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2.
J Chem Inf Model ; 64(8): 3477-3487, 2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38605537

RESUMO

Allostery is an essential biological phenomenon in which perturbation at one site in a biomolecule elicits a functional response at a distal location(s). It is integral to biological processes, such as cellular signaling, metabolism, and transcription regulation. Understanding allostery is also crucial for rational drug discovery. In this work, we focus on an allosteric S100B protein that belongs to the S100 class of EF-hand Ca2+-binding proteins. The Ca2+-binding affinity of S100B is modulated allosterically by TRTK-12 peptide binding 25 Å away from the Ca2+-binding site. We investigated S100B allostery by carrying out nuclear magnetic resonance (NMR) measurements along with microsecond-long molecular dynamics (MD) simulations on S100B/Ca2+ with/without TRTK-12 at different NaCl salt concentrations. NMR HSQC results show that TRTK-12 reorganizes how S100B/Ca2+ responds to different salt concentrations at both orthosteric and allosteric sites. The MD data suggest that TRTK-12 breaks the dynamic aromatic and hydrogen-bond interactions (not observed in X-ray crystallographic structures) between the hinge/helix and Ca2+-binding EF-hand loop of the two subunits in the homodimeric protein. This triggers rearrangement in the protein network architectures and leads to allosteric communication. Finally, computational studies of S100B at distinct ionic strengths suggest that ligand-bound species are more robust to the changing environment relative to the S100B/Ca2+ complex.


Assuntos
Proteína de Capeamento de Actina CapZ , Simulação de Dinâmica Molecular , Subunidade beta da Proteína Ligante de Cálcio S100 , Regulação Alostérica , Subunidade beta da Proteína Ligante de Cálcio S100/química , Subunidade beta da Proteína Ligante de Cálcio S100/metabolismo , Cálcio/metabolismo , Humanos , Transdução de Sinais , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/metabolismo , Oligopeptídeos/química , Oligopeptídeos/metabolismo , Ligação Proteica , Conformação Proteica
3.
Wilderness Environ Med ; 35(2): 198-218, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38651342

RESUMO

The Wilderness Medical Society (WMS) convened an expert panel to develop evidence-based guidelines for the management of pain in austere environments. Recommendations are graded based on the quality of supporting evidence as defined by criteria put forth by the American College of Chest Physicians. This is an update of the 2014 version of the "WMS Practice Guidelines for the Treatment of Acute Pain in Remote Environments" published in Wilderness & Environmental Medicine 2014; 25:41-49.


Assuntos
Dor Aguda , Manejo da Dor , Sociedades Médicas , Medicina Selvagem , Medicina Selvagem/normas , Medicina Selvagem/métodos , Humanos , Dor Aguda/terapia , Dor Aguda/tratamento farmacológico , Manejo da Dor/métodos , Manejo da Dor/normas , Região de Recursos Limitados
5.
Open Forum Infect Dis ; 11(3): ofae040, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38449922

RESUMO

N95 respirator contamination with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during clinical care of patients with coronavirus disease 2019 is poorly understood. We performed a prospective observational study on healthcare provider's (HCP's) N95 respirators' and face shields' SARS-CoV-2 contamination during aerosol-generating procedures on SARS-CoV-2-positive patients housed in a COVID-19-specific unit. Medical masks worn on top of HCP's N95 respirators, and under face shields, during study aerosol-generating procedures were used as surrogates to detect contamination to avoid waste. Thirty-three HCPs were studied, and a total of 33 mask and 27 face shields were sampled. Masks were cut into 9 pieces and face shields were sampled twice, front and back, to determine locality of contamination; however, no positive samples were identified using standard polymerase chain reaction techniques with a CT value up to 40. All 9 mask piece samples were then pooled, as were face shield samples, using centrifugal concentration with polyethersulfone membranes. Once pooled and concentrated, overall, 9 (15%) samples were positive via real-time polymerase chain reaction: 5 from masks (15.2%) and 4 from face shields (14.8%).

