Effectiveness of a quality improvement intervention for adolescent depression in primary care clinics: a randomized controlled trial.
Depression is a common condition associated with significant morbidity in adolescents. Few depressed adolescents receive effective treatment for depression in primary care settings. To evaluate the effectiveness of a quality improvement intervention aimed at increasing access to evidence-based treatments for depression (particularly cognitive-behavior therapy and antidepressant medication), relative to usual care, among adolescents in primary care practices. Randomized controlled trial conducted between 1999 and 2003 enrolling 418 primary care patients with current depressive symptoms, aged 13 through 21 years, from 5 health care organizations purposively selected to include managed care, public sector, and academic medical center clinics in the United States. Usual care (n = 207) or 6-month quality improvement intervention (n = 211) including expert leader teams at each site, care managers who supported primary care clinicians in evaluating and managing patients' depression, training for care managers in manualized cognitive-behavior therapy for depression, and patient and clinician choice regarding treatment modality. Participating clinicians also received education regarding depression evaluation, management, and pharmacological and psychosocial treatment. Depressive symptoms assessed by Center for Epidemiological Studies-Depression Scale (CES-D) score. Secondary outcomes were mental health-related quality of life assessed by Mental Health Summary Score (MCS-12) and satisfaction with mental health care assessed using a 5-point scale. Six months after baseline assessments, intervention patients, compared with usual care patients, reported significantly fewer depressive symptoms (mean [SD] CES-D scores, 19.0 [11.9] vs 21.4 [13.1]; P = .02), higher mental health-related quality of life (mean [SD] MCS-12 scores, 44.6 [11.3] vs 42.8 [12.9]; P = .03), and greater satisfaction with mental health care (mean [SD] scores, 3.8 [0.9] vs 3.5 [1.0]; P = .004). Intervention patients also reported significantly higher rates of mental health care (32.1% vs 17.2%, P<.001) and psychotherapy or counseling (32.0% vs 21.2%, P = .007). A 6-month quality improvement intervention aimed at improving access to evidence-based depression treatments through primary care was significantly more effective than usual care for depressed adolescents from diverse primary care practices. The greater uptake of counseling vs medication under the intervention reinforces the importance of practice interventions that include resources to enable evidence-based psychotherapy for depressed adolescents.


Neurofilament inclusion body disease: a new proteinopathy?
We describe four cases of a new clinicopathological entity presenting with either a frontotemporal dementia or corticobasal degeneration syndrome with a mean age of onset of 45 years (range 41-50) characterized pathologically by deposition of neurofilament proteins. All four patients had a rapidly progressive course and have become mute and non-ambulatory, and three have died after mean illness duration of only 3 years (range 2 1/2 -4). Both structural (MRI) and functional (PET and SPECT) imaging demonstrated frontal and temporal lobe and basal ganglia involvement. Gross neuropathological examination in the three deceased patients (the fourth patient, still alive, was diagnosed by brain biopsy) revealed changes affecting predominantly the frontal and temporal cortices, basal ganglia and brainstem. There was superficial linear spongiosis affecting the frontal lobes in all three autopsied patients, and severe caudate atrophy was noted in two of them and demonstrated on MRI in the living patient. On routine staining, there were numerous intracytoplasmic inclusions, which ranged from eosinophilic to basophilic. Some had a clearly defined basophilic margin, while others were granular with a hyaline core. With modified Bielschowsky silver technique, a small number of the inclusions were intensely stained. Inclusions were not labelled with other silver stains. Immuno histochemistry revealed that the inclusions were immunoreactive with antibodies to neurofilament heavy and light chain subunits and to ubiquitin, but not with antibodies to tau and alpha-synuclein. These neurofilament- and ubiquitin-positive inclusions were widespread, specific to neurons and occasionally intranuclear. The frequency and distribution of the inclusions and the silver and immunohistochemical profiles in these four cases is novel and has not been described in detail before. We propose the term neurofilament inclusion body disease for this entity.


A role for topoisomerase I in Fusarium graminearum and F. culmorum pathogenesis and sporulation.
Fusarium graminearum and F. culmorum are the causal agents of Fusarium ear blight (FEB) in wheat. A forward genetics approach was taken to discover novel pathogenicity genes in the genome of F. graminearum. A library of transformants created by random plasmid insertional mutagenesis was screened on wheat ears for virulence defects. Plasmid rescue on one of the reduced-virulence mutants revealed a single-copy plasmid insertion in the gene coding for the DNA interacting enzyme, topoisomerase I. Targeted topoisomerase I gene-deletion mutants were created in strains of both F. graminearum and F. culmorum. The top1 mutants of both species exhibited greatly reduced virulence in wheat ear infection assays (GO:0009405 and GO:0044145). Detailed microscopy analyses revealed that top1 hyphal growth was restricted to palea tissue whereas host responses were discernable 1,000 mum further away in the rachis node. Asexual sporulation was reduced in the F. graminearum mutants and was absent from the F. culmorum mutants. The F. graminearum mutant did not develop sexual spores when subjected to an in vitro perithecia production assay. During in vitro growth, the top1 mutants of both species were still able to produce the trichothecene mycotoxin, deoxynivalenol.


Exercise and biomarkers for cancer prevention studies.
The International Agency for Research on Cancer estimates that 25% of cancer cases worldwide are caused by overweight or obesity and a sedentary lifestyle. These lifestyle patterns may increase cancer risk by several mechanisms including increased estrogens and testosterone, hyperinsulinemia and insulin resistance, increased inflammation, and depressed immune function. Several randomized clinical trials have shown that physical activity and diet interventions can change biomarkers of cancer risk. In a controlled physical activity trial, we found decreases in serum estrogen, testosterone, and insulin in overweight, sedentary postmenopausal women with a 1-y exercise program consisting of moderate-intensity aerobic exercise, 45 min/d, 5 d/wk. In another controlled trial in middle-aged to older persons, we found that a 1-y exercise intervention of 60 min/d, 6 d/wk, reduced colon crypt cell proliferation in men who adhered closely to the program. Only 1 trial, the Women's Health Initiative Dietary Modification Trial, has published results of a dietary intervention on breast cancer incidence and reported a statistically nonsignificant 9% reduction in invasive breast cancer incidence in postmenopausal women following a low-fat dietary pattern for 8-12 y. Other trials under way are testing effects of weight loss, physical activity, and dietary patterns on other cancer biomarkers. The NCI-funded Transdisciplinary Research on Energetics and Cancer centers are exploring novel research into mechanisms linking energy balance with cancer risk and prevention. The worldwide trends toward increasing overweight and obesity and decreasing physical activity may lead to an increased incidence of several cancers unless other means of risk reduction counteract these effects. Thus, adoption of lifestyle changes by individuals and populations may have a large impact on the future incidence of cancer.


The clamp-loading complex for processive DNA replication.
DNA polymerase requires two processing factors, sliding clamps and clamp loaders, to direct rapid and accurate duplication of genomic DNA. In eukaryotes, proliferating cell nuclear antigen (PCNA), the ring-shaped sliding clamp, encircles double-stranded DNA within its central hole and tethers the DNA polymerases onto DNA. Replication factor C (RFC) acts as the clamp loader, which correctly installs the sliding clamp onto DNA strands in an ATP-dependent manner. Here we report the three-dimensional structure of an archaeal clamp-loading complex (RFC-PCNA-DNA) determined by single-particle EM. The three-dimensional structure of the complex, reconstituted in vitro using a nonhydrolyzable ATP analog, reveals two components, a closed ring and a horseshoe-shaped element, which correspond to PCNA and RFC, respectively. The atomic structure of PCNA fits well into the closed ring, suggesting that this ternary complex represents a state just after the PCNA ring has closed to encircle the DNA duplex.


Detection and precise mapping of germline rearrangements in BRCA1, BRCA2, MSH2, and MLH1 using zoom-in array comparative genomic hybridization (aCGH).
Disease-predisposing germline mutations in cancer susceptibility genes may consist of large genomic rearrangements that are challenging to detect and characterize using standard PCR-based mutation screening methods. Here, we describe a custom-made zoom-in microarray comparative genomic hybridization (CGH) platform of 60mer oligonucleotides. The 4 x 44 K array format provides high-resolution coverage (200-300 bp) of 400-700 kb genomic regions surrounding six cancer susceptibility genes. We evaluate its performance to accurately detect and precisely map earlier described or novel large germline deletions or duplications occurring in BRCA1 (n=11), BRCA2 (n=2), MSH2 (n=7), or MLH1 (n=9). Additionally, we demonstrate its applicability for uncovering complex somatic rearrangements, exemplified by zoom-in analysis of the PTEN and CDKN2A loci in breast cancer cells. The sizes of rearrangements ranged from several 100 kb, including large flanking regions, to <500-bp deletions, including parts of single exons that would be missed by standard multiplex ligation-dependent probe amplification (MLPA) methods. Zoom-in CGH arrays accurately defined the borders of rearrangements, allowing convenient design of primers for sequence determination of the breakpoints. The array platform can be streamlined for a particular application, e.g., focusing on breast cancer susceptibility genes, with increased capacity using multiformat design, and represents a valuable new tool and complement for genetic screening in clinical diagnostics.


When the struggle against dejection becomes a part of everyday life: a qualitative study of coping strategies in older abused people.
Abuse of older people is a serious issue and is associated with an increased risk of morbidity and mortality, and professionals will encounter elderly victims of abuse in all areas of the health care system. An important health determinant is behavioral factors, including coping style, which will impact on how older people manage stress and maintain control in their lives, and thereby protect themselves from abuse. The aim of this study was to explore the coping strategies elderly people abused by their offspring used to manage everyday life. A qualitative approach was used and 14 elderly victims of abuse were interviewed. The interviews were recorded, transcribed, and subjected to qualitative content analysis. Five main coping strategies were identified. The main strategy was linked to the role of parent. Another prominent strategy was attitude towards being victimized. Further strategies were associated with hope for a better relationship with offspring in the future, while others felt that they had done the best they could, or that their offspring were no longer their responsibility. The results are discussed in light of theoretical perspectives related to coping and resilience. Abuse of older people by their offspring imposes severe stress on victims and challenges the values and beliefs about the caring nature of families. The findings of this study indicate that victims of abuse use a wide range of coping techniques to manage everyday life, and that some strategies help them to maintain their self-respect in their role as parents and find some sort of resilience.


