Diabetes and tuberculosis: An emerging dual threat to healthcare.

Tuberculosis (TB) remains a huge global healthcare challenge even in the 21st century though the prevalence has dropped in developed countries in recent decades. Diabetes mellitus (DM) is an important risk factor for the development and perpetuation of TB owing to the immune dysfunction in patients with DM. The coexistence of both diseases in the same individual also aggravates disease severity, complications, and chance of treatment failure because of gross immune alterations posed by DM as well as TB. Various complex cellular and humoral immunological factors are involved in the dangerous interaction between TB and DM, some of which remain unknown even today. It is highly important to identify the risk factors for TB in patients with DM, and vice versa, to ensure early diagnosis and management to prevent complications from this ominous coexistence. In their research study published in the recent issue of the World Journal of Diabetes, Shi et al elaborate on the factors associated with the development of TB in a large cohort of DM patients from China. More such research output from different regions of the world is expected to improve our knowledge to fight the health devastation posed by TB in patients with diabetes.

An Integrated Module Performs Selective 'On-Line' Epoxidation in the Biosynthesis of the Antibiotic Mupirocin.

The delineation of the complex biosynthesis of the potent antibiotic mupirocin, which consists of a mixture of pseudomonic acids (PAs) isolated from Pseudomonas fluorescens NCIMB 10586, presents significant challenges and the timing and mechanisms of several key transformations remain elusive.   Particularly intriguing are the steps that process the linear backbone from the initial polyketide assembly phase to generate the first cyclic intermediate PA-B. These include epoxidation as well as incorporation of the tetrahydropyran (THP) ring and fatty acid sidechain required for biological activity. Here, we show that the mini-module MmpE performs a rare online (ACP-substrate) epoxidation and is integrated ('in-cis') into the polyketide synthase via a docking domain. A linear polyketide fragment with 6 asymmetric centres was synthesised using a convergent approach and used to demonstrate substrate flux via an atypical KS0 and a previously unannotated ACP (MmpE_ACP). MmpE_ACP-bound synthetic substrates were critical in demonstrating successful epoxidation in vitro by the purified MmpE oxidoreductase domain. Alongside feeding studies, these results confirm the timing as well as chain length dependence of this selective epoxidation. These mechanistic studies pinpoint the location and nature of the polyketide substrate prior to the key formation of the THP ring and esterification that generate PA-B.

Screens and Sleep Health-It's Almost Bedtime, Time to Put Your Phone Away.

This Viewpoint discusses the National Sleep Foundation consensus panel's recommendations for screen-based media use and sleep health among children and teenagers.

Femoral head decentration on hip MRI: comparison between imaging planes, methods of contrast administration, and hip deformities.

OBJECTIVES: To compare the prevalence of femoral head decentration (FHD) on different MR imaging planes in patients undergoing direct/indirect hip MR arthrography (MRA) with asymptomatic controls and to evaluate its association with osseous deformities. METHODS: IRB-approved retrospective single-center study of symptomatic hips undergoing direct or indirect hip MRA at 3 T. Asymptomatic participants underwent non-contrast hip MRI at 3 T. FHD was defined as a continuous fluid layer between the acetabulum and femoral head and assessed on axial, sagittal and radial images. The association of intra-articular/intra-venous contrast agents and the prevalence of FHD was evaluated. The association of FHD with osseous deformities and joint damage was assessed using multiple logistic regression analysis. RESULTS: Three-hundred ninety-four patients (447 hips, mean age 31 ± 9 years, 247 females) were included and compared to 43 asymptomatic controls (43 hips, mean age 31 ± 6 years, 26 females). FHD was most prevalent on radial images and more frequent in symptomatic hips (30% versus 2%, p < 0.001). FHD prevalence was not associated with the presence/absence of intra-articular contrast agents (30% versus 22%, OR = 1.5 (95% CI 0.9-2.5), p = 0.125). FHD was associated with hip dysplasia (OR = 6.1 (3.3-11.1), p < 0.001), excessive femoral torsion (OR = 3.0 (1.3-6.8), p = 0.010), and severe cartilage damage (OR = 3.6 (2.0-6.7), p < 0.001). CONCLUSION: While rare in asymptomatic patients, femoral head decentration in symptomatic patients is associated with osseous deformities predisposing to hip instability, as well as with extensive cartilage damage. CRITICAL RELEVANCE STATEMENT: Decentration of the femoral head on radial MRA may be interpreted as a sign of hip instability in symptomatic hips without extensive cartilage defects. Its presence could unmask hip instability and yield promise in surgical decision-making. KEY POINTS: The best method of identifying femoral head decentration is radial MRI. The presence/absence of intra-articular contrast is not associated with femoral head decentration. Femoral head decentration is associated with hip deformities predisposing to hip instability.

