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1.
PeerJ ; 11: e16557, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38107569

RESUMO

Sex differences in strength have been attributed to differences in body anthropometrics and composition; these factors are often ignored when generating workplace guidelines. These differences directly impact the upper extremity, leaving female workers exposed to injury risk. The wide range of tools and techniques for measuring upper extremity strength presents a challenge to ergonomists and work task designers; collating outcomes to provide a clear outlook of differences between males and females is essential and the purpose of this work. Four online databases were searched (PROSPERO ID: CRD42022339023) with a focus on articles assessing sex differences in wrist strength. A total of 2,378 articles were screened for relevancy; 25 full-text articles were included in this systematic review. Articles examined movement pairs (ulnar/radial deviation, pronation/supination, and flexion/extension), as well as contraction types (isometric and isokinetic) to observe sex differences in wrist strength. Across all articles, females produced ∼60-65% of male flexion/extension strength, ∼55-60% pronation/supination strength, and ∼60-70% ulnar/radial deviation strength. Overall, females presented lower strength-producing abilities than males, but when considering strength relative to body mass, male-female differences were less pronounced and occasionally females surpassed male strength metrics; typically, this occurred during flexion/extension, particularly in isokinetic contractions. This review has identified a scarcity of articles examining ulnar/radial deviation, pronation/supination, as well as isokinetic contractions; these are needed to supplement workplace exposure guidelines.


Assuntos
Caracteres Sexuais , Punho , Feminino , Masculino , Humanos , Articulação do Punho , Ulna , Rádio (Anatomia)
2.
Cancer Res Commun ; 3(9): 1756-1769, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37674528

RESUMO

Mechanisms for Helicobacter pylori (Hp)-driven stomach cancer are not fully understood. In a transgenic mouse model of gastric preneoplasia, concomitant Hp infection and induction of constitutively active KRAS (Hp+KRAS+) alters metaplasia phenotypes and elicits greater inflammation than either perturbation alone. Gastric single-cell RNA sequencing showed that Hp+KRAS+ mice had a large population of metaplastic pit cells that expressed the intestinal mucin Muc4 and the growth factor amphiregulin. Flow cytometry and IHC-based immune profiling revealed that metaplastic pit cells were associated with macrophage and T-cell inflammation. Accordingly, expansion of metaplastic pit cells was prevented by gastric immunosuppression and reversed by antibiotic eradication of Hp. Finally, MUC4 expression was significantly associated with proliferation in human gastric cancer samples. These studies identify an Hp-associated metaplastic pit cell lineage, also found in human gastric cancer tissues, whose expansion is driven by Hp-dependent inflammation. Significance: Using a mouse model, we have delineated metaplastic pit cells as a precancerous cell type whose expansion requires Hp-driven inflammation. In humans, metaplastic pit cells show enhanced proliferation as well as enrichment in precancer and early cancer tissues, highlighting an early step in the gastric metaplasia to cancer cascade.


Assuntos
Helicobacter pylori , Neoplasias Gástricas , Humanos , Animais , Camundongos , Proteínas Proto-Oncogênicas p21(ras) , Modelos Animais de Doenças , Inflamação
3.
J Hand Surg Am ; 2023 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-37256248

RESUMO

PURPOSE: Injectable collagenase Clostridium histolyticum has been an effective and well-tolerated nonsurgical treatment option for the management of Dupuytren contracture of the hand. The purpose of this study was to determine the efficacy of collagenase injection and adverse event rate in patients who had undergone previous collagenase treatment. METHODS: A retrospective chart review was performed on 332 patients treated with collagenase injection for Dupuytren contracture by three fellowship-trained hand surgeons at a single institution from 2009 to 2019. Fifty-nine joints in 45 patients underwent repeat collagenase therapy for recurrent contracture in the same digit. Pretreatment and posttreatment total metacarpophalangeal and proximal interphalangeal joint flexion contractures were recorded, with complete correction defined as <5° residual digital flexion contracture. Postmanipulation skin tears and adverse events were recorded. A comparison was made between average contracture improvement after initial collagenase injection and that after repeat injection. RESULTS: Forty-five patients with an average duration of 30 months (range, 6-73 months) between initial and repeat collagenase therapies were identified. The mean improvement after first collagenase injection was 45° ± 24° (39° for metacarpophalangeal joint and 50° for proximal interphalangeal joint) compared with a mean improvement of 43° ± 23° (41° for metacarpophalangeal joint and 44° for proximal interphalangeal joint) after second injection. Although similar complete correction rates and skin tear rates (32.2 % for initial and 30.5% for repeat) were observed between initial (80%) and repeat injections (73%), the occurrence of adverse events was 3 times higher (3.4% for initial and 10.2% for repeat) in the latter group. CONCLUSIONS: Collagenase treatment of Dupuytren contracture yields effective total flexion contracture correction. Repeat collagenase treatment of previously treated digits yields similar deformity correction and complete correction rates but a higher incidence of adverse events. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

