Effects of clonidine in women with fecal incontinence.
Some women with urge-predominant fecal incontinence (FI) have diarrhea-predominant irritable bowel syndrome and a stiffer and hypersensitive rectum. We evaluated the effects of the α2-adrenergic agonist clonidine on symptoms and anorectal functions in women with FI in a prospective, placebo-controlled trial. We assessed bowel symptoms and anorectal functions (anal pressures, rectal compliance, and sensation) in 43 women (age, 58 ± 2 y) with urge-predominant FI, randomly assigned to groups given oral clonidine (0.1 mg, twice daily) or placebo for 4 weeks. Before and after administration of the medication, anal pressures were evaluated by manometry, and rectal compliance and sensation were measured using a barostat. Anal sphincter injury was evaluated by endoanal magnetic resonance imaging. Bowel symptoms were recorded in daily and weekly diaries. The primary end point was the FI and Constipation Assessment symptom severity score. FI scores decreased from 9.1 ± 0.3 to 7.6 ± 0.5 among subjects given placebo and from 8.1 ± 0.4 to 6.5 ± 0.6 among patients given clonidine. Clonidine did not affect FI symptom severity, bowel symptoms (stool consistency or frequency), anal pressures, rectal compliance, or sensation compared with placebo. However, when baseline data were used to categorize subjects as those with or without diarrhea, clonidine reduced the proportion of loose stools in patients with diarrhea only (P = .018). Clonidine also reduced the proportion of days with FI in patients with diarrhea (P = .0825). Overall, clonidine did not affect bowel symptoms, fecal continence, or anorectal functions, compared with placebo, in women with urge-predominant FI. Among patients with diarrhea, clonidine increased stool consistency, with a borderline significant improvement in fecal continence. ClinicalTrials.gov, Number NCT00884832.


[Effect of the consumption of a food supplement on plasma zinc concentrations of free-living Chilean elderly adults].
Zinc intake is well below recommendation among Chilean free living elderly adults of low socioeconomic level. To assess the effect of the consumption of a food supplement on plasma zinc concentrations in elderly adults (EA). Ambulatory EA (> or = 70) with controlled type 2 diabetes mellitus or high blood pressure, ascribed to public family health centers were studied. They were separated in a control and intervention group, without blinding techniques. The intervention group consumed daily 50 g of a special nutritional supplement prepared as a soup or porridge, provided by the Government, for 3 months. The control group did not receive the supplement. A good compliance with the supplement was defined as a consumption of 7 portions per week. A fasting venous blood sample was obtained to determine plasma zinc at the beginning and end of the study. Forty three supplemented EA aged 76+/-5 years (21 women) and 31 non supplemented EA aged 78+/-5 years (20 women), completed 3 months of follow up. Mean compliance with the supplement was 40.5% (95% confidence intervals (CI) 40.3-40.6%). General characteristics of the study subjects upon recruitment were similar, except for the literacy that was higher in the intervention group. We fitted a multiple linear regression model which explained 39% of the variance, where the consumption of the nutritional supplement increased the concentration of plasmatic zinc by 4.14 microg/dL (95% CI 0.25-8.02) (p<0.037), after controlling for sex, age, energy, vitamin E and calcium consumption. The consumption of a food supplement significantly increased plasma zinc concentrations in Chilean elderly adults.


Percutaneous insertion of peritoneal dialysis catheters using ultrasound and fluoroscopic guidance: A single centre experience and review of literature.
Various methods of peritoneal dialysis (PD) catheter insertion are available. The purpose of this study was to evaluate a percutaneous insertion technique using ultrasound (US) and fluoroscopy performed under conscious sedation and as day case procedure. Data of 87 percutaneous inserted dialysis catheters were prospectively collected, including patients' age, gender, body mass index, history of previous abdominal surgery and cause of end stage renal failure. Length of hospital stay, early complications and time to first use were also recorded. Institutional review board approval was obtained. A 100% technical success rate was observed. Early complications included bleeding (n = 3), catheter dysfunction (n = 6), exit site infection (n = 1) and exit site leakage (n = 1). All cases of catheter dysfunction and one case of bleeding required surgical revision. Median time of follow-up was 18 months (range 3-35), and median time from insertion to first use was days 14 (1-47). Of the 82 patients who started dialysis, 20 (23%) ceased PD at some stage during follow-up. Most frequently encountered reasons include deteriorating patient cognitive or functional status (n = 5), successful transplant kidney (n = 4) and pleuro-peritoneal fistula (n = 4). Sixty-two (71%) PD catheter insertions were performed as day case. The remaining insertions were performed on patients already admitted to the hospital. Percutaneous insertion of dialysis catheter using US and fluoroscopy is not only safe but can be performed as day case procedure in most patients, even with a medical history of abdominal surgery and/or obesity.


Experiences of responsiveness to exercise in people with chronic whiplash: A qualitative study.
Exercise is recommended in clinical guidelines for the treatment of chronic whiplash associated disorders (WAD). However, randomised controlled trials have shown similar effects for comprehensive exercise programs and advice. To date, there is no clear understanding of why some individuals with WAD appear to respond to exercise whilst others do not. The aim of this study was to explore the experiences and self-reported characteristics of people with chronic whiplash identifying as 'responders' and 'non-responders' to exercise. Semi-structured interviews were conducted with 13 people with chronic whiplash (patients) and seven treating physiotherapists. Patients were asked whether they responded to the exercise program, and what contributed to this. Physiotherapists were asked to share their experiences about the characteristics of people that appear to respond to exercise, and those that do not. An interpretive descriptive approach was selected to facilitate the generation of discipline-specific knowledge. Four themes were generated from patient and physiotherapist interviews, including: (1) the therapeutic relationship, (2) exercise experiences and beliefs, (3) self-efficacy and acceptance, (4) physical and psychological determinants of responsiveness. Responsiveness to exercise is complex and multifaceted. Clinicians may seek to identify the presence of discrete physical impairment(s) (e.g., range of motion restriction), and where present, determine whether targeted exercise results in an immediate and positive response. Clinicians may also focus their efforts on developing aspects of the therapeutic relationship identified as important to patients, such as hope, partnership and rapport.


Pterostilbene Protects the Optic Nerves and Retina in a Murine Model of Experimental Autoimmune Encephalomyelitis via Activation of SIRT1 Signaling.
Optic neuritis and retinal damage are common manifestations of multiple sclerosis (MS). Pterostilbene (PT) has been used to treat multiple diseases for its anti-inflammatory, anti-apoptosis and neuroprotective activities. This study aimed to investigate whether PT exerts a therapeutic effect on optic neuritis and retinal damage triggered by MS. Here, experimental autoimmune encephalomyelitis (EAE), an experimental model for MS, was induced in female C57BL/6 mice by immunizing with MOG35-55 peptide and treating with pertussis toxin. The mice were intraperitoneally injected with 20 mg/kg and 40 mg/kg PT once daily for 25 days at 24 h post immunization. We found that PT alleviated EAE severity and delayed EAE onset. Moreover, PT mitigated EAE-induced optic nerves and retinal inflammation, as indicated by the decreased Iba-1+ and GFAP+ cells and mRNA levels of interleukin-6, tumor necrosis factor-α and interleukin-1β and the increased Iba-1+sirtuin 1 (SIRT1)+ and GFAP+SIRT1+ cells in the optic nerves and retina. PT also protected the optic nerves against demyelination and axonal loss and the retina against disorders in retinal morphology and apoptosis of retinal ganglion cells. High-dose PT had a more significant effect on protection of the optic nerves and retina in EAE than low-dose PT. In addition, PT activated SIRT1 signaling in the optic nerves and retina. Notably, EX-527, an inhibitor of SIRT1, reversed the effect of high-dose PT on the optic nerves and retina, indicating that PT exerted the protective effect via activating SIRT1 signaling. This study provides a potential candidate for treating MS.


ANALYSIS OF THE NEW REGULATORY BIOETHICAL REVIEW FRAMEWORK FOR CLINICAL TRIALS IN TURKEY.
We conducted a descriptive study of the existing research ethics committee (REC) review structure in Turkey with respect to clinical trials and discuss what can be expected in the future under the new regulation that came into effect in April 2013. We identified 78 RECs in Turkey under the Ministry of Health (MOH) as of September 2012, categorised under geographic location, type and institution. We identified REC member lists from the MOH in the same month and further characterize them under: membership number, gender, and speciality. MOH, universities, national nongovernmental organizations such as the Turkish Medical Association and the Turkish Bioethics Association, as well as clinical research and pharmaceutical bodies are intensively interested in the enhancement of the current system of research ethics review in the country. The European Union and Council directives have been important sources that have guided new developments. Proper evaluation of the existing system and introduction of new regulatory framework are expected to further clarify the obstacles and offer opportunities for institutions, researchers, REC members and administrators.


Burden of disease in Japan: using national and subnational data to inform local health policy.
The Global Burden of Disease (GBD) study has been instrumental in guiding global health policy development since the early 1990s. The GBD 2010 project provided rich information about the key causes of mortality, disability-adjusted life years, and their associated risk factors in Japan and provided a unique opportunity to incorporate these data into health planning. As part of the latest update of this project, GBD 2013, the Japanese GBD collaborators plan to update and refine the available burden of disease data by incorporating sub-national estimates of the burden of disease at the prefectural level. These estimates will provide health planners and policy makers at both the national and prefectural level with new, more refined tools to adapt local public health initiatives to meet the health needs of local populations. Moreover, they will enable the Japanese health system to better respond to the unique challenges in their rapidly aging population and as a complex combination of non-communicable disease risk factors begin to dominate the policy agenda. Regional collaborations will enable nations to learn from the experiences of other nations that may be at different stages of the epidemiological transition and have different exposure profiles and associated health effects. Such analyses and improvements in the data collection systems will further improve the health of the Japanese, maintain Japan's excellent record of health equity, and provide a better understanding of the direction of health policy in the region.


