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.

Endoscopic assessment of failed fundoplications differs between endoscopists.

BACKGROUND: Despite excellent long-term outcomes, a small proportion of patients who undergo fundoplication with hiatal hernia repair (laparoscopic antireflux surgery [ARS]) for treatment of gastroesophageal reflux disease (GERD) may require reoperation. Esophagogastroduodenoscopy (EGD) assessment in patients presenting with symptom recurrence plays a critical role in surgical planning of redo-ARS by confirming failure of the fundoplication and revealing the pattern of failure. We aimed to compare the findings documented by external endoscopists (i.e., outside physicians) to those documented by internal endoscopists (i.e., operating foregut or thoracic surgeons) before redo-ARS. METHODS: After IRB approval, we conducted a retrospective chart review of patients who underwent redo-ARS at a tertiary surgical center between November 2016 and March 2023. Patients with both external and internal EGD reports were included, and findings from the two reports were compared. RESULTS: Of 197 patients who underwent redo-ARS, both preoperative EGD reports were available for 181 (136 [75.1%] women; median age, 61 years [IQR 53-69]; median BMI, 27.9 kg/m2 [IQR 24.9-31.3]). The median time between primary and redo-ARS was 89 months (IQR 38-153), and the median time between external and internal endoscopic evaluation was 5 months (IQR 2-12). Only 38.9% of external reports mentioned a prior fundoplication. Compared to the operating surgeons, external physicians reported a significantly lower proportion of Barrett's esophagus (52.4%, p < .001), slipped fundoplications (28.8%, p < .001), paraesophageal hernias (20.5%, p < .001), disrupted fundoplications (20%, p < .001), intrathoracic fundoplications (0%, p < .001), and twisted fundoplications (0%, p < .001). CONCLUSIONS: External endoscopists' reports of failed fundoplications are often incomplete and lack relevant details. Discrepancies between nonsurgical endoscopists and experienced surgeons are likely explained by a lack of training and experience to discern and document fundoplication changes accurately. To reduce this gap, we strongly recommend the adoption of standard definitions describing post-fundoplication endoscopic changes and the inclusion of relevant training within educational programs.

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.

pHoenix score: development and validation of a novel approach to decrease the number of inconclusive GERD diagnoses.

BACKGROUND: The Johnson-DeMeester composite score (DMS) is the historical gold standard for diagnosing gastroesophageal reflux disease (GERD). The Lyon Consensus outlines criteria for diagnosing GERD by pH monitoring, defining normal acid exposure time (AET) as < 4% and pathological as > 6%, presenting diagnostic uncertainty from 4 to 6%. We aimed to (i) calculate the proportion of borderline studies defined by total AET alone that are reclassified as normal or pathological by the DMS, (ii) determine the importance of supine AET for reclassification, and (iii) propose a new classification system using a composite score that considers positional changes. METHODS: This single-center, retrospective, observational study analyzed data from patients with an overall total AET from 2 to 6% on 48-h pH monitoring (Bravo pH capsule). Preselected predictors (supine and upright AET) were included in a model to create a composite score (i.e., pHoenix score) using the regression coefficients. The model was internally validated, and discriminative ability was tested against the DMS and compared to the total AET. RESULTS: We identified 114 patients (80 [70.2%] women; median age, 55 years). Using the total AET, 26 (22.8%) were classified as normal and 88 (77.2%) as borderline; however, using the DMS, 45 (39.5%) were classified as normal and 69 (60.5%) as pathological. The new pHoenix score demonstrated strong discriminative ability (AUC: 0.957 [95% CI 0.917, 0.998]) with high sensitivity and specificity (lower threshold, 94.4% and 79.2%; upper threshold, 87 and 95.8%). Compared to the total AET alone, the pHoenix score significantly decreased the proportion of inconclusive cases (77.2% vs. 13.2%, p < 0.001). CONCLUSION: Total AET has low sensitivity to identify pathological reflux as it disregards supine versus upright reflux. The pHoenix score improves the distinction between normal and pathological cases and reduces ambiguity, offering an alternative approach to diagnosing GERD that addresses the limitations of using total AET alone or the DMS.

Noninvasive biomarkers for the detection of GERD-induced pulmonary injury.

