C4d deposits in acute "cell-mediated" rejection: a marker for renal prognosis?
Accumulation of C4d along peritubular capillaries (PTC) of renal allografts is normally attributed to antibody-mediated rejection. The prognostic implication of these deposits associated with "cell-mediated" rejection on graft survival remains uncertain. Our study aims to evaluate the impact of C4d deposits along PTC of patients with acute cell- mediated rejection on graft function and survival. We retrospectively analyzed patients transplanted between 2005 and 2010 with histopathologic diagnosis of acute rejection (AR). Eleven patients with "pure" antibody-mediated rejection were excluded. The remaining 79 patients were divided into two groups according to type of AR by Banff 2003 criteria: type I (69.6%) versus type II (30.4%). In each group, comparisons were made between C4d-negative (-) and C4d-positive (+) biopsies. Fifty-five patients presented with type I AR: 35 (63.6%) C4d- and 20 (36.4%) C4d+. Twenty-four patients presented with type II AR: 13 (54.2%) C4d- and 11 (45.8%) C4d+. In the type I AR group, graft survival at the first and second years was similar in C4d- and C4d+ patients (94% and 91% versus 75% and 75%, respectively, log-rank P = .26). No differences were encountered in estimated glomerular filtration rate (eGFR) between subgroups at the first, second, and final years of follow-up. Graft loss occurred in 14.7% of C4d- patients versus 25% in C4d+ patients (P = NS). In the type II AR group, graft survival at the first and second years was similar in C4d- and C4d+ patients (85% and 85% versus 72% and 61%, respectively, log-rank P = .50). No differences were encountered in eGFR between subgroups at the first, second, and final years of follow-up. Graft loss occurred in 30.8% of C4d- patients versus 45.5% in C4d+ patients (P = NS). Our results suggest that detection of C4d staining in acute "cell-mediated" rejection does not imply a worse renal prognosis.


Influence of continuity of care on self-management ability and quality of life in outpatient maintenance hemodialysis patients.
The objective of this study was to evaluate the effect of continuity of care on self-management ability and quality of life (QOL) in patients undergoing maintenance hemodialysis (MHD). One hundred patients were randomly assigned to the observation group and the control group. In the observation group, patients received a 12-month continuity of care. In the control group, patients were given with routine nursing. Evaluate the patients' self-management ability and QOL between two groups 1 week before discharge and 6 and 12 months outpatient MHD. Observation group had higher Hemodialysis Self-Management Instrument (HD-SMI) scores and Kidney Disease Quality of Life-Short Form (KDQOL-SF™) scores than control group at 6 and 12 months outpatient MHD. But patients in observation group had a much lower systolic blood pressure than those in control group at 12 months outpatient MHD. Our study suggested that continuity of care in the form of online education, telephone visit, and outpatient visit could improve self-management ability and QOL of patients undergoing MHD.


Comparative study between idiopathic and non-idiopathic dystonia: a prospective observational study.
There are very few studies based on the updated dystonia classification. However, a comparison of the idiopathic and non-idiopathic dystonias based on the newer classification has not been done previously. To study and compare the clinicoetiological profile of patients with idiopathic and non-idiopathic dystonia attending a movement disorder clinic of a tertiary care teaching institution. All the consecutive dystonia patients from October 2017 to September 2019 fulfilling the inclusion criteria were subjected to a detailed clinical evaluation. Investigations were performed as per requirement. Patients were classified according to the consensus update on phenomenology and classification of dystonia. A total of 183 patients with dystonia were included, with 61.7% (113) males and 38.3% (70) females. The idiopathic group revealed a significantly earlier age of onset with cases slightly outnumbering (n = 96/183, 52.5%) the non-idiopathic group (n = 87/183, 47.5%). Focal dystonias were the commonest type in both the idiopathic (n = 58/96, 60.4%) and non-idiopathic groups (n = 30/87, 34.5%), while generalized dystonia accounted for 26.4% (n = 23/87) of the non-idiopathic cases and only 3.1% (n = 3/96) of the idiopathic cases. The majority of idiopathic cases were isolated dystonia (n = 93/96, 96.9%), while all hemidystonias were non-idiopathic. Focal dystonias were the commonest in both idiopathic and non-idiopathic groups, while generalized dystonia was significantly commoner in the non-idiopathic group. Acquired causes like drugs, perinatal insult were the commonest etiology in the non-idiopathic group. Hemidystonia was found exclusively in the non-idiopathic acquired group.


Validation of the Chinese version OSA-18 quality of life questionnaire in Taiwanese children with obstructive sleep apnea.
The OSA-18 questionnaire is one of the most widely-used sleep quality measurements in children. We tested the applicability and cross-cultural validation of the traditional Chinese version OSA-18 questionnaire. This cross-sectional study was conducted in a tertiary medical referral center. The translation and cultural adaptation of the OSA-18 questionnaire were performed based on Brislin's revised model. A total of 109 children aged 2-18 years old with sleep problems were recruited. Overnight polysomnography and the OSA-18 questionnaire were administered. The reliability and validity of the traditional Chinese version of OSA-18 questionnaire were verified. Excellent test-retest reliability and good internal consistency were achieved, and the validity of OSA-18 with overnight polysomnography was confirmed. The domain of sleep disturbance, daytime function, caregiver concerns, and the OSA-18 total scores were significantly higher in sleep apnea patients. The domain of caregiver concern had the highest score, while those of emotional distress had the lowest scores. The optimal cut-off point of the OSA-18 total scores for detecting obstructive sleep apnea was 67. The traditional Chinese version of OSA-18 demonstrated high reliability and good validity in our study. The domain of caregiver concern is the major element in Taiwanese children with sleep-disordered breathing.


Responding to the global cholera pandemic.
An increase in cholera outbreaks is prompting renewed calls for urgent multisectoral action. Fid Thomson reports.


Fatal hypoglycemia after cytotoxic chemotherapy: a report of two cases and a review of the literature.
Two cases, one of leukemia and one of a trophoblastic testicular teratoma, are described in which hypoglycemia occurred as a terminal event. The rarity of this association with these types of malignancy, together with possible mechanism, is discussed in a brief review of the literature.


VISTA in Soft Tissue Sarcomas: A Perspective for Immunotherapy?
(1) Background: V domain immunoglobulin suppressor of T cell activation (VISTA) plays a critical role in antitumor immunity and may be a valuable target in cancer immunotherapy. To date, it has never been studied in a large and well-characterised cohort of soft tissue sarcomas (STS). (2) Methods: Using immunohistochemistry, we examined VISTA expression in tumour tissues of 213 high-risk STS. We then analysed whether VISTA was associated with other clinicopathological parameters, including tumour-infiltrating lymphocyte (TIL) counts, programmed death receptor-1 (PD1), programmed death ligand-1 (PDL1), CD3, grading, and long-term survival. (3) Results: We observed VISTA expression in 96 (45%) of 213 specimens with distinct patterns ranging from 26 to 63% for histological subtypes. VISTA was associated with higher grade (G3 vs. G2, p = 0.019), higher TIL counts (p = 0.033), expression of PD1 (p = 0.046), PDL1 (p = 0.031), and CD3+ (p = 0.023). In patients without CD3+ TILs, 10-year survival was higher when VISTA was expressed compared to when there was no VISTA expression (p = 0.013). In a multivariate analysis, VISTA expression was independently associated with prolonged survival (p = 0.043). (4) Conclusions: VISTA is expressed in different STS subtypes and is associated with increased TILs, PD-1, PD-L1, and CD3 expression. Patients with VISTA+ tumours show improved survival. These results may help define future immunotherapeutic approaches in STS.


Identification of long regulatory elements in the genome of Plasmodium falciparum and other eukaryotes.
Long regulatory elements (LREs), such as CpG islands, polydA:dT tracts or AU-rich elements, are thought to play key roles in gene regulation but, as opposed to conventional binding sites of transcription factors, few methods have been proposed to formally and automatically characterize them. We present here a computational approach named DExTER (Domain Exploration To Explain gene Regulation) dedicated to the identification of candidate LREs (cLREs) and apply it to the analysis of the genomes of P. falciparum and other eukaryotes. Our analyses show that all tested genomes contain several cLREs that are somewhat conserved along evolution, and that gene expression can be predicted with surprising accuracy on the basis of these long regions only. Regulation by cLREs exhibits very different behaviours depending on species and conditions. In P. falciparum and other Apicomplexan organisms as well as in Dictyostelium discoideum, the process appears highly dynamic, with different cLREs involved at different phases of the life cycle. For multicellular organisms, the same cLREs are involved in all tissues, but a dynamic behavior is observed along embryonic development stages. In P. falciparum, whose genome is known to be strongly depleted of transcription factors, cLREs are predictive of expression with an accuracy above 70%, and our analyses show that they are associated with both transcriptional and post-transcriptional regulation signals. Moreover, we assessed the biological relevance of one LRE discovered by DExTER in P. falciparum using an in vivo reporter assay. The source code (python) of DExTER is available at https://gite.lirmm.fr/menichelli/DExTER.


Genotoxic effect induced by hydrogen peroxide in human hepatoma cells using comet assay.
Hydrogen peroxide (H(2)O(2)) is a common reactive oxygen intermediate generated by various forms of oxidative stress. The aim of this study was to investigate the DNA damage capacity of H(2)O(2) in HepG2 cells. Cells were treated with H(2)O(2) at concentrations of 25 µM or 50 µM for 5 min, 30 min, 40 min, 1 h, or 24 h in parallel. The extent of DNA damage was assessed by the comet assay. Compared to the control, DNA damage by 25 and 50 µM H(2)O(2) increased significantly with increasing incubation time up to 1 h, but it was not increased at 24 h. Our findings confirm that H(2)O(2) is a typical DNA damage-inducing agent and thus is a good model system to study the effects of oxidative stress. DNA damage in HepG2 cells increased significantly with H(2)O(2) concentration and time of incubation but later decreased likely due to DNA repair mechanisms and antioxidant enzymes.