[Sociotherapy in German social law. Indication, contents, and aspects of public health].
In German mental health services, the ill-defined term "sociotherapy" has been used to designate nonmedical, social, and work-related components of the care process. Recently, a new component of outpatient/community mental health care called "sociotherapy" (according to Paragraph 37a of the Fifth German Social Code) which is funded by the public health insurance system has been introduced and is now in the process of being implemented. The paper describes (a) patients eligible for the service and (b) the aims and scope of this case management module. The key objectives are to motivate patients with schizophrenia to utilise mental health services and antipsychotic medication and to liaise with psychosocial services. Therefore, sociotherapy is distinct from (a) multidisciplinary inpatient care for people with severe mental illness, (b) assertive community treatment, (c) community care provided by social workers or community psychiatric nurses, and (d) family interventions. So far there has been little evaluation of sociotherapy.


Sexual cycle of Cryptococcus neoformans var. grubii and virulence of congenic a and alpha isolates.
Cryptococcus neoformans is a human-pathogenic fungus that has evolved into three distinct varieties that infect most prominently the central nervous system. A sexual cycle involving haploid cells of a and alpha mating types has been reported for two varieties (C. neoformans var. neoformans, serotype D, and C. neoformans var. gattii, serotypes B and C), yet the vast majority of infections involve a distinct variety (C. neoformans var. grubii, serotype A) that has been thought to be clonal and restricted to the alpha mating type. We recently identified the first serotype A isolate of the a mating type which had been thought to be extinct (strain 125.91). Here we report that this unusual strain can mate with a subset of pathogenic serotype A strains to produce a filamentous dikaryon with fused clamp connections, basidia, and viable recombinant basidiospores. One meiotic segregant mated poorly with the serotype A reference strain H99 but robustly with a crg1 mutant that lacks a regulator of G protein signaling and is hyperresponsive to mating pheromone. This meiotic segregant was used to create congenic a and alpha mating type serotype A strains. Virulence tests with rabbit and murine models of cryptococcal meningitis showed that the serotype A congenic a and alpha mating type strains had equivalent virulence in animal models, in contrast to previous studies linking the alpha mating type to increased virulence in congenic serotype D strains. Our studies highlight a role for sexual recombination in the evolution of a human fungal pathogen and provide a robust genetic platform to establish the molecular determinants of virulence.


Adherence of Candida albicans and other Candida species to mucosal epithelial cells.
To study the possible involvement of candidal adherence in mucosal colonization, we examined the in vitro adherence capabilities of seven Candida species. Adherence was evaluated by direct microscopic examination and by a quantitative radiometric adherence test. The results indicate that C. albicans adheres to vaginal and buccal epithelial cells to a significantly greater degree (P less than 0.01) than the other species tested. C. tropicalis and C. stellatoidea demonstrated moderate adherence capabilities, while C. parapsilosis adhered only to a slight degree. Other species failed to interact with isolated mucosal cells. These findings suggest that there is a relationship between the adherence capabilities of the Candida species and their abilities to colonize mucosal surfaces, since those species which adhere are those which most frequently colonize mucosal surfaces. C. albicans was found to be adherent under a variety of environmental conditions. Stationary-phase blastospores of C. albicans were found to be more adherent than logarithmic-phase yeasts, and larger blastospore cell-to-epithelial cell ratios resulted in greater adherence values. The actual number of adherent yeasts varied considerably when epithelial cells were obtained from different donors.


A formal theory of the selfish gene.
Adaptation is conventionally regarded as occurring at the level of the individual organism. In contrast, the theory of the selfish gene proposes that it is more correct to view adaptation as occurring at the level of the gene. This view has received much popular attention, yet has enjoyed only limited uptake in the primary research literature. Indeed, the idea of ascribing goals and strategies to genes has been highly controversial. Here, we develop a formal theory of the selfish gene, using optimization theory to capture the analogy of 'gene as fitness-maximizing agent' in mathematical terms. We provide formal justification for this view of adaptation by deriving mathematical correspondences that translate the optimization formalism into dynamical population genetics. We show that in the context of social interactions between genes, it is the gene's inclusive fitness that provides the appropriate maximand. Hence, genic selection can drive the evolution of altruistic genes. Finally, we use the formalism to assess the various criticisms that have been levelled at the theory of the selfish gene, dispelling some and strengthening others.


Cell intercalation in a simple epithelium.
Cell intercalation is a key topological transformation driving tissue morphogenesis, homeostasis and diseases such as cancer cell invasion. In recent years, much work has been undertaken to better elucidate the fundamental mechanisms controlling intercalation. Cells often use protrusions to propel themselves in between cell neighbours, resulting in topology changes. Nevertheless, in simple epithelial tissues, formed by a single layer of densely packed prism-shaped cells, topology change takes place in an astonishing fashion: cells exchange neighbours medio-laterally by conserving their apical-basal architecture and by maintaining an intact epithelial layer. Medio-lateral cell intercalation in simple epithelia is thus an exemplary case of both robustness and plasticity. Interestingly, in simple epithelia, cells use a combinatory set of mechanisms to ensure a topological transformation at the apical and basal sides. This article is part of the discussion meeting issue 'Contemporary morphogenesis'.


Using nonequilibrium thin-disc and batch equilibrium techniques to evaluate herbicide sorption.
Nonequilibrium disc-flow techniques may better reproduce dynamic soil-pesticide interactions than traditional batch sorption studies. Batch kinetic and equilibrium experiments and dual-label thin-disc flow experiments were conducted with atrazine (6-chloro-N-ethyl-N'-isopropyl-1,3,5-triazine-2,4-diamine) and imazaquin [2-(4,5-dihydro-4-methyl-4-(1-methylethyl)-5-oxo-1H-imidazol-2-yl)-3-quinolinecarboxylic acid] using a Demopolis silt loam (loamy-skeletal, carbonatic, thermic, shallow Typic Udorthent; 8% clay, 62 g kg(-1) organic matter, 7.6 pH). Batch kinetic studies with both herbicides revealed an almost instantaneous rapid phase and a much slower gradual phase. The rapid phase was complete after 5 min and equilibrium was reached at 24 h. The rapid phase accounted for 74% and 12 to 30% of the total amounts adsorbed for atrazine and imazaquin, respectively. The sorption of both the rapid and 24-h isotherms for each herbicide best fit the Freundlich equation. The rapid and 24-h K(f) values of atrazine were 1.38 and 2.41, respectively, and the N value of both phases was approximately 0.93. For imazaquin, the rapid and 24-h K(f) values were 0.056 and 035, respectively, and the N value for the rapid phase of imazaquin was 0.71, compared with 0.86 for the 24-h isotherm. In the dual-label thin-disc flow experiments, the average partition coefficient for atrazine at the peak soil concentration point was 1.54. This value closely agreed with the observed rapid-phase K(f) value of 1.38. In contrast, the thin-disc flow experiments failed to detect any imazaquin retention. The thin-disc flow method can allow for a greater resolution of rapid sorption kinetics, which is impractical with batch studies. Along with dynamic partitioning data, the thin-disc flow method may provide kinetics data that may better complement environmental models than coefficients generated with batch techniques.


Regioisomer-manipulating thio-perylenediimide nanoagents for photothermal/photodynamic theranostics.
Thionated perylenediimides (PDIs) can potentially generate thermal and reactive oxygen species and thus can be used as theranostic agents for photothermal/photodynamic therapy. Herein, thionated cis-/trans-isomer PDI-CS and PDI-TS were designed and prepared to investigate thionation engineering on therapeutic performance. The results revealed that the photodynamic performance is less associated with the positon of sulfur atoms. By contrast, trans-isomer PDI-TS showed a photothermal conversion efficiency of up to 58.4%, which was 40% higher than that of PDI-CS (∼41.6%). An in vitro half-maximal inhibitory concentration of ∼7.78 μg mL-1 was achieved for PDI-TS, which was 1.7-fold smaller than that of PDI-CS, strongly reasserting the regioisomer-modulated phototheranostic performance. Notably, the strong π-π and CS interactions in PDI-TS nanoagents are essential factors attributed to their excellent photothermal performance, indicating that the optimization of non-bonding interactions is an ingenious way to improve phototheranostic performance. This work provides a facile means of creating thio-perylenediimides that possess excellent antitumor properties and a novel proof of concept to improve therapeutic performance through the optimization of non-bonding interactions.


A re-examination of twitching motility in Pseudomonas aeruginosa.
Twitching motility is a form of solid surface translocation which occurs in a wide range of bacteria and which is dependent on the presence of functional type IV fimbriae or pili. A detailed examination of twitching motility in Pseudomonas aeruginosa under optimal conditions in vitro was carried out. Under these conditions (at the smooth surface formed between semi-solid growth media and plastic or glass surfaces) twitching motility is extremely rapid, leading to an overall radial rate of colony expansion of 0.6 mm h(-1) or greater. The zones of colony expansion due to twitching motility are very thin and are best visualized by staining. These zones exhibit concentric rings in which there is a high density of microcolonies, which may reflect periods of expansion and consolidation/cell division. Video microscopic analysis showed that twitching motility involves the initial formation of large projections or rafts of aggregated cells which move away from the colony edge. Behind the rafts, individual cells move rapidly up and down trails which thin and branch out, ultimately forming a fine lattice-like network of cells. The bacteria in the lattice network then appear to settle and divide to fill out the colonized space. Our observations redefine twitching motility as a rapid, highly organized mechanism of bacterial translocation by which P. aeruginosa can disperse itself over large areas to colonize new territories. It is also now clear, both morphologically and genetically, that twitching motility and social gliding motility, such as occurs in Myxococcus xanthus, are essentially the same process.


[Mechanisms of change in the tonus of depolarized smooth muscle (guinea pig taenia coli) during application of a hyperpolarizing current].
Using double sucrose-gap technique three types of contractile responses of depolarized smooth muscle (guinea-pig taenia-coli) current-induced hyperpolarization were investigated: 1) contractions, 2) relaxations and 3) biphasic responses (relaxation followed by contraction). Every preparation generated generally only one type of responses (of different amplitude) when passing the currents of various strength. These responses were attributed to the changes of calcium fluxes through the cellular membranes under hyperpolarization. The phenomena observed were analysed on the mathematical model. Quantitative analysis showed that description of calcium current changes with equations of Hogkin-Huxley types was not sufficient; the model predicts the existence of non-inactivating channels in the smooth muscle cellular membrane. This very assumption allows to describe correctly all three types of cintractile responses.


