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Background: Minoritized communities in the United States have had higher COVID-19 mortality and lower vaccine uptake. The influence of previous SARS-CoV-2 infection, initial disease severity, and persistent symptoms on COVID-19 vaccine uptake in Black and Latinx communities has not been examined., Objective: To investigate whether initial COVID-19 severity, persistent symptoms, and other correlates affected vaccine uptake in a predominantly minoritized cohort hospitalized for COVID-19 during the early pandemic in New York City., Design: In this historical cohort study, we abstracted electronic health record data on demographics, comorbidities, hospital oxygen requirements, symptoms at 3 and 6 months post-admission, COVID-19 vaccinations through November 2022, and influenza vaccinations during the 2018-2019 through 2021-2022 seasons. Unadjusted and adjusted odds ratios were estimated through logistic regression analyses of correlates of COVID-19 vaccination, on-time vaccination, and boosting., Participants: Survivors among the first 1186 adult patients hospitalized for COVID-19 between March 1 and April 8, 2020 at a large quaternary care medical center in Northern Manhattan., Main Measures: Uptake of at least one COVID-19 vaccine dose, uptake of at least one booster, and on-time vaccination., Key Results: The 890 surviving individuals were predominantly Latinx (54%) and Non-Hispanic Black (15%). Most had one or more comorbidities (67%), and received at least one COVID-19 vaccine dose (78%). Among those vaccinated, 57% received at least one booster, and 31% delayed vaccination. 67% experienced persistent symptoms. Multiple logistic regression showed no association between vaccine uptake and disease severity or symptom persistence. However, older age and influenza vaccination during the COVID-19 era were associated with increased vaccination, booster uptake, and on-time vaccination., Conclusions: Pinpointing drivers of vaccine uptake and hesitancy is critical to increasing and sustaining COVID-19 vaccination as the field transitions to annual boosters. The association between influenza vaccination and increased vaccine uptake suggests that bundling vaccines for adults may be an effective delivery strategy., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Delivette Castor and Magdalena Sobieszczyk report financial support was provided by Gilead Sciences, Inc. Magdalena Sobieszczyk reports a relationship with Bill & Melinda Gates Foundation that includes: funding grants. Magdalena Sobieszczyk reports a relationship with Merck & Co Inc. that includes: funding grants. Magdalena Sobieszczyk reports a relationship with Sanofi that includes: funding grants. Magdalena Sobieszczyk reports a relationship with Pfizer Inc. that includes: funding grants. Jason Zucker reports a relationship with Centers for Disease Control and Prevention that includes: funding grants. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. JZ has received a grant from the Centers for Disease Control and Prevention within the past 3 years. MES has received grants from the Gates Foundation, Merck, Sanofi, and Pfizer within the past 3 years for work outside the scope of this manuscript. Otherwise, the authors have no relevant financial or non-financial interests to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Small molecule inhibitors of the mitochondrial electron transport chain (ETC) hold significant promise to provide valuable insights to the field of mitochondrial research and aging biology. In this study, we investigated two molecules: mycothiazole (MTZ) - from the marine sponge C. mycofijiensis and its more stable semisynthetic analog 8-O-acetylmycothiazole (8-OAc) as potent and selective chemical probes based on their high efficiency to inhibit ETC complex I function. Similar to rotenone (Rote), MTZ, a newly employed ETC complex I inhibitor, exhibited higher cytotoxicity against cancer cell lines compared to certain non-cancer cell lines. Interestingly, 8-OAc demonstrated greater selectivity for cancer cells when compared to both MTZ and Rote, which has promising potential for anticancer therapeutic development. Furthermore, in vivo experiments with these small molecules utilizing a C. elegans model demonstrate their unexplored potential to investigate aging studies. We observed that both molecules have the ability to induce a mitochondria-specific unfolded protein response (UPR MT ) pathway, that extends lifespan of worms when applied in their adult stage. We also found that these two molecules employ different pathways to extend lifespan in worms. Whereas MTZ utilizes the transcription factors ATFS-1 and HSF1, which are involved in the UPR MT and heat shock response (HSR) pathways respectively, 8-OAc only required HSF1 and not ATFS-1 to mediate its effects. This observation underscores the value of applying stable, potent, and selective next generation chemical probes to elucidate an important insight into the functional roles of various protein subunits of ETC complexes and their regulatory mechanisms associated with aging., (© 2024. The Author(s).)

Objective: The objective of this study is to investigate the influence of metal artifact reduction (MAR) on two cone beam computed tomography (CBCT) units in the evaluation of bone graft loss adjacent to titanium (Ti) and zirconium (Zr) implants., Material and Methods: Twelve Ti and twelve Zr implants were placed in the posterior region of dry human mandibles. Bone graft was applied to the level of the cover screw. Bone graft loss was simulated in half of the sample (6 Ti and 6 Zr) by removing the graft material up to the third implant thread on the buccal surface. CBCT images were acquired on two units, varying the application of MAR (OP300-off and on; Eagle 3D-standard, intermediate, and extreme). The images were assessed by five evaluators that scored the presence of graft loss according to a 5-point scale. The diagnostic values were calculated and compared by non-parametric tests with a significance level of 5%., Results: Higher diagnostic values were achieved with MAR activated in the OP300 unit, for Ti and Zr (p < 0.05). On the Eagle 3D unit, MAR in extreme mode resulted in lower diagnostic values for both types of implants (p < 0.05). The diagnostic values of Ti implants were higher than Zr implants (p < 0.05)., Conclusion: The application of MAR influences the diagnosis of bone graft loss adjacent to Ti and Zr dental implants. However, the extreme mode of MAR in the Eagle 3D unit can impair the diagnostic task in both types of implants and should be avoided., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Squamous cell carcinoma of the nail unit (nSCC) is a rare malignant tumor of the hand and nail. Although skin cancer rarely affects individuals with phototypes IV-VI, its occurrence in these groups is often associated with greater morbidity and mortality. This study aims to characterize the clinical symptoms, presentations, and treatments of nSCC in patients with darker skin types. A systematic review of PubMed and Embase was performed in May 2023 for all peer-reviewed, English-language nSCC studies involving individuals with Fitzpatrick types IV-VI. Most tumors were located on the fingernails (84%), with the right third finger being the most frequently affected (31%). The nail bed (67%) exhibited a higher prevalence than the lateral/proximal nail folds (33%). The duration of symptoms before diagnosis ranged from 1 month to 7 years. nSCC was most commonly treated with Mohs surgery (38%), followed by amputation (35%). Our study was limited to case reports because of a lack of large nSCC studies that provide information on race or images of each patient. These tumors are generally slow-growing yet often misdiagnosed, leading to delays in presentation and diagnosis. Increased awareness about nSCC in phototype IV-VI individuals will reduce misdiagnoses, unnecessary treatment, and recurrences., (© 2024 the International Society of Dermatology.)

