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In 2 experiments, we investigated whether diet composition plays a role in pathogen-induced anorexia, the voluntary reduction in ADFI during infection in broilers. We hypothesized that either energy or CP dietary content could influence the extent of anorexia in Ross 308 broilers and infection outcomes with Eimeria maxima. From d 13 of age, half of the birds were infected, and half were uninfected. ADFI was measured daily, and BW every 3 d until d 29. Oocyst excretion was measured daily from d 17 to 23. The impact of parasitism on the small intestine was assessed on d 19 and 25. In Experiment 1, 336 birds were offered diets progressively diluted with lignocellulose, starting from a diet with 3,105 (kcal ME/kg) and 20% CP. There was a significant interaction between infection and diet on ADFI during the acute stage of infection (d 17 to 21) for control birds diet dilution decreased ADFI and consequently reduced energy and CP intake. For infected birds, diet dilution increased ADFI, leading to the same energy and CP intake across diets. Oocyst excretion and villi length to crypt depth ratio (VCR) were constant across infected treatments. In Experiment 2, 432 birds were offered diets with constant ME (3,105 kcal/kg), but different CP contents (24, 20, 26, and 12%). Infection significantly reduced ADFI. Although there was no interaction between infection and diet on ADFI, there was an interaction on CP intake during the acute stage of infection. Infected birds on the 20% CP diet achieved the same CP intake as uninfected birds. There were no differences in the VCR and ADG of the infected birds on 24, 20 and 16% CP treatments, but birds on 12% had the lowest ADG and excreted more oocysts. We suggest that during infection, birds target a nutrient resource intake, which appears to be beneficial for infection outcomes, while at the same time they avoid excess protein intake. We conclude that different mechanisms regulate ADFI in infected and uninfected birds.Immunosuppressive CD4+Foxp3+ regulatory T cells (Tregs) promote tumor immune evasion and thus targeting of Tregs has become an strategy in cancer immunotherapy. Tumor necrosis factor receptor 2 (TNFR2) is highly expressed and important for the immunosuppressive function of Tregs in humans and mice. Thus, the benefit of targeting TNFR2 in cancer immunotherapy merits more investigation. A previous report identified a new murine monoclonal anti-TNFR2 antibody (designated TY101), which showed therapeutic efficacy in murine cancer models, but its mechanism of action was less understood. In this study, the capacity of a combination of immunostimulants to enhance the effect of this inhibitor of Tregs was investigated. We examined the efficacy of TY101 as an anti-tumor immune reagent combined with HMGN1 (N1, a dendritic cell activating TLR4 agonist) and R848 (a synthetic TLR7/8 agonist). This immunotherapeutic combination exerted synergistic antitumor effects as compared with any single treatment. The antitumor response was mainly mediated by the depletion of Tregs and stimulation of cytotoxic CD8 T cell activation. The result also suggested that the effect of TY101 was similar to that of anti-PD-L1 when used in combination with these immunostimulants. Therefore, we propose that treatment strategies of antagonizing TNFR2 on Tregs would behave as potent checkpoint inhibitors and can potentially be utilized to develop a novel antitumor immunotherapy.
To clarify the frequency and correlates of using applications for monitoring and increase of health and well-being among middle-aged and older adults during the COVID-19 pandemic in Germany.
Data were used from the nationally representative German Ageing Survey (n=3,174 individuals in the analytical sample; June/July 2020). The frequency of using applications for monitoring and increasing health and well-being (from daily to never) was used as main outcome measure.
Among individuals with access to the internet, 76% never used applications for monitoring and increase of health and well-being, whereas about 13% were rare and 11% were frequent users of such applications. Multinomial regressions showed that the likelihood of being a rare user (compared to never users of such applications) was positively associated with being male [RRR 0.74, 95% CI 0.59-0.93], the frequency of walks [e.g., several times a week compared to never RRR 2.76, 95% CI 1.15-6.59] and worse self-rated health [RRR 1.33, 95% CI 1.11-1.59]. Furthermore, the likelihood of being a frequent user (compared to never users) was positively associated with younger age [RRR 0.96, 95% CI 0.94-0.98] and the frequency of walks [daily compared to never RRR 2.61, 95% CI 1.07-6.35].
Applications for monitoring and increasing health and well-being are used by about one out of four middle-aged and older individuals with access to the internet in Germany during the COVID-19 pandemic. In international comparison, the proportion of users is rather low. Determining the factors associated with such use may help to address non-users.