The effect of microprocessor controlled exo-prosthetic knees on limited community ambulators: systematic review and meta-analysis.
The clinical benefits of microprocessor-controlled prosthetic knees (MPKs) in community ambulators have been well-established. A systematic review in limited community ambulators published in 2014 found benefits in safety, performance-based, and patient-reported outcomes. This work updates the previous analysis to the current state of the published evidence. Systematic review and meta-analysis of the effect of MPKs in limited community ambulators. Thirteen research projects presented in 15 publications were identified. Overall validity was "high" in nine studies, "moderate" in three, and "low" in one. The literature described a total of 2366 patients, with 704 classified as limited community ambulators. The use of MPKs in limited community ambulators led to a reduction in falls (SMD g: -0.59; 95% confidence interval (CI) [-0.85, -0.32; I2=0%]), fear of falling (SMD g: 1.2; 95%CI [0.55, 1.85; I2=80%]), risk of falling as indicated by the TUG (SMD g: -0.45, 95%CI [-0.87, -0.02; I2=0%]), an improvement in mobility grade (0.51; 95%CI [0.47,0.55]), self-selected walking speed (SMD g: 0.47; 95%CI [0.14,0.81; I2=0%]), and patient-reported ambulation (MD 9.32; 95%CI [3.61, 15.02; I2=7%]), and utility (MD 7.76; 95%CI [2.05-13.47; I2=0%]). Other outcomes exhibited trends in favor of MPK use or remained insensitive. No outcome was identified favoring non-MPKs. These results suggest that MPKs may be considered a valuable therapeutic option in limited community ambulators with a transfemoral amputation.Implications for rehabilitationAbove knee amputees may be treated with a large variety of artificial exo-prosthetic knee components.Microprocessor-controlled prosthetic knees have proven to be advantageous and cost effective for community ambulators.The current analysis shows similar effects in safety, mobility, and patient perception also for limited community ambulators.Microprocessor-controlled prosthetic knees are a viable therapeutic option for limited community ambulators.


Telemedicine model to prevent blindness from familial glaucoma.
To develop, implement and evaluate a telemedicine model to reduce glaucoma blindness through the early detection of undiagnosed glaucoma in high-risk individuals. Prospective study, private ophthalmology practice and public outpatient clinics in Tasmania. One hundred and thirty-three individuals with primary open-angle glaucoma were invited to enrol their first-degree relatives (FDRs) to undergo an eye examination. Within the study period, 211 FDRs were available for examination. A registered nurse was trained to perform the required assessments. Clinical data were entered into a purpose-built database, converted to a portable document format and graded offsite by an ophthalmologist to determine the presence, absence or risk of developing glaucoma. Participants were notified of the grading result and recommendations for review. Incidence of undiagnosed glaucoma in a high-risk population. Previously undiagnosed glaucoma was identified in 5% of those examined. For every 19 participants screened, one new case of previously undiagnosed case of glaucoma was identified. Additionally 15% of participants showed suspicious signs of glaucoma, and 6% had ocular hypertension. A telemedicine model is an efficient method for screening, grading and notifying participants of examination results. Nurses can be adequately trained to undertake the initial screening examinations, with grading of the results performed offsite by a suitably qualified ophthalmologist. Targeted screening for glaucoma increases the yield of identifying individuals with undiagnosed glaucoma or those at greatest risk. Cost efficiencies for this model of glaucoma screening should be further explored and implemented to prevent blindness from familial glaucoma.


Echocardiographic characteristics in Fontan patients before the onset of protein-losing enteropathy or plastic bronchitis.
It was this study's objective to evaluate the echocardiographic characteristics and flow patterns in abdominal arteries of Fontan patients before the onset of protein-losing enteropathy (PLE) or plastic bronchitis (PB). In this retrospective cohort investigation, we examined 170 Fontan patients from 32 different centers who had undergone echocardiographic and Doppler ultrasound examinations between June 2006 and May 2013. Follow-up questionnaires were completed by 105 patients a median of 5.3 (1.5-8.5) years later to evaluate whether one of the complications had occurred since the examinations. A total of 91 patients never developed PLE or PB ("non-PLE/PB"); they were compared to 14 affected patients. Eight of the 14 patients had already been diagnosed with "present PLE/PB" when examined. Six "future PLE/PB" patients developed those complications later on and were identified on follow-up. The "future PLE/PB" patients presented significantly slower diastolic flow velocities in the celiac artery (0.1 (0.1-0.5) m/s vs 0.3 (0.1-1.0) m/s (P = .04) and in the superior mesenteric artery (0.0 (0.0-0.2) m/s vs 0.2 (0.0-0.6) m/s, P = .02) than the "non-PLE/PB" group. Median resistance indices in the celiac artery were significantly higher (0.9 (0.8-0.9) m/s vs 0.8 (0.6-0.9) m/s, (P = .01)) even before the onset of PLE or PB. An elevated flow resistance in the celiac artery may prevail in Fontan patients before the clinical manifestation of PLE or PB.


Effects of species of origin, purification levels, and formulation on insulin immunogenicity.
The immunogenicity of purified pork insulins (PPI) with and without (groups 1 and 2, respectively) trace contamination of beef insulin was contrasted with mixed beef pork insulin of lower purity (MBP, group 3) in 137 patients who had not previously been treated with insulin. Patients and physicians were blinded with regard to the species source of insulin and studies were conducted for a minimum of 1 yr. Antibody development to insulin was assessed by species-specific binding of 125I-insulin by acid charcoal extracted sera, as well as by measurement of insulin prebound to immunoglobulins by a polyethylene glycol precipitation method. NPH- and lente-treated individuals had equivalent antibody responses with regard to the rate of development of antibodies, and maximum immune responses to insulin. In all patient groups, antibody bound insulin as well as species-specific binding of 125I-insulin increased significantly over time (all P less than 0.01 for specific binding of pork and beef insulins SBP and SBB, as well as bound insulin). Maximum bound insulin and SBB as well as bound insulin and SBB over the entire course of the study were significantly greater in group 1 than in group 2 patients (both P less than 0.05). The rate of development and magnitude of antibodies' responses in both PPI-treated groups were significantly less than that seen in the MBP group (all P less than 0.01). New formation of antibeef proinsulin antibodies was seen in one patient from groups 1 and 3, but not in group 2. In all groups, insulin dose per day and fasting serum glucose concentrations increased by about 5 U/day and 10 mg/dl over 1 yr, but groups did not differ. MBP insulin used in these studies proved to be significantly less immunogenic than previously available Argentine pure beef insulin, purified by gel filtration. PPI containing even trace contamination of beef insulin was more immunogenic than PPI alone.


Nitrogen and phosphorus removal from an abattoir wastewater in a SBR with aerobic granular sludge.
The formation and performance of granular sludge was studied in an 8l sequencing batch reactor (SBR) treating an abattoir (slaughterhouse) wastewater. Influent concentrations averaged 1,520 mg l(-1) volatile suspended solids (VSS), 7,685 mg l(-1) Chemical oxygen demand (COD), 1,057 mg l(-1) total kjeldahl nitrogen (TKN), 217 mg l(-1) total P. The COD loading was 2.6 kgm(-3)d(-1). The SBR was seeded with flocculating sludge from a SBR with an 1h settle time, but granules developed within 4 days by reducing the settle time to 2 min. The SBR cycle also had 120 min mixed (anaerobic) fill, 220 min aerated react, and 18 min draw/idle. The granules had a mean diameter of 1.7 mm, a specific gravity of 1.035, a density of 62 g VSS l(-1), a zone settling velocity (ZSV) of 51 mh(-1), and a sludge volume index (SVI) of 22 ml g(-1). Without optimizing process conditions, removal of COD and P were over 98%, and removal of N and VSS were over 97%. Nitrification and denitrification occurred simultaneously during react. The results indicate that conventional SBRs treating wastewaters with flocculating sludge can be converted to granular SBRs by reducing the settle time.


Differential inhibitory effects of baicalein and baicalin on LPS-induced cyclooxygenase-2 expression through inhibition of C/EBPbeta DNA-binding activity.
To evaluate the possible mechanisms responsible for the anti-inflammatory effects of baicalein or baicalin, lipopolysaccharide (LPS)-induced inflammatory responses in cultured Raw 264.7 cells were studied. In the present study, baicalein and baicalin, a flavonoid present in the root of Scutellaria baicalensis Georgi, were examined for their effects on LPS-induced cyclooxygenase-2 (COX-2) gene expression in Raw 264.7 macrophages. Baicalein, but not baicalin, inhibited COX-2 gene expression in LPS-induced Raw 264.7 cells. However, both polyphenolic compounds inhibited LPS-induced inducible nitric oxide synthase (iNOS) protein expression, iNOS mRNA expression, and NO production in a dose-dependent manner. To investigate the mechanism by which baicalein inhibits COX-2 gene expression, we examined activation of mitogen-activated protein kinases (MAPKs) in Raw 264.7 cells. We did not observe any significant change in the phosphorylation of MAPKs between baicalein- and baicalin-treated cells. Baicalein and baicalin had no effect on LPS-induced nuclear factor-kappaB (NF-kappaB) and cAMP response element binding protein (CREB) DNA binding activity. Baicalein, but not baicalin, significantly inhibited the DNA binding activity of CCAAT/enhancer binding protein beta (C/EBPbeta) These results indicated that differential effects of baicalein and baicalin on COX-2 gene expression in LPS-induced Raw 264.7 cells were mediated through inhibition of C/EBPbeta DNA binding activity. Taken together, these results suggest that baicalein acts to inhibit inflammation through inhibition of COX-2 gene expression through blockade of C/EBPbeta DNA binding activity.


Analysis of 13C and 15N CPMAS NMR-spectra of soil organic matter and composts.
15N and 13C CPMAS spectra of composted plants are presented. The plants (L. rigidium and Zea mays) were grown in 15N enriched medium and fermented for several months until an approx. 80% of the dry matter was lost. In all 15N spectra the secondary amide/peptide peaks at 87 ppm contributes more than 80% of the total intensity. No new 15N peaks are formed during the fermentation process. Older attempts to assign a significant fraction of humic acid nitrogen to heteroaromatic structures formed in the fermentation process are thus most probably wrong.


GC-MS analysis of soil faecal biomarkers uncovers mammalian species and the economic management of the archeological site "Le Colombare di Negrar".
The identification of the mammalian species based on faecal sediments in modern and ancient environments is the aim of the research of archaeologists, forensic scientists and ecologists. Here, we set up and validated an optimized gas chromatography-mass spectrometry (GC-MS) method, characterized by a time-saving sample preparation protocol, for the simultaneous analysis of faecal biomarkers (6 sterols/stanols and 5 bile acids) in 14 soil samples from the archaeological site of "Le Colombare di Negrar" in northern Italy. Although the archaeological sediment samples examined are numerically exiguous, a comparative reading of our faecal biomarkers findings with new studies on faunal materials collected in the same stratigraphic detail during recent excavation campaigns will allow to better clarify the economic interest of the animal species farmed in the Colombare site (such as bovines, goats, sheep and pigs) and to shed light on the management of breeding. Together with archaeozoological and archaeobotanical analyses, the investigation of faecal biomarkers can increase our knowledge of how ancient local communities exploited natural resources and may allow us to deduce what their impact on the landscape was.


