Hereditary palmoplantar keratoderma - phenotypes and mutations in 64 patients

Background Hereditary palmoplantar keratodermas (PPK) represent a heterogeneous group of rare skin disorders with epidermal hyperkeratosis of the palms and soles, with occasional additional manifestations in other tissues. Mutations in at least 69 genes have been implicated in PPK, but further novel candidate genes and mutations are still to be found. Objectives To identify mutations underlying PPK in a cohort of 64 patients. Methods DNA of 48 patients was analysed on a custom-designed in-house panel for 35 PPK genes, and 16 patients were investigated by a diagnostic genetic laboratory either by whole-exome sequencing, gene panels or targeted single-gene sequencing. Results Of the 64 PPK patients, 32 had diffuse (50%), 19 focal (30%) and 13 punctate (20%) PPK. None had striate PPK. Pathogenic mutations in altogether five genes were identified in 31 of 64 (48%) patients, the majority (22/31) with diffuse PPK. Of them, 11 had a mutation in AQP5, five in SERPINB7, four in KRT9 and two in SLURP1. AAGAB mutations were found in nine punctate PPK patients. New mutations were identified in KRT9 and AAGAB. No pathogenic mutations were detected in focal PPK. Variants of uncertain significance (VUS) in PPK-associated and other genes were observed in 21 patients that might explain their PPK. No suggestive pathogenic variants were found for 12 patients. Conclusions Diffuse PPK was the most common (50%) and striate PPK was not observed. We identified pathogenic mutations in 48% of our PPK patients, mainly in five genes: AQP5, AAGAB, KRT9, SERPINB7 and SLURP1.Peer reviewe

Migraine patients should be cautiously followed for risk factors leading to cardiovascular disease

Migraine and ischemic strokes are two of the most prevalent diseases worldwide. Besides having a coincident symptomatology, for long researchers have been searching for a possible causal relation between these diseases. Current evidence based on data suggest that patients with aura migraine could have a doubled risk of developing an ischemic stroke, when compared to the rest of the population. At the same time, migraine sufferers apparently have higher incidences of risk factors for cardiovascular events. The aim of this review was not only to dissect some of the more compelling evidence based on data regarding this association, but also to discuss the possible clinical and therapeutic implications

Age and frailty are independently associated with increased COVID-19 mortality and increased care needs in survivors: results of an international multi-centre study

Introduction Increased mortality has been demonstrated in older adults with coronavirus disease 2019 (COVID-19), but the effect of frailty has been unclear. Methods This multi-centre cohort study involved patients aged 18 years and older hospitalised with COVID-19, using routinely collected data. We used Cox regression analysis to assess the impact of age, frailty and delirium on the risk of inpatient mortality, adjusting for sex, illness severity, inflammation and co-morbidities. We used ordinal logistic regression analysis to assess the impact of age, Clinical Frailty Scale (CFS) and delirium on risk of increased care requirements on discharge, adjusting for the same variables. Results Data from 5,711 patients from 55 hospitals in 12 countries were included (median age 74, interquartile range [IQR] 54–83; 55.2% male). The risk of death increased independently with increasing age (>80 versus 18–49: hazard ratio [HR] 3.57, confidence interval [CI] 2.54–5.02), frailty (CFS 8 versus 1–3: HR 3.03, CI 2.29–4.00) inflammation, renal disease, cardiovascular disease and cancer, but not delirium. Age, frailty (CFS 7 versus 1–3: odds ratio 7.00, CI 5.27–9.32), delirium, dementia and mental health diagnoses were all associated with increased risk of higher care needs on discharge. The likelihood of adverse outcomes increased across all grades of CFS from 4 to 9. Conclusion Age and frailty are independently associated with adverse outcomes in COVID-19. Risk of increased care needs was also increased in survivors of COVID-19 with frailty or older age

Search for a Higgs boson decaying into a b-quark pair and produced in association with b quarks in proton-proton collisions at 7 TeV

