Predictors of parents' physical disciplinary practices.
This study examined how childhood history of discipline (1) related to ratings of how severe and typical punishments were; and (2) predicted parents' use of discipline techniques. The influence of child culpability on these ratings was also investigated. Ninety-nine New Zealand parents rated 12 physical discipline scenarios varying in discipline severity and perceived child culpability. Parents judged how severe and typical they considered the disciplines depicted in the scenarios and reported on how often they had experienced such discipline as children and how often they had used them with their own children. When the child was perceived to be at fault, parents rated the discipline depicted as less severe, considered the technique more typical, reported they had been similarly disciplined more frequently, and applied such discipline to their child more frequently. Childhood history of a discipline was related to the parent's use of that method, and the parents judged techniques they used with their own children as less severe and more typical of methods of discipline. History of discipline and severity judgments were the best predictors of parents' disciplinary practices. Although the findings support the cycle of violence theory, more complex potential pathways to abusive parenting, including the variables in this study, are proposed.


Characterization of the Fishing Lines in Titiwai (=Arachnocampa luminosa Skuse, 1890) from New Zealand and Australia.
Animals use adhesive secretions in a plethora of ways, either for attachment, egg anchorage, mating or as either active or passive defence. The most interesting function, however, is the use of adhesive threads to capture prey, as the bonding must be performed within milliseconds and under unsuitable conditions (movement of prey, variable environmental conditions, unfavourable attack angle, etc.) to be nonetheless successful. In the following study a detailed characterization of the prey capture system of the world-renowned glowworm group Arachnocampa from the macroscopic to the ultrastructural level is performed. The data reveal that the adhesive droplets consist mostly of water and display hygroscopic properties at varying humidity levels. The droplet core of Arachnocampa luminosa includes a certain amount of the elements sodium, sulphur and potassium (beside carbon, oxygen and nitrogen), while a different element composition is found in the two related species A. richardsae and A. tasmaniensis. Evidence for lipids, carbohydrates and proteins was negative on the histochemical level, however X-ray photoelectron spectroscopy confirm the presence of peptides within the droplet content. Different to earlier assumptions, the present study indicates that rather than oxalic acid, urea or uric acid are present in the adhesive droplets, presumably originating from the gut. Comparing the capture system in Arachnocampa with those of orb-spiders, large differences appear not only regarding the silky threads, but also, in the composition, hygroscopic properties and size of the mucous droplets.


Dark roast coffee is more effective than light roast coffee in reducing body weight, and in restoring red blood cell vitamin E and glutathione concentrations in healthy volunteers.
Recent results from prospective cohort studies have shown that moderate coffee consumption is associated with a reduced risk for diabetes mellitus type II or Alzheimer's disease. Since reactive oxygen species (ROS) are believed to be involved in the pathogenesis of these diseases, antioxidants in coffee might contribute to this risk reduction. We aimed at elucidating whether a dark roast coffee beverage (CB) rich in N-methylpyridinium ions (NMP: 785 μmol/L) and low in chlorogenic acids (CGA: 523 μmol/L) has stronger antioxidant effects on human erythrocytes than a CB prepared from a light roast with opposite proportions (CGA: 4538 μmol/L; NMP: 56 μmol/L). Following a 2-wk wash out period, 500 mL of the respective CB was administered to 30 subjects daily for 4-wk. Blood and spot urine samples were collected at the beginning and at the end of each intervention. Intake of the dark roast CB most effectively improved the antioxidant status of erythrocytes: superoxide dismutase and glutathione peroxidase activity decreased by 5.8 and 15%, respectively, whereas tocopherol and total glutathione concentrations increased by 41 and 14%, respectively. Furthermore, administration of the NMP-rich CB led to a significant body weight reduction in pre-obese subjects, whereas the CGA-rich CB did not.


Effects of dexmedetomidine on procedural pain and discomfort associated with central venous catheter insertion.
Central venous catheter (CVC) insertion induces pain and discomfort to a conscious patient despite application of a local anaesthetic (LA) field block and this pain can be greatly lessened by using additional analgesics. The aim of this study was to evaluate the efficacy of dexmedetomidine along with LA field infiltration in controlling pain and discomfort associated with CVC insertion. A prospective, randomised, double-blind, placebo-controlled trial of 54 patients scheduled for planned CVC insertion was undertaken. Patients were randomly assigned into two groups of 27 each, to receive either dexmedetomidine (1 μg/kg) or 0.9% normal saline, along with LA field infiltration. Pain and discomfort score was measured at 5 time points. The median pain score was worst for placebo group at local anaesthetic injection (6 [4-7]) and at the end of procedure (5 [4-5]), which was significantly attenuated in the dexmedetomidine group (4 [4-5] and 4 [3-5]; P = 0.007 and 0.040 respectively). The lower procedure related discomfort score in the immediate post-procedural period was statistically significant in dexmedetomidine group compared to placebo (4 [4-5] vs. 5 [4-6]; P = 0.008). Pre-procedural bolus dexmedetomidine infusion provides adequate analgesia and patient comfort for CVC insertion along LA field block. However, the tendency for excessive sedation and bradycardia associated with dexmedetomidine render it less desirable for this purpose.


Seroquel: biochemical profile of a potential atypical antipsychotic.
Seroquel and the atypical antipsychotic clozapine were compared using a number of biochemical measures in rats which are indicative of potential antipsychotic activity and possible extrapyramidal side effect liability. Both in vitro and in vivo, these compounds are low potency D-2 dopamine (DA) receptor antagonists and are relatively more potent 5-HT2 antagonists than typical antipsychotic drugs. Seroquel also exhibited low affinity for D-1 DA receptors in vitro, but D-1 receptor occupancy was not detectable in vivo. Unlike clozapine, Seroquel lacks appreciable activity at either D-1 DA or muscarinic receptors. Following IP administration, both compounds produce similar elevations in DA metabolite concentrations. Following 1 month of daily administration, at doses which produce large increases in striatal DA metabolite concentrations, both Seroquel and clozapine fail, unlike typical antipsychotics, to increase the number of striatal D-2 receptors, but do decrease the number of 5-HT2 receptors in frontal cortex. ICI 204,636 produces a short-lasting increase in plasma prolactin levels, but these increases are much greater than those that are produced by clozapine. One day after 3 weeks of daily administration, tolerance, to the ability of Seroquel to elevate DA metabolite and plasma PRL concentrations is not observed. These biochemical observations are discussed with regard to the atypical profile of Seroquel in behavioral and electrophysiological studies.


Interactions of head-kidney leucocytes from giant grouper, Epinephelus lanceolatus, with pathogenic Streptococcus agalactiae strains from marine and terrestrial origins.
Streptococcus agalactiae (Group B Streptococcus, GBS) is emerging as a genetically diverse species infecting farmed and wild fish, including commercially and culturally important groupers. To better understand how S. agalactiae are pathogenic in fish, we investigated interactions between isolates from fish and terrestrial hosts and the cellular immune system of Queensland grouper Epinephelus lanceolatus using flow cytometry. Adherent head-kidney leucocytes (HKL) from Queensland grouper displayed two main cell populations with distinct forward and side scatter by flow cytometry. The population of smaller and less complex cells (P1) was composed of monocytes, lymphocytes and thrombocytes, while the population of primarily larger and more complex cells (P2) comprised predominantly of macrophages and neutrophils. The cells in P2 had higher phagocytic index and capacity when incubated with fluorescent latex beads. HKL were activated by phorbol myristate acetate (PMA) but were unresponsive to lipopolysaccharide (LPS) and peptidoglycan (PTG), suggesting the absence of specific receptors on the surface of these cells for these ligands or a requirement for intermediates. In in vitro phagocytosis assays, all fish isolates of GBS activated a respiratory burst in P2 indicated by significant production of intracellular reactive oxygen species (ROS). Similarly, dog and cat isolates of different serotype and sequence type also induced ROS production in grouper HKL. However, human, crocodile and bovine isolates of GBS did not elicit significant ROS in HKL although they coincided with the highest phagocytic index. This suggests that these strains are capable of quenching ROS production. Terrestrial isolates significantly increased mortality of Queensland grouper leucocytes in vitro, aligned with a more diverse repertoire of cellular toxins in these strains. Opsonisation of a marine strain and terrestrial strain of GBS with antiserum raised against the marine strain resulted in an increase in ROS production by HKL in both cases although there was low antigenic cross reactivity between the two strains by flow cytometry, reflecting their diverse serotypes (Ib vs III). However, pre-incubation of either strain with normal serum from grouper also increased ROS production of HKL suggesting other opsonins may be involved. Based on these results it appears that piscine and terrestrial GBS isolates have contrasting strategies when interacting with the cellular immune system of Queensland grouper; the former seemingly evading phagocytosis, whilst the latter are readily phagocytosed but counteract ROS production.


Do alterations in placental 11beta-hydroxysteroid dehydrogenase (11betaHSD) activities explain differences in fetal hypothalamic-pituitary-adrenal (HPA) function following periconceptional undernutrition or twinning in sheep?
Periconceptional undernutrition (UN) in sheep accelerates fetal hypothalamic-pituitary-adrenal (HPA) axis activation, resulting in preterm birth. In contrast, twin conception suppresses fetal HPA function and delays prepartum HPA activation. We hypothesized that these dissimilar effects on fetal HPA activity result from different influences of maternal glucocorticoid (GC) on maturation of the fetal HPA axis, mediated via different activities of placental 11beta-hydroxysteroid dehydrogenase (11betaHSD) isozymes. We examined the effects of twinning and maternal periconceptional UN from 60 days before until 30 days after mating on the ontogeny of placental 11betaHSD-1 and -2 enzyme activities. At day 85 of gestation, placental 11betaHSD-2 activity was lower in UN than in normally nourished (N) fetuses (P < .05) and was higher in twins than in singletons (P < .05). Furthermore, placental 11betaHSD-1 activity was not different between nutritional groups but was higher in twins than in singletons (P = .01). At day 85, fetal plasma cortisol (P < .001) and cortisone (P < .001) concentrations were lower in UN than in N fetuses, but the cortisol to cortisone ratio was higher in UN than in N fetuses (P = .01). There was no effect of fetus number on plasma cortisol or cortisone concentrations or on the ratio of cortisol to cortisone at day 85. Therefore, periconceptional UN and twinning may result in the alterations of placental 11betaHSD isozyme activities at particular times during gestation. Changes in these activities during critical periods of fetal development could affect transplacental transfer or placental generation of GCs that reach the fetus, potentially influencing the timing of activation of the fetal HPA axis, fetal maturation, and hence the development and health later in life.


