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1.
BMJ Open Respir Res ; 11(1)2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38697677

RESUMEN

BACKGROUND: Singing for lung health (SLH) is an arts-based breathing control and movement intervention for people with long-term respiratory conditions, intended to improve symptoms and quality of life. Online, remotely delivered programmes might improve accessibility; however, no previous studies have assessed the effectiveness of this approach. METHODS: We conducted an assessor-blind randomised controlled trial comparing the impact of 12 weeks of once-weekly online SLH sessions against usual care on health-related quality of life, assessed using the RAND 36-Item Short Form Health Survey (SF-36) Mental Health Composite (MHC) and Physical Health Composite (PHC) scores. RESULTS: We enrolled 115 people with stable chronic obstructive pulmonary disease (COPD), median (IQR) age 69 (62-74), 56.5% females, 80% prior pulmonary rehabilitation, Medical Research Council dyspnoea scale 4 (3-4), forced expiratory volume in 1 s % predicted 49 (35-63). 50 participants in each arm completed the study. The intervention arm experienced improvements in physical but not mental health components of RAND SF-36; PHC (regression coefficient (95% CI): 1.77 (95% CI 0.11 to 3.44); p=0.037), but not MHC (0.86 (95% CI -1.68 to 3.40); p=0.504). A prespecified responder analysis based on achieving a 10% improvement from baseline demonstrated a response rate for PHC of 32% in the SLH arm and 12.7% for usual care (p=0.024). A between-group difference in responder rate was not found in relation to the MHC (19.3% vs 25.9%; p=0.403). DISCUSSION AND CONCLUSION: A 12-week online SLH programme can improve the physical component of quality of life for people with COPD, but the overall effect is relatively modest compared with the impact seen in research using face-to-face group sessions. Further work on the content, duration and dose of online interventions may be useful. TRIAL REGISTRATION NUMBER: NCT04034212.


Asunto(s)
Enfermedad Pulmonar Obstructiva Crónica , Calidad de Vida , Canto , Humanos , Enfermedad Pulmonar Obstructiva Crónica/terapia , Enfermedad Pulmonar Obstructiva Crónica/rehabilitación , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Femenino , Masculino , Persona de Mediana Edad , Anciano , Resultado del Tratamiento , Pulmón/fisiopatología , Volumen Espiratorio Forzado , Ejercicios Respiratorios/métodos , Método Simple Ciego
2.
Res Sq ; 2024 Apr 19.
Artículo en Inglés | MEDLINE | ID: mdl-38699337

RESUMEN

Voriconazole exposure is associated with skin cancer, but it is unknown how the full spectrum of its metabolizer phenotypes impacts this association. We conducted a retrospective cohort study to determine how variation in metabolism of voriconazole as measured by metabolizer status of CYP2C19 is associated with the total number of skin cancers a patient develops and the rate of development of the first skin cancer after treatment. There were 1,739 organ transplant recipients with data on CYP2C19 phenotype. Of these, 134 were exposed to voriconazole. There was a significant difference in the number of skin cancers after transplant based on exposure to voriconazole, metabolizer phenotype, and the interaction of these two (p < 0.01 for all three). This increase was driven primarily by number of squamous cell carcinomas among rapid metabolizes with voriconazole exposure (p < 0.01 for both). Patients exposed to voriconazole developed skin cancers more rapidly than those without exposure (Fine-Grey hazard ratio 1.78, 95% confidence interval 1.19-2.66). This association was similarly driven by development of SCC (Fine-Grey hazard ratio 1.83, 95% confidence interval 1.14-2.94). Differences in voriconazoles metabolism are associated with an increase in the number of skin cancers developed after transplant, particularly SCC.

