Seroprevalence of hepatitis B virus and its co-infection with hepatitis D virus and hepatitis C virus in Iranian adult population

Context: Hepatitis B virus (HBV) infection is one of the most prevalent public health problems worldwide (especially in developing countries). Aims: This study was carried out to determine the seroprevalence of HBV and its co-infection with hepatitis D (HDV) and C (HCV) viruses in the northeastern part of Iran. Setting and Design: A population-based cross-sectional study in Iran. Materials and Methods: As many as 1,850 subjects were explored for HBsAg. Anti-HDV and anti-HCV antibodies were assessed in HBsAg-positive cases. Statistical Analysis Used: Proportions were compared by Chi-square and Fisher's exact tests. Results: The mean age of subjects was 43.86 ± 11.2 years. The age- and sex-standardized prevalence for HBsAg positivity was 9.7%. It was higher in males than in females (OR: 1.28; 95% CI: 0.9-1.7). The risk of infection in singles was significantly higher than in married cases (OR: 2.13). Eight (5.8%) of HBsAg-positive cases were infected with HDV, and 17 (12.3%) were positive for anti-HCV antibody. Conclusion: This study demonstrates that the prevalence of HBsAg seropositivity in Golestan province of Iran is higher than the levels reported by WHO and previous studies from Iran. It is very important, especially for health providers and policy makers, to recognize the risk factors of HBV infection and its co-infection with HDV and HCV in this area and design effective preventive programs

Electron Transfer Precedes ATP Hydrolysis during Nitrogenase Catalysis

The biological reduction of N2 to NH3 catalyzed by Mo-dependent nitrogenase requires at least eight rounds of a complex cycle of events associated with ATP-driven electron transfer (ET) from the Fe protein to the catalytic MoFe protein, with each ET coupled to the hydrolysis of two ATP molecules. Although steps within this cycle have been studied for decades, the nature of the coupling between ATP hydrolysis and ET, in particular the order of ET and ATP hydrolysis, has been elusive. Here, we have measured first-order rate constants for each key step in the reaction sequence, including direct measurement of the ATP hydrolysis rate constant: kATP = 70 s−1, 25 °C. Comparison of the rate constants establishes that the reaction sequence involves four sequential steps: (i) conformationally gated ET (kET = 140 s−1, 25 °C), (ii) ATP hydrolysis (kATP = 70 s−1, 25 °C), (iii) Phosphate release (kPi = 16 s−1, 25 °C), and (iv) Fe protein dissociation from the MoFe protein (kdiss = 6 s−1, 25 °C). These findings allow completion of the thermodynamic cycle undergone by the Fe protein, showing that the energy of ATP binding and protein–protein association drive ET, with subsequent ATP hydrolysis and Pi release causing dissociation of the complex between the Feox(ADP)2 protein and the reduced MoFe protein

A Sensorised Surgical Glove to Analyze Forces During Neurosurgery

BACKGROUND: Measuring intraoperative forces in real time can provide feedback mechanisms to improve patient safety and surgical training. Previous force monitoring has been achieved through the development of specialized and adapted instruments or use designs that are incompatible with neurosurgical workflow. OBJECTIVE: To design a universal sensorised surgical glove to detect intraoperative forces, applicable to any surgical procedure, and any surgical instrument in either hand. METHODS: We created a sensorised surgical glove that was calibrated across 0 to 10 N. A laboratory experiment demonstrated that the sensorised glove was able to determine instrument-tissue forces. Six expert and 6 novice neurosurgeons completed a validated grape dissection task 20 times consecutively wearing the sensorised glove. The primary outcome was median and maximum force (N). RESULTS: The sensorised glove was able to determine instrument-tissue forces reliably. The average force applied by experts (2.14 N) was significantly lower than the average force exerted by novices (7.15 N) (P = .002). The maximum force applied by experts (6.32 N) was also significantly lower than the maximum force exerted by novices (9.80 N) (P = .004). The sensorised surgical glove’s introduction to operative workflow was feasible and did not impede on task performance. CONCLUSION: We demonstrate a novel and scalable technique to detect forces during neurosurgery. Force analysis can provide real-time data to optimize intraoperative tissue forces, reduce the risk of tissue injury, and provide objective metrics for training and assessment

Distinct Metabolic Requirements of Exhausted and Functional Virus-Specific CD8 T Cells in the Same Host.

