Systematic review on the use of activated charcoal for gastrointestinal decontamination following acute oral overdose.
The use of activated charcoal in poisoning remains both a pillar of modern toxicology and a source of debate. Following the publication of the joint position statements on the use of single-dose and multiple-dose activated charcoal by the American Academy of Clinical Toxicology and the European Association of Poison Centres and Clinical Toxicologists, the routine use of activated charcoal declined. Over subsequent years, many new pharmaceuticals became available in modified or alternative-release formulations and additional data on gastric emptying time in poisoning was published, challenging previous assumptions about absorption kinetics. The American Academy of Clinical Toxicology, the European Association of Poison Centres and Clinical Toxicologists and the Asia Pacific Association of Medical Toxicology founded the Clinical Toxicology Recommendations Collaborative to create a framework for evidence-based recommendations for the management of poisoned patients. The activated charcoal workgroup of the Clinical Toxicology Recommendations Collaborative was tasked with reviewing systematically the evidence pertaining to the use of activated charcoal in poisoning in order to update the previous recommendations. The main objective was: Does oral activated charcoal given to adults or children prevent toxicity or improve clinical outcome and survival of poisoned patients compared to those who do not receive charcoal? Secondary objectives were to evaluate pharmacokinetic outcomes, the role of cathartics, and adverse events to charcoal administration. This systematic review summarizes the available evidence on the efficacy of activated charcoal. A medical librarian created a systematic search strategy for Medline (Ovid), subsequently translated for Embase (via Ovid), CINAHL (via EBSCO), BIOSIS Previews (via Ovid), Web of Science, Scopus, and the Cochrane Library/DARE. All databases were searched from inception to December 31, 2019. There were no language limitations. One author screened all citations identified in the search based on predefined inclusion/exclusion criteria. Excluded citations were confirmed by an additional author and remaining articles were obtained in full text and evaluated by at least two authors for inclusion. All authors cross-referenced full-text articles to identify articles missed in the searches. Data from included articles were extracted by the authors on a standardized spreadsheet and two authors used the GRADE methodology to independently assess the quality and risk of bias of each included study. From 22,950 titles originally identified, the final data set consisted of 296 human studies, 118 animal studies, and 145 in vitro studies. Also included were 71 human and two animal studies that reported adverse events. The quality was judged to have a Low or Very Low GRADE in 469 (83%) of the studies. Ninety studies were judged to be of Moderate or High GRADE. The higher GRADE studies reported on the following drugs: paracetamol (acetaminophen), phenobarbital, carbamazepine, cardiac glycosides (digoxin and oleander), ethanol, iron, salicylates, theophylline, tricyclic antidepressants, and valproate. Data on newer pharmaceuticals not reviewed in the previous American Academy of Clinical Toxicology/European Association of Poison Centres and Clinical Toxicologists statements such as quetiapine, olanzapine, citalopram, and Factor Xa inhibitors were included. No studies on the optimal dosing for either single-dose or multiple-dose activated charcoal were found. In the reviewed clinical data, the time of administration of the first dose of charcoal was beyond one hour in 97% (n = 1006 individuals), beyond two hours in 36% (n = 491 individuals), and beyond 12 h in 4% (n = 43 individuals) whereas the timing of the first dose in controlled studies was within one hour of ingestion in 48% (n = 2359 individuals) and beyond two hours in 36% (n = 484) of individuals. This systematic review found heterogenous data. The higher GRADE data was focused on a few select poisonings, while studies that addressed patients with unknown and or mixed ingestions were hampered by low rates of clinically meaningful toxicity or death. Despite these limitations, they reported a benefit of activated charcoal beyond one hour in many clinical scenarios.


Loss of K-Cl co-transporter KCC3 causes deafness, neurodegeneration and reduced seizure threshold.
K-Cl co-transporters are encoded by four homologous genes and may have roles in transepithelial transport and in the regulation of cell volume and cytoplasmic chloride. KCC3, an isoform mutated in the human Anderman syndrome, is expressed in brain, epithelia and other tissues. To investigate the physiological functions of KCC3, we disrupted its gene in mice. This severely impaired cell volume regulation as assessed in renal tubules and neurons, and moderately raised intraneuronal Cl(-) concentration. Kcc3(-/-) mice showed severe motor abnormalities correlating with a progressive neurodegeneration in the peripheral and CNS. Although no spontaneous seizures were observed, Kcc3(-/-) mice displayed reduced seizure threshold and spike-wave complexes on electrocorticograms. These resembled EEG abnormalities in patients with Anderman syndrome. Kcc3(-/-) mice also displayed arterial hypertension and a slowly progressive deafness. KCC3 was expressed in many, but not all cells of the inner ear K(+) recycling pathway. These cells slowly degenerated, as did sensory hair cells. The present mouse model has revealed important cellular and systemic functions of KCC3 and is highly relevant for Anderman syndrome.


Physical and rehabilitation medicine (PRM) care pathways: "spinal cord injury".
This document is part of a series of documents designed by the French Physical and Rehabilitation Medicine Society (SOFMER) and the French Federation of PRM (FEDMER). These documents describe the needs for or a specific type of patients; PRM care objectives, human and material resources to be implemented, chronology as well as expected outcomes. "Care pathways in PRM" is a short document designed to enable the reader (physicians, decision-maker, administrator, lawyer or finance manager) to quickly apprehend the needs of these patients and the available therapeutic care structures for proper organization and pricing of these activities. The patients after spinal cord injury are divided into five categories according to the severity of the impairments, each one being treated according to the same six parameters according to the International Classification of Functioning, Disability and Health (WHO), while taking into account personal and environmental factors that could influence the needs of these patients.


An active drop counting device using condenser microphone for superheated emulsion detector.
An active device for superheated emulsion detector is described. A capacitive diaphragm sensor or condenser microphone is used to convert the acoustic pulse of drop nucleation to electrical signal. An active peak detector is included in the circuit to avoid multiple triggering of the counter. The counts are finally recorded by a microprocessor based data acquisition system. Genuine triggers, missed by the sensor, were studied using a simulated clock pulse. The neutron energy spectrum of (252)Cf fission neutron source was measured using the device with R114 as the sensitive liquid and compared with the calculated fission neutron energy spectrum of (252)Cf. Frequency analysis of the detected signals was also carried out.


[The helminth fauna of wild boars of the west Berlin forests].
Samples of muscles and internal organs obtained from 96 wild boars in the forests of West Berlin between September 1989 and August 1990, were examined for helminths. Nine nematode species, Metastrongylus pudendotectus, M. salmi, M. confusus, M. apri, Physocephalus sexalatus, Ascarops strongylina, Globocephalus urosubulatus, Ascaris suum and Trichuris suis belonging to five families could be found. Larvae of Toxocara spp. were isolated from most of the enzymatically digested samples of the gastrointestinal tract. In a few cases juvenile forms of Cysticercus tenuicollis could be identified. Trichinella spiralis and trematodes were not found. The correlation between helminth infection and age and sex of the wild boars as well as time and site of shooting are discussed.


Analysis of two interacting bacterial populations with opposite substrate preferences.
Interactions between two bacterial species which exhibit opposite substrate preferences in response to the same environmental conditions were investigated. Klebsiella oxytoca preferentially utilizes glucose over citrate as a substrate while Pseudomonas aeruginosa utilizes citrate over glucose. Both species were grown on single as well as mixed substrates, namely, D-glucose and citrate, with various ratios of inocula and substrates. Competition is observed between the two species with citrate alone while amensalism is observed with glucose alone. In mixed cultures-mixed substrates experiments, amensalism of K. oxytoca on P. aeruginosa prevailed until the exhaustion of glucose.


Efficiency of guva and lemon grass fine dusts on the potato tuber moth Phthorimaea operculella (Zeller) (Lepidoptera: Gelechiidae).
The present study was initiated to elucidate the effect of potato tubers treatment using fine dusts of Psidium guajava, Cymbopogon citratus, talc powder and their progressive dilutions(w/w) on the fitness components of raised generations of the potato tuber moth (PTM), Phthorimaea operculella. Results showed a direct as well as cumulative delayed effect of the tested plants fine dusts, either alone or admixed with talc powder in progressive dilutions from 5% up to 50% w/w on the viability of developing immatures and potentiality of adult moths. The revealed effects of each of the tested crude plant fine dusts or talc powder alone and/or their progressive dilutions (w/w) could be explained briefly as gradual significant shortening of life span of both sexes, prolongation of larval duration, reduction in number of raised pupae, increase of malformed ones, sharp decrease in the rate of emerged moths, deposited eggs, and developing of immatures; According to lower used dilutions of each tested plant fine dust from 5% to 20%, the complete inhibition of reproductive potential of both adult sexes, the going on metamorphic development of deposited eggs and/or raised immatures of the following generation, after the treatment of parent one, had been revealed the following distinct failure of: a) F1 development after former treatment of parent generation with the higher concentrations of 30-50% of both tested plant fine dusts and the lower prepared dilutions (10% and 20% (w/w)) of both the tested Psidium guajava and (20% (w/w)) Cymbopogom citratus plant fine dusts, resulted in fewer number of the emerged moths that were unviable, weak, sterile and died before induction the F1 progeny, b) F2 development due to the former treatment of the parents with talc powder, Psidium guajava fine dusts alone or its prepared dilutions of (5% (w/w)) and Cymbopogom citratus dilution of (10%(w/w)) gave unviable weak and sterile moths unable to induce the F2 progeny, c) F3 development post former treatment of the parent generations with Cymbopogom citratus dilution of 5% (w/w) induced unviable sterile moths and died after emergence and d) F4 development owing to the former parent treatment with Cymbopogon citratus fine dust alone; The complete failure of each of the above mentioned generations could be attributed to the cumulative effect of induced recessive lethal genes in both sexes along the extended period of each of these following generations, post former treatment of parent one, causing apparent undesirable effects, that appeared at the beginning of each of them.


