Deleuraniqbal5420

BACKGROUND A blunted heart rate reserve (HRR) during dipyridamole stress echocardiography (DSE) is a prognostically unfavorable sign of cardiac autonomic dysfunction. Short-term adjustments of heart rate (HR) are thought to rise from changes in neural input to the heart. DSE is applied in potential heart donors to rule out underlying coronary artery disease and left ventricular dysfunction. AIM to assess HRR during DSE in brain death. METHODS We enrolled 2 Groups Group 1 (n=49, 22 men, 54.6±8.8 years) with patients in brain death enrolled in the nationwide marginal donor heart recruiting program; Group 2 (n=49, 18 men, 66.4±12.0 years) referred to DSE for suspected or known coronary artery disease. All underwent DSE (0.84 mg/kg in 6') by quality-controlled readers certified via web-based training (1487/CE Lazio-1). We assessed left ventricular contractile reserve (LVCR) as stress/rest ratio of force (systolic blood pressure /end-systolic volume). HRR was calculated as the peak/rest HR ratio from 12-lead EKG. RESULTS The 2 groups were similar for prevalence of inducible ischemia (4/49 vs 9/49, p=ns). Group 1 showed higher resting HR (Group 1= 88.1±15.5 vs Group 2= 66.5±11.5 bpm, p less then 0.01) and similar peak HR (Group 1=94.7±15.3 vs Group 2=89.5±19.3 bpm, p=0.144), with blunted HRR (Group 1= 1.08±0.10 vs Group 2= 1.36±0.31 bpm, p less then 0.01). HRR was unrelated to LVCR. CONCLUSIONS HRR is almost abolished and unrelated to LVCR in brain-dead patients during DSE. The modulation of neural input to the heart is essential to determine HRR, and plays no significant role in determining the inotropic response during DSE.BACKGROUND Disease Management Programs (DMPs) for heart failure (HF) patients have been developed to better control patients' well-being as well as their daily drug intake. DMPs for HF are not always accepted by the patients, and the reasons for this phenomenon are largely unknown. We hypothesized that patients from rural areas accept a DMP more likely than patients living in a big city. Thus, a pilot study investigated differences in the attitude towards DMPs between HF-patients in one rural and one urban hospital in Austria. METHODS Patients admitted because of HF to 2 hospitals, one with rural and one with urban populations, were included prospectively by using a questionnaire. RESULTS Included were 60 patients, 43% females with a mean age of 76 years, in each hospital 30 patients. Rural patients were more interested in a nurse-based DMP than urban (n=30) (p=0.029). After discharge, urban patients planned more often to attend a specialist than rural (p=0.005). No differences were found regarding gender, age, willingness to be included into a telenursing-based program and estimation of knowledge about HF. CONCLUSIONS Structures of the health care system and patients' attitudes must be considered when planning DMPs. Development of DMPs which are accepted by urban patients will be relevant for the future.Graft-versus-host disease (GvHD) is a commonly occurring immunological reaction and frequent complication following allogeneic hematopoietic stem cell transplantation. Its highly diverse manifestations including skin involvement as the most common appearance of GvHD, can dramatically influence patient's quality of life, in particular in the chronic stage, in addition to patient's decreased survival outcome. Hence, the role of the dermatologist has become very crucial in an interdisciplinary setting, particularly since appearances of GvHD in the skin can be multifaceted and challenging. Clinical manifestation of the acute GvHD (aGvHD) is limited to erythematous maculopapular rash and oral mucosal lesions while the chronic form manifests in a wider range in a localized area or disseminated including involvement of nail, scalp and genital area. This article aims to provide a comprehensive overview on the variable cutaneous presentations of acute and chronic GvHD for a proper and early diagnosis on the one hand, and to discuss updated therapeutic options for both acute and chronic GvHD on the other hand, to initiate an adequate treatment to obtain the most beneficial clinical outcome.Nevus-associated melanoma (NAM) is defined on histopathological basis by the coexistence of melanoma and nevus components. Melanomas developing on pre-existing congenital or acquired nevi are usually of the superficial spreading subtype and harbor the BRAFV600E mutation. NAM accounts for almost one-third of melanoma cases As compared to de novo melanoma, NAM develops on younger patients, is more frequently located on the trunk, and is associated with a high nevus count, light eye color and history of frequent sunburns. NAM has been regarded as a model to investigate melanoma origin. Molecular analysis defining the mutation profile of NAM's nevus and melanoma components supported the existence of two pathways of melanoma development, the first not involving clinically visible precursors, the second involving melanocytic nevi as precursors. Concerning diagnosis, dermatoscopy may identify nevus and melanoma components when located side-by-side, but no specific criteria have been described when superimposed. In-vivo reflectance confocal microscopy significantly enhances the recognition of NAM by allowing the detection of nevus remnants when superficially located. Regarding prognosis, NAM is generally thinner and more frequently in-situ than de-novo melanoma. Furthermore, studies reporting survival analysis demonstrated a trend towards better overall, distant-metastasis-free and recurrence-free survival. Although a clinical, phenotypic and