Aims: Lysosomal β-glucocerebrosidase (GBA) deficiency causes Gaucher disease (GD), a recessive disorder caused by bi-allelic mutations in GBA. The prevalence of GD is associated with ethnicity, but largely unknown and potentially underestimated in many countries. GD may manifest with organomegaly, bone involvement and neurological symptoms as well as abnormal laboratory biomarkers. This study attempted to screen for GD in patients using abnormal platelet, alkaline phosphatase (ALP) and ferritin results from laboratory databases. Methods: Electronic laboratory databases were interrogated using a 2-4 year time interval to identify from clinical biochemistry records patients with a phenotype of reduced platelets (<150x109/L) and either elevated ALP (>130iu/L) or ferritin (>150 (female) or >250µg/L(male)). The mean value over the screening window was used to reduce variability in results. A dried blood spot sample was collected for the determination of GBA activity in patients meeting these criteria. If low GBA activity was found then the concentration of the GD-specific biomarker glucosyl-sphingosine (lyso-GB1) was assayed, and the GBA gene sequenced. Results: Samples were obtained from 1058 patients; 232 patients had low GBA activity triggering further analysis. No new cases of GD with homozygosity for pathogenic variants were identified but 12 patients (1%) were identified to be carriers of a pathogenic variant in GBA. Conclusions: Pathology databases hold routine information that can be used to screen for patients with inherited errors of metabolism. However, biochemical screening using mean platelets, ALP and ferritin has a low yield for unidentified cases of Gaucher Disease.

COVID-19 IgM/IgG false-positivity in a rheumatoid arthritis patient negative for RF and ACPA: exist of other serological interference?To the editor:The outbreak of coronavirus disease 2019 (COVID-19) which rapidly spread throughout the world is still threatening the global health safety. Diagnostic tests for COVID-19 divided into two main categories: detection of viral RNA and serological detection of anti-SARS-CoV-2 immunoglobulins including specific IgM and IgG[1].Recently, we came up with an 89-year-old RA patient. She was diagnosed of rheumatoid arthritis for interphalangeal joint pain and rheumatic factor (RF) positive over 15 years ago and had been taking prednisone 5mg per day. Since the spread of COVID-19, we gave her the test of SARS-Cov-2 IgM/IgG and nucleic acid routinely. The confusing results showed IgM and IgG positive and nucleic acid negative. This old woman had no epidemiological history due to poor lung function. To further clarify the diagnosis, we retest SARS-Cov-2 nucleic acid from throat, nasopharyngeal and anal swab specimen and got negative results again. Diagnosis of COVID-19 was eliminated. 6 months later, this lady was readmitted with persistent positive result of specific IgM and IgG and negative result of nucleic acid. Serological test of RF and anti-cyclic citrullinated peptide antibody (ACPA) showed negative.According current reports, serum IgM arrived peak need 16-30 days and rapid decayed, while IgG remained relatively stable up to 105 days post-symptoms onset[2,3]. In our reported case, the IgM and IgG had persisted for more than 6 months.Recent study reported that no cross-reactivity was observed between autoantibodies in autoimmune disease and SARS-CoV-2 antibodies[4]. Controversially, the false-positivity of anti-SARS-CoV-2 IgM was reported in RF IgM-positive serum[5]. Considering this case, some unknown factors besides RF IgM and ACPA may exist in serum of RA patients which cause persist false positivity of anti-SARS-CoV-2 immunoglobulin.In conclusion, medical history combined with nucleic acid tests still played the key role in diagnosis of COVID-19 when come with positive result of SARS-Cov-2 IgM and IgG. The false positivity could involve either IgM or IgG which may be caused by other cross-reactive factors besides RF antibody and ACPA. The potential mechanism remained further explored.

