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1.
J Occup Environ Med ; 2024 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-38739926

RESUMO

OBJECTIVE: Adverse respiratory outcomes in post-9/11 Veterans with elevated urinary metal measures and enrolled in the VA's Toxic Embedded Fragment registry were compared to those without elevated urinary metals. METHODS: Veterans completed questionnaires, pulmonary physiology tests (pulmonary function and oscillometry) and provided urine samples for analysis of 13 metals. Respiratory symptoms, diagnoses and physiology measures were compared in Veterans with ≥1 urine metal elevation to those without metal elevations, adjusted for covariates, including smoking. RESULTS: Among 402 study participants, 24% had elevated urine metals, often just exceeding upper limits of reference values. Compared to Veterans without elevated metals, those with elevated metals had had higher FEV1 values but similar frequencies of respiratory symptoms and diagnoses and abnormalities on pulmonary physiology tests. CONCLUSIONS: Mild systemic metal elevations in post 9/11 Veterans are not associated with adverse respiratory health outcomes.

2.
BMJ Qual Saf ; 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38782579

RESUMO

BACKGROUND: Hospital-onset bacteraemia and fungaemia (HOB) is being explored as a surveillance and quality metric. The objectives of the current study were to determine sources and preventability of HOB in hospitalised patients in the USA and to identify factors associated with perceived preventability. METHODS: We conducted a cross-sectional study of HOB events at 10 academic and three community hospitals using structured chart review. HOB was defined as a blood culture on or after hospital day 4 with growth of one or more bacterial or fungal organisms. HOB events were stratified by commensal and non-commensal organisms. Medical resident physicians, infectious disease fellows or infection preventionists reviewed charts to determine HOB source, and infectious disease physicians with training in infection prevention/hospital epidemiology rated preventability from 1 to 6 (1=definitely preventable to 6=definitely not preventable) using a structured guide. Ratings of 1-3 were collectively considered 'potentially preventable' and 4-6 'potentially not preventable'. RESULTS: Among 1789 HOB events with non-commensal organisms, gastrointestinal (including neutropenic translocation) (35%) and endovascular (32%) were the most common sources. Overall, 636/1789 (36%) non-commensal and 238/320 (74%) commensal HOB events were rated potentially preventable. In logistic regression analysis among non-commensal HOB events, events attributed to intravascular catheter-related infection, indwelling urinary catheter-related infection and surgical site infection had higher odds of being rated preventable while events with neutropenia, immunosuppression, gastrointestinal sources, polymicrobial cultures and previous positive blood culture in the same admission had lower odds of being rated preventable, compared with events without those attributes. Of 636 potentially preventable non-commensal HOB events, 47% were endovascular in origin, followed by gastrointestinal, respiratory and urinary sources; approximately 40% of those events would not be captured through existing healthcare-associated infection surveillance. DISCUSSION: Factors identified as associated with higher or lower preventability should be used to guide inclusion, exclusion and risk adjustment for an HOB-related quality metric.

3.
Nat Nanotechnol ; 19(5): 698-704, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38228804

RESUMO

Protein adsorption onto nanomaterials often results in denaturation and loss of bioactivity. Controlling the adsorption process to maintain the protein structure and function has potential for a range of applications. Here we report that self-assembled poly(propylene sulfone) (PPSU) nanoparticles support the controlled formation of multicomponent enzyme and antibody coatings and maintain their bioactivity. Simulations indicate that hydrophobic patches on protein surfaces induce a site-specific dipole relaxation of PPSU assemblies to non-covalently anchor the proteins without disrupting the protein hydrogen bonding or structure. As a proof of concept, a nanotherapy employing multiple mast-cell-targeted antibodies for preventing anaphylaxis is demonstrated in a humanized mouse model. PPSU nanoparticles displaying an optimized ratio of co-adsorbed anti-Siglec-6 and anti-FcεRIα antibodies effectively inhibit mast cell activation and degranulation, preventing anaphylaxis. Protein immobilization on PPSU surfaces provides a simple and rapid platform for the development of targeted protein nanomedicines.


