Causal Relationship and Shared Genetic Loci between Psoriasis and Type 2 Diabetes through Trans-Disease Meta-Analysis.
Psoriasis and type 2 diabetes (T2D) are complex conditions with significant impacts on health. Patients with psoriasis have a higher risk of T2D (∼1.5 OR) and vice versa, controlling for body mass index; yet, there has been a limited study comparing their genetic architecture. We hypothesized that there are shared genetic components between psoriasis and T2D. Trans-disease meta-analysis was applied to 8,016,731 well-imputed genetic markers from large-scale meta-analyses of psoriasis (11,024 cases and 16,336 controls) and T2D (74,124 cases and 824,006 controls), adjusted for body mass index. We confirmed our findings in a hospital-based study (42,112 patients) and tested for causal relationships with multivariable Mendelian randomization. Mendelian randomization identified a causal relationship between psoriasis and T2D (P = 1.6 × 10‒4, OR = 1.01) and highlighted the impact of body mass index. Trans-disease meta-analysis further revealed four genome-wide significant loci (P < 5 × 10‒8) with evidence of colocalization and shared directions of effect between psoriasis and T2D not present in body mass index. The proteins coded by genes in these loci (ACTR2, ERLIN1, TRMT112, and BECN1) are connected through NF-κB signaling. Our results provide insight into the immunological components that connect immune-mediated skin conditions and metabolic diseases, independent of confounding factors.


Neighborhood Fast-Food Environments and Hypertension in Canadian Adults.
Hypertension is a leading cause of cardiovascular disease and premature death worldwide. Neighborhoods characterized by a high proportion of fast-food outlets may also contribute to hypertension in residents; however, limited research has explored these associations. This cross-sectional study assessed the associations between neighborhood fast-food environments, measured hypertension, and self-reported hypertension. Data from 10,700 adults living in urban areas were obtained from six Canadian Health Measures Survey cycles (2007-2019). Each participant's blood pressure was measured at a mobile clinic six times. Measured hypertension was defined as having an average systolic blood pressure ≥140 or a diastolic blood pressure ≥90 mm Hg or being on blood pressure-lowering medication. Participants were also asked whether they had been diagnosed with high blood pressure or whether they take blood pressure-lowering medication (i.e., self-reported hypertension). The proportion of fast-food outlets relative to the sum of fast-food outlets and full-service restaurants in each participant's neighborhood was obtained from the Canadian Food Environment Dataset, and analyses were conducted in 2022. The mean proportion of fast-food outlets was 23.3% (SD=26.8%). A one SD increase in the proportion of fast-food outlets was associated with higher odds of measured hypertension in the full sample (OR=1.17, 95% CI=1.05, 1.31) and in sex-specific models (women: OR=1.14, 95% CI=1.01, 1.29; men: OR=1.21, 95% CI=1.03, 1.43). Associations between the proportion of fast-food outlets and self-reported hypertension were inconclusive. Findings suggest that reducing the proportion of fast-food restaurants in neighborhoods may be a factor that could help reduce hypertension rates.


Neuropathic or systemic chronic intoxication with Karwinskia humboldtiana (Buckthorn) fruit? Histopathological effect in myocardial and skeletal muscle.
In accidental intoxicated animals and humans, Karwinskia humboldtiana (Kh) causes lesions in the central and peripheral nervous system and organs like the kidney, liver, and lung. The objective was to evaluate the histology of myocardium and skeletal muscle after experimental chronic intoxication with mature fruit of Kh in Wistar rat. Twenty-five rats were used and divided into five groups (n = 5): four intoxicated and one control. Kh fruit was ground, dried, sieved, and administered by an orogastric tube. Intoxicated rats received 3.5 g/kg body weight fractionated in 5 doses. Control rats received only water. Animals were euthanized at 24, 48, 58, and 112 days, respectively. Samples of the myocardium and skeletal muscle were obtained and processed for light microscopy evaluation. Morphological analyses were performed, including a microdensitometric analysis. Results showed areas of necrosis in the muscle fibers, fibers with vacuolated cytoplasm, and disorganization of myofilaments, as well as staining variations in both myocardium and skeletal muscle time-depending. Zones with loss of continuity of the external lamina were identified with PAS with the diastase histochemical method. Immunolabeling with specific antibodies demonstrated diminution of actin and desmin myofilaments. The microdensitometric analysis showed a statistically significant difference between the intoxicated vs control group. These findings demonstrate that chronic intoxication of Kh fruit also causes damage in myocardial and skeletal muscle, these alterations will be useful to understand that the toxic effects of Kh fruit in accidently intoxicated humans are systemic, and not only over the nervous system.


Novel factor Xa inhibitor, maslinic acid, with antiplatelet aggregation activity.
As antithrombotic effects of maslinic acid (MA) have not yet been studied, MA-mediated downregulation of coagulation factor Xa (FXa) and platelet aggregation was studied. We show that MA inhibited the enzymatic activity of FXa and platelet aggregation, induced by adenosine diphosphate (ADP) and a thromboxane A2 (TXA2 ) analog, U46619 with a similar antithrombotic efficacy to rivaroxaban, a direct FXa inhibitor used as a positive control. Mechanistically, MA suppressed U46619- or ADP-induced phosphorylation of myristoylated alanine-rich C kinase substrate, and the expression of P-selectin, and activated PAC-1 in platelets. MA increased generation of nitric oxide, but downregulated excessive secretion of endothelin-1 in ADP- or U46619-treated human umbilical vein endothelial cells. In arterial and pulmonary thrombosis mouse model, MA showed prominent anticoagulant and antithrombotic effects. Our data suggest MA as a candidate molecule for a new class of drugs targeting anti-FXa and antiplatelet.


Glucocorticoid-mediated gene suppression of rat cytokine-induced neutrophil chemoattractant CINC/gro, a member of the interleukin-8 family, through impairment of NF-kappa B activation.
The glucocorticoid dexamethasone inhibited the production of the rat cytokine-induced neutrophil chemoattractant CINC/gro, a counterpart of human melanoma growth-stimulating activity that belongs to the interleukin-8 (IL-8) family, in the normal rat kidney epithelial cell line NRK-52E stimulated with interleukin-1 beta (IL-1 beta), lipopolysaccharide, or tumor necrosis factor alpha. The accumulation of CINC/gro mRNA induced by these activators was also decreased comparably by dexamethasone. A nuclear run-on assay revealed that dexamethasone decreased the IL-1 beta-induced transcription of the CINC/gro gene. The half-life of CINC/gro mRNA transcripts did not change significantly after exposure to dexamethasone, suggesting that this glucocorticoid acts mainly at the transcriptional level. Transfection with luciferase expression vectors containing 5'-deleted and mutated CINC/gro gene sequences demonstrated that the 5'-flanking region containing the NF-kappa B binding site is involved in the IL-1 beta- and dexamethasone-induced activation and repression of the CINC/gro gene expression, respectively. Furthermore, a tandem repeat of the NF-kappa B sequence in the CINC/gro gene conferred the inducibility by IL-1 beta and suppression of luciferase activity by dexamethasone. In an electrophoretic mobility shift assay, dexamethasone diminished the IL-1 beta-induced formation of NF-kappa B complexes, which consisted of p65 and p50. Western blotting revealed that dexamethasone inhibited the IL-1 beta-induced translocation of p65 from the cytoplasm into the nucleus, while the nuclear level of NF-kappa B p50 remained almost unchanged. In addition, the degradation of I kappa B-alpha induced by IL-1 beta was not inhibited by dexamethasone. These results indicated that the suppression of the CINC/gro gene transcription by glucocorticoid occurs through the impairment of NF-kappa B activation, possibly by interference with the translocation of NF-kappa B p65 from the cytoplasm into the nucleus, thereby suppressing transactivation of the CINC/gro gene.


The measurement of clinical pain intensity: a comparison of six methods.
The measurement of subjective pain intensity continues to be important to both researchers and clinicians. Although several scales are currently used to assess the intensity construct, it remains unclear which of these provides the most precise, replicable, and predictively valid measure. Five criteria for judging intensity scales have been considered in previous research: ease of administration of scoring; relative rates of incorrect responding; sensitivity as defined by the number of available response categories; sensitivity as defined by statistical power; and the magnitude of the relationship between each scale and a linear combination of pain intensity indices. In order to judge commonly used pain intensity measures, 75 chronic pain patients were asked to rate 4 kinds of pain (present, least, most, and average) using 6 scales. The utility and validity of the scales was judged using the criteria listed above. The results indicate that, for the present sample, the scales yield similar results in terms of the number of subjects who respond correctly to them and their predictive validity. However, when considering the remaining 3 criteria, the 101-point numerical rating scale appears to be the most practical index.


Femtosecond LIPSS on indium-tin-oxide thin films at IR wavelengths.
We investigated laser-induced periodic surface structures (LIPSS) generated on indium-tin-oxide thin films with femtosecond laser pulses in the infrared region. Using pulses between 1.6 and 2.4 µm central wavelengths, we observed robust LIPSS morphologies with a periodicity close to λ/10. Supporting finite-difference time-domain calculations suggests that the surface forms are rooted in the field localization in the surface pits leading to a periodically increased absorption of the laser pulse energy that creates the observed periodic structures.


Elevated thrombin generation levels in the left atrial appendage in patients with atrial fibrillation.
Atrial Fibrillation (AF) is the most common sustained tachi-arrhythmia. Thrombus formation in the left atrial appendage (LAA) increases the risk of stroke and systemic embolism in patients with AF. The aim of this study was to compare thrombin generation in the LAA to the LA among patients with AF. A cross-sectional study of consecutive patients with AF undergoing pulmonary veins catheter ablation. Blood samples from the femoral vein (FV), right atrium (RA), left atrium (LA), and LAA were collected during the catheter ablation procedures. Thrombin generation was assessed by a Calibrated Automated Thrombogram. The LAA-calibrated automated thrombogram parameters were compared with the RA, LA, and FV. A total of 47 consecutive patients were enrolled in the study. The endogenous thrombin potential and peak height were significantly higher in the LAA compared with the LA, the mean differences and 95% CI between the LA and LAA were -378.9 (-680.5, -77.2) (nM∗min) and -66.7 (-119.6, -13.8) (nM) in the endogenous thrombin potential and peak height respectively. In patients with AF undergoing catheter ablation, the LAA demonstrated increased thrombin generation compared with the LA. This finding might contribute to the understanding of why the LAA is more predisposed to thrombus formation than the LA. NCT03795883.