Frying stability of two virgin (VSO) and refined (RSO) sesame oils was compared with that of a refined olive oil (ROO). The oils were used to fry potato stripes at 180 °C and conjugated dienes (CDV), total carbonyls (CV), and thermo-oxidative and hydrolytic polar components were monitored over time. The rate of change in CDV (mmol l–1 h–1) was significantly lower for ROO (0.72) than for VSO (1.00) and RSO (1.84). The change in CV for ROO (2.31 μmol g–1 h–1) was significantly much faster than those for RSO (1.89) and VSO (1.17). Based on the thermo-oxidative polar components, the calculated frying times for VSO, RSO, and ROO were on the order of 32.1, 13.9, and 15.4 h. However, VSO contained significantly the highest contents of hydrolytic polar components over time and RSO exhibited more resistance than ROO on this basis.

Objective: To estimate the causal impact of small for gestational age (SGA) births on caesarean delivery, with and without trial of labour (TOL); and to quantify how much of the association is mediated through gestational age at delivery. Design: Cross-sectional analysis. Setting: Para 2 women who delivered non-anomalous, singleton live births from 22-44 weeks’ gestation in the US (2015-2018). Main outcomes and measures: Caesarean delivery with and without TOL. The exposure was SGA births (sex-specific birthweight <5th and <3rd percentiles for gestational age), and AGA births (10-89th percentile). We performed causal mediation analysis to determine the impact of gestational age at delivery (22-33, 34-36, 37-38, 39-40 and ≥41 weeks) as intermediate. Results: Of the 3,755,798 subjects, compared to AGA (29.6%), caesarean risks were higher for SGA <5th (34.3%) and SGA <3rd (36.4%) percentiles. For SGA <5th percentile, the adjusted excess risk of caesarean delivery without TOL had a “U” shaped association, with increased risk at preterm gestations, nadir at 39-40 weeks, and increased thereafter. The decomposition analysis revealed the driver of this excess risk was SGA births. The risk of caesarean delivery with TOL was highest <34 weeks’ gestation and was primarily an interaction effect. As gestation advanced, SGA births contributed proportionately greater to the risk. Associations were stronger for SGA <3rd percentile. Conclusions: Exposure to SGA drives high rates of prelabour caesareans and contributes to high risks of caesarean deliveries after TOL at >41 weeks gestation; a different mechanism drives high rates of caesareans after TOL at preterm gestations.

En este artículo argumento que la necesidad de las leyes proviene del hecho de que son derivaciones. Estas derivaciones, al menos de los ejemplos clásicos, dependen de la teoría de proporciones. Al ser un caso de derivación lógica, las leyes son sólo necesarias en este sentido. Esto quiere decir que niego que lo que capturan las leyes son conexiones necesarias entre fenómenos. Keywords: regularismo nómico, humeanismo, anti-humeanismo, leyes de la naturaleza

Introduction Allergic rhinitis, beginning from childhood, is a global health problem. According to the literature, allergic rhinitis has been found to be associated with asthma and other allergic manifestations. In this study we like to find out the significance and prognostic importance of pulmonary function test (PFT) in allergic rhinitis. Design and setting: The study was carried out over a period of 2 years, with 63 cases and controls each. Subjects in the age of 20-55 years with allergic rhinitis and SFAR score of >/=7 were included as a case. Participants were interviewed and sent for PFT. Controls were recruited from the retrospective data of healthy individuals with pulmonary function parameters done for health checkup. These controls had an SFAR score of <7. Main outcome measures: Clinical data and PFT of cases and controls was used for the study. SFAR score was used to recruit the cases and controls. All the data obtained were analyzed and compared between cases and controls. Results The mean age of the cases and controls were 33.17 +/- 10.817 and 44.41 +/- 7.4, respectively. Majority of cases and controls were males (60.3% and 57.1%). A statistically significant difference in FEF25-75% among cases and controls was noted (p=0.00), thus proving probability of developing small airway obstruction in subjects with allergic rhinitis. Conclusion Subjects with allergic rhinitis have a probability of developing small airway obstruction with subclinical changes, hence necessitating the need of regular follow-up.

