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The complete genome sequence of a double-stranded RNA (dsRNA) virus, Rhizoctonia solani dsRNA virus 11 (RsRV11), isolated from Rhizoctonia solani AG-1 IA strain 9-11 was determined. The RsRV11 genome is 9,555 bp in length and contains three conserved domains: structural maintenance of chromosomes (SMC) superfamily, phosphoribulokinase (PRK), and RNA-dependent RNA polymerase (RdRp). The RsRV11 genome has two non-overlapping open reading frames (ORFs). ORF1 is predicted to encode a 204.12-kDa protein that shares low but significant amino acid sequence similarity with a putative protein encoded by Rhizoctonia solani RNA virus HN008 (RsRV-HN008). ORF2 potentially encodes a 132.41-kDa protein that contains the conserved domain of the RdRp. Phylogenetic analysis indicated that RsRV11 clustered with RsRV-HN008 in a separate clade from other virus families. This implies that RsRV11 and RsRV-HN008 should be included in a new mycovirus taxon close to the family Megabirnaviridae and that RsRV11 is a new mycovirus., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Purpose: The aim of this study was to compare the effect of antral resection versus antral preservation sleeve gastrectomy on the post-operative GLP-1, glycemic control, and weight loss in adolescents suffering from severe obesity and type 2 diabetes (T2D)., Materials and Methods: This study included 36 adolescents. Patients were randomly divided into 2 groups: group (A) and group (B). Each group included 18 patients who underwent LSG, starting transection at 2 cm or 5 cm from the pyloric ring in group (A) and group (B), respectively. They were followed up at 1, 3, 6, 12, and 24 months post-operatively. The outcomes were the post-operative GLP-1 response, glycemic control, weight loss, and safety., Results: The improvements in the body mass index and the percentage of excess weight loss (%EWL) were statistically significant within each group. The mean GLP-1 levels showed significant increase at the 1, 3, and 6 months but not in the 12 and 24 months in all the studied samples within each group. The mean HbA1c levels and post-prandial serum C-peptide significantly improved within each group (P < 0.05). No statistical differences in the weight loss, %EWL, GLP-1, HbA1c, C-peptide changes, and complication rates were observed between both groups. Diabetic remission was significantly higher (88.9%) in group (A)., Conclusions: LSG resulted in generalized significant GLP-1 initial response that decreased over time. The reduced antrum size did not influence the GLP-1 response, glycemic control, or insulin resistance, but resulted in significantly better T2D remission. Since the study examines a small number of patients, further studies are needed., Trial Registration: ClinicalTrials.gov Identifier: NCT04388059., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A unique capsidless virus with a positive-sense, single-stranded RNA genome (hadakavirus 1, HadV1), a member of the extended picorna-like supergroup, was isolated previously from the phytopathogenic fungus Fusarium oxysporum. Here, we describe the molecular and biological characterisation of a second hadakavirus strain from Fusarium nygamai, which has not been investigated in detail previously as a virus host. This virus, hadakavirus 1 strain 1NL (HadV1-1NL), has features similar to the first hadakavirus, HadV1-7n, despite having a different number of segments (10 for HadV1-1NL vs. 11 for HadV1-7n). The 10 genomic RNA segments of HadV1-1NL range in size from 0.9 kb to 2.5 kb. All HadV1-1NL segments show 67% to 86% local nucleotide sequence identity to their HadV1-7n counterparts, whereas HadV1-1NL has no homolog of HadV1-7n RNA8, which encodes a zinc-finger motif. Another interesting feature is the possible coding incapability of HadV1-1NL RNA10. HadV1-1NL was predicted to be capsidless based on the RNase A susceptibility of its replicative form dsRNA. Phenotypic comparison of multiple virus-infected and virus-free single-spore isolates indicated asymptomatic infection by HadV1-1NL. Less-efficient vertical transmission via spores was observed as the infected fungal colonies from which the spores were derived became older, as was observed for HadV1-7n. This study shows a second example of a hadakavirus that appears to have unusual features., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Poly(glycerol sebacate) (PGS), an emerging promising thermosetting polymer synthesized from sebacic acid and glycerol, has attracted considerable attention due to its elasticity, biocompatibility, and tunable biodegradation properties. But it also has some drawbacks such as harsh synthesis conditions, rapid degradation rates, and low stiffness. To overcome these challenges and optimize PGS performance, various modification methods and fabrication techniques for PGS-based scaffolds have been developed in recent years. Outlining the current modification approaches of PGS and summarizing the fabrication techniques for PGS-based scaffolds are of great importance to accelerate the development of new materials and enable them to be appropriately used in potential applications. Thus, this review comprehensively overviews PGS derivatives, PGS composites, PGS blends, processing for PGS-based scaffolds, and their related applications. It is envisioned that this review could instruct and inspire the design of the PGS-based materials and facilitate tissue engineering advances into clinical practice., (© 2021 Wiley-VCH GmbH.)

Background: Head and neck squamous cell carcinoma (HNSCC) is characterised by a dismal prognosis; nonetheless, limited studies have unveiled the mechanisms underlying HNSCC relapse., Methods: Next-generation sequencing was performed to identify the somatic mutations in 188 matched samples, including primary tumours, tumour-adjacent tissues (TATs), pre- and post-operative plasma, saliva and peripheral blood lymphocytes (PBLs) from 27 patients. The evolutionary relationship between TATs and tumours were analysed. The dynamic changes of tumour- and TAT-specific mutations in liquid biopsies were monitored together with survival analysis., Results: Alterations were detected in 27 out of 27 and 19 out of 26 tumours and TATs, respectively. TP53 was the most prevalently mutated gene in TATs. Some TATs shared mutations with primary tumours, while some other TATs were evolutionarily unrelated to tumours. Notably, TP53 mutations in TATs are stringently associated with premalignant transformation and are indicative of worse survival (hazard ratio = 14.01). TAT-specific mutations were also detected in pre- and/or post-operative liquid biopsies and were indicative of disease relapse., Conclusions: TATs might undergo the processes of premalignant transformation, tumorigenesis and eventually relapse by either inheriting tumorigenic mutations from ancestral clones where the tumour originated or gaining private mutations independent of primary tumours. Detection of tumour- and/or TAT-specific genetic alterations in post-operative biopsies shows profound potential in prognostic use., (© 2021. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Orbital inflammatory disease encompasses a spectrum of disorders. Idiopathic orbital inflammation (IOI) is often a diagnosis of exclusion, which needs to be differentiated from infections, systemic inflammatory disease, and neoplasms. IOI includes anterior inflammation with dacryoadenitis, myositis, perineuritis of the optic nerve, periscleritis, diffuse sclerosing inflammation, and orbital apex inflammation., Objective: A differential diagnostic overview of IOI is presented, including its subcategories, diagnosis, and treatment., Conclusion: The diagnosis of IOI is often made by exclusion with typical clinical findings, CT and MRI scans, and pathology. Treatment includes corticosteroids, immunomodulators, immunosuppressants, and radiotherapy., (© 2021. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.)

Supercritical fluid-based extraction technologies are currently being increasingly utilized in high purity extract products for food industries. In recent years, supercritical fluid-based extraction technology is transformed in biomaterials process fields to be further utilized for tissue engineering and other biomedical applications. In particular, supercritical fluid-based decellularization protocols have great advantage over the conventional decellularization as it may allow preservation of extracellular matrix components and structures. In this review, the latest technological development utilizing the supercritical fluid-based decellularization for regenerative medicine is introduced., (© 2021 Wiley-VCH GmbH.)

Silk is a natural fibrous polymer with application potential in regenerative medicine. Increasing interest remains for silk materials in bone tissue engineering due to their characteristics in biocompatibility, biodegradability and mechanical properties. Plenty of the in vitro and in vivo studies confirmed the advantages of silk in accelerating bone regeneration. Silk is processed into scaffolds, hydrogels, and films to facilitate different bone regenerative applications. Bioactive factors such as growth factors and drugs, and stem cells are introduced to silk-based matrices to create friendly and osteogenic microenvironments, directing cell behaviors and bone regeneration. The recent progress in silk-based bone biomaterials is discussed and focused on different fabrication and functionalization methods related to osteogenesis. The challenges and potential targets of silk bone materials are highlighted to evaluate the future development of silk-based bone materials., (© 2021 Wiley-VCH GmbH.)