Preparation and biodistribution of copper-67-labeled porphyrins and porphyrin-A6H immunoconjugates.
The synthetic porphyrins, N-benzyl-5,10,15,20-tetrakis (4-carboxyphenyl) porphine (N-bzHTCPP) and N-4-nitrobenzyl-5-(4-carboxyphenyl)-10,15,20-tris(4-sulfophenyl) porphine (N-bzHCS3P), represent excellent radiocopper chelating agents that may find utility in antibody-mediated diagnosis and/or therapy. N-bzHCS3P was conjugated to an anti-renal cell carcinoma (RCC) antibody, A6H, and labeled with copper-67. 67CuCS3P-A6H was studied for its biodistribution in human RCC xenograft-bearing nude mice, along with the radiolabeled free porphyrins. The porphyrins resulted in tumor:blood ratios in the range of 3 to 4 after 48 h. The radiolabeled antibody achieved a tumor:blood ratio of over 16 after 45 h, indicating accumulation at the desired site. However, unwanted localization also occurred in the liver and spleen, which will have to be rectified before realizing the full potential of this approach.


Combined heart-liver-kidney transplant: The university of Chicago medicine experience.
Until recently, combined heart-liver-kidney transplantation was considered too complex or too high-risk an option for patients with end-stage heart failure who present with advanced liver and kidney failure as well. The objective of this paper is to present our institution's best practices for successfully executing this highly challenging operation. At our institution, referral patterns are most often initiated through the cardiac team. Determinants of successful outcomes include diligent multidisciplinary patient selection, detailed perioperative planning, and choreographed care transition and coordination among all transplant teams. The surgery proceeds in three distinct phases with three different teams, linked seamlessly in planned handoffs. The selection and perioperative care are executed with determined collaboration of all of the invested care teams. Combined heart-liver-kidney transplantation can be successfully done by careful selection, coordination, and execution.


NPR-1 Modulates Plasticity in C. elegans Stress-Induced Sleep.
Sleep is beneficial yet antagonistic to critical functions such as foraging and escape, and we aim to understand how these competing drives are functionally integrated. C. elegans, which lives in reduced oxygen environments, engages in developmentally timed sleep (DTS) during larval stage transitions and engages in stress-induced sleep (SIS) during recovery from damaging conditions. Although DTS and SIS use distinct mechanisms to coordinate multiple sleep-associated behaviors, we show that movement quiescence in these sleep states is similarly integrated with the competing drive to avoid oxygen. Furthermore, by manipulating oxygen to deprive animals of SIS, we observe sleep rebound in a wild C. elegans isolate, indicating that sleep debt accrues during oxygen-induced SIS deprivation. Our work suggests that multiple sleep states adopt a common, highly plastic effector of movement quiescence that is suppressed by aversive stimuli and responsive to homeostatic sleep pressure, providing a limited window of opportunity for escape.


Cloning, characterization, expression, and copper sensitivity of the metallothionein-1 gene in the Chinese mitten crab, Eriocheir sinensis.
A full-length metallothionein-1(MT-1) cDNA was cloned from the Chinese mitten crab, Eriocheir sinensis, based upon the hepatopancreas cDNA library. The full-length cDNA contained a single 180 bp open reading frame that encoded a 59 amino acid protein. The deduced amino acid sequence was cysteine (Cys)-rich, with residues observed in patterns characteristic of other reported MTs: Cys-X-Cys, Cys-X-X-Cys, or Cys-X-X-X-Cys. Gene structure obtained via PCR yielded a 3816 bp gene, which was comprised of three exons and two introns arranged in a "3 + 2" pattern. The cloned 5'flanking region (1,735 bp) contained several predicted binding sites, which included MREs, AP-1, SP1, USF, GATA, HNF-1, and HSF. MT-1 mRNA expression analysis revealed that while levels were highest in the hepatopancreas, expression was abundant in testis and thoracic ganglia, moderate in intestine (P<0.05), and weak in other tissues (P<0.05). MT-1 mRNA expression exhibited reproductive variation in the male, with levels approximately tenfold greater in August, during seasonal gonadal maturation, compared to other times of the year. Cu2+ exposure via tank water (0-1 mg/l for 7 days) resulted in a dose-dependent bell curve response in MT-1 mRNA expression, with peak expression observed after exposure to 0.1 mg/l Cu2+. A time course experiment (0.1 mg/l Cu2+ over 9 days) revealed MT-1 mRNA expression peaked sharply on day 5 before gradually decreasing with prolonged exposure. In the present report, we provide sequence analysis of the first MT-1 gene cloned in E. sinensis, and evidence that its physiological and toxicological regulation is evolutionary conserved.


Derivation, expansion, and characterization of human embryonic stem cell lines from aneuploid embryos.
Human embryonic stem cells (hESCs) are an invaluable cell source to study human embryogenesis and development and for exploring the nature of human diseases. Moreover, hESCs can serve as an unlimited source of cells for cell therapy. The first hESC lines were derived from frozen blastocyst-stage embryos. In the past 12 years, the field evolved and the hESC lines are derived from pre-embryos in various developmental stages using several techniques. In parallel, the wide use of hESCs triggered the development of materials and methods for expansion of the cell lines derived. Here, we describe our method for derivation, expansion, and characterization of hESC lines from pre-embryos that were diagnosed to carry aneuploid cells and were destined to be discarded.


Linear-nonlinear optical and quantum chemical studies on Quinolinium 3,5-dinitrobenzoate: A novel third order non-linear optical material for optoelectronic applications.
An organic non-linear optical (NLO) crystal of Quinolinium 3,5-dinitrobenzoate (DNBAQ) was synthesized and good quality single crystals of DNBAQ were grown by conventional slow evaporation solution growth technique. Single crystal XRD was utilized to confirm the formation of the charge transfer complex. The crystalline property and the presence of required functional groups was verified employing Powder XRD and FTIR spectral analysis. UV-Vis-NIR and Fluorescence study was performed to determine the optical transmittance and the emission property of the grown crystal. The thermal, mechanical and surface damage threshold stability of the complex was analysed using thermal studies, Vicker's micro hardness studies and Laser damage threshold measurement. The solid state parameter of electronic polarizability of DNBAQ compound was computed through dielectric studies. The non-linear optical characterizations like Kurtz Perry powder technique and Z-Scan technique ensures the non-linear optical activity of the compound. The frequency conversion efficiency of the grown crystal was estimated to be 70% that of the standard Potassium Dihydrogen Phosphate (KDP). Z-Scan analysis confirms the suitability of the grown crystal for optical limiting and switching applications. Quantum chemical studies were adopted on the optimized geometry of DNBAQ molecule using Density Functional Theory (DFT). Frontier Molecular Orbital (FMO) analysis and Molecular Electrostatic Potential (MEP) analysis were performed. The non-linear optical behaviour of the complex was established by evaluating dipole moment, polarizability and hyperpolarizability features. All the above results confirm the resourceful candidature of DNBAQ material for optoelectronic and photonic applications.


[Capability to work in vocational rehabilitation of the severe mentally ill: initial predictors and change after six months].
Persons with severe mental illnesses often need additional vocational rehabilitation in order to gain or regain an adequate capability to work. The objective of this paper is the assessment of work capability and its development throughout the rehabilitation process, as well as clarification of its correlating variables, and predictors. We present data obtained at two different points in time (at rehabilitation program intake and at the six month mark of being in the program) from a sample of 117 rehabilitants. Capability to work was assessed by using the adapted German version of the Work Personality Profile (WPP), called the Arbeitsfähigkeitenprofil (AFP). Additionally, sociodemographic, intellectual, psychopathological, and subjective quality of life measures were examined. The AFP sum score revealed a significant change after six months' participation in the rehabilitation program. More precisely, for the subscales "capability to learn" and "communication skills", a significant increase was obtained, whereas "social adaptation" showed a non-significant improvement. Our results show that the rehabilitants' "capability to work" had improved at the six month mark of the rehabilitation program. It appears that baseline variables of the AFP subscales at program intake were largely related to psychopathology and subjective quality of life measures. Sociodemographic parameters, educational level, and attention measures were associated with work capability improvement after six months.


A risk-specific anesthesia consent form may hinder the informed consent process.
To evaluate the effect of a preprinted, risk-specific consent form on the amount of anesthetic risk information patients retain from the preoperative interview. Postoperative survey of consecutive inpatients to determine risk information retained before and after implementation of a preprinted anesthesia consent form, using standard preoperative risk discussions. Inpatient units of a university medical center. Two groups of patients, both of whom received a standard oral discussion of anesthetic risk information, were compared. Patients in the control group (125 consecutive inpatients) received this information only orally and were interviewed two weeks prior to implementation of a preprinted anesthesia consent form. Patients in the study group (92 consecutive inpatients) received this information orally and via a preprinted consent form and were interviewed between the fourth and sixth weeks after implementation of a preprinted anesthesia consent form. Anesthesia residents discussed five standard anesthetic risks with elective, adult inpatients (n = 233) during a two-week period immediately before and between the fourth and sixth weeks after instituting the mandatory use of a risk-specific anesthesia consent form. These patients were interviewed postoperatively by one of the authors to determine the amount of anesthesia risk information they retained. Results of the postoperative survey showed that patients in the control group retained more information concerning anesthetic risks than did those in the study group (33% vs 19%, p less than 0.01). To improve the informed consent process, either a better method of presenting the preprinted, risk-specific consent form or another method of simultaneously conveying and documenting risk information is needed.


Psychological Impact of the COVID-19 Pandemic on Chinese Health Care Workers: Cross-Sectional Survey Study.
The outbreak of COVID-19 has dominated headlines worldwide. The number of infections has continued to rise and had reached 30,000 worldwide at the time this paper was written. Because of the high risk of nosocomial transmission, medical health care workers may be experiencing substantial psychological stress. This descriptive study aimed to identify psychosocial effects on hospital staff associated with working in a hospital environment during the COVID-19 outbreak. Our survey participants included 57 frontline clinicians working at Wuhan First Hospital and 157 medical students working at Jiangsu Provincial People's Hospital during the COVID-19 outbreak. The questionnaire we adopted included questions regarding the participants' personal well-being, sociodemographic characteristics, and psychological status. 57 frontline clinicians working in Wuhan First Hospital and 157 medical training students working in Jiangsu Provincial Peoples Hospital during this outbreak participated in our survey. The questionnaire we adopted included questions regarding the participants' personal well-being, sociodemographic characteristics and the psychological status. The COVID-19 outbreak had psychological impacts both on formal workers and medical students. The psychological effects included sleep disorders, anxiety, and depression. There was no significant difference between the group of formal workers and medical students (P=.85), and more than 50% (30/54, 56%, vs. 83/157, 52.9%) of the respondents reported pandemic-related mental disorders. Our study indicates that the high risk of SARS-CoV-2 exposure caused substantial psychological stress among health care workers. This finding emphasizes the need to promote psychological crisis intervention for medical personnel during this epidemic.