T cells undergo profound metabolic changes to meet the increased energy demands of maintaining an antiviral response. We postulated that differences in metabolic reprogramming would shape the efficacy of CD8 T cells mounted against persistent viral infections. We found that the poorly functional PD-1(hi) T cell response against hepatitis B virus (HBV) had upregulated the glucose transporter, Glut1, an effect recapitulated by oxygen deprivation to mimic the intrahepatic environment. Glut1(hi) HBV-specific T cells were dependent on glucose supplies, unlike the more functional cytomegalovirus (CMV)-specific T cells that could utilize oxidative phosphorylation in the absence of glucose. The inability of HBV-specific T cells to switch to oxidative phosphorylation was accompanied by increased mitochondrial size and lower mitochondrial potential, indicative of mitochondrial dysfunction. Interleukin (IL)-12, which recovers HBV-specific T cell effector function, increased their mitochondrial potential and reduced their dependence on glycolysis. Our findings suggest that mitochondrial defects limit the metabolic plasticity of exhausted HBV-specific T cells.A.S., J.W., and M.K.M. are funded by a Wellcome Trust Senior Investigator Award (to M.K.M.); L.J.P. and M.K.M. are funded by MRC Project grant no. MR/M020126/; I.O. is funded by an EASL post-doctoral fellowship; U.S.G. is funded by the Wellcome Trust Clinical Research Training Fellowship; and N.H. and P.T.K. are funded by a grant from Barts and The London Charity. A.S. was also funded by a UCLH CIDC/NIHR Fast Track Grant, and D.J. was funded by the Wolfson Foundation.This is the final version of the article. It first appeared from Elsevier via http://dx.doi.org/10.1016/j.celrep.2016.06.07

Characterization of patients with idiopathic normal pressure hydrocephalus using natural language processing within an electronic healthcare record system

OBJECTIVE: Idiopathic normal pressure hydrocephalus (iNPH) is an underdiagnosed, progressive, and disabling condition. Early treatment is associated with better outcomes and improved quality of life. In this paper, the authors aimed to identify features associated with patients with iNPH using natural language processing (NLP) to characterize this cohort, with the intention to later target the development of artificial intelligence–driven tools for early detection. / METHODS: The electronic health records of patients with shunt-responsive iNPH were retrospectively reviewed using an NLP algorithm. Participants were selected from a prospectively maintained single-center database of patients undergoing CSF diversion for probable iNPH (March 2008–July 2020). Analysis was conducted on preoperative health records including clinic letters, referrals, and radiology reports accessed through CogStack. Clinical features were extracted from these records as SNOMED CT (Systematized Nomenclature of Medicine Clinical Terms) concepts using a named entity recognition machine learning model. In the first phase, a base model was generated using unsupervised training on 1 million electronic health records and supervised training with 500 double-annotated documents. The model was fine-tuned to improve accuracy using 300 records from patients with iNPH double annotated by two blinded assessors. Thematic analysis of the concepts identified by the machine learning algorithm was performed, and the frequency and timing of terms were analyzed to describe this patient group. / RESULTS: In total, 293 eligible patients responsive to CSF diversion were identified. The median age at CSF diversion was 75 years, with a male predominance (69% male). The algorithm performed with a high degree of precision and recall (F1 score 0.92). Thematic analysis revealed the most frequently documented symptoms related to mobility, cognitive impairment, and falls or balance. The most frequent comorbidities were related to cardiovascular and hematological problems. / CONCLUSIONS: This model demonstrates accurate, automated recognition of iNPH features from medical records. Opportunities for translation include detecting patients with undiagnosed iNPH from primary care records, with the aim to ultimately improve outcomes for these patients through artificial intelligence–driven early detection of iNPH and prompt treatment

DUOX1 mediates persistent epithelial EGFR activation, mucous cell metaplasia, and airway remodeling during allergic asthma

Chronic inflammation with mucous metaplasia and airway remodeling are hallmarks of allergic asthma, and these outcomes have been associated with enhanced expression and activation of EGFR signaling. Here, we demonstrate enhanced expression of EGFR ligands such as amphiregulin as well as constitutive EGFR activation in cultured nasal epithelial cells from asthmatic subjects compared with nonasthmatic controls and in lung tissues of mice during house dust mite-induced (HDM-induced) allergic inflammation. EGFR activation was associated with cysteine oxidation within EGFR and the nonreceptor tyrosine kinase Src, and both amphiregulin production and oxidative EGFR activation were diminished by pharmacologic or genetic inhibition of the epithelial NADPH oxidase dual oxidase 1 (DUOX1). DUOX1 deficiency also attenuated several EGFR-dependent features of HDM-induced allergic airway inflammation, including neutrophilic inflammation, type 2 cytokine production (IL-33, IL-13), mucous metaplasia, subepithelial fibrosis, and central airway resistance. Moreover, targeted inhibition of airway DUOX1 in mice with previously established HDM-induced allergic inflammation, by intratracheal administration of DUOX1-targeted siRNA or pharmacological NADPH oxidase inhibitors, reversed most of these outcomes. Our findings indicate an important function for DUOX1 in allergic inflammation related to persistent EGFR activation and suggest that DUOX1 targeting may represent an attractive strategy in asthma management

