Modulating the phototoxicity and selectivity of a porphyrazine towards epidermal tumor cells by coordination with metal ions.

Porphyrazines (Pzs) are porphyrin derivatives that show potential application as photosensitizers for photodynamic therapy (PDT), but are still far less explored in the literature. In this work, we evaluate how the photophysics and phototoxicity of the octakis(trifluoromethylphenyl)porphyrazine (H2Pz) against tumor cells can be modulated by coordination with Mg(II), Zn(II), Cu(II) and Co(II) ions. Fluorescence and singlet oxygen quantum yields for the Pzs were measured in organic solvents and in soy phosphatidylcholine (PC) liposomes suspended in water. While H2Pz and the respective complexes with Cu(II) and Co(II) showed very low efficiency to fluoresce and to produce 1O2, the Mg(II) and Zn(II) complexes showed significantly higher quantum yields in organic solvents. The fluorescence of these two Pzs in the liposomes was sensitive to the fluidity of the membrane, showing potential use as viscosity markers. The cytotoxicity of the compounds was tested in HaCaT (normal) and A431 (tumor) cells using soy PC liposomes as drug carriers. Despite the low 1O2 quantum yields in water, the Mg(II) and Zn(II) complexes showed IC50 values against A431 cells in the nanomolar range when activated with low doses of red LED light. Their phototoxicity was ca. three times higher for the tumor cells compared to the normal ones, showing promising application as photosensitizers for PDT protocols. Considering that H2Pz and the respective Co(II) and Cu(II) complexes were practically non-phototoxic to the cells, we demonstrate the importance of the central metal ion in the modulation of the photodynamic activity of porphyrazines.

A multi-state evaluation of extreme risk protection orders: a research protocol.

BACKGROUND: Extreme Risk Protection Orders (ERPOs) are civil court orders that prohibit firearm purchase and possession when someone is behaving dangerously and is at risk of harming themselves and/or others. As of June 2024, ERPOs are available in 21 states and the District of Columbia to prevent firearm violence. This paper describes the design and protocol of a six-state study of ERPO use. METHODS: The six states included are California, Colorado, Connecticut, Florida, Maryland, and Washington. During the 3-year project period (2020-2023), ERPO case files were obtained through public records requests or through agreements with agencies with access to these data in each state. A team of over four dozen research assistants from seven institutions coded 6628 ERPO cases, abstracting 80 variables per case under domains related to respondent characteristics, events and behaviors leading to ERPO petitions, petitioner types, and court outcomes. Research assistants received didactic training through an online learning management system that included virtual training modules, quizzes, practice coding exercises, and two virtual synchronous sessions. A protocol for gaining strong interrater reliability was used. Research assistants also learned strategies for reducing the risk of experiencing secondary trauma through the coding process, identifying its occurrence, and obtaining help. DISCUSSION: Addressing firearm violence in the U.S. is a priority. Understanding ERPO use in these six states can inform implementation planning and ERPO uptake, including promising opportunities to enhance safety and prevent firearm-related injuries and deaths. By publishing this protocol, we offer detailed insight into the methods underlying the papers published from these data, and the process of managing data abstraction from ERPO case files across the multi-state and multi-institution teams involved. Such information may also inform future analyses of this data, and future replication efforts. REGISTRATION: This protocol is registered on Open Science Framework ( https://osf.io/kv4fc/ ).

Individual, firearm, and purchasing characteristics associated with risk of firearm-related violent crime arrest: a nested case-control study.

