To determine the change in modified star excursion balance test scores in patients between 6 and 12 months following anterior cruciate ligament (ACL) reconstruction and the change in the proportion of patients who met recommended thresholds at each timepoint. A secondary aim was to assess whether change over time differed according to age, sex, graft type or activity level. Longitudinal cohort. Orthopaedic Clinic. 115 patients that completed 6- and 12-month testing after ACL reconstruction. Modified star excursion balance test scores (composite and individual reach scores). There was a significant increase of test scores for the surgical limb at 12-months compared to 6-months (p < 0.005) with no differences in limb symmetry index. Most patients (92%) reached threshold composite scores >90% equivalent to individual leg length at 6-months. This proportion did not change at 12-months. Patient-related factors had no effect on change in test scores across time. The modified star excursion balance test may be more applicable to assess dynamic balance performance 6-months post-surgery. Almost all patients met pre-determined criteria for dynamic balance performance by 6-months following surgery. There was no impact of patient age, sex, graft type or activity level on change in performance between 6- and 12-months.
Adoptive T-cell therapies engineered with T-cell receptors (TCRs) or TCR-like antibodies have shown considerable promise in cancer immunotherapy. However, identifying tumor antigen-specific TCR-like antibodies, particularly against human leukocyte antigen-presented neoantigens, remains challenging. Here, we present a function-based, rather than affinity-based, antibody screening platform utilizing Synthetic T-cell receptor and Antigen Receptor (STAR)-T cell libraries. We found that antigen engagement in STAR-T cells triggers synchronous receptor endocytosis and T-cell activation, and we integrated these paired processes into an Endocytosis-Activation (E-A) functional readout for antibody screening. Applying E-A functional screening, we rapidly identified multiple nanobodies targeting the cell-surface antigen CD22 as well as the intracellular neoantigen P53R175H. STAR-T cells engineered with these nanobodies mediated potent anti-tumor efficacy both in vitro and in vivo. Furthermore, this platform yielded nanobodies that can be directly reformatted into other therapeutic modalities, including chimeric antigen receptors and bispecific antibodies, while maintaining cytotoxic function. Overall, the E-A screening platform links antibody discovery directly to T-cell function, providing a robust approach for identifying therapeutic antibodies, especially neoantigen-specific nanobodies, for T cell-based cancer immunotherapy.
Convectional heat transfer continues to receive extensive research attention due to its importance in vital applications such as solar energy collectors and cooling of nuclear reactors. This research investigates natural convection and associated entropy generation within a porous wavy enclosure with a star-shaped hot cylinder. The fluid saturated in the porous medium is assumed to be a water-Cu-Al2O3 hybrid nanofluid. The energy balance equation accounts for thermal non-equilibrium between the hybrid nanofluid and the local structure of the porous medium (LTNE). The effects of the number of lobes of the star-shaped cylinder (N), the Rayliegh number (Ra), the Darcy number (Da), the porosity of the medium (ε), and the volume fraction of the different nanoparticles (φAl2O3 and φCu) are inspected using numerical FEM analysis and optimized by the aid of artificial neural network (ANN). The results show that it is not possible to increase the Nusselt number without increasing entropy, and it is not possible to decrease entropy without decreasing heat transfer. The objective function (OBF), defined as the ratio of the Nusselt number to the total entropy generation, indicates that the best design is achieved with low obstacle waviness and low nanoparticle loading. The number of lobes and the nanoparticle volume fraction often increase entropy faster than they improve heat transfer. The maximum OBF = 3.877 (Nuavg = 38.705, ST = 9.9824) occurs at N = 1, φAl2O3 = 0, φCu = 0, Ra = 103, Da = 10-4, ε = 0.1. This study demonstrates the advantages of using artificial neural networks (ANN) to optimize the design of heat exchangers filled with nanofluids. This approach minimizes losses caused by thermal and flow irreversibility, thereby contributing to energy savings.
