The opportunistic pathogen Serratia marcescens utilizes type VI secretion to target bacterial competitors.
The type VI secretion system (T6SS) is the most recently described and least understood of the protein secretion systems of Gram-negative bacteria. It is widely distributed and has been implicated in the virulence of various pathogens, but its mechanism and exact mode of action remain to be defined. Additionally there have been several very recent reports that some T6SSs can target bacteria rather than eukaryotic cells. Serratia marcescens is an opportunistic enteric pathogen, a class of bacteria responsible for a significant proportion of hospital-acquired infections. We describe the identification of a functional T6SS in S. marcescens strain Db10, the first report of type VI secretion by an opportunist enteric bacterium. The T6SS of S. marcescens Db10 is active, with secretion of Hcp to the culture medium readily detected, and is expressed constitutively under normal growth conditions from a large transcriptional unit. Expression of the T6SS genes did not appear to be dependent on the integrity of the T6SS. The S. marcescens Db10 T6SS is not required for virulence in three nonmammalian virulence models. It does, however, exhibit dramatic antibacterial killing activity against several other bacterial species and is required for S. marcescens to persist in a mixed culture with another opportunist pathogen, Enterobacter cloacae. Importantly, this antibacterial killing activity is highly strain specific, with the S. marcescens Db10 T6SS being highly effective against another strain of S. marcescens with a very similar and active T6SS. We conclude that type VI secretion plays a crucial role in the competitiveness, and thus indirectly the virulence, of S. marcescens and other opportunistic bacterial pathogens.


Effect of digoxin on right ventricular function in severe chronic airflow obstruction. A controlled clinical trial.
The effect of digoxin on the right and left ventricular ejection fractions in 15 patients with pulmonary heart disease caused by severe chronic airflow obstruction was studied in a double-blind, randomized, placebo-controlled trial. All patients were ambulatory and had clinical features of right but not left ventricular dysfunction. Equilibrium radionuclide angiography showed reduced right ventricular ejection fraction in all patients and reduced left ventricular ejection fraction in four. After 8 weeks of digoxin treatment, the abnormal left ventricular ejection fractions were normal; right ventricular ejection fractions increased only in those patients who had had abnormal left ventricular ejection fractions. We conclude that in patients with pulmonary heart disease, the right ventricular ejection fraction is abnormal and improves with digoxin treatment only when the left ventricular ejection fraction also is initially abnormal.


Effects on weight loss in adults of replacing diet beverages with water during a hypoenergetic diet: a randomized, 24-wk clinical trial.
Obese people believe that drinking diet beverages (DBs) may be a simple strategy to achieve weight loss. However, nutritionists advise drinking water when attempting to lose weight. It is unclear how important drinking water instead of DBs is during a weight-loss program. In this study, we compared the effect on weight loss of either replacing DBs with water or continuing to consume DBs in adults during a 24-wk weight-loss program. Overweight and obese women [n = 89; body mass index (BMI; in kg/m(2)): 27-40; age: 18-50 y] who usually consumed DBs in their diet were asked to either substitute water for DBs (water group) or continue drinking DBs 5 times/wk after their lunch for 24 wk (DB group) while on a weight-loss program. Sixty-two participants (71%) completed the trial (32 in the DB group, 30 in the water group). Baseline variables were not statistically significantly different between groups. A statistically significant reduction in anthropometric measurements and statistically significant improvements in cardiometabolic risk characteristics were observed over 24 wk in both groups. Compared with the DB group, the water group had a greater decrease in weight (mean ± SD: water: -8.8 ± 1.9 kg; DBs: -7.6 ± 2.1 kg; P = 0.015, time × group), fasting insulin (mean ± SD: water: -2.84 ± 0.77 mU/L; DBs: -1.78 ± 1.25 mU/L, P < 0.001), homeostasis model assessment of insulin resistance (mean ± SD: water: -0.097 ± 0.049; DBs: -0.057 ± 0.042, P < 0.001), and 2-h postprandial glucose (mean ± SD: water: -1.02 ± 0.25 mmol/L; DBs: -0.72 ± 0.27 mmol/L; P < 0.001) over the 24 wk. However, there was no significant time × group interaction for waist circumference, fasting plasma glucose, and lipid profiles within both groups over 24 wk. Replacement of DBs with water after the main meal may lead to greater weight reduction during a weight-loss program. It may also offer clinical benefits to improve insulin resistance. This trial was registered at www.irct.ir/ as IRCT201402177754N5.


A model for the phenotypic presentation of Werner's syndrome.
Werner's syndrome (WS) is a valuable model of accelerated ageing and results from mutations in a recQ helicase (wrn). WS fibroblasts show a mutator phenotype, replication fork stalling, increased rates of mean telomeric loss and accelerated cellular senescence. Senescence has been proposed as a candidate mechanism for the ageing of mitotic tissue. However, some mitotic tissues (such as the immune system) seem unaffected in WS. Is this evidence against a role for cell senescence in ageing? Two experiments resolve this paradox (i) the demonstration that the abbreviated replicative lifespan of WS fibroblasts can be corrected by the ectopic expression of telomerase and (ii) the demonstration that T cells derived from WS patients have the mutator phenotype characteristic of the disease but show no reduction in replicative potential. Since T cells can upregulate telomerase naturally these findings are consistent with a model in which the only wrn-mediated deletions that have a significant effect on replicative lifespan are those at or near the telomere. These data are thus supportive of a role for senescence in the ageing of the immune system. Emerging data on divisional counting mechanisms have the potential to produce many other apparent WS "paradoxes". Accordingly, we propose a general model for the phenotypic presentation of WS, which includes a modification of the Olovnikov model of telomere erosion. Somewhat unexpectedly, this predicts that accelerated senescence should not be observed in all telomerase-negative WS cell types.


The Resistance Mechanism and Clonal Distribution of Tigecycline-Nonsusceptible Klebsiella pneumoniae Isolates in Korea.
Tigecycline is one of the drugs used to treat multi-drug resistant Klebsiella pneumoniae (K. pneumoniae) infections, including complicated skin and soft tissue infections, complicated intra-abdominal infection, and community-acquired pneumonia in the Republic of Korea. However, since its commercial release, K. pneumoniae resistance against tigecycline has been reported, and there is a serious concern about the spread of tigecycline resistant bacteria. In this study, we collected and analyzed 342 isolates from 23 hospitals in the Republic of Korea to determine the mechanisms of tigecycline susceptibility and their clonal types. The hospitals include several from each province in the Republic of Korea, except Jeju, an island province, and nonsusceptibility among the isolates was tested by the disk diffusion method. In our lab, susceptibility was checked again using the broth dilution method, and clonal types were determined using the multilocus sequence typing protocol. Real-time PCR was performed to measure the ramR mutation in the isolates nonsusceptible to tigecycline, which would suggest an increased expression of the AcrAB multidrug pump. Fifty-six K. pneumoniae isolates were found to be nonsusceptible, 16% of the 342 collected. Twenty-seven and nine isolates of the tigecycline nonsusceptible isolates had mutations in the ramR and rpsJ genes, respectively; while 18 nonsusceptible isolates harbored the tetA gene. Comparison of isolates with and without ramR mutation showed a significant statistical difference (p<0.05) for expression of AcrAB. Moreover, the most common clonal types, as observed in our study, appear to be ST11 and ST789. Several dominate clonal types infer tigecycline resistance to K. pneumoniae, including ST11, ST768, ST15, ST23, ST48, and ST307. There does not seem to be a transferrable medium, such as plasmid, for the resistance yet, although mutation of the ramR gene may be a common event, accounting for 48% of the nonsusceptibility in this study.


Evaluation of histocompatibility as a factor in the repair of nerve with a frozen nerve allograft.
Host axons in dogs can regenerate through a long nerve allograft provided that the allograft bears only minor transplantation antigens, and is frozen and thawed before transplantation. The authors have tried to confirm this important observation in rats. Host rats received a 4-cm fresh or frozen nerve isograft (that is, a non-antigenic nerve), or a fresh or frozen nerve allograft with cells containing only minor transplantation antigens. The results showed that after 2 and 9 months only a fresh isograft permitted many host axons to traverse its entire length. Only a few host axons grew into the proximal 1 to 2 cm of a frozen isograft or into an allograft (fresh or frozen). Because frozen grafts failed, the authors examined some specimens after 2 weeks and found that freezing killed most of the Schwann cells. on the other hand, many proliferating Schwann cells were found in 2-week fresh isografts. In addition, hosts that received a frozen nerve allograft underwent regrafting after 9 months with an isograft and allograft (of the same genotype as th original nerve allograft) of nodose ganglion. These rats accepted the isograft but rejected the allograft of ganglion. It is concluded that axonal regeneration through a long frozen nerve graft fails in rats because freezing destroys Schwann cells. Moreover, a frozen nerve allograft does not induce a state of immunological tolerance, as has been suggested, because these recipients reject a second allograft. Since the present data failed to confirm findings obtained in dogs, the clinical use of a frozen nerve allograft is not recommended.


Selective versus routine intraoperative shunting during carotid endarterectomy: a multivariate outcome analysis.
The use of intraluminal shunting during carotid endarterectomy (CEA) remains controversial. Over the years, different shunting strategies have been used. More recently, the use of intraoperative electroencephalography and somatosensory evoked potential monitoring with selective intraluminal shunting has been explored. No studies have assessed the independent association of selective versus routine intraluminal shunting to outcomes after CEA. The clinical and radiological records of all patients undergoing CEA from 1994 to 2006 at an academic institution were reviewed retrospectively to assess outcomes at 72 hours. The independent association of selective intraluminal carotid artery shunting during CEA and perioperative stroke within 72 hours was assessed through multivariate logistic regression analysis. In 1411 patients with both symptomatic and asymptomatic extracranial carotid artery disease, there were a total of 49 (3.5%) perioperative strokes after CEA. There were two (1%) cases of perioperative strokes among 194 patients in the selective shunting group compared with 47 out of 1217 (4%) in the routine shunting group (P = 0.04). Symptomatic carotid artery disease was associated with a twofold increase in the odds of experiencing perioperative stroke (odds ratio, 1.95; 95% confidence interval, 1.08-3.52; P = 0.03). Patients undergoing electrophysiological monitoring with selective intraluminal carotid artery shunting were more than seven times less likely to experience a perioperative stroke (odds ratio, 0.05; 95% confidence interval, 0.01-0.40; P < 0.01). Increasing cumulative surgical volume, particularly more than 200 total cases, was associated with more than a twofold decrease in perioperative stroke (odds ratio, 0.38; 95% confidence interval, 0.20-0.74; P < 0.01). Regardless of symptomatic carotid artery disease or cumulative surgical volume, patients undergoing CEA with intraoperative electroencephalography and somatosensory evoked potential monitoring with selective intraluminal carotid artery shunting had a stroke rate lower than that of the routine shunting group. Selective shunting based on electroencephalography and somatosensory evoked potential monitoring may be superior to the nonselective strategy.