6.
Ann Hum Biol ; 51(1): 2298474, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38293777

RESUMO

BACKGROUND: Lack of paediatric reference data limits the utility of handgrip strength as a measure of fitness and well-being. AIM: To develop paediatric handgrip reference curves and evaluate associations with body size and composition and race/ethnicity group. SUBJECTS AND METHODS: Handgrip, body size and composition data were obtained from National Health and Nutrition Examination Survey 2011-2014 participants aged 6-20 years. Densitometry-derived fat and appendicular lean soft tissue mass index Z-scores (FMIZ, ALSTMIZ) were generated in participants >8 years. Dominant and non-dominant handgrip reference curves were created using the LMS method. Analyses included sample weights to produce nationally representative estimates. RESULTS: Differences in handgrip strength according to hand dominance increased with age. Handgrip strength was associated with height and arm length Z-scores (R = 0.42 to 0.47) and ALSTMIZ (R = 0.54). Handgrip strength was higher in the non-Hispanic Black group and lower in the Mexican American compared to non-Hispanic White group. Group differences were attenuated when adjusted for height, arm length or ALSTMIZ. CONCLUSION: Paediatric handgrip reference curves were generated from which individual Z-scores can be calculated separately for dominant versus non-dominant hand and adjusted for body size. Association with ALSTMIZ suggests handgrip Z-score may be used as a measure of functional body composition.


Assuntos
Composição Corporal , Força da Mão , Humanos , Criança , Inquéritos Nutricionais , Tamanho Corporal , Valores de Referência
7.
Open Forum Infect Dis ; 11(1): ofae009, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38293246

RESUMO

Few studies have described changes in SARS-CoV-2 antibody levels in response to infection and vaccination at frequent intervals and over extended follow-up periods. The purpose of this study was to assess changes in SARS-CoV-2-specific antibody responses among a prospective cohort of health care personnel over 18 months with up to 22 samples per person. Antibody levels and live virus neutralization were measured before and after mRNA-based vaccination with results stratified by (1) SARS-CoV-2 infection status prior to initial vaccination and (2) SARS-CoV-2 infection at any point during follow-up. We found that the antibody response to the first dose was almost 2-fold higher in individuals who were seropositive prior to vaccination, although neutralization titers were more variable. The antibody response induced by vaccination appeared to wane over time but generally persisted for 8 to 9 months, and those who were infected at any point during the study had slightly higher antibody levels over time vs those who remained uninfected. These findings underscore the need to account for SARS-CoV-2 natural infection as a modifier of vaccine responses, and they highlight the importance of frequent testing of longitudinal antibody titers over time. Together, our results provide a clearer understanding of the trajectories of antibody response among vaccinated individuals with and without prior SARS-CoV-2 infection.

8.
Infect Control Hosp Epidemiol ; 45(5): 557-561, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38167421

RESUMO

We performed a literature review to describe the risk of surgical-site infection (SSI) in minimally invasive surgery (MIS) compared to standard open surgery. Most studies reported decreased SSI rates among patients undergoing MIS compared to open procedures. However, many were observational studies and may have been affected by selection bias. MIS is associated with reduced risk of surgical-site infection compared to standard open surgery and should be considered when feasible.


Assuntos
Procedimentos Cirúrgicos Minimamente Invasivos , Infecção da Ferida Cirúrgica , Humanos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento
9.
Am J Infect Control ; 52(4): 381-386, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38069921

RESUMO

BACKGROUND: Infection precautions (IP) facilitate standardized and safe patient care. Research has demonstrated several barriers to IP adherence among health care personnel (HCP) but potential exposure risk to SARS-CoV-2 and job role has not been considered. METHODS: Researchers used self-reported baseline surveys with 191 HCPs at a university medical center to examine factors that may have affected IP adherence (eg, personal protective equipment [PPE] and hand hygiene errors) over the 2 weeks prior to the survey. Chi-square tests were used to determine if differences existed first, among job role and IP adherence, and second, the potential risk of exposure to SARS-CoV-2 and IP adherence. A binary logistic regression estimated if PPE nonadherence was associated with COVID-19 stress, job role, and potential exposure risk to SARS-CoV-2. RESULTS: PPE nonadherence varied by job role. Those in the Other group (ie, nonphysician/non-nursing HCP) reported significantly fewer errors (9.6%) compared to Physicians (26.5%) and Registered Nurses (33.3%). Hand/glove hygiene errors between COVID-19 patient rooms varied by job role. Respondents who had higher risks of exposure to SARS-CoV-2 were 5.74 times more likely to experience errors. CONCLUSIONS: The results provide implications for adopting systems-level approaches to support worker knowledge and engagement across job roles to improve IP adherence.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Equipamento de Proteção Individual , Pessoal de Saúde
10.
Infect Control Hosp Epidemiol ; 45(5): 684-687, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38088177