Abstract: It is well established that cohorts of individuals exposed to ionizing radiation demonstrate increased risks of cardio- and cerebrovascular diseases. However, mechanisms of these radiation-induced diseases developing in individuals exposed to ionizing radiation remain unclear. To identify biomarkers of the atherosclerotic vessel damage in workers chronically exposed to ionizing radiation, this study considered 49 workers of the Russian nuclear production facility-the Mayak Production Association (mean age of 68.73 ± 6.92 years)-and 38 unexposed individuals (mean age of 68.84 ± 6.20 y) who had never been exposed to ionizing radiation (control). All workers were chronically exposed to combined radiation (external gamma rays and internal alpha particles). The mean cumulative liver absorbed dose from external gamma-ray exposure was 0.18 ± 0.12 Gy; the mean cumulative liver absorbed dose from internal alpha-particles was 0.14 ± 0.21 Gy. Levels of biomarkers in blood serum of the study participants were measured using the ELISA method. Elevated levels of apolipoprotein B, superoxide dismutase, monocyte chemoattractant protein 1, vascular cell adhesion protein 1, and a decreased level of endothelin-1 were observed in blood serum of Mayak PA workers chronically exposed to combined radiation compared to control individuals. A significant positive correlation was demonstrated between the vascular cell adhesion protein 1 level and cumulative liver absorbed doses from external gamma radiation and internal alpha radiation. Findings of the study suggest that molecular changes in blood of individuals occupationally exposed to ionizing radiation (combined internal exposure to alpha particles and external exposure to gamma rays) may indicate dyslipidemia, oxidative stress, inflammation, and endothelial dysfunction involved in atherosclerosis development., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Health Physics Society.)

Cyclophosphamide is an antitumor agent that causes disorders in fertility. This study aimed to evaluate the protective effects of Spirulina platensis against Cyclophosphamide-induced testicular toxicity. 42 male Wistar rats were randomly divided into six groups. Experimental groups included three groups. The first experimental group received Cyclophosphamide at a dose of 5 mg/kg body weight (BW) orally. The second and third experimental groups received 5 mg/kg BW Cyclophosphamide and 500 and 1,000 mg/kg BW S. platensis orally, respectively. The control groups included a control group, and two S. platensis control groups. Following 28 days, two flow cytometry techniques were used to determine sperm apoptosis and testicular protein expression of tumor protein (p53) and B-cell lymphoma 2 (Bcl-2). p53 is a tumor suppressor protein that causes the cell to enter the apoptosis cycle after DNA damage and Bcl-2 is an anti-apoptotic protein that acts through the mitochondrial pathway of apoptosis. FITC-Annexin V assay was used for sperm apoptosis evaluation. For protein expression assay, primary and secondary antibodies staining were performed. The Cyclophosphamide group showed a significant increase in sperm apoptosis compared to the control group. Cyclophosphamide significantly increased p53 and decreased Bcl-2 expression compared to the control group. S. platensis co-treated groups exhibited a significant decrease in sperm apoptosis compared to the Cyclophosphamide group. Moreover, S. platensis co-treated groups displayed a significant decreasing in p53 and increasing in Bcl-2 expression compared to the Cyclophosphamide group. The results of this study indicated that S. platensis protected rats against Cyclophosphamide-induced reproductive toxicity. PRACTICAL APPLICATIONS: Cyclophosphamide is the chemotherapy agent used to treat different cancers. Cyclophosphamide has side effects on the male reproductive system. Spirulina plantesis has a protective effect because of its antioxidant and anti-apoptotic properties. Co-administration of Spirulina plantesis with Cyclophosphamide reduces sperm apoptosis also decreases P53 protein expression and increases Bcl-2 protein expression. This study validated the anti-apoptotic potential of Spirulina plantesis against Cyclophosphamide-induced male reproductive toxicity., (© 2021 Wiley Periodicals LLC.)

Classical swine fever (CSF) is a highly contagious dreadful disease of pigs leading to 100% mortality in acute form in susceptible population thereby causing huge economic loss to pig farmers. This study was undertaken to assess the seroprevalence of CSF at national level. A two-stage random sampling methodology was adopted that included 271 villages from 115 districts of India. A total of 5848 pig serum samples from twenty-five states and one Union Territory of India were collected during 2018-2019. A percent positivity of 38.52 was found at national level. Puducherry and Sikkim showed the highest and lowest percent positivity respectively. Pigs from the west zone showed the highest seroprevalence of 55.83% and those from the south zone showed the lowest of 30.25%. Adult pigs in the north and east zones showed highest percent positivity of 81.8, whereas pigs of more than 3 years of age showed highest percent positivity of 54.9, 75 and 62.5 in the north east, west and central zones respectively. Young ones showed percent positivity of 41.5 in the south zone. Higher rainfall (> 3 mm/day) and lower temperature (< 26 °C) favoured the existence of disease in the north east region combined with high density of pig population. Amidst no fool proof alert system, seroprevalence is the best method to assess the status of CSF in herd/population that provides the policymakers to plan for control of disease.

Purpose of Review: This review will focus on how the extent of Barrett's metaplasia influences the risk of esophageal adenocarcinoma (EAC). More specifically, this review will discuss the concepts of long and short-segment Barrett's metaplasia and irregular Z line as they relate to EAC risk., Recent Findings: The Prague classification can standardize reporting of Barrett's metaplasia. Recent literature has found significant associations between the length of Barrett's metaplasia and increased progression risk to EAC in multiple geographically distinct populations. Length of Barrett's metaplasia has been incorporated into the Progression of Barrett's esophagus (PIB) model that can predict individualized life-time risks of progression. The risk of malignant transformation appears to be very low in patients with irregular Z line., Summary: Length of Barrett's metaplasia has emerged as an important predictor that can influence the risk of EAC and should be reported using the Prague classification. The PIB model, if further validated, could help a practicing gastroenterologist to inform patients with Barrett's metaplasia about their personal risk of progression to tailor surveillance intervals. Current guidelines do not recommend surveillance in patients with irregular Z line, but careful examination is recommended., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

The methanol extract of Camellia sinensis (MES) and acetone extract of Camellia assamica (AEA) were subjected to the thin layer chromatography to separate the bioactive compounds. The antimicrobial activity of all the fractions was carried out against pathogenic microorganisms by the agar-well diffusion method. The most effective bioactive fraction of each plant species was analysed by GC-MS. Fraction L of methanol extract of C. sinensis (MES) and fraction 5 of acetone extract of C. assamica (AEA) were found very effective against selected pathogenic strains. GC-MS analysis of this fraction showed the presence of n-heptadecanol-1 (68.63%) in MES and 2',6'dihydroxyacetophenone, bis(trimethylsilyl) (17.58%) in AEA with the highest area. The compounds n-heptadecanol-1 and 2',6'dihydroxyacetophenone, bis(trimethylsilyl) ether were used for docking to analyse its therapeutic potential. The ligand compound n-heptadecanol-1 (HEP) from MES of C. sinensis and 2',6'dihydroxyacetophenone, bis(trimethylsilyl) ether from AEA of C. assamica were docked with the target protein dihydropteoate synthase (DHPS) active sites of Escherichia coli and Staphylococcus aureus active sites via Auto Dock Vina, thereby forecasting the finest binding position of ligands. AutoDock Vina docked results revealed the involvement of binding energy for the establishment of the protein-ligand structure complex, besides generating an interpretation of all apparent molecular interactions accountable for its activity. Further, the protein-ligand complex of MES, EcDHPS + HEP and SaDHPS + HEP exhibiting the best binding affinity were - 4.8 kcal/mol and - 3.6 kcal/mol. The protein-ligand complex of AEA, i.e., EcDHPS + DHA and SaDHPS + DHA exhibited the best binding affinity of - 4.8 kcal/mol and - 4.8 kcal/mol.

