Novel mutations in the BRCA1 and BRCA2 genes in Iranian women with early-onset breast cancer

BACKGROUND: Breast cancer is the most common female malignancy and a major cause of death in middle-aged women. So far, germline mutations in the BRCA1 and BRCA2 genes in patients with early-onset breast and/or ovarian cancer have not been identified within the Iranian population. METHODS: With the collaboration of two main centres for cancer in Iran, we obtained clinical information, family history and peripheral blood from 83 women under the age of 45 with early-onset breast cancer for scanning of germline mutations in the BRCA1 and BRCA2 genes. We analysed BRCA1 exons 11 and BRCA2 exons 10 and 11 by the protein truncation test, and BRCA1 exons 2, 3, 5, 13 and 20 and BRCA2 exons 9, 17, 18 and 23 with the single-strand conformation polymorphism assay on genomic DNA amplified by polymerase chain reaction. RESULTS: Ten sequence variants were identified: five frameshifts (putative mutations – four novel); three missense changes of unknown significance and two polymorphisms, one seen commonly in both Iranian and British populations. CONCLUSIONS Identification of these novel mutations suggests that any given population should develop a mutation database for its programme of breast cancer screening. The pattern of mutations seen in the BRCA genes seems not to differ from other populations studied. Early-onset breast cancer (less than 45 years) and a limited family history is sufficient to justify mutation screening with a detection rate of over 25% in this group, whereas sporadic early-onset breast cancer (detection rate less than 5%) is unlikely to be cost-effective

Investigating Ca II emission in the RS CVn binary ER Vulpeculae using the Broadening Function Formalism

The synchronously rotating G stars in the detached, short-period (0.7 d), partially eclipsing binary, ER Vul, are the most chromospherically active solar-type stars known. We have monitored activity in the Ca II H & K reversals for almost an entire orbit. Rucinski's Broadening Function Formalism allows the photospheric contribution to be objectively subtracted from the highly blended spectra. The power of the BF technique is also demonstrated by the good agreement of radial velocities with those measured by others from less crowded spectral regions. In addition to strong Ca II emission from the primary and secondary, there appears to be a high-velocity stream flowing onto the secondary where it stimulates a large active region on the surface 30 - 40 degrees in advance of the sub-binary longitude. A model light curve with a spot centered on the same longitude also gives the best fit to the observed light curve. A flare with approximately 13% more power than at other phases was detected in one spectrum. We suggest ER Vul may offer a magnified view of the more subtle chromospheric effects synchronized to planetary revolution seen in certain `51 Peg'-type systems.Comment: Accepted to AJ; 17 pages and 16 figure

Ultrasound - guided access during percutaneous nephrolithotomy: Entering desired calyx with appropriate entry site and angle

Objectives: To evaluate the success of ultrasonography directed renal access in entering the target calyx from proper entry site and in the direction of renal pelvis during percutaneous nephrolithotomy (PCNL). Materials and Methods: PCNL cases who were operated on by one fellow from May- June 2014 were included in this study. A vertically placed ultrasound probe on the patient flank in prone position was used to identify the preselected target calyx. Needle was advanced through needle holder and fluoroscopy was used to document the entered calyx, site and angle of entry. Results: Successful entering to the target calyx was achieved in 43 cases (91). Successful entry with appropriate entry site and angle was observed in 34 cases (72). Reasons for failure were minimal hydronephrosis, upper pole access and high lying kidneys. Conclusions: Although it is feasible to access a preselected calyx by ultrasonography guidance during PCNL, but entry to the calyx from the appropriate site and direction is another problem and needs more experience. In cases of minimal hydronephrosis, superior pole access or high lying kidneys, ultrasonography is less successful and should be used with care

Lessons of 10 years experience on CCHF in Iran

International audienceCrimean-Congo Hemorrhagic Fever (CCHF) is a viral zoonotic disease with high mortality rate in humans caused by CCHF virus (CCHFV) belonging to the genus Nairovirus, family Bunyaviridae, and congaing a three segment single-stranded RNA genome. The CCHFV is transmitted to humans by bite of infected ticks, by direct contact with blood or tissues of infected livestock and nosocomially. After Chaharmahal-va-Bakhtiari outbreak in 1999 whose serum samples was sent to South Africa for diagnosis, Arboviruses and Viral Hemorrhagic Fevers Laboratory (As National Reference Lab) was established in 2000 to precise and on time laboratory diagnosis of CCHF in the country. The Lab along with CDC of Iran (national health regulator) and Veterinary organization (control program of tick populations and livestock monitoring) are members of National Expert Committee on Viral Hemorrhagic Fevers (NECVHFs) for surveillance and control of CCHF in Ir

Recessive mutation in tetraspanin CD151 causes Kindler syndrome-like epidermolysis bullosa with multi-systemic manifestations including nephropathy

Epidermolysis bullosa (EB) is caused by mutations in as many as 19 distinct genes. We have developed a next-generation sequencing (NGS) panel targeting genes known to be mutated in skin fragility disorders, including tetraspanin CD151 expressed in keratinocytes at the dermal-epidermal junction. The NGS panel was applied to a cohort of 92 consanguineous families of unknown subtype of EB. In one family, a homozygous donor splice site mutation in CD151 (NM_139029; c.351 + 2T > C) at the exon 5/intron 5 border was identified, and RT-PCR and whole transcriptome analysis by RNA-seq confirmed deletion of the entire exon 5 encoding 25 amino acids. Immunofluorescence of proband's skin and Western blot of skin proteins with a monoclonal antibody revealed complete absence of CD151. Transmission electron microscopy showed intracellular disruption and cell-cell dysadhesion of keratinocytes in the lower epidermis. Clinical examination of the 33-year old proband, initially diagnosed as Kindler syndrome, revealed widespread blistering, particularly on pretibial areas, poikiloderma, nail dystrophy, loss of teeth, early onset alopecia, and esophageal webbing and strictures. The patient also had history of nephropathy with proteinuria. Collectively, the results suggest that biallelic loss-of-function mutations in CD151 underlie an autosomal recessive mechano-bullous disease with systemic features. Thus, CD151 should be considered as the 20th causative, EB-associated gene

Experimental study of fire containment using water mist curtains in a reduced-scale deck of a ro-ro ship

Experiments have been conducted to evaluate the containment of smoke and heat using water mist curtains in a model setup of a ro-ro ship's cargo deck with a scale of 1:13, providing practical insights into the application of such fire protection systems in the cargo deck as well as valuable data for future numerical simulations. In this regard, the requirements of the international convention of Safety of Life at Sea (SOLAS) are studied for the side openings of so-called ‘open decks’ in comparison with ‘closed decks’, especially to examine the feasibility of using water mist curtains for creating isolated subdivisions in the ro-ro space as a fire management strategy. The water mist curtains are created with one or two rows of water mist nozzles at pressures ranging from 3 to 8 bar, while the source of smoke and heat is a liquid pool fire, and inert cargo items are used in some experiments. Correspondingly, the interaction between the water mist curtain(s) and the fire is evaluated in terms of its heat release rate, and the containment effect is quantified via measurements of smoke flow through the deck and through the windows, concentrations of gaseous species, as well as gas temperatures at various key locations. The study shows that water mist curtains have a strong effect on fire dynamics and smoke propagation, but containment is dependent on the configuration of side openings and the location of fire, among other important factors