Phenotypical heterogeneity in RAG-deficient patients from a highly consanguineous population

Mutations affecting recombination activation genes RAG1 and RAG2 are associated with variable phenotypes, depending on the residual recombinase activity. The aim of this study is to describe a variety of clinical phenotypes in RAG-deficient patients from the highly consanguineous Egyptian population. Thirty-one patients with RAG mutations (from 28 families) were included from 2013 to 2017. On the basis of clinical, immunological and genetic data, patients were subdivided into three groups; classical T^–B^– severe combined immunodeficiency (SCID), Omenn syndrome (OS) and atypical SCID. Nineteen patients presented with typical T^–B^–SCID; among these, five patients carried a homozygous RAG2 mutation G35V and five others carried two homozygous RAG2 mutations (T215I and R229Q) that were detected together. Four novel mutations were reported in the T^–B^–SCID group; three in RAG1 (A565P, N591Pfs*14 and K621E) and one in RAG2 (F29S). Seven patients presented with OS and a novel RAG2 mutation (C419W) was documented in one patient. The atypical SCID group comprised five patients. Two had normal B cell counts; one had a previously undescribed RAG2 mutation (V327D). The other three patients presented with autoimmune cytopaenias and features of combined immunodeficiency and were diagnosed at a relatively late age and with a substantial diagnostic delay; one patient had a novel RAG1 mutation (C335R). PID disorders are frequent among Egyptian children because of the high consanguinity. RAG mutations stand behind several variable phenotypes, including classical SCID, OS, atypical SCID with autoimmunity and T^–B⁺ CID.     

Hormonal and Psychogenic Risk Factors for Erectile Dysfunction in Men with HTLV-1

IntroductionErectile dysfunction (ED) is associated with neurological damage due to human T-lymphotropic virus 1 (HTLV-1) infection, but hormonal and psychogenic factors also cause ED.AimTo evaluate the association of psychogenic and hormonal factors with ED in men infected with HTLV-1.MethodsIn this cross-sectional study, we compared total testosterone, follicle stimulating hormone, luteinizing hormone, prolactin, anxiety symptoms, depressive symptoms, and neurologic manifestations in HTLV-1-infected men with or without ED. The International Index of Erectile Function was used to determine the degree of ED. Participants were grouped according to Osame’s Motor Disability Scale and the Expanded Disability Status Scale: HTLV-1-associated myelopathy or tropical spastic paraparesis (HAM/TSP), probable HAM/TSP, or HTLV-1 carrier. Chi-square and Fisher’s exact tests were used to compare the groups, and regression analyses were used to show predictors of ED.Main Outcome MeasureSexual hormonal levels, psychogenic factors, and neurologic disabilities were found to be associated with ED.ResultsED was associated with age older than 60 years (P < .001), degree of neurologic involvement (P < .001), depression (P = .009), and anxiety (P = .008). In the multivariate analyses, only age and degree of neurological injury remained as risk factors for ED.Clinical ImplicationsNeurological manifestations are a stronger predictor of ED than hormonal and psychogenic factors in HTLV-1-infected men.Strengths & LimitationsThe statistical power of the study was limited due to the low number of participants, but neurologic manifestations were clearly associated with ED. There was no strong association between hormonal and psychogenic factors and ED.ConclusionHormonal and psychogenic factors did not show a strong association with ED in individuals with HTLV-1, but neurological manifestations were strongly associated with ED in these individuals.de Oliveira CJV, Neto, JAC, Andrade RCP, et al. Hormonal and Psychogenic Risk Factors for Erectile Dysfunction in Men with HTLV–1. J Sex Med 2019; 16:1763–1768.     

