Neutrophils in the Spotlight-An Analysis of Neutrophil Function and Phenotype in ARDS.

Acute respiratory distress syndrome (ARDS) is a complex disease pattern in which pathogenesis polymorphonuclear neutrophil granulocytes (PMN) play a key role. In previous experiments, we could show that interaction with collagen III (an important component of pulmonary tissue) is a possible trigger of neutrophil reactive oxygen species (ROS) production. To investigate possible correlations, further elucidate ARDS pathophysiology, and maybe find pharmacological targets, we evaluated PMNs from blood (circulating PMNs: cPMNs) and tracheal secretion (tPMNs) from patients with and without ARDS with regard to function and phenotype.

Modeling the acute mucosal toxicity to fractionated radiotherapy combined with the ATM inhibitor WSD0628.

ATM inhibitors are being developed as radiosensitizers to improve the antitumor effects of radiotherapy, but ATM inhibition can also radiosensitize normal tissues. Therefore, understanding the elevated risk for normal tissue toxicities is critical for radiosensitizer development. This study focused on modeling the relationship between acute mucosal toxicity, radiation dose, fractionation schedule, and radiosensitizer exposure.

Highly neurogenic glia from human and mouse myenteric ganglia generate functional neurons following culture and transplantation into the gut.

Enteric neural stem cell (ENSC) therapy offers great promise for neurointestinal diseases; however, current isolation methods yield insufficient neurons for regenerative applications. Multiomic profiling of enteric glial cells (EGCs) suggests that subpopulations within myenteric ganglia (MyGa) are a reservoir of highly neurogenic ENSCs. Here, we describe protocols to enrich for intraganglionic EGCs by isolating intact fragments of MyGa, generating cultures with higher neuronal purity than traditional methodologies isolating intramuscular single cells (IM-SCs).

DNA-PK inhibition shows differential radiosensitization in orthotopic GBM PDX models based on DDR pathway deficits.

Glioblastoma (GBM) remains one of the most therapy-resistant malignancies with frequent local failures despite aggressive surgery, chemotherapy, and ionizing radiation (IR). Small molecule inhibitors of DNA-dependent protein kinase (DNA-PKi's) are potent radiosensitizers currently in clinical trials. Determining which patients may benefit from radiosensitization with DNA-PKi's is critical to avoid unnecessary increased risk of normal tissue toxicity.

Gender differences in the observation of gesture direction: a physiological study.

Intransitive gestures are expressive and symbolic, whereas pantomimes are object-related actions. These gestures convey different meanings depending on whether they are directed toward (TB) or away from the body (AB). TB gestures express mental states (intransitive) or hygiene/nutritional activities (pantomime), while AB gestures modify the behaviour of the observer (intransitive) or demonstrate tool use with an object (pantomime).

Resolving Resident Colonic Muscularis Macrophage Diversity and Plasticity During Colitis.

Background: Immune cell populations in the intestinal muscularis propria during colitis are poorly resolved. Maintaining homeostasis in this niche is critical, highlighted by the poorer prognosis of inflammatory bowel disease associated with muscularis propria inflammation.

Methods: This study utilizes single-cell RNA sequencing to survey the immune cell populations within the muscularis propria of normal colon and dextran sodium sulfate-induced colitis.

Enteric neural stem cell transplant restores gut motility in mice with Hirschsprung disease.

The goal of this study was to determine if transplantation of enteric neural stem cells (ENSCs) can rescue the enteric nervous system, restore gut motility, reduce colonic inflammation, and improve survival in the Ednrb-KO mouse model of Hirschsprung disease (HSCR). ENSCs were isolated from mouse intestine, expanded to form neurospheres, and microinjected into the colons of recipient Ednrb-KO mice. Transplanted ENSCs were identified in recipient colons as cell clusters in "neo-ganglia.

Mature enteric neurons have the capacity to reinnervate the intestine with glial cells as their guide.

