YokoCo

Little direction exists on how to effectively implement palliative care for patients with COPD. In the COMPASSION study, we developed, executed, and evaluated a multifaceted implementation strategy to improve the uptake of region-tailored palliative care intervention components into routine COPD care. We evaluated the implementation strategy and assessed the implementation process, barriers, and facilitators.

Colebrookea oppositifolia Sm. is a valuable traditional therapeutic plant belonging to the family Lamiaceae. It is a dense and wool-like shrub that is mostly found in subtropical regions of some countries of Asia, such as China and India. It has been widely used for the mitigation of nervous system disorders like epilepsy. The active constituents of the plant have exhibited antioxidant, anti-microbial, and antifungal properties, which are considered due to the presence of polyphenols and flavonoids as chief chemical constituents. Flavonoids like quercetin, landenein, chrysin, and 5, 6, 7-trimethoxy flavones cause protein denaturation of the microbial cell wall.

The present disclosure relates to p38α mitogen-activated protein kinase inhibitors, pharmaceutical compositions thereof, and the use of the p38α mitogen-activated protein kinase inhibitors and pharmaceutical compositions thereof for treating various diseases such as cancer, rheumatoid arthritis, amyotrophic lateral sclerosis, cystic fibrosis, cardiovascular disease, multiple sclerosis, inflammatory bowel disease, chronic obstructive pulmonary disease (COPD), asthma, COVID-19, acute respiratory distress syndrome (ARDS), and acute lung injury (ALI).

The Cervical Flexion-Rotation Test (CFRT) is widely used in the assessment of upper cervical spine mobility impairments and in the diagnosis of cervicogenic headache (CGH) by physiotherapist. Many studies investigated its different properties, and the results show that the CFRT has good construct validity in the measurement of C1-C2 rotation as well as good to excellent reliability.

Lumbar disc herniation is one of the leading causes of chronic low back pain. Surgery remains the therapy of choice when conservative approaches fail. Full-endoscopic approaches represent a promising alternative to the well-established microsurgical technique. However, high-grade evidence comparing these techniques is still scarce.

This retrospective study aimed to introduce a novel method for simultaneous Y-shape osteotomy combined with subtalar arthrodesis for calcaneus malunion and to evaluate the feasibility of this method.

High-frequency repetitive transcranial magnetic stimulation (HF-rTMS) remains a promising strategy for neurorehabilitation. The stimulation intensity (SI) influences the after-effects observed. Here, we examined if single sessions of a HF-rTMS protocol, administered at different suprathreshold SI, can be safely administered to able-bodied (AB) individuals.

Neuroprognostication in severe traumatic brain injury (sTBI) is challenging and occurs in critical care settings to determine withdrawal of life sustaining therapies (WSLT). However, formal pediatric sTBI neuroprognostication guidelines are lacking, brain death criteria vary and dilemmas regarding WLST persist which lead to institutional differences. We studied WLST practice and outcome in pediatric sTBI to provide insight into WLST-associated factors and survivor recovery trajectory ≥ 1 year post-sTBI. This retrospective, single center observational study included patients < 18 years admitted to the Pediatric Intensive Care Unit (PICU) of Erasmus MC-Sophia (a tertiary university hospital) between 2012 and 2020 with sTBI defined as a Glasgow Coma Scale (GCS) ≤ 8 and requiring intracranial pressure (ICP) monitoring. Clinical, neuroimaging and electroencephalogram (EEG) data were reviewed. Multidisciplinary follow-up included the Pediatric Cerebral Performance Category (PCPC) score, educational level and commonly cited complaints. Seventy-eight children with sTBI were included (median age 10.5 years; IQR 5.0 – 14.1; 56% male; 67% traffic-related accidents). Median ICP monitoring was 5 days [IQR 3-8], 19 (24%) underwent decompressive craniectomy. PICU mortality was 21% (16/78): clinical brain death (cBD, 5/16), WLST due to poor neurological prognosis (WLST_neuro, 11/16). Significant differences (p < 0.001) between survivors and nonsurvivors: first GCS score, first pupillary reaction and first lactate, Injury Severity Score (ISS), pre-hospital cardiopulmonary resuscitation and Rotterdam CT score. WLST_neuro decision timing ranged from 0 to 31 days [median 2 days, IQR 0-5]. WLST_neuro decision (n=11) was based on neurologic examination (100%), brain imaging (100%) and refractory intracranial hypertension (5/11; 45%). WLST discussions were multidisciplinary with 100% agreement. Immediate agreement between medical team and caregivers was 81%. The majority (42/62, 68%) of survivors were poor outcome (PCPC score 3 to 5) at PICU discharge, of which 12 (19%) in a vegetative state. One year post-injury no patients were in a vegetative state and the median PCPC score had improved to 2 [IQR 2-3]. No patients died after PICU discharge. Twenty percent of survivors could not attend school two years post-injury. Survivors requiring an adjusted educational level increased to 45% within this timeframe. Chronic complaints were headache, behavioral and sleeping problems. In conclusion, two thirds of sTBI PICU mortality was secondary to WLST_neuro and occurred early post-injury. Median survivor PCPC score improved from 4 to 2 with no vegetative patients one year post-sTBI. Our findings show the WLST decision process was multidisciplinary and guided by specific clinical features at presentation, clinical course and (serial) neurological diagnostic modalities of which the testing combination was determined by case-to-case variation. This stresses the need for international guidelines to provide accurate neuroprognostication within an appropriate timeframe whereby overall survivor outcome data provides valuable context and guidance in the acute phase decision process.