Association of handgrip strength with chronic diseases and multimorbidity: a cross-sectional study.
The prevalence of chronic diseases has risen along with increased longevity. Co-occurrence of two or more chronic diseases in an individual (multimorbidity) is prevalent and poses a huge burden to individuals and the society. However, determinants of multimorbidity are largely unknown. Handgrip strength is a general indicator of muscle strength and linked with premature mortality. However, its role in multimorbidity has never been evaluated. To investigate the relationships between handgrip strength and multiple chronic diseases and multimorbidity, and to assess the usefulness of age and handgrip as a marker of chronic diseases and multimorbidity in a community dwelling sample of men and women, we analyzed a cross-sectional cohort with 1,145 subjects (748 men and 397 women) aged 50 years and older living in Hong Kong. Low handgrip strength was significantly associated with increased odds of having five and three chronic diseases in men and women, respectively, after controlling for age, body mass index, history of smoking, educational level, marital level and comorbidity. Multivariable-adjusted handgrip strength was significantly decreased with the number of chronic diseases in men (trend, P = 0.001), but the trend in women was marginal (trend, P = 0.06). Conversely, multivariable-adjusted age was significantly increased with the number of chronic diseases in women (trend, P = 0.033), but not in men (trend, P = 0.118). In conclusion, handgrip strength is associated with multiple chronic diseases and multimorbidity in men and women after adjustment of confounding factors. It shows a linear trend of association with the number of chronic diseases in men, but not in women. Since handgrip strength is a biomarker of multiple physiological systems, its augmentation may be a feasible strategy to improve general health and decrease likelihood of having multiple chronic diseases and hence, premature mortality.


Effects of aqueous extract of celery (Apium graveolens L.) leaves on spermatogenesis in healthy male rats.
Nowadays, a lot of attention has been paid to the therapeutic properties of herbs, including evaluation of the effects of these plants on fertility in laboratory animals. Apium graveolens L. (celery) has been widely used in traditional medicine for treatment of various disorders including impotency. Therefore, this study was designed to investigate the effects of aqueous extract of A. graveolens on testicular tissue and spermatogenesis in healthy male rats. In this research, 24 apparently healthy male rats were divided into three groups, including eight rats in each. The first group as control received only distilled water 1 ml/animal/day. The second and third groups orally received 100 and 200 mg/kg b.w. of the extract, respectively, for 30 days. The day after the last administration of the extract, the rats were sacrificed, the testes were removed entirely, and the morphometric studies were carried out. Epididymal sperm count and histological studies of testicular tissue were conducted. The comparison between the treated and control groups revealed a remarkable increase in the seminiferous tubules diameter, testes volume (p≤0.001), and the number of spermatogonia, primary spermatocytes and spermatozoa. Furthermore, the increase in the number of spermatids and epididymal weight were only significant at high doses of the extract (p≤ 0.05). The results from this study indicated that administration of celery leaf extract may improve spermatogenesis process and also be useful for some sperm fertility parameters.


Modernizing Diabetes Care Quality Measures.
The proliferation of diabetes quality measures in the US since the mid-1990s has increased the burden of measurement without commensurate improvements in the quality of care or health outcomes. Measures in use today do not represent or incentivize achievement of care goals in all domains of quality that are necessary to achieve optimal diabetes health. We recommend reimagining and improving diabetes quality measurement through the following propositions: widespread adoption of new measures and modernization of existing measures across six domains of quality; use of a subset of new and modernized metrics as top-line measures for reporting and reimbursement; and optional use of the remaining new and modernized measures for evaluative purposes at all levels of the care delivery system to identify and address gaps in care quality and outcomes. These propositions would support practices and policies at all levels of the health care system to improve the health of people with diabetes.


Midterm Outcomes After Endovascular Intervention for Occluded vs Stenosed External Iliac Arteries.
To evaluate the association between a chronic total occlusion (CTO) and long-term outcomes among patients undergoing endovascular intervention to the external iliac artery (EIA). A 2-center retrospective study was conducted of 331 patients (mean age 64.7±12.7 years; 221 men) who underwent endovascular intervention for 481 EIA atherosclerotic lesions between 2006 and 2016. A quarter of the lesions (115, 23.9%) were CTOs. The majority of patients (184, 60.9%) were treated for claudication; 172 (38%) lesions were TransAtlantic Inter-Society Consensus type C or D. Target lesion revascularization (TLR) and major adverse limb event (MALE) rates were compared between lesions with or without an EIA CTO. A Cox proportional hazard model was subsequently developed to determine baseline variables associated with long-term outcomes after successful endovascular intervention of stented EIAs; outcomes are presented as the hazard ratio (HR) and 95% confidence interval (CI). The mean lesion length was longer (84 vs 50 mm, p<0.001) among patients treated for CTOs. While overall the target lesion failure rates were very low (2.8%), vessel perforation (2.7% vs 0.3%, p=0.02) and distal embolization (2.7% vs 0.9%, p=0.02) were more common in the CTO group. Among 377 successfully crossed and stented lesions (93 CTOs), the overall 1-year primary patency was 78% and secondary patency was 92%. One-year and 5-year TLR rates were 8.2% and 15.4%, respectively. CTO intervention was associated with higher 5-year TLR rates in the unadjusted analysis (HR 1.72, 95% CI 1.00 to 2.56, p=0.050), but the association did not remain significant after multivariable adjustment. Intervention to EIA CTOs is associated with increased intraprocedural complexity but with similar midterm outcomes, including high patency and low rates of TLR to 5 years.


A cost-minimization analysis of dexmedetomidine compared with midazolam for long-term sedation in the intensive care unit.
To compare the intensive care unit costs and determine factors influencing these costs in mechanically ventilated patients randomized to dexmedetomidine or midazolam by continuous infusion. Cost minimization analysis of a double-blind, multicenter clinical trial randomizing patients 2:1 to receive dexmedetomidine or midazolam from the institutional perspective. Sixty-eight intensive care units in the United States, Australia, New Zealand, Brazil, and Argentina. A total of 366 intubated intensive care unit patients anticipated to require sedation for >24 hrs. Intensive care unit resource use was compared within the two treatment arms, using the U.S. representative costs for these resources. The analyses characterized patient costs from start of study drug until intensive care unit discharge including costs associated with the intensive care unit stay, costs during mechanical ventilation, study drug acquisition cost, and costs of treating adverse drug reactions probably or possibly related to study drugs. Blinded to treatment group, costs were calculated using Medicare reimbursement schedules, average IMS drug costs, expert opinion, and peer-reviewed literature. Censored lengths of intensive care unit stay and mechanical ventilation were imputed, using a nonparametric adjustment algorithm. Crude and multivariate median regressions were performed to relate intensive care unit cost and treatment. Including drug acquisition cost, sedation with dexmedetomidine was associated with a median total intensive care unit cost savings of $9679 (confidence interval, $2314-$17,045) compared with midazolam. The primary cost drivers were reduced costs of intensive care unit stay (median savings, $6584, 95% confidence interval, $727-$12,440) and reduced costs of mechanical ventilation (median savings, $2958, 95% confidence interval, $698-$5219). Continuous sedation with dexmedetomidine results in significantly lower total intensive care unit costs compared with midazolam infusion for intensive care unit sedation, primarily due to decreased intensive care unit stay costs and reduced mechanical ventilation costs.


Temporomandibular joint dysfunction and orthognathic surgery: a retrospective study.
Relations between maxillo-mandibular deformities and TMJ disorders have been the object of different studies in medical literature and there are various opinions concerning the alteration of TMJ dysfunction after orthognathic surgery. The purpose of the present study was to evaluate TMJ disorders changes before and after orthognathic surgery, and to assess the risk of creating new TMJ symptoms on asymptomatic patients. A questionnaire was sent to 176 patients operated at the Maxillo-Facial Service of the Lille's 2 Universitary Hospital Center (Chairman Pr Joël Ferri) from 01.01.2006 to 01.01.2008. 57 patients (35 females and 22 males), age range from 16 to 65 years old, filled the questionnaire. The prevalence and the results on pain, sounds, clicking, joint locking, limited mouth opening, and tenseness were evaluated comparing different subgroups of patients. TMJ symptoms were significantly reduced after treatment for patients with pre-operative symptoms. The overall subjective treatment outcome was: improvement for 80.0% of patients, no change for 16.4% of patients, and an increase of symptoms for 3.6% of them. Thus, most patients were very satisfied with the results. However the appearance of new onset of TMJ symptoms is common. There was no statistical difference in the prevalence of preoperative TMJ symptoms and on postoperative results in class II compared to class III patients. These observations demonstrate that: there is a high prevalence of TMJ disorders in dysgnathic patients; most of patients with preoperative TMJ signs and symptoms can improve TMJ dysfunction and pain levels can be reduced by orthognathic treatment; a percentage of dysgnathic patients who were preoperatively asymptomatic can develop TMJ disorders after surgery but this risk is low.


Does a fine line exist between regional and metastatic pelvic lymph nodes in rectal cancer-striking discordance between national guidelines and treatment recommendations by US radiation oncologists.
Management of rectal cancer with involved lateral pelvic lymph nodes (LPLNs) at the time of diagnosis-the stage we refer institutionally to as Stage 3.5-is controversial. The American Joint Committee on Cancer's 7th edition classifies internal iliac lymph nodes (LNs) as regional (Stage III), but both external and common iliac LNs as metastatic (Stage IV). However, in many Asian countries all LPLNs are considered regional and patients are treated with curative intent, with literature supporting improved outcomes with LPLN dissection. Management patterns of these patients by US radiation oncologists (ROs) are unknown. American ROs completed an anonymous institutional review board-approved online questionnaire regarding rectal cancer management. Among the 220 completed responses, 45% treat more than 10 patients annually and 39% work in academia. We found 10.5% and 34.2% recommend biopsy of clinically involved internal and common iliac LNs, respectively. The vast majority of responders-98.6% and 94.5%-treat involved internal and common iliac LNs with curative intent, respectively. Respondents recommend treatment intensification to involved internal iliac LNs by dissection of the nodal basin (88.2%) and radiation therapy (RT) boost (59.1%), and treatment intensification to involved common iliac LNs by LN dissection (76.4%) and RT boost (63.6%). Our analysis reveals that the vast majority of US ROs approach patients with involved LPLNs, both regional (internal iliac) and metastatic (common iliac), with curative intent. They recommend treatment intensification with surgical resection and/or RT boost to involved nodes. Prospective clinical trials need to determine the appropriate management of patients with Stage 3.5 rectal cancer.