Here, we establish that plasticity exists within the postnatal enteric nervous system by demonstrating the reinnervation potential of post-mitotic enteric neurons (ENs). Employing BAF53b-Cre mice for selective neuronal tracing, the reinnervation capabilities of mature postnatal ENs are shown across multiple model systems. Isolated ENs regenerate neurites in vitro, with neurite complexity and direction influenced by contact with enteric glial cells (EGCs).

The contribution of eye gaze and movement kinematics to the expression and identification of social intention in object-directed motor actions.

The intention to include another person in an interaction (i.e., social intention) is known to influence the spatio-temporal characteristics of motor performances.

Short-chain fatty acids inhibit bacterial plasmid transfer through conjugation and in chicken tissue explants.

The animal gut acts as a potent reservoir for spreading and maintaining conjugative plasmids that confer antimicrobial resistance (AMR), fitness, and virulence attributes. Interventions that inhibit the continued emergence and expansion of AMR and virulent strains in agricultural and clinical environments are greatly desired. This study aims to determine the presence and efficacy of short-chain fatty acids (SCFA) inhibitory effects on the conjugal transfer of AMR plasmids.

Mutation analysis in individual circulating tumor cells depicts intratumor heterogeneity in melanoma.

Circulating tumor DNA (ctDNA) is the cornerstone of liquid biopsy diagnostics, revealing clinically relevant genomic aberrations from blood of cancer patients. Genomic analysis of single circulating tumor cells (CTCs) could provide additional insights into intra-patient heterogeneity, but it requires whole-genome amplification (WGA) of DNA, which might introduce bias. Here, we describe a novel approach based on mass spectrometry for mutation detection from individual CTCs not requiring WGA and complex bioinformatics pipelines.

Anterior pituitary gland volume mediates associations between pubertal hormones and changes in transdiagnostic symptoms in youth.

The pituitary gland (PG) plays a central role in the production and secretion of pubertal hormones, with documented links to the emergence and increase in mental health symptoms known to occur during adolescence. Although much of the literature has focused on examining whole PG volume, recent findings suggest that there are associations among pubertal hormone levels, including dehydroepiandrosterone (DHEA), subregions of the PG, and elevated mental health symptoms (e.g.

Everyday home radon exposure is associated with altered structural brain morphology in youths.

The refinement of brain morphology extends across childhood, and exposure to environmental toxins during this period may alter typical trends. Radon is a highly common radiologic toxin with a well-established role in cancer among adults. However, effects on developmental populations are understudied in comparison.

Optogenetic Activation of Cholinergic Enteric Neurons Reduces Inflammation in Experimental Colitis.

Background & Aims: Intestinal inflammation is associated with loss of enteric cholinergic neurons. Given the systemic anti-inflammatory role of cholinergic innervation, we hypothesized that enteric cholinergic neurons similarly possess anti-inflammatory properties and may represent a novel target to treat inflammatory bowel disease.

Methods: Mice were fed 2.

Status of prosody in the practices of speech-language pathologists in France: A survey on theoretical and clinical dimensions.

Purpose: Many populations in the scope of speech and language pathologists (SLPs) are at risk of prosodic disorders that can impact communicative ability. While a few studies have examined the importance of prosody in the clinical practice of English-speaking SLPs, there is a lack of similar research in non-English-speaking countries. The current study aimed to establish an overview of the situation in France and to determine factors that might be associated with assessing and treating prosody.

Open preperitoneal inguinal hernia repair has superior 1-year patient-reported outcomes compared to Shouldice non-mesh repair.

Introduction: The Shouldice method for inguinal hernia repair remains the gold standard for prosthesis-free repairs. Nonetheless, international guidelines have favored posterior mesh reinforcement as the standard of care for inguinal hernia repair due to lower risk of recurrence and chronic pain, avoidance of general anesthesia, and favorable biomechanical properties. Recent publications have shown the benefits of an open approach to posterior repairs.

Pete and the Missing Scissors: a primary literature-focused case study that highlights the impact of SARS-CoV-2 on splicing.

This case study was designed to help students explore the molecular mechanisms of the spliceosome and how SARS-CoV-2 impacts host cell spliceosomal function while interpreting figures from primary literature (A. K. Banjeree, et al.