3.
Infect Immun ; 92(5): e0008024, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38534100

RESUMEN

Traditional folk treatments for the prevention and management of urinary tract infections (UTIs) and other infectious diseases often include plants and plant extracts that are rich in phenolic compounds. These have been ascribed a variety of activities, including inhibition of bacterial interactions with host cells. Here, we tested a panel of four well-studied phenolic compounds-caffeic acid phenethyl ester (CAPE), resveratrol, catechin, and epigallocatechin gallate-for the effects on host cell adherence and invasion by uropathogenic Escherichia coli (UPEC). These bacteria, which are the leading cause of UTIs, can bind and subsequently invade bladder epithelial cells via an actin-dependent process. Intracellular UPEC reservoirs within the bladder are often protected from antibiotics and host defenses and likely contribute to the development of chronic and recurrent infections. In cell culture-based assays, only resveratrol had a notable negative effect on UPEC adherence to bladder cells. However, both CAPE and resveratrol significantly inhibited UPEC entry into the host cells, coordinate with attenuated phosphorylation of the host actin regulator Focal Adhesion Kinase (FAK or PTK2) and marked increases in the numbers of focal adhesion structures. We further show that the intravesical delivery of resveratrol inhibits UPEC infiltration of the bladder mucosa in a murine UTI model and that resveratrol and CAPE can disrupt the ability of other invasive pathogens to enter host cells. Together, these results highlight the therapeutic potential of molecules like CAPE and resveratrol, which could be used to augment antibiotic treatments by restricting pathogen access to protective intracellular niches.IMPORTANCEUrinary tract infections (UTIs) are exceptionally common and increasingly difficult to treat due to the ongoing rise and spread of antibiotic-resistant pathogens. Furthermore, the primary cause of UTIs, uropathogenic Escherichia coli (UPEC), can avoid antibiotic exposure and many host defenses by invading the epithelial cells that line the bladder surface. Here, we identified two plant-derived phenolic compounds that disrupt activation of the host machinery needed for UPEC entry into bladder cells. One of these compounds, resveratrol, effectively inhibited UPEC invasion of the bladder mucosa in a mouse UTI model, and both phenolic compounds significantly reduced host cell entry by other invasive pathogens. These findings suggest that select phenolic compounds could be used to supplement existing antibacterial therapeutics by denying uropathogens shelter within host cells and tissues and help explain some of the benefits attributed to traditional plant-based medicines.


Asunto(s)
Adhesión Bacteriana , Catequina/análogos & derivados , Infecciones por Escherichia coli , Fenoles , Alcohol Feniletílico/análogos & derivados , Infecciones Urinarias , Escherichia coli Uropatógena , Escherichia coli Uropatógena/efectos de los fármacos , Animales , Ratones , Infecciones por Escherichia coli/tratamiento farmacológico , Infecciones por Escherichia coli/microbiología , Infecciones Urinarias/microbiología , Infecciones Urinarias/tratamiento farmacológico , Fenoles/farmacología , Humanos , Adhesión Bacteriana/efectos de los fármacos , Resveratrol/farmacología , Células Epiteliales/microbiología , Células Epiteliales/efectos de los fármacos , Vejiga Urinaria/microbiología , Vejiga Urinaria/efectos de los fármacos , Vejiga Urinaria/patología , Extractos Vegetales/farmacología , Femenino , Quinasa 1 de Adhesión Focal/metabolismo , Quinasa 1 de Adhesión Focal/antagonistas & inhibidores , Línea Celular , Catequina/farmacología , Ácidos Cafeicos/farmacología
4.
Thorax ; 79(4): 363-365, 2024 Mar 15.
Artículo en Inglés | MEDLINE | ID: mdl-38307845

RESUMEN

Remote Vision-Based digital Patient Monitoring (VBPM) of pulse (PR) and respiratory rate (RR) was set up in six single rooms in an acute medical and an orthopaedic ward. We compared 102 PR and 154 RR VBPM measurements (from 27 patients) with paired routine nurse measurements. VBPM measurements of RR were validated by reviewing video footage. Nurse measurements of RR were often 16-18 breaths/minute, and did not match VBPM RR (overestimating at low RR and underestimating at high RR). Nurse measurements of pulse were on average 3.9 beats per minute greater than matched VBPM measurements. VBPM was unobtrusive and well accepted.