DUOX1 mediates persistent epithelial EGFR activation, mucous cell metaplasia, and airway remodeling during allergic asthma

Chronic inflammation with mucous metaplasia and airway remodeling are hallmarks of allergic asthma, and these outcomes have been associated with enhanced expression and activation of EGFR signaling. Here, we demonstrate enhanced expression of EGFR ligands such as amphiregulin as well as constitutive EGFR activation in cultured nasal epithelial cells from asthmatic subjects compared with nonasthmatic controls and in lung tissues of mice during house dust mite-induced (HDM-induced) allergic inflammation. EGFR activation was associated with cysteine oxidation within EGFR and the nonreceptor tyrosine kinase Src, and both amphiregulin production and oxidative EGFR activation were diminished by pharmacologic or genetic inhibition of the epithelial NADPH oxidase dual oxidase 1 (DUOX1). DUOX1 deficiency also attenuated several EGFR-dependent features of HDM-induced allergic airway inflammation, including neutrophilic inflammation, type 2 cytokine production (IL-33, IL-13), mucous metaplasia, subepithelial fibrosis, and central airway resistance. Moreover, targeted inhibition of airway DUOX1 in mice with previously established HDM-induced allergic inflammation, by intratracheal administration of DUOX1-targeted siRNA or pharmacological NADPH oxidase inhibitors, reversed most of these outcomes. Our findings indicate an important function for DUOX1 in allergic inflammation related to persistent EGFR activation and suggest that DUOX1 targeting may represent an attractive strategy in asthma management

Gathering Global Perspectives to Establish the Research Priorities and Minimum Data Sets for Degenerative Cervical Myelopathy:Sampling Strategy of the First Round Consensus Surveys of AO Spine RECODE-DCM

STUDY DESIGN: Survey.INTRODUCTION: AO Spine Research Objectives and Common Data Elements for Degenerative Cervical Myelopathy (AO Spine RECODE-DCM) is an international initiative that aims to accelerate knowledge discovery and improve outcomes by developing a consensus framework for research. This includes defining the top research priorities, an index term and a minimum data set (core outcome set and core data elements set - core outcome set (COS)/core data elements (CDE)).OBJECTIVE: To describe how perspectives were gathered and report the detailed sampling characteristics.METHODS: A two-stage, electronic survey was used to gather and seek initial consensus. Perspectives were sought from spinal surgeons, other healthcare professionals and people with degenerative cervical myelopathy (DCM). Participants were allocated to one of two parallel streams: (1) priority setting or (2) minimum dataset. An email campaign was developed to advertise the survey to relevant global stakeholder individuals and organisations. People with DCM were recruited using the international DCM charity Myelopathy.org and its social media channels. A network of global partners was recruited to act as project ambassadors. Data from Google Analytics, MailChimp and Calibrum helped optimise survey dissemination.RESULTS: Survey engagement was high amongst the three stakeholder groups: 208 people with DCM, 389 spinal surgeons and 157 other healthcare professionals. Individuals from 76 different countries participated; the United States, United Kingdom and Canada were the most common countries of participants.CONCLUSION: AO Spine RECODE-DCM recruited a diverse and sufficient number of participants for an international PSP and COS/CDE process. Whilst PSP and COS/CDE have been undertaken in other fields, to our knowledge, this is the first time they have been combined in one process.</p

A randomized prospective multicenter trial for stroke prevention by prophylactic surgical closure of the left atrial appendage in patients undergoing bioprosthetic aortic valve surgery--LAA-CLOSURE trial protocol

Patients undergoing surgical aortic valve replacement (SAVR) are at high risk for atrial fibrillation (AF) and stroke after surgery. There is an unmet clinical need to improve stroke prevention in this patient population. The LAA-CLOSURE trial aims to assess the efficacy and safety of prophylactic surgical closure of the left atrial appendage for stroke and cardiovascular death prevention in patients undergoing bioprosthetic SAVR. This randomized, open-label, prospective multicenter trial will enroll 1,040 patients at 13 European sites. The primary endpoint is a composite of cardiovascular mortality, stroke and systemic embolism at 5 years. Secondary endpoints include cardiovascular mortality, stroke, systemic embolism, bleed fulfilling academic research consortium (BARC) criteria, hospitalization for decompensated heart failure and health economic evaluation. Sample size is based on 30% risk reduction in time to event analysis of primary endpoint. Prespecified reports include 30-daysafety analysis focusing on AF occurrence and short-term outcomes and interim analyses at 1 and 3 years for primary and secondary outcomes. Additionally, substudies will be performed on the completeness of the closure using transesophageal echocardiography/cardiac computed tomography and long-term ECG recording at one year after the operation. (Am Heart J 2021;237:127-134.