STAT2/IRF9 directs a prolonged ISGF3-like transcriptional response and antiviral activity in the absence of STAT1.
Evidence is accumulating for the existence of a signal transducer and activator of transcription 2 (STAT2)/interferon regulatory factor 9 (IRF9)-dependent, STAT1-independent interferon alpha (IFNα) signalling pathway. However, no detailed insight exists into the genome-wide transcriptional regulation and the biological implications of STAT2/IRF9-dependent IFNα signalling as compared with interferon-stimulated gene factor 3 (ISGF3). In STAT1-defeicient U3C cells stably overexpressing human STAT2 (hST2-U3C) and STAT1-deficient murine embryonic fibroblast cells stably overexpressing mouse STAT2 (mST2-MS1KO) we observed that the IFNα-induced expression of 2'-5'-oligoadenylate synthase 2 (OAS2) and interferon-induced protein with tetratricopeptide repeats 1 (Ifit1) correlated with the kinetics of STAT2 phosphorylation, and the presence of a STAT2/IRF9 complex requiring STAT2 phosphorylation and the STAT2 transactivation domain. Subsequent microarray analysis of IFNα-treated wild-type (WT) and STAT1 KO cells overexpressing STAT2 extended our observations and identified ∼120 known antiviral ISRE-containing interferon-stimulated genes (ISGs) commonly up-regulated by STAT2/IRF9 and ISGF3. The STAT2/IRF9-directed expression profile of these IFN-stimulated genes (ISGs) was prolonged as compared with the early and transient response mediated by ISGF3. In addition, we identified a group of 'STAT2/IRF9-specific' ISGs, whose response to IFNα was ISGF3-independent. Finally, STAT2/IRF9 was able to trigger an antiviral response upon encephalomyocarditis virus (EMCV) and vesicular stomatitis Indiana virus (VSV). Our results further prove that IFNα-activated STAT2/IRF9 induces a prolonged ISGF3-like transcriptome and generates an antiviral response in the absence of STAT1. Moreover, the existence of 'STAT2/IRF9-specific' target genes predicts a novel role of STAT2 in IFNα signalling.


Strategies for increasing the physician workforce: the Oregon model for expansion.
The physician workforce shortage and inequity of physician distribution throughout Oregon require the Oregon Health & Science University (OHSU) School of Medicine to graduate more physicians and increase the number committed to practice in nonurban areas. The most cost-effective and expedient method to accomplish these goals has been to develop community partnerships and regional campuses. However, expansion must be strategically developed to maintain educational quality and to minimize the impact on available resources. Leveraging partnerships with existing health care delivery systems and major state universities makes expansion more expedient and economical. In 2001, the OHSU School of Medicine began implementing a four-phase plan to increase medical student enrollment. Phase 1 (2001-2006) used only capital budget resources to increase enrollment incrementally at the school of medicine's Portland site; Phase 2 (2006-2007) creates community partnerships to develop regional sites using the physical facilities of partners, again avoiding the need for capital investment; Phase 3 (2007-2010) builds on the prototype developed in Phase 2 to create additional regional educational sites; and Phase 4 (2010-2015) involves a feasibility study and subsequent capital campaign for a facility on Portland's south waterfront. Establishing regional campuses and matriculating the student population best suited for the physician workforce of the future are key elements of the OHSU model of expansion, particularly in addressing the state's physician distribution inequities.


Mothers' experiences of the time after the diagnosis of an intrauterine death until the induction of the delivery: a qualitative Internet-based study.
This study aims to describe how mothers spend the period of time between being diagnosed with a dead baby in utero and the induction of the delivery. Data were collected using a web questionnaire. Five hundred and fifteen women who had experienced a stillbirth after the 22nd week of gestation answered the open question: 'What did you do between the diagnosis of the child's death and the beginning of the delivery?' A qualitative content analysis method was used. The results show that some mothers received help to adapt to the situation, while for others, waiting for the induction meant further stress and additional psychological trauma in an already strained situation. There is no reason to wait with the induction unless the parents themselves express a wish to the contrary. Health care professionals, together with the parents, should try to determine the best time for the induction of the birth after the baby's death in utero. That time may vary, depending on the parents' preferences.


Posttraumatic complications in pediatric skull fracture: dural sinus thrombosis, arterial dissection, and cerebrospinal fluid leakage.
OBJECTIVE Skull fracture is associated with several intracranial injuries. The object of this study was to determine the rate of fracture associated with venous thrombosis, intracranial arterial dissection (ICAD), and cerebrospinal fluid (CSF) leakage in pediatric patients. Further, the authors aimed to highlight the features of pediatric skull fracture that predict poor neurological outcomes. METHOD In this retrospective study, the authors evaluated the records of 258 pediatric patients who had incurred a traumatic skull fracture in the period from 2009 to 2015. All the patients had undergone CT imaging, which was used to characterize the type of skull fracture and other important features, including intracranial hemorrhage. Patients with fracture extending to a dural sinus or proximal to major intracranial vessels had undergone vascular imaging to evaluate for venous thrombosis or arterial dissection. Clinical data were also reviewed for patients who had CSF leakage. RESULTS Two hundred fifty-eight patients had 302 skull fractures, with 11.6% having multiple fractures. Falling was the most common mechanism of injury (52.3%), and the parietal bone was most frequently involved in the fracture (43.4%). Diastatic fracture was associated with increased intracranial hemorrhage (p < 0.05). The rate of venous thrombosis was 0.4%, and the rate of ICAD was also 0.4%. The rate of CSF leakage was 2.3%. Skull base fracture was the only significant risk factor associated with an increased risk of CSF leakage (p < 0.05). There was a significant difference in fracture-related morbidity in patients younger than versus older than 2 years of age. Patients younger than 2 years had fewer intracranial hemorrhages (21.8% vs 38.8%) and fewer neurosurgical interventions (3.0% vs 12.7%) than the patients older than 2 years (p < 0.001). Moreover, skull fracture in the younger group was mostly caused by falling (81.2% vs 33.1%); in the older group, fracture was most often caused by vehicle-related accidents (35.7% vs 4.0%) and being struck by or against an object (19.1% vs 7.9%). Additionally, skull fracture location was analyzed based on the mechanism of injury. Parietal bone fracture was closely associated with falling, and temporal bone fracture was associated with being struck by or against an object (p < 0.05). Frontal bone fracture was more associated with being struck by or against an object and vehicle-related injury (p < 0.05) than with falling. Vehicle-related accidents and being struck by or against an object, as opposed to falling, were associated with increased surgical intervention (13.3% vs 16.2% vs 3.7%, respectively). CONCLUSIONS Pediatric skull fracture usually has a benign outcome in patients who fall and are younger than 2 years of age. Poor prognostic factors include diastasis, an age > 2 years, and fracture caused by vehicle-related accidents or being struck by or against an object. In this series, the rates of venous thrombosis and ICAD were low, and the authors do not advocate vascular imaging unless these disease entities are clinically suspected. Patients with skull base fracture should be closely monitored for CSF leakage.


Epigenetic properties and identification of an imprint mark in the Nesp-Gnasxl domain of the mouse Gnas imprinted locus.
The Gnas locus in the mouse is imprinted with a complex arrangement of alternative transcripts defined by promoters with different patterns of monoallelic expression. The Gnas transcript is subject to tissue-specific imprinted expression, Nesp is expressed only from the maternal allele, and Gnasxl is expressed only from the paternal allele. The mechanisms controlling these expression patterns are not known. To identify potential imprinting regulatory regions, particularly for the reciprocally expressed Nesp and Gnasxl promoters, we examined epigenetic properties of the locus in gametes, embryonic stem cells, and fetal and adult tissues. The Nesp and Gnasxl promoter regions are contained in extensive CpG islands with methylation of the paternal allele at Nesp and the maternal allele at Gnasxl. Parental allele-specific DNase I-hypersensitive sites were found at these regions, which correlate with hypomethylation rather than actual expression status. A germ line methylation mark was identified covering the promoters for Gnasxl and the antisense transcript Nespas. Prominent DNase I-hypersensitive sites present on paternal alleles in embryonic stem cells are contained within this mark. This is the second gametic mark identified at Gnas and suggests that the Nesp and Gnasxl promoters are under separate control from the Gnas promoter. We propose models to account for the regulation of imprinting at the locus.


Phase I study of the orally administered butyrate prodrug, tributyrin, in patients with solid tumors.
Butyrates have been studied as cancer differentiation agents in vitro and as a treatment for hemoglobinopathies. Tributyrin, a triglyceride with butyrate molecules esterified at the 1, 2, and 3 positions, induces differentiation and/or growth inhibition of a number of cell lines in vitro. When given p.o. to rodents, tributyrin produces substantial plasma butyrate concentrations. We treated 13 patients with escalating doses of tributyrin from 50 to 400 mg/kg/day. Doses were administered p.o. after an overnight fast, once daily for 3 weeks, followed by a 1-week rest. Intrapatient dose escalation occurred after two courses without toxicity greater than grade 2. The time course of butyrate in plasma was assessed on days 1 and 15 and after any dose escalation. Grade 3 toxicities consisted of nausea, vomiting, and myalgia. Grades 1 and 2 toxicities included diarrhea, headache, abdominal cramping, nausea, anemia, constipation, azotemia, lightheadedness, fatigue, rash, alopecia, odor, dysphoria, and clumsiness. There was no consistent increase in hemoglobin F with tributyrin treatment. Peak plasma butyrate concentrations occurred between 0.25 and 3 h after dose, increased with dose, and ranged from 0 to 0.45 mM. Peak concentrations did not increase in three patients who had dose escalation. Butyrate pharmacokinetics were not different on days 1 and 15. Because peak plasma concentrations near those effective in vitro (0.5-1 mM) were achieved, but butyrate disappeared from plasma by 5 h after dose, we are now pursuing dose escalation with dosing three times daily, beginning at a dose of 450 mg/kg/day.


