Adipose-tissue Treg cells restrain differentiation of stromal adipocyte precursors to promote insulin sensitivity and metabolic homeostasis.

Regulatory T (Treg) cells in epidydimal visceral adipose tissue (eVAT) of lean mice and humans regulate metabolic homeostasis. We found that constitutive or punctual depletion of eVAT-Treg cells reined in the differentiation of stromal adipocyte precursors. Co-culture of these precursors with conditional medium from eVAT-Treg cells limited their differentiation in vitro, suggesting a direct effect. Transcriptional comparison of adipocyte precursors, matured in the presence or absence of the eVAT-Treg-conditioned medium, identified the oncostatin-M (OSM) signaling pathway as a key distinction. Addition of OSM to in vitro cultures blocked the differentiation of adipocyte precursors, while co-addition of anti-OSM antibodies reversed the ability of the eVAT-Treg-conditioned medium to inhibit in vitro adipogenesis. Genetic depletion of OSM (specifically in Treg) cells or of the OSM receptor (specifically on stromal cells) strongly impaired insulin sensitivity and related metabolic indices. Thus, Treg-cell-mediated control of local progenitor cells maintains adipose tissue and metabolic homeostasis, a regulatory axis seemingly conserved in humans.

The gut microbiota promotes distal tissue regeneration via RORγ+ regulatory T cell emissaries.

Specific microbial signals induce the differentiation of a distinct pool of RORγ+ regulatory T (Treg) cells crucial for intestinal homeostasis. We discovered highly analogous populations of microbiota-dependent Treg cells that promoted tissue regeneration at extra-gut sites, notably acutely injured skeletal muscle and fatty liver. Inflammatory meditators elicited by tissue damage combined with MHC-class-II-dependent T cell activation to drive the accumulation of gut-derived RORγ+ Treg cells in injured muscle, wherein they regulated the dynamics and tenor of early inflammation and helped balance the proliferation vs. differentiation of local stem cells. Reining in IL-17A-producing T cells was a major mechanism underlying the rheostatic functions of RORγ+ Treg cells in compromised tissues. Our findings highlight the importance of gut-trained Treg cell emissaries in controlling the response to sterile injury of non-mucosal tissues.

Human NLRP1 is a sensor of pathogenic coronavirus 3CL proteases in lung epithelial cells.

Inflammation observed in SARS-CoV-2-infected patients suggests that inflammasomes, proinflammatory intracellular complexes, regulate various steps of infection. Lung epithelial cells express inflammasome-forming sensors and constitute the primary entry door of SARS-CoV-2. Here, we describe that the NLRP1 inflammasome detects SARS-CoV-2 infection in human lung epithelial cells. Specifically, human NLRP1 is cleaved at the Q333 site by multiple coronavirus 3CL proteases, which triggers inflammasome assembly and cell death and limits the production of infectious viral particles. Analysis of NLRP1-associated pathways unveils that 3CL proteases also inactivate the pyroptosis executioner Gasdermin D (GSDMD). Subsequently, caspase-3 and GSDME promote alternative cell pyroptosis. Finally, analysis of pyroptosis markers in plasma from COVID-19 patients with characterized severe pneumonia due to autoantibodies against, or inborn errors of, type I interferons (IFNs) highlights GSDME/caspase-3 as potential markers of disease severity. Overall, our findings identify NLRP1 as a sensor of SARS-CoV-2 infection in lung epithelia.

Adipose-tissue regulatory T cells are a consortium of subtypes that evolves with age and diet.