Assuntos
Mastócitos , Nanopartículas , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Animais , Camundongos , Adsorção , Humanos , Nanopartículas/química , Nanomedicina/métodos , Anafilaxia , Polipropilenos/química , Degranulação Celular/efeitos dos fármacos
4.
Front Immunol ; 14: 1283370, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37928558

RESUMO

Sialic acid-binding immunoglobulin-like lectin (Siglec)-8 is a sialoside-binding receptor expressed by eosinophils and mast cells that exhibits priming status- and cell type-dependent inhibitory activity. On eosinophils that have been primed with IL-5, GM-CSF, or IL-33, antibody ligation of Siglec-8 induces cell death through a pathway involving the ß2 integrin-dependent generation of reactive oxygen species (ROS) via NADPH oxidase. In contrast, Siglec-8 engagement on mast cells inhibits cellular activation and mediator release but reportedly does not impact cell viability. The differences in responses between cytokine-primed and unprimed eosinophils, and between eosinophils and mast cells, to Siglec-8 ligation are not understood. We previously found that Siglec-8 binds to sialylated ligands present on the surface of the same cell (so-called cis ligands), preventing Siglec-8 ligand binding in trans. However, the functional relevance of these cis ligands has not been elucidated. We therefore explored the potential influence of cis ligands of Siglec-8 on both eosinophils and mast cells. De-sialylation using exogenous sialidase profoundly altered the consequences of Siglec-8 antibody engagement on both cell types, eliminating the need for cytokine priming of eosinophils to facilitate cell death and enabling Siglec-8-dependent mast cell death without impacting anti-Siglec-8 antibody binding. The cell death process licensed by de-sialylation resembled that characterized in IL-5-primed eosinophils, including CD11b upregulation, ROS production, and the activities of Syk, PI3K, and PLC. These results implicate cis ligands in restraining Siglec-8 function on eosinophils and mast cells and reveal a promising approach to the selective depletion of mast cells in patients with mast cell-mediated diseases.


Assuntos
Eosinófilos , Mastócitos , Humanos , Ligantes , Espécies Reativas de Oxigênio/metabolismo , Interleucina-5/metabolismo , Antígenos CD/metabolismo , Morte Celular , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/metabolismo , Citocinas/metabolismo
5.
Contemp Clin Trials Commun ; 35: 101193, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37546228

RESUMO

Background: Suicide is a leading cause of death among Veterans, with rates significantly higher than the general population. To address this issue, it is crucial to develop and implement more effective treatments for Veterans with suicidal thoughts and/or behaviors, particularly those in the post-acute suicidal episode (PASE) stage. The present study aims to establish the feasibility and acceptability of a novel, recovery-oriented treatment called Continuous Identity Cognitive Therapy (CI-CT) for PASE Veterans. Methods: This 3-year open-label pilot study will include three one-arm trials and a pilot randomized controlled trial (RCT). A total of 57 Veterans with a history of an acute suicidal episode within the previous year will be recruited. Primary outcome measures will include changes in personal recovery, suicidal thoughts, and behaviors. Secondary outcomes will include changes in self-identity, life satisfaction, and hopefulness. Feasibility and acceptability will be assessed through attendance and retention rates, drop-out rates, and client satisfaction. Conclusion: This study aims to develop and evaluate the feasibility and acceptability of a novel recovery-oriented intervention for Veterans experiencing PASE. If the intervention is found to be feasible and acceptable, a manualized version will be finalized and a large-scale multi-site RCT will be designed to assess its clinical efficacy on a broader Veteran population. The results of this trial will aid in the development of effective treatment and provide valuable insights into the preliminary feasibility, acceptability, and effectiveness of this approach in reducing suicidal thoughts and behaviors and promoting recovery and rehabilitation in this population.

6.
ACS Synth Biol ; 12(8): 2252-2261, 2023 08 18.
Artigo em Inglês | MEDLINE | ID: mdl-37553068

RESUMO

Allergens are used in the clinical diagnosis (e.g., skin tests) and treatment (e.g., immunotherapy) of allergic diseases. With growing interest in molecular allergy diagnostics and precision therapies, new tools are needed for producing allergen-based reagents. As a step to address this need, we demonstrate a cell-free protein synthesis approach for allergen production of a clinically relevant allergen panel composed of common allergens spanning a wide range of phylogenetic kingdoms. We show that allergens produced with this approach can be recognized by allergen-specific immunoglobulin E (IgE), either monoclonals or in patient sera. We also show that a cell-free expressed allergen can activate human cells such as peripheral blood basophils and CD34+ progenitor-derived mast cells in an IgE-dependent manner. We anticipate that this cell-free platform for allergen production will enable diagnostic and therapeutic technologies, providing useful tools and treatments for both the allergist and allergic patient.


Assuntos
Alérgenos , Imunoglobulina E , Humanos , Filogenia
7.
PLoS One ; 18(7): e0288664, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37450555

RESUMO

The reliability of surface electromyography (sEMG) has not been adequately demonstrated in the equine literature and is an essential consideration as a methodology for application in clinical gait analysis. This observational study investigated within-session, intra-subject (stride-to-stride) and inter-subject reliability, and between-session reliability of normalised sEMG activity profiles, from triceps brachii (triceps), latissimus dorsi (latissimus), longissimus dorsi (longissimus), biceps femoris (biceps), superficial gluteal (gluteal) and semitendinosus muscles in n = 8 clinically non-lame horses during in-hand trot. sEMG sensors were bilaterally located on muscles to collect data during two test sessions (session 1 and 2) with a minimum 24-hour interval. Raw sEMG signals from ten trot strides per horse and session were DC-offset removed, high-pass filtered (40 Hz), full-wave rectified, and low-pass filtered (25 Hz). Signals were normalised to peak amplitude and percent stride before calculating intra- and inter-subject ensemble average sEMG profiles across strides for each muscle and session. sEMG profiles were assessed using waveform similarity statistics: the coefficient of variation (CV) to assess intra- and inter-subject reliability and the adjusted coefficient of multiple correlation (CMC) to evaluate between-session reliability. Across muscles, CV data revealed that intra-horse sEMG profiles within- and between-sessions were comparatively more reliable than inter-horse profiles. Bilateral gluteal, semitendinosus, triceps and longissimus (at T14 and L1) and right biceps showed excellent between-session reliability with group-averaged CMCs > 0.90 (range 0.90-0.97). Bilateral latissimus and left biceps showed good between-session reliability with group-averaged CMCs > 0.75 (range 0.78-0.88). sEMG profiles can reliably describe fundamental muscle activity patterns for selected equine muscles within a test session for individual horses (intra-subject). However, these profiles are more variable across horses (inter-subject) and between sessions (between-session reliability), suggesting that it is reasonable to use sEMG to objectively monitor the intra-individual activity of these muscles across multiple gait evaluation sessions at in-hand trot.


Assuntos
Músculo Esquelético , Cavalos , Animais , Reprodutibilidade dos Testes , Músculo Esquelético/fisiologia , Eletromiografia/métodos
8.
Contemp Clin Trials Commun ; 33: 101155, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37228902