Big beautiful women: the body size preferences of male fat admirers.
This study examined the body size ideals of a group of male fat admirers (FAs) in comparison with an age- and body mass index (BMI)-matched control sample. Forty-seven men, who were involved in the fat acceptance community, and 64 control individuals rated a series of 10 images of women that varied in BMI from emaciated to obese. As expected, the results showed that FAs rated a significantly higher BMI as the most physically attractive compared with the control sample. FAs also rated figures with higher BMIs, particularly those in overweight and obese categories, more positively than did the control group. In addition, FAs perceived a wider range of body sizes to be physically attractive than the control group. Participant demographics did not predict ratings over and above affiliation with either the FA or control groups. These results are discussed in relation to the growing body of work examining fat admiration.


The role of circulating glucose and triglyceride concentrations and their interactions with other "risk factors" as determinants of arterial disease in nine diabetic population samples from the WHO multinational study.
In 9 of the 14 national samples of diabetic patients assembled for the WHO Multinational Study of Vascular Disease in Diabetes additional laboratory data made it possible to relate manifestations of macrovascular disease to blood glucose concentrations as well as to diabetes duration and to other potential determinants. In five of the samples, serum triglyceride concentrations were also measured and were included in simple and multivariate analyses. Ischemic heart disease defined from Minnesota-coded EKGs and standardized WHO questionnaires was more strongly associated with serum triglyceride concentrations than with serum cholesterol concentrations, an association less notable in non-insulin-dependent diabetic patients. Ischemic heart disease was not related to the single fasting plasma glucose estimated for this study. Stroke and amputation were much more strongly related to the known duration of diabetes than was ischemic heart disease, and they were both related to blood glucose concentration measured at the time of study. Despite major variation in arterial disease prevalence rates between collaborating centers, risk for diabetic women appeared to equal that for diabetic men. The major variation in arterial disease prevalence between national groups could be accounted for only in part by the risk factors studied. Other factors, genetic or more likely environmental, are likely to contribute to the variation in arterial disease susceptibility and, if definable, may be potentially preventable.


Payer Policy Behavior Towards Opioid Pharmacotherapy Treatment in Ohio.
Few studies examine how payers address the need for improved access to pharmacotherapy for opioid use disorders and the influence of environmental variables on access to opioid agonist and antagonist medications. The 52 Ohio Addiction Drug Abuse and Mental Health Services (ADAMHS) Boards that disburse funds for treatment services for the uninsured and underinsured were surveyed to assess coverage for opioid agonist and antagonist treatment medications. Analyses examined public health data on regional opioid addiction patterns, characteristics of the local health insurance market, and their associations with coverage for opioid addiction pharmacotherapy. Most (70%) of the 44 participating ADAMHS Boards paid for opioid treatment medications. For payment policy, all Boards required behavioral therapy to be provided in conjunction with opioid agonist or opioid antagonist therapy, and 27% of the Boards limited length of a buprenorphine therapy regimen. Higher local opioid treatment admission rates were associated with higher rates of Board funding for opioid treatment pharmacotherapy. Environmental variables (eg, overdose fatality rates or the behaviors of private insurance payers) were not associated with ADAMHS support for opioid agonist or antagonist medication. The analysis highlights the policy preferences of these payers. Follow-up studies should examine the payer decision-making processes, preferences, and attitudes that affect support for pharmacotherapy for opioid dependence.


Functional characterization of iPSC-derived arterial- and venous-like endothelial cells.
The current work reports the functional characterization of human induced pluripotent stem cells (iPSCs)- arterial and venous-like endothelial cells (ECs), derived in chemically defined conditions, either in monoculture or seeded in a scaffold with mechanical properties similar to blood vessels. iPSC-derived arterial- and venous-like endothelial cells were obtained in two steps: differentiation of iPSCs into endothelial precursor cells (CD31pos/KDRpos/VE-Cadmed/EphB2neg/COUP-TFneg) followed by their differentiation into arterial and venous-like ECs using a high and low vascular endothelial growth factor (VEGF) concentration. Cells were characterized at gene, protein and functional levels. Functionally, both arterial and venous-like iPSC-derived ECs responded to vasoactive agonists such as thrombin and prostaglandin E2 (PGE2), similar to somatic ECs; however, arterial-like iPSC-derived ECs produced higher nitric oxide (NO) and elongation to shear stress than venous-like iPSC-derived ECs. Both cells adhered, proliferated and prevented platelet activation when seeded in poly(caprolactone) scaffolds. Interestingly, both iPSC-derived ECs cultured in monoculture or in a scaffold showed a different inflammatory profile than somatic ECs. Although both somatic and iPSC-derived ECs responded to tumor necrosis factor-α (TNF-α) by an increase in the expression of intercellular adhesion molecule 1 (ICAM-1), only somatic ECs showed an upregulation in the expression of E-selectin or vascular cell adhesion molecule 1 (VCAM-1).


Patterns of preconception, prenatal and postnatal care for diabetic women by obstetrician-gynecologists.
To assess barriers to and quality of care received by diabetic pregnant women from obstetrician-gynecologists. A questionnaire was mailed to 1,000 representative practicing Fellows of the American College of Obstetricians and Gynecologists; 74 did not treat pregnant patients and 510 (55.1%) returned completed surveys. Respondents were divided into 3 groups: maternal-fetal medicine specialists, physicians with high minority/low insurance patient populations, and physicians with low minority/ high insurance patient populations. Reported preconception and prenatal care was generally consistent with guidelines. Regarding gestational diabetes mellitus patients the 3 physician groups differed in assessing postpartum glycemic status, counseling about lifestyle changes, and counseling patients to consult a doctor before their next pregnancy. Patient demographics and perceived barriers to care were similar between maternal-fetal medicine specialists and physicians with high minority/low insurance patient populations. These two physician groups were more likely to agree that lack of educational materials, arranging specialist referrals, patient compliance with recommendations, and patients' ability to afford healthful food were barriers to quality care. According to physician self-report, pregnant diabetic patients with access to an obstetrician receive quality care regardless of insurance status. Postpartum care is more variable. Physicians with high minority/low insurance patient populations may lack access to resources.


Silk garments plus standard care compared with standard care for treating eczema in children: A randomised, controlled, observer-blind, pragmatic trial (CLOTHES Trial).
The role of clothing in the management of eczema (also called atopic dermatitis or atopic eczema) is poorly understood. This trial evaluated the effectiveness and cost-effectiveness of silk garments (in addition to standard care) for the management of eczema in children with moderate to severe disease. This was a parallel-group, randomised, controlled, observer-blind trial. Children aged 1 to 15 y with moderate to severe eczema were recruited from secondary care and the community at five UK medical centres. Participants were allocated using online randomisation (1:1) to standard care or to standard care plus silk garments, stratified by age and recruiting centre. Silk garments were worn for 6 mo. Primary outcome (eczema severity) was assessed at baseline, 2, 4, and 6 mo, by nurses blinded to treatment allocation, using the Eczema Area and Severity Index (EASI), which was log-transformed for analysis (intention-to-treat analysis). A safety outcome was number of skin infections. Three hundred children were randomised (26 November 2013 to 5 May 2015): 42% girls, 79% white, mean age 5 y. Primary analysis included 282/300 (94%) children (n = 141 in each group). The garments were worn more often at night than in the day (median of 81% of nights [25th to 75th centile 57% to 96%] and 34% of days [25th to 75th centile 10% to 76%]). Geometric mean EASI scores at baseline, 2, 4, and 6 mo were, respectively, 9.2, 6.4, 5.8, and 5.4 for silk clothing and 8.4, 6.6, 6.0, and 5.4 for standard care. There was no evidence of any difference between the groups in EASI score averaged over all follow-up visits adjusted for baseline EASI score, age, and centre: adjusted ratio of geometric means 0.95, 95% CI 0.85 to 1.07, (p = 0.43). This confidence interval is equivalent to a difference of -1.5 to 0.5 in the original EASI units, which is not clinically important. Skin infections occurred in 36/142 (25%) and 39/141 (28%) of children in the silk clothing and standard care groups, respectively. Even if the small observed treatment effect was genuine, the incremental cost per quality-adjusted life year was £56,811 in the base case analysis from a National Health Service perspective, suggesting that silk garments are unlikely to be cost-effective using currently accepted thresholds. The main limitation of the study is that use of an objective primary outcome, whilst minimising detection bias, may have underestimated treatment effects. Silk clothing is unlikely to provide additional benefit over standard care in children with moderate to severe eczema. Current Controlled Trials ISRCTN77261365.


Type 1 diabetes and osteoporosis: A review of literature.
With better care and intensive insulin therapy, microvascular complications have reduced and longevity has increased in patients with type 1 diabetes (T1DM). Therefore, there is a need to change the focus from microvascular complications to cardiovascular disease and osteoporosis. Though number of studies from other parts of the world show that patients with T1DM are at increased risk of osteoporosis and fractures, there is a paucity of data from India. A number of factors and mechanisms affecting bone health in patients with T1DM have been proposed. The main defect in genesis of osteoporosis is osteoblastic function, rather than osteoclastic overfunction. Assessment of bone mineral density by dual X-ray absorptiometry and other risk factors for osteoporosis, as a part of diagnostic procedure can help to design tailored treatment plans. A physically active healthy lifestyle, prevention of diabetic complications and adequate calcium and vitamin D supplementation are the mainstay for prevention of osteoporosis. Treatment of osteoporosis is not evidence based but it is proposed to be similar to osteoporosis associated with other conditions. Bisphosphonates are the mainstay for treatment of osteoporosis in patients with T1DM. However, more studies are needed to make definitive guidelines on prevention and treatment of osteoporosis in patients with T1DM.