4.
Cureus ; 15(4): e37926, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37228547

RESUMO

The SARS-CoV-2 virus (COVID-19) became a global pandemic in March 2020. This novel, highly infectious virus caused millions of infections and deaths around the world. Currently, there are few medications that are available for the treatment of COVID-19. Those affected are most commonly given supportive care, with some experiencing symptoms for months. We report a series of four cases depicting the successful use of acyclovir in the treatment of the virus SARS-CoV-2 in patients with long-haul symptoms, especially those in the realm of encephalopathy and neurological problems. Treatment with acyclovir in these patients resolved their symptoms and lowered their IgG and IgM titers, supporting the use of acyclovir as a safe and effective treatment for COVID-19 neurologic symptoms. We suggest the use of the antiviral medication, acyclovir, as a treatment for patients with long-term symptoms and unusual presentations of the virus, such as encephalopathy or coagulopathy.

5.
J Food Sci Technol ; 60(5): 1621-1632, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37033314

RESUMO

In recent years, food irradiation using γ-rays is one of the most valuable practices for insect disinfestation in rice grains for extended shelf life. In this study, flours from four pigmented rice cultivars were exposed to γ-irradiation using 60Co at different doses (0, 5, 10, and 15 kGy). The impact of γ-irradiation on the physico-chemical, functional, and morphological characteristics of pigmented rice flours were analyzed. Results revealed that reduction in amylose content, pH, bulk density, tapped density, and syneresis, while solubility, water absorption capacity, and swelling power values increased significantly (p < 0.05). Pasting characteristics of pigmented rice flours also reduced after exposure to γ-irradiation. Morphological features of pigmented rice flour granules revealed no evidence of physical destruction after irradiation except for black kavuni flour. The structural analysis by FTIR confirms no effect of γ-irradiation on pigmented rice flours. Overall, the study revealed that irradiated pigmented rice flours with enhanced functional properties of less than 10 kGy can be effectively used in the development of value-added rice-based food products considering all the beneficial and safety aspects. Supplementary Information: The online version contains supplementary material available at 10.1007/s13197-023-05709-z.

6.
J Pediatr ; 253: 286-291.e4, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36220349

RESUMO

OBJECTIVE: To identify and prioritize opportunities to improve the psychiatric boarding experience for youth awaiting admission or transfer to inpatient psychiatric care. STUDY DESIGN: This study utilized an exploratory mixed methods design. The study team convened multidisciplinary stakeholder focus groups to discuss proposed hospital-based solutions to mental health boarding, potential psychosocial interventions deliverable during boarding, and outcomes measurement. Focus group responses were transcribed and analyzed to extract themes pertaining to these improvement opportunities. These results informed a follow-up survey which was then sent to the stakeholders to rate the feasibility and importance of modifications using a modified RAND-UCLA Appropriateness Method. RESULTS: Qualitative analyses revealed 9 themes across 2 domains related to psychiatric boarding care: in-hospital improvements and transitions of care. The follow-up survey identified 6 improvement opportunities rated as both feasible and important. Additionally, 6 psychosocial interventions, 2 delivery modalities, and 5 outcomes were rated as both feasible and important. CONCLUSIONS: Stakeholders concerned with the psychiatric boarding of youth identified numerous opportunities for improving the boarding process within 2 domains of in-hospital improvements and transitions of care. Most of the improvements were considered feasible and important with several serving as particularly viable strategies. These have the potential for implementation to improve the care of this vulnerable population and inform local and national quality improvement efforts.


