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Reducing greenhouse gas (GHG) emissions in crop production while ensuring emission equity is crucial for sustainable agriculture in China, yet long-term large-scale data on GHG emissions intensity (GEI) are limited. Using an extensive dataset based on surveyed farm households (n > 430,000 households) from 1993 to 2020, we reveal that 2015 was a turning point for GEI levels, which dropped 16% in 2020, while inequality-measured as average GHG emissions per unit planted area-increased 13%. The key driving forces behind such trends included farmland input, all other inputs, agricultural labour input and total factor productivity but not capital input. Notably, farmland input and all other inputs contributed to 80% of the inequality, while contribution of total factor productivity gradually declined and was replaced by migration-induced agricultural labour input differences. Reducing GEI levels and guarding against widening inequality require optimizing production factor inputs.
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(1) Background: Wearable sensors support healthcare professionals in clinical decision-making by measuring vital parameters such as heart rate (HR), respiration rate (RR), and blood oxygenation saturation (SpO2). This study assessed the validity and reliability of two types of wearable sensors, based on electrocardiogram or photoplethysmography, compared with continuous monitoring of patients recovering from trauma surgery at the postanesthesia care unit. (2) Methods: In a prospective observational study, HR, RR, SpO2, and temperature of patients were simultaneously recorded with the VitalPatch and Radius PPG and compared with reference monitoring. Outcome measures were formulated as correlation coefficient for validity and mean difference with 95% limits of agreement for reliability for four random data pairs and 30-min pairs per vital sign per patient. (3) Results: Included were 60 patients. Correlation coefficients for VitalPatch were 0.57 to 0.85 for HR and 0.08 to 0.16 for RR, and for Radius PPG, correlation coefficients were 0.60 to 0.83 for HR, 0.20 to 0.12 for RR, and 0.57 to 0.61 for SpO2. Both sensors presented mean differences within the cutoff values of acceptable difference. (4) Conclusions: Moderate to strong correlations for HR and SpO2 were demonstrated. Although mean differences were within acceptable cutoff values for all vital signs, only limits of agreement for HR measured by electrocardiography were considered clinically acceptable.
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Frecuencia Cardíaca , Signos Vitales , Dispositivos Electrónicos Vestibles , Humanos , Masculino , Femenino , Monitoreo Fisiológico/métodos , Monitoreo Fisiológico/instrumentación , Signos Vitales/fisiología , Persona de Mediana Edad , Frecuencia Cardíaca/fisiología , Adulto , Estudios Prospectivos , Fotopletismografía/métodos , Fotopletismografía/instrumentación , Frecuencia Respiratoria/fisiología , Electrocardiografía/métodos , Anciano , Heridas y Lesiones/cirugía , Reproducibilidad de los Resultados , Saturación de Oxígeno/fisiología , Periodo Posoperatorio , Cirugía de Cuidados IntensivosRESUMEN
Dermal substitutes have been introduced in burn care to improve wound healing outcomes; however, their use remains limited in standard treatments. This systematic review and meta-analysis aimed to evaluate the outcomes of dermal substitutes in patients with burns and patients requiring burn scar reconstruction and subsequently contribute to optimising the integration of dermal substitutes into clinical practice and reducing the knowledge gap. A comprehensive search across various databases included human studies from peer-reviewed journals on dermal substitutes for deep dermal and full-thickness burns, and scar reconstruction across all ages. Data from comparative trials were extracted, focusing on patient and wound characteristics, treatment specifics, and outcomes related to wound healing and scar quality. Meta-analysis was performed on trials reporting similar post-burn measures, with statistical heterogeneity assessed. Outcomes were presented using mean differences or odds ratios with 95% confidence intervals. A total of 31 comparative trials were included. The overall quality of the studies was considered moderate. The meta-analysis indicated delayed re-epithelialization 4-7 days after treatment with a collagen-elastin matrix compared to split-thickness skin graft in acute burns (-7.30%, p = 0.02). Significant improvement in subjective scar quality was observed with acellular dermal matrix compared to split-thickness skin graft in acute burn wounds 6 months post-operative (-1.95, p <0.01). While acknowledging the initially delayed wound healing, incorporating dermal substitutes into the surgical treatment of burn patients holds promise for enhancing scar quality. However, future research must prioritise outcome measure uniformity, address variations in dermal substitute application, and standardise indications for consistent and effective practices.