Acute and hard-to-heal wounds are a significant burden to both a patient's quality of life and resources in healthcare systems. Here, we evaluate the outcomes of a non-comparative case series study in which Ringer's solution-preactivated polyacrylate dressings were used to treat acute and hard-to-heal wounds (the presence of Ringer's solution provides a wound dressing that allows, upon application, the immediate hydration of the underlying wound tissue).

Oropouche virus (OROV; genus Orthobunyavirus) is the etiological agent of Oropouche fever, a debilitating febrile illness common in South America. We used recombinant expression of the OROV M polyprotein, which encodes the surface glycoproteins Gn and Gc plus the nonstructural protein NSm, to probe the cellular determinants for OROV assembly and budding. Gn and Gc self-assemble and are secreted independently of NSm. Mature OROV Gn has two predicted transmembrane domains that are crucial for glycoprotein translocation to the Golgi complex and glycoprotein secretion, and unlike related orthobunyaviruses, both transmembrane domains are retained during Gn maturation. Disruption of Golgi function using the drugs brefeldin A and monensin inhibits glycoprotein secretion. Infection studies have previously shown that the cellular endosomal sorting complexes required for transport (ESCRT) machinery is recruited to Golgi membranes during OROV assembly and that ESCRT activity is required for virus secretion. A dominant-negative form of the ESCRT-associated ATPase VPS4 significantly reduces recombinant OROV glycoprotein secretion and blocks virus release from infected cells, and VPS4 partly colocalizes with OROV glycoproteins and membranes costained with Golgi markers. Furthermore, immunoprecipitation and fluorescence microscopy experiments demonstrate that OROV glycoproteins interact with the ESCRT-III component CHMP6, with overexpression of a dominant-negative form of CHMP6 significantly reducing OROV glycoprotein secretion. Taken together, our data highlight differences in M polyprotein processing across orthobunyaviruses, indicate that Golgi and ESCRT function are required for glycoprotein secretion, and identify CHMP6 as an ESCRT-III component that interacts with OROV glycoproteins. Oropouche virus causes Oropouche fever, a debilitating illness common in South America that is characterized by high fever, headache, myalgia, and vomiting. The tripartite genome of this zoonotic virus is capable of reassortment, and there have been multiple epidemics of Oropouche fever in South America over the last 50 years, making Oropouche virus infection a significant threat to public health. However, the molecular characteristics of this arbovirus are poorly understood. We developed a recombinant protein expression system to investigate the cellular determinants of OROV glycoprotein maturation and secretion. We show that the proteolytic processing of the M polypeptide, which encodes the surface glycoproteins (Gn and Gc) plus a nonstructural protein (NSm), differs between OROV and its close relative Bunyamwera virus. Furthermore, we demonstrate that OROV M glycoprotein secretion requires the cellular endosomal sorting complexes required for transport (ESCRT) membrane-remodeling machinery and identify that the OROV glycoproteins interact with the ESCRT protein CHMP6.