BACKGROUND: Firearm purchasing records offer a potentially important administrative data source to identify individuals at elevated risk of perpetrating firearm violence. In this study, we describe individual, firearm, and transaction characteristics of purchasers in California who were arrested for a firearm-related violent crime (FRV) as compared to the general population of registered purchasers in the state. METHODS: Relying on a dataset of all individuals with transaction records in California (1996-2021), linked to criminal records (1980-2021), we enrolled a cohort of individuals for whom we could capture the legal firearm purchase history. We identified those arrested for FRV post purchase, and using incidence density sampling, gender-matched cases to ten purchasers (controls) who remained "at risk" at the time the case was arrested. We focused on the purchase closest in time prior to the arrest ("index" purchase). We implemented conditional logistic regression and included models with controls for individual- and community-level demographics, as well as interactions between firearm and purchasing characteristics and criminal history. RESULTS: The cohort included 1,212,144 individuals, of whom 6153 were arrested for FRV (0.5%). Cases were matched to 61,530 controls to form the study sample. The largest risk factor was a prior criminal history: purchasers had 5.84 times the risk of FRV if they had a prior arrest within three years of the index purchase (CI 5.44-6.27). Several transaction and firearm characteristics were also associated with FRV. For example, risk increased if the firearm was redeemed at a pawn shop (aIRR: 1.37, CI 1.05-1.77) and decreased if the transaction was a registered private party transfer (vs. retail purchase) (aIRR: 0.83, CI 0.76-0.90) or the firearm was a bolt action firearm (vs. semi-automatic) (aIRR: 0.64, CI 0.51-0.79). In the interaction models, most of the purchase and firearm features only remained significant among those with no criminal history. CONCLUSIONS: Given limited data on firearm transactions, there has been little research on whether the type of firearm an individual purchases or the nature of the purchase might serve as indicators of risk for FRV. We found several transaction and firearm features were associated with risk of FRV. Notably, these features provided little evidence of additional risk for those with a prior criminal record.

Dendritic spine head diameter predicts episodic memory performance in older adults.

Episodic memory in older adults is varied and perceived to rely on numbers of synapses or dendritic spines. We analyzed 2157 neurons among 128 older individuals from the Religious Orders Study and Rush Memory and Aging Project. Analysis of 55,521 individual dendritic spines by least absolute shrinkage and selection operator regression and nested model cross-validation revealed that the dendritic spine head diameter in the temporal cortex, but not the premotor cortex, improved the prediction of episodic memory performance in models containing ß amyloid plaque scores, neurofibrillary tangle pathology, and sex. These findings support the emerging hypothesis that, in the temporal cortex, synapse strength is more critical than quantity for memory in old age.

Suicide Prevention Effects of Extreme Risk Protection Order Laws in Four States.

More than half of suicide deaths in the United States result from self-inflicted firearm injuries. Extreme risk protection order (ERPO) laws in 21 states and the District of Columbia temporarily limit access to firearms for individuals found in a civil court process to pose an imminent risk of harm to themselves or others. Research with large multistate study populations has been lacking to determine effectiveness of these laws. This study assembled records pertaining to 4,583 ERPO respondents in California, Connecticut, Maryland, and Washington. Matched records identified suicide decedents and self-injury method. Researchers applied case fatality rates for each suicide method to estimate nonfatal suicide attempts corresponding to observed deaths. Comparison of counterfactual to observed data patterns yielded estimates of the number of lives saved and number of ERPOs needed to avert one suicide. Estimates varied depending on the assumed probability that a gun owner who attempts suicide will use a gun. Two evidence-based approaches yielded estimates of 17 and 23 ERPOs needed to prevent one suicide. For the subset of 2,850 ERPO respondents with documented suicide concern, comparable estimates were 13 and 18, respectively. This study's findings add to growing evidence that ERPOs can be an effective and important suicide prevention tool.

Confounder selection in firearm policy research: A scoping review.

Legislative firearm policies are often proposed as a way of preventing firearm-related harm. Confounding is a substantial threat to accurately estimating the causal effects of firearm policies. This scoping review characterizes selection of potential confounders in US firearm policy evaluations in the health sciences literature. We identified empirical research articles indexed in PubMed from 1/1/2000-9/1/2021 that examined any of 18 pre-specified firearm policies and extracted key study elements, including the exposure (firearm policy), outcomes, potential confounders adjusted for in analyses, and study approach (i.e., static, uncontrolled pre-post, and controlled pre-post). There was wide variation in potential confounders within study approach-policy-outcome combinations. The most common potential confounders included sociodemographic and economic variables, rurality/urbanicity, violent crime, law enforcement-related variables, alcohol use, and firearm access (mostly measured via proxies for firearm ownership). Firearm policies other than the policy being evaluated were included in the adjustment set in 23-44% of studies, depending on the study approach. Confounder selection was most often said to be based on prior research (n=49, 40%) or not explicitly stated (n=48, 39%). This scoping review provides a comprehensive resource for critically appraising the firearm policy literature and offers considerations to support more rigorous confounding control in future firearm policy research.