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BACKGROUND: Nutrition and nutritional care are essential for optimal outcomes, and, therefore of importance for patients with chronic limb threatening ischemia (CLTI) given their high risk of complications. However, insight is lacking in how healthcare professionals directly involved in the care of patients with CLTI perceive nutritional care, as well as in the perceived barriers and facilitators regarding optimal nutritional care. METHODS: In this qualitative study with a phenomenological approach, three online focus groups were conducted with various healthcare professionals directly involved in the care of patients with CLTI. Sample size was guided by information power. Focus group recordings were transcribed verbatim, and reflexive thematic analysis was performed. RESULTS: Seventeen healthcare professionals participated, including vascular surgeons, fellows in vascular surgery, a medical doctor and researcher, nurse specialized in wound care, general nurse, physical therapists, dietitians, and nutrition assistants. Four themes were generated: (1) nutritional care is crucial for optimal clinical outcomes and a healthy life, (2) insufficient attention to undernutrition and nutritional care by healthcare professionals, (3) patient-related factors challenge healthcare professionals in providing nutritional care, and (4) need for optimizing the organizational process related to nutritional care. Perceived barriers regarding nutritional care included knowledge deficits, nutritional care not being part of the healthcare professionals' routine, missing tools to identify undernutrition, patient-related factors, and time constraints. Facilitators regarding nutritional care included more scientific evidence regarding the effect of nutritional care on clinical outcomes and optimization of organizational processes related to nutritional care. CONCLUSION: Healthcare professionals perceive nutritional care as important for optimal outcomes, but nutritional care is not routinely implemented in the care of patients with CLTI. This lack of implementation of nutritional care may be due to the barriers perceived in various domains. The findings of this study stress the need to optimize nutritional care, with the aim of improving outcomes in the CLTI population.
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OBJECTIVE: To evaluate the feasibility of performing a full-scale, adequately powered, multi-center randomized controlled trial (RCT) assessing the effectiveness of office hysteroscopy (OH) for the treatment of retained pregnancy tissue (RPT) after miscarriage, compared with standard treatment (ST) (expectant/medical/surgical), on future pregnancy outcome. STUDY DESIGN: Single-center pilot RCT performed at Birmingham Women's Hospital, UK. Patients opting for non-surgical miscarriage management at ≤14 weeks gestation who wanted to conceive as soon as possible were recruited and offered a transvaginal ultrasound scan (TVUS) eight weeks later to check for the presence of RPT. Patients with RPT were randomized in a 1:1 ratio using a computer-generated online random allocation sequence to either OH (performed using the TruClear 5.0 hysteroscopic tissue retrieval system) or ST (the type of which was recommended based on symptoms, urinary pregnancy test and scan findings). RESULTS: 158 participants were approached for inclusion into the trial, of which 149 (94.3%) agreed. Of the 126 that underwent TVUS, RPT were diagnosed in 42 patients (33.3%). 21 patients were randomized to OH, of whom 18 underwent the procedure because three fell pregnant after their TVUS. OH was deemed acceptable to all patients without any serious complications. 21 patients were randomized to ST where 16 patients (76%) were recommended expectant management and five (24%) were recommended surgical management. 115 patients (91%) were able to provide pregnancy data, however, the study was not powered to show a clinically significant difference. CONCLUSION: A full-scale, adequately powered, randomized clinical trial investigating OH against ST for the treatment of RPT following miscarriage is clinically relevant and feasible owing to high rates of participation, acceptability and satisfaction and low rates of attrition associated with the proposed interventions.