A Computer-Aided Analysis Method of SPECT Brain Images for Quantitative Treatment Monitoring: Performance Evaluations and Clinical Applications.
The objective and quantitative analysis of longitudinal single photon emission computed tomography (SPECT) images are significant for the treatment monitoring of brain disorders. Therefore, a computer aided analysis (CAA) method is introduced to extract a change-rate map (CRM) as a parametric image for quantifying the changes of regional cerebral blood flow (rCBF) in longitudinal SPECT brain images. The performances of the CAA-CRM approach in treatment monitoring are evaluated by the computer simulations and clinical applications. The results of computer simulations show that the derived CRMs have high similarities with their ground truths when the lesion size is larger than system spatial resolution and the change rate is higher than 20%. In clinical applications, the CAA-CRM approach is used to assess the treatment of 50 patients with brain ischemia. The results demonstrate that CAA-CRM approach has a 93.4% accuracy of recovered region's localization. Moreover, the quantitative indexes of recovered regions derived from CRM are all significantly different among the groups and highly correlated with the experienced clinical diagnosis. In conclusion, the proposed CAA-CRM approach provides a convenient solution to generate a parametric image and derive the quantitative indexes from the longitudinal SPECT brain images for treatment monitoring.


Lower dosages of phentermine-fenfluramine given in the afternoon: five cases with significant weight loss.
Phentermine and fenfluramine are widely used in the treatment of obesity. Despite the fact that primary pulmonary hypertension and mitral valve insufficiency have been associated with fenfluramine use, many of these patients need medication to achieve weight loss. Small degrees of weight loss have been shown to significantly improve obesity-related medical conditions such as hypertension, hypercholesterolemia, and noninsulin-dependent diabetes mellitus. Current practice is to give phentermine and fenfluramine in the morning and afternoon. Doses for phentermine have ranged from 15 to 37.5 mg and for fenfluramine from 20 to 120 mg per day. We report five cases of severely obese women with medical complications who were treated with phentermine 8 mg twice per day (at 1:00 p.m. and 4:00 p.m.) and fenfluramine 20 mg per day (at 4:00 p.m.). Because many obese patients skip breakfast and eat more in the afternoon and evening, medication was dosed in order to cover these high-risk eating periods. Overall, these patients lost a mean of 22.4% of their initial weight (range 18.6% to 32.8%) over an average of 8.4 months (range 3.5 to 16 months). These cases suggest that short-term weight loss can be achieved with a low dose of fenfluramine when both medications are given in the afternoon to better target the eating patterns of obese subjects.


Prediction of survival time at sea based on observed body cooling rates.
The prediction of survival time (ST) of individuals stranded at sea is particularly difficult since reliable controlled data are unavailable. An individual's rate of body cooling is governed by the difference between heat loss and heat production. It has been suggested that the rate of deep body cooling can be extrapolated to estimate ST. The observed linearity of this cooling rate against water temperature is consistent with the predictions of an independently-developed mathematical model of ST. This model has been extended to simulate conditions of partial immersion and wet clothing, and subsequently calibrated against observed human cooling rates. The resultant modification allows a much broader range of ST predictions involving calm and rough seas, and non-immersion wet conditions. Predictions are presented for lean vs. fat individuals, a "worst" case scenario where shivering is absent, and partial immersion. While these predictions must be considered speculative and subject to change as better information becomes available, the model can be useful as a decision aid. It would be prudent, however, to consider the predictions in a relative vs. absolute sense; i.e., for comparative purposes.


Plasmolysis during the division cycle of Escherichia coli.
Cells of Escherichia coli were plasmolyzed with sucrose. They were classified according to length by way of electron micrographs taken from samples prepared by agar filtration. The percentage of plasmolyzed cells increased about two- and threefold between mean cell sizes of newborn and separating cells. However, dividing cells were less frequently plasmolyzed than nondividing cells of the same length class. Analysis of cell halves (prospective daughters) in dividing cells showed that they behaved as independent cellular units with respect to plasmolysis. The results indicate that compressibility of the protoplast (given a certain plasmolysis space) is inversely related to cell size. That a dividing cell does not react as one osmotic compartment to osmotic stress may suggest that cell size-dependent strength of the cell membrane-cell wall association, rather than variation in turgor, plays a role during the cell division cycle.


Dietary cholesterol and human coronary heart disease. The epidemiologic evidence.
For decades, dietary cholesterol has been recognized as the "materia peccans" (Anitschkow) for the induction of atherosclerosis in animals. In rabbits, chickens, and monkeys, long-term feeding of small amounts of cholesterol leads to atherosclerosis despite little or no rise in serum total cholesterol, indicating an independent contribution of dietary cholesterol to atherogenesis over-and-above its influence on serum cholesterol, possibly through effects on serum cholesterol fractions (eg, increased low-density lipoprotein-cholesterol and decreased high-density lipoprotein-cholesterol). In humans, ingestion of dietary cholesterol raises serum cholesterol, largely through its effect on low-density lipoprotein-cholesterol. Over the range of intake in usual American diets, this effect is substantial, eg, with 300 mg of cholesterol intake per 1000 kcal, rather than 100, serum cholesterol is on average about 6% to 7% higher, equivalent to a 12% to 14% greater risk of coronary heart disease (CHD). In international studies based on the Food and Agriculture Organization and the World Health Organization (Geneva) data, mean per capita dietary cholesterol levels are consistently related to CHD mortality rates. In addition, since 1981, four prospective within-population studies have shown that dietary cholesterol intake of individuals is significantly related to their long-term CHD risk, independent of and in addition to serum cholesterol, blood pressure, and cigarette use. On average, a 200-mg/1000 kcal higher intake of cholesterol at baseline was associated with a 30% higher CHD rate (95% confidence interval, 1.1 to 1.5). Conversely, lower intakes of cholesterol were associated with significantly lower risks of CHD, and of all causes mortality as well. For example, with 19 years of follow-up in the Chicago Western Electric Study, a 200-mg/1000 kcal habitual lower cholesterol intake was associated with a 37% lower risk of death from any cause, equivalent to a life expectancy longer by 3.4 years. The importance of a low-dietary cholesterol intake for prevention of CHD merits increased emphasis.


Oxidant regulation of the Saccharomyces cerevisiae GSH1 gene.
Glutathione (gamma-L-glutamyl-L-cysteinylglycine) is an important antioxidant molecule, helping to protect the cell against oxidative stress. Expression of the Saccharomyces cerevisiae GSH1 gene, coding for the first enzyme involved in glutathione biosynthesis, is regulated at the level of transcription by oxidants and heavy metals. We have characterised the sequences of the GSH1 promoter responsible for the amino acid-dependent H(2)O(2) regulation of transcription. We show that there are at least two H(2)O(2)-responsive elements in the promoter, neither of which map to the putative Yap1 binding site. Our results suggest that the Yap1 protein plays an important, but indirect role in the H(2)O(2)-dependent regulation of GSH1 transcription.


Comparison between betamethasone gel applied over endotracheal tube and ketamine gargle for attenuating postoperative sore throat, cough and hoarseness of voice.
Tracheal intubation for general anesthesia often leads to trauma of the airway mucosa resulting in postoperative sore throat, hoarseness of voice and cough. The aim of this study was to evaluate two different methods as regard their efficacy for controlling the postoperative pharyngo-laryngo-tracheal sequelae (sore throat, cough, hoarseness of voice) after general anesthesia with laryngoscopy and tracheal intubation. We compared between the effects of betamethasone gel applied over the endotracheal tube and gargling with ketamine solution in reducing these complications during the first 24 postoperative hours after elective surgical procedures in a prospective randomized controlled single blind clinical trial. Seventy five patients ASA physical status I and II, undergoing elective surgery under general anesthesia using endotracheal intubation were enrolled in this prospective, randomized, single-blind study. Patients were randomly divided into 3 groups of 25 patients each: Group (K): (n: 25) Patients in this group were asked to gargle with ketamine 40 mg in 30 ml saline for 60 seconds as repeated smaller attempts, 5 minutes before induction of anesthesia. Group (B) (n: 25): Endotracheal tubes were lubricated with 0.05% betamethasone gel. Group (C) (n: 25): patients did not receive ketamine gargle nor betamethasone gel. The incidence and the severity of Postoperative sore throat, cough, and hoarseness of voice were graded at 0, 2, 4, and 24 h after operation by a blinded investigator. The incidence and severity of sore throat were significantly lower in group (K) and group (B) than group (C) (p < 0.05) at all time intervals. While there was no significant difference between group (K) and group (B) (p > 0.05). The incidence and severity of cough and hoarseness of voice were significantly lower in group (B) than group (C) and group (k) (p < 0.05) at all time intervals. Gargling with ketamine before induction of anesthesia is comparable with application of 0.05% betamethasone gel over the Endotracheal tubes in decreasing postoperative sore throat. In addition, Betmethasone application decreased the incidence and severity of postoperative cough and hoarsness of voice.


Antibody Reactivity of B Cells in Lupus Patients with Increased Disease Activity and ARID3a Expression.
Earlier studies showed that the DNA-binding protein, Bright/ARID3a bound to a subset of human and mouse immunoglobulin heavy chain promoters where it enhanced expression. Indeed, mice with transgenic expression of ARID3a in all B lymphocytes have expanded MZ B cells and produce anti-nuclear antibodies (ANAs). Consistent with our findings in mice, we observed that human systemic lupus erythematosus (SLE) patients had expanded numbers of peripheral blood ARID3a+ B cells that were associated with increased disease activity (p = 0.0038). We hypothesized that ARID3a+ naïve B cells would eventually produce autoantibodies, explaining associations between ARID3a expression and disease activity in lupus. Unlike healthy controls, ARID3a was expressed in the naïve B cell population in SLE patients, and we hypothesized that these might represent expansions of autoreactive cells. Therefore, monoclonal antibodies were generated from single-sorted naïve B cells derived from patients with normal (ARID3aN) and high (ARID3aH) numbers of ARID3a+ B cells. We found that ARID3a expression did not correlate with autoantibody expression. Furthermore, measures of antigen specificities of autoreactive antibodies did not reveal skewing toward particular proteins. These data suggest that the association of increased disease activity in SLE with numbers of ARID3a+ B lymphocytes may be mediated by an antibody-independent mechanism.