Background: With the historical complications when using total shoulder arthroplasty (TSA) to revise failed arthroplasties, and the success of the reverse prosthesis in the revision setting, the question arises whether revision to TSA is still a reasonable option? This systematic review examines revision to TSA and the factors associated with outcomes., Methods: A systematic review was performed for studies of TSA used to revise a failed hemiarthroplasty or TSA. The primary outcome was implant failure leading to a repeat revision arthroplasty. Secondary outcomes included visual analog scale (VAS) pain scores, shoulder motion and other clinical outcomes of shoulder function. Data were pooled to generate representative frequency-weighted means., Results: Thirteen studies were included, totaling 312 shoulders. Etiologies for revision included glenoid arthrosis (62%), glenoid component failure (36%), and other (2%). Of which, 39% of cases experienced complications and 12% required another arthroplasty revision. Secondary outcomes such as VAS pain, Constant, ASES and UCLA score improved, but none were statistically significant. Unsatisfactory outcomes were higher among patients with glenoid bone loss, instability, and soft tissue deficiencies., Discussion: Revision to anatomic TSA can be an acceptable option in certain patients. However, the high rate of complications and glenoid loosening, makes this a limited approach for a revision to anatomic TSA procedure., Competing Interests: The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: JMW receives consulting fees from Smith & Nephew, Stryker, and ConMed, and institutional research support Smith & Nephew, Stryker, ConMed, Arthrex, Zimmer-Biomet, and Ossur. MBG receives institutional research support from Stryker Corporation and Konica Minolta. He is a board or committee member of the American Society for Surgery of the Hand. He is an editor for Journal of Hand Surgery and Surgical Techniques In Orthopaedics. ERW receives consulting fees from Stryker, Biomet, Acumed, and Osteoremedies and institutional research support Konica Minolta., (© The Author(s) 2024.)

Introduction: In this study, we reviewed proximal humeral fractures surgically treated with open reduction and internal fixation (ORIF) to test the null hypothesis that there is no association between fracture characteristics and surgeon characteristics in outcomes after surgical management of displaced proximal humeral fractures with ORIF., Methods: A retrospective review of surgically treated proximal humeral fractures was done at a tertiary-level hospital. The data were organized into two categories: fracture characteristics and surgeon characteristics., Results: There were 314 proximal humeral fractures treated with ORIF. In total, there were 112 failures (36%). Bivariate Pearson correlations demonstrated that the number of proximal humerus fixation surgeries performed by an individual surgeon was associated with adequate calcar reduction (r = 0.995, P < 0.001) and greater tuberosity reduction (r = 0.994, P < 0.001). Years of experience was positively associated with adequate calcar reduction (r = 0.594, P = 0.012) and greater tuberosity reduction (r = 0.589, P = 0.013). Regression analysis of two surgeons versus the rest of the cohort demonstrated significantly lower failure rates (P = 0.001)., Discussion: Complex proximal humeral fractures (3-part and 4-part) have better calcar reduction and tuberosity reduction when treated by surgeons with greater volume of proximal humeral fracture surgery. Among surgeons with high volume, there may be individuals who have the unique ability to provide markedly better results., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

The activation of inert C( sp 3 )-H bonds by non-heme Fe enzymes plays a key role in metabolism, epigenetics, and signaling, while providing a powerful biocatalytic platform for the chemical synthesis of molecules with increased sp 3 complexity. In this context, Fe II /α-ketoglutarate-dependent radical halogenases represent a broadly interesting system, as they are uniquely capable of carrying out transfer of a diverse array of bound anions following C-H activation. Here, we provide the first experimental evidence that bifurcation of H-atom abstraction and radical rebound is driven both by the ability of a dynamic metal coordination sphere to reorganize as well as by a second-sphere hydrogen-bond network where only two residues (Asn224 and Ile151) are necessary and sufficient. The identification of this minimal motif provides a paradigm for understanding the evolution of catalytic plasticity in these enzymes and yields new insight into the design principles by which to expand their reaction scope.

Introduction: Health literacy is the ability of individuals to use basic health information and services to make well-informed decisions. Low health literacy among surgical patients has been associated with nonadherence to preoperative and/or discharge instructions as well as poor comprehension of surgery. It likely poses as a barrier to patients considering foregut surgery which requires an understanding of different treatment options and specific diet instructions. The objective of this study was to assess and compare the readability of online patient education materials (PEM) for foregut surgery., Methods: Using Google, the terms "anti-reflux surgery, "GERD surgery," and "foregut surgery" were searched and a total of 30 webpages from universities and national organizations were selected. The readability of the text was assessed with seven instruments: Flesch Reading Ease formula (FRE), Gunning Fog (GF), Flesch-Kincaid Grade Level (FKGL), Coleman Liau Index (CL), Simple Measure of Gobbledygook (SMOG), Automated Readability Index (ARI), and Linsear Write Formula (LWF). Mean readability scores were calculated with standard deviations. We performed a qualitative analysis gathering characteristics such as, type of information (preoperative or postoperative), organization, use of multimedia, inclusion of a version in another language., Results: The overall average readability of the top PEM for foregut surgery was 12th grade. There was only one resource at the recommended sixth grade reading level. Nearly half of PEM included some form of multimedia., Conclusions: The American Medical Association and National Institute of Health have recommended that PEMs to be written at the 5th-6th grade level. The majority of online PEM for foregut surgery is above the recommended reading level. This may be a barrier for patients seeking foregut surgery. Surgeons should be aware of the potential gaps in understanding of their patients to help them make informed decisions and improve overall health outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The Ministry of Public Health and Population in Haiti is committed to malaria elimination. In 2017, we used novel methods to conduct a census, monitor progress, and return to sampled households (HH) before a cross-sectional survey in La Chapelle and Verrettes communes in Artibonite department ("the 2017 Artibonite HH census"). Geospatial PDFs with digitized structures and basemaps were loaded onto tablets. Enumerators captured GPS coordinates and details of each HH and points of interest. The census used 1 km2 enumeration areas (EAs) to draw a representative sample. Three remote sampling frames were compared with the 2017 Artibonite HH census. First, 2003 census EAs with 2012 population estimates from the Haitian Institute of Statistics and Informatics were standardized to the study EAs. The second sampling frame used the 2016 LandScanTM population estimates and study EAs. The third sampling frame used structures ≥3 m2 manually digitized using Maxar satellite images. In each study EA, 70% of structures were estimated to be inhabited with 4.5 persons/HH. The census identified 33,060 inhabited HHs with an estimated population of 121,593 and 6,126 points of interest. Using daily coverage maps and including digitized structures were novel methods that improved the census quality. Manual digitization was closest to the census sampling frame results with 30,514 digitized structures in the study area. The LandScanTM method performed better in urban areas; however, it produced the highest number of HHs to sample. If a census is not possible, when feasible, remotely digitizing structures and estimating occupancy may provide a close estimate.