Bovine mastitis in selected areas of southern Ethiopia.
A study on bovine mastitis, designed to determine the causal agents, prevalence of infection and impact of risk factors in three cattle breeds, was conducted in selected areas of southern Ethiopia. A total of 307 lactating and non-lactating cows, of which 162 were indigenous Zebu, 85 Jersey and 60 Holstein-Friesian. were examined by clinical examination and the California mastitis (CMT) test. Of these, 40.4% were positive by CMT and bacteriology for clinical or subclinical mastitis, with prevalence rates of 37.1% and 62.9%, respectively. Out of 1133 quarters examined, 212 (18.7%) were found to be infected, 83 (39.21%) clinically and 129 (60.8%) subclinically. The prevalence of mastitis was significantly higher in Holstein-Friesian than in indigenous Zebu, in non-lactating cows than in lactating cows, in the early lactation stage than in the mid-lactation stage, in cows with lesions and/or tick infestation on skin of udder and/or teats than in cows without this factor, and in the wet season than in the dry season. Mastitis increased with parity number (R = 0.9). Of 248 CMT and clinically positive udder quarter samples analysed microbiologically, 212 were culturally positive for known mastitis pathogens and 36 were negative. Of the 199 positive samples. Staphylococcus accounted for 39.2%. Streptococcus for 23.6%, coliforms for 14.1%, Micrococcus and Bacillus species for 8.0% each and Actinomyces or Arcanobacterium (Corynebacterium) for 7.0%. It was concluded that there was a high prevalence of clinical and subclinical mastitis, mainly caused by Staphylococcus aureus, Streptococcus agalactiae and Escherichia coli, in this study area.


Glycerol as an ionic liquid co-solvent for pretreatment of rice hulls to enhance glucose and xylose yield.
Rice hulls, a widely-available secondary agricultural residue, can be pretreated with ionic liquids (IL) prior to enzymatic hydrolysis to enhance glucose and xylose yields. The high cost of ILs is a deterrent to commercial deployment at present. ILs 1-ethyl-3-methylimidazolium acetate, 1-ethyl-3-methylimidazolium formate, 1,3-dimethylimidazolium dimethylphosphate, and 1-ethyl-3-methylimidazolium diethylphosphate were investigated for rice hull pretreatment. Effects of diluting ILs with glycerol were investigated for biomass pretreatment efficacy, and for solvent recovery. When diluted with 50% glycerol, rice hulls treated in 1-ethyl-3-methylimidazolium formate was found to give glucose and xylose yields after enzymatic hydrolysis better than rice hulls treated in pure 1-ethyl-3-methylimidazolium formate. Dilution in glycerol resulted in an increased rate of solvent recovery after pretreatment, as much as six times that when pure 1-ethyl-3-methylimidazolium formate was used. Diluting 1-ethyl-3-methylimidazolium formate with 50% glycerol was found to decrease solvent viscosity at the pretreatment temperature (110 °C) helping explain improved biomass pretreatment.


Effective assessment of biopolymer-based multifunctional sorbents for the remediation of environmentally hazardous contaminants from aqueous solutions.
Persistent contaminants in wastewater effluent pose a significant threat to aquatic life and are one of the most significant environmental concerns of our time. Although there are a variety of traditional methods available in wastewater treatment, including adsorption, coagulation, flocculation, ion exchange, membrane filtration, co-precipitation and solvent extraction, none of these have been found to be significantly cost-effective in removing toxic pollutants from the water environment. The upfront costs of these treatment methods are extremely high, and they require the use of harmful synthetic chemicals. For this reason, the development of new technologies for the treatment and recycling of wastewater is an absolute necessity. Our way of life can be made more sustainable by the synthesis of adsorbents based on biomass, making the process less harmful to the environment. Biopolymers offer a sustainable alternative to synthetic polymers, which are manufactured by joining monomer units through covalent bonding. This review presents a detailed classification of biopolymers such as pectin, alginate, chitosan, lignin, cellulose, chitin, carrageen, certain proteins, and other microbial biomass compounds and composites, with a focus on their sources, methods of synthesis, and prospective applications in wastewater treatment. A concise summary of the extensive body of knowledge on the fate of biopolymers after adsorption is also provided. Finally, consideration is given to open questions about future developments leading to environmentally friendly and economically beneficial applications of biopolymers.


Genetic Evidence Supporting Causal Roles of mTOR-Dependent Proteins in Rheumatic Fever: A Two-Sample Randomized Mendelian Study.
The expression of signaling molecules downstream of the mammalian target of rapamycin (mTOR) is dysregulated in patients with rheumatic fever (RF), but the causality of mTOR on RF remains unknown. This study aimed to investigate the causal effects of the mTOR-dependent proteins in RF. The summary data for targets of the mTOR signaling were acquired from the publicly available INTERVAL study GWAS data. Data on RF have been obtained from the Integrated Epidemiology Unit GWAS database (38,209 cases and 156,711 healthy controls). A two-sample Mendelian randomization (MR) study was conducted to examine the association of RF risk and mTOR-dependent proteins (EIF4EBP2, EIF-4E, EIF-4G, EIF-4A, RP-S6K, and ATG7), including the inverse-variance weighted (IVW) method, MR-Egger, and weighted median, which was followed by sensitivity analyses. RP-S6K is associated with a lowered risk of RF with an odds ratio (OR) of 0.97, 95% confidence interval (95% CI) of 0.94-0.99 (p = 0.027). In contrast, ATG7 accounts for higher risk of RF with an OR of 1.05 (95% CI = 1.00-1.12, p = 0.047). No apparent heterogeneity and no horizontal pleiotropy were observed in the sensitivity analysis (p > 0.05). No statistical significance was identified for levels of EIF4A, EIF4G, EIF4E-BP2, and RP-S6K with RF risk (p > 0.05). MR found robust evidence of a causal association between RF and mTOR. RP-S6K and ATG7 may be targeted for intervention by repurposing existing therapeutics to reduce the risk of RF.


Quantitative Gait Analysis of Patients with Severe Symptomatic Spinal Stenosis Utilizing the Gait Profile Score: An Observational Clinical Study.
Lumbar spine stenosis (LSS) typically manifests with neurogenic claudication, altering patients' gait. The use of optoelectronic systems has allowed clinicians to perform 3D quantitative gait analysis to quantify and understand these alterations. Although several authors have presented analysis of spatiotemporal gait parameters, data concerning kinematic parameters is lacking. Fifteen patients with LSS were matched with 15 healthy controls. Quantitative gait analysis utilizing optoelectronic techniques was performed for each pair of subjects in a specialized laboratory. Statistical comparison of patients and controls was performed to determine differences in spatiotemporal parameters and the Gait Profile Score (GPS). Statistically significant differences were found between patient and control groups for all spatiotemporal parameters. Patients had significantly different overall GPS (p = 0.004) and had limited internal/external pelvic rotation (p < 0.001) and cranial/caudal movement (p = 0.034), limited hip extension (p = 0.012) and abduction/adduction (p = 0.012) and limited ankle plantar flexion (p < 0.001). In conclusion, patients with LSS have significantly altered gait patterns in three regions (pelvis, hip and ankle) compared to healthy controls. Analysis of kinematic graphs has given insight into gait pathophysiology of patients with LSS and the use of GPS will allow us to quantify surgical results in the future.


Differential proteomics of Picrorhiza kurrooa Royle ex Benth. in response to dark stress.
Picrorhiza (Picrorhiza kurrooa Royle ex Benth.) an important medicinal herb of western Himalayan region has been used to treat various diseases and disorders. Over-harvesting and lack of cultivation has led to its entry in Red Data Book as an endangered species. Further, its very restrictive habitat and lesser biomass production are major limitations for bringing it under commercial cultivation. All these issues necessitate deeper insights into mechanisms governing its growth and interaction with the environmental cues. Light may be one of the important factors to be studied for its role in regulating growth and adaptation of Picrorhiza as in natural habitat it prefers shady niches. Keeping this in view, proteome of Picrorhiza kept under light vis-à-vis under dark was analysed and compared. Leaf as well as root proteome of Picrorhiza was studied. Denaturing two dimensional gel electrophoresis and mass spectrometry techniques were used to detect and identify differentially expressed proteins, respectively. Twenty two proteins from leaf and 25 proteins from root showed differential expression levels under dark and light conditions. Among the differentially expressed proteins, majority were those involved in metabolism, protein synthesis, and stress and defense response. Other differentially expressed proteins were those involved in photosynthetic process, photorespiration and few proteins were with unknown function indicating that many different processes work together to establish a new cellular homeostasis in response to dark and light conditions. Proteins found to be differentially expressed under light vis-à-vis dark conditions suggested a range of biochemical pathways and processes being associated with response of plant to dark conditions. The identified proteins may be utilized for developing strategies for improving the biomass production/performance of Picrorhiza under varied light/dark habitats.


Genome-wide association study identifying genetic variants associated with carcass backfat thickness, lean percentage and fat percentage in a four-way crossbred pig population using SLAF-seq technology.
Carcass backfat thickness (BFT), carcass lean percentage (CLP) and carcass fat percentage (CFP) are important to the commercial pig industry. Nevertheless, the genetic architecture of BFT, CLP and CFP is still elusive. Here, we performed a genome-wide association study (GWAS) based on specific-locus amplified fragment sequencing (SLAF-seq) to analyze seven fatness-related traits, including five BFTs, CLP, and CFP on 223 four-way crossbred pigs. A total of 227, 921 highly consistent single nucleotide polymorphisms (SNPs) evenly distributed throughout the genome were used to perform GWAS. Using the mixed linear model (MLM), a total of 20 SNP loci significantly related to these traits were identified on ten Sus scrofa chromosomes (SSC), of which 10 SNPs were located in previously reported quantitative trait loci (QTL) regions. On SSC7, two SNPs (SSC7:29,503,670 and rs1112937671) for average backfat thickness (ABFT) exceeded 1% and 10% Bonferroni genome-wide significance levels, respectively. These two SNP loci were located within an intron region of the COL21A1 gene, which was a protein-coding gene that played an important role in the porcine backfat deposition by affecting extracellular matrix (ECM) remodeling. In addition, based on the other three significant SNPs on SSC7, five candidate genes, ZNF184, ZNF391, HMGA1, GRM4 and NUDT3 were proposed to influence BFT. On SSC9, two SNPs for backfat thickness at 6-7 ribs (67RBFT) and one SNP for CLP were in the same locus region (19 kb interval). These three SNPs were located in the PGM2L1 gene, which encoded a protein that played an indispensable role in glycogen metabolism, glycolysis and gluconeogenesis as a key enzyme. Finally, one significant SNP on SSC14 for CLP was located within the PLBD2 gene, which participated in the lipid catabolic process. A total of two regions on SSC7 and SSC9 and eight potential candidate genes were found for fatness-related traits in pigs. The results of this GWAS based on SLAF-seq will greatly advance our understanding of the genetic architecture of BFT, CLP, and CFP traits. These identified SNP loci and candidate genes might serve as a biological basis for improving the important fatness-related traits of pigs.


