Notes

A true Chance of the Transatlantic Alliance on Weather Plan.
H and E staining was applied to observe the pathological changes of neurons in the spinal dorsal horn, TUNEL staining to detect neuronal apoptosis, and immunohistochemistry to measure RAB1A level.Plantar incision surgery caused decreased PWT and PWL values, enhanced levels of XIST, RAB1A, and inflammatory cytokines, along with an increased proportion of apoptotic neurons. The pain sensitivity and inflammation of rats were motivated after plantar incision surgery. Intrathecal injection of sh-XIST or miR-340-5p mimic ameliorated the pain and inflammation of PIP rats, while silencing of miR-340-5p or overexpression of RAB1A partly reversed the effect of sh-XIST on PIP rats. XIST targeted miR-340-5p and miR-340-5p negatively regulated RAB1A. The XIST/miR-340-5p/RAB1A axis activated the NF-κB signaling pathway.LncRNA XIST aggravates inflammatory response and postoperative pain of PIP rats by activating the NF-κB pathway via the miR-340-5p/RAB1A axis.
Poisoning from psychoactive drugs and substance use disorders (SUD) have been reported among non-medical cannabis users. However, little is known about medical cannabis users and their risk for poisoning and/or development of SUD. This study assessed the risk of emergency department (ED) visits or hospitalization for 1) poisoning by psychoactive drugs and 2) mental/behavioural disorders due to the use of psychoactive drugs and other substances, in medically authorized cannabis patients in Ontario, Canada from 2014-2017.

A cohort study of adult patients authorized for medical cannabis that were matched to population-based controls. ED visit/hospitalization were assessed with a main diagnostic code for 1) poisoning by psychoactive drugs; 2) mental and behavioural disorder due to psychoactive drugs or other substance use. Conditional Cox proportional hazards regressions were conducted.

18,653 cannabis patients were matched to 51,243 controls. During a median follow-up of 243 days, the incidence rate for poisoning was 4.71 per 1,000 person-years (95%CI 3.71-5.99) for cases and 1.73 per 1,000 person-years (95% CI 1.36-2.19) for controls. The adjusted hazard ratio (aHR) was 2.45 (95%CI 1.56-3.84). For mental/behavioural disorders, the incident rates were 8.89 (95% CI 7.47-10.57) and 5.01 (95% CI 4.36-5.76) in the cannabis and the controls group. The aHR was 2.27 (95%CI 1.66-3.11). No difference was observed between males and females (
-value for interaction > 0.05).

Our study observed a short-term increased risk of ED visit/hospitalization for poisoning or for mental/behavioural disorders (from use of psychoactive drugs and other substances)- in medically authorized cannabis patients.
Our study observed a short-term increased risk of ED visit/hospitalization for poisoning or for mental/behavioural disorders (from use of psychoactive drugs and other substances)- in medically authorized cannabis patients.Caring for the Family Caregiver is published by Oxford University Press and introduces the novel framework of the Family Caregiver Communication Typology. The volume offers a close analysis of caregiver health literacy and patient outcomes and invites readers to consider the family system as the driver in shaping how family caregivers deal with chronic illness demands. The expertise of all authors (three health communication scholars and one nurse who is a health literacy expert) in the analysis illuminates the delicate balance between caregivers' ability to understand and communicate in the context of social determinants of health. The book shares the interwoven challenges of palliative care, family caregiving, and health literacy. Caring for the Family Caregiver establishes the urgent call to address family caregiver information and communication needs and leaves the reader empowered to make changes in their own clinical practice communication and/or develop family caregiving research that addresses cultural and social factors.Respiratory compromise after cervical spinal cord injury (SCI) is a leading cause of mortality and morbidity. Most SCIs are incomplete, and spinal respiratory motoneurons as well as proprio- and bulbospinal synaptic pathways provide a neurological substrate to enhance respiratory output. Ampakines are allosteric modulators of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, which are prevalent on respiratory neurons. We hypothesized that low dose ampakine treatment could safely and effectively increase diaphragm electromyography (EMG) activity that has been impaired as a result of acute- or sub-acute cervical SCI. Diaphragm EMG was recorded using chronic indwelling electrodes in unanesthetized, freely moving rats. A spinal hemi-lesion was induced at C2 (C2Hx), and rats were studied at 4 and 14 days post-injury during room air breathing and acute respiratory challenge accomplished by inspiring a 10% O2, 7% CO2 gas mixture. Once a stable baseline recording was established, one of two different ampakines (CX717 or CX1739, 5 mg/kg, intravenous) or a vehicle (2-hydroxypropyl-beta-cyclodextrin [HPCD]) was delivered. At 4 days post-injury, both ampakines increased diaphragm EMG output ipsilateral to C2Hx during both baseline breathing and acute respiratory challenge. Only CX1739 treatment also led to a sustained (15 min) increase in ipsilateral EMG output. At 14 days post-injury, both ampakines produced sustained increases in ipsilateral diaphragm EMG output and enabled increased output during the respiratory challenge. We conclude that low dose ampakine treatment can increase diaphragm EMG activity after cervical SCI, and therefore may provide a pharmacological strategy that could be useful in the context of respiratory rehabilitation.Significance Skin wounds and disorders compromise the protective functions of skin and patient quality of life. Although accessible on the surface, they are challenging to address due to paucity of effective therapies. Exogenous extracellular vesicles (EVs) and cell-free derivatives of adult multipotent stromal cells (MSCs) are developing as a treatment modality. Knowledge of origin MSCs, EV processing, and mode of action is necessary for directed use of EVs in preclinical studies and methodical translation. Recent Advances Nanoscale to microscale EVs, although from nonskin cells, induce functional responses in cutaneous wound cellular milieu. EVs allow a shift from cell-based to cell-free/derived modalities by carrying the MSC beneficial factors but eliminating risks associated with MSC transplantation. EVs have demonstrated striking efficacy in resolution of preclinical wound models, specifically within the complexity of skin structure and wound pathology. Critical Issues To facilitate comparison across studies, tissue sources and processing of MSCs, culture conditions, isolation and preparations of EVs, and vesicle sizes require standardization as these criteria influence EV types and contents, and potentially determine the induced biological responses. Procedural parameters for all steps preceding the actual therapeutic administration may be the key to generating EVs that demonstrate consistent efficacy through known mechanisms. We provide a comprehensive review of such parameters and the subsequent tissue, cellular and molecular impact of the derived EVs in different skin wounds/disorders. Future Directions We will gain more complete knowledge of EV-induced effects in skin, and specificity for different wounds/conditions. The safety and efficacy of current preclinical xenogenic applications will favor translation into allogenic clinical applications of EVs as a biologic.
Using vitamin K for correction of coagulopathy in critically ill patients is controversial with limited evidence. This study aims to evaluate the efficacy and safety of vitamin K in the correction of international normalized ratio (INR) elevation secondary to liver disease in critically ill patients.