Intensive morphometric analysis of enormous alterations in skeletal bone system with micro-CT for AHNAK-/- mice.
AHNAK has been reported to be involved in actin cytoskeleton rearrangement of some cell types, calcium homeostasis, and activation of T cells. Although the functional role of AHNAK in muscle cells, epidermis, and brain has been determined, its association with apparent clinical impairment has not been found yet. During phenotypic analysis of AHNAK knock out (KO) mice for many years, we observed that AHNAK KO mice showed very slow growth. Snouts of these animals were very short, and their bones were easily broken compared to normal mice. It is known that AHNAK is closely related to calcium. However, intensive morphological studies on phenotypes of bone have yet been reported for AHNAK. Thus, the objective of the present study was to analyze the morphology of skull, mandibular, limbs, and caudal bones of AHNAK KO mice intensively using micro-CT with many factors for various ages of these mice (6 weeks, 18 weeks, and 40 weeks). As a result, it was found that the facial region of AHNAK KO mouse showed a large difference in mandible than skull. Their both femur and tibia were shortened, and bone strength was also significantly decreased compared to normal mice. Particularly, the tail bone of AHNAK KO mice exhibited morphological abnormality by age. Taken together, these results suggest that AHNAK plays an important role in bone shape, development, and metabolism. Although our results demonstrated that AHNAK has a distinct role in bone, further investigations are needed to determine various features of bone metabolism related to AHNAK in the future.


Anti-Yo-associated paraneoplastic cerebellar degeneration in a man with adenocarcinoma of the gastroesophageal junction.
Anti-Yo-associated paraneoplastic cerebellar degeneration is a cancer-related syndrome affecting the nervous system. This syndrome occurs almost exclusively in middle-aged women with gynecological cancers and it is rarely found in patients with other types of cancer or in males. In this report we describe a male patient adenocarcinoma of the gastroesophageal junction and PCD with anti-Yo antibodies. To our knowledge, this is only the third report of PCD with positive anti-Yo antibodies in an esophageal tumor and the first report in a tumor of the gastroesophageal junction.


A case of adult onset medulloblastoma during maintenance chemotherapy for anaplastic astrocytoma one year after radiotherapy.
Multiple primitive intracranial tumors with different histological characteristics are uncommon. Although coexistence of a medulloblastoma with glial tumors has been reported in children, medulloblastoma is rarely found in adults, especially those older than 40 years of age. We present an extremely rare case of a medulloblastoma developing in a 40-year-old male undergoing maintenance chemotherapy for anaplastic astrocytoma for 21 months after radiotherapy. Initially, he complained of intractable epilepsy characterized by complex partial seizures. Magnetic resonance imaging (MRI) revealed a slightly enhanced mass lesion in the left insula region. He underwent subtotal removal of the tumor and it was histologically diagnosed as anaplastic astrocytoma. After 19 months of treatment with temozolomide (TMZ) and radiotherapy, he presented with vertigo and headache. A homogeneously enhanced mass had developed in the left cerebellar hemisphere. He received gross total resection of the second tumor, pathologically diagnosed as medulloblastoma. In conclusion, this is the first case report of an adult medulloblastoma coexisting with anaplastic astrocytoma.


Evidence for similar patterns of neural activity elicited by picture- and word-based representations of natural scenes.
A long-standing core question in cognitive science is whether different modalities and representation types (pictures, words, sounds, etc.) access a common store of semantic information. Although different input types have been shown to activate a shared network of brain regions, this does not necessitate that there is a common representation, as the neurons in these regions could still differentially process the different modalities. However, multi-voxel pattern analysis can be used to assess whether, e.g., pictures and words evoke a similar pattern of activity, such that the patterns that separate categories in one modality transfer to the other. Prior work using this method has found support for a common code, but has two limitations: they have either only examined disparate categories (e.g. animals vs. tools) that are known to activate different brain regions, raising the possibility that the pattern separation and inferred similarity reflects only large scale differences between the categories or they have been limited to individual object representations. By using natural scene categories, we not only extend the current literature on cross-modal representations beyond objects, but also, because natural scene categories activate a common set of brain regions, we identify a more fine-grained (i.e. higher spatial resolution) common representation. Specifically, we studied picture- and word-based representations of natural scene stimuli from four different categories: beaches, cities, highways, and mountains. Participants passively viewed blocks of either phrases (e.g. "sandy beach") describing scenes or photographs from those same scene categories. To determine whether the phrases and pictures evoke a common code, we asked whether a classifier trained on one stimulus type (e.g. phrase stimuli) would transfer (i.e. cross-decode) to the other stimulus type (e.g. picture stimuli). The analysis revealed cross-decoding in the occipitotemporal, posterior parietal and frontal cortices. This similarity of neural activity patterns across the two input types, for categories that co-activate local brain regions, provides strong evidence of a common semantic code for pictures and words in the brain.


Trends of reported human cases of brucellosis, Kingdom of Saudi Arabia, 2004-2012.
Human brucellosis is an important zoonotic disease and is especially concerning in the Kingdom of Saudi Arabia (KSA), where livestock importation is significant. We analyzed reported human brucellosis disease trends in KSA over time to help policymakers understand the magnitude of the disease and guide the design of prevention and control measures. By using data from the national registry from 2004 to 2012, we calculated the cumulative numbers by age group and months. Trends of incidence rates (IRs) by gender, nationality, and region were also calculated. We found that there was a greater number of cases (19,130) in the 15-44 years age group than in any other age group. The IRs significantly decreased from 22.9 in 2004 [95% confidence interval (CI)=22.3, 23.5] to 12.5 in 2012 (95% CI=12.1, 13). Males had a significantly greater IR than females. Most cases were reported during spring and summer seasons. The IR of Saudi citizens was significantly greater than that of non-Saudis, but this difference reduced over time. The IRs of Al-Qassim, Aseer, and Hail were in the highest 25th percentile. Young, male Saudi citizens living in highly endemic areas were at greatest risk of acquiring brucellosis. We recommend vaccinating susceptible animals against brucellosis and increasing the public's awareness of preventive measures.


Angiosarcoma of the thoracic wall responded well to nanoparticle albumin-bound paclitaxel: A case report.
An 81-year-old woman visited a local clinic due to chest pain and a skin induration on the right precordia. She had a history of right breast cancer, and she had undergone a mastectomy and radiation therapy 10 years prior. Computed tomography (CT) imaging of the chest demonstrated a lobular mass that involved the right anterior thoracic wall and partially extruded from the thoracic cavity into the subcutaneous tissue. The tumor was surgically excised, and pathological analyses yielded a diagnosis of angiosarcoma. Five months after the operation, CT imaging showed multiple masses on the right pleura, indicating a local relapse and pleural dissemination of the angiosarcoma. Systemic chemotherapy composed of nanoparticle albumin-bound paclitaxel (nab-PTX) (80 mg/m(2)) was delivered weekly. After 4 courses of chemotherapy, the tumors regressed remarkably. Nab-PTX may be an effective treatment option for recurrent or metastatic angiosarcoma.


Effect of diabetes and fasting on GLUT-4 (muscle/fat) glucose-transporter expression in insulin-sensitive tissues. Heterogeneous response in heart, red and white muscle.
1. GLUT-4 glucose-transporter protein and mRNA levels were assessed in heart, red muscle and white muscle, as well as in brown and white adipose tissue from 7-day streptozotocin-induced diabetic and 48 h-fasted rats. 2. In agreement with previous data, white adipose tissue showed a substantial decrease in GLUT-4 mRNA and protein levels in response to both diabetes and fasting. Similarly, GLUT-4 mRNA and protein markedly decreased in brown adipose tissue in both insulinopenic conditions. 3. Under control conditions, the level of expression of GLUT-4 protein content differed substantially in heart, red and white skeletal muscle. Thus GLUT-4 protein was maximal in heart, and red muscle had a greater GLUT-4 content compared with white muscle. In spite of the large differences in GLUT-4 protein content, GLUT-4 mRNA levels were equivalent in heart and red skeletal muscle. 4. In heart, GLUT-4 mRNA decreased to a greater extent than GLUT-4 protein in response to diabetes and fasting. In contrast, red muscle showed a greater decrease in GLUT-4 protein than in mRNA in response to diabetes or fasting, and in fact no decrease in GLUT-4 mRNA content was detectable in fasting. On the other hand, preparations of white skeletal muscle showed a substantial increase in GLUT-4 mRNA under both insulinopenic conditions, and that was concomitant to either a modest decrease in GLUT-4 protein in diabetes or to no change in fasting. 5. These results indicate that (a) the effects of diabetes and fasting are almost identical and lead to changes in GLUT-4 expression that are tissue-specific, (b) white adipose tissue, brown adipose tissue and heart respond similarly to insulin deficiency by decreasing GLUT-4 mRNA to a larger extent than GLUT-4 protein, and (c) red and white skeletal muscle respond to insulinopenic conditions in a heterogeneous manner which is characterized by enhanced GLUT-4 mRNA/protein ratios.


Group acceptance and commitment therapy for patients and caregivers in psychosis services: Feasibility of training and a preliminary randomized controlled evaluation.
Psychological interventions reduce the impact of psychosis, but widescale implementation is problematic. We tested the feasibility of group acceptance and commitment therapy for Psychosis (G-ACTp), delivered by frontline staff, and co-facilitated by service-user experts-by-experience (SU-EbyE), for service-users and informal caregivers (ISRCTN: 68540929). We estimated recruitment/retention rates and outcome variability for future evaluation. Staff and SU-EbyE facilitators completed 1-day workshops, then delivered closely supervised G-ACTp, comprising four sessions (weeks 1-4) and two boosters (10 and 12 weeks). Participants recruited from adult community psychosis services were randomized to receive G-ACTp immediately or after 12 weeks, completing outcome assessments at 0, 4, and 12 weeks. Service-use/month was calculated for 1-year pre-randomization, weeks 0-12, and 5-year uncontrolled follow-up. Of 41 facilitators trained (29 staff, 12 SU-EbyE), 29 (71%; 17 staff, 12 SU-EbyE) delivered 18 G-ACTp courses. Participant refusal rates were low (9% of service-users [10/112]; 5% of caregivers [4/79]); 60% of those invited to participate attended ≥1 G-ACTp session (64% of service-users [39/61]; 56% of caregivers [35/63]). Randomization of facilitators and participants proved problematic and participant follow-up was incomplete (78% [66/85]; 82% of service-users [36/44]; 73% of caregivers [30/41]). Effect sizes ranged from very small to large mostly favouring treatment. Service-use reductions require cautious interpretation, as very few participants incurred costs. Implementation appears feasible for service-users; for caregivers, retention needs improving. Outcome variability indicated n = 100-300/arm followed up (α = 0.05, 90% power). Methodological limitations' mean replication is needed: identified sources of potential bias may be reduced in a cluster randomized design with sessional outcome completion. Group acceptance and commitment therapy can be successfully adapted for people with psychosis and their caregivers. Implementation (training and delivery) is possible in routine community mental health care settings. Clinical and economic outcomes are promising, but replication is needed. Recommendations are made for future studies.