Metyrapone reveals that previous chronic stress differentially impairs hippocampal-dependent memory.
Chronic stress facilitates fear conditioning in rats with hippocampal neuronal atrophy and in rats in which the atrophy is prevented with tianeptine, a serotonin re-uptake enhancer. The purpose of this study was to determine whether the lack of dissociation between fear conditioning performance and hippocampal integrity was masked by the presence of endogenous corticosteroids during training. As in previous studies, rats were stressed by daily restraint (6 h/day for 21 days), trained in the conditioning chamber (day 23), and then assessed for conditioned fear (day 25) at a time when hippocampal dendritic atrophy persists. On the training day, half of the control and stressed rats were. injected with metyrapone to reduce corticosterone release. Two hours later, two paired or unpaired presentations of tone and footshock were delivered. Although metyrapone reduced conditioned fear in all rats, only stressed rats showed dissociated fear conditioning (i.e. tone conditioning was reduced while contextual conditioning was eliminated). Chronically stressed rats, regardless of metyrapone treatment displayed more rearing in the open field when tested immediately after the completion of fear conditioning. These data support the hypothesis that increased emotionality and enhanced fear conditioning exhibited by chronically stressed rats maybe due to endogenous corticosterone secretion at the time of fear conditioned training. Moreover,these data suggest that chronic stress impairs hippocampal-dependent processes more robustly than hippocampal-independent processes after metyrapone to reduce corticosterone secretion during aversive training.


Effects of distraction and pictorial illustration on memory for countries in older adults with probable Alzheimer's disease.
Eight participants with probable Alzheimer's disease (AD) were trained to recall names of countries using the spaced-retrieval memory intervention. Six training sessions were administered on alternate days over a 2-week period. Half of the participants studied a target country alone and the other half studied a target country along with eight distractor countries. Training stimuli appeared in text-only format in half of the sessions and text with a color photograph of the country in the other sessions. On each trial, participants selected the target at increasingly longer retention intervals, contingent upon successful recall. Results indicated that the mean proportion of correct trials and longest duration achieved increased across training sessions, confirming the success of the spaced-retrieval intervention. Pictorial illustrations enhanced explicit memory for target country names. Implications of these data for current views on memory remediation in cognitively impaired older adults are discussed.


Angiogenesis and tumor metastasis.
Angiogenesis, the recruitment of new blood vessels, is an essential component of the metastatic pathway. These vessels provide the principal route by which tumor cells exit the primary tumor site and enter the circulation. For many tumors, the vascular density can provide a prognostic indicator of metastatic potential, with the highly vascular primary tumors having a higher incidence of metastasis than poorly vascular tumors. Tumor angiogenesis is regulated by the production of angiogenic stimulators including members of the fibroblast growth factor and vascular endothelial growth factor families. In addition, tumors may activate angiogenic inhibitors such as angiostatin and endostatin that can modulate angiogenesis both at the primary site and at downstream sites of metastasis. The potential use of these and other natural and synthetic angiogenic inhibitors as anticancer drugs is currently under intense investigation. Such agents may have reduced toxicity and be less likely to generate drug resistance than conventional cytotoxic drugs. Clinical trials are now underway to develop optimum treatment strategies for antiangiogenic agents.


Epidemiologic overview of malignant lymphoma.
Malignant lymphoma encompasses a wide variety of distinct disease entities. It is generally more common in developed countries and less common in developing countries. The East Asia region has one of the lowest incidence rates of malignant lymphoma. The incidence of malignant lymphoma around the world has been increasing at a rate of 3-4% over the last 4 decades, while some stabilization has been observed in developed countries in recent years. The reasons behind this lymphoma epidemic are poorly understood, although improving diagnostic accuracy, the recent AIDS epidemic, an aging world population and the increasing adoption of cancer-causing behaviors are suggested as contributing factors. Etiologies of malignant lymphoma include infectious agents, immunodeficiency, autoimmune disease, exposure to certain organic chemicals, and pharmaceuticals. The distribution of many subtypes exhibit marked geographic variations. Compared to the West, T/natural killer (NK) cell lymphomas (T/NK-cell lymphoma) and extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) are relatively more common, whereas other B-cell lymphomas, particularly follicular lymphoma and chronic lymphocytic leukemia/small lymphocytic lymphoma, are less common in Asia. Some subtypes of T/NK-cell lymphomas defined by Epstein-Barr virus association are predominantly Asian diseases, if not exclusively so. Both ethnic and environmental factors play roles in such diversity. In this review, we discuss the geographic distribution and etiology of malignant lymphoma, as well as the trend.


Predictors of return to work following motor vehicle related orthopaedic trauma.
Work disability following motor vehicle related orthopaedic trauma is a significant contributor to the burden of injury and disease. Early identification of predictors for return to work (RTW) is essential for developing effective interventions to prevent work disability. The study aim was to determine the predictors (including compensation related factors) of time to RTW following motor vehicle related orthopaedic trauma. Admitted patients were recruited prospectively from two trauma hospitals with upper and/or lower extremity fractures following a motor vehicle crash. Baseline and follow up data were collected by written questionnaire. For baseline, this occurred in person within 2 weeks of injury. For follow up, this occurred by mail at six, 12 and 24 months. Additional demographic and injury-related information was retrieved from hospital databases. Analysis involved: descriptive statistics; logrank test to detect survival distributions of categorical variables; and Cox proportional hazards regression models for risks of time to RTW using baseline characteristic and compensation related variables (at 6 months). Of 452 study participants 334 (74%) were working pre-injury: results are based on this subset. Baseline characteristics were mean age 36 years (13.9 Standard Deviation [SD]), 80% male; 72% self-assessed very good-excellent pre-injury health, 83% household income > AU$40,000 (Australian Dollar). Follow up data was available for 233 (70%), 210 (63%), and 182 (54%) participants at six, 12 and 24 months respectively. Significant risks of a longer time to RTW were greater injury severity, as measured by the New Injury Severity Score (NISS) (Hazards Rate Ratio [HRR] = 0.54, 95% CI 0.35-0.82); and lower occupational skill levels (HRR = 0.53, 95% CI 0.34-0.83). Significant risks of a shorter time to RTW were: recovery expectations for usual activities within 90 days (HRR = 2.10, 95% CI 1.49-2.95); full-time pre-injury work hours (HRR = 1.99, 95% CI 1.26-3.14); and very good self-assessed pre-injury health status (HRR = 1.41, 95% CI 0.98-2.02). Legal representation (analysed at six months only) was not associated with time to RTW. At each time period, there were 146 (63%), 149 (71%), and 137 (76%) working participants. A longer time to RTW was associated with greater injury severity and lower occupational skill levels; while a shorter time to RTW was associated with recovery expectations for usual activities within 90 days, full-time pre-injury work hours, and very good self-assessed pre-injury health status. Our findings reinforce existing research. There is an opportunity to trial interventions that address potentially modifiable factors. The issues surrounding legal representation are complex and require further research.


Molecular genetic techniques for gene manipulation in Candida albicans.
Candida albicans is one of the most common fungal pathogen in humans due to its high frequency as an opportunistic and pathogenic fungus causing superficial as well as invasive infections in immunocompromised patients. An understanding of gene function in C. albicans is necessary to study the molecular basis of its pathogenesis, virulence and drug resistance. Several manipulation techniques have been used for investigation of gene function in C. albicans, including gene disruption, controlled gene expression, protein tagging, gene reintegration, and overexpression. In this review, the main cassettes containing selectable markers used for gene manipulation in C. albicans are summarized; the advantages and limitations of these cassettes are discussed concerning the influences on the target gene expression and the virulence of the mutant strains.


Protective effects of kolaviron and gallic acid against cobalt-chloride-induced cardiorenal dysfunction via suppression of oxidative stress and activation of the ERK signaling pathway.
Cobalt (Co) toxicity is a potential public health problem due to recent renewed use of Co in orthopedic implants, dietary supplements, and blood doping in athletes and horses. We investigated the protective roles of kolaviron (KV), a bi-flavonoid of Garcinia kola, and gallic acid (GA) on cobalt chloride (CoCl2)-induced cardiorenal damage in rats. CoCl2 caused significant increases (p < 0.05) in serum creatine kinase-myocardial band (CK-MB), lactate dehydrogenase (LDH), aspartate transaminase (AST), xanthine oxidase (XO), urea, creatinine, malondialdehyde, H2O2, nitric oxide, as well as C-reactive protein expression, along with significant (p < 0.05) reduction in cardiac and renal expression of extracellular signal regulated kinase (ERK) and the activities of superoxide dismutase, catalase, and glutathione S-transferase. KV and GA prevented the toxic effects of CoCl2 by stimulating ERK expression and reversing Co-induced biochemical changes. Administration of CoCl2 alone did not significantly alter ECG patterns in the rats, although co-treatment with KV (200 mg/kg) produced QT-segment prolongation and also appeared to potentiate Co hypotension. Histopathology of the heart and kidneys of rats treated with KV and GA confirmed the biochemical data. KV and GA thus protected against cardiac and renal damage in Co intoxication via antioxidant and (or) cell survival mechanisms, possibly involving ERK activation.


Infant feeding practices in complex emergencies: a case study approach.
The majority of deaths associated with complex emergencies are attributed to infants and children under the age of five years. Most of these deaths are related to preventable diseases such as malnutrition, diarrhea, and malaria. Infant feeding emergencies have emerged as a major factor in complex emergencies. This paper reviews the current information relative to infant feeding, and uses four case studies as educational tools for the management of infant feeding emergencies. Child mortality rates in refugee population have been linked directly to protein-energy malnutrition (PEM). Breast feeding has many advantages over all other forms of feeding for children up to the age of two years of age. These advantages are discussed in detail in this paper. In addition, the appropriate and inappropriate uses of breast-milk substitutes (BMS) are discussed. Breast feeding also may play a role in the spread of HIV infections from the mother to the infant. However, in the setting of complex emergencies in the developing world, the risk of an infant dying of malnutrition and infection when not breastfed is likely to be greater than is the risk of death due to HIV acquisition through breastfeeding. The physiology of lactation is reviewed with particular reference to the roles of prolactin, oxytocin, and the feedback inhibitor of lactation (FIL) hormone. No medications have been demonstrated to augment milk production that can be used in a practical sense in complex emergencies. Lastly, the principles promulgated by the WHO and UNHCR for the feeding of infants and children in emergencies and for milk powder distribution are summarized.