Marine phycosphere harbors unique cross-kingdom associations with enormous ecological significance in aquatic ecosystems as well as relevance for algal biotechnology industry. During our investigating the microbial composition and bioactivity of marine phycosphere microbiota (PM), a novel lightly yellowish and versatile bacterium designated strain AM1-D1 T was isolated from cultivable PM of marine dinoflagellate Alexandrium minutum amtk4 that produces high levels of paralytic shellfish poisoning toxins (PSTs). Strain AM1-D1 T demonstrates notable bioflocculanting bioactivity with bacterial exopolysaccharides (EPS), and microalgae growth-promoting (MGP) potential toward its algal host. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain AM1-D1 T was affiliated to the members of genus Sulfitobacter within the family Rhodobacteraceae, showing the highest sequence similarity of 97.9% with Sulfitobacter noctilucae NB-68 T , and below 97.8% with other type strains. The complete genome of strain AM1-D1 T consisted of a circular 3.84-Mb chromosome and five circular plasmids (185, 95, 15, 205 and 348 Kb, respectively) with the G+C content of 64.6%. Low values obtained by phylogenomic calculations on the average nucleotide identity (ANI, 77.2%), average amino acid identity (AAI, 74.7%) and digital DNA-DNA hybridization (dDDH, 18.6%) unequivocally separated strain AM1-D1 T from its closest relative. The main polar lipids were identified as phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, diphosphatidylglycerol, one unidentified phospholipid and one unidentified lipid. The predominant fatty acids (> 10%) were C 18:1 ω7c, C 19:0 cyclo ω8c and C 16:0 . The respiratory quinone was Q-10. The genome of strain AM1-D1 T was predicted to encode series of gene clusters responsible for sulfur oxidation (sox) and utilization of dissolved organic sulfur exometabolites from marine dinoflagellates, taurine (tau) and dimethylsulfoniopropionate (DMSP) (dmd), as well as supplementary vitamin B 12 (cob), photosynthesis carotenoids (crt) which are pivotal components during algae-bacteria interactions. Based on the evidences by the polyphasic characterizations, strain AM1-D1 T represents a novel species of the genus Sulfitobacter, for which the name Sulfitobacter alexandrii sp. nov. is proposed. The type strain is AM1-D1 T (= CCTCC 2017277T = KCTC 62491 T ).

Hydrogel biomaterials have many favorable characteristics including tuneable mechanical behavior, cytocompatibility, optical properties suitable for regeneration and restoration of the damaged cornea tissue. The cornea is a tissue susceptible to various injuries and traumas with a complicated healing cascade, in which conserving its transparency and integrity is critical. Accordingly, the hydrogels' known properties along with the stimulation of nerve and cell regeneration make them ideal scaffold for corneal tissue engineering. Hydrogels have been used extensively in clinical applications for the repair and replacement of diseased organs. The development and optimizing of novel hydrogels to repair/replace corneal injuries have been the main focus of researches within the last decade. This research aims to critically review in vitro, preclinical, as well as clinical trial studies related to corneal wound healing using hydrogels in the past 10 years, as this is considered as an emerging technology for corneal treatment. Several unique modifications of hydrogels with smart behaviors have undergone early phase clinical trials and showed promising outcomes. Financially, this considers a multibillion dollars industry and with huge interest from medical devices as well as pharmaceutical industries with several products may emerge within the next five years., (© 2021 Wiley-VCH GmbH.)

Objectives: Low back pain (LBP) is the leading cause of disability and a global public health concern. Studies indicate that pain self-efficacy is associated with the development of disability in chronic LBP (CLBP) patients. The Pain Self-Efficacy Questionnaire (PSEQ) is a commonly used questionnaire to assess pain self-efficacy in patients with CLBP. It is essential to examine the psychometric properties of the PSEQ in the population in which it is to be used. Thus, the aim of this study is to evaluate the reliability and smallest detectable change of the Danish version of the Pain Self-Efficacy Questionnaire (PSEQ-DK) in patients with CLBP before implementing it as an outcome measure in an inpatient rehabilitation context., Methods: This observational study including 92 patients with CLBP was conducted in a multidisciplinary rehabilitation facility in Denmark. The psychometric properties statistically tested included reliability, smallest detectable change and floor and ceiling effect of the PSEQ-DK., Results: The reliability analysis included 92 patients and revealed an weighted kappa of 0.82 (95% Cl 0.75; 0.88) and Intraclass correlation coefficient of 0.83 (95% CI 0.75; 0.88), which corresponds to a good reliability. The smallest detectable change was 12.67., Conclusions: The present study demonstrated that the PSEQ-DK had a good reliability in patients with CLBP in an inpatient rehabilitation context. The current results expand our knowledge of the reliability and smallest detectable change of the PSEQ-DK. In order to implement PSEQ-DK in a rehabilitation context for evaluative purposes future studies should focus on examining responsiveness and interpretability., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Caffeine is worldwide used for its power to increase cognitive and physical performance. The ergogenic effects of caffeine, however, do not depend on a direct action on muscles. Actually, the actions of caffeine on skeletal muscles, take place at millimolar concentrations which are far above the micromolar level reached after a regular consumption of coffee or similar drinks, and close to a lethal concentration. At millimolar concentrations caffeine exerts a powerful effect on sarcoplasmic reticulum (SR) activating the release of calcium via ryanodine receptors and, possibly, inhibiting calcium reuptake. For this reason caffeine has become a valuable tool for studying SR function and for diagnostics of SR related muscle disorders. This review aims to briefly describe the effects and the mechanism of action of caffeine on sarcoplasmic reticulum and to focus on its use to study intracellular calcium dynamics in human muscle fibers in physiological and pathological conditions., (© 2020. Springer Nature Switzerland AG.)

Purpose: This study aimed to assess how the contamination rate of organ-cultured corneas has evolved and to analyze the evolution of microorganisms involved., Methods: Data from the Besançon eye bank were reviewed over 14 years (2005-2018). The changes in the contamination rate and the contaminant species found during the organ culture storage were analyzed. Microbiological tests were performed twice on the storage media-at day 5 and before the deswelling phase., Results: Among the 17,979 donor corneas collected, 1240 corneas were microbiological-test positive. The average annual contamination rate was 6.8% (range: 5.2%-8.9%). Seventy-five percent of contaminations were bacterial. The most frequently found bacterium was Staphylococcus spp. (31.3%), followed by non-Enterobacteriaceae Gram-negative Bacilli (GNB) (27.3%), with most Sphingomonas spp. and Pseudomonas spp. Fungal contamination (21.9%) was dominated by Candida (82.7%). Seventy-seven types of microorganisms were identified. The Staphylococcus rate tended to decrease, whereas non-Enterobacteriaceae GNB rate has increased in the past few years to reach 46% of bacteria. Most of the contaminations were detected in the early phase of organ culture at day 5 (89.2%). The second microbiological test found 44.8% of fungal contaminations (predominantly Candida spp.)., Conclusions: The annual contamination rate was stable and remains low, but the types of contaminating microorganisms varied from year to year. Staphylococcus spp. and non-Enterobacteriaceae GNB accounted for a significant proportion of the contaminations. We found a significant proportion of contamination, especially fungal, at the late phase of storage. Reassessing the antibiotics and antifungals in the storage medium may be useful to limit corneal disposal., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Piperine (PIP) is an alkaloid present in several species of piper, mainly Piper nigrum Linn. and P. longum, among other species. The present article provides a comprehensive review of PIP research in the last years concerning its chemical properties, synthesis, absorption, metabolism, bioavailability and toxicity. The reviewed PIP literature has shown many pharmacological properties, such as antidiabetic, antidiarrheal, antioxidant, antibacterial, and anti-parasitic activity of PIP. However, its low solubility and absorption make its application challenging. This review also includes advances in the development of nanosystems containing PIP, including liposomes, micelles, metal nanoparticles, nanofibers, polymeric nanoparticles, and solid-lipid nanoparticles. Finally, we discuss different in vitro and in vivo studies to evaluate the biological activity of this drug, as well as some methods for the synthesis of nanosystems and their physical characteristics.

Ginseng saponins (GS) are the main active compounds in Panax ginseng and have been proven to be highly effective in attenuating the side effects of chemotherapy. However, there have been no reports on the mechanism of action of GS. Treatment with GS has certain benefits, including decreasing the toxicity levels in the liver [alanine aminotransferase (ALT), albumin (ALB), alkaline phosphatase (ALP), aspartate transaminase (AST)], reducing oxidative stress [malondialdehyde (MDA), nitric oxide (NO)], diminishing inflammatory factors [interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) levels], and augmenting the levels of glutathione (GSH) and superoxide dismutase (SOD). The pharmacokinetics study showed that the area under the curve from 0 to 24 hr (AUC 0-24 hr) of 4-ketocyclophosphamide (4-KetoCTX) and carboxyphosphamide (CPM) was significantly increased after GS treatment. This study found that GS treatment can reduce chloroacetaldehyde (CAA) production by affecting CYP3A4, CYP2B6, and CYP2C9 protein expression in the liver. For the metabolomics study, GS attenuated the abnormalities of amino acid metabolic pathways in CP-induced liver injuries of rats and significantly enhanced the l-arginine level while reducing the serum nitric oxide (NO) level. This outcome was confirmed by the inhibition of the activities of NO synthase in the liver of rats., (© 2021 John Wiley & Sons Ltd.)

