, EMBASE, the Cochrane Library and Web of Science databases from inception to mid-2017. Randomised controlled trials, non-randomised experimental studies and controlled pre-post studies written in English, Portuguese, French or Spanish will be included. The Cochrane Collaboration's tool and The Quality Assessment Tool for Quantitative Studies will be used to assess the risk of bias for studies included in the systematic review. Standardised pre-post intervention mean differences of HbA1c will be calculated as the primary outcome. Subgroup analyses will be performed based on the characteristics of physical activity intervention and population included in the studies. ETHICS AND DISSEMINATION: This systematic review will synthesise evidence on the association of physical activity and HbA1c in non-diabetic populations. This study is important from the clinical and public health point because it will estimate the effect of physical activity on the glycemic control, and it will also examine which is the type of physical activity that should be recommended for preventing type 2 diabetes and its complications. The results will be disseminated by publication in a peer-reviewed journal. Ethical approval will not be required because the data used for this systematic review will be obtained from published studies and there will be no concerns about privacy. TRIAL REGISTRATION NUMBER: PROSPERO CRD42016050991.

Hipospadias del varón: ¿anomalía de la diferenciación sexual? / Male hypospadias: abnormal sexual differentiation

El síndrome de insensibilidad a los andrógenos se caracteriza por un cariotipo 46 XY con gónadas masculinas pero con una presentación fenotípica variable, con presencia de genitales ambiguos, que puede ir desde una feminización de completa a leve (hipospadias); está causado por una anomalía genética en el receptor de andrógenos localizado en el cromosoma X, lo que genera una resistencia a la acción de los andrógenos. Se presenta un caso de síndrome de insensibilidad a los andrógenos con estudio cito-genético y su posterior seguimiento (AU)

The androgen insensitivity síndrome it is characterized by a karyotype 46 XY with male gonads, but with a variable phenotypic presentation, with the presence of ambiguous genitalia, Which can range from mild to complete feminization. It is caused by a genetic defect in the androgen receptor located on the X chromosome, which generates a resistance to the action of androgens. A case of androgen insensitivity syndrome is presented With cyto-genetic study, and the subsequent monitoring (AU)

Glycosylated haemoglobin as a predictor of cardiovascular events and mortality: a protocol for a systematic review and meta-analysis.

INTRODUCTION: Glycosylated haemoglobin level (HbA1c) is an indicator of the average blood glucose concentrations over the preceding 2-3 months and is used as a convenient and well-known biomarker in clinical practice. Currently, epidemiological evidence suggests that HbA1c level is an independent risk factor for cardiovascular events such as myocardial infarction, stroke, coronary heart disease and heart failure. This protocol aim is to conduct a systematic review and meta-analysis to determine relationships of HbA1c levels with cardiovascular outcomes and cause of death, and to analyse the range of HbA1c levels that is a predictor of cardiovascular disease and/or mortality based on data from published observational studies. METHODS AND ANALYSIS: The search will be conducted using Medline, EMBASE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Web of Science databases from their inception. Observational studies written in Portuguese, Spanish or English will be included. The Quality In Prognosis Studies tool will be used to assess the risk of bias for the studies included in the systematic review or meta-analysis. HRs for cardiovascular outcomes and causes of death with 95% CIs will be determined as primary outcomes. Subgroup analyses will be performed based on cardiovascular outcomes, cause of death studied, and type of population included in the studies. ETHICS AND DISSEMINATION: This systematic review will synthesise evidence on the potential of using HbA1c level as a prognostic marker for cardiovascular disease outcomes and/or mortality. The results will be disseminated by publication in a peer-reviewed journal. Ethics approval will not be needed because the data used for this systematic review will be obtained from published studies and there will be no concerns about privacy. TRIAL REGISTRATION NUMBER: PROSPERO CRD42015032552.

Neuropatías y moda en la adolescencia: presentación de 2 casos clínicos / Neuropathy and style in adolescence: Presentation of two cases

Introducción: Las neuropatías localizadas adquiridas, no posquirúrgicas ni postraumáticas (excluida la afectación de pares craneales), son raras en la infancia. Se presentan 2 casos clínicos de adolescentes con neuropatía periférica secundaria a fenómenos compresivos en relación con hábitos estéticos. Casos clínicos: El caso 1 corresponde a una niña de 13 años con neuropatía del ciático poplíteo externo; presenta una pérdida ponderal en un breve periodo de tiempo y practica ejercicio físico intenso a diario. El caso 2 corresponde a una niña de 14 años con meralgia parestésica del nervio femorocutáneo; habitualmente viste pantalones elásticos ajustados. Conclusiones: Ambos casos presentan neuropatías periféricas debido a fenómenos compresivos, favorecidos por la pérdida de peso, el ejercicio físico y el uso de ropa ajustada; ponen de manifiesto los peligros de algunos hábitos estéticos y relacionados con la moda y pueden ocultar otras patologías subyacentes, como trastornos de la conducta alimentaria. El tratamiento conservador es efectivo en la mayoría de los casos, pero en casos refractarios puede desarrollarse una discapacidad, por lo que es importante su identificación precoz (AU)

