Explore the vast range of titles available.

Spread through air spaces (STAS) is reportedly associated with worse prognosis in sublobar resections of lung adenocarcinoma. Recently, it was proposed that STAS detected on frozen sections can be an indication for lobectomy instead of sublobar resection. We undertook this study to evaluate the reliability of STAS assessment on frozen sections compared to permanent sections, as well as the associations among STAS, tumor grade, and recurrence-free survival (RFS) after sublobar resection. A total of 163 stage I lung adenocarcinoma resections with frozen sections were identified retrospectively. For each case, and for frozen and permanent sections separately, the presence or absence of STAS, as well as the tumor grade, were recorded. Compared to permanent sections, STAS detection on frozen sections had low sensitivity (55%), low positive predictive value (48%), and fair agreement ( K  = 0.34), whereas there was higher specificity (80%) and negative predictive value (85%). Accuracy was 74%. Tumor grade assessment on frozen sections showed higher sensitivity (77%), positive predictive value (90%), agreement ( K  = 0.72), specificity (94%), and accuracy (87%), and the same negative predictive value (85%). High-grade histology on frozen sections was associated with shorter RFS ( p  = 0.02), whereas STAS on frozen sections was not ( p  = 0.47). Our results suggest that the intraoperative detection of STAS has low sensitivity and positive predictive value. False-positive results may lead to overtreatment of patients with lung cancer. The determination of tumor grade on frozen sections offers better sensitivity and specificity, plus it is associated with RFS, whereas STAS on frozen sections is not. Further study is needed to explore the utility of assessing tumor grade on frozen sections.

Abstract The impact of lipotoxicity on the development of lung fibrosis is unclear. Saturated fatty acids, such as palmitic acid (PA), activate endoplasmic reticulum (ER) stress, a cellular stress response associated with the development of idiopathic pulmonary fibrosis (IPF). We tested the hypothesis that PA increases susceptibility to lung epithelial cell death and experimental fibrosis by modulating ER stress. Total liquid chromatography and mass spectrometry were used to measure fatty acid content in IPF lungs. Wild-type mice were fed a high-fat diet (HFD) rich in PA or a standard diet and subjected to bleomycin-induced lung injury. Lung fibrosis was determined by hydroxyproline content. Mouse lung epithelial cells were treated with PA. ER stress and cell death were assessed by Western blotting, TUNEL staining, and cell viability assays. IPF lungs had a higher level of PA compared with controls. Bleomycin-exposed mice fed an HFD had significantly increased pulmonary fibrosis associated with increased cell death and ER stress compared with those fed a standard diet. PA increased apoptosis and activation of the unfolded protein response in lung epithelial cells. This was attenuated by genetic deletion and chemical inhibition of CD36, a fatty acid transporter. In conclusion, consumption of an HFD rich in saturated fat increases susceptibility to lung fibrosis and ER stress, and PA mediates lung epithelial cell death and ER stress via CD36. These findings demonstrate that lipotoxicity may have a significant impact on the development of lung injury and fibrosis by enhancing pro-death ER stress pathways.

Voltage sensor domains (VSDs) transducer changes in the electrical field across cell membranes into conformational changes that alter the activation state of an effector domain. Structural and biophysical data on the VSD from Ci-VSP reveal the first view of this domain in the resting state, providing new insight into voltage-dependent structural transitions. The transduction of transmembrane electric fields into protein motion has an essential role in the generation and propagation of cellular signals. Voltage-sensing domains (VSDs) carry out these functions through reorientations of positive charges in the S4 helix. Here, we determined crystal structures of the Ciona intestinalis VSD (Ci-VSD) in putatively active and resting conformations. S4 undergoes an ~5-Å displacement along its main axis, accompanied by an ~60° rotation. This movement is stabilized by an exchange in countercharge partners in helices S1 and S3 that generates an estimated net charge transfer of ~1 e o . Gating charges move relative to a ''hydrophobic gasket' that electrically divides intra- and extracellular compartments. EPR spectroscopy confirms the limited nature of S4 movement in a membrane environment. These results provide an explicit mechanism for voltage sensing and set the basis for electromechanical coupling in voltage-dependent enzymes and ion channels.

Hypertension (HTN) is the leading cause of premature deaths worldwide and the main preventable risk factor for cardiovascular diseases. Therefore, there is a current need for new therapeutics to manage this condition. In this regard, protein hydrolysates containing antihypertensive bioactive peptides are of increasing interest. Thus, agri-food industry byproducts have emerged as a valuable source to obtain these hydrolysates as they are rich in proteins and inexpensive. Among these, byproducts from animal origin stand out as they are abundantly generated worldwide. Hence, this review is focused on evaluating the potential role of chicken slaughterhouse byproducts as a source of peptides for managing HTN. Several of these byproducts such as blood, bones, skins, and especially, chicken feet have been used to obtain protein hydrolysates with angiotensin-converting enzyme (ACE)-inhibitory activity and blood pressure-lowering effects. An increase in levels of endogenous antioxidant compounds, a reduction in ACE activity, and an improvement of HTN-associated endothelial dysfunction were the mechanisms underlying their effects. However, most of these studies were carried out in animal models, and further clinical studies are needed in order to confirm these antihypertensive properties. This would increase the value of these byproducts, contributing to the circular economy model of slaughterhouses.

