Autosomal recessive deafness 1A (DFNB1A) in Yakut population isolate in Eastern Siberia: extensive accumulation of the splice site mutation IVS1+1G>A in GJB2 gene as a result of founder effect

Hereditary forms of hearing impairment (HI) caused by GJB2 (Cx26) mutations are the frequent sensory disorders registered among newborns in various human populations. In this study, we present data on the molecular, audiological and population features of autosomal recessive deafness 1A (DFNB1A) associated with the donor splicing site IVS1+1G>A mutation of GJB2 gene in Yakut population isolate of the Sakha Republic (Yakutia) located in Eastern Siberia (Russian Federation). The Yakut population exhibits high frequency of some Mendelian disorders, which are rare in other populations worldwide. Mutational analysis of GJB2 gene in 86 unrelated Yakut patients with congenital HI without other clinical features has been performed. In this study, we registered a large cohort of Yakut patients homozygous for the IVS1+1G>A mutation (70 unrelated deaf subjects in total). Detailed audiological analysis of 40 deaf subjects with genotype IVS1+1G>A/IVS1+1G>A revealed significant association of this genotype with mostly symmetrical bilateral severe to profound HI (85% severe-to-profound HI versus 15% mild-to-moderate HI, P<0.05). The highest among six investigated Eastern Siberian populations carrier frequency of the IVS1+1G>A mutation (11.7%) has been found in Yakut population. Reconstruction of 140 haplotypes with IVS1+1G>A mutation demonstrates the common origin of all mutant chromosomes found in Yakuts. The age of mutation was estimated to be approximately 800 years. These findings characterize Eastern Siberia as the region with the most extensive accumulation of the IVS1+1G>A mutation in the world as a result of founder effect.     

Dissociation versus posttraumatic stress: cortisol and physiological correlates in adults highly exposed to the World Trade Center attack on 9/11

Nine months on average after the World Trade Center (WTC) attack, 21 highly exposed adults and 10 healthy controls without major exposure did not differ in cortisol and physiologic measures. Dissociation and posttraumatic stress symptoms were quantified in the exposed group. Dissociation was associated with greater peritraumatic dissociation and, marginally, childhood trauma, lower plasma cortisol levels at 08.00h, and blunted heart rate reactivity to psychosocial stress. Posttraumatic stress was associated with exposure, peritraumatic distress, and early posttraumatic stress, and marginally associated with peritraumatic dissociation; it was not associated with cortisol or physiologic measures. Urinary cortisol differed significantly in its relationship to dissociation versus posttraumatic stress. This small study emphasizes the importance of dissecting the neurobiology of posttraumatic stress versus dissociative traumatic responses.     

Enlargement of umbilical incision in standard laparoscopic cholecystectomy is frequently necessary: An argument for the single incision approach?

Objective: Cosmetic result after cholecystectomy is up for debate. The aim of this study was to investigate the incidence and extent of enlargement of initial skin and fascia incision in standard laparoscopic cholecystectomy and to detect predictive factors for such an enlargement. Material and methods: The size of the umbilical incision was measured before and after standard laparoscopic gallbladder removal in 391 patients from August 2009 to October 2012. Predisposing factors for the need of enlargement of the umbilical incision were analysed. Results: Additional enlargement of the umbilical incision for gallbladder removal was required in 35.8% of the patients at skin level, and in 40.4% at fascia level. The median enlargement of the umbilical skin incision was 11 mm, from 25 mm to 36 mm. Gallbladder weight, total stone weight, maximum diameter of largest stone and shorter initial length of incision were independent predisposing factors for enlargement of the incision. Conclusions: In standard laparoscopic cholecystectomy the umbilical incision frequently requires secondary enlargement, especially if a large stone mass is involved. Therefore, the cosmetic result after laparoscopic cholecystectomy depends on more than only the technique used for access and the surgical technique for cholecystectomy should be chosen individually for each patient according to the stone mass.     

Mapping frailty in people living with HIV: A nationwide study in Greece

Objectives

Frailty is known to affect people living with HIV prematurely, compared to the ageing seronegative population. In this cross-sectional study, we aimed to assess frailty prevalence in people living with HIV in Greece and find associations of frailty criteria with clinical data.

Methods

Demographic and clinical data were collected from 477 participants in six HIV clinics. Fried's frailty phenotype was used to assess frailty prevalence, and participants were classified as frail, pre-frail or robust. Associations of several factors with overall frailty phenotype, as well as with frailty criteria, were explored.

Results

The median age was 43 years old (IQR = 51.5) and 444/477 (93%) were men. Most of the participants (429/477, 93.5%) had an undetectable HIV viral load, and a CD4 cell count over 500 cells/μl (366/477, 76.7%). Frailty assessment classified 285/477 (62.1%) as robust, 155/477 (33.8%) as pre-frail and 19/477 (4.1%) as frail. Weakness in grip strength was the most prevalent criterion (128/477, 26.8%), followed by exhaustion (46/477, 9.6%). Lower CD4 cell count, history of AIDS diagnosis, CNS disorders, psychiatric diagnoses, and polypharmacy were strongly associated with frailty.

Conclusions

Although the prevalence of frailty in people living with HIV in Greece is uncommon, when combined with pre-frailty over a third of people are affected, which requires attention in clinical practice. The physical and psychological aspects of frailty highlight the need for a holistic approach to prevent or counteract it. The diverse associations of frailty criteria with HIV-related and non-HIV-related factors suggest a possible variation in people's different healthcare needs.