Improving compliance around protected areas through fair administration of rules.

Protected area management often depends heavily on law enforcement to secure compliance with rules. However, this can contribute to conflict between protected area authorities and local people, negatively affecting both human well-being and conservation outcomes. Compliance is affected by many factors, including whether those who enforce rules are perceived to do so fairly, as well as the perceived rule-related behavior of others. We used factorial survey experiments to explore how fair respondents living around protected areas in Indonesia and Tanzania perceive sanctions distributed by law enforcers to be. We presented scenarios to respondents to assess how crime type, offender characteristics, and corruption influenced their judgments regarding the fairness of administered sanctions. We also assessed how descriptive norms and corruption influenced individuals' willingness to obey protected area rules. Data were collected from 229 people in Indonesia and 217 in Tanzania. Results showed that in both locations, lawful sanctions, such as arrests or warnings, were perceived as fairer, and sanctions that involved corruption were perceived as least fair. Attitudes toward protected area rules, corruption, and descriptive norms all influenced people's willingness to comply, whereas multidimensional poverty did not. Our results highlight the need for conservation policy and practice to move beyond narratives that focus on the need for more law enforcement. To improve protected area compliance and secure better outcomes for people and nature, conservation must focus on ensuring the fair administration of rules and enhancing the legitimacy of rules themselves.

Mejoras en el cumplimiento alrededor de las áreas protegidas mediante la administración imparcial de reglas Resumen El manejo de áreas protegidas casi siempre depende de la aplicación de la ley para asegurar el cumplimiento de las reglas. Sin embargo, esto puede contribuir al conflicto entro las autoridades de las áreas protegidas y los locales, lo que afecta negativamente al bienestar humano y a los resultados de conservación. El cumplimiento se ve afectado por muchos factores, incluido si se percibe que quienes aplican las reglas lo hacen de manera imparcial, así como el comportamiento relacionado a las reglas de las demás. Aplicamos experimentos de censo factorial para explorar cómo los respondientes imparciales que viven en torno a las áreas protegidas en Indonesia y Tanzania perciben las sanciones distribuidas por los agentes de la ley. Les presentamos escenarios para analizar cómo el tipo de crimen, características del ofensor y la corrupción influyen sobre sus juicios con respecto a la imparcialidad de las sanciones administradas. También analizamos cómo las normas descriptivas y la corrupción influyen sobre la voluntad individual de obedecer las reglas del área protegida. Recolectamos los datos de 299 personas en Indonesia y 217 en Tanzania. Los resultados mostraron que, en ambas localidades, las sanciones legales, como arrestos o advertencias, eran percibidas como más justas, y las sanciones que involucraban corrupción eran percibidas como las menos justas. Todas las actitudes hacia las reglas de las áreas protegidas, la corrupción y las normas descriptivas influyeron sobre la voluntad de las personas para obedecer, mientras que la pobreza multidimensional no influyó. Nuestros resultados enfatizan la necesidad de que las políticas y prácticas de conservación vayan más allá de las narrativas que se enfocan en la necesidad de una mayor aplicación de la ley. Para incrementar el cumplimiento en las áreas protegidas y asegurar mejores resultados para las personas y la naturaleza, la conservación debe enfocarse en garantizar la administración imparcial de las reglas e incrementar su legitimidad.

Photoluminescence and magnetic properties of isostructural europium(III), gadolinium(III) and terbium(III) oxamate-based coordination polymers.