Results From Thailand's 2016 Report Card on Physical Activity for Children and Youth.
Physical activity (PA) is recognized as one of the core modifiable risk factors of noncommunicable diseases. However, little is known about PA in the Thai population, particularly in children. The report card (RC) project provided Thailand with an opportunity to assess PA behaviors in children. This paper summarizes the methodology, grading process, and the final grades of the Thai RC. A school-based survey was conducted to collect data from a nationally representative sample of children aged 6 to 17 years. Survey results provided the primary source for the RC. Nine indicators were graded using the Global Matrix 2.0 framework. Grading was undertaken by a national committee comprising experts from key stakeholders. Grades ranged from F to B. Overall PA and Sedentary Behaviors both received the grade D-. Organized Sport Participation scored a C. Active Play scored the grade F. Active Transport and support from Family and Peers were both graded B. School, Community, and Government indicators were scored C. In Thai children, participation in PA and active play is very low; conversely, sedentary behaviors are high. These first data on patterns of activity for the Thailand RC will serve to guide national actions and advocacy aimed at increasing PA in children.


Patterns of tobacco use across rural, urban, and urban-slum populations in a north Indian community.
Tobacco is the leading cause of mortality globally and in India. The magnitude and the pattern of tobacco consumption are likely to be influenced by the geographical setting and with rapid urbanization in India there is a need to study this differential pattern. The aim was to study the rural, urban, and urban-slum differences in patterns of tobacco use. The study was conducted in Ballabgarh block, Faridabad district, Haryana, and was a community-based cross-sectional study. The study was conducted in years 2003-2004 using the WHO STEPS approach with 7891 participants, approximately equal number of males and females, selected using multistage sampling from urban, urban-slum, and rural strata. The analysis was done using the SPSS 12.0 statistical package (SPSS Inc., Chicago, IL, USA). Direct standardization to the WHO world standard population was done to and chi-square and ANOVA tests were used for comparison across three study settings. Self-reported tobacco use among males was as follows: urban 35.2%; urban-slums 48.3%; and rural 52.6% (P value <0.05). Self-reported tobacco use among females was as follows: Urban 3.5%; urban-slums 11.9%; and rural 17.7% (P value <0.05). More males reported daily bidi (tobacco wrapped in temburini leaf) smoking (urban 17.8%, urban-slums 36.7%, rural 44.6%) than cigarette use (urban 9.6%, urban-slums 6.3%, rural 2.9%). Females using smoked tobacco were almost exclusively using bidis (urban 1.7%, 7.9%, 11% in rural). Daily chewed tobacco use had urban, urban-slum, and rural gradients of 12%, 10.5%, and 6.8% in males respectively. Its use was low in females. The antitobacco policies of India need to focus on bidis in antitobacco campaigns. The program activities must find ways to reach the rural and urban-slum populations.


Improvement of the resonant cavity applicator for brain tumor hyperthermia - Computer simulation results -.
This paper discusses new methods to control the heating pattern of the prototype resonant cavity applicator for deep tumor hyperthermia treatment. We have already confirmed the effectiveness of the developed heating system with experiments using agar phantoms and computer simulations. Here, the following two methods to control the heating pattern were proposed. In the first method, a human body, which was placed in the gap between the two inner electrodes, was only moved towards the electrode. In the second method, in addition to the first method, the diametric ratio of the inner electrodes was changed. According to our computer simulation of heating agar phantoms, we found that the hot spot was moved about 35% of the distance from the center of the agar phantom. It was found that the proposed heating methods were applicable to both deep and regional hyperthermia treatments.


Self-paced timing detects and tracks change in prodromal Huntington disease.
This study compares self-paced timing performance (cross-sectionally and longitudinally) between participants with prodromal Huntington's disease (pr-HD) and a comparison group of gene non-expanded participants from affected families (NC). Participants (747 pr-HD: 188 NC) listened to tones presented at 550-ms intervals, matched that pace by tapping response keys and continued the rhythm (self-paced) after the tone had stopped. Standardized cross-sectional and longitudinal linear models examined the relationships between self-paced timing precision and estimated proximity to diagnosis, and other demographic factors. Pr-HD participants showed significantly less timing precision than NC. Comparison of pr-HD and NC participants showed a significant performance difference on two task administration conditions (dominant hand: p < .0001; alternating thumbs: p < .0001). Additionally, estimated proximity to diagnosis was related to timing precision in both conditions, (dominant hand: t = -11.14, df = 920, p < .0001; alternating thumbs: t = -11.32, df = 918, p < .0001). Longitudinal modeling showed that pr-HD participants worsen more quickly at the task than the NC group, and rate of decline increases with estimated proximity to diagnosis in both conditions (dominant hand: t = -2.85, df = 417, p = .0045; alternating thumbs: t = -3.56, df = 445, p = .0004). Effect sizes based on adjusted mean annual change ranged from -0.34 to 0.25 in the longitudinal model. The self-paced timing paradigm has potential for use as a screening tool and outcome measure in pr-HD clinical trials to gauge therapeutically mediated improvement or maintenance of function.


Paramutation-like features of multiple natural epialleles in tomato.
Freakish and rare or the tip of the iceberg? Both phrases have been used to refer to paramutation, an epigenetic drive that contravenes Mendel's first law of segregation. Although its underlying mechanisms are beginning to unravel, its understanding relies only on a few examples that may involve transgenes or artificially generated epialleles. By using DNA methylation of introgression lines as an indication of past paramutation, we reveal that the paramutation-like properties of the H06 locus in hybrids of Solanum lycopersicum and a range of tomato relatives and cultivars depend on the timing of sRNA production and conform to an RNA-directed mechanism. In addition, by scanning the methylomes of tomato introgression lines for shared regions of differential methylation that are absent in the S. lycopersicum parent, we identify thousands of candidate regions for paramutation-like behaviour. The methylation patterns for a subset of these regions segregate with non Mendelian ratios, consistent with secondary paramutation-like interactions to variable extents depending on the locus. Together these results demonstrate that paramutation-like epigenetic interactions are common for natural epialleles in tomato, but vary in timing and penetrance.


Fibromyalgia criteria and severity scales for clinical and epidemiological studies: a modification of the ACR Preliminary Diagnostic Criteria for Fibromyalgia.
To develop a fibromyalgia (FM) survey questionnaire for epidemiologic and clinical studies using a modification of the 2010 American College of Rheumatology Preliminary Diagnostic Criteria for Fibromyalgia (ACR 2010). We also created a new FM symptom scale to further characterize FM severity. The ACR 2010 consists of 2 scales, the Widespread Pain Index (WPI) and the Symptom Severity (SS) scale. We modified these ACR 2010 criteria by eliminating the physician's estimate of the extent of somatic symptoms and substituting the sum of 3 specific self-reported symptoms. We also created a 0-31 FM Symptom scale (FS) by adding the WPI to the modified SS scale. We administered the questionnaire to 729 patients previously diagnosed with FM, 845 with osteoarthritis (OA) or with other noninflammatory rheumatic conditions, 439 with systemic lupus erythematosus (SLE), and 5210 with rheumatoid arthritis (RA). The modified ACR 2010 criteria were satisfied by 60% with a prior diagnosis of FM, 21.1% with RA, 16.8% with OA, and 36.7% with SLE. The criteria properly identified diagnostic groups based on FM severity variables. An FS score ≥ 13 best separated criteria+ and criteria- patients, classifying 93.0% correctly, with a sensitivity of 96.6% and a specificity of 91.8% in the study population. A modification to the ACR 2010 criteria will allow their use in epidemiologic and clinical studies without the requirement for an examiner. The criteria are simple to use and administer, but they are not to be used for self-diagnosis. The FS may have wide utility beyond the bounds of FM, including substitution for widespread pain in epidemiological studies.


Incident reporting in post-operative patients managed by acute pain service.
Incident reporting is a reliable and inexpensive tool used in anaesthesia to identify errors in patient management. A hospital incident reporting system was already present in our hospital, but we were unable to find any incident related to acute pain management. Hence, acute pain service (APS) was started for voluntary incident reporting in post-operative patients to identify critical incidents, review the root cause and suggest remedial measures. All post-operative patients managed by APS were included in this observational study. A proforma was developed by APS, which included information about the type of incident (equipment and patient-related, human errors), severity of incident, person responsible and suggestions to prevent the same incident in the future. Patients and medical staff were informed about the reporting system. Whenever an incident was identified, a proforma was filled out by APS resident and data entered in SPSS programme. Total of 98 (1.80%) incidents were reported in 5432 patients managed by APS during 3 years period. Average age of the patients was 46 ± 17 years. Majority of incidents were related to epidural care (71%) and occurred in surgical wards (87%). Most of the incidents occurred due to human error and infusion delivery set-related defects. Incident reporting proved to be a feasible method of improving quality care in developing countries. It not only provides valuable information about areas which needed improvement, but also helped in developing strategies to improve care. Knowledge and attitudes of medical and paramedical staff are identified as the targeted area for improvement.