Foxp3+CD4+ regulatory T (Treg) cells found within tissues regulate local immunity, inflammation, and homeostasis. Tregs in epididymal visceral adipose tissue (eVAT) are critical regulators of local and systemic inflammation and metabolism. During aging and under obesogenic conditions, eVAT Tregs undergo transcriptional and phenotypic changes and are important for containing inflammation and normalizing metabolic indices. We have employed single-cell RNA sequencing, single-cell Tra and Trb sequencing, adoptive transfers, photoconvertible mice, cellular interaction analyses, and in vitro cultures to dissect the evolving heterogeneity of eVAT Tregs with aging and obesity. Distinct Treg subtypes with distinguishable gene expression profiles and functional roles were enriched at differing ages and with differing diets. Like those in lean mice, eVAT Tregs in obese mice were not primarily recruited from the circulation but instead underwent local expansion and had a distinct and diversified T cell receptor repertoire. The different eVAT-Treg subtypes were specialized in different functions; for example, the subtypes enriched in lean, but not obese, mice suppressed adipogenesis. The existence of functionally divergent eVAT-Treg subtypes in response to obesogenic conditions presents possibilities for precision therapeutics in the context of obesity.

Chimeric oncolytic adenovirus evades neutralizing antibodies from human patients and exhibits enhanced anti-glioma efficacy in immunized mice.

Oncolytic viruses are a promising treatment for patients with high-grade gliomas, but neutralizing antibodies can limit their efficacy in patients with prior virus exposure or upon repeated virus injections. Data from a previous clinical trial using the oncolytic adenovirus Delta-24-RGD showed that generation of anti-viral neutralizing antibodies may affect the long-term survival of glioma patients. Past studies have examined the effects of neutralizing antibodies during systemic virus injections, but largely overlooked their impact during local virus injections into the brain. We found that immunoglobulins colocalized with viral proteins upon local oncolytic virotherapy of brain tumors, warranting a strategy to prevent virus neutralization and maximize oncolysis. Thus, we generated a chimeric virus, Delta-24-RGD-H43m, by replacing the capsid protein HVRs from the serotype 5-based Delta-24-RGD with those from the rare serotype 43. Delta-24-RGD-H43m evaded neutralizing anti-Ad5 antibodies and conferred a higher rate of long-term survival than Delta-24-RGD in glioma-bearing mice. Importantly, Delta-24-RGD-H43m activity was significantly more resistant to neutralizing antibodies present in sera of glioma patients treated with Delta-24-RGD during a phase 1 clinical trial. These findings provide a framework for a novel treatment of glioma patients that have developed immunity against Delta-24-RGD.

Characterization of the Edge States in Colloidal Bi2Se3 Platelets.

The remarkable development of colloidal nanocrystals with controlled dimensions and surface chemistry has resulted in vast optoelectronic applications. But can they also form a platform for quantum materials, in which electronic coherence is key? Here, we use colloidal, two-dimensional Bi2Se3 crystals, with precise and uniform thickness and finite lateral dimensions in the 100 nm range, to study the evolution of a topological insulator from three to two dimensions. For a thickness of 4-6 quintuple layers, scanning tunneling spectroscopy shows an 8 nm wide, nonscattering state encircling the platelet. We discuss the nature of this edge state with a low-energy continuum model and ab initio GW-Tight Binding theory. Our results also provide an indication of the maximum density of such states on a device.

Single Specialty-Operated Renal Stone Removal: Initial Experience from 3 Interventional Radiology Centers.

This retrospective analysis of the feasibility and safety of percutaneous renal stone removal using single-use flexible ureteroscopes was conducted at 3 academic centers. Twelve patients (58% men) underwent 14 percutaneous renal stone removal procedures between December 2021 and March 2023. All patients experienced symptom improvement and resolution of obstruction after stone removal. The procedural success rate was 92%. Only 1 patient required an additional stone removal procedure. No major adverse events occurred during or after the procedures. The percutaneous nephrostomy removal rate was 92%, with a median tube removal time of 5 weeks. The median procedural and pulsed fluoroscopy times were 106.5 and 16.3 minutes, respectively. Preliminary findings demonstrated that percutaneous renal stone removal using single-use endoscopes by interventional radiologists is feasible and safe.

Cruroplasty with or without mesh? A systematic literature review with a novel time-organized proportion meta-analysis.

