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Charcot-Marie-Tooth disease is an inherited peripheral neuropathy that is clinically and genetically heterogenous. Mutations in IGHMBP2, a ubiquitously expressed DNA/RNA helicase, have been shown to cause the infantile motor neuron disease spinal muscular atrophy with respiratory distress type 1 (SMARD1), and, more recently, juvenile-onset Charcot-Marie-Tooth disease Type 2S (CMT2S). Using CRISPR-cas9 mutagenesis we developed the first mouse models of CMT2S (p.Glu365del (E365del) and p.Tyr918Cys (Y918C)). E365del is the first CMT2S mouse model to be discovered and Y918C is the first human CMT2S allele knock-in model. Phenotypic characterization of the homozygous models found progressive peripheral motor and sensory axonal degeneration. Neuromuscular and locomotor assays indicate that both E365del and Y918C mice have motor deficits, while neurobehavioral characterization of sensory function found that E365del mutants have mechanical allodynia. Analysis of femoral motor and sensory nerves identified axonal degeneration, which does not impact nerve conduction velocities in E365del mice, but does in the Y918C model. Based on these results, the E365del mutant mouse, as well as the human allele knock-in, Y918C, represent mouse models with the hallmark phenotypes of CMT2S, which will be critical for understanding the pathogenic mechanisms of IGHMBP2. These mice will complement existing Ighmbp2 alleles modeling SMARD1 to help understand the complex phenotypic and genotypic heterogeneity that is observed in patients with IGHMBP2 variants.

Rheumatoid Arthritis (RA) is a disease with a heavy functional, psychological and socioeconomic impact. The management of Quality of Life (QoL) as a therapeutic objective is a fairly recent notion, especially in Tunisia. We aimed to evaluate QoL in RA patients and to identify its affecting factors.

Migraine and tension-type headache (TTH) are important health problems because cause loss of workforce, affect quality of life and are frequently associated with anxiety and depression. Illness perception is defined as a cognitive aspect of illness. The aim of this study is to determinethe relationship of migraine and TTH with quality of life, illness perception, anxiety and depression.

Catecholamine secreting tumors are a rare type of neuroendocrine tumors whose embryological origin is neural crest cells. 80 % to 90 % arise from the chromaffin cells of adrenal medulla while 10 % to 20 % arise from sympathetic and parasympathetic ganglia. Paragangliomas can be symptomatic due to excess catecholamine secretion or can be asymptomatic. Definitive treatment of paragangliomas is surgical resection.

Systematic Review.

Chronic pain involves both central and peripheral neuronal plasticity that encompasses changes in the brain, spinal cord, and peripheral nociceptors. Within the forebrain, mesocorticolimbic regions associated with emotional regulation have recently been shown to exhibit lasting gene expression changes in models of chronic pain. To better understand how such enduring transcriptional changes might be regulated within brain structures associated with processing of pain or affect, we examined epigenetic modifications involved with active or permissive transcriptional states (histone H3 lysine 4 mono and trimethylation, and histone H3 lysine 27 acetylation) in periaqueductal gray (PAG), lateral hypothalamus (LH), nucleus accumbens (NAc), and ventral tegmental area (VTA) 5 weeks after sciatic nerve injury in mice to model chronic pain. For both male and female mice in chronic pain, we observed an overall trend for a reduction of these epigenetic markers in periaqueductal gray, LH, and NAc, but not VTA. Moreover, we discovered that some epigenetic modifications exhibited changes associated with pain history, while others were associated with individual differences in pain sensitivity. When taken together, these results suggest that nerve injury leads to chronic chromatin-mediated suppression of transcription in key limbic brain structures and circuits, which may underlie enduring changes in pain processing and sensitivity within these systems.

Retrospective study of 36 individuals with sickle cell disease (SCD) certified for medical cannabis. We sought to examine whether medical cannabis certification was associated with a change in utilization of acute care medical services for patients with SCD. We identified patients with SCD certified for medical cannabis use between July 2014 and December 2021 using the New York State Prescription Monitoring Program (NYS PMP) and cross-matching to our electronic medical record. We estimated the mean incidences of Emergency Department (ED) visits, hospital admissions, inpatient days, and total acute encounters for SCD-related pain per month pre- and post-medical cannabis certification and used paired -tests to assess the statistical significance of changes in hospital use. We stratified incidence based on whether patients had received a bone marrow transplant (BMT) at any point before or during the research period, since BMT is potentially an important covariate. Recertification rates and patients' reasons for choosing to recertify were qualitatively investigated through retrospective chart review. The incidence of ED visits, hospital admissions, and total acute encounters per month for SCD-related pain decreased pre- to post-certification (=0.02; =0.02; =0.01). These decreases lost statistical significance after stratifying patients based on BMT history. There was no statistically significant change in the number of days per month patients spent hospitalized in either the primary analysis or after stratification by BMT status. Forty-four percent of patients chose to be recertified. Thirty-six percent of patients cited concerns regarding the cost of medical cannabis. Our study did not show a statistically significant relationship between certification for medical cannabis and hospital use after addressing BMT history as a potentially important covariate. However, we were likely underpowered to detect any existing difference after patient data were stratified due to our small sample size. Regardless, 44% of patients chose to be recertified, indicating a perceived benefit and utility in further investigation of medical cannabis for this population with a larger analytic sample. Patient-reported benefits were improvement of pain and other symptoms, decreased opiate requirements, and decreased side effects compared to opiates.

Sickle cell disease (SCD) is the most frequent inherited disorder in the world. It is the consequence of a single amino acid mutation on beta-globin chain, leading to red blood cells deformation, haemolysis and chronic inflammation. Clinical consequences are vaso-occlusives crisis, acute chest syndrome, thrombosis, infection and chronic endothelial lesions.

To characterize the clinical features of long COVID, 286 patients who received care in our outpatient clinic for long COVID from May 2021 through December 2021 were surveyed. The recovery periods of each symptom and the key factors contributing to early recovery were statistically analysed. The median age of the patients was 35.8 years, with 137 men and 149 women. The median number of symptoms was 2.8. The most frequent symptoms were respiratory manifestations (52.1%), followed by fatigue (51.4%). Respiratory symptoms, fatigue and headache/arthralgia were major complaints in the initial phase, whereas hair loss was a major complaint in the late phase, suggesting that the chief complaint of patients with long COVID may vary temporally. The best treatment outcome was observed for pulmonary symptoms, and hair loss had the worst outcome. COVID-19 severity, the number of manifestations and delay in starting treatment exerted a negative effect on the recovery period of long COVID. In addition, a smoking habit was an independent risk factor for slowing the recovery period from long COVID. This study provides insights into the clinical course of each manifestation and therapeutic options with a more certain future of long COVID to meet the unmet medical needs. This article is protected by copyright. All rights reserved.

Effective pain control is crucial to postoperative recovery and is affected by biopsychosocial factors. This study aimed to evaluate how non-English primary language, gender, and marital status may influence pain, length of stay, and mortality after general surgery.