The relationship between employment and health and health care among working-age adults with and without disabilities in the United States.
Purpose: To better understand the relationship between employment and health and health care for people with disabilities in the United States (US). Methods: We pooled US Medical Expenditure Panel Survey (2004-2010) data to examine health status, and access to health care among working-age adults, comparing people with physical disabilities or multiple disabilities to people without disabilities, based on their employment status. Logistic regression and least squares regression were conducted, controlling for sociodemographics, health insurance (when not the outcome), multiple chronic conditions, and need for assistance. Results: Employment was inversely related to access to care, insurance, and obesity. Yet, people with disabilities employed in the past year reported better general and mental health than their peers with the same disabilities who were not employed. Those who were employed were more likely to have delayed/forgone necessary care, across disability groups. Part-time employment, especially for people with multiple limitations, was associated with better health and health care outcomes than full-time employment. Conclusion: Findings highlight the importance of addressing employment-related causes of delayed or foregone receipt of necessary care (e.g., flex-time for attending appointments) that exist for all workers, especially those with physical or multiple disabilities. Implications for rehabilitation These findings demonstrate that rehabilitation professionals who are seeking to support employment for persons with physical limitations need to ensure that overall health concerns are adequately addressed, both for those seeking employment and for those who are currently employed. Assisting clients in prioritizing health equally with employment can ensure that both areas receive sufficient attention. Engaging with employers to develop innovative practices to improve health, health behaviors and access to care for employees with disabilities can decrease turnover, increase productivity, and ensure longer job tenure.


The effect of dietary glutamate on fibromyalgia and irritable bowel symptoms.
To examine the effects of a challenge with monosodium glutamate (MSG) as compared to placebo on the symptoms of fibromyalgia (FM), in participants who initially experienced >30% remission of symptoms on an excitotoxin elimination diet. Fifty-seven FM patients who also had irritable bowel syndrome (IBS) were placed on a 4-week diet that excluded dietary additive excitotoxins including MSG and aspartame. Thirty-seven people completed the diet and 84% of those reported that >30% of their symptoms resolved, thus making them eligible to proceed to challenges. Subjects who improved on the diet were then randomised to a 2-week double-blind placebo-controlled crossover challenge with MSG or placebo for 3 consecutive days each week. The primary outcome measure was total symptom score. Secondary outcome measures included visual analogue pain scales (VAS for FM and IBS), an IBS Quality of Life Questionnaire (IBS QOL) and the Fibromyalgia Impact Questionnaire-Revised (FIQR). Repeated measures ANOVA was used to analyse crossover challenge results. The MSG challenge, as compared to placebo, resulted in a significant return of symptoms (total symptom score, p<0.02); a worsening of fibromyalgia severity as determined by the FIQR (p<0.03); decreased quality of life in regards to IBS symptoms (IBS QOL, p<0.05); and a non-significant trend toward worsening FM pain based on visual analogue scale (VAS, p<0.07). These findings suggest that dietary glutamate may be contributing to FM symptoms in some patients. Future research on the role of dietary excitotoxins in FM is warranted.


Development of a PNA probe for fluorescence in situ hybridization detection of Prorocentrum donghaiense.
Prorocentrum donghaiense is a common but dominant harmful algal bloom (HAB) species, which is widely distributed along the China Sea coast. Development of methods for rapid and precise identification and quantification is prerequisite for early-stage warning and monitoring of blooms due to P. donghaiense. In this study, sequences representing the partial large subunit rDNA (D1-D2), small subunit rDNA and internal transcribed spacer region (ITS-1, 5.8S rDNA and ITS-2) of P. donghaiense were firstly obtained, and then seven candidate DNA probes were designed for performing fluorescence in situ hybridization (FISH) tests on P. donghaiense. Based on the fluorescent intensity of P. donghaiense cells labeled by the DNA probes, the probe DP0443A displayed the best hybridization performance. Therefore, a PNA probe (PP0443A) analogous to DP0443A was used in the further study. The cells labeled with the PNA probe displayed more intensive green fluorescence than that labeled with its DNA analog. The PNA probe was used to hybridize with thirteen microalgae belonging to five families, i.e., Dinophyceae, Prymnesiophyceae, Raphidophyceae, Chlorophyceae and Bacillariophyceae, and showed no visible cross-reaction. Finally, FISH with the probes PP0443A and DP0443A and light microscopy (LM) analysis aiming at enumerating P. donghaiense cells were performed on the field samples. Statistical comparisons of the cell densities (cells/L) of P. donghaiense in the natural samples determined by FISH and LM were performed using one-way ANOVA and Duncan's multiple comparisons of the means. The P. donghaiense cell densities determined by LM and the PNA probe are remarkably higher than (p<0.05) that determined by the DNA probe, while no significant difference is observed between LM and the PNA probe. All results suggest that the PNA probe is more sensitive that its DNA analog, and therefore is promising for the monitoring of harmful algal blooms of P. donghaiense in the future.


Agility and change of direction in soccer: differences according to the player ages.
The goal of this study was to compare the changes of direction speed (CODS) and reactive agility (RA) in soccer players of different ages, in order to optimize the best training of these skills. One hundred eighty-seven players, divided into bi-annual age-groups, U12, U14, U16 and U18, performed two tests: Y-Agility Test, carried out in planned and reactive mode (Y-PLAN and Y-REAC) and Illinois for Change of Direction Test (ICODT). Difference between Y-REAC minus Y-PLAN represents the index of reactivity (REAC-INDEX). MANOVA showed significant differences among groups (F3,182=14.591; P<0.01; η2p=0.244). Y-PLAN showed significant differences only between U12 and the other groups (P<0.01). ICODT results were significantly different between the groups U12 and U14 and the other groups (P<0.01). Significant Pearson's correlations between Y-TEST and ICODT, for the three categories of young players (0.398 P<0.05; 0.615 P<0.01; 0.608 P<0.01 respectively), were found, whereas no significant correlation was found in U18 group. The best performance of Y-PLAN and ICODT, through age, depends on physical skill level, whereas the best RA results depend on technique and experience that help the players to use anticipatory skill. The high correlations between CODS and RA performances, differently than adult athletes, suggest that an effective work program for young players may include RA and CODS training at the same time.


Autocrine transforming growth factor-alpha is associated with progression of transformed properties in human colon cancer cells.
The GEO colon carcinoma cell line is weakly tumorigenic in athymic mice and shows differentiated properties both in tissue culture and in xenografts. Proliferating monolayer cultures of GEO cells which normally require exogenous epidermal growth factor (EGF) for optimal growth displayed a marked inhibition in growth upon addition of antibodies that block binding to the EGF receptor or neutralize TGF-alpha. These results indicated that GEO cells utilize TGF-alpha in a weak autocrine loop. The availability of a weakly malignant model system in which TGF-alpha had demonstrable, but low level autocrine activity, permitted the investigation of the role of TGF-alpha in tumorigenesis by generating a stronger autocrine loop through the overexpression of the polypeptide. GEO cells were electroporated with an expression vector containing the human TGF-alpha cDNA, and stable clones were isolated that constitutively expressed the TGF-alpha cDNA in a strong autocrine loop. However, the growth rate of the parental cells in EGF-supplemented medium was the same as that of transfected cells with or without growth factor-supplemented medium. Thus, any biological changes generated by the overexpression of TGF-alpha were due to the autocrine nature of the growth mechanism rather than due to any decrease in doubling time leading to a faster growth rate. Transfected GEO cells showed an increase in anchorage-independent growth and formed tumors more readily in athymic nude mice indicating that TGF-alpha plays a role in progression of transformed properties.


Current Approach in the Diagnosis and Management of Allergic Bronchopulmonary Aspergillosis in Children With Cystic Fibrosis.
Allergic bronchopulmonary aspergillosis (ABPA) is a complex pulmonary disorder characterized by a hypersensitivity reaction to Aspergillus fumigatus, and almost always seen in patients with cystic fibrosis (CF) and asthma. Fungal hyphae leads to an ongoing inflammation in the airways that may result in bronchiectasis, fibrosis, and eventually loss of lung function. Despite the fact that ABPA is thought to be more prevalent in CF than in asthma, the literature on ABPA in CF is more limited. The diagnosis is challenging and may be delayed because it is made based on a combination of clinical features, and radiologic and immunologic findings. With clinical deterioration of a patient with CF, ABPA is important to be kept in mind because clinical manifestations mimic pulmonary exacerbations of CF. Early diagnosis and appropriate treatment are important in preventing complications related to ABPA. Treatment modalities involve the use of anti-inflammatory agents to suppress the immune hyperreactivity and the use of antifungal agents to reduce fungal burden. Recently, in an effort to treat refractory patients or to reduce adverse effects of steroids, other treatment options such as monoclonal antibodies have started to be used. Intensive research of these new agents in the treatment of children is being conducted to address insufficient data.


Development of a double-antibody sandwich ELISA for rapid detection of Bacillus Cereus in food.
Bacillus cereus is increasingly recognized as one of the major causes of food poisoning in the industrialized world. In this paper, we describe a sensitive double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) that was developed for rapid detection of B. cereus in food to minimize the risk of contamination. The polyclonal antibody (pAb) and monoclonal antibodies (mAbs) specific to B. cereus were generated from rabbit antiserum and mouse ascites, respectively, using the octanoic acid/saturated ammonium sulfate precipitation method and protein A-sepharose columns. IgG-isotype mAbs were specially developed to undergo a novel peripheral multiple sites immunization for rapid gain of hybridomas and a subtractive screen was used to eliminate cross reactivity with closely related species such as Bacillus thuringiensis, B. subtilis, B. licheniformis and B. perfringens. The linear detection range of the method was approximately 1 × 10(4)-2.8 × 10(6) cells/mL with a detection limit (LOD) of 0.9 × 10(3) cells/mL. The assay was able to detect B. cereus when the samples were prepared in meat with various pathogens. The newly developed analytical method provides a rapid method to sensitively detect B. cereus in food specimens.


