A case with CMTX1 disease showing transient ischemic-attack-like episodes

Charcot-Marie-Tooth (CMT) disease is a hereditary neurologic disease which affects the sensorial and motor fibers of the peripheral nerves. CMTX1 is an X-linked dominantly inherited subtype of CMT and is caused by mutations in gap junction beta 1 gene (GJB1). A small proportion of GJB1 mutations are associated with recurrent central nervous system findings. We describe a 15-year-old male patient with CMTX1 who had stroke-like findings along with foot deformities and peripheral neuropathy. Strokes and stroke-like attacks are rarely seen in children and adolescents. Herein, neurological signs, MRI findings and genetic results of a CMTX1 case are presented and discussed.     

IL-1β is induced in reactive astrocytes in the somatosensory cortex of rats with genetic absence epilepsy at the onset of spike-and-wave discharges, and contributes to their occurrence

Interleukin (IL)-1β plays a crucial role in the mechanisms of limbic seizures in rodent models of temporal lobe epilepsy. We addressed whether activation of the IL-1β signaling occurs in rats with genetic absence epilepsy (GAERS) during the development of spike-and-wave discharges (SWDs). Moreover, we studied whether inhibition of IL-1β biosynthesis in GAERS could affect SWD activity.IL-1β expression and glia activation were studied by immunocytochemistry in the forebrain of GAERS at postnatal days (PN)14, PN20, and PN90 and in age-matched non-epileptic control Wistar rats. In PN14 GAERS, when no SWDs have developed yet, IL-1β immunostaining was undetectable, and astrocytes and microglia showed a resting phenotype similar to control Wistar rats. In 3 out of 9 PN20 GAERS, IL-1β was observed in activated astrocytes of the somatosensory cortex; the cytokine expression was associated with the occurrence of immature-type of SWDs. In all adult PN90 GAERS, when mature SWDs are established, IL-1β was observed in reactive astrocytes of the somatosensory cortex but not in adjacent cortical areas or in extra-cortical regions.An age-dependent c-fos activation was found in the somatosensory cortex of GAERS with maximal levels reached in PN90 rats; c-fos was also induced in some thalamic nuclei in PN20 and PN90 GAERS.Inhibition of IL-1β biosynthesis in PN90 GAERS by 4-day systemic administration of a specific ICE/Caspase-1 blocker, significantly reduced both SWD number and duration.These results show that IL-1β is induced in reactive astrocytes of the somatosensory cortex of GAERS at the onset of SWDs. IL-1β has pro-ictogenic properties in this model, and thus it may play a contributing role in the mechanisms underlying the occurrence of absence seizures.     

COVID-19-related oral mucosa lesions among confirmed SARS-CoV-2 patients: a systematic review

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for coronavirus disease 2019 (COVID-19), which manifests as a flu-like respiratory infection affecting multiple organ systems, including the gastrointestinal system, central nervous system, cardiovascular system, skin, and mucosa. In this review, we investigated the literature on specific manifestations of COVID-19 in the oral mucosa. An online literature search in PubMed, Scopus, Google Scholar, and Medline was conducted to retrieve relevant studies on confirmed COVID-19 patients with oral mucosa findings published between December 31, 2019, and April 07, 2021. After an independent review by two authors, 39 articles considering 59 laboratory-confirmed cases of SARS-CoV-2 infection were included in the final analysis. The most common finding, reported in 29 patients (43.9%), was Kawasaki-like syndrome. In addition, oral ulcers including aphthous, hemorrhagic, and necrotic ulcers were reported in 24 patients (36.3%). Other lesions reported included pustules, macules, bullae, maculopapular enanthema, and erythema multiforme-like lesions. Concomitant skin lesions were present in 60.6% of patients. Fever was reported in 86.2% of patients. Forty-eight patients (76.1%) were hospitalized. Loss of taste and smell was present in 30.8% of the patients. A comprehensive understanding of the dermatologic manifestations of COVID-19 can improve and facilitate patient management and referrals.     

Neuropathic pain: is it an underestimated symptom in systemic sclerosis?

Pain is one of the most common symptoms in systemic sclerosis (SSc) patients, yet not considered in the assessment of disease severity. This study aimed to investigate the frequency of neuropathic pain (NP) and to evaluate its interference with the quality of life (QoL) in SSc patients. Diffuse and Limited SSc patients diagnosed by American College of Rheumatology 2013 criteria were included in the study. Pain was evaluated with Visual Analogue Scale (VAS); presence of NP was screened with The Leeds Assessment of Neuropathic Symptoms and Signs (LANNS) questionnaire; disease activity was evaluated with modified Medsger Severity Scale (MSS) and QoL with short-form 36 (SF-36). One hundred twenty patients were included in the study (mean age 53.64?±?11.44 years, female/male 83.3–16.7%). Total pain frequency was found 69.2% and NP was 35.9% in the entire patient group. Pain was most frequently seen in wrist-hand (50.6%) and ankle-foot (43.4%) regions; albeit, NP rates were highest in face (94.4%), lower leg (87.5%), and hip-thigh (78.6%) regions. SF-36 scores were significantly lower in patients with NP than the patients without NP (P?<?0.05). The most associated factors with NP were MSS score for muscle involvement and drug consumption of the patient. According to our results, high frequency of NP is seen in SSc patients, and NP is associated with low QoL. Differential diagnosis of NP is important to consider right treatment options and accurate management of pain in all rheumatologic diseases including SSc.     