Evaluating the Biomechanical Effects of Pedicle Subtraction Osteotomy at Different Lumbar Levels: A Finite Element Investigation.

BACKGROUND: Pedicle subtraction osteotomy (PSO) is effective for correcting spinal malalignment but is associated with high complication rates. The biomechanical effect of different PSO levels remains unclear, and no finite element (FE) analysis has compared L2-, L3-, L4-, and L5-PSOs. PURPOSE: To assess the effects of PSO level on the spine's global range of motion, stresses on posterior instrumentation, load sharing with the anterior column, and proximal junctional stresses. STUDY DESIGN: A computational biomechanical analysis. METHODS: A validated 3D spinopelvic FE model (T10-Pelvis) was used to perform PSOs at L2, L3, L4 and L5. Each model was instrumented with a four-rod configuration (primary rods + in-line satellite rods) from T11-Pelvis. Simulation included a 2-step analysis; (1) applying 300 N to thoracic, 400 N to lumbar, and 400 N to sacrum, and (2) applying a 7.5 Nm moment to the top endplate of the T10 vertebral body. Acetabulum surfaces were fixed in all degrees of freedom. The range of motion, spinopelvic parameters (lumbar lordosis (LL), sacral slope (SS), pelvic incidence (PI), and pelvic tilt (PT)), PSO force, and von Mises stresses were measured. All models were compared with the L3-PSO model and percentage differences were captured. RESULTS: Compared to the intact alignment: LL increased by 48%, 45%, 59%, and 56% in the L2-, L3-, L4-, and L5-PSO models; SS increased by 25%, 15%, and 11% while PT decreased by 76%, 53%, and 45% in L2-, L3-, and L4-PSOs (SS and PT approximated intact model in L5-PSO); Lumbar osteotomy did not affect the PI. Compared to L3-PSO: L2-, L4-, and L5-PSOs showed up to 32%, 34%, and 34% lower global ROM. The least T10-T11 ROM was observed in L5-PSO. The left and right SIJ ROM were approximately similar in each model. Amongst all, the L5-PSO model showed the least ROM at the SIJ. Compared to L3-PSO, the L2-, L4-, and L5-PSO models showed up to 67%, 61%, and 78% reduced stresses at the UIV, respectively. Minimum stress at UIV+ was observed in the L3-PSO model. The L2-and L3-PSOs showed the maximum PSO force. The L5-PSO model showed the lowest stresses on the primary rods in all motions. CONCLUSION: Our FE investigation indicates that L5-PSO results in the greatest lumbar lordosis and lowest global, SIJ, and T10-T11 ROMs and stresses on the primary rods, suggesting potential mechanical benefits in reducing the risk of rod breakage. However, L4- and L5-PSOs led to the least force across the osteotomy site, which may increase the risk of pseudarthrosis. These findings provide biomechanical insights that may inform surgical planning, though further clinical investigation is essential to determine the optimal PSO level and validate these results. CLINICAL SIGNIFICANCE: Understanding the biomechanical impact of PSO level is crucial for optimizing surgical outcomes and minimizing the risks of post-operative complications.

Investigating the biosynthesis and roles of the auxin phenylacetic acid during Pseudomonas syringae-Arabidopsis thaliana pathogenesis.