Amino acids (AAs) are modular building blocks which nature uses to synthesize both macromolecules, such as proteins, and small molecule natural products, such as alkaloids and non-ribosomal peptides. While the 20 main proteinogenic AAs display relatively limited side chain diversity, a wide range of non-canonical amino acids (ncAAs) exist that are not used by the ribosome for protein synthesis, but contain a broad array of structural features and functional groups. In this communication, we report the discovery of the biosynthetic pathway for a new ncAA, pazamine, which contains a cyclopropane ring formed in two steps. In the first step, a chlorine is added onto the C 4 position of lysine by a radical halogenase, PazA. The cyclopropane ring is then formed in the next step by a pyridoxal-5'-phosphate-dependent enzyme, PazB, via an S N 2-like attack at C 4 to eliminate chloride. Genetic studies of this pathway in the native host, Pseudomonas azotoformans, show that pazamine potentially inhibits ethylene biosynthesis in growing plants based on alterations in the root phenotype of Arabidopsis thaliana seedlings. We further show that PazB can be utilized to make an alternative cyclobutane-containing AA. These discoveries may lead to advances in biocatalytic production of specialty chemicals and agricultural biotechnology., (© 2024 Wiley-VCH GmbH.)

While existing psychological frameworks and their accompanying measures focus on death as anxiety-inducing and debilitating, we highlight an overlooked perspective of death-that death can be a basis for living with more meaning and presence. The present research adapts and validates the Death Mindsets Measure (DMM), which assesses the mindset that "death-is-life-enhancing," for a Norwegian context. Firstly, we translated the DMM and consulted with Norwegian bereavement experts and bereaved Norwegians on items' clarity and relevance to cultural perspectives of death. Secondly, we validated the Norwegian DMM (NDMM) on a predominantly bereaved community sample of Norwegians ( N  = 241). Using structural equation modeling, we confirmed the hierarchical two-factor structure of our measure. The NDMM also demonstrated high internal consistency and discriminant validity with existing death anxiety and death attitudinal measures. Finally, our measure explained additional variance in psychological well-being beyond existing death anxiety and attitudinal measures.

Living systems contain a vast network of metabolic reactions, providing a wealth of enzymes and cells as potential biocatalysts for chemical processes. The properties of protein and cell biocatalysts-high selectivity, the ability to control reaction sequence and operation in environmentally benign conditions-offer approaches to produce molecules at high efficiency while lowering the cost and environmental impact of industrial chemistry. Furthermore, biocatalysis offers the opportunity to generate chemical structures and functions that may be inaccessible to chemical synthesis. Here we consider developments in enzymes, biosynthetic pathways and cellular engineering that enable their use in catalysis for new chemistry and beyond., (© 2024. Springer Nature Limited.)

The past decade has witnessed a revolution in cancer treatment, shifting from conventional drugs (chemotherapies) towards targeted molecular therapies and immune-based therapies, in particular immune-checkpoint inhibitors (ICIs). These immunotherapies release the host's immune system against the tumor and have shown unprecedented durable remission for patients with cancers that were thought incurable, such as metastatic melanoma, metastatic renal cell carcinoma (RCC), microsatellite instability (MSI) high colorectal cancer and late stages of non-small cell lung cancer (NSCLC). However, about 80% of the patients fail to respond to these immunotherapies and are therefore left with other less effective and potentially toxic treatments. Identifying and understanding the mechanisms that enable cancerous cells to adapt to and eventually overcome therapy can help circumvent resistance and improve treatment. In this review, we describe the recent discoveries on the onco-immunological processes which govern the tumor microenvironment and their impact on the resistance to PD-1/PD-L1 checkpoint blockade., Competing Interests: MI has received honoraria for travel support and consulting/advisory roles for AstraZeneca, Bristol-Myers Squibb, Roche, Boehringer-Ingelheim and Merck & Co. outside the submitted work. PH has received honoraria for travel support and consulting/advisory roles for AstraZeneca, Roche, Bristol-Myers Squibb, Novartis, Pfizer, MSD, Qiagen, Thermo-Fisher Scientist, Janssen, Abbvie, Biocartis, Pierre Fabre, Sanofi, and Merck & Co. outside the submitted work. The remaining author declares that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Berland, Gabr, Chang, Ilié, Hofman, Rignol, Ghiringhelli, Mograbi, Rashidian and Hofman.)

Background: Due to low numbers of active infections and persons presenting to health facilities for malaria treatment, case-based surveillance is inefficient for understanding the remaining disease burden in low malaria transmission settings. Serological data through the detection of IgG antibodies from previous malaria parasite exposure can fill this gap by providing a nuanced picture of where sustained transmission remains. Study enrollment at sites of gathering provides a potential approach to spatially estimate malaria exposure and could preclude the need for more intensive community-based sampling., Methods: This study compared spatial estimates of malaria exposure from cross-sectional school- and community-based sampling in Haiti. A total of 52,405 blood samples were collected from 2012 to 2017. Multiplex bead assays (MBAs) tested IgG against P. falciparum liver stage antigen-1 (LSA-1), apical membrane antigen 1 (AMA1), and merozoite surface protein 1 (MSP1). Predictive geospatial models of seropositivity adjusted for environmental covariates, and results were compared using correlations by coordinate points and communes across Haiti., Results: Consistent directional associations were observed between seroprevalence and environmental covariates for elevation (negative), air temperature (negative), and travel time to urban centers (positive). Spearman's rank correlation for predicted seroprevalence at coordinate points was lowest for LSA-1 (ρ = 0.10, 95% CI: 0.09-0.11), but improved for AMA1 (ρ = 0.36, 95% CI: 0.35-0.37) and MSP1 (ρ = 0.48, 95% CI: 0.47-0.49)., Conclusions: In settings approaching P. falciparum elimination, case-based prevalence data does not provide a resolution of ongoing malaria transmission in the population. Immunogenic antigen targets (e.g., AMA1, MSP1) that give higher population rates of seropositivity provide moderate correlation to gold standard community sampling designs and are a feasible approach to discern foci of residual P. falciparum transmission in an area., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Importance: Cultural humility training is of growing interest, yet the religious and cultural accommodations of Muslim patients in dermatology have not been studied., Objective: To explore the perceptions of Muslim patients of their dermatology care., Design, Setting, and Participants: This qualitative mixed-methods study, consisting of surveys and semistructured interviews, recruited participants from 2 clinical sites within a large academic health care system in California. Participants were adult, English-speaking, Muslim patients who were evaluated at least once by a medical or surgical dermatologist between January 2022 and January 2023., Main Outcomes and Measures: A survey obtained the following data: demographics, religious practices pertinent to dermatology care, and experiences of bias outside and inside the dermatology clinic. Semistructured interviews covered topics related to positive and negative experiences in the dermatology clinic, accommodation of cultural and religious needs in dermatology, and future interventions., Results: A total of 21 patients (mean [SD] age, 36.4 [11.6] years; range, 26-71 years) participated in the study: 5 male individuals (24%) and 16 female individuals (76%), including 10 female individuals who wore hijab. Eleven participants identified as Middle Eastern (52%), 8 as South Asian (38%), 1 as North African (5%), and 1 as Pacific Islander (5%). Survey results showed variations in the impact of Islamic practices on dermatology care. Interviews showed that Muslim participants did not perceive dermatology care as a priority and expressed interest in community events focused on general dermatology education. They also experienced stigmatization of their skin disease and cosmetic care. Prior experiences with Islamophobia and colorism hindered the Muslim patient-dermatologist relationship and disclosure of the need for accommodations. There were instances when participants experienced bias and poor cultural humility from dermatologists. Finally, Muslim participants had unique religious and cultural needs pertinent to their care, including clinician gender concordance, medication timing adjustment while fasting, and halal medication ingredients., Conclusions and Relevance: This qualitative mixed-methods study explored the experiences of Muslim patients in dermatology in the US. Recommendations supported by this study include incorporating religion into cultural humility training, increasing diversity in the dermatology workforce, implementing policies for clearer medication labeling, supporting dermatology research in subpopulations of Muslim individuals in the US, and partnering with community organizations for dermatology education.