Capture zone of a multi-well system in bounded peninsula-shaped aquifers.
In this paper we present the equation of capture zone for multi-well system in peninsula-shaped confined and unconfined aquifers. The aquifer is rectangular in plan view, bounded along three sides, and extends to infinity at the fourth side. The bounding boundaries are either no-flow (impervious) or in-flow (constant head) so that aquifers with six possible boundary configurations are formed. The well system is consisted of any number of extraction or injection wells or combination of both with any flow rates. The complex velocity potential equations for such a well-aquifer system are derived to delineate the capture envelop. Solutions are provided for the aquifers with and without a uniform regional flow of any directions. The presented equations are of general character and have no limitations in terms of well numbers, positions and types, extraction/injection rate, and regional flow rate and direction. These solutions are presented in form of capture type curves which are useful tools in hands of practitioners to design in-situ groundwater remediation systems, to contain contaminant plumes, to evaluate the surface-subsurface water interaction and to verify numerical models.


Effects of acute ethanol exposure upon in vivo leucine uptake and protein synthesis in the fetal rat.
Tritiated L-leucine ((3H)L-leu) was injected into the amniotic sacs of 19-day gestation rat fetuses during a brief (4-hr) period of elevation in maternal serum ethanol. The pregnant rats received 47.5% ethanol at "high dose" (0.29 to 0.33 g/100 g body weight) or "low dose" (0.12 to 0.14 g/100 gm body weight) by intraperitoneal injection. Fetal brain and liver were removed and analyzed for tissue uptake (TU) and protein incorporation (PI) of (3H)L-leu. Relative protein synthesis, independent of alterations in TU, was expressed by the ratio PI/TU x 100. Delayed fetal effects of acute maternal ethanol exposure were studied by injecting the fetal amniotic sacs with (3H)L-leu 24 hr after maternal ethanol administration. Both TU and PI were decreased in high dose fetal brain. Liver PI, but not TU, was depressed. High dose ethanol treatment caused a reduction in protein synthesis (PI/TU x 100) in fetal brain but not liver. Low dose ethanol enhanced brain PI and both liver and brain PI/TU x 100. Utilization of (3H)L-leu was related to fourth-hour (sacrifice) maternal serum ethanol levels. Fetal brain was more strikingly affected than liver. Ethanol concentrations greater than 200 mg/dl caused a decrease in brain TU (control, 1879 +/- 185 versus ethanol, 1219 +/- 123 dpm/mg protein) and PI/TU x 100 (control, 48.9 +/- 3.3 versus ethanol, 31.5 +/- 2.9). At levels less than 100 mg/dl, PI/TU x 100 was enhanced in both brain (control, 48.9 +/- 3.3 versus ethanol, 67.3 +/- 2.8) and liver (control, 45.3 +/- 4.2 versus ethanol, 62.3 +/- 1.7). Tissue uptake of (3H)L-leu 24 hr after high dose maternal ethanol exposure was increased in fetal brain. The results support the hypothesis that a brief period of maternal/fetal ethanol exposure, similar to that found in "social" drinking humans, alters normal fetal metabolism.


Bullous pemphigoid induced by dipeptidyl peptidase-4 (DPP-4) inhibitors: a pharmacovigilance-pharmacodynamic/pharmacokinetic assessment through an analysis of the vigibase®.
Objectives: To examine the signals of bullous pemphigoid (BP) with dipeptidyl peptidase-4 inhibitors (DPP-4i) in VigiBase® and the potential role of their pharmacodynamic/pharmacokinetic parameters in the occurrence of BP. Methods: Case/non-case analyses were performed in VigiBase® to examine the signal of BP [reporting odds ratio (ROR)] for gliptins. Secondly, the authors performed linear regression analyses to explore the association between DPP-4i signals for BP and their affinities toward different target enzymes (DPP-2, DPP-4, DPP-8, and DPP-9) and their volume of distribution (Vd). Results: A significant BP signal was found for DPP-4i. The ROR for pooled DPP-4i was 179.48 (95% CI: 166.41-193.58). The highest ROR was found for teneligliptin 975.04 (801.70-1185.87) and lowest for saxagliptin 18.9 (11.5-30.9). Linear regression analyses showed a considerable trend to significance for the linear correlation between the BP signal and gliptin affinity at DPP-4 (slope = 1.316 [-0.4385-3.21], p = 0.067, R2 = 0.40) but not the other enzyme targets, nor for Vd. Conclusion: The findings suggest a clinical relevance of gliptins selectivity for DDP-4 in the development of BP as a result of exposure to these drugs. Future preclinical and clinical studies are needed for a better understanding of this correlation.


Helicobacter pylori infection in patients with gastric involvement by adult T-cell leukemia/lymphoma.
Gastrointestinal involvement is seen frequently in patients with adult T-cell leukemia/lymphoma (ATLL). The authors previously showed a relatively low prevalence of Helicobacter pylori infection in individuals with human T-cell lymphotropic virus 1 (HTLV-1) infection, including patients with ATLL; however, the correlation between H. pylori infection and ATLL gastric involvement has not been investigated. The authors studied 71 patients with ATLL. Gastric involvement was confirmed by endoscopy and biopsy. H. pylori infection was detected by serology, rapid urease test, and immunohistochemistry on biopsy samples. The expression of adhesion molecules on ATLL cells or their ligands on the vasculature in gastric mucosa was analyzed immunohistochemically. The expression of mucosal addressin cell adhesion molecule 1 (MAdCAM-1) was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. Gastric involvement was detected in 21 patients (30%), including 8 patients with acute clinical subtype ATLL and 13 patients with lymphoma type ATLL. The prevalence of H. pylori infection was 86% (18 of 21 patients) in the patients with gastric involvement but only 38% (19 of 50 patients) in the patients without such involvement (P < 0.001). The expression of lymphocyte function-associated antigen 1 (LFA-1) and its ligand, intercellular adhesion molecule 1 (ICAM-1), was most frequent on ATLL cells infiltrating the stomach and was enhanced substantially on vascular endothelium in H. pylori-infected gastric mucosa. Human mucosal lymphocyte antigen 1 also was expressed on infiltrating ATLL cells in the stomach. The expression of MAdCAM-1 mRNA assessed by RT-PCR also was seen selectively in H. pylori-infected patients. ATLL cells infiltrate gastric tissues infected with H. pylori, probably through the interaction of adhesion molecules on these cells and their ligands on the vasculature, i.e., through the LFA-1/ICAM-1 pathway.


Risk factors for proximal disease extension and colectomy in left-sided ulcerative colitis.
The primary objective of this study was to assess proximal disease extension of ulcerative colitis (UC) over time, with disease behaviour pattern and risk factors for proximal disease extension and colectomy as secondary aims. All cumulative incident cases diagnosed with UC at the Academic Medical Center between January 1990 and December 2009 were studied. The cumulative risk of colectomy was calculated by Kaplan-Meier analysis. The Cox proportional hazards regression was used to identify risk factors associated with proximal disease extension and colectomy. In total, 506 UC patients were included with a median age of 33 years (IQR 23-41) at diagnosis. Ninety-five (18.8%) patients underwent colectomy during follow-up. Median follow-up was 10 years (IQR 5-15). Initial disease extent was evaluable in 416 patients, of whom 142 (34.1%) had proctitis, 155 (37.3%) left-sided colitis and 119 (28.6%) pancolitis. Proximal disease extension was observed in 120 (28.8%) patients during follow-up (51 proctitis to left-sided colitis, 39 proctitis to extensive colitis and 30 left-sided to extensive colitis). Disease behaviour was evaluable in 378 patients, of whom 244 (64.6%) had less than one relapse per year. Younger age at diagnosis (HR 0.98, 95% CI 0.96-0.99) and continuous active disease (HR 2.18, 95% CI 1.27-3.73) were independent risk factors for proximal disease extension. The cumulative risk of colectomy did not change over time between patients diagnosed before and after the year 2000 (p = 0.341). Continuous active disease (HR 7.05, 95% CI 4.23-11.77), systemic steroids (HR 3.25, 95% CI 1.37-7.71) and cyclosporine treatment (HR 2.80, 95% CI 1.66-4.72) were independent risk factors for colectomy, whereas proctitis at diagnosis (HR 0.43, 95% CI 0.22-0.86) carried a lower risk. In one-third of UC patients, left-sided disease at diagnosis will extend proximally during 10 years of follow-up. Proximal disease extension was not a risk factor for colectomy, but the risk of colectomy is rather determined by continuous disease activity, and use of systemic steroids and cyclosporine.


On-line high-performance liquid chromatography for the determination of cephalosporin C and by-products in complex fermentation broths.
A fully automated high-performance liquid chromatographic system was developed for optimization of cephalosporin C production. Using a simple, isocratic, reversed-phase method, cephalosporin C, deacetylcephalosporin C, deacetoxycephalosporin C, penicillin N, methionine and its decomposition product 2-hydroxy-4-methylmercaptobutyric acid were determined. The method worked reliably for 250 h and supplied information on the influence of many parameters of the process.


Microdissection of the Prader-Willi syndrome chromosome region and identification of potential gene sequences.
The Prader-Willi syndrome chromosome region on the long arm of human chromosome 15 was microdissected and microcloned from 20 GTG-banded metaphase chromosomes, and 5000 recombinant clones were obtained. Of these clones, 39% identify single-copy human DNA sequences, most of which map to the dissected chromosome region and are evolutionarily conserved in other species. Three of eleven clones studied in detail are deleted in several patients with Prader-Willi syndrome. The microclones will be useful for the physical characterization of the Prader-Willi syndrome chromosome region and the identification of the affected genes in this disease.


Does face-to-face pre-operative joint replacement education reduce hospital costs in a regional Australian hospital? A descriptive retrospective clinical audit.
To evaluate whether attending a face-to-face pre-operative joint replacement education in a regional setting reduces overall hospital costs and length of stay (LOS) following total knee replacement (TKR) or total hip replacement (THR). A retrospective clinical audit reviewed the medical records of all patients who underwent an elective THR or TKR at Rockhampton Hospital in regional Queensland, Australia, between 03/2015 and 12/2016 (22 months). The pre-operative joint replacement education class was provided by a multidisciplinary team that included a physiotherapist, an occupational therapist, a dietician, a pharmacist and a social worker. In addition to demographic data, we extracted and analysed data related to total acute care and total healthcare cost, prevalence of post-operative complications, discharge destination and comorbidities (using the Functional Comorbidity Index). Out of 326 cases that were included in the analysis, 115 cases with TKR and 51 cases with THR attended a pre-operative education class. Demographic characteristics between those attending and not attending the class were largely similar, except from more females attending in the THR group. There was no difference in hospital costs or LOS between those who attended the class compared to those who did not for both the TKR and THR groups. Outcomes related to total acute stay costs, total cost including travel and education and score for Functional Comorbidities Index were similar between those who attended the class and those who did not. Pre-operative education does not reduce hospital costs (surgery and hospital stay) in Central Queensland.