Hypertension Prevalence, Awareness, Treatment, and Control in Selected LMIC Communities: Results From the NHLBI/UHG Network of Centers of Excellence for Chronic Diseases.
Hypertension is the leading cause of cardiovascular disease and premature death worldwide. The prevalence of this public health problem is increasing in low- and middle-income countries (LMICs) in both urban and rural communities. The aim of this study was to examine hypertension prevalence, awareness, treatment, and control in adults 35 to 74 years of age from urban and rural communities in LMICs in Africa, Asia, and South America. The authors analyzed data from 7 population-based cross-sectional studies in selected communities in 9 LMICs that were conducted between 2008 and 2013. Age- and sex-standardized prevalence rates of pre-hypertension and hypertension were calculated. The prevalence rates of awareness, treatment, and control of hypertension were estimated overall and by subgroups of age, sex, and educational level. In selected communities, age- and sex-standardized prevalence rates of hypertension among men and women 35 to 74 years of age were 49.9% (95% confidence interval [CI]: 42.3% to 57.4%) in Kenya, 54.9% (95% CI: 51.3% to 58.4%) in South Africa, 52.5% (95% CI: 50.1% to 54.8%) in China, 32.5% (95% CI: 31.7% to 33.3%) in India, 42.3% (95% CI: 40.4% to 44.2%) in Pakistan, 45.4% (95% CI: 43.6% to 47.2%) in Argentina, 39.9% (95% CI: 37.8% to 42.1%) in Chile, 19.2% (95% CI: 17.8% to 20.5%) in Peru, and 44.1% (95% CI: 41.6% to 46.6%) in Uruguay. The proportion of awareness varied from 33.5% in India to 69.0% in Peru, the proportion of treatment among those who were aware of their hypertension varied from 70.8% in South Africa to 93.3% in Pakistan, and the proportion of blood pressure control varied from 5.3% in China to 45.9% in Peru. The prevalence of hypertension varies widely in different communities. The rates of awareness, treatment, and control also differ in different settings. There is a clear need to focus on increasing hypertension awareness and control in LMICs.


Drastically enhanced visible light-driven H2 evolution by anchoring TiO2 nanoparticles on molecularly grafted carbon nitride nanosheets via a multiple modification strategy.
The development of graphitic carbon nitride (CN) based photocatalysts towards efficient visible light-driven H2 evolution is highly desired for solar energy conversion. It is well-known that bulk CN materials possess three intrinsic problems, namely, high charge recombination loss, low specific surface area, and limited sunlight harvesting range. To simultaneously overcome the abovementioned drawbacks of CN, we report an innovative multiple modification strategy, involving molecular grafting of the CN network, exfoliation to ultrathin nanosheets, and hybridization with TiO2 photocatalysts. The visible light utilization ability, specific surface area, and charge separation efficiency of the CN materials improved accordingly. As expected, the TiO2/CNX-NS heterojunction photocatalyst exhibited remarkably enhanced visible light-driven H2 production rate of 138.4 μmol h-1, which was about 4.6 times higher than that of pristine CN. The excellent photocatalytic performance under visible light confirmed the successful improvement in the corresponding drawbacks of CN by each modification. In this study, we propose the possibility of combining multiple modifications in the same system to synthesize an excellent visible light-driven photocatalyst for solar-to-fuel conversion.


Nanostructures Control the Hepatocellular Responses to a Cytotoxic Agent "Cisplatin".
In drug discovery programs, the alteration between in vivo and in vitro cellular responses to drug represents one of the main challenges. Since the variation in the native extracellular matrix (ECM) between in vivo and 2D in vitro conditions is one of the key reasons for such discrepancies, thus the utilization of substrate that likely mimics ECM characteristics (topography, stiffness, and chemical composition) is needed to overcome such problem. Here, we investigated the role of substrate nanotopography as one of the major determinants of hepatic cellular responses to a chemotherapeutic agent "cisplatin." We studied the substratum induced variations in cisplatin cytotoxicity; a higher cytotoxic response to cisplatin was observed for cells cultured on the nanopattern relative to a flat substrate. Moreover, the nanofeatures with grating shapes that mimic the topography of major ECM protein constituents (collagen) induced alterations in the cellular orientation and chromatin condensation compared to flat surfaces. Accordingly, the developments of biomimetic substrates with a particular topography could have potentials in drug development analyses to reflect more physiological mimicry conditions in vitro.


Frusemide-sensitive sodium and potassium transport by human leucocytes.
Frusemide-sensitive sodium and potassium transport by normal human leucocytes has been studied in vitro by both isotopic and net flux techniques. In physiological media the leucocyte exhibits a frusemide-sensitive influx of sodium and potassium of equal magnitude compatible with a 1:1 co-transport system. Cells exposed to zero external sodium and potassium (osmolality maintained with choline) demonstrated a frusemide-sensitive sodium and potassium efflux. Frusemide-sensitive potassium influx was dependent on the presence of external sodium but frusemide-sensitive sodium influx persisted unchanged in the absence of external potassium. Frusemide-sensitive potassium influx was dependent on external chloride but frusemide-sensitive sodium influx was chloride-independent. These last two observations make it likely that the frusemide-sensitive pathway is capable of operating in modes other than sodium-potassium co-transport.


The Grand Challenges of Organ Banking: Proceedings from the first global summit on complex tissue cryopreservation.
The first Organ Banking Summit was convened from Feb. 27 - March 1, 2015 in Palo Alto, CA, with events at Stanford University, NASA Research Park, and Lawrence Berkeley National Labs. Experts at the summit outlined the potential public health impact of organ banking, discussed the major remaining scientific challenges that need to be overcome in order to bank organs, and identified key opportunities to accelerate progress toward this goal. Many areas of public health could be revolutionized by the banking of organs and other complex tissues, including transplantation, oncofertility, tissue engineering, trauma medicine and emergency preparedness, basic biomedical research and drug discovery - and even space travel. Key remaining scientific sub-challenges were discussed including ice nucleation and growth, cryoprotectant and osmotic toxicities, chilling injury, thermo-mechanical stress, the need for rapid and uniform rewarming, and ischemia/reperfusion injury. A variety of opportunities to overcome these challenge areas were discussed, i.e. preconditioning for enhanced stress tolerance, nanoparticle rewarming, cyroprotectant screening strategies, and the use of cryoprotectant cocktails including ice binding agents.


Synthesis, chaperoning, and metabolism of proteins are regulated by NT-3/TrkC signaling in the medulloblastoma cell line DAOY.
The human medulloblastoma cell line DAOY was transfected with Tropomyosin receptor kinase (TrkC), a marker for good prognostic outcome. Following TrkC-activation by its ligand neurotrophin-3, protein extracts from DAOY cells were run on 2DE with subsequent MALDI-TOF-TOF analysis and quantification in order to detect downstream effectors. Protein levels of translational, splicing, processing, chaperone, protein handling, and metabolism machineries were shown to depend on neurotrophin-3-induced TrkC activation probably representing pharmacological targets.


Breastfeeding initiation: impact of obesity in a large Canadian perinatal cohort study.
To evaluate incidence of breastfeeding initiation according to maternal pre-pregnancy body mass index (BMI) in "Grossesse en Santé", a large prospective birth cohort in Quebec City. Breastfeeding initiation in the post-partum period, pre-pregnancy BMI, sociodemographic determinants and obstetrical and neonatal factors were collected from years 2005 to 2010 in 6592 women with single pregnancies. Prenatal non-intention to breastfeed was documented in a subgroup of the cohort (years 2009-2010). Log-binomial regression analyses were performed to assess relative risk (RR) of non-initiation of breastfeeding between maternal BMI categories in models including pre- and post-natal determinants, after exclusion of variables with a mediating effect. Twenty percent (20%) of obese women did not initiate breastfeeding in the post-natal period at hospital compared to 12% for normal weight women. Compared with those having a normal pre-pregnancy BMI, obese women had a higher risk of non-initiation of breastfeeding (RRunadj 1.69, 95% CI 1.44-1.98), even after adjustment for prenatal and sociodemographic factors (RRadj 1.26, 95% CI 1.08-1.46). Furthermore, the risk of non-initiation of breastfeeding in obese women still remained higher after introduction of per- and post-natal factors (RR 1.22, 95% CI 1.04-1.42). The prenatal non-intention to breastfeed was strongly associated with the non-initiation of breastfeeding for all categories of BMI. Maternal obesity is associated with a two-fold rate of non-initiation of breastfeeding. Considering the benefits of breastfeeding and the increasing obesity rate, adapted interventions and specialized support should target both pre- and immediate post-natal periods in this population.


Status of hepatocellular cancer in Europe.
Hepatocellular cancer (HCC) accounts for 47,000 deaths per year in Europe and the incidence is expected to increase over the next 10-15 years. The highest incidence is found in Southern Europe, mainly attributable to chronic hepatitis C infection. The most widely used staging system used is the Barcelona-Clinic Liver Cancer (BCLC) classification according to which, 30-40% patients are suitable for potentially curative therapies including transplantation, resection or ablative therapy while the remainder are offered palliative therapy with transarterial therapy, systemic therapy or supportive care. Here we review the indications and outcomes of these interventions as applied to the European population.


What arguments and from whom are most influential in shaping public health policy: thematic content analysis of responses to a public consultation on the regulation of television food advertising to children in the UK.
We explore one aspect of the decision making process-public consultation on policy proposals by a national regulatory body-aiming to understand how public health policy development is influenced by different stakeholders. We used thematic content analysis to explore responses to a national consultation on the regulation of television advertising of foods high in fat, salt and sugar aimed at children. UK. 139 responses from key stakeholder groups were analysed to determine how they influenced the regulator's initial proposals for advertising restrictions. The regulator's priorities were questioned throughout the consultation process by public health stakeholders. The eventual restrictions implemented were less strict in many ways than those originally proposed. These changes appeared to be influenced most by commercial, rather than public health, stakeholders. Public health policy making appears to be considered as a balance between commercial and public health interests. Tactics such as the questioning and reframing of scientific evidence may be used. In this example, exploring the development of policy regulating television food advertising to children, commercial considerations appear to have led to a watering down of initial regulatory proposals, with proposed packages not including the measures public health advocates considered to be the most effective. This seems likely to have compromised the ultimate public health effectiveness of the regulations eventually implemented.