Audit of minimally-invasive surgery for submandibular sialolithiasis

Sialolithiasis is one of most common diseases to affect major salivary glands, with a symptomatic incidence of 27 cases per million per annum. The majority form within the submandibular gland where minimally-invasive treatments have all but eliminated adenectomy. All records of patients presenting with submandibular stones between 1997 and 2015 were reviewed. Stones <5 mm were retrieved through endoscopic or radiographic techniques, 5-7 mm stones were initially considered for extra-corporeal shock wave lithotripsy, but after poor results were treated through intraoral surgical removal with those >7 mm. Follow up was performed at 1 week and 3 months with current status performed with postal and telephone questionnaires. 378 patients had 424 stones removed, successful retrieval in 94% (n = 356), with 50 having had previous failures. Median number of stones per patient was 1 (range 1-4), with a mean size of 8.6 mm (SD 4.5 mm) mainly located at the hilum (50.5%), anterior duct (30%) and Genu (17%). 256 patients (65%) treated through intraoral surgical extraction, 92 (24%) endoscopic alone. Inpatient stay was 1.4 days in first third and 0.5 days in final third. Adenectomy occurred in 14 patients, due to failure to retrieve the sialolith or unresolved symptoms. Complications involved 11 patients with permanent paraesthesia, 7 ranulas and 14 strictures. Patients with preoperative strictures were more likely to develop complications (p = 0.002) with paraesthesia being most common. Intraoral minimally-invasive surgery is aesthetic, curative and spares the risk to marginal mandibular nerve and submandibular gland. Length of inpatient stay improved and ranula risk reduced throughout the study.     

Subtyping of intraductal papillary mucinous neoplasms – pitfalls of MUC1 immunohistochemistry

Intraductal papillary mucinous neoplasms (IPMNs) are precursor lesions of pancreatic ductal adenocarcinoma (PDAC). Current edition of WHO Classification of Tumors of the Digestive System recognizes four different subtypes (gastric, intestinal, pancreatobiliary, and oncocytic) and recommends analysis of mucin expression (MUC1, MUC2, MUC5AC, MUC6) as well as evaluation of architectural and cell differentiation patterns for correct classification. However, there is no consensus on MUC1 expression of IPMN‐lesions in the literature. Current recommendations are based on studies where antibodies against the core MUC1 protein or sialylated MUC1 (tumor associated MUC1), not the fully glycosylated MUC1 were used. We have recently reported that MUC1 is strongly expressed in both gastric and intestinal types IPMN specimens from the cystic wall, obtained by endoscopic ultrasound guided microbiopsy procedure. We have used a commercial MUC1 antibody, validated and recommended for diagnostic use, which recognizes fully glycosylated MUC1. Based on the above, we propose a revision of the WHO Classification, specifying that antibodies against tumor associated MUC1 should be used for IPMN subtyping.     

Volatile Oil from Acorus gramineus Ameliorates the Injury Neurons in the Hippocampus of Amyloid Beta 1-42 Injected Mice

In recent years, the extraction fraction of volatile oil from Acorus gramineus has significant effects on anti-dementia and improving the learning and memory of animals. To date, limited studies have determined whether volatile oil from A. gramineus has the protective effect on neuronal damage. The aim of this study was to investigate the protective effects of volatile oil from A. gramineus on Alzheimer's disease (AD) mice, by means of behavior test, immunohistochemistry and western blot methods. In this study, mice were injected with Aβ_1-42 in the bilateral hippocampus to establish the AD model. On the seventh day after modeling, the mice with cognitive dysfunction were selected by the novel object recognition task. Subsequently, the volatile oil treatment groups underwent intragastric administration for per 10 g body weight 2.5 or 5 μL volatile oil from A. gramineus for 3 weeks. The control group and the AD group were given the same amount of saline. Our results showed that after treatment of volatile oil from A. gramineus, the number of Doublecortin and Nestin positive cells increased significantly, suggesting that the volatile oil from A. gramineus may induce the regeneration of hippocampal neurons in mice, and promote the growth of hippocampal neurons by upregulation of brain-derived neurotrophic factor, tyrosine protein kinase B, and neurotrophin-3 expression. These results might provide more experimental evidences for underlying mechanism about the neuroprotective effects of volatile oil from A. gramineus against AD relevant symptoms. Anat Rec, 302:2261–2270, 2019. © 2019 American Association for Anatomy