Assuntos
Serviços de Saúde Mental , Saúde Mental , Humanos , Adolescente , Hospitalização , Grupos Focais , Hospitais
8.
Nat Struct Mol Biol ; 29(8): 791-800, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35927584

RESUMO

Proteasome inhibitors are widely used as therapeutics and research tools, and typically target one of the three active sites, each present twice in the proteasome complex. An endogeneous proteasome inhibitor, PI31, was identified 30 years ago, but its inhibitory mechanism has remained unclear. Here, we identify the mechanism of Saccharomyces cerevisiae PI31, also known as Fub1. Using cryo-electron microscopy (cryo-EM), we show that the conserved carboxy-terminal domain of Fub1 is present inside the proteasome's barrel-shaped core particle (CP), where it simultaneously interacts with all six active sites. Targeted mutations of Fub1 disrupt proteasome inhibition at one active site, while leaving the other sites unaffected. Fub1 itself evades degradation through distinct mechanisms at each active site. The gate that allows substrates to access the CP is constitutively closed, and Fub1 is enriched in mutant CPs with an abnormally open gate, suggesting that Fub1 may function to neutralize aberrant proteasomes, thereby ensuring the fidelity of proteasome-mediated protein degradation.


Assuntos
Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae , Microscopia Crioeletrônica , Citoplasma/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética
9.
J Hosp Med ; 17(10): 783-792, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35797488

RESUMO

BACKGROUND: Following initial evaluation and management, youth requiring inpatient psychiatric care often experience boarding, defined as being held in the emergency department or another location while awaiting inpatient care. Although mental health boarding is common, little research has examined the quality of healthcare delivery during the boarding period. OBJECTIVE: This study aimed to explore the perspectives and experiences of multidisciplinary clinicians and parents regarding mental health boarding and to develop a conceptual model to inform quality improvement efforts. DESIGN, SETTING, & PARTICIPANTS: We conducted semistructured interviews with clinicians and parents of youth experiencing boarding. Interviews focused on experiences of care and perceived opportunities for improvement were continued until thematic saturation was reached. Interviews were recorded, transcribed, and analyzed to identify emergent themes using a general inductive approach. Axial coding was used to inform conceptual framework development. RESULTS: Interviews were conducted with 19 clinicians and 11 parents. Building on the Donabedian structure-process-outcome model of quality evaluation, emergent domains, and associated themes included: (1) infrastructure for healthcare delivery, including clinician training, healthcare team composition, and the physical environment; (2) processes of healthcare delivery, including clinician roles and responsibilities, goals of care, communication with families, policies/procedures, and logistics of inter-facility transfer; and (3) measurable outcomes, including patient safety, family experience, mental health status, timeliness of care, and clinician moral distress. CONCLUSION: This qualitative study summarizes clinician and family perspectives about care for youth experiencing boarding. The conceptual model resulting from this analysis can be applied to implement and evaluate quality improvement endeavors to support this vulnerable population.


Assuntos
Serviços de Saúde Mental , Saúde Mental , Adolescente , Criança , Serviço Hospitalar de Emergência , Hospitalização , Humanos , Pesquisa Qualitativa , Melhoria de Qualidade
10.
J Arthroplasty ; 37(9): 1726-1730, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35405265

RESUMO

BACKGROUND: No evidence-based guidelines exist for the perioperative use of clopidogrel in elective hip and knee arthroplasty patients. This study compares the preoperative, intraoperative, and postoperative outcomes of total hip and knee arthroplasty in patients maintained on clopidogrel and with patients whose clopidogrel was held before surgery. METHODS: We retrospectively identified 158 patients taking clopidogrel before undergoing elective total hip or knee arthroplasty. Patients were stratified for having clopidogrel held or continued, based on the interval between latest dose and date of surgery. The primary end points were receipt of transfusion and readmission within 90 days of surgery. Secondary end points were the incidence of complications such as bleeding, infection, re-operation, and major cardiac or neurologic events such as myocardial infarction or stroke during the 90-day postoperative period. RESULTS: The two cohorts had similar demographics. Patients who continued clopidogrel were more likely to receive a blood transfusion postoperatively (9.1% vs 0%, P = .005), but there was no difference in wound drainage (P = .65), wound infection (P = .24), readmission (P = .74), major complications (P = .64), length of stay (P = .70), or mortality (P = .42). Patients who continued clopidogrel before surgery were more likely to have received general anesthesia (P < .001) per anesthesia protocol, however, three such patients did receive spinal anesthesia without any complications. With cementless implants, blood loss was not different between clopidogrel groups. CONCLUSION: Patients undergoing elective total hip and knee arthroplasty may be safely maintained on clopidogrel without an increased risk of wound complications, infections, length of stay, readmission, reoperation, major medical complications, or mortality. Further prospective research is warranted to confirm the effects of continuing clopidogrel in patients undergoing elective hip and knee arthroplasty.


