Revision Rotator Cuff Repair Versus Primary Repair: An Assessment of Longitudinal Outcomes Outcomes in Revision Rotator Cuff Repair.

BACKGROUND: Information about outcomes after revision rotator cuff repair (RCR) is limited. A more thorough investigation of pain, range of motion (ROM), strength, and functional outcomes is needed. Comparing outcomes between primary and revision rotator cuff repair patients can help surgeons guide patient expectations of the revision procedure. The aim of this study was to compare the outcomes of a revision repair group to a control group of primary RCR patients. We expect revision RCR patients to have worse clinical outcomes than primary RCR patients. METHODS: A retrospective review of patients who underwent primary or revision RCR between 2012 to 2020 was performed. The case group included 104 revision patients, and the control group included 414 primary RCR patients. Patient visual analog score (VAS) for pain, ROM, strength, Simple Shoulder Test (SST), American Shoulder and Elbow Surgeons (ASES), and Constant-Murley scores were collected at baseline, 12 months, 24 months, and final follow-up. RESULTS: The average final follow-up was 43.9 months for primary patients and 63.8 months for revision patients. 352 primary patients and 55 revision patients had a final follow-up of 2 or more years. By final follow-up, primary patients had less pain than revision patients (Δ of 2.11, P < .0001), but both groups improved overall. Primary patients had significant improvements in forward flexion, external rotation, internal rotation, and abduction at 2 years that were lost by final follow-up, but revision patients did not experience any long-term improvement in ROM. These differences in ROM between groups were not significant. Supraspinatus strength in the revision group did not improve nor decline by final follow-up. By final follow-up, both primary and revision patients had improved SST and ASES scores from baseline. Primary patient ASES scores were 17.9 points higher (P < .0001) than revision patients by final follow-up, and there was no difference between groups in SST scores at this time. CONCLUSION: Revision RCR significantly improves patient pain, SST score, and ASES score at 4 years. Revision patients should not expect to see the improvements in range of motion that may occur after primary repair.

A Guide for Aspiring Neurology Educators.

Deans of medical schools have diverse roles and responsibilities. In this article, we use the career development trajectories of neurologists who have become education deans in student affairs and curriculum to offer advice to aspiring clinician educators of all levels and backgrounds. Although their roles differ, the advice they share is universal and essential for the career development of future clinician educators. ANN NEUROL 2024.

Light-driven C-H activation mediated by 2D transition metal dichalcogenides.

C-H bond activation enables the facile synthesis of new chemicals. While C-H activation in short-chain alkanes has been widely investigated, it remains largely unexplored for long-chain organic molecules. Here, we report light-driven C-H activation in complex organic materials mediated by 2D transition metal dichalcogenides (TMDCs) and the resultant solid-state synthesis of luminescent carbon dots in a spatially-resolved fashion. We unravel the efficient H adsorption and a lowered energy barrier of C-C coupling mediated by 2D TMDCs to promote C-H activation and carbon dots synthesis. Our results shed light on 2D materials for C-H activation in organic compounds for applications in organic chemistry, environmental remediation, and photonic materials.

Modeling interactions between rubidium atom and magnetometer cell wall molecules.

Magnetometer cell wall coat molecules play an important role in preserving the lifetime of pumped alkali metal atoms for use in magnetometers that are capable of measuring very small magnetic fields. The goal of this study is to help rationalize the design of the cell coat molecules. Rubidium-87 is studied in terms of its interaction with three template cell coat molecules: ethane, ethene, and methyltrichlorosilane (MeTS). Ab initio electronic structure methods are applied to investigate the effect that the coat molecules have on the 2S ground state and 2P excited state of 87Rb. We find that, from the ab initio results, the three template molecules have differing effects, with MeTS having the largest effect on the ground state and ethane or ethene having the largest effect on the non-degenerate excited states.

Epidemiology of Clostridioides difficile infection at one hospital 10 years after an outbreak of the epidemic C. difficile strain BI/027: changing strain prevalence, antimicrobial susceptibilities, and patient antibiotic exposures.