Use of dexmedetomidine as a sedative and analgesic agent in critically ill adult patients: a meta-analysis.
To assess the effects of using dexmedetomidine as a sedative and analgesic agent on length of intensive care unit (ICU) stay, duration of mechanical ventilation, risk of bradycardia, and hypotension in critically ill adult patients. Two researchers searched MEDLINE, EMBASE, and the Cochrane controlled trial register independently for randomized controlled trials comparing dexmedetomidine with a placebo or an alternative sedative agent, without any language restrictions. A total of 2,419 critically ill patients from 24 trials were subject to meta-analysis. Dexmedetomidine was associated with a significant reduction in length of ICU stay [weighted mean difference -0.48 days, 95% confidence interval (CI) -0.18 to -0.78 days, P = 0.002], but not duration of mechanical ventilation, when compared with an alternative sedative agent. There was, however, significant heterogeneity in these two outcomes between the pooled studies. Dexmedetomidine was associated with increased risk of bradycardia requiring interventions in studies that used both a loading dose and maintenance doses >0.7 microg kg(-1) h(-1) [relative risk (RR) 7.30, 95% CI 1.73-30.81, P = 0.007]. Risks of hypotension requiring interventions (RR 1.43, 95% CI 0.78-2.6, P = 0.25), delirium (RR 0.79, 95% CI 0.56-1.11, P = 0.18), self-extubation, myocardial infarction, hyperglycemia, atrial fibrillation, and mortality were not significantly different between dexmedetomidine and traditional sedative and analgesic agents. Significant heterogeneity existed between the pooled studies. The limited evidence suggested that dexmedetomidine might reduce length of ICU stay in some critically ill patients, but the risk of bradycardia was significantly higher when both a loading dose and high maintenance doses (>0.7 microg kg(-1) h(-1)) were used.


Impact of life stories on college students' positive and negative attitudes toward older adults.
Gerontological educators are increasingly interested in reducing college students' negative, and promoting their positive, attitudes toward older adults. Over the course of a semester, students from six 4-year institutions viewed three life story videos (documentaries) of older adults and completed pre- and posttest surveys that assessed their positive (Allophilia Scale) and negative (Fraboni Scale of Ageism) attitudes. The authors assessed changes in attitudinal scales between treatment (with videos, n = 80) and control (no video, n = 40) groups. Change score analysis with 95% bias-corrected bootstrap confidence intervals estimated the effects of the documentaries on students' attitudes. The treatment group showed significant increases in kinship, engagement, and enthusiasm, and decreases in antilocution and avoidance (all ps <.05). There was no significant change in affect, comfort, or discrimination. This study demonstrated how video stories impact students' attitudes about older adults.


High-efficiency hydrocracking of phenanthrene into BTX aromatics over a Ni-modified lamellar-crystal HY zeolite.
A new Ni-HY zeolite with lamellar-crystals was prepared as a catalyst for phenanthrene hydrocracking. It showed significantly improved reactivity and BTX (benzene, toluene and xylene) selectivity (up to 99.1% and 75.6%, respectively), depending on a reasonable synergistic effect between its excellent internal-diffusion and the high-efficiency concerted catalysis of surface metal-Ni active sites and acid sites. In particular, compared with a conventional Ni-HY with diamond-shaped crystals, its significantly shortened diffusion-reaction path of the micropore system in the lamellar crystals greatly enhanced the diffusion-reaction efficiency of large-molecule phenanthrene and polycyclic intermediates and remarkably improved the utilization of both pores and internal reactive sites, powerfully promoting phenanthrene into benzene series conversion. The much decreased diffusion-residence time of benzene-series products in shortened channels also effectively weakened the further cracking loss of the benzene-ring, leading to enhanced BTX selectivity. Moreover, this shorter-channel Ni-HY catalyst with a higher external surface area and mesoporous volume also exhibited greatly improved catalytic stability attributed to its stronger capabilities of accommodating coke and resisting coke-deposition. The phenanthrene conversion of >76.3% and the BTX yield of >46.3% were obtained during a 60 h on-stream reaction.


Nonhematopoietic/endothelial SSEA-1+ cells define the most primitive progenitors in the adult murine bone marrow mesenchymal compartment.
It is believed that a primitive cell type that maintains the mesenchymal compartment exists in the bone marrow. However, this putative mesenchymal stem/progenitor cell is yet to be identified and isolated. We are reporting the identification, isolation, and detailed characterization of the most primitive mesenchymal progenitor cells in the adult murine bone marrow, based on the expression of stage-specific embryonic antigen-1 (SSEA-1). This primitive subset can be identified in mesenchymal cell cultures and also directly in the bone marrow, thus ascertaining for the first time their existence in an adult organism. Characterization of SSEA-1+ mesenchymal cells revealed that upon purification these cells gave rise to SSEA-1- mesenchymal cells, whereas the reverse could not be observed. Also, these SSEA-1+ cells have a much higher capacity to differentiate than their negative counterparts, not only to several mesenchymal cell types but also to unconventional cell types such as astrocyte-, endothelial-, and hepatocyte-like cells in vitro. Most importantly, a single-cell-derived population was capable of differentiating abundantly into different mesenchymal cell types in vivo. Altogether we are proposing a hierarchical organization of the mesenchymal compartment, placing SSEA-1+ cells at the apex of this hierarchy.


Assessment of Factors Associated with the Effectiveness of Premarital Screening for Hemoglobinopathies in the South of Saudi Arabia.
Southern region of Saudi Arabia has one of the highest prevalence of sickle cell disease and thalassemia in the kingdom. This study aims to assess the factors associated with the rejection of premarital clinical counselling in the Jazan region. This is a cross-sectional investigation conducted in the Jazan region of Saudi Arabia. The investigation targeted subjects who performed premarital screening and, with their screened partners, were identified as high-risk couples and proceeded with their marriage. Data were collected via a web-based self-administered questionnaire. A section of the questionnaire targeted those who attended the premarital counselling clinic in the Jazan region and assessed the factors that led to the rejection of premarital counselling advice. A total of 413 participants were recruited. The mean age of the respondents was 33 years, and the majority of the respondents were female (62.5%). The majority of the respondents were related to their partners (66.8%) and were carriers of sickle cell disease (67.8%). Among the respondents, only 192 had attended premarital counselling clinics in the Jazan region. More than half of the attendees rejected the premarital counseling advice because they believed that their marriage was their unavoidable destiny. About 30% of the attendees reported that disease complications were not well explained during the counselling. Thirty-five attendees (18.2%) proceeded with the marriage because they thought the risk of transmitting the disease to their children was small and 10 attendees (5.2%) proceeded with their marriage because they believed their children's lives would not be affected by the disease. The findings explain the limited influence of the premarital counselling advice in raising the awareness of the attendees about inherited blood disorders. The findings indicate a strong cultural influence leading to the reduced effectiveness of premarital counselling in the Jazan region.


Teenager With Abdominal Pain and Decreased Appetite.
A 16-year-old girl presented to her primary care physician with a one-month history of decreased appetite and abdominal pain. She had normal bowel movements and no vomiting, but her periumbilical pain limited her ability to finish most meals. She had gradual weight loss over the previous 2 years, and during the previous 4 years, she intermittently received counseling for depression after the loss of her mother. Her initial physical examination and laboratory evaluation were unremarkable. She was referred to a nutritionist, adolescent medicine, and pediatric gastroenterology. Her presentation evolved over time, which ultimately led to a definitive diagnosis.


Development of monoclonal antibodies reacting against mycobacterial 65 kDa heat shock protein by using recombinant truncated products.
A mycobacterial 65 kDa molecule is a member of the GroEL heat shock protein family. We developed mAbs reacting against recombinant 65 kDa protein by using a gene (pTB12) which encodes this protein. Three mAbs (B20, B97 and B167) reacted selectively with 65 kDa proteins of Mycobacterium tuberculosis, BCG and Mycobacterium leprae, although B20 and B167 may weakly react with a 15 kDa molecule of mammalian cells. One (B108) was obviously cross-reactive between mycobacterial 65 kDa and the mammalian intracytoplasmic protein. We also developed deletion mutants of pTB12. The localization of these mAb-defined epitopes was determined by using truncated proteins of the Mycobacterium tuberculosis 65 kDa molecule produced in E. coli. Immunohistochemical analysis showed that B20, B97 and B167 mAbs could detect this antigen in experimental granulomas induced by injection of BCG in the subcutaneous tissue of rats. These mAbs should be useful for analyzing the immunobiologic roles of mycobacterial 65 kDa molecules.


Synthesis of Five Known Brassinosteroid Analogs from Hyodeoxycholic Acid and Their Activities as Plant-Growth Regulators.
Brassinosteroids (BRs) are plant hormones that promote growth in different plant organs and tissues. The structural requirements that these compounds should possess to exhibit this biological activity have been studied. In this work, a series of known BR analogs 5-15, were synthesized starting from hyodeoxycholic acid 4, and maintaining the alkyl side chain as cholic acid or its methyl ester. The growth-promoting effects of brassinolide (1) and synthesized analogs were evaluated by using the rice lamina inclination assay at concentrations ranging from 1 × 10-8-1 × 10-6 M. Our results indicate that in this concentration range the induced bending angle of rice seedlings increases with increasing concentration of BRs. Analysis of the activities, determined at the lowest tested concentration, in terms of BR structures shows that the 2α,3α-dihydroxy-7-oxa-6-ketone moiety existing in brassinolide is required for the plant growing activity of these compounds, as it has been proposed by some structure-activity relationship studies. The effect of compound 8 on cell elongation was assessed by microscopy analysis, and the results indicate that the growth-promoting effect of analog 8 is mainly due to cell elongation of the adaxial sides, instead of an increase on cell number.


Quantitative, chemical, and mineralogical characterization of flue gas desulfurization by-products.
The objective of this study was to demonstrate that simple fractionation and selective dissolution techniques can be used to provide detailed chemical and mineralogical analyses of flue gas desulfurization by-products. The material studied was a mine grout prepared as a 1:1 mixture (wt./wt.) of fly ash (FA) and filter cake (FC) with hydrated lime (50 g kg(-1)) added to improve handling. The hydrated lime was composed mostly of calcite (CaCO3), portlandite [Ca(OH)2], lime (CaO), and brucite [Mg(OH)2] (515, 321, 55, and 35 g kg(-1), respectively) and had low (<6 g kg(-1)) concentrations of most trace elements. The FC contained hannebachite (CaSO3 x 0.5H2O) (786 g kg(-1)) with smaller quantities (<10 g kg(-1)) of calcite, quartz (SiO2), brucite, and gypsum (CaSO4 x 2H2O). Except for B and Cu, trace element concentrations were comparable to those in the hydrated lime. The FA contained both magnetic (222 g kg(-1)) and nonmagnetic (778 g kg(-1)) fractions. The former was composed mostly of hematite (Fe2O3), magnetite (Fe3O4), and glass (272, 293, and 287 g kg(-1), respectively), whereas the latter was enriched in glass, quartz, and mullite (Al6Si2O13) (515, 243, and 140 g kg(-1), respectively). Etching with 1% HF showed that 60 to 100% of trace elements were concentrated in the glass, although some metals (Co, Cr, and Mn) were clearly enriched in the magnetic phase. The aged grout contained 147 g kg(-1) ettringite [Ca6Al2(SO4)3(OH)12 x 26H2O] in addition to 314 g kg(-1) hannebachite and 537 g kg(-1) insoluble phases (mullite, quartz, hematite, magnetite, and glass).