The Oxidative Stress and Nervous Distress Connection in Gastrointestinal Disorders.

Oxidative stress is increasingly recognized as a central player in a range of gastrointestinal (GI) disorders, as well as complications stemming from therapeutic interventions. This article presents an overview of the mechanisms of oxidative stress in GI conditions and highlights a link between oxidative insult and disruption to the enteric nervous system (ENS), which controls GI functions. The dysfunction of the ENS is characteristic of a spectrum of disorders, including neurointestinal diseases and conditions such as inflammatory bowel disease (IBD), diabetic gastroparesis, and chemotherapy-induced GI side effects.

Innate immune cellular therapeutics in transplantation.

Successful organ transplantation provides an opportunity to extend the lives of patients with end-stage organ failure. Selectively suppressing the donor-specific alloimmune response, however, remains challenging without the continuous use of non-specific immunosuppressive medications, which have multiple adverse effects including elevated risks of infection, chronic kidney injury, cardiovascular disease, and cancer. Efforts to promote allograft tolerance have focused on manipulating the adaptive immune response, but long-term allograft survival rates remain disappointing.

Dehydroepiandrosterone mediates associations between trauma-related symptoms and anterior pituitary volume in children and adolescents.

Introduction: The anterior pituitary gland (PG) is a potential locus of hypothalamic-pituitary-adrenal (HPA) axis responsivity to early life stress, with documented associations between dehydroepiandrosterone (DHEA) levels and anterior PG volumes. In adults, elevated anxiety/depressive symptoms are related to diminished DHEA levels, and studies have shown a positive relationship between DHEA and anterior pituitary volumes. However, specific links between responses to stress, DHEA levels, and anterior pituitary volume have not been established in developmental samples.

Developmental changes in endogenous testosterone have sexually-dimorphic effects on spontaneous cortical dynamics.

The transition from childhood to adolescence is associated with an influx of sex hormones, which not only facilitates physical and behavioral changes, but also dramatic changes in neural circuitry. While previous work has shown that pubertal hormones modulate structural and functional brain development, few of these studies have focused on the impact that such hormones have on spontaneous cortical activity, and whether these effects are modulated by sex during this critical developmental window. Herein, we examined the effect of endogenous testosterone on spontaneous cortical activity in 71 typically-developing youth (ages 10-17 years; 32 male).

Oxidative Stress and Neural Dysfunction in Gastrointestinal Diseases: Can Stem Cells Offer a Solution?

Oxidative stress is involved in many gastrointestinal (GI) disorders as either the primary pathogenesis (radiation, chemotherapy, toxicity, ischemia-reperfusion) or a secondary driving force of disease progression (inflammation and diabetes). The GI tract is innervated intrinsically by the enteric nervous system (ENS) with a diverse role in maintaining gut homeostasis and GI motility. Complications in the physiological functioning of the ENS results in GI dysfunction that can result in debilitating sequelae from dysmotility greatly impacting quality of life and leading to potentially fatal complications.

Primary Tissue Repair for Inguinal Hernias: The Shouldice Repair Technique and Patient Selection.

It is estimated that approximately one in four men and one in 20 women will develop an inguinal hernia over the course of their lifetime. A non-mesh inguinal hernia repair via the Shouldice technique is a unique approach that necessitates dissection of the entire groin region as well as careful assessment for any secondary hernias. Subsequently, a pure tissue laminated closure allows the repair to be performed without tension.

Segmented filamentous bacteria-based treatment to elicit protection against in Layer chickens.

Introduction: Gut microbes like segmented filamentous bacteria (SFB) play a key role in gut maturation during early life, as demonstrated in humans and mice. Our previous study demonstrated oral inoculation of ileum-spores containing SFB to chickens after hatch increases early SFB gut colonization, which increases immune maturation and resistance to bacteria, like , as tested ; however, more studies are needed for treatment optimization and testing. The objectives of this study were to (1) test a treatment that includes both spores and filamentous SFB, (2) validate antimicrobial ability of the treatment in layer hens and (3) elucidate its molecular mechanism.