The Gait Disorientation Test: A New Method for Screening Adults With Dizziness and Imbalance.
To develop and evaluate a new method for identifying gait disorientation due to vestibular dysfunction. The gait disorientation test (GDT) involves a timed comparison of the ability to walk 6.096 m with eyes open versus eyes closed. In this prospective study, participants were grouped based on vestibular function. All participants completed a clinical examination, self-report- and performance-based measures relevant to vestibular rehabilitation, and the tasks for the GDT. Vestibular-impaired participants underwent the criterion standard, videonystagmography and/or rotational chair testing. Ambulatory clinic, tertiary referral center. Participants (N=40) (20 vestibular-impaired, 30 women, 49.9±16.1years old) were enrolled from a convenience/referral sample of 52 adults. We determined test-retest reliability using the intraclass correlation coefficient model 3,1; calculated the minimal detectable change (MDC); examined concurrent validity through Spearman correlation coefficients; assessed criterion validity with the area under the curve (AUC) from receiver operator characteristic analysis; and computed the sensitivity, specificity, diagnostic odds ratio (DOR), likelihood ratios for positive (LR+) and negative (LR-) tests, and posttest probabilities of a diagnosis of vestibulopathy. The 95% confidence interval demonstrates measurement uncertainty. Test-retest reliability was 0.887 (0.815, 0.932). The MDC was 3.7 seconds. Correlations with other measures ranged from 0.59 (0.34, 0.76) to -0.85 (-0.92, -0.74). The AUC was 0.910 (0.822, 0.998), using a threshold of 4.5 seconds. The sensitivity and specificity were 0.75 (0.51, 0.91) and 0.95 (0.75, 1), respectively. The DOR=57 (6, 541.47), LR+ =15 (2.18, 103.0), and LR- =0.26 (0.12, 0.9). Positive posttest probabilities were 89%-94%. The GDT has good reliability, excellent discriminative ability, strong convergent validity, and promising clinical utility.


Both matrix proteins of Ebola virus contribute to the regulation of viral genome replication and transcription.
Ebola virus (EBOV) causes severe hemorrhagic fevers in humans and non-human primates. While the role of the EBOV major matrix protein VP40 in morphogenesis is well understood, nothing is known about its contributions to the regulation of viral genome replication and/or transcription. Similarly, while it was reported that the minor matrix protein VP24 impairs viral genome replication, it remains unclear whether it also regulates transcription, since all common experimental systems measure the combined products of replication and transcription. We have developed systems that allow the independent monitoring of viral transcription and replication, based on qRT-PCR and a replication-deficient minigenome. Using these systems we show that VP24 regulates not only viral genome replication, but also transcription. Further, we show for the first time that VP40 is also involved in regulating these processes. These functions are conserved among EBOV species and, in the case of VP40, independent of its budding or RNA-binding functions.


Effect of the cryopreservation conditions on the viability of the rumen ciliate Diploplastron (Metadinium) affine.
To study the viability of Diploplastron (Metadinium) affine after its cryopreservation at two cooling rates, and the effect of procedure conditions on viability. There were differences in viability between cooling rates (1 and 4 degrees C min(-1)) at 15 or 5 degrees C, but not after thawing. When the equilibrium temperature (25 or 5 degrees C), the cryopreservant (glycerol or dimethyl sulfoxide [DMSO]) and the use of membrane protector were tested, there were no differences caused by the cryopreservant or the membrane protector. However, the equilibrium at 25 degrees C increased the viability (P = 0.005) compared with 5 degrees C. Viability after thawing was 0.10-0.19. Adding the cryopreservant (either glycerol or DMSO) at 25 degrees C instead of 5 degrees C improves viability of D. affine after thawing. Conditions of cryopreservation are largely dependent on the species of rumen protozoa. Number of viable cells after thawing would indicate the possibility of culture recovery for D. affine.


Fear of cancer recurrence in patients undergoing germline genome sequencing.
Fear of cancer recurrence/occurrence (FCR/O) is prevalent and associated with poorer psychological outcomes but can also motivate individuals to pursue genomic information about cancer risk. Guided by Protection Motivation Theory, this study investigated FCR/O prevalence and associated factors among probands previously diagnosed with a cancer of likely heritable origin, and their relatives, who had agreed to have germline genome sequencing. Three hundred and forty-eight probands and 167 relatives completed the Concerns about Recurrence Questionnaire (adapted for occurrence for some relatives) within 1 month of agreeing to undertake genome sequencing. Linear regressions investigated demographic, disease, attitude and behavioral associations with FCR/O. Probands demonstrated greater FCR compared to relatives. In probands, greater FCR was associated with being female, non-English speaking at home, less time since diagnosis, greater intention to change behavior if gene variant found, lower perceived ability to cope with results, higher perceived susceptibility to having a recurrence, and more negative attitudes towards uncertainty. For relatives with cancer, greater FCR was associated with being male, greater intention to change behavior if a gene variant found, and higher perceived susceptibility to recurrence. In relatives without cancer, greater FCO was associated with not having had genetic testing prior to this study, lower perceived ability to cope with results, and higher perceived susceptibility to developing cancer. Current findings on FCR/O prevalence and associated demographic and attitudinal variables in those who pursue genomic risk information might be used to target interventions that can prevent adverse psychological outcomes in vulnerable patients.


Predictors of Quality of Life in Patients With Rheumatoid Arthritis in Pakistan: A Cross-Sectional Study.
Introduction Rheumatoid arthritis (RA) is a chronic, progressive inflammatory illness that primarily affects peripheral joints and belongs to systemic connective tissue diseases. Rheumatoid arthritis can cause varied and significant impacts on patients' health, including mental and physical wellbeing. The aim of this study is to analyze the factors affecting the quality of life of rheumatoid arthritis patients. Methodology A cross-sectional study was conducted in the outpatient orthopedics department of Indus Hospital and Health Network. The survey questionnaire was used to collect data from participants. The study's 36-item short-form survey (SF-36) questionnaire was used to assess the quality of life (QoL) among RA patients. Linear regression was used to assess the factors associated with the mental and physical components of QoL. Results A total of 154 patients were interviewed in this study. The mean age of participants was 48.96 (±51.35). Factors that contributed to the physical component of QoL included severity of disease, income, age, comorbidity, and anxiety while factors affecting the mental component of QoL included quality of sleep, anxiety, education, comorbidity, and disease severity. Conclusion Healthcare professionals need to work closely with patients to increase their capabilities of being more independent and controlling all the factors that can affect their QoL.


Structure and cytotoxic activity of enzymatic hydrolysis products of secoiridoid glucosides, isoligustroside and isooleuropein.
Hydrolysis of isoligustroside (1) and isooleuropein (2), secoiridoid glucosides, in the presence of β-glucosidase provided 2-(4-hydroxyphenyl)methyl (2R,3S,4S)-3-formyl-3,4-dihydro-4-(2-methoxy-2-oxoethyl)-2-methyl-2H-pyran-5-carboxylate (3) and 2-(3,4-dihydroxyphenyl)methyl (2R,3S,4S)-3-formyl-3,4-dihydro-4-(2-methoxy-2-oxoethyl)-2-methyl-2H-pyran-5-carboxylate (4), respectively. The structures of 3 and 4 were elucidated on the basis of extensive spectral analyses, including 2D-NMR experiments. Compounds 3 and 4 were found to be new rearrangement products of the aglycones of 1 and 2. The cytotoxic activities of 3 and 4 were evaluated using a disease-oriented panel of 39 human cancer cell lines and showed moderate cytotoxic activity for 4, while 3 exhibited weaker activity compared to that of 4.


Changing intergenerational patterns of emotional dysregulation in families with perinatal borderline personality disorder.
A pilot study with women with borderline personality disorder (BPD) and their infants showed promising results. This clinical research program sought to discover whether ongoing implementation confirmed preliminary results in relation to maternal mental health and, in addition, whether parenting and the mother-infant relationship showed sufficient improvement. Women with BPD and their infants were referred to a 25-week group program of Mother-Infant Dialectical Behavior Therapy (MI-DBT). During groups, infants were provided care by childcare workers while mothers took part in a skills training session. Mothers and infants then reunited and took part in an activity together that incorporated skills taught in the teaching session. Sixty-nine of 98 women commencing MI-DBT completed the program, demonstrating a 71% completion rate. Women showed improvement on all measures of mental health including depression, anxiety, and BPD symptoms. While women reported improvement in parenting confidence, an objective measure of the mother-infant relationship showed continuation of concerning relationships in a significant percentage. MI-DBT was found to be effective at improving mothers' mental health, both at the initial site and in community settings, with different clinicians and with different childcare options. While there were some improvements found in measures of the mother's perception of the infant-parent relationship, there were no significant improvements in currently used observational measures of the interaction or the infant's social-emotional development, suggesting that additional intervention such as infant-parent therapy may be needed to augment the benefits of MI-DBT to improve outcomes in these areas.


Palliative cancer care: costs in a Brazilian quaternary hospital.
Palliative care (PC) improves the quality of life of patients with diseases such as cancer, and several studies have shown a reduction in costs among patients who use PC services when compared with those receiving standard oncological treatments. Most studies on PC costs are carried out in high-income countries. There is a lack of these types of studies in middle-income and low-income countries and of better evidence about this intervention. To describe resource utilisation and costs among patients with cancer in a Brazilian quaternary hospital by cancer localisation and per month of treatment before death. This study is a description of retrospective costs to estimate the costs of formal healthcare sector associated with PCs, from the perspective of a public quaternary cancer hospital. Unit costs were estimated using microcosting and macrocosting approaches. Patients older than 18 years old who died from 2010 to 2013 and who had at least two visits in PC and/or made use of hospice care. Among the 2985 patients included in the study, the average cost per patient was US$12 335, ranging from US$8269 for patients with pancreatic cancer to US$19 395 for patients with brain cancer. The main costing item was hospital admission (47.6% of the total cost), followed by hospice care (29.5%) and medical and other supplies (11.1%). The study clarified the direct medical costs and the profile and use of resources of patients with cancer who need PC, and can help in the planning and allocation of resources in cancer care.


Cytomegalovirus Uveitis: Taiwan expert consensus.
Cytomegalovirus (CMV) uveitis, a type of herpetic uveitis, is a major cause of infectious uveitis. Anterior and posterior CMV uveitis have diverse clinical presentations and treatment modalities. Based on expert consensus in Taiwan, this article provides suggestions regarding clinical manifestations, diagnosis, and treatment strategies for CMV uveitis based on clinical practice experience in Taiwan. CMV uveitis may have a distinct clinical presentation. Polymerase chain reaction (PCR) is an essential diagnostic tool to confirm a diagnosis. Antiviral therapy is the mainstay of treatment. Different agents, routes, and other supplemental treatments have been summarized and discussed in this article. Early diagnosis and appropriate treatment of CMV uveitis are crucial to avoid irreversible complications and vision loss. This consensus provides practical guidelines for ophthalmologists in Taiwan.