Living organisms carry out a wide range of remarkable functions, including the synthesis of thousands of simple and complex chemical structures for cellular growth and maintenance. The manipulation of this reaction network has allowed for the genetic engineering of cells for targeted chemical synthesis, but it remains challenging to alter the program underlying their fundamental chemical behavior. By taking advantage of the unique ability of living systems to use evolution to find solutions to complex problems, we have achieved yields of up to ∼95% for three C 4 commodity chemicals, n -butanol, 1,3-butanediol, and 4-hydroxy-2-butanone. Genomic sequencing of the evolved strains identified pcnB and rpoBC as two gene loci that are able to alter carbon flow by remodeling the transcriptional landscape of the cell, highlighting the potential of synthetic pathways as a tool to identify metabolic control points., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Objective: To identify demographic and clinical factors predictive of having a missed opportunity (MO) for HIV screening., Design: Retrospective cohort study., Methods: Electronic medical records were queried for individuals newly diagnosed with HIV in different sites within a large urban academic medical center in New York City between 2018 and 2022. The primary outcome was having one or more MO for HIV screening within the institution, defined as any encounter at which screening was not performed in the 365 days preceding the HIV diagnosis., Results: Over one third of new diagnoses had at least one MO in the preceding year. Older individuals, cisgender women and those assigned female sex at birth, and heterosexual individuals were more likely to have at least one MO. An initial CD4 < 200 cells/ul was more likely among men who have sex with women specifically. Most MOs occurred in the emergency department and outpatient settings, with minimal HIV prevention discussions documented during each MO., Conclusions: These findings suggest that populations perceived to be at lower risk for HIV are more likely to have MOs and possibly late diagnoses, and that universal HIV screening must be implemented into the workflows of emergency department and outpatient settings to facilitate early diagnosis and reduce the incidence of HIV., Competing Interests: All authors have no conflicts of interest to disclose in relation to this study., (Copyright: © 2023 Paer et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

An aliphatic halogenase requires four substrates: 2-oxoglutarate (2OG), halide (Cl - or Br - ), the halogenation target ("prime substrate"), and dioxygen. In well-studied cases, the three nongaseous substrates must bind to activate the enzyme's Fe(II) cofactor for efficient capture of O 2 . Halide, 2OG, and (lastly) O 2 all coordinate directly to the cofactor to initiate its conversion to a cis -halo-oxo-iron(IV) (haloferryl) complex, which abstracts hydrogen (H • ) from the non-coordinating prime substrate to enable radicaloid carbon-halogen coupling. We dissected the kinetic pathway and thermodynamic linkage in binding of the first three substrates of the l-lysine 4-chlorinase, BesD. After addition of 2OG, subsequent coordination of the halide to the cofactor and binding of cationic l-Lys near the cofactor are associated with strong heterotropic cooperativity. Progression to the haloferryl intermediate upon the addition of O 2 does not trap the substrates in the active site and, in fact, markedly diminishes cooperativity between halide and l-Lys. The surprising lability of the BesD•[Fe(IV)=O]•Cl•succinate•l-Lys complex engenders pathways for decay of the haloferryl intermediate that do not result in l-Lys chlorination, especially at low chloride concentrations; one identified pathway involves oxidation of glycerol. The mechanistic data imply (i) that BesD may have evolved from a hydroxylase ancestor either relatively recently or under weak selective pressure for efficient chlorination and (ii) that acquisition of its activity may have involved the emergence of linkage between l-Lys binding and chloride coordination following the loss of the anionic protein-carboxylate iron ligand present in extant hydroxylases.

Targeting malaria interventions in elimination settings where transmission is heterogeneous is essential to ensure the efficient use of resources. Identifying the most important risk factors among persons experiencing a range of exposure can facilitate such targeting. A cross-sectional household survey was conducted in Artibonite, Haiti, to identify and characterize spatial clustering of malaria infections. Household members (N = 21,813) from 6,962 households were surveyed and tested for malaria. An infection was defined as testing positive for Plasmodium falciparum by either a conventional or novel highly sensitive rapid diagnostic test. Seropositivity to the early transcribed membrane protein 5 antigen 1 represented recent exposure to P. falciparum. Clusters were identified using SaTScan. Associations among individual, household, and environmental risk factors for malaria, recent exposure, and living in spatial clusters of these outcomes were evaluated. Malaria infection was detected in 161 individuals (median age: 15 years). Weighted malaria prevalence was low (0.56%; 95% CI: 0.45-0.70%). Serological evidence of recent exposure was detected in 1,134 individuals. Bed net use, household wealth, and elevation were protective, whereas being febrile, over age 5 years, and living in either households with rudimentary wall material or farther from the road increased the odds of malaria. Two predominant overlapping spatial clusters of infection and recent exposure were identified. Individual, household, and environmental risk factors are associated with the odds of individual risk and recent exposure in Artibonite; spatial clusters are primarily associated with household-level risk factors. Findings from serology testing can further strengthen the targeting of interventions.

For a malaria elimination strategy, Haiti's National Malaria Control Program piloted a mass drug administration (MDA) with indoor residual spraying (IRS) in 12 high-transmission areas across five communes after implementing community case management and strengthened surveillance. The MDA distributed sulfadoxine-pyrimethamine and single low-dose primaquine to eligible residents during house visits. The IRS campaign applied pirimiphos-methyl insecticide on walls of eligible houses. Pre- and post-campaign cross-sectional surveys were conducted to assess acceptability, feasibility, drug safety, and effectiveness of the combined interventions. Stated acceptability for MDA before the campaign was 99.2%; MDA coverage estimated at 10 weeks post-campaign was 89.6%. Similarly, stated acceptability of IRS at baseline was 99.9%; however, household IRS coverage was 48.9% because of the high number of ineligible houses. Effectiveness measured by Plasmodium falciparum prevalence at baseline and 10 weeks post-campaign were similar: 1.31% versus 1.43%, respectively. Prevalence of serological markers were similar at 10 weeks post-campaign compared with baseline, and increased at 6 months. No severe adverse events associated with the MDA were identified in the pilot; there were severe adverse events in a separate, subsequent campaign. Both MDA and IRS are acceptable and feasible interventions in Haiti. Although a significant impact of a single round of MDA/IRS on malaria transmission was not found using a standard pre- and post-intervention comparison, it is possible there was blunting of the peak transmission. Seasonal malaria transmission patterns, suboptimal IRS coverage, and low baseline parasitemia may have limited the effectiveness or the ability to measure effectiveness.