RESUMO

In this quasi-experimental study, implementing PX-UV to the standard environmental cleaning protocol was associated with a reduction in the overall incidence of multidrug-resistant (MDR) gram-negative organisms (P = .01) and MDR Acinetobacter baumannii (P = .001) in intervention intensive care units. However, the intervention did not reduce patient length of stay and 30-day mortality.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , Infecção Hospitalar , Humanos , Tailândia/epidemiologia , Incidência , Farmacorresistência Bacteriana Múltipla , Infecções por Acinetobacter/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Unidades de Terapia Intensiva , Atenção à Saúde , Antibacterianos/uso terapêutico
11.
Infect Control Hosp Epidemiol ; 45(4): 520-525, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38073548

RESUMO

Intravesical Bacillus Calmette-Guérin (BCG) is a standard therapy for non-muscle-invasive bladder cancer used in urology clinics and inpatient settings. We present a review of infection risks to patients receiving intravesical BCG, healthcare personnel who prepare and administer BCG, and other patients treated in facilities where BCG is prepared and administered. Knowledge of these risks and relevant regulations informs appropriate infection prevention measures.


Assuntos
Vacina BCG , Neoplasias da Bexiga Urinária , Humanos , Vacina BCG/efeitos adversos , Administração Intravesical , Neoplasias da Bexiga Urinária/tratamento farmacológico , Pacientes , Atenção à Saúde
14.
Wilderness Environ Med ; 35(1_suppl): 20S-44S, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37945433

RESUMO

To provide guidance to the general public, clinicians, and avalanche professionals about best practices, the Wilderness Medical Society convened an expert panel to revise the evidence-based guidelines for the prevention, rescue, and resuscitation of avalanche and nonavalanche snow burial victims. The original panel authored the Wilderness Medical Society Practice Guidelines for Prevention and Management of Avalanche and Nonavalanche Snow Burial Accidents in 2017. A second panel was convened to update these guidelines and make recommendations based on quality of supporting evidence.


Assuntos
Avalanche , Neve , Acidentes , Sepultamento , Sociedades Médicas , Humanos
15.
J Clin Microbiol ; 61(12): e0073123, 2023 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-38014985

RESUMO

IMPORTANCE: Despite the relatively high mortality and the difficulty in diagnosis, nearly one-third of patients hospitalized with a documented diagnosis of encephalitis did not undergo a lumbar puncture (LP). When an LP was performed, pathogen-specific testing was greatly underutilized. Infectious etiologies were most common, but over 40% of cases were idiopathic at discharge. These findings suggest that there is a substantial opportunity to improve the quality of care through more accurate and timely diagnosis.


Assuntos
Líquidos Corporais , Encefalite , Humanos , North Carolina/epidemiologia , Encefalite/diagnóstico , Encefalite/epidemiologia , Punção Espinal
16.
iScience ; 26(11): 108014, 2023 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-37965155

RESUMO

Previous studies showed that the neoantigen candidate load is an imperfect predictor of immune checkpoint blockade (ICB) efficacy. Further studies provided evidence that the response to ICB is also affected by the qualitative properties of a few or even single candidates, limiting the predictive power based on candidate quantity alone. Here, we predict ICB efficacy based on neoantigen candidates and their neoantigen features in the context of the mutation type, using Multiple-Instance Learning via Embedded Instance Selection (MILES). Multiple instance learning is a type of supervised machine learning that classifies labeled bags that are formed by a set of unlabeled instances. MILES performed better compared with neoantigen candidate load alone for low-abundant fusion genes in renal cell carcinoma. Our findings suggest that MILES is an appropriate method to predict the efficacy of ICB therapy based on neoantigen candidates without requiring direct T cell response information.