Towards blood flow in the virtual human: efficient self-coupling of HemeLB.
Many scientific and medical researchers are working towards the creation of a virtual human-a personalized digital copy of an individual-that will assist in a patient's diagnosis, treatment and recovery. The complex nature of living systems means that the development of this remains a major challenge. We describe progress in enabling the HemeLB lattice Boltzmann code to simulate 3D macroscopic blood flow on a full human scale. Significant developments in memory management and load balancing allow near linear scaling performance of the code on hundreds of thousands of computer cores. Integral to the construction of a virtual human, we also outline the implementation of a self-coupling strategy for HemeLB. This allows simultaneous simulation of arterial and venous vascular trees based on human-specific geometries.


A prospective randomized controlled trial comparing two different treatments of intrauterine adhesions.
Intrauterine adhesions (IUA) are primarily caused by trauma to the endometrium, and hysteroscopy is presently the main treatment for IUA. However, high rates of post-operative adhesion re-formation remain a problem. In this study, the combination of an intrauterine device (IUD) with a Foley catheter and the balloon uterine stent were investigated to evaluate their efficacy in preventing adhesion re-formation and the subsequent reproductive outcomes in patients with moderate to severe adhesions. A prospective randomized controlled study was conducted in a university-affiliated hospital. A total of 171 women with Asherman's syndrome were initially recruited between August 2016 and December 2017 and were randomized to undergo either balloon uterine stent insertion or placement of a contraceptive IUD plus a Foley catheter after hysteroscopic adhesiolysis. Reduction of adhesion scores, incidence of adhesion re-formation, changes in menstrual flow and reproductive outcomes were analysed. A total of 118 participants were eligible for analysis. The American Fertility Society (AFS) scores were not significantly different between groups before hysteroscopic adhesiolysis. At the second-look hysteroscopy, the AFS scores and adhesion recurrence rates were significantly higher in the balloon uterine stent group compared with the combination group (P < 0.01 and P = 0.024, respectively). There were no statistically significant differences in pregnancy and live birth rates between the two groups. The combination of an IUD and a Foley balloon catheter had better efficacy in preventing adhesion re-formation than the balloon uterine stent alone; however, it did not produce better reproductive outcomes.


Sox9/CXCL5 axis facilitates tumour cell growth and invasion in hepatocellular carcinoma.
High rates of metastasis and postsurgical recurrence contribute to the higher mortality of hepatocellular carcinoma (HCC), partly due to cancer stem cell (CSC)-dependent tumorigenesis and metastasis. Sex-determining region Y-box 9 (Sox9) has been previously characterized as a candidate CSC marker of HCC. Here, we observed that the increase of Sox9 significantly promoted HCC cell growth and invasion in cell cultures, whereas knockdown of Sox9 showed the opposite effects, suggesting that Sox9 may regulate the proliferation and invasion of hepatoma cells in an autocrine manner. RNA sequencing, together with functional assays and clinical analyses, identified CXCL5 as a key mediator downstream of Sox9 in HCC cells. Mechanistic studies revealed that Sox9 induced CXCL5 expression by directly binding to a promoter region. Using gain- and loss-of-function approaches, we demonstrated that the intrinsic effective role of Sox9 in hepatoma cell growth and invasion depended on CXCL5, and that blockade of CXCL5/CXCR2 signalling abolished Sox9-triggered HCC cell proliferation and migration. Furthermore, the Sox9/CXCL5 axis activated PI3K-AKT and ERK1/2 signalling which are implicated in regulating HCC cell proliferation and invasion. Finally, the Sox9/CXCL5 axis contributed to the infiltration of neutrophils and macrophages in both tumour and peritumoral tissues from the orthotopic xenograft model. In summary, our data identify the Sox9/CXCL5 axis as an endogenous factor in controlling HCC cell growth and invasion, thereby raising the possibility of pharmacologic intervention with CXCL5/CXCR2 pathway inhibitors in therapy for HCC patients with higher Sox9 expression.


Presymptomatic transmission of SARS-CoV-2 infection: a secondary analysis using published data.
To estimate the proportion of presymptomatic transmission of SARS-CoV-2 infection that can occur, and the timing of transmission relative to symptom onset. Secondary analysis of international published data. Meta-analysis of COVID-19 incubation period and a rapid review of serial interval and generation time, which are published separately. Data from China, the Islamic Republic of Iran, Italy, Republic of Korea, Singapore and Vietnam from December 2019 to May 2020. Simulations were generated of incubation period and of serial interval or generation time. From these, transmission times relative to symptom onset, and the proportion of presymptomatic transmission, were estimated. Transmission time of SARS-CoV-2 relative to symptom onset and proportion of presymptomatic transmission. Based on 18 serial interval/generation time estimates from 15 papers, mean transmission time relative to symptom onset ranged from -2.6 (95% CI -3.0 to -2.1) days before infector symptom onset to 1.4 (95% CI 1.0 to 1.8) days after symptom onset. The proportion of presymptomatic transmission ranged from 45.9% (95% CI 42.9% to 49.0%) to 69.1% (95% CI 66.2% to 71.9%). There is substantial potential for presymptomatic transmission of SARS-CoV-2 across a range of different contexts. This highlights the need for rapid case detection, contact tracing and quarantine. The transmission patterns that we report reflect the combination of biological infectiousness and transmission opportunities which vary according to context.


G protein-coupled receptor-in-paper, a versatile chromatographic platform to study receptor-drug interaction.
High-performance affinity chromatography is limited by its high cost and high pressure. Paper is made up of porous fiber networks and has the properties of low cost, ease of fabrication, and biodegradable. Due to these advantages, herein, we immobilized beta2-adrenoceptor (β2-AR) onto the surface of the polytetrafluoroethylene membrane, a paper-based material, and constructed a G protein-coupled receptor (GPCR)-in-paper chromatographic platform. This platform was characterized by Fourier transform infrared spectroscopy, fluorescence analysis, X-ray photoelectron spectroscopy, and chromatographic studies. These morphological and elemental analysis showed that β2-AR was successfully immobilized on the paper surface. The specific drugs have good retentions on the GPCR-in-paper chromatographic platform. The association constants of salbutamol, terbutaline and bambuterol to β2-AR were calculated to be 2.02 × 104 M-1, 1.15 × 104 M-1, 1.75 × 104 M-1 by adsorption energy distribution, which were in good line with the values from frontal analysis, zonal elution and previous literatures. We demonstrated that the GPCR-in-paper platform was cost-effective, easy to be modified for protein immobilization, and applicable in the receptor-drug interaction analysis. We believe such a platform sheds new light on paper chromatography for receptor-drug interaction analysis and other applications.


Where Do We Go From Here?: The Impact of COVID-19 on Practice Readiness and Considerations for Nurse Leaders.
The COVID-19 pandemic has impacted nurses transitioning to practice in a variety of ways over the past 2 years. Analysis from the Versant Database comparing new graduate nurses (NGNs) from 2018-2021 revealed a widened practice gap for NGNs in these specialty areas of practice: critical care, perinatal, and emergency. Additionally, NGNs achieved 100% competency validation sooner in 2020-2021. The analysis also revealed greater diversity of NGNs who participated in a transition to practice program in 2020-2021. Based on these findings, this article proposes recommendations for nurse leaders to consider as NGNs transition into the workforce.


Perception of primary caregiver toward virtual pediatric clinics for type 1 diabetes mellitus during COVID-19 pandemic in Jeddah, Saudi Arabia: A cross-sectional study.
Virtual phone clinics were adopted at King Abdulaziz Medical City, Jeddah, Saudi Arabia, as an alternative to in-person routine outpatient visits amid the COVID-19 pandemic. This study aimed to assess primary caregiver perceptions of the virtual phone clinics towards routine care of pediatric patients with type 1 diabetes mellitus (T1DM). A cross-sectional research design was employed through a web-based research tool where the primary caregivers of pediatric patients with T1DM participated. Data were analyzed descriptively and statistically using independent t-tests and one-way analysis of variance. In total, 214 participants were included in this study. The average primary caregiver perception value towards virtual phone clinics was 66.71 ± 23.1%, which suggested a satisfactory perception of their experience. Statistically significant differences (p > 0.05) were not found between the mean perception values and demographic characteristics. Higher mean primary caregiver perception values were associated with those who: (1) agreed or strongly agreed to be contented with their current state of health, (2) did not ask their physicians to be physically seen during a virtual visit, (3) preferred having four virtual visits or more, and (4) preferred having single to no in-person visits at all. This study revealed a generally acceptable primary caregiver perception regarding virtual clinics. Telemedicine is recommended for routine treatment alongside regular in-clinic appointments to improve the quality of care for pediatric patients with T1DM.


The development of a new three-step protocol to determine the efficacy of disinfectant wipes on surfaces contaminated with Staphylococcus aureus.
We developed a three-step protocol to quantify the efficacy of disinfectant wipes, their ability to remove and prevent microbial transfer from surfaces and their overall antimicrobial activity. Meticillin-resistant (MRSA) or -susceptible (MSSA) Staphylococcus aureus (6-7 log(10)cfu) were inoculated onto stainless steel discs with or without organic load and dried. Grapefruit extract-containing test wipes and unmedicated control wipes were used. In step 1, wipes were mechanically rotated against surfaces for 10s at 60rpm, exerting a weight of 100+/-5g. Bacterial removal was assessed by transferring the steel discs to neutraliser, resuspending and counting remaining bacteria. In step 2, bacterial transfer from wipes was assessed by eight consecutive mechanical adpression transfers to agar/neutraliser plates. Step 3 was the measurement of antimicrobial activity by direct inoculation of the wipes for 10s followed by neutralisation and enumeration. Test wipes achieved a significantly higher bacterial cell removal than control wipes on all surfaces (P<0.05). The low bactericidal activity of the wipes (<1 log(10) reduction when directly inoculated) and the subsequent survival of bacteria on the wipes, however, led to repeated microbial transfer when initially high contamination levels were present. There were no differences between MRSA and MSSA in removal, transfer or antimicrobial activity. The three-step method is a useful tool for developing future guidelines to assess the ability of wipes to disinfect surfaces.


Task instructions and implicit theory of mind.
It has been hypothesized that humans are able to track other's mental states efficiently and without being conscious of doing so using their implicit theory of mind (iToM) system. However, while iToM appears to operate unconsciously recent work suggests it does draw on executive attentional resources (Schneider, Lam, Bayliss, & Dux, 2012) bringing into question whether iToM is engaged efficiently. Here, we examined other aspects relating to automatic processing: The extent to which the operation of iToM is controllable and how it is influenced by behavioral intentions. This was implemented by assessing how task instructions affect eye-movement patterns in a Sally-Anne false-belief task. One group of subjects was given no task instructions (No Instructions), another overtly judged the location of a ball a protagonist interacted with (Ball Tracking) and a third indicated the location consistent with the actor's belief about the ball's location (Belief Tracking). Despite different task goals, all groups' eye-movement patterns were consistent with belief analysis, and the No Instructions and Ball Tracking groups reported no explicit mentalizing when debriefed. These findings represent definitive evidence that humans implicitly track the belief states of others in an uncontrollable and unintentional manner.