Developing and investigating advanced multifunctional materials with magnetic properties as candidates for assembling spin qubits for quantum computing is imperative. A new polytopic ligand based on oxamate and aniline was used to promote the synthesis of three neutral homometallic lanthanide-coordinated polymers. New complexes with the formula {Ln(phox)3(DMSO)2(H2O)}n, where Ln = Eu3+ (1), Gd3+ (2), and Tb3+ (3) [phox = N-(phenyl)oxamate and DMSO = dimethylsulfoxide], were synthesized and well characterized by spectroscopic methods as well as X-ray crystallographic analysis. All crystalline structures comprise neutral zigzag chains. The lanthanide ions are linked by three phox ligands, in which two oxygen atoms from two different ligands are responsible for connecting the trivalent lanthanide ions, and one phox ligand completes the coordination sphere in a bis-bidentate mode, together with two DMSO molecules and one water coordination molecule. The coordination sphere of lanthanide ions consisted of spherical capped square antiprism (CSAPR-9) symmetry. The magnetic properties of 1-3 were investigated in the 2-300 K temperature range. The dynamic (ac) magnetic properties of 2 reveal a frequency dependence involving the phonon bottleneck mechanism below 33 K under nonzero applied dc magnetic fields, resulting in an example of a field-induced single-molecule magnet. Solid-state photophysical measurements for Eu3+ (1) and Tb3+ (3) complexes indicate that the N-(phenyl)oxamate ligands are very efficient in sensitizing the lanthanide(III) ions in the visible region of the electromagnetic spectrum. Compounds 1 and 3 exhibited an emission in the red and green regions, respectively. Experimental results and theoretical calculations using the Sparkle/RM1 method support a quantum efficiency of ∼72% for 1, suggesting its potential as a candidate for light conversion molecular devices (LCMDs).

Weight-Reduction Preferences Among OBSERVE Study Participants With Obesity or Overweight: Opportunities for Shared Decision-Making.

OBJECTIVE: Limited recent evidence exists regarding weight-reduction preferences among people with obesity in the United States (US). We assessed preferred magnitudes of weight reduction among adults with obesity and how these preferences differ by participant characteristics. METHODS: The Perceptions, Barriers, and Opportunities for Anti-obesity Medications in Obesity Care: A Survey of Patients, Providers and Employers was a cross-sectional study assessing perceptions of obesity and anti-obesity medications among people with obesity, healthcare providers, and employers in the US. Adults with obesity and overweight with obesity-related complications self-reported current weight and weight they associated with 5 preferences ("dream," "goal," "happy," "acceptable," and "disappointed.") Preferred percent weight reductions for each preference were calculated. Multivariable regression analyses were performed identifying associations between weight-reduction preferences and participant characteristics. RESULTS: The study included 1007 participants (women: 63.6%; White: 41.0%; Black or African American: 28.9%; Asian: 6.5%; Hispanic: 15.3%; and median body mass index (BMI): 34.2 kg/m2). Median preferred percent weight reductions were dream = 23.5%; goal = 16.7%; happy = 14.6%; acceptable = 10.3%; and disappointed = 4.8%. Women reported higher preferred weight reductions than men. Preferred weight reductions among Black/African American participants were lower than White participants. Regression analyses indicated significant associations, with higher preferred magnitudes of weight reduction within females, higher weight self-stigma, and BMI class in Hispanic participants compared to White. CONCLUSION: In this large, real-world study, preferred magnitudes of weight reduction exceeded outcomes typically achieved with established nonsurgical obesity treatments but may be attained with bariatric procedures and newer and emerging anti-obesity medications. Respecting patients' preferences for treatment goals with obesity management could help support shared decision-making. Evaluating for an individual's contributors to weight preferences, such as weight self-stigma, can further benefit holistic obesity care.

Effect of carbohydrate type in silages and concentrates on feed intake, enteric methane, and milk yield from dairy cows.