Several plant-associated microbes synthesize the auxinic plant growth regulator phenylacetic acid (PAA) in culture; however, the role of PAA in plant-pathogen interactions is not well understood. In this study, we investigated the role of PAA during interactions between the phytopathogenic bacterium Pseudomonas syringae strain PtoDC3000 (PtoDC3000) and the model plant host, Arabidopsis thaliana. Previous work demonstrated that indole-3-acetaldehyde dehydrogenase A (AldA) of PtoDC3000 converts indole-3-acetaldehyde (IAAld) to the auxin indole-3-acetic acid (IAA). Here, we further demonstrated the biochemical versatility of AldA by conducting substrate screening and steady-state kinetic analyses, and showed that AldA can use both IAAld and phenylacetaldehyde as substrates to produce IAA and PAA, respectively. Quantification of auxin in infected plant tissue showed that AldA-dependent synthesis of either IAA or PAA by PtoDC3000 does not contribute significantly to the increase in auxin levels in infected A. thaliana leaves. Using available arogenate dehydratase (adt) mutant lines of A. thaliana compromised for PAA synthesis, we observed that a reduction in PAA-Asp and PAA-Glu is correlated with elevated levels of IAA and increased susceptibility. These results provide evidence that PAA/IAA homeostasis in A. thaliana influences the outcome of plant-microbial interactions.

Targeting axonal guidance dependencies in glioblastoma with ROBO1 CAR T cells.

Resistance to genotoxic therapies and tumor recurrence are hallmarks of glioblastoma (GBM), an aggressive brain tumor. In this study, we investigated functional drivers of post-treatment recurrent GBM through integrative genomic analyses, genome-wide genetic perturbation screens in patient-derived GBM models and independent lines of validation. Specific genetic dependencies were found consistent across recurrent tumor models, accompanied by increased mutational burden and differential transcript and protein expression compared to its primary GBM predecessor. Our observations suggest a multi-layered genetic response to drive tumor recurrence and implicate PTP4A2 (protein tyrosine phosphatase 4A2) as a modulator of self-renewal, proliferation and tumorigenicity in recurrent GBM. Genetic perturbation or small-molecule inhibition of PTP4A2 acts through a dephosphorylation axis with roundabout guidance receptor 1 (ROBO1) and its downstream molecular players, exploiting a functional dependency on ROBO signaling. Because a pan-PTP4A inhibitor was limited by poor penetrance across the blood-brain barrier in vivo, we engineered a second-generation chimeric antigen receptor (CAR) T cell therapy against ROBO1, a cell surface receptor enriched across recurrent GBM specimens. A single dose of ROBO1-targeted CAR T cells doubled median survival in cell-line-derived xenograft (CDX) models of recurrent GBM. Moreover, in CDX models of adult lung-to-brain metastases and pediatric relapsed medulloblastoma, ROBO1 CAR T cells eradicated tumors in 50-100% of mice. Our study identifies a promising multi-targetable PTP4A-ROBO1 signaling axis that drives tumorigenicity in recurrent GBM, with potential in other malignant brain tumors.

Sustainable, aqueous exfoliation of MoS2via bio-inspired avenues.

Two dimensional (2D) nanosheets of MoS2 were succesfully produced by an exfoliation process in aqueous media with the support from peptides and sonication. The exfoliation process assisted by uncapped MoSBP1 peptides was found to have enhanced efficiency in comparison to the capped counterpart. MoS2 nanosheets obtained using uncapped MoSBP1 have thinner structures containing one layer of MoS2, while in capped version of peptides, MoS2 nanosheets tend to form multilayer (up to 4) structures of exfoliated sheets. Molecular dynamics simulations indicate that inter-sheet gaps generated by sonication in MoS2 nanostacks cannot be maintained by water only; the gaps closed after ∼11 ns. Both capped CMoSBP1 and uncapped MoSBP1 were seen to spontaneously insert into the gap in nanostacks of MoS2 and they can ultimately maintain the inter-sheet gap for longer (≥20 ns). Potential of mean force profiles for the association of two MoS2 nanosheets decorated with CMoSBP1 and MoSBP1 versions of peptides revealed that uncapped MoSBP1 peptides provide good protection from MoS2 nanosheet re-unification. Such protection can prevent the nanosheets from reassociation and subsequent aggregation, whereas the capped CMoSBP1 peptides can offer protection, but over a shorter range. These simulation results could explain the experimental observation of greater efficiency of exfoliation in uncapped MoSBP1 peptides.