Competing Interests: Conflicts of interest Dr Lipner is a consultant for Ortho-Dermatologics, Hoth therapeutics, and BelleTorus Corporation. Chang, Lee, and Desai have no conflicts of interest to declare.

Background: Recurrent anterior glenohumeral instability is a disabling pathology that can be successfully treated by arthroscopic Bankart repair or open Latarjet. However, there is a paucity of studies comparing the postoperative recovery. The purpose of this study is to evaluate the postoperative pain and functional recovery following arthroscopic Bankart versus open Latarjet., Methods: This is a retrospective analysis of a multicenter prospective outcomes registry database. Postoperative recovery outcomes of either a primary or revision arthroscopic Bankart and open Latarjet procedures were compared. A minimum of 1-year follow-up was required. Outcomes measures included pain visual analog scale (VAS), American Shoulder and Elbow Surgeons (ASES) function score, ASES index score, and single assessment numeric evaluation (SANE) score. Overall, 787 patients underwent primary arthroscopic Bankart, 36 underwent revision arthroscopic Bankart and 75 underwent an open Latarjet procedure., Results: When compared to primary arthroscopic Bankart, open Latarjet demonstrated significantly lower VAS scores at 6 weeks (p = 0.03), 3 months (p = 0.01), and 2 years (p < 0.05). Medium-term outcomes for ASES scores and SANE score, at 1 and 2 years showed no difference. Latarjet demonstrated significantly lower (p < 0.05) preoperative early postoperative VAS pain scores with no difference at 1 year or 2 years when compared to primary Bankart. There was no difference in ASES function or index between Bankart and Latarjet. Revision Bankart provided inferior outcomes for VAS, ASES function, and ASES index when compared to primary Bankart and Latarjet at 1 year and 2 years., Conclusions: Primary arthroscopic Bankart repair and open Latarjet provided nearly equivalent improvements in pain (VAS) and functional outcomes (ASES, SANE, VR-12) during the early recovery phase (2 years). This study supports the use of either procedure in the primary treatment of anterior glenohumeral instability. Revision arthroscopic Bankart repair demonstrated deteriorating outcomes at 1 and 2 years postoperatively., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

In 2018, a mass drug administration (MDA) campaign for malaria elimination was piloted in Haiti. The pilot treated 36,338 people with sulfadoxine-pyrimethamine (SP) and primaquine; no severe adverse events were detected. In 2020, another MDA campaign using the same medications was implemented to mitigate an upsurge in malaria cases during the COVID-19 pandemic. Four cases of Stevens-Johnson syndrome (SJS) were identified among the 42,249 people who took the medications. Three of these individuals required hospitalization; all survived. In addition to SP ingestion, an investigation of potential causes for increased SJS cases identified that all four cases had human leukocyte antigens A*29 and/or B*44:03, another known risk factor for SJS. Additionally, three of the four case individuals had antibodies to SARS-CoV-2, and the fourth may have been exposed around the same time. These findings raise the possibility that recent SARS-CoV-2 infection may have contributed to the increased risk for SJS associated with SP exposure during the 2020 campaign.

Background: There has been a rising trend in robotic surgery. Thus, there is demand for a robotic surgery curriculum (RSC) for training surgical trainees and practicing surgeons. There are limited data available about current curricular designs and the extent to which they have incorporated educational frameworks. Our aim was to study the existing robotic surgery curricula using Kern's 6-step approach in curriculum development., Methods: A systematic review was conducted using PubMed, PubMed Central, Cochrane, Embase, and Scopus (we searched studies from 2001 to 2021). PRISMA Guidelines was used to guide the search. Curriculum designed for general surgery and its subspecialties were included. Urology and gynecology were excluded. The articles were reviewed by five reviewers., Results: Our review yielded 71 articles, including 39 curricula at 9 different settings. Using Kern's framework, we demonstrated that the majority of robotic surgery curricula contained all the elements of Kern's curricular design. However, there were significant deficiencies in important aspects of these curricula i.e., implementation, the quality of assessment tools for measurement of performance and evaluation of the educational value of these interventions. Most institutions used commercial virtual reality simulators (VRS) as the main component of their RSC and 23% of curricula only used VRS., Conclusions: Although majority of these studies contained all the elements of Kern's framework, there are critical deficiencies in the components of existing curricula. Future curricula should be designed using established educational frameworks to improve the quality of robotic surgery training., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Biocatalytic C-H activation has the potential to merge enzymatic and synthetic strategies for bond formation. Fe II /αKG-dependent halogenases are particularly distinguished for their ability both to control selective C-H activation as well as to direct group transfer of a bound anion along a reaction axis separate from oxygen rebound, enabling the development of new transformations. In this context, we elucidate the basis for the selectivity of enzymes that perform selective halogenation to yield 4-Cl-lysine (BesD), 5-Cl-lysine (HalB), and 4-Cl-ornithine (HalD), allowing us to probe how site-selectivity and chain length selectivity are achieved. We now report the crystal structure of the HalB and HalD, revealing the key role of the substrate-binding lid in positioning the substrate for C 4 vs C 5 chlorination and recognition of lysine vs ornithine. Targeted engineering of the substrate-binding lid further demonstrates that these selectivities can be altered or switched, showcasing the potential to develop halogenases for biocatalytic applications.

Background: The management of massive posterosuperior rotator cuff tears is controversial, with no gold standard. Two recently developed techniques that have shown promising initial results include arthroscopic superior capsular reconstruction (SCR) and tendon transfers (latissimus or lower trapezius). However, there remains a scarcity of studies examining each procedure's early postoperative clinical outcomes individually or in comparison to each other. The purpose of this study is to compare the early postoperative recovery outcomes of tendon transfers (TTs) to SCR., Methods: Using the surgical outcomes system global database (Arthrex Inc.), we assessed the postoperative recovery outcomes for all patients who had outcomes recorded at least 6 months after SCR or TT. The time points analyzed included preoperative and postoperative (2 weeks, 6 weeks, 3 months, 6 months, 1 year, 2 years). The outcomes analyzed included pain visual analog scale (VAS) score, American Shoulder and Elbow Surgeons Standardized Shoulder Assessment Form (ASES) score, VR-12 physical, and Single Assessment Numeric Evaluation (SANE)., Results: Overall, 163 patients underwent SCR and 24 arthroscopically assisted TT. The mean age for SCR and TT was 60 and 56 years, respectively. Postoperative recovery curves demonstrate that both procedures produced improved outcomes at each postoperative time point compared to preoperative. The pain and functional outcomes measures, including VAS, ASES, SANE, and VR-12 physical, were comparable for TT and SCRs, with similar recovery curves between the 2 techniques. Ultimately at 2 years postoperatively, there were no significant differences between the 2 techniques., Conclusions: Analysis of the early outcomes associated with arthroscopic treatment of massive posterosuperior rotator cuff tears demonstrated that the arthroscopically assisted tendon transfers and arthroscopic superior capsular reconstruction had similar pain and functional outcomes throughout the 2-year postoperative recovery period. Overall, the process of recovery appears equivalent between the 2 techniques. Future studies are needed to assess the outcomes of each technique and specific indications in an attempt to delineate an algorithm for the treatment of irreparable rotator cuff tears., (Copyright © 2022 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.)

