Influence of short- and long-term administration of Melengestrol acetate on estrus activity and reproductive performance of nulliparous Barki ewes

In Egypt, research focusing on estrous synchronization in small ruminants based on Melengestrol acetate (MGA) supplementation, particularly in nulliparous ewes, is still lacking. The present work aimed to evaluate effect of long-term and short-term administration of melengestrol acetate (MGA) treatments on estrus synchronization and reproductive performance of nulliparous Barki Ewes. This study was performed in Siwa Oasis Research Station (Tegzerty Experimental Farm for animal production), belonged to Desert Research Center, Egypt. Forty five nulliparous Barki ewes with age ranging from 15.5 to 16.5 months, and 38 ± 0.23 kg average live body weight were assigned to one of three groups: (1) control (C, n = 15); (2) long-term treatment with MGA (n = 15, 0.22 mg/ewe/d for 14 days) and (3) short-term treatment with MGA (n = 15, 0.22 mg/ewe/d for 7 days). At the end of MGA treatment (14 or 7 d) all treated ewes were injected by 600 IU PMSG intramuscularly. The results showed that, ewes treated with MGA exhibited highest (

Investigation and Statistical Analysis for Optimizing Surface Roughness, Cutting Forces, Temperature, and Productivity in Turning Grey Cast Iron

This paper investigated the influence of cutting parameters, including feed rate, cutting speed, tool nose radius, and wet or dry cutting conditions, on the resultant force, cutting edge/workpiece temperature, and surface roughness when turning grey cast iron. Results showed that increasing the feed rate increased the resultant force, cutting temperature, and surface roughness. At the same time, increasing the cutting speed and nose radius increased the cutting temperature, which in turn reduced the resultant force. For practical applications, basic mathematical calculations based on the sole effect of each parameter on the output of the experiments were used to estimate the extent of percentage increase in cutting temperature due to increasing feed rate, cutting speed, and nose radius. Similarly, the same approach was used to estimate the effect of increasing feed rate, cutting speed, and nose radius on average surface roughness. Results showed that increasing the feed rate increases the cutting temperature by 5 to 11% depending on the nose radius and cutting speed. On the other hand, increasing the cutting speed was found to have limited effect on cutting temperature with small nose radius whereas this effect increases with increasing the nose radius reaching about 11%. Increasing the nose radius also increases the cutting temperature, depending mainly on cutting speed, reaching a maximum of 21% at higher cutting speeds. Results also showed that increasing the feed rate increased the average surface roughness considerably to about 120% at high cutting speeds and a large nose radius. On the other hand, increasing the cutting speed and nose radius reduced the surface roughness (i.e., improved surface quality) by a maximum of 29 and 23%, respectively. In order to study the combined effects of the cutting parameters on the three responses, namely, the resultant cutting force, cutting temperature, and surface roughness, full factorial design and ANOVA were used, where it was found to be in good agreement with mathematical calculations. Additionally, the desirability function optimization tool was used to minimize the measured responses whilst maximizing the material removal rate

Diffuse alveolar damage (DAD) resulting from coronavirus disease 2019 Infection is Morphologically Indistinguishable from Other Causes of DAD

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162704/2/his14180.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162704/1/his14180_am.pd

Nicotinic Receptor M3 Transmembrane Domain: Position 8Ј Contributes to Channel Gating

ABSTRACT The nicotinic acetylcholine receptor (nAChR) is a pentamer of homologous subunits with composition ␣ 2 ␤⑀␦ in adult muscle. Each subunit contains four transmembrane domains (M1-M4). Position 8Ј of the M3 domain is phenylalanine in all heteromeric ␣ subunits, whereas it is a hydrophobic nonaromatic residue in non-␣ subunits. Given this peculiar conservation pattern, we studied its contribution to muscle nAChR activation by combining mutagenesis with single-channel kinetic analysis. Construction of nAChRs carrying different numbers of phenylalanine residues at 8Ј reveals that the mean open time decreases as a function of the number of phenylalanine residues. Thus, all subunits contribute through this position independently and additively to the channel closing rate. The impairment of channel opening increases when the number of phenylalanine residues at 8Ј increases from two (wild-type nAChR) to five. The gating equilibrium constant of the latter mutant nAChR is 13-fold lower than that of the wild-type nAChR. The replacement of ␣F8Ј, ␤L8Ј, ␦L8Ј, and ⑀V8Ј by a series of hydrophobic amino acids reveals that the structural bases of the observed kinetic effects are nonequivalent among subunits. In the ␣ subunit, hydrophobic amino acids at 8Ј lead to prolonged channel lifetimes, whereas they lead either to normal kinetics (␦ and ⑀ subunits) or impaired channel gating (␤ subunit) in the non-␣ subunits. The overall results indicate that 8Ј positions of the M3 domains of all subunits contribute to channel gating

Birth weight influences cardiac structure, function and disease risk: evidence of a causal association