Biomineralized structures produced by living organisms are widely recognized for their exceptional mechanical performance, yet their potential optical roles are relatively less explored. Here, we demonstrate that within the calcitic ossicle-based skeleton of the sea star Protoreaster nodosus, where each ossicle represents a discrete skeletal element, one specialized ossicle, known as the terminal plate, contains a radially arranged array of light-guiding structures (LGSs). These LGSs exhibit an elongated, cone-like geometry (~250 μm in length) and are embedded within the porous stereom, a characteristic meshwork architecture of echinoderms analogous to open-cell cellular solids and composed of magnesium-containing single-crystalline calcite. Optical experiments demonstrate that, unlike other skeletal elements, the terminal plate can transmit and focus light into an internal cavity via the LGS array. Combined optical analyses using ray-tracing and finite-difference time-domain simulations reveal that each LGS transmits ca. 70% of incident light at normal incidence and concentrates it up to 2.8-fold at its exiting surface. Furthermore, when acting collectively as the LGS array within the terminal plate, the LGSs capture light over a broad field of view (~120°), resulting in an integrated transmitted intensity that is sixfold to eightfold greater than the incoming intensity perceived by a single LGS. Although the biological function of this optical capability remains uncertain, this natural porous structure demonstrates that cellular solids can integrate efficient light-guiding behavior while enhancing mechanical properties (i.e., threefold increase in stiffness compared with random stereom), offering design insights for lightweight, multifunctional structures.
A new study examines how distinct neuronal ensembles underlie the encoding and retrieval of complex spatial memories. The paper also explores how distinct memory representations interact with one another to drive appropriate behavior in a rodent foraging task.
Dark matter (DM) models with a conserved particle-antiparticle number, n_{χ}-n_{χ[over ˜]}, and the asymmetry in the cosmological abundance n_{χ}≠n_{χ[over ˜]}, are known to be challenged by the existence of old neutron stars (NSs), as the sufficient accumulation of DM will lead to the collapse of NSs into black holes. We demonstrate that the applicability of these constraints is much wider and covers models with symmetric populations of DM, n_{χ}=n_{χ[over ˜]}, as the process of DM capture regulated by a nucleon-DM scattering can be inherently asymmetric, σ_{χn}≠σ_{χ[over ˜]n}. The asymmetry is induced by the interference of different types of χ-n interactions, provided that their combination is odd under charge conjugation in the DM sector, C_{χ}, and even under combined parity P_{χ+n}. We provide a complete analysis of DM-nucleon bilinear χ-n interactions and find that this asymmetry is very generic. Using canonical NS parameters and local DM halo inputs, we exclude spin-averaged scattering cross sections down to σ_{nχ}≳10^{-46}  cm^{2} at DM mass m_{χ}≲10^{10}  GeV for the maximally asymmetric capture rate and show that the constraints persist down to very small values of the cross-section asymmetry, A=(σ_{χn}-σ_{χ[over ˜]n})/(σ_{χn}+σ_{χ[over ˜]n})≳10^{-5}.
The World Health Organization has identified health literacy as a key pillar for resilient health systems in its current global strategy for 2025-2028. In this editorial, we argue that effectively addressing health literacy requires its integration into key strategic frameworks at both the global and national levels, as this represents a fundamental precondition for a more coordinated and systematic approach to the issue. Slovenia has followed these global directions by adopting the National Health Literacy Strategy 2025-2035 in 2025, establishing a ten-year strategic framework to strengthen health literacy. The country is also adhering to recommendations for ongoing research in this field; in 2026, the second national health literacy survey will be conducted. Looking ahead, the focus should be on developing and implementing practical public health interventions, and on strengthening coordination with existing health promotion and prevention programmes in Slovenia that are already delivering measurable impact. A key challenge will be to strengthen collaboration between researchers, policy-makers, and practitioners to help create a supportive, health-literate environment in Slovenia. Svetovna zdravstvena organizacija je v svoji aktualni globalni strategiji za obdobje 2025—2028 poudarila, da je zdravstvena pismenost eden ključnih stebrov odpornosti zdravstvenih sistemov. V tem uvodniku zato razpravljamo, da je za učinkovito naslavljanje zdravstvene pismenosti nujno njeno umeščanje v ključne strateške dokumente tako na globalni kot nacionalni ravni, saj to predstavlja temeljni pogoj za bolj usklajeno in sistematično obravnavo tega področja. Slovenija tem globalnim usmeritvam sledi, saj je leta 2025 sprejela Nacionalno strategijo zdravstvene pismenosti 2025—2035, s čimer je vzpostavila dolgoročni strateški okvir za razvoj in krepitev zdravstvene pismenosti. Hkrati sledimo usmeritvam glede kontinuiranega raziskovanja na tem področju – v letu 2026 poteka druga nacionalna raziskava zdravstvene pismenosti, ki bo omogočila vpogled v trenutno stanje in spremljanje trendov skozi čas. V prihodnje bo pomemben poudarek na razvoju in implementaciji konkretnih javnozdravstvenih intervencij ter na boljši koordinaciji z že obstoječimi promocijskimi in preventivnimi programi v Sloveniji, ki izkazujejo pomembne javnozdravstvene učinke. Ključni izziv bo predvsem krepitev povezovanja med raziskovalci, odločevalci in strokovnjaki iz prakse, saj bo le s takšnim sodelovanjem mogoče soustvarjati podporno zdravstveno pismeno okolje v Sloveniji.
