Efficacy of BNT162b2 and CoronaVac in patients diagnosed with COVID-19

This retrospective observational study is aimed to determine the efficacy of BNT162b2 (Pfizer-BioNTech) and CoronaVac (Sinovac) vaccines against symptomatic or severe disease in COVID-19-diagnosed patients. The secondary aim was to define the differences between vaccinated and un-vaccinated patients in terms of age, comorbidities and course of the disease, and to determine the survival rates. Of the 1463 PCR-positive patients, 55.3 % were vaccinated, and 44.7 % were unvaccinated. While 959 patients had mild-moderate symptoms, 504 patients had severe-critical symptoms and were treated in the intensive care unit. There was a statistically significant difference in the distribution of the type and doses of vaccines between the patient groups (p = 0.021). The rate of receiving 2 doses of Biontech was 18.9 % in the mild-moderate patient group but lower in the severe patient group (12.6 %). The rate of two doses of Sinovac and two doses of Biontech vaccine (four doses of vaccine) was 5 % in the mild-moderate patient group and 1.9 % in the severe patient group. The mortality rates were statistically significantly different (p < 0.001) between the patient groups: 65.3 % in the severe patient group and 1 % in the mild-moderate patient group. The multivariate model showed that the mortality risk of the unvaccinated patients was 1.5 times higher than the vaccinated ones (p = 0.042). In addition to being unvaccinated, advanced age, coronary artery disease (CAD), diabetes mellitus (DM), chronic obstructive pulmonary disease (COPD), chronic kidney disease (CKD), and obesity were found to be associated with higher mortality risk. Besides, the reduction in mortality rate was more evident in individuals vaccinated with at least 2 doses of the BNT162b2 (Pfizer-BioNTech) vaccine than in CoronaVac group

Targeting the liver to treat the eye

Over the last two decades, gene therapy has given hope of potential cure for many rare diseases. In the simplest form, gene therapy is the transfer or editing of a genetic material to cure a disease via nonviral or viral vehicles. Gene therapy can be performed either in vivo by injecting a vector carrying the gene or tools for gene editing directly into a tissue or into the systemic circulation, or ex vivo when patient cells are genetically modified outside of the body and then introduced back into the patient (Yilmaz et al, 2022). Adeno-associated viral vectors (AAV) have been the vectors of choice for in vivo gene therapy. There has been a lot of promising research on the development of novel tissue and cell-specific serotypes in order to improve efficacy and safety for clinical applications (Kuzmin et al, 2021). In this issue of EMBO Molecular Medicine, Boffa and colleagues present a novel AAV-based liver-directed gene therapy for ornithine aminotransferase deficiency

AAV-mediated gene therapy for rare metabolic disorders: turning a promise into a reality

Gene therapy is emerging as the realistic treatment option for inborn errors of metabolism (IEMs) and, with the promising safety and efficacy evidence from the proof-of-concept studies, adeno-associated virus (AAV) has become the frontrunner among viral vector candidates for these monogenic disorders. Different AAV capsids exhibit specific tissue tropisms, which can considerably increase the efficiency of gene transfer to particular organs. Here, we will discuss two distinct diseases: ornithine transcarbamylase (OTC) deficiency and Niemann–Pick disease type C, in which significant advances have been achieved in AAV-based gene therapy trials

Genetic Therapy Approaches for Ornithine Transcarbamylase Deficiency

Ornithine transcarbamylase deficiency (OTCD) is the most common urea cycle disorder with high unmet needs, as current dietary and medical treatments may not be sufficient to prevent hyperammonemic episodes, which can cause death or neurological sequelae. To date, liver transplantation is the only curative choice but is not widely available due to donor shortage, the need for life-long immunosuppression and technical challenges. A field of research that has shown a great deal of promise recently is gene therapy, and OTCD has been an essential candidate for different gene therapy modalities, including AAV gene addition, mRNA therapy and genome editing. This review will first summarise the main steps towards clinical translation, highlighting the benefits and challenges of each gene therapy approach, then focus on current clinical trials and finally outline future directions for the development of gene therapy for OTCD