Mechanical ventilation guided by driving pressure optimizes local pulmonary biomechanics in an ovine model.

Mechanical ventilation exposes the lung to injurious stresses and strains that can negatively affect clinical outcomes in acute respiratory distress syndrome or cause pulmonary complications after general anesthesia. Excess global lung strain, estimated as increased respiratory system driving pressure, is associated with mortality related to mechanical ventilation. The role of small-dimension biomechanical factors underlying this association and their spatial heterogeneity within the lung are currently unknown. Using four-dimensional computed tomography with a voxel resolution of 2.4 cubic millimeters and a multiresolution convolutional neural network for whole-lung image segmentation, we dynamically measured voxel-wise lung inflation and tidal parenchymal strains. Healthy or injured ovine lungs were evaluated as the mechanical ventilation positive end-expiratory pressure (PEEP) was titrated from 20 to 2 centimeters of water. The PEEP of minimal driving pressure (PEEPDP) optimized local lung biomechanics. We observed a greater rate of change in nonaerated lung mass with respect to PEEP below PEEPDP compared with PEEP values above this threshold. PEEPDP similarly characterized a breaking point in the relationships between PEEP and SD of local tidal parenchymal strain, the 95th percentile of local strains, and the magnitude of tidal overdistension. These findings advance the understanding of lung collapse, tidal overdistension, and strain heterogeneity as local triggers of ventilator-induced lung injury in large-animal lungs similar to those of humans and could inform the clinical management of mechanical ventilation to improve local lung biomechanics.

Microbiological analysis of tunneled hemodialysis catheters isolated from patients receiving hemodialysis in Saskatchewan.

Aim: To compare the microbial communities inside hemodialysis catheters from symptomatic and asymptomatic patients to determine their differences.Materials & methods: Catheters (n = 41) were removed from patients in the Saskatchewan Health Authority over an 18-month period. The catheter section inside the body was flushed and the contents were evaluated using culture-dependent and culture-independent analysis.Results: All catheters were colonized by bacteria, with considerable overlap between groups based on microbial communities and the individual species detected. More Gram-negative species were detected by sequencing, whereas predominantly Gram-positive strains were cultured. Antibiotic resistance and biofilm formation was widespread and not correlated with either catheter group.Conclusion: Common pathogens were detected in each set of catheters, therefore predicting infections based on the microbiology is difficult.

Many patients use catheters to help clean their blood, a process called hemodialysis. The use of catheters is also associated with complications, such as blood infections. We looked at the types of bacteria associated with catheters from patients who had infections (n = 21) and compared them to catheters from patients who had no signs of infection (n = 20). Once removed from the patient, we flushed out each catheter and tried to grow bacteria in different conditions. We also looked at DNA from within the catheter to identify bacterial species that were present. All 41 catheters had bacteria and there were many common species detected. We detected species known to cause illness such as Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli and Pseudomonas, Enterobacter, Morganella and Stenotrophomonas species. S. aureus was only grown from patients that had infections. Resistance to antibiotics was found to be common in bacteria grown from catheters. This did not seem to be influenced by whether patients were infected or not. Finally, we identified several catheters where two species, S. epidermidis and P. aeruginosa, were detected together. Our main conclusion was that bacteria are commonly present inside catheters that are used for hemodialysis, regardless of whether patients are infected or not.

Does an improvement in cord-level intraoperative neuromonitoring data lead to a reduced risk for postoperative neurologic deficit in spine deformity surgery?