Muscle Injuries in Sports: A New Evidence-Informed and Expert Consensus-Based Classification with Clinical Application.
Muscle injuries are among the most common injuries in sport and continue to be a major concern because of training and competition time loss, challenging decision making regarding treatment and return to sport, and a relatively high recurrence rate. An adequate classification of muscle injury is essential for a full understanding of the injury and to optimize its management and return-to-play process. The ongoing failure to establish a classification system with broad acceptance has resulted from factors such as limited clinical applicability, and the inclusion of subjective findings and ambiguous terminology. The purpose of this article was to describe a classification system for muscle injuries with easy clinical application, adequate grouping of injuries with similar functional impairment, and potential prognostic value. This evidence-informed and expert consensus-based classification system for muscle injuries is based on a four-letter initialism system: MLG-R, respectively referring to the mechanism of injury (M), location of injury (L), grading of severity (G), and number of muscle re-injuries (R). The goal of the classification is to enhance communication between healthcare and sports-related professionals and facilitate rehabilitation and return-to-play decision making.


Evidence supporting dual-process theory of medical diagnosis: a functional near-infrared spectroscopy study.
The objective of this study was to determine the extent to which the dual-process theory of medical diagnosis enjoys neuroscientific support. To that end, the study explored whether neurological correlates of system-2 thinking could be located in the brain. It was hypothesised that system-2 thinking could be observed as the activation of the prefrontal cortex. An experimental paradigm was applied that consisted of a learning and a test phase. During the learning phase, 22 medical students were trained in diagnosing chest X-rays. Four of these eight cases were presented repeatedly, to develop a high level of expertise for these cases. During the test phase, all eight cases were presented and the participants' prefrontal cortex was scanned using functional near-infrared spectroscopy. Response time and diagnostic accuracy were recorded as behavioural indicators. The results revealed that participants' diagnostic accuracy in the test phase was significantly higher for the trained cases as compared with the untrained cases (F[1, 21] = 138.80, p < 0.001, η2 = 0.87). Also, their response time was significantly shorter for these cases (F[1, 21] = 18.12, p < 0.001, η2 = 0.46). Finally, the results revealed that only for the untrained cases, could a significant activation of the anterolateral prefrontal cortex be observed (F[1, 21] = 21.00, p < 0.01, η2 = 0.34). The fact that only untrained cases triggered higher levels of blood oxygenation in the prefrontal cortex is an indication that system-2 thinking is a cognitive process distinct from system 1. Implications of these findings for the validity of the dual-process theory are discussed.


Personal genomics services: whose genomes?
New companies offering personal whole-genome information services over the internet are dynamic and highly visible players in the personal genomics field. For fees currently ranging from US$399 to US$2500 and a vial of saliva, individuals can now purchase online access to their individual genetic information regarding susceptibility to a range of chronic diseases and phenotypic traits based on a genome-wide SNP scan. Most of the companies offering such services are based in the United States, but their clients may come from nearly anywhere in the world. Although the scientific validity, clinical utility and potential future implications of such services are being hotly debated, several ethical and regulatory questions related to direct-to-consumer (DTC) marketing strategies of genetic tests have not yet received sufficient attention. For example, how can we minimize the risk of unauthorized third parties from submitting other people's DNA for testing? Another pressing question concerns the ownership of (genotypic and phenotypic) information, as well as the unclear legal status of customers regarding their own personal information. Current legislation in the US and Europe falls short of providing clear answers to these questions. Until the regulation of personal genomics services catches up with the technology, we call upon commercial providers to self-regulate and coordinate their activities to minimize potential risks to individual privacy. We also point out some specific steps, along the trustee model, that providers of DTC personal genomics services as well as regulators and policy makers could consider for addressing some of the concerns raised below.


Ring1-mediated ubiquitination of H2A restrains poised RNA polymerase II at bivalent genes in mouse ES cells.
Changes in phosphorylation of the carboxy-terminal domain (CTD) of RNA polymerase II (RNAP) are associated with transcription initiation, elongation and termination. Sites of active transcription are generally characterized by hyperphosphorylated RNAP, particularly at Ser 2 residues, whereas inactive or poised genes may lack RNAP or may bind Ser 5-phosphorylated RNAP at promoter proximal regions. Recent studies have demonstrated that silent developmental regulator genes have an unusual histone modification profile in ES cells, being simultaneously marked with Polycomb repressor-mediated histone H3K27 methylation, and marks normally associated with gene activity. Contrary to the prevailing view, we show here that this important subset of developmental regulator genes, termed bivalent genes, assemble RNAP complexes phosphorylated on Ser 5 and are transcribed at low levels. We provide evidence that this poised RNAP configuration is enforced by Polycomb Repressor Complex (PRC)-mediated ubiquitination of H2A, as conditional deletion of Ring1A and Ring1B leads to the sequential loss of ubiquitination of H2A, release of poised RNAP, and subsequent gene de-repression. These observations provide an insight into the molecular mechanisms that allow ES cells to self-renew and yet retain the ability to generate multiple lineage outcomes.


Nonreceptor-mediated intestinal vasoconstriction in portal hypertensive rats.
Previous studies have demonstrated that receptor-mediated vasoconstriction is impaired in chronic portal hypertension (PH). Furthermore, it has been suggested that altered vasoconstrictor effectiveness in chronic PH is due to a defect in the intracellular events associated with smooth muscle activation and not to impaired coupling of vasoconstrictors with vascular smooth muscle receptors. The present study was designed to determine whether nonreceptor-mediated vasoconstrictor responses are impaired in the PH intestinal microcirculation. Specifically, we examined the effects of aluminum fluoride-induced activation of G proteins, KCl-induced depolarization, caffeine-induced release of intracellular Ca2+, and l-indolactam-induced activation of protein kinase C on the intestinal microcirculation of normal (Norm, n = 39) and PH (n = 42) rats. The small intestine was prepared for microcirculatory studies and transferred to a video microscope. First-order arteriolar (1A) diameter and red cell velocity were measured on-line. Blood flow was calculated from the product of velocity and microvessel cross-sectional area. After a control period, the microvasculature was exposed to a solution containing aluminum chloride plus sodium fluoride, potassium chloride, caffeine, or l-indolactam. Maximal decreases in arteriolar diameter produced by aluminum fluoride, KCl, caffeine, and l-indolactam were significantly greater in Norm rats when compared with PH rats. Changes in arteriolar blood flow were also larger in Norm than in PH rats. The results of the present study provide the first direct evidence of an impaired response to second-messenger activation in the PH circulation.


Quantification of nonlinear elasticity for the evaluation of submillimeter crack length in cortical bone.
The objective of this study was to investigate the sensitivity of the nonlinear elastic properties of cortical bone to the presence of a single submillimetric crack. Nonlinear elasticity was measured by nonlinear resonant ultrasound spectroscopy (NRUS) in 14 human cortical bone specimens. The specimens were parallelepiped beams (50×2×2 mm(3)). A central notch of 500 µm was made to control crack initiation and propagation during four-point bending. The nonlinear hysteretic elastic and dissipative parameters αf and αQ, and Young׳s modulus Eus were measured in dry condition for undamaged (control) specimens and in dry and wet conditions for damaged specimens. The length of the crack was assessed using synchrotron radiation micro-computed tomography (SR-μCT) with a voxel size of 1.4 μm. The initial values of αf, measured on the intact specimens, were remarkably similar for all the specimens (αf =-5.5±1.5). After crack propagation, the nonlinear elastic coefficient αf increased significantly (p<0.006), with values ranging from -4.0 to -296.7. Conversely, no significant variation was observed for αQ and Eus. A more pronounced nonlinear elastic behavior was observed in hydrated specimens compared to dry specimens (p<0.001) after propagation of a single submillimetric crack. The nonlinear elastic parameter αf was found to be significantly correlated to the crack length both in dry (R=0.79, p<0.01) and wet (R=0.84, p<0.005) conditions. Altogether these results show that nonlinear elasticity assessed by NRUS is sensitive to a single submillimetric crack induced mechanically and suggest that the humidity must be strictly controlled during measurements.


Budget Impact Analysis of Cancer Screening: A Methodological Review.
Budget impact analyses (BIAs) describe changes in intervention- and disease-related costs of new technologies. Evidence on the quality of BIAs for cancer screening is lacking. We systematically reviewed the literature and methods to assess how closely BIA guidelines are followed when BIAs are performed for cancer-screening programs. Systematic searches were conducted in MEDLINE, EMBASE, EconLit, CRD (Centre for Reviews and Dissemination, University of York), and CEA registry of the Tufts Medical Center. Eligible studies were BIAs evaluating cancer-screening programs published in English, 2010-2018. Standardized evidence tables were generated to extract and compare study characteristics outlined by the ISPOR BIA Task Force. Nineteen studies were identified evaluating screening for breast (5), colorectal (6), cervical (3), lung (1), prostate (3), and skin (1) cancers. Model designs included decision-analytic models (13) and simple cost calculators (6). From all studies, only 53% reported costs for a minimum of 3 years, 58% compared to a mix of screening options, 42% reported model validation, and 37% reported uncertainty analysis for participation rates. The quality of studies appeared to be independent of cancer site. "Gray" literature was not searched, misinterpretation is possible due to limited information in publications, and focus was on international methodological guidelines rather than regional guidelines. Our review highlights considerable variability in the extent to which BIAs evaluating cancer-screening programs followed recommended guidelines. The annual budget impact at least over the next 3-5 years should be estimated. Validation and uncertainty analysis should always be conducted. Continued dissemination efforts of existing best-practice guidelines are necessary to ensure high-quality analyses.


Improving the Development, Monitoring and Reporting of Stroke Rehabilitation Research: Consensus-Based Core Recommendations from the Stroke Recovery and Rehabilitation Roundtable.
Recent reviews have demonstrated that the quality of stroke rehabilitation research has continued to improve over the last four decades but despite this progress, there are still many barriers in moving the field forward. Rigorous development, monitoring and complete reporting of interventions in stroke trials are essential in providing rehabilitation evidence that is robust, meaningful and implementable. An international partnership of stroke rehabilitation experts committed to develop consensus-based core recommendations with a remit of addressing the issues identified as limiting stroke rehabilitation research in the areas of developing, monitoring and reporting stroke rehabilitation interventions. Work exploring each of the three areas took place via multiple teleconferences and a two-day meeting in Philadelphia in May 2016. A total of 15 recommendations were made. To validate the need for the recommendations, the group reviewed all stroke rehabilitation trials published in 2015 (n=182 papers). Our review highlighted that the majority of publications did not clearly describe how interventions were developed or monitored during the trial. In particular, under-reporting of the theoretical rationale for the intervention and the components of the intervention call into question many interventions that have been evaluated for efficacy. More trials were found to have addressed the reporting of interventions recommendations than those related to development or monitoring. Nonetheless, the majority of reporting recommendations were still not adequately described. To progress the field of stroke rehabilitation research and to ensure stroke patients receive optimal evidence-based clinical care, we urge the research community to endorse and adopt our recommendations.