Enhancing linkage analysis of complex disorders: an evaluation of high-density genotyping.
To explore the potential value of recently developed high-density linkage mapping methods in the analysis of complex disease we have regenotyped five nuclear families first studied in the 1996 UK multiple sclerosis linkage genome screen, using Applied Biosystems high-density microsatellite linkage mapping set, the Illumina BeadArray linkage mapping panel (version 3) and the Affymetrix GeneChip Human Mapping 10K array. We found that genotyping success, information extraction and genotyping accuracy were improved with all systems. These improvements were particularly marked with the SNP-based methods (Illumina and Affymetrix), with little difference between these. The extent of additional information extracted is considerable, indicating that reanalysis of existing multiplex families using these newer systems would substantially increase power.


Evaluation of inhibitory effects of thiobarbituric acid derivatives targeting HCV NS5B polymerase.
A series of thiobarbituric acid derivatives were constructed and evaluated for inhibitory activity on hepatitis C virus NS5B polymerase. In biochemical assays using purified viral polymerase and RNA template, the IC(50) value was improved to 0.41 microM from the original compound's 1.7 microM value. In HCV subgenomic replicon assay, the EC(50) value was improved to 3.7 microM from the original compound's 12.3 microM value. CC(50) was higher than 77 microM for all compounds tested, suggesting that they are useful candidates for anti-HCV therapy.


Apoptosis, bcl-2 expression, and proliferative activity in human endometrial stroma and endometrial granulated lymphocytes.
Human endometrial leukocytes undergo regular cyclical changes during the menstrual cycle, with a striking increase in the phenotypically unusual population of CD56+ CD16- endometrial granulated lymphocytes (eGLs) in the late secretory phase and early pregnancy. The factors that regulate this increase in eGL numbers are unclear; their unusual morphology, however, has led to the suggestion that they undergo apoptosis at the end of the menstrual cycle. Apoptosis, bcl-2 expression, and proliferative activity were examined in the stroma of normal cycling, progesterone-treated, and early-pregnancy endometrium. The expression of bcl-2 and the Ki67 proliferation marker by highly purified (> 98% CD56+) eGLs from endometrium during the menstrual cycle and from first-trimester decidua was also studied. Apoptotic cells were rarely observed in the endometrial stroma of any of the samples examined. Stromal bcl-2 expression, however, increased from the proliferative to the premenstrual phase, and double immunohistochemical labeling demonstrated large numbers of bcl-2+ CD56+ eGLs. In contrast, Ki67 expression was high in the endometrial stroma during the proliferative phase, fell during the secretory phase, and rose again premenstrually, because of expression by eGLs. Isolated CD56+ eGLs also showed high bcl-2 and Ki67 expression at the end of the menstrual cycle. Unlike premenstrual endometrium, progesterone-treated endometrium and first-trimester decidua contained few proliferating cells, expressed high levels of bcl-2, and showed no evidence of apoptosis. Thus, eGLs do not undergo apoptosis in premenstrual endometrium, and their regulatory mechanisms remain to be clarified.


Safety of Recombinant Zoster Vaccine in Patients with Inflammatory Bowel Disease.
Patients with inflammatory bowel disease [IBD] have an increased risk of contracting herpes zoster [HZ] infection. However, vaccination rates for HZ are low among IBD patients. A contributing factor may be fear of an IBD flare associated with vaccination. Our aim here was to evaluate if recombinant zoster vaccine [RZV] is associated with an IBD flare. This was a retrospective cohort study using data from the Veterans Affairs Healthcare System [VAHS]. The exposure of interest was receiving RZV. We randomly matched such exposed patients with unexposed individuals. The primary outcome was the first episode of IBD flare within 90 days of the index date. Baseline characteristics were compared between groups using a t-test for continuous variables and Chi-square test for categorical variables. Conditional logistic regression was used to estimate the odds ratio [OR] and 95% confidence interval [CI]. Among the eligible study cohort, 1677 patients received RZV. Thirty-six patients, 20 in the exposed group and 16 in the unexposed group, had a confirmed flare by chart review. The 90-day cumulative incidence of IBD flare was not different between the vaccinated and unvaccinated groups [1.2% among those exposed vs 1.0% among those unexposed, p = 0.503]. The OR for IBD flare associated with RZV vaccination was 1.25 [95% CI: 0.65-2.41]. In a nationwide cohort of stable IBD patients, administration of RZV was not associated with the risk of IBD flare within 90 days. These findings should motivate further use of this highly effective vaccine.


Cystic thymoma coexisting with vascular dysplasia.
We report the case of a 23-year-old female patient, who was admitted to our hospital because of aggravating pain in the right shoulder, right chest and ear accompanied by cough and dyspnea. Imaging revealed a soft tissue mass in the mediastinum in close relation with an additional large mass extending in the right upper thorax, right axilla and neck. The tissue obtained during surgery showed the former mass to be a cystic thymoma, being in contact with an extensive vascular dysplasia. The characteristic clinical presentation, the contribution of imaging, the results of operation, and the follow-up are rather unique. The review of the literature did not reveal similar cases.


Heterogeneity of cognitive style among depressed inpatients.
An inference from the cognitive theories of depression is that only a subset of depressed individuals should exhibit distinctively negative cognitive styles. Although this inference has been supported by previous research, attempts to characterize these depressives have yielded few identifying variables. This study of psychiatric inpatients and normal control subjects identified several characteristics of depressives with very negative cognitive styles by (a) examining traditional depression subtypes, (b) grouping depressives on the basis of clinical observations, and (c) asking whether sex, developmental events, and history and severity of depression predict cognitive styles. We found that borderline personality disorder, negative family dynamics during childhood, a history of sexual abuse, and severity of depression predict cognitive styles. We speculate that aversive developmental events may contribute to cognitive vulnerability to depression.


Targeted strategies directed at the molecular defect: Toward precision medicine for select primary immunodeficiency disorders.
Primary immunodeficiency disorders (PIDs) represent a range of genetically determined diseases that typically have increased susceptibility to infections and in many cases also have evidence of immune dysregulation that often presents as autoimmunity. Most recently, the concept of gain-of-function mutations associated with PIDs has become well recognized and adds a new dimension to the understanding of this group of disorders, moving beyond the more commonly seen loss-of-function mutations. The rapidly expanding genetic defects that have been identified in patients with previously uncharacterized PIDs has opened up the potential for targeted therapy directed at the specific disease-causing abnormality. This has been driven by linking PID-specific genetic defects to the associated unique abnormalities in cellular signaling pathways amenable to directed therapies. These include agents that either block overactive or enhance underresponsive cellular pathways. Selected primary immunodeficiencies were chosen, the genetic defects of which have been recently characterized and are amenable to targeted therapy, as a reflection of the power of precision medicine.


Screening for neural-tube defects and maternal anxiety.
Anxiety levels were studied in 176 women with raised serum alpha-fetoprotein levels at 16-18 weeks gestation, at the time they attended a central assessment clinic, and again 2-3 weeks later in those not found to have a fetus with a neural-tube defect. Methods of imparting information about the serum screening tests and the manner in which a normal amniotic fluid result was conveyed to the patient were also studied. Overall, women attending the clinic for further assessment were extremely anxious, irrespective of the source of their information. Anxiety scores 2-3 weeks after testing were greatly influenced by whether the patient had been given a definite normal result or whether she was told to assume that the result was normal if she did not hear from the clinic. Patients who, after reassessment, did not require amniocentesis had some residual anxiety in spite of verbal reassurance.


Meiotic failure in cyclin A1-deficient mouse spermatocytes triggers apoptosis through intrinsic and extrinsic signaling pathways and 14-3-3 proteins.
Cyclin A1 (Ccna1), a member of the mammalian A type cyclins, is most abundantly expressed in spermatocytes and is essential for spermatogenesis in the mouse. Ccna1- deficient spermatocytes arrest at late meiotic prophase and undergo apoptosis. To further delineate the mechanisms and key factors involved in this process, we have examined changes in expression of genes involved in both intrinsic and extrinsic signaling pathways that trigger apoptosis in the mutant spermatocytes. Our results show that both pathways are involved, and that the factors involved in the intrinsic pathway were expressed earlier than those involved in the extrinsic pathway. We have also begun to identify in vivo Ccna1-interacting proteins, using an unbiased biochemical approach, and identified 14-3-3, a key regulator of apoptosis, as a Ccna1-interacting protein. Expression levels of 14-3-3 proteins remain unchanged between wild type and mutant testes but there were differences in the subcellular distribution. In wild type control, 14-3-3 is detected in both cytosolic and nuclear fractions whereas it is restricted to the cytoplasm in mutant testes. This differential distribution of 14-3-3 may contribute to the induction of apoptosis in Ccna1-deficient spermatocytes. These results provide insight into the apoptotic mechanisms and pathways that are triggered when progression through the meiotic cell cycle is defective in male gametogenesis.


Cervical ectopic thymic cyst: a rare preoperative diagnosis.
We present a case of a 5-year-old child with a painless swelling on the neck. Imaging revealed a multilocular cystic lesion lying in close proximity to carotid vessels. Based on imaging a possibility of ectopic thymic cyst was considered, which was confirmed on histopathology. Ectopic cervical cyst is an infrequent cause of neck cyst in a child which is rarely diagnosed preoperatively.