Background: The ISCHEMIA trial (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) compared an initial invasive versus an initial conservative management strategy for patients with chronic coronary disease and moderate or severe ischemia, with no major difference in most outcomes during a median of 3.2 years. Extended follow-up for mortality is ongoing., Methods: ISCHEMIA participants were randomized to an initial invasive strategy added to guideline-directed medical therapy or a conservative strategy. Patients with moderate or severe ischemia, ejection fraction ≥35%, and no recent acute coronary syndromes were included. Those with an unacceptable level of angina were excluded. Extended follow-up for vital status is being conducted by sites or through central death index search. Data obtained through December 2021 are included in this interim report. We analyzed all-cause, cardiovascular, and noncardiovascular mortality by randomized strategy, using nonparametric cumulative incidence estimators, Cox regression models, and Bayesian methods. Undetermined deaths were classified as cardiovascular as prespecified in the trial protocol., Results: Baseline characteristics for 5179 original ISCHEMIA trial participants included median age 65 years, 23% women, 16% Hispanic, 4% Black, 42% with diabetes, and median ejection fraction 0.60. A total of 557 deaths accrued during a median follow-up of 5.7 years, with 268 of these added in the extended follow-up phase. This included a total of 343 cardiovascular deaths, 192 noncardiovascular deaths, and 22 unclassified deaths. All-cause mortality was not different between randomized treatment groups (7-year rate, 12.7% in invasive strategy, 13.4% in conservative strategy; adjusted hazard ratio, 1.00 [95% CI, 0.85-1.18]). There was a lower 7-year rate cardiovascular mortality (6.4% versus 8.6%; adjusted hazard ratio, 0.78 [95% CI, 0.63-0.96]) with an initial invasive strategy but a higher 7-year rate of noncardiovascular mortality (5.6% versus 4.4%; adjusted hazard ratio, 1.44 [95% CI, 1.08-1.91]) compared with the conservative strategy. No heterogeneity of treatment effect was evident in prespecified subgroups, including multivessel coronary disease., Conclusions: There was no difference in all-cause mortality with an initial invasive strategy compared with an initial conservative strategy, but there was lower risk of cardiovascular mortality and higher risk of noncardiovascular mortality with an initial invasive strategy during a median follow-up of 5.7 years., Registration: URL: https://www., Clinicaltrials: gov; Unique identifier: NCT04894877.

Introduction: Physiological changes in skin and hair are common during pregnancy. There are limited data on nail changes during pregnancy. Therefore, our study objectives were to determine prevalence and types of nail changes in pregnant women., Methods: A prospective study was conducted in the Weill Cornell Obstetrics and Gynecology waiting room, where a 32-question survey was administered to pregnant and nonpregnant patients., Results: There was a total of 167 subjects (73 pregnant, 94 nonpregnant). Nail changes were reported by 25/73 (34.2%) and 12/94 (12.8%) pregnant and nonpregnant women, respectively ( p < 0.05). Onychocryptosis and leukonychia were more common in pregnant (12.3% and 13.7%, respectively) versus nonpregnant women (5.3% and 0%, respectively) ( p < 0.05). The majority of patients reported no changes in nail growth, thickness, brittleness, during their pregnancies., Discussion/conclusion: Most nail changes in pregnant and nonpregnant women are similar. Physicians should educate women that onychocryptosis and leukonychia are common and benign findings during pregnancy., Competing Interests: The authors have no conflicts of interest relevant to the content of the submission., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)

Background: The ISCHEMIA and the ISCHEMIA-CKD trials found no statistical difference in the primary clinical endpoint between initial invasive management and initial conservative management of patients with chronic coronary disease and moderate to severe ischemia on stress testing without or with advanced chronic kidney disease (CKD). In ISCHEMIA, there was numerically lower cardiovascular mortality but higher non-cardiovascular mortality with no significant difference in all-cause death with an initial invasive strategy when compared with a conservative strategy. However, an invasive strategy increased peri-procedural myocardial infarction (MI) but decreased spontaneous MI with continued separation of curves over time, which potentially may lead to reduced risk of cardiovascular and all-cause mortality. Thus, the long-term effect of invasive management strategy on mortality remains unclear. In ISCHEMIA-CKD, the treatment and cause-specific mortality rates were similar during follow-up., Methods: Funded by the National Heart, Lung, and Blood Institute, the ISCHEMIA-EXTEND observational study is the long-term follow-up of surviving participants (projected median of 10 years) with chronic coronary disease from the ISCHEMIA trial. In the ISCHEMIA trial, 5,179 participants with moderate or severe stress-induced ischemia were randomized to initial invasive management with angiography, revascularization when feasible, and guideline-directed medical therapy (GDMT), or initial conservative management with GDMT alone and angiography reserved for failure of medical therapy. ISCHEMIA-CKD EXTEND is the long-term follow-up of surviving participants (projected median of 9 years) from the ISCHEMIA-CKD trial, a companion trial that included 777 patients with advanced CKD. Ascertainment of death will be conducted via direct participant contact, medical record review, and/or vital status registry search. The overarching objective of long-term follow-up is to assess whether there are between-group differences in long-term all-cause, cardiovascular, and non-cardiovascular mortality, and increase precision around the treatment effect estimates for risk of all-cause, cardiovascular, and non-cardiovascular mortality. We will conduct Bayesian survival modeling to take advantage of rich inferences using the posterior distribution of the treatment effect., Conclusions: The long-term effect of an initial invasive versus conservative strategy on all-cause, cardiovascular, and non-cardiovascular mortality will be assessed. The findings of ISCHEMIA-EXTEND and ISCHEMIA-CKD EXTEND will inform patients, practitioners, practice guidelines, and health policy., (Copyright © 2022 Elsevier Inc. All rights reserved.)

