Modeling Gastrointestinal Tract Wet Pool Size in Small Ruminants.

The gastrointestinal tract (GIT) wet pool size (GITwps) refers to the total amount of wet contents in GIT, which in small ruminants can reach up to 19% of their body weight (BW). This study aimed to develop models to comprehensively predict GITwps in small ruminants using a meta-regression approach. A dataset was created based on 21 studies, comprising 750 individual records of sheep and goats. Various predictor variables, including BW, sex, breed, species, intake level, physiological states, stages and types of pregnancy, dry matter intake, and neutral detergent fiber intake (NDFI), were initially analyzed through simple linear regression. Subsequently, the variables were fitted using natural logarithm transformations, considering the random effect of the study and residual error, employing a supervised forward selection procedure. Overall, no significant relationship between GITwps and BW (p = 0.326) was observed for animals fed a milk-based diet. However, a strong negative linear relationship (p < 0.001) was found for animals on a solid diet, with the level of restriction influencing GITwps only at the intercept. Furthermore, the prediction of GITwps was independent of sex and influenced by species in cases where individuals were fed ad libitum. Pregnant females showed a noticeable reduction in GITwps, which was more pronounced in cases of multiple pregnancies, regardless of species (p < 0.01). The composition of the diet was found to be the primary factor affecting the modulation of GITwps, with NDFI able to override the species effect (p < 0.0001). Overall, this study sheds light on the factors influencing GITwps in small ruminants, providing valuable insights into their digestive processes and nutritional requirements.

An Update in Anticoagulant Therapy for Patients with Cancer-Associated Venous Thromboembolism.

PURPOSE OF REVIEW: This review aims to assess the treatment options for cancer-associated venous thromboembolism (VTE) based on the most robust level of evidence recommendations and suggestions based on expert opinion. RECENT FINDINGS: Several classes of anticoagulants have been studied in the treatment of cancer-associated thrombosis (CAT). Since the CLOT trial, guidelines recommend the use of low-molecular-weight heparin (LMWH) for the treatment of this condition. However, since 2018, some direct oral anticoagulants became an alternative first-line treatment for CAT. Three Xa antagonists (rivaroxaban, apixaban, and edoxaban) proved to be at least as effective as the LMWH strategy for the short-term prevention of VTE recurrence. The right choice of treatment in the context of anticoagulation strategy, thrombo-hemorrhagic risk management, and a patient's comorbidities represents a challenge. The correct management of CAT and a more individualized approach are needed to identify risk factors and offer the best treatment for each patient.

Dexmedetomidine Alone or Combined With Morphine for Epidural Anesthesia in Bitches Undergoing Elective Ovariohysterectomy.

The purpose of this study was to assess perioperative analgesia provided by the combination of epidural dexmedetomidine and morphine in bitches undergoing elective ovariohysterectomy. Twenty-four bitches were included in the study and allocated into 3 groups: GM, morphine 0.1 mg/kg; GD, dexmedetomidine 2 µg/kg; and GDM, dexmedetomidine and morphine at the same doses. All solutions were diluted in saline to a total of 0.36 mL/kg. Heart rate (HR), respiratory rate (FR) and systolic blood pressure (SAP) were recorded prior to epidural analgesia (TB), immediately following epidural analgesia (TEA), at surgical incision (TSI), at the first ovarian pedicle clamping (TOP1), at the second pedicle clamping (TOP2), at uterine stump clamping (TUC), at the start of abdominal cavity closure (TSC) and at the end of skin closure (TEC). Rescue analgesia with fentanyl was administered at 2 µg/kg IV if nociception corresponding to a 20% increase of any cardiorespiratory variables was noted. Postoperative pain assessment was performed using a modified composite Glasgow pain scale along the first 6 hours following the end of surgery. Numeric data were compared using ANOVA for repeated measures followed by Tukey test and ovarian ligament relaxation was analyzed using chi-square test under 5% significance. No differences were found on FR among times or groups, although HR showed significant differences between GM and GD at TSI, TOP1, TOP2, TSC and TEC and between GM and GDM at TEA and TSI (significantly lower HR values recorded in dexmedetomidine groups). Differences among time points were found on HR between TB and TEA in GD and on PAS between TOP1 and TSC in GM and between TOP1 and TUC in GDM (P < .05). Ovarian ligament relaxation was significantly more present in groups using dexmedetomidine, although the number of rescue analgesia administrations did not differ among groups. Kaplan-Meyer analysis failed to show significant differences on time of rescue analgesia administration among groups (P > .05). In conclusion, the combination of epidural dexmedetomidine and morphine is a more interesting choice for elective ovariohysterectomy in bitches for producing analgesia comparable to that of each drug alone, with noticeable relaxation of ovarian ligaments and lesser cardiovascular consequences.

