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Charcot-Marie-Tooth disease (CMT) represents a phenotypically and genetically heterogeneous disorder of the peripheral nervous system. Biallelic variants in SLC12A6 have been reported as the cause of autosomal-recessive (AR) hereditary motor and sensory neuropathy with agenesis of the corpus callosum (HMSN/ACC). Here we identified an autosomal-dominant (AD) heterozygous mutation in SLC12A6 in a Chinese patient with intermediate CMT. The patient presented with slowly progressive distal muscle weakness and atrophy. Electrophysiological examination showed a mixed axonal/demyelinating neuropathy. Cognition and brain MRI were normal. A single heterozygous missense mutation c.620G>A (p.R207H) in exon 5 of SLC12A6 was identified as the likely pathogenic mutation by whole-exome sequencing consistent with two previously published cases. It affects evolutionarily highly conserved amino acid residue and is predicted to be deleterious by using in silico tools. Modelling of the mutant KCC3 cotransporter showed altered formation of hydrogen bonds and weakened interaction force between the mutated site and its surrounding amino acid residues. Our findings expand the genotypic and phenotypic spectrum associated with SLC12A6 mutations from AR-HMSN/ACC to AD-CMT. The differences in the inheritance pattern might be associated with a dominant-negative pathomechanism.
The increase in COVID-19 cases is generating fear and concern in society, which generates an emotional response that influences the adoption of health-related behaviors. The objective of the study is to design and validate the Scale of Worry for Contagion of COVID-19 (PRE-COVID-19).
The study had a descriptive cross-sectional design. The population were young people and adults who resided in the cities of Lima and Callao (Perú) during the declaration of the national health emergency due to the COVID-19 pandemic, during the period from March 16 to 27, 2020, who were recruited through a non-probability sample. The PRE-COVID-19, the WHO-Five Well-Being Index, the Generalized Anxiety Disorder Scale-2 and a single item were applied to measure the general perception of health. The scales were shared using a Google form through social networks. An internal consistency reliability analysis and structural equation models were performed, specifically confirmatory factor analysis. The recommendations of the Declaration of Helsinki and the principles that guide the ethical practice of online studies were followed.
Eight hundred and sixteen young people and adults from Lima and Callao (200 men and 616 women; mean age 28.40, SD 7.10) participated. The results show a one-dimensional model with satisfactory goodness-of-fit indices χ
(9)=52.00; CFI=0.99; RMSEA=0.09 [0.07, 0.12]; WRMR=0.85. The λ of the model were higher than 0.50 and the reliability had an excellent value (ω=0.90). Likewise, the convergent and discriminant validity is evident between PRE-COVID-19 and measures of anxiety, well-being and self-reported health.
The results indicate that the PRE-COVID-19 is a valid and reliable instrument to measure concern about the spread of COVID-19 and the emotional impact on people.
The results indicate that the PRE-COVID-19 is a valid and reliable instrument to measure concern about the spread of COVID-19 and the emotional impact on people.
To evaluate the effects of transcranial direct current stimulation on pain and other symptoms of knee osteoarthritis.
We performed a single-blind randomized sham-controlled trial with two parallel arms in an outpatient clinic of physical medicine and rehabilitation at a teaching hospital. We randomized 54 patients, 30-70 years of age, with knee osteoarthritis into two groups. They had morning stiffness ≤ 30 min, knee pain ≥ 3 months, joint crepitus, and Kellgren-Lawrence grade 1 or 2 on radiographs. For the active stimulation we administered 2 mA current, 20 min for each session and for the sham group 30 s stimulation and 20 min no current. Using the 10/20 International EEG system, the anode was fixed over the contralateral primary motor cortex (C3 or C4), and the cathode was placed on the ipsilateral supraorbital region (Fp1 or Fp2), with respect to the included knee. The program was repeated once daily over 5 consecutive days. Both groups received acetaminophen. We assessed the patients before and afterfect.
This study aimed to evaluate the safety of applying zinc oxide nanoparticles (ZnO NPs) to pathological skin. The majority of previous studies confirmed the safety of applying ZnO NPs to normal skin. However, we know very little about the risks of using sunscreen, cosmetics and topical drugs containing ZnO NPs for individuals with skin diseases.
ZnO NPs passed through gaps between keratinocytes and entered stratum basale of epidermis and dermis in imiquimod-induced psoriasis-like skin lesions. Application of a ZnO NP-containing suspension for 3 connective days delayed the healing of the epidermal barrier; increased the expression levels of inflammatory cytokines; promoted keratinocyte apoptosis and disturbed redox homeostasis. In TNF-α-stimulated HaCaT cells, QNZ and JSH-23 (NFκB inhibitors) blocked ZnO NP-induced inflammation. JSH-23 and NAC (a precursor of cysteine) inhibited ZnO NP-induced nuclear translocation of p-NFκB p65, cysteine deficiency and apoptosis. Additionally, ZnO NPs decreased CD98 level in main pathway and failed to activate transsulfuration pathway in cysteine biosynthesis.
ZnO NPs can enter psoriasis-like skin lesions and promote inflammation and keratinocyte apoptosis through nuclear translocation of p-NFκB p65 and cysteine deficiency. This work reminds the public that ZnO NPs have harmful effects on the recovery of inflammatory skin diseases.
ZnO NPs can enter psoriasis-like skin lesions and promote inflammation and keratinocyte apoptosis through nuclear translocation of p-NFκB p65 and cysteine deficiency. This work reminds the public that ZnO NPs have harmful effects on the recovery of inflammatory skin diseases.Keloid is a type of skin fibroproliferative disease, characterized by excessive deposition of collagen in the extracellular matrix, myofibroblast activation and invasive growth to the surrounding normal skin tissue. However, the specific pathogenesis of keloids is not yet fully understood and existing treatment strategies are unsatisfied. It is therefore urgent to explore new biomarkers associated with its progression for keloids. In this study, the microarray dataset GSE113620 was downloaded from the Gene Expression Omnibus (GEO) database to screen out the differential expression of miRNAs (DEMs). see more The DEMs with large variance were applied to construct a weighted gene co-expression network to identify miRNA modules that are closely relevant to keloid progression. It is worth noting that miR-424-3p in the blue module (r = 0.98, p = 1e-18) is considered to be the ultimate target most relevant to keloid progression through co-expressed network analysis. Subsequently, the results of molecular biology experiments determine that miR-424-3p targeting Smad7 significantly enhanced the ability of cell proliferation, migration and collagen secretion after transfection with miR-424-3p mimic, while the apoptosis rate was significantly reduced.
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