Applications for monitoring and increasing health and well-being are used by about one out of four middle-aged and older individuals with access to the internet in Germany during the COVID-19 pandemic. In international comparison, the proportion of users is rather low. Determining the factors associated with such use may help to address non-users.Selenoproteins are a small family of proteins containing the trace element selenium in form of the rare amino acid selenocysteine (Sec), which is decoded by the UGA codon. In humans, a number of pathogenic variants in genes encoding distinct selenoproteins or selenoprotein biosynthesis factors have been identified. Pathogenic variants in selenocysteine synthase (SEPSECS), which catalyzes the last step in Sec-tRNA[Ser]Sec biosynthesis, were reported in children suffering from progressive cerebello-cerebral atrophy. To understand the pathomechanism associated with SEPSECS deficiency, we generated a novel mouse model recapitulating the respective human pathogenic p.Y334C variant in the murine Sepsecs gene (SepsecsY334C). Unlike in patients, pups homozygous for the p.Y334C variant died perinatally with signs of cardio-respiratory failure. Perinatal death is reminiscent of the Sedaghatian spondylometaphyseal dysplasia disorder in humans, which is caused by pathogenic variants in the gene encoding the selenoprotein incompletely compensate for impaired GPX4 activity.Peroxisome proliferator-activated receptor gamma (PPARγ), a member of the nuclear receptor superfamily is an excellent example of targets that orchestrates cancer, inflammation, lipid and glucose metabolism. We report a protocol for the development of novel PPARγ antagonists by employing 3D QSAR based virtual screening for the identification of ligands with anticancer properties. The models are generated based on a large and diverse set of PPARγ antagonist ligands by the HYPOGEN algorithm using Discovery Studio 2019 drug design software. Among the 10 hypotheses generated, Hypotheses 2 showed the highest correlation coefficient values of 0.95 with less RMS deviation of 1.193. Validation of the developed pharmacophore model was performed by Fischer's randomization and screening against test and decoy set. The GH score or goodness score was found to be 0.81 indicating moderate to a good model. The selected pharmacophore model Hypo 2 was used as a query model for further screening of 11,145 compounds from the PubChem, sc-PDB structure database, and designed novel ligands. Based on fit values and ADMET filter, the final 10 compounds with the predicated activity of ≤ 3 nM were subjected for docking analysis. Docking analysis revealed the unique binding mode with hydrophobic amino acid that can cause destabilization of the H12 which is an important molecular mechanism to prove its antagonist action. Based on high CDocker scores, Cpd31 was synthesized, purified, analyzed and screened for PPARγ competitive binding by TR-FRET assay. The biochemical protein binding results matched the predicted results. Further, Cpd31 was screened against cancer cells and validated the results.
To explore models of maternal healthcare for African refugee women and their acceptability, cost and associated outcomes.
A systematic review and content analysis SETTING High-income countries PARTICIPANTS African refugee women REVIEW METHODS Seven databases were searched to identify peer-reviewed literature using defined keywords and inclusion criteria. Two authors independently screened the search findings and the full texts of eligible studies. The quality of the included studies was appraised, and the findings were analysed using a template.
Nine studies met the criteria. Four studies were qualitative, two quantitative and three studies used mixed methods. Four models of care were identified midwifery-led care, hospital-based integrated care, primary care physician-led integrated care and a holistic refugee-specific primary healthcare model (one-stop shop). Issues affecting care delivery were identified as communication barriers, low health literacy, high transport costs and low engagement of refugeecurity to cover costs.
Cerebrospinal fluid (CSF) leak that occurred in the lateral sphenoid sinus is a rare and difficult case. This paper aims to report a case of defect closure in the lateral recess of the sphenoid sinus endoscopically with a transpterygoid approach.
A 38-year-old Indonesian woman reported a CSF leak, and identified a defect in the lateral recess of the left sphenoid sinus. CSF leak was repaired with endoscopic transethmoid-pterygoid or transpterygoid endoscopic surgery and no CSF leak was found. The surgical procedure was successful even though it was only performed by an otorhinolaryngologist.
Endoscopic transethmoid-pterygoid or transpterygoid endoscopic surgery is effective in repairing defects in the lateral recess of the sphenoid sinus in which surgical procedure is performed by a single otorhinolaryngologist.
Endoscopic transpterygoid approach gained access to lateral site of sphenoid sinus was an effective approach in managing CSF leak of lateral sphenoid recess. Closure of the defect using a bone graft and mucosa of the middle turbinate was proven to be effective. It had been carried out successfully in Indonesia.
Endoscopic transpterygoid approach gained access to lateral site of sphenoid sinus was an effective approach in managing CSF leak of lateral sphenoid recess. Closure of the defect using a bone graft and mucosa of the middle turbinate was proven to be effective. It had been carried out successfully in Indonesia.
Paraganglioma of the urinary bladder is unusual and reported rarely. The patient usually presents with the complaint of hematuria and fluctuating blood pressure.
We discuss the case of a 21-year old male, who had been experiencing gross hematuria, was found to have a mass on ultrasonography. Further evaluation with contrast-enhanced computerized tomography (CECT) revealed an irregular soft tissue density of endophytic mass arising from the left posterior wall of the urinary bladder. The histopathological examination of the excised mass was suggestive of a tumor of neural origin, which was further confirmed as paraganglioma by immunohistochemistry.
Imaging prior to the surgery must be done for a provisional diagnosis of paraganglioma to avoid fluctuating blood pressure during elective surgery. GW806742X On histopathological examination tumor cells are arranged in the nest like fashion forming a specific 'Zellballen' pattern. Positive staining for synaptophysin and chromogranin in immunohistochemistry confirms the diagnosis.
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