Macromineral requirements for maintenance and growth in male and female hair sheep.

A better understanding of the nutritional requirements of sheep, especially in terms of minerals, is crucial for improving production. We estimated the net requirements for Ca, P, K, Mg, and Na for gain (NCag, NPg, NKg, NMgg, and NNag) and maintenance (NCam, NPm, NKm, NMgm, and NNam) in male and female hair sheep. Six datasets with 248 individual records of hair sheep (139 non-castrated males, 75 castrated males and 34 females) were used to estimate the net macromineral requirements for gain. To estimate the net macromineral requirements for maintenance, 52 observations (26 non-castrated and 26 castrated males) were used. A meta-analytical approach was applied, using non-linear mixed effects models and the study as a random effect. Based on information criteria for model selection, heterogeneous variance functions were more likely to describe mineral requirements with a low level of model selection uncertainty. The adopted criteria allowed the choice of the best models to represent the macromineral requirements. The chosen models explained the observed variability in the sex, and the choices were based on a low level of uncertainty (w ≥ 0.90). Irrespective of sex, NCag and NPg decreased with increasing BW from 10 to 30 kg and average daily gain (ADG) of 150 g/day, ranging from 1.71-1.38; 1.83-1.57; 1.82-1.51 of Ca and 0.86-0.66; 0.92-0.78; 0.92-0.75 of P for non-castrated males, castrated males, and females, respectively. The NKg remained constant, with mean values of 0.26 g/day. The NNag range was 0.17 to 0.14 g/day for non-castrated males, 0.20 to 0.25 g/day for females, and constant (0.18 g/day) for castrated males with an increase in BW from 10 to 30 kg and an ADG of 150 g/day. Macromineral requirements for maintenance (mg/kg BW) and retention (%) were 23.70 and 54.30 for Ca, 25.33 and 79.80 for P, 11.74 and 5.00 for K, 2.63 and 8.50 for Mg, and 7.01 and 8.10 for Na for males. The International Committees did not provide inferences about the sex influence on mineral requirements. Our study indicates that sex is one factor that influences the macromineral requirements for gain. The information generated in this study can be used to optimize the mineral management of hair sheep in the growing phase in tropical regions.

Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse Liver.

Proton pump inhibitors (PPIs) are one of the most prescribed drugs around the world. PPIs induce microbiota modulation such as obesity both in humans and in animal models. However, since PPIs can induce microbiota modulation despite the absence of a high-fat diet or weight gain, it is an interesting model to correlate microbiota modulation with the establishment of non-alcoholic fatty liver disease (NAFLD). We investigated the effect of pantoprazole treatment on TLR4 signaling and liver histology in C57BL/6J mice for 60 days, trying to correlate microbiota modulation with some aspects of liver injury. We performed glucose (GTT) and insulin (ITT) tolerance tests, serum lipopolysaccharide (LPS) dosage, liver histology, liver and intestine extraction for Western blot and qPCR. Fecal microbiota were investigated via metagenomics. Chronic treatment with pantoprazole induced microbiota modulation and impaired ileum barrier integrity, without an association with insulin resistance. Furthermore, increased circulating LPS and increased Toll-like receptor 4 (TLR4) and TGFß downstream signaling may have an important role in the development of the observed liver microvesicular steatosis and fibrosis. Finally, this model of PPI-induced changes in microbiota might be useful to investigate liver microvesicular steatosis and fibrosis.