The influence of single and multiple applications of pyrene on the evolution of pyrene catabolism in soil.
The influence of pyrene added in a single application (0, 50, 100 and 200 mg kg(-1)) was investigated in multiple applications (1 x 50, 2 x 50 and 4 x 50 mg kg(-1)) on the evolution of catabolic activity in a pristine pasture soil. The microbial community's ability to degrade pyrene was assessed at 0, 4, 8 and 12 weeks by the mineralization of added 14C-pyrene. Significant mineralization (>5%) of added 14C-pyrene only occurred after 4 weeks soil-pyrene contact time in most of the pyrene-amended soils. Pyrene-amended soils showed statistically significantly shorter (P<0.05) lag times compared to the control soil after 8 and 12 weeks soil-pyrene contact time. Further, the rates of degradation increased in the presence of pyrene, peaking at 8 weeks. In terms of the overall extents of pyrene mineralization, there were statistically significant increases (P<0.05) between 4 and 8 weeks, with little difference between 8 and 12 weeks, with the general trend that an increase in pyrene concentration resulted in higher levels of mineralization. Increasing the concentration and number of pyrene additions can have a significant impact on the adaptation of the soil microflora to degrade pyrene over time.


Anti-inflammatory activity of Ajmodadi Churna extract against acute inflammation in rats.
Ayurvedic polyherbal formulations are widely prescribed for a wide range of inflammatory conditions, yet, despite widespread use, there has been no systematic documentation of their safety and efficacy. The present study was undertaken to evaluate the anti-inflammatory activity of aqueous extracts of Ajmodadi churna (AJM) in rats. Carrageenan-induced hind paw edema and air pouch inflammation models were used for the study. The extracts showed significant antiinflammatory activity, reducing paw edema volume by 0.417 ± 0.097 and 0.379 ± 0.049, respectively. In the carrageenan-induced air pouch model, AJM reduced total leukocyte count by 73.09 ± 7.13 and 62.17 ± 10.53, granulocyte count by 69.48 ± 5.44 and 63.33 ± 4.13, and myeloperoxidase activity by 14.84 ± 0.91 and 18.44 ± 3.18, respectively, compared to controls. AJM significantly reduced paw edema, during the second phase of edema development. In the carrageenan-induced air pouch model, AJM inhibited cellular infiltration into the air pouch fluid. We conclude that AJM is an effective candidate for prevention or treatment of acute inflammation.


Clinical characteristics of enteroviral meningitis without pleocytosis in children: a retrospective single center observational study in the Republic of Korea.
We aimed to study the prevalence of enterovirus (EV) meningitis without the presence of cerebrospinal fluid (CSF) pleocytosis and identify patient factors and clinical features associated with it. This was a retrospective analysis of patients aged < 18 years old who were diagnosed with EV meningitis by CSF reverse-transcriptase polymerase chain reaction (RT-PCR) testing between January 2015 and December 2016. Clinical variables were compared with regard to the presence of CSF pleocytosis. A total of 305 patients were enrolled in study; 169 (55.4%) had no pleocytosis. Patients without pleocytosis were younger (median age 2 months vs. 67.0 months, p < 0.01) and had lower white blood cell (WBC) count (median, 8600/mm3 vs. 10,300/mm3, p < 0.01). Also absolute neutrophil (ANC) count were lower than pleocytosis group (median, 4674/mm3 vs. 7600/mm3, p < 0.01). Comparing three age groups, CSF apleocytosis was present in 106 of 128 patients (82.8%) aged ≤3 months, 7 of 13 patients (53.8%) aged 3 months-3 years and 56 of 164 patients (34.1%) aged > 3 years. Younger age groups had higher prevalence of CSF apleocytosis (p < 0.01). In patients aged ≤3 months, 94.5% underwent lumbar puncture within 24 h of symptom onset. The frequency of not having pleocytosis was higher than the frequency of having pleocytosis during peak EV infection prevalent months (summer and fall) (p < 0.01). This study shows that EV meningitis in young infants, with early lumbar puncture, or occurring during peak EV meningitis prevalent seasons cannot be solely excluded by pleocytosis. Also, a confirmation test for EV meningitis should be performed using RT-PCR.


DMRT1-mediated regulation of TOX3 modulates expansion of the gonadal steroidogenic cell lineage in the chicken embryo.
During gonadal sex determination, the supporting cell lineage differentiates into Sertoli cells in males and pre-granulosa cells in females. Recently, single cell RNA-seq data have indicated that chicken steroidogenic cells are derived from differentiated supporting cells. This differentiation process is achieved by a sequential upregulation of steroidogenic genes and downregulation of supporting cell markers. The exact mechanism regulating this differentiation process remains unknown. We have identified TOX3 as a previously unreported transcription factor expressed in embryonic Sertoli cells of the chicken testis. TOX3 knockdown in males resulted in increased CYP17A1-positive Leydig cells. TOX3 overexpression in male and female gonads resulted in a significant decline in CYP17A1-positive steroidogenic cells. In ovo knockdown of the testis determinant DMRT1 in male gonads resulted in a downregulation of TOX3 expression. Conversely, DMRT1 overexpression caused an increase in TOX3 expression. Taken together, these data indicate that DMRT1-mediated regulation of TOX3 modulates expansion of the steroidogenic lineage, either directly, via cell lineage allocation, or indirectly, via signaling from the supporting to steroidogenic cell populations.


Impaired expression of hypoxia-inducible factor-1α in cystic fibrosis airway epithelial cells - a role for HIF-1 in the pathophysiology of CF?
The continuous infection-inflammation cycle plays a crucial role in the progression of cystic fibrosis (CF) disease. This noxious loop can be aggravated by a reduced partial pressure of oxygen in the blood, hypoxemia, present in CF patients. These interconnected factors, hypoxia, inflammation and infection, by stabilizing the hypoxia-inducible factor-1α (HIF-1α) protein subunit, are able to activate the transcription factor HIF-1. To date, data investigating the potential role of HIF-1 in CF are scarce. Our results demonstrated that HIF-1α protein expression was altered in CF-affected compared to CFTR-corrected airway epithelial cells in unsimulated and simulated hypoxic conditions. In contrast, when CF-affected cells were infected with Pseudomonas aeruginosa, HIF-1α was more stabilized compared to CFTR-corrected cells. As HIF-1 is linked with an efficient immune response and pulmonary complications in cystic fibrosis, this difference in HIF-1α protein levels could have an impact in the CF pathology and the persistence of P. aeruginosa infection.


Retrograde Transseptal Pulmonary Vein Transcatheter Plug Closure for Pulmonary Arteriovenous Malformation.
Pulmonary arteriovenous malformations (PAVMs) may manifest with bleeding or embolic events necessitating intervention. Transcatheter coil embolization through the pulmonary artery (PA) is an established approach. We present a case of recurrent PAVMs despite numerous PA coil embolizations. PAVM occlusion was achieved through plug placement by a transseptal and pulmonary venous approach. (Level of Difficulty: Advanced.).


Congenital disorders of the optic nerve: excavations and hypoplasia.
The principal congenital abnormalities of the optic disc that can significantly impair visual function are excavation of the optic disc and optic nerve hypoplasia. The excavated optic disc abnormalities comprise optic disc coloboma, morning glory syndrome, and peripapillary staphyloma. Optic nerve hypoplasia manifests as a small optic nerve, which may or may not be accompanied by a peripapillary ring (the double ring sign). In addition, the optic disc cupping, which occurs as a sequel to some cases of periventricular leucomalacia, can arguably be classified as a type of optic nerve hypoplasia. All of these conditions can be unilateral or bilateral and can impair visual function mildly or severely. It is essential that children with poor vision due to any of these conditions are managed by treating refractive errors, giving occlusion therapy in selected cases, and optimising the conditions at home and at school in an attempt to ensure that impaired vision does not impede development or education.


Respiratory and Otolaryngology Symptoms Following the 2019 Spring Floods in Quebec.
Although floods may have important respiratory health impacts, few studies have examined this issue. This study aims to document the long-term impacts of the spring floods of 2019 in Quebec by (1) describing the population affected by the floods; (2) assessing the impacts on the respiratory system according to levels of exposure; and (3) determining the association between stressors and respiratory health. A population health survey was carried out across the six most affected regions 8-10 months post-floods. Data were collected on self-reported otolaryngology (ENT) and respiratory symptoms, along with primary and secondary stressors. Three levels of exposure were examined: flooded, disrupted and unaffected. One in ten respondents declared being flooded and 31.4% being disrupted by the floods. Flooded and disrupted participants reported significantly more ENT symptoms (adjusted odds ratio (aOR): 3.18; 95% CI: 2.45-4.14; aOR: 1.76; 95% CI: 1.45-2.14) and respiratory symptoms (aOR: 3.41; 95% CI: 2.45-4.75; aOR: 1.45; 95% CI: 1.10-1.91) than the unaffected participants. All primary stressors and certain secondary stressors assessed were significantly associated with both ENT and respiratory symptoms, but no "dose-response" gradient could be observed. This study highlights the long-term adverse effects of flood exposure on respiratory health.


Distribution and Prevalence of Plant-Parasitic Nematodes of Turfgrass at Golf Courses in China.
We sampled 127 turfgrass soil samples from 33 golf courses in NC, EC, and SC for plant-parasitic nematodes (PPNs). PPNs were extracted from soil samples using the shallow dish method and were identified at the genus or species levels with a combination of morphological and molecular methods. The results revealed 41 species of nematode belonging to 20 genera and 10 families. Nine genera are new records of PPNs associated with turfgrass in China. The PPNs show strong geographical distributions. Of the 20 genera, Helicotylenchus, Paratrichodorus, Hoplolaimus, Meloidogyne, Hemicriconemoides, and Mesocriconema showed higher infestation and frequency, and most of these genera had numbers in soil samples above established damage thresholds. Four golf courses had soil samples with PPNs > 30%, indicating the potential for nematode damage. The biodiversity indices H', SR, J', λ, and H2 showed significant differences among different regions and turfgrass species; H', SR, J', and H2 were significantly higher in EC than in NC and SC, while λ was lowest in EC. Creeping bentgrass had the highest H', SR, J', and H2 and the lowest λ in comparison with seashore paspalum and hybrid bermudagrass. These findings provide baseline information on the occurrence of turfgrass-associated PPNs in China, and have important implications for the effective management of PPNs causing damage on turfgrass.