Reactive transport codes are today one of the cornerstones of environmental research. They now contain multiphysics with very complex algorithms, including flow, transport, chemical and sometimes heat transport, mechanical and/or biological algorithms. Because of this complexity, some parts of these algorithms still have not been sufficiently studied. Here, we present a comparison of 3 algorithms for activity correction, a specific subset of equilibrium chemistry algorithms. We show that the most used algorithm (the inner fixed-point algorithm) or the most rigorous algorithm (the full Newton) might not be the most efficient, and we propose the outer fixed-point algorithm, which is more robust and faster than other algorithms.

Objectives Endoscopic approaches constitute a newly introduced and promising technique in the field of stapes surgery, presenting favorable outcomes, so far. This study aims to compare endoscopic and microscopic stapes surgery based on current literature evidence, in terms of their efficacy and safety characteristics. Design We conducted a systematic literature search of three medical databases (Pubmed, Cochrane Library, and Scopus). We focused on randomized controlled studies or observational studies comparing microscopic to endoscopic stapes surgery. Data related to the efficacy and safety of each technique were extracted. Outcome data were summarized using the pooled mean differences or pooled odds ratio along with their 95% confidence intervals, according to the available data. The quality of evidence was assessed according to the GRADE recommendations. Results Thirteen studies with 705 patients were included in the meta-analysis. Success rate was evaluated by estimating air-bone gap improvement, resulting in comparable outcomes for the two techniques (mean difference: -0.20; 95% CI: -0.53, 0.14). No statistically significant difference was detected concerning postoperative complications, except for dysgeusia that was in favor of the endoscopic approach (OR: -1.46; 95% CI: -2.45, -.047). The overall quality of evidence was assessed to range from “Low” to “Very Low”. Conclusion Endoscopic stapes surgery is an innovative alternative to the microscopic technique, resulting in commensurate outcomes in terms of success rate and complications. Further high-quality studies are needed, to adequately compare the two approaches, particularly in terms of operation time, learning curve, cost-effectiveness, and otology surgical skills acquisition.

Crystal methamphetamine is an extremely addictive stimulant that increases sexual arousal while reducing inhibition and judgment. Its use is associated with a range of high-risk sexual behaviors that increase the likelihood of acquiring or transmitting HIV. Given the relatively high prevalence of crystal methamphetamine use among people living with HIV and among men who have sex with men, there is great concern that this drug is fueling the HIV epidemic. Equally worrisome are the effects that crystal methamphetamine use can have on the prognosis and overall health of HIV-infected patients. This article reports the results of a pilot study that is part of a larger project exploring the correlates of antiretroviral therapy drug resistance.

This paper investigates the problem of $H_\infty$ state estimation of delayed recurrent memristive neural networks (DRMNNs) with both continuous-time and discrete-time cases. By utilizing Lyapunov-Krasovskii functional (LKF) and linear matrix inequalities (LMIs), two criterions are provided to guarantee the asymptotically stable of the estimation error systems with a $H_\infty$ performance. The connection weight parameters of DRMNNs are dealed with logical switching signals, which greatly reduces the computational complexity. The given conditions can be easily checked by solving LMIs, the obtained theoretical results are supported demonstrated by two numerical examples.

RNA sequencing is a promising technique for detecting normal and aberrant RNA isoforms. Here, we present a new single-gene, straightforward 1-day hands-on protocol for detection of splicing alterations with deep RNA sequencing from blood. We have validated our method's accuracy by detecting all normal splicing isoforms of STK11 gene that were previously published. Additionally, the same technique was used to provide the first comprehensive catalogue of naturally occurring alternative splicing events of the NBN gene in blood. Furthermore, we demonstrate that our approach can be used for detection of splicing impairment caused by genetics variants. Due to the simplicity of our approach it can be incorporated into any molecular diagnostics laboratory for determination of variant's impact on splicing.

Personalized External Aortic Root support (PEARS) is an evolving method of treatment for patients with dilated aortic root or ascending aorta. The treatment is adopted in still more centres. For the sake of the safety of the procedure a standardized surgical technique is necessary. The authors describe surgical technique of the implantation that is derived from their extensive experience.