Symptomatic and asymptomatic candidiasis in a pediatric intensive care unit

<p>Abstract</p> <p>Introduction</p> <p>This study aimed to examine the incidence, epidemiology, and clinical characteristics of symptomatic and asymptomatic candidiasis in a pediatric intensive care unit (PICU), and to determine the risk factors associated with symptomatic candidiasis.</p> <p>Methods</p> <p>This retrospective study included 67 patients from a 7-bed PICU in a tertiary care hospital that had Candida-positive cultures between April 2007 and July 2009. Demographic and clinical characteristics of the patients, Candida isolates, antimicrobial and antifungal treatments, and previously identified risk factors for symptomatic candidiasis were recorded, and symptomatic and asymptomatic patients were compared.</p> <p>Results</p> <p>In all, 36 (53.7%) of the patients with Candida-positive cultures had asymptomatic candidiasis and 31 (46.3%) had symptomatic candidiasis. Candida albicans was the most common Candida sp. in the asymptomatic patients (n = 20, 55.6%), versus Candida parapsilosis in the symptomatic patients (n = 15, 48.4%). The incidence of central venous catheter indwelling, blood transfusion, parenteral nutrition, and surgery was higher in the symptomatic patient group than in the asymptomatic patient group (P < 0.5). Surgery was the only independent predictor of symptomatic candidiasis according to forward stepwise multivariate logistic regression analysis (OR: 6.1; 95% CI: 1.798-20.692).</p> <p>Conclusion</p> <p>Surgery was the only risk factor significantly associated with symptomatic candidiasis and non-albicans Candida species were more common among the patients with symptomatic candidiasis. While treating symptomatic candidiasis in any PICU an increase in the incidence of non-albicans candidiasis should be considered.</p

Diagnostic and Management Issues in Patients with Late-Onset Ornithine Transcarbamylase Deficiency

Ornithine transcarbamylase deficiency (OTCD) is the most common inherited disorder of the urea cycle and, in general, is transmitted as an X-linked recessive trait. Defects in the OTC gene cause an impairment in ureagenesis, resulting in hyperammonemia, which is a direct cause of brain damage and death. Patients with late-onset OTCD can develop symptoms from infancy to later childhood, adolescence or adulthood. Clinical manifestations of adults with OTCD vary in acuity. Clinical symptoms can be aggravated by metabolic stressors or the presence of a catabolic state, or due to increased demands upon the urea. A prompt diagnosis and relevant biochemical and genetic investigations allow the rapid introduction of the right treatment and prevent long-term complications and mortality. This narrative review outlines challenges in diagnosing and managing patients with late-onset OTCD

Prolonged respiratory failure responds to conventional therapy in isolated homocysteine remethylation defects

Isolated remethylation defects are rare inherited diseases caused by a defective remethylation of homocysteine to methionine, preventing various essential methylation reactions to occur. Patients present with a systemic phenotype, which can especially affect the central and peripheral nervous systems leading to epileptic encephalopathy, developmental delay and peripheral neuropathy. Respiratory failure has been described in some cases, caused by both central and peripheral neurological involvement. In published cases, the genetic diagnosis and initiation of appropriate therapy were rapidly performed following respiratory failure and led to a rapid recovery of respiratory insufficiency within days. Here, we present two infantile-onset cases of isolated remethylation defects, cobalamine (Cbl)G and methylenetetrahydrofolate reductase (MTHFR) deficiencies, which were diagnosed after several months of respiratory failure. Disease modifying therapy based on hydroxocobalamin and betaine was initiated and shows a progressive improvement and enabled weaning off respiratory support after 21 and 17 months in CblG and MTHFR patients respectively. We show that prolonged respiratory failure responds to conventional therapy in isolated remethylation defects, but can require a sustained period of time before observing a full response to therapy

User Selection for NOMA based MIMO with Physical Layer Network Coding in Internet of Things Applications

Non-orthogonal multiple access (NOMA) based multiple-input multiple-output (MIMO), which has the potential to provide both massive connectivity and high spectrum efficiency, is considered as one of the efficient techniques for sixth generation (6G) wireless systems. In massive Internet of Things (IoT) networks, user-set selection is crucial for enhancing the overall performance of NOMA based systems when compared with orthogonal multiple access (OMA) techniques. In this paper, we propose a user-set selection algorithm for IoT uplink transmission to improve the sum data rate of the NOMA based MIMO systems. In order to exchange data between the selected IoT pairs, we propose to employ wireless physical layer network coding (PNC) to further improve the spectral efficiency and reduce the delay to fulfill the requirements of future IoT applications. Performance evaluations are provided based on both sum data rate and bit error rate for the proposed NOMA based MIMO with PNC in the considered massive IoT scenarios