A severe acute respiratory syndrome is an unusual type of contagious pneumonia that is caused by SARS coronavirus. At present, the whole world is trying to combat this coronavirus disease and scientific communities are putting rigorous efforts to develop vaccines. However, there are only a few specific medical treatments for SARS-CoV-2. Apart from other public health measures taken to prevent this virus, we can boost our immunity with natural products. In this article, we have highlighted the potential of common spices and herbs as antiviral agents and immunity boosters. A questionnaire-based online survey has been conducted on home remedies during COVID-19 among a wide range of peoples (n-531) of different age groups (13-68 years) from various countries. According to the survey, 71.8% of people are taking kadha for combating infection and boosting immunity. Most people (86.1%) think that there is no side effect of kadha while 13.9% think vice versa. A total of 93.6% of people think that spices are helpful in curing coronavirus or other viral infection as well as boosting immunity. Most people are using tulsi drops, vitamin C, and chyawanprash for boosting their immunity. Therefore, we conclude from the survey and available literature that spices and herbs play a significant role against viral infections., (© 2021 John Wiley & Sons, Ltd.)

Leishmaniasis is a zoonotic disease in humans caused by the bite of a parasite-infected sandfly. The disease, widely referred to as "poor man's disease," affects millions of people worldwide. The clinical manifestation of the disease depends upon the species of the parasite and ranges from physical disfigurement to death if left untreated. Here, we review the past, present, and future of leishmaniasis in detail. The life cycle of Leishmania sp., along with its epidemiology, is discussed, and in addition, the line of therapeutics available for treatment currently is examined. The current status of the disease is critically evaluated, keeping emerging threats like human immunodeficiency virus (HIV) coinfection and post kala-azar dermal leishmaniasis (PKDL) into consideration. In summary, the review proposes a dire need for new therapeutics and reassessment of the measures and policies concerning emerging threats. New strategies are essential to achieve the goal of leishmaniasis eradication in the next few decades.

Objectives: Child marriage is one of the most important challenges of the current era that threatens women's health and violates human rights. The present study aimed to systematically review studies evaluating the challenges and strategies to overcome child marriage., Content: Medical databases (CINAHL, EMBASE, MEDLINE, EMBASE, PsycINFO, SCOPUS, Web of Science, ProQuest Nursing and Allied Health Source, and Social Science Research Network, as databases for English studies and IranMedex, Google Scholar, SID, Magiran, and Iran Doc as databases for Persian studies) were systematically searched from January 2010 to February 2020. To better identify appropriate studies, reference lists of relevant studies were searched. All potentially relevant abstracts and full-text were screened by two independent reviewers. Disagreements between two reviewers that could not be resolved were resolved via arbitration or consultation of a third author., Summary and Outlook: From 225 articles included in this review, 16 research articles met our inclusion criteria. Most of the articles were dedicated to negative health outcomes related to child marriage. Ten studies addressed the program of overcoming the Child marriage and six studies reported challenges of it. Although, many studies have shown the efficacy of strategies to decline Child marriage. On the basis of the available evidence, it seems there are a number of obstacles to end Child marriage. To delineate the most effective strategy to end Child marriage is required further research., (© 2021 Walter de Gruyter GmbH, Berlin/Boston.)

Importance: Ocular hypertension is an important risk factor for the development of primary open-angle glaucoma (POAG). Data from long-term follow-up can be used to inform the management of patients with ocular hypertension., Objective: To determine the cumulative incidence and severity of POAG after 20 years of follow-up among participants in the Ocular Hypertension Treatment Study., Design, Setting, and Participants: Participants in the Ocular Hypertension Treatment Study were followed up from February 1994 to December 2008 in 22 clinics. Data were collected after 20 years of follow-up (from January 2016 to April 2019) or within 2 years of death. Analyses were performed from July 2019 to December 2020., Interventions: From February 28, 1994, to June 2, 2002 (phase 1), participants were randomized to receive either topical ocular hypotensive medication (medication group) or close observation (observation group). From June 3, 2002, to December 30, 2008 (phase 2), both randomization groups received medication. Beginning in 2009, treatment was no longer determined by study protocol. From January 7, 2016, to April 15, 2019 (phase 3), participants received ophthalmic examinations and visual function assessments., Main Outcomes and Measures: Twenty-year cumulative incidence and severity of POAG in 1 or both eyes after adjustment for exposure time., Results: A total of 1636 individuals (mean [SD] age, 55.4 [9.6] years; 931 women [56.9%]; 1138 White participants [69.6%]; 407 Black/African American participants [24.9%]) were randomized in phase 1 of the clinical trial. Of those, 483 participants (29.5%) developed POAG in 1 or both eyes (unadjusted incidence). After adjusting for exposure time, the 20-year cumulative incidence of POAG in 1 or both eyes was 45.6% (95% CI, 42.3%-48.8%) among all participants, 49.3% (95% CI, 44.5%-53.8%) among participants in the observation group, and 41.9% (95% CI, 37.2%-46.3%) among participants in the medication group. The 20-year cumulative incidence of POAG was 55.2% (95% CI, 47.9%-61.5%) among Black/African American participants and 42.7% (95% CI, 38.9%-46.3%) among participants of other races. The 20-year cumulative incidence for visual field loss was 25.2% (95% CI, 22.5%-27.8%). Using a 5-factor baseline model, the cumulative incidence of POAG among participants in the low-, medium-, and high-risk tertiles was 31.7% (95% CI, 26.4%-36.6%), 47.6% (95% CI, 41.6%-53.0%), and 59.8% (95% CI, 53.1%-65.5%), respectively., Conclusions and Relevance: In this study, only one-fourth of participants in the Ocular Hypertension Treatment Study developed visual field loss in either eye over long-term follow-up. This information, together with a prediction model, may help clinicians and patients make informed personalized decisions about the management of ocular hypertension., Trial Registration: ClinicalTrials.gov Identifier: NCT00000125.

Background: Laparoscopic sleeve gastrectomy (LSG) is safe and effective in type 2 diabetes mellitus (T2DM) with body mass index (BMI) ≥ 35 kg/m 2 . However, the effect and safety of LSG in the treatment of T2DM patients with BMI less than 35 kg/m 2 , especially in patients with BMI less than 30 kg/m 2 , are still debatable., Methods: A total of 51 T2DM patients with BMI less than 35 kg/m 2 treated successfully with LSG were included in our study. All patients were divided into two groups for subgroup analysis, namely group A (BMI 23.23-29.97 kg/m 2 ) and group B (BMI 30.0-34.9 kg/m 2 ). The weight loss and diabetic characteristics of LSG in the two groups at 3 months, 6 months, and 12 months after operation were compared, respectively., Results: In group A, the complete remission rates of T2DM were 20%, 36%, and 44% at 3, 6, and 12 months after operation, respectively. In group B, the complete remission rates of T2DM were 30.8%, 61.5%, and 88.5% at 3, 6, and 12 months after operation, respectively. Besides, none of the patients with a duration more than 15 years achieved complete remission. For T2DM patients with BMI < 30 kg/m 2 at 12 months after LSG, the complete remission rate of T2DM was 15.4% in patients with ABCD scores ≤ 2, and the complete remission rate of T2DM was 100% in patients with ABCD scores ≥ 5., Conclusion: LSG is safe and effective for T2DM patients with BMI less than 35 kg/m 2 in the short-term. However, the complete remission rate of T2DM in patients with BMI less than 30 kg/m 2 is far from the diabetes patients with BMI at 30-34.9 kg/m 2 .

G-quadruplexes (G4) play crucial roles in biology, analytical chemistry and nanotechnology. The stability of G4 structures is impacted by the number of G-quartets, the length and positions of loops, flanking motifs, as well as additional structural elements such as bulges, capping base pairs, or triads. Algorithms such as G4Hunter or Quadparser may predict if a given sequence is G4-prone by calculating a quadruplex propensity score; however, experimental validation is still required. We previously demonstrated that this validation is not always straightforward, and that a combination of techniques is often required to unambiguously establish whether a sequence forms a G-quadruplex or not. In this article, we adapted the well-known FRET-melting assay to characterize G4 in batch, where the sequence to be tested is added, as an unlabeled competitor, to a system composed of a dual-labeled probe (F21T) and a specific quadruplex ligand. PhenDC3 was preferred over TMPyP4 because of its better selectivity for G-quadruplexes. In this so-called FRET-MC (melting competition) assay, G4-forming competitors lead to a marked decrease of the ligand-induced stabilization effect (∆T m ), while non-specific competitors (e.g., single- or double-stranded sequences) have little effect. Sixty-five known sequences with different typical secondary structures were used to validate the assay, which was subsequently employed to assess eight novel sequences that were not previously characterized., (© 2020 Wiley Periodicals LLC.)