Asunto(s)
Frecuencia Respiratoria , Humanos , Monitoreo Fisiológico , Frecuencia Cardíaca
5.
bioRxiv ; 2023 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-38045282

RESUMEN

Traditional folk treatments for the prevention and management of urinary tract infections (UTIs) and other infectious diseases often include plants and plant extracts that are rich in phenolic and polyphenolic compounds. These have been ascribed a variety of activities, including inhibition of bacterial interactions with host cells. Here we tested a panel of four well-studied phenolic compounds - caffeic acid phenethyl ester (CAPE), resveratrol, catechin, and epigallocatechin gallate - for effects on host cell adherence and invasion by uropathogenic Escherichia coli (UPEC). These bacteria, which are the leading cause of UTIs, can bind and subsequently invade bladder epithelial cells via an actin-dependent process. Intracellular UPEC reservoirs within the bladder are often protected from antibiotics and host defenses, and likely contribute to the development of chronic and recurrent infections. Using cell culture-based assays, we found that only resveratrol had a notable negative effect on UPEC adherence to bladder cells. However, both CAPE and resveratrol significantly inhibited UPEC entry into the host cells, coordinate with attenuated phosphorylation of the host actin regulator Focal Adhesion Kinase (FAK, or PTK2) and marked increases in the numbers of focal adhesion structures. We further show that the intravesical delivery of resveratrol inhibits UPEC infiltration of the bladder mucosa in a murine UTI model, and that resveratrol and CAPE can disrupt the ability of other invasive pathogens to enter host cells. Together, these results highlight the therapeutic potential of molecules like CAPE and resveratrol, which could be used to augment antibiotic treatments by restricting pathogen access to protective intracellular niches.

6.
Bioinformatics ; 39(11)2023 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-37930895

RESUMEN

MOTIVATION: Phecodes are widely used and easily adapted phenotypes based on International Classification of Diseases codes. The current version of phecodes (v1.2) was designed primarily to study common/complex diseases diagnosed in adults; however, there are numerous limitations in the codes and their structure. RESULTS: Here, we present phecodeX, an expanded version of phecodes with a revised structure and 1,761 new codes. PhecodeX adds granularity to phenotypes in key disease domains that are under-represented in the current phecode structure-including infectious disease, pregnancy, congenital anomalies, and neonatology-and is a more robust representation of the medical phenome for global use in discovery research. AVAILABILITY AND IMPLEMENTATION: phecodeX is available at https://github.com/PheWAS/phecodeX.


Asunto(s)
Estudio de Asociación del Genoma Completo , Fenómica , Polimorfismo de Nucleótido Simple , Fenotipo
7.
Am J Hum Genet ; 110(9): 1522-1533, 2023 09 07.
Artículo en Inglés | MEDLINE | ID: mdl-37607538

RESUMEN

Population-scale biobanks linked to electronic health record data provide vast opportunities to extend our knowledge of human genetics and discover new phenotype-genotype associations. Given their dense phenotype data, biobanks can also facilitate replication studies on a phenome-wide scale. Here, we introduce the phenotype-genotype reference map (PGRM), a set of 5,879 genetic associations from 523 GWAS publications that can be used for high-throughput replication experiments. PGRM phenotypes are standardized as phecodes, ensuring interoperability between biobanks. We applied the PGRM to five ancestry-specific cohorts from four independent biobanks and found evidence of robust replications across a wide array of phenotypes. We show how the PGRM can be used to detect data corruption and to empirically assess parameters for phenome-wide studies. Finally, we use the PGRM to explore factors associated with replicability of GWAS results.