Significant functional differences in differentiated Conditionally Reprogrammed (CRC)- and Feeder-free Dual SMAD inhibited-expanded human nasal epithelial cells

BackgroundPatient-derived airway cells differentiated at Air Liquid Interface (ALI) are valuable models for Cystic fibrosis (CF) precision therapy. Different culture expansion methods have been established to extend expansion capacity of airway basal cells, while retaining functional airway epithelium physiology. Considerable variation in response to CFTR modulators is observed in cultures even within the same CFTR genotype and despite the use of similar ALI culture techniques. We aimed to address culture expansion method impact on differentiation.MethodsNasal epithelial brushings from 14 individuals (CF=9; non-CF=5) were collected, then equally divided and expanded under conditional reprogramming culture (CRC) and feeder-serum-free “dual-SMAD inhibition” (SMADi) methods. Expanded cells from each culture were differentiated with proprietary PneumaCult?-ALI media. Morphology (Immunofluorescence), global proteomics (LC-MS/MS) and function (barrier integrity, cilia motility, and ion transport) were compared in CRC^ALI and SMADi^ALI under basal and CFTR corrector treated (VX-809) conditions.ResultsNo significant difference in the structural morphology or baseline global proteomics profile were observed. Barrier integrity and cilia motility were significantly different, despite no difference in cell junction morphology or cilia abundance. Epithelial Sodium Channels and Calcium-activated Chloride Channel activity did not differ but CFTR mediated chloride currents were significantly reduced in SMADi^ALI compare to their CRC^ALI counterparts.ConclusionAlteration of cellular physiological function in vitro were more prominent than structural and differentiation potential in airway ALI. Since initial expansion culture conditions significantly influence CFTR activity, this could lead to false conclusions if data from different labs are compared against each other without specific reference ranges.     

Dermatological aspects of synthetic cannabinoid addiction

Context: Synthetic cannabinoids (SCs) have recently become one of the most abused substances among young population and have caused severe health consequences in our country and worldwide.

Objective: The aim of this study was to investigate sociodemographic and dermatological findings in SC addicts.

Materials and methods: A total of 136 SC users who applied to our hospital’s Substance Dependence Center outpatient clinic and diagnosed with drug addiction according to DSM-4 criteria between September 2014 and September 2015 were enrolled to our study. Patients were evaluated by dermatologist and psychiatrist with sociodemographic and clinical data sheets. Data were obtained by direct conversation with patients, clinical examination findings, and laboratory tests, if necessary.

Results: Of 136 patients, 12 (8.8%) were female and 124 (91.2%) were male, aged between 17 and 53 with mean age of 25.8?±?9.2. Most common use way of SC was smoking and patients majorly used opiates before SC. The majority of the patients enrolled to our study were low-educated and almost 50% did not have a regular job. The most frequent dermatologic complaints were periorbital darkening, hallowed-cheeks and premature aging, hair loss and gray hair, and acnes, whereas most frequent dermatologic examination findings were artifact lesions such as blade scars and tobacco scars-stains, tattoos, and acnes.

Discussion and conclusions: Given the increased prevalence of SC use in our country and around the world, dermatologists should continue to familiarize themselves with the common mucocutaneous markers of this substance use. Awareness of signs of SCs use will facilitate earlier diagnose, intervention, and directed treatment.     

Lack of MEF2A mutations in coronary artery disease

Mutations in MEF2A have been implicated in an autosomal dominant form of coronary artery disease (adCAD1). In this study we sought to determine whether severe mutations in MEF2A might also explain sporadic cases of coronary artery disease (CAD). To do this, we resequenced the coding sequence and splice sites of MEF2A in approximately 300 patients with premature CAD and failed to find causative mutations in the CAD cohort. However, we did identify the 21-bp MEF2A coding sequence deletion originally implicated in adCAD1 in 1 of 300 elderly control subjects without CAD. Further screening of approximately 1,500 additional individuals without CAD revealed 2 more subjects with the MEF2A 21-bp deletion. Genotyping of 19 family members of the 3 probands with the 21-bp deletion in MEF2A revealed that the mutation did not cosegregate with early CAD. These studies support that MEF2A mutations are not a common cause of CAD in white people and argue strongly against a role for the MEF2A 21-bp deletion in autosomal dominant CAD.     

A Late Presentation of Tetralogy of Fallot with Pulmonary Atresia and Coronary‐Pulmonary Artery Collateral and a Congenital Aortic Stenosis

We report a 40‐year‐old man with an unoperated tetralogy of Fallot with pulmonary atresia and congenital aortic valvular stenosis. A well‐developed coronary‐pulmonary arterial collateral arising from the left main coronary artery was also demonstrated. Although rare cases of tetralogy of Fallot with congenital aortic stenosis has been reported, this is the first particular case demonstrating a triad of these abnormalities.