Whether obstructive sleep apnea (OSA) severity is independently associated with sarcopenia, beyond the effects of age, obesity and sex, has not been established in a single-centre cohort using standardised ultrasound-based assessment. We examined sarcopenia prevalence and its components across OSA severity strata in a Kuwaiti cohort using the ISarcoPRM sarcopenia algorithm. Cross-sectional within-cohort analysis of 110 adults aged 50 years or older with confirmed OSA (apnea-hypopnea index [AHI] 5 or more events/h by Level 3 portable monitoring; SomnoTouch, Somnomedics, Germany), stratified as mild (AHI 5-14.99, n = 28), moderate (AHI 15-29.99, n = 39) or severe (AHI 30 or more, n = 43). Sarcopenia was assessed using the ISarcoPRM algorithm: quadriceps muscle thickness by ultrasound, Sonographic Thigh Adjustment Ratio (STAR), handgrip strength (Jamar dynamometer) and chair stand test (CST). Demographic and comorbidity profiles were balanced across severity groups (all p > 0.05). Quadriceps muscle thickness, STAR and handgrip strength did not differ significantly across severity strata (all Kruskal-Wallis p > 0.05). CST time showed a significant gradient across severity strata (Kruskal-Wallis p = 0.047), and both AHI and ODI correlated modestly with CST time (r = +0.209, p = 0.029 and r = +0.203, p = 0.034, respectively). Sarcopenia prevalence was 21.4%, 30.8% and 34.9% in mild, moderate and severe OSA, respectively, with no significant trend (Cochran-Armitage p = 0.237). Age (OR 1.12 per year, 95%CI 1.05-1.19, p < 0.001) and BMI (OR 1.10 per kg/m2, 95%CI 1.02-1.18, p = 0.009) were the independent predictors of sarcopenia; OSA severity was not (adjusted OR 1.19, 95%CI 0.65-2.18, p = 0.577). Low STAR prevalence was 83.6%, driven by the high-obesity burden in this cohort and the origin of STAR cut-offs in a lower BMI Turkish reference population. In this Kuwaiti OSA cohort, age and BMI are the dominant determinants of sarcopenia, with no independent contribution from OSA severity. A modest association between OSA severity indices and CST time suggests that physical function may be more sensitive to OSA-related changes than muscle mass per se. The near-universal low STAR prevalence points to the need for population-specific normative data in high-obesity cohorts.