A retrospective study of critically ill patients with coagulopathy secondary to liver disease. The primary outcome was to evaluate the association between vitamin K administration and the incidence of new bleeding events in critically ill patients with INR elevation; other outcomes were considered secondary. Patients were categorized into two groups based on vitamin K administration to correct INR elevation. The propensity score was generated based on disease severity scores and the use of pharmacological DVT prophylaxis.

A total of 98 patients were included in the study. Forty-seven patients (48%) received vitamin K during the study period. The odds of the new bleeding event was not statistically different between groups (OR 2.4, 95% CI 0.28-21.67,
 = .42). Delta of INR reduction was observed with a median of 0.63 when the first dose is given (
-value <.0001). However the INR reduction with other subsequent doses of vitamin K was not statistically significant.

The administration of vitamin K for INR correction in critically ill patients with coagulopathy secondary to liver disease was not associated with a lower odds of new bleeding events. Further studies are needed to assess the value of vitamin K administration in critically ill patients with liver diseases related coagulopathy.
The administration of vitamin K for INR correction in critically ill patients with coagulopathy secondary to liver disease was not associated with a lower odds of new bleeding events. Further studies are needed to assess the value of vitamin K administration in critically ill patients with liver diseases related coagulopathy.The clinical evaluation of spinal afferents is an important diagnostic and prognostic marker for neurological and functional recovery after spinal cord injury (SCI). Particularly important regarding neuropathic pain following SCI is the function of the spinothalamic tract (STT) conveying nociceptive and temperature information. Here, we investigated the added value of neurophysiological methods revealing discomplete STT lesions; that is, residual axonal sparing in clinically complete STT lesions. Specifically, clinical pinprick testing and thermal thresholds were compared with objective contact heat-evoked potentials (CHEPs) and a novel measure of pain-autonomic interaction employing heat-induced sympathetic skin responses (SSR). The test stimuli (i.e., contact heat, pinprick) were applied below the lesion level in 32 subjects with thoracic SCI while corresponding heat-evoked responses (i.e., CHEPs and SSR) were recorded above the lesion (i.e., scalp and hand, respectively). Readouts of STT function were related to neuropathic pain characteristics. In subjects with abolished pinprick sensation, measures of thermosensation (10%), CHEPs (33%), and SSR (48%) revealed residual STT function. Importantly, SSRs can be used as an objective readout and when abolished, no other proxy indicated residual STT function. No relationship was found between STT function readouts and spontaneous neuropathic pain intensity and extent. However, subjects with clinically preserved STT function presented more often with allodynia (54%) than subjects with discomplete (13%) or complete STT lesions (18%). In individuals with absent pinprick sensation, discomplete STT lesions can be revealed employing pain-autonomic measures. The improved sensitivity to discerning STT lesion completeness might support the investigation of its association with neuropathic pain following SCI.
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