molecular profile of NAM has been defined, controversies still exist. In the current review, we widely report and discuss facts and controversies on NAM.BACKGROUND/AIMS Mitochondrial ATP synthase, in addition to being involved in ATP synthesis, is involved in permeability transition pore (PTP) formation, which precedes apoptosis in mammalian cells and programmed cell death in yeast. Mutations in genes encoding ATP synthase subunits cause neuromuscular disorders and have been identified in cancer samples. PTP is also involved in pathology. We previously found that in Saccharomyces cerevisiae, two mutations in ATP synthase subunit a (atp6-P163S and atp6-K90E, equivalent to those detected in prostate and thyroid cancer samples, respectively) in the OM45-GFP background affected ROS and calcium homeostasis and delayed yeast PTP (yPTP) induction upon calcium treatment by modulating the dynamics of ATP synthase dimer/oligomer formation. The Om45 protein is a component of the porin complex, which is equivalent to mammalian VDAC. buy Dubermatinib We aimed to investigate yPTP function in atp6-P163S and atp6-K90E mutants lacking the e and g dimerization subunits of ATP synthase. METHODST215C stabilized ATP synthase dimers and restored the yPTP properties in Tim11∆ cells. In OM45-GFP cells, in which Tim11 is present, these mutations increased the fraction of swollen mitochondria by up to 85% vs 60% in the wild type, although the time required for calcium release doubled. CONCLUSION ATP synthase subunit e is essential in the S. cerevisiae atp6-P163S and atp6-K90E mutants. In addition to subunits e and g, subunit a is critical for yPTP induction and conduction. The increased yPTP conduction decrease the S. cerevisiae cell fitness. © Copyright by the Author(s). Published by Cell Physiol Biochem Press.Heart failure (HF) is rapidly growing, conferring considerable mortality, morbidity, and costs. Dedicated HF clinics improve patient outcomes, and the development of a national HF clinics network aims at addressing this need at national level. Such a network should respect the existing health care infrastructures, and according to the capacities of hosting facilities, it can be organized into three levels. Establishing the continuous communication and interaction among the components of the network is crucial, while supportive actions that can enhance its efficiency include involvement of multidisciplinary health care professionals, use of structured HF-specific documents, such as discharge notes, patient information leaflets, and patient booklets, and implementation of an HF-specific electronic health care record and database platform. © 2020 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of the European Society of Cardiology.BACKGROUND Agnathia-otocephaly is a rare and lethal anomaly affecting craniofacial structures derived from the first pharyngeal arch. It is characterized by agnathia, microstomia, aglossia, and abnormally positioned auricles with or without associated anomalies. Variants affecting function of OTX2 and PRRX1, which together regulate the neural crest cells and the patterning of the first pharyngeal arch as well as skeletal and limb development, were identified to be causal for the anomaly in a few patients. METHODS Family-based exome sequencing (ES) on a fetus with severe agnathia-otocephaly, cheilognathopalatoschisis, laryngeal hypoplasia, fused lung lobes and other organ abnormalities and mRNA expression analysis were performed. RESULTS Exome sequencing detected a de novo SMAD3 missense variant in exon 6 (c.860G>A) associated with decreased mRNA expression. Variants in SMAD3 cause Loeys-Dietz syndrome 3 presenting with craniofacial anomalies such as mandibular hypoplasia, micro- or retro-gnathia, bifid uvula and cleft palate as well as skeletal anomalies and arterial tortuosity. The SMAD3 protein acts as a transcriptional regulator in the transforming growth factor β (TGFB) and bone morphogenetic (BMP) signaling pathways, which play a key role in the development of craniofacial structures originating from the pharyngeal arches. CONCLUSION Agnathia-otocephaly with or without associated anomalies may represent the severe end of a phenotypic spectrum related to variants in genes in the interacting SMAD/TGFB/BMP/SHH/FGF developmental pathways. © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.BACKGROUND Panel-based targeted exome sequencing was used to analyze the genetic and clinical findings of targeted genes in a cohort of northeast Chinese with retinitis pigmentosa. METHODS A total of 87 subjects, comprising 23 probands and their family members (total patients 32) with confirmed retinitis pigmentosa were recruited in the study. Panel-based targeted exome sequencing was used to sequence the patients and family members, all subjects with retinitis pigmentosa underwent a complete ophthalmologic examination. RESULTS Of the 23 probands, the clinical manifestations include night blindness, narrowing of vision, secondary cataracts, choroidal atrophy, color blindness, and high myopia, the average age of onset of night blindness is 12.9 ± 14 (range, 0-65; median, 8). Posterior subcapsular opacities is the most common forms of secondary cataracts (nine cases, 39.1%), and peripheral choroidal atrophy is the most common form of secondary choroidal atrophy (12 cases, 52.2%). Of these probands with complical mutations, recognized different combinations forms of variants, and extended the mutational spectrum of retinitis pigmentosa and depicted common variants in northeast China. © 2020 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc.