ASAH1-related disorders: Description of 15 novel pediatric patients and expansion of the clinical phenotype

Acid ceramidase deficiency is an orphan lysosomal disorder caused by ASAH1 pathogenic variants and presenting with either Farber disease or spinal muscle atrophy with progressive myoclonic epilepsy (SMA-PME). Phenotypic and genotypic features are rarely explored beyond the scope of case reports. Furthermore, the new biomarker C26-Ceramide requires validation in a clinical setting. We evaluated the clinical, biomarker and genetic spectrum of 15 Egyptian children from 14 unrelated families with biallelic pathogenic variants in ASAH1 (12 Farber and 3 SMA-PME). Recruited children were nine females/six males ranging in age at diagnosis from 13 to 118 months. We detected ASAH1 pathogenic variants in all 30 alleles including three novel variants (c.1126A>G (p.Thr376Ala), c.1205G>A (p.Arg402Gln), exon-5-deletion). Both total C26-Ceramide and its trans- isomer showed 100% sensitivity for the detection of ASAH1-related disorders in tested patients. A 10-year-old girl with the novel variant c.1205G>A (p.Arg402Gln) presented with a new peculiar phenotype of PME without muscle atrophy. We expanded the phenotypic spectrum of ASAH1-related disorders and validated the biomarker C26-Ceramide for supporting diagnosis in symptomatic patients.     

Radiation effect on positronium formation in solid state nuclear track detector.

The effect of alpha-particles on CR-39, a material used in solid state nuclear track detectors (SSNTDs), has been investigated using the positron annihilation lifetime (PAL) technique. The samples were irradiated using a (238)Pu alpha-source of energy ranging from 1 to 5 MeV and with different doses ranging from 0 to 57.87 mGy. The ortho-positronium (o-Ps) lifetime, tau(3), shows a slight increase as the irradiation dose increases, while a rapid change in the o-Ps intensity, I(3) at 10 mGy was found. In addition, the PAL parameters (tau(3), I(3)) have been studied as a function of the energy of alpha-particles. The obtained results indicate that the o-Ps lifetime increases slightly with increasing energy of the alpha-particle. On the other hand, the o-Ps intensity decreases exponentially with increasing alpha-particle energy, plateaus, and finally increases. The data show that the track diameter increases with decreasing energy of the alpha-particle, while the track density increases with increasing the irradiation dose. A correlation between the track diameter and the o-Ps hole diameter was observed.     

Diffusion-weighted magnetic resonance imaging and micro-RNA in the diagnosis of hepatic fibrosis in chronic hepatitis C virus

BACKGROUND Diffusion-weighted magnetic resonance imaging has shown promise in the detection and quantification of hepatic fibrosis. In addition, the liver has numerous endogenous micro-RNAs(miRs) that play important roles in the regulation of biological processes such as cell proliferation and hepatic fibrosis.AIM To assess diffusion-weighted magnetic resonance imaging and miRs in diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.METHODS This prospective study included 208 patients and 82 age-and sex-matched controls who underwent diffusion-weighted magnetic resonance imaging of the abdomen, miR profiling, and liver biopsy. Pathological scoring was classified according to the METAVIR scoring system. The apparent diffusion coefficient (ADC) and miR were calculated and correlated with pathological scoring.RESULTS The ADC value decreased significantly with the progression of fibrosis, from controls(F0) to patients with early fibrosis(F1 and F2) to those with late fibrosis(F3 and F4)(median 1.92, 1.53, and 1.25 × 10~(-3) mm~2/s, respectively)(P = 0.001).The cut-off ADC value used to differentiate patients from controls was 1.83 × 10~(-3) mm~2/s with an area under the curve(AUC) of 0.992. Combining ADC and miR-200 b revealed the highest AUC(0.995) for differentiating patients from controls with an accuracy of 96.9%. The cut-off ADC used to differentiate early fibrosis from late fibrosis was 1.54 × 10~(-3) mm~2/s with an AUC of 0.866. The combination of ADC and miR-200 b revealed the best AUC(0.925) for differentiating early fibrosis from late fibrosis with an accuracy of 80.2%. The ADC correlated with miR-200 b(r =-0.61, P = 0.001), miR-21(r =-0.62, P = 0.001), and miR-29(r = 0.52,P = 0.001).CONCLUSION Combining ADC and miRs offers an alternative surrogate non-invasive diagnostic tool for diagnosing and staging hepatic fibrosis in patients with chronic hepatitis C.     

Effects of estrogen variation on neural correlates of emotional response inhibition

Despite behavioral evidence that variation in ovarian hormones is associated with changes in affect, the neural basis of these processes is poorly understood. We combined functional magnetic resonance imaging (fMRI) with quantitative analysis of ovarian hormones in a within-subject design to investigate brain activation patterns during affective response inhibition, comparing activation between the early follicular (low estrogen and progesterone) and mid-luteal (high estrogen and progesterone) phases of the menstrual cycle in healthy women. There was significantly increased activation in the anterior cingulate and dorsolateral prefrontal cortex (DLPFC) while inhibiting response to positive words during the luteal, compared to the follicular phase. Furthermore, luteal phase estradiol level positively correlated with DLPFC activation while inhibiting response to positive words and negatively correlated with activation in several structures while inhibiting response to negative words, supporting estrogen's modulation of affective processing.     