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Aborto Espontáneo , Histeroscopía , Humanos , Femenino , Histeroscopía/métodos , Proyectos Piloto , Adulto , Embarazo , Aborto Espontáneo/terapia , Estudios de Factibilidad , Resultado del EmbarazoRESUMEN
OBJECTIVES: Early treatment of individuals at risk of developing rheumatoid arthritis (RA-risk) in the preclinical phase has the potential to positively impact both patients and society by preventing disease onset and improving patients' quality of life. The PRAIRI study was a randomised, double-blind, placebo-controlled trial with the B-cell depleting agent rituximab (RTX), which resulted in a significant delay of arthritis development of up to 12 months in seropositive RA-risk individuals. Here, we report our findings on patient-reported outcomes (PROs) in this study population. METHODS: Seventy-eight RA-risk individuals were treated with one single dose of either placebo (PBO) or 1000 mg RTX plus 100 mg methylprednisolone (MP) and anti-histamines, regardless of treatment allocation, as co-medication. Data on quality of life were collected at baseline and 1, 4, 6, 12 and 24 months using established PRO questionnaires (visual analogue scale (VAS) pain, health assessment questionnaire disability index (HAQ-DI) score, EuroQol five dimension (EQ-5D) and both physical and mental component score of the 36-item short-form heath survey (SF-36)). RESULTS: No significant changes in quality of life over a 2 year follow-up were observed in at-risk individuals treated with RTX compared to PBO given the PRO scores at 24 months (mean difference±SEM: HAQ score=0.07±0.16; EQ-5D=-0.02±0.05; VAS pain=11.11±7.40). Furthermore, no significant effect of treatment on perceived arthritis severity at the time of clinically manifest disease (arthritis) was found. CONCLUSION: One single dose of RTX plus MP administered to RA-risk individuals does not have a meaningful and measurable positive effect on PROs after 2 years of follow-up and/or perceived disease severity at the time of arthritis development. TRIAL REGISTRATION NUMBER: Trial registered at EU Clinical Trial Register, EudraCT Number: 2009-010955-29 (https://www.clinicaltrialsregister.eu/ctr-search/search?query=Prevention+of+RA+by+B+cell+directed+therapy).
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Antirreumáticos , Artritis Reumatoide , Medición de Resultados Informados por el Paciente , Calidad de Vida , Rituximab , Humanos , Artritis Reumatoide/tratamiento farmacológico , Rituximab/uso terapéutico , Rituximab/administración & dosificación , Masculino , Femenino , Persona de Mediana Edad , Antirreumáticos/uso terapéutico , Antirreumáticos/administración & dosificación , Método Doble Ciego , Resultado del Tratamiento , Adulto , Anciano , Metilprednisolona/administración & dosificación , Metilprednisolona/uso terapéuticoRESUMEN
BACKGROUND AND AIMS: Osteopontin (OPN) promotes the ductular reaction and is a major driver of chronic liver disease (CLD) progression. Although CLD is characterised by the accumulation of inflammatory cells including macrophages around the peri-portal regions, the influence of OPN on recruitment is unclear. We investigated the role of OPN in cholangiocyte chemokine production and macrophage recruitment by combining in vivo, in vitro, and in silico approaches. METHODS: The effects of OPN on cholangiocyte chemokine production and macrophage migration were assessed in culture, alongside RNA-sequencing to identify genes and pathways affected by OPN depletion. Murine liver injury models were used to assess liver chemokine expression and liver macrophage/monocyte recruitment. OPN and chemokine expression were analysed in liver tissue and plasma from biopsy-proven metabolic dysfunction-associated alcoholic steatohepatitis (MASH) patients. RESULTS: OPN-knockdown in cholangiocytes reduced chemokine secretion. RNA-sequencing showed OPN-related effects clustered around immunity, chemotaxis and chemokine production. Macrophage exposure to cholangiocyte-conditioned media showed OPN-supported migration via chemokines chemokine (C-C motif) ligand (CCL)2, CCL5 and chemokine (C-X-C motif) ligand (CXCL)1. These effects were related to NF-κB signalling. Murine liver fibrosis was accompanied by upregulated liver OPN, CCL2, CCL5 and CXCL1 mRNA, and accumulation of liver cluster of differentiation (CD)11b/F4/80+CC chemokine receptors (CCR2)high macrophages but treatment with OPN-specific neutralising aptamers reduced fibrosis, chemokine mRNAs and accumulation of liver CD11b/F4/80+CCR2high/lymphocyte antigen 6 complexhigh inflammatory monocytes. In human MASH, liver OPN correlated with chemokines CCL2 and IL8 in association with portal injury and fibrosis. Plasma OPN, serum CCL2 and IL8 also increased with fibrosis stage. CONCLUSIONS: OPN promotes cholangiocyte chemokine secretion and the accumulation of pro-inflammatory monocytes. These data support neutralisation of OPN as an anti-inflammatory and anti-fibrotic strategy.
