Detection of amyloid beta aggregates in the brain of BALB/c mice after Chlamydia pneumoniae infection

Neuroinflammation, initiated by cerebral infection, is increasingly postulated as an aetiological factor in neurodegenerative diseases such as Alzheimer’s disease (AD). We investigated whether Chlamydia pneumoniae (Cpn) infection results in extracellular aggregation of amyloid beta (Aβ) in BALB/c mice. At 1 week post intranasal infection (p.i.), Cpn DNA was detected predominantly in the olfactory bulbs by PCR, whereas brains at 1 and 3 months p.i. were Cpn negative. At 1 and 3 months p.i., extracellular Aβ immunoreactivity was detected in the brain of Cpn-infected mice but also in the brain of mock-infected mice and mice that were neither Cpn infected nor mock infected. However, these extracellular Aβ aggregates showed morphological differences compared to extracellular Aβ aggregates detected in the brain of transgenic APP751SL/PS1M146L mice. These data do not unequivocally support the hypothesis that Cpn infection induces the formation of AD-like Aβ plaques in the brain of BALB/c mice, as suggested before. However, future studies are required to resolve these differences and to investigate whether Cpn is indeed an etiological factor in AD pathogenesis

Polygenic burden in focal and generalized epilepsies

Rare genetic variants can cause epilepsy, and genetic testing has been widely adopted for severe, paediatric-onset epilepsies. The phenotypic consequences of common genetic risk burden for epilepsies and their potential future clinical applications have not yet been determined. Using polygenic risk scores (PRS) from a European-ancestry genome-wide association study in generalized and focal epilepsy, we quantified common genetic burden in patients with generalized epilepsy (GE-PRS) or focal epilepsy (FE-PRS) from two independent non-Finnish European cohorts (Epi25 Consortium, n = 5705; Cleveland Clinic Epilepsy Center, n = 620; both compared to 20 435 controls). One Finnish-ancestry population isolate (Finnish-ancestry Epi25, n = 449; compared to 1559 controls), two European-ancestry biobanks (UK Biobank, n = 383 656; Vanderbilt biorepository, n = 49 494), and one Japaneseancestry biobank (BioBank Japan, n = 168 680) were used for additional replications. Across 8386 patients with epilepsy and 622 212 population controls, we found and replicated significantly higher GE-PRS in patients with generalized epilepsy of European-ancestry compared to patients with focal epilepsy (Epi25: P = 1.64 710-15; Cleveland: P = 2.85 710-4; Finnish-ancestry Epi25: P = 1.80 710-4) or population controls (Epi25: P = 2.35 710-70; Cleveland: P = 1.43 710-7; Finnish-ancestry Epi25: P = 3.11 710-4; UK Biobank and Vanderbilt biorepository meta-analysis: P = 7.99 710-4). FE-PRS were significantly higher in patients with focal epilepsy compared to controls in the non-Finnish, non-biobank cohorts (Epi25: P = 5.74 710-19; Cleveland: P = 1.69 710-6). European ancestry-derived PRS did not predict generalized epilepsy or focal epilepsy in Japanese-ancestry individuals. Finally, we observed a significant 4.6-fold and a 4.5-fold enrichment of patients with generalized epilepsy compared to controls in the top 0.5% highest GE-PRS of the two non-Finnish European cohorts (Epi25: P = 2.60 710-15; Cleveland: P = 1.39 710-2). We conclude that common variant risk associated with epilepsy is significantly enriched in multiple cohorts of patients with epilepsy compared to controls-in particular for generalized epilepsy. As sample sizes and PRS accuracy continue to increase with further common variant discovery, PRS could complement established clinical biomarkers and augment genetic testing for patient classification, comorbidity research, and potentially targeted treatment

Genome-wide identification and phenotypic characterization of seizure-associated copy number variations in 741,075 individuals

Copy number variants (CNV) are established risk factors for neurodevelopmental disorders with seizures or epilepsy. With the hypothesis that seizure disorders share genetic risk factors, we pooled CNV data from 10,590 individuals with seizure disorders, 16,109 individuals with clinically validated epilepsy, and 492,324 population controls and identified 25 genome-wide significant loci, 22 of which are novel for seizure disorders, such as deletions at 1p36.33, 1q44, 2p21-p16.3, 3q29, 8p23.3-p23.2, 9p24.3, 10q26.3, 15q11.2, 15q12-q13.1, 16p12.2, 17q21.31, duplications at 2q13, 9q34.3, 16p13.3, 17q12, 19p13.3, 20q13.33, and reciprocal CNVs at 16p11.2, and 22q11.21. Using genetic data from additional 248,751 individuals with 23 neuropsychiatric phenotypes, we explored the pleiotropy of these 25 loci. Finally, in a subset of individuals with epilepsy and detailed clinical data available, we performed phenome-wide association analyses between individual CNVs and clinical annotations categorized through the Human Phenotype Ontology (HPO). For six CNVs, we identified 19 significant associations with specific HPO terms and generated, for all CNVs, phenotype signatures across 17 clinical categories relevant for epileptologists. This is the most comprehensive investigation of CNVs in epilepsy and related seizure disorders, with potential implications for clinical practice