Assuntos
Artroplastia de Quadril , Artroplastia do Joelho , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Clopidogrel , Procedimentos Cirúrgicos Eletivos/efeitos adversos , Hemorragia/etiologia , Humanos , Tempo de Internação , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos
11.
Protoplasma ; 259(1): 61-73, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33811539

RESUMO

Rice sheath blight (ShB) disease, caused by the fungal pathogen Rhizoctonia solani AG1-IA, is one of the devastating diseases and causes severe yield losses all over the world. No completely resistant germplasm is known till now, and as a result, the progress in resistance breeding is unsatisfactory. Basic studies to identify candidate genes, QTLs, and to better understand the host-pathogen interaction are also scanty. In this study, we report the identification of a new ShB-tolerant rice germplasm, CR 1014. Further, we investigated the basis of tolerance by exploring the disease responsive differentially expressed transcriptome and comparing them with that of a susceptible variety, Swarna-Sub1. A total of 815 and 551 genes were found to be differentially regulated in CR 1014 and Swarna-Sub1, respectively, at two different time points. The result shows that the ability to upregulate genes for glycosyl hydrolase, secondary metabolite biosynthesis, cytoskeleton and membrane integrity, the glycolytic pathway, and maintaining photosynthesis make CR 1014 a superior performer in resisting the ShB pathogen. We discuss several putative candidate genes for ShB resistance. The present study, for the first time, revealed the basis of ShB tolerance in the germplasm CR1014 and should prove to be particularly valuable in understanding molecular response to ShB infection. The knowledge could be utilized to devise strategies to manage the disease better.


Assuntos
Oryza , Perfilação da Expressão Gênica , Genótipo , Oryza/genética , Doenças das Plantas/genética , Transcriptoma/genética
12.
Nat Struct Mol Biol ; 28(5): 418-425, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33846632

RESUMO

The proteasome mediates most selective protein degradation. Proteolysis occurs within the 20S core particle (CP), a barrel-shaped chamber with an α7ß7ß7α7 configuration. CP biogenesis proceeds through an ordered multistep pathway requiring five chaperones, Pba1-4 and Ump1. Using Saccharomyces cerevisiae, we report high-resolution structures of CP assembly intermediates by cryogenic-electron microscopy. The first structure corresponds to the 13S particle, which consists of a complete α-ring, partial ß-ring (ß2-4), Ump1 and Pba1/2. The second structure contains two additional subunits (ß5-6) and represents a later pre-15S intermediate. These structures reveal the architecture and positions of Ump1 and ß2/ß5 propeptides, with important implications for their functions. Unexpectedly, Pba1's N terminus extends through an open CP pore, accessing the CP interior to contact Ump1 and the ß5 propeptide. These results reveal how the coordinated activity of Ump1, Pba1 and the active site propeptides orchestrate key aspects of CP assembly.


Assuntos
Chaperonas Moleculares , Complexo de Endopeptidases do Proteassoma , Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae/metabolismo , Domínio Catalítico , Modelos Moleculares , Chaperonas Moleculares/química , Chaperonas Moleculares/metabolismo , Complexo de Endopeptidases do Proteassoma/química , Complexo de Endopeptidases do Proteassoma/metabolismo , Conformação Proteica , Subunidades Proteicas , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/metabolismo
13.
Clin Nucl Med ; 46(2): e125-e126, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33156051

RESUMO

ABSTRACT: We report the case of a 9-year-old girl who presented with acute fevers, cough, and epistaxis with nasal swelling, and found to have a nasal mass. On 18F-FDG PET/CT, she was found to have marked nodal and pulmonary parenchymal disease with diffuse and symmetrical mural FDG uptake within the trachea and bronchial tree. The differential diagnosis was broad, and she was diagnosed with IgG4-RD (IgG4-related disease) and improved on appropriate treatment. To our knowledge, there are only 2 other pediatric cases of IgG4-related pulmonary disease in the literature, and our case serves as a unique constellation of intrapulmonary IgG4-RD imaging findings.