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Autologous fat grafting (AFG), mostly in combination with adhesiolysis, has become the workhorse for reconstructing a dysfunctional or absent subcutaneous layer. In a previous study we showed that fat grafts isolated by centrifuging led to more than 20 % improvement in scar pliability. Nevertheless, there is still debate on which technique should be used to process and purify fat grafts. Therefore, a cohort with matured scars was obtained using the same study protocol but with filtration as processing technique. Scar quality was evaluated by the Patient and Observer Scar Assessment Scale (POSAS version 2.0), the Cutometer (pliability) and the DSM II ColorMeter (erythema and melanin). Scar evaluation was performed pre-operatively (baseline) and at 3 and 12 months after AFG. Between 2014 and 2018, 46 patients were included. Mean scar age was 20 ± 17 years and the majority of scars was caused by burns. Compared with baseline, patients showed improvement in scar quality measured by POSAS items at 12 months follow-up. The item score of 'pliability' improved the most from 7.4 to 5.8 (p = 0.001). Item scores of 'pain', 'itch' and 'color' also improved significantly. Clinicians also scored 'pliability' as most improved, but this was not statistically significant (p = 0.111). Objectively measured pliability and erythema and melanin showed no statistically significant differences at 12 months follow-up. Patient-reported outcomes revealed a significant improvement in scar quality, especially scar pliability, after AFG processed by filtration in patients with adherent scars. However, no scar quality improvement was found when assessed with objective tools.
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Objective: To determine the validity of telephone or video interviews, compared to face-to-face, for psychiatric diagnosis.Data Sources: We searched MEDLINE, Embase, and PsycINFO from inception to June 22, 2023, and performed backward and forward citation analysis on all included studies on August 3, 2023.Study Selection: We included primary studies comparing live telehealth (via telephone or videoconferencing) with face-to-face interviews using the same standardized diagnostic criteria for a mental health condition. Each patient had to undergo both modes of interviewing. Risk of bias was assessed using Quality Assessment of Diagnostic Accuracy Studies-2.Results: This review included 35 studies. Seven are clinical studies that compare telehealth with face-to-face consultations for initial psychiatric diagnosis; telehealth via video or telephone is a reliable alternative for some specific disorders or for use in some specific populations that were studied. The other 28 studies compared telehealth to face-to-face interviews for the use of mental health standardized diagnostic instruments for a broad range of conditions, including depression, bipolar disorder, posttraumatic stress disorder, social anxiety disorder, and autism spectrum disorder, demonstrating good agreement and reliability. Telehealth holds promise for psychiatric assessments, especially when in-person evaluations are not feasible.Conclusions: From the limited studies primarily conducted before the expansion of telehealth during the COVID-19 pandemic, several small studies suggest that telehealth's psychiatric diagnoses or assessments of various psychiatric conditions seem to be a viable option and should be considered for certain patients during situations, settings, or environments. More research is needed, as telehealth has become more broadly utilized.
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Trastornos Mentales , Telemedicina , Comunicación por Videoconferencia , Humanos , Trastornos Mentales/diagnóstico , Teléfono , Entrevista Psicológica/métodos , Entrevista Psicológica/normasRESUMEN
Necrotizing soft tissue infection (NSTI) is a life-threatening illness that can seriously harm a person. Over the last years the incidence of NSTI has increased. A rapid and thorough debridement is crucial to let patients survive. After this debridement, patients will often end up with large skin defects. A burn center is specialized in treating skin defects. Patients with large skin defects after the acute phase of NSTI can be referred to this for a multidisciplinary approach. In this article we describe the surgical treatment of the complex wounds of three referred patients with NSTI in our burn center.
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Desbridamiento , Infecciones de los Tejidos Blandos , Humanos , Infecciones de los Tejidos Blandos/terapia , Masculino , Resultado del Tratamiento , Necrosis , Persona de Mediana Edad , Fascitis Necrotizante/terapia , Fascitis Necrotizante/cirugía , Femenino , Adulto , Cicatrización de HeridasRESUMEN
BACKGROUND: Little is known about how COVID-19 impacted acute surgical activity for children and young people (CYP) across England. Appendicitis and testicular torsion are common surgical conditions where treatment delays can lead to avoidable complications. We undertook a retrospective national cohort study. PRIMARY AIM: To describe monthly acute surgical activity in CYP during the COVID-19 pandemic. Secondary aim: To investigate evidence of delayed diagnosis and adverse outcomes, describing variations by age and socioeconomic deprivation. METHODS: Acute hospital admissions with appendicitis or testicular pain for those under 18 were extracted using Hospital Episode Statistics. Interrupted time series modelling, Mann-Whitney and Pearson's Chi-Squared tests compared the first 14 pandemic months with the previous five years. Results were stratified by age (0-4s, 5-9s and 10-17s) and appendicitis type (all, simple and complex). RESULTS: Admissions for appendicitis and testicular torsion fell significantly early in the COVID-19 pandemic. The proportion of children with complex appendicitis also increased during this time. Orchidectomy rates rose in April 2020 for the 0-4s (+15.6% (95% CI 7.9-23.3)) and 10-17s (+11.5% (4.9-18.2)), but when the pre-pandemic period was compared with the pandemic period as a whole, there were no overall statistically significant differences in orchidectomy rates between the study periods. Overall, there was a statistically significant rise in the orchidopexy rate during the pandemic period for the 10-17s when compared with the pre-pandemic period (Pre-pandemic: 17.0% vs Pandemic: 20.9%, p < 0.0001). CONCLUSION: A consistent reduction in activity, with short-lived periods of delayed presentations during COVID-19 pandemic peaks, occurred without persisting overall increased complication rates. These results provide useful national context for smaller sized studies that reported complications due to delays in surgery. Future research could examine how reduced activity impacted other healthcare settings and treatment pathways. LEVEL OF EVIDENCE: II.