A novel HLA-B allele, HLA-B*15:325, is identified by sequence-based typing in a HIV infected individual.
The novel allele B*15:325 shows difference from B*15:02:01 at codon 127 resulting in changes from Asn to Ser.


Analytical methods for identifying and quantitating deamidated sialic acid (2-keto-3-deoxy-D-glycero-D-galactonononic acid) and alpha 2----8-linked poly(oligo)nonulosonate residues in glycoconjugates.
In 1986 we reported the natural occurrence of deaminated neuraminic acid (2-keto-3-deoxy-D-glycero-D-galactonononic acid, KDN) in fish egg glycoprotein. Subsequently, we have shown that many types of sialic acid as well as KDN occur in polymeric chains, poly(oligo)-Sia and poly(oligo)KDN in nature. In this study we demonstrate that the conventional colorimetric and gas-liquid chromatographic methods used in the analysis of sialic acid can be applied to analysis of these new nonulosonate and poly(oligo)nonulosonates. We report that the thiobarbituric acid reaction can be used to analyze both free and bound KDN, but gives lower extinction values when applied to poly(oligo)KDN without prior hydrolysis. Further, the published hydrolytic and/or methanolytic procedures are suitable to release the terminal sialic acid residues, but are not appropriate for quantitative release of the nonulosonic acids from poly(oligo)nonulosonates. A new gas-liquid chromatographic procedure for the identification-quantitation of nonulosonates in poly(oligo)meric forms is described.


Epilepsy with typical absence seizures with onset during the first year of life.
Absence epilepsy with multiple daily seizures and onset at the age of 6 and 1/2 months in a healthy female child with normal development is described. EEG-video recording revealed typical absence seizures (vacant staring and interruption of motor activity) and complex absences (as above, plus raising of the eyeballs, slight beatings of the eyebrows, and forward propulsion of head and shoulders). The absences were accompanied by bilateral symmetrical 3-Hz spike-wave discharges preceded, and at times followed, by bilateral frontoparietal theta activity coinciding with onset and termination of the absence seizures. The seizures regressed with nitrazepam therapy. At age 3-years, the child is seizure-free and shows normal neurologic development.


Intravascular papillary endothelial hyperplasia in the cecum: a case report.
Intravascular papillary endothelial hyperplasia (IPEH), also known as Masson's tumor, is a benign, non-neoplastic vascular lesion that is characterized by reactive proliferation of papillary endothelial cells associated with a thrombus. These lesions typically develop in the vascular regions of the head and neck, oral cavity, or extremities; however, other organ systems have been affected. IPEH in the gastrointestinal tract is rare, with only a few cases reported to date. Thus, the pathogenesis and clinical features of IPEH in the gastrointestinal tract are not entirely understood. Moreover, the local excision of certain subtypes of IPEH can be curative; this makes timely diagnosis essential. We present the case of a patient with IPEH in the cecum that was discovered while investigating the cause of severe anemia. A 29-year-old woman visited a general practitioner (GP) with the complaint of abdominal pain. She was diagnosed with acute appendicitis and was prescribed antibiotics. After treatment, her abdominal pain disappeared. However, she was found to be severely anemic (hemoglobin level, 6.5 g/dl). To determine the cause of her anemia, the GP referred her to our hospital for further examination and treatment. Computed tomography scan revealed cecal wall thickening. Further, a lower gastrointestinal endoscopy revealed a 2-cm raised mass-like lesion in the cecum. This lesion was pathologically identified as an inflammatory granuloma. The cause of her anemia was determined to be bleeding from the lesion in the cecum. She underwent laparoscopic ileocecal resection. Histopathological examination of the surgical specimen revealed a spongy structure comprising many small papillary fibrous tissues lined by a typical monolayer endothelium. Further, immunohistochemical analysis showed that the cells of the endothelium monolayer expressed CD31, CD34. The Ki-67 labeling index was < 1%. Based on these findings, the lesion was identified as an IPEH in the cecum. The patient's postoperative course was uneventful, and there was no evidence of recurrence during the 1.3 years of follow-up. IPEH rarely arises within the abdominal cavity. Surgery remains the only treatment for IPEH and is associated with an excellent prognosis and a low recurrence rate. More aggressive lesions such as angiosarcoma should be excluded when considering the histologic diagnoses of IPEH, and expert pathologic review is vital. This is the first report of IPEH occurring in the cecum and represents a novel cause of gastrointestinal bleeding which the clinician should consider when evaluating a patient with atypical or difficult gastrointestinal bleeding sources.


State-level emergency preparedness and response capabilities.
Prior assessments of public health readiness had identified gaps in radiation preparedness. In recent years, preparedness planning has involved an "all-hazards" approach. Current assessment of the national status related to radiation public health emergency preparedness capabilities at the state and local health department levels was needed. A survey of state health departments related to radiation readiness was undertaken in 2010 by the Council of State and Territorial Epidemiologists (CSTE). States with nuclear power plants were instructed to consider their responses exclusive of capabilities and resources related to the plants given that the emergency response plans for nuclear power plants are specific and unique. Thirty-eight (76%) state health departments responded to the survey, including 26 of the 31 states with nuclear power plants. Specific strengths noted at the state level included that the majority of states had a written radiation response plan and most plans include a detailed section for communications issues during a radiation emergency. In addition, more than half of the states indicated that their relationship with federal partners is sufficient to provide resources for radiation emergencies, indicating the importance states placed on federal resources and expertise. Specific weaknesses are discussed and include that most states had completed little to no planning for public health surveillance to assess potential human health impacts of a radiation event; less than half had written plans to address exposure assessment, environmental sampling, human specimen collection and analysis, and human health assessment. Few reported having sufficient resources to do public health surveillance, radiation exposure assessment, laboratory functions and other capabilities. Levels of planning, resources and partnerships varied among states, those with nuclear power plants were better prepared. Gaps were evident in all states; however and additional training and resources are needed to ensure adequate levels of preparedness. Overall results of this assessment indicate that in most measures of public health capacity and capability, states are poorly prepared to adequately respond to a major radiation emergency event. Specific recommendations are noted in the discussion.


Lipopolysaccharide administration to the allergic nose contributes to lower airway inflammation.
Allergic rhinitis (AR) is an inflammatory reaction not confined to a single local compartment, but rather involving the whole airway system. Allergens known to induce AR are not always the sole trigger of the inflammatory reaction as infections and organic dust might also cause exacerbations of rhinitis and associated conditions. To examine the effects of intranasal lipopolysaccharide (LPS) exposure, as a surrogate for upper airway bacterial infections, in patients with symptomatic AR. Fourteen patients with a history of moderate to severe pollen-induced AR were challenged intranasally with LPS. After 3-6 weeks, the same patients were challenged again, first with allergen and 24 h later with LPS. Nasal symptom scores, nasal lavage leucocyte counts and nasal airway resistance were assessed at 6-24 h after each provocation along with measurements of nitric oxide (NO) levels in the nose and lung. Six hours after the LPS challenge, an increased level of leucocytes could be obtained in the lavage fluid, but no symptoms were experienced and no increase in nasal resistance could be recorded. The NO production in the upper and lower airways was similar before and 6 h after the provocation. In contrast, in patients exposed to pollen before the LPS challenge, both the nasal and the pulmonary NO levels were enhanced. This was accompanied by an increase in leucocytes. The present study demonstrates a priming effect of allergen on the nasal response to LPS as well as the presence of a systemic link between airway mucosal sites in the upper and lower airways. This suggests that exogenously derived signals, like upper airway infections, can interfere with the initiation, maintenance and progression of asthma.


Classification of Covid-19 misinformation on social media based on neuro-fuzzy and neural network: A systematic review.
The spread of Covid-19 misinformation on social media had significant real-world consequences, and it raised fears among internet users since the pandemic has begun. Researchers from all over the world have shown an interest in developing deception classification methods to reduce the issue. Despite numerous obstacles that can thwart the efforts, the researchers aim to create an automated, stable, accurate, and effective mechanism for misinformation classification. In this paper, a systematic literature review is conducted to analyse the state-of-the-art related to the classification of misinformation on social media. IEEE Xplore, SpringerLink, ScienceDirect, Scopus, Taylor & Francis, Wiley, Google Scholar are used as databases to find relevant papers since 2018-2021. Firstly, the study begins by reviewing the history of the issues surrounding Covid-19 misinformation and its effects on social media users. Secondly, various neuro-fuzzy and neural network classification methods are identified. Thirdly, the strength, limitations, and challenges of neuro-fuzzy and neural network approaches are verified for the classification misinformation specially in case of Covid-19. Finally, the most efficient hybrid method of neuro-fuzzy and neural networks in terms of performance accuracy is discovered. This study is wrapped up by suggesting a hybrid ANFIS-DNN model for improving Covid-19 misinformation classification. The results of this study can be served as a roadmap for future research on misinformation classification.


Diagnosing and monitoring pleural effusion using parametric electrical impedance tomography - a computational 3D model and preliminary experimental results.
Diagnosing and monitoring pleural effusion (PE) is challenging due unsuitability of existing modalities. In the present study, a novel parametric electrical impedance tomography (pEIT) technique, tailored to a clinically feasible system to diagnose PE is presented. An electrical impedance tomography (EIT) numeric solver was applied to a 3D realistic normal model and five PE models to simulate sets of surface measurements. Simulations were triggered by a series of eight independent projections using five electrodes positioned around the thorax. The relative changes in the potential between the PE models and the normal model were assessed and the error in the estimated PE volume was examined at varying signal to noise ratio (SNR) levels. For experimental feasibility, measurements were performed in four healthy subjects and were correlated with the potentials that were calculated from the normal model. Relative potential changes were notable (reached until ~55%) and increased with the increasing PE volumes. Maximal error of ± 20 [mL] was obtained for SNR levels >50 [dB]. The feasibility real measurements in healthy subjects showed a strong linear correlation (R2 > 0.85) and a successful diagnosis for all subjects. The proposed technique can estimate PE volumes from a redundant set of measurements in a realistic 3D human model and may be utilized for monitoring PE patients.


Efficacy of Sodium-Glucose Cotransporter-2 inhibitors in heart failure patients treated with dual angiotensin receptor blocker-neprilysin inhibitor: An updated meta-analysis.
Recent data suggest that the prevalence of heart failure has increased to approximately 23 million people globally. With increasing advancement in pharmacotherapeutics, Sodium-Glucose Cotransporter-2 inhibitors (SGLT2i) have garnered attention among clinicians to treat Heart failure with reduced ejection fraction (HFrEF) in diabetic as well as non-diabetic patients. MEDLINE, Scopus, Embase and Cochrane CENTRAL database were searched using relevant keywords and MeSH terms. Studies were considered only if they were randomized in nature and had a sample size >1000 HF patients. Our comprehensive search strategy yielded 864 articles, of which three RCTs met the inclusion criteria with a total population of 9696. Pooled analysis revealed an association between the use of SGLT2i and decreased frequency of primary outcome irrespective of background ARNI use (HR 0.73, 95% CI [0.58-0.93], p = 0.0106; HR 0.73, 95% CI [0.66-0.81], p < 0.0001). This meta-analysis provides substantial evidence, to safely use SGLT2i atop ARNI therapy in select HF patients to further improve outcomes.


