MORC2 gene encodes a ubiquitously expressed nuclear protein involved in chromatin remodeling, DNA repair, and transcriptional regulation. Heterozygous mutations in MORC2 gene have been associated with a spectrum of disorders affecting the peripheral nervous system such as Charcot-Marie-Tooth (CMT2Z), spinal muscular atrophy-like (SMA-like) with or without cerebellar involvement, and a developmental syndrome associated with impaired growth, craniofacial dysmorphism and axonal neuropathy (DIGFAN syndrome). Such variability in clinical manifestations associated with the increasing number of variants of unknown significance detected by next-generation sequencing constitutes a serious diagnostic challenge. Here we report the characterization of an in vitro model to evaluate the pathogenicity of variants of unknown significance based on MORC2 overexpression in a neuroblastoma cell line SH-EP or in cortical neurons. Likewise, we show that MORC2 mutants affect survival and trigger apoptosis over time in SH-EP cell line. Furthermore, overexpression in primary cortical neurons increases apoptotic cell death and decreases neurite outgrowth. Altogether, these approaches establish the pathogenicity of two new variants p.G444R and p.H446Q in three patients from two families. These new mutations in MORC2 gene are associated with autosomal dominant CMT and with adult late onset SMA-like phenotype, further increasing the spectrum of clinical manifestations associated with MORC2 mutations.

Cases of aspergillosis superinfection have been reported as acute complications of Covid-19. Here we report a case of combined chronic necrotizing pulmonary aspergillosis, aspergilloma and fibrosing aspergillosis in a 31-year-old woman with a history of Covid-19. This unusual association deserves special attention in a secondary immunocompromised patient after Covid-19.

Systemic juvenile idiopathic arthritis (sJIA, also called Still’s disease) is a rare childhood auto-inflammatory disease with significant morbidity. This case report illustrates the clinical course and highlights diagnostic challenges. FDG-PET/CT imaging may be beneficial in the diagnostic process for some cases, in order to achieve rapid diagnosis and early treatment.

Waldmann’s disease / Primary intestinal lymphangiectasia, is an unusual cause of protein losing enteropathy primarily characterized by lymphopenia, hypoalbuminemia and hypogammaglobulinemia. However, variable clinical presentation results in diagnostic dilemma and effective management. We present a toddler diagnosed with Waldmann’s disease managed with high protein diet and medium chain triglycerides supplementation.

A document by Gauthier Toutain. Click on the document to view its contents.

Sentinel lymph node mapping in patients with axillary breast carcinoma is technically challenging and poorly described in the literature. We report a patient with primary ectopic breast carcinoma of the axilla in whom concurrent peri-tumoral and intra-tumoral injection of radionuclide tracer allowed for identification and biopsy of sentinel lymph nodes.

Small cell osteosarcoma is a rare sub-type of osteogenic malignant tumors. Rib localization is uncommon. Histological examination is an important step to make the difference with similar tumors like Ewing sarcoma. Surgical resection is the unique curative treatment. Prognosis remains poor even with adjuvant treatment

In this paper we propose a numerical method for American multi-asset options under jump-diffusion model based on the combination of the exponential time differencing (ETD) technique for the differential operator and Gauss-Hermite quadrature for the integral term. In order to simplify the computational stencil and improve characteristics of the ETD-scheme mixed derivative eliminating transformation is applied. The results are compared with recently proposed methods.

Other editorials do not seem to include editorials. If you are sure you want one, let me know.

vHPvSD ablation represents a quantum leap from the RF settings that have traditionally been used in electrophysiology. If used to its full potential, it may improve procedural efficiency by reducing ablation and procedure times. However, with great power comes great responsibility; we need to ensure that we use it judiciously and safely.

Catheter based cardioneuroablation is increasingly being utilized to improve outcomes in patients with vasovagal syncope and functional atrioventricular block. There is now increasing convergence amongst enthusiasts on its various aspects, including patient selection, technical steps, and procedural end-points. This pragmatic review aims to take the reader through a step-by-step approach to cardioneuroablation: we begin with a brief overview of the anatomy of intrinsic cardiac autonomic nervous system, before focusing on the indications, pre- and post-procedure management, necessary equipment, and its potential limitations.

Through the comprehensive analysis of ab initio and experimental results of a large number of diatomic systems, the systematic deviation of ab initio method in vibrational energies prediction caused by physical/mathematical simplification is located. A joint ab initio and machine learning method based on information across molecules is proposed to deal with the problem. Starting from an ab initio model, and then systematically modifying it through machine learning, the vibrational energies prediction of many diatomic systems (SiC, HBr, NO, PC, N2, SiO, O2, ClF, etc.) have been improved, and significantly surpassed the more complex ab initio model. In addition to the improvement of accuracy, the new method also greatly reduces the computational expense, and is applicable for the systems without experimental data.