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Autism Spectrum Disorder (ASD) is a neurological illness that degrades communication and interaction among others. Autism can be detected at any stage. Early detection of ASD is important in preventing the communication, interaction and behavioral outcomes of individuals. Hence, this research introduced the Fractional Whale-driving Driving Training-based Based Optimization with Convolutional Neural Network-based Transfer learning (FWDTBO-CNN_TL) for identifying ASD. Here, the FWDTBO is modelled by the incorporation of Fractional calculus (FC), Whale optimization algorithm (WOA) and Driving Training-based Optimization (DTBO) that trains the hyperparameters of CNN-TL. Moreover, the Convolutional Neural Networks (CNN) utilize the hyperparameters from trained models, like Alex Net and Shuffle Net in such a way that the CNN-TL is designed. To improve the detection efficiency, the nub region was extracted and carried out with the functional connectivity-based Whale Driving Training Optimization (WDTBO) algorithm. Moreover, the TL is tuned by the FWDTBO algorithm. The result reveals that the ASD detection technique, FWDTBO-CNN-TL acquired 90.7â¯% accuracy, 95.4â¯% sensitivity, 93.7â¯% specificity and 93â¯% f-measure with the ABIDE-II dataset.
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Drained wetlands are thought to be carbon (C) source hotspots, and rewetting is advocated to restore C storage in drained wetlands for climate change mitigation. However, current assessments of wetland C balance mainly focus on vertical fluxes between the land and atmosphere, frequently neglecting lateral carbon fluxes and land-use effects. Here, we conduct a global synthesis of 893 annual net ecosystem C balance (NECB) measures that include net ecosystem exchange of CO2, along with C input via manure fertilization, and C removal through biomass harvest or hydrological exports of dissolved organic and inorganic carbon, across wetlands of different status and land uses. We find that elevating water table substantially reduces net ecosystem C losses, with the annual NECB decreasing from 2579 (95% interval: 1976 to 3214) kg C ha-1 year-1 in drained wetlands to -422 (-658 to -176) kg C ha-1 year-1 in natural wetlands, and to -934 (-1532 to -399) kg C ha-1 year-1 in rewetted wetlands globally. Climate, land-use history, and time since water table changes introduce variabilities, with drainage for (sub)tropical agriculture or forestry uses showing high annual C losses, while the net C losses from drained wetlands can continue to affect soil C pools for several decades. Rewetting all types of drained wetlands is needed, particularly for those formerly agriculture-used (sub)tropical wetlands where net ecosystem C losses can be largely reduced. Our findings suggest that elevating water table is an important initiative to reduce C losses in degraded wetlands, which could contribute to policy decisions for managing wetlands to enhance their C sequestration.