RESUMO

The Cooling to Help Injured Lungs (CHILL) trial is an open label, two group, parallel design multicenter, randomized phase IIB clinical trial assessing the efficacy and safety of targeted temperature management with combined external cooling and neuromuscular blockade to block shivering in patients with early moderate-severe acute respiratory distress syndrome (ARDS). This report provides the background and rationale for the clinical trial and outlines the methods using the Consolidated Standards of Reporting Trials guidelines. Key design challenges include: [1] protocolizing important co-interventions; [2] incorporation of patients with COVID-19 as the cause of ARDS; [3] inability to blind the investigators; and [4] ability to obtain timely informed consent from patients or legally authorized representatives early in the disease process. Results of the Reevaluation of Systemic Early Neuromuscular Blockade (ROSE) trial informed the decision to mandate sedation and neuromuscular blockade only in the group assigned to therapeutic hypothermia and proceed without this mandate in the control group assigned to a usual temperature management protocol. Previous trials conducted in National Heart, Lung, and Blood Institute ARDS Clinical Trials (ARDSNet) and Prevention and Early Treatment of Acute Lung Injury (PETAL) Networks informed ventilator management, ventilation liberation and fluid management protocols. Since ARDS due to COVID-19 is a common cause of ARDS during pandemic surges and shares many features with ARDS from other causes, patients with ARDS due to COVID-19 are included. Finally, a stepwise approach to obtaining informed consent prior to documenting critical hypoxemia was adopted to facilitate enrollment and reduce the number of candidates excluded because eligibility time window expiration.

9.
Psychiatr Rehabil J ; 46(2): 156-162, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37155287

RESUMO

OBJECTIVE: Previous research has established the impact of psychiatric symptoms on social functioning, while there is a paucity of research examining how social functioning relates to personal recovery, an individual's self-assessment of their mental health recovery. This study examined the mediating effect of social engagement, interpersonal communication, and satisfaction with support in the relationship between distinct psychiatric symptom clusters and perceived mental health recovery. METHODS: In a cross-sectional study, both patient self-report and provider assessment data were collected for 250 patients with serious mental illness (SMI) across four mental health service sites. Parallel mediation analytic models were used. RESULTS: Interpersonal communication partially mediated the relationship between positive and negative symptom clusters and personal recovery. Satisfaction with social supports partially mediated the relationship between excited symptoms and personal recovery. Both interpersonal communication and satisfaction with social supports partially mediated the relationship between general psychological distress and depressive symptoms and personal recovery. Collectively, social functioning mediators explained nearly half of the relationship between general psychological distress and excited symptoms and personal recovery and nearly all of the relationship between positive symptoms and personal recovery. CONCLUSIONS AND IMPLICATIONS FOR PRACTICE: Clinical providers working with persons with SMI should regularly assess social functioning in addition to assessing psychiatric symptoms and personal recovery factors and should incorporate social skills education into SMI group and individual treatments. Social functioning as a target of treatment may be especially beneficial for patients who are dissatisfied with other interventions or feel they have experienced the maximum benefit from treatment and are seeking additional methods to support personal recovery. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Assuntos
Transtornos Mentais , Veteranos , Humanos , Interação Social , Estudos Transversais , Síndrome , Transtornos Mentais/psicologia , Seguridade Social
10.
Psychol Serv ; 2023 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-36892916

RESUMO

Internalized or self-stigma can be damaging to psychological and social functioning and recovery, especially for people with serious mental illness. Most studies have focused on the effects of high self-stigma, which has included both moderate and high self-stigma, versus low levels of self-stigma which has included no, minimal, or mild self-stigma. Therefore, little is known about the variation within these categories (e.g., minimal versus mild self-stigma) and its impact on recovery. This article examines differences in the demographic, clinical, and psychosocial variables associated with different levels of self-stigma severity. Baseline data (N = 515) from two concurrent randomized controlled trials of a psychosocial intervention aimed at reducing internalized stigma, and its effects among adults with serious mental illnesses were examined. We found that participants with greater psychological sense of belonging, and greater perceived recovery were significantly less likely to have mild or moderate/high internalized stigma than minimal stigma. Those reporting a greater frequency of stigma experiences, however, were more likely to have mild or moderate/high internalized stigma than minimal stigma. Our findings further underscore the multifaceted nature and impact of self-stigma, particularly in interpersonal relationships and interactions, and demonstrate the importance of attending to even mild levels of self-stigma endorsement. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

