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

Autosomal recessive congenital ichthyosis: CERS3 mutations identified by a next generation sequencing panel targeting ichthyosis genes

There are at least 38 mutant genes known to be associated with the ichthyosis phenotypes, and autosomal recessive congenital ichthyosis (ARCI) is a specific subgroup caused by mutations in 13 different genes. Mutations in some of these genes, such as CERS3 with only two previous reports, are rare. In this study, we identified mutations in candidate genes in consanguineous families with ARCI with a next generation sequencing (NGS) array that incorporates 38 ichthyosis associated genes. We applied this sequencing array to DNA from 140 ichthyosis families with high prevalence of consanguinity. Among these patients we identified six distinct, previously unreported mutations in CERS3 in six Iranian families. These mutations in each family co-segregated with the ichthyosis phenotype. The patients demonstrated collodion membrane at birth, acrogeria, generalized scaling, and hyperlinearity of the palms and soles. The presence of a significant percentage of CERS3 mutations in our cohort depicts a marked difference between the etiology of ichthyoses in genetically poorly characterized regions and well-characterized western populations. Also, it shows that rare alleles are more prevalent in the gene pool of consanguineous populations and emphasizes the importance of these population studies for better understanding of ichthyosis pathogenesis

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

Mutational spectrum of autosomal recessive limb-girdle muscular dystrophies in a cohort of 112 Iranian patients and reporting of a possible founder effect

Background: Limb-girdle muscular dystrophies are a group of genetically heterogeneous diseases that are inherited in both autosomal dominant (LGMDD) and autosomal recessive forms (LGMDR), the latter is more common especially in populations with high consanguineous marriages like Iran. In the present study, we aimed to investigate the genetic basis of patients who are suspicious of being affected by LGMDR. DNA samples of 60 families suspected of LGMD were extracted from their whole blood. Four short tandem repeat (STR) markers for each candidate genes related to LGMD R1 (calpain3 related)- R6 (δ-sarcoglycan-related) were selected, and all these 24 STRs were applied in two sets of multiplex PCR. After autozygosity mapping, Sanger sequencing and variant analysis were done. Predicting identified variants' effect was performed using in-silico tools, and they were interpreted according to the American College of Medical Genomics and Genetics (ACMG) guideline. MLPA was used for those patients who had large deletions. Fresh muscle specimens were taken from subjects and were evaluated using the conventional panel of histochemical stains. Results: forty out of sixty families showed homozygote haplotypes in CAPN3, DYSF, SGCA, and SGCB genes. The exons and intron-exon boundaries of the relevant genes were sequenced and totally 38 mutations including CAPN3 (n = 15), DYSF (n = 9), SGCB (n = 11), and SGCA (n = 3) were identified. Five out of them were novel. The most prevalent form of LGMDs in our study was calpainopathy followed by sarcoglycanopathy in which beta-sarcoglycanopathy was the most common form amongst them. Exon 2 deletion in the SGCB gene was the most frequent mutation in this study. We also reported evidence of a possible founder effect in families with mutations in DYSF and SGCB genes. We also detected a large consanguineous family suffered from calpainopathy who showed allelic heterogeneity. Conclusions: This study can expand our knowledge about the genetic spectrum of LGMD in Iran, and also suggest the probable founder effects in some Iranian subpopulations which confirming it with more sample size can facilitate our genetic diagnosis and genetic counseling. © 2020 The Author(s)

Evaluation of the relative contribution of meteorological and oceanic forces to the drift of ice islands offshore Newfoundland

On 29 April 2015, four beacons were deployed onto an ice island in the Strait of Belle Isle to record positional data. The ice island later broke up into many fragments, four of which were tracked by the beacons. The relative influences of wind drag, current drag, Coriolis force, sea surface height gradient and sea-ice force on the drift of the tracked ice island fragments were analyzed. Using atmospheric and oceanic model outputs, the sea-ice force was calculated as the residual of the fragments' net forces and the sum of all other forces. This was compared against the force obtained through ice concentration-dependent relationships when sea ice was present. The sea-ice forces calculated from the residual approach and concentration-dependent relationships were significant only when sea ice was present at medium-high concentrations in the vicinity of the ice island fragments. The forces from ocean currents and sea surface tilt contributed the most to the drift of the