PURPOSE: To determine if an improvement in cord-level intraoperative neuromonitoring (IONM) data following data loss results in a reduced risk for new postoperative motor deficit in pediatric and adult spinal deformity surgery. METHODS: A consecutive series of 1106 patients underwent spine surgery from 2015 to 2023 by a single surgeon. Cord alerts were defined by Somatosensory-Evoked Potentials (SSEP; warning criteria: 10% increase in latency or > 50% loss in amplitude) and Motor-Evoked Potentials (MEP; warning criteria: 75% loss in amplitude without return to acceptable limits after stimulation up 100 V above baseline level). Timing of IONM loss and recovery, interventions, and baseline/postoperative day 1 (POD1) lower extremity motor scores were analyzed. RESULTS: IONM Cord loss was noted in 4.8% (53/11,06) of patients and 34% (18/53) with cord alerts had a POD1 deficit compared to preoperative motor exam. MEP and SSEP loss attributed to 98.1% (52/53) and 39.6% (21/53) of cord alerts, respectively. Abnormal descending neurogenic-evoked potential (DNEP) was seen in 85.7% (12/14) and detected 91.7% (11/12) with POD1 deficit. Abnormal wake-up test (WUT) was seen in 38.5% (5/13) and detected 100% (5/5) with POD1 deficit. Most cord alerts occurred during a three-column osteotomy (N = 23/53, 43%); decompression (N = 12), compression (N = 7), exposure (N = 4), and rod placement (N = 14). Interventions were performed in all 53 patients with cord loss and included removing rods/less correction (N = 11), increasing mean arterial pressure alone (N = 10), and further decompression with three-column osteotomy (N = 9). After intervention, IONM data improved in 45(84.9%) patients (Full improvement: N = 28; Partial improvement: 17). For those with full and partial IONM improvement, the POD1 deficit was 10.7% (3/28) and 41.2% (7/17), respectively. For those without any IONM improvement (15.1%, 8/53), 100% (8/8) had a POD1 deficit, P < 0.001. CONCLUSION: A full or partial improvement in IONM data loss after intraoperative intervention was significantly associated with a lower risk for POD1 deficit with an absolute risk reduction of 89.3% and 58.8%, respectively. All patients without IONM improvement had a POD1 neurologic deficit.

Sex specific emergence of trisomic Dyrk1a-related skeletal phenotypes in the development of a Down syndrome mouse model.

Skeletal insufficiency affects all individuals with Down syndrome (DS) or Trisomy 21 (Ts21) and may alter bone strength throughout development due to a reduced period of bone formation and early attainment of peak bone mass compared to typically developing individuals. Appendicular skeletal deficits also appear in males before females with DS. In femurs of male Ts65Dn DS model mice, cortical deficits were pronounced throughout development, but trabecular deficits and Dyrk1a overexpression were transitory until postnatal day (P) 30 when there were persistent trabecular and cortical deficits and Dyrk1a was trending overexpression. Correction of DS-related skeletal deficits by a purported DYRK1A inhibitor or through genetic means beginning at P21 was not effective at P30, but germline normalization of Dyrk1a improved male bone structure by P36. Trabecular and cortical deficits in female Ts65Dn mice were evident at P30 but subsided by P36, typifying periodic developmental skeletal normalizations that progressed to more prominent bone deficiencies. Sex-dependent differences in skeletal deficits with a delayed impact of trisomic Dyrk1a are important to find temporally specific treatment periods for bone and other phenotypes associated with Ts21.

Innervated breast reconstruction: a narrative review of neurotization techniques and outcomes.