A critical examination of summary measures of population health.
In the past decade, interest has been rising in the development, calculation and use of summary measures of population health, which combine information on mortality and non-fatal health outcomes. This paper reviews the issues and challenges in the design and application of summary measures and presents a framework for evaluating different alternatives. Summary measures have a variety of uses, including comparisons of health in different populations and assessments of the relative contributions of different diseases, injuries and risk factors to the total disease burden in a population. Summary measures may be divided into two broad families: health expectancies and health gaps. Within each family, there are many different possible measures, but they share a number of inputs, including information on mortality, non-fatal health outcomes, and health state valuations. Other critical points include calculation methods and a range of conceptual and methodological issues regarding the definition, measurement and valuation of health states. This paper considers a set of basic criteria and desirable properties that may lead to rejection of certain summary measures and the development of new ones. Despite the extensive developmental agenda that remains, applications of summary measures cannot await the final resolution of all methodological issues, so they should focus on those measures that satisfy as many basic criteria and desirable properties as possible.


Adapting health interventions for local fit when scaling-up: a realist review protocol.
Scaling-up is essential to ensure universal access of effective health interventions. Scaling-up is a complex process, which occurs across diverse systems and contexts with no one-size-fits-all approach. To date, little attention has been paid to the process of scaling-up in how to make adaptations for local fit. The aim of this research is to develop theory on what actions can be used to make adaptations to health interventions for local fit when scaling-up across diverse contexts that will have practical application for implementers involved in scaling-up. Given the complexity of this subject, a realist review methodology was selected. Specifically, realist review emphasises an iterative, non-linear process, whereby the review is refined as it progresses. The identification of how the context may activate mechanisms to achieve outcomes is used to generate theories on what works for whom in what circumstances. This protocol will describe the first completed stage of development of an initial programme theory framework, which identified potential actions, contexts, mechanisms and outcomes that could be used to make adaptations when scaling-up. It will then outline the methods for future stages of the review which will focus on identifying case examples of scale-up and adaptation in practice. This realist review consists of six stages: (i) clarifying scope and development of a theoretical framework, (ii) developing a search strategy, (iii) selection and appraisal, (iv) data extraction, (v) data synthesis and analysis and (vi) further theory refinement with stakeholders. This review will develop theory on how adaptations can be made when scaling-up. Findings will be disseminated in a peer-reviewed journal and through stakeholder engagement as part of the research process. Ethical approval has been received through Health Policy and Management/Centre for Global Health Research Ethics Committee of Trinity College Dublin.


'Motherhood penalty' and 'fatherhood premium'? Fertility effects on parents in China.
Many previous empirical findings on 'motherhood penalty' and 'fatherhood premium' remain inconclusive due to potential selection biases. China's regional variation in exemptions to the one-child policy enables us to use the gender of the first child as a powerful instrumental variable (IV) in identifying the gendered fertility effects. We aim to estimate the causal effects of fertility on fathers' and mothers' various outcomes in China. Using the IV approach, this paper examines the gender-specific fertility effects on parents' time use, income, and subjective well-being, using data for 2010 from the China Family Panel Studies. Results show that while fathers spend more time at work and less time taking care of family members with more children, mothers report better subjective well-being. Moreover, fathers gain self-confidence in both their careers and the future, and mothers are happier, more satisfied with life and report better social ability. Our findings do not directly support the gendered fertility effects on parents. However, the differential fertility effects on specific domains for mothers versus fathers are consistent with household specialisation. By interpreting this conclusion within the context of China's one-child family planning policy, our research suggests that parents would do better if the one-child policy were abolished - i.e., if parents were allowed to have more children.


Preferred Features of E-Mental Health Programs for Prevention of Major Depression in Male Workers: Results From a Canadian National Survey.
Major depression is a prevalent mental disorder and imposes considerable burden on health and productivity. Men are not immune to major depression, yet they often delay seeking help because of perceived stigma and gender norms. E-mental health programs hold potential for early prevention of major depression. However, we have little knowledge about men's preferences for design features of e-mental health programs. The objective of this study was to (1) estimate and compare the proportions of Internet use for medical information, preferred design features, and likely use of e-mental health programs; (2) examine factors associated with the likely use of e-mental health programs; and (3) understand potential barriers to the use of e-mental health programs among Canadian working men, who were at high risk of a major depressive episode (MDE). A cross-sectional survey in 10 Canadian provinces was conducted between March and December 2015. Random digit dialing method was used through household landlines and cell phones to collect data from 511 working men who were at high risk of having an MDE and 330 working men who were at low risk of having an MDE. High-risk men were more likely to endorse the importance of accessing health resources on the Internet than low-risk men (83.4% vs 75.0%, respectively; P=.01). Of the 17 different features assessed, the top three features most likely to be used by high-risk men were: "information about improving sleep hygiene" (61.3%), "practice and exercise to help reduce symptoms of stress and depression" (59.5%), and "having access to quality information and resources about work stress issues" (57.8%). Compared with men at low risk for MDE, men at high risk for MDE were much more likely to consider using almost every one of the different design features. Differences in preferences for the design features by age among men at high risk of MDE were found only for 3 of 17 features. Differences in preferences for design features between English- and French-speaking participants were found only for 4 out of the 17 features. Analysis of qualitative data revealed that privacy issues, perceived stigma, ease of navigation, personal relevance, and lack of personal interaction, time, and knowledge were identified as barriers to the use of e-mental health programs in working men who were at high risk of MDE. E-mental health programs may be a promising strategy for prevention of depression in working men. Development of e-mental health programs should consider men's preferences and perceived barriers to enhance the acceptability of this approach.


Annexin A1 mediates the anti-inflammatory effects during the granulocytic differentiation process in all-trans retinoic acid-treated acute promyelocytic leukemic cells.
Annexin A1 (AnxA1) originating from mature neutrophils and their microparticles (MPs) plays an important anti-inflammatory role during the resolution phase of inflammation. However, the role of AnxA1 during the process of granulocytic differentiation is still unknown. All-trans retinoic acid (ATRA) can induce acute promyelocytic leukemic (APL) cells to differentiate along the granulocytic lineage and has been used successfully in treating APL patients. In this study, we investigated whether or not AnxA1 contributed to the anti-inflammatory properties of ATRA-treated APL (NB4; ATRA-NB) cells using the transmigratory and adhesive assays. We found that ATRA was able to enhance the surface expression of AnxA1 and its receptor (FPR2/ALX) and the release of AnxA1-containing MPs from ATRA-NB4 cells, while the expression of annexin V was not elevated on the latter cells. Further studies demonstrated that exogenous AnxA1 could inhibit ATRA-NB4 cells in their transmigratory activity and adhesion to endothelial cells. In addition, the transmigratory activity of ATRA-NB4 cells can be significantly enhanced by pretreatment with a FPR2/ALX neutralizing antibody, suggesting that endogenous AnxA1 may contribute to the anti-migratory effects. Finally, ATRA-NB4-derived MPs could also inhibit recipient cells in their transmigratory and adhesive activities and these anti-inflammatory effects could be inhibited by pretreatment of MPs with a specific anti-AnxA1 antibody. Flowcytometry studies further demonstrated that FITC-labeled AnxA1 could be transported from MPs to the membrane of recipient ATRA-NB4 cells. We conclude that biologically active AnxA1 may play a role in the anti-inflammatory properties of ATRA-treated APL cells during the process of granulocytic differentiation.


Pathology of asbestosis- An update of the diagnostic criteria: Report of the asbestosis committee of the college of american pathologists and pulmonary pathology society.
Asbestosis is defined as diffuse pulmonary fibrosis caused by the inhalation of excessive amounts of asbestos fibers. Pathologically, both pulmonary fibrosis of a particular pattern and evidence of excess asbestos in the lungs must be present. Clinically, the disease usually progresses slowly, with a typical latent period of more than 20 years from first exposure to onset of symptoms. IDIOPATHIC PULMONARY FIBROSIS: The pulmonary fibrosis of asbestosis is interstitial and has a basal subpleural distribution, similar to that seen in idiopathic pulmonary fibrosis, which is the principal differential diagnosis. However, there are differences between the 2 diseases apart from the presence or absence of asbestos. First, the interstitial fibrosis of asbestosis is accompanied by very little inflammation, which, although not marked, is better developed in idiopathic pulmonary fibrosis. Second, in keeping with the slow tempo of the disease, the fibroblastic foci that characterize idiopathic pulmonary fibrosis are infrequent in asbestosis. Third, asbestosis is almost always accompanied by mild fibrosis of the visceral pleura, a feature that is rare in idiopathic pulmonary fibrosis. RESPIRATORY BRONCHIOLITIS: Asbestosis is believed to start in the region of the respiratory bronchiole and gradually extends outward to involve more and more of the lung acinus, until the separate foci of fibrosis link, resulting in the characteristically diffuse pattern of the disease. These early stages of the disease are diagnostically problematic because similar centriacinar fibrosis is often seen in cigarette smokers and is characteristic of mixed-dust pneumoconiosis. Fibrosis limited to the walls of the bronchioles does not represent asbestosis. Histologic evidence of asbestos inhalation is provided by the identification of asbestos bodies either lying freely in the air spaces or embedded in the interstitial fibrosis. Asbestos bodies are distinguished from other ferruginous bodies by their thin, transparent core. Two or more asbestos bodies per square centimeter of a 5- mu m-thick lung section, in combination with interstitial fibrosis of the appropriate pattern, are indicative of asbestosis. Fewer asbestos bodies do not necessarily exclude a diagnosis of asbestosis, but evidence of excess asbestos would then require quantitative studies performed on lung digests. Quantification of asbestos load may be performed on lung digests or bronchoalveolar lavage material, employing either light microscopy, scanning electron microscopy, or transmission electron microscopy. Whichever technique is employed, the results are only dependable if the laboratory is well practiced in the method chosen, frequently performs such analyses, and the results are compared with those obtained by the same laboratory applying the same technique to a control population.