Limbal stem cells (LSCs) are already used in cell-based treatments for ocular surface disorders. Clinical translation of LSCs-based therapies critically depends on the successful delivery, survival, and retention of these therapeutic cells to the desired region. Such a major bottleneck could be overcome by using an appropriate carrier to provide anchoring sites and structural support to LSC culture and transplantation. Bacterial nanocellulose (BNC) is an appealing, yet unexplored, candidate for this application because of its biocompatibility, animal-free origin and mechanical stability. Here, BNC as a vehicle for human embryonic stem cells-derived LSC (hESC-LSC) are investigated. To enhance cell-biomaterial interactions, a plasma activation followed by a Collagen IV and Laminin coating of the BNC substrates is implemented. This surface functionalization with human extracellular matrix proteins greatly improved the attachment and survival of hESC-LSC without compromising the flexible, robust and semi-transparent nature of the BNC. The surface characteristics of the BNC substrates are described and a preliminary ex vivo test in simulated transplantation scenarios is provided. Importantly, it is shown that hESC-LSC retain their self-renewal and stemness characteristics up to 21 days on BNC substrates. These results open the door for future research on hESC-LSC/BNC constructs to treat severe ocular surface pathologies., (© 2021 Wiley-VCH GmbH.)

Objective: The purpose of this systematic review and meta-analysis was to determine the effectiveness of intravenous magnesium sulfate when used to attenuate hemodynamic fluctuations associated with the creation of pneumoperitoneum in adults undergoing laparoscopic surgery., Introduction: Laparoscopic surgery has gained popularity as a result of improved patient outcomes postoperatively, but pneumoperitoneum alters the patient's physiology and hemodynamic profile during the intraoperative period. Magnesium sulfate is a nonopioid agent known for its ability to blunt the physiologic sympathetic response associated with exposure to noxious stimuli. Magnesium sulfate may be efficacious in promoting anesthetic management that optimizes a patient's cardiopulmonary function while minimzing opioid use., Inclusion Criteria: Studies with participants at least 18 years old undergoing any elective laparoscopic surgery using pneumoperitoneum with CO2 insufflation were included. Studies were excluded if patients were being treated for pheochromocytoma. Studies eligible for inclusion employed any intravenous dosing strategy of magnesium sulfate, administered at any point in the perioperative period for the purpose of blunting the sympathetic response to creation of a pneumoperitoneum. The comparator utilized was normal saline., Methods: A systematic search of MEDLINE, CINAHL, Cochrane Library, Google Scholar, Trip Database, MedNar, Grey Literature Report, ClinicalTrials.gov, and ProQuest Dissertations and Theses was conducted to identify both published and unpublished studies. The search was limited to studies written in the English language and performed on human subjects. Studies were selected for review based on inclusion criteria and were appraised by two reviewers using the appropriate JBI standardized appraisal tool. Data extraction was performed for all outcome variables. Data were pooled using the JBI System for the Unified Management, Assessment and Review of Information. Mean differences (95% confidence interval) were calculated for all continuous variables. Meta-analysis using a fixed effects model was performed at various time points for heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure. Standard GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) evidence assessment was also reported., Results: A total of six randomized controlled trials were included in the review. Meta-analysis of data for biophysical parameters (heart rate, systolic blood pressure, diastolic blood pressure, and mean arterial pressure) at five minutes, 10 to 15 minutes, 30 minutes after pneumoperitoneum, and at the end of surgery showed a consistent reduction in the magnesium groups compared to placebo. Support for all outcome variables was determined to be high using the GRADE criteria., Conclusion: The administration of magnesium sulfate consistently demonstrated improved hemodynamic measurements during laparoscopic surgery. All doses administered in the included studies proved beneficial compared to placebo. Magnesium sulfate should be considered as an adjunct agent in laparoscopic surgery to blunt the sympathetic nervous system response to surgical stimulation. The quality of the included studies was high, but small sample sizes and selection of healthy participants may limit the generalizability of the results. The use of magnesium sulfate may have improved effects on patients with significant health comorbidities, but the limitations of the included studies related to sample demographics make the evidence inconclusive., Systematic Review Registration Number: PROSPERO (CRD42019139991)., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 JBI.)

Traumatic brain injury (TBI) accounts for significant global health burden. Effects of TBI can become chronic even following mild injury. There is a need to develop effective therapies to attenuate the damaging effects of TBI and improve recovery outcomes. This literature review using a priori criteria (PROSPERO; CRD42018100623) summarized 43 studies between January 1998 and July 2019 that investigated nutritional interventions (NUT) delivered with the objective of altering neurophysiological (NP) outcomes following TBI. Risk of bias was assessed for included studies, and NP outcomes recorded. The systematic search resulted in 43 of 3,748 identified studies met inclusion criteria. No studies evaluated the effect of a NUT on NP outcomes of TBI in humans. Biomarkers of morphological changes and apoptosis, oxidative stress, and plasticity, neurogenesis, and neurotransmission were the most evaluated NP outcomes across the 43 studies that used 2,897 animals. The risk of bias was unclear in all reviewed studies due to poorly detailed methodology sections. Taking these limitations into account, anti-oxidants, branched chain amino acids, and ω-3 polyunsaturated fatty acids have shown the most promising pre-clinical results for altering NP outcomes following TBI. Refinement of pre-clinical methodologies used to evaluate effects of interventions on secondary damage of TBI would improve the likelihood of translation to clinical populations., (© 2020 Wiley Periodicals LLC.)

Many studies have established the functional properties of Lacticaseibacillus rhamnosus GG, previously known as Lactobacillus rhamnosus GG, marketed worldwide as a probiotic. The extraordinary capacity of L. rhamnosus GG to bind to human mucus and influence the immune system especially stand out. Earlier, we have shown the key role of its SpaCBA sortase-dependent pili encoded by the spaCBA-srtC1 gene cluster herein. These heterotrimeric pili consist of a shaft pilin SpaA, a basal pilin SpaB, and tip pilin SpaC that contains a mucus-binding domain. Here, we set out to characterize a food-grade non-GMO mutant of L. rhamnosus GG, strain PA11, which secretes its pilins, rather than coupling them to the cell surface, due to a defect in the housekeeping sortase A. The sortase-negative strain PA11 was extensively characterized using functional genomics and biochemical approaches and found to secrete the SpaCBA pili into the supernatant. Given the functional importance and uniqueness of the mucus-binding pili of L. rhamnosus GG, strain PA11 offers novel opportunities towards the characterization and further therapeutic application of SpaCBA pili and their low-cost, large-scale production. KEY POINTS: •Creation of pilus-secreting mutant (PA11) of the key probiotic LGG. •Strain PA11 is defective in a functional housekeeping sortase SrtA. •Strain PA11 opens novel biotherapeutic application avenues. Graphical abstract.

In this study, we sequenced the V3-V4 region of 16S rRNA gene amplicon using paired-end Illumina HiSeq to study the bacterial community in the gills of fish from the bank of the trans-border river of Brahmaputra, Northeast India. Metagenome data consisted of 278,784 reads, 248-bp length, and 56.48% GC content with 85% sequence having a Phred score Q = 30. Community metagenomics revealed a total of 631 genera belonging to 22 different phyla, dominated by Proteobacteria (118,222 features), Firmicutes (101,043 features), Actinobacteria (34,189 features), Bacteroidetes (17,977 features), and Cyanobacteria (2730 features). The bacterial community identified was composed of both pathogenic zoonotic and non-harmful groups. The pathway or functional analysis of the fish gill microbiome exhibited 21 different pathways which also included the pathogenic-related functions. Our data detected a wide group of bacterial communities that will be useful in further isolating and characterizing the pathogenic bacteria from the fish and also to understand the bacterial association in highly consumed fish.

Serratiopeptidase (EC 3.4.24.40), a proteolytic enzyme, is one of the most promising enzymes being used in biopharmaceutical industry. Mulberry phyllosphere, being an unexplored niche for exploration of protease production, was chosen for the present study. Protease producing bacteria were isolated from the tissues of mulberry plant as well as its rhizospheric soil. Two protease producing bacteria belonging to Serratia genus were found to be potential serratiopeptidase producers. Among them, the endophyte, i.e., Serratia marcescens MES-4 presented 95 Units/mL activity, while the soil isolate i.e., Serratia marcescens MRS-11 presented 156 Units/mL activity.