Environmental and economic benefits of electric, hybrid and conventional vehicle treatment: A case study of Lithuania.
Reuse, recovery, and recycling of end-of-life vehicles (ELVs) are encouraged owing to various economic and environmental benefits. Automotive remanufacturing serves as a specific circular marketing system for the reuse of recovered parts that can bring economic benefits for both dismantling companies and consumers. This study aimed to reveal the economic and environmental benefits of the end-of-life treatment of electric, hybrid, and conventional passenger cars. This research presents an economic assessment of the reuse of ELV parts based on a material flow analysis (MFA) and a practical analysis of the prices of these parts in the Lithuanian market. The environmental assessment of the reuse of ELV parts was performed using an MFA, the CO2 equivalents for the production of different materials, and a life cycle assessment methodology. The results showed that 38% of all electric and hybrid ELV parts, and 27% and 28% of diesel- and petrol-powered ELV parts, respectively, can be sold (reused). The economic benefit across all four types of ELVs could amount to savings of up to 12,739 Eur and 51,281 Eur for the dismantlers and passenger car consumers, respectively. The greatest CO2 savings result from reusing the parts of electric ELVs, whilst the lowest savings come from petrol ELVs.


Pain Management in Patients with Heart Failure: A Survey of Nurses' Perception.
Over 50% of patients with heart failure (HF) report suffering from pain and pain-related burdens; however, pain in HF patients has not been recognized or well treated. Few studies have comprehensively examined pain management in patients with HF from nurses' perception. To investigate nurses' perception of pain management in HF patients. Members of American Association of Heart Failure Nurses (AAHFN) were invited to participate in a cross-sectional online survey. A total of 147 nurses responded and completed the survey. The majority agreed that pain in HF patients was related to anxiety, depression, fatigue, and unplanned hospitalization, and that pain should be individually assessed and managed. More than 80% thought pain management practice in HF patients should be improved, and 78.1% were interested in getting more information and believed an online education module was the most preferable approach. Lack of pain assessment tools, drug addiction, side effect, overuse, underuse, and contraindication with other medications were the main concerns regarding opioid use in pain management in HF. The gaps in pain management in HF patients included lack of knowledge of opioid use, lack of consideration and awareness of pain, no clinical guidelines for pain assessment and treatment, and complicated pain management with multiple chronic conditions. The impact of pain and need for individual assessment and management of pain in HF patients were perceived by nurses; improvement in pain management practice in HF patients is needed. Concerns regarding opioid use and gaps in pain management of HF patients should be addressed.


Discontinuity of sarcoplasmic reticulum in the mid-sarcomere region in flight muscle of dragonflies.
The sarcoplasmic reticulum organization of dragonfly flight muscles is analyzed, with particular reference to the doubling existing at H-band level. This doubling could be explained as a consequence of a regular discontinuity in the sarcoplasmic reticulum covering myofibrils. In each sarcomere, two sleeves of the sarcoplasmic reticulum seem to overlap forming a telescopic system which can slide outside each other during the lengthening and shortening movements of the fiber.


Series resistance errors in whole cell voltage clamp measured directly with dual patch-clamp recordings: not as bad as you think.
Whole cell patch clamp has provided much insight into the function of voltage-gated ion channels in central neurons. However, voltage errors caused by the resistance of the recording electrode [series resistance (Rs)] limit its application to relatively small ionic currents. Ohm's law is often applied to estimate and correct the membrane potential for these voltage errors. We tested this assumption in brainstem motoneurons of adult frogs with dual patch-clamp recordings, one performing whole cell voltage clamp of K+ currents and the other directly recording the membrane potential. We hypothesized that Ohm's law-based correction would approximate the measured voltage error. We found that voltage errors averaged <5 mV for currents considered to be large for patch clamp (∼7-13 nA) and <10 mV for massive currents thought to be experimentally intractable (25-30 nA), each error falling within commonly accepted inclusion limits. In most cases Ohm's law-based correction overpredicted these measured voltage errors by roughly 2.5-fold. Consequently, the use of Ohm's law to correct for voltage errors led to erroneous current-voltage (I-V) relationships, showing the greatest distortion for inactivating currents. Finally, recordings with low electrode Rs compensated moderately by the amplifier circuitry appeared to have smaller voltage errors than those with larger Rs and high compensation despite the same "effective Rs" and current magnitude. Therefore, when Rs is low, large currents may be studied with better-than-expected voltage control. These results suggest that patch-clamp may be used to study ionic currents often interpreted to be off limits because of size.NEW & NOTEWORTHY Voltage errors occur in whole cell voltage clamp. We make, to our knowledge, the first direct measurements of these errors and find that voltage errors are far smaller than standard calculations would predict. Since voltage errors were often minimal during the measurement of large ion channel currents, this technique may be applied to large neurons of adults to gain insight into ion channel function across the life span and progression of disease.


Surgical outcomes of medically failed prolactinomas: a systematic review and meta-analysis.
In Prolactinomas, surgery or radiation are reserved for DA failure due to tumor resistance, intolerance to medication-induced side-effects, or patient preference. This systematic review and meta-analysis summarizes the currently available literature regarding the effectiveness of surgery to treat prolactinomas in patients who have failed DA therapy. A literature search was conducted according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines for studies that reported outcomes of medically resistant and intolerant prolactinoma treated surgically. 10 articles (Total N = 816, Surgery N = 657) met the inclusion criteria. 38% of patients who underwent surgery following DA failure achieved remission without need for further treatment (p < 0.001, I2 = 67.09%) with a median follow-up of 49.2 +/- 40 months. 62% achieved remission with multimodal treatment (p < 0.001, I2 = 93.28%) with a median follow-up of 53 +/- 39.8 months. 16% of cases demonstrated recurrence after early remission (p = 0.02, I2 = 62.91%) with recurrence occurring on average at 27 +/- 9 months. Overall, 46% of patients required reinstitution of postoperative DA therapy at last follow up (p < 0.001, I2 = 82.57%). Subgroup analysis of macroprolactinoma and microprolactinoma has demonstrated that there is no statistical significance in achieving long-term remission with surgery stand-alone in macroprolactinoma group (p = 0.49) although 43% of patients were able to achieve remission with multimodal therapy at last follow-up in the same group (p < 0.001, I2 = 86.34%). This systematic review and meta-analysis revealed 38% of operated patients achieved remission, while 62% achieved remission when additional modes of therapy were implemented. Therefore, although surgery has not been initial therapeutic choice for prolactinoma, it plays a significant role in medically failed prolactinoma care.


Centriole signaling restricts hepatocyte ploidy to maintain liver integrity.
Hepatocyte polyploidization is a tightly controlled process that is initiated at weaning and increases with age. The proliferation of polyploid hepatocytes in vivo is restricted by the PIDDosome-P53 axis, but how this pathway is triggered remains unclear. Given that increased hepatocyte ploidy protects against malignant transformation, the evolutionary driver that sets the upper limit for hepatocyte ploidy remains unknown. Here we show that hepatocytes accumulate centrioles during cycles of polyploidization in vivo. The presence of excess mature centrioles containing ANKRD26 was required to activate the PIDDosome in polyploid cells. As a result, mice lacking centrioles in the liver or ANKRD26 exhibited increased hepatocyte ploidy. Under normal homeostatic conditions, this increase in liver ploidy did not impact organ function. However, in response to chronic liver injury, blocking centriole-mediated ploidy control leads to a massive increase in hepatocyte polyploidization, severe liver damage, and impaired liver function. These results show that hyperpolyploidization sensitizes the liver to injury, posing a trade-off for the cancer-protective effect of increased hepatocyte ploidy. Our results may have important implications for unscheduled polyploidization that frequently occurs in human patients with chronic liver disease.


Accurate Drug Repositioning through Non-tissue-Specific Core Signatures from Cancer Transcriptomes.
Experimental large-scale screens for drug repositioning are limited by restriction to in vitro conditions and lack of applicability to real human conditions. Here, we developed an in silico screen in human in vivo conditions using a reference of single gene mutations' non-tissue-specific "core transcriptome signatures" (CSs) of 8,476 genes generated from the TCGA database. We developed the core-signature drug-to-gene (csD2G) software to scan 3,546 drug treatment profiles against the reference signatures. csD2G significantly outperformed conventional cell line-based gene perturbation signatures and existing drug-repositioning methods in both coverage and specificity. We highlight this with 3 demonstrated applications: (1) repositioned category of psychiatric drugs to inhibit the TGF-β pathway; (2) antihypertensive calcium channel blockers predicted to activate AMPK and inhibit AKT pathways, and validated by clinical electronic medical records; and (3) 7 drugs predicted and validated to selectively target the AKT-FOXO and AMPK pathways and thus regulate worm lifespan.


Amplified ribosomal DNA in meiotic prophase oocyte nuclei of acipenserid fishes.
In situ hybridization has been performed in sections through ovaries ofAcipenser ruthenus andAcipenser güldenstädti in order to detect the rDNA sequences. Hybridization resulted in specific labelling of the "caps" of extrachromosomal DNA present in pachytene oocyte nuclei and of the chromatin granules distributed beneath the nuclear envelope in early diplotene nuclei. In the same sections, the nuclei of all ovarian cells in both species (oogonia, leptotene, and zygotene stage oocytes, follicular cells, connective tissue cells) showed a very low, but similar labelling.Amplification of genes for rRNA thus occurs at the pachytene stage in early oogenesis ofAcipenseridae. No rDNA amplification could be detected in the previous stages.


Use of low-cost video recording device in reflective practice in cataract surgery.
Reflective surgical practice is invaluable for surgeons at all levels of experience. For trainees in particular, every surgical opportunity must be optimized for its learning potential. Recording and reviewing cataract surgery is an invaluable tool. We describe a video recording device that has the advantages of ease of use; low cost; portability; and ease of review, editing, and dissemination, all of which encourage regular use and reflective surgical practice.


Co-occurrence of blaNDM-1, rmtC, and mcr-9 in multidrug-resistant Enterobacter kobei strain isolated from an infant with urinary tract infection.
The co-emergence of mcr and carbapenem resistance genes in Gram-negative bacteria is a serious problem. This study aims to clarify the genetic characteristic of one novel multidrug-resistant Enterobacter kobei EC1382 with mcr-9 causing urinary tract inflammation in an infant. Antimicrobial drug susceptibility testing was performed for this isolate using the broth microdilution method. Whole-genome sequencing was performed using the Illumina PacBio RS II platform and HiSeq platform, and the antimicrobial resistance genes, mobile elements, and plasmid replicon types were identified. Conjugation analysis was performed using Escherichia coli C600 as recipients. Enterobacter kobei EC1382 was resistant to carbapenem, aminoglycoside, and cephalosporin. Twenty-five antimicrobial resistance genes were identified, including genes conferring resistance to carbapenem (blaNDM-1), colistin (mcr-9), and aminoglycosides (rmtC). The blaNDM-1 gene, accompanied by bleMBL and rmtC located downstream of an ISCR14 element, was detected in the IncFII(Yp) type plasmid pEC1382-2. Interestingly, although E. kobei EC1382 was susceptible to colistin, it had three identical mcr-9 genes (two in the chromosome and one in the IncHI2-type plasmid pEC1382-1). The backbone (∼12.2-kb genetic fragment) of these mcr-9 (flanked by IS903B and IS481-IS26) regions were conserved in this strain, and they were found to be present in various bacteria as three types, implying a silent distribution. To the best of our knowledge, this is the first study to demonstrate the coexistence of blaNDM-1, rmtC, and mcr-9 in E. kobei. The silent prevalence of mcr-9 in bacteria may be a threat to public health.