IgG serology can be utilized to estimate exposure to Anopheline malaria vectors and the Plasmodium species they transmit. A multiplex bead-based assay simultaneously detected IgG to Anopheles albimanus salivary gland extract (SGE) and four Plasmodium falciparum antigens (CSP, LSA-1, PfAMA1, and PfMSP1) in 11,541 children enrolled at 350 schools across Haiti in 2016. Logistic regression estimated odds of an above-median anti-SGE IgG response adjusting for individual- and environmental-level covariates. Spatial analysis detected statistically significant clusters of schools with students having high anti-SGE IgG levels, and spatial interpolation estimated anti-SGE IgG levels in unsampled locations. Boys had 11% (95% CI: 0.81, 0.98) lower odds of high anti-SGE IgG compared to girls, and children seropositive for PfMSP1 had 53% (95% CI: 1.17, 2.00) higher odds compared to PfMSP1 seronegatives. Compared to the lowest elevation, quartiles 2-4 of higher elevation were associated with successively lower odds (0.81, 0.43, and 0.34, respectively) of high anti-SGE IgG. Seven significant clusters of schools were detected in Haiti, while spatially interpolated results provided a comprehensive picture of anti-SGE IgG levels in the study area. Exposure to malaria vectors by IgG serology with SGE is a proxy to approximate vector biting in children and identify risk factors for vector exposure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jaramillo-Underwood, Herman, Impoinvil, Sutcliff, Knipes, Worrell, Fox, Desir, Fayette, Javel, Monestime, Mace, Chang, Lemoine, Won, Udhayakumar and Rogier.)

Serological data can provide estimates of human exposure to both malaria vector and parasite based on antibody responses. A multiplex bead-based assay was developed to simultaneously detect IgG to Anopheles albimanus salivary gland extract (SGE) and 23 Plasmodium falciparum antigens among 4185 participants enrolled in Artibonite department, Haiti in 2017. Logistic regression adjusted for participant- and site-level covariates and found children under 5 years and 6-15 years old had 3.7- and 5.4-fold increase in odds, respectively, of high anti-SGE IgG compared to participants >15 years. Seropositivity to P. falciparum CSP, Rh2&#95;2030, and SEA-1 antigens was significantly associated with high IgG response against SGE, and participant enrolment at elevations under 200 m was associated with higher anti-SGE IgG levels. The ability to approximate population exposure to malaria vectors through SGE serology data is very dependent by age categories, and SGE antigens can be easily integrated into a multiplex serological assay., Competing Interests: Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (Published by Oxford University Press on behalf of Infectious Diseases Society of America 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Longitudinal melanonychia (LM) is a common dermatologic finding in clinical practice with a broad differential diagnosis. Melanocytic activation is the most common LM etiology., Objective: To investigate clinical and dermoscopic differences of benign LM based on Fitzpatrick skin type and in biopsied versus nonbiopsied patients., Methods: A 10-year retrospective cohort of 248 benign LM cases at Weill Cornell Dermatology was identified and analyzed., Results: Darker-skinned versus lighter-skinned patients had higher band width percentage (P = .0125), had lower band brightness (P < .001), had more band changes (P = .0071), and received more biopsies (P = .032). Biopsied (n = 47) versus nonbiopsied patients (n = 201) had less multidigit band involvement (P = .0008), higher band width percentage (P = .0213), lower band brightness (P = .0003), and more band changes (P < .0001). Darker skin types more often had brown versus gray coloration on dermoscopy (P = .0232). The mean band width percentage for all biopsied patients was 30.81% (range: 5.80%-100%)., Limitations: Single-center retrospective design. Subungual melanoma and other benign LM etiologies were not analyzed. Only 18.95% of patients received a biopsy., Conclusion: Darker versus lighter skin types more often present with darker and wider bands, present with brown versus gray coloration on dermoscopy, and receive more biopsies. Multi-institutional studies on LM are needed to determine nail matrix biopsy criteria in different skin types., Competing Interests: Conflicts of interest Dr Lipner is a consultant for Ortho Dermatologics, Hoth Therapeutics, Verrica, BelleTorus Corporation, and Hexima. Ms. Lee, Ms. Chang, and Mr. Desai have no conflicts of interest to disclose., (Copyright © 2022 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Plasmodium blood-stage infections can be identified by assaying for protein products expressed by the parasites. While the binary result of an antigen test is sufficient for a clinical result, greater nuance can be gathered for malaria infection status based on quantitative and sensitive detection of Plasmodium antigens and machine learning analytical approaches., Methods: Three independent malaria studies performed in Angola and Haiti enrolled persons at health facilities and collected a blood sample. Presence and parasite density of P. falciparum infection was determined by microscopy for a study in Angola in 2015 (n = 193), by qRT-PCR for a 2016 study in Angola (n = 208), and by qPCR for a 2012-2013 Haiti study (n = 425). All samples also had bead-based detection and quantification of three Plasmodium antigens: pAldolase, pLDH, and HRP2. Decision trees and principal component analysis (PCA) were conducted in attempt to categorize P. falciparum parasitemia density status based on continuous antigen concentrations., Results: Conditional inference trees were trained using the known P. falciparum infection status and corresponding antigen concentrations, and PCR infection status was predicted with accuracies ranging from 73-96%, while level of parasite density was predicted with accuracies ranging from 59-72%. Multiple decision nodes were created for both pAldolase and HRP2 antigens. For all datasets, dichotomous infectious status was more accurately predicted when compared to categorization of different levels of parasite densities. PCA was able to account for a high level of variance (>80%), and distinct clustering was found in both dichotomous and categorical infection status., Conclusions: This pilot study offers a proof-of-principle of the utility of machine learning approaches to assess P. falciparum infection status based on continuous concentrations of multiple Plasmodium antigens., Competing Interests: The authors have declared that no competing interests exist.

Although natural products and synthetic small molecules both serve important medicinal functions, their structures and chemical properties are relatively distinct. To expand the molecular diversity available for drug discovery, one strategy is to blend the effective attributes of synthetic and natural molecules. A key feature found in synthetic compounds that is rare in nature is the use of fluorine to tune drug behavior. We now report a method to site-selectively incorporate fluorine into complex structures to produce regioselectively fluorinated full-length polyketides. We engineered a fluorine-selective trans-acyltransferase to produce site-selectively fluorinated erythromycin precursors in vitro. We further demonstrated that these analogs could be produced in vivo in Escherichia coli on engineering of the fluorinated extender unit pool. By using engineered microbes, elaborate fluorinated compounds can be produced by fermentation, offering the potential for expanding the identification and development of bioactive fluorinated small molecules., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Integrated surveillance for multiple diseases can be an efficient use of resources and advantageous for national public health programs. Detection of IgG antibodies typically indicates previous exposure to a pathogen but can potentially also serve to assess active infection status. Serological multiplex bead assays have recently been developed to simultaneously evaluate exposure to multiple antigenic targets. Haiti is an island nation in the Caribbean region with multiple endemic infectious diseases, many of which have a paucity of data for population-level prevalence or exposure., Methods: A nationwide serosurvey occurred in Haiti from December 2014 to February 2015. Filter paper blood samples ( n = 4,438) were collected from participants in 117 locations and assayed for IgG antibodies on a multiplex bead assay containing 15 different antigens from 11 pathogens: Plasmodium falciparum, Toxoplasma gondii , lymphatic filariasis roundworms, Strongyloides stercoralis , chikungunya virus, dengue virus, Chlamydia trachomatis, Treponema pallidum , enterotoxigenic Escherichia coli, Entamoeba histolytica , and Cryptosporidium parvum ., Results: Different proportions of the Haiti study population were IgG seropositive to the different targets, with antigens from T. gondii, C. parvum , dengue virus, chikungunya virus, and C. trachomatis showing the highest rates of seroprevalence. Antibody responses to T. pallidum and lymphatic filariasis were the lowest, with <5% of all samples IgG seropositive to antigens from these pathogens. Clear trends of increasing seropositivity and IgG levels with age were seen for all antigens except those from chikungunya virus and E. histolytica . Parametric models were able to estimate the rate of seroconversion and IgG acquisition per year for residents of Haiti., Conclusions: Multiplex serological assays can provide a wealth of information about population exposure to different infectious diseases. This current Haitian study included IgG targets for arboviral, parasitic, and bacterial infectious diseases representing multiple different modes of host transmission. Some of these infectious diseases had a paucity or complete absence of published serological studies in Haiti. Clear trends of disease burden with respect to age and location in Haiti can be used by national programs and partners for follow-up studies, resource allocation, and intervention planning., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chan, Martin, Mace, Jean, Stresman, Drakeley, Chang, Lemoine, Udhayakumar, Lammie, Priest and Rogier.)