[Comparative efficacy of mezakol and sulfasalazine in treating chronic relapsing ulcerative colitis].
This research testifies to the fact that it is more preferable to use mesacol than sulfasalazine in treatment of common forms of ulcerative colitis of light and average severity. Mesacol acts faster in arresting inflammations in proximal parts of the larger intestine. One can assume that the pH-dependent release of 5-aminosalicylic acid in these forms of the disease suffers less than the destruction of the diazo link by the anaerobic microflora, due to which a higher concentration of the preparation is formed in the large intestine. Another alternative explanation can be the dose-dependent effect. Thus, 2.4. g of mesacol correspond to 6 g of sulfasalazine. The dose of sulfasalazine was smaller in our study. Mesacol had no advantages over sulfasalazine in treatment of distal colitis, which can and must be treated with rectal introduction of corticosteroids and 5-aminosalicylic acid preparations. Thus, mesacol must be reserved for treatment of patients with common ulcerative colitis of light and average severity in case of intolerance to sulfasalazine or impossibility to increase the preparation dose over 4 g/day. Its efficiency and price make the preparation available for most patients and patient care institutions.


Toxicity and antitumor activity of hexamethylmelamine and its N-demethylated metabolites in mice with transplantable tumors.
N-Demethylated metabolites of the antineoplastic agent hexamethylmelamine were synthesized, and their toxicities and antitumor activities were determined in vivo. Determinations of the lethal dose for 10% of the male C57BL X DBA/2 F1 (hereafter called BD2F1) mice showed hexamethylmelamine toxicity to be decreased by N-demethylation; the metabolites showed a direct relationship between potency (mmoles/kg/day) and number of methyl groups present. In BD2F1 mice bearing Sarcoma 180 or Lewis lung carcinoma, the antitumor activities of the methylmelamines decreased with a reduction in number of methyl groups, but were similar at equitoxic levels. Results were similar in L1210 leukemic mice treated with lethal dose levels of the metabolites for 10% of the mice when mean survival times were measured. The therapeutic equality produced with equitoxic levels, together with the ineffectiveness of melamine, suggested that the presence of a methyl group, rather than the number, was the determining factor in the antitumor activity of the methylmelamines.


Probing crystal structure and mesoscale assembly of cellulose microfibrils in plant cell walls, tunicate tests, and bacterial films using vibrational sum frequency generation (SFG) spectroscopy.
This study reports that the noncentrosymmetry and phase synchronization requirements of the sum frequency generation (SFG) process can be used to distinguish the three-dimensional organization of crystalline cellulose distributed in amorphous matrices. Crystalline cellulose is produced as microfibrils with a few nanometer diameters by plants, tunicates, and bacteria. Crystalline cellulose microfibrils are embedded in wall matrix polymers and assembled into hierarchical structures that are precisely designed for specific biological and mechanical functions. The cellulose microfibril assemblies inside cell walls are extremely difficult to probe. The comparison of vibrational SFG spectra of uniaxially-aligned and disordered films of cellulose Iβ nanocrystals revealed that the spectral features cannot be fully explained with the crystallographic unit structure of cellulose. The overall SFG intensity, the alkyl peak shape, and the alkyl/hydroxyl intensity ratio are sensitive to the lateral packing and net directionality of the cellulose microfibrils within the SFG coherence length scale. It was also found that the OH SFG stretch peaks could be deconvoluted to find the polymorphic crystal structures of cellulose (Iα and Iβ). These findings were used to investigate the cellulose crystal structure and mesoscale cellulose microfibril packing in intact plant cell walls, tunicate tests, and bacterial films.


Serious game training improves performance in combat life-saving interventions.
In modern warfare, almost 25% of combat-related deaths are considered preventable if life-saving interventions are performed. Therefore, Tactical Combat Casualty Care (TCCC) training for soldiers is a major challenge. In 2014, the French Military Medical Service supported the development of 3D-SC1®, a serious game designed for the French TCCC program, entitled Sauvetage au Combat de niveau 1 (SC1). Our study aimed to evaluate the impact on performance of additional training with 3D-SC1®. The study assessed the performance of soldiers randomly assigned to one of two groups, before (measure 1) and after (measure 2) receiving additional training. This training involved either 3D-SC1® (Intervention group), or a DVD (Control group). The principal measure was the individual performance (on a 16-point scale), assessed by two investigators during a hands-on simulation. First, the mean performance score was compared between the two measures for Intervention and Control groups using a two-tailed paired t-test. Second, a multivariable linear regression was used to determine the difference in the impacts of 3D-SC1® and DVD training, and the order of presentation of the two scenarios, on the mean change from baseline in performance scores. A total of 96 subjects were evaluated: seven could not be followed-up, while 50 were randomly allocated to the Intervention group, and 39 to the Control group. Between measure 1 and measure 2, the mean (SD) performance score increased from 9.9 (3.13) to 14.1 (1.23), and from 9.4 (2.97) to 12.5 (1.83), for the Intervention group and Control group, respectively (p<0.0001). The adjusted mean difference in performance scores between 3D-SC1® and DVD training was 1.1 (95% confidence interval -0.3, 2.5) (p=0.14). Overall, the study found that supplementing SC1 training with either 3D-SC1® or DVD improved performance, assessed by a hands-on simulation. However, our analysis did not find a statistically significant difference between the effects of these two training tools. 3D-SC1® could be an efficient and pedagogical tool to train soldiers in life-saving interventions. In the current context of terrorist threat, a specifically-adapted version of 3D-SC1®may be a cost-effective and engaging way to train a large civilian public.


Search for unpublished data by systematic reviewers: an audit.
We audited a selection of systematic reviews published in 2013 and reported on the proportion of reviews that researched for unpublished data, included unpublished data in analysis and assessed for publication bias. Audit of systematic reviews. We searched PubMed and Ovid MEDLINE In-Process & Other Non-Indexed Citations between 1 January 2013 and 31 December 2013 for the following journals: Journal of the American Medical Association, The British Medical Journal, Lancet, Annals of Internal Medicine and the Cochrane Database of Systematic Reviews. We also searched the Cochrane Library and included 100 randomly selected Cochrane reviews. Systematic reviews published in 2013 in the selected journals were included. Methodological reviews were excluded. Two reviewers independently reviewed each included systematic review. The following data were extracted: whether the review searched for grey literature or unpublished data, the sources searched, whether unpublished data were included in analysis, whether publication bias was assessed and whether there was evidence of publication bias. 203 reviews were included for analysis. 36% (73/203) of studies did not describe any attempt to obtain unpublished studies or to search grey literature. 89% (116/130) of studies that sought unpublished data found them. 33% (68/203) of studies included an assessment of publication bias, and 40% (27/68) of these found evidence of publication bias. A significant fraction of systematic reviews included in our study did not search for unpublished data. Publication bias may be present in almost half the published systematic reviews that assessed for it. Exclusion of unpublished data may lead to biased estimates of efficacy or safety in systematic reviews.


Macaque monkey type D retrovirus replicates in vitro in a distinct subpopulation of B lymphocytes.
Type D retroviruses have recently been shown to induce a wasting syndrome with associated lymphadenopathy, thymic atrophy and transient decreased peripheral blood lymphocyte blastogenic responsiveness in juvenile macaque monkeys. The replication in vitro of D/New England virus was assessed in various lymphocyte subpopulations to determine the possible pathogenesis of the immune dysfunction induced by this virus. While D/New England did not replicate in cultured T lymphocytes or induce any demonstrable dysfunction of T cells in vitro, it did grow in the cells of the B lymphocyte lineage. D/New England growth occurred in vitro in African Burkitt's lymphoma and pre-B cell lines, but not in Epstein-Barr virus-transformed normal B lymphocytes. The infection of a restricted B lymphocyte population by this primate type D retrovirus may play a role in the aetiology of the immune abnormalities which it induces.


Intra-cervical application of Misoprostol at estrus alters the content of cervical hyaluronan and the mRNA expression of follicle stimulating hormone receptor (FSHR), luteinizing hormone receptor (LHR) and cyclooxygenase-2 in the ewe.
The complex anatomy the of ovine cervix limits the success of transcervical artificial insemination in sheep, but Misoprostol (a PGE(1) analogue) relaxes the cervix and facilitates transcervical artificial insemination. However, the mechanism by which Misoprostol causes cervical relaxation is not known. This study examined if intra-cervical Misoprostol altered the hyaluronan content and the mRNA expression of COX-2, LHR, or FSHR in the cervix of the estrus ewe. Estrus was synchronized in cyclic ewes with progestagen pessaries and 48 h after sponge removal ewes were treated intra-cervically with 0 (controls), 200, or 400 microg Misoprostol. Hyaluronan content was determined by ELISA and mRNA expression of LHR, FSHR, and COX-2 was analyzed by in situ hybridization using digoxigenin-11-uridine-5'-triphosphate labeled riboprobes. The hyaluronan content of the cervix was significantly higher in sheep that received 200 (P<0.05) or 400 (P<0.05) microg Misoprostol compared to controls. Moreover, it was significantly (P<0.05) higher in the vaginal region compared to mid and uterine regions. Misoprostol increased (P<0.05) the mRNA expression of LHR and COX-2 but not FSHR. The expression for all three genes was highest in the vaginal region and lowest in uterine region. The luminal epithelium and circular smooth muscle layers had higher (P<0.05) expression for LHR, FSHR, and COX-2 mRNAs, and the sub-epithelial stroma had the lowest (P<0.05). We propose that the intra-cervical application of Misoprostol induces the mRNA expression of LHR, FSHR, and COX-2 through a positive feedback loop. The data suggest that softening of the cervix by Misoprostol is caused by an increase in the hyaluronan content of the cervix.