BACKGROUND: Improved outcomes with the use of non-absorbable mesh (NAM) for inguinal hernia repairs led to its rapid adoption for hiatal hernia (HH) repairs; however, feared complications occurred, and the trend shifted toward using absorbable mesh (AM). We aimed to analyze the literature assessing objective HH recurrence rates after primary laparoscopic cruroplasty with or without the use of different mesh types. METHODS: A systematic literature review with both pairwise and time-organized proportion meta-analyses of articles published between January 1993 and September 2022 was performed using the MEDLINE, EMBASE, and Taylor & Francis databases to identify relevant studies comparing groups undergoing cruroplasty with suture repair (SR) alone, AM, NAM, or partially absorbable mesh (PAM). Studies documenting an objective follow-up ≥ 6 months were included. The primary outcome was the HH recurrence rate confirmed by barium esophagram or upper GI endoscopy. RESULTS: A total of 34 studies met the inclusion criteria, including 6 randomized clinical trials, 25 retrospectives studies, and 3 prospective cohort studies. A total of 2170 subjects underwent laparoscopic HH repair and completed an objective follow-up ≥ 6 months after surgery; the objective recurrence rate was 20.8% (99/477) at a mean follow-up of 25.8 ± 16.4 months for the SR group, 20.6% (244/1187) at 28.1 ± 13.8 months for the AM group, 13.7% (65/475) at 30.8 ± 15.3 months for the NAM group, and 0% (0/31) at 32.5 ± 13.5 months for the PAM group. However, the pairwise meta-analysis revealed that overall mesh use was not superior to SR in preventing long-term HH recurrence. CONCLUSION: The use of AM does not appear to reduce HH recurrence compared to SR alone. Although the data favors NAM to decrease objective HH recurrence in the mid-term, the long-term (≥ 48 months) recurrence rate was similar with or without any type of mesh.

Prevalence and severity of abdominal bloating in patients with gastroesophageal reflux disease.

Abdominal bloating (AB) is a common symptom among patients with gastroesophageal reflux disease (GERD); however, in clinical practice, its prevalence is likely underestimated due to the lack of objective tools to measure its frequency and severity. It is associated with dissatisfaction and worse quality of life, but data on its prevalence before and after mechanical control of GERD (i.e. fundoplication, magnetic sphincter augmentation, and antireflux mucosectomy) are lacking. To assess and determine the pre- and postoperative prevalence and severity of AB among patients with GERD, we conducted a structured literature search using MeSH and free-text terms in MEDLINE (via Pubmed), EMBASE, and Taylor & Francis Online between January 1977 and October 2022. Fifteen articles reporting the prevalence or severity of AB using quality-of-life questionnaires before or after antireflux surgery (ARS) were included. Overall, a high prevalence of AB before ARS was found. A decline in the prevalence and severity of AB was documented postoperatively in most cases independent of the surgical approach. Among surgical approaches, a complete fundoplication had the highest reported postoperative AB. Overall, patients reported less severe and less frequent AB after ARS than before. The traditional belief that postoperative bloating is a sequela of ARS should be reevaluated.

Impaired esophagogastric junction relaxation and lung transplantation outcomes.

The implications of impaired esophagogastric junction relaxation (i.e. esophagogastric junction outflow obstruction and achalasia) in lung transplants recipients (LTRs) are unclear. Thus, we examined the prevalence and clinical outcomes of LTRs with an abnormally elevated integrated relaxation pressure (IRP) on high-resolution manometry before lung transplantation (LTx). After IRB approval, we reviewed data on LTRs who underwent LTx between January 2019 and August 2022 with a preoperative median IRP >15 mmHg. Differences in overall survival and chronic lung allograft dysfunction (CLAD)-free survival between LTRs with a normalized median IRP after LTx (N-IRP) and those with persistently high IRP (PH-IRP) were assessed using Kaplan-Meier curves and the log-rank test. During the study period, 352 LTx procedures were performed; 44 (12.5%) LTRs had an elevated IRP before LTx, and 37 (84.1%) completed a postoperative manometry assessment (24 [70.6%] males; mean age, 65.2 ± 9.1 years). The median IRP before and after LTx was 18.7 ± 3.8 mmHg and 12 ± 5.6 mmHg, respectively (P < 0.001); the median IRP normalized after LTx in 24 (64.9%) patients. Two-year overall survival trended lower in the N-IRP group than the PH-IRP group (77.2% vs. 92.3%, P = 0.086), but CLAD-free survival (P = 0.592) and rates of primary graft dysfunction (P = 0.502) and acute cellular rejection (P = 0.408) were similar. An abnormally elevated IRP was common in LTx candidates; however, it normalized in roughly two-thirds of patients after LTx. Two-year survival trended higher in the PH-IRP group, despite similar rates of primary graft dysfunction and acute cellular rejection as well as similar CLAD-free survival between the groups.