Psychometric evaluation of medication adherence rating scale (MARS) among Nigerian patients with schizophrenia.
The Medication Adherence Rating Scale (MARS) is a 10-item self-report measure of medication adherence in psychosis which is a vital predictor of illness course and outcome in patient with schizophrenia. The initial and subsequent studies have shown that MARS has good reliability and validity scores after correction for the small sample size in the index study. This study aimed to determine the psychometric properties of MARS among outpatients with schizophrenia at the outpatient clinic of the Neuropsychiatric Hospital Aro Abeokuta Ogun State Nigeria. Intra-class correlation coefficient (ICC) was used to determine the internal consistency, item-total correlations, and reliability of the instrument. Factor analysis was done using principal component analysis with varimax rotation. The intra-class correlation coefficient (ICC) for these 10 items (at time T1) was 0.6 with a P value of <0.001 while for the test--retest analysis was 0.7 with a P value of 0.04. A principal components factor analysis with varimax rotation produced a four-factor solution and factor 4 was found to be the most internally consistent, with Cronbach's alpha of 0.63. This study supports the internal consistency, test--retest reliability, and constructs validity of the MARS.


Effectiveness of olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia after discontinuing perphenazine: a CATIE study.
The relative effectiveness of newly started antipsychotic drugs for individuals with schizophrenia may depend on multiple factors, including each patient's previous treatment response and the reason for a new medication trial. This randomized, double-blind study compared olanzapine, quetiapine, and risperidone in patients who had just discontinued the older antipsychotic perphenazine. Subjects with schizophrenia (N=114) who had been randomly assigned to and then discontinued perphenazine in phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia study were reassigned randomly to double-blinded treatment with olanzapine, 7.5-30.0 mg/day (N=38); quetiapine, 200-800 mg/day (N=38); or risperidone, 1.5-6.0 mg/day (N=38). The primary aim was to determine whether there were differences among these three treatments in effectiveness, as measured by time to treatment discontinuation for any reason. Secondary outcomes included reasons for treatment discontinuation and measures of drug tolerability. The time to treatment discontinuation was longer for patients treated with quetiapine (median, 9.9 months) and olanzapine (7.1 months) than with risperidone (3.6 months). There were no significant differences between treatments on discontinuation due to inefficacy, intolerability, or patient decision. Among this group of patients with chronic schizophrenia who had just discontinued the older antipsychotic perphenazine, quetiapine and olanzapine were more effective than risperidone, as reflected by longer time to discontinuation for any reason. In the context of other results from the CATIE study, the effectiveness and acceptability of antipsychotic drugs appears to vary considerably according to clinical circumstances.


Loss of Complement Factor H in Plasma Increases Endothelial Cell Migration.
Tumor growth depends on angiogenesis, the growth of new blood vessels. Complement factor H (CFH) is a plasma glycoprotein that functions as a regulator of the complement system. The aim of this study is to delineate the role of CFH in angiogenesis. A conditional null allele of the Cfh gene was generated in C57BL/6J mice by flanking the exon 3 with loxP sites. The Cfhflox/flox mice were crossed with Rosa26-Cre mice to obtain the mice homozygotes of Cfh deletion (Cfh-/-). The Cfh-/- mice were examined by in vivo angiogenesis assays. Mouse endothelial cells were treated with media containing 5% of mouse plasma from the wildtype or Cfh-/- mice and assayed for proliferation, viability and migration. The Cfh-/- mice did not display any obvious abnormalities. They demonstrated a pro-angiogenic phenotype in matrigel plug assay, but not in aorta ring assay. In vitro, loss of Cfh in plasma does not affect proliferation or viability, but significantly increases migration of mouse endothelial cells. Our findings suggest that plasma CFH inhibits angiogenesis by reduction of endothelial cell migration. Thus the mutation of CFH might lead to excessive tumor angiogenesis.


Uncovering tacit knowledge: a pilot study to broaden the concept of knowledge in knowledge translation.
All sectors in health care are being asked to focus on the knowledge-to-practice gap, or knowledge translation, to increase service effectiveness. A social interaction approach to knowledge translation assumes that research evidence becomes integrated with previously held knowledge, and practitioners build on and co-create knowledge through mutual interactions. Knowledge translation strategies for public health have not provided anticipated positive changes in evidence-based practice, possibly due in part to a narrow conceptualization of knowledge. More work is needed to understand the role of tacit knowledge in decision-making and practice. This pilot study examined how health practitioners applied tacit knowledge in public health program planning and implementation. This study used a narrative approach, where teams from two public health units in Ontario, Canada were conveniently selected. Respondents participated in individual interviews and focus groups at each site. Questions were designed to understand the role of tacit knowledge as it related to the program planning process. Data were analyzed through a combination of content analysis and thematic comparison. The findings highlighted two major aspects of knowledge that arose: the use of tacit knowledge and the integration of tacit and explicit knowledge. Tacit knowledge included: past experiences, organization-specific knowledge, community contextual knowledge, and the recognition of the tacit knowledge of others. Explicit knowledge included: research literature, the Internet, popular magazines, formal assessments (surveys and interviews), legislation and regulations. Participants sometimes deliberately combined tacit and explicit knowledge sources in planning. This pilot demonstrated that front-line public health workers draw upon both tacit knowledge and explicit knowledge in their everyday lived reality. Further, tacit knowledge plays an important role in practitioners' interpretation and implementation of explicit research findings. This indicates a need to broaden the scope of knowledge translation to include other forms of knowledge beyond explicit knowledge acquired through research. Strategies that recognize and support the use of tacit knowledge, such as communities of practice or networks, may be important components of a comprehensive approach to knowledge translation. This study provides support for further investigation of the role of tacit knowledge in the planning and delivery of effective public health services.


Responses to telomere erosion in plants.
In striking contrast to animals, plants are able to develop and reproduce in the presence of significant levels of genome damage. This is seen clearly in both the viability of plants carrying knockouts for key recombination and DNA repair genes, which are lethal in vertebrates, and in the impact of telomere dysfunction. Telomerase knockout mice show accelerated ageing and severe developmental phenotypes, with effects on both highly proliferative and on more quiescent tissues, while cell death in Arabidopsis tert mutants is mostly restricted to actively dividing meristematic cells. Through phenotypic and whole-transcriptome RNAseq studies, we present here an analysis of the response of Arabidopsis plants to the continued presence of telomere damage. Comparison of second-generation and seventh-generation tert mutant plants has permitted separation of the effects of the absence of the telomerase enzyme and the ensuing chromosome damage. In addition to identifying a large number of genes affected by telomere damage, many of which are of unknown function, the striking conclusion of this study is the clear difference observed at both cellular and transcriptome levels between the ways in which mammals and plants respond to chronic telomeric damage.


Sp1 functions in a chromatin-dependent manner to augment human alpha-globin promoter activity.
The 5' flanking region of the human alpha-globin gene is highly G + C rich and contains multiple copies of the consensus sequence for the Sp1 binding site. We investigated the role of this G + C-rich region in augmenting alpha-globin promoter activity in the presence of the far-upstream alpha-globin enhancer, HS-40. We show that in transiently transfected erythroid cells, deletion of the alpha-globin G + C-rich 5' flanking region has no effect on alpha-globin promoter activity. However, upon stable integration into chromatin, deletion of this region causes a nearly 90% decrease in promoter activity compared with expression from an alpha-globin promoter retaining this region. These results suggest that the alpha-globin G + C-rich 5' flanking region augments alpha-globin promoter activity in a chromatin-dependent manner. We further show that this G + C-rich region is required for the activation of alpha-globin gene expression during erythroid differentiation. Finally, we show by both footprint analysis and functional assays that the ability of the G + C-rich region to increase alpha-globin promoter activity from a stably integrated alpha-globin gene is mediated by its multiple binding sites for the transcription factor Sp1.


Effects of Electrode Configurations and Injected Current Intensity on the Electrical Field of Transcranial Direct Current Stimulation: A Simulation Study.
Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technology that modulates the excitability of the brain by delivering weak electric currents to the brain via scalp electrodes. Electrode configuration and injected current intensity are two important parameters in the tDCS design. This simulation study examined three commercially available electrode configurations, i.e. conventional low definition rectangular pad, high-definition Disc, and high-definition 4 x 1 with different electrode distances and different injected current intensity. Simulation results show that increasing the injected current intensity of HD-tDCS mainly increases the electrical field strength for all configurations. Both Disc and 4 x 1 high definition tDCS (HD-tDCS) have better focality than the conventional low-definition rectangular pad. Increasing the inter-electrode distance in HD-tDCS enlarges the electrical field strength and the depth of stimulation but reduces the focality. In motor rehabilitation, a trade-off needs to be made in the tDCS design to allow the electrical field reaching the white matter to facilitate the usage of the cortico-spinal tract without influencing other undesirable regions in the brain.


Understanding Patients' Perspectives and Information Needs Following a Positive Home Human Papillomavirus Self-Sampling Kit Result.
We explored patient perspectives after a positive human papillomavirus (HPV) self-sampling result to describe experiences and information needs for this home-based screening modality. We recruited women who tested high-risk (hr) HPV positive during a pragmatic trial evaluating mailed hrHPV self-sampling kits as an outreach strategy for women overdue for Pap screening in a U.S. integrated health care system. Telephone interviews were conducted from 2014 to 2017. Five independent coders analyzed transcripts using iterative content analysis. Forty-six women (61% of invited; median age 55.5 years) completed a semistructured interview. Six themes emerged: (1) convenience of home-based screening, (2) intense feelings and emotions after receiving positive kit results, (3) importance of seeing provider and discussing kit results, (4) information seeking from various sources, (5) confusion about purpose and meaning of HPV versus Pap tests, and (6) concern that HPV self-sampling is inaccurate when the subsequent Pap test is normal. Although women liked the kit's convenience, discussion about discordant home HPV and in-clinic Pap results led them to question the accuracy of HPV self-sampling. Patient-provider communication around home HPV kits is more complex than for reflex or cotesting because clinician-collected Pap results are unknown at the time of the positive kit result. Patients need education about differences between HPV and Pap tests and how they are used for screening and follow-up. To reassure patients and keep them interested in self-sampling, education should be provided at multiple time points during the screening process.