In contrast to the epidemiology 10 years earlier at our hospital when the epidemic restriction endonuclease analysis (REA) group strain BI accounted for 72% of Clostridioides difficile isolates recovered from first-episode C. difficile infection (CDI) cases, BI represented 19% of first-episode CDI isolates in 2013-2015. Two additional REA group strains accounted for 31% of isolates (Y, 16%; DH, 12%). High-level resistance to fluoroquinolones and azithromycin was more common among BI isolates than among DH, Y, and non-BI/DH/Y isolates. Multivariable analysis revealed that BI cases were 2.47 times more likely to be associated with fluoroquinolone exposure compared to non-BI cases (95% confidence interval [CI]: 1.12-5.46). In addition, the odds of developing a CDI after third- or fourth-generation cephalosporin exposure was 2.83 times for DH cases than for non-DH cases (95% CI: 1.06-7.54). Fluoroquinolone use in the hospital decreased from 2005 to 2015 from a peak of 113 to a low of 56 antimicrobial days/1,000 patient days. In contrast, cephalosporin use increased from 42 to 81 antimicrobial days/1,000 patient days. These changes correlated with a decrease in geometric mean MIC for ciprofloxacin (61.03 to 42.65 mg/L, P = 0.02) and an increase in geometric mean MIC for ceftriaxone (40.87 to 86.14 mg/L, P < 0.01) among BI isolates. The BI strain remained resistant to fluoroquinolones, but an overall decrease in fluoroquinolone use and increase in cephalosporin use were associated with a decrease in the prevalence of BI, an increased diversity of C. difficile strain types, and the emergence of strains DH and Y.

Density of a cryptic Australian small mammal: The threatened Julia Creek dunnart (Sminthopsis douglasi).

Globally, hundreds of mammal species face the threat of extinction in the coming decades, and in many cases, their ecology remains poorly understood. Fundamental ecological knowledge is crucial for effective conservation management of these species, but it is particularly lacking for small, cryptic mammals. The Julia Creek dunnart (Sminthopsis douglasi), a threatened, cryptic carnivorous marsupial that occurs in scattered populations in the central west of Queensland, Australia, was once so poorly studied that it was believed extinct. Sporadic research since its rediscovery in the early 1990s has revealed that S. douglasi is distributed across land at risk from many threats. Fundamental knowledge of S. douglasi population density is urgently required to inform conservation management at key sites, yet the species has historically proven hard to detect. Indeed, the status of the largest known population of S. douglasi, in Bladensburg National Park, is unknown. Here, we conducted a population study on S. douglasi at two sites within Bladensburg National Park via live mark-recapture surveys during 2022 and 2023. From likelihood-based spatially explicit capture-recapture (SECR) modelling we provide the first estimates of density and population size for S. douglasi. Live trapping resulted in captures of 49 individual S. douglasi (with 83 captures total, including recaptures). We estimated S. douglasi to occur at a density of 0.38 individuals ha-1 (0.25-0.58) at one site and 0.16 individuals ha-1 (0.09-0.27) at another site, with an estimated mean population size in suitable habitat at Bladensburg National Park of 1211 individuals (776-1646). Our S. douglasi density estimates were similar to that reported for other threatened small mammals in Australia. We also found evidence of extreme S. douglasi population fluctuations over time at Bladensburg National Park, which is of concern for its future conservation. Our study has provided the first estimate of density for S. douglasi, a threatened dasyurid species from the Mitchell Grass Downs of central western Queensland, Australia. Our research provides crucial population data to assist the management of this poorly studied species. We demonstrate a method that can be applied to species with low detection probability to ultimately help address the mammal extinction crisis faced by Australia and the rest of the world.

Direct Imaging of the Crystalline Domains and Their Orientation in the PS-b-PEO Block Copolymer with 4D-STEM.

