Activity Level and Severity of Dysplasia Predict Age at Bernese Periacetabular Osteotomy for Symptomatic Hip Dysplasia.
The age when patients present for treatment of symptomatic developmental dysplasia of the hip with periacetabular osteotomy (PAO) varies widely. Modifiable factors influencing age at surgery include preexisting activity level and body mass index (BMI). The severity of the hip dysplasia has also been implicated as a factor influencing the age at arthritis onset. The purpose of this study was to determine whether activity level, BMI, and severity of dysplasia are independent predictors of age of presentation for PAO. A retrospective, institutional review board-approved review of prospectively collected data from a multicenter study group identified 708 PAOs performed for developmental dysplasia of the hip. Demographic factors that were considered in the analysis included age at surgery, BMI, history of hip disorder or treatment, and duration of symptoms. The severity of the developmental dysplasia of the hip was assessed by radiographic measurement of the lateral and anterior center-edge angles and acetabular inclination. Activity level was assessed with the University of California, Los Angeles (UCLA) activity score. Spearman correlations and t tests were used for univariable analysis. Multivariable regression analysis using generalized estimating equations was applied to determine independent predictors of age at PAO. Univariable analysis indicated that age at presentation for treatment of PAO correlated with the lateral and anterior center-edge angles (p < 0.001), UCLA score (p < 0.001), and BMI (p = 0.04). Since the lateral and anterior center-edge angles were similarly correlated (Spearman rho = 0.61, p < 0.001), the lateral center-edge angle alone was used to classify the severity of the developmental dysplasia of the hip. Multivariable linear regression confirmed that a high UCLA score and severe hip dysplasia were independent predictors of age at PAO (p < 0.001). A high activity level and severe dysplasia lead to the development of symptoms and presentation for PAO at significantly younger ages. The combination of these two factors has an even greater effect on decreasing the age at presentation for hip-preserving surgery. An increased BMI was not independently associated with a younger age at surgery. Modifying activity level may be beneficial in terms of delaying the onset of symptoms from developmental dysplasia of the hip. Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.


Nuclear magnetic resonance solution structure of an N(2)-guanine DNA adduct derived from the potent tumorigen dibenzo[a,l]pyrene: intercalation from the minor groove with ruptured Watson-Crick base pairing.
The most potent tumorigen identified among the polycyclic aromatic hydrocarbons (PAH) is the nonplanar fjord region dibenzo[a,l]pyrene (DB[a,l]P). It is metabolically activated in vivo through the widely studied diol epoxide (DE) pathway to form covalent adducts with DNA bases, predominantly guanine and adenine. The (+)-11S,12R,13R,14S DE enantiomer forms adducts via its C14 position with the exocyclic amino group of guanine. Here, we present the first nuclear magnetic resonance solution structure of a DB[a,l]P-derived adduct, the 14R-(+)-trans-anti-DB[a,l]P-N(2)-dG (DB[a,l]P-dG) lesion in double-stranded DNA. In contrast to the stereochemically identical benzo[a]pyrene-derived N(2)-dG adduct (B[a]P-dG) in which the B[a]P rings reside in the B-DNA minor groove on the 3'-side of the modifed deoxyguanosine, in the DB[a,l]P-derived adduct the DB[a,l]P rings intercalate into the duplex on the 3'-side of the modified base from the sterically crowded minor groove. Watson-Crick base pairing of the modified guanine with the partner cytosine is broken, but these bases retain some stacking with the bulky DB[a,l]P ring system. This new theme in PAH DE-DNA adduct conformation differs from (1) the classical intercalation motif in which Watson-Crick base pairing is intact at the lesion site and (2) the base-displaced intercalation motif in which the damaged base and its partner are extruded from the helix. The structural considerations that lead to the intercalated conformation of the DB[a,l]P-dG lesion in contrast to the minor groove alignment of the B[a]P-dG adduct, and the implications of the DB[a,l]P-dG conformational motif for the recognition of such DNA lesions by the human nucleotide excision repair apparatus, are discussed.