PPARγ marks splenic precursors of multiple nonlymphoid-tissue Treg compartments.

Foxp3+CD4+ regulatory T cells (Tregs) regulate most types of immune response as well as several processes important for tissue homeostasis, for example, metabolism and repair. Dedicated Treg compartments-with distinct transcriptomes, T cell receptor repertoires, and growth/survival factor dependencies-have been identified in several nonlymphoid tissues. These Tregs are specifically adapted to function and operate in their home tissue-When, where, and how do they take on their specialized characteristics? We recently reported that a splenic Treg population expressing low levels of the transcription factor PPARγ (peroxisome proliferator-activated receptor gamma) contains precursors of Tregs residing in visceral adipose tissue. This finding made sense given that PPARγ, the "master regulator" of adipocyte differentiation, is required for the accumulation and function of Tregs in visceral adipose tissue but not in lymphoid tissues. Here we use single-cell RNA sequencing, single-cell Tcra and Tcrb sequencing, and adoptive-transfer experiments to show that, unexpectedly, the splenic PPARγlo Treg population is transcriptionally heterogeneous and engenders Tregs in multiple nonlymphoid tissues beyond visceral adipose tissue, such as skin and liver. The existence of a general pool of splenic precursors for nonlymphoid-tissue Tregs opens possibilities for regulating their emergence experimentally or therapeutically.

Analysis of reasons for failure to return to sport after Latarjet surgery: a systematic review.

BACKGROUND: The purpose of this study was to perform a systematic review of the literature to identify Shoulder Instability Return to Sport after Injury (SIRSI) scores in athletes who underwent open Latarjet surgery, determine the reasons why athletes failed to return to play (RTP) after Latarjet surgery, and compare SIRSI scores of those who did vs. did not RTP. METHODS: According to PRISMA guidelines, the PubMed, SportDiscus, and Ovid MEDLINE databases were queried to identify studies evaluating return to sport after Latarjet surgery. Study quality was assessed using the MINORS criteria. Studies were included if RTP after Latarjet surgery and a psychological factor were evaluated, with potential psychological factors including readiness to RTP and reasons for failure to RTP. RESULTS: Fourteen studies, 10 of level III evidence and 4 of level IV evidence, with 1034 patients were included. A total of 978 athletes were eligible to RTP. Of these, 792 (79%) successfully returned to play and 447 (56.4%) returned to play at their previous level of play. Mean RTP time was 6.2 months. Postoperative SIRSI scores averaged 71.2 ± 8.8 at a mean of 21 months' follow-up. Postoperative SIRSI scores for those able to RTP was 73.2, whereas athletes unable to RTP scored an average of 41.5. Mean postoperative SIRSI scores for those in contact sports was 71.4, whereas those in noncontact sports was 86.5. There were 31 athletes with a documented reason why they did not RTP, with postoperative shoulder injury being the most common reason (54.5%). Fear of reinjury and feeling "not psychologically confident" each represented 6.5% of the total. CONCLUSION: Athletes who RTP have higher average SIRSI scores than those who are unable to RTP. Of the athletes who documented why they did not RTP, more than half cited a shoulder injury as their reason for not returning to play, whereas fear of reinjury and lack of psychological readiness were other common reasons.

A Past Genetic Bottleneck from Argentine Beans and a Selective Sweep Led to the Race Chile of the Common Bean (Phaseolus vulgaris L.).