Mitochondrial and nuclear genes of mitochondrial components in cancer.
Although the observation of aerobic glycolysis of tumor cells by Otto v. Warburg had demonstrated abnormalities of mitochondrial energy metabolism in cancer decades ago, there was no clear evidence for a functional role of mutant mitochondrial proteins in cancer development until the early years of the 21(st) century. In the year 2000, a major breakthrough was achieved by the observation, that several genes coding for subunits of the respiratory chain (ETC) complex II, succinate dehydrogenase (SDH) are tumor suppressor genes in heritable paragangliomas, fulfilling Knudson's classical two-hit hypothesis. A functional inactivation of both alleles by germline mutations and chromosomal losses in the tumor tissue was found in the patients. Later, SDH mutations were also identified in sporadic paragangliomas and pheochromocytomas. Genes of the mitochondrial ATP-synthase and of mitochondrial iron homeostasis have been implicated in cancer development at the level of cell culture and mouse experiments. In contrast to the well established role of some nuclear SDH genes, a functional impact of the mitochondrial genome itself (mtDNA) in cancer development remains unclear. Nevertheless, the extremely high frequency of mtDNA mutations in solid tumors raises the question, whether this small circular genome might be applicable to early cancer detection. This is a meaningful approach, especially in cancers, which tend to spread tumor cells early into bodily fluids or faeces, which can be screened by non-invasive methods.


The value of needle renal allograft biopsy. I. A retrospective study of biopsies performed during putative rejection episodes.
Following renal transplantation, immunosuppression is usually increased to treat presumed rejection episodes. However, a) many conditions mimic rejection in the post-transplant period, and b) many rejection episodes are irreversible. As increased immunosuppressive therapy is associated with an increased risk of infection, it would be ideal to limit antirejection therapy to only the rejection episodes that are reversible. The role of percutaneous allograft biopsy was studied as an aid to decide which patients to treat for rejection, to limit unnecessary immunosuppression and to predict allograft survival. One hundred thirty-five patients with suspected rejection underwent 206 allograft biopsies without complication. Two hundred four biopsies were available for study. Biopsies were coded on a 1-4 scale (minimal, mild, moderate, severe) for acute and chronic tubulointerstitial infiltrate and vascular rejection, as well as no rejection (e.g., recurrence of original disease). Treatment decisions were made on the basis of the biopsy combined with clinical data. All patients have been followed two years and outcome correlated with biopsy findings (death, nephrectomy, and return to dialysis defined as kidney loss). The results were the following: 1) biopsies represented changes within the kidney. Of 16 kidneys removed within one month of biopsy, no nephrectomy specimen showed less rejection than that seen on biopsy. 2) Eighty-one biopsies (39.7%) led to tapering or not increasing immunosuppression (either no rejection, minimal rejection, or irreversible changes). 3) Kidneys having either severe acute or chronic vascular rejection (less than 30% function at three months) had significantly (p less than 0.05) decreased survival three to 24 months postbiopsy than those with minimal or mild vascular rejection or tubulointerstitial infiltrate (83% function at three months). 4) Kidneys with moderate chronic vascular rejection and those with severe acute tubulointerstitial infiltrate had significantly (p less than 0.05) decreased survival at six to 24 months. 5) Kidneys with moderate chronic vascular rejection (MCV) without an acute infiltrate (ATI) had significantly better survival than those having both MCV and ATI. 6) Similarly, kidneys having severe ATI alone had better survival than those with ATI plus vascular rejection. It was concluded that a) percutaneous allograft biopsy can be done without graft loss or infection; b) biopsy represents changes throughout the kidney; c) biopsy aids in deciding when to treat for rejection and in deciding when to withhold increased immunosuppression, and d) allograft biopsy predicts the outcome of treatment of a rejection episode.


Revisiting Functional Dysconnectivity: a Review of Three Model Frameworks in Schizophrenia.
Over the last decade, evidence suggests that a combination of behavioral and neuroimaging findings can help illuminate changes in functional dysconnectivity in schizophrenia. We review the recent connectivity literature considering several vital models, considering connectivity findings, and relationships with clinical symptoms. We reviewed resting state fMRI studies from 2017 to 2023. We summarized the role of two sets of brain networks (cerebello-thalamo-cortical (CTCC) and the triple network set) across three hypothesized models of schizophrenia etiology (neurodevelopmental, vulnerability-stress, and neurotransmitter hypotheses). The neurotransmitter and neurodevelopmental models best explained CTCC-subcortical dysfunction, which was consistently connected to symptom severity and motor symptoms. Triple network dysconnectivity was linked to deficits in executive functioning, and the salience network (SN)-default mode network dysconnectivity was tied to disordered thought and attentional deficits. This paper links behavioral symptoms of schizophrenia (symptom severity, motor, executive functioning, and attentional deficits) to various hypothesized mechanisms.


Ultrasensitive and reproducible SERS platform of coupled Ag grating with multibranched Au nanoparticles.
Surface-enhanced Raman scattering (SERS) spectroscopy is an extremely sensitive analytical technique that is capable of identifying the vibration signatures of target molecules up to single-molecule sensitivity. In this work, the ultrahigh sensitivity of SERS has been achieved through the immobilization of sharp-edges specific nanoparticles - so-called gold multibranched NPs (AuMs) on the silver grating surface through the biphenyl dithiol. This approach allows combining the extremely high SERS enhancement factor (better than that in the case of AuMs immobilized on the flat Ag film) with perfect reproducibility of Raman signals. The grating was created on the polymer substrate using the excimer laser modification and further metal deposition and has an "active" area 5 × 10 mm2, enabling the macroscale SERS substrate preparation. The wet-chemistry synthesized AuMs were then immobilized on the grating surface and the produced structure allows SERS measurements with a portable Raman spectrophotometer. The prepared structures were checked using the AFM, UV-Vis, and Raman spectroscopy techniques.


Fine mapping titin's C-zone: Matching cardiac myosin-binding protein C stripes with titin's super-repeats.
Titin is largely comprised of serially-linked immunoglobulin (Ig) and fibronectin type-III (Fn3) domains. Many of these domains are arranged in an 11 domain super-repeat pattern that is repeated 11 times, forming the so-named titin C-zone in the A-band region of the sarcomere. Each super-repeat is thought to provide binding sites for thick filament proteins, such as cMyBP-C (cardiac myosin-binding protein C). However, it remains to be established which of titin's 11 C-zone super-repeats anchor cMyBP-C as titin contains 11 super-repeats and cMyBP-C is found in 9 stripes only. To study the layout of titin's C-zone in relation to MyBP-C, immunolabeling studies were performed on mouse skinned myocardium with antibodies to titin and cMyBP-C, using both immuno-electron microscopy and super-resolution optical microscopy. Results indicate that cMyBP-C locates near the interface between titin's C-zone super-repeats. Studies on a mouse model in which two of titin's C-zone repeats have been genetically deleted support that the first Ig domain of a super-repeat is important for anchoring cMyBP-C but also Fn3 domains located at the end of the preceding repeat. Furthermore, not all super-repeat interfaces are equal as the interface between super-repeat 1 and 2 (close to titin's D-zone) does not contain cMyBP-C. Finally, titin's C-zone does not extend all the way to the bare zone but instead terminates at the level of the second myosin crown. This study enhances insights in the molecular layout of the C-zone of titin, its relation to cMyBP-C, and its possible roles in cardiomyopathies.


[Stalking: unwelcome company. The psychopathology of a modern phenomenon].
The term stalking describes a pattern of behavior in which the victim is pursued, pestered and threatened. In many cases, the stalker resorts to physical violence, and may even commit murder. In the German-speaking areas, the phenomenon is to date not much discussed in the psychiatric and psychological literature, despite the fact that it is a widespread occurrence. While stalkers are diagnosed as suffering from schizophrenia and/or narcissistic as well as borderline disorders, victims have no typical "victim personality". They do, however, respond to stalking with anxiety, depression and post-traumatic stress disorders, which need to be recognized and treated.


Migration of epidermal keratinocytes: mechanisms, regulation, and biological significance.
Keratinocytes are the prevalent cell type of the epidermis, a multilayered cornified epithelium which provides the cellular basis of the outermost barrier between the organism and its environment. By this barrier function the epidermis protects the organism against a variety of environmental hazards such as dehydration and mechanical stress. Under normal conditions, keratinocytes of all layers are interconnected by desmosomes and anchored by hemidesmosomes to a specialised type of extracellular matrix, the basement membrane. When the epidermis is injured, a vitally important response is initiated with the aim to restore the protective function of the epithelium. A fast but provisional sealing is achieved by the deposition of the fibrin clot before within 24 h after wounding keratinocytes from the wound margins begin to migrate into the wound bed, where they start to proliferate and to form the new epithelium. The development of new high-resolution assays for the study of cell migration and motility has potentiated major progress in our understanding of keratinocyte migration in vitro and in situ. The data reviewed here point to a sophisticated cooperation between soluble motogenic growth factors, cell-matrix interactions, and cell-to-cell communications as major parts of the machinery regulating keratinocyte migration.


Varied acceptance of clinical trial results.
The subject of varied acceptance of clinical trial results is discussed in the context of review of trials with which I have been involved and my subjective evaluation of their impact on the practice of clinical medicine. My experience goes back to 1949 and a World Health Organization trial of hyperimmune gamma globulin against rabies. This was followed by a large trial of secondary prevention of poliomyelitis. I participated in the planning and initiation of the first chronic disease trial, the University Group Diabetes Program (UGDP). The latter lasted for 15 years and its ramifications continue to this day. My next trial was the Coronary Drug Project (CDP), a complex trial with more than 8,000 patients. The trials of aspirin and aspirin combined with persantine (the CDPA, AMIS, PARIS I, and PARIS II) followed. My last three trials were a trial of photocoagulation in diabetic retinopathy (DRS), a six-country trial of the antiarrhythmic drug mexiletine (IMPACT), and a study involving two diagnostic procedures for pulmonary embolism (PIOPED). When one considers, in retrospect, the plethora of trials one is struck by the uniform absence of a priori considerations of the impact on medical practice, or likely lack thereof, of possible outcomes.