Asunto(s)
Bancos de Muestras Biológicas , Ciencia de los Datos , Humanos , Fenómica , Fenotipo , Genotipo
8.
J Am Med Inform Assoc ; 30(7): 1257-1265, 2023 06 20.
Artículo en Inglés | MEDLINE | ID: mdl-37164621

RESUMEN

OBJECTIVE: Knowledgebases are needed to clarify correlations observed in real-world electronic health record (EHR) data. We posit design principles, present a unifying framework, and report a test of concept. MATERIALS AND METHODS: We structured a knowledge framework along 3 axes: condition of interest, knowledge source, and taxonomy. In our test of concept, we used hypertension as our condition of interest, literature and VanderbiltDDx knowledgebase as sources, and phecodes as our taxonomy. In a cohort of 832 566 deidentified EHRs, we modeled blood pressure and heart rate by sex and age, classified individuals by hypertensive status, and ran a Phenome-wide Association Study (PheWAS) for hypertension. We compared the correlations from PheWAS to the associations in our knowledgebase. RESULTS: We produced PhecodeKbHtn: a knowledgebase comprising 167 hypertension-associated diseases, 15 of which were also negatively associated with blood pressure (pos+neg). Our hypertension PheWAS included 1914 phecodes, 129 of which were in the PhecodeKbHtn. Among the PheWAS association results, phecodes that were in PhecodeKbHtn had larger effect sizes compared with those phecodes not in the knowledgebase. DISCUSSION: Each source contributed unique and additive associations. Models of blood pressure and heart rate by age and sex were consistent with prior cohort studies. All but 4 PheWAS positive and negative correlations for phecodes in PhecodeKbHtn may be explained by knowledgebase associations, hypertensive cardiac complications, or causes of hypertension independently associated with hypotension. CONCLUSION: It is feasible to assemble a knowledgebase that is compatible with EHR data to aid interpretation of clinical correlation research.


Asunto(s)
Estudio de Asociación del Genoma Completo , Hipertensión , Humanos , Fenotipo , Estudios de Cohortes , Presión Sanguínea , Polimorfismo de Nucleótido Simple
9.
Sci Total Environ ; 892: 164485, 2023 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-37257593

RESUMEN

Warming could facilitate the intensification of toxic algal blooms, two important stressors for marine organisms that are predicted to co-occur more frequently in the future. We investigated the immediate and delayed effects of a heatwave and a simulated bloom (3 × 106 cells L-1) of the diarrhetic shellfish toxin (DST)-producing benthic dinoflagellate Prorocentrum lima on the survival, physiology (oxygen consumption rate, condition index, immune parameters), and toxin accumulation in the Pacific rock oyster Magallana (Crassostrea) gigas. Oysters exposed to both stressors contained higher mean DST concentrations (mean ± 1 SE: 173.3 ± 19.78 µg kg-1 soft tissue) than those exposed to P. lima bloom alone (120.4 ± 20.90 µg kg-1) and exceeded the maximum permitted levels for human consumption. Exposure to individual stressors and their combination modified the physiology of M. gigas. Oysters exposed to heatwave alone had significantly higher oxygen consumption rates (0.7 ± 0.06 mg O2 h-1 g-1) than the control (0.3 ± 0.06 mg O2 h-1 g-1). However, this was not observed in oysters exposed to both heatwave and P. lima (0.5 ± 0.06 mg O2 h-1 g-1). This alteration of the metabolic response to warming in the presence of P. lima may affect the ability of rock oysters to adapt to environmental stressors (i.e., a heatwave) to ensure survival. Immunomodulation, through changes in total hemocyte count, was observed in oysters exposed to P. lima alone and in combination with warming. Individual stressors and their combination did not influence the condition index, but one mortality was recorded in oysters exposed to both stressors. The findings of this study highlight the vulnerability of rock oysters to the predicted increased frequency of heatwaves and toxic algal blooms, and the increased likelihood of shellfish containing higher than regulatory levels of DST in warming coasts.