Background and Objective: While significant sensation recovery improvements in neurotized breasts following reconstruction have been reported, sensation testing methods and surgical techniques have been widely variable. This narrative review aims to summarize available literature on current neurotization practices and sensory recovery outcomes in patients undergoing innervated breast reconstruction. Methods: A comprehensive literature search of PubMed Medline, Web of Science, and Embase was conducted to identify all studies reporting outcomes of neurotization in breast reconstruction surgeries. Data analyzed included operative times, neurotization techniques, sensory outcomes, and methods as well as patient reported outcomes. Key Content and Findings: Despite the heterogeneity of various studies reviewed, all forms of neurotization achieved earlier and superior sensory recovery throughout the reconstructed breast skin compared to non-innervated breasts. In absence of randomized controlled trials or high-quality comparative studies, further evidence is required to objectively confirm this technique offers better sensory recovery. Conclusions: Neurotization at the time of breast reconstruction may lead to improved sensation and patient reported outcomes delineating improved quality of life compared to non-innervated breasts. Future studies need to standardize the way that breast sensation is measured and determine pre-operative variables leading to expected changes in final sensation recovery to help manage surgical outcome expectations of both the surgeon and the patient.

Positive pressure in bamboo is generated in stems and rhizomes, not in roots.

Bamboos stand out among other tall plants in being able to generate positive pressure in the xylem at night, pushing water up to the leaves and causing drops to fall from leaf tips as guttation that can amount to a steady nocturnal 'bamboo rain'. The location and mechanism of nocturnal pressure generation in bamboos are unknown, as are the benefits for the plants. We conducted a study on the tall tropical bamboo species Bambusa oldhamii (giant timber bamboo) growing outdoors in southern California under full irrigation to determine where in the plant the nocturnal pressure is generated, when it rises in the evening, and when it dissipates in the morning. We hypothesized that the build-up of positive pressure would be triggered by the cessation of transpiration-driven sap flow and that resumption of sap flow in the morning would cause the pressure to dissipate. Nocturnal pressure was observed in mature stems and rhizomes, but never in roots. The pressure was episodic and associated with stem swelling and was usually, but not always, higher in rhizomes and basal stems than in stems at greater height. Time series analyses revealed that dry atmospheric conditions were followed by lower nocturnal pressure and rainfall events by higher stem pressure. Nocturnal pressure was unrelated to sap flow and even was generated for a short time in isolated stem pieces placed in water. We conclude that nocturnal pressure in bamboo is not 'root pressure' but is generated in the pseudo-woody rhizomes and stems. It is unrelated to the presence or absence of sap flow and therefore must be created outside of vessels, such as in phloem, parenchyma, or fibres. It is unlikely to be a drought adaptation and may benefit the plants by maximizing stem water storage for daytime transpiration or by transporting nutrients to the leaves.

Analysis of beta-cell maturity and mitochondrial morphology in juvenile non-human primates exposed to maternal Western-style diet during development.

Introduction: Using a non-human primate (NHP) model of maternal Western-style diet (mWSD) feeding during pregnancy and lactation, we previously reported altered offspring beta:alpha cell ratio in vivo and insulin hyper-secretion ex vivo. Mitochondria are known to maintain beta-cell function by producing ATP for insulin secretion. In response to nutrient stress, the mitochondrial network within beta cells undergoes morphological changes to maintain respiration and metabolic adaptability. Given that mitochondrial dynamics have also been associated with cellular fate transitions, we assessed whether mWSD exposure was associated with changes in markers of beta-cell maturity and/or mitochondrial morphology that might explain the offspring islet phenotype. Methods: We evaluated the expression of beta-cell identity/maturity markers (NKX6.1, MAFB, UCN3) via florescence microscopy in islets of Japanese macaque pre-adolescent (1 year old) and peri-adolescent (3-year-old) offspring born to dams fed either a control diet or WSD during pregnancy and lactation and weaned onto WSD. Mitochondrial morphology in NHP offspring beta cells was analyzed in 2D by transmission electron microscopy and in 3D using super resolution microscopy to deconvolve the beta-cell mitochondrial network. Results: There was no difference in the percent of beta cells expressing key maturity markers in NHP offspring from WSD-fed dams at 1 or 3 years of age; however, beta cells of WSD-exposed 3 year old offspring showed increased levels of NKX6.1 per beta cell at 3 years of age. Regardless of maternal diet, the beta-cell mitochondrial network was found to be primarily short and fragmented at both ages in NHP; overall mitochondrial volume increased with age. In utero and lactational exposure to maternal WSD consumption may increase mitochondrial fragmentation. Discussion: Despite mWSD consumption having clear developmental effects on offspring beta:alpha cell ratio and insulin secretory response to glucose, this does not appear to be mediated by changes to beta-cell maturity or the beta-cell mitochondrial network. In general, the more fragmented mitochondrial network in NHP beta cells suggests greater ability for metabolic flexibility.