Hyperpolarization-activated currents are differentially expressed in mice brainstem auditory nuclei.
The hyperpolarization-activated cation current (I(h)) may influence precise auditory processing by modulating resting membrane potential and cell excitability. We used electrophysiology and immunohistochemistry to investigate the properties of I(h) in three auditory brainstem nuclei in mice: the anteroventral cochlear nucleus (AVCN), the medial nucleus of the trapezoid body (MNTB) and the lateral superior olive (LSO). I(h) amplitude varied considerably between these cell types, with the order of magnitude LSO > AVCN > MNTB. Kinetically, I(h) is faster in LSO neurons, and more active at rest, compared with AVCN and MNTB cells. The half-activation voltage is -10 mV more hyperpolarized for AVCN and MNTB cells compared with LSO neurons. HCN1 immunoreactivity strongly labelled AVCN and LSO neurons, while HCN2 staining was more diffuse in all nuclei. The HCN4 subunit displayed robust membrane staining in AVCN and MNTB cells but weak labelling of the LSO. We used a dynamic clamp, after blocking I(h), to reinsert I(h) to the different cell types. Our results indicate that the native I(h) for each cell type influences the resting membrane potential and can delay the generation of action potentials in response to injected current. Native I(h) increases rebound depolarizations following hyperpolarizations in all cell types, and increases the likelihood of rebound action potentials (particularly in multiple-firing LSO neurons). This systematic comparison shows that I(h) characteristics vary considerably between different brainstem nuclei, and that these differences significantly affect the response properties of cells within these nuclei.


Endogenous IL-12 is required for control of Th2 cytokine responses capable of exacerbating leishmaniasis in normally resistant mice.
We investigated the mechanisms by which treatment with anti-IL-12 Ab prevents cure of infection with Leishmania major in resistant C57BL/6 mice. Consistent with delayed production of IL-12, anti-IL-12 Abs could be administered as late as 2 wk after infection to exacerbate disease. Starting at 2 wk of infection, the cultured lymph node cells from mice treated with either polyclonal or monoclonal anti-IL-12 Abs persistently generated 3- to 10-fold more IL-4 and IL-10 in response to L. major Ag compared with cells from mice receiving preimmune goat IgG. Reciprocal decreases in Ag-specific IFN-gamma production were observed in mice receiving anti-IL-12 Abs. A similar reversal of IFN-gamma and IL-4 production accompanied progressive disease induced by pretreatment with a single dose of anti-IFN-gamma mAb. Although IFN-gamma production was suppressed for up to 4 wk in mice treated with monoclonal anti-IL-12 or anti-IFN-gamma, coadministration of neutralizing anti-IL-4 IgG reversed progressive illness. These findings demonstrate that IL-12 produced in vivo is necessary for both the emergence of IFN-gamma producing cells and the down-regulation of Th2 cell responses during murine leishmaniasis. Furthermore, the uninhibited production of IL-4 was required to sustain progressive infection initiated by the decreased IFN-gamma synthesis observed in anti-IL-12 and anti-IFN-gamma-treated mice.


Interaction of monotopic membrane enzymes with a lipid bilayer: a coarse-grained MD simulation study.
Monotopic membrane proteins bind tightly to cell membranes but do not generally span the lipid bilayer. Their interactions with lipid bilayers may be studied via coarse-grained molecular dynamics (CG-MD) simulations. Understanding such interactions is important as monotopic enzymes frequently act on hydrophobic substrates, while X-ray structures rarely provide direct information about their interactions with membranes. CG-MD self-assembly simulations enable prediction of the orientation and depth of insertion into a lipid bilayer of a monotopic protein, and also of the interactions of individual protein residues with lipid molecules. The CG-MD method has been evaluated via comparison with extended (>30 ns) atomistic simulations of monoamine oxidase, revealing good agreement between the results of coarse-grained and atomistic simulations. CG-MD simulations have been applied to a set of 11 monotopic proteins for which three-dimensional structures are available. These proteins may be divided into two groups on the basis of the results of the simulations. One group consists of those proteins which are inserted into the lipid bilayer to a limited extent, interacting mainly at the phospholipid-water interface. The second group consists of those which are inserted more deeply into the bilayer. Those monotopic proteins which are inserted more deeply cause significant local perturbation of bilayer properties such as bilayer thickness. Deeper insertion seems to correlate with a greater number of basic residues in the "foot" whereby a monotopic protein interacts with the membrane.


New trends in the surgical treatment of outlet obstruction: clinical and functional results of two novel transanal stapled techniques from a randomised controlled trial.
A randomised trial was undertaken to compare the clinical and functional results of two novel transanal stapled techniques in patients with outlet obstruction syndrome. Ninety-six females with outlet obstruction were treated with medical therapy and biofeedback for 2 months; 67 non-responders were evaluated by the Constipation Scoring and Continence Grading Systems, clinical examination, endoscopy, dynamic defecography, anorectal manometry, transanal ultrasound and anal EMG, and 50 of them, all affected with descending perineum, intussusception and rectocele, were randomly assigned to two groups and operated on: 25 patients (mean age 53.2+/-15.3 years) underwent a single Stapled Trans-Anal Prolapsectomy, associated with Perineal Levatorplasty (STAPL Group), and the other 25 (mean 54.6+/-14.2 years) underwent a double Stapled Trans-Anal Rectal Resection (STARR Group). Patients were followed-up for a mean period of 23.4+/-5.1 months in STAPL Group and 22.3+/-4.8 in STARR Group. STARR Group showed a significantly (p<0.0001) lower pattern of postoperative pain and a greater decrease (P=0.0117) of the rectal sensitivity threshold volume; otherwise, no differences were found in operative time, hospital stay, or time of inability to work. Complications included delayed healing of the perineal wound (ten), dyspareunia (five), urinary retention (two) and stenosis (one) in STAPL Group, and urge to defecate (four), transitory incontinence to flatus (two), urinary retention (two), bleeding (one) and stenosis (one) in STARR Group. All constipation symptoms significantly improved without worsening of anal continence and with excellent/good outcome at 20 months in 76 and 88% of patients of STAPL Group and STARR Group, respectively. Seven patients of STAPL Group had a little residual rectocele, while both intussusception and rectocele were corrected in all patients of STARR Group. Neither operation modified anal pressures or caused lesions of anal sphincters. Both techniques are safe and effective in the treatment of outlet obstruction; nevertheless, the double Stapled Trans-Anal Rectal Resection seems to be preferable due to less pain, absence of dyspareunia, reduced rectal sensitivity threshold volume and absence of residual rectocele at defecography.


To rebound or dissociate? This is the mechanistic question in C-H hydroxylation by heme and nonheme metal-oxo complexes.
Enzymatic reactions that involve C-H bond activation of alkanes by high-valent iron-oxo species can be explained by the rebound mechanism (RM). Hydroxylation reactions of alkane substrates effected by the reactive compound I (Cpd I) species of cytochrome P450 enzymes are good examples. There was initially little doubt that the rebound paradigm could be carried over in the same form to the arena of synthetic nonheme high-valent iron-oxo or other metal-oxo complexes. However, the active reaction centres of these synthetic systems are not well-caged, in contrast to the active sites of enzymes; therefore, the relative importance of the radical dissociation pathway can become prominent. Indeed, accumulating experimental and theoretical evidence shows that introduction of the non-rebound mechanism (non-RM) is necessary to rationalise the different reactivity patterns observed for synthetic nonheme complexes. In this tutorial review, we discuss several specific examples involving the non-RM while making frequent comparisons to the RM, mainly from the perspective of computational chemistry. We also provide a technical guide to DFT calculations of RM and non-RM and to the interpretations of computational outcomes.


The purification, crystallization and structural elucidation of dTDP-D-glucose 4,6-dehydratase (RmlB), the second enzyme of the dTDP-L-rhamnose synthesis pathway from Salmonella enterica serovar typhimurium.
dTDP-D-glucose 4,6-dehydratase (RmlB) is the second of four enzymes involved in the dTDP-L-rhamnose pathway and catalyzes the dehydration of dTDP-D-glucose to dTDP-4-keto-6-deoxy-D-glucose. The ultimate product of the pathway, dTDP-L-rhamnose, is the precursor of L-rhamnose, which is a key component of the cell wall of many pathogenic bacteria. RmlB from Salmonella enterica serovar Typhimurium has been overexpressed and purified, and crystals of the enzyme have been grown using the sitting-drop vapour-diffusion technique with lithium sulfate as precipitant. Diffraction data have been obtained to a resolution of 2.8 A on a single frozen RmlB crystal which belongs to space group P2(1), with unit-cell parameters a = 111.85, b = 87.77, c = 145.66 A, beta = 131.53 degrees. The asymmetric unit contains four monomers in the form of two RmlB dimers with a solvent content of 62%. A molecular-replacement solution has been obtained and the model is currently being refined.


L-Cysteine metabolism and its nutritional implications.
L-Cysteine is a nutritionally semiessential amino acid and is present mainly in the form of L-cystine in the extracellular space. With the help of a transport system, extracellular L-cystine crosses the plasma membrane and is reduced to L-cysteine within cells by thioredoxin and reduced glutathione (GSH). Intracellular L-cysteine plays an important role in cellular homeostasis as a precursor for protein synthesis, and for production of GSH, hydrogen sulfide (H(2)S), and taurine. L-Cysteine-dependent synthesis of GSH has been investigated in many pathological conditions, while the pathway for L-cysteine metabolism to form H(2)S has received little attention with regard to prevention and treatment of disease in humans. The main objective of this review is to highlight the metabolic pathways of L-cysteine catabolism to GSH, H(2)S, and taurine, with special emphasis on therapeutic and nutritional use of L-cysteine to improve the health and well-being of animals and humans.