Pharmacologic Targeting of MMP2/9 Decreases Peritoneal Metastasis Formation of Colorectal Cancer in a Human Ex Vivo Peritoneum Culture Model.
Matrix metalloproteinases (MMPs) play a crucial role in tumour initiation, progression, and metastasis, including peritoneal carcinosis (PC) formation. MMPs serve as biomarkers for tumour progression in colorectal cancer (CRC), and MMP overexpression is associated with advanced-stage metastasis and poor survival. However, the molecular mechanisms of PC from CRC remain largely unclear. We investigated the role of MMPs during peritoneal colonisation by CRC cell lines in a human ex vivo peritoneum model and in patient-derived CRC and corresponding PC samples. MMP2 and MMP9 were inhibited using the small-molecule inhibitors batimastat and the specific MMP2/9 inhibitor III. MMP2 and MMP9 were strongly upregulated in patient-derived samples and following peritoneal colonisation by CRC cells in the ex vivo model. MMP inhibition with batimastat reduced colonisation of HT29 and Colo205 cells by 36% and 68%, respectively (p = 0.0073 and p = 0.0002), while MMP2/9 inhibitor III reduced colonisation by 50% and 41%, respectively (p = 0.0003 and p = 0.0051). Fibronectin cleavage was enhanced in patient-derived samples of PC and during peritoneal colonisation in the ex vivo model, and this was inhibited by MMP2/9 inhibition. MMPs were upregulated in patient-derived samples and during peritoneal attachment of CRC cell lines in our ex vivo model. MMP2/9 inhibition prevented fibronectin cleavage and peritoneal colonisation by CRC cells. MMP inhibitors might thus offer a potential treatment strategy for patients with PC.


Effects of acute ethanol intoxication combined with secobarbital abuse on hemostasis.
Male Sprague-Dawley rats were treated with 0.5 ml of 46% ETOH, 2.8 mg/kg of secobarbital or 14.3 mg/kg secobarbital or combinations thereof. Twenty-four hours following treatment, blood clotting data was determined. The data indicated that either ethanol or secobarbital alone is just as detrimental to hemostasis as is the combined abuse of both. Likewise, a lesser concentration of alcohol was just as disruptive on hemostasis as was the greater concentration of ethanol.


Value of circulating miRNA-1 detected within 3 h after the onset of acute chest pain in the diagnosis and prognosis of acute myocardial infarction.
To explore the significance of circulating miRNA-1 (miR-1) released within 3 h after the onset of acute chest pain in the diagnosis and prognosis of acute myocardial infarction (AMI). A total of 337 patients with acute chest pain within 3 h were enrolled in this study and divided into AMI group and non-AMI group. The AMI diagnostic efficacy of miR-1 was determined and compared with that of cardiac troponin I (cTnI). The patients were followed up for 720 d after treatment. The significance of circulating miR-1 in AMI prognosis was assessed using univariate and COX regression analysis. There were 174 patients in AMI group, 163 in non-AMI group. Circulating miR-1 level was significantly higher in AMI group than in non-AMI group (P < 0.001). The AMI diagnostic efficacy of miR-1 and cTnI were similar (P > 0.05). We established two AMI diagnostic models, the AUC values of which were larger than that of cTnI or miR-1 (P < 0.05). When miR-1 combined with CK-MB, cTnI, and other clinical and laboratory parameters (model 2), the AUC was the largest (AUC: 0.961) and had the highest diagnostic efficiency. Circulating miR-1, Killip classification, and treatment method were influencing factors for AMI prognosis (P < 0.05). Circulating miR-1 within 3 h of acute chest pain has the potential diagnostic value for AMI, and which is an independent risk factor for the prognosis of AMI and can be used to predict AMI prognosis.


Flow cytometry's contribution to the measurement of cell functions.
Flow cytometry has important advantages over conventional techniques. It is rapid, highly sensitive and allows multi-parametric analysis and cell sorting. Potential exists for the measurement of many cell functions by flow cytometry. The technique can be used to determine cell viability, intracellular calcium and pH, membrane potential, enzyme activities, membrane fluidity and endocytosis. Numerous examples are given on the applications of flow cytometry for cell functions measurements in the fundamental and biomedical fields.


Urinary excretion of complement C3d in patients with renal diseases.
Complement-mediated tubular injury may play an important role in the progression of renal diseases. C3d is a presumed marker of complement activation. Its precursor C3dg has been detected in the urine of patients with membranous nephropathy. However, little is known of the renal handling of C3d or its excretion in other renal diseases. We measured the urinary excretion of albumin, IgG, beta2-microglobulin (beta2m), and of complement C3d in patients with tubulo-interstitial nephritis (TIN; n= 8), in patients with membranous nephropathy (n = 35) and in patients with nonmembranous glomerular diseases (23 nonproliferative and 21 proliferative). Fractional excretions (FE) were calculated using creatinine clearance as marker of GFR. C3d was not measurable in the urine of the healthy controls, but was detectable in seven out of eight of the TIN patients (median excretion 0.11 mU min-1, range 0.006-2.4 mU min-1). In these patients the urinary excretion of beta2m was clearly elevated (median 26.6 micro g min-1, range 1.0-103 micro g min-1). The FE of C3d correlated with the FE of beta2microglobulin (r = 0.83, P = 0.01), and their ratio amounted to 0.03 (range 0.003-0.06), a value in agreement with the expected sieving coefficient. Urine C3d was detectable in all but three of the patients with glomerular diseases (median excretion 0.36 mU min-1, range 0.004-7.9 mU min-1); C3d-excretion did not differ between the three subgroups of patients with glomerular diseases. FEC3d correlated with FEIgG (r = 0.88, P < 0.01). The ratio FEC3d/FEbeta2m was 0.78 (range 0.04-9.99). Selected patients with membranous nephropathy were re-analyzed after (partial) remission of proteinuria. Reduction of proteinuria resulted in a decrease of C3d excretion. Urinary excretion of C3d is elevated in patients with TIN, most likely as a mere consequence of decreased tubular reabsorption. In patients with glomerular diseases urinary excretion of C3d is increased and related to proteinuria, independent of the underlying glomerular disease. In these patients there is evidence of increased local formation of C3d.


Deceleration area and capacity during labour-like umbilical cord occlusions identify evolving hypotension: a controlled study in fetal sheep.
Cardiotocography is widely used to assess fetal well-being during labour. The positive predictive value of current clinical algorithms to identify hypoxia-ischaemia is poor. In experimental studies, fetal hypotension is the strongest predictor of hypoxic-ischaemic injury. Cohort studies suggest that deceleration area and deceleration capacity of the fetal heart rate trace correlate with fetal acidaemia, but it is not known whether they are indices of fetal arterial hypotension. Prospective, controlled study. Laboratory. Near-term fetal sheep. One minute of complete umbilical cord occlusions (UCOs) every 5 minutes (1:5 min, n = 6) or every 2.5 minutes (1:2.5 min, n = 12) for 4 hours or until fetal mean arterial blood pressure fell <20 mmHg. Deceleration area and capacity during the UCO series were related to evolving hypotension. The 1:5 min group developed only mild metabolic acidaemia, without hypotension. By contrast, 10/12 fetuses in the 1:2.5-min group progressively developed severe metabolic acidaemia and hypotension, reaching 16.8 ± 0.9 mmHg after 71.2 ± 6.7 UCOs. Deceleration area and capacity remained unchanged throughout the UCO series in the 1:5-min group, but progressively increased in the 1:2.5-min group. The severity of hypotension was closely correlated with both deceleration area (P < 0.001, R2 = 0.66, n = 18) and capacity (P < 0.001, R2 = 0.67, n = 18). Deceleration area and capacity predicted development of hypotension at a median of 103 and 123 minutes before the final occlusion, respectively. Both deceleration area and capacity were strongly associated with developing fetal hypotension, supporting their potential to improve identification of fetuses at risk of hypotension leading to hypoxic-ischaemic injury during labour. Deceleration area and capacity of fetal heart rate identify developing hypotension during labour-like hypoxia.


Mexiletine and quinidine in ventricular ectopy.
The antidysrhythmic efficacy and tolerance of mexiletine and quinidine were compared in 26 ambulatory patients with chronic ventricular ectopy. Thirteen patients were treated with mexiletine and 13 with quinidine. The treatment groups were comparable in age and cardiac diagnoses, in frequency of untreated ventricular ectopy, in the presence of complex forms, and in previous drug failures. After two 24-hr ambulatory ECG recordings, the patients were treated according to a double-blind, dose-ranging protocol. Efficacy was defined as reduction in ventricular ectopic frequency by at least 70% in a comparison of two 24-hr ambulatory ECG recordings after drug with the two pretreatment recordings. Suppression of ventricular ectopic frequency by at least 70% was achieved in seven mexiletine-treated patients and eight quinidine-treated patients. Neither drug consistently abolished complex forms of ectopy. The incidence of adverse effects was of the same order in the two groups. We conclude that mexiletine is as effective as quinidine in the suppression of ventricular ectopy. Use of both drugs is limited by adverse effects.


Self-rated health among undocumented and newly regularized migrants in Geneva: a cross-sectional study.
In Europe, knowledge about the social determinants of health among undocumented migrants is scarce. The canton of Geneva, Switzerland, implemented in 2017-2018 a pilot public policy aiming at regularizing undocumented migrants. We sought to test for associations between self-rated health, proven eligibility for residence status regularization and social and economic integration. This paper reports data from the first wave of the Parchemins Study, a prospective study whose aim is to investigate the effect of residence status regularization on undocumented migrants' living conditions and health. The convenience sample included undocumented migrants living in Geneva for at least 3 years. We categorized them into those who were in the process of receiving or had just been granted a residence permit (eligible or newly regularized) and those who had not applied or were ineligible for regularization (undocumented). We conducted multivariate regression analyses to determine factors associated with better self-rated health, i.e., with excellent/very good vs. good/fair/poor self-rated health. Among these factors, measures of integration, social support and economic resources were included. Of the 437 participants, 202 (46%) belonged to the eligible or newly regularized group. This group reported better health more frequently than the undocumented group (44.6% versus 28.9%, p-value < .001), but the association was no longer significant after adjustment for social support and economic factors (odds ratio (OR): 1.12; 95% confidence interval (CI): 0.67-1.87). Overall, better health was associated with larger social networks (OR: 1.66; 95% CI: 1.04-2.64). This association remained significant even after adjusting for health-related variables. At the onset of the regularization program, access to regularization was not associated with better self-rated health. Policies aiming at favouring undocumented migrants' inclusion and engagement in social networks may promote better health. Future research should investigate long-term effects of residence status regularization on self-rated health.