The domestication process of the common bean gave rise to six different races which come from the two ancestral genetic pools, the Mesoamerican (Durango, Jalisco, and Mesoamerica races) and the Andean (New Granada, Peru, and Chile races). In this study, a collection of 281 common bean landraces from Chile was analyzed using a 12K-SNP microarray. Additionally, 401 accessions representing the rest of the five common bean races were analyzed. A total of 2543 SNPs allowed us to differentiate a genetic group of 165 accessions that corresponds to the race Chile, 90 of which were classified as pure accessions, such as the bean types 'Tórtola', 'Sapito', 'Coscorrón', and 'Frutilla'. Our genetic analysis indicates that the race Chile has a close relationship with accessions from Argentina, suggesting that nomadic ancestral peoples introduced the bean seed to Chile. Previous archaeological and genetic studies support this hypothesis. Additionally, the low genetic diversity (π = 0.053; uHe = 0.53) and the negative value of Tajima' D (D = -1.371) indicate that the race Chile suffered a bottleneck and a selective sweep after its introduction, supporting the hypothesis that a small group of Argentine bean genotypes led to the race Chile. A total of 235 genes were identified within haplotype blocks detected exclusively in the race Chile, most of them involved in signal transduction, supporting the hypothesis that intracellular signaling pathways play a fundamental role in the adaptation of organisms to changes in the environment. To date, our findings are the most complete investigation associated with the origin of the race Chile of common bean.

Different anatomic patterns of the indirect tendon of the rectus femoris.

PURPOSE: The rectus femoris forms the anterior portion of the quadriceps muscle. It has a proximal tendinous complex, which is constituted by a direct tendon, an indirect tendon, and a variable third tendon. Direct and indirect tendons converge into a common tendon. The purposes of this study are to add anatomical knowledge about the proximal tendinous complex and describe anatomical variants of the indirect tendon and, on these basis, categorize different anatomical patterns. METHOD: In this study, 48 hemipelvis from bodies donated to the Universitat Autònoma de Barcelona have been dissected to examine the proximal tendinous complex of the rectus femoris. RESULTS: The following anatomical variants of the indirect tendon were described: inferior aponeurotic expansion in 23/48 cases (47.9%); superior aponeurotic expansion in 21/48 cases (43.7%); and an unusual origin of the myotendinous junction of the rectus femoris in the free portion of the indirect tendon in 19/48 cases (39.6%). On the basis of the aponeurotic expansions, the following anatomical patterns of the indirect tendon were defined: standard (19/48 cases, 39.6%), superior and inferior complex (15/48 cases, 31.2%), inferior complex (8/48 cases, 16.7%), and superior complex (6/48 cases, 12.5%). CONCLUSION: We can categorize four different anatomical patterns of the indirect tendon, three of which are complex. We suggest that complex patterns can cause an increased stiffness of the indirect tendon and so be considered non-modifiable risk factors for rectus femoris injuries. Finally, it would be useful to identify complex patterns and perform injury prevention actions through specific physical preparation programs.

Brief guidelines for beginners on how to perform and analyze esophageal high-resolution manometry.

High-resolution manometry (HRM) is a diagnostic tool for surgeons, gastroenterologists and other healthcare professionals to evaluate esophageal physiology. The Chicago Classification (CC) system is based on a consensus of worldwide experts to minimize ambiguity in HRM data acquisition and diagnosis of esophageal motility disorders. The most updated version, CCv4.0, was published in 2021; however, it does not provide step-by-step guidelines (i.e., for beginners) on how to assess the most important HRM metrics. This paper aims to summarize the basic guidelines for conducting a high-quality HRM study including data acquisition and interpretation, based on CCv4.0, using Manoview ESO analysis software, version 3.3 (Medtronic, Minneapolis, MN).

Multi-tissue transcriptomic and serum metabolomic assessment reveals systemic implications of acute ozone-induced stress response in male Wistar Kyoto rats.