Occupational health, safety and environmental risk assessment in textile production industry through a Bayesian BWM-VIKOR approach

Occupational risk assessment (ORA) is a process that consists of evaluating, ranking, and classifying the hazards and associated risks arising in any workplace from the viewpoint of occupational health and safety. Many ORA methods have been proposed in the literature, from a single independent expert to participatory methodologies made by group decision and simple to complex ones. In this paper, a holistic ORA is presented, which uses two important multi-attribute decision methods named Bayesian Best-Worst Method (Bayesian BWM) and VIseKriterijumska Optimizacija I Kompromisno Resenje (VIKOR). Bayesian BWM is used to determine the importance weights of six different assessment criteria, which are the probability of hazardous event (P), frequency (F), severity (S), detectability (D), cost (C) and sensitivity not to use personal protective equipment (SNP). Since the classical BWM finds solution to the weights of a number of criteria from only one expert's judgment, Bayesian BWM is preferred in this paper (1) to enable participation of a group of experts, (2) to aggregate the preferences of these multiple experts into consensus without loss of information and (3) to follow a probabilistic way for solving the ORA problem. The hazards are then ranked by VIKOR. The approach is implemented in the ORA process of a textile production plant. Results of risk analysis showed that electricity hazard and associated risks constitute the highest risk ratings. These hazards arise from the product, process, human and working environment. The associated risks are evaluated, prioritized, and detailed control measures are proposed. This study made comparisons with the classical BWM-VIKOR approach to demonstrate the proposed approach's difference and practicality. Results can also help practitioners and risk analysts in formulating the improvement measures to increase the overall safety of the working environment further

NEONATAL PERITONITIS

WOS: A1992KK38400006PubMed ID: 1485383A retrospective study was undertaken over an eight year period to assess the mortality rate of 66 newborns who had undergone surgery in our clinic because of peritonitis. The mortality rate for the patients admitted in poor condition was 95.2 percent, whereas it was 45.5 percent for those in good condition. There was a 100 percent mortality associated with newborns that had hypothermia and with those that had severe respiratory difficulties, whereas it was 92 3 percent for low-birth-weight infants and 86.5 percent for dehydrated infants All babies with sclerema neonatorum died. The newborns with white blood cell counts under 5,000/mm3 also did not survive (83.3%). Etiologically, congenital megacolon, meconium ileus and spontaneous gastrointestinal perforations were the most frequent anomalies leading to death (100%). In the newborns with gastrointestinal perforations, most deaths occurred in patients with perforations of the cecum, duodenum and stomach (100%) Mortality seemed to be greater in patients with complications (77.3%), and it rose to 83.3 percent for patients who had to undergo a repeat operation due to complications. The overall mortality rate was found to be 71.2 percent

Comparison of electromagnetic field stimulation on the healing of small and large intestinal anastomoses

Nayci, Ali/0000-0002-0534-1205WOS: 000170453000023PubMed: 11535860PURPOSE: Magnetic fields have been shown to affect biologic processes. Accordingly, an experimental study was designed to investigate the effect of electromagnetic field stimulation on intestinal healing and to compare small and large intestinal anastomoses. METHODS: An ileal or a colonic anastomosis was constructed in rats. Beginning the day after surgery, randomly assigned groups were exposed to sinusoidal electromagnetic field stimulation of 10.76-mT intensity and 50-Hz frequency, with 2-hour-on/10-hour-off cycles. After seven days, intestinal anastomoses were assessed for hydroxyproline content and breaking strength. Statistical comparison between each experimental and control group yielded significance (P g/mg (P = 0.0249) and in colon from 1.526 +/- 0.11 to 1.922 +/- 0.11 mug/mg (P = 0.0135). Breaking strength also increased significantly in ileum from 0.213 +/- 0.01 to 0.255 +/- 0.01 MPa (P = 0.001) and in colon from 0.227 +/- 0.01 to 0.270 +/- 0.01 MPa (P = 0.006). CONCLUSIONS: Electromagnetic field stimulation provided a significant gain in anastomotic healing in both small and large intestine. There were no apparent differences detected between the healing of small and large intestinal anastomoses except for slight differences in the tune sequences of events and magnitude. The study demonstrated a significant increase in both biochemical and mechanical parameters. Additional investigations are needed to determine optimal conditions and promote selective biologic responses

Effect of electromagnetic fields and early postoperative 5-fluorouracil on the healing of colonic anastomoses

