A Homozygous Frameshift Mutation in the HOXC13 Gene Underlies Pure Hair and Nail Ectodermal Dysplasia in a Syrian Family

Pure hair and nail ectodermal dysplasia (PHNED) is a rare genetic disorder characterized by hypotrichosis or complete alopecia, as well as nail dystrophy. Mutations in the type II hair keratin gene KRT85 and the HOXC13 gene on chromosome 12q have recently been identified in families with autosomal‐recessive PHNED. In the present study, we have analyzed a consanguineous Syrian family with an affected girl having complete alopecia and nail dystrophy since birth. The family clearly showed linkage to chromosome 12q13.13–12q14.3, which excluded the KRT85 gene. Sequencing of another candidate gene HOXC13 within the linkage interval identified a homozygous frameshift mutation (c.355delC; p.Leu119Trpfs*20). Expression studies in cultured cells revealed that the mutant HOXC13 protein mislocalized within the cytoplasm, and failed to upregulate the promoter activities of its target genes. Our results strongly suggest crucial roles of the HOXC13 gene in the development of hair and nails in humans.     

Homogeneous liquid–liquid microextraction based on liquid nitrogen-induced phase separation followed by GFAAS for sensitive extraction and determination of lead in lead-adulterated opium and refined opium

Herein, we developed a novel homogeneous liquid–liquid microextraction based on liquid nitrogen-induced phase separation (HLLME-LNPS) for the extraction and determination of lead (Pb) in Pb-adulterated opium and refined opium by GFAAS analysis. In this procedure, first, 400 μl of acetonitrile (extractant) containing 7.0 μl of diethyl dithiophosphoric acid (DDTP) is injected into a sample solution and a homogeneous solution is formed. Subsequently, the homogeneous mixture is cooled using liquid nitrogen for 16 seconds. By this process, due to the difference in the freezing points of the organic and aqueous phases, the homogeneous state is broken and the Pb-DDTP species are extracted into the liquid organic phase collected on top of the frozen aqueous phase. The introduced method exhibited a good linearity with a coefficient of determination (r²) of 0.9988 and an acceptable linear range of 0.6–100 μg l⁻¹. Accordingly, the detection limit was 0.2 μg l⁻¹ (S/N = 3) for Pb ions, and a high enrichment factor was obtained. The proposed method was successfully utilized to determine trace levels of Pb in opium samples. The results of the sample analysis showed that 65% of the opium samples and 85% of the refined opium samples had much higher than expected levels of contaminating Pb, and this contamination poses a serious threat to drug users.

Herein, we developed a novel homogeneous liquid–liquid microextraction based on liquid nitrogen-induced phase separation (HLLME-LNPS) for the extraction and determination of lead (Pb) in Pb-adulterated opium and refined opium by GFAAS analysis.     

Clinical Presentation and Management of Severe Acute Renal Failure in McArdle Disease

McArdle disease, also known as glycogen storage disease type V, is an autosomal recessive disease due to the absence of myophosphorylase activity, leading to the complete disruption of glycogen breakdown in muscles. We present a rare case of a Caucasian male, aged 26 years, who developed rhabdomyolysis-induced acute renal failure and uremic encephalopathy. Neurological examination and histopathological studies supported the diagnosis of McArdle disease. The severity of his symptoms necessitated urgent hemodialysis, upon which the patient reported improvement in status. Acute renal failure in McArdle disease usually resolves with supportive treatment and maintenance of regular physical activity. Nevertheless, in more severe cases, intensive care with urgent hemodialysis may be needed. A multidisciplinary approach is necessary for the adequate management of similar cases.     

Elevated IL-38 Serum Levels in Newly Diagnosed Multiple Sclerosis and Systemic Sclerosis Patients

ObjectiveInterleukin (IL)-38 is a newly discovered member of the IL-1 cytokine family with a proposed anti-inflammatory profile. We studied the probable role of this cytokine in the pathogenesis of two autoimmune diseases: multiple sclerosis (MS) and systemic sclerosis (SSc).Subjects and MethodsA total of 87 MS patients and 86 SSc patients (40 new and recently untreated cases and 46 treated cases) were selected for this study. Eighty-seven and 80 age- and sex-matched healthy subjects were included as controls for MS and SSc, respectively. Clinical and paraclinical features of the patients were recorded at the time of sampling. Serum IL-38 was measured by ELISA.ResultsLevels of serum IL-38 did not significantly differ between the total MS or SSc patients compared to controls. However, levels of IL-38 were significantly higher in newly diagnosed patients of MS (206.43 ± 38.97 pg/mL, p < 0.0001) than in those previously treated (158.04 ± 39.45 pg/mL). Similarly, new/recently untreated cases of SSc patients showed increased IL-38 levels (185.19 ± 36.27 pg/mL, p = 0.001) compared to treated patients (166.82 ± 33.08 pg/mL). IL-38 levels in newly diagnosed MS patients (p = 0.007) and new/recently untreated SSc patients (p = 0.032) were significantly higher than those in healthy controls.ConclusionThe higher serum levels of IL-38 in new or recently untreated cases of MS and SSc patients than in treated patients and healthy controls suggest the possible role of this cytokine in the development of these diseases or as part of a feedback loop to attenuate the inflammatory conditions in early stages of these diseases.     