Controlled assembly of hydrogenase-CdTe nanocrystal hybrids for solar hydrogen production.
We present a study of the self-assembly, charge-transfer kinetics, and catalytic properties of hybrid complexes of CdTe nanocrystals (nc-CdTe) and Clostridium acetobutylicum [FeFe]-hydrogenase I (H(2)ase). Molecular assembly of nc-CdTe and H(2)ase was mediated by electrostatic interactions and resulted in stable, enzymatically active complexes. The assembly kinetics was monitored by nc-CdTe photoluminescence (PL) spectroscopy and exhibited first-order Langmuir adsorption behavior. PL was also used to monitor the transfer of photogenerated electrons from nc-CdTe to H(2)ase. The extent to which the intramolecular electron transfer (ET) contributed to the relaxation of photoexcited nc-CdTe relative to the intrinsic radiative and nonradiative (heat dissipation and surface trapping) recombination pathways was shown by steady-state PL spectroscopy to be a function of the nc-CdTe/H(2)ase molar ratio. When the H(2)ase concentration was lower than the nc-CdTe concentration during assembly, the resulting contribution of ET to PL bleaching was enhanced, which resulted in maximal rates of H(2) photoproduction. Photoproduction of H(2) was also a function of the nc-CdTe PL quantum efficiency (PLQE), with higher-PLQE nanocrystals producing higher levels of H(2), suggesting that photogenerated electrons are transferred to H(2)ase directly from core nanocrystal states rather than from surface-trap states. The duration of H(2) photoproduction was limited by the stability of nc-CdTe under the reactions conditions. A first approach to optimization with ascorbic acid present as a sacrificial donor resulted in photon-to-H(2) efficiencies of 9% under monochromatic light and 1.8% under AM 1.5 white light. In summary, nc-CdTe and H(2)ase spontaneously assemble into complexes that upon illumination transfer photogenerated electrons from core nc-CdTe states to H(2)ase, with low H(2)ase coverages promoting optimal orientations for intramolecular ET and solar H(2) production.


Zebrafish screen identifies novel compound with selective toxicity against leukemia.
To detect targeted antileukemia agents we have designed a novel, high-content in vivo screen using genetically engineered, T-cell reporting zebrafish. We exploited the developmental similarities between normal and malignant T lymphoblasts to screen a small molecule library for activity against immature T cells with a simple visual readout in zebrafish larvae. After screening 26 400 molecules, we identified Lenaldekar (LDK), a compound that eliminates immature T cells in developing zebrafish without affecting the cell cycle in other cell types. LDK is well tolerated in vertebrates and induces long-term remission in adult zebrafish with cMYC-induced T-cell acute lymphoblastic leukemia (T-ALL). LDK causes dephosphorylation of members of the PI3 kinase/AKT/mTOR pathway and delays sensitive cells in late mitosis. Among human cancers, LDK selectively affects survival of hematopoietic malignancy lines and primary leukemias, including therapy-refractory B-ALL and chronic myelogenous leukemia samples, and inhibits growth of human T-ALL xenografts. This work demonstrates the utility of our method using zebrafish for antineoplastic candidate drug identification and suggests a new approach for targeted leukemia therapy. Although our efforts focused on leukemia therapy, this screening approach has broad implications as it can be translated to other cancer types involving malignant degeneration of developmentally arrested cells.


Components of the cytoskeleton in the retinal pigmented epithelium of the chick.
The retinal pigmented epithelium (RPE) is a simple cuboidal epithelium with apical processes which, unlike many epithelia, do not extend freely into a lumen but rather interdigitate closely with the outer segments of the neural retina. To determine whether this close association was reflected in the cytoskeletal organization of the RPE, we studied the components of the cytoskeleton of the RPE and their localization in the body of the cell and in the apical processes. By relative mobility on SDS gels and by immunoblotting, we identified actin, vimentin, myosin, spectrin (240/235), and alpha-actinin as major components, and vinculin as a minor component. In addition, the RPE cytoskeleton contains polypeptides of Mr 280,000 and 250,000; the latter co-electrophoreses with actin-binding protein. By immunofluorescence, the terminal web region appeared similar to the comparable region of the intestinal epithelium that consists of broad belts of microfilaments containing myosin, actin, spectrin, and alpha-actinin. However, the components of the apical processes were very different from those of intestinal microvilli. We observed staining along the process for myosin, actin, spectrin, alpha-actinin, and vinculin. The presence in the apical processes of contractile proteins and also of proteins typically found at sites of cell attachments suggests that the RPE may actively adhere to, and exert tension on, the neural retina.


Videolaryngoscopy versus direct laryngoscopy for adult patients requiring tracheal intubation.
Successful tracheal intubation during general anaesthesia traditionally requires a line of sight to the larynx attained by positioning the head and neck and using a laryngoscope to retract the tongue and soft tissues of the floor of the mouth. Difficulties with intubation commonly arise, and alternative laryngoscopes that use digital and/or fibreoptic technology have been designed to improve visibility when airway difficulty is predicted or encountered. Among these devices, a rigid videolaryngoscope (VLS) uses a blade to retract the soft tissues and transmits a lighted video image to a screen. Our primary objective was to assess whether use of videolaryngoscopy for tracheal intubation in adults requiring general anaesthesia reduces risks of complications and failure compared with direct laryngoscopy. Our secondary aim was to assess the benefits and risks of these devices in selected population groups, such as adults with obesity and those with a known or predicted difficult airway. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE and Embase on 10 February 2015. Our search terms were relevant to the review question and were not limited by outcomes. We carried out clinical trials register searches and forward and backward citation tracking. We reran the search on 12 January 2016; we added potential new studies of interest from the 2016 search to a list of 'Studies awaiting classification', and we will incorporate these studies into the formal review during the review update. We considered all randomized controlled trials and quasi-randomized studies with adult patients undergoing laryngoscopy performed with a VLS or a Macintosh laryngoscope in a clinical, emergency or out-of-hospital setting. We included parallel and cross-over study designs. Two review authors independently assessed trial quality and extracted data, consulting a third review author to resolve disagreements. We used standard Cochrane methodological procedures, including assessment of risk of bias. We included 64 studies identified during the 2015 search that enrolled 7044 adult participants and compared a VLS of one or more designs with a Macintosh laryngoscope. We identified 38 studies awaiting classification and seven ongoing studies. Of the 64 included studies, 61 included elective surgical patients, and three were conducted in an emergency setting. Among 48 studies that included participants without a predicted difficult airway, 15 used techniques to simulate a difficult airway. Seven recruited participants with a known or predicted difficult airway, and the remaining studies did not specify or included both predicted and not predicted difficult airways. Only two studies specifically recruited obese participants. It was not possible to blind the intubator to the device, and we noted a high level of inevitable heterogeneity, given the large number of studies.Statistically significantly fewer failed intubations were reported when a VLS was used (Mantel-Haenszel (M-H) odds ratio (OR), random-effects 0.35, 95% confidence Interval (CI) 0.19 to 0.65; 38 studies; 4127 participants), and fewer failed intubations occurred when a VLS was used in participants with an anticipated difficult airway (M-H OR, random-effects 0.28, 95% CI 0.15 to 0.55; six studies; 830 participants). We graded the quality of this evidence as moderate on the basis of the GRADE system. Failed intubations were fewer when a VLS was used in participants with a simulated difficult airway (M-H OR, random-effects 0.18, 95% CI 0.04 to 0.77; nine studies; 810 participants), but groups with no predicted difficult airway provided no significant results (M-H OR, random-effects 0.61, 95% CI 0.22 to 1.67; 19 studies; 1743 participants).Eight studies reported on hypoxia, and only three of these described any events; results showed no differences between devices for this outcome (M-H OR, random-effects 0.39, 95% CI 0.10 to 1.44; 1319 participants). Similarly, few studies reported on mortality, noting no differences between devices (M-H OR, fixed-effect 1.09, 95% CI 0.65 to 1.82; two studies; 663 participants), and only one study reporting on the occurrence of respiratory complications (78 participants); we graded these three outcomes as very low quality owing to lack of data. We found no statistically significant differences between devices in the proportion of successful first attempts (M-H OR, random-effects 1.27, 95% CI 0.77 to 2.09; 36 studies; 4731 participants) nor in those needing more than one attempt. We graded the quality of this evidence as moderate. Studies reported no statistically significant differences in the incidence of sore throat in the postanaesthesia care unit (PACU) (M-H OR, random-effects 1.00 (95% CI 0.73 to 1.38); 10 studies; 1548 participants) nor at 24 hours postoperatively (M-H OR random-effects 0.54, 95% CI 0.27 to 1.07; eight studies; 844 participants); we graded the quality of this evidence as moderate. Data combined to include studies of cross-over design revealed statistically significantly fewer laryngeal or airway traumas (M-H OR, random-effects 0.68, 95% CI 0.48 to 0.96; 29 studies; 3110 participants) and fewer incidences of postoperative hoarseness (M-H OR, fixed-effect 0.57, 95% CI 0.36 to 0.88; six studies; 527 participants) when a VLS was used. A greater number of laryngoscopies performed with a VLS achieved a view of most of the glottis (M-H OR, random-effects 6.77, 95% CI 4.17 to 10.98; 22 studies; 2240 participants), fewer laryngoscopies performed with a VLS achieved no view of the glottis (M-H OR, random-effects 0.18, 95% CI 0.13 to 0.27; 22 studies; 2240 participants) and the VLS was easier to use (M-H OR, random-effects 7.13, 95% CI 3.12 to 16.31; seven studies; 568 participants).Although a large number of studies reported time required for tracheal intubation (55 studies; 6249 participants), we did not present an effects estimate for this outcome owing to the extremely high level of statistical heterogeneity (I2 = 96%). Videolaryngoscopes may reduce the number of failed intubations, particularly among patients presenting with a difficult airway. They improve the glottic view and may reduce laryngeal/airway trauma. Currently, no evidence indicates that use of a VLS reduces the number of intubation attempts or the incidence of hypoxia or respiratory complications, and no evidence indicates that use of a VLS affects time required for intubation.