The decade-long effect of work insecurity on husbands' and wives' midlife health mediated by anxiety: A dyadic analysis.
Although the detrimental physical health effects of work insecurity have been noted in previous research, less is known about the mediating processes, such as anxiety symptoms, that link work insecurity to physical health. Even less research has explored these effects at specific life stages and how these effects may impact significant others, even though the impact of this stress may vary across the life course and the mutual influences between married partners may cause dyadic effects stemming from partners' work insecurity. To fill these gaps, the current study incorporates theories that emphasize the stress-work connection, such as stress appraisal theory (Lazarus, 1999) and resource conservation theory (Hobfoll, 1989), into a neurobiological stress-health perspective. This study uses a sample of 330 consistently married, dual-earner husbands and wives who provided data at multiple time points over a 10-year period from 1991 to 2001. Results from a model including growth curves of work insecurity and anxiety symptoms when respondents were in their early middle years and reports of physical illness in their later middle years generally supported the hypothesized model. Both the level and rate of change in work insecurity were related to the change in anxiety symptoms over time. Similarly, the level and rate of change in anxiety symptoms from 1991 to 1994 were linked to subsequent illness years later in 2001. There was only partial support for the existence of partner effects. Findings are discussed as they relate to previous research as well as policy and clinical implications. (PsycINFO Database Record


Comparison of the oligosaccharide structure of the glycoprotein of vesicular stomatitis virus and a thermolabile mutant (tl-17).
As a means of examining the extent to which the polypeptide structure of a virus glycoprotein contributes to the overall structure and composition of the carbohydrate moieties, we have made a detailed comparison of the structure of the oligosaccharide moieties of wild-type vesicular stomatitis virus (VSV) glycoprotein with those of a glycoprotein-defective mutant of VSV, tl-17 (VSV). Characterization of the oligosaccharides by ion-exchange and gel filtration chromatography after sequential enzymic degradation reveals similar structures in the wt and mutant glycoproteins. However, the altered polypeptide structure of the tl-17 glycoprotein affects the extent of addition of sialic acid and fucose, both of which are added late in the maturation of the glycoprotein.


Isolated meniscus allograft transplantation with soft-tissue technique effectively reduces knee laxity in the presence of previous meniscectomy: In-vivo navigation of 18 consecutive cases.
Although meniscal allograft transplantation (MAT) is a well-established procedure with satisfactory clinical results, limited in vivo kinematic information exists on the effect of medial and lateral MAT performed in the clinical setting. The purpose of the present study was to evaluate the biomechanical effect of arthroscopic isolated medial and lateral MAT with a soft-tissue fixation on pre- and post-operative knee laxity using a surgical navigation system. 18 consecutive patients undergoing MAT (8 medial, 10 lateral) were enrolled. A surgical navigation system was used to quantify the anterior-posterior displacement at 30 and 90 degrees of knee flexion (AP30 and AP90), the varus-valgus rotation at 0 and 30 degrees of knee flexion (VV0 and VV30) and the dynamic laxity on the pivot-shift test (PS), which was determined through the anterior displacement of the lateral tibial compartment (APlat) and posterior acceleration of the lateral tibial compartment during tibial reduction (ACC). Data from laxity before and after MAT were compared through paired t-test (p < 0.05). After medial MAT, there was a significant decrease in tibial translation of 3.1 mm (31%; p = 0.001) for AP30 and 2.3 mm (27%; p = 0.020) for AP90, a significant difference of 2.5° (50%; p = 0.002) for VV0 and 1.7° (27%; p = 0.012) for VV30. However, medial MAT did not determine any reduction in the PS kinematic data. Lateral MAT determined a significant decrease in the tibial translation of 2.5 mm (38%; p < 0.001) for AP30 and 1.9 mm (34%; p = 0.004) for AP90 as well as a significant difference of 3.4° (59%; p < 0.001) for VV0 and of 1.7° (23%; p = 0.011) for VV30. There was also a significant reduction of the PS of 4.4 mm (22%; p = 0.028) for APlat and 384.8 mm/s2 (51%; p = 0.005) for ACC. MAT with soft-tissue fixation results in a significant laxity reduction in an in-vivo setting. Medial MAT improved knee kinematics by determining a significant reduction with particular emphasis on AP translation and VV manoeuvre. Conversely, Lateral MAT determined a massive reduction of the PS and a mild decrease of the AP translation and VV manoeuvre. Controlled laboratory study.


Genome sequencing of Aspergillus glaucus 'CCHA' provides insights into salt-stress adaptation.
Aspergillus, as a genus of filamentous fungi, has members that display a variety of different behavioural strategies, which are affected by various environmental factors. The decoded genomic sequences of many species vary greatly in their evolutionary similarities, encouraging studies on the functions and evolution of the Aspergillus genome in complex natural environments. Here, we present the 26 Mb de novo assembled high-quality reference genome of Aspergillus glaucus 'China Changchun halophilic Aspergillus' (CCHA), which was isolated from the surface of plants growing near a salt mine in Jilin, China, based on data from whole-genome shotgun sequencing using Illumina Solexa technology. The sequence, coupled with data from comprehensive transcriptomic survey analyses, indicated that the redox state and transmembrane transport might be critical molecular mechanisms for the adaptation of A. glaucus 'CCHA' to the high-salt environment of the saltern. The isolation of salt tolerance-related genes, such as CCHA-2114, and their overexpression in Escherichia coli demonstrated that A. glucus 'CCHA' is an excellent organism for the isolation and identification of salt tolerant-related genes. These data expand our understanding of the evolution and functions of fungal and microbial genomes, and offer multiple target genes for crop salt-tolerance improvement through genetic engineering.


Antifluorescein affinity columns. Isolation and immunocompetence of lymphocytes that bind fluoresceinated antigens in vivo or in vitro.
A new method for the isolation of specific immunocompetent lymphocytes has been described in which lymphocyte populations are exposed to fluoresceinated antigens (FLAGs) in vivo or in vitro, and the FLAG-binding cells retained on antifluorescein affinity columns. Specific cells are then eluted with an unrelated FL-labeled protein and shown to be fully immunocompetent. This methodology has been applied successfully in diverse antigenic systems including polymerized flagellin and TNP-specific B cells and alloantigen-reactive cytotoxic T lymphocytes. The method is rapid, inexpensive (requiring only antifluorescein beads), and can be applied to any antigens (or antibodies) in which a fluorescein group can be introduced.


Detection of four serotypes of avian adenovirus in New Zealand.
Twenty agents with adenovirus morphology were recovered from New Zealand domestic hens by means of chick kidney cell cultures. All the agents gave distinct cytopathic effects (CPE) in cell cultures, with two different types of CPE observed. On the basis of neutralization tests, the twenty agents were assigned to four distinct serological groups. Physicochemical tests on a "prototype" strain from each serological group confirmed that these agents are adenoviruses. The four prototype strains recovered in New Zealand are related to established overseas strains. One strain is serologically related to agents that cause IBH.


Extended-release carbamazepine capsules as monotherapy for acute mania in bipolar disorder: a multicenter, randomized, double-blind, placebo-controlled trial.
Although carbamazepine has long been used for the treatment of acute mania, only recently was its efficacy confirmed in a large, multicenter, parallel-group, placebo-controlled, randomized trial. In the present study, we further evaluated the efficacy and safety of monotherapy with beaded, extended-release carbamazepine capsules (ERC-CBZ) in patients with bipolar I disorder experiencing manic or mixed episodes. Hospitalized bipolar I disorder (DSM-IV criteria) patients (N = 239) with manic or mixed episodes were randomly assigned on a double-blind basis to receive ERC-CBZ or placebo for 3 weeks, following a single-blind placebo lead-in. Treatment with ERC-CBZ was initiated at 200 mg twice daily, and investigators were encouraged to increase doses, as necessary and tolerated, by 200 mg/day up to 1600 mg/day. Efficacy was assessed weekly with the Young Mania Rating Scale (YMRS), Clinical Global Impressions scale (CGI), and Hamilton Rating Scale for Depression. The study was conducted from July 23, 2002, to April 1, 2003. 144 patients (60.3%) completed the study, with a significant number of placebo patients discontinuing due to lack of efficacy (p < .001). Extended-release carbamazepine treatment was associated with significant improvements in mean YMRS total and CGI total scores, using last-observation-carried-forward analyses, beginning at day 7 (p < .05). Adverse events occurring more frequently in the ERC-CBZ-treated group included dizziness (39.3%), somnolence (30.3%), and nausea (23.8%) [corrected] Patients taking ERC-CBZ experienced a significant increase in total cholesterol, composed of increases in both high-density and low-density lipoproteins. Extended-release carbamazepine monotherapy had significantly greater efficacy compared with placebo in the treatment of acute mania in this large, randomized, double-blind, placebo-controlled trial.


The role of G protein-coupled receptors in the early evolution of neurotransmission and the nervous system.
The origin and evolution of the nervous system is one of the most intriguing and enigmatic events in biology. The recent sequencing of complete genomes from early metazoan organisms provides a new platform to study the origins of neuronal gene families. This review explores the early metazoan expansion of the largest integral transmembrane protein family, the G protein-coupled receptors (GPCRs), which serve as molecular targets for a large subset of neurotransmitters and neuropeptides in higher animals. GPCR repertories from four pre-bilaterian metazoan genomes were compared. This includes the cnidarian Nematostella vectensis and the ctenophore Mnemiopsis leidyi, which have primitive nervous systems (nerve nets), the demosponge Amphimedon queenslandica and the placozoan Trichoplax adhaerens, which lack nerve and muscle cells. Comparative genomics demonstrate that the rhodopsin and glutamate receptor families, known to be involved in neurotransmission in higher animals are also widely found in pre-bilaterian metazoans and possess substantial expansions of rhodopsin-family-like GPCRs. Furthermore, the emerging knowledge on the functions of adhesion GPCRs in the vertebrate nervous system provides a platform to examine possible analogous roles of their closest homologues in pre-bilaterians. Intriguingly, the presence of molecular components required for GPCR-mediated neurotransmission in pre-bilaterians reveals that they exist in both primitive nervous systems and nerve-cell-free environments, providing essential comparative models to better understand the origins of the nervous system and neurotransmission.