18.
Crit Care Med ; 51(11): 1570-1586, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-37902340

RESUMO

RATIONALE: Fever is frequently an early indicator of infection and often requires rigorous diagnostic evaluation. OBJECTIVES: This is an update of the 2008 Infectious Diseases Society of America and Society (IDSA) and Society of Critical Care Medicine (SCCM) guideline for the evaluation of new-onset fever in adult ICU patients without severe immunocompromise, now using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. PANEL DESIGN: The SCCM and IDSA convened a taskforce to update the 2008 version of the guideline for the evaluation of new fever in critically ill adult patients, which included expert clinicians as well as methodologists from the Guidelines in Intensive Care, Development and Evaluation Group. The guidelines committee consisted of 12 experts in critical care, infectious diseases, clinical microbiology, organ transplantation, public health, clinical research, and health policy and administration. All task force members followed all conflict-of-interest procedures as documented in the American College of Critical Care Medicine/SCCM Standard Operating Procedures Manual and the IDSA. There was no industry input or funding to produce this guideline. METHODS: We conducted a systematic review for each population, intervention, comparison, and outcomes question to identify the best available evidence, statistically summarized the evidence, and then assessed the quality of evidence using the GRADE approach. We used the evidence-to-decision framework to formulate recommendations as strong or weak or as best-practice statements. RESULTS: The panel issued 12 recommendations and 9 best practice statements. The panel recommended using central temperature monitoring methods, including thermistors for pulmonary artery catheters, bladder catheters, or esophageal balloon thermistors when these devices are in place or accurate temperature measurements are critical for diagnosis and management. For patients without these devices in place, oral or rectal temperatures over other temperature measurement methods that are less reliable such as axillary or tympanic membrane temperatures, noninvasive temporal artery thermometers, or chemical dot thermometers were recommended. Imaging studies including ultrasonography were recommended in addition to microbiological evaluation using rapid diagnostic testing strategies. Biomarkers were recommended to assist in guiding the discontinuation of antimicrobial therapy. All recommendations issued were weak based on the quality of data. CONCLUSIONS: The guidelines panel was able to formulate several recommendations for the evaluation of new fever in a critically ill adult patient, acknowledging that most recommendations were based on weak evidence. This highlights the need for the rapid advancement of research in all aspects of this issue-including better noninvasive methods to measure core body temperature, the use of diagnostic imaging, advances in microbiology including molecular testing, and the use of biomarkers.


Assuntos
Doenças Transmissíveis , Estado Terminal , Humanos , Adulto , Estado Terminal/terapia , Febre/diagnóstico , Cuidados Críticos/métodos , Unidades de Terapia Intensiva , Biomarcadores
20.
Am J Infect Control ; 51(11S): A114-A119, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37890940

RESUMO

BACKGROUND: Biofilms are surface-attached communities of bacteria embedded in an extracellular matrix. This matrix shields the resident cells from desiccation, chemical perturbation, invasion by other bacteria, and confers reduced susceptibility to antibiotics and disinfectants. There is growing evidence that biofilms on medical instruments (especially endoscopes) and environmental surfaces interfere with cleaning and disinfection. METHODS: The English literature on the impact of biofilms in medicine was reviewed with a focus on the impact of biofilms on reusable semicritical medical instruments and hospital environmental surfaces. RESULTS: Biofilms are frequently present on hospital environmental surfaces and reusable medical equipment. Important health care...associated pathogens that readily form biofilms on environmental surfaces include Staphylococcus aureus, Pseudomonas aeruginosa, and Candida auris. Evidence has demonstrated that biofilms interfere with cleaning and disinfection. DISCUSSION: New technologies such as ..úself-disinfecting..Ñ surfaces or continuous room disinfection systems may reduce or disrupt biofilm formation and are under study to reduce the impact of the contaminated surface environment on health care...associated infections. CONCLUSIONS: Future research is urgently needed to develop methods to reduce or eliminate biofilms from forming on implantable medical devices, reusable medical equipment, and hospital surfaces.


Assuntos
Infecção Hospitalar , Desinfetantes , Humanos , Desinfecção/métodos , Pseudomonas aeruginosa , Hospitais , Bactérias , Biofilmes , Infecção Hospitalar/prevenção & controle
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