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1.
Vaccine ; 42(26): 126260, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39265456

RESUMEN

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.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39316721

RESUMEN

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.


Asunto(s)
Fijación Interna de Fracturas , Fracturas del Hombro , Humanos , Fracturas del Hombro/cirugía , Estudios Retrospectivos , Masculino , Fijación Interna de Fracturas/métodos , Femenino , Persona de Mediana Edad , Anciano , Reducción Abierta/métodos , Competencia Clínica , Adulto , Resultado del Tratamiento , Cirujanos Ortopédicos , Anciano de 80 o más Años , Cirujanos
3.
bioRxiv ; 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39345585

RESUMEN

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.

4.
Am J Trop Med Hyg ; 111(4): 770-779, 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39137752

RESUMEN

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.


Asunto(s)
Censos , Composición Familiar , Malaria , Haití/epidemiología , Humanos , Malaria/epidemiología , Estudios Transversales , Sistemas de Información Geográfica
5.
Nat Chem Biol ; 20(9): 1100-1102, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39080419
6.
Death Stud ; : 1-10, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38950562

RESUMEN

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.

7.
Surg Endosc ; 38(9): 5259-5265, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39009725

RESUMEN

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.


Asunto(s)
Comprensión , Alfabetización en Salud , Internet , Educación del Paciente como Asunto , Humanos , Educación del Paciente como Asunto/métodos
8.
Nature ; 631(8019): 37-48, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38961155

RESUMEN

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.


Asunto(s)
Biocatálisis , Vías Biosintéticas , Ingeniería Celular , Enzimas , Humanos , Ingeniería Celular/métodos , Enzimas/metabolismo , Enzimas/química , Especificidad por Sustrato , Técnicas de Química Sintética
9.
Front Immunol ; 15: 1384121, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38903504

RESUMEN

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.


Asunto(s)
Resistencia a Antineoplásicos , Inhibidores de Puntos de Control Inmunológico , Neoplasias , Microambiente Tumoral , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Resistencia a Antineoplásicos/inmunología , Microambiente Tumoral/inmunología , Neoplasias/inmunología , Neoplasias/tratamiento farmacológico , Neoplasias/terapia , Animales , Inmunoterapia/métodos , Antígeno B7-H1/antagonistas & inhibidores , Antígeno B7-H1/inmunología , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Receptor de Muerte Celular Programada 1/inmunología
10.
Int J Dermatol ; 2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38736165

RESUMEN

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.

11.
Geroscience ; 2024 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-38570396

RESUMEN

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 (UPRMT) 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 UPRMT 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.

12.
Angew Chem Int Ed Engl ; 63(31): e202319344, 2024 07 29.
Artículo en Inglés | MEDLINE | ID: mdl-38519422

RESUMEN

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 C4 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 SN2-like attack at C4 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.


Asunto(s)
Aminoácidos , Halogenación , Aminoácidos/metabolismo , Aminoácidos/química , Aminoácidos/biosíntesis , Fosfato de Piridoxal/metabolismo , Fosfato de Piridoxal/química , Arabidopsis/metabolismo , Arabidopsis/enzimología , Pseudomonas/metabolismo , Pseudomonas/enzimología , Ciclopropanos/química , Ciclopropanos/metabolismo
13.
BMC Med ; 22(1): 31, 2024 01 23.
Artículo en Inglés | MEDLINE | ID: mdl-38254075

RESUMEN

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.


Asunto(s)
Malaria Falciparum , Malaria , Humanos , Plasmodium falciparum , Estudios Transversales , Proteína 1 de Superficie de Merozoito , Estudios Seroepidemiológicos , Malaria Falciparum/epidemiología , Inmunoglobulina G
14.
JAMA Dermatol ; 160(1): 45-53, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37966806

RESUMEN

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.


Asunto(s)
Dermatología , Islamismo , Adulto , Humanos , Masculino , Femenino , Atención a la Salud , Prejuicio , Blanco
15.
bioRxiv ; 2023 Nov 27.
Artículo en Inglés | MEDLINE | ID: mdl-38077060

RESUMEN

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), a widely used ETC complex I inhibitor, these two molecules showed cytotoxicity to cancer cells but strikingly demonstrate a lack of toxicity to non-cancer cells, a highly beneficial feature in the development of anti-cancer therapeutics. Furthermore, in vivo experiments with these small molecules utilizing 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 (UPRMT) pathway, that extends lifespan of worms when applied in their adult stage. Interestingly, we also found that these two molecules employ different pathways to extend lifespan in worms. Whereas MTZ utilize the transcription factors ATFS-1 and HSF-1, which are involved in the UPRMT and heat shock response (HSR) pathways respectively, 8-OAc only required HSF-1 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.

16.
Chem Sci ; 14(42): 11718-11726, 2023 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-37920356

RESUMEN

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 C4 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.

17.
PLoS One ; 18(9): e0290414, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37676864

RESUMEN

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.


Asunto(s)
Infecciones por VIH , Hospitales , Recién Nacido , Masculino , Humanos , Femenino , Ciudad de Nueva York/epidemiología , Estudios Retrospectivos , Instituciones de Salud , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiología
18.
Biochemistry ; 62(16): 2480-2491, 2023 08 15.
Artículo en Inglés | MEDLINE | ID: mdl-37542461

RESUMEN

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 O2. Halide, 2OG, and (lastly) O2 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 O2 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.


Asunto(s)
Cloruros , Lisina , Oxigenasas de Función Mixta/química , Hierro/química , Oxidación-Reducción , Oxígeno/química
19.
Am J Trop Med Hyg ; 109(2): 258-272, 2023 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-37277106

RESUMEN

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.


Asunto(s)
Malaria Falciparum , Malaria , Humanos , Adolescente , Preescolar , Plasmodium falciparum , Haití/epidemiología , Estudios Transversales , Malaria/epidemiología , Malaria Falciparum/epidemiología , Factores de Riesgo , Prevalencia , Análisis por Conglomerados
20.
Am J Trop Med Hyg ; 108(6): 1140-1144, 2023 06 07.
Artículo en Inglés | MEDLINE | ID: mdl-37127264

RESUMEN

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.


Asunto(s)
Antimaláricos , COVID-19 , Malaria , Síndrome de Stevens-Johnson , Humanos , Primaquina/efectos adversos , Antimaláricos/efectos adversos , Síndrome de Stevens-Johnson/etiología , Síndrome de Stevens-Johnson/tratamiento farmacológico , Síndrome de Stevens-Johnson/epidemiología , Haití/epidemiología , Administración Masiva de Medicamentos , Pandemias , SARS-CoV-2 , Pirimetamina/efectos adversos , Sulfadoxina/efectos adversos , Combinación de Medicamentos , Malaria/tratamiento farmacológico , Malaria/epidemiología , Malaria/prevención & control
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