The arrangement of crystalline domains in semicrystalline polymers is key to understanding how to optimize the nanostructured morphology for enabling better properties. For example, in polystyrene-b-poly(ethylene oxide) (PS-b-PEO), the degree of crystallinity and arrangement of the crystallites within the PEO phase plays a crucial role in determining the physical properties of the electrolyte. Here, we used four-dimensional scanning transmission electron microscopy to directly visualize the crystal domains within the PEO-rich region of the PS-b-PEO block copolymer and show the relative angle of the domain with respect to the PEO-PS interface. As demonstrated here, our analysis method is applicable to other electron-beam sensitive materials, especially semicrystalline polymers, to unveil their local phase condition and distribution.

Neuroanatomical dimensions in medication-free individuals with major depressive disorder and treatment response to SSRI antidepressant medications or placebo.

Major depressive disorder (MDD) is a heterogeneous clinical syndrome with widespread subtle neuroanatomical correlates. Our objective was to identify the neuroanatomical dimensions that characterize MDD and predict treatment response to selective serotonin reuptake inhibitor (SSRI) antidepressants or placebo. In the COORDINATE-MDD consortium, raw MRI data were shared from international samples (N = 1,384) of medication-free individuals with first-episode and recurrent MDD (N = 685) in a current depressive episode of at least moderate severity, but not treatment-resistant depression, as well as healthy controls (N = 699). Prospective longitudinal data on treatment response were available for a subset of MDD individuals (N = 359). Treatments were either SSRI antidepressant medication (escitalopram, citalopram, sertraline) or placebo. Multi-center MRI data were harmonized, and HYDRA, a semi-supervised machine-learning clustering algorithm, was utilized to identify patterns in regional brain volumes that are associated with disease. MDD was optimally characterized by two neuroanatomical dimensions that exhibited distinct treatment responses to placebo and SSRI antidepressant medications. Dimension 1 was characterized by preserved gray and white matter (N = 290 MDD), whereas Dimension 2 was characterized by widespread subtle reductions in gray and white matter (N = 395 MDD) relative to healthy controls. Although there were no significant differences in age of onset, years of illness, number of episodes, or duration of current episode between dimensions, there was a significant interaction effect between dimensions and treatment response. Dimension 1 showed a significant improvement in depressive symptoms following treatment with SSRI medication (51.1%) but limited changes following placebo (28.6%). By contrast, Dimension 2 showed comparable improvements to either SSRI (46.9%) or placebo (42.2%) (ß = -18.3, 95% CI (-34.3 to -2.3), P = 0.03). Findings from this case-control study indicate that neuroimaging-based markers can help identify the disease-based dimensions that constitute MDD and predict treatment response.

Motor vehicle collision characteristics and hospitalization outcomes associated with mild traumatic brain injury and concomitant whiplash injury.

OBJECTIVE: Few large studies have investigated the factors and outcomes related to concomitant injuries occurring alongside mild traumatic brain injury (mTBI) after motor vehicle collisions (MVCs). Thus, the objective of this study was to assess whether MVC characteristics predict which patients with mTBI will have concomitant whiplash injury, and whether concomitant whiplash injury affects care utilization for these patients. METHODS: This retrospective cohort study included 22,213 patients with mTBI after MVC identified from the American College of Surgeons Trauma Quality Programs dataset. A hierarchical logistic regression model was constructed to investigate patient and MVC factors associated with concomitant whiplash injury. Propensity score matching on whiplash status, in conjunction with a multivariable logistic regression model, assessed if concomitant whiplash affected odds of hospitalization. In the subgroup of patients who were hospitalized, associations with hospital length of stay (LOS) and discharge disposition were investigated. RESULTS: The median (IQR) age was 34 (24-51) years, with a median Glasgow Coma Scale score at presentation of 15 (15-15). Patients with concomitant whiplash were older (median 36 years vs 34 years, p = 0.03) and had higher rates of hospitalization (75% vs 64%, p < 0.001). In the hierarchical model for associations with concomitant whiplash injury, patients with blood alcohol content (BAC) greater than the federal driving limit had lower odds of concomitant whiplash (OR 0.63, 95% CI 0.49-0.81) along with those who had airbag deployment (OR 0.80, 95% CI 0.68-0.95), but seatbelt use was associated with greater odds (OR 1.41, 95% CI 1.16-1.71). After matching, concomitant whiplash was independently associated with increased odds of hospitalization (OR 1.67, 95% CI 1.40-1.99) while seatbelt use was associated with decreased odds (OR 0.88, 95% CI 0.81-0.95). Among hospitalized patients, concomitant whiplash was not associated with hospital LOS or discharge disposition. CONCLUSIONS: MVC characteristics such as alcohol consumption and airbag deployment were protective toward development of concomitant whiplash for mTBI patients, while seatbelt use was associated with higher risk. Concomitant whiplash increases the odds of hospitalization for mTBI patients but does not affect hospital LOS or discharge disposition, while seatbelt use is associated with lower rates of hospitalization and a more favorable hospital course. These findings provide context to injury patterns and care provision after a common mechanism of injury.