Recurrent or refractory trigeminal neuralgia after microvascular decompression, radiofrequency ablation, or radiosurgery.
Trigeminal neuralgia (TN) is characterized by paroxysmal lancinating pain in the trigeminal nerve distribution. When TN is refractory to medical management, patients are referred for microvascular decompression (MVD), radiofrequency ablation, or radiosurgery. After the initial treatment, patients may have refractory or recurrent symptoms requiring retreatment. The purpose of this study was to determine what factors are associated with the need for retreatment and which modality is most effective. To define this population further, the authors evaluated a cohort of patients who required retreatment for TN. The mean follow-up periods were 51 months from the first treatment and 23 months from the last one, and these were comparable among treatment groups. Trigeminal neuralgia can recur after neurosurgical treatment. In this study the authors demonstrate that the number of patients requiring retreatment is not negligible. Lower retreatment rates were seen in patients who initially underwent radiosurgery, compared with those in whom MVD or radiofrequency ablation were performed. Radiosurgery was more likely to be the final treatment for recurrent TN regardless of the initial treatment. After retreatment, the majority of patients attained complete or very good pain relief. Pain relief after retreatment correlates with postoperative facial numbness.


Diabetic Neuropathy Is a Substantial Burden in People With Type 1 Diabetes and Is Strongly Associated With Socioeconomic Disadvantage: A Population-Representative Study From Scotland.
To assess the contemporaneous prevalence of diabetic peripheral neuropathy (DPN) in people with type 1 diabetes (T1D) in Scotland and study its cross-sectional association with risk factors and other diabetic complications. We analyzed data from a large representative sample of adults with T1D (N = 5,558). We assessed the presence of symptomatic neuropathy using the dichotomized (≥4) Michigan Neuropathy Screening Instrument Patient Questionnaire score. Logistic regression models were used to investigate associations between DPN and risk factors, as well as with other complications. The burden of DPN is substantial with 13% prevalence overall. Adjusting for attained age, diabetes duration, and sex, the odds of DPN increased mainly with waist-to-hip ratio, lipids, poor glycemic control (odds ratio 1.51 [95% CI 1.21-1.89] for levels of 75 vs. 53 mmol/mol), ever versus never smoking (1.67 [1.37-2.03]), and worse renal function (1.96 [1.03-3.74] for estimated glomerular filtration rate levels <30 vs. ≥90 mL/min/1.73 m2). The odds significantly decreased with higher HDL cholesterol (0.77 [0.66-0.89] per mmol/L). Living in more deprived areas was associated with DPN (2.17 [1.78-2.65]) for more versus less deprived areas adjusted for other risk factors. Finally, individuals with prevalent DPN were much more likely than others to have other diabetes complications. Diabetic neuropathy remains substantial, particularly affecting those in the most socioeconomically deprived groups. Those with clinically manifest neuropathy also have a higher burden of other complications and elevated levels of modifiable risk factors. These data suggest that there is considerable scope to reduce neuropathy rates and narrow the socioeconomic differential by better risk factor control.


The role of nutraceuticals in anti-aging medicine.
'Nutraceuticals' is a wide term including all kinds of food with health or medical effect. Regulations in the world on functional food and nutraceuticals are developed along with the development of new products. This nomenclature is not aligned across legal regulations in different countries. There are several theories trying to interpret the phenomenon of aging and the most interesting theory in terms of nutrition is free radical theory and the possible role of antioxidants in aging process. A large group of substances including vitamins, carotenoids, flavonoids and minerals have in vitro or in vivo clinically significant antioxidant characteristics. There is great interest in anti-aging substances derived from food, and the most popular ingredients are antioxidants, especially coenzyme Q10, phytoestrogens, probiotics and omega-3 fatty acids. These substances have beneficial effect on digestive and immune systems, and modulate inflammatory and degenerative processes in the body. The challenge in the future will be strategic combining of cosmeceuticals and nutraceuticals in order to intervene in biological aging processes and degenerative skin changes.