Atualização no Tratamento da Hipertensão Arterial Pulmonar / Update on the Treatment of Pulmonary Arterial Hypertension

Resumo Muitos avanços ocorreram nas últimas décadas na terapêutica da hipertensão arterial pulmonar (HAP), uma doença grave, progressiva, incurável e potencialmente fatal. Para seu tratamento adequado, são fundamentais o diagnóstico hemodinâmico e a classificação de sua etiologia, em que várias delas (colagenoses, hipertensão portal, cardiopatia congênitas, esquistossomose) requerem medidas específicas, além do tratamento farmacológico característico para HAP. O tratamento com fármacos-alvo para HAP baseia-se em produtos farmacêuticos que interferem em três vias fisiopatológicas moleculares: da prostaciclina, da endotelina e do óxido nítrico. Tais fármacos apresentam múltiplas apresentações (oral, endovenosa, subcutânea e inalatória) e mudaram a história da HAP. Essas medicações e suas estratégias de uso, assim como particularidades das diferentes formas de HAP, são o foco desta revisão.

Abstract In the last decades, important advances have been made in the treatment of pulmonary arterial hypertension (PAH), a severe, progressive, incurable, and potentially fatal disease. For an adequate therapy, correct hemodynamic diagnosis and etiology classification are fundamental. Many etiologies - rheumatic disease, portal hypertension, congenital heart diseases, schistosomiasis - require specific measures, in addition to drug therapy for PAH. The specific therapy for PAH is based on medications that act on three pathophysiological pathways - prostacyclin, endothelin, and nitric oxide pathways. These drugs have multiple presentations (oral, intravenous, subcutaneous, and inhaled) and have changed the history of PAH. This review presents an overview of drug therapy strategies and different forms and peculiarities of PAH.

Dihydrolipoamide dehydrogenase, pyruvate oxidation, and acetylation-dependent mechanisms intersecting drug iatrogenesis.

In human metabolism, pyruvate dehydrogenase complex (PDC) is one of the most intricate and large multimeric protein systems representing a central hub for cellular homeostasis. The worldwide used antiepileptic drug valproic acid (VPA) may potentially induce teratogenicity or a mild to severe hepatic toxicity, where the underlying mechanisms are not completely understood. This work aims to clarify the mechanisms that intersect VPA-related iatrogenic effects to PDC-associated dihydrolipoamide dehydrogenase (DLD; E3) activity. DLD is also a key enzyme of α-ketoglutarate dehydrogenase, branched-chain α-keto acid dehydrogenase, α-ketoadipate dehydrogenase, and the glycine decarboxylase complexes. The molecular effects of VPA will be reviewed underlining the data that sustain a potential interaction with DLD. The drug-associated effects on lipoic acid-related complexes activity may induce alterations on the flux of metabolites through tricarboxylic acid cycle, branched-chain amino acid oxidation, glycine metabolism and other cellular acetyl-CoA-connected reactions. The biotransformation of VPA involves its complete ß-oxidation in mitochondria causing an imbalance on energy homeostasis. The drug consequences as histone deacetylase inhibitor and thus gene expression modulator have also been recognized. The mitochondrial localization of PDC is unequivocal, but its presence and function in the nucleus were also demonstrated, generating acetyl-CoA, crucial for histone acetylation. Bridging metabolism and epigenetics, this review gathers the evidence of VPA-induced interference with DLD or PDC functions, mainly in animal and cellular models, and highlights the uncharted in human. The consequences of this interaction may have significant impact either in mitochondrial or in nuclear acetyl-CoA-dependent processes.

Update on the Treatment of Pulmonary Arterial Hypertension. / Atualização no Tratamento da Hipertensão Arterial Pulmonar.