NR5A1 encodes a transcription factor essential for adrenal and gonadal development. Gene variants are a known cause of heterogeneous 46,XY disorders of sex development (DSD), but the mechanisms underlying the phenotypic variability remain unclear. We investigated how different NR5A1 variants affect downstream gene regulation and contribute to DSD pathogenesis. We analyzed four naturally occurring NR5A1 variants identified in patients with 46,XY DSD-two novel (p.Cys65Ser, p.His310Arg) and two previously reported (p.Cys30Ser, p.Gln329*). We performed protein and transcriptomic analyses to characterize variant effects and identify dysregulated and candidate target genes, validated by qPCR and luciferase assays. Transcriptomic and CUT&Tag analyses focused on the p.Gln329* truncating variant. All four variants occurred at conserved residues and resulted in reduced NR5A1 protein expression and impaired nuclear localization upon transfection in HEK293T cells. Transcriptomic analysis using the p.Gln329* variant revealed broad downregulation of genes involved in steroidogenesis, including CYP11A1, STAR, and CYP17A1. Notably, AMHR2 and STARD8 were significantly downregulated and showed reduced CUT&Tag signal in variant-transfected cells. Promoter assays confirmed that all variants diminished CYP11A1 and AMHR2 promoter activity. Only the p.Gln329* variant affected STARD8 promoter activity. These findings indicate that NR5A1 variants impair protein expression and localization, leading to transcriptional dysregulation of genes involved in steroid hormone biosynthesis and sexual development. Based on analysis of the p.Gln329* truncating variant, AMHR2 and STARD8 are strong candidate novel downstream targets of NR5A1, offering further insight into the mechanisms driving 46,XY DSD. Differences in sex development can occur when the genetic instructions for building male reproductive organs are disrupted before birth. This study focuses on a key gene called NR5A1, which acts like a master switch to turn on other genes essential for testis development and hormone production. We investigated four variants in this gene found in children with 46,XY differences in sex development. Using cell models, we showed that these variants cause the NR5A1 protein to be produced at lower levels and prevent it from reaching the cell’s nucleus, where it normally works. As a result, the variant proteins fail to properly switch on several crucial target genes involved in making male hormones. We identified two new candidate genes controlled by NR5A1, called AMHR2 and STARD8, which may play important roles in this process. Our research helps explain how changes in a single gene can lead to a broad range of developmental outcomes and provides a clearer picture of the molecular steps involved in human sex development.
Community-level sociodemographic factors and hospital quality are associated with access to cancer care and outcomes. Using Medicare data (2016-2018), we evaluated the association between social determinants of health (SDoH) and hospital quality with 30-day mortality and readmission after selected elective cancer surgery. Separate multivariable logistic regression models sequentially adjusted for comorbidities and SDoH factors (Social Vulnerability Index (SVI) and Distressed Communities Index (DCI)) and then Hospital Star Rating. Among 16,869 patients, the "At Risk" DCI group and higher SVI were associated with higher 30-day mortality, and higher SVI was associated with higher odds of 30-day readmission and mortality. Subsequent models demonstrated that higher Hospital Star Rating was associated with lower odds of 30-day mortality and readmission and SDoH factors lost significance after adjusting for Hospital Star Rating. Hospital quality may have a greater impact on short-term outcomes than SDoH factors.
Adaptive optics aims to restore diffraction limited resolution in an imaging system in the presence of optical aberrations. To this end, the wavefront error needs to be measured prior to its compensation. Traditional wavefront sensors typically measure the local gradient of the wavefront emitted from a guide star (or another known point source) using a microlens array in front of a camera. They are typically dedicated devices that need to be integrated into an imaging system. Here we have tested the concept of estimating the wavefront error directly from an image of a guide star by training a machine learning model. We produce a two-photon laser spot in a water fluorescein media, and introduce random, but known aberrations using a deformable mirror to form a large training set. After validation, we integrated the machine learning wavefront sensor in an AO feedback loop with the deformable mirror. We demonstrate proof of principle compensation of sample-introduced optical aberrations with this system.
To test whether baseline depressive symptom profiles are associated with remission in Major Depressive Disorder (MDD) and to replicate previous findings from GSRD and STAR∗D in the PANDORA trial. We performed a secondary analysis of 215 adults with MDD enrolled in PANDORA and starting a new antidepressant. Baseline severity was assessed with the 17-item Hamilton Depression Rating Scale (HAM-D). Remission at week 12 was defined as HAM-D ≤ 7. Logistic regression models examined associations between baseline HAM-D total and item scores and remission overall and by sex, adjusting for age and sex and other covariates; sensitivity analyses further adjusted for treatment allocation (treatment as usual vs genetically guided therapy). Remission was achieved by 53% of patients (n = 114). Higher baseline HAM-D total score and higher scores on depressed mood, suicide, psychomotor retardation and hypochondriasis were associated with lower odds of remission in the total sample. In women, higher baseline severity, suicide and psychomotor retardation were associated with non-remission, whereas in men hypochondriasis was the only significant prognostic marker. These associations remained significant after adjustment for the treatment arm. Baseline depressive severity and selected symptom dimensions, particularly suicidal ideation and worry-related symptoms, relate to remission in MDD and may inform sex-sensitive, symptom-guided treatment strategies.