AİM: To determine the frequency, demographic and clinical features of the heterotopic gastric mucosa (inlet patch). MATERIALS AND METHODS: This retrospective study involves 244 patients who applied to the gastroenterology outpatient clinic with different symptoms between September 2016 and December 2019, and who were diagnosed with inlet patch in elective esophagogastroduodenoscopy. All endoscopic procedures were performed by the same clinical endoscopist. All medical records of patients including demographic and clinical features and endoscopy findings were reviewed. RESULTS: Considering 2823 patients who underwent elective esophagogastroduodenoscopy in the same study period, inlet patch was detected in 224 (8.6%). 56.6% of the patients diagnosed with inlet patch were male and there was no statistical difference between the two genders. The mean age of the patients was 37.73 ± 13.01 years. 83.6% of the patients had only one lesion, and 58.2% had a lesion larger than 1 cm, with the largest one being 4.5 cm. Size of the smallest lesion was 0.3 cm. All of the lesions were in the proximal esophagus. 54 patients (22.1%) had at least one supraesophageal or upper esophageal symptom. The most common symptom was globus sensation (64.8%). Patients with large lesions were more likely to experience symptoms (28.2% vs. 13.7%, p=0.008). CONCLUSION: Careful examination of the proximal esophagus may increase the chance of detecting inlet patch and may explain persistent symptoms in patients without a specific cause. Further understanding of the clinical significance of the disease may also prevent unnecessary diagnostic interventions.

Aim: Through this review, the authors intend to accumulate existing knowledge of VEXAS for referral, and to serve as an inspiration for further discovery, funding and research into the discipline. Methods: The non systematic literature review was conducted in January 2021, using Google Scholar and PubMed as the major extensive search engines. The keyword ‘VEXAS’ was used to narrow search results, and data was restricted to only those articles published in English. Results: The search, followed by the selection for relevancy led to a total of 5 pieces of literature being used for the purpose of this review; the lack of a huge number of results arises from the fact that the disease has been recently discovered. Discussion: Adult-onset inflammatory conditions are of increasing interest to medical professionals, and a number of patients with these conditions present with symptoms for which a concrete diagnosis is difficult to establish. In recent times, using an unconventional, yet remarkably effective genotype – based approach, researchers at the NIH have been able to discover a number of somatic mutations in UBA 1, which give rise to a unique disease. The disease, which has been named VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic syndrome) by the founders, arises from specific somatic mutations in the UBA 1 gene, and patients presenting with VEXAS have clinical manifestations - as sporadic fevers, chronic inflammation of the lungs and cartilage, and atypical vacuoles in myeloid cells, venous thromboembolism, ear and nose chondritis and macrocytic anaemia. VEXAS stems from accumulated somatic mutations in UBA 1, typically manifesting in three major variants, severely impairing the natural ubiquitylation process in cells, and shows no observable pattern of inheritance, according to the preliminary research conducted at NIH. Conclusion: Further study into VEXAS is needed for a better understanding of the syndrome.

Objectives: Coronavirus disease 2019 (COVID-19) is an infectious disease, that’s the reason for the currently ongoing pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Angiotensin-converting enzyme (ACE2) has been recognized as the specific receptor of the SARS-CoV-2 virus. Although the possible effect of ACE2 gene polymorphism remains unknown, human ACE2 receptor expression influences SARS-CoV-2 susceptibility and COVID-19 disease outcome. In this study, we aimed to investigate the relationship between ACE gene I/D polymorphism, ACE2 receptor gene polymorphism, and Covid-19 severity. Methods: ACE gene I/D polymorphism and ACE2 receptor gene rs2106809 and rs2285666 polymorphisms were determined using PCR and PCR-RFLP methods, respectively in 155 Covid19 patients who were divided into 3 groups (mild, moderate, and severe) according to clinical symptoms. Results: However, the distribution of genotype and allele frequencies of ACE gene I/D, ACE2 receptor gene rs2106809, and rs2285666 polymorphisms was not statistically significant in all groups. Conclusions: In conclusion, in the study population, ACE gene I/D, ACE2 receptor gene rs2106809, and rs2285666 polymorphisms were not associated with the severity of Covid-19 infection. Although, ACE2 receptor gene expression may affect the susceptibility to Covid-19, there is no existing evidence that the ACE or ACE2 gene polymorphisms are directly associated with Covid-19 severity. Interindividual differences in covid-19 severity might be related to epigenetic mechanisms of ACE2 receptor gene expression or variations in other genes suggested to have critical role in COVID-19 pathogenesis such as proinflammatory cytokines, coagulation indicators. Keywords: COVID-19 , ACE , ACE2, rs2106809, rs2285666