Assuntos
Fluordesoxiglucose F18/metabolismo , Doença Relacionada a Imunoglobulina G4/complicações , Pneumopatias/complicações , Pneumopatias/diagnóstico por imagem , Transporte Biológico , Criança , Feminino , Humanos , Inflamação/complicações , Inflamação/diagnóstico por imagem , Inflamação/metabolismo , Pneumopatias/metabolismo , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada
14.
Sci Rep ; 10(1): 16186, 2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32999331

RESUMO

Chronic lung disease (CLD) is a common co-morbidity for HIV-positive children and adolescents on antiretroviral therapy (ART) in sub-Saharan Africa. In this population, distinct airway microbiota may differentially confer risk of CLD. In a cross-sectional study of 202 HIV-infected children aged 6-16 years in Harare, Zimbabwe, we determined the association of sputum microbiota composition (using 16S ribosomal RNA V4 gene region sequencing) with CLD defined using clinical, spirometric, or radiographic criteria. Forty-two percent of children were determined to have CLD according to our definition. Dirichlet multinomial mixtures identified four compositionally distinct sputum microbiota structures. Patients whose sputum microbiota was dominated by Haemophilus, Moraxella or Neisseria (HMN) were at 1.5 times higher risk of CLD than those with Streptococcus or Prevotella (SP)-dominated microbiota (RR = 1.48, p = 0.035). Cell-free products of HMN sputum microbiota induced features of epithelial disruption and inflammatory gene expression in vitro, indicating enhanced pathogenic potential of these CLD-associated microbiota. Thus, HIV-positive children harbor distinct sputum microbiota, with those dominated by Haemophilus, Moraxella or Neisseria associated with enhanced pathogenesis in vitro and clinical CLD.


Assuntos
Infecções por HIV/complicações , Pneumopatias/microbiologia , Pulmão/microbiologia , Microbiota , Escarro/microbiologia , Adolescente , Criança , Estudos Transversais , Feminino , Infecções por HIV/microbiologia , Humanos , Pulmão/virologia , Pneumopatias/virologia , Masculino , Zimbábue
15.
Cell Host Microbe ; 27(6): 849-851, 2020 06 10.
Artigo em Inglês | MEDLINE | ID: mdl-32526178

RESUMO

Childhood undernutrition is associated with dysbiosis and dampened vaccine responses. Understanding how nutrients influence the microbiota and immunity is critical for vaccine efficacy. In this issue of Cell Host & Microbe, Di Luccia et al. and Huus et al. reveal that nutrition affects IgA responses to the microbiota and oral vaccines.


Assuntos
Imunidade nas Mucosas , Microbiota , Bactérias , Criança , Disbiose , Humanos , Imunoglobulina A
16.
BMC Med Educ ; 20(1): 126, 2020 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-32326951

RESUMO

BACKGROUND: While the Association of American Medical Colleges encourages medical schools to incorporate quality improvement and patient safety (QI/PS) into their curriculum, medical students continue to have limited QI/PS exposure. To prepare medical students for careers that involve QI/PS, the Institute for Healthcare Improvement chapter at an allopathic medical school and school of allied health professions initiated self-directed learning by offering student-led workshops to equip learners with skills to improve the quality and safety of healthcare processes. METHODS: In this prospective cohort study, workshops were hosted for medical students between 2015 and 2018 on five QI/PS topics: Process Mapping, Root-Cause Analysis (RCA), Plan-Do-Study-Act (PDSA) Cycles, Evidence Based Medicine (EBM), and Patient Handoffs. Each workshop included a hands-on component to engage learners in practical applications of QI/PS skills in their careers. Change in knowledge, attitudes, and behaviors was assessed via pre- and post-surveys using 5-point Likert scales, and analyzed using either the McNemar test or non-parametric Wilcoxon signed-rank test. Surveys also gathered qualitative feedback regarding strengths, future areas for improvement, and reasons for attending the workshops. RESULTS: Data was collected from 88.5% of learners (n = 185/209); 19.5% of learners reported prior formal instruction in these topics. Statistically significant improvements in learners' confidence were observed for each workshop. Additionally, after attending workshops, learners felt comfortable teaching the learned QI/PS skill to colleagues (mean pre/post difference 1.96, p < 0.0001, n = 139) and were more likely to pursue QI/PS projects in their careers (mean pre/post difference 0.45, p < 0.0001, n = 139). Lastly, learners demonstrated a statistically significant increase in knowledge in four out of five skills workshop topics. CONCLUSION: Few medical students have formal instruction in QI/PS tools. This pilot study highlights advantages of incorporating an innovative, student-directed modified 'flipped classroom' methodology, with a focus on active experiential learning and minimal didactic instruction.