Cross-sectional study to investigate the seroprevalence and risk factors of Toxoplasma gondii among women attending the antenatal clinic in Namwala, Zambia.

BACKGROUND: Toxoplasmosis is a zoonotic parasitic disease caused by Toxoplasma gondii (T. gondii). It has a wide host range and is capable of vertical transmission in pregnant women, which may lead to undesirable pregnancy outcomes such as congenital malformations, miscarriage, premature birth and stillbirth. This study investigated the seroprevalence of T. gondii infection among pregnant women attending the antenatal clinic at Namwala District Hospital in Southern Zambia. METHODS: This was a cross-sectional study where blood was collected, and the serum was tested for Toxoplasma IgG and IgM. A questionnaire was administered to participants on demographic characteristics and risk factors. Data were entered in Microsoft Excel and exported to STATA version 14 for analysis. RESULTS: A total of 401 women were enrolled in the study from 3 March to 5 August 2021. The seroprevalence of Toxoplasma IgG was 4.2% (n=17), while the seroprevalence of Toxoplasma IgM was 0.7% (n=3). The median age was 27 (IQR: 24-30) years, and a larger proportion had primary-level education (n=223, 55.6%). The majority (81.6%) of the women were married. None of the risk factors investigated in this study were significant for T. gondii infection. CONCLUSION: There was a low seroprevalence of T. gondii infection among pregnant women in the Namwala district of Southern Province, Zambia, and regular screening may not be warranted in this population. Continued research on toxoplasmosis is recommended to understand its epidemiology across Zambia.

Multisite Validation of a Functional Assay to Adjudicate SCN5A Brugada Syndrome-Associated Variants.

BACKGROUND: Brugada syndrome is an inheritable arrhythmia condition that is associated with rare, loss-of-function variants in SCN5A. Interpreting the pathogenicity of SCN5A missense variants is challenging, and ≈79% of SCN5A missense variants in ClinVar are currently classified as variants of uncertain significance. Automated patch clamp technology enables high-throughput functional studies of ion channel variants and can provide evidence for variant reclassification. METHODS: An in vitro SCN5A-Brugada syndrome automated patch clamp assay was generated and independently studied at Vanderbilt University Medical Center and Victor Chang Cardiac Research Institute. The assay was calibrated according to ClinGen Sequence Variant Interpretation recommendations using high-confidence variant controls (n=49). Normal and abnormal ranges of function were established based on the distribution of benign variant assay results. Odds of pathogenicity values were derived from the experimental results according to ClinGen Sequence Variant Interpretation recommendations. The calibrated assay was then used to study SCN5A variants of uncertain significance observed in 4 families with Brugada syndrome and other arrhythmia phenotypes associated with SCN5A loss-of-function. RESULTS: Variant channel parameters generated independently at the 2 research sites showed strong correlations, including peak INa density (R2=0.86). The assay accurately distinguished benign controls (24/25 concordant variants) from pathogenic controls (23/24 concordant variants). Odds of pathogenicity values yielded 0.042 for normal function and 24.0 for abnormal function, corresponding to strong evidence for both American College of Medical Genetics and Genomics/Association for Molecular Pathology benign and pathogenic functional criteria (BS3 and PS3, respectively). Application of the assay to 4 clinical SCN5A variants of uncertain significance revealed loss-of-function for 3/4 variants, enabling reclassification to likely pathogenic. CONCLUSIONS: This validated high-throughput assay provides clinical-grade functional evidence to aid the classification of current and future SCN5A-Brugada syndrome variants of uncertain significance.