Vaccination Against Lawsonia intracellularis Decreases Shedding of Salmonella enterica serovar Typhimurium in Co-Infected Pigs and Alters the Gut Microbiome.
Salmonella enterica serovar Typhimurium continues to be a major cause of foodborne illness worldwide and pork can serve as a source of infection. Co-infection of S. enterica with Lawsonia intracellularis, a common intestinal pathogen of swine, has been found as risk factor for increased S. enterica shedding. The objective of this study was to investigate if vaccination against L. intracellularis could lead to decreased S. Typhimurium shedding. To test this hypothesis, pigs were challenged with either S. Typhimurium or S. Typhimurium and L. intracellularis, with and without L. intracellularis vaccination (n = 9 per group). A non-challenged group served as a negative control. Vaccination decreased the shedding of S. Typhimurium in co-infected animals by 2.12 log10 organisms per gram of feces at 7 days post infection. Analysis of the microbiome showed that vaccination led to changes in the abundance of Clostridium species, including Clostridium butyricum, in addition to other compositional changes that may explain the protection mediated against S. Typhimurium. These results indicate that vaccination against L. intracellularis in co-infected herds may provide a new tool to increase food safety by helping to prevent S. enterica without the need for antibiotics.


In-Vivo Histological Analysis of a Fractional CO2 Laser System Intended for Treatment of Soft Tissue.

BACKGROUND: Fractional ablative lasers have been shown to be safe and effective for improving wrinkles, scars, skin texture, and dyspigmentation. However, the exact effects of this technology in vivo on epidermal and dermal skin constituents have not been delineated. This study evaluated the in vivo histological effects over time of treatment with a fractional ablative CO2 system, using different treatment parameters. Healthy adult volunteers were enrolled in this multicenter clinical study. Study participants, previously scheduled for abdominoplasty, received fractional CO2 laser treatment on the abdomen at a predetermined time prior to surgery. Biopsies were taken at baseline and after CO2 treatment. Morphological and morphometric analyses were performed in the ablated and coagulated tissue areas. Nine healthy adult volunteers were treated. Histologic evaluation showed 800-900 micron diameter zones of ablation and coagulation confined to the upper most layer of the skin in the mode with the greatest fractional skin coverage using Light Mode 30 - 50% (spot diameter of 150 microns, 30-60 millijoules fluence), while ablation to levels of up to 900 microns in depth using the Deep Mode (spot diameter 150 microns, 50-80 millijoules). Healing times of treated tissue varied from 1-day post-treatment with the Light Mode, and up to 10 days post-treatment with the Deep Mode. No remnants of ablation or coagulation were seen after 30 days post CO2 treatment with either mode. There were no adverse events associated with treatments. Treatment of the skin using the fractional CO2 device leads to skin resurfacing via ablation and coagulation of the treated area at a depth proportional to the delivered energy. The higher the energy used, the greater the degree of ablation and coagulation in tissue, which can lead to a greater tissue response in terms of fibroblast activity, collagen remodeling, and new collagen formation.

J Drugs Dermatol. 2017;16(11):1085-1090.
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Stellate-cell lipidosis in liver biopsy specimens. Recognition and significance.
Hepatic stellate-cell lipidosis due to hypervitaminosis A can lead to cirrhosis, which can be averted by restricting vitamin A intake. Other causes, including the use of synthetic retinoids, have been postulated. We studied the frequency and etiology of stellate-cell lipidosis in patients undergoing liver biopsy for reasons other than vitamin A abuse. Fourteen cases (1.1%) were identified retrospectively among 1,235 nontransplant liver biopsy specimens examined from January 1995 through December 1999. Diagnostic criteria included the following: lipid-laden cells in the space of Disse; small, dark, crescent-shaped nuclei with inconspicuous nucleoli; and wispy cytoplasmic strands separating fat droplets. Patient details, reason for biopsy, and medication use were studied. Reasons for biopsy included hepatitis C (10 cases), abnormal liver enzyme levels (2 cases), methotrexate use (1 case), and alcohol abuse (1 case). Hypervitaminosis A was not suspected clinically in the 5 patients who used oral vitamin A or 3 who used topical tretinoin (Retin-A). In 6 patients, no cause of stellate-cell lipidosis was discerned. Stellate-cell lipidosis should be reported to alert clinicians to a potentially preventable form of liver injury.


Heritability of ischaemic stroke in women compared with men: a genetic epidemiological study.
Ischaemic stroke is partly heritable. However, although the genetic and non-genetic factors responsible could be sex-specific, interactions between the sex of the parent affected and the sex of the proband or affected siblings are unknown. We sought to assess the relation between the sex and phenotype of affected probands and the sex of affected first-degree relatives. We determined the prevalence of history of stroke in the mother, father, and other first-degree relatives in female and male probands with ischaemic stroke or transient ischaemic attack in the population-based Oxford Vascular Study (OXVASC). We validated our findings using unpublished individual patient data from two independent Oxford studies. In OXVASC, detailed family history was available in 806 (93%) probands. Female probands were more likely than males to have at least one affected first-degree relative (146/423 vs 104/383; OR 1.4, 95% CI 1.1-2.0, p=0.02) due entirely to an excess of affected female relatives in female probands (female relative vs male relative OR=1.7, 1.3-2.4, p=0.0004; female only vs male only OR=2.1, 1.4-3.1, p=0.0001). Maternal stroke was more common than paternal stroke in female probands (OR=1.8, 1.2-2.7, p=0.001) but not in males (OR=1.1, 0.7-1.7, p=0.38), and female probands were more likely than males to have an affected sister (OR=3.1, 1.5-6.7, p=0.004) but not an affected brother (OR=1.1, 0.6-2.1, p=0.80). Ages at first stroke were also correlated within families among affected females (r=0.36, p=0.004) but not among affected males, such that the excess of affected female relatives of female probands was greatest when the difference in age at first stroke was less than 5 years (OR=3.7, 1.6-8.6, p=0.0007) and fell as the age difference increased (p for trend=0.004). These findings were independent of traditional risk factors and stroke subtype. Data from the other Oxford studies confirmed the excess maternal history of stroke in female probands (OR=2.3, 1.5-3.8, p<0.00001) and the lack in males (OR=1.0, 0.7-1.4, p=0.58). Heritability of ischaemic stroke is greater in women than in men, with an excess of affected mothers and affected sisters in female probands independent of traditional vascular risk factors, which could be explained by sex-specific genetic, epigenetic, or non-genetic mechanisms.


Probability distribution of turbulent irradiance in a saturation regime.
Application of the central limit theorem to the stochastic equation of propagation suggests that the probability distribution of the complex wave amplitude defined on the geometrical phase front is approximately normal. The resulting irradiance probability density function, valid in the strong scintillation regime, is an exponential multiplied by the modified Bessel function I(0) both of argument proportional to the irradiance; it is not the Rice-Nakagami density function. Quantitative tests show that this exponential-Bessel function constitutes as good a fit as the log-normal to the irradiance probability data reported in this paper. Since the normal distribution hypothesis is consistent with the stochastic wave equation, the model proposed here should be a simple substitute to the often used but theoretically incorrect log-normal irradiance probability distribution model.


Above-threshold ionization by an elliptically polarized field: interplay between electronic quantum trajectories
Measurements of energy-resolved angular distributions of electrons generated in above-threshold ionization of rare gases in a field with elliptical polarization are presented, with emphasis on the high-energy part of the spectra. The data show a second plateau at a specific angle with respect to the large component of the laser field. The results are compared to a calculation based on a strong-field rescattering approximation. This is interpreted in terms of the superposition of quantum trajectories. The second plateau is associated with the interference of electrons that do and that do not rescatter.


Oscillation of an anuran hybrid zone: morphological evidence spanning 50 years.
The hybrid zone between the primarily forest-dwelling American toad, Anaxyrus americanus, and the prairie-adapted Canadian toad, A. hemiophrys, in southeastern Manitoba is known to have shifted its position during the past 50 years. Hybrid zones are areas of interbreeding between species and their movement across a landscape should reflect their underlying dynamics and environmental change. However, empirical demonstrations of hybrid zone movements over long periods of time are rare. This hybrid zone is dominated by individuals of intermediate morphology and genetic composition. We sought to determine if it had continued to move and if that movement was associated with shifts in habitat, as predicted. We used variation in the toads' most diagnostic morphological feature, the separation between their interorbital cranial crests, to determine the geographic position of the hybrid zone center at four times between 1960 and 2009 using maximum likelihood methods. The hybrid zone center moved west by 38 km over 19 years and then east again by 10 km over the succeeding 29 years. The position of the hybrid zone did not track either the direction or the magnitude of movement of the forest-prairie habitat transition over the same time period. This is the first reported evidence of oscillation in the position of a hybrid zone. The back and forth movement indicates that neither species maintains a selective advantage over the other in the long term. However, the movement of the hybrid zone was not bounded by the breadth of the habitat transition. Its oscillation suggests that the hybrid zone is better described as being elastically tethered to the habitat transition.


Concept of robotic gamma knife microradiosurgery and results of its clinical application in benign skull base tumors.
The availability of advanced computer-aided robotized devices for the Gamma Knife (i.e., an automatic positioning system and PerfeXion) resulted in significant changes in radiosurgical treatment strategy. The possibility of applying irradiation precisely and the significantly improved software for treatment planning led to the development of the original concept of robotic Gamma Knife microradiosurgery, which is comprised of the following: (1) precise irradiation of the lesion with regard to conformity and selectivity; (2) intentional avoidance of excessive irradiation of functionally important anatomical structures, particularly cranial nerves, located both within the target and in its vicinity; (3) delivery of sufficient radiation energy to the tumor with a goal of shrinking it while keeping the dose at the margins low enough to prevent complications. Realization of such treatment principles requires detailed evaluation of the microanatomy of the target area, which is achieved with an advanced neuroimaging protocol. From 2003, we applied the described microradiosurgical concept in our clinic for patients with benign skull base tumors. Overall, 75 % of neoplasms demonstrated shrinkage, and 47 % showed ≥50 % and more volume reduction. Treatment-related complications were encountered in only 6 % of patients and were mainly related to transient cranial nerve palsy. Just 2 % of neoplasms showed regrowth after irradiation. In conclusion, applying the microradiosurgical principles based on advanced neuroimaging and highly precise treatment planning is beneficial for patients, providing a high rate of tumor shrinkage and a low morbidity rate.