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

How increasingly powerful PRE modeling tools allow to unlock the full potential of FRP and RDRP in aqueous emulsion

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Estimating source-attributable health impacts of ambient fine particulate matter exposure: global premature mortality from surface transportation emissions in 2005

Exposure to ambient fine particular matter (PM2.5) was responsible for 3.2 million premature deaths in 2010 and is among the top ten leading risk factors for early death. Surface transportation is a significant global source of PM2.5 emissions and a target for new actions. The objective of this study is to estimate the global and national health burden of ambient PM2.5 exposure attributable to surface transportation emissions. This share of health burden is called the transportation attributable fraction (TAF), and is assumed equal to the proportional decrease in modeled ambient particulate matter concentrations when surface transportation emissions are removed. National population-weighted TAFs for 190 countries are modeled for 2005 using the MOZART-4 global chemical transport model. Changes in annual average concentration of PM2.5 at 0.5 × 0.67 degree horizontal resolution are based on a global emissions inventory and removal of all surface transportation emissions. Global population-weighted average TAF was 8.5 percent or 1.75 μg m−3 in 2005. Approximately 242 000 annual premature deaths were attributable to surface transportation emissions, dominated by China, the United States, the European Union and India. This application of TAF allows future Global Burden of Disease studies to estimate the sector-specific burden of ambient PM2.5 exposure. Additional research is needed to capture intraurban variations in emissions and exposure, and to broaden the range of health effects considered, including the effects of other pollutants

Limitations of spinal anesthesia for patient and surgeon during percutaneous nephrolithotomy

Purpose: To evaluate the intraoperative pain score of patients who undergo percutaneous nephrolithotomy under spinal anesthesia and to evaluate surgeons' and patients' convenience with this type of anesthesia. Materials and Methods: PCNL cases who were performed by two endourology fellows under spinal anesthesia during June to July 2014 were included. Spinal anesthesia was performed using injection of 0.25mg/kg bupivacaine 0.5 in the intrathecal space. All procedures were performed with the patient in the prone position. Stone access was made by using fluoroscopic guidance, and the tract was dilated using a single-stage technique. Visual analogue pain score was used to assess patients' pain during operation, immediately after, and 2 hours later. Results: 50 patients were enrolled during the study period. Visual analogue pain score of 10 and 8 were observed in 5 and three patients respectively. In two patients the operation was terminated because of patient anxiety and pain. In another patient a second access was not obtained to remove a staghorn stone because of patient's agitation. Gross agitation was observed in six patients. Apart from flank pain, intraoperative pain was felt in the flank, scapula, abdomen and/or chest. Conclusion: Spinal anesthesia does not provide enough analgesia for the patient in a limited frequency of percutaneous nephrolithotomy operations. We could not find statistically significant predictors of insufficient analgesia based on patients' demographics, stone characteristics or access location. © 2017, Urology and Nephrology Research Centre

Measurements of branching fraction ratios and CP-asymmetries in suppressed B^- -> D(-> K^+ pi^-)K^- and B^- -> D(-> K^+ pi^-)pi^- decays

We report the first reconstruction in hadron collisions of the suppressed decays B^- -> D(-> K^+ pi^-)K^- and B^- -> D(-> K^+ pi^-)pi^-, sensitive to the CKM phase gamma, using data from 7 fb^-1 of integrated luminosity collected by the CDF II detector at the Tevatron collider. We reconstruct a signal for the B^- -> D(-> K^+ pi^-)K^- suppressed mode with a significance of 3.2 standard deviations, and measure the ratios of the suppressed to favored branching fractions R(K) = [22.0 \pm 8.6(stat)\pm 2.6(syst)]\times 10^-3, R^+(K) = [42.6\pm 13.7(stat)\pm 2.8(syst)]\times 10^-3, R^-(K)= [3.8\pm 10.3(stat)\pm 2.7(syst]\times 10^-3, as well as the direct CP-violating asymmetry A(K) = -0.82\pm 0.44(stat)\pm 0.09(syst) of this mode. Corresponding quantities for B^- -> D(-> K^+ pi^-)pi^- decay are also reported.Comment: 8 pages, 1 figure, accepted by Phys.Rev.D Rapid Communications for Publicatio