Influence of Sex and Gender on Musculoskeletal Conditions and How They Are Reported.

ABSTRACT: There is increasing evidence that musculoskeletal tissues are differentiallys regulated by sex hormones in males and females. The influence of sex hormones, in addition to other sex-based differences such as in anatomical alignment and immune-system function, impact the prevalence and severity of disease as well as the types of injuries that affect the musculoskeletal system and the outcomes of prevention measures and treatment. Literature specifically addressing sex differences related to the musculoskeletal system is limited, underscoring the imperative for both basic and clinical research on this topic. This review highlights areas of research that have implications for bone and cartilage health, including growth and development, sports injuries, osteoarthritis, osteoporosis, and bone frailty. It is clear that important aspects of the musculoskeletal system have been understudied. Consideration of how sex hormone therapy will affect musculoskeletal tissues in prepuberty, during puberty, and in adults is vital, yet little is known. The purpose of this article is to foster awareness and interest in advancing our understanding of how sex differences influence orthopaedic practice.

Situational prevention: Pharmacotherapy during periods of increased risk for migraine attacks.

The small molecule calcitonin gene-related peptide receptor antagonists (gepants) are the only drug class with medicines indicated for both the acute and preventive treatment of migraine. Given this dual capacity to both treat and prevent, along with their favorable tolerability profiles and lack of an association with medication-overuse headache, headache specialists have begun to use gepants in ways that transcend the traditional categories of acute and preventive treatment. One approach, called situational prevention, directs patients to treat during the interictal phase, before symptoms develop, in situations of increased risk for migraine attacks. Herein, we present three patients to illustrate scenarios of gepant use for situational prevention. In each case, a gepant was started in anticipation of a period of increased headache probability (vulnerability) and continued for a duration of 1 day to 5 consecutive days. Although this approach may expose patients to medication when headache may not have developed, the tolerability and safety profile and preventive effect of gepants may represent a feasible approach for some patients. Situational prevention is an emerging strategy for managing migraine before symptoms develop in individuals who can identify periods when the probability of headache is high. This paper is intended to increase awareness of this strategy and stimulate future randomized, placebo-controlled trials to rigorously assess this strategy.

Transglutaminase 2 knockout mice are protected from bleomycin-induced lung fibrosis with preserved lung function and reduced metabolic derangements.

Pulmonary fibrosis is an interstitial scarring disease of the lung characterized by poor prognosis and limited treatment options. Tissue transglutaminase 2 (TG2) is believed to promote lung fibrosis by crosslinking extracellular matrix components and activating latent TGFß. This study assessed physiologic pulmonary function and metabolic alterations in the mouse bleomycin model with TG2 genetic deletion. TG2-deficient mice demonstrated attenuated the fibrosis and preservation of lung function, with significant reduction in elastance and increases in compliance and inspiratory capacity compared to control mice treated with bleomycin. Bleomycin induced metabolic changes in the mouse lung that were consistent with increased aerobic glycolysis, including increased expression of lactate dehydrogenase A and increased production of lactate, as well as increased glutamine, glutamate, and aspartate. TG2-deficient mice treated with bleomycin exhibited similar metabolic changes but with reduced magnitude. Our results demonstrate that TG2 is required for a typical fibrosis response to injury. In the absence of TG2, the fibrotic response is biochemically similar to wild-type, but lesions are smaller and lung function is preserved. We also show for the first time that profibrotic pathways of tissue stiffening and metabolic reprogramming are interconnected, and that metabolic disruptions in fibrosis go beyond glycolysis.