Effect of micro-aerobic process on improvement of anaerobic digestion sewage sludge treatment: flow cytometry and ATP assessment

Micro-aeration as a pretreatment method improves the efficiency of anaerobic digestion of municipal sewage sludge and consequently promotes the methane production. In this study, adenosine triphosphate (ATP) and flow cytometry (FCM) were employed to monitor the performance of the micro-aerobic process and investigate the survival of bacterial cells within the process. At first, the effect of air flow rate (AFR) (0.1, 0.2, 0.3 and 0.5 vvm) on hydrolysis of mixed sludge in 5 aeration cycles (20, 30, 40, 48 and 60 hours) was examined. Then, the effects of the micro aerobic process on methane (CH₄) production in anaerobic digestion were surveyed. The highest VSS reduction was 30.6% and 10.4% for 40 hours in the reactor and control, respectively. Soluble COD also fluctuated between 40.87 and 65.14% in micro-aerobic conditions; the highest SCOD was achieved at the time of 40 h. Microbial activities were increased by 597%, 170% and 79.4% for 20, 30 and 40 h pretreatment with the micro-aerobic process, respectively. Apoptosis assay showed that micro-aerobic pre-treatment at 20, 30 and 40 h increased the percentage of living cells by 57.4, 62.8 and 67.9%, respectively. On the other hand, FCM results showed that the highest percentage of viable bacteria (i.e., 67.9%) was observed at 40 h pretreating which was approximately 40% higher the ones for the control. Variation in cumulative methane production shows that methane production was increased by 221% compared to anaerobic digestion (control group). Therefore, ATP and FCM can be employed as two appropriate, accurate, relatively specific indicators for monitoring the process and bacteria viability.

Micro-aeration as a pretreatment method improves the efficiency of anaerobic digestion of municipal sewage sludge and consequently promotes the methane production.     

Optimization and evaluation of venlafaxine hydrochloride fast dissolving oral films

Three factors, three levels (3³) full factorial design was used to develop venlafaxine HCl fast dissolving oral films (FDOFs) to optimize the concentrations of the film forming polymer; hydroxypropyl methylcellulose HPMC (X1), superdisintegrant; sodium starch glycolate SSG, (X2) and glycerol as the film plasticizer (X3). Effects of the three factors on the disintegration time (Y1), swelling index (Y2), and dissolution efficiency at 15 min; DE%15 (Y3) of the prepared FDOFs were evaluated by using statistical models. The optimized film formula was characterized in term of x-ray powder diffraction (XRPD), differential scanning calorimetry (DSC) and morphological characteristics.Disintegration time was found to increase with the increase in HPMC (X1) concentration, and the shortest disintegration time (21.67 ± 2.08 s) was observed in case of F2 formula (lowest HPMC level and highest glycerol level in absence of SSG). The highest swelling index (3.64 ± 0.59) was observed in case of film formula F1 (medium concentrations of both HPMC and glycerol and highest SSG concentration. The results also indicated that as the concentration of HPMC increased the DE%15 decreased. SSG (X2), with highest value (72.33 ± 1.71%) was recorded for in case of F12 (using 2% HPMC, 5%SSG and 1.5% glycerol). The optimized FDOF formula derived by the statistical models suggested 2% HPMC, 5% SSG, and 1% glycerol.The data obtained from DSC and XRPD revealed no interaction between drug and FDOT excipients. In addition, XRPD studies proved that the venlafaxine HCl was homogeneously dispersed in the film matrix.     

Cardiac MR assessment of cardiac myxomas

Cardiac myxomas are the most common benign primary cardiac tumour to present in adulthood. While most patients present with symptoms of cardiac obstruction, embolic phenomena or constitutional impairment, up to a fifth of patients remain asymptomatic and are incidentally diagnosed on imaging. Although echocardiography is usually the initial imaging modality used to evaluate these patients, cardiac MRI (CMR) has emerged over the past decade as the primary imaging modality in the assessment of patients with cardiac tumours. The superior tissue characterization capability of CMR means that it is able to determine the nature of some tumours pre-operatively and performs well in differentiating myxomas from thrombus. We present a pictorial review highlighting the key CMR features of myxomas and show how these lesions can be differentiated from thrombus and other cardiac masses.Primary cardiac tumours are uncommon with a reported prevalence at autopsy of 0.002%.¹ The majority are benign, with myxomas accounting for almost 50% of all primary cardiac tumours.² Myxomas are more common in female patients, and while they can occur at any age, they usually present in adults between the fourth and seventh decades of life.^3,4 Most patients typically present with at least one manifestation of the classic triad of cardiac obstructive symptoms, embolic phenomena and constitutional symptoms, but 20% are identified in asymptomatic patients as an incidental imaging finding.³Echocardiography is usually the initial imaging modality used in the assessment of a suspected cardiac mass but remains rather operator dependent with a restricted field of view and can be particularly challenging in patients with large body habitus.^2,4,5 Cardiac MRI (CMR) enables accurate assessment of the location and functional impact of cardiac masses in any imaging plane without exposing patients to ionizing radiation.^2,5 In particular, CMR performs better than echocardiography at determining the nature of cardiac lesions and can differentiate myxomas from thrombus.^2,5 Given that most cardiac lesions are not easily amenable to catheter-directed biopsy, accurate imaging differentiation of cardiac myxomas from other types of cardiac masses is of vital importance in guiding further management.     

The effects of diode laser (660 nm) on the rate of tooth movements: an animal study

Lasers in Medical Science - Low-level laser has been indicated to have the capability to facilitate the differentiation of the osteoclastic and osteoblastic cells which are responsible for the bone...