Asunto(s)
Dinoflagelados , Eutrofización , Calor Extremo , Venenos de Moluscos , Ostreidae , Agua de Mar , Calor Extremo/efectos adversos , Ostreidae/metabolismo , Ostreidae/fisiología , Hemocitos/citología , Venenos de Moluscos/análisis , Venenos de Moluscos/metabolismo , Agua de Mar/química , Océanos y Mares , Intoxicación por Mariscos , Calentamiento Global , Humanos , Animales , Dinoflagelados/crecimiento & desarrollo , Dinoflagelados/metabolismo , Acuicultura
10.
Front Genet ; 14: 1094908, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37124606

RESUMEN

Background: The recent integration of genomic data with electronic health records has enabled large scale genomic studies on a variety of perioperative complications, yet genome-wide association studies on acute kidney injury have been limited in size or confounded by composite outcomes. Genome-wide association studies can be leveraged to create a polygenic risk score which can then be integrated with traditional clinical risk factors to better predict postoperative complications, like acute kidney injury. Methods: Using integrated genetic data from two academic biorepositories, we conduct a genome-wide association study on cardiac surgery-associated acute kidney injury. Next, we develop a polygenic risk score and test the predictive utility within regressions controlling for age, gender, principal components, preoperative serum creatinine, and a range of patient, clinical, and procedural risk factors. Finally, we estimate additive variant heritability using genetic mixed models. Results: Among 1,014 qualifying procedures at Vanderbilt University Medical Center and 478 at Michigan Medicine, 348 (34.3%) and 121 (25.3%) developed AKI, respectively. No variants exceeded genome-wide significance (p < 5 × 10-8) threshold, however, six previously unreported variants exceeded the suggestive threshold (p < 1 × 10-6). Notable variants detected include: 1) rs74637005, located in the exonic region of NFU1 and 2) rs17438465, located between EVX1 and HIBADH. We failed to replicate variants from prior unbiased studies of post-surgical acute kidney injury. Polygenic risk was not significantly associated with post-surgical acute kidney injury in any of the models, however, case duration (aOR = 1.002, 95% CI 1.000-1.003, p = 0.013), diabetes mellitus (aOR = 2.025, 95% CI 1.320-3.103, p = 0.001), and valvular disease (aOR = 0.558, 95% CI 0.372-0.835, p = 0.005) were significant in the full model. Conclusion: Polygenic risk score was not significantly associated with cardiac surgery-associated acute kidney injury and acute kidney injury may have a low heritability in this population. These results suggest that susceptibility is only minimally influenced by baseline genetic predisposition and that clinical risk factors, some of which are modifiable, may play a more influential role in predicting this complication. The overall impact of genetics in overall risk for cardiac surgery-associated acute kidney injury may be small compared to clinical risk factors.

11.
Eur Respir J ; 61(6)2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37024133

RESUMEN

BACKGROUND: Dysfunctional breathing is common among people with and without primary respiratory pathology. While anxiety can contribute to dysfunctional breathing, the underpinning mechanism is unclear. One explanation is that anxiety induces conscious, vigilant monitoring of breathing, disrupting "automatic" breathing mechanics. We validated a new tool that quantifies such breathing-related "vigilance": the Breathing Vigilance Questionnaire (Breathe-VQ). METHODS: 323 healthy adults (mean (range) age 27.3 (18-71) years; 161 males) were analysed. We developed an initial Breathe-VQ (11 items, 1-5 Likert scale) based on the Pain Vigilance and Awareness Scale, using feedback from the target population and clinicians. At baseline, participants completed the Breathe-VQ, Nijmegen Questionnaire (NQ), State-Trait Anxiety Inventory form 2 and Movement-Specific Reinvestment Scale (assessing general conscious processing). 83 people repeated the Breathe-VQ 3 weeks later. RESULTS: Five items were removed based on item-level analysis. The resulting six-item Breathe-VQ questionnaire (score range 6-30) has excellent internal (α=0.892) and test-retest reliability (intraclass correlation 0.810), a minimal detectable change of 6.5 and no floor/ceiling effects. Validity was evidenced by significant positive correlations with trait anxiety and conscious processing scores (r=0.35-0.46). Participants at high risk of having dysfunctional breathing (NQ >23; n=76) had significantly higher Breathe-VQ score (mean±sd 19.1±5.0) than low-risk peers (n=225; mean±sd 13.8±5.4; p<0.001). In this "high risk of dysfunctional breathing" group, Breathe-VQ and NQ scores were significantly associated (p=0.005), even when controlling for risk factors (e.g. trait anxiety). CONCLUSIONS: The Breathe-VQ is a valid and reliable tool to measure breathing vigilance. High breathing vigilance may contribute to dysfunctional breathing and could represent a therapeutic target. Further research is warranted to test Breathe-VQ's prognostic value and assess intervention effects.