Reduced appropriate implantable cardioverter-defibrillator therapy after cardiac resynchronization therapy-induced left ventricular function recovery: a meta-analysis and systematic review.
For patients undergoing cardiac resynchronization therapy (CRT) with implantable cardioverter-defibrillator (ICD; CRT-D), the effect of an improvement in left ventricular ejection fraction (LVEF) on appropriate ICD therapy may have significant implications regarding management at the time of ICD generator replacement. We conducted a meta-analysis to determine the effect of LVEF recovery following CRT on the incidence of appropriate ICD therapy. A search of multiple electronic databases identified 709 reports, of which 6 retrospective cohort studies were included (n = 1740). In patients with post-CRT LVEF ≥35% (study n = 4), the pooled estimated rate of ICD therapy (5.5/100 person-years) was significantly lower than patients with post-CRT LVEF <35% [incidence rate difference (IRD): -6.5/100 person-years, 95% confidence interval (95% CI): -8.8 to -4.2, P < 0.001]. Similarly, patients with post-CRT LVEF ≥45% (study n = 4) demonstrated lower estimated rates of ICD therapy (2.3/100 person-years) compared with patients without such recovery (IRD: -5.8/100 person-years, 95% CI: -7.6 to -4.0, P < 0.001). Restricting analysis to studies discounting ICD therapies during LVEF recovery (study n = 3), patients with LVEF recovery (≥35 or ≥45%) had significantly lower rates of ICD therapy compared with patients without such recovery (P for both <0.001). Patients with primary prevention indication for ICD, regardless of LVEF recovery definition, had very low rates of ICD therapy (0.4 to 0.8/100-person years). Recovery of LVEF post-CRT is associated with significantly reduced appropriate ICD therapy. Patients with improvement of LVEF ≥45% and those with primary prevention indication for ICD appear to be at lowest risk.


Nonlinear frequency compression: effects on sound quality ratings of speech and music.
Frequency lowering technologies offer an alternative amplification solution for severe to profound high frequency hearing losses. While frequency lowering technologies may improve audibility of high frequency sounds, the very nature of this processing can affect the perceived sound quality. This article reports the results from two studies that investigated the impact of a nonlinear frequency compression (NFC) algorithm on perceived sound quality. In the first study, the cutoff frequency and compression ratio parameters of the NFC algorithm were varied, and their effect on the speech quality was measured subjectively with 12 normal hearing adults, 12 normal hearing children, 13 hearing impaired adults, and 9 hearing impaired children. In the second study, 12 normal hearing and 8 hearing impaired adult listeners rated the quality of speech in quiet, speech in noise, and music after processing with a different set of NFC parameters. Results showed that the cutoff frequency parameter had more impact on sound quality ratings than the compression ratio, and that the hearing impaired adults were more tolerant to increased frequency compression than normal hearing adults. No statistically significant differences were found in the sound quality ratings of speech-in-noise and music stimuli processed through various NFC settings by hearing impaired listeners. These findings suggest that there may be an acceptable range of NFC settings for hearing impaired individuals where sound quality is not adversely affected. These results may assist an Audiologist in clinical NFC hearing aid fittings for achieving a balance between high frequency audibility and sound quality.


Reducing the nicotine content of combusted tobacco products sold in New Zealand.
Large reductions in nicotine content could dramatically reduce reinforcement from and dependence on cigarettes. In this article, we summarise the potential benefits of reducing nicotine in combusted tobacco and address some of the common concerns. We focus specifically on New Zealand because it may be ideally situated to implement such a policy. The available data suggest that, in current smokers, very low nicotine content (VLNC) cigarettes decrease nicotine exposure, decrease cigarette dependence, reduce the number of cigarettes smoked per day and increase the likelihood of contemplating, making and succeeding at a quit attempt. New smokers would almost certainly be exposed to far less nicotine as a result of smoking VLNC cigarettes and, consequently, would probably be less likely to become chronic, dependent, smokers. Many of the concerns about reducing nicotine including compensatory smoking, an exacerbation of psychiatric symptoms, the perception that VLNC cigarettes are less harmful, and the potential for a black market are either not supported by the available data, likely mitigated by other factors including the availability of nicotine-containing e-cigarettes, or unlikely to offset the potential benefit to public health. Although not all concerns have been addressed or can be a priori, the magnitude of the potential benefits and the growing evidence of relatively few potential harms should make nicotine reduction one of the centrepieces for discussion of how to rapidly advance tobacco control. Policies that aim to render the most toxic tobacco products less addictive could help New Zealand attain their goal of becoming smokefree by 2025.


[Pars plana vitrectomy for idiopathic vitreous floaters].
The aim of this study was to evaluate the role of pars plana vitrectomy (PPV) in patients with persistent vitreous floaters (VF) in phakic (56.7 %) or pseudophakic (43.3 %) eyes. A retrospective study of 24 consecutive patients (30 eyes) who underwent a 2-port-PPV using indirect opthalmoscopy between 1992 and 2003 was carried out. Main outcome measures were postoperative visual acuity (PVA), incidence of postoperative complications and patient satisfaction, which has been assessed retrospectively using a detailed questionnaire. Symptoms resolved in all patients. PVA was significantly better (0.91 +/- 0.2 vs. 0.84 +/- 0.2 preoperative visual acuity) or equal in 25 patients (83.3 %). One pseudophakic patient (3.3 %) experienced a retinal detachment 48 months after surgery. In 5 of 17 phakic eyes (35 %) a cataract extraction had to be performed during the follow-up period. All patients were satisfied with their overall visual function. This study shows PPV to be a safe and effective primary treatment for visually disturbing VF. In spite of the small number of cases with a lower PVA (5 eyes/16.7 %), which in the most severe case corresponded to a reduction of VA from 1.0 to 0.6 due to a nuclear sclerosis of the lens, all patients were satisfied. As vitreoretinal complications may occur, a critical patient selection and a careful preoperative assessment of specific risks of vitrectomy are mandatory.


Multiscale Charge Transport in van der Waals Thin Films: Reduced Graphene Oxide as a Case Study.
Large area van der Waals (vdW) thin films are assembled materials consisting of a network of randomly stacked nanosheets. The multiscale structure and the two-dimensional (2D) nature of the building block mean that interfaces naturally play a crucial role in the charge transport of such thin films. While single or few stacked nanosheets (i.e., vdW heterostructures) have been the subject of intensive works, little is known about how charges travel through multilayered, more disordered networks. Here, we report a comprehensive study of a prototypical system given by networks of randomly stacked reduced graphene oxide 2D nanosheets, whose chemical and geometrical properties can be controlled independently, permitting to explore percolated networks ranging from a single nanosheet to some billions with room-temperature resistivity spanning from 10-5 to 10-1 Ω·m. We systematically observe a clear transition between two different regimes at a critical temperature T*: Efros-Shklovskii variable-range hopping (ES-VRH) below T* and power law behavior above. First, we demonstrate that the two regimes are strongly correlated with each other, both depending on the charge localization length ξ, calculated by the ES-VRH model, which corresponds to the characteristic size of overlapping sp2 domains belonging to different nanosheets. Thus, we propose a microscopic model describing the charge transport as a geometrical phase transition, given by the metal-insulator transition associated with the percolation of quasi-one-dimensional nanofillers with length ξ, showing that the charge transport behavior of the networks is valid for all geometries and defects of the nanosheets, ultimately suggesting a generalized description on vdW and disordered thin films.


Teaching information literacy skills to sophomore-level biology majors.
Many undergraduate students lack a sound understanding of information literacy. The skills that comprise information literacy are particularly important when combined with scientific writing for biology majors as they are the foundation skills necessary to complete upper-division biology course assignments, better train students for research projects, and prepare students for graduate and professional education. To help undergraduate biology students develop and practice information literacy and scientific writing skills, a series of three one-hour hands-on library sessions, discussions, and homework assignments were developed for Biological Literature, a one-credit, one-hour-per-week, required sophomore-level course. The embedded course librarian developed a learning exercise that reviewed how to conduct database and web searches, the difference between primary and secondary sources, source credibility, and how to access articles through the university's databases. Students used the skills gained in the library training sessions for later writing assignments including a formal lab report and annotated bibliography. By focusing on improving information literacy skills as well as providing practice in scientific writing, Biological Literature students are better able to meet the rigors of upper-division biology courses and communicate research findings in a more professional manner.


Effects of curcumin or dexamethasone on lung ischaemia-reperfusion injury in rats.
The present study aimed to investigate potential effects of curcumin (CUR) and dexamethasone (DXM) on ischaemia-reperfusion (I/R) induced lung injury in rats. Experimental rats were pre-treated with a single i.p. dose of vehicle, CUR (50 mg.kg(-1) or 200 mg.kg(-1)) or DXM (5 mg.kg(-1)), 2 h before anaesthesia and subjected to left lung hilus clamping with 90-min ischaemia followed by 4 h of reperfusion. Pre-treatment with CUR (200 mg.kg(-1)) or DXM markedly attenuated I/R-induced barrier disruption, lung oedema, tissue inflammation, hypoxaemia 4 h after reperfusion, and overactivation of nuclear factor-kappaB, inflammatory cytokines, myeloperoxidase and malondialdehyde. It appears that curcumin attenuates acute lung injury, probably through improving oxidative stress and inhibiting nuclear factor-kappaB-mediated expression of inflammatory cytokines. Thus, curcumin may be an alternative therapy for improving the outcomes of ischaemia-reperfusion-induced lung injury.