Dietary carbohydrate manipulation can be used to reduce enteric CH4 emission, but few studies have focused on the interaction of the different types of carbohydrates that can affect feed intake and ruminal fermentation. Understanding this interaction is necessary to make the most out of CH4 mitigation feeding strategies using different dietary carbohydrates. The aim of this study was to test the effect on enteric CH4 emission, feed intake, and milk production response when cows were fed either grass-clover silage (GCS) or corn silage (CS) as the sole forage source (55% of dry matter, DM), in combination with either barley (BAR) or dried beet pulp (DBP) as a concentrate (21.5% of DM). A total of 24 (half first-parity and half second-parity) cows were used in a crossover design with 2 periods of 21 d each, receiving 2 of 4 diets obtained from a 2 × 2 factorial arrangement of the experimental diet. Feed intake, CH4 emission metrics, and milk production were recorded at the end of the experimental periods. The diets had NDF concentrations between 258 and 340 g/kg of DM and starch concentrations between 340 and 7.45 g/kg of DM (CS-BAR and GCS-DBP, respectively). The effects of silage and concentrate on dry matter intake (DMI) were additive, with the highest feed intake in cows fed CS-BAR, followed by cows fed CS-DBP, GCS-BAR, and GCS-DBP (21.2, 19.9, 19.1, and 18.3 kg/d, respectively). Energy corrected milk (ECM) yield was not affected by silage source in first parity cows, but it was higher for cows fed CS than cows fed GCS in second parity. The effects of silage and concentrate on CH4 production (g/d), yield (g/kg of DMI), and intensity (g/kg of ECM) were not additive, as cows fed GCS had similar responses regardless of the concentrate used, but cows fed CS had lower CH4 production, yield, and intensity when fed BAR instead of DBP. The lower CH4 production, yield, and intensity in cows fed CS-BAR compared with other diets could be partially explained by the nonlinear relationship between ruminal VFA and carbohydrates (NDF and starch) concentration reported in the literature; however, we observed a linear relationship between the acetate/propionate ratio and CH4 yield, suggesting possible other effects. The effects of silage and concentrate on the ruminal VFA were additive in first parity cows, but not in second parity cows. The interaction between dietary carbohydrate type and parity might indicate an effect of feed intake or the energy balance of the cow. Feeding cows silage and concentrate both rich in starch can result in the lowest enteric CH4 emission.

Tirzepatide for the Treatment of Obstructive Sleep Apnea and Obesity.

BACKGROUND: Obstructive sleep apnea is characterized by disordered breathing during sleep and is associated with major cardiovascular complications; excess adiposity is an etiologic risk factor. Tirzepatide may be a potential treatment. METHODS: We conducted two phase 3, double-blind, randomized, controlled trials involving adults with moderate-to-severe obstructive sleep apnea and obesity. Participants who were not receiving treatment with positive airway pressure (PAP) at baseline were enrolled in trial 1, and those who were receiving PAP therapy at baseline were enrolled in trial 2. The participants were assigned in a 1:1 ratio to receive either the maximum tolerated dose of tirzepatide (10 mg or 15 mg) or placebo for 52 weeks. The primary end point was the change in the apnea-hypopnea index (AHI, the number of apneas and hypopneas during an hour of sleep) from baseline. Key multiplicity-controlled secondary end points included the percent change in AHI and body weight and changes in hypoxic burden, patient-reported sleep impairment and disturbance, high-sensitivity C-reactive protein (hsCRP) concentration, and systolic blood pressure. RESULTS: At baseline, the mean AHI was 51.5 events per hour in trial 1 and 49.5 events per hour in trial 2, and the mean body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) was 39.1 and 38.7, respectively. In trial 1, the mean change in AHI at week 52 was -25.3 events per hour (95% confidence interval [CI], -29.3 to -21.2) with tirzepatide and -5.3 events per hour (95% CI, -9.4 to -1.1) with placebo, for an estimated treatment difference of -20.0 events per hour (95% CI, -25.8 to -14.2) (P<0.001). In trial 2, the mean change in AHI at week 52 was -29.3 events per hour (95% CI, -33.2 to -25.4) with tirzepatide and -5.5 events per hour (95% CI, -9.9 to -1.2) with placebo, for an estimated treatment difference of -23.8 events per hour (95% CI, -29.6 to -17.9) (P<0.001). Significant improvements in the measurements for all prespecified key secondary end points were observed with tirzepatide as compared with placebo. The most frequently reported adverse events with tirzepatide were gastrointestinal in nature and mostly mild to moderate in severity. CONCLUSIONS: Among persons with moderate-to-severe obstructive sleep apnea and obesity, tirzepatide reduced the AHI, body weight, hypoxic burden, hsCRP concentration, and systolic blood pressure and improved sleep-related patient-reported outcomes. (Funded by Eli Lilly; SURMOUNT-OSA ClinicalTrials.gov number, NCT05412004.).