Hip microinstability and its association with femoroacetabular impingement: A scoping review.

Introduction: Hip microinstability has become a recognized cause of non-arthritic hip pain and disability in young patients. However, its pathophysiology remains unclear. We want to (1) present an overview of the evidence of hip microinstability and of its association with femoroacetabular impingement (FAI), (2) map out the type of evidence available, and (3) make recommendations for future research. Methods: A deductive analysis and extraction method was used to extract information. In addition, diagnostic accuracy statistics were extracted or calculated. Results: Of the 2,808 identified records, 123 were eligible for inclusion. Different definitions for microinstability exist. A standardized terminology and clear diagnostic criteria are lacking. FAI and microinstability may be associated and may aggravate each other. Conservative treatment strategies for FAI and microinstability are similar. The reported prevalence of microinstability in combination with FAI ranges from 21% to 42% in adults undergoing hip arthroscopy or magnetic resonance arthrography (MRA) of the hip. Conclusion: Hip microinstability and FAI may be associated, occur together, or exacerbate each other. To better address this topic, a standardized terminology for microinstability is essential. Achieving consensus on physical examination and diagnosis is also necessary. Initial efforts to establish uniform diagnostic criteria have been made, but further work is needed. Specifically, randomized controlled trials are required to evaluate the effectiveness of training programmes aimed at reducing symptoms in individuals with microinstability, with or without FAI. Such studies will enable clinicians to manage microinstability with greater confidence within this context.

An Update on the Independent Plastic Surgery Match (2019-2022): Trends, Predictors, and Program Leaders' Perspectives.

Background: A previous study by the authors noted a decline in independent plastic surgery residency programs and rising applicant participation. This study provides updates on match trends and influential predictors, and gathers program leaders' views on the future of the independent track. Methods: Match data (2019-2022) were obtained from the San Francisco match after American Council of Educators in Plastic Surgery approval. Variables influencing match success were analyzed, and program leaders were surveyed about desirable applicant traits and program trajectories. Results: From 2019 to 2022, 243 of 428 applicants matched. Programs and positions declined by 10% and 9.5%, respectively. Applicants rose to 42.3%, but match rates fell from 82% to 56%. Osteopathic graduates doubled, whereas international graduates increased to 53.8%. Successful matches were associated with US allopathic medical school graduates, university-affiliated general surgery residencies, eight or more interviews, United States Medical Licensing Examination scores greater than 230, and high post graduate year (PGY)1-3 American Board of Surgery In-service Training Examination scores (PGY1-64.7%, PGY2-61.2%, PGY3-60.7%; P < 0.05). Of surveyed programs, 55.6% aimed to continue running the independent track in the next year. Conversely, 7.4% planned to discontinue in the next year, 22.2% within 2-5 years, 7.4% within the next decade, and 7.4% were unsure. Conclusions: Although support for the independent plastic surgery track remains, program participation diminishes as applicant interest increases, intensifying match challenges. Increasing number of interviews improves match potential. Program leaders display varied commitments, with looming plans for some programs to discontinue offering this track. Applicant evaluation pivots on strong recommendations, research, and test scores.

Effect of metabolic status on response to SIV infection and antiretroviral therapy in nonhuman primates.