12.
J Hand Surg Am ; 48(4): 348-353, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36737280

RESUMO

PURPOSE: Trapeziectomy with suspensionplasty is the most popular treatment for thumb carpometacarpal arthritis. However, carpometacarpal denervation has recently shown promise as an alternative treatment option. This study was designed to compare functional outcomes, pain reduction, and quality of life between denervation and suspension arthroplasty in patients treated for thumb carpometacarpal osteoarthritis. METHODS: We conducted a prospective clinical trial between June 2020 and December 2021. Preoperative and postoperative evaluations were conducted on patients, including the evaluation of functional outcomes via the Michigan Hand Outcomes Questionnaire, pain with the visual analog score, quality of life with the EuroQol-5D, and the evaluation of time to return to function. Outcomes and complications were compared between patients undergoing denervation versus arthroplasty. RESULTS: Forty-eight patients were included in the study, 34 of whom underwent denervation and 14 underwent suspension arthroplasty of the thumb carpometacarpal joint. Patients in the denervation group were younger, with an average age of 59 years compared with 67 years in the arthroplasty group. All other patient characteristics were similar. Pain reduction, functional outcomes, and quality of life scores showed equal improvement in both groups. Denervation patients had a reduced time to return to function (3.3 weeks vs 4.5 months in the arthroplasty group). CONCLUSIONS: Carpometacarpal denervation appears to provide similar short-term outcomes as suspension arthroplasty for the treatment of thumb carpometacarpal arthritis. Treatment with denervation may offer a quicker return to function. The long-term outcomes of denervation remain unknown. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.


Assuntos
Articulações Carpometacarpais , Osteoartrite , Humanos , Pessoa de Meia-Idade , Artroplastia , Articulações Carpometacarpais/cirurgia , Denervação , Osteoartrite/cirurgia , Dor , Estudos Prospectivos , Qualidade de Vida , Polegar/cirurgia
13.
Schizophr Res ; 252: 262-270, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36682317

RESUMO

People living with schizophrenia often face challenges engaging in social and community activities. A critical barrier is negative symptoms that reflect diminished feelings and thoughts that support social interaction. Several years ago, we began a process of specifying an intervention for individuals with schizophrenia and clinically meaningful negative symptoms that could be delivered in an integrated fashion with mental health services offered in VA medical centers with the primary focus of improving social and community engagement. In the present study, we examined the impact of a multi-component intervention to improve social and community participation in a group of Veterans living with schizophrenia and negative symptoms. We compared an intervention called Engaging in Community Roles and Experiences (EnCoRE) - a 12-week program of individual and group meetings that support learning and implementing skills with the goal of helping participants increase engagement in personally-relevant social and community activities - to an active wellness education control condition. Participants in both conditions attended on average of at least half of the groups that were offered, indicating that many individuals living with negative symptoms are willing to participate in an intervention to improve social and community participation. Although there were no significant differences on the two primary outcomes, those in EnCoRE showed better social and general functioning at post treatment and improved social motivational negative symptoms and decreases in perceived limitations at a 3-month follow-up. EnCoRE may be especially beneficial for participants who endorsed more dysfunctional attitudes about their abilities.


Assuntos
Esquizofrenia , Veteranos , Humanos , Esquizofrenia/terapia , Resultado do Tratamento , Participação da Comunidade
14.
Expert Opin Drug Deliv ; 20(2): 205-222, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36629456