Asunto(s)
Ansiedad , Respiración , Masculino , Adulto , Humanos , Reproducibilidad de los Resultados , Encuestas y Cuestionarios , Ansiedad/epidemiología , Factores de Riesgo , Psicometría
12.
J Clin Transl Sci ; 7(1): e29, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36845316

RESUMEN

Background: Many clinical trials leverage real-world data. Typically, these data are manually abstracted from electronic health records (EHRs) and entered into electronic case report forms (CRFs), a time and labor-intensive process that is also error-prone and may miss information. Automated transfer of data from EHRs to eCRFs has the potential to reduce data abstraction and entry burden as well as improve data quality and safety. Methods: We conducted a test of automated EHR-to-CRF data transfer for 40 participants in a clinical trial of hospitalized COVID-19 patients. We determined which coordinator-entered data could be automated from the EHR (coverage), and the frequency with which the values from the automated EHR feed and values entered by study personnel for the actual study matched exactly (concordance). Results: The automated EHR feed populated 10,081/11,952 (84%) coordinator-completed values. For fields where both the automation and study personnel provided data, the values matched exactly 89% of the time. Highest concordance was for daily lab results (94%), which also required the most personnel resources (30 minutes per participant). In a detailed analysis of 196 instances where personnel and automation entered values differed, both a study coordinator and a data analyst agreed that 152 (78%) instances were a result of data entry error. Conclusions: An automated EHR feed has the potential to significantly decrease study personnel effort while improving the accuracy of CRF data.

13.
Eur Respir J ; 61(4)2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36796833

RESUMEN

BACKGROUND: Lung volume reduction surgery (LVRS) and bronchoscopic lung volume reduction (BLVR) with endobronchial valves can improve outcomes in appropriately selected patients with emphysema. However, no direct comparison data exist to inform clinical decision making in people who appear suitable for both procedures. Our aim was to investigate whether LVRS produces superior health outcomes when compared with BLVR at 12 months. METHODS: This multicentre, single-blind, parallel-group trial randomised patients from five UK hospitals, who were suitable for a targeted lung volume reduction procedure, to either LVRS or BLVR and compared outcomes at 1 year using the i-BODE score. This composite disease severity measure includes body mass index, airflow obstruction, dyspnoea and exercise capacity (incremental shuttle walk test). The researchers responsible for collecting outcomes were masked to treatment allocation. All outcomes were assessed in the intention-to-treat population. RESULTS: 88 participants (48% female, mean±sd age 64.6±7.7 years, forced expiratory volume in 1 s percent predicted 31.0±7.9%) were recruited at five specialist centres across the UK and randomised to either LVRS (n=41) or BLVR (n=47). At 12 months follow-up, the complete i-BODE was available in 49 participants (21 LVRS/28 BLVR). Neither improvement in the i-BODE score (LVRS -1.10±1.44 versus BLVR -0.82±1.61; p=0.54) nor in its individual components differed between groups. Both treatments produced similar improvements in gas trapping (residual volume percent predicted: LVRS -36.1% (95% CI -54.6- -10%) versus BLVR -30.1% (95% CI -53.7- -9%); p=0.81). There was one death in each treatment arm. CONCLUSION: Our findings do not support the hypothesis that LVRS is a substantially superior treatment to BLVR in individuals who are suitable for both treatments.