Objective: We sought to investigate the contribution of delayed 18 F-FDG imaging data to epileptogenic zone (EZ) identification using a hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) system., Methods: Forty-one patients with epilepsy underwent a brain dual time point 18 F-FDG PET/MRI examination. All early imaging was acquired at approximately 40 min. Late imaging was classified as short delay (150.1 ± 20.2 min) or long delay (247.8 ± 24.6 min). Visual evaluation and scoring of 18 F-FDG uptake at dual time points were performed. An SUV mean asymmetry index (AI) was calculated representing the difference in uptake between the EZ and the contralateral side. The EZ location was defined by a multidisciplinary team based on findings on video electroencephalography, 18 F-FDG, and MRI. EZ location was classified as extratemporal lobe epilepsy (extra-TLE) or temporal lobe epilepsy (TLE). MRI findings were classified as positive if there were signal/structural abnormalities, or negative. AI of dual time points was compared between MRI-positive and MRI-negative, between extra-TLE and TLE, and between short delay and long delay of the late imaging time point., Results: The AI at the delayed time points was increased by a mean of 3.7 over the early time point in all patients (P < 0.01). The biggest AIs were found in the MRI-positive group. The ΔAI between two imaging points were 3.71 ± 3.50 and 4.67 ± 7.94 for MRI-positive and MRI-negative; 4.52 ± 6.70 and 2.51 ± 2.42 for extra-TLE and TLE; and 4.24 ± 6.52 and 3.46 ± 2.90 for short delay and long delay groups, respectively. There were more patients with increased AI at the delayed time with MRI-positive (95.8%, 23/24), with extra-TLE (96.8%, 30/31), and with short delay time (93.7%, 30/32). Two observers who had no knowledge of the images chose 85.4% and 82.9% of the delay-time point images as the more obvious asymmetry from all images. The kappa value between the two observers was 0.66 with good agreement., Conclusion: Delayed 18 F-FDG PET imaging can be used to better identify EZs with relatively greater metabolic asymmetry between the EZ and contralateral regions.

The genus Colletotrichum comprises a large number of filamentous fungi responsible for anthracnose diseases in many tropical and subtropical fruits and vegetables. In particular, Colletotrichum higginsianum infects Brassicaceae species, including Arabidopsis. The C. higginsianum strain IMI349063A is naturally infected with a dsRNA virus, named Colletorichum higginsianum non-segmented virus (ChNRV1). Here, we investigated the biological effect of ChNRV1 in C. higginsianum by comparing strains with and without the virus. ChNRV1 does not have an effect on C. higginsianum growth under salt and cell-wall stress conditions. However, thermal stress reduced C. higginsianum growth rate, this effect being more evident in the wild-type C. higginsianum strain containing the virus. Although ChNRV1 had no effect in conidiation, conidia were narrower when the virus is present. More importantly, ChNRV1 causes a mild increase in C. higginsianum virulence (hypervirulence) when infecting Arabidopsis plants. These findings indicated that, whereas the ChNRV1 mycovirus does not impair growth and conidiation of C. higginsianum, it confers hypervirulence to the fungal host. These findings will help in future research on the effect of mycoviral infection on pathogenic fungi in plant species of agronomical relevance.

Lycopodii herba (SJC), a traditional Chinese medicine, has the effect of dispelling wind and eliminating dampness (a therapeutic principle and method of traditional Chinese medicine for rheumatoid arthritis), relaxing tendon and activating collaterals. However, the major effective components and its therapeutic mechanism were unclear. In this study, different SJC samples with slightly different compositions were prepared by extracting with different concentrations of ethanol. Then, the therapeutic effects on rheumatoid arthritis (RA) of different SJC samples were evaluated. Finally, the spectrum-effect relationship between UPLC-Q-TOF/MS fingerprints and the effect of RA was explored to screen the effective components. Western blotting was used to study the potential mechanism. The volume of hind paw and the level of RF, TNF-α, and IL-1β were lower after administrating with different SJC samples, compared with the model group. Histopathological findings also confirmed that SJC could relieve the symptoms of RA. Combined with identification of the components in plasm from SJC, lycojaponicumin C, des-N-methyl-α-obscurine, 8β-acetoxy-12β-hydroxy-lycopodine or 8β-acetoxy-11α-hydroxy-lycopodine or 8β-hydroxy-11α-acetoxylycopodine were considered to be the major effective components. The mechanism may be related to AChE/NF-κB signaling pathway. This work provides a general method to screen the potential effective components of herb medicines and would be benefit to understand the mechanism of SJC for the treatment of RA.

Toll-like receptors (TLRs), TLR2 in particular, are shown to recognize various glycans and glycolipid ligands resulting in various immune effector functions. As barley β-glucan and zymosan are the glycans implicated in immunomodulation, we examined whether these ligands interact with Dectin-1, a lectin-type receptor for glycans, and TLR2 and induce immune responses that can be used against Leishmania infection in a susceptible host. The binding affinity of barley β-glucan and zymosan with Dectin-1 and TLR2 was studied in silico. Barley β-glucan- and zymosan-induced dectin-1 and TLR2 co-localization was studied by confocal microscopy and co-immunoprecipitation. These ligands-induced signalling and effector functions were assessed by Western blot analyses and various immunological assays. Finally, the anti-leishmanial potential of barley β-glucan and zymosan was tested in Leishmania donovani -infected macrophages and in L. donovani-infected BALB/c mice. Both barley β-glucan and zymosan interacted with TLR2 and dectin-1, but with a much stronger binding affinity for the latter, and therefore induced co-localization of these two receptors on BALB/c-derived macrophages. Both ligandsactivated MyD88- and Syk-mediated downstream pathways for heightened inflammatory responses in L. donovani-infected macrophages. These two ligands induced T cell-dependent host protection in L. donovani-infected BALB/c mice. These results establish a novel modus operandi of β-glucans through dectin-1 and TLR2 and suggest an immuno-modulatory potential against infectious diseases., (© 2020 The Scandinavian Foundation for Immunology.)

Microsporidia are a large group of fungal-related obligate intracellular parasites. They are responsible for infections in humans as well as in agriculturally and environmentally important animals. Although microsporidia are abundant in nature, many of the molecular mechanisms employed during infection have remained enigmatic. In this review, we highlight recent work showing how microsporidia invade, proliferate and exit from host cells. During invasion, microsporidia use spore wall and polar tube proteins to interact with host receptors and adhere to the host cell surface. In turn, the host has multiple defence mechanisms to prevent and eliminate these infections. Microsporidia encode numerous transporters and steal host nutrients to facilitate proliferation within host cells. They also encode many secreted proteins which may modulate host metabolism and inhibit host cell defence mechanisms. Spores exit the host in a non-lytic manner that is dependent on host actin and endocytic recycling proteins. Together, this work provides a fuller picture of the mechanisms that these fascinating organisms use to infect their hosts., (© 2020 John Wiley & Sons Ltd.)

Anthropogenic activities pose challenges on security of water quality. Identifying potential sources of pollution and quantifying their corresponding contributions are essential for water management and pollution control. In our study, 2-year (2017-2018) water quality dataset of 15 parameters from eight sampling sites in tributaries and mainstream of the Min River was analyzed with multivariate statistical analysis methods and absolute principal component score-multiple linear regression (APCS-MLR) receptor modeling technique to reveal potential sources of pollution and apportion their contributions. Temporal and spatial cluster analysis (CA) classified 12 months into three periods exactly consistent with dry, wet, and normal seasons, and eight monitoring sites into two regions, lightly polluted (LP) and highly polluted (HP) regions, based on different levels of pollution caused by physicochemical properties and anthropogenic activities. The principal component analysis (PCA) identified five latent factors accounting for 75.84% and 73.46% of the total variance in the LP and HP regions, respectively. The main pollution sources in the two regions included agricultural activities, domestic sewage, and industrial wastewater discharge. APCS-MLR results showed that in the LP region, contribution of five potential pollution sources was ranked as agricultural non-point source pollution (22.13%) > seasonal effect and phytoplankton growth (19.86%) > leakage of septic tanks (15.73%) > physicochemical effect (12.86%) > industrial effluents and domestic sewage (11.59%), while in the HP region ranked as point source pollution from domestic and industrial discharges (20.81%) > municipal sewage (16.66%) > agricultural non-point source pollution (15.23%) > phytoplankton growth (14.82%) > natural and seasonal effects (12.67%). Based on the quantitative assessment of main pollution sources, the study can help policymakers to formulate strategies to improve water quality in different regions.