A search for a neutral Higgs boson decaying to a pair of b quarks, and produced in association with at least one additional b quark, is presented. Multijet final states with three jets identified as originating from b quarks, at least one of which may include a non-isolated muon, are studied. The data used in this analysis correspond to an integrated luminosity of 2.7-4.8 fb(-1), collected by the CMS experiment in proton-proton collisions at the LHC at a center-of-mass energy of 7 TeV. This search is particularly sensitive to Higgs bosons in scenarios of the Minimal Supersymmetric Model (MSSM) with large values of tan beta. No excess over the predicted background from standard model processes is observed. Stringent upper limits on cross section times branching fraction are derived and interpreted as bounds in the MSSM tan beta and m(A) parameter-space. Observed 95% confidence level upper limits reach as low as tang beta approximate to 18 for M-A approximate to 100 GeV

Measurement of the t(t)over-bar production cross section in pp collisions at root s=7 TeV in dilepton final states containing a tau

The top quark pair production cross section is measured in dilepton events with one electron or muon, and one hadronically decaying tau lepton from the decay t (t) over bar -> (l nu(l))((sic)(h)nu((sic)))b (b) over bar, (l = e, mu). The data sample corresponds to an integrated luminosity of 2.0 fb(-1) for the electron channel and 2.2 fb(-1) for the muon channel, collected by the CMS detector at the LHC. This is the first measurement of the t (t) over bar cross section explicitly including tau leptons in proton- proton collisions at root s = 7 TeV. The measured value sigma(t (t) over bar) = 143 +/- 14(stat) +/- 22(syst) +/- 3(lumi) pb is consistent with the standard model predictions

Search for new physics in events with same-sign dileptons and b jets in pp collisions at root s=8 TeV

A search for new physics is performed using events with isolated same-sign leptons and at least two bottom-quark jets in the final state. Results are based on a sample of proton-proton collisions collected at a center-of-mass energy of 8TeV with the CMS detector and corresponding to an integrated luminosity of 10.5 fb(-1). No excess above the standard model background is observed. Upper limits are set on the number of events from non-standard-model sources and are used to constrain a number of new physics models. Information on acceptance and efficiencies is also provided so that the results can be used to confront an even broader class of new physics models

Search for top-squark pair production in the single-lepton final state in pp collisions at

This paper presents a search for the pair production of top squarks in events with a single isolated electron or muon, jets, large missing transverse momentum, and large transverse mass. The data sample corresponds to an integrated luminosity of 19.5 fb(-1) of pp collisions collected in 2012 by the CMS experiment at the LHC at a center-of-mass energy of . No significant excess in data is observed above the expectation from standard model processes. The results are interpreted in the context of supersymmetric models with pair production of top squarks that decay either to a top quark and a neutralino or to a bottom quark and a chargino. For small mass values of the lightest supersymmetric particle, top-squark mass values up to around 650 GeV are excluded

Search for a W ' or Techni-rho Decaying into WZ in pp Collisions at root s=7 TeV

A search is performed in pp collisions at root s 7 TeV for exotic particles decaying via WZ to final states with electrons and muons. The data sample corresponds to an integrated luminosity of approximately 5 fb(-1). No significant excess is observed in the data above the expected standard model background. Upper bounds at 95% confidence level are set on the production cross section of the W' boson described by the sequential standard model and on the W' WZ coupling. W' bosons with masses below 1143 GeV are excluded. Limits are also set in the context of low-scale technicolor models, under a range of assumptions concerning the model parameters

Search for new physics in events with opposite-sign leptons, jets, and missing transverse energy in pp collisions at root s=7 TeV

A search is presented for physics beyond the standard model (BSM) in final states with a pair of opposite-sign isolated leptons accompanied by jets and missing transverse energy. The search uses LHC data recorded at a center-of-mass energy root s = 7 TeV with the CMS detector, corresponding to an integrated luminosity of approximately 5 fb(-1). Two complementary search strategies are employed. The first probes models with a specific dilepton production mechanism that leads to a characteristic kinematic edge in the dilepton mass distribution. The second strategy probes models of dilepton production with heavy, colored objects that decay to final states including invisible particles, leading to very large hadronic activity and missing transverse energy. No evidence for an event yield in excess of the standard model expectations is found. Upper limits on the BSM contributions to the signal regions are deduced from the results, which are used to exclude a region of the parameter space of the constrained minimal supersymmetric extension of the standard model. Additional information related to detector efficiencies and response is provided to allow testing specific models of BSM physics not considered in this Letter. (C) 2012 CERN. Published by Elsevier B.V. All rights reserved