In the USA, the government certifies nursing homes to receive government funding and uses a 5-star rating system to share information about the quality of care in these nursing homes with the public on the CMS website. However, a star rating is not posted for the poorest performing nursing homes, the "Special Focus Facilities." We interviewed older adults to get their perspectives on the information posted online about SFFs. Respondents reported the term "Special Focus Facility" is misleading and confusing and the posted information incomplete and inadequate. Their suggestions for communication improvement about SFFs are included.
Atopic dermatitis (AD) is the most common inflammatory skin disease and carries the highest disability-adjusted life-years burden, ranking 15th among all non-fatal diseases globally. It is characterized by intensely itchy skin and is associated with multiple comorbidities, such as food allergy, asthma, allergic rhinitis and eosinophilic oesophagitis, which are mainly driven by type 2 immune responses. Other comorbidities include mental health disorders, disordered bone health, and cutaneous and extracutaneous infections. AD is also associated with other immune-mediated inflammatory diseases, including alopecia areata, vitiligo and inflammatory bowel disease. AD most often starts in the first 2 years of life but can occur at any life stage and onset at >60 years of age is increasingly common. The twenty-first century has brought greater insights into disease pathology, with an understanding of the complex interplay between the skin barrier, cutaneous and systemic immune pathways, cutaneous microbiome and neural networks. This improved mechanistic understanding has enabled rational drug design and a shift from non-specific broad immunomodulation to targeted biologic therapies and small molecules for severe disease and from topical corticosteroids to next-generation therapies for mild and moderate disease. Yet, considerable global inequity remains in access to these novel therapeutics.
Severe tricuspid regurgitation (TR) is associated with substantial morbidity and increased mortality. Transcatheter edge-to-edge repair (TEER) and transcatheter tricuspid valve replacement (TTVR) have emerged as less-invasive options for patients remaining symptomatic despite optimal medical therapy (OMT). We conducted a network meta-analysis of randomized controlled trials (RCTs) to evaluate the efficacy and safety of TEER and TTVR versus OMT. Three RCTs were included after systematic search of PubMed, Embase, and ScienceDirect (inception to December 2025). A frequentist network meta-analysis (random-effects) was performed in R. A Bayesian NMA with vague priors was conducted in parallel to obtain posterior rank probabilities and SUCRA values. Relative effects were translated into absolute risk differences and number-needed-to-treat (NNT) / number-needed-to-harm (NNH) using pooled OMT baseline event rates, with 95% CIs via parametric bootstrap. The network comprised 1,050 patients (star-shaped, OMT common comparator; no direct TEER-TTVR comparison). Neither TEER (RR 0.99, 95% CI 0.56-1.76) nor TTVR (RR 0.85, 95% CI 0.51-1.41) significantly reduced all-cause mortality. Both interventions improved NYHA class ≥ 1 class (TEER RR 1.46, 95% CI 1.30-1.64, NNT 8; TTVR RR 3.28, 95% CI 2.41-4.47, NNT 2), KCCQ-OS (TEER MD + 11.00, 95% CI 7.46-14.54; TTVR MD + 17.80, 95% CI 12.78-22.82; both exceeding the 5-point MCID with ≥ 95% confidence), and 6MWD (TEER MD + 17.53 m; TTVR MD + 30.90 m; neither clearly exceeding the 30-m MCID). Both increased major bleeding (TEER NNH 29; TTVR NNH 21) and new pacemaker implantation (TEER NNH 91; TTVR NNH 10). Bayesian posterior probability that TTVR was best was 100% for NYHA improvement, 99% for KCCQ-OS, and 82% for 6MWD, but only 1% for avoidance of pacemaker implantation. In patients with symptomatic moderate-to-severe TR, both TEER and TTVR plus OMT provide consistent and clinically meaningful improvements in functional status and quality of life. Longer-term trials with direct head-to-head comparisons are warranted. Not applicable. This study is a systematic review and meta-analysis of previously published randomized controlled trials.