Red Blood Cell Docosapentaenoic Acid (DPA n-3) is Inversely Associated with Triglycerides and C-reactive Protein (CRP) in Healthy Adults and Dose-Dependently Increases Following n-3 Fatty Acid Supplementation.
The role of the long-chain omega-3 (n-3) fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in lipid metabolism and inflammation has been extensively studied; however, little is known about the relationship between docosapentaenoic acid (DPA, 22:5 n-3) and inflammation and triglycerides (TG). We evaluated whether n-3 DPA content of red blood cells (RBC) was associated with markers of inflammation (interleukin-6 (IL-6), tumor necrosis factor α (TNF-α), and C-reactive protein (CRP) and fasting TG prior to n-3 supplementation in two studies (Study 1: n = 115, aged 20-44 years, body mass index (BMI) 20-30 kg/m2, TG = 34-176 mg/dL; Study 2: n = 28, aged 22-65 years, BMI 24-37 kg/m2, TG = 141-339 mg/dL). We also characterized the dose-response effects of n-3 fatty acid supplementation on RBC n-3 DPA after five months of supplementation with fish oil (Study 1: 0, 300, 600, 900, and 1800 mg/day EPA + DHA) and eight weeks of prescription n-3 ethyl esters (Study 2: 0, 850, and 3400 mg/day EPA + DHA). In Study 1, RBC n-3 DPA was inversely correlated with CRP (R2 = 36%, p < 0.001) and with fasting TG (r = -0.30, p = 0.001). The latter finding was replicated in Study 2 (r = -0.33, p = 0.04). In both studies, n-3 supplementation significantly increased RBC n-3 DPA dose-dependently. Relative increases were greater for Study 1, with increases of 29%-61% vs. 14%-26% for Study 2. The associations between RBC n-3 DPA, CRP, and fasting TG may have important implications for the prevention of atherosclerosis and chronic inflammatory diseases and warrant further study.


Effects of Visual Experience on the Human MT+ Functional Connectivity Networks: An fMRI Study of Motion Perception in Sighted and Congenitally Blind Individuals.
Human middle temporal complex (hMT+) responds also to the perception of non-visual motion in both sighted and early blind individuals, indicating a supramodal organization. Visual experience, however, leads to a segregation of hMT+ into a more anterior subregion, involved in the supramodal representation of motion, and a posterior subregion that processes visual motion only. In contrast, in congenitally blind subjects tactile motion activates the full extent of hMT+. Here, we used fMRI to investigate brain areas functionally connected with the two hMT+ subregions (seeds) during visual and tactile motion in sighted and blind individuals. A common functional connectivity network for motion processing, including bilateral ventral and dorsal extrastriate, inferior frontal, middle and inferior temporal areas, correlated with the two hMT+ seeds both in sighted and blind individuals during either visual or tactile motion, independently from the sensory modality through which the information was acquired. Moreover, ventral premotor, somatosensory, and posterior parietal areas correlated only with the anterior but not with the posterior portion of hMT+ in sighted subjects, and with both hMT+ seeds in blind subjects. Furthermore, a correlation between middle temporal and occipital areas with primary somatosensory seeds was demonstrated across conditions in both sighted and blind individuals, suggesting a cortico-cortical pathway that conveys non-visual information from somatosensory cortex, through posterior parietal regions, to ventral extrastriate cortex. These findings expand our knowledge about the development of the functional organization within hMT+ by showing that distinct patterns of brain functional correlations originate from the anterior and posterior hMT+ subregions as a result of visual experience.


Diffusive search and trajectories on tubular networks: a propagator approach.
Several organelles in eukaryotic cells, including mitochondria and the endoplasmic reticulum, form interconnected tubule networks extending throughout the cell. These tubular networks host many biochemical pathways that rely on proteins diffusively searching through the network to encounter binding partners or localized target regions. Predicting the behavior of such pathways requires a quantitative understanding of how confinement to a reticulated structure modulates reaction kinetics. In this work, we develop both exact analytical methods to compute mean first passage times and efficient kinetic Monte Carlo algorithms to simulate trajectories of particles diffusing in a tubular network. Our approach leverages exact propagator functions for the distribution of transition times between network nodes and allows large simulation time steps determined by the network structure. The methodology is applied to both synthetic planar networks and organelle network structures, demonstrating key general features such as the heterogeneity of search times in different network regions and the functional advantage of broadly distributing target sites throughout the network. The proposed algorithms pave the way for future exploration of the interrelationship between tubular network structure and biomolecular reaction kinetics.


Opioid use patterns and health care resource utilization in patients prescribed opioid therapy with and without constipation.
The main objective of this study was to compare the opioid use patterns, resource utilization, and costs of patients on opioid therapy who have constipation with those who do not. Retrospective, observational matched cohort design Patients initiating opioid therapy between Jan. 1, 1999 and Dec. 31, 2005 were identified from a longitudinal insurance claims database. Patients had > or = 30 days of opioid use and continuous plan coverage for > or = 6 months before and > or = 12 months after their index date, defined as the date of the first pharmacy claim for an opioid. Constipation was defined as having one or more ICD-9 codes of 564.0 during the follow-up period. Patterns of opioid use and resource utilization were compared between patients with constipation and a demographically matched (1:1) cohort of opioid initiators without consti- pation using t-tests and Chi-square (chi2) tests. We identified 39,485 patients, of whom 2,519 (6.4%) had constipation. Most patients with constipation were female (66%) and > or = 45 years old (68%). Compared to controls, the constipation group had significantly higher rates of concurrent use of > or = 2 opioids (p < 0.0001), discontinuation, and switching between opioids. Patients with constipation had statistically significant higher hospital admissions, emergency room visits, home health services, nursing home care, physician office visits, other outpatient/ ancillary care, and laboratory tests. Patients with constipation had significantly higher mean all-cause costs for emergency, physician visits, nursing facility, home health, and prescription drug services compared to patients without constipation. Opioid-treated patients with constipation were found to have significant differences in opioid use patterns and significantly higher health care utilization and associated costs.


Practicum in adapted physical activity: a Dewey-inspired action research project.
The purpose of this study was to investigate what adapted physical activity (APA) students learn from their practicum experiences. One cohort of APA students participated, and data were generated from an action research project that included observations, reflective journals, and a focus group interview. The theoretical framework for the study was Dewey's and Wackerhausen's theories of reflections. The findings show the objects of students' reflections, the kind of conceptual resources they draw on while reflecting, and their knowledge interests. In addition, two paradoxes are identified: the tension between reflecting from and on own values, and how practicum as a valued experience of reality can become too difficult to handle. In conclusion, we reflect on how practicum learning can be facilitated.


G(olf) and Gs in rat basal ganglia: possible involvement of G(olf) in the coupling of dopamine D1 receptor with adenylyl cyclase.
Using specific antibodies and cDNA probes, we have investigated, in rat basal ganglia, the distribution and the regulation of the expression of the alpha subunits of Gs and G(olf), two GTP-binding proteins (G-proteins) that stimulate adenylyl cyclase. We confirmed that G(olf) alpha is highly expressed in caudate-putamen, nucleus accumbens, and olfactory tubercle, whereas Gs alpha is less abundant in these areas than in the other brain regions. Intrastriatal injections of quinolinic acid decreased dramatically the levels of G(olf) alpha protein in the striatum and the substantia nigra, and those of G(olf) alpha mRNA in the striatum. Retrograde lesions of striatonigral neurons with volkensin reduced markedly the levels of D1 dopamine (DA) binding sites, as well as those of G(olf) alpha protein and mRNA in the striatum, without altering D2 binding sites. In contrast, both types of lesions increased the levels of Gs alpha protein in the striatum and substantia nigra. Immunocytochemistry showed the presence of G(olf) alpha protein in striatal medium-sized neurons and in several other neuronal populations. These results demonstrate that striatonigral neurons contain high levels of G(olf) alpha and little, if any, Gs alpha, suggesting that the coupling of D1 receptor to adenylyl cyclase is provided by G(olf) alpha. The levels of G(olf) alpha were five- to sixfold higher in the striatum than in the substantia nigra, indicating a preferential localization of G(olf) alpha in the somatodendritic region of striatonigral neurons and providing a basis for the low efficiency of D1 receptor coupling in the substantia nigra. Six weeks after 6-hydroxydopamine lesions of DA neurons, an increase in G(olf) alpha (+53%) and Gs alpha (+64%) proteins was observed in the striatum. This increase in G(olf) alpha levels may account for the DA-activated adenylyl cyclase supersensitivity, without change in D1 receptors density, that follows destruction of DA neurons. Fine regulation of the levels of G(olf) alpha in physiological or pathological situations may be a critical parameter for the efficiency of DA neurotransmission.


Lack of effect of 94 GHz radio frequency radiation exposure in an animal model of skin carcinogenesis.
Although there is no evidence that electromagnetic energy in the radio frequency radiation (RFR) band is mutagenic, there have been suggestions that RFR energy might serve as either a promoter or co-promoter in some animal models of carcinogenesis. Recent developments in electromagnetic technology have resulted in the manufacture of RFR sources capable of generating frequencies in the millimeter wavelength (MMW) range (30-300 GHz). Because absorption of MMW energy occurs in the skin, it is to be expected that long-term detrimental health effects, if any, would most likely be manifest in the skin. In this study we investigated whether a single (1.0 W/cm(2) for 10 s) or repeated (2 exposures/week for 12 weeks, 333 mW/cm(2) for 10 s) exposure to 94 GHz RFR serves as a promoter or co-promoter in the 7,12-dimethylbenz[a]anthracene (DMBA)-induced SENCAR mouse model of skin carcinogenesis. Neither paradigm of MMW exposure significantly affected papilloma development, as evidenced by a lack of effect on tumor incidence and multiplicity. There was also no evidence that MMW exposure served as a co-promoter in DMBA-induced animals repeatedly treated with 12-O-tetradecanoylphorbol 13-acetate. Therefore, we conclude that exposure to 94 GHz RFR under these conditions does not promote or co-promote papilloma development in this animal model of skin carcinogenesis.