Numerical study of plasmonic efficiency of gold nanostripes for molecule detection.
In plasmonics, the accurate computation of the electromagnetic field enhancement is necessary in determining the amplitude and the spatial extension of the field around nanostructures. Here, the problem of the interaction between an electromagnetic excitation and gold nanostripes is solved. An optimization scheme, including an adaptive remeshing process with error estimator, is used to solve the problem through a finite element method. The variations of the electromagnetic field amplitude and the plasmonic active zones around nanostructures for molecule detection are studied in this paper taking into account the physical and geometrical parameters of the nanostripes. The evolution between the sizes and number of nanostripes is shown.


Factors associated with emergency department length of stay for patients with hip fracture.
Time to surgery, which includes time in the emergency department (ED), is important for all patients with hip fracture. We hypothesized that patients with hip fracture spend significantly more time in the ED than do patients with the top 5 most common conditions. In addition, we hypothesized that there are patient, physician, and hospital factors that affect the length of time spent in the ED. We retrospectively reviewed our institution's hip fracture database and identified 147 elderly patients with hip fractures who presented to our ED from December 18, 2005, through April 30, 2009. We reviewed their records for patient, practitioner, and hospital factors of interest associated with ED time and for 6 specified time intervals. Average working, boarding (waiting for an inpatient room), and total times were calculated and compared with respective averages for admitted ED patients with the top 5 most common conditions. Univariate and multivariate analyses were performed before and after adjusting for confounders (significance, P = .05). The mean total ED time (7 hours and 25 minutes) and working time (4 hours and 31 minutes) for patients with hip fracture were similar to the respective overall averages for admitted ED patients. However, the average boarding time for patients with hip fracture was 2 hours 44 minutes, longer than that for other patients admitted through the ED. Factors significantly associated with longer ED times were a history of hypertension, history of atrial fibrillation, the number of computed tomography scans ordered, and the occupancy rate. Admission to the hip fracture service decreased working time but not overall time. Substantial multidisciplinary work among the ED, hospital admission services, and physicians is needed to dramatically decrease the boarding time and thus the overall time to surgery.


MOFs-Based Nanoagents Enable Sequential Damage to Cancer-Associated Fibroblast and Tumor Cells for Phototriggered Tumor Microenvironment Regulation.
A composite nanoagent capable of phototriggered tumor microenvironment (TME) regulation is developed based on copper (II) metal-organic frameworks (MOFs) with encapsulation of blebbistatin (Bb) and surface modification of fibroblast activation protein-αtargeted peptide (Tp). Tp enables active targeting of the nanoagents to cancer-associated fibroblast (CAF) while near-infrared light triggers Cu2+ -to-Cu+ photoreduction in MOFs, which brings about the collapse of MOFs and the release of Bb and Cu+ . Bb mediates photogeneration of hydroxyl radicals (•OH) and therefore inhibits extracellular matrix production by inducing CAF apoptosis, which facilitates the penetration of nanoagent to deep tumor tissue. The dual-channel generation of •OH based on Bb and the Cu+ species, via distinct mechanisms, synergistically reinforces oxidative stress in TME capable of inducing immunogenic cell death, which activates the antitumor immune response and therefore reverses the immunosuppressive TME. The synergistic antitumor phototherapy efficacy of such a type of nanoagent based on the abovementioned TME remodeling is unequivocally verified in a cell-derived tumor xenograft model.


Multivisceral transplantation for pediatric intestinal pseudo-obstruction: single center's experience of 16 cases.
Chronic intestinal pseudo-obstruction (CIPO) in children may be life-threatening due to the complications of parenteral nutrition (PN) or catheter-related sepsis. Multivisceral transplantation (MVTx) is a lifesaving option but limited experience is available. We report our experience with MVTx in pediatric CIPO patients. Sixteen children with CIPO underwent MVTx at median age of 4 years. Indications for MVTx were liver failure (n = 10), loss of venous access (n = 3), or sepsis (n = 3). Modified MVTx without the liver was performed in six patients. Induction immunosuppression included tacrolimus, steroid with adjunctive agent in period I (April 1996 to December 2000), namely, OKT3 (n = 1), mycophenolate mofetil (n = 4), or daclizumab (n = 2); and in period II (January 2001 to present), Campath 1H (n = 4) or daclizumab (n = 5). The grade of rejection was severe in 12.5% and mild to moderate in 87.5% of cases. Isolated rejection of the transplanted stomach or pancreas was not diagnosed during clinical course or on autopsy. Actuarial patient survival for 1 year/2 years for period, I and II were 57.1%/42.9% and 88.9%/77.8%. None of the long-term survivors is on PN and all tolerate enteral feedings. Pancreatic enzyme supplementation or insulin therapy is not needed in survivors. Gastric emptying was substantially affected in one case. Bladder function did not improve in those with urinary retention problems. MVTx for CIPO offers a lifesaving option with excellent function of the transplanted pancreas and stomach among survivors.


Linear and quasi-linear viscoelastic characterization of ankle ligaments.
The objective of this study was to produce linear and nonlinear viscoelastic models of eight major ligaments in the human ankle/foot complex for use in computer models of the lower extremity. The ligaments included in this study were the anterior talofibular (ATaF), anterior tibiofibular (ATiF), anterior tibiotalar (ATT), calcaneofibular (CF), posterior talofibular (PTaF), posterior tibiofibular (PTiF), posterior tibiotalar (PTT), and tibiocalcaneal (TiC) ligaments. Step relaxation and ramp tests were performed. Back-extrapolation was used to correct for vibration effects and the error introduced by the finite rise time in step relaxation tests. Ligament behavior was found to be nonlinear viscoelastic, but could be adequately modeled up to 15 percent strain using Fung's quasilinear viscoelastic (QLV) model. Failure properties and the effects of preconditioning were also examined.


Ruptured-plaque-like appearance of restenotic tissue following sirolimus-eluting stent implantation: an optical coherence tomography case study.
A 57-year-old man was admitted for exertional angina pectoris. Coronary angiography showed a 99% stenosis in the left circumflex artery. A sirolimus-eluting stent was deployed in the culprit lesion and excellent angiographic results were obtained. Six-month routine follow-up coronary angiography showed a 90% focal restenosis at the proximal edge of the stent. At this site, optical coherence tomography imaging revealed restenotic tissue with a ruptured-plaque-like appearance overlying the stent struts. Also, a low intensity area suggestive of the presence of a lipid core was evident within the neointimal tissue in another cross section.


Deconstructing the epigenomic architecture of human neurodegeneration.
The past 10 years have seen a rapid advance in our ability to profile the epigenome from human pathologic material, opening up new study designs to investigate the role of epigenomic features in human disease. Moderate to large scale studies have now been conducted in the target tissue of neurodegenerative diseases, the brain, and, through the use of rigorous statistical methodologies, have laid a foundation of validated observations and successful study designs that inform our perspective on the role of the epigenome in these diseases, generate new hypotheses, and guide our path forward for a second generation of studies. It is clear that sampling the epigenome is not redundant with other "omic" profiling of the same tissue and that it can serve as an important vehicle for the integration of the effect of multiple environmental exposures on risk of disease. In some cases, change in the epigenome may thus have a causal impact on disease, but we now have evidence that such changes may also mediate some of the effect of tau proteinopathy and that other changes may moderate the impact of genetic risk factors. Thus, the epigenome may be involved at multiple different stages of the sequence of events that leads to human neurodegeneration, and we review the study designs that may begin to guide the development of a more comprehensive perspective on the aging brain's epigenome.


Oxytocin selectively modulates brain processing of disgust in Huntington's disease gene carriers.
People with Huntington's disease (HD) exhibit altered processing of emotional information, especially disgust and other negative emotions. These impairments are likely due to the effects of the disease on underlying brain networks. We examined whether oxytocin, when given intranasally, would normalise aberrant brain reactivity to emotional faces in participants with the gene-expansion for HD. In a double-blind placebo-controlled cross-over design, we measured brain activity, using functional magnetic resonance imaging, whilst nine medication-free HD carriers, and ten control participants viewed emotional (disgust, fear, angry, sad, surprise, happy) and neutral faces, following acute intranasal oxytocin (24IU) and placebo. Subjective mood changes were assessed before and after the neuroimaging on each visit. Permutation-based non-parametric statistical testing for the whole brain, showed significant group×drug interactions (p's<0.05, TFCE corrected) in areas of the left frontal pole, superior frontal, and middle frontal gyri cortically, and left putamen and thalamus sub-cortically. Parameter estimates extracted from the middle frontal gyrus and putamen showed that, under placebo, the HD group had lower brain activity to disgust stimuli, compared with controls. After intranasal oxytocin, the pattern of activation to disgust stimuli was normalised in the HD group to similar levels as controls; eight of the nine HD carriers showed increased response in the middle frontal gyrus, and seven of the nine HD carriers showed increased response in the putamen. The observed effects of oxytocin occurred in the absence of changes in subjective mood or state anxiety. These findings provide early evidence for a physiological role of oxytocin in the neuropathology of HD. Our findings are the first reported oxytocin effects in a neurodegenerative disease. Further research should examine the therapeutic benefits of oxytocin in alleviating emotional and social cognition deficits in HD and related disorders.


A qualitative study of a mental health awareness intervention for Jordanian and resettled Syrian refugees in host communities.
Mental health disorders significantly contribute to the global burden of disease, however, prevention and treatment programs are often inaccessible in low- and middle-income countries. The goal of this qualitative evaluation was to examine participants experiences of the healthy community clinic (HCC-MH), an integrated mental health awareness intervention delivered in primary care clinics to Jordanians and resettled Syrians in a border community in Jordan. Four focus group discussions (FGDs) with Jordanians and Syrians (N = 21) who participated in the HCC-MH were conducted. FGDs examined knowledge, acceptability, and applicability of the intervention. Open coding and the constant comparison method were used to identify themes that emerged from the FGDs. Six central themes emerged from the data including : (1) awareness; (2) behavior changes; (3) reduction in stigma; (4) connecting physical and mental health; (5) relationships; and (6) coping. Notably, female participants stated participation in the intervention fostered awareness of their own emotional needs, which led to positive lifestyle and behavior changes. Participants also described how the information provided in the intervention normalized emotional distress and aided understanding of the interconnection between physical and mental health. The amplification of healthy coping strategies to reduce stress and distress was also a prominent theme. Findings are discussed within the cultural and contextual setting of the study, and implications for mental health awareness interventions in complex settings are provided.