RESUMO

INTRODUCTION: Current and developing mast cell therapeutics are reliant on small molecule drugs and biologics, but few are truly selective for mast cells. Most have cellular and disease-specific limitations that require innovation to overcome longstanding challenges to selectively targeting and modulating mast cell behavior. This review is designed to serve as a frame of reference for new approaches that utilize nanotechnology or combine different drugs to increase mast cell selectivity and therapeutic efficacy. AREAS COVERED: Mast cell diseases include allergy and related conditions as well as malignancies. Here, we discuss the targets of existing and developing therapies used to treat these disease pathologies, classifying them into cell surface, intracellular, and extracellular categories. For each target discussed, we discuss drugs that are either the current standard of care, under development, or have indications for potential use. Finally, we discuss how novel technologies and tools can be used to take existing therapeutics to a new level of selectivity and potency against mast cells. EXPERT OPINION: There are many broadly and very few selectively targeted therapeutics for mast cells in allergy and malignant disease. Combining existing targeting strategies with technology like nanoparticles will provide novel platforms to treat mast cell disease more selectively.


Assuntos
Produtos Biológicos , Hipersensibilidade , Transtornos da Ativação de Mastócitos , Neoplasias , Humanos , Sistemas de Liberação de Medicamentos , Mastócitos/metabolismo , Mastócitos/patologia , Neoplasias/tratamento farmacológico , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/metabolismo , Hipersensibilidade/patologia
15.
Arthroscopy ; 39(2): 384-389.e6, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36207000

RESUMO

PURPOSE: To examine the trends in physician professional fees and inpatient and outpatient facility fees in orthopaedic surgery in the United States. METHODS: Physician professional fees and inpatient and outpatient facility fees were tracked from 2008 to 2021 for the most common orthopaedic procedures in each orthopaedic subspecialty. Using common procedure codes for physician and outpatient procedures and Medicare severity diagnosis related group codes for inpatient procedures, the Medicare Physician Fee Schedules were used to obtain the national payment amounts for physician professional fees and inpatient and outpatient facility fees. Trends in fees were tracked over time after adjustment for inflation. RESULTS: From 2008 to 2021, physician professional fees decreased by an average of 20%, whereas inpatient facility fees increased by 15%, and outpatient facility fees increased by 72%. The orthopaedic subspecialty with the largest decrease in physician professional fees was oncology, with an average decrease of 23.5%, followed by general orthopaedics (23.1%), and sports medicine (22.8%). The largest increase in outpatient facility fees was seen in the subspecialties of general orthopaedics (149.8%), spine (130.1%), and trauma (123.0%). CONCLUSIONS: Over the past 13 years, physician professional fees for the most common orthopaedic procedures have declined while inpatient and outpatient facility fees have increased. Understanding these changes is important to the practice of orthopaedic surgery in the United States. LEVEL OF EVIDENCE: IV, economic.


Assuntos
Procedimentos Ortopédicos , Ortopedia , Idoso , Humanos , Estados Unidos , Medicare , Pacientes Internados , Pacientes Ambulatoriais
16.
Respir Med ; 202: 106963, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36108488

RESUMO

BACKGROUND: Blast lung overpressure has received interest as a cause of chronic respiratory disease in Service members who deployed in support of U.S. military operations in Southwest Asia and Afghanistan since 2001. We studied whether veterans who experienced blast exposure report more chronic respiratory symptoms and diagnoses compared to deployed veterans who did not. METHODS: 9,000 veterans included in the Department of Veterans Affairs Toxic Embedded Fragment Registry were invited to complete a survey assessing chronic respiratory symptoms, diagnoses, and exposures. Blast exposure was assessed using the Brief Traumatic Brain Injury Screen and by presence of other symptoms such as blast-induced loss of consciousness. RESULTS: Participants (n = 2147) were predominantly <40 years old, served in the Army, and injured on average 12.8 years previously. 91% reported blast exposure. Blast-exposed veterans were significantly more likely to report cough (OR 1.8), wheeze (OR 2.4), and dyspnea (OR 1.8), even after adjustment for covariates including smoking and occupational exposures to dust, fume, and gas. Veterans reporting higher severity of blast impact, such as traumatic brain injury or loss of consciousness, were more likely to report cough, wheeze, or dyspnea. Veterans with higher severity of blast impact by multiple measures were also more likely to report having COPD. Those reporting a physician-diagnosis of traumatic brain injury were significantly more likely to report having both asthma (OR 1.5) and COPD (OR 1.5). CONCLUSIONS: Blast exposure is associated with respiratory symptoms and COPD. Respiratory system evaluation may warrant inclusion as a standard part of barotrauma health assessment.