Analysis of genetic and serology of hepatitis A virus infection during and after outbreak in two junior high schools in Surabaya, Indonesia.
Outbreaks of hepatitis A have occurred in some cities in Indonesia. In Surabaya, the capital city of East Java province, Indonesia, hepatitis A outbreaks have been reported since2013, with a marked increase in the number of cases in 2015. The aim of the present study was to analyze the genetic and serology of acute symptomatic cases (early infection) during a hepatitis A outbreak and asymptomatic cases after the outbreak in two junior high schools in Surabaya in 2015 to 2016. Students with acute symptomatic hepatitis A during the outbreak and other students who were asymptomatic 3 to 4 months after the outbreak were enrolled. Asymptomatic students had no symptoms from the outbreak until they were enrolled. Sera were collected to identify anti-hepatitis A virus (HAV) IgM (by enzyme-linked immunosorbent assay) and HAV genetic variations/genotypes (using polymerase chain reaction [PCR]-sequencing and phylogenetic analysis). A total of 33 (97.1%) out of 34 sera of students with acute symptoms were positive for anti-HAV IgM and 18% of them were positive by PCR, identified as HAV subgenotype IA. No prominent amino acid variations were observed from reported HAV sequences from Indonesia. Among 38 sera of asymptomatic students, most (55.3%) were positive for anti-HAV IgM, while none were positive by PCR. In conclusion, HAV-IA was the only subgenotype identified in acute symptomatic cases during the outbreak. The percentage of HAV-specific IgM-positive cases was very high among acute symptomatic students, but that was also high among asymptomatic students, which might contribute as the important source of infection during the outbreak.


Dilated neonatal cisterna magna and Marfan syndrome.
The authors report the incidental finding of a dilated cisterna magna with an abnormal configuration to the falx in a newborn infant with Marfan syndrome who was recruited to a research study involving whole body MRI. To our knowledge, dilation of the cisterna magna has not previously been reported in patients with Marfan syndrome. Potential implications for antenatal diagnosis, the ethics of recruiting healthy volunteers for research and directions for future work are discussed.


Predation strongly limits demography of a keystone migratory herbivore in a recovering transfrontier ecosystem.
Large herbivore migrations are imperiled globally; however the factors limiting a population across its migratory range are typically poorly understood. Zambia's Greater Liuwa Ecosystem (GLE) contains one of the largest remaining blue wildebeest (Connochaetes taurinus taurinus) migrations, yet the population structure, vital rates, and limiting factors are virtually unknown. We conducted a long-term demographic study of GLE wildebeest from 2012 to 2019 of 107 collared adult females and their calves, 7352 herd observations, 12 aerial population surveys, and concurrent carnivore studies. We applied methods of vital rate estimation and survival analysis within a Bayesian estimation framework. From herd composition observations, we estimated rates of fecundity, first-year survival, and recruitment as 68%, 56%, and 38% respectively, with pronounced interannual variation. Similar rates were estimated from calf-detections with collared cows. Adult survival rates declined steadily from 91% at age 2 years to 61% at age 10 years thereafter dropping more sharply to 2% at age 16 years. Predation, particularly by spotted hyena, was the predominant cause of death for all wildebeest ages and focused on older animals. Starvation only accounted for 0.8% of all unbiased known natural causes of death. Mortality risk differed substantially between wet and dry season ranges, reflecting strong spatio-temporal differences in habitat and predator densities. There was substantial evidence that mortality risk to adults was 27% higher in the wet season, and strong evidence that it was 45% higher in the migratory range where predator density was highest. The estimated vital rates were internally consistent, predicting a stable population trajectory consistent with aerial estimates. From essentially zero knowledge of GLE wildebeest dynamics, this work provides vital rates, age structure, limiting factors, and a plausible mechanism for the migratory tendency, and a robust model-based foundation to evaluate the effects of potential restrictions in migratory range, climate change, predator-prey dynamics, and poaching.


A phylogenetic test of the Red Queen Hypothesis: outcrossing and parasitism in the Nematode phylum.
Sexual outcrossing is costly relative to selfing and asexuality, yet it is ubiquitous in nature, a paradox that has long puzzled evolutionary biologists. The Red Queen Hypothesis argues that outcrossing is maintained by antagonistic interactions between host and parasites. Most tests of this hypothesis focus on the maintenance of outcrossing in hosts. The Red Queen makes an additional prediction that parasitic taxa are more likely to be outcrossing than their free-living relatives. We test this prediction in the diverse Nematode phylum using phylogenetic comparative methods to evaluate trait correlations. In support of the Red Queen, we demonstrate a significant correlation between parasitism and outcrossing in this clade. We find that this correlation is driven by animal parasites, for which outcrossing is significantly enriched relative to both free-living and plant parasitic taxa. Finally, we test hypotheses for the evolutionary history underlying the correlation of outcrossing and animal parasitism. Our results demonstrate that selfing and asexuality are significantly less likely to arise on parasitic lineages than on free-living ones. The findings of this study are consistent with the Red Queen Hypothesis. Moreover, they suggest that the maintenance of genetic variation is an important factor in the persistence of parasitic lineages.


Chondroitin sulphate distribution in broiler chicken carcasses.
1. The content of chondroitin sulphate (CS), known as a nutraceutical, was estimated in broiler chicken carcasses by analysing sulphated glycosaminoglycan uronic acid in posterior sternum (keel) cartilage and bones from 4 parts (wing, leg, front and hind) of carcasses. 2. The results of the present study suggested that approximately 0.63 g CS uronic acid (or 1.9 g as CS) can be extracted from a 1.66 kg whole broiler chicken carcass. The amount of extractable CS from keel cartilage, which has been reported as a valuable source of CS in broiler chicken carcasses, was surprisingly low (<10% of total CS).


ON THE EVOLUTION OF PARTHENOGENESIS. II. INBREEDING AND THE COST OF MEIOSIS.
Quantitative models of genetic change were analyzed to study the effect of inbreeding on the conditions for the evolution of parthenogenesis. Although inbreeding has been proposed as a key factor that may resolve the apparent paradox between the success of biparental reproduction and the genetic advantages of uniparental reproduction, the results indicate that inbreeding does not greatly change the cost of meiosis in diploids and actually increases it in haplodiploids. Inbreeding increases parent-offspring relatedness and the reproductive value of females. These direct effects act antagonistically on the cost of meiosis: higher relatedness between parents and biparentally-derived offspring promotes biparental reproduction, and high reproductive value of females promotes thelytoky. In diploids the two effects cancel one another, while in haplodiploids the latter predominates. A survey by Hamilton (1967) showed that a high proportion of haplodiploid species that undergo close inbreeding have thelytokous relatives, an association that is consistent with the result obtained here that, apart from its effect on the sex ratio, inbreeding directly promotes parthenogenesis in haplodiploids.


Combinatorial discovery of two-photon photoremovable protecting groups.
A design principle for a two-photon photochemically removable protecting group based on sequential one-photon processes has been established. The expected performance of such groups in spatially directed photoactivation/photodeprotection has been shown by a kinetic analysis. One particular molecular class fitting into this design, the nitrobenzyl ethers of o-hydroxycinnamates, has been presented. An initial demonstration of two-photon deprotection of one such group prompted further optimization with respect to photochemical deprotection rate. This was accomplished by the preparation and screening of a 135-member indexed combinatorial library. Optimum performance for lambda >350 nm deprotection in organic solvent was found with 4,5-dialkoxy and -cyano substitution in the nitrobenzyl group and 4-methoxy substitution in the cinnamate.


Quality Sleep Is Associated With Overnight Metabolic Rate in Healthy Older Adults.
Increasing age is associated with an increase in overnight metabolic rate. To determine the relationship between quality sleep, sleep efficiency, and overnight metabolic rate as measured in a respiration chamber in older participants. The study design was cross sectional. Forty participants, aged 50 to 83 years (17 males, age 63±7 years, body mass index 25.7±2.3kg/m2) spent one night in a respiration chamber to measure sleep stages by polysomnography and overnight metabolic rate (OMR). Data were collected between 23:00 and 07:00. Subsequently basal metabolic rate (BMR) was measured under a ventilated hood. Quality sleep was calculated as time spent in rapid-eye movement (REM) sleep and slow wave sleep divided by total sleep time, and sleep efficiency was calculated as total sleep time divided by the sleep period time. Body movement was measured between 23:00 and 07:00 with an accelerometer on the wrist. Overnight metabolic rate was adjusted for body size by dividing by basal metabolic rate (OMR/BMR). OMR/BMR was positively associated with age (r = 0.48, p < .001), and quality sleep was negatively associated with age (r = -0.51, p < .001). The variance of OMR/BMR was significantly explained by quality sleep (r = -0.58, p < 0.001). Body movement was negatively related to sleep efficiency (r = -0.38, p<0.01) with no effect on OMR/BMR. When OMR/BMR was adjusted for quality sleep, the effect of age was non significant. Quality sleep is inversely associated with the age-related rise in overnight metabolic rate, suggesting that increased overnight metabolic rate is a biological sign of ageing as a consequence of diminished quality sleep.


Rapid solid-phase extraction coupled with GC-MS method for the determination of venlafaxine in rat plasma: Application to the drug-drug pharmacokinetic interaction study of venlafaxine combined with fluoxetine.
A rapid and sensitive gas chromatography with mass spectrometry method for the determination of venlafaxine in rat plasma has been developed and applied to a drug-drug interaction study of fluoxetine on pharmacokinetics of venlafaxine in rats. Rat plasma was spiked with 2% aqueous ammonia before subjected to preactivated C18 solid-phase extraction columns and eluted with methanol. No endogenous interferences were observed under optimal condition. The calibration curve was linear (R2 = 0.9994) in the range of 10-1000 ng/mL. The quantification limit of venlafaxine in rat plasma was 10 ng/mL. The accuracy was in the range of 85-110%, and the extraction recovery was no less than 50%. Both the intra- and interday precision were 5.0-10.7%. The concentration-time curve showed that plasma concentrations of the coadministration group (group B) were higher than that of single dose group (group A). Both values of Cmax (0.069 mg/L) and AUC0→∞ (0.291 mg h/L) in group B were statistically greater than that of Cmax (0.046 mg/L) and AUC0→∞ (0.181 mg·h/L) in group A (P < 0.05). The results indicated that a significant effect of fluoxetine was shown on the pharmacokinetics of venlafaxine, suggesting that drug-drug interactions are of concern for the treatment of depression with the combined use of venlafaxine and fluoxetine.