Asunto(s)
Neumonectomía , Enfisema Pulmonar , Humanos , Femenino , Persona de Mediana Edad , Anciano , Masculino , Neumonectomía/métodos , Método Simple Ciego , Pulmón/cirugía , Enfisema Pulmonar/cirugía , Volumen Espiratorio Forzado , Resultado del Tratamiento , Broncoscopía/métodos
14.
Clin Gerontol ; : 1-8, 2023 Feb 02.
Artículo en Inglés | MEDLINE | ID: mdl-36732327

RESUMEN

OBJECTIVES: Few studies of exposure therapy with adults 85 years and older exist. This case report presents results of prolonged exposure (PE) for posttraumatic stress disorder (PTSD) modified for an 85-year-old Native American Cajun man with late-onset deafness, who used a cochlear implant, and reported high Western/non-Native American acculturation. The following modifications were made primarily in response to the client's individual, disability-related barriers to completing the standard PE protocol: (a) inclusion of the client's spouse in aspects of treatment planning and homework assignments; (b) variable session length and frequency; (c) homework was limited to the daily practice of breathing retraining and in vivo exposure to triggering images; and (d) therapist reliance on nonverbal indicators of distress during imaginal exposures. METHODS: The PTSD Checklist for DSM-5 (PCL-5) and 15-item Geriatric Depression Scale (GSD-15) were primary progress and outcome measures. RESULTS: The modified treatment was associated with clinically significant decreases in baseline PTSD (19 points) and depressive (8 points) symptoms. CONCLUSIONS: PE protocol modifications did not compromise treatment outcomes for this client. CLINICAL IMPLICATIONS: PE protocols should be modified based on the individual needs of diverse older adults underrepresented in efficacy research.

15.
BMJ Open Respir Res ; 10(1)2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36627142

RESUMEN

OBJECTIVES: To explore physiotherapists' opinions of physiotherapy assessment of Breathing Pattern Disorder (BPD). METHODS: Qualitative study using focus groups (FGs) with reflexive thematic analysis and survey methods. The survey was distributed via social media and email to UK specialist physiotherapy interest groups. Two FGs, conducted in different settings, included physiotherapists based in hospital outpatients/community, private practice and higher education. RESULTS: One-hundred-and-three physiotherapists completed the survey. Respondents identified a lack of consensus in how to define BPD, but some agreement in the components to include in assessment. Fifteen physiotherapists participated in the FGs. Three themes emerged from FG discussions: (1) nomenclature and language of breathing, (2) BPD and breathlessness and (3) The value of assessment of breathlessness. CONCLUSION: The inconsistent nomenclature of dysfunctional breathing pattern impacts assessment, management and understanding of the diagnosis. Clarity in diagnosis, informing consistency in assessment, is fundamental to improving recognition and treatment of BPD. The findings are useful in the planning of education, training, future research and guideline development in BPD assessment.


Asunto(s)
Actitud del Personal de Salud , Trastornos Respiratorios , Humanos , Investigación Cualitativa , Modalidades de Fisioterapia , Disnea , Respiración
16.
J Chem Theory Comput ; 19(1): 25-32, 2023 Jan 10.
Artículo en Inglés | MEDLINE | ID: mdl-36508260

RESUMEN

We demonstrate the use of Googles cloud-based Tensor Processing Units (TPUs) to accelerate and scale up conventional (cubic-scaling) density functional theory (DFT) calculations. Utilizing 512 TPU cores, we accomplish the largest such DFT computation to date, with 247848 orbitals, corresponding to a cluster of 10327 water molecules with 103270 electrons, all treated explicitly. Our work thus paves the way toward accessible and systematic use of conventional DFT, free of any system-specific constraints, at unprecedented scales.