Environmental management practices in the Lebanese pharmaceutical industries: implementation strategies and challenges.
This research attempts to provide an understanding of the Lebanese pharmaceutical industries' environmental management strategies, priorities, and perceptions as well as drivers, barriers, and incentives regarding the implementation of the voluntary ISO 14001 Environmental Management System. Accordingly, a semistructured in-depth interview was conducted with the pharmaceutical industries. The findings revealed a significant lack of knowledge about the standard among the industries. The main perceived drivers for adopting the ISO 14001 are improving the companies' image and overcoming international trade. The main perceived barriers for acquiring the standard are the lack of government support and the fact that ISO 14001 is not being legally required or enforced by the government. Moreover, results revealed that adopting the ISO 14001 standard is not perceived as a priority for the Lebanese pharmaceutical industries. Although the cost of certification was not considered as a barrier for the implementation of ISO 14001, the majority of the pharmaceutical industries are neither interested nor willing to adopt the Standard if they are not exposed to any regulatory pressure or external demand. They are more concerned with quality and safety issues with the most adopted international standard among the industries being the ISO 9001 quality management system. This study highlights the aspect that financial barriers are not always the hurdles for implementing environmental management strategies in developing countries and underscores the need for regulatory frameworks and enforcement.


Evaluation of the benefit of corticosteroid injection before exercise therapy in patients with osteoarthritis of the knee: a randomized clinical trial.
Osteoarthritis (OA) of the knee is the most frequent form of arthritis and a cause of pain and disability. Combined nonpharmacologic and pharmacologic treatments are recommended as the optimal treatment approach, but no evidence supports the recommendation. To assess the clinical benefits of an intra-articular corticosteroid injection given before exercise therapy in patients with OA of the knee. We performed a randomized, blinded, placebo-controlled clinical trial evaluating the benefit of intra-articular corticosteroid injection vs placebo injection given before exercise therapy at an OA outpatient clinic from October 1, 2012, through April 2, 2014. The participants had radiographic confirmation of clinical OA of the knee, clinical signs of localized inflammation in the knee, and knee pain during walking (score >4 on a scale of 0 to 10). Participants were randomly allocated (1:1) to an intra-articular 1-mL injection of the knee with methylprednisolone acetate (Depo-Medrol), 40 mg/mL, dissolved in 4 mL of lidocaine hydrochloride (10 mg/mL) (corticosteroid group) or a 1-mL isotonic saline injection mixed with 4 mL of lidocaine hydrochloride (10 mg/mL) (placebo group). Two weeks after the injections, all participants started a 12-week supervised exercise program. The primary outcome was change in the Pain subscale of the Knee Injury and Osteoarthritis Outcome Score (KOOS) questionnaire (range, 0-100; higher scores indicate greater improvement) at week 14. Secondary outcomes included the remaining KOOS subscales and objective measures of physical function and inflammation. Outcomes were measured at baseline, week 2 (exercise start), week 14 (exercise stop), and week 26 (follow-up). One hundred patients were randomized to the corticosteroid group (n = 50) or the placebo group (n = 50); 45 and 44 patients, respectively, completed the trial. The mean (SE) changes in the KOOS Pain subscale score at week 14 were 13.6 (1.8) and 14.8 (1.8) points in the corticosteroid and placebo groups, respectively, corresponding to a statistically insignificant mean difference of 1.2 points (95% CI, -3.8 to 6.2; P = .64). We found no statistically significant group differences in any of the secondary outcomes at any time point. No additional benefit results from adding an intra-articular injection of 40 mg of corticosteroid before exercise in patients with painful OA of the knee. Further research is needed to establish optimal and potentially synergistic combinations of conservative treatments. clinicaltrialsregister.eu Identifier: 2012-002607-18; clinicaltrials.gov Identifier: NCT01945749.


Colloidal crystal order and structure revealed by tabletop extreme ultraviolet scattering and coherent diffractive imaging.
Colloidal crystals with specific electronic, optical, magnetic, vibrational properties, can be rationally designed by controlling fundamental parameters such as chemical composition, scale, periodicity and lattice symmetry. In particular, silica nanospheres -which assemble to form colloidal crystals- are ideal for this purpose, because of the ability to infiltrate their templates with semiconductors or metals. However characterization of these crystals is often limited to techniques such as grazing incidence small-angle scattering that provide only global structural information and also often require synchrotron sources. Here we demonstrate small-angle Bragg scattering from nanostructured materials using a tabletop-scale setup based on high-harmonic generation, to reveal important information about the local order of nanosphere grains, separated by grain boundaries and discontinuities. We also apply full-field quantitative ptychographic imaging to visualize the extended structure of a silica close-packed nanosphere multilayer, with thickness information encoded in the phase. These combined techniques allow us to simultaneously characterize the silica nanospheres size, their symmetry and distribution within single colloidal crystal grains, the local arrangement of nearest-neighbor grains, as well as to quantitatively determine the number of layers within the sample. Key to this advance is the good match between the high harmonic wavelength used (13.5nm) and the high transmission, high scattering efficiency, and low sample damage of the silica colloidal crystal at this wavelength. As a result, the relevant distances in the sample - namely, the interparticle distance (≈124nm) and the colloidal grains local arrangement (≈1μm) - can be investigated with Bragg coherent EUV scatterometry and ptychographic imaging within the same experiment simply by tuning the EUV spot size at the sample plane (5μm and 15μm respectively). In addition, the high spatial coherence of high harmonics light, combined with advances in imaging techniques, makes it possible to image near-periodic structures quantitatively and nondestructively, and enables the observation of the extended order of quasi-periodic colloidal crystals, with a spatial resolution better than 20nm. In the future, by harnessing the high time-resolution of tabletop high harmonics, this technique can be extended to dynamically image the three-dimensional electronic, magnetic, and transport properties of functional nanosystems.


The "first hit" toward alcohol reinforcement: role of ethanol metabolites.
This review analyzes literature that describes the behavioral effects of 2 metabolites of ethanol (EtOH): acetaldehyde and salsolinol (a condensation product of acetaldehyde and dopamine) generated in the brain. These metabolites are self-administered into specific brain areas by animals, showing strong reinforcing effects. A wealth of evidence shows that EtOH, a drug consumed to attain millimolar concentrations, generates brain metabolites that are reinforcing at micromolar and nanomolar concentrations. Salsolinol administration leads to marked increases in voluntary EtOH intake, an effect inhibited by mu-opioid receptor blockers. In animals that have ingested EtOH chronically, the maintenance of alcohol intake is no longer influenced by EtOH metabolites, as intake is taken over by other brain systems. However, after EtOH withdrawal brain acetaldehyde has a major role in promoting binge-like drinking in the condition known as the "alcohol deprivation effect"; a condition seen in animals that have ingested alcohol chronically, are deprived of EtOH for extended periods, and are allowed EtOH re-access. The review also analyzes the behavioral effects of acetate, a metabolite that enters the brain and is responsible for motor incoordination at low doses of EtOH. Also discussed are the paradoxical effects of systemic acetaldehyde. Overall, evidence strongly suggests that brain-generated EtOH metabolites play a major role in the early ("first-hit") development of alcohol reinforcement and in the generation of relapse-like drinking.


The first global screening of protein substrates bearing protein-bound 3,4-Dihydroxyphenylalanine in Escherichia coli and human mitochondria.
Protein hydroxylation at proline and lysine residues is known to have important effects on cellular functions, such as the response to hypoxia. However, protein hydroxylation at tyrosine residues (called protein-bound 3,4-dihydroxy-phenylalanine (PB-DOPA)) has not been carefully examined. Here we report the first proteomics screening of the PB-DOPA protein substrates and their sites in Escherichia coli and human mitochondria by nano-liquid chromatography/tandem mass spectrometry (nano-LC/MS/MS) and protein sequence alignment using the PTMap algorithm. Our study identified 67 novel PB-DOPA sites in 43 E. coli proteins and 9 novel PB-DOPA sites in 7 proteins from HeLa mitochondria. Bioinformatics analysis indicates that the structured region is more favored than the unstructured regions of proteins for the PB-DOPA modification. The PB-DOPA substrates in E. coli were dominantly enriched in proteins associated with carbohydrate metabolism. Our study showed that PB-DOPA may be involved in regulation of the specific activity of certain evolutionarily conserved proteins such as superoxide dismutase and glyceraldehyde 3-phosphate dehydrogenase, suggesting the conserved nature of the modification among distant biological species. The substrate proteins identified in this study offer a rich source for determining their regulatory enzymes and for further characterization of the possible contributions of this modification to cellular physiology and human diseases.


Operative Times Can Predict and Are Correlated With Lengths-of-Stay in Primary Total Knee Arthroplasty: A Nationwide Database Study.
The specific influence of operative times on lengths-of-stay (LOS) has not been well assessed and is therefore an important topic of evaluation for multiple reasons, including potential economic implication. The purpose of this study is to (1) identify predictors of longer operative times; (2) identify predictors of longer LOS; and (3) evaluate the effects of operative times on LOS in primary total knee arthroplasty (TKA). The National Surgical Quality Improvement Program database was queried for primary TKAs performed between 2008 and 2016, yielding 225,344 cases. Multivariate analysis was performed to determine the effect of operative times on LOS after adjusting for patient factors. Univariate analyses were performed with 1-way analysis of variance (ANOVA), linear regression, and independent sample t-tests where appropriate. Multivariate analysis was performed with a multiple linear regression model adjusted for patient age, sex, and body mass index (BMI). The mean operative time was 93 ± 35 minutes and the mean LOS was 3 ± 3 days. Young age, male sex, and obesity were predictors of longer operative times (P < .001). Similarly, there were significant associations of age, sex, and BMI with LOS (P < .001). Increasing 30-minute operative time intervals were associated with increasing LOS (P < .001). Longer operative times had significant associations with longer LOS even after adjusting for patient factors (β = 0.076, SE < 0.001, P value < .001). Out of all study covariates, operative times had the greatest effect on LOS. This study provides unique insight by directly correlating operative times to LOS in over 200,000 TKAs. The results from this study indicate that there is a strong correlation between operative times and LOS, so that operative time had a greater association than age, sex, and BMI with postoperative TKA LOS.