A systematic review of the untreated mortality of murine typhus.
Murine typhus is an acute febrile, flea-borne disease caused by the bacteria Rickettsia typhi. The disease occurs worldwide but is likely underrecognized due to its non-specific symptoms, causing significant morbidity. A systematic review found disease complications in one-fourth of all patients and a long fever duration in those untreated. Although mortality in treated cases is estimated to be very low, some case series have shown a notably higher mortality in untreated patients. This study aimed to describe the outcomes and estimate the mortality of untreated murine typhus through a comprehensive systematic literature review. We systematically searched the literature for articles describing untreated murine typhus patients, excluding cases with no laboratory assay confirmed diagnosis, those who received efficacious treatment, had incomplete information on primary outcome and articles describing less than 10 patients and performed a narrative synthesis of the study findings. The study protocol followed the PRISMA guidelines and was part of a more extensive protocol registered at PROSPERO (CRD42018101991). Twelve studies including a total of 239 untreated patients matched the eligibility criteria. Only a single study reported one death in 28 patients, giving a patient series mortality of 3.6% and an overall mortality of 0.4% in 239 untreated patients. Complications were reported in 10 of the 12 studies and included involvement of the central nervous system, kidney and lung, with a hospitalisation rate of 70% and ICU admission rate of 27% in one study. The mean duration of fever in untreated patients was 15 days in two and 12.7 days in one study. Although the untreated mortality in this study was low, the sample size was small. Murine typhus caused significant morbidity when untreated, leading to high hospitalisation rates and highlighting the importance of early diagnosis and treatment of this neglected disease to reduce disease burden and health-care related costs.


The falling asleep process in adolescents.
To investigate the pre-sleep psychophysiological state and the arousal deactivation process across the sleep onset (SO) transition in adolescents. Data were collected from a laboratory overnight recording in 102 healthy adolescents (48 girls, 12-20 years old). Measures included pre-sleep self-reported cognitive/somatic arousal, and cortical electroencephalographic (EEG) and electrocardiographic activity across the SO transition. Adolescent girls, compared with boys, reported higher pre-sleep cognitive activation (p = 0.025) and took longer to fall asleep (p < 0.05), as defined with polysomnography. Girls also showed a less smooth progression from wake-to-sleep compared with boys (p = 0.022). In both sexes, heart rate (HR) dropped at a rate of ~0.52 beats per minute in the 5 minutes preceding SO, and continued to drop, at a slower rate, during the 5 minutes following SO (p < 0.05). Older girls had a higher HR overall in the pre-sleep period and across SO, compared to younger girls and boys (p < 0.05). The EEG showed a progressive cortical synchronization, with increases in Delta relative power and reductions in Alpha, Sigma, Beta1, and Beta2 relative powers (p < 0.05) in the approach to sleep, in both sexes. Delta relative power was lower and Theta, Alpha, and Sigma relative powers were higher in older compared to younger adolescents at bedtime and across SO (p < 0.05). Our findings show the dynamics of the cortical-cardiac de-arousing process across the SO transition in a non-clinical sample of healthy adolescents. Findings suggest a female-specific vulnerability to inefficient sleep initiation, which may contribute to their greater risk for developing insomnia.


Participation in activities and secondary health complications among persons aging with traumatic spinal cord injury.
Cross-sectional study. To describe participation in activities and explore the relationship with secondary complications among persons aging with a traumatic spinal cord injury (SCI). A regional SCI outpatient center in Sweden. Data were collected through a phone survey, which included 10 activities from the instrument PARTS/M-v3 (PARTicipation Survey/Mobility version-3) together with data from the participants' medical records. Cross-tabulation and χ2 were used for data analysis. In this study, 121 persons matched the inclusion criteria and the final study sample comprised 73 participants (60% response rate): 55 men and 18 women. Mean age was 63.7±9.4 years, and mean time since injury was 36.3±9.2 years. Regardless of duration of SCI, all 73 participated in dressing, bathing and leisure activities. Women reported better health than men. Particularly for those who lived 36-55 years after injury; increasing pain, fatigue, spasticity and decreased muscle strength were negatively affecting participation in activities, especially exercise and active recreation. Additionally, a need to save strength/energy was also a reason for not participating in the activities. Perceived future support and concerns in relation to personal assistance, assistive devices and rehabilitation was also reported. Increasing secondary health complications and a need to save strength/energy influenced participation in activities. Laws and/or governmental policies regarding personal assistance and assistive devices did not always support participation in activities. Interventions should aim to create a balance among activities in everyday life.


Tetrahydrobiopterin Biosynthesis as a Potential Target of the Kynurenine Pathway Metabolite Xanthurenic Acid.
Tryptophan metabolites in the kynurenine pathway are up-regulated by pro-inflammatory cytokines or glucocorticoids, and are linked to anti-inflammatory and immunosuppressive activities. In addition, they are up-regulated in pathologies such as cancer, autoimmune diseases, and psychiatric disorders. The molecular mechanisms of how kynurenine pathway metabolites cause these effects are incompletely understood. On the other hand, pro-inflammatory cytokines also up-regulate the amounts of tetrahydrobiopterin (BH4), an enzyme cofactor essential for the synthesis of several neurotransmitter and nitric oxide species. Here we show that xanthurenic acid is a potent inhibitor of sepiapterin reductase (SPR), the final enzyme in de novo BH4 synthesis. The crystal structure of xanthurenic acid bound to the active site of SPR reveals why among all kynurenine pathway metabolites xanthurenic acid is the most potent SPR inhibitor. Our findings suggest that increased xanthurenic acid levels resulting from up-regulation of the kynurenine pathway could attenuate BH4 biosynthesis and BH4-dependent enzymatic reactions, linking two major metabolic pathways known to be highly up-regulated in inflammation.


Work stress precipitates depression and anxiety in young, working women and men.
Rates of depression have been rising, as have rates of work stress. We tested the influence of work stress on diagnosed depression and anxiety in young working adults. Participants were enrolled in the Dunedin study, a 1972-1973 longitudinal birth cohort assessed most recently in 2004-2005, at age 32 (n=972, 96% of 1015 cohort members still alive). Work stress (psychological job demands, work decision latitude, low work social support, physical work demands) was ascertained by interview. Major depressive disorder (MDD) and generalized anxiety disorder (GAD) were ascertained using the Diagnostic Interview Schedule (DIS) and diagnosed according to DSM-IV criteria. Participants exposed to high psychological job demands (excessive workload, extreme time pressures) had a twofold risk of MDD or GAD compared to those with low job demands. Relative risks (RRs) adjusting for all work characteristics were: 1.90 [95% confidence interval (CI) 1.22-2.98] in women, and 2.00 (95% CI 1.13-3.56) in men. Analyses ruled out the possibility that the association between work stress and disorder resulted from study members' socio-economic position, a personality tendency to report negatively, or a history of psychiatric disorder prior to labour-market entry. Prospective longitudinal analyses showed that high-demand jobs were associated with the onset of new depression and anxiety disorder in individuals without any pre-job history of diagnosis or treatment for either disorder. Work stress appears to precipitate diagnosable depression and anxiety in previously healthy young workers. Helping workers cope with work stress or reducing work stress levels could prevent the occurrence of clinically significant depression and anxiety.


Proof of concept trial for a new theory-based intervention to promote child and adult behavior change.
Interventions to change children's behavior typically target adults or children, but rarely both. The aims were to: (a) evaluate acceptability and feasibility of an innovative theory-based intervention designed to change both child and adult behavior, and (b) generate effect sizes for a definitive randomized controlled trial. The oral health of sixty children aged 5-9 years with a repaired cleft lip and/or palate was assessed before randomization to one of three conditions: (a) control group, (b) intervention group in which children and adults were asked to form implementation intentions, or (c) intervention plus booster group in which adults were additionally sent a reminder about the implementation intentions they and their children formed. Oral health assessments were repeated at 6-month follow-up alongside exit interviews. The procedures proved popular and participants exposed to the intervention additionally reported believing that forming implementation intentions was effective. Descriptive statistics generally showed oral health improvements across all conditions, although the effects were more marked in the intervention plus booster condition, where plaque improved by 44.53%, gingivitis improved by 20.00% and free sugar consumption improved by 8.92% (vs. 6.43% improvement, 15.00% deterioration and 15.58% improvement in the control group, respectively). Data collection procedures were acceptable and the intervention feasible. The effect sizes suggest that the intervention plus booster condition has sufficient promise to proceed to a fully-powered randomized controlled trial. The intervention has the potential to be adapted to tackle other child health behaviors and to be deployed at scale.


A humanized mouse model of tuberculosis.
Mycobacterium tuberculosis (M.tb) is the second leading infectious cause of death worldwide and the primary cause of death in people living with HIV/AIDS. There are several excellent animal models employed to study tuberculosis (TB), but many have limitations for reproducing human pathology and none are amenable to the direct study of HIV/M.tb co-infection. The humanized mouse has been increasingly employed to explore HIV infection and other pathogens where animal models are limiting. Our goal was to develop a small animal model of M.tb infection using the bone marrow, liver, thymus (BLT) humanized mouse. NOD-SCID/γc(null) mice were engrafted with human fetal liver and thymus tissue, and supplemented with CD34(+) fetal liver cells. Excellent reconstitution, as measured by expression of the human CD45 pan leukocyte marker by peripheral blood populations, was observed at 12 weeks after engraftment. Human T cells (CD3, CD4, CD8), as well as natural killer cells and monocyte/macrophages were all observed within the human leukocyte (CD45(+)) population. Importantly, human T cells were functionally competent as determined by proliferative capacity and effector molecule (e.g. IFN-γ, granulysin, perforin) expression in response to positive stimuli. Animals infected intranasally with M.tb had progressive bacterial infection in the lung and dissemination to spleen and liver from 2-8 weeks post infection. Sites of infection in the lung were characterized by the formation of organized granulomatous lesions, caseous necrosis, bronchial obstruction, and crystallization of cholesterol deposits. Human T cells were distributed throughout the lung, liver, and spleen at sites of inflammation and bacterial growth and were organized to the periphery of granulomas. These preliminary results demonstrate the potential to use the humanized mouse as a model of experimental TB.