Purpose: To test whether intraoperative stereotactic navigation during orbital decompression surgery resulted in quantifiable surgical benefit., Methods: This retrospective cohort study examined all consecutive patients who underwent primary orbital decompression surgery for thyroid associated orbitopathy performed by a single surgeon (A.K.) during the periods of 2012-2014 (non-navigated), and 2017-2018 (navigated). The study was HIPAA-compliant, was approved by the Institutional Review Board, and adhered to the tenets of the Helsinki declaration. Recorded parameters included patient age, sex, race, decompression technique (side of operation and walls decompressed), estimated blood loss (EBL), intraoperative complications, times that patient entered and exited the operating room (OR), times of surgical incision and dressing completion, pre- and postoperative best corrected visual acuity (BCVA), proptosis, diplopia, postoperative change in strabismus deviation, and need for subsequent strabismus surgery. Recorded times were used to calculate operating time (initial incision to dressing) and maintenance time (time between OR entry and initial incision and time between dressings and OR exit). The total maintenance time was averaged over total number of operations. Student t test was used to compare surgical times, maintenance times, EBL, and proptosis reduction. Fisher exact test was used to compare BCVA change, strabismus deviation change, resolution or onset of diplopia, and need for corrective strabismus surgery., Results: Twenty-two patients underwent primary orbital decompression surgery without navigation, and 23 patients underwent navigation-guided primary orbital decompression surgery. There were no intraoperative complications in either group. The average operative time was shorter in the navigated group for a unilateral balanced decompression (n = 10 vs. 19; 125.8 ± 13.6 vs. 141.3 ± 19.4 min; p-value = 0.019), and a unilateral lateral wall only decompression (n = 13 vs. 3; 80.5 ± 12.8 vs. 93.0 ± 6.1 min; p-value = 0.041). The average maintenance time per surgery was not significantly different between the non-navigated group (51.3 ± 12.7 min) and the navigated group (50.5 ± 6.4 min). There was no significant difference between the navigated and non-navigated groups in average EBL per surgery. There was no significant difference in BCVA change. Average proptosis reduction was larger in the navigated group, but this was not significant. There was a significantly lower proportion of patients who required corrective strabismus surgery following decompression in the navigated group than in the non-navigated group (39.1% vs. 77.3%, p-value = 0.012)., Conclusions: Intraoperative stereotactic navigation during orbital decompression surgery has the potential to provide the surgeon with superior spatial awareness to improve patient outcomes. This study found that use of intraoperative navigation reduced operative time (even without factoring in a resident teaching component) while also reducing the need for subsequent strabismus surgery. This study is limited by its size but illustrates that use of intraoperative navigation guidance has substantive benefits in orbital decompression surgery.

The recent development of next-generation sequencing technologies has offered valuable insights into individual cells. This technology is centered on the characterization of single cells for epigenomics, genomics, and transcriptomics. Ever since the first report appeared in 2009, the single-cell RNA-sequencing saga started to explore deeper into the mechanics intrigued within a single cell. microRNA (miRNA) has been increasingly recognized as an essential molecule triggering an additional layer for gene regulation. Therefore, single-cell sequencing of miRNAs is crucial to explore the logical riddles surrounding the epigenomics, genomics, and transcriptomics of an individual cell. Scientists from the Vienna Biocenter Campus have lately performed single-cell sequencing of miRNAs in the fly, Drosophila, and nematode, Caenorhabditis elegans. In this review, we present the latest scientific explorations supported by all-inclusive data on this novel subject matter of next-generation sequencing., (© 2020 International Federation for Cell Biology.)

In Kenya, globally circulating HIV surveillance techniques are implicated in an emergent experimental terrain that merges scientific interest with health administration agendas. Sex worker activists reroute and repurpose this technocratic knowledge to more precisely pinpoint and defy the undemocratic imperatives of an encroaching experimental order that aims to govern the health of key populations. Reconstructing the conditions of emergence of these evidentiary politics reveals growing interdependencies between sex workers and scientific and technical experts as they are brought into increasing interaction with each other., (© 2020 by the American Anthropological Association.)

Objective: Insula epilepsy is rare and can be evaluated effectively by Stereotactic intracerebral EEG (SEEG). Many previous studies of insulo-opercular seizures have been unable to separate insular and opercular onset. With adequate sampling of the insula, this study shows this is possible., Methods: We analyzed intrainsular dynamics and extrainsular propagation in 12 patients with "pure" insula epilepsy (n = 9) or insular and only deepest opercular involvement (n = 3) at seizure onset. Review of semiology defined clinical groups, agglomerative cluster, and principal component analysis of semiological features were performed. Quantitative epileptogenicity, and intrainsular and extrainsular propagation were computed via time frequency analysis and epileptogenicity mapping., Results: Seizure onset patterns were heterogeneous; the seizure onset zone was focal. Seizure onset and first ictal change within insula functional subdivision correlated with aura and reflex component. No paninsular spread occurred; contralateral insular spread was very early. While the discharge was intrainsular, clinical signs related to aura or vegetative signs. Extrainsular propagation was early and related to the emergence of the majority of clinical signs. Cluster analysis found an anterior, intermediate, and posterior insula seizure onset group. The largest principal component separated anterior insula manifestations, including early hypermotor signs, early recovery, and no aura from posterior insula features of early dystonia, early tonic motor features, and sensorimotor aura., Interpretation: Aura is vital to identifying seizure onset and relates to insula functional subdivision. Seizures are heterogenous; extrainsular propagation occurs early, accounting for most of the semiology. With adequate sampling, "pure" insula epilepsy can be identified and focal curative resection is possible. ANN NEUROL 2020;88:477-488., (© 2020 American Neurological Association.)

Background and Aim: The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is very poor. This study aimed to evaluate hepatic arterial infusion chemotherapy (HAIC) versus sorafenib (SORF) in the treatment of HCC with PVTT., Methods: Studies were identified online in Embase and MEDLINE before October 31, 2019. The end-points were overall survival (OS), progression-free survival (PFS), disease control rate (DCR), and safety., Results: Six studies with 417 cases were included in this systematic review. Meta-analyses demonstrated that HAIC is superior to SORF with respect to OS (hazard ratio [HR]: 0.50, 95% confidence interval: 0.38-0.66, P < 0.001) and PFS (HR: 0.47, 95% confidence interval: 0.31-0.73, P = 0.001) irrespective of research territoriality and study quality. Our systematic review also demonstrated that HAIC is superior to SORF with respect to DCR. Subgroup analysis demonstrated that the advantage is more obvious in the treatment of types III-IV PVTT with respect to OS (HR: 0.29, P < 0.001) and PFS(HR: 0.39, P < 0.001). HAIC caused more grades 3-4 neutropenia (HR: 10.71), anemia (HR: 7.55), leukopenia (HR: 10.38), and thrombocytopenia (HR: 13.09) than SORF. However, HAIC caused fewer cases of grades 3-4 aspartate aminotransferase rising (HR: 0.21), diarrhea (HR: 0.14), and hand-foot syndrome (HR: 0.14) than SORF., Conclusions: This systematic review demonstrated that HAIC is superior to SORF in HCC with PVTT with respect to OS, PFS, and DCR, especially in HCC with types III-IV PVTT. HAIC caused more myelosuppression, whereas SORF is associated with diarrhea and hand-foot syndrome. Further randomized controlled trials are warranted., (© 2020 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Post-transplantation diabetes mellitus (PTDM) is a major complication in kidney transplant recipients leading to reduced allograft and patient survival. Given the high prevalence of diabetes in Qatar, which is twice the global average, we were interested in determining the incidence of PTDM, identifying risk factors, and comparing clinical outcomes in kidney transplant recipients with and without diabetes. We retrospectively followed up 191 adult kidney allograft recipients transplanted between January 1, 2012, and December 31, 2016, for a median of 41 months. A total of 76 patients (40%) had pre-existing diabetes. A total of 39 patients developed PTDM during follow-up; they represent 34% of patients who did not have diabetes prior to transplantation. Two thirds of PTDM occurred within 3-6 months post-transplantation. Prediabetes before transplant [OR = 6.07 (1.24-29.74), P = .026] older recipient's age at the time of transplantation [OR = 1.10 (1.00-1.20), P = .039] and average fasting blood sugar during 3-6 months post-transplant [OR = 1.06 (1.01-1.11), P = .010] were independently associated with PTDM. Patient and kidney allograft survival rates exceeded 97% in all groups. The incidence of PTDM in kidney transplant recipients living in Qatar is high. Older age and prediabetes are independent risk factors for developing PTDM., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Patient education (PE) is recommended as an integral part of disease management for people with chronic inflammatory arthritis (IA). There is no consensus on how PE should be evaluated and which outcome measures should be used., Objectives: This study had three aims: (a) to identify core aspects that PE for patients with IA may impact on; (b) to identify outcome measures to assess changes in these aspects; (c) to test the feasibility and responsiveness of the identified outcome measures., Methods: A Delphi process was conducted to identify core aspects and outcome measures. Feasibility and responsiveness were tested in a pre-/post-test study with 3 months follow-up, including 104 patients attending PE programmes., Results: Seven core aspects were identified: communication with health professionals, coping strategies, empowerment, knowledge about healthy life style, self-efficacy, understanding disease and treatment, and sharing experiences. Four outcome measures were identified; Arthritis Self Efficacy Scale (ASES-11), Effective Consumer scale (EC-17), Health Education Impact Questionnaire (heiQ) and Patient Activation Measure (PAM). At baseline, all measures had low rates of missing data. All measures except two heiQ subscales exhibited ceiling effects. Internal consistency was acceptable. At follow-up, statistically significant, but small improvements were found in EC-17 and three heiQ subscales., Conclusion: ASES and EC-17 were found to be the most valid and feasible outcome measures to evaluate the identified core aspects of PE and can be recommended as outcome measures to assess PE programmes for patients with IA., (© 2020 John Wiley & Sons, Ltd.)