Methane intestinal production and poor metabolic control in type I diabetes complicated by autonomic neuropathy.
At the state of art it's unknown the correlation between diabetes and lower gastrointestinal disorders. Some studies show a significantly higher prevalence of small intestinal bacterial overgrowth in patients with type I diabetes in particular complicated by autonomic neuropathy. No data exists about gastrointestinal methane production in patients with diabetes and autonomic diabetic neuropathy. The aim of this paper was to evaluate the correlation of small intestinal bacterial overgrowth and gastrointestinal methane production with metabolic control and daily insulin requirements in patients with type 1 diabetes and. autonomic diabetic neuropathy. Thirty subjects with type 1 diabetes and autonomic diabetic neuropathy were underwent hydrogen and methane lactulose breath test (LBT) to evaluate the presence of small intestinal bacterial overgrowth (double peak of hydrogen) and methane production. The metabolic control was evaluated through the glycated hemoglobin and the daily insulin requirement (calculated as ratio between total insulin units in a day and body weight). Methane producers were treated with metronidazole (500 mg bid for 10 days) and perform a LBT 8 weeks after the end of therapy Eight over thirty patients (26.6%) met the diagnostic criteria for small intestinal bacterial overgrowth. 11/30 patients (36%) were methane-producers (mean baseline value 16.37 ± 13.01 ppm; mean peak 26.62 ± 11.41 ppm); interestingly this subset of patients showed a worse glycemic control (mean HbA1c 8.16 ± 0.9% vs. 7.49 ± 0.8%, P<0.05). After metronidazole therapy 7/11 (63.3%) reduced CH4 production and they showed a mean HbA1c significantly lower than corresponding value before antibiotic therapy (7.63 ± 0.7% vs. 8.25 ± 0.8%). Our study showed for the first time a possible role of CH4 production in metabolic control. In particular, the most interesting data is that an increased values of HbA1c seems to be related to a gut CH4 production as confirmed by its significant improvement after eradication therapy. We are not yet able to determine whether poor glycemic control is the cause or the consequence of the selection of methanogenic flora.


Trauma to the nail unit including occupational sports injuries.
Trauma to the nail unit is one of the most common causes of onychodystrophy and may be acute (a single overwhelming injury) or chronic (repeated minor injury). Immediate effects of acute trauma include splinter hemorrhages, subungual hematomas, and nail shedding. Delayed deformities include splits and ridges, pterygium, hook nails, pigment bands, and ectopic nail. Also discussed are the results of chronic trauma, including self-inflicted injury and repeated indirect injury.


Caution in interpreting FTIR/ATR spectral intensity values.
We discuss and demonstrate why FTIR/ATR spectra can only be calibrated in wavelength, not intensity, for comparison with other data sets at present. This is because the intensity calibration must remove the instrument response function. To address this problem, we suggest a possible approach.


The CD47-signal regulatory protein alpha (SIRPa) interaction is a therapeutic target for human solid tumors.
CD47, a "don't eat me" signal for phagocytic cells, is expressed on the surface of all human solid tumor cells. Analysis of patient tumor and matched adjacent normal (nontumor) tissue revealed that CD47 is overexpressed on cancer cells. CD47 mRNA expression levels correlated with a decreased probability of survival for multiple types of cancer. CD47 is a ligand for SIRPα, a protein expressed on macrophages and dendritic cells. In vitro, blockade of CD47 signaling using targeted monoclonal antibodies enabled macrophage phagocytosis of tumor cells that were otherwise protected. Administration of anti-CD47 antibodies inhibited tumor growth in orthotopic immunodeficient mouse xenotransplantation models established with patient tumor cells and increased the survival of the mice over time. Anti-CD47 antibody therapy initiated on larger tumors inhibited tumor growth and prevented or treated metastasis, but initiation of the therapy on smaller tumors was potentially curative. The safety and efficacy of targeting CD47 was further tested and validated in immune competent hosts using an orthotopic mouse breast cancer model. These results suggest all human solid tumor cells require CD47 expression to suppress phagocytic innate immune surveillance and elimination. These data, taken together with similar findings with other human neoplasms, show that CD47 is a commonly expressed molecule on all cancers, its function to block phagocytosis is known, and blockade of its function leads to tumor cell phagocytosis and elimination. CD47 is therefore a validated target for cancer therapies.


Advancing the application of systems thinking in health: a realist evaluation of a capacity building programme for district managers in Tumkur, India.
Health systems interventions, such as capacity-building of health workers, are implemented across districts in order to improve performance of healthcare organisations. However, such interventions often work in some settings and not in others. Local health systems could be visualised as complex adaptive systems that respond variously to inputs of capacity building interventions, depending on their local conditions and several individual, institutional, and environmental factors. We aim at demonstrating how the realist evaluation approach advances complex systems thinking in healthcare evaluation by applying the approach to understand organisational change within local health systems in the Tumkur district of southern India. We collected data on several input, process, and outcome measures of performance of the talukas (administrative sub-units of the district) and explore the interplay between the individual, institutional, and contextual factors in contributing to the outcomes using qualitative data (interview transcripts and observation notes) and quantitative measures of commitment, self-efficacy, and supervision style. The talukas of Tumkur district responded differently to the intervention. Their responses can be explained by the interactions between several individual, institutional, and environmental factors. In a taluka with committed staff and a positive intention to make changes, the intervention worked through aligning with existing opportunities from the decentralisation process to improve performance. However, commitment towards the organisation was neither crucial nor sufficient. Committed staff in two other talukas were unable to actualise their intentions to improve organisational performance. In yet another taluka, the leadership was able to compensate for the lack of commitment. Capacity building of local health systems could work through aligning or countering existing relationships between internal (individual and organisational) and external (policy and socio-political environment) attributes of the organisation. At the design and implementation stage, intervention planners need to identify opportunities for such triggering alignments. Local health systems may differ in their internal configuration and hence capacity building programmes need to accommodate possibilities for change through different pathways. By a process of formulating and testing hypotheses, making critical comparisons, discovering empirical patterns, and monitoring their scope and extent, a realist evaluation enables a comprehensive assessment of system-wide change in health systems.


The heart cell in silico: successes, failures and prospects.
The development of computer models of heart cells is used to illustrate the interaction between simulation and experimental work. At each stage, the reasons for new models are explained, as are their defects and how these were used to point the way to successor models. As much, if not more, was learnt from the way in which models failed as from their successes. The insights gained are evident in the most recent developments in this field, both experimental and theoretical. The prospects for the future are discussed.


Antioxidant properties of pyroligneous acid obtained by thermochemical conversion of Schisandra chinensis Baill.
Sustainable development of renewable resources is a major challenge globally. Biomass is an important renewable energy source and an alternative to fossil fuels. Pyrolysis of biomass is a promising method for simultaneous production of biochar, bio-oil, pyroligneous acid (PA), and gaseous fuels. The purpose of this study was to investigate the pyrolysis process and products yields of Schisandra chinensis fruits with different pyrolysis powers. The obtained PA was extracted with organic solvents, including ethyl formate, dichloromethane, methanol and tetrahydrofuran. The antioxidant activities, including the free radical scavenging activity and ferric reducing power, of the PA extracts were investigated. The synthetic antioxidants butylated hydroxyanisole and butylated hydroxytoluene were used as positive controls. A dichloromethane extract of PA showed excellent antioxidant properties compared to the other extracts. The chemical compositions of the PA extracts were determined by GC-MS, and further proved that the dichloromethane extract had the best antioxidant characteristics among the extracts tested.


Psychosocial Moderators the Effects of Transitioning Into Filial Caregiving on Mental and Physical Health.
A life-course theoretical perspective guided this study to examine how effects on mental and physical health (depressive symptoms, hostility, global happiness, self-esteem, personal mastery, psychological wellness, self-rated physical health) of transitioning into filial caregiving for a sole surviving parent are moderated by prior relationship quality, filial obligation, race or ethnicity, education, income, employment status, marital status, and parental status. Results from models estimated using longitudinal data from 1,060 adults aged 25 to 65 years at baseline (National Survey of Families and Households, 1987 to 1994) suggested that life-course and contextual factors do contribute to patterning health risks of caregiving, often in different ways for men and women: For example, low income puts daughter caregivers at greater risk for decline in physical health, combining employment with filial caregiving is more problematic for daughters' mental health, and being an unmarried filial caregiver is more problematic for men. Heterogeneity in the experience of filial care needs further attention in future research.


Prevalence of probable kerosene dermatoses among ball-bearing factory workers.
The objective of this study was to investigate the prevalence rate of dermatoses among workers in a ball-bearing factory and its possible association with their exposure to kerosene. Two groups of female workers participated in the study. The first group included 79 persons with major kerosene exposure during work, while the second, a reference group, was composed of 263 zipper-manufacturing workers with a similar age distribution, educational background, and income. Dermatologic examinations were used to determine the prevalence rate of hand dermatoses (erythema, scaling, and eczema). In the exposed group 51 persons (65%) had erythema with or without desquamation over the interdigital spaces, 12 persons (15%) had eczematous lesions, 3 persons (4%) had defatting dermatitis, and only 13 persons (16%) were apparently asymptomatic. In the reference group only one person had hand eczema (less than 1%). The difference in the occurrence of dermatoses between the two groups was significant according to the Mantel-Haenszel summary chi-square test. Patch tests on five workers with eczematous lesions revealed one to be sensitive to mercury. The findings indicate that kerosene is a skin irritant. Antirust oil used on the ball-bearings may also contribute to the irritant effect.


Anti-Asthmatic Effects of Portulaca Oleracea and its Constituents, a Review.
The medicinal plants are believed to enhance the natural resistance of the body to infections. Some of the main constituents of the plant and derived materials such as, proteins, lectins and polysaccharides have anti-inflammatory effects. Portulaca oleracea (P. oleracea) were used traditionally for dietary, food additive, spice and various medicinal purposes. This review article is focus on the anti-asthmatic effects of P. oleracea and its constituents. Various databases, such as the PubMed, Scopus, and Google Scholar, were searched the keywords including "Portulaca oleracea", "Quercetin", "Anti-inflammatory", "Antioxidant", "Cytokines", "Smooth muscle ", and " Relaxant effects " until the end of Jul 2018. P. oleracea extracts and its constituents increased IFN-γ, IL-2, IFNγ/IL-4 and IL- 10/IL-4 ratio, but decreased secretion of TNF-α, IL-4 and chemokines in both in vitro and in vivo studies. P. oleracea extracts and quercetin also significantly decreased production of NO, stimulated β-adrenoceptor and/or blocking muscarinic receptors in tracheal smooth muscles. Conclusion: P. oleracea extracts and quercetin showed relatively potent anti-asthmatic effects due to decreased production of NO, inflammatory cytokines and chemokines, reduced oxidant while enhanced antioxidant markers, and also showed potent relaxant effects on tracheal smooth muscles via stimulatory on β-adrenoceptor or/and blocking muscarinic receptors.