Introduction: Acquire neuropathies with different post-surgical or post-traumatic etiology (excluding cranial nerves affection) are uncommon in children. Two cases of peripherical neuropathy in teenagers caused by compressive phenomenon as a consequence of aesthetic habits are presented. Clinical cases: Case 1: a 13 year old patient with external popliteal sciatic neuropathy. An important weight loss in few months is referred associated with intense physical activity. Case 2: a 14 year old patient with meralgia paresthetica. She usually wears 'skinny jeans'. Conclusions: Both cases present peripheral neuropathies in teenagers, due to compressive phenomenons, increased by diet, weight loss and tight-fitting clothes. These cases remind us the dangerous effect of aesthetic habits and fashion which can hide important diseases like alimentary disorders. Conservative treatment is effective in most cases, but an early diagnosis is needed because of the important disability they can cause in some refractory cases (AU)

Periprandial changes and effects of short- and long-term fasting on ghrelin, GOAT, and ghrelin receptors in goldfish (Carassius auratus).

The periprandial profile and effects of short- (7 days) and long-term (30 days) fasting on the ghrelinergic system were studied in goldfish (Carassius auratus). Plasma levels of acyl-ghrelin, desacyl-ghrelin, and ghrelin O-acyl transferase (GOAT) were analyzed by enzymoimmunoassays, and expression of preproghrelin, goat and growth hormone secretagogue receptors (ghs-r) was quantified by real-time PCR. Circulating levels of acyl-ghrelin and GOAT rise preprandially, supporting the role of acyl-ghrelin as a meal initiator in this teleost. Consistently, preproghrelin and ghs-r1a1 expression increases 1 h before feeding time in intestinal bulb, suggesting that this receptor subtype might be involved in the preprandial action of ghrelin in this tissue. Significant postfeeding variations are detected for preproghrelin in telencephalon, goat in telencephalon and hypothalamus, ghs-r1a1 in vagal lobe, ghs-r1a2 and ghs-r2a1 in hypothalamus and ghs-r2a2 in telencephalon and vagal lobe, especially in unfed fish. Short- and long-term fasting significantly increase preproghrelin expression in telencephalon and gut. Goat expression is upregulated by short-term fasting in telencephalon and hypothalamus, and by both short- and long-term fasting in gut. Expression of ghs-r increases by fasting in telencephalon, while an upregulation of type 2, but not type 1, receptors is observed in vagal lobe. In intestinal bulb, ghs-r1a2 transcripts increase after both short- and long-term fasting. These results show a high dependence of the ghrelinergic system on feeding and nutritional status in fish, and demonstrate for the first time a differential implication of the various components of this system suggesting different roles for the four ghrelinergic receptor subtypes.

Fibroblast growth factor 21 protects against cardiac hypertrophy in mice.

Fibroblast growth factor 21 is an endocrine factor, secreted mainly by the liver, that exerts metabolic actions that favour glucose metabolism. Its role in the heart is unknown. Here we show that Fgf21(-/-) mice exhibit an increased relative heart weight and develop enhanced signs of dilatation and cardiac dysfunction in response to isoproterenol infusion, indicating eccentric hypertrophy development. In addition, Fgf21(-/-) mice exhibit enhanced induction of cardiac hypertrophy markers and pro-inflammatory pathways and show greater repression of fatty acid oxidation. Most of these alterations are already present in Fgf21(-/-) neonates, and treatment with fibroblast growth factor 21 reverses them in vivo and in cultured cardiomyocytes. Moreover, fibroblast growth factor 21 is expressed in the heart and is released by cardiomyocytes. Fibroblast growth factor 21 released by cardiomyocytes protects cardiac cells against hypertrophic insults. Therefore, the heart appears to be a target of systemic, and possibly locally generated, fibroblast growth factor 21, which exerts a protective action against cardiac hypertrophy.

Monitoring of the Bagaza virus epidemic in wild bird species in Spain, 2010.

By the end of August 2010, high mortalities in red-legged partridges (Alectoris rufa) and pheasants (Phasianus colchicus) were detected in several hunting states in the province of Cádiz (southern Spain). Retrospective epidemiological studies revealed that the first clinical signs had been observed in late July-early August. The most common clinical signs were incoordination, disorientation and ataxia. The estimated mean morbidity rates were 37% in partridges and 11% in pheasants. The estimated mean mortality rates were 23% in partridges and 6% in pheasants. The estimated mean case-fatality rates were 38% and 8% in partridges and pheasants, respectively. A total of 19 clinically affected birds from 18 affected hunting states were analysed between August and November 2011. Histopathological analyses revealed encephalitis, myocarditis, leiomyositis, meningoencephalitis and neuritis as the most frequently observed lesions. Molecular analyses identified Bagaza virus (BAGV) as the causative agent of the epidemic. Further studies are needed to determine the source of introduction of the virus into Europe and to elucidate whether wild birds play a role in the epidemiology of BAGV. Surveillance in susceptible bird species, including partridges and pheasants, may be useful for the early detection of BAGV in an area.