Air pollutant exposures have been linked to systemic disease; however, the underlying mechanisms between responses of the target tissue and systemic effects are poorly understood. A prototypic inducer of stress, ozone causes respiratory and systemic multiorgan effects through activation of a neuroendocrine stress response. The goal of this study was to assess transcriptomic signatures of multiple tissues and serum metabolomics to understand how neuroendocrine and adrenal-derived stress hormones contribute to multiorgan health outcomes. Male Wistar Kyoto rats (12-13 weeks old) were exposed to filtered air or 0.8 ppm ozone for 4-hours, and blood/tissues were collected immediately post-exposure. Each tissue had distinct expression profiles at baseline. Ozone changed 1,640 genes in lung, 274 in hypothalamus, 2,516 in adrenals, 1,333 in liver, 1,242 in adipose, and 5,102 in muscle (adjusted p-value < 0.1, absolute fold-change > 50%). Serum metabolomic analysis identified 863 metabolites, of which 447 were significantly altered in ozone-exposed rats (adjusted p-value < 0.1, absolute fold change > 20%). A total of 6 genes were differentially expressed in all 6 tissues. Glucocorticoid signaling, hypoxia, and GPCR signaling were commonly changed, but ozone induced tissue-specific changes in oxidative stress, immune processes, and metabolic pathways. Genes upregulated by TNF-mediated NFkB signaling were differentially expressed in all ozone-exposed tissues, but those defining inflammatory response were tissue-specific. Upstream predictor analysis identified common mediators of effects including glucocorticoids, although the specific genes responsible for these predictors varied by tissue. Metabolomic analysis showed major changes in lipids, amino acids, and metabolites linked to the gut microbiome, concordant with transcriptional changes identified through pathway analysis within liver, muscle, and adipose tissues. The distribution of receptors and transcriptional mechanisms underlying the ozone-induced stress response are tissue-specific and involve induction of unique gene networks and metabolic phenotypes, but the shared initiating triggers converge into shared pathway-level responses. This multi-tissue transcriptomic analysis, combined with circulating metabolomic assessment, allows characterization of the systemic inhaled pollutant-induced stress response.

Diagnosis and management of anastomotic leaks after Ivor Lewis esophagectomy: a single-center experience.

PURPOSE: Esophageal anastomotic leaks (ALs) after esophagectomy are a common and serious complication. The incidence, diagnostic approach, and management have changed over time. We described the diagnosis and management of patients who developed an esophageal AL after an Ivor Lewis esophagectomy at our center. METHODS: After IRB approval, we queried our prospectively maintained database for patients who developed an esophageal AL after esophagectomy from August 2016 through July 2022. Data pertaining to demographics, comorbidities, surgical and oncological characteristics, and clinical course were extracted and analyzed. RESULTS: During the study period, 145 patients underwent an Ivor Lewis esophagectomy; 10 (6.9%) developed an AL, diagnosed a median of 7.5 days after surgery, and detected by enteric contents in wound drains (n = 3), endoscopy (n = 3), CT (n = 2), and contrast esophagogram (n = 2). Nine patients (90%) had an increasing white blood cell count and additional signs of sepsis. One asymptomatic patient was identified by contrast esophagography. All patients received enteral nutritional support, intravenous antibiotics, and antifungals. Primary treatment of ALs included endoscopic placement of a self-expanding metal stent (SEMS; n = 6), surgery (n = 2), and SEMS with endoluminal vacuum therapy (n = 2). One patient required surgery after SEMS placement. The median length of ICU and total hospital stays were 11.5 and 22.5 days, respectively. There was no 30-day mortality. CONCLUSION: The incidence of esophageal ALs at our center is similar to that of other high-volume centers. Most ALs can be managed without surgery; however, ALs remain a significant source of postoperative morbidity despite clinical advancements that have improved mortality.

Air Pollutant impacts on the brain and neuroendocrine system with implications for peripheral organs: a perspective.