Assuntos
Traumatismos por Explosões , Lesões Encefálicas Traumáticas , Doença Pulmonar Obstrutiva Crônica , Transtornos de Estresse Pós-Traumáticos , Veteranos , Adulto , Campanha Afegã de 2001- , Traumatismos por Explosões/complicações , Traumatismos por Explosões/diagnóstico , Traumatismos por Explosões/epidemiologia , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/etiologia , Tosse/complicações , Poeira , Dispneia/complicações , Humanos , Guerra do Iraque 2003-2011 , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Sistema Respiratório , Autorrelato , Transtornos de Estresse Pós-Traumáticos/complicações , Transtornos de Estresse Pós-Traumáticos/diagnóstico , Inconsciência/complicações
17.
Plast Reconstr Surg Glob Open ; 10(8): e4488, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36032374

RESUMO

Background: Targeted muscle reinnervation (TMR) has shown promise in reducing postsurgical limb pain in amputees. However, there has been little evidence on the increased risk of complications and cost as compared with traditional amputations. This study was designed to assess the rate of complications and healthcare costs between those treated with TMR and traditional amputations. Methods: Patients undergoing amputation were selected from the PearlDiver Mariner dataset and categorized into one of two treatment groups depending on the use of TMR versus traditional amputation. Rates of postsurgical complications and overall healthcare costs were compared between the two groups, while controlling for differences in patient demographics and comorbidities. Results: One hundred sixteen TMR procedures and 76,412 traditional amputations were included in the study. The rate of complications did not differ between groups, with a complication rate of 77% in the TMR and 87% in the traditional amputation groups. Overall healthcare costs also did not differ 1 year after surgery, with an average cost of $32,632 in the TMR group and $36,219 in the traditional amputation group. Conclusions: Amputees experience high rates of postsurgical complications, morbidity, and mortality. However, there is no increased risk of complications or cost with the use of TMR. TMR has the potential benefits of reducing overall postsurgical pain and reestablishing activities of daily living. Although TMR is more expensive up front, it may reduce the overall healthcare costs by reducing the need for subsequent care. Further work is needed in large, randomized trials to examine these findings.

18.
Cells ; 11(7)2022 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-35406705

RESUMO

Mast cells are tissue-resident cells that contribute to allergic diseases, among others, due to excessive or inappropriate cellular activation and degranulation. Therapeutic approaches to modulate mast cell activation are urgently needed. Siglec-6 is an immunoreceptor tyrosine-based inhibitory motif (ITIM)-bearing receptor selectively expressed by mast cells, making it a promising target for therapeutic intervention. However, the effects of its engagement on mast cells are poorly defined. Siglec-6 expression and endocytosis on primary human mast cells and mast cell lines were assessed by flow cytometry. SIGLEC6 mRNA expression was examined by single-cell RNAseq in esophageal tissue biopsy samples. The ability of Siglec-6 engagement or co-engagement to prevent primary mast cell activation was determined based on assessments of mediator and cytokine secretion and degranulation markers. Siglec-6 was highly expressed by all mast cells examined, and the SIGLEC6 transcript was restricted to mast cells in esophageal biopsy samples. Siglec-6 endocytosis occurred with delayed kinetics relative to the related receptor Siglec-8. Co-crosslinking of Siglec-6 with FcεRIα enhanced the inhibition of mast cell activation and diminished downstream ERK1/2 and p38 phosphorylation. The selective, stable expression and potent inhibitory capacity of Siglec-6 on human mast cells are favorable for its use as a therapeutic target in mast cell-driven diseases.