Anticancer mechanisms of cannabinoids.
In addition to the well-known palliative effects of cannabinoids on some cancer-associated symptoms, a large body of evidence shows that these molecules can decrease tumour growth in animal models of cancer. They do so by modulating key cell signalling pathways involved in the control of cancer cell proliferation and survival. In addition, cannabinoids inhibit angiogenesis and decrease metastasis in various tumour types in laboratory animals. In this review, we discuss the current understanding of cannabinoids as antitumour agents, focusing on recent discoveries about their molecular mechanisms of action, including resistance mechanisms and opportunities for their use in combination therapy. Those observations have already contributed to the foundation for the development of the first clinical studies that will analyze the safety and potential clinical benefit of cannabinoids as anticancer agents.


Amitriptyline for neuropathic pain in adults.
This is an updated version of the original Cochrane review published in Issue 12, 2012. That review considered both fibromyalgia and neuropathic pain, but the effects of amitriptyline for fibromyalgia are now dealt with in a separate review.Amitriptyline is a tricyclic antidepressant that is widely used to treat chronic neuropathic pain (pain due to nerve damage). It is recommended as a first line treatment in many guidelines. Neuropathic pain can be treated with antidepressant drugs in doses below those at which the drugs act as antidepressants. To assess the analgesic efficacy of amitriptyline for relief of chronic neuropathic pain, and the adverse events associated with its use in clinical trials. We searched CENTRAL, MEDLINE, and EMBASE to March 2015, together with two clinical trial registries, and the reference lists of retrieved papers, previous systematic reviews, and other reviews; we also used our own hand searched database for older studies. We included randomised, double-blind studies of at least four weeks' duration comparing amitriptyline with placebo or another active treatment in chronic neuropathic pain conditions. We performed analysis using three tiers of evidence. First tier evidence derived from data meeting current best standards and subject to minimal risk of bias (outcome equivalent to substantial pain intensity reduction, intention-to-treat analysis without imputation for dropouts; at least 200 participants in the comparison, 8 to 12 weeks' duration, parallel design), second tier from data that failed to meet one or more of these criteria and were considered at some risk of bias but with adequate numbers in the comparison, and third tier from data involving small numbers of participants that were considered very likely to be biased or used outcomes of limited clinical utility, or both. We included 15 studies from the earlier review and two new studies (17 studies, 1342 participants) in seven neuropathic pain conditions. Eight cross-over studies with 302 participants had a median of 36 participants, and nine parallel group studies with 1040 participants had a median of 84 participants. Study quality was modest, though most studies were at high risk of bias due to small size.There was no first-tier or second-tier evidence for amitriptyline in treating any neuropathic pain condition. Only third-tier evidence was available. For only two of seven studies reporting useful efficacy data was amitriptyline significantly better than placebo (very low quality evidence).More participants experienced at least one adverse event; 55% of participants taking amitriptyline and 36% taking placebo. The risk ratio (RR) was 1.5 (95% confidence interval (CI) 1.3 to 1.8) and the number needed to treat for an additional harmful outcome was 5.2 (3.6 to 9.1) (low quality evidence). Serious adverse events were rare. Adverse event and all-cause withdrawals were not different, but were rarely reported (very low quality evidence). Amitriptyline has been a first-line treatment for neuropathic pain for many years. The fact that there is no supportive unbiased evidence for a beneficial effect is disappointing, but has to be balanced against decades of successful treatment in many people with neuropathic pain. There is no good evidence of a lack of effect; rather our concern should be of overestimation of treatment effect. Amitriptyline should continue to be used as part of the treatment of neuropathic pain, but only a minority of people will achieve satisfactory pain relief. Limited information suggests that failure with one antidepressant does not mean failure with all.