Adipokine resistin predicts anti-inflammatory effect of glucocorticoids in asthma.
Adipokines are protein mediators secreted by adipose tissue. Recently, adipokines have also been involved in the regulation of inflammation and allergic responses, and suggested to affect the risk of asthma especially in obese female patients. We assessed if adipokines predict responsiveness to glucocorticoids and if plasma adipokine levels are associated with lung function or inflammatory activity also in non-obese (body mass index (BMI) ≤ 30 kg/m2) women with newly-diagnosed steroid-naïve asthma. Lung function, exhaled NO, plasma levels of adipokines leptin, resistin, adiponectin and adipsin, and inflammatory markers were measured in 35 steroid-naïve female asthmatics and in healthy controls. The measurements were repeated in a subgroup of asthmatics after 8 weeks of treatment with inhaled fluticasone. Adipokine concentrations in plasma were adjusted for BMI. High baseline resistin concentrations were associated with a more pronounced decrease in serum levels of eosinophil cationic protein (ECP) (r = -0.745, p = 0.013), eosinophil protein X (EPX) (r = -0.733, p = 0.016) and myeloperoxidase (MPO) (r = -0.721, p = 0.019) during fluticasone treatment. In asthmatics, leptin correlated positively with asthma symptom score and negatively with lung function. However, no significant differences in plasma adipokine levels between non-obese asthmatics and healthy controls were found. The effects of resistin were also investigated in human macrophages in cell culture. Interestingly, resistin increased the production of proinflammatory factors IL-6 and TNF-α and that was inhibited by fluticasone. High resistin levels predicted favourable anti-inflammatory effect of inhaled glucocorticoids suggesting that resistin may be a marker of steroid-sensitive phenotype in asthma. High leptin levels were associated with a more severe disease suggesting that the link between leptin and asthma is not restricted to obesity.


Perioperative synbiotic treatment to prevent infectious complications in patients after elective living donor liver transplantation: a prospective randomized study.
Although the effect of synbiotic therapy using prebiotics and probiotics has been reported in hepatobiliary surgery, there are no reports of the effect on elective living-donor liver transplantation (LDLT). Fifty adult patients undergoing LDLT between September 2005 and June 2009 were randomized into a group receiving 2 days of preoperative and 2 weeks of postoperative synbiotic therapy (Bifidobacterium breve, Lactobacillus casei, and galactooligosaccharides [the BLO group]) and a group without synbiotic therapy (the control group). Postoperative infectious complications were recorded as well as fecal microflora before and after LDLT in each group. Only 1 systemic infection occurred in the BLO group (4%), whereas the control group showed 6 infectious complications (24%), with 3 cases of sepsis and 3 urinary tract infections with Enterococcus spp (P = .033 vs BLO group). No other type of complication showed any difference between the groups. Infectious complications after elective LDLT significantly decreased with the perioperative administration of synbiotic therapy.


Spatially nonrandom tree mortality and ingrowth maintain equilibrium pattern in an old-growth Pseudotsuga-Tsuga forest.
Mortality processes in old-growth forests are generally assumed to be driven by gap-scale disturbance, with only a limited role ascribed to density-dependent mortality, but these assumptions are rarely tested with data sets incorporating repeated measurements. Using a 12-ha spatially explicit plot censused 13 years apart in an approximately 500-year-old Pseudotsuga-Tsuga forest, we demonstrate significant density-dependent mortality and spatially aggregated tree recruitment. However, the combined effect of these strongly nonrandom demographic processes was to maintain tree patterns in a state of dynamic equilibrium. Density-dependent mortality was most pronounced for the dominant late-successional species, Tsuga heterophylla. The long-lived, early-seral Pseudotsuga menziesii experienced an annual stem mortality rate of 0.84% and no new recruitment. Late-seral species Tsuga and Abies amabilis had nearly balanced demographic rates of ingrowth and mortality. The 2.34% mortality rate for Taxus brevifolia was higher than expected, notably less than ingrowth, and strongly affected by proximity to Tsuga. Large-diameter Tsuga structured both the regenerating conspecific and heterospecific cohorts with recruitment of Tsuga and Abies unlikely in neighborhoods crowded with large-diameter competitors (P < 0.001). Density-dependent competitive interactions strongly shape forest communities even five centuries after stand initiation, underscoring the dynamic nature of even equilibrial old-growth forests.


Asthma, Airway Symptoms and Rhinitis in Office Workers in Malaysia: Associations with House Dust Mite (HDM) Allergy, Cat Allergy and Levels of House Dust Mite Allergens in Office Dust.
A prevalence study was conducted among office workers in Malaysia (N= 695). The aim of this study was to examine associations between asthma, airway symptoms, rhinitis and house dust mites (HDM) and cat allergy and HDM levels in office dust. Medical data was collected by a questionnaire. Skin prick tests were performed for HDM allergens (Dermatophagoides pteronyssinus, Dermatophagoides farinae) and cat allergen Felis domesticus. Indoor temperature and relative air humidity (RH) were measured in the offices and vacuumed dust samples were analyzed for HDM allergens. The prevalence of D. pteronyssinus, D. farinae and cat allergy were 50.3%, 49.0% and 25.5% respectively. Totally 9.6% had doctor-diagnosed asthma, 15.5% had current wheeze and 53.0% had current rhinitis. The Der p 1 (from D. pteronyssinus) and Der f 1 (from D. farinae) allergens levels in dust were 556 ng/g and 658 ng/g respectively. Statistical analysis was conducted by multilevel logistic regression, adjusting for age, gender, current smoking, HDM or cat allergy, home dampness and recent indoor painting at home. Office workers with HDM allergy had more wheeze (p= 0.035), any airway symptoms (p= 0.032), doctor-diagnosed asthma (p= 0.005), current asthma (p= 0.007), current rhinitis (p= 0.021) and rhinoconjuctivitis (p< 0.001). Cat allergy was associated with wheeze (p= 0.021), wheeze when not having a cold (p= 0.033), any airway symptoms (p= 0.034), doctor-diagnosed asthma (p= 0.010), current asthma (p= 0.020) and nasal allergy medication (p= 0.042). Der f 1 level in dust was associated with daytime breathlessness (p= 0.033) especially among those with HDM allergy. Der f 1 levels were correlated with indoor temperature (p< 0.001) and inversely correlated with RH (p< 0.001). In conclusion, HDM and cat allergies were common and independently associated with asthma, airway symptoms and rhinitis. Der f 1 allergen can be a risk factor for daytime breathlessness.


High-resolution 3D imaging uncovers organ-specific vascular control of tissue aging.
Blood vessels provide supportive microenvironments for maintaining tissue functions. Age-associated vascular changes and their relation to tissue aging and pathology are poorly understood. Here, we perform 3D imaging of young and aging vascular beds. Multiple organs in mice and humans demonstrate an age-dependent decline in vessel density and pericyte numbers, while highly remodeling tissues such as skin preserve the vasculature. Vascular attrition precedes the appearance of cellular hallmarks of aging such as senescence. Endothelial VEGFR2 loss-of-function mice demonstrate that vascular perturbations are sufficient to stimulate cellular changes coupled with aging. Age-associated tissue-specific molecular changes in the endothelium drive vascular loss and dictate pericyte to fibroblast differentiation. Lineage tracing of perivascular cells with inducible PDGFRβ and NG2 Cre mouse lines demonstrated that increased pericyte to fibroblast differentiation distinguishes injury-induced organ fibrosis and zymosan-induced arthritis. To spur further discoveries, we provide a freely available resource with 3D vascular and tissue maps.


Toll-like receptor and its roles in myocardial ischemic/reperfusion injury.
The innate immune system, mediated via toll-like receptors (TLRs), represents the first line of defensive mechanisms that protects hosts from invading microbial pathogens. TLRs are a family of pattern recognition receptors (PRRs), and are pathologically activated by a set of pathogen-associated microbial patterns (PAMPs) and damage-associated molecular patterns (DAMPs). TLRs deliver signals via a specific intracellular signaling pathway involving distinctive adaptor proteins and protein kinases, and ultimately initiate transcriptional factors resulting in inflammatory responses. TLR4 is a paramount type of TLRs, located in the heart, and plays an important role in mediating myocardial ischemic reperfusion (I/R) injury. Loss-of-function experiments and animal models using genetic techniques have found that the MyD88-independent and the MyD88-dependent pathways together participate in the pathological process of myocardial I/R injury. Some other distinctive signaling pathways, such as the PI3K/AKt and AMPK/ERK pathways, interacting with the TLR4 signaling pathway, were also found to be causes of myocardial I/R injury. These different pathways activate a series of downstream transcriptional factors, produced a great quantity of inflammatory cytokines, such as IL, TNF, and initiate inflammatory response. This results in cardiac injury and dysfunction, such as myocardial stunning, no reflow phenomenon, reperfusion arrhythmias and lethal reperfusion injury, and other related complication such as ventricular remodeling. In the future, blockades aimed at blocking the signaling pathway could benefit developments in pharmacology.<br />


Cranial rhythmic impulse related to the Traube-Hering-Mayer oscillation: comparing laser-Doppler flowmetry and palpation.
The primary respiratory mechanism (PRM) as manifested by the cranial rhythmic impulse (CRI), a fundamental concept to cranial osteopathy, and the Traube-Hering-Mayer (THM) oscillation bear a striking resemblance to one another. Because of this, the authors developed a protocol to simultaneously measure both phenomena. Statistical comparisons demonstrated that the CRI is palpably concomitant with the low-frequency fluctuations of the THM oscillation as measured with the Transonic Systems BLF 21 Perfusion Monitor laser-Doppler flowmeter. This opens new potential explanations for the basic theoretical concepts of the physiologic mechanism of the PRM/CRI and cranial therapy. Comparison of the PRM/CRI with current understanding of the physiology of the THM oscillation is therefore warranted. Additionally, the recognition that these phenomena can be simultaneously monitored and recorded creates a new opportunity for further research into what is distinctive about the science and practice of osteopathic medicine.


Exploring the mobility preferences and perceived difficulties in using transport and driving with a sample of healthy and outpatient older adults in Singapore.
While activity engagement is important to older adults, limitations in ability can affect transport mode choice and subsequent activity participation. Therefore, this study aimed to explore the mobility preferences and difficulties in using public transport and driving with a sample of older adults in Singapore, with specific reference to accessing everyday activities. One hundred and sixty-two persons aged 50 years and over were recruited through a community event, and an outpatient occupational therapy department. They self-completed structured questionnaire forms which were analysed using parametric and non-parametric statistics, including t-tests and ANOVAs. The majority of the participants were in the paid workforce and no significant differences were found between gender and the importance of transport for access to various activities, but a significant association was found for age and use of transport for going to work, F(5,101) = 3.07, P = 0.01. The majority of the drivers drove at least once a day, and 19% of them reported having noticed declines in their driving capabilities in the past four years, and indicated driving less often because of these concerns. This study explored public transport and car use among a sample of older adults in Singapore to access desired activities. It identified difficulties with both public and private transportation use, such as difficulty maintaining balance/obtaining a seat, and concerns with decreased ability to respond quickly to traffic situations. This study has highlighted that transportation methods should be considered in occupational therapy practice with older adults.