In the last decades, important advances have been made in the treatment of pulmonary arterial hypertension (PAH), a severe, progressive, incurable, and potentially fatal disease. For an adequate therapy, correct hemodynamic diagnosis and etiology classification are fundamental. Many etiologies - rheumatic disease, portal hypertension, congenital heart diseases, schistosomiasis - require specific measures, in addition to drug therapy for PAH. The specific therapy for PAH is based on medications that act on three pathophysiological pathways - prostacyclin, endothelin, and nitric oxide pathways. These drugs have multiple presentations (oral, intravenous, subcutaneous, and inhaled) and have changed the history of PAH. This review presents an overview of drug therapy strategies and different forms and peculiarities of PAH.

Muitos avanços ocorreram nas últimas décadas na terapêutica da hipertensão arterial pulmonar (HAP), uma doença grave, progressiva, incurável e potencialmente fatal. Para seu tratamento adequado, são fundamentais o diagnóstico hemodinâmico e a classificação de sua etiologia, em que várias delas (colagenoses, hipertensão portal, cardiopatia congênitas, esquistossomose) requerem medidas específicas, além do tratamento farmacológico característico para HAP. O tratamento com fármacos-alvo para HAP baseia-se em produtos farmacêuticos que interferem em três vias fisiopatológicas moleculares: da prostaciclina, da endotelina e do óxido nítrico. Tais fármacos apresentam múltiplas apresentações (oral, endovenosa, subcutânea e inalatória) e mudaram a história da HAP. Essas medicações e suas estratégias de uso, assim como particularidades das diferentes formas de HAP, são o foco desta revisão.

Phylogenetic relationships of the shearwater taxa Puffinus/ (sensu/ lato) and Calonectris/ (Aves: Procellariiformes: Procellariidae) based on osteological characters.

Shearwaters are among the most diverse groups of Procellariiformes, and the systematics of genera Calonectris, Ardenna and Puffinus (sensu stricto) is particularly complex. Here we present the first morphology-based phylogenetic hypothesis for the group, using 104 osteological characters (23 continuous and 81 discrete) scored for 20 extant species of shearwaters, representing 62.5% of species currently recognized. Both equal and implied weighting were used for phylogenetic analyses, and the final hypothesis presented herein is the strict consensus of the most stable trees produced by the latter. Calonectris was recovered as monophyletic (Relative Bremer Support = 75), while all other members of shearwaters were included in a single, monophyletic grouping: Puffinus (sensu lato) (RBS = 76). The monophyly of Ardenna, as suggested by all molecular-based hypotheses, was not recovered, whereas a monophyletic Puffinus (sensu stricto) is present within the larger clade. The final hypothesis, wherein shearwaters fall into the sister taxa Calonectris and Puffinus (sensu lato), is consistent with earlier classifications based on osteological evidence.

Correction: Correlation between hospitalized patients' demographics, symptoms, comorbidities, and COVID-19 pandemic in Bahia, Brazil.

[This corrects the article DOI: 10.1371/journal.pone.0243966.].

Electrical impedance tomography in pulmonary arterial hypertension.

The characterization of pulmonary arterial hypertension (PAH) relies mainly on right heart catheterization (RHC). Electrical impedance tomography (EIT) provides a non-invasive estimation of lung perfusion that could complement the hemodynamic information from RHC. To assess the association between impedance variation of lung perfusion (ΔZQ) and hemodynamic profile, severity, and prognosis, suspected of PAH or worsening PAH patients were submitted simultaneously to RHC and EIT. Measurements of ΔZQ were obtained. Based on the results of the RHC, 35 patients composed the PAH group, and eight patients, the normopressoric (NP) group. PAH patients showed a significantly reduced ΔZQ compared to the NP group. There was a significant correlation between ΔZQ and hemodynamic parameters, particularly with stroke volume (SV) (r = 0.76; P < 0.001). At 60 months, 15 patients died (43%) and 1 received lung transplantation; at baseline they had worse hemodynamics, and reduced ΔZQ when compared to survivors. Patients with low ΔZQ (≤154.6%.Kg) presented significantly worse survival (P = 0.033). ΔZQ is associated with hemodynamic status of PAH patients, with disease severity and survival, demonstrating EIT as a promising tool for monitoring patients with pulmonary vascular disease.

Inhaled iloprost as third add-on therapy in idiopathic pulmonary arterial hypertension.