Lymphoid cell lines as a model system for the study of Wolman's disease: enzymatic, metabolic and ultrastructural investigations.
Epstein-Barr virus (EBV) transformed lymphoid cell lines (LCL) were established from blood lymphocytes of a patient affected with Wolman's disease (WD) and from her parents. These LCL showed a severe deficiency in acid lipase activity using every substrate in comparison to LCL from normal subjects, in which acid lipase activity was similar to that in blood lymphocytes. In the LCL from Wolman's disease a major accumulation of neutral lipids was observed, mainly cholesteryl esters, CE (amount around 7 times higher than in normal cells and ratio of esterified/free cholesterol increased by 10 times) and to a lesser extent triglycerides, TG (amount increased by 1.5 times). Electron microscopy showed the storage vacuoles of neutral lipids quite characteristic of this lysosomal disease. The reported data demonstrated the validity of transformed LCL as a cellular model system in culture for experimental studies of Wolman's disease and for investigating the lysosomal metabolism of neutral lipids.


Inpatient Kangaroo Care Predicts Early Cognitive Development at 6 and 12 Months in Infants Born Very Preterm.
Limited research links hospital-based experiences of Kangaroo Care (KC), or skin-to-skin holding to longer-term neurodevelopmental outcomes in preterm children. The present study examined relations between inpatient KC and cognitive abilities measured at 6- and 12-months of age in a sample of very preterm (VPT) infants. Retrospective study reviewing medical records of 132 (54% male) VPT infants (<32 weeks gestational age (GA)). We calculated KC frequency (instances/day), KC rate (minutes/day), and KC duration (minutes/instance). Scores on the Cognitive-Adaptive Test were available as part of routine follow-up care at 6 ( n =77) and 12 ( n = 37) months. Families engaged in KC about 2 days/week, 20 minutes/day, and 70 minutes/session, on average, although there was substantial variability. Variation in KC was positively associated with cognitive outcomes at both 6 (frequency: r=0.32; rate: r=0.29) and 12 (frequency: r=0.53; rate: r=0.59; duration: r=0.38) months. KC significantly predicted 7 to 27% unique variance in 6- and 12-month cognitive outcomes, after controlling for GA, socioeconomic status, health acuity, visitation frequency, and prior cognitive scores. Small increases in KC frequency (e.g., 1 day/week), rate (e.g., 20 minutes/day) or duration (e.g., 20 minutes/instance) were associated with 0.5 to 1.0 SD increases in cognitive outcomes at 12 months. SES, GA, and infant health acuity did not moderate these relations. VPT infants with more KC during hospitalization demonstrated higher scores on 6- and 12- month assessments of cognitive development. Results provide strong evidence that KC may confer neuroprotection on VPT infants through the first year of life. Variation in family-delivered Kangaroo Care in the NICU predicted infants' higher cognitive performance at 6 and 12 months, beyond visitation, clinical, and demographic factors. Kangaroo Care is a developmental care practice associated with positive short-term outcomes for preterm infants. Kangaroo Care is thought to mitigate adverse neurodevelopmental outcomes associated with preterm birth, but direct evidence of effects beyond hospital discharge is limited. In this retrospective cohort study, frequency, amount, and duration of family-delivered Kangaroo Care in the NICU predicted cognitive abilities at 6 and 12 months. Kangaroo care may be a long-term neuroprotective clinical strategy for infants born preterm.


Repeated Use of 6-min Walk Test with Immediate Knowledge of Results for Walking Capacity in Chronic Stroke: Clinical Trial of Fast versus Slow Walkers.
This study aimed to determine the effects of repeated use of the 6-minute walk test (6MWT) with immediate knowledge of results (KR) on the walking capacity by comparing fast and slow walkers in patients with chronic hemiparesis. Twenty-five subjects were allocated to 2 groups depending on their walking speed1: Group 1 (fast walkers, n1 = 11): greater than equal to .8 m/s and2 Group 2 (slow walkers, n2 = 14): less than .8 m/s. All subjects underwent the 6MWT once a day, 5 days a week, for 4 weeks (a total of 20 sessions). The 6MWT was performed on a 30-m path with immediate KR; subjects informed the time taken to walk each 30-m path. Outcome measures included the 6MWT and 10-meter walk test (10MWT). Measurements were taken before and after 4 weeks. Results of within-group comparisons showed significant improvements in the 10MWT and 6MWT for both groups pre- and post-test (P < .05). Furthermore, in between-group comparison, results of Group 1 differences were greater between pre- and post-test in the 10MWT and 6MWT values as compared to Group 2 (P < .05). These findings indicate that repeated use of the 6MWT with immediate KR may be beneficial to enhance walking capacity in patients with chronic stroke, with more favorable changes in better poststroke walking speed.


Universal Health Insurance coverage and utilization among women in urban slum of Rajnandgaon, Chhattisgarh.
Universal Health Coverage refers to health care system that provides health care and financial protection to all the citizen. Rashtriya Swasthya Bima Yojna as National Health Insurance Scheme initiated in Chhattisgarh State in 2009 for below poverty line families. Second scheme is Mukhyamantri Swasthya Bima Yojna initiated in 2012, which covers non below poverty line families. To assess socio demographic factors among women residing in slum of Rajnandgaon, to find their universal health insurance coverage under RSBY/ MSBY and to assess the extent of concerned treatment under RSBY/MSBY. It was a community based cross sectional study, conducted in the urban slum area of Rajnandgaon amongst 188 women above 18 years of age who were hospitalized 6 months prior to the study using snow ball technique as a sampling method. They were interviewed using semi structured questionnaires by the investigator with the help of anganwadi worker. 77.65% respondents/study subjects were enrolled under the universal health insurance (RSBY card/ MSBY card). Subjects belonging to Lower socio-economic status and having BPL card were enrolled under scheme more than upper socio-economic group. Out of 146 smart card holders, a mere 1.36% subjects incurred catastrophic OOPE. Out of 42 respondents not having smart card, 40.47% subjects incurred catastrophic OOPE. The RSBY card reduced the inpatient OOPE. RSBY card prevented catastrophic OOP in most of the respondent. RSBY has made health services accessible to all sections of community at minimal cost.


The effect of fatty acids on the surface potential of phospholipid vesicles measured by condensed phase radioluminescence.
(1) The carboxyl group of fatty acids has a very low pK value, which is shifted into the physiological pH range when they are incorporated in a phospholipid membrane. As a result of a pH increase the surface charge and surface potential of the membrane increase. (2) The titration of the carboxyl group was observed with condensed phase radioluminescence. This technique uses the electron emitted by the tritiated membrane probe (oleic acid or cholesterol) to excite a fluorophore also incorporated in the bilayer. (3) The phase transition of dimyristoyl phosphatidylcholine vesicles labelled within 12-(9-anthroyloxy)stearic acid was measured by condensed phase radioluminescence at different pH values. (4) We related the condensed phase radioluminescence signal to the asymmetrical distribution of the fluorophore between the inner and outer layer of the lipid membrane which is induced by the repulsion of the negatively charged fatty acids. (5) We showed that the condensed phase radioluminescence signal is proportional to the protonation of the carboxyl group. On this basis, the broadening of the titration curve can be explained as an effect of the self-induced membrane potential calculated using the Gouy-Chapman theory. (6) Ca2+ drastically reduces the flip-flop rate of fatty acids across the membrane and also caused a decrease in the asymmetric distribution. (7) We concluded that a fatty acid can act as a membrane surface buffer. The pK value of 12-(9-anthroyloxy)stearic acid in a dimyristoyl phosphatidylcholine membrane is 7.0 +/- 0.3. (8) We discuss the results with respect to aggregation, fusion and clustering.


Oral immunization against porcine pleuropneumonia using the cubic phase of monoolein and purified toxins of Actinobacillus pleuropneumoniae.
The main goal of this work was to obtain an orally administered immunogen that would protect against infections by Actinobacillus pleuropneumoniae. The Apx I, II and III toxins were obtained from the supernatants of cultures of serotypes 1 and 3 of A. pleuropneumoniae. The capacity of monoolein gel to trap and protect the Apx toxins, and the effect of their incorporation on the stability of the cubic phase were evaluated. The gel was capable of trapping a 400-μg/ml concentration of the antigen with no effects on its structure. Approximately 60% of the protein molecules were released from the gel within 4h. Four experimental groups were formed, each one with four pigs. All challenges were conducted in a nebulization chamber. Group A: Control (-) not vaccinated and not challenged; Group B: Control (+) not vaccinated but challenged; Group C: vaccinated twice intramuscularly with ToxCom (a commercial toxoid) at an interval of 15 days and then challenged; and Group D: vaccinated orally twice a week for 4 weeks with ToxOral (an oral toxoid) and challenged on day 28 of the experiment with a same dose of 2.0 × 10(4) UFC of A. pleuropneumoniae serotypes 1 and 3. The lesions found in group B covered 27.7-43.1% of the lungs; the pigs in group C had lesions over 12.3-28%; and those in group D over 15.4-32.3%. No lesions were found in the Group A pigs. A. pleuropneumoniae induced macroscopic lesions characteristic of infection by and lesions microscopic detected by histopathology. The etiologic agent was recovered from the infected lungs, tonsils and spleen. The serotypes identified were 1 and 3. An indirect ELISA test identified the antibodies against the Apx toxins in the serum of the animals immunized orally.


Molecular mechanisms involved in the adaptive response to cadmium-induced apoptosis in human myelomonocytic lymphoma U937 cells.
We examined the molecular mechanisms involved in the adaptive response to cadmium (Cd)-induced apoptosis in human myelomonocytic lymphoma U937 cells. When U937 cells were treated with 50 μM cadmium chloride (CdCl2) for 12 h, significant apoptosis occurred. This was associated with an increase in intracellular reactive oxygen species (ROS), sustained phosphorylation of JNK, activation of caspase-3, a decrease in Mcl-1 (anti-apoptotic Bcl-2 proteins), and increases in Bim, Noxa and tBid (a pro-apoptotic protein under the Bcl-2 family). No apoptosis occurred when the cells were treated with 1 μM CdCl2 for 72 h. However, pretreatment with low-dose CdCl2 dramatically altered the sensitivity of the cells to 50 μM CdCl2 with inhibition of apoptosis. Concomitantly, there were significant decreases in the generation of intracellular ROS and the activation of JNK. Pretreatment with 1 μM CdCl2 also attenuated the decrease in Mcl-1 and the increases in Bim, Noxa and tBid induced by 50 μM CdCl2. In conclusion, pretreatment with low-dose Cd inhibited apoptosis induced by high-dose Cd. The mechanism involves inhibition of intracellular ROS generation and JNK activation, and modulating the balance between the expression of Mcl-1 and its binding partners, Bim, Noxa and tBid.