An office-based immunodiagnostic assay for detecting urinary nuclear matrix protein 52 in patients with bladder cancer

OBJECTIVE: To report the rapid (5 min) and simple detection of a nuclear matrix protein (NMP) in the urine of patients with bladder cancer, using a newly developed office-based dot-enzyme-linked immunosorbent assay (ELISA). PATIENTS AND METHODS: Western blot and specific immunoglobulin-G antibody were used to identify the urinary NMP marker. Urine samples from 149 patients with bladder cancer and 72 controls were evaluated using the developed dot-ELISA. The initial responses of 43 patients treated by irradiation were followed using the assay. RESULTS: The NMP marker was identified in the urine of patients with bladder cancer at 52 kDa (NMP-52) by Western blot. The dot-ELISA detected the urinary NMP-52 marker in 92% of patients with squamous cell carcinoma, 98% with transitional cell carcinoma, and all six of those with adenocarcinoma of the bladder, with a specificity of 94%. The positive and negative predictive values (97% and 94%, respectively) and efficiency (96%) of the dot-ELISA were high. In addition, the NMP-52 tumour marker was not detected in the urine of patients who showed a response after radiotherapy. CONCLUSION: Detecting the urinary NMP-52 marker using dot-ELISA would be helpful in the rapid diagnosis and follow-up of patients with bladder cancer.     

Menstrual hygiene among adolescent schoolgirls in Mansoura, Egypt

Learning about menstrual hygiene is a vital aspect of health education for adolescent girls. This study among 664 schoolgirls aged 14-18 in Mansoura, Egypt, asked about type of sanitary protection used, frequency of changing pads or cloths, means of disposal and bathing during menstruation. Girls were selected by cluster sampling technique in public secondary schools in urban and rural areas. Data were collected through an anonymous, self-administered, open-ended questionnaire during class time. The significant predictors of use of sanitary pads were availability of mass media at home, high and middle social class and urban residence. Use of sanitary pads may be increasing, but not among girls from rural and poor families, and other aspects of personal hygiene were generally found to be poor, such as not changing pads regularly or at night, and not bathing during menstruation. Lack of privacy was an important problem. Mass media were the main source of information about menstrual hygiene, followed by mothers, but a large majority of girls said they needed more information. Instruction in menstrual hygiene should be linked to an expanded programme of health education in schools. A supportive environment for menstrual hygiene has to be provided both at home and in school and sanitary pads made more affordable.     

Immunological and viral factors associated with the response of vulval intraepithelial neoplasia to photodynamic therapy

Topical 5-aminolevulinic acid-based photodynamic therapy (PDT) has produced complete response rates of >90% for nonmelanoma skin carcinomas, which are mostly human papillomavirus (HPV) negative. Using a similar treatment protocol, we observed a short-term response in only one third (10 of 32) of high-grade vulval intraepithelial neoplasia (VIN 2-3) lesions. Unifocal lesions were found more responsive than multifocal and pigmented lesions. Animal model studies have suggested that long-term PDT response involves an immune reaction in which CTLs play a crucial role. In this study, we have assessed: (a) HPV infection; (b) HLA expression; and (c) immune infiltrating cells in VIN biopsies from responders and nonresponders to determine whether these factors may limit response to topical 5-aminolevulinic acid-based PDT. Tissues from normal vulva (n = 9), vulval carcinoma (n = 11), and VIN (32 patients from which 19 pre- and 43 post-PDT biopsies were taken) were investigated for immune cell infiltration and HLA class I expression by immunohistochemistry and HPV infection by PCR. There was a greater likelihood of HPV positivity associated with a lack of response of VIN to PDT (P = 0.002), and VIN nonresponders were more likely to show HLA class I loss compared with responders (P = 0.030). HLA class I down-regulation was significantly greater in the carcinomas (82%, total loss) than the VIN (28%, 19%, total loss; and 9%, allele loss; P = 0.004). None of the cases with class I down-regulation responded to PDT, whereas 3 of 6 (50%) of cases that showed total class I loss subsequently developed superficial invasion. Compared with normal vulval skin, VIN lesions showed increased infiltration by CD4 (T-helper) and CD68 (macrophages) but not CD1a (Langerhans cells) or CD8 (CTLs). There was, however, a significant increase of CD8 infiltration in posttreatment VIN responders compared with nonresponders (P = 0.0001). These data clearly support the contention that high-risk HPV infection and lack of cell-mediated immunity may play a role in the observed poor response of lower genital lesions to topical PDT.     

Crystallographic study of rhinoliths

Five nasal stones were extracted from five patients. The etiology and clinical picture have been discussed. The stones were analysed by a crystallographic method, using an X-ray diffraction technique. Their composition was identified as calcium phosphate.