Background and Aims Low birth weight is a common pregnancy complication, which has been associated with higher risk of cardiometabolic disease in later life. Prior Mendelian randomization (MR) studies exploring this question do not distinguish the mechanistic contributions of variants that directly influence birth weight through the foetal genome (direct foetal effects), vs. variants influencing birth weight indirectly by causing an adverse intrauterine environment (indirect maternal effects). In this study, MR was used to assess whether birth weight, independent of intrauterine influences, is associated with cardiovascular disease risk and measures of adverse cardiac structure and function. Methods Uncorrelated (r2 < .001), genome-wide significant (P < 5 × 10−8) single nucleotide polymorphisms were extracted from genome-wide association studies summary statistics for birth weight overall, and after isolating direct foetal effects only. Inverse-variance weighted MR was utilized for analyses on outcomes of atrial fibrillation, coronary artery disease, heart failure, ischaemic stroke, and 16 measures of cardiac structure and function. Multiple comparisons were accounted for by Benjamini–Hochberg correction. Results Lower genetically-predicted birth weight, isolating direct foetal effects only, was associated with an increased risk of coronary artery disease (odds ratio 1.21, 95% confidence interval 1.06–1.37; P = .031), smaller chamber volumes, and lower stroke volume, but higher contractility. Conclusions The results of this study support a causal role of low birth weight in cardiovascular disease, even after accounting for the influence of the intrauterine environment. This suggests that individuals with a low birth weight may benefit from early targeted cardiovascular disease prevention strategies, independent of whether this was linked to an adverse intrauterine environment during gestation

Exploiting inflammation for therapeutic gain in pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy associated with &#60;5% 5-year survival, in which standard chemotherapeutics have limited benefit. The disease is associated with significant intra- and peritumoral inflammation and failure of protective immunosurveillance. Indeed, inflammatory signals are implicated in both tumour initiation and tumour progression. The major pathways regulating PDAC-associated inflammation are now being explored. Activation of leukocytes, and upregulation of cytokine and chemokine signalling pathways, both have been shown to modulate PDAC progression. Therefore, targeting inflammatory pathways may be of benefit as part of a multi-target approach to PDAC therapy. This review explores the pathways known to modulate inflammation at different stages of tumour development, drawing conclusions on their potential as therapeutic targets in PDAC

Probiotics versus antibiotic decontamination of the digestive tract: infection and mortality

Purpose: Selective decontamination of the digestive tract (SDD) has been shown to decrease the infection rate and mortality in intensive care units (ICUs); Lactobacillus plantarum 299/299v plus fibre (LAB) has been used for infection prevention and does not harbour the potential disadvantages of antibiotics. The objective was to assess whether LAB is not inferior to SDD in infection prevention. Methods: Two hundred fifty-four consecutive ICU patients with expected mechanical ventilation ≥48 h and/or expected ICU stay ≥72 h were assigned to receive SDD: four times daily an oral paste (polymyxin E

Targeting CXCR4 (CXC Chemokine Receptor Type 4) for Molecular Imaging of Aldosterone-Producing Adenoma

Primary aldosteronism is the most frequent cause of secondary hypertension and is associated with increased morbidity and mortality compared with hypertensive controls. The central diagnostic challenge is the differentiation between bilateral and unilateral disease, which determines treatment options. Bilateral adrenal venous sampling, currently recommended for differential diagnosis, is an invasive procedure with several drawbacks, making it desirable to develop novel noninvasive diagnostic tools. When investigating the expression pattern of chemokine receptors by quantitative real-time polymerase chain reaction and immunohistochemistry, we observed high expression of CXCR4 (CXC chemokine receptor type 4) in aldosterone-producing tissue in normal adrenals, adjacent adrenal cortex from adrenocortical adenomas, and in aldosterone-producing adenomas (APA), correlating strongly with the expression of CYP11B2 (aldosterone synthase). In contrast, CXCR4 was not detected in the majority of nonfunctioning adenomas that are frequently found coincidently. The specific CXCR4 ligand 68Ga-pentixafor has recently been established as radiotracer for molecular imaging of CXCR4 expression and showed strong and specific binding to cryosections of APAs in our study. We further investigated 9 patients with primary aldosteronism because of APA by 68Ga-pentixafor-positron emission tomography. The tracer uptake was significantly higher on the side of increased adrenocortical aldosterone secretion in patients with APAs compared with patients investigated by 68Ga-pentixafor-positron emission tomography for other causes. Molecular imaging of aldosterone-producing tissue by a CXCR4-specific ligand may, therefore, be a highly promising tool for noninvasive characterization of patients with APAs

Pancreatic cancer cells resistance to gemcitabine: the role of MUC4 mucin

BACKGROUND: A major obstacle to the successful management of pancreatic cancer is to acquire resistance to the existing chemotherapeutic agents. Resistance to gemcitabine, the standard first-line chemotherapeutic agent for advanced and metastatic pancreatic cancer, is mainly attributed to an altered apoptotic threshold in the pancreatic cancer. The MUC4 transmembrane glycoprotein is aberrantly overexpressed in the pancreatic cancer and recently, has been shown to increase pancreatic tumour cell growth by the inhibition of apoptosis. METHODS: Effect of MUC4 on pancreatic cancer cells resistance to gemcitabine was studied in MUC4-expressing and MUC4-knocked down pancreatic cancer cell lines after treatment with gemcitabine by Annexin-V staining, DNA fragmentation assay, assessment of mitochondrial cytochrome c release, immunoblotting and co-immunoprecipitation techniques. RESULTS: Annexin-V staining and DNA fragmentation experiment demonstrated that MUC4 protects CD18/HPAF pancreatic cancer cells from gemcitabine-induced apoptosis. In concert with these results, MUC4 also attenuated mitochondrial cytochrome c release and the activation of caspase-9. Further, our results showed that MUC4 exerts anti-apoptotic function through HER2/extracellular signal-regulated kinase-dependent phosphorylation and inactivation of the pro-apoptotic protein Bad. CONCLUSION: Our results elucidate the function of MUC4 in imparting resistance to pancreatic cancer cells against gemcitabine through the activation of anti-apoptotic pathways and, thereby, promoting cell survival