Triple combination therapy is suggested in current pulmonary arterial hypertension guidelines in case of unsatisfactory treatment with oral double combination therapy. However, there is a lack of evidence concerning some of the drug combinations currently employed. We demonstrate the clinical and hemodynamical benefits of inhaled iloprost as third add-on therapy in idiopathic pulmonary arterial hypertension.

Correlation between hospitalized patients' demographics, symptoms, comorbidities, and COVID-19 pandemic in Bahia, Brazil.

In this paper, we provide a retrospective cohort study with patients that have been hospitalized for general or intensive care unit admission due to COVID-19, between March 3 and July 29, 2020, in the state of Bahia, Brazil. We aim to correlate those patients' demographics, symptoms and comorbidities, with the risk of mortality from COVID-19, length of hospital stay, and time from diagnosis to definitive outcome. On the basis of a dataset provided by the Health Secretary of the State of Bahia, we selected 3,896 hospitalized patients from a total of 154,868 COVID-19 patients that included non-hospitalized patients and patients with invalid registration in the dataset. Then, we statistically analyzed whether there was a significant correlation between the patient record data and the COVID-19 pandemic, and our main findings reinforced by the use of a multivariable logistic regression were that older age (Odds Ratio [OR] = 1.03, 95% Confidence Interval [CI] = 1.03-1.04, p-value (p) <0.001), an initial symptom of shortness of breath (OR = 1.88, 95% CI = 1.60-2.20, p < 0.001), and the presence of comorbidities, mainly chronic kidney disease (OR = 2.41, 95% CI = 1.67-3.48, p < 0.001) are related to an increased risk of mortality from COVID-19. On the other hand, sore throat (OR = 0.74, 95% CI = 0.58-0.95, p = 0.02) and length of hospital stay (OR = 0.96, 95% CI = 0.58-0.95, p < 0.001) are more related to a reduced risk of mortality from COVID-19. Moreover, a multivariable linear regression conducted with statistically significant variables (p < 0.05) showed that age (OR = 0.97, 95% CI = 0.95-0.98, p < 0.001) and time from diagnosis to definitive outcome (OR = 1.67, 95% CI = 1.64-1.71, p < 0.001) are associated with the length of hospital stay.

Shear stress-exposed pulmonary artery endothelial cells fail to upregulate HSP70 in chronic thromboembolic pulmonary hypertension.

The pathophysiological mechanisms underlying chronic thromboembolic pulmonary hypertension (CTEPH) are still unclear. Endothelial cell (EC) remodeling is believed to contribute to this pulmonary disease triggered by thrombus and hemodynamic forces disbalance. Recently, we showed that HSP70 levels decrease by proatherogenic shear stress. Molecular chaperones play a major role in proteostasis in neurological, cancer and inflammatory/ infectious diseases. To shed light on microvascular responses in CTEPH, we characterized the expression of molecular chaperones and annexin A2, a component of the fibrinolytic system. There is no animal model that reproduces microvascular changes in CTEPH, and this fact led us to isolated endothelial cells from patients with CTEPH undergoing pulmonary endarterectomy (PEA). We exposed CTEPH-EC and control human pulmonary endothelial cells (HPAEC) to high- (15 dynes/cm2) or low- (5 dynes/cm2) shear stress. After high-magnitude shear stress HPAEC upregulated heat shock protein 70kDa (HSP70) and the HSP ER paralogs 78 and 94kDa glucose-regulated protein (GRP78 and 94), whereas CTEPH-ECs failed to exhibit this response. At static conditions, both HSP70 and HSP90 families in CTEPH-EC are decreased. Importantly, immunohistochemistry analysis showed that HSP70 expression was downregulated in vivo, and annexin A2 was upregulated. Interestingly, wound healing and angiogenesis assays revealed that HSP70 inhibition with VER-155008 further impaired CTEPH-EC migratory responses. These results implicate HSP70 as a novel master regulator of endothelial dysfunction in type 4 PH. Overall, we first show that global failure of HSP upregulation is a hallmark of CTEPH pathogenesis and propose HSP70 as a potential biomarker of this condition.