Nayci, Ali/0000-0002-0534-1205WOS: 000181357100008PubMed: 12548416Background and aims: Studies have indicated a deleterious effect of perioperative 5-fluorouracil (5-FU) administration on the healing of intestinal anastomoses. This study examined the effect of early postoperative 5-FU on the healing of colonic anastomoses and investigated the effect of electromagnetic fields (EMF) on colonic anastomotic repair under normal physiological conditions and in the presence of 5-FU therapy in a rat model. Materials and methods: Forty male Wistar rats were randomly assigned into four groups and underwent a standardized left colonic resection and anastomoses. The animals then served as control or received intraperitoneal 5-FU (20 mg/kg per day, 5 days), EMF stimulation (10.76 mT, 50 Hz; 2-h on/10-h off cycles, 7 days) or both, starting on the day of surgery. After 7 days anastomotic healing was assessed by measurement of hydroxyproline content and breaking strength. Results: Hydroxyproline content increased in EMF exposed group (1.53+/-0.11 to 1.92+/-0.11 mug/mg) and in EMF + 5-FU group (1.53+/-0.11 to 1.89+/-0.12 mug/mg). Breaking strength also increased in the EMF group (0.23+/-0.02 to 0.27+/-0.01 MPa) and in the EMF + 5-FU group (0.23+/-0.02 to 0.28+/-0.01 MPa. No differences were found in hydroxyproline content or breaking strength between the 5-FU group and controls. Conclusion: Early postoperative 5-FU administration did not impair the healing of colonic anastomoses in rats. Additionally, EMF stimulation provided a significant gain in colonic anastomotic strength, in rat intestines in control animals and in animals exposed to 5-FU

A multicriteria approach to integrating occupational safety & health performance and industry systems productivity in the context of aging workforce: A case study

Aging represents one of the greatest challenges that mankind will have to face in the 21st century. In this regard, there is a need to deepen the technical and organizational aspects for rebalancing the job/employee relationship. Nevertheless, there are no robust approaches assisting decision-makers in the effective management of Occupational Safety & Health Performance (OSHP) and Industry Systems Productivity (ISP) convergence with a focus on Aging Workforce (AW). There is no single and unique solution. Therefore, in a win-to-win logic that favors the characteristic of the reference scenario, the aim of this paper is to propose a multicriteria approach to integrate OSHP and ISP in the context of AW. More specifically, Intuitionistic Fuzzy Analytic Hieararchy Process (IF-AHP) was used to elicit the criteria and sub-criteria under uncertainty considering degree of belongingness and non-belongingness. Decision Making Trial and Evaluation Laboratory (DEMATEL) was applied to evaluate the presence and strength of the interrelations and feedback among OSHP and ISP criteria and sub-criteria. Finally, Combined Compromise Solution (CoCoSo) was implemented to calculate a Working Suitability Index (WSI) per aging. Based on this index, interventions on each worker are proposed to underpin redesign of the company while to provide a flexible management propelling high performance in terms of OSHP and ISP. A real case study in Colombia is presented. The results revealed that Efficiency and Quality with 0.162 were found to be the most important factors in evaluating the performance of aging electrical engineers while Psychosocial risk and Occupational Safety were concluded to be the main drivers for a joint OSHP-ISP aging workforce management. The model can be an useful tool for policy and business decision-makers from the electrical sector and can be replicated with slight changes in other industries

Ultrastructural changes in the contralateral lung tissue following unilateral lung ischemia: An experimental study in rabbits

WOS: 000187918400009PubMed: 14714228Purpose. To investigate the acute ultrastructural changes that may occur in the contralateral nonischemic lung tissue after unilateral ischemia of a lung in a rabbit model. Methods. The animals were divided into three main groups of eight; namely, a 2-h procedure group, a 4-h procedure group, and an 8-h procedure group. Each of these groups was further divided into two subgroups of four rabbits each; namely, a control group, given a sham operation without any ischemic insult, and an ischemia group, in which the main pulmonary arteries, the pulmonary veins, and the main bronchi of the left lungs were ligated after thoracotomy. Tissue samples were taken from the left and right lungs to examine the ultrastructural changes after 2, 4, and 8 h of ischemia. Each sample was given a semiquantitative histological injury score. Statistical analysis was done by the Mann-Whitney U-test. Results. Contralateral ultrastructural damage, evident by heterochromatin in the nuclei, mitochondrial degeneration, cisternal widening of the endoplasmic reticulum, increased lipid droplets, and lysosomes, was determined by electron microscopy after unilateral lung ischemia. The contralateral lung injury was significantly correlated with the duration of ischemia. Conclusions. Unilateral lung ischemia affected the bilateral lungs in a rabbit model. Therefore, in operations such as single-lung transplantation, pulmonectomy, or lobectomy, if the procedure is unnecessarily prolonged, the contralateral lung may be damaged, which could seriously affect the prognosis of the patient