Daily heat stress treatment rescues denervation-activated mitochondrial clearance and atrophy in skeletal muscle.
Traumatic nerve injury or nerve disease leads to denervation and severe muscle atrophy. Recent evidence shows that mitochondrial loss could be a key mediator of skeletal muscle atrophy. Here, we show that daily heat stress treatment rescues denervation-induced loss of mitochondria and concomitant muscle atrophy. We also found that denervation-activated autophagy-dependent mitochondrial clearance (mitophagy) was suppressed by daily heat stress treatment. The molecular basis of this observation is explained by our results showing that heat stress treatment attenuates the increase of key proteins that regulate the tagging step for mitochondrial clearance and the intermediate step of autophagosome formation in denervated muscle. These findings contribute to the better understanding of mitochondrial quality control in denervated muscle from a translational perspective and provide a mechanism behind the attenuation of muscle wasting by heat stress. Traumatic nerve injury or motor neuron disease leads to denervation and severe muscle atrophy. Recent evidence indicates that loss of mitochondria and the related reduction in oxidative capacity could be key mediators of skeletal muscle atrophy. As our previous study showed that heat stress increased the numbers of mitochondria in skeletal muscle, we evaluated whether heat stress treatment could have a beneficial impact on denervation-induced loss of mitochondria and subsequent muscle atrophy. Here, we report that daily heat stress treatment (mice placed in a chamber with a hot environment; 40°C, 30 min day(-1) , for 7 days) rescues the following parameters: (i) muscle atrophy (decreased gastrocnemius muscle mass); (ii) loss of mitochondrial content (decreased levels of ubiquinol-cytochrome c reductase core protein II, cytochrome c oxidase subunits I and IV and voltage-dependent anion channel protein); and (iii) reduction in oxidative capacity (reduced maximal activities of citrate synthase and 3-hydroxyacyl-CoA dehydrogenase) in denervated muscle (produced by unilateral sciatic nerve transection). In order to gain a better understanding of the above mitochondrial adaptations, we also examined the effects of heat stress on autophagy-dependent mitochondrial clearance (mitophagy). Daily heat stress normalized denervation-activated induction of mitophagy (increased mitochondrial microtubule-associated protein 1A/1B-light chain3-II (LC3-II) with and without blocker of autophagosome clearance). The molecular basis of this observation was explained by the results that heat stress attenuated the denervation-induced increase in key proteins that regulate the following steps: (i) the tagging step of mitochondrial clearance (increased mitochondrial Parkin, ubiquitin-conjugated, P62/sequestosome 1 (P62/SQSTM1)); and (ii) the elongation step of autophagosome formation (increased Atg5-Atg12 conjugate and Atg16L). Overall, our results contribute to the better understanding of mitochondrial quality control and the mechanisms behind the attenuation of muscle wasting by heat stress in denervated skeletal muscle.


Modelling cultural selection on biological fitness to integrate social transmission and adaptive explanations for human behaviour.
One of the difficulties with cultural group selection theory highlighted in the review by Smith (2020, Evol. Hum. Sci., 2, e7) is its inability to separate the evolutionary effects of selection of cultural traits based on biological fitness (Cultural Selection 1) from the effects of selection based on cultural fitness (Cultural Selection 2). Confusing these two processes can hinder the integration of adaptive explanations for human behaviour, which focus on biological fitness, and cultural evolution explanations, which often focus on social transmission. Recent empirical work is starting to bridge this gap, but progress in mathematical modelling has been considerably slower. Here, I suggest that modellers can contribute to achieving this integration by further developing models of Cultural Selection 1, where behaviours are influenced by culturally inherited traits selected on the basis of their effects on biological fitness. These models should build on existing social evolution theory methods and replace genetic relatedness with cultural relatedness, that is the probability that two individuals share a cultural variant.


Self-reported traumatic brain injury during key developmental stages: examining its effect on co-occurring psychological symptoms in an adjudicated sample.
Primary Objective: Prior research has demonstrated that traumatic brain injury (TBI) is associated with individual psychological symptoms. These findings, however, may not pertain to the influence of TBI during key developmental stages on the co-occurrence of negative psychological symptoms.Research Design: It was hypothesized that (H1) self-reported TBI is associated with adverse psychological effects, that (H2) self-reported TBI during adolescences is associated with both immediate and delayed adverse psychological effects, and finally, (H3) self-reported TBI during the early stages of adulthood is not associated with immediate psychological effects.Methods and Procedures: The current study employed a sample of adjudicated youth (N: 419 to 562) and structural equation modeling to estimate the association between self-reported TBI and subsequent adverse psychological effects.Results: Findings suggested that higher levels of self-reported TBI during adolescence were associated with higher levels of adverse psychological effects. These effects were both immediate and delayed. However, higher levels of self-reported TBI during adulthood were not associated with immediate adverse psychological effects.Conclusion: Overall, the findings suggest that deleterious outcomes related to self-reported TBI during key developmental stages include proximal and long-term adverse psychological effects.


An integrated metagenomic/metaproteomic investigation of microbiota in dajiang-meju, a traditional fermented soybean product in Northeast China.
Dajiang-meju have been used as major ingredients for the preparation of traditional spontaneously fermented soybean paste in Northeast China. In this work, we sequenced and analyzed the metagenome of 12 dajiang-meju samples. To complement the metagenome analysis, we analyzed the taxonomic and functional diversity of the microbiota by metaproteomics (LC-MS/MS). The analysis of metagenomic data revealed that the communities were primarily dominated by Enterobacter, Enterococcus, Leuconostoc, Lactobacillus, Citrobacter and Leclercia. Moreover, changes in the functional levels were monitored, and metaproteomic analysis revealed that most of the proteins were mainly expressed by members of Rhizopus, Penicillium and Geotrichum. The number of sequences allocated to fungi in the fermentation process decreased, whereas the number of sequences assigned to bacteria increased with time of fermentation. In addition, functional metagenomic profiling indicated that a series of sequences related to carbohydrates and amino acids metabolism were enriched. Additionally, enzymes associated with glycolysis metabolic pathways were presumed to contribute to the generation of flavor in dajiang-meju. Proteins from different dajiang-meju samples involved in global and overview maps, carbohydrate metabolism, nucleic acid metabolism and energy metabolism were differentially expressed. This information improves the understanding of microbial metabolic patterns with respect to the metaproteomes of dajiang-meju and provides a powerful tool for studying the fermentation process of soybean products.


The aggregation of an alkyl-C60 derivative as a function of concentration, temperature and solvent type.
Contrast-variation small-angle neutron scattering (CV-SANS), small-angle X-ray scattering (SAXS), nuclear magnetic resonance (NMR) measurements of diffusion and isothermal titration calorimetry (ITC) are used to gain insight into the aggregation of an alkyl-C60 derivative, molecule 1, in n-hexane, n-decane and toluene as a function of concentration and temperature. Results point to an associative mechanism of aggregation similar to other commonly associating molecules, including non-ionic surfactants or asphaltenes in non-aqueous solvents. Little aggregation is detected in toluene, but small micelle-like structures form in n-alkane solvents, which have a C60-rich core and alkyl-rich shell. The greatest aggregation extent is found in n-hexane, and at 0.1 M the micelles of 1 comprise around 6 molecules at 25 °C. These micelles become smaller when the concentration is lowered, or if the solvent is changed to n-decane. The solution structure is also affected by temperature, with a slightly larger aggregation extent at 10 °C than at 25 °C. At higher concentrations, for example in solutions of 1 above 0.3 M in n-decane, a bicontinuous network becomes apparent. Overall, these findings aid our understanding of the factors driving the assembly of alkyl-π-conjugated hydrophobic amphiphiles such as 1 in solution and thereby represent a step towards the ultimate goal of exploiting this phenomenon to form materials with well-defined order.


Investigation into Mode Localization of Electrostatically Coupled Shallow Microbeams for Potential Sensing Applications.
With the constant need for the development of smart devices, Micro-Electro-Mechanical Systems (MEMS) based smart sensors have been developed to detect hazard materials, micro-particles or even toxic substances. Identifying small particles using such micro-engineering technology requires designing sensors with high sensitivity, selectivity and ease of integration with other electronic components. Nevertheless, the available detection mechanism designs are still juvenile and need more innovative ideas to be even more competitive. Therefore, this work aims to introduce a novel, smart and innovative micro-sensor design consisting of two weakly electrostatically coupled microbeams (both serving as sensors) and electrically excited using a stationary electrode assuming a dc/ac electric signal. The sensor design can be tuned from straight to eventually initially curved microbeams. Such an arrangement would develop certain nonlinear phenomena, such as the snap-through motion. This behavior would portray certain mode veering/mode crossing and ultimately mode localization and it would certainly lead in increasing the sensitivity of the mode-localized based sensing mechanism. These can be achieved by tracking the change in the resonance frequencies of the two microbeams as the coupling control parameter is varied. To this extent, a nonlinear model of the design is presented, and then a reduced-order model considering all geometric and electrical nonlinearities is established. A Long-Time Integration (LTI) method is utilized to solve the static and dynamics of the coupled resonators under primary lower-order and higher-order resonances, respectively. It is shown that the system can display veering and mode coupling in the vicinity of the primary resonances of both beams. Such detected modal interactions lead to an increase in the sensitivity of the sensor design. In addition, the use of two different beam's configurations in one device uncovered a possibility of using this design in detecting two potential substances at the same time using the two interacting resonant peaks.