In this paper the concept of a new method for the estimation of the heat flux distribution and the total power in CSP applications is presented. This method requires appropriate analysis of the temperature evolution on a target, or directly on a receiver. A 3-D thermal conduction model with boundary conditions to take into account the convection and radiation losses has been developed. A parametric analysis was performed and we checked how the physical parameters affect the applicability of the method. Having proven numerically the potential of this method, it was experimentally implemented in the central tower CSP plant of The Cyprus Institute at PROTEAS facilities successfully. The experience gained from the numerical and experimental application of this method is discussed.

Background: Seasonal influenza is a burden for emergency departments. The aim of this study was to investigate whether point-of-care (POC) PCR testing can be used to reduce staff sick days and improve diagnostic and therapeutic procedures. Methods: Using a cross-over design, the cobas® Liat® Influenza A/B POC PCR test (Liat) was compared to standard clinical practice during the 2019/2020 influenza season. All adult patients (aged ≥18 years) with fever (≥38°C) and respiratory symptoms were included. Primary endpoints were prevalence of influenza infections in the ED and staff sick days. Secondary endpoints were frequency of antiviral and antibacterial therapy, time between admission and test result or treatment initiation, patient disposition, ED length of stay (LOS) and for in-patients mortality and LOS. Nurses were interviewed about handling and integration of POC testing. The occurrence of SARS-CoV-2 infections coincided with the second half of the study. Results: A total of 828 patients were enrolled in the study. All 375 patients of the intervention group were tested with Liat, 103 of them (27.6%) tested positive. During the intervention period staff sick days were reduced by 34.4% (p=0.023). Significantly more patients in the intervention group received antiviral therapy with neuraminidase-inhibitors (7.2% vs. 3.8%, p=0.028) and tested patients received antibiotics more frequently (40.0% vs. 31.6%, p=0.033). Patients with POC test were transferred to external hospitals significantly more often (5.6% vs. 1.3%, p=0.01). Conclusion: We conclude that POC testing for influenza is useful in the ED, especially if it is heavily frequented by patients with respiratory symptoms.

A document by Yunus E. B. . Click on the document to view its contents.

Vaccination against the COVID-19 virus began in December 2020 in the UK and is now running at 5% population/week. High Levels of social restrictions were implemented for the third time in January 2021 to control the second wave and resulting increases in hospitalisations and deaths. Easing those restrictions must balance multiple challenging priorities, weighing the risk of more deaths and hospitalisations against damage done to mental health, incomes and standards of living, education outcomes and provision of non-Covid-19 healthcare. Weekly and monthly officially published values in 2020/21 were used to estimate the impact of seasonality and social restrictions on the spread of COVID-19 by age group, on the economy and healthcare services. These factors were combined with the estimated impact of vaccinations and immunity from past infections into a model that retrospectively reflected the actual numbers of reported deaths closely both in 2020 and early 2021. It was applied prospectively to the next 6 months to evaluate the impact of different speeds of easing social restrictions. The results show vaccinations are significantly reducing the number of hospitalisations and deaths. The central estimate is that relative to a rapid easing, the avoided loss of 57,000 life years from a strategy of relatively slow easing over the next 4 months comes at a cost in terms of GDP reduction of around £0.4 million/life-year loss avoided. This is over 10 times higher than the usual limit the NHS uses for spending against Quality Adjusted Life Years (QALYs) saved. Alternative assumptions for key factors affecting give significantly different trade-offs between costs and benefits of different speeds of easing. Disruption of non-Covid-19 Healthcare provision also increases in times of higher levels of social restrictions. In most cases, the results favour a somewhat faster easing of restrictions in England than current policy implies.