Current perspectives on bisphosphonate treatment in Paget's disease of bone.
Paget's disease of bone is a chronic metabolic bone disease with focal increase in bone turnover. The exact etiology of the disease is uncertain, although genetic and environmental factors are believed to be important. Bisphosphonate is the main class of medication being used to control disease activity via its antiresorptive effect. This review discusses the controversies concerning the use of bisphosphonates in the treatment of Paget's disease of bone, the efficacy of different bisphosphonates in controlling disease activity, and the possible rare side effects of bisphosphonates. Symptoms are the main indication for treatment in Paget's disease of bone. As treatment benefits in asymptomatic individuals remain controversial and nonevidence based, the decision to treat these patients should be individualized to their risk and benefit profiles. There are several trials conducted to evaluate and compare the efficacy of different regimes of bisphosphonates for treating Paget's disease of bone. Most trials used biochemical markers rather than clinical symptoms or outcomes as parameters for comparison. Zoledronate is an attractive option as it can achieve high rates of biochemical remission and sustain long duration of suppression by a single dose. Atypical femoral fracture and osteonecrosis of the jaw are two rare and severe side effects reported, possibly related to the use of bisphosphonates in patients with osteoporosis and malignancy-induced hypercalcemia. As the regimes of bisphosphonates used for treating Paget's disease of bone are different from those two diseases, the risks of developing these two possible side effects are expected to be very low, although this remains unknown. Vitamin D and calcium supplement should be given to patients at risk of vitamin D insufficiency when given zoledronate, as symptomatic hypocalcemia may develop. For those intolerant of bisphosphonates, subcutaneous calcitonin can be used for a limited period due to its associated risk of malignancy.


Thiopental improves renal ischemia-reperfusion injury.
Ischemia/reperfusion (I/R) occurs in a number of pathological conditions, including myocardial infarction, stroke, aortic surgery, cardiopulmonary bypass surgery, organ transplantation, resuscitation, and critical care. Massive and abrupt release of oxygen-free radicals after reperfusion triggers oxidative damage. Before critical operations or after resuscitation, it would be wise to find a suitable prophylactic treatment to avoid I/R damage. We aimed to determine whether several commonly used intravenous anesthetics protect against renal I/R injury. Animals were randomly divided into seven groups, each consisting of six animals: sham group, control group, thiopental group, propofol group, intralipid group, etomidate group, and ketamine group. At the end of the 60-min ischemic period, 60 min reperfusion was established and the materials administered 15 min before the reperfusion. At the end of the reperfusion period, the samples of blood and tissue were reaped for biochemical and serological evaluation. I/R procedure significantly increased malondialdehyde (MDA) levels, decreased catalase (CAT) activities, and superoxide dismutase (SOD) levels. The lowest MDA mean level was in the thiopental group and the highest MDA mean level was in control group. The lowest CAT mean level was in the intralipid group and the highest CAT mean level was in the etomidate group. The lowest SOD mean level was in the control group and the highest SOD mean level was in the propofol group. Thiopental and propofol, especially thiopental, are more effective to protect renal I/R injury.


Ultracompact photonic-waveguide circuits in Si-pillar photonic-crystal structures for integrated nanophotonic switches.
Highly integrated optical device technology based on square-lattice Si-pillar photonic-crystal-(PC) waveguides is described. The Si-pillar PC waveguides are now ready to use, since efficient optical coupling structures to Si-wire waveguides have been devised. Nanophotonic switches using the Si-pillar-PC waveguides were experimentally demonstrated. The nanophotonic switches make use of two of the features of Si-pillar photonic crystal waveguides. One is the property of slow-light and the other is the usability of zero-radius 90 degrees bends, both of which enable waveguide-based optical devices to be greatly miniaturized. Even apart from the cut-off wavelength, the group index of the pillar-PC waveguides was about 7.8, which was about twice that of a Si-wire waveguide for the entire C-band of telecommunications wavelengths. The 3-dB couplers we fabricated were only 3.2-microm long thanks to the 90 degrees sharp bends, and they operated throughout the entire C-band. Waveguide-cross operation was also demonstrated in the entire C-band. Asymmetric Mach-Zehnder interferometers (MZIs) were configured by using the 3-dB couplers in an area of 13.2 x 37.2 microm. An MZI with a Si-wire heater successfully operated with an extinction ratio of about 20 dB at a heating power of 17 mW. It is strongly suggested that Si-pillar PC photonic-waveguide technology should help us to achieve densely integrated optical-matrix switches demanded for future photonic-telecommunication systems.


PRODUCTION, MANAGEMENT AND THE ENVIRONMENT SYMPOSIUM: Measurement and mitigation of reactive nitrogen species from swine and poultry production.
Reactive nitrogen (Nr) species include oxides of nitrogen [N; nitric oxide, nitrogen dioxide and nitrous oxide (NO)], anions (nitrate and nitrite), and amine derivatives [ammonia (NH), ammonium salts and urea]. Of the different Nr species, air emissions from swine and poultry facilities are predominantly NH followed by NO. Excreta emissions are NH, ammonium ions, and urea with trace amounts of nitrate and nitrite. Farm systems and practices that handle manure as a wet product without pH modification favor almost exclusive NH production. Systems and practices associated with dry manure handling and bedded systems emit more NH than NO. Results from a turkey grow-out study estimated that just under 1% of consumed N was emitted as NO from housing, compared with just under 11% emitted as NH. Despite generally less NO emissions from animal housing compared with crop field emissions, NO emissions from housing are often greater than estimated. Lagoon systems emit more NO than either slurry or deep pit swine systems. Deep pit swine buildings emit only one-third the NO that is emitted from deep bedded swine systems. Laying hen, broiler chicken, and turkey buildings emit over 4 times as much NO as swine housing, on a weight-adjusted basis. Critical control points for mitigation center on: 1) reducing the amount of N excreted and, therefore, excreted N available for loss to air or water during housing, manure storage, or following land application of manures; 2) capturing excreted N to prevent release of N-containing compounds to air, water, or soil resources; or 3) conversion or treatment of N-containing compounds to non-reactive N gas.


The effect of sleep deprivation on postural stability among physically active young adults.
The study aimed to evaluate the effect of sleep deprivation on postural stability among physically active young adults. The study involved 22 physical education students. Average velocities and spatial distribution of the center of pressure displacements were taken as indicators of postural stability (double and one-leg standing). Two-way ANOVA with two factors of repeated measurements-"session" (control-experimental) and "daytime" (evening-morning)-was used. For indicators of the spatial distribution of the center of pressure in double stance with eyes open and eyes closed, and for average velocities for measurements with eyes closed, statistically significant interaction effects were found (at least p < 0.01, ƞ2 > 0.36, power statistics > 0.90) with the general tendency of higher results in the morning in the session with sleep deprivation than in the control session. In one-leg standing, an increase of average velocities was observed in the control session, and no differences in the session with sleep deprivation (interaction effect: at least p < 0.01, ƞ2 > 0.37, power statistics > 0.90). Besides spatial distribution indicators in double stance, there were no statistical differences between evening-morning tests in the session with sleep deprivation. Despite significant interaction effects, only the results of spatial distribution indicators in double stance were higher in the morning than in the evening in the session with sleep deprivation. So, no clear decline in postural stability after sleep deprivation was observed. This may suggest that sleep deprivation prevents natural regeneration rather than significantly worsening postural stability among physically active adults. It's possible that systematic physical activity might be one of the factors decreasing the risk of accidents among people exposed to sleep deprivation.


Anti-DR5 mAb inhibits proliferation of human fibroblast-like synovial cells and reduces their cytokine secretion in vitro.
We have previously reported that anti-death receptor 5 (DR5) monoclonal antibody (mAb) is therapeutically effective in the treatment of rheumatoid arthritis (RA) in a collagen-induced arthritis rat model. However, the molecular mechanism and the effect of anti-DR5 mAb on proapoptotic genes and cytokine secretion in the human fibroblast-like synovial cells (FLS) requires further clarification. This study may provide new evidence for the application of anti-DR5 mAb as a treatment for RA. Human FLS were isolated from patients with RA and were treated with anti-DR5 mAb. An MTT assay and flow cytometry were used to detect the induction of apoptosis in vitro. Cytokine secretion by the FLS was detected using the enzyme-linked immunosorbent assay. The mRNA expression was assessed by reverse transcription polymerase chain reaction, and the protein expression was analyzed by Western blot. The apoptotic pathway was investigated further using a caspase inhibition assay. Anti-DR5 mAb-induced apoptosis in human RA FLS in vitro. The protein expressions of caspase-8, -3, and -9 were decreased in human anti-DR5 mAb-treated FLS in a dose-dependent manner through exposure to a caspase inhibitor, indicating that anti-DR5 mAb induction of apoptosis is through the caspase pathway. Decreased levels of tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) were detected after treatment with anti-DR5 mAb in vitro. Anti-DR5 mAb may induce apoptosis in human FLS through the caspase pathway and through decreased secretions of TNF-α and IFN-γ.


Comparative study of the characteristics of family planning service users and non-users in northwest Ethiopia.
Three hundred and forty-four (49.6%) family planning users and 350 (50.4%) non-family planning users were included in a study to assess the factors that are associated with utilisation of family planning services at different levels of health institutions in northwest Ethiopia. Desire for (more) children was the most common reason (51.4%) for not using family planning services, followed by inadequate knowledge about family planning services (14.6%). A higher proportion of the non-users were illiterate, of lower parity, and had their last child under one year of age (P<0.05). In logistics regression analysis family planning was significantly lower in the illiterate. Positive husband's attitude had the strongest association (OR 9.3, 95% CI 4.6, 18.7) with family planning. In addition to programs that create demand for smaller well-spaced children, IEC and family planning services should target men and strong emphasis should be given to use of family planning methods in as early period after birth as possible.


Histological Phenotyping in Eosinophilic Esophagitis: Localized Proximal Disease Is Infrequent but Associated with Less Severe Disease and Better Disease Outcome.
It is still unknown whether eosinophilic esophagitis (EoE) patients with localized disease are different from those with extended disease. We evaluated prospectively included patients in the Swiss EoE cohort. Data on all patients with active disease at baseline, no concomitant gastroesophageal reflux disease, no strictures at baseline, and at least one follow-up visit were analyzed. We compared patients with histologically localized proximal versus distal versus extended (=proximal and distal) disease with regard to patient, disease characteristics, disease presentation, and development of complications. We included 124 patients with a median of 2.5 years of follow-up (73.4% males, median age 35.0 years). Ten patients had proximal (8.1%), 46 patients had distal (37.1%), and 68 patients had extended disease (54.8%). Patients with proximal disease were significantly more often females (80%) compared with patients with distal (26.1%, p = 0.002) or extended disease (19.1%, p < 0.001) and reported less severe symptoms (VAS 0 vs. VAS 1, p = 0.001). Endoscopic and histological disease was less pronounced in the proximal esophagus of proximal EoE compared to extended disease (EREFS 1.0 vs. 3.0, p = 0.001; 27.0 eos/hpf vs. 52.5 eos/hpf, p = 0.008). Patients with proximal disease were less likely to undergo dilation compared to patients with distal disease in the follow-up (3.3% vs. 23.3%, p = 0.010). In a multivariate Cox regression model, proximal eosinophilia was less likely to be associated with treatment failure compared to distal eosinophilia. Although isolated proximal EoE is infrequent, it is associated with less severe disease and better disease outcome. Proximal disease appears to present a unique EoE phenotype.