Facilitation and competition among invasive plants: a field experiment with alligatorweed and water hyacinth.
Ecosystems that are heavily invaded by an exotic species often contain abundant populations of other invasive species. This may reflect shared responses to a common factor, but may also reflect positive interactions among these exotic species. Armand Bayou (Pasadena, TX) is one such ecosystem where multiple species of invasive aquatic plants are common. We used this system to investigate whether presence of one exotic species made subsequent invasions by other exotic species more likely, less likely, or if it had no effect. We performed an experiment in which we selectively removed exotic rooted and/or floating aquatic plant species and tracked subsequent colonization and growth of native and invasive species. This allowed us to quantify how presence or absence of one plant functional group influenced the likelihood of successful invasion by members of the other functional group. We found that presence of alligatorweed (rooted plant) decreased establishment of new water hyacinth (free-floating plant) patches but increased growth of hyacinth in established patches, with an overall net positive effect on success of water hyacinth. Water hyacinth presence had no effect on establishment of alligatorweed but decreased growth of existing alligatorweed patches, with an overall net negative effect on success of alligatorweed. Moreover, observational data showed positive correlations between hyacinth and alligatorweed with hyacinth, on average, more abundant. The negative effect of hyacinth on alligatorweed growth implies competition, not strong mutual facilitation (invasional meltdown), is occurring in this system. Removal of hyacinth may increase alligatorweed invasion through release from competition. However, removal of alligatorweed may have more complex effects on hyacinth patch dynamics because there were strong opposing effects on establishment versus growth. The mix of positive and negative interactions between floating and rooted aquatic plants may influence local population dynamics of each group and thus overall invasion pressure in this watershed.


Network meta-analysis of direct-acting antivirals in combination with peginterferon-ribavirin for previously untreated patients with hepatitis C genotype 1 infection.
To conduct a network meta-analysis (NMA) to determine the comparative efficacy, as measured by sustained virological response (SVR), between boceprevir (BOC), telaprevir (TEL), faldaprevir (FAL), simeprevir (SIM) and sofosbuvir (SOF) in combination with peginterferon-ribavirin (PR) against a control of PR. A literature search was conducted to identify randomized controlled trials (RCTs) including adult patients with hepatitis C virus genotype 1 who were naive to any prior therapy. RCTs assessing standard duration therapy (SDT) or response-guided therapy (RGT) BOC, TEL, FAL, SIM or SOF in combination with PR against a control of PR were eligible for inclusion. All RCTs must have provided SVR at either 12 or 24 weeks post-therapy cessation. We included nine RCTs. All direct-acting antivirals (DAAs) were found to perform better than PR. Additionally, SDT FAL was found to be better than the 240 mg RGT FAL regimen with the PR lead-in. A sensitivity analysis excluding RCTs with only SVR at 12 weeks was consistent with the results of the primary analysis. A sensitivity analysis removing an RCT assessing SIM that reported SVR of >60% in the PR control group additionally found that RGT SIM was superior to the 240 mg RGT FAL regimen with the PR lead-in. Our analyses indicate that SDT and RGT regimens of DAAs plus PR do not differ greatly in terms of SVR among treatment-naive hepatitis C genotype 1 patients. More advanced Bayesian network meta-analyses are likely needed to incorporate a comprehensive evidence base, expanding beyond randomized clinical trials.


Controversies in neurology: asymptomatic carotid stenosis--intervention or just stick to medical therapy. The argument for carotid endarterectomy.
Patients with a significant carotid stenosis are at an increased risk of suffering from a potentially fatal or disabling stroke. The current management strategies available to a patient with an asymptomatic carotid stenosis are either medical therapy alone, or in combination with either carotid endarterectomy, or carotid angioplasty and stenting. Medical therapy alone can reduce the incidence of stroke in general, but whether there is any reduction in stroke attributable to a significant carotid stenosis is less clear. Carotid endarterectomy, on the other hand, has been shown to reduce the incidence of ipsilateral ischaemic stroke in both symptomatic and asymptomatic patients, with the benefits extending into the long-term. Carotid angioplasty and stenting is a newer technique with the benefit of being minimally invasive. The results of trials comparing the technique to endarterectomy have had conflicting results, and the results of large multi-centre trials are awaited. Currently the safest strategy for a patient with a significant asymptomatic carotid stenosis consists of optimal medical therapy with carotid endarterectomy for those less than 75 years of age, who are suitable for surgery.


Rapid Training and Implementation of the Pollock Technique, a Safe, Effective Newborn Circumcision Procedure, in a Low-Resource Setting.
Male circumcision is highly protective against urinary tract infections, inflammatory conditions of the penis, sexually transmitted infections, and urogenital cancers. We aimed to reintroduce newborn male circumcision through the creation of a training program in Port-au-Prince, Haiti-an area with a considerable burden of preventable urogenital infections, sexually transmitted infections, and low circumcision rate-after an earlier study reported that a majority of Haitian medical providers were in need of and wanted newborn circumcision training. The program was conducted at the GHESKIO Health Centers, a large, non-governmental clinic offering comprehensive pediatric and adult health services. Two Haitian obstetricians and seven nurses learned circumcision procedures. On training completion, one of two obstetricians achieved surgical competence. Introduction of a newborn male circumcision training program was feasible, achieving an acceptable rate of procedural competency and high-quality services. Permanent resources now exist in Haiti to train additional providers to perform newborn male circumcisions.


Physiological and perceived health effects from daily changes in air pollution and weather among persons with heart failure: a panel study.
We carried out this daily diary panel study in Montreal, Quebec, to determine whether oxygen saturation, pulse rate, blood pressure, self-rated health, and shortness of breath at night were associated with concentrations of indoor carbon monoxide (CO), and indoor and outdoor fine particles (PM2.5), temperature, and relative humidity. Over a 2-month consecutive period between 2008 and 2010, we measured daily indoor and outdoor levels of the air pollutants and weather variables and 55 subjects measured their daily health and other variables. To estimate the associations between the health outcomes and the environmental exposures, we used a mixed effects regression model using an autoregressive model of order-one and we adjusted for month and day and personal variables. The general pattern of associations can be summarized as follows: oxygen saturation was reduced for increases in indoor- and outdoor-PM2.5 and temperature. Pulse rate increased on the concurrent day for increases in indoor CO and PM2.5. Diastolic blood pressure increased with increasing indoor and outdoor PM2.5 and relative humidity. Systolic blood pressure increased with indoor PM2.5 and decreased with increasing indoor and outdoor temperature. Self-rated health diminished with increases in outdoor PM2.5 and indoor and outdoor temperature. Self-reported shortness of breath at night increased with increasing indoor and outdoor temperatures. Health in heart failure is affected in the short term by personal and environmental conditions that are manifest in intermediate physiological parameters.


Outcomes of early pubertal timing in young women: a prospective population-based study.
Early pubertal timing in girls is associated with psychosocial problems throughout adolescence, but it is unclear whether these problems persist into young adulthood. The authors analyzed outcomes in adolescence and young adulthood in girls in a longitudinal study. The data for this study were from the prospective population-based Great Smoky Mountains Study (N=1,420), which initially recruited children at ages 9, 11, and 13 and followed them into young adulthood. Pubertal timing was defined on the basis of self-reported Tanner stage and age at menarche. Outcome measures included functioning related to crime, substance use, school/peer problems, family relationships, sexual behavior, and mental health in adolescence (ages 13 to 16) as well as crime, substance use, education/socioeconomic status, sexual behavior, and mental health in young adulthood (ages 19 and 21). In adolescence, early-maturing girls displayed higher levels of self-reported criminality, substance use problems, social isolation, early sexual behavior, and psychiatric problems. By young adulthood, most of these differences had attenuated. Functioning for early maturers improved in some areas; in others, on-time and late maturers had caught up with their early-maturing peers. Nevertheless, early-maturing girls, particularly those with a history of adolescent conduct disorder, were more likely to be depressed in young adulthood compared to their counterparts. Early maturers were also more likely to have had many sexual partners. The effects of early pubertal timing on adolescent psychosocial problems were wide ranging but diminished by young adulthood for all but a small group.


Effect of primary medical care on addiction and medical severity in substance abuse treatment programs.
To examine whether the availability of primary medical care on-site at addiction treatment programs or off-site by referral improves patients' addiction severity and medical outcomes, compared to programs that offer no primary care. Secondary analysis of a prospective cohort study of patients admitted to a purposive national sample of substance abuse treatment programs. Substance abuse treatment programs in major U.S. metropolitan areas eligible for demonstration grant funding from the federal Substance Abuse and Mental Health Services Administration. Administrators at 52 substance abuse treatment programs, and 2,878 of their patients who completed treatment intake, discharge, and follow-up interviews. Program administrators reported whether the program had primary medical care available on-site, only off-site, or not at all. Patients responded to multiple questions regarding their addiction and medical status in intake and 12-month follow-up interviews. These items were combined into multi-item composite scores of addiction and medical severity. The addiction severity score includes items measuring alcohol and drug use, employment, illegal activities, legal supervision, family and other social support, housing, physical conditions, and psychiatric status. The medical severity score includes measures of perceived health, functional limitations, and comorbid physical conditions. After controlling for treatment modality, geographic region, and multiple patient-level characteristics, patients who attended programs with on-site primary medical care experienced significantly less addiction severity at 12-month follow-up (regression coefficient, -25.9; 95% confidence interval [95% CI], -43.2 to -8.5), compared with patients who attended programs with no primary medical care. However, on-site care did not significantly influence medical severity at follow-up (coefficient, -0.28; 95% CI, -0.69 to 0.14). Referral to off-site primary care exerted no detectable effects on either addiction severity (coefficient, -9.0; 95% CI, -26.5 to 8.5) or medical severity (coefficient, -0.03; 95% CI, -0.37 to 0.44). On-site primary medical care improves substance abuse treatment patients' addiction-related outcomes, but not necessarily their health-related outcomes. Further study is needed to discern the mechanism through which on-site primary care might improve the addiction-related outcomes of substance abuse treatment.