Longitudinal Follow-Up of Facial Growth of Patients With Unilateral Cleft Lip and Palate Following Modified Veau-Wardill-Kilner Palatoplasty.
To evaluate facial growth after modified Veau-Wardill-Kilner/pushback (PB) palatoplasty from childhood to adulthood in patients with unilateral cleft lip and palate (UCLP). Retrospective longitudinal study. Single center. Sixty-two (29 males and 33 females) consecutive patients with nonsyndromic UCLP. Pushback palatoplasty and subsequent cleft palate treatment. Lateral and posterior-anterior cephalograms were taken at 3 different phases: phase 1 (before first-stage orthodontic treatment; N = 58; average age, 4.9 ± 1.1 years), phase 2 (before second-stage orthodontic treatment; N = 58; 15.9 ± 1.1 years), and phase 3 (after orthodontic retention; N = 51; 22.1 ± 3.2 years). The majority of patients had skeletal class III morphology in all 3 phases due to retrognathic maxilla. Maxillary growth did not improve in phase 2 despite first-stage orthodontic treatment in phase 1. Maxillary morphology improved in phase 3 but retardation occurred, although 77.42% of patients received orthognathic surgery during second-stage orthodontic treatment. Mandibular growth was slightly reduced in phases 1 and 2 and the mandible remained retrognathic in phase 3, following mandibular setback orthognathic surgery. The horizontal occlusal cant was slightly upward and toward the cleft side with respect to the reference plane, and the upper midline was deviated to the cleft side in phases 1 and 3. Patients with UCLP who undergo phased PB palatoplasty, orthodontic treatment, and orthognathic surgeries do not maintain skeletal class I facial morphology.


Fetal rhabdomyomatous nephroblastoma-a variant of Wilms' tumor.
The fetal rhabdomyomatous nephroblastoma is considered to be a predominantly monophasic mesenchymal variant of Wilms' tumor, which has not been seen in patients older than four years. It acts less aggressively than a Wilms tumor despite its much larger size. Its better prognosis appears to be related to either the absence of or the insignificant amounts of neoplastic epithelium. The bilaterality of this tumor in one-third of the cases, however, may negatively affect the overall prognosis, because complete resection may be impossible or because renal failure ensues.


An acute phase protein α1-acid glycoprotein mitigates AKI and its progression to CKD through its anti-inflammatory action.
The molecular mechanism for acute kidney injury (AKI) and its progression to chronic kidney disease (CKD) continues to be unclear. In this study, we investigated the pathophysiological role of the acute phase protein α1-acid glycoprotein (AGP) in AKI and its progression to CKD using AGP KO mice. Plasma AGP levels in WT mice were increased by about 3.5-fold on day 1-2 after renal ischemia-reperfusion (IR), and these values then gradually decreased to the level before renal IR on day 7-14. On day 1 after renal IR, the AGP KO showed higher renal dysfunction, tubular injury and renal inflammation as compared with WT. On day 14, renal function, tubular injury and renal inflammation in WT had recovered, but the recovery was delayed, and renal fibrosis continued to progress in AGP KO. These results obtained from AGP KO were rescued by the administration of human-derived AGP (hAGP) simultaneously with renal IR. In vitro experiments using RAW264.7 cells showed hAGP treatment suppressed the LPS-induced macrophage inflammatory response. These data suggest that endogenously induced AGP in early renal IR functions as a renoprotective molecule via its anti-inflammatory action. Thus, AGP represents a potential target molecule for therapeutic development in AKI and its progression CKD.


A National Study on Drinking Game Behaviors and Related Consequences Among NCAA Student-Athletes: Racial/Ethnic and Sex Differences.
Research indicates that college student-athletes report more alcohol use and negative drinking consequences than non-student-athletes. One drinking practice that has been linked to heavy alcohol use and related consequences is playing drinking games. In the present study, we investigated which segment of the student-athlete population is most at risk for frequent drinking game participation, elevated alcohol consumption while playing drinking games, and negative drinking game consequences. We examined sex and racial/ethnic differences in behaviors and consequences associated with drinking games in a national sample of White, Hispanic, Black, and Asian American/Pacific Islander (AAPI) student-athletes. A total of 11,839 student-athletes (51.4% women) from 165 National Collegiate Athletic Association (NCAA) member institutions who endorsed lifetime participation in drinking games completed a confidential online survey. Hierarchical linear modeling revealed that being a White (vs. Black or Hispanic) student-athlete was associated with more frequent drinking game participation, and among AAPI and Black (but not White or Hispanic) student-athletes, men played drinking games more frequently than women. Being a Black (vs. White) student-athlete was associated with more drinking game consumption; no sex differences in drinking game consumption were found among Black student-athletes. Among White, AAPI, and Hispanic student-athletes, being a male student-athlete was associated with more drinking game consumption. Finally, female student-athletes had a higher likelihood of experiencing one or more negative consequences from drinking games than did male student-athletes. The association between drinking game participation and negative drinking game consequences was also stronger for women compared with men. Student-athletes are heterogeneous with regard to drinking game behaviors and related consequences. Knowing who is at greatest risk for drinking game participation and related outcomes is an important first step in developing targeted intervention approaches for student-athletes.


Autocatalytic modification of human carbonyl reductase by 2-oxocarboxylic acids.
Carbonyl reductase occurs in multiple molecular forms. Sequence analysis has yielded a carboxyethyllysine residue in one of the enzyme forms, suggesting that pyruvate has been incorporated in a posttranslational enzymatic reaction [Krook, M., Ghosh, D., Strömberg R., Carlquist, M. and Jörnvall, H. (1993) Proc. Natl. Acad. Sci. USA 90, 502-506]. Using highly purified carbonyl reductase from human brain we show that pyruvate and other 2-oxocarboxylic acids are bound to the enzyme in an autocatalytic reaction. The resulting enzyme forms were indistinguishable from the native enzyme forms by electrophoresis and isoelectric focusing.


Early and sustained systemic and renal hemodynamic effects of intravenous radiocontrast.
To measure the extended renal hemodynamic changes induced by intravenous radiocontrast. Cross-ewes were studied in a randomized cross-over study. Intravenous saline or radiocontrast were administered, and continuous measurement of cardiac output and renal blood flow (RBF) was performed with flow probes. Radiocontrast induced early but transient increases in cardiac output with vasodilatation, followed by return to baseline values within 2 h. There was an initial decline in RBF (-5.2 +/- 4.5 vs. 2.1 +/- 5.3%; p < 0.0001) and decreased renal vascular conductance (-4.0 +/- 7.2 vs. 3.3 +/- 7.1%, p < 0.0001; vasoconstriction). This renal vasoconstriction resolved within 2 h and was followed by sustained (72 h) renal vasodilatation with higher RBF (270 +/- 13 vs. 236 +/- 11 ml/min; p < 0.0001). Radiocontrast induces short renal vasoconstriction followed by sustained vasodilatation and increased RBF. Short-term studies are not representative of the overall sustained renal hemodynamic effects of radiocontrast.


Leucine induces cardioprotection in vitro by promoting mitochondrial function via mTOR and Opa-1 signaling.
Coronary heart disease is a major global health concern. Further, severity of this condition is greatly influenced by myocardial ischemia/reperfusion (I/R) injury. Branched-chain amino acids (BCAAs) have cardioprotective effects against I/R via mammalian target of rapamycin (mTOR) activity, wherein Leu is considered to particularly regulate mTOR activation. However, the mechanism underlying cardioprotective effects of Leu via mTOR activity is not fully elucidated. Here, we aimed to study the signaling pathway of cardioprotection and mitochondrial function induced by Leu treatment. Cardiac myocytes isolated from adult male Wistar rats were incubated and exposed to simulated I/R (SI/R) injury by replacing the air content. Cardiac myocytes were treated with Leu and subsequently, their survival rate was calculated. To elucidate the signaling pathway and mitochondrial function, immunoblots and mitochondrial permeability transition pore were examined. Cell survival rate was decreased with SI/R but improved by 160 μM Leu (38.5 ± 3.6% vs. 64.5 ± 4.2%, respectively, p < 0.001). Although rapamycin (mTOR inhibitor) prevented this cardioprotective effect induced by Leu, wortmannin (PI3K inhibitor) did not interfere with this effect. In addition, we indicated that overexpression of Opa-1 and mitochondrial function are ameliorated via Leu-induced mitochondrial biogenesis. In contrast, knockdown of Opa-1 suppressed Leu-induced cardioprotection. Leu treatment is critical in rendering a cardioprotective effect exhibited by BCAAs via mTOR signaling. Furthermore, Leu improved mitochondrial function.


Neuraxial anesthesia in a parturient with common variable immunodeficiency: a case report.
Choosing whether or not to initiate neuraxial anesthesia in pregnant women with immune system defects may be challenging. Anesthesiologists have the responsibility of making the best decision in terms of anesthesia management for both mother and baby during the labor and delivery process. Whether neuraxial anesthesia is associated with an increased risk of central nervous system infection in immunocompromised compared with healthy patients is unknown. It is also unclear if maternal immune modulation required for fetal tolerance makes pregnant women susceptible to pathogens and causes an altered immune response. Infection-related complications of neuraxial anesthesia are rare but may be severe, especially in immunocompromised parturients. There are no guidelines regarding the indications and limitations of regional anesthesia procedures in these patients. Immunocompromised patients are now seen more commonly, and it is essential to adopt a multidisciplinary approach to their care while tailoring anesthetic plans to the individual. We present the case of a 37-year-old parturient who had a congenital immune deficiency and who developed aseptic meningitis after receiving spinal anesthesia for cesarean delivery.


Ciprofloxacin resistance in methicillin- and gentamicin-resistant Staphylococcus aureus.
A total of 112 Staphylococcus aureus strains resistant to methicillin and gentamicin were collected from 31 centres in 22 countries worldwide. Many strains were multi-resistant. In tests to determine the susceptibility of the organisms to ciprofloxacin 16 strains (14.3%), originating from France, the FRG, Israel and Italy, were shown to be resistant to this agent. To limit ciprofloxacin resistance, a reappraisal is necessary of fluoroquinolone usage against methicillin- and gentamicin-resistant Staphylococcus aureus.