Introduction: In dermoscopic studies on dermatofibromas, some publications divide the appearance of lesions into standardized patterns, and some publications classify the clinical appearance of the lesions by comparing them with existing dermatological lesions. Objectives: This study aims to re-evaluate the dermoscopic findings and patterns of dermatofibromas from a different perspective. Methods: In this study, 142 lesions of 72 patients were evaluated dermoscopically and their patterns were schematized. Results: In our study, a total of 15 patterns consisting of main and sub-patterns were created. The most common patterns we detected were pattern 1 (1a: 13.4%, 1b: 8.5%), pattern 8 (8a: 10.6%, 8b: 4.2%), pattern 2 (2a: 9.2%, 2b: 4.2%), respectively. Conclusions: Patterns of DFs were reclassified while preserving basic patterns. We think that the new sub-patterns and schematization with this study can contribute to better understanding of DFs.

Abstract  An instantaneous velocity where a moment of the clock only corresponds to an arbitrary distance or position in space cannot be implied in Axiom 1, but it indicates that there is only one dimensional existence, space or time, where a certain moment only corresponds to itself specifically, not to any other time or any given length of space. Further , a definition of velocity that consists of two dimensions representing the relationship between space and time is not valid and there is only one-dimensional space or time that is independent of each other in Axiom 1. As a result, the principle of relativity and the principle of the constant velocity of light are replaced by the principle of an inertial system and the principle of universal invariant velocity in Axiom 1. Unlike two dimensions whose magnitude is determined by the ratio, the magnitude of a single dimension is determined by the unit values of one dimension, which indicates that an infinitely great velocity is meaningless. Further, if the two inertial systems are infinite versus finite in Axiom 3, then this extension of the infinitely great velocity can be defined as inextensible.

This article specically deals with the asymptotic synchronization of non-identical complex dynamic fractional order networks with uncertainty. Initially, by using the Riemann-Liouville derivative, we developed a model for the general non-identical complex network, and based on the properties of fractional order calculus and the direct Lyapunov method in fractional order, we proposed that drive and response system if nonidentical complex networks ensuring asymp-totic synchronization by using neoteric control. Second, taking into account the uncertainties of non-identical complex networks in state matrices and evaluating theirrequirements forasymptotic synchronization. In addition, to explain the eectiveness of the proposed approach, two numerical simulations are given.

The intricacy of the thermo-hydro-chemically coupled process of hydrate phase transition requires real-time in-situ observations, therefore, thermometry maps are of particular value to reveal the heat transfer process during crystal growth and dissociation. By using the temperature dependence of water proton chemical shift, the temporally- and spatially-resolved thermometry of tetrahydrofuran hydrate growths is presented in this study. Images of temperature changes were synchronously obtained by a 9.4 T 1H Magnetic Resonance Imaging (MRI) system, in order to predict the saturation of aqueous solution, solid hydrate phases, and the positive temperature anomaly of exothermic reaction. Variations of MRI signal decrease and histories of temperature rise differ significantly in space and time, which have a great use for analyzing the physical micro-mechanism and the heat transfer process of hydrate growth. The extension of these predicted results could have important implications for optimizing the phase transition process of gas hydrates.

Heterotopic pregnancy (HP) describes the simultaneous presence of two pregnancies at different implantation sites. One is intrauterine and the other is ectopic. It is challenging to diagnose HP. We present a very rare case of HP diagnosed in the first trimester by US and MRI and managed successfully.