18.
Toxins (Basel) ; 14(11)2022 11 18.
Artículo en Inglés | MEDLINE | ID: mdl-36422978

RESUMEN

Cyanobacterial blooms are often associated with the presence of harmful natural compounds which can cause adverse health effects in both humans and animals. One family of these compounds, known as anatoxins, have been linked to the rapid deaths of cattle and dogs through neurotoxicological action. Here, we report the findings resulting from the death of a dog at a freshwater reservoir in SW England. Poisoning was rapid following exposure to material at the side of the lake. Clinical signs included neurological distress, diaphragmatic paralysis and asphyxia prior to death after 45 min of exposure. Analysis by HILIC-MS/MS of urine and stomach content samples from the dog revealed the detection of anatoxin-a and dihydroanatoxin-a in both samples with higher concentrations of the latter quantified in both matrices. Detection and quantitative accuracy was further confirmed with use of accurate mass LC-HRMS. Additional anatoxin analogues were also detected by LC-HRMS, including 4-keto anatoxin-a, 4-keto-homo anatoxin-a, expoxy anatoxin-a and epoxy homo anatoxin-a. The conclusion of neurotoxicosis was confirmed with the use of two independent analytical methods showing positive detection and significantly high quantified concentrations of these neurotoxins in clinical samples. Together with the clinical signs observed, we have confirmed that anatoxins were responsible for the rapid death of the dog in this case.


Asunto(s)
Toxinas Bacterianas , Síndromes de Neurotoxicidad , Humanos , Perros , Animales , Bovinos , Toxinas Marinas/análisis , Espectrometría de Masas en Tándem , Toxinas Bacterianas/química , Toxinas de Cianobacterias , Lagos/análisis
20.
Mar Drugs ; 20(10)2022 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-36286458

RESUMEN

Harmful algal blooms are an increasing worldwide threat to the seafood industry and human health as a consequence of the natural production of biotoxins that can accumulate in shellfish. In the Argentine Sea, this has been identified as an issue for the offshore fisheries of Patagonian scallops (Zygochlamys patagonica), leading to potentially harmful effects on consumers. Here we assess spatial and temporal patterns in marine biotoxin concentrations in Patagonian scallops harvested in Argentinian waters between 2012-2017, based on analyses for paralytic shellfish toxins, lipophilic toxins, and amnesic shellfish toxins. There was no evidence for concentrations of lipophilic or amnesic toxins above regulatory acceptance thresholds, with trace concentrations of pectenotoxin 2, azaspiracid 2 and okadaic acid group toxins confirmed. Conversely, paralytic shellfish toxins were quantified in some scallops. Gonyautoxins 1 and 2 dominated the unusual toxin profiles (91%) in terms of saxitoxin equivalents with maximum concentrations reaching 3985 µg STX eq/kg and with changes in profiles linked in part to seasonal changes. Total toxin concentrations were compared between samples of the adductor muscle and whole tissue, with results showing the absence of toxins in the adductor muscle confirming toxin accumulation in the digestive tracts of the scallops and the absence of a human health threat following the processing of scallop adductor meat. These findings highlight that paralytic shellfish toxins with an unusual toxin profile can occur in relatively high concentrations in whole Patagonian scallops in specific regions and during particular time periods, also showing that the processing of scallops on board factory ships to obtain frozen adductor muscle is an effective management process that minimizes the risk of poisonings from final products destined for human consumption.


Asunto(s)
Toxinas Marinas , Pectinidae , Animales , Humanos , Toxinas Marinas/análisis , Ácido Ocadaico/análisis , Saxitoxina/análisis , Alimentos Marinos/análisis
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