Assuntos
Antígenos CD , Antígenos de Diferenciação Mielomonocítica , Lectinas , Mastócitos , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico , Antígenos CD/genética , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/genética , Linhagem Celular , Humanos , Lectinas/genética , Mastócitos/metabolismo , Lectinas Semelhantes a Imunoglobulina de Ligação ao Ácido Siálico/genética
19.
Ecol Evol ; 12(1): e8244, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35126997

RESUMO

Fire is a major selective force on arid grassland communities, favoring traits such as the smoke-induced seed germination response seen in a wide variety of plant species. However, little is known about the relevance of smoke as a cue for plants beyond the seedling stage.We exposed a fire-adapted savanna tree, Vachellia (=Acacia) drepanolobium, to smoke and compared nutrient concentrations in leaf and root tissues to unexposed controls. Experiments were performed on three age cohorts: 2-year-old, 9-month-old, and 3-month-old plants.For the 2-year-old plants exposed to smoke, carbon and nitrogen concentrations were lower in the leaves and higher in the roots than controls. Less pronounced trends were found for boron and magnesium.In contrast, smoke-exposed 3-month-old plants had lower root nitrogen concentrations than controls. No significant differences were found in the 9-month-old plants, and no significant shifts in other nutrient concentrations were observed between plant tissues for any of the three age cohorts. Synthesis: Our findings are consistent with smoke-induced translocation of nutrients from leaves to roots in 2-year-old V. drepanolobium. This could represent a novel form of fire adaptation, with variation over the course of plant development. The translocation differences between age cohorts highlight the need to investigate smoke response in older plants of other species. Accounting for this adaptation could better inform our understanding of savanna community structure and nutrient flows under fire regimes altered by anthropogenic land use and climate change.

20.
Orthopedics ; 45(3): 139-144, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35201937

RESUMO

Preventing postoperative complications is crucial for patients, surgeons, and health care facilities. We developed a risk stratification scoring system to optimize postoperative outcomes for patients undergoing foot and ankle surgery. A total of 35,580 patients who underwent foot and ankle procedures from 2005 to 2017 were identified as part of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). To assess the risk of a postoperative complication, we identified several independent risk factors associated with 30-day postoperative complications, then proceeded to develop a point-based risk scoring system. To validate our scoring system, we used it on a cohort of patients from the database who underwent foot and ankle surgery. Risk factors that correlated with postoperative complications included tobacco abuse, age (≥65 years), diabetes mellitus, hypertension, elevated creatinine level (≥1.3 mg/dL), hypoalbuminemia (<3.5 g/dL), chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), hyponatremia (<135 mEq/L), and anemia (hematocrit value, men <42%; women <38%). Point scores for each factor were: anemia, +10; hypoalbuminemia, +9; elevated creatinine level, +6; CHF, +4; diabetes mellitus, +3; hyponatremia, +3; COPD, +2; hypertension, +2; age, +1; and tobacco abuse, +1. For the validation cohort, we stratified patients according to risk as low (0-20 points), medium (21-30 points), and high (≥31 points) risk. In terms of having a postoperative complication, compared with low-risk patients, patients who were at medium risk had an odds ratio of 4.7 (95% CI, 2.8-7.9) and those at high risk had an odds ratio of 8.3 (95% CI, 4.8-14.5). [Orthopedics. 2022;45(3):139-144.].


Assuntos
Anemia , Hipertensão , Hipoalbuminemia , Hiponatremia , Doença Pulmonar Obstrutiva Crônica , Idoso , Tornozelo/cirurgia , Creatinina , Feminino , Humanos , Hipoalbuminemia/complicações , Hiponatremia/complicações , Masculino , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Doença Pulmonar Obstrutiva Crônica/complicações , Estudos Retrospectivos , Medição de Risco/métodos , Fatores de Risco
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