Obesity, besides being a problem of metabolic dysfunction, constitutes a risk factor for psychological disorders. Experimental models of diet-induced obesity have revealed that obese animals are prone to anxious and depressive-like behaviors. The present study aimed to evaluate whether Bifidobacterium pseudocatenulatum CECT 7765 could reverse the neurobehavioral consequences of obesity in a high-fat diet (HFD) fed mouse model via regulation of the gut–brain axis. Adult male wild-type C57BL-6 mice were fed a standard diet or HFD, supplemented with either placebo or the bifidobacterial strain for 13 weeks. Behavioral tests were performed, and immune and neuroendocrine parameters were analyzed including leptin and corticosterone and their receptors, Toll-like receptor 2 (TLR2) and neurotransmitters. We found that obese mice showed anhedonia ( p  < 0.050) indicative of a depressive-like behavior and an exaggerated hypothalamic-pituitary axis (HPA)-mediated stress response to acute physical ( p  < 0.001) and social stress ( p  < 0.050), but these alterations were ameliorated by B. pseudocatenulatum CECT 7765 ( p  < 0.050). These behavioral effects were parallel to reductions of the obesity-associated hyperleptinemia ( p  < 0.001) and restoration of leptin signaling ( p  < 0.050), along with fat mass loss ( p  < 0.010). B. pseudocatenulatum CECT 7765 administration also led to restoration of the obesity-induced reductions in adrenaline in the hypothalamus ( p  < 0.010), involved in the hypothalamic control of energy balance. Furthermore, the bifidobacterial strain reduced the obesity-induced upregulation of TLR2 protein or gene expression in the intestine ( p  < 0.010) and the hippocampus ( p  < 0.050) and restored the alterations of 5-HT levels in the hippocampus ( p  < 0.050), which could contribute to attenuating the obesity-associated depressive-like behavior ( p  < 0.050). In summary, the results indicate that B. pseudocatenulatum CECT 7765 could play a role in depressive behavior comorbid with obesity via regulation of endocrine and immune mediators of the gut–brain axis.

An ever-growing body of evidence has shown that voltage-gated ion channels are likely molecular systems that display hysteresis in their activity. This phenomenon manifests in the form of dynamic changes in both their voltage dependence of activity and their deactivation kinetics. The goal of this review is to provide a clear definition of hysteresis in terms of the behavior of voltage-gated channels. This review will discuss the basic behavior of voltage-gated channel activity and how they make these proteins into systems displaying hysteresis. It will also provide a perspective on putative mechanisms underlying hysteresis and explain its potential physiological relevance. It is uncertain whether all channels display hysteresis in their behavior. However, the suggested notion that ion channels are hysteretic systems directly collides with the well-accepted notion that ion channel activity is stochastic. This is because hysteretic systems are regarded to have “memory” of previous events while stochastic processes are regarded as “memoryless.” This review will address this apparent contradiction, providing arguments for the existence of processes that can be simultaneously hysteretic and stochastic.

We diagnosed neuroinvasive tularemia in a neonate in Utah who had culture-negative pleocytosis in cerebrospinal fluid, rim-enhancing lesions on brain magnetic resonance imaging, and blood microbial cell-free DNA Francisella tularensis detection. Maternal history, serologic testing, and Francisella sp. identified in the fallopian tube by immunohistochemistry and 16S rRNA gene PCR strongly support congenital infection.

Murine typhus, a fleaborne disease caused by the bacterium Rickettsia typhi, is found throughout temperate and tropical regions of the world. Transmission of R. typhi to humans involves several species of fleas, and most infections result from direct inoculation of R. typhi-infected flea feces into abrasions in the skin. We describe the transmission of R. typhi from an organ donor in Texas, USA, to 2 kidney transplant recipients. The donor and 1 recipient died from the infection. The occurrence of R. typhi transmission via transplantation is a harbinger for the reemergence of murine typhus in some of the most densely populated metropolitan areas of the United States. Our findings reinforce the need to improve healthcare provider and public awareness of this life-threatening but treatable infection.

Tickborne infections are challenging to diagnose, particularly among solid organ transplant recipients. We report a US case of donor-derived ehrlichiosis from a living kidney donation that highlights how screening for living donors may miss tickborne infections. Clinicians should consider the epidemiology of the donor when screening donations and evaluating recipients for donor-derived infection.

Serum prostate-specific antigen (PSA) is the most widely used marker for diagnosing prostate cancer (PCa). It lacks specificity and predictive value, resulting in inaccurate diagnoses and overtreatment of the disease. The aim of this study was to assess the usefulness of plasma telomerase reverse transcriptase (hTERT) mRNA as a diagnostic and prognostic tool for PCa and its association with clinicopathological parameters of tumors. Plasma hTERT mRNA levels were determined by qRT-PCR in 105 consecutive patients with elevated PSA levels and in 68 healthy volunteers. The diagnostic accuracy, the efficacy as a prognostic factor of biochemical recurrence and the association with tumor clinicopathological parameters of plasma hTERT mRNA and serum PSA tests were determined using univariate and multivariate analyses. The results show that plasma hTERT mRNA is a non-invasive biomarker for PCa diagnosis that shows higher sensitivity (85% vs. 83%), specificity (90% vs. 47%), positive predictive value (83% vs. 56%), and negative predictive value (92% vs. 77%) than serum PSA. Plasma hTERT mRNA is significantly associated with poor prognosis tumor clinicopathological parameters and is a significant independent predictor of PCa (p<0.0001). Univariate analysis identified plasma hTERT mRNA (but not serum PSA) as a significant prognostic factor of biochemical recurrence. Plasma hTERT mRNA Kaplan-Meier curves confirmed the significant differences between groups and patients with higher levels than the cut-off value showed diminished recurrence-free survival (p=0.004), whereas no differences were observed with serum PSA (p=0.38). Multivariate analysis indicated that plasma hTERT mRNA (but not serum PSA) and stage were significantly associated with biochemical recurrence. Overall, these findings indicate that hTERT mRNA is a useful non-invasive tumor marker for the molecular diagnosis of PCa, affording a greater diagnostic and prognostic accuracy than the PSA assay and may be of relevance in the follow-up of the disease.