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Ciclo del Carbono , Cambio Climático , Humedales , Carbono/análisis , Carbono/metabolismo , Agua Subterránea/química , Agua Subterránea/análisis , Agricultura/métodos , Biomasa , Ecosistema , Secuestro de CarbonoRESUMEN
OBJECTIVE: Penthrox® (methoxyflurane) is a convenient, portable, self-administered disposable single-use handheld inhaler licenced as an emergency, rapid-onset, short-acting, analgesic in adult trauma patients. Outpatient hysteroscopy is one of the commonest procedures in contemporary gynecology but it can be associated with significant pain leading to poor patient experience and failed procedures. We evaluated the feasibility and acceptability of Penthrox® in women undergoing outpatient hysteroscopic procedures and its potential efficacy to reduce pain and improve patient experience. STUDY DESIGN: We conducted a prospective observational cohort study on women undergoing hysteroscopy or other intrauterine procedures, such as coil fitting, endometrial biopsy, polypectomy, endometrial ablation and manual vacuum aspiration in an outpatient setting. Women were offered Penthrox® inhalers for pain control, instructed how to use it and asked to record the intra-procedural pain they expected and actually experienced using a 10â¯cm Visual Analogue Scale. The acceptability, side effects and ease of use of the Penthrox® device were also recorded. RESULTS: 122/146 (83.6â¯%) women chose to use Penthrox®. 116 out of the 122 (95.1â¯%) underwent an intrauterine procedure, including 59 hysteroscopic polypectomies and 34 global endometrial ablations. The average pain expected during the procedure was 6.0 (SDâ¯=â¯2.8) and the pain experienced during the procedure was 5.1 (SDâ¯=â¯2.8). The intended procedure was completed in 117 (96â¯%) women. Penthrox® was considered easy to use by 118 (97â¯%) women and 111 (91â¯%) would use it again, although 22 (18â¯%) women would prefer general anaesthesia in the future. No adverse events occurred but 88 (72â¯%) women reported mild, self-limiting side effects. CONCLUSION: Penthrox® appears safe, feasible and acceptable as a pain relief option during outpatient hysteroscopy and other intrauterine procedures. The effectiveness of Penthrox® should be evaluated against conventional pain control in an adequately powered multicentre randomised controlled trial.
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Histeroscopía , Metoxiflurano , Humanos , Femenino , Histeroscopía/métodos , Adulto , Persona de Mediana Edad , Estudios Prospectivos , Metoxiflurano/administración & dosificación , Metoxiflurano/uso terapéutico , Administración por Inhalación , Anestésicos por Inhalación/administración & dosificación , Procedimientos Quirúrgicos Ambulatorios/métodos , Manejo del Dolor/métodos , Dolor Asociado a Procedimientos Médicos/prevención & control , Dolor Asociado a Procedimientos Médicos/etiología , Dimensión del Dolor , AncianoRESUMEN
BACKGROUND: Intralesional corticosteroid administration (ICA) is a first-line keloid treatment. However, it faces significant variability in current clinical and scientific practice, which hinders comparability of treatment results. OBJECTIVES: The aim of the study was to reach consensus on different aspects of ICA using hypodermic needles in keloids among an international group of dermatologists and plastic surgeons specialized in keloid treatment to provide consensus-based clinical treatment recommendations for all physicians treating keloids. METHODS: The keloid expert panel of 12 dermatologists and 11 plastic surgeons rated 30 statements. Two online e-Delphi rounds were held, both with a response rate of 100%. Fifteen (65%) keloid experts participated in the final consensus meetings. Consensus was defined as ≥ 75% of the participants choosing agree or strongly agree on a 7-point Likert scale. RESULTS: Consensus was reached on treatment goals, indication for ICA, triamcinolone acetonide (TAC) 40 mg/mL as the preferred corticosteroid administered at a maximum of 80 mg per month and at intervals of 4 weeks, minimizing pain during ICA, the use of 1 mL syringes and 25 or 27 Gauge needles, blanching as endpoint of successful infiltration, caution of not injecting subcutaneously, and the option of making multiple passes in very firm keloids prior to infiltration. Consensus could not be reached on TAC dosing, methods of prior local anesthesia, and location of injection. CONCLUSIONS: This e-Delphi study provides important clinical treatment recommendations on essential aspects of ICA in keloids. By implementing these recommendations, uniformity of ICA in keloid treatment will increase and better treatment results may be achieved.
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Consenso , Técnica Delphi , Glucocorticoides , Inyecciones Intralesiones , Queloide , Triamcinolona Acetonida , Humanos , Queloide/tratamiento farmacológico , Triamcinolona Acetonida/administración & dosificación , Glucocorticoides/administración & dosificación , Resultado del Tratamiento , Dermatólogos , Cirugía Plástica/normas , Agujas , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéuticoRESUMEN
Ubiquitin signaling controls many aspects of eukaryotic biology, including targeted protein degradation and immune defense. Remarkably, invading bacterial pathogens have adapted secreted effector proteins that hijack host ubiquitination to gain control over host responses. These ubiquitin-targeted effectors can exhibit, for example, E3 ligase or deubiquitinase activities, often without any sequence or structural homology to eukaryotic ubiquitin regulators. Such convergence in function poses a challenge to the discovery of additional bacterial virulence factors that target ubiquitin. To overcome this, we have developed a workflow to harvest natively secreted bacterial effectors and functionally screen them for ubiquitin regulatory activities. After benchmarking this approach on diverse ligase and deubiquitinase activities from Salmonella Typhimurium, Enteropathogenic Escherichia coli, and Shigella flexneri, we applied it to the identification of a cryptic E3 ligase activity secreted by Pseudomonas aeruginosa. We identified an unreported P. aeruginosa E3 ligase, which we have termed Pseudomonas Ub ligase 1 (PUL-1), that resembles none of the other E3 ligases previously established in or outside of the eukaryotic system. Importantly, in an animal model of P. aeruginosa infection, PUL-1 ligase activity plays an important role in regulating virulence. Thus, our workflow for the functional identification of ubiquitin-targeted effector proteins carries promise for expanding our appreciation of how host ubiquitin regulation contributes to bacterial pathogenesis.