A self-fitting scaffold could enable a regenerative engineering approach to treat irregular craniomaxillofacial (CMF) bone defects. We have previously reported conformally fitting, shape memory polymer (SMP) scaffolds based on poly(ε-caprolactone) (PCL). The fitting temperature (i.e., melt temperature, T m ) was tuned based on PCL architecture: linear-PCL-diacrylate (linear-PCL-DA; T m = ~55 °C) or star-PCL-tetraacrylate (star-PCL-TA, T m = ~45 °C). Scaffolds were also formed as semi-interpenetrating networks (semi-IPNs) by incorporating thermoplastic poly(L-lactic acid) (PLLA). The inclusion of a polydimethylsiloxane-dimethacrylate (PDMS-DMA) macromer and 45S5 Bioglass® (BG) were independently shown to promote hydroxyapatite (HAp) mineralization, as well as to accelerate degradation. In this study, PDMS-containing, composite SMP scaffolds were prepared with varying macromer compositions and BG concentrations. PCL/PDMS co-matrix scaffolds were formed with either linear-PCL-DA or star-PCL-TA, and PDMS-DMA (75:25 wt%). PCL/PLLA/PDMS (75:12.5:12.5 wt%) co-matrix-semi-IPNs were also formed. BG was included at relatively low concentrations (5 and 10 wt%). Composite scaffolds were fabricated to concentrate BG on the pore walls via a modified solvent-cast particulate leaching (SCPL) approach with a fused salt/BG template. PDMS-containing scaffolds preserved shape memory behavior and were non-brittle. In vitro degradation rates were accelerated for PDMS-containing composite scaffolds, owing to a combination of phase separation of polymer components and hydrophilicity imparted by the BG. Additionally, robust bioactivity was observed for PDMS-containing composite scaffolds with HAp mineralization commencing in just 1 day (1X simulated body fluid; SBF).
Furosemide (FSD) is a widely prescribed loop diuretic; however, its potential reproductive toxicity and its underlying mechanism have not been explored yet. The current study assessed the dose-dependent effects of FSD on testicular function in Sprague Dawley rats. Thirty-two male Sprague Dawley rats were apportioned into four groups i.e., control, FSD (10 mg/kg), FSD (20 mg/kg), and FSD (30 mg/kg) treated group. FSD exposure significantly downregulated the expression of blood-testis barrier genes (CLDN11, OCLN, TJP1, F11R, CDH2, GJA1), as well as upregulated pro-inflammatory mediators (NF-κB, TNF-α, IL-1β, IL-6, COX-2) in a dose-dependent manner, which indicates disruption of intercellular junctions and testicular inflammation. Oxidative stress was significantly increased, as revealed by increased ROS and MDA concentrations and decreased antioxidant enzymes (CAT, SOD, GPx, GSR, HO-1) after FSD exposure. Moreover, FSD intoxication suppressed the levels of reproductive hormones (LH and FSH, testosterone), indicating the impairment of the hypothalamic-gonadal axis. Apoptotic indices showed increased Bax, Caspase-3, Caspase-9 and decreased Bcl-2 after FSD administration, confirming activation of mitochondrial-mediated germ cell death. Similarly, semen analysis showed FSD exposure reduced the number, motility, sperm membrane integrity, and viability while increasing sperm abnormalities. Steroidogenic enzymes (StAR, 3β-HSD, 17β-HSD) were suppressed, which may indicate impaired biosynthesis of testosterone and spermatogenesis. Histopathological evaluations revealed severe degree of seminiferous tubule degeneration, reduction of germ cell population, and structure change of testicular architecture following the administration of FSD. Collectively, these findings demonstrate the multifaceted testicular toxicity of FSD, via disruption of BTB, oxidative stress, hormonal dysregulation, apoptosis and structural degeneration, leading to eventual consequences on male reproductive health. These results distinguish the potential reproductive risk caused by FSD exposure, warranting clinical trials for validation in humans.
I embody the quintessential Californian spirit: Raised in Los Angeles, I spent weekends either at the beach or skiing at Big Bear, rode motorcycles, hiked the Sierras, and cherished the sounds of the Beach Boys and Creedence Clearwater Revival. Restless, undisciplined, and irreverent, I applied to only one college-UC Santa Barbara-mainly because that is where my high school friends were going. Although we like to think our intellect transcends culture, my childhood and teenage years were shaped by the rhythms of the 1960s: space flight, NASA, and virtually every episode of Star Trek (often watched multiple times). Unmoored, I entered college intending to major in biochemistry but drifted into chemistry while also immersing myself in the physics curriculum. I earned a PhD in chemical physics at Caltech, yet chose to work with a chemical engineer. When my thesis advisor was suddenly killed, I completed my dissertation at Xerox Palo Alto Research Center, working on solar cell materials alongside Cambridge-educated physicists. While my chemistry peers pursued academic postdocs, I went instead to IBM Yorktown Heights, dividing my time between silane reactor engineering and amorphous semiconductor physics. Would I ever become anchored? Here is the rest of the story that led to 43 years on the Berkeley faculty. Including motorcycles.