Thrombolysis in acute pulmonary embolism.

OBJECTIVES: Acute pulmonary embolism (APE) is an important cause of cardiovascular mortality, due mainly to hemodynamic instability. In these cases, the recommendation is to perform some reperfusion procedure, with systemic thrombolysis being the main therapy used. However, national data evaluating the efficacy and safety of thrombolysis are scarce. METHODS: Retrospective analysis of a case series. We included 13 patients diagnosed with high-risk APE and 4 patients with intermediate-high risk from a single-center, who were treated with alteplase 100mg. RESULTS: The mean age of the patients was 55 years, most of them female (76.4%). Among the risk factors for VTE were immobilization (41.17%), contraceptive use (35.29%), cancer (17.63%), and previous history of DVT (11.76%). The most frequent clinical manifestations of APE were dyspnea (88.23%), hypoxia (82.35%), hypotension (82.35%), and tachycardia (64.70%). 82.35% of the patients had echocardiographic signs of right ventricular dysfunction, and 52.94% had increased troponin and BNP. Severe bleeding associated with thrombolysis occurred in 17.54% of cases. No patient died due to bleeding. There were 8 deaths from right ventricular failure (47%), 6 in the cases of patients presenting as high-risk APE (35.3%), and 2 in the cases of intermediate-high risk (11.8%). CONCLUSION: Thrombolysis in patients with high-risk APE or intermediate-high risk had a severe bleeding rate of 17.6%. However, the high mortality of this population (47%) due to right ventricular failure justifies the use of this therapeutic modality.

Thrombolysis in acute pulmonary embolism

SUMMARY OBJECTIVES Acute pulmonary embolism (APE) is an important cause of cardiovascular mortality, due mainly to hemodynamic instability. In these cases, the recommendation is to perform some reperfusion procedure, with systemic thrombolysis being the main therapy used. However, national data evaluating the efficacy and safety of thrombolysis are scarce. METHODS Retrospective analysis of a case series. We included 13 patients diagnosed with high-risk APE and 4 patients with intermediate-high risk from a single-center, who were treated with alteplase 100mg. RESULTS The mean age of the patients was 55 years, most of them female (76.4%). Among the risk factors for VTE were immobilization (41.17%), contraceptive use (35.29%), cancer (17.63%), and previous history of DVT (11.76%). The most frequent clinical manifestations of APE were dyspnea (88.23%), hypoxia (82.35%), hypotension (82.35%), and tachycardia (64.70%). 82.35% of the patients had echocardiographic signs of right ventricular dysfunction, and 52.94% had increased troponin and BNP. Severe bleeding associated with thrombolysis occurred in 17.54% of cases. No patient died due to bleeding. There were 8 deaths from right ventricular failure (47%), 6 in the cases of patients presenting as high-risk APE (35.3%), and 2 in the cases of intermediate-high risk (11.8%). CONCLUSION Thrombolysis in patients with high-risk APE or intermediate-high risk had a severe bleeding rate of 17.6%. However, the high mortality of this population (47%) due to right ventricular failure justifies the use of this therapeutic modality.

RESUMO OBJETIVOS A embolia pulmonar aguda (EAP) é uma causa importante de mortalidade cardiovascular ao causar instabilidade hemodinâmica. Nesses casos, a recomendação é a realização de algum procedimento de reperfusão, sendo a trombólise sistêmica a principal terapia utilizada. No entanto, dados nacionais avaliando a eficácia e a segurança da trombólise são escassos. MÉTODO Análise retrospectiva de uma série de casos. Foram incluídos 13 pacientes com o diagnóstico de EAP de alto risco e quatro pacientes de risco intermediário-alto, de um único centro, e que foram tratados com alteplase 100 mg. RESULTADOS A média de idade dos pacientes foi 55 anos, sendo a maioria do gênero feminino (76,4%). Dos fatores de risco para TEV, estavam presentes a imobilização (41,17%), o uso de anticonceptivos (35,29%), câncer (17,63%) e história prévia de TVP (11,76%). As manifestações clínicas mais frequentes da EAP foram dispneia (88,23%), hipóxia (82,35%), hipotensão (82,35%) e taquicardia (64,70%); 82,35% dos pacientes apresentaram sinais ecocardiográficos de disfunção ventricular direita e 52,94% apresentaram aumento da troponina e BNP. Sangramento grave associado à trombólise ocorreu em 17,54% dos casos. Nenhum paciente faleceu em decorrência de sangramento. Houve oito mortes por insuficiência ventricular direita (47%): seis nos casos de paciente que se apresentaram como EAP de alto risco (35,3%) e duas nos casos de risco intermediário-alto (11,8%). CONCLUSÃO A trombólise nos pacientes com EAP de alto risco ou risco intermediário-alto apresentou uma taxa de sangramento grave de 17,6%. No entanto, a alta mortalidade dessa população (47%) por insuficiência ventricular direita justifica o uso desta modalidade terapêutica.