Title pageTitle: Letter to the Editor: Aortic valve repair in patients with ventricular septal defectArticle type: Letter to the editorDeepak RajaniContact: +923350326757 Email: [email protected]: Shaheed Mohtarma Benazir Bhutto Medical College Liyari,KarachiAddress: Maira garden,Garden west, KarachiCo-author: Zoaib Habib TharwaniContact: +923343975434 Email: [email protected]: Dow University of health Sciences (DUHS), Dow Medical College, KarachiAddress: Al-Yasrab, Garden East, KarachiSatesh KumarContact:+92-3325252902 Email: [email protected]: Shaheed Mohtarma Benazir Bhutto Medical College Liyari,KarachiAddress: Parsa citi near police headquarter Garden East Karachi

Cancer is one of the major health-related issues affecting the population worldwide and subsequently accounts for the second-largest death. Genetic and epigenetic modifications in oncogenes or tumor suppressor genes affect the regulatory systems that lead to the initiation and progression of cancer. Conventional methods, including chemotherapy/radiotherapy/appropriate combinational therapy and surgery, are being widely used for theranostics of cancer patients. Surgery is useful in treating localized tumors, but it is ineffective in treating metastatic tumors, which spread to other organs and result in a high recurrence rate and death. Also, the therapeutic application of free drugs is related to substantial issues such as poor absorption, solubility, bioavailability, high degradation rate, short shelf-life, and low therapeutic index. Therefore, these issues can be sorted out using nano lipid-based carriers (NLBCs) as promising drug delivery carriers. Still, at most, they fail to achieve site targeted drug delivery and detection. This can be achieved by selecting a specific ligand/antibody for its cognate receptor molecule expressed on the cancer cell surface. In this review, we have mainly discussed the various types of ligands used to decorate NLBCs. A list of the ligands used to design nanocarriers to target malignant cells specifically has been extensively undertaken, and the approved ligand decorated lipid-based nanomedicines with their clinical status has been explained in tabulated form to provide a wider scope to the readers regarding ligand coupled NLBCs.

Background: With the emergence of SARS-CoV-2, influenza surveillance systems in Spain were transformed into a new syndromic sentinel surveillance system. The Acute Respiratory Infection Surveillance System (SiVIRA in Spanish) is based on a sentinel network for Acute Respiratory Infection (ARI) surveillance in Primary care, and a network of sentinel hospitals for Severe ARI (SARI) surveillance in hospitals. Methods: Using a test-negative design and data from SARI admissions notified to SiVIRA between January 1 and October 3, 2021, we estimated COVID-19 VE against hospitalization, by age group, vaccine type, time since vaccination and SARS-CoV-2 variant. Results: VE was 89% (95% CI: 83-93) against COVID-19 hospitalization overall in persons aged 20 years and older. VE was higher for mRNA vaccines, and lower for those aged 80 years and older, with a decrease in protection beyond 3 months of completing vaccination, and a further decrease after 5 months. We found no differences between periods with circulation of Alpha or Delta SARS-CoV-2 variants, although variant-specific VE was slightly higher against Alpha. Conclusions: The SiVIRA surveillance system, with a network of sentinel hospitals in Spain was able to describe clinical and epidemiological characteristics of SARI hospitalizations, monitor the circulation of SARS-CoV-2 and other respiratory viruses, and provide data to measure the effectiveness of COVID-19 vaccination in the population under surveillance. Our results add to evidence of high VE of mRNA vaccines against severe COVID-19 and waning protection with time since vaccination.

We measured the content of nitrogen and phosphorus, as well as nitrogen stable isotopes in plant biomass and marmot faeces in a distance gradient up to 20 meters from marmot burrows in an extremely arid glacier valley in Eastern Pamir, Tajikistan. The goal of this study was to test well-known mechanisms of ecosystem engineering by burrowing animals in previously unstudied conditions. We captured aerial images of the area inhabited by marmots to study the spatial distribution of vegetation. There was no relationship between the presence of burrows and vegetation cover. Burrow mounds were not colonised by plants, as opposed to other ecosystems, where mounds are often microhabitats that enhance plant diversity. A significant increase in N and P in aboveground green plant biomass in the proximity of burrows was found in one out of six studied species. Stable N isotopes did not give further insight into N routing, contrary to our expectations. We assume that plant growth is strongly limited by water availability, which prevents them from utilizing the local increase in nutrients, certainly provided by marmot activity. The results are contrary to numerous studies which showed that the role of burrowing animals as ecosystem engineers increases with increasing abiotic stress, including aridity. This shows a lack of this type of study in the end of the gradient of abiotic factors.

Esomeprazole is a proton pump inhibitor being investigated for treatment of preeclampsia. Esomeprazole pharmacokinetics during pregnancy is unknown. We used data from 10 pregnant patients with preterm preeclampsia, and 49 non-pregnant individuals to develop a population pharmacokinetic model of esomeprazole. A two-compartment model described the data well. In pregnant patients after single dose, clearance was 42.2% (14.9%– 61.6%) lower compared to non-pregnant, most likely due to downregulation of CYP2C19. In non-pregnant after repeated dosing, clearance was 54.9% (48.2% – 63.5%) lower in extensive metabolizers and bioavailability was 33% (10.0% – 52.0%) higher compared to single dosing, which could be due to autoinhibition of CYP2C19. Esomeprazole pharmacokinetics during pregnancy appears to be more dependent on CYP3A4.

We evaluated uptake and factors associated with COVID-19 vaccination among health workers (HWs) in Azerbaijan. Among 1,575 HWs, 73% had received at least one dose and 67% received two doses; all received CoronaVac. Factors associated with vaccination uptake included no previous COVID-19 infection, older age, belief in the vaccine’s safety, previous vaccination for influenza, having patient-facing roles, and good or excellent health by self-assessment. These findings could inform strategies to increase vaccination uptake as the campaign continues.