Weight reduction and the impact on apnea-hypopnea index: A systematic meta-analysis.

Obstructive sleep apnea (OSA) is strongly associated with obesity. While the relationship between weight reduction and apnea-hypopnea index improvement has been documented, to our knowledge, it has not been quantified adequately. Therefore, this study aimed to quantify the relationship between weight reduction and AHI change. METHODS: A systematic literature search was performed using meta-analyses (PRISMA) guidelines for studies reporting AHI and weight loss in people with obesity/overweight and OSA between 2000 and 2023. A linear and quadratic model (weighted by treatment arm sample size) predicted percent change from baseline AHI against mean percent change from baseline weight. The quadratic term was statistically significant (P < 0.05), so the quadratic model (with 95 % prediction interval) was used. RESULTS: The literature search identified 27 studies/32 treatment arms: 15 using bariatric surgery and lifestyle intervention each and 2 using pharmacological interventions. Included studies were ≥3 months with weight intervention and participants had AHI ≥15/h. Weight reduction in people with OSA and obesity was associated with improvements in the severity of OSA. BMI reduction of 20 % was associated with AHI reduction of 57 %, while further weight reduction beyond 20 % in BMI was associated with a smaller effect on AHI. As the prediction intervals are relatively wide, a precise relationship could not be conclusively established. CONCLUSION: The degree of AHI index improvement was associated with the magnitude of weight reduction. The model suggests that with progress in weight reduction beyond 20 %, the incremental decrease in BMI appeared to translate to a smaller additional effect on AHI.

Outer Retinal Thickness Is Associated With Cognitive Function in Normal Aging to Intermediate Age-Related Macular Degeneration.

Purpose: Research on Alzheimer's disease (AD) and precursor states demonstrates a thinner retinal nerve fiber layer (NFL) compared to age-similar controls. Because AD and age-related macular degeneration (AMD) both impact older adults and share risk factors, we asked if retinal layer thicknesses, including NFL, are associated with cognition in AMD. Methods: Adults ≥ 70 years with normal retinal aging, early AMD, or intermediate AMD per Age-Related Eye Disease Study (AREDS) nine-step grading of color fundus photography were enrolled in a cross-sectional study. Optical coherence tomography (OCT) volumes underwent 11-line segmentation and adjustments by a trained operator. Evaluated thicknesses reflect the vertical organization of retinal neurons and two vascular watersheds: NFL, ganglion cell layer-inner plexiform layer complex (GCL-IPL), inner retina, outer retina (including retinal pigment epithelium-Bruch's membrane), and total retina. Thicknesses were area weighted to achieve mean thickness across the 6-mm-diameter Early Treatment of Diabetic Retinopathy Study (ETDRS) grid. Cognitive status was assessed by the National Institutes of Health Toolbox cognitive battery for fluid and crystallized cognition. Correlations estimated associations between cognition and thicknesses, adjusting for age. Results: Based on 63 subjects (21 per group), thinning of the outer retina was significantly correlated with lower cognition scores (P < 0.05). No other retinal thickness variables were associated with cognition. Conclusions: Only the outer retina (photoreceptors, supporting glia, retinal pigment epithelium, Bruch's membrane) is associated with cognition in aging to intermediate AMD; NFL was not associated with cognition, contrary to AD-associated condition reports. Early and intermediate AMD constitute a retinal disease whose earliest, primary impact is in the outer retina. Our findings hint at a unique impact on the brain from the outer retina in persons with AMD.

Variables associated with the prevalence of self-reported work-related musculoskeletal disorders in veterinary laparoscopic surgeons.

OBJECTIVE: To investigate the relationship between physical attributes and difficulty performing laparoscopic maneuvers with the prevalence of self-reported musculoskeletal injury. STUDY DESIGN: Online survey. SAMPLE POPULATION: Surgeons (n = 140) with 3 or more years of laparoscopic experience. METHODS: Electronic survey distributed via LISTSERVEs and Facebook groups. Responses collected included surgeon attributes, presence of musculoskeletal injuries, and surgical practice data. Statistical analysis was performed using the Shapiro-Wilk test, linear regression, logistic regression, and Wilcoxon rank sum tests. RESULTS: A total of 52 of the 140 respondents reported a musculoskeletal injury with 38 specifying at least one injury (72%). Neck strain was the most prevalent reported musculoskeletal injury (18/52, 34.6%), followed by shoulder tendinopathies (16/52, 30.8%), arm/hand tendonitis (8/52, 15.4%), carpal tunnel (7/52, 13.5%), back pain (4/52, 7.7%) and arm/hand arthritis (1/52, 1.9%). Women were significantly more likely to report a musculoskeletal problem than men (p = .011) with the odds of women reporting a musculoskeletal injury 2.59 times greater than men. Women and surgeons with smaller glove sizes were significantly more likely to report shoulder tendonitis (p = .034, p = .1) and neck strain (p = .009, p = .001). Respondents with a musculoskeletal problem experienced significantly more difficulty using rotating cup biopsy forceps (p < .001) and perceived this as difficult a greater amount of time (p = .006). CONCLUSION: Female surgeons report more musculoskeletal injuries than their male counterparts. Surgeons with musculoskeletal injuries experience more difficulty performing particular laparoscopic maneuvers. CLINICAL SIGNIFICANCE: Improving ergonomics for women and surgeons with smaller glove sizes must be prioritized to improve surgeon health and laparoscopic instrument use.

Collaborative model of care between orthopaedics and allied healthcare professionals (CONNACT) in knee osteoarthritis: Effectiveness-implementation hybrid randomized controlled trial of a community-based, multidisciplinary, stratified intervention.

OBJECTIVE: To compare the clinical and cost effectiveness of the Collaborative Model of Care between Orthopaedics and Allied Healthcare Professionals (CONNACT), a community-based, stratified, multidisciplinary intervention consisting of exercise, education, psychological and nutrition delivered through a chronic care model to usual hospital care in adults with knee osteoarthritis (OA). METHODS: Pragmatic, parallel-arm, single-blinded superiority RCT trial. Community-dwelling, ambulant adults with knee OA (Kellgren-Lawrence grade > 1; Knee Injury and OA Outcome Score (KOOS4) ≤75) were enrolled. Primary outcome was KOOS4 at 12-months; secondary outcomes included: quality of life, physical performance measures, symptom satisfaction, psychological outcomes, dietary habits, and global perceived effect. Intention-to-treat analysis using generalized linear model (GLM) and regression modeling were conducted. Economic evaluation through a societal approach was embedded. RESULTS: 110 participants (55 control, 55 intervention) were randomized. No between-group difference found for the primary outcome (MD [95%CI]: -1.86 [-9.11. 5.38]), although both groups demonstrated within-group improvement over 12-months. Among the secondary outcomes, the CONNACT group demonstrated superior dietary change (12 months) and physical performance measures (3 months), and global perceived effect (6 months). While there was no between-group difference in total cost, significant productivity gains (reduced indirect cost) were seen in the CONNACT group. CONCLUSION: CONNACT was not superior to usual care at 1 year. Further efforts are needed to understand the underlying contextual and implementation factors in order to further improve and refine such community-based, stratified care models moving forward. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT03809975. Registered January 18, 2019. https://clinicaltrials.gov/ct2/show/NCT03809975.

In silico analysis of non-structural protein 12 sequences from SARS-COV-2 found in Manaus, Amazonas, Brazil, reveals mutations linked to higher transmissibility.

The disease coronavirus COVID-19 has been the cause of millions of deaths worldwide. Among the proteins of SARS-CoV-2, non-structural protein 12 (NSP12) plays a key role during COVID infection and is part of the RNA-dependent RNA polymerase complex. The monitoring of NSP12 polymorphisms is extremely important for the design of new antiviral drugs and monitoring of viral evolution. This study analyzed the NSP12 mutations detected in circulating SARS-CoV-2 during the years 2020 to 2022 in the population of the city of Manaus, Amazonas, Brazil. The most frequent mutations found were P323L and G671S. Reports in the literature indicate that these mutations are related to transmissibility efficiency, which may have contributed to the extremely high numbers of cases in this location. In addition, two mutations described here (E796D and R914K) are close and have RMSD that is similar to the mutations M794V and N911K, which have been described in the literature as influential on the performance of the NSP12 enzyme. These data demonstrate the need to monitor the emergence of new mutations in NSP12 in order to better understand their consequences for the treatments currently used and in the design of new drugs.

Cohort Study of Downgraded Misdemeanor Convictions and Subsequent Violent Crime: Differences by Defendant Race and Ethnicity.

Introduction: Criminal convictions may be imperfect markers of criminalized behavior, in part because of criminal legal system processes (e.g., plea bargaining). In this retrospective cohort study of individuals convicted of misdemeanors, authors compared the risk of subsequent criminal charges for a violent crime among those initially charged with a felony with that among those initially charged with only misdemeanors, overall and by defendant race and ethnicity. Methods: The study population included individuals aged ≥18 years who were convicted of a misdemeanor in Washington Superior Courts from January 1, 2015 to December 31, 2019. Those with and without initial felony charges were age/gender matched in a 4:1 ratio. The primary outcome was the first subsequent violent crime charge in Washington Superior Courts through December 31, 2020. Data were analyzed with Fine-Gray hazard models from June 2022 to November 2023. Results: There were 3,841 individuals with initial felony charges and 956 with initial misdemeanor charges only. Median follow-up was 2.4 years for both groups. During follow-up, there were 166 new violent crime charges. In multivariable models, White defendants with initial felony charges had a greater risk of subsequent violent crime charges (subdistribution hazard ratio=2.58; 95% CI=1.24, 5.36) than White defendants with initial misdemeanor charges only. Among Black and Hispanic/Latinx defendants, initial felony versus misdemeanor charges were not associated with subsequent violent crime charges (subdistribution hazard ratio=0.93; 95% CI=0.44, 1.97 among Black defendants; subdistribution hazard ratio=0.49; 95% CI=0.15, 1.57 among Hispanic/Latinx defendants). Conclusions: Findings suggest differential associations between downgrading of felony charges to misdemeanor convictions and future violent crime charges by defendant race and ethnicity, with implications for inequitable collateral consequences of criminal convictions.

Measuring interpersonal firearm violence: natural language processing methods to address limitations in criminal charge data.

OBJECTIVE: Firearm violence constitutes a public health crisis in the United States, but comprehensive data infrastructure is lacking to study this problem. To address this challenge, we used natural language processing (NLP) to classify court record documents from alleged violent crimes as firearm-related or non-firearm-related. MATERIALS AND METHODS: We accessed and digitized court records from the state of Washington (n = 1472). Human review established a gold standard label for firearm involvement (yes/no). We developed a key term search and trained supervised machine learning classifiers for this labeling task. Results were evaluated in a held-out test set. RESULTS: The decision tree performed best (F1 score: 0.82). The key term list had perfect recall (1.0) and a modest F1 score (0.65). DISCUSSION AND CONCLUSION: This case report highlights the accuracy, feasibility, and potential time-saved by using NLP to identify firearm involvement in alleged violent crimes based on digitized narratives from court documents.