Current antiretroviral therapy (ART) regimens efficiently limit HIV replication, thereby improving life expectancy of people living with HIV, but also cause metabolic side effects. The ongoing obesity epidemic has resulted in more people with metabolic comorbidities at the time of HIV infection, yet the impact of pre-existing metabolic dysregulation on infection sequelae and response to ART is unclear. Here, to investigate the impact of preexisting obesity and insulin resistance on acute infection and subsequent long-term ART, we infected a cohort of lean and obese adult male macaques with SIV and administered ART. The responses of lean and obese macaques to SIV and ART were similar with respect to plasma and cell-associated viral loads, ART drug levels in plasma and tissues, SIV-specific immune responses, adipose tissue and islet morphology, and colon inflammation, with baseline differences between lean and obese groups largely maintained. Both groups exhibited a striking depletion of CD4+ T cells from adipose tissue that did not recover with ART. However, differential responses to SIV and ART were observed for body weight, omental adipocyte size, and the adiponectin/leptin ratio, a marker of cardiometabolic risk. Thus, obesity and insulin resistance had limited effects on multiple responses to acute SIV infection and ART, while several factors that underlie long-term metabolic comorbidities were influenced by prior obesity and insulin resistance. These studies provide the foundation for future investigations into the efficacy of adjunct therapies such as metformin and glucagon-like peptide-1 receptor agonists in the prevention of metabolic comorbidities in people living with HIV.

FDA-approved disulfiram inhibits the NLRP3 inflammasome by regulating NLRP3 palmitoylation.

The NLRP3 inflammasome is dysregulated in autoinflammatory disorders caused by inherited mutations and contributes to the pathogenesis of several chronic inflammatory diseases. In this study, we discovered that disulfiram, a safe US Food and Drug Administration (FDA)-approved drug, specifically inhibits the NLRP3 inflammasome but not the NLRC4 or AIM2 inflammasomes. Disulfiram suppresses caspase-1 activation, ASC speck formation, and pyroptosis induced by several stimuli that activate NLRP3. Mechanistically, NLRP3 is palmitoylated at cysteine 126, a modification required for its localization to the trans-Golgi network and inflammasome activation, which was inhibited by disulfiram. Administration of disulfiram to animals inhibited the NLRP3, but not NLRC4, inflammasome in vivo. Our study uncovers a mechanism by which disulfiram targets NLRP3 and provides a rationale for using a safe FDA-approved drug for the treatment of NLRP3-associated inflammatory diseases.

Effect of sorghum bran addition on antioxidant activities, sensory properties, and in vitro starch digestibility of Chinese southern-style steamed bread.

BACKGROUND: Chinese steamed bread (CSB) is one of the most important staple foods in China and is also popular in South-East Asia. Developing functional CSB could improve people's resistance to inflammatory and non inflammatory diseases. This work investigated the effect of sorghum bran addition on antioxidant activities, sensory properties, and in vitro starch digestibility of Chinese southern-style steamed bread (CSSB). RESULTS: In this study, the enhanced CSSB with 0-200 g kg-1 of fine black and tannin (sumac) sorghum bran addition was developed. A small change in phenol content and antioxidant activity was observed at various stages in the processing procedure before steaming. Moreover, a high retention of antioxidant phenolics CSSB with sorghum bran addition was observed. Sorghum bran addition significantly increased the total phenol content and antioxidant activity of CSSB by 4.5-10 times, on average, relative to control. Sorghum bran addition significantly also increased the content of resistant starch, and significantly decreased in vitro starch digestibility in CSSB; these effects were likely due to the joint inhibitory effect of tannins and ferulic acid on starch digestibility. Interestingly, the sorghum bran breads scored higher or similar to control in sensory color preference and overall appearance, but lower on most textural and mouthfeel attributes. CONCLUSION: Sorghum bran addition significantly increased the antioxidant activity of CSSB and significantly decreased starch digestibility. Moreover, the color and appearance properties were maintained or improved. However, the sensorial textural attributes were negatively impacted by the sorghum bran substitutions. Strategies to improve the texture of bran-fortified breads would likely enhance their consumer acceptability. © 2024 Society of Chemical Industry.