Metastatic placental lymphoma associated with maternal human immunodeficiency virus infection.
Pregnancy complicated by maternal human immunodeficiency virus (HIV) infection is increasing in frequency. This report describes a maternal malignancy associated with HIV infection that may complicate pregnancy. A 33-year-old primigravida was delivered by cesarean. Histologic examination of the placenta revealed the presence of metastatic non-Hodgkin lymphoma of B-cell origin. The patient was then found to be infected with HIV. Nine months postpartum, she was diagnosed with immunoblastic lymphoma. She is currently undergoing chemotherapy. Non-Hodgkin lymphoma of B-cell origin is an indication of AIDS. Pregnancies associated with maternal HIV infection may be complicated by this malignancy, which may metastasize to the products of conception. Careful examination of the placenta can detect metastases in women with non-Hodgkin B-cell lymphoma.


Toxicity of Silver Nanoparticles Supported by Surface-Modified Zirconium Dioxide with Dihydroquercetin.
The antibacterial performance and cytotoxic examination of in situ prepared silver nanoparticles (Ag NPs), on inorganic-organic hybrid nanopowder consisting of zirconium dioxide nanoparticles (ZrO2 NPs) and dihydroquercetin (DHQ), was performed against Gram (-) bacteria Escherichia coli and Gram (+) bacteria Staphylococcus aureus, as well as against human cervical cancer cells HeLa and healthy MRC-5 human cells. The surface modification of ZrO2 NPs, synthesized by the sol-gel method, with DHQ leads to the interfacial charge transfer (ICT) complex formation indicated by the appearance of absorption in the visible spectral range. The prepared samples were thoroughly characterized (TEM, XRD, reflection spectroscopy), and, in addition, the spectroscopic observations are supported by the density functional theory (DFT) calculations using a cluster model. The concentration- and time-dependent antibacterial tests indicated a complete reduction of bacterial species, E. coli and S. aureus, for all investigated concentrations of silver (0.10, 0.25, and 0.50 mg/mL) after 24 h of contact. On the other side, the functionalized ZrO2 NPs with DHQ, before and after deposition of Ag NPs, do not display a significant decrease in the viability of HeLa MRC-5 cells in any of the used concentrations compared to the control.


Early recurrence during the blanking period and left atrial reverse remodeling after catheter ablation for non-paroxysmal atrial fibrillation.
Early recurrence of atrial tachyarrhythmia (ERAT) during a 90-day blanking period (BP) often occurs after atrial fibrillation (AF) ablation. Left atrial reverse remodeling (LARR), which is the reduction in LA volume (LAV), also occurs during the BP. Both ERAT and LARR are associated with late recurrence (LR, greater than 90 days after ablation). We investigated the association between ERAT and LARR following non-paroxysmal AF (NPAF) ablation. We retrospectively reviewed 330 consecutive patients undergoing initial NPAF ablation (median follow-up: 4.0 years). Based on the timing of the final ERAT, we divided the patients into No-ERAT (N = 154, without ERAT), Early (N = 39, 0-7 days after ablation), Intermediate (N = 67, 8-30), and Late-ERAT (N = 70, 31-90) groups. We assessed the extent of LARR, defined as the percentage of decrease in LAV (%ΔLAV). The %ΔLAV cutoff value was determined by receiver operating characteristic analysis, and incorporated into a multivariate analysis to assess the association between ERAT and LARR. Late-ERAT was associated with LR (hazard ratio: 6.31, 95% confidence interval (CI): 4.21-9.47, p = 0.0001). The %ΔLAV in the Late-ERAT group was significantly smaller than the other groups (p < 0.0001). The predictive power of %ΔLAV for LR was slight (AUC, 0.604; best cutoff, 18.8% decrease; p = 0.0011). In the multivariate logistic regression analysis, Late-ERAT was associated with poor LARR (%ΔLAV < 18.8% decrease) (odds ratio, 0.13; 95%CI, 0.06-0.27; p < 0.001), whereas Early- and Intermediate-ERAT did not show any correlation. Late-ERAT was strongly associated with poor LARR after NPAF ablation. Both Late-ERAT and poor LARR might reflect a residual arrhythmogenic substrate causing LR.


Long-term delta superinfection in hepatitis B surface antigen carriers and its relationship to the course of chronic hepatitis.
To assess the prevalence and clinical significance of delta-infection in chronic hepatitis B surface antigen carriers, we examined 326 liver biopsies from 192 retrospectively selected carriers by immunofluorescence. Delta antigen was detected in 102 specimens from 50 carriers (26.2%) with peak prevalence in patients with active cirrhosis (51.5%) and generally in close association with progressive liver disease (94%). The antigen was located in the nuclei of 2%-50% of the hepatocytes, without any disease-specific pattern of fluorescence. Patients with intrahepatic delta-antigen, however, had more severe liver disease than those without it. Histologic follow-up of 101 cases showed that the rates of worsening of the liver disease were similar in delta-antigen-positive and in delta-antigen-negative patients. It is concluded that delta-superinfection does play a role in worsening the histologic picture of hepatitis B surface antigen-positive chronic active hepatitis, possibly by liver injury induced acutely at the moment of infection.


Opening Fukushima floodgates: Modelling 137Cs impact in marine biota.
A numerical model was applied to simulate the transport of 137Cs released with the waters which were used to cool Fukushima reactors. These stored waters will be released to the Pacific Ocean according to Japanese government plans. The radionuclide transport model is Lagrangian and includes radionuclide interactions with sediments and an integrated dynamic foodweb model for biota uptake. Calculations made from a conservative approach indicate that expected concentrations in sediments and marine fish would be orders of magnitude below those detected after Fukushima accident and also lower than those resulting from global fallout background.


Significance of phospho-vascular endothelial growth factor receptor-2 expression in pancreatic cancer.
Vascular endothelial growth factor receptors (VEGFRs) are mainly expressed by endothelial cells, but they are also expressed by some cancer cells, including pancreatic cancer. The objective of this study was to evaluate the significance of VEGFRs expression in pancreatic cancer cells. A total of 107 primary pancreatic tumors were stained with antibodies against VEGFR-1, VEGFR-2, phospho-VEGFR-2 (pVEGFR-2), VEGFR-3, VEGF-A, VEGF-C, and VEGF-D. VEGFR-2 and pVEGFR-2 expression were positive in 74 (69%) and 54 (50%) of 107 pancreatic cancers. There was a significant correlation (P < 0.001) between VEGFR-2 expression and pVEGFR-2 expression. pVEGFR-2 was significantly associated with invasion to the anterior capsule of pancreas (P = 0.032) and arterial invasion (P = 0.012). In contrast, VEGFR-1 and VEGFR-3 expression was only observed in 13 (12%) and 15 (14%) of 107 pancreatic cancers, and was not associated with any clinicopathological features. The prognosis of pVEGFR-2 positive patients with stage IIA tumors was significantly (P = 0.0441) poorer than that of pVEGFR-2-negative patients. VEGF-A, VEGF-C, and VEGF-D expression was positive in 42 (39%), 82 (77%), and 39 (36%) of 107 pancreatic cancers, respectively. The prognosis for VEGF-A-positive patients was significantly (P = 0.0425) poor, but not for VEGF-C-positive and VEGF-D-positive patients. A multivariate analysis indicated pVEGFR-2 expression to be an independent prognostic factor, but not VEGF-A. These findings suggested that VEGFR-2 signaling might therefore be associated with the prognosis of patients with pancreatic cancer. The expression of pVEGFR-2 might be a novel predictive prognostic marker for patients with pancreatic cancers, especially at clinical stage IIA.


Hemodynamics of the central nervous system arteriovenous malformation nidus during particulate embolization. A computer model.
We have modelled the hemodynamics of the nidus of the central nervous system (CNS) arteriovenous malformation (AVM) during the process of particulate embolization. The model accurately reproduces the visually apparent incremental slowing observed during such embolization of CNS AVMs. The model is simple and proposes that the nidus is composed of many identical microchannels. As the microchannels are occluded by particles at a constant rate, the rate of change of flow reduction with each bolus of emboli constantly increases exponentially. A rapid reduction in apparent flow rate occurs immediately prior to complete occlusion. With a more accurate understanding of the working of the nidus of CNS AVMs we can increase the safety of therapeutic particulate embolization.


Current knowledge about Na2SO4 effects on plants: what is different in comparison to NaCl?
In some areas of the world, high levels of sodium sulfate (Na2SO4) are found in the soil together with sodium chloride (NaCl). However, most studies on salinity are performed utilizing only NaCl as a salinizing agent. Generally, plant species have different tolerance/susceptibility responses when grown in the presence of these salts. Some studies showed that Na2SO4 seems to be more inhibitory than NaCl for the growth of species such as barley, wheat, sugar cane, beet, tomato, wild potato, and others. However, studies focusing on how Na2SO4 can affect the biochemical and physiological processes of plants are very scarce. This review provides an overview on the effects of Na2SO4 on different crops and plants species with a special emphasis on the tolerance/non-tolerance mechanisms of the halophyte Prosopis strombulifera under elevated NaCl and Na2SO4. A better understanding of the tolerance mechanisms in this particular species will help to identify cultivars of crop species that are more tolerant to Na2SO4. This knowledge could be used to extent cultivation of certain crop plants on Na2SO4 containing soils.


Role of changes in plasma prolactin concentrations on ram and buck sperm cryoresistance.
Seasonal endocrine changes may modify sperm cryoresistance in certain small ruminant species. The present work examines the effect of prolactin (PRL) on ram and buck sperm cryoresistance. A dopamine agonist (bromocriptine [BCR] 60 mg i.m. twice per week from May 15 to June 15, that is, approaching the summer solstice) or antagonist (sulpiride [SLP] 100 mg s.c. daily from December 15 to January 15, that is, around the winter solstice) was administered under solstice-appropriate photoperiod conditions to modify PRL secretion. Control animals received the vehicle only. Compared to the corresponding controls, BCR reduced PRL secretion to basal levels in both the rams and bucks. In rams, the cryoresistance ratios for sperm curvilinear velocity (P < 0.05) and lateral head displacement (P < 0.01) were higher for the BCR-treated animals. In bucks, neither the characteristics of fresh nor frozen-thawed sperm were affected by BCR treatment. After the administration of SLP, PRL levels increased and remained high for more than 5 h in the rams though they immediately began to fall in the bucks. By 24 h, PRL had returned to basal concentrations in both species. In rams treated with SLP, the cryoresistance ratios for sperm progressive motility, straight line velocity, sperm mean path velocity, cross beat frequency, and the progression ratios linearity, straightness and oscillation, were all lower compared to the controls (P < 0.05), while the amplitude of lateral head displacement was higher (P < 0.01). In bucks, sperm cryoresistance was not affected by SLP administration. Together, these results suggest that high levels of PRL negatively affect the cryoresistance of ram sperm, while buck sperm seems unaffected.