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OBJECTIVE: To report technical success and evaluate clinical outcomes of fenestrated and branched endovascular aortic repair (F/B-EVAR) incorporating a contralateral inverted limb. METHODS: Patients who underwent F/B-EVAR with a custom-made bifurcated device containing an inverted limb between January 2010 and September 2023 were retrospectively analyzed. Time-to-event data were analyzed using the Kaplan-Meier method. RESULTS: A total of 32 patients (26 men; mean age 77±6.2 years) were included in the analysis. Technical success was achieved in 28 patients (87.5%). Two technical failures resulted from misplaced contralateral limbs in patients with previous endovascular aortic repair (EVAR), necessitating one open conversion due to a type 3b endoleak, and one femoro-femoral crossover bypass after occlusion of a misplaced contralateral limb. Additionally, two technical failures were attributed to a type 3c endoleak and a type 1c endoleak, originating from a fenestrated device at the level of the left and right renal artery, respectively. One patient (3.1%) died <30 days post-operatively due to a subdural hemorrhage. Estimated patient survival after 1 and 2 years was 92.7%±5.1%, and 74.3%±10.1%, respectively. No aneurysm-related deaths were observed. During the median follow-up of 13 months, one (3.1%) inverted limb occluded, in addition to the occlusion resulting from a misplaced contralateral limb, and was treated with a femoro-femoral crossover bypass. One target vessel (right renal artery) occluded (0.9%), resulting in a permanent, significantly reduced renal function. Freedom from overall reintervention after 1 and 2 years was 73.5%±8.0% and 68.3%±9.0%, respectively. An additional four patients (12.5%) presented with a type 3c endoleak during follow-up scans, three of which originated from fenestrations at the level of the renal stents. There were no junctional problems between the inverted limb device and the main endograft, and no significant correlation was found between the one-sealing-stent inverted limb device design and the onset of type 3 endoleak (log-rank P=.064). CONCLUSIONS: F/B-EVAR incorporating an inverted limb can be a viable endovascular option to manage complex aneurysms with a short renal artery to bifurcation distance. However, using the inverted limb presents a notable technical challenge and could be associated with a higher need for reintervention. Carefully confirming correct cannulation of the inverted limb is warranted.
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BACKGROUND: Few studies have quantified multimorbidity and frailty trends within hospital settings, with even fewer reporting how much is attributable to the ageing population and individual patient factors. Studies to date have tended to focus on people over 65, rarely capturing older people or stratifying findings by planned and unplanned activity. As the UK's national health service (NHS) backlog worsens, and debates about productivity dominate, it is essential to understand these hospital trends so health services can meet them. METHODS: Hospital Episode Statistics inpatient admission records were extracted for adults between 2006 and 2021. Multimorbidity and frailty was measured using Elixhauser Comorbidity Index and Soong Frailty Scores. Yearly proportions of people with Elixhauser conditions (0, 1, 2, 3 +) or frailty syndromes (0, 1, 2 +) were reported, and the prevalence between 2006 and 2021 compared. Logistic regression models measured how much patient factors impacted the likelihood of having three or more Elixhauser conditions or two or more frailty syndromes. Results were stratified by age groups (18-44, 45-64 and 65 +) and admission type (emergency or elective). RESULTS: The study included 107 million adult inpatient hospital episodes. Overall, the proportion of admissions with one or more Elixhauser conditions rose for acute and elective admissions, with the trend becoming more prominent as age increased. This was most striking among acute admissions for people aged 65 and over, who saw a 35.2% absolute increase in the proportion of admissions who had three or more Elixhauser conditions. This means there were 915,221 extra hospital episodes in the last 12 months of the study, by people who had at least three Elixhauser conditions compared with 15 years ago. The findings were similar for people who had one or more frailty syndromes. Overall, year, age and socioeconomic deprivation were found to be strongly and positively associated with having three or more Elixhauser conditions or two or more frailty syndromes, with socioeconomic deprivation showing a strong dose-response relationship. CONCLUSIONS: Overall, the proportion of hospital admissions with multiple conditions or frailty syndromes has risen over the last 15 years. This matches smaller-scale and anecdotal reports from hospitals and can inform how hospitals are reimbursed.