The pathogenesis of transfusion-related acute lung injury (TRALI).
In recent years, transfusion-related acute lung injury (TRALI) has developed from an almost unknown transfusion reaction to the most common cause of transfusion-related major morbidities and fatalities. A clinical definition of TRALI was established in 2004, based on acute respiratory distress, non-cardiogenic lung oedema temporal association with transfusion and hypoxaemia. Histological findings reveal lung oedema, capillary leucostasis and neutrophil extravasation. However, the pathogenesis of TRALI remains controversial. Leucocyte antibodies, present in fresh frozen plasma and platelet concentrates from multiparous donors, and neutrophil priming agents released in stored cellular blood components have been considered to be causative. As neutrophils and endothelial cells are pivotal in the pathogenesis of TRALI, a threshold model was established to try to unify the various reported findings on pathogenesis. This model comprises the priming of neutrophils and/or endothelium by the patient's co-morbidity, neutrophil and/or endothelial cell activation by the transfused blood component, and the severity of the TRALI reaction.


Transoral obesity surgery: endoluminal gastroplasty with an endoscopic suture device.
Surgical creation of a small gastric pouch with a restricted outlet is a well-established option for the treatment of morbid obesity. This report describes initial experience with endoscopic transoral stomach partition using a newly designed suturing apparatus. A fresh porcine stomach was placed in the Erlangen model. A prototype suture device, incorporating a curved needle and an intracorporeal tightening mechanism, was used in this procedure. A long fishing line was first introduced into the stomach, with the two ends left outside. The suturing device, premounted outside a standard gastroscope, was inserted into the stomach and delivered several stitches attaching the fishing line to both the anterior and posterior walls along the line for the stomach to be partitioned. Five throws of half-hitches were tied onto the fishing line extracorporeally and separately pushed into place, creating a gastric pouch just below the esophagogastric junction. A flexible sheath of 8 cm long was then put on one side of the fishing line and pushed into the stomach. Additional extracorporeal knots were tied on the fishing line, forming a restrictive ring at the outlet of the pouch. The ring was then anchored to the stomach wall with similar endosutures. The proximal gastric pouch, with an estimated volume of approximately 100 ml, was successfully created with a restrictive band at its outlet. All of the stitches were securely sutured, with consistent penetration of the muscular layer of the stomach wall. In a bench model, it is technically possible to accomplish transoral gastroplasty endoscopically with an intraluminal suturing device. Further live animal studies will be needed in order to confirm the efficacy and safety of this procedure before clinical application.


Epidemiology of naturally occurring rotavirus infection in rabbits.
The epidemiology of naturally acquired rotavirus infection in commercial rabbitries was studied. Antibody titers to rotavirus were determined by an enzyme linked immunosorbent assay (ELISA). Studies of antibody levels over time within individual rabbit litters and in a colony of rabbits of different ages showed that transplacentally derived maternal antibodies had declined to low levels by about one month of age. More than half of the 88 rabbits 1 to 2 months of age had antibody titers of less than 1/100. All 98 rabbits over 2 months old had titers above 1/100 and 83 had titers over 1/1000. Rotavirus was detected in 25% of diarrheic feces and in 10% of normal feces.


Monitoring forced degradation of drugs using silica coated AgNPs with surface-enhanced Raman scattering.
Potential degradation products (DPs), even in small concentrations, can cause changes in pharmacological and toxicological properties of a drug with a significant impact on product quality and safety. Thus, their stability and understanding of possible degradation mechanisms have a significant importance. Although liquid chromatography is the conventional technique used for forced degradation studies with excellent accuracy and reproducibility, the main disadvantages of the technique are being expensive and time-consuming. As a powerful technique, surface-enhanced Raman scattering (SERS) can be an alternative with its high sensitivity, easy sample preparation and low cost. In this study, the degradation of both tofacitinib (TOF), a Janus kinase inhibitor, and methotrexate (MTX), an inhibitor of tetrahydrofolate dehydrogenase, are studied using SERS under hydrolytic, oxidative and thermal conditions using mesoporous silica coated silver nanoparticles (Si@AgNPs) as SERS substrates. The study demonstrated that the degradation of the tested drugs using Si@AgNPs as SERS substrates could be monitored through the spectral changes on SERS spectra of drugs under several degradation conditions.


Fecal contamination of drinking water within peri-urban households, Lima, Peru.
We assessed fecal contamination of drinking water in households in 2 peri-urban communities of Lima, Peru. We measured Escherichia coli counts in municipal source water and, within households, water from principal storage containers, stored boiled drinking water, and water in a serving cup. Source water was microbiologically clean, but 26 (28%) of 93 samples of water stored for cooking had fecal contamination. Twenty-seven (30%) of 91 stored boiled drinking water samples grew E. coli. Boiled water was more frequently contaminated when served in a drinking cup than when stored (P < 0.01). Post-source contamination increased successively through the steps of usage from source water to the point of consumption. Boiling failed to ensure safe drinking water at the point of consumption because of easily contaminated containers and poor domestic hygiene. Hygiene education, better point-of-use treatment and storage options, and in-house water connections are urgently needed.


Predictors of participation in parenting workshops for improving adolescent behavioral and mental health: results from the common sense parenting trial.
Engaging and retaining participants are crucial to achieving adequate implementation of parenting interventions designed to prevent problem behaviors among children and adolescents. This study examined predictors of engagement and retention in a group-based family intervention across two versions of the program: a standard version requiring only parent attendance for six sessions and an adapted version with two additional sessions that required attendance by the son or daughter. Families included a parent and an eighth grader who attended one of five high-poverty schools in an urban Pacific Northwest school district. The adapted version of the intervention had a higher rate of engagement than the standard version, a difference that was statistically significant after adjusting for other variables assessed at enrollment in the study. Higher household income and parent education, younger student age, and poorer affective quality in the parent-child relationship predicted greater likelihood of initial attendance. In the adapted version of the intervention, parents of boys were more likely to engage with the program than those of girls. The variables considered did not strongly predict retention, although retention was higher among parents of boys. Retention did not significantly differ between conditions. Asking for child attendance at workshops may have increased engagement in the intervention, while findings for other predictors of attendance point to the need for added efforts to recruit families who have less socioeconomic resources, as well as families who perceive they have less need for services.


Nutrigenomics: from molecular nutrition to prevention of disease.
Until recently, nutrition research concentrated on nutrient deficiencies and impairment of health. The advent of genomics-interpreted broadly as a suite of high throughput technologies for the generation, processing, and application of scientific information about the composition and functions of genomes-has created unprecedented opportunities for increasing our understanding of how nutrients modulate gene and protein expression and ultimately influence cellular and organismal metabolism. Nutritional genomics (nutrigenomics), the junction between health, diet, and genomics, can be seen as the combination of molecular nutrition and genomics. The diverse tissue and organ-specific effects of bioactive dietary components include gene-expression patterns (transcriptome); organization of the chromatin (epigenome); protein-expression patterns, including posttranslational modifications (proteome); as well as metabolite profiles (metabolome). Nutrigenomics will promote an increased understanding of how nutrition influences metabolic pathways and homeostatic control, how this regulation is disturbed in the early phases of diet-related disease, and the extent to which individual sensitizing genotypes contribute to such diseases. Eventually, nutrigenomics will lead to evidence-based dietary intervention strategies for restoring health and fitness and for preventing diet-related disease. In this review, we provide a brief overview of nutrigenomics from our point of view by describing current strategies, future opportunities, and challenges.


Could lowering the tackle height in rugby union reduce ball carrier inertial head kinematics?
There is mounting evidence of reduced long-term cognitive ability in rugby players, even in those without a reported history of concussion. The tackle height law is an area of controversy. However, little is known about the effects of repetitive inertial head loading in rugby. Furthermore, the magnitude and influencing factors for head kinematics are generally unknown. In this exploratory study, 45 multibody front-on shoulder tackles simulated with the MADYMO pedestrian model and 20 staged rugby tackles executed by professional rugby players in a marker-based 3D motion laboratory were used to assess the effect of tackle height on ball carrier head kinematics. The peak resultant head linear accelerations, angular accelerations and change in angular velocities were measured and examined. The results suggest that tackle height strongly affects the head kinematics experienced by the ball carrier. In particular, higher ball carrier head kinematic values were identified for upper trunk tackles compared to mid/lower trunk tackles in both the multibody simulations and the staged rugby tackles. Average ball carrier peak resultant head linear acceleration, angular acceleration and change in angular velocity values for upper trunk tackles were greater than for mid/lower trunk tackles by a factor of 1.5, 2.5 and 1.7, in the multibody simulations, respectively, and 1.8 (p = 0.102), 2.2 (p = 0.025) and 2.3 (p = 0.004), in the staged tackles, respectively. The results of the study support the proposition of lowering the current tackle height laws to below the chest.


The design of studies testing the effectiveness of risk-guided care has many challenges: a scoping review addressing key considerations.
Studies evaluating the effectiveness of care based on patients' risk of adverse outcomes (risk-guided care) use a variety of study designs. In this scoping review, using examples, we review characteristics of relevant studies and present key design features to optimize the trustworthiness of results. We searched five online databases for studies evaluating the effect of risk-guided care among adults on clinical outcomes, process, or cost. Pairs of reviewers independently performed screening and data abstraction. We descriptively summarized the study design and characteristics. Among 14,561 hits, we identified 116 eligible studies. Study designs included randomized controlled trials (RCTs), post hoc analysis of RCTs, and retrospective or prospective cohort studies. Challenges and sources of bias in the design included limited performance of predictive models, contamination, inadequacy to address the credibility of subgroup effects, absence of differences in care across risk strata, reporting only process measures as opposed to clinical outcomes, and failure to report benefits and harms. To assess the benefit of risk-guided care, RCTs provide the most trustworthy evidence. Observational studies offer an alternative but are hampered by confounding and other limitations. Reaching valid conclusions when testing risk-guided care requires addressing the challenges identified in our review.