Purpose of Review: Epilepsy surgery is the therapy of choice for 30-40% of people with focal drug-resistant epilepsy. Currently only ∼60% of well selected patients become postsurgically seizure-free underlining the need for better tools to identify the epileptogenic zone. This article reviews the latest neurophysiological advances for EZ localization with emphasis on ictal EZ identification, interictal EZ markers, and noninvasive neurophysiological mapping procedures., Recent Findings: We will review methods for computerized EZ assessment, summarize computational network approaches for outcome prediction and individualized surgical planning. We will discuss electrical stimulation as an option to reduce the time needed for presurgical work-up. We will summarize recent research regarding high-frequency oscillations, connectivity measures, and combinations of multiple markers using machine learning. This latter was shown to outperform single markers. The role of NREM sleep for best identification of the EZ interictally will be discussed. We will summarize recent large-scale studies using electrical or magnetic source imaging for clinical decision-making., Summary: New approaches based on technical advancements paired with artificial intelligence are on the horizon for better EZ identification. They are ultimately expected to result in a more efficient, less invasive, and less time-demanding presurgical investigation.

Objective: This scoping review aims to identify and map the use of technology in measuring and analyzing older adults' social networks in the context of health and social care., Introduction: Research has shown that social networks impact the health and well-being of older adults. Advancements in the internet, electronic and digital devices, social media, and healthcare technology enhance our ability to collect social network and health data. These rapidly evolving technologies present opportunities to overcome limitations in social network measurement and promote improved understanding of the impact of social networks on the health and well-being of older adults., Inclusion Criteria: This scoping review will include studies of older adults that measured social networks using technology and were related to health or health and social care. Studies published in English from 2004 to the present will be included. Books, editorials, letters, and commentaries will be excluded., Methods: PubMed (MEDLINE), Sociological Abstracts, SocINDEX, CINAHL, and Web of Science will be searched for related articles. Gray literature will be included by searching conference abstracts via Conference Papers Index and hand-searching conference proceedings from the American Sociological Society and the Gerontological Society of America. Data will be extracted by two independent reviewers using an a priori data extraction tool. Tables and summary narratives will be used to map and synthesize existing approaches to measuring social networks using technology, the settings for measurement development or testing, and the use of approaches in discovery science, implementation science, or clinical care.

Membrane transport proteins, also known as transporters, control the movement of ions, nutrients, metabolites, and waste products across the membranes of a cell and are central to its biology. Proteins of this type also serve as drug targets and are key players in the phenomenon of drug resistance. The malaria parasite has a relatively reduced transportome, with only approximately 2.5% of its genes encoding transporters. Even so, assigning functions and physiological roles to these proteins, and ascertaining their contributions to drug action and drug resistance, has been very challenging. This review presents a detailed critique and synthesis of the disruption phenotypes, protein subcellular localisations, protein functions (observed or predicted), and links to antimalarial drug resistance for each of the parasite's transporter genes. The breadth and depth of the gene disruption data are particularly impressive, with at least one phenotype determined in the parasite's asexual blood stage for each transporter gene, and multiple phenotypes available for 76% of the genes. Analysis of the curated data set revealed there to be relatively little redundancy in the Plasmodium transportome; almost two-thirds of the parasite's transporter genes are essential or required for normal growth in the asexual blood stage of the parasite, and this proportion increased to 78% when the disruption phenotypes available for the other parasite life stages were included in the analysis. These observations, together with the finding that 22% of the transportome is implicated in the parasite's resistance to existing antimalarials and/or drugs within the development pipeline, indicate that transporters are likely to serve, or are already serving, as drug targets. Integration of the different biological and bioinformatic data sets also enabled the selection of candidates for transport processes known to be essential for parasite survival, but for which the underlying proteins have thus far remained undiscovered. These include potential transporters of pantothenate, isoleucine, or isopentenyl diphosphate, as well as putative anion-selective channels that may serve as the pore component of the parasite's 'new permeation pathways'. Other novel insights into the parasite's biology included the identification of transporters for the potential development of antimalarial treatments, transmission-blocking drugs, prophylactics, and genetically attenuated vaccines. The syntheses presented herein set a foundation for elucidating the functions and physiological roles of key members of the Plasmodium transportome and, ultimately, to explore and realise their potential as therapeutic targets., (© 2019 Cambridge Philosophical Society.)

The broad application of ß cell transplantation for type 1 diabetes is hindered by the requisite of lifelong systemic immunosuppression. This study examines the utility of localized islet graft drug delivery to subvert the inflammatory and adaptive immune responses. Herein, we have developed and characterized dexamethasone (Dex) eluting Food and Drug Administration-approved micro-Poly(lactic-co-glycolic acid) micelles and examined their efficacy in a fully major histocompatibility complex-mismatch murine islet allograft model. A clinically relevant dose of 46.6 ± 2.8 μg Dex per graft was confirmed when 2 mg of micelles was implemented. Dex-micelles + CTLA-4-Ig (n = 10) resulted in prolonged allograft function with 80% of the recipients demonstrating insulin independence for 60 days posttransplant compared to 40% in empty micelles + CTLA-4-Ig recipients (n = 10, P = .06). Recipients of this combination therapy (n = 8) demonstrated superior glucose tolerance profiles, compared to empty micelles + CTLA-4-Ig recipients (n = 4, P < .05), and significantly reduced localized intragraft proinflammatory cytokine expression. Histologically, increased insulin positive and FOXP3 + T cells were observed in Dex-micelles + CTLA-4-Ig grafts compared to empty micelles + CTLA-4-Ig grafts (P < .01 and P < .05, respectively). Localized drug delivery via micelles elution has the potential to alter the inflammatory environment, enhances allograft survival, and may be an important adjuvant approach to improve clinical islet transplantation outcomes., (© 2019 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Disturbances in adipocytokine profiles can contribute to peripheral insulin resistance and impairment of insulin production, which are 2 primary pathophysiological mechanisms involved in type 2 diabetes mellitus (T2DM). Previous studies of disturbed adipocytokine profiles have resulted in ambiguous findings; therefore, we conducted the current study comparing leptin, resistin, and adiponectin concentrations in patients with newly diagnosed T2DM who had normal body mass index (BMI) and those who were obese.We studied a population-based cohort of healthy participants and those with newly diagnosed T2DM. A normal BMI group was randomly selected; age- and sex-matched obese participants were recruited. Circulating leptin, resistin, and adiponectin concentrations were measured and compared between groups using analysis of variance; binary logistic regression analysis was then performed to compare the normal BMI and obese groups.In total, 85 healthy participants and 38 patients with diabetes (19 with normal BMI and 17 who were obese) were enrolled. After adjustment for BMI and waist circumference, the median leptin concentration was higher in the obese group (6.77 (3.89-10.73) ng/mL) than in the normal BMI group (1.69 (0.80-3.89) ng/mL) (P = .007), whereas the median adiponectin concentration was lower in the obese group (1.03 (0.75-2.36) μg/mL vs 3.36 (0.59-7.63) μg/mL, P = .03). In addition, the adiponectin/leptin ratio was higher in the normal BMI group (145.6 (41.3-495.9) ng/mL) than in the obese group (20.55 (8.74-36.94) ng/mL, P = .002).Compared with the normal BMI T2DM group, the obese T2DM group exhibited a disturbed adipocytokine profile in the form of a significantly increased leptin concentration and reduced adiponectin level. Further studies are needed to determine the causal relationship for this difference and evaluate its importance for personalized diabetic treatment.