To establish a non-invasive predictive model for microdissection testicular sperm extraction (micro-TESE) outcomes in FSH-normal non-obstructive azoospermia (NOA) patients by integrating gut microbiota profiling with serum biomarkers. We conducted a retrospective clinical analysis of 58 men and established a busulfan-induced FSH-normal NOA mouse model. Serum hormone levels (FSH, INH-B, AMH, testosterone) were measured by ELISA, and gut microbiota was analyzed via 16S rRNA sequencing. Testicular histology and ultrastructure were assessed by H&E staining and TEM, while protein expression was evaluated by IHC, IF, and Western blot. Receiver operating characteristic (ROC) curve analysis was used to evaluate the predictive efficacy of the serum AMH/INH-B ratio for sperm retrieval outcomes. In both patients and model mice, serum INH-B, AMH, and the AMH/INH-B ratio were significantly decreased (P < 0.01), correlating with severe spermatogenic impairment. Mice exhibited a marked reduction in the abundance of Bacteroidales and Muribaculaceae. Fecal microbiota transplantation (FMT) restored these microbial populations, improved testicular function, and upregulated key proteins involved in proliferation (PCNA, PGK2), blood-testis barrier integrity (ZO-1, Claudin11), and steroidogenesis (StAR, CYP17A1) (P < 0.05). Mechanistically, FMT increased serum short-chain fatty acid (SCFA) levels, which served as the chemical messengers correlating directly with the recovery of BTB proteins and steroidogenic enzymes. Clinically, the serum AMH/INH-B ratio showed strong predictive efficacy for micro-TESE outcomes, with an area under the ROC curve (AUC) of 0.92 (95% CI: 0.86-0.98), optimal cut-off value of 0.65, sensitivity of 88.2%, and specificity of 85.7%. The gut Bacteroidales abundance (from mouse data) was mechanistically linked to spermatogenic function, suggesting its potential as a future clinical biomarker pending validation. Our findings elucidate an SCFA-mediated gut-testis axis, highlighting the therapeutic potential of microbiota modulation and providing a novel tool to guide clinical decision-making, potentially reducing unnecessary surgeries in FSH-normal NOA.Additionally, the serum AMH/INH-B ratio serves as a robust non-invasive biomarker for predicting micro-TESE outcomes in FSH-normal NOA, while gut Bacteroidales abundance may represent a complementary mechanistic target for future clinical investigation.
Alpha-gal syndrome (AGS) is an IgE-mediated hypersensitivity reaction to galactose-α-1,3-galactose (alpha-gal) following exposure to lone star tick bites. While classically associated with anaphylactic and delayed gastrointestinal-predominant allergic reactions to mammalian meat products, emerging evidence suggests an association between alpha-gal sensitization and accelerated coronary atherosclerosis. This case is presented to highlight the potential cardiovascular implications of AGS and its impact on acute coronary syndrome presentation and management. We report a case of a 51-year-old man with a medical history significant only for AGS who presented with a two-day history of severe retrosternal chest pain radiating to the left shoulder. Electrocardiography revealed ST-segment elevations in the inferior leads and severely elevated high-sensitivity troponin levels, prompting activation of an ST-elevation myocardial infarction protocol. Emergent coronary angiography revealed a 100% occlusion of the distal right coronary artery and a 90% stenosis of a marginal artery. Successful percutaneous coronary intervention was performed, followed by a staged intervention guided by intravascular ultrasound. Given the patient's AGS, bivalirudin was used for anticoagulation to avoid porcine- or bovine-derived heparin products. This case supports a growing body of evidence linking AGS with coronary atherosclerosis and acute coronary syndrome. It highlights AGS as a potential isolated risk factor for coronary artery disease and underscores the importance of individualized diagnostic and therapeutic decision-making in affected patients.