Two novel AIRE mutations in autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) among Indians

Autoimmune polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED) is a rare recessive disorder resulting from mutations in the autoimmune regulator ( AIRE ) gene. There is no information on AIRE mutations in Indians. In a cross-sectional study, nine patients (eight families), from four referral hospitals in India, were studied for AIRE mutations by direct sequencing. We screened for new mutations in 150 controls by allele-specific PCR. The patients had 1–7 known components of APECED. Three patients had unusual manifestations: presentation with type 1 diabetes; chronic sinusitis and otitis media; and facial dysmorphism. All patients carried homozygous, probably recessive, AIRE mutations. Two unrelated patients from a small in-bred community (Vanika Vaisya) in south India carried an unreported missense mutation, p.V80G, in the N-terminal caspase recruitment domain. Another unique mutation, p.C302X, resulting in a truncated protein with deletion of both zinc-finger domains, was detected in a patient from Gujarat. Neither mutation was detected in controls. Other mutations, previously described in Caucasians, were: 13 base pair deletion (p.C322fsX372) in 4 (38%), and Finn-major (p.R257X) and p.R139X (Sardinian) mutation in one subject each. In conclusion, in this first series of APECED in Indians, we detected AIRE mutations previously reported in Caucasians, as well as unique mutations. Of these, p.V80G is possibly an ancestral mutation in an in-bred community.     

The structure of alcohol dependence in the community

BACKGROUND: Although dependence on alcohol appears to be a reliable unitary construct, abuse has not found a similar level of support as a separate construct. This paper describes a confirmatory factor analysis of the DSM-IV alcohol abuse and dependence criteria in a general population sample. METHODS: Data from alcohol drinkers (n = 7746) were obtained from a cross-sectional study of a large, representative sample of the Australian general population. One- and two-factor solutions for the DSM-IV criteria for abuse and dependence (assessed by CIDI-Auto) were compared using confirmatory factor analysis. RESULTS: Approximately 74% of Australians had used alcohol 12 or more times in the past year and 19% met at least one DSM-IV alcohol abuse or dependence criterion. Overall 6% met criteria for an alcohol use disorder (1.9% abuse, 4.1% dependence). More men than women met criteria for an alcohol use disorder and the prevalence of alcohol use disorders decreased with increasing age. Both one- and two-factor solutions from the confirmatory factor analyses provided an adequate fit to the data for the overall sample. The correlation between the abuse and dependence factors in the two-factor model was extremely high (0.95). CONCLUSION: Alcohol abuse and dependence criteria were most parsimoniously described by a single continuous construct incorporating all eleven abuse and dependence criteria.     

Does the publication of NICE guidelines for venous thromboembolism chemical prophylaxis influence the prescribing patterns of UK hip and knee surgeons?

IntroductionWe assessed the practice of surgeons regarding venous thromboembolism (VTE) chemical prophylaxis for total hip replacement (THR) and total knee replacement (TKR), before and after issuing of updated National Institute for Health and Care Excellence (NICE) guidance in 2018.MethodsA survey, circulated through the British Hip Society and regional trainee networks/collaboratives, was completed by 306 UK surgeons at 187 units. VTE chemical prophylaxis prescribing patterns for surgeons carrying out primary THR (n=258) and TKR (n=253) in low-risk patients was assessed after publication of 2018 NICE recommendations. Prescribing patterns before and after the NICE publication were subsequently explored.ResultsFollowing the new guidance, 34% (n=87) used low-molecular-weight heparin (LMWH) alone, 33% (n=85) aspirin (commonly preceded by LMWH) and 31% (n=81) direct oral anticoagulants (DOACs: with/without preceding LMWH) for THR. For TKR, 42% (n=105) used aspirin (usually monotherapy), 31% (n=78) LMWH alone and 27% (n=68) DOAC (with/without preceding LMWH). NICE guidance changed the practice of 34% of hip surgeons and 41% of knee surgeons, with significantly increased use of aspirin preceded by LMWH for THR (before=25% vs after=73%; p<0.001), and aspirin for TKR (before=18% vs after=84%; p<0.001). Significantly more regimens were NICE guidance compliant after the 2018 update for THR (before=85.7% vs after=92.6%; p=0.011) and TKR (before=87.0% vs after=98.8%; p<0.001).ConclusionOver one-third of surveyed surgeons changed their VTE chemical prophylaxis in response to 2018 NICE recommendations, with more THR and TKR surgeons now compliant with latest NICE guidance. The major change in practice was an increased use of aspirin for VTE chemical prophylaxis.     

Effects of electroacupuncture on gastric mucosal blood flow and transmucosal potential difference in stress rats

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Radiologically guided balloon dilation of gastrointestinal strictures. Part I. Technique and factors influencing procedural success

Radiologically guided balloon catheters were used to dilate 94 gastrointestinal strictures in 92 patients over a 6-year period. Fifty strictures were esophageal and 44 nonesophageal (22 gastroenterostomies, 11 antral-pyloric strictures, four colorectal strictures, four enteroenterostomies, and three miscellaneous strictures). Factors influencing the success of stricture intubation included patient age, stricture location (esophageal vs. nonesophageal and proximal vs. distal esophageal), and association with a surgical anastomosis. Malignancy was associated with greater postdilation irregularity and a smaller increase in stricture diameter, as measured radiographically. Procedural failures occurred in 8% of cases (2% of esophageal and 30% of nonesophageal lesions). Two small, asymptomatic mucosal tears were seen after dilation (one esophageal and one colonic); no other procedural complications occurred. Following successful dilation, 16 patients (17%; six with esophageal and ten with non-esophageal strictures) had recurrence of symptoms during short-term (30-day) follow-up.     

Non-ionic surfactant vesicles, niosomes, as a delivery system for the anti-leishmanial drug, sodium stibogluconate

Liver and serum concentrations of antimony in the mouse have been determined after administration of sodium stibogluconate in the free, liposomal and niosomal form. High liver and low serum values were attained by the use of both vesicular formulations. Niosomal sodium stibogluconate was shown to be more active than free drug against experimental murine visceral leishmaniasis, an effect apparently dependent on maintaining high drug levels in the infected reticuloendothelial system.