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Fragilidad , Hospitalización , Multimorbilidad , Humanos , Anciano , Multimorbilidad/tendencias , Persona de Mediana Edad , Estudios Retrospectivos , Inglaterra/epidemiología , Fragilidad/epidemiología , Masculino , Femenino , Adulto , Hospitalización/tendencias , Hospitalización/estadística & datos numéricos , Adolescente , Adulto Joven , Anciano de 80 o más Años , PrevalenciaRESUMEN
The study was conducted to inform risk assessments concerning microbial exposure to quaternary ammonium biocides (QUATs) by investigating their effects on 10 microbial strains of hygiene relevance. Biocides were divided into three categories: simple aqueous solutions, biocide mixtures, and formulated biocides. Organisms were grown in the presence of biocides for 10 generations and then subsequently for another 10 generations in biocide-free media. Control organisms were passaged 20 times in biocide-free media. Strains were then assessed for biocide and antibiotic susceptibility, changes in growth dynamics, and single nucleotide polymorphisms (SNPs). Biocide mixtures demonstrated greater antimicrobial potency than singular and formulated biocides. Susceptibility changes of under twofold were observed for all biocides tested. Susceptibility decreased significantly for organisms passaged with singular biocides (1.29- to 4.35-fold) and biocide mixtures (1.4- to 1.5-fold), but not for formulated biocides (1.3- to 1.84-fold) compared to controls. Antibiotic susceptibility both increased and decreased in passaged organisms, with heightened susceptibility occurring more frequently in the singular biocide group. Changes in susceptibility and growth dynamics were similar in the passaged and unexposed controls for fitness measures of adapted bacteria; there were no significant differences between biocide groups, but significantly lower generation and doubling times in organisms exposed to singular biocides. Similar frequencies in SNPs occurred for the three biocide groups and unexposed controls. While some adaptations occurred, particularly with singular biocides, the impact on antibiotic resistance and genomic mutations was limited. These findings suggest that the use of formulated QUATs may pose a comparatively lower risk for antimicrobial resistance.IMPORTANCEBiocides are used globally to control microbial growth and effective assessment of the risks and benefits of their use is therefore a high priority. Much of the data used to assess risk has been based on sub-lethal exposure of bacteria to singular biocides in simple aqueous solutions. This work builds on limited prior realism-based studies to demonstrate enhanced potency in biocidal mixtures; the mitigation of resistance selection by formulations and inconsistent cross-resistance effects with both increases and decreases in susceptibility for a wide range of antibiotics. These data can be used to better inform risk assessments of biocide deployment.
Asunto(s)
Desinfectantes , Compuestos de Amonio Cuaternario , Desinfectantes/farmacología , Compuestos de Amonio Cuaternario/farmacología , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Adaptación Fisiológica , Bacterias/efectos de los fármacos , Bacterias/genética , Bacterias/clasificación , Polimorfismo de Nucleótido Simple , Farmacorresistencia BacterianaRESUMEN
Peanut (Arachis hypogaea L.) is a globally important oil and food crop frequently grown in arid, semi-arid, or dryland environments. Improving drought tolerance is a key goal for peanut crop improvement efforts. Here we present the genome assembly and gene model annotation for 'Line8', a peanut genotype bred from drought tolerant cultivars. Our assembly and annotation are the most contiguous and complete peanut genome resources currently available. The high contiguity of the Line8 assembly allowed us to explore structural variation both between peanut genotypes and subgenomes. We detect several large inversions between Line8 and other peanut genome assemblies, and there is a trend for the inversions between more genetically diverged genotypes to have higher gene content. We also relate patterns of subgenome exchange to structural variation between Line8 homeologous chromosomes. Unexpectedly, we discover that Line8 harbors an introgression from A.cardenasii, a diploid peanut relative and important donor of disease resistance alleles to peanut breeding populations. The fully resolved sequences of both haplotypes in this introgression provide the first in situ characterization of A.cardenasii candidate alleles that can be leveraged for future targeted improvement efforts. The completeness of our genome will support peanut biotechnology and broader research into the evolution of hybridization and polyploidy.