Clinical Conundrum: Return to High Altitude After Cerebral Venous Sinus Thrombosis.

Luks, Andrew M., Thomas G. DeLoughery, Jeffrey H. Gertsch, and Suzy Stokes. Clinical conundrum: return to high altitude after cerebral venous sinus thrombosis. High Alt Med Biol. 00:00-00, 2024.

Timing decisions as the next frontier for collective intelligence.

The past decade has witnessed a growing interest in collective decision making, particularly the idea that groups can make more accurate decisions compared with individuals. However, nearly all research to date has focused on spatial decisions (e.g., food patches). Here, we highlight the equally important, but severely understudied, realm of temporal collective decision making (i.e., decisions about when to perform an action). We illustrate differences between temporal and spatial decisions, including the irreversibility of time, cost asymmetries, the speed-accuracy tradeoff, and game theoretic dynamics. Given these fundamental differences, temporal collective decision making likely requires different mechanisms to generate collective intelligence. Research focused on temporal decisions should lead to an expanded understanding of the adaptiveness and constraints of living in groups.

Fabrication and assessment of a bio-inspired synthetic tracheal tissue model for tracheal tube cuff leakage testing.

Introduction: Leakage of orogastric secretions past the cuff of a tracheal tube is a contributory factor in ventilator-associated pneumonia. Current bench test methods specified in the International Standard for Anaesthetic and Respiratory Equipment (EN ISO 5361:2023) to test cuff leakage involve using a glass or plastic rigid cylinder model of the trachea. There is a need for more realistic models to inform cuff leakage. Methods: We used human computerised tomography data and additive manufacturing (3D printing), combined with casting techniques to fabricate a bio-inspired synthetic tracheal model with analogous tissue characteristics. We conducted cuff leakage tests according to EN ISO 5361:2023 and compared results for high-volume low-pressure polyvinyl chloride and polyurethane cuffs between the rigid cylinder trachea with our bio-inspired model. Results: The tracheal model demonstrated close agreement with published tracheal tissue hardness for cartilaginous and membranous soft tissues. For high-volume low-pressure polyvinyl chloride cuffs the leakage rate was >50% lower in the bio-inspired tracheal model compared with the rigid cylinder model (151 [8] vs 261 [11] ml h-1). For high-volume low-pressure polyurethane cuffs, much lower leakage rates were observed than polyvinyl chloride cuffs in both models with leakage rates higher for the bio-inspired trachea model (0.1 [0.2] vs 0 [0] ml h-1). Conclusion: A reproducible tracheal model that incorporates the mechanical properties of the human trachea can be manufactured from segmented CT images and additive manufactured moulds, providing a useful tool to inform future cuff development, leakage testing for industrial applications, and clinical decision-making. There are differences between cuff leakage rates between the bio-inspired model and the rigid cylinder recommended in EN ISO 5361:2023. The bio-inspired model could lead to more accurate and realistic cuff leakage rate testing which would support manufacturers in refining their designs. Clinicians would then be able to choose better tracheal tubes based on the outcomes of this testing.

Geministatins: new depside antibiotics from the fungus Austroacremonium gemini.

Two new depside antibiotics, geministatins A (1) and B (2), were isolated from the fungus Austroacremonium gemini MST-FP2131 (Sordariomycetes, Ascomycota), which was recovered from rotting wood in the wet tropics of northern Australia. The structures of the geministatins were elucidated by detailed spectroscopic analysis, chemical degradation and comparison with literature values. Chemical degradation of 1 and 2 yielded three new analogues, geministatins C-E (3-5), as well as a previously reported compound dehydromerulinic acid A (6). Compounds 1, 2 and 6 exhibited antibacterial activity against the Gram-positive bacteria Bacillus subtilis (MIC 0.2-1.6 µg mL-1) and Staphylococcus aureus (MIC 0.78-6.3 µg mL-1), including methicillin-resistant S. aureus (MRSA), while 4 exhibited antifungal activity against the yeast Saccharomyces cerevisiae (MIC 13 µg mL-1).