Influence of storage on the volatile profile, mechanical, optical properties and antioxidant activity of strawberry spreads made with isomaltulose

[EN] This work represents the final step of a series of studies on the formulation of strawberry products with partial replacement of sucrose by healthier sugars such as fructose and isomaltulose. Previously, quality parameters of the formulated products such as colour, texture, rheology, aromatic profile and sensory evaluation were assessed. As a final step, in the present work, the volatile profile evolution of a strawberry spread-product during 90 days of storage at room temperature (20 °C), and its relation with some physicochemical properties (aw, pH, texture and colour) and antioxidant activity as well as anthocyanin content were studied. Most of the volatile compounds modified their concentration during storage; some of them totally disappeared but 13 new compounds were formed: (methyl-2-methyl butyrate, E-2-butenal, 2-butenal-2-methyl, 2-buten-1-ol, 2-penten-1-ol, 2-etil-1-hexanol, 6-methyl-5-hepten-2-one, acetic acid, propanoic-2-methyl acid, butyric acid and butyric-2-methyl acid). Storage led to a dark pink colour and an increase in consistency and adhesiveness while the antioxidant activity considerably increased (from 18±2% to 94±2% DPPH inhibition). Levels of citric acid and pectin influenced colour, texture and antioxidant activity as well as retention and formation of aromatic compounds, especially in fructose isomaltulose products. Correlations via a PLS were found between the aromatic profile of the products after storage and some of their quality parameters such as texture, colour and antioxidant content. Future research might involve correlation and identification of specific volatiles with different quality parameters.Authors would like to thank Ministry of Science and Education's General directorate of Research (AGL2008-01745/ALI) for the financial support given to this investigation.Peinado Pardo, I.; Rosa Barbosa, EM.; Heredia Gutiérrez, AB.; Escriche Roberto, MI.; Andrés Grau, AM. (2016). Influence of storage on the volatile profile, mechanical, optical properties and antioxidant activity of strawberry spreads made with isomaltulose. Food Bioscience. 14:10-20. https://doi.org/10.1016/j.fbio.2016.02.001S10201

Liver transplantation in ornithine transcarbamylase deficiency: A retrospective multicentre cohort study

Ornithine transcarbamylase deficiency (OTCD) is an X-linked defect of ureagenesis and the most common urea cycle disorder. Patients present with hyperammonemia causing neurological symptoms, which can lead to coma and death. Liver transplantation (LT) is the only curative therapy, but has several limitations including organ shortage, significant morbidity and requirement of lifelong immunosuppression. This study aims to identify the characteristics and outcomes of patients who underwent LT for OTCD. // We conducted a retrospective study for OTCD patients from 5 UK centres receiving LT in 3 transplantation centres between 2010 and 2022. Patients' demographics, family history, initial presentation, age at LT, graft type and pre- and post-LT clinical, metabolic, and neurocognitive profile were collected from medical records.// A total of 20 OTCD patients (11 males, 9 females) were enrolled in this study. 6/20 had neonatal and 14/20 late-onset presentation. 2/20 patients had positive family history for OTCD and one of them was diagnosed antenatally and received prospective treatment. All patients were managed with standard of care based on protein-restricted diet, ammonia scavengers and supplementation with arginine and/or citrulline before LT. 15/20 patients had neurodevelopmental problems before LT. The indication for LT was presence (or family history) of recurrent metabolic decompensations occurring despite standard medical therapy leading to neurodisability and quality of life impairment. Median age at LT was 10.5 months (6–24) and 66 months (35–156) in neonatal and late onset patients, respectively. 15/20 patients had deceased donor LT (DDLT) and 5/20 had living related donor LT (LDLT). Overall survival was 95% with one patient dying 6 h after LT. 13/20 had complications after LT and 2/20 patients required re-transplantation. All patients discontinued dietary restriction and ammonia scavengers after LT and remained metabolically stable. Patients who had neurodevelopmental problems before LT persisted to have difficulties after LT. 1/5 patients who was reported to have normal neurodevelopment before LT developed behavioural problems after LT, while the remaining 4 maintained their abilities without any reported issues. // LT was found to be effective in correcting the metabolic defect, eliminates the risk of hyperammonemia and prolongs patients' survival