Transcriptome Analysis and Gene Identification in the Pulmonary Artery of Broilers with Ascites Syndrome.
Pulmonary arterial hypertension, also known as Ascites syndrome (AS), remains a clinically challenging disease with a large impact on both humans and broiler chickens. Pulmonary arterial remodeling presents a key step in the development of AS. The precise molecular mechanism of pulmonary artery remodeling regulating AS progression remains unclear. We obtained pulmonary arteries from two positive AS and two normal broilers for RNA sequencing (RNA-seq) analysis and pathological observation. RNA-seq analysis revealed a total of 895 significantly differentially expressed genes (DEGs) with 437 up-regulated and 458 down-regulated genes, which were significantly enriched to 12 GO (Gene Ontology) terms and 4 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways (Padj<0.05) regulating pulmonary artery remodeling and consequently occurrence of AS. These GO terms and pathways include ribosome, Jak-STAT and NOD-like receptor signaling pathways which regulate pulmonary artery remodeling through vascular smooth cell proliferation, inflammation and vascular smooth cell proliferation together. Some notable DEGs within these pathways included downregulation of genes like RPL 5, 7, 8, 9, 14; upregulation of genes such as IL-6, K60, STAT3, STAT5 Pim1 and SOCS3; IKKα, IkB, P38, five cytokines IL-6, IL8, IL-1β, IL-18, and MIP-1β. Six important regulators of pulmonary artery vascular remodeling and construction like CYP1B1, ALDH7A1, MYLK, CAMK4, BMP7 and INOS were upregulated in the pulmonary artery of AS broilers. The pathology results showed that the pulmonary artery had remodeled and become thicker in the disease group. Our present data suggested some specific components of the complex molecular circuitry regulating pulmonary arterial remodeling underlying AS progression in broilers. We revealed some valuable candidate genes and pathways that involved in pulmonary artery remodeling further contributing to the AS progression.


Medical students' perception of the learning environment at King Saud University Medical College, Saudi Arabia, using DREEM Inventory.
The students' perception of the learning environment is an important aspect for evaluation and improvement of the educational program. The College of Medicine at King Saud University (KSU) reformed its curriculum in 2009 from a traditional to a system-oriented hybrid curriculum. The objective of the present study was to determine the perception of the second batch (reformed curriculum) of medical graduates about the educational environment at the College of Medicine, KSU, using the Dundee Ready Education Environment Measure (DREEM) scale. The fifth year medical students were asked to evaluate the educational program after graduation in May 2014. The questionnaire was distributed to the graduate students electronically. The DREEM questionnaire consisted of 50 items based on Likert's scale; and five domains, namely, students' perceptions of learning, perceptions of teachers, academic self-perceptions, perceptions of atmosphere, and social self-perceptions. Data were analyzed using SPSS. A total of 62 students participated in the study. The score for students' perception of learning among medical students ranged from 2.93 to 3.64 (overall mean score: 40.17). The score for students' perception of teachers ranged from 2.85 to 4.01 (overall mean score: 33.35). The score for students' academic self-perceptions ranged from 3.15 to 4.06 (overall mean score: 28.4). The score for students' perception of atmosphere ranged from 2.27 to 3.91 (overall mean score: 41.32). The score for students' social self-perceptions ranged from 2.85 to 4.33 (overall mean score: 24.33). The general perceptions of the students in all five sub-scales were positive. The overall student's perception about the educational environment was satisfactory. This study was important to evaluate the students' perception of the learning environment among medical graduates of the reformed curriculum and provided guidance on areas of improvement in the curriculum.


Promotion of frequent tanning sessions by indoor tanning facilities: two studies.
Indoor tanning may increase the risk of melanoma and other health problems. Frequent users of indoor tanning facilities may be at particularly high risk. In study 1 our purpose was to assess the prevalence and nature of indoor tanning advertisements; in study 2 we aimed to assess tanning facility compliance to recommended exposure schedules. In study 1, tanning facility advertisements over a 4-month period from 24 San Diego County newspapers were monitored. In study 2, we assessed compliance with recommended exposure schedules via a telephone interview of 60 San Diego County tanning facilities. Approximately 75% of the indoor tanning advertisements promoted unlimited tanning. Only 5% of facilities were in compliance with recommended tanning schedules, and 100% offered "unlimited" tanning packages. These findings suggest that the indoor tanning industry, through pricing incentives that allow frequent sessions, may be promoting overexposure to UVR. Stronger legislation is needed to address this issue.


Instructional design and the emergency department.
This paper studies the effectiveness of different educational programmes. A number of cohorts of junior doctors received one of two different induction training packages. These programmes differed principally in the length of time over which they were administered. The junior doctors were then assessed using a structured questionnaire. There was a noticeable difference in the factual recall between the cohorts depending on what programme they had attended. Those attending the programme delivered over an extended period showed better performance on assessment. The interpretations and implications of these findings are discussed.


Economic evaluation of four treatment strategies for postmenopausal patients with osteoporosis and a recent fracture in mainland China: a cost-effectiveness analysis.
Postmenopausal patients with osteoporosis who have a recent fracture are at very high risk of fracture, and this study finds that stratified treatment based on fracture risk would be a cost-effective treatment option for this population. To evaluate the cost-effectiveness of four anti-osteoporosis medications (denosumab, zoledronate, teriparatide, and alendronate) for postmenopausal osteoporotic women in mainland China, using a stratified treatment strategy recommended by the American Association of Clinical Endocrinologists and the American College of Endocrinology (AACE/ACE). A microsimulation Markov model was used to compare the cost-effectiveness of the four treatments in postmenopausal osteoporotic patients of different ages (65, 70, 75, and 80 years), with a recent fracture from the Chinese healthcare perspective. The primary outcome was the incremental cost-effectiveness ratio (ICER), which represent the incremental cost per quality-adjusted life-year (QALY) obtained. One-way deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA) were performed to assess the robustness of model findings. Alendronate was dominated by denosumab-to-alendronate and zoledronate at all ages examined, indicating that the costs of the two drugs were lower, but QALYs was greater. However, teriparatide-to-alendronate yielded an ICER of $76,432.07/ QALY, compared with alendronate at age 65, which exceeded the pre-determined willingness-to-pay threshold of $37,653/ QALY. The results were similar at other ages. The DSA showed that the most sensitive parameters were drug efficacy for vertebral and wrist fractures, the relative risk of vertebral fractures, and the persistence of the drugs. The PSA showed that zoledronate had a 100% probability of being the most cost-effective treatment, with a willingness-to-pay threshold of $37,653/ QALY. Stratified treatment based on very high fracture risk is more cost-effective than conventional pills in mainland China. Among the stratified treatments, zoledronate is the optimal option.


Role of microRNA miR171 in plant development.
MicroRNAs (miRNAs) are endogenous non-coding small RNA with 19-24 nucleotides (nts) in length, which play an essential role in regulating gene expression at the post-transcriptional level. As one of the first miRNAs found in plants, miR171 is a typical class of conserved miRNAs. The miR171 sequences among different species are highly similar, and the vast majority of them have both "GAGCCG" and "CAAUAU" fragments. In addition to being involved in plant growth and development, hormone signaling and stress response, miR171 also plays multiple and important roles in plants through interactions with microbe and other small-RNAs. The miRNA functions by regulating the expression of target genes. Most of miR171's target genes are in the GRAS gene family, but also include some NSP, miRNAs, lncRNAs, and other genes. This review is intended to summarize recent updates on miR171 regarding its function in plant life and hopefully provide new ideas for understanding miR171 function and regulatory mechanisms.


MHC-DRB exon 2 allele polymorphism in Indian river buffalo (Bubalus bubalis).
The polymorphism of the major histocompatibility complex (MHC) class II DRB gene of riverine buffalo (Bubalus bubalis) was studied. Second exon sequences from the buffalo DRB locus, homologous to the cattle DRB3 gene, were amplified and characterized. A combination of single strand conformation polymorphism (SSCP) and heteroduplex analysis (HA) in a non-denaturing gel was used to identify new DRB second exon sequences. SSCP, HA and finally sequencing allowed the identification of 22 MHC-DRB exon 2 alleles from 25 unrelated Indian river buffalo. These are the first river buffalo DRB second exon sequences reported. A high degree of polymorphism in the sequences encoding the peptide binding regions was observed and some amino acid substitutions were found unique to the river buffalo.


Coordinate modulation of murine hepatic xanthine oxidase activity and the cytochrome P-450 system by interferons.
The role of xanthine oxidase (XO) in the interferon (IFN)-dependent modulation of the hepatic cytochrome P-450 system was assessed in SENCAR mice. Intraperitoneal administration of 10(4)-10(5) units of IFN-gamma resulted in dose-dependent increases in hepatic XO activities. XO activity was significantly elevated within 12 h of IFN-gamma treatment, and reached a maximum between 24-48 h, and returned to basal levels within 72-96 h. Although the kinetics of increase and decline of XO activity correlated with the loss and subsequent recovery of hepatic P-450 levels, there was no quantitative correlation between hepatic XO activity and P-450 content. Comparable results were obtained in mice pretreated with the P-450 inducer Aroclor 1254 3 days prior to IFN-gamma administration. The increases in XO activity following IFN-gamma treatment were the consequence of increases in xanthine dehydrogenase (XD), and the conversion of XD to XO. The ad libitum administration of allopurinol to IFN-gamma-treated mice reduced XO specific activity to approximately 4% of the basal activity of control mice, but did not prevent reductions in cytochrome P-450 levels or the activities of two P-450 dependent monooxygenases. Collectively, these data suggest that the reductions in the hepatic P-450 system noted after IFN administration are not a consequence of elevated XO activities.