Purpose: To evaluate the role of concomitant partial rotator cuff repair (RCR) (i.e., infraspinatus) on patient-reported clinical outcomes following superior capsule reconstruction (SCR)., Methods: Postoperative recovery outcomes of SCR alone were compared with SCR with concomitant infraspinatus rotator cuff repair (SCR+RCR) at 3, 6, 12, and 24 months. Patients were included if they had an SCR surgery with or without a concomitant infraspinatus repair. Patients were excluded if they did not have a minimum of 6 months' follow-up or if a preoperative baseline questionnaire was not performed. Outcome measures included pain visual analog scale, American Shoulder and Elbow Surgeons (ASES) Shoulder Function, ASES Shoulder Index, and Single Assessment Numeric Evaluation (SANE) score., Results: Overall, 180 patients were evaluated, including 163 patients who underwent SCR alone and 17 patients who underwent concomitant infraspinatus repair (SCR+RCR). There was no difference in demographic data including age, sex, and body mass index. The postoperative recovery curves demonstrated SCR alone and SCR+RCR both provide significantly improved pain and functional scores at 2 years postoperatively ( P < .001). When we compared the 2 groups, SCR+RCR provided significantly improved ASES Index (87.6 vs 78.2, P = .048) and ASES Function (25.5 vs 21.7, P  = .02). There was no statistically significant difference in SANE scores (75.5 vs 64.2, P  = .07) at 24 months' follow-up., Conclusions: SCR provides modest improvements in pain and function at 2 years postoperatively in patients with irreparable rotator cuff tears. Patients who underwent SCR and concomitant infraspinatus repair demonstrated significantly improved ASES Index and ASES Function scores and statistically nonsignificant improvement in SANE scores at 24 months postoperatively when compared with SCR alone., Level of Evidence: III, retrospective cohort study., (© 2022 Published by Elsevier Inc. on behalf of the Arthroscopy Association of North America.)

The conversion of CO2 to value-added products allows both capture and recycling of greenhouse gas emissions. While plants and other photosynthetic organisms play a key role in closing the global carbon cycle, their dependence on light to drive carbon fixation can be limiting for industrial chemical synthesis. Methanogenic archaea provide an alternative platform as an autotrophic microbial species capable of non-photosynthetic CO2 fixation, providing a potential route to engineered microbial fermentation to synthesize chemicals from CO2 without the need for light irradiation. One major challenge in this goal is to connect upstream carbon-fixation pathways with downstream biosynthetic pathways, given the distinct differences in metabolism between archaea and typical heterotrophs. We engineered the model methanogen, Methanococcus maripaludis, to divert acetyl-coenzyme A toward biosynthesis of value-added chemicals, including the bioplastic polyhydroxybutyrate (PHB). A number of studies implicated limitations in the redox pool, with NAD(P)(H) pools in M. maripaludis measured to be <15% of that of Escherichia coli, likely since methanogenic archaea utilize F420 and ferredoxins instead. Multiple engineering strategies were used to precisely target and increase the cofactor pool, including heterologous expression of a synthetic nicotinamide salvage pathway as well as an NAD+-dependent formate dehydrogenase from Candida boidinii. Engineered strains of M. maripaludis with improved NADH pools produced up to 171 ± 4 mg/L PHB and 24.0 ± 1.9% of dry cell weight. The metabolic engineering strategies presented in this study broaden the utility of M. maripaludis for sustainable chemical synthesis using CO2 and may be transferable to related archaeal species.

Fluorine is a critical element for the design of bioactive compounds, driving advances in selective and sustainable fluorination. However, stereogenic tertiary fluorides pose a synthetic challenge and are thus present in only a few approved drugs (fluticasone, solithromycin, and sofosbuvir). The aldol reaction of fluorinated donors provides an atom-economical approach to asymmetric C-F motifs via C-C bond formation. We report that the type II pyruvate aldolase HpcH and engineered variants perform addition of β-fluoro-α-ketoacids (including fluoropyruvate, β-fluoro-α-ketobutyrate, and β-fluoro-α-ketovalerate) to diverse aldehydes. The reactivity of HpcH towards these fluoro-donors grants access to enantiopure secondary or tertiary fluorides. In addition to representing the first synthesis of tertiary fluorides via biocatalytic carboligation, the afforded products could improve the diversity of fluorinated building blocks and enable the synthesis of fluorinated drug analogs., (© 2022 Wiley-VCH GmbH.)

Background: Haiti is planning targeted interventions to accelerate progress toward malaria elimination. In the most affected department (Grande-Anse), a combined mass drug administration (MDA) and indoor residual spraying (IRS) campaign was launched in October 2018. This study assessed the intervention's effectiveness in reducing Plasmodium falciparum prevalence., Methods: An ecological quasi-experimental study was designed, using a pretest and posttest with a nonrandomized control group. Surveys were conducted in November 2017 in a panel of easy access groups (25 schools and 16 clinics) and were repeated 2-6 weeks after the campaign, in November 2018. Single-dose sulfadoxine-pyrimethamine and primaquine was used for MDA, and pirimiphos-methyl as insecticide for IRS., Results: A total of 10 006 participants were recruited. Fifty-two percent of the population in the intervention area reported having received MDA. Prevalence diminished between 2017 and 2018 in both areas, but the reduction was significantly larger in the intervention area (ratio of adjusted risk ratios, 0.32 [95% confidence interval, .104-.998])., Conclusions: Despite a moderate coverage, the campaign was effective in reducing P. falciparum prevalence immediately after 1 round. Targeted MDA plus IRS is useful in preelimination settings to rapidly decrease the parasite reservoir, an encouraging step to accelerate progress toward malaria elimination., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America.)