Air pollutants are being increasingly linked to extrapulmonary multi-organ effects. Specifically, recent studies associate air pollutants with brain disorders including psychiatric conditions, neuroinflammation and chronic diseases. Current evidence of the linkages between neuropsychiatric conditions and chronic peripheral immune and metabolic diseases provides insights on the potential role of the neuroendocrine system in mediating neural and systemic effects of inhaled pollutants (reactive particulates and gases). Autonomically-driven stress responses, involving sympathetic-adrenal-medullary and hypothalamus-pituitary-adrenal axes regulate cellular physiological processes through adrenal-derived hormones and diverse receptor systems. Recent experimental evidence demonstrates the contribution of the very stress system responding to non-chemical stressors, in mediating systemic and neural effects of reactive air pollutants. The assessment of how respiratory encounter of air pollutants induce lung and peripheral responses through brain and neuroendocrine system, and how the impairment of these stress pathways could be linked to chronic diseases will improve understanding of the causes of individual variations in susceptibility and the contribution of habituation/learning and resiliency. This review highlights effects of air pollution in the respiratory tract that impact the brain and neuroendocrine system, including the role of autonomic sensory nervous system in triggering neural stress response, the likely contribution of translocated nano particles or metal components, and biological mediators released systemically in causing effects remote to the respiratory tract. The perspective on the use of systems approaches that incorporate multiple chemical and non-chemical stressors, including environmental, physiological and psychosocial, with the assessment of interactive neural mechanisms and peripheral networks are emphasized.

Intratracheal instillation of respirable particulate matter elicits neuroendocrine activation.

OBJECTIVE: Inhalation of ozone activates central sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal stress axes. While airway neural networks are known to communicate noxious stimuli to higher brain centers, it is not known to what extent responses generated from pulmonary airways contribute to neuroendocrine activation. MATERIALS AND METHODS: Unlike inhalational exposures that involve the entire respiratory tract, we employed intratracheal (IT) instillations to expose only pulmonary airways to either soluble metal-rich residual oil fly ash (ROFA) or compressor-generated diesel exhaust particles (C-DEP). Male Wistar-Kyoto rats (12-13 weeks) were IT instilled with either saline, C-DEP or ROFA (5 mg/kg) and necropsied at 4 or 24 hr to assess temporal effects. RESULTS: IT-instillation of particulate matter (PM) induced hyperglycemia as early as 30-min and glucose intolerance when measured at 2 hr post-exposure. We observed PM- and time-specific effects on markers of pulmonary injury/inflammation (ROFA>C-DEP; 24 hr>4hr) as corroborated by increases in lavage fluid injury markers, neutrophils (ROFA>C-DEP), and lymphocytes (ROFA). Increases in lavage fluid pro-inflammatory cytokines differed between C-DEP and ROFA in that C-DEP caused larger increases in TNF-α whereas ROFA caused larger increases in IL-6. No increases in circulating cytokines occurred. At 4 hr, PM impacts on neuroendocrine activation were observed through depletion of circulating leukocytes, increases in adrenaline (ROFA), and decreases in thyroid-stimulating-hormone, T3, prolactin, luteinizing-hormone, and testosterone. C-DEP and ROFA both increased lung expression of genes involved in acute stress and inflammatory processes. Moreover, small increases occurred in hypothalamic Fkbp5, a glucocorticoid-sensitive gene. CONCLUSION: Respiratory alterations differed between C-DEP and ROFA, with ROFA inducing greater overall lung injury/inflammation; however, both PM induced a similar degree of neuroendocrine activation. These findings demonstrate neuroendocrine activation after pulmonary-only PM exposure, and suggest the involvement of pituitary- and adrenal-derived hormones.

Magnetic sphincter augmentation for gastroesophageal reflux in overweight and obese patients.

Magnetic sphincter augmentation (MSA) is a successful treatment option for chronic gastroesophageal reflux disease; however, there is a paucity of data on the efficacy of MSA in obese and morbidly obese patients. To assess the relationship between obesity and outcomes after MSA, we conducted a literature search using MeSH and free-text terms in MEDLINE, EMBASE, Cochrane and Google Scholar. The included articles reported conflicting results regarding the effect of obesity on outcomes after MSA. Prospective observational studies with larger sample sizes and less statistical bias are necessary to understand the effectiveness of MSA in overweight and obese patients.