Updating the application of Metarhizium anisopliae to control cattle tick Rhipicephalus microplus (Acari: Ixodidae).

The bovine tick, Rhipicephalus microplus, is the main ectoparasite of cattle and causes loss of billions of dollars worldwide in lost meat, milk, and leather production, as well as control expenses. In addition to systemically impacting the host during the parasitic act, this parasite is also an important disease vector. Traditionally, the main commercial control of the tick is achieved through application of chemical acaricides, which can leave residues in the meat and milk. Moreover, ticks can become resistant to these chemicals due to their massive and incorrect use. Many alternative methods have been tested including vaccines and natural products from plant origin. However, the efficacy of these treatments is variable and limited, especially when used alone. Arthropod-pathogenic fungi, such as Metarhizium anisopliae, are among the natural microbial agents with promising potential to be used alone or in association with other products, for example with chemical acaricides. This article discusses several aspects of bovine tick control related to the use of M. anisopliae, which is one of the most studied and viable alternative tools for effective tick control.

In Utero Dexamethasone Exposure Exacerbates Hepatic Steatosis in Rats That Consume Fructose During Adulthood.

Distinct environmental insults might interact with fructose consumption and contribute to the development of metabolic disorders. To address whether in utero glucocorticoid exposure and fructose intake modulate metabolic responses, adult female Wistar rats were exposed to dexamethasone (DEX) during pregnancy, and the offspring were administered fructose at a later time. Briefly, dams received DEX during the third period of pregnancy, while control dams remained untreated. Offspring born to control and DEX-treated mothers were defined as CTL-off and DEX-off, respectively, while untreated animals were designated CTL-off-CTL and DEX-off-CTL. CLT-off and DEX-off treated with 10% fructose in the drinking water for 8 weeks are referred to as CTL-off-FRU and DEX-off-FRU. We found that fructose promoted glucose intolerance and whole-body gluconeogenesis in both CTL-off-FRU and DEX-off-FRU animals. On the other hand, hepatic lipid accumulation was significantly stimulated in DEX-off-FRU rats when compared to the CTL-off-FRU group. The DEX-off-FRU group also displayed impaired very-low-density lipoprotein (VLDL) production and reduced hepatic expression of apoB, mttp, and sec22b. DEX-off-FRU has lower hepatic levels of autophagy markers. Taken together, our results support the unprecedented notion that in utero glucocorticoid exposure exacerbates hepatic steatosis caused by fructose consumption later in life.

Extended anticoagulation after venous thromboembolism: should it be done?

Most physicians understand venous thromboembolism (VTE) to be an acute and time-limited disease. However, pathophysiological and epidemiological data suggest that in most patients VTE recurrence risk is not resolved after the first 6 months of anticoagulation. Recurrence rates are high and potentially life-threatening. In these cases, it would make sense to prolong anticoagulation for an undetermined length of time. However, what about the bleeding rates, induced by prolonged anticoagulation? Would they not outweigh the benefit of reducing the VTE recurrent risk? How long should anticoagulation be continued, and should all patients suffering from VTE be provided with extended anticoagulation? This review will address the most recent data concerning extended anticoagulation in VTE secondary prophylaxis. The reviews of this paper are available via the supplementary material section.