BACKGROUND: The role of gastroesophageal reflux in progressive lung damage is increasingly recognized. We have proposed, based on our work with lung transplant recipients, a novel immune mechanism of pulmonary injury after aspiration of gastric contents, during which higher levels of normally sequestered lung self-antigens (SAgs) collagen V (Col-V) and K-alpha-1 tubulin (Kα1T) in circulating small extracellular vesicles (EVs) induce the production of self-antibodies (SAbs) anti-Col-V and anti-Kα1T. Thus, we aimed to determine whether levels of SAbs or SAgs increased in an animal model of aspiration-induced lung damage in a nontransplant setting. METHODS: We created a murine model of repetitive lung aspiration using C57BL/6J mice. Mice were aspirated weekly with 1 mL/kg of hydrochloric acid (n = 9), human gastric contents (n = 9), or combined (1:1) fluid (n = 9) once, three, or six times (n = 3 in each subgroup; control group, n = 9). Blood samples were periodically obtained, and all animals were sacrificed at day 90 for pathological assessment. SAbs were measured using an enzyme-linked immunosorbent assay; SAgs and NF-κB contained in small EVs were assessed by western blot. RESULTS: Aspirated mice weighed significantly less than controls throughout the study and had histological evidence of pulmonary injury at day 90. Overall, aspirated mice developed higher concentrations of anti-Col-V at day 28 (53.9 ± 28.7 vs. 29.9 ± 4.5 ng/mL, p < 0.01), day 35 (42.6 ± 19.8 vs. 28.6 ± 7.2 ng/mL, p = 0.038), and day 90 (59.7 ± 27.7 vs. 34.1 ± 3.2 ng/mL, p = 0.014) than the control group. Circulating small EVs isolated from aspirated mice on day 90 contained higher levels of Col-V (0.7 ± 0.56 vs. 0.18 ± 0.6 m.o.d., p = 0.009) and NF-κB (0.42 ± 0.27 vs. 0.27 ± 0.09 m.o.d., p = 0.095) than those from controls. CONCLUSIONS: This experimental study supports the theory that gastroesophageal reflux leads to the development of lung damage and an increase of humoral markers that may serve as noninvasive biomarkers to detect asymptomatic lung injury among patients with gastroesophageal reflux disease.

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.

Comparative Outcomes of Autologous Chondrocyte Implantation and Osteochondral Allograft Transplantation with Patellar Realignment for Patellar Instability with Associated Cartilage Defects.

PURPOSE: The purpose of this study was to determine clinical and functional outcomes in patients treated with autologous chondrocyte implantation (ACI) or osteochondral allograft (OCA) transplantation for chondral defects secondary to patellar instability with concomitant medial patellofemoral ligament (MPFL) reconstruction and tibial tubercle osteotomy (TTO) for patellar realignment. METHODS: A retrospective review identified patients who underwent ACI or OCA transplantation with concomitant MPFL reconstruction and TTO . Patients were excluded if they did not have concomitant MPFL reconstruction and TTO, had the presence of other intra-articular pathologies, or failed to complete postoperative subjective outcome evaluations at a minimum of 2 years following surgery. Subjective outcome measures included the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement (KOOS JR), International Knee Documentation Committee (IKDC) evaluation, and Short Form Health Survey (SF-12) physical scores, collected a minimum of 2 years after surgery. Defect location, size, complications, and rate of subsequent surgery were determined. RESULTS: Eighteen total patients were included in this study. The ACI cohort included 11 patients with 13 total defects that were treated with ACI. The OCA cohort included 7 patients with 10 total defects that were treated with OCA. This was due to a number of patients in either group having multiple cartilage defects. Twenty-three total chondral defects were compared to analyze clinical and functional outcomes following surgical correction (ACI: n=13, OCA: n=10). Five defects were noted on the femoral condyle and 18 on the patellar facets/central ridge. Defects were comparable between groups including, size measured during index-arthroscopy (ACI = 3.34 cm2, 95% CI [2.3 cm2 - 4.4 cm2] vs OCA = 4.03 cm2, 95% CI [3.1 cm2 - 5.0 cm2]; P=.351), Outerbridge classification (ACI = 54.8% grade 4 vs OCA = 60.0% grade 4; P=1.000), and AMADEUS score (ACI = 47.1 vs OCA = 58.6; P=.298). Postoperative outcomes were comparable including revision rate (ACI = 15.4% vs OCA = 10.0%; P=1.000) and 2-year IKDC scores (ACI = 74.2, 95% CI [65.2 - 83.2] vs OCA = 51.2, 95% CI [30.3 - 72.1]; P=.077). ACI did have significantly higher 2-year KOOS JR (85.1, 95% CI [76.9 - 93.3] vs 63.7, 95% CI [49.1 - 78.3]; P=.031) and SF-12 scores (54.1, 95% CI [52.0 - 56.2] vs 42.6, 95% CI [35.8 - 49.4]; P=.007) compared to OCA. CONCLUSION: ACI or OCA transplantation for chondral defects with concomitant MPFL reconstruction and TTO can be safely performed in an outpatient setting with functional and clinical outcomes being comparable. LEVEL OF EVIDENCE: Retrospective Case Series Study (Level 3).

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.