Assuntos
Currículo , Segurança do Paciente/normas , Melhoria de Qualidade , Educação de Graduação em Medicina , Feedback Formativo , Humanos , Grupo Associado , Projetos Piloto , Aprendizagem Baseada em Problemas/organização & administração , Avaliação de Programas e Projetos de Saúde , Estudos Prospectivos , Estudantes de Medicina , Inquéritos e Questionários
17.
Pediatrics ; 145(3)2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32107285

RESUMO

OBJECTIVES: Children with asthma are at increased risk of complications from influenza; hospitalization represents an important opportunity for vaccination. We aimed to increase the influenza vaccination rate among eligible hospitalized patients with asthma on the pediatric hospital medicine (PHM) service from 13% to 80% over a 4-year period. METHODS: Serial Plan-Do-Study-Act cycles were implemented to improve influenza vaccination rates among children admitted with status asthmaticus and included modifications to the electronic health record (EHR) and provider and family education. Success of the initial PHM pilot led to the development of a hospital-wide vaccination tracking tool and an institutional, nurse-driven vaccine protocol by a multidisciplinary team. Our primary outcome metric was the inpatient influenza vaccination rate among PHM patients admitted with status asthmaticus. Process measures included documentation of influenza vaccination status and use of the EHR asthma order set and a history and physical template. The balance measure was adverse vaccine reaction within 24 hours. Data analysis was performed by using statistical process control charts. RESULTS: The inpatient influenza vaccination rate increased from 13% to 57% over 4 years; special cause variation was achieved. Overall, 50% of eligible patients were vaccinated during asthma hospitalization in the postintervention period. Documentation of influenza vaccination status significantly increased from 51% to 96%, and asthma history and physical and order set use also improved. No adverse vaccine reactions were documented. CONCLUSIONS: A bundle of interventions, including EHR modifications, provider and family education, hospital-wide tracking, and a nurse-driven vaccine protocol, increased influenza vaccination rates among eligible children hospitalized with status asthmaticus.


Assuntos
Hospitalização , Vacinas contra Influenza , Influenza Humana/prevenção & controle , Estado Asmático , Vacinação/estatística & dados numéricos , Criança , Estudos de Coortes , Feminino , Humanos , Influenza Humana/etiologia , Masculino , Estado Asmático/complicações
18.
Xenobiotica ; 50(7): 815-821, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31755347

RESUMO

Recent approvals of beta-lactamase inhibitor (BLI) drug in combination with cephalosporins/penems have provided the right impetus for novel BLIs. One important research question, hitherto not addressed, is pertaining to the relevance of preclinical pharmacokinetics for pairing the antibiotic with existing/novel BLI.Two BLI combination drugs: (a) approved (i.e. ceftazidime/avibactam); (b) clinical development (i.e. cefepime/zidebactam) were explored to provide insights to address the research question.Individual intravenous dosing of ceftazidime, avibactam, cefepime and zidebactam was done at 1 mg/kg by intravenous route in Balb/c mice and Wistar rats. Serial blood samples were collected and analysed by LC-MS/MS method.Examination of the ratios of pharmacokinetic parameters (CL, VSS and T1/2) for individual drugs in combinations (for instance, CL (ceftazidime)/CL (avibactam); CL (cefepime)/CL (zidebactam)) suggested that the pharmacokinetic data gathered in rats were generally within 0.5- to 2-fold; but mouse data revealed larger disparity for VSS (0.11- to 8.25-fold) or CL (0.49- to 4.03-fold).The observed ratio for CL/VSS observed in rats agreed with corresponding human ratios for the pairwise comparison of the individual drugs in the combinations.Retrospectively, current pharmacokinetic findings suggest rat pharmacokinetic data may aid the combination of BLI with an appropriate antibiotic.