Targeting non-coding RNAs with the CRISPR/Cas9 system in human cell lines.
The CRISPR/Cas has been recently shown to be a powerful genome-editing tool in a variety of organisms. However, these studies are mainly focused on protein-coding genes. The present study aims to determine whether this technology can be applied to non-coding genes. One of the challenges for knockout of non-coding genes is that a small deletion or insertion generated by the standard CRISPR/Cas system may not necessarily lead to functional loss of a given non-coding gene because of lacking an open reading frame, especially in polyploidy human cell lines. To overcome this challenge, we adopt a selection system that allows for marker genes to integrate into the genome through homologous recombination (HR). Moreover, we construct a dual guide RNA vector that can make two cuts simultaneously at designated sites such that a large fragment can be deleted. With these approaches, we are able to successfully generate knockouts for miR-21, miR-29a, lncRNA-21A, UCA1 and AK023948 in various human cell lines. Finally, we show that the HR-mediated targeting efficiency can be further improved by suppression of the non-homologous end joining pathway. Together, these results demonstrate the feasibility of knockout for non-coding genes by the CRISPR/Cas system in human cell lines.


Light-induced transformation of alkylurea derivatives in aqueous TiO2 dispersion.
The light-induced degradation of alkylurea derivatives under simulated solar irradiation has been investigated in aqueous solutions containing TiO(2) as a photocatalyst. Herein, we will focus on how the presence of one or more methyl (or ethyl) groups on urea modifies the kinetics of disappearance and influences both the ratio and the extent of the inorganic nitrogen formation caused by different degradation pathways. In the present work, we have elucidated a mechanism for the formation of transformation products of the alkyl derivatives by combining several analytical and spectroscopic procedures and the theoretical simulation of ab initio calculations. In all cases, N-demethylation represents only a secondary pathway, while the main transformation proceeds through an unexpected cyclization, involving (m)ethyl- and di(m)ethylureas with the formation of (methyl)amino-2,3-dihydro-1,2,4-oxadiazol-3-one as the principal intermediate of the reaction (with a yield of 60 %). This behaviour is rather unexpected and in contrast with the typical photocatalyzed transformation pathways, which proceed through the formation of more simple structures.


Dropout From an eHealth Intervention for Adults With Type 2 Diabetes: A Qualitative Study.
Adequate self-management is the cornerstone of type 2 diabetes treatment, as people make the majority of daily treatment measures and health decisions. The increasing prevalence of type 2 diabetes mellitus (T2DM) and the complexity of diabetes self-management demonstrate the need for innovative and effective ways to deliver self-management support. eHealth interventions are promoted worldwide and hold a great potential in future health care for people with chronic diseases such as T2DM. However, many eHealth interventions face high dropout rates. This led to our interest in the experiences of participants who dropped out of an eHealth intervention for adults with T2DM, based on the Guided Self-Determination (GSD) counseling method. In this study, we aimed to explore experiences with an eHealth intervention based on GSD in general practice from the perspective of those who dropped out and to understand their reasons for dropping out. To the best of our knowledge, no previous qualitative study has focused on participants who withdrew from an eHealth self-management support intervention for adults with T2DM. A qualitative design based on telephone interviews was used to collect data. The sample comprised 12 adults with type 2 diabetes who dropped out of an eHealth intervention. Data were collected in 2016 and subjected to qualitative content analysis. We identified one overall theme: "Losing motivation for intervention participation." This theme was illustrated by four categories related to the participants' experiences of the eHealth intervention: (1) frustrating technology, (2) perceiving the content as irrelevant and incomprehensible, (3) choosing other activities and perspectives, and (4) lacking face-to-face encounters. Our findings indicate that the eHealth intervention based on GSD without face-to-face encounters with nurses reduced participants' motivation for engagement in the intervention. To maintain motivation, our study points to the importance of combining eHealth with regular face-to-face consultations. Our study also shows that the perceived benefit of the GSD eHealth intervention intertwined with choosing to focus on other matters in complex daily lives are critical aspects in motivation for such interventions. This indicates the importance of giving potential participants tailored information about the aim, the content, and the effort needed to remain engaged in complex interventions so that eligible participants are recruited. Finally, motivation for engagement in the eHealth intervention was influenced by the technology used in this study. It seems important to facilitate more user-friendly but high-security eHealth technology. Our findings have implications for improving the eHealth intervention and to inform researchers and health care providers who are organizing eHealth interventions focusing on self-management support in order to reduce dropout rates.


Mechanism of the size dependence of the superconducting transition of nanostructured Nb.
A direct measurement of the superconducting energy gap by point contact spectroscopy in nanostructured Nb films shows that the gap decreases with a reduction in the average particle size. The superconducting T(c), obtained from transport and magnetic measurements, also decreases with size and scales with the energy gap. The size dependence of the superconducting properties in this intermediate coupling type II superconductor is therefore governed by changes in the electronic density of states rather than by phonon softening. Consistent with the Anderson criterion, no T(c) was observed for sizes below 8 nm.


[Structure of nuclear pre-mRNA. XIII. Hybridization properties of triphosphorylated 5'-end fragments].
Triphosphorylated 5'-end fragments about 100 nucleotides long were prepared from purified nuclear pre-mRNA using a modified hydroxyapatite method. These fragments as well as fragments of total pre-mRNA were polyadenylated by ATP:RNA adenyl-transferase and used as templates for the synthesis of [32P]cDNA by reverse transcriptase in the presence of an oligo(dT)-primer, cDNA transcribed from total fragments of pre-mRNA and from 5'-end fragments (5'-cDNA) were hybridized with excess of nuclear pre-mRNA. The extent of hybridization was 65-70 and 80-85% in different experiments. 18% of total cDNA and 35% of 5'-cDNA hybridized with mRNA from polysomes. A high homology between mRNA and triphosphorylated 5'-ends of pre-mRNA may be explained in the terms of splicing. The sequences adjacent to the triphosphorylated 5'-ends of pre-mRNA represent a specific class with complexity about 2.10(5) nucleotides. Less than 30% of 5'-cDNA hybridized with intermediately repetitive DNA, while the main portion hybridized with unique DNA sequences. About 15% of 5'-cDNA contain oligo (dA) sequences, originated from oligo (U) in the pre-mRNA.


Pulp Vitality of Maxillary Canines After Alveolar Cleft Bone Grafting: Pulse Oximetry Versus Electric Pulp Test Versus Cold Test.
Assessment of pulp vitality is necessary prior to any dental treatment. The purpose of this study was to assess pulp vitality of bilateral canines in unilateral cleft patients following alveolar bone graft surgery using pulse oximetry, electrical pulp test, and cold test. This analytical, cross-sectional study was conducted on canines of 20 unilateral cleft patients who had alveolar bone graft surgery. Pulp vitality of canines was evaluated postoperatively by pulse oximetry, electrical pulp test, and cold test. Data were analyzed using t test, Mann-Whitney test, and χ2 test. P ≤0.05 was considered statistically significant. The mean pulp SpO2 was significantly lower in canines at the cleft side compared with the normal side (85.04 ± 4.65 versus 87.78 ± 4.01, P = 0.05). The response to cold test was not significantly different (P = 0.056). The mean response to electrical pulp was not significantly different between the 2 sides either (P = 0.62). The mean SpO2 of canines was lower at the cleft side than normal side but both sides had adequate blood supply and were vital.


Non-invasive anatomical and functional imaging for the detection of coronary artery disease.
Coronary artery disease (CAD) is still an important cause of morbidity and mortality in the Western world. The gold standard for assessing significant coronary artery stenosis is invasive coronary angiography. Several disadvantages of the technique in combination with the fact that a substantial number of patients referred for conventional angiography appear free from significant stenosis have led to the pursuit of non-invasive imaging modalities for the diagnosis of CAD. The traditional modalities for this purpose are gated single-photon emission computed tomography, position emission tomography, (contrast) stress echocardiography and cardiac magnetic resonance (CMR), and these techniques can be characterized as functional imaging techniques as they detect ischaemia. Although the presence of a flow-limiting stenosis can be adequately ruled out with these techniques, atherosclerosis cannot be visualized with functional techniques. For this purpose, non-invasive coronary angiography techniques (computed tomography and CMR) are currently under development. The purpose of this review is to provide the reader an overview of the currently used imaging modalities to detect CAD.


Comparing the Energy-Stretch Properties of Two Compression Bandage Systems in a Laboratory-Based Test under Controlled Conditions.
To compare the characteristics of two commercially available compression systems, a dual-compression bandage system (DCS) and a traditional two-layer bandage (TLB), using a laboratory bench test. The compression systems were evaluated in a computer-controlled tensile test to generate force-deflection curves for each sample. The compressive work and the theoretical pressure applied to the limb by the respective compression bandages were calculated at the maximum stretch and a stretch instructed by the manufacturers. The manufacturer of the DCS provides reference points on how much the bandage should be stretched to provide the desired pressure, and the TLB stretch was calculated from the product's datasheet. The combined results of layers 1 and 2 for the DCS showed greater load and work than the TLB at both the maximum and recommended stretch. The recommended stretch for DCS and TLB was less than 50% of the deflection up to the breaking point. The high work provided by the two layers of the DCS suggests a wider range of performance than the TLB when applied to the lower limb, especially after the limb volume is initially reduced by compression. Moreover, using the tensile test and the guide of the reference points on layers 1 and 2 from DCS, the calculated pressure achieved the expected values stated by the manufacturer. Human studies should be conducted to determine whether the reference points provided by DCS are beneficial for obtaining repeatable values.


XRCC3 Thr241Met gene polymorphism and risk of colorectal cancer in Kashmir: a case control study.
XRCC (X-ray cross-complementing group) genes contribute to important DNA repair mechanisms that play roles in the repair of single strand breaks (SSBs) induced by a variety of external and internal factors, including ionizing radiation, alkylating agents and reactive oxygen species. These repair genes have a pivotal role in maintaining genomic stability through different pathways of base excision repair (BER). The aim of this study was to investigate the XRCC3 Thr241Met gene polymorphism in colorectal cancer (CRC) in Kashmir. We investigated the genotype distribution of XRCC3 gene in 120 CRC cases in comparison with 150 healthy subjects and found a significant association between XRCC3 genotypes and CRC (p≤0.05). Both heterozygous genotype (Thr/Met) as well as homozygous variant genotype (Met/Met) were moderately associated with elevated risk of CRC [OR=2.53; OR=2.29 respectively]. Also, Thr/Met and Met/Met genotypes demonstrated a significant association with the risk of CRC (p=0.003). This study displayed a significantly elevated risk for CRC in individuals with XRCC3 Thr/Met and Met/Met Genotype of about 2.5 times that with the Thr/Thr wild genotype.