Comparative effectiveness and safety of sodium-glucose cotransporter-2 inhibitors versus metformin in patients with type 2 diabetes: An observational study using data from routine care.
To assess the effectiveness and safety of sodium-glucose cotransporter-2 (SGLT2) inhibitors in treatment-naïve patients compared with metformin. We conducted a cohort study of US adults with type 2 diabetes mellitus who had not filled a prescription for a diabetes medication in the preceding year. We then identified patients who newly filled a prescription for an SGLT2 inhibitor or metformin between 2013 and 2018. The primary outcome was a composite of heart failure, myocardial infarction or stroke. Safety outcomes included hypoglycaemia, diabetic ketoacidosis, genital infection, lactic acidosis and acute kidney injury. After 1:1 propensity-score (PS) matching, proportional hazards models were fit to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). We identified 9964 individuals newly prescribed an SGLT2 inhibitor who were PS-matched to 9964 individuals newly prescribed metformin. The mean age was 54 years, 52% were women, and the duration of follow-up was 213 days for metformin and 147 days for SGLT2 inhibitors. The primary outcome occurred in 54 patients (7.2 events per 1000 person-years) who received an SGLT2 inhibitor, compared to 84 patients (8.5 per 1000 person-years) who received metformin (HR 0.82, 95% CI 0.58, 1.15). Similar results (HR 0.87, 95% CI 0.69, 1.09) were observed in an analysis with longer follow-up (ie, approximately 600 days). The rates of genital infection (HR 2.28, 95% CI 1.87, 2.78) and diabetic ketoacidosis (HR 1.58, 95% CI 0.92, 2.70) were higher for patients prescribed an SGLT2 inhibitor compared to metformin, while the rates of acute kidney injury (HR 0.94, 95% CI 0.60, 1.47) or hypoglycaemia (HR 0.83, 95% CI 0.48, 1.42) were not. We observed a numerically lower rate of short-/mid-term cardiovascular events for patients newly prescribed an SGLT2 inhibitor compared to metformin, albeit with wide CIs that include the possibility of a null effect. SGLT2 inhibitors were associated with a higher rate of genital infection and diabetic ketoacidosis. Larger cohort studies and long-term clinical trials powered to assess cardiovascular events are necessary to understand the risk-benefit profile of SGLT2 inhibitors as first-line therapy for adults with type 2 diabetes mellitus.


Progress in the use of mesenchymal stromal cells for osteoarthritis treatment.
LITERATURE REVIEW OF MSCS IN THE TREATMENT OF OSTEOARTHRITIS IN THE PAST FIVE YEARS: Osteoarthritis (OA) is one of the most common chronic joint diseases, with prominent symptoms caused by many factors. However, current medical interventions for OA have resulted in poor clinical outcomes, demonstrating that there are huge unmet medical needs in this area. Cell therapy has opened new avenues of OA treatment. Different sources of mesenchymal stromal cells (MSCs) may have different phenotypes and cellular functions. Pre-clinical and clinical studies have demonstrated the feasibility, safety and efficacy of MSC therapy. Mitogen-activated protein kinase, Wnt and Notch signaling pathways are involved in the chondrogenesis of MSC-mediated treatments. MSCs may also exert effective immunoregulatory and paracrine effects to stimulate tissue repair. Therapy with extracellular vesicles containing cytokines, which are secreted by MSCs, might be a potential treatment for OA.


Behind the ChatGPT Hype: Are Its Suggestions Contributing to Addiction?
ChatGPT has been a frequent topic of discussion lately. All over the Internet, from YouTube to blogs, there have been reports about how ChatGPT is able to plan people's daily activities, even for a whole month. However, what matters is what activities ChatGPT recommends. When ChatGPT was trained on a vast amount of data from the Internet, we wondered if it would suggest activities that can lead to addiction. In our test, not once did ChatGPT recommend an activity related to alcohol, drug use, or any other activity that can lead to addiction with serious health consequences. Suggestions seemed more like self-improvement posts on blogs than discussion forums where people might mention drinking in the evenings. Thus, if a person were to use ChatGPT as a personal lifestyle advisor, it does not appear on the basis of this test that ChatGPT would recommend activities that would be fundamentally detrimental to their health. However, more detailed long-term testing of similar tools is needed before recommendations for use in practice can be made.


Implementation strategies, and barriers and facilitators for implementation of physical activity at work: a scoping review.
Inactivity and sedentary lifestyle have led experts to recommend an increase in structured, workplace-based physical activity (PA) initiatives. Previous studies on workplace-based PA have only shown moderate and short-term effects. This has been attributed to the lack of clear implementation strategies and understanding of factors that may hinder or enable uptake of PA. To ensure long-term, sustainable outcomes, there is a need for a better understanding of implementation strategies, and barriers and facilitators to workplace-based PA. A scoping review of studies investigating implementation approaches and factors affecting uptake of workplace-based PA was conducted. Qualitative and quantitative articles published in MEDLINE, Embase, Scopus, or PsycINFO between 2008 and 2018 evaluating the implementation of PA were included. Data on study characteristics, evaluation, and implementation methods applied were systematically extracted. Two reviewers extracted, coded, and organised factors affecting uptake using the Theoretical Domains Framework (TDF). After dual, blinded screening of titles and abstracts, 16 articles reporting on eight studies were included in the review. Several different methods of implementation were applied, including information meeting, kick-off events, and "change agents" as the most common. A total of 109 factors influencing implementation were identified, consisting of 57 barriers and 52 facilitators. Barriers most often related to the TDF domains Environmental Context and Resources (n = 34, 36.2%), Social influences (n = 13, 13.8%), and Social/Professional Role and Identity (n = 8, 8.5%). Likewise, facilitators most often related to the TDF domains Social influences (n = 17, 19.5%), Environmental Context and Resources (n = 16, 18.4%), and Social/Professional Role and Identity (n = 9, 10.3%). Our review has highlighted the multilevel factors affecting the uptake of workplace-based PA and underpins the complexities in implementation of such initiatives. The published literature predominantly provides details from the employees' perspectives on factors that need to be addressed and a lack of attention to these factors will cause them to hamper uptake of PA. The analysis of barriers and facilitators provides a theoretical foundation to guide future intervention design. However, further research is needed to fully understand the success or failure of implementation processes.


Chemical changes in hydroxyapatite biomaterial under in vivo and in vitro biological conditions.
The introduction of a synthetic calcium phosphate into a biological environment is likely to result in surface-mediated chemical events. On the basis of such an assessment, we studied the chemical changes occurring in the mineral after exposure of a synthetic hydroxyapatite ceramic to both in vivo (implantation in human) and in vitro (cell culture) conditions. A small amount of the material was phagocytized but the major remaining part behaved as a secondary nucleator as evidenced by the appearance of a newly formed mineral. Morphologically, the newly formed mineral appeared as tiny crystals precipitated and grown from the surface of the initial synthetic crystals. The density of the additional mineral increased from the periphery to the core of each biomaterial aggregate. Chemically, it was identified by IR spectroscopy as a carbonated apatitic mineral. We propose that the adsorption of biomolecules could inhibit precipitation, accounting for the increasing amount of precipitate from the periphery to the core of the aggregates.


[Specular microscopy findings in active uveitis].
To study the effect of ocular inflammation in active uveitis on the corneal endothelium. This is a prospective cross-sectional study involving 63 eyes of 38 patients with active newly-diagnosed uveitis. Eighty-four eyes of 42 non-uveitic subjects served as a control group. All patients underwent detailed ophthalmic examination, laser flare photometry, and non-contact specular microscopy. Eyes with uveitis had a follow-up visit at one month after initiation of treatment, including laser flare photometry and specular microscopy. The mean age of the active uveitis patients was 33 (range: 9-67 years) with 21 men (55%) and 17 women (45%). For the uveitis patients at baseline, the mean flare value was 32ph/ms (range: 15-100ph/ms) with flare photometry value ≥50ph/ms in 13 eyes (21%) and<50ph/ms in 50 eyes (79%). At baseline, cell density (CD) of the uveitis patients was similar to CD in control eyes (p꞊0.16). The percent of hexagonality was significantly lower (p<0.0001), and the coefficient of variance (CV) (p<0.0001) and central corneal thickness (CCT) (p<0.0001) were significantly higher than in the control group. After one month, there was a significant decrease in flare photometry values (p<0.0001), with a mean flare value of 14.5ph/ms (range: 4-60ph/ms). In the active uveitis group, the overall results of specular microscopy did not significantly vary between the initial examination and the 1-month examination. For eyes with flare photometry value ≥50ph/ms at baseline, CD and hexagonal cell count significantly increased on the 1-month examination (p꞊0.01 and p꞊0.02 respectively), while CV and CCT decreased significantly at the one-month follow-up visit (p꞊0.007/p꞊0.03 respectively). For eyes with flare photometry value at baseline <50ph/ms, there was no significant differences in specular microscopy results between the initial examination and the 1-month examination. In eyes with newly-diagnosed uveitis and active anterior chamber inflammation, specular microscopy shows transient qualitative abnormalities of the corneal endothelium that depend on the severity of the anterior chamber inflammation as measured by the laser flare meter.


Pd-PEPPSI-IPent(Cl): a highly effective catalyst for the selective cross-coupling of secondary organozinc reagents.
No migration? No problem! A series of new N-heterocyclic carbene based Pd complexes has been created and evaluated in the Negishi cross-coupling of aryl and heteroaryl chlorides, bromides, and triflates with a variety of secondary alkylzinc reagents. The direct elimination product is nearly exclusively formed; in most examples there is no migratory insertion at all.


Sulfur bentonite-organic-based fertilizers as tool for improving bio-compounds with antioxidant activities in red onion.
Red onion is popular in cuisines worldwide and is valued for its potential medicinal properties. Red onion is an important source of several phytonutrients such as flavonoids, thiosulfinates and other sulfur compounds, recognized as important elements of the diet. Nowadays, there is the need of producing food enriched in health benefit compounds. In this study, pads of sulfur bentonite (SB) with the addition of orange residue (OR) or olive pomace (OP) were used to improve the quality of red onion. The experiment was conducted for 3 months in the field to evaluate the phytochemicals of differently amended red onion. Treated plants were better in quality than controls. Antioxidant activity, detected as DPPH, ORAC and ABTS, was highest in plants grown in the presence of SB enriched with agricultural wastes, particularly SB-OR. Polyphenols increased in all treated plants. The volatile fraction was clearly dominated by sulfur compounds that are strictly related to the concentration of the aroma precursors S-alkenyl cysteine sulfoxides. The greater amount of thiosulfinates in treated compared with untreated onion evidenced that SB pelletized with agricultural wastes can represent a new formulation of organic fertilizer able to improve the beneficial properties of onion. The results highlighted that the best red onion quality was obtained using SB-OR pads. The use of SB bound with agricultural wastes represents a novel strategy to increase bio-compounds with beneficial effects on human health, to enhance the medical and economic values of sulfur-loving crops, with important consequences on the bio and green economy. © 2019 Society of Chemical Industry.