Assuntos
Compostos Azabicíclicos/metabolismo , Ceftazidima/metabolismo , Inibidores de beta-Lactamases/metabolismo , Animais , Ciclo-Octanos , Combinação de Medicamentos , Camundongos , Testes de Sensibilidade Microbiana , Piperidinas , Ratos , Roedores
19.
Genome Med ; 11(1): 77, 2019 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-31783775

RESUMO

BACKGROUND: The 2015 American College of Medical Genetics and Genomics (ACMG) and the Association for Molecular Pathology (AMP) guidelines for clinical sequence variant interpretation state that "well-established" functional studies can be used as evidence in variant classification. These guidelines articulated key attributes of functional data, including that assays should reflect the biological environment and be analytically sound; however, details of how to evaluate these attributes were left to expert judgment. The Clinical Genome Resource (ClinGen) designates Variant Curation Expert Panels (VCEPs) in specific disease areas to make gene-centric specifications to the ACMG/AMP guidelines, including more specific definitions of appropriate functional assays. We set out to evaluate the existing VCEP guidelines for functional assays. METHODS: We evaluated the functional criteria (PS3/BS3) of six VCEPs (CDH1, Hearing Loss, Inherited Cardiomyopathy-MYH7, PAH, PTEN, RASopathy). We then established criteria for evaluating functional studies based on disease mechanism, general class of assay, and the characteristics of specific assay instances described in the primary literature. Using these criteria, we extensively curated assay instances cited by each VCEP in their pilot variant classification to analyze VCEP recommendations and their use in the interpretation of functional studies. RESULTS: Unsurprisingly, our analysis highlighted the breadth of VCEP-approved assays, reflecting the diversity of disease mechanisms among VCEPs. We also noted substantial variability between VCEPs in the method used to select these assays and in the approach used to specify strength modifications, as well as differences in suggested validation parameters. Importantly, we observed discrepancies between the parameters VCEPs specified as required for approved assay instances and the fulfillment of these requirements in the individual assays cited in pilot variant interpretation. CONCLUSIONS: Interpretation of the intricacies of functional assays often requires expert-level knowledge of the gene and disease, and current VCEP recommendations for functional assay evidence are a useful tool to improve the accessibility of functional data by providing a starting point for curators to identify approved functional assays and key metrics. However, our analysis suggests that further guidance is needed to standardize this process and ensure consistency in the application of functional evidence.


Assuntos
Gerenciamento Clínico , Suscetibilidade a Doenças , Informática Médica/métodos , Software , Prova Pericial , Predisposição Genética para Doença , Testes Genéticos , Variação Genética , Genômica/métodos , Humanos , Guias de Prática Clínica como Assunto
20.
Public Health Nutr ; 22(14): 2688-2699, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31111809

RESUMO

OBJECTIVE: Dietary guidelines are an essential policy tool for facilitating optimal dietary patterns and healthy eating behaviours. We report: (i) the methodological approach adopted for developing the National Dietary Guidelines of Greece (NDGGr) for Infants, Children and Adolescents; and (ii) the guidelines for children aged 1-18 years. DESIGN: An evidence-based approach was employed to develop food-based recommendations according to the methodologies of the WHO, FAO and European Food Safety Authority. Physical activity recommendations were also compiled. Food education, healthy eating tips and suggestions were also provided. SETTING: The NDGGr encompass food-based nutritional and physical activity recommendations for promoting healthy dietary patterns and eating behaviours and secondarily to serve as a helpful tool for the prevention of childhood overweight and obesity. RESULTS: The NDGGr include food-based recommendations, food education and health promotion messages regarding: (i) fruits; (ii) vegetables; (iii) milk and dairy products; (iv) cereals; (v) red and white meat; (vi) fish and seafood; (vii) eggs; (viii) legumes; (ix) added lipids, olives, and nuts; (x) added sugars and salt; (xi) water and beverages, and (xii) physical activity. A Nutrition Wheel, consisting of the ten most pivotal key messages, was developed to enhance the adoption of optimal dietary patterns and a healthy lifestyle. The NDGGr additionally provide recommendations regarding the optimal frequency and serving sizes of main meals, based on the traditional Greek diet. CONCLUSIONS: As a policy tool for promoting healthy eating, the NDGGr have been disseminated in public schools across Greece.


Assuntos
Dieta Saudável , Comportamento Alimentar , Promoção da Saúde , Política Nutricional , Obesidade Infantil/prevenção & controle , Adolescente , Criança , Pré-Escolar , Dieta , Ingestão de Energia , Exercício Físico , Grécia , Humanos , Lactente , Sobrepeso/prevenção & controle , Recomendações Nutricionais
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