Trust and cooperative behavior: Evidence from the realm of data-sharing.
Trust is praised by many social scientists as the foundation of functioning social systems owing to its assumed connection to cooperative behavior. The existence of such a link is still subject to debate. In the present study, we first highlight important conceptual issues within this debate. Second, we examine previous evidence, highlighting several issues. Third, we present findings from an original experiment, in which we tried to identify a "real" situation that allowed us to measure both trust and cooperation. People's expectations and behavior when they decide to share (or not) their data represents such a situation, and we make use of corresponding data. We found that there is no relationship between trust and cooperation. This non-relationship may be rationalized in different ways which, in turn, provides important lessons for the study of the trust-behavior nexus beyond the particular situation we study empirically.


Venous Thromboembolism (VTE) Prophylaxis for Hip and Knee Arthroplasty: Changing Trends.
Venous thromboembolism (VTE) has been identified as an immediate threat to patients undergoing major orthopedic procedures such as total hip arthroplasty (THA) and total knee arthroplasty (TKA). Given the known dangers of VTE, arthroplasty surgeons are sensitive to the need for VTE thromboprophylaxis. However, the modalities of thromboprophylaxis used to minimize the risks to patients have been variable. Clinical practice guidelines have been published by several professional organizations, while some hospitals have established their own protocols. The 2 most popular guidelines are those published by the Academy of Orthopaedic Surgeons (AAOS) and American College of Chest Physicians (ACCP), both from North America. Prior to 2012, these recommendations varied depending on underlying definitions, methodology, and goals of the 2 groups. For the first time, both groups have similar recommendations that focus on minimizing symptomatic VTE and bleeding complications. The key to determining the appropriate chemoprophylaxis for patients is to balance efficacy of a prophylactic agent, while being safe in regards to bleeding complications. However, a multimodal approach that focuses on early postoperative mobilization and the use of mechanical prophylaxis, in addition to chemoprophylaxis, is essential.


Sporadic primary hyperparathyroidism in young individuals: different disease and treatment?
Younger individuals with hyperparathyroidism may experience severe disease with a higher incidence of multigland disease (MGD) and operative failure, thereby requiring subtotal parathyroidectomy. This study examines the characteristics and surgical outcome of younger compared with older patients with sporadic primary hyperparathyroidism (SPHPT). Prospectively collected data of 1101 patients with SPHPT who underwent parathyroidectomy at a single institution were retrospectively reviewed. Patients with multiple endocrine neoplasia (MEN), familial, secondary, or tertiary hyperparathyroidism, parathyroid carcinoma, rickets, or lithium induced disease were excluded. Patients were subdivided into two groups: (1) younger individuals < or = 40 y of age (n = 110) and (2) older individuals > 40 y of age (n = 991). Both age groups were compared for gender, clinical manifestations, pre- and postoperative laboratory values, MGD, operative success, and recurrent disease. There was greater male predominance in younger compared with older patients treated for SPHPT (41% versus 25%, P = 0.0004). Of the clinical manifestations of SPHPT, kidney stones were more common in younger compared with older individuals (45% versus 29%, P = 0.0006). Conversely, bone pain was more common in older compared with younger patients (32% versus 14%, P = 0.0002). There was no statistical difference in biochemical values, MGD, and outcome between both groups. Despite male predominance and few differences in symptoms, SPHPT is a similar disease entity in both younger and older individuals. Patients from both age groups can be similarly treated for SPHPT with a high rate of operative success. Routine BNE and subtotal parathyroidectomy is not necessary in younger individuals.


Cross-habitat impacts of species decline: response of estuarine sediment communities to changing detrital resources.
Food webs of many ecosystems are sustained by organic matter from other habitats. Human activities and climatic change are increasingly modifying the quality and supply of these resources, yet for most ecosystems it is unknown how the taxonomic composition of organic matter influences community composition. Along the coastline of Sydney, Australia, the once abundant habitat-forming macroalga, Phyllospora comosa, is now locally extinct. Shallow reefs are now primarily occupied by Sargassum sp. and, to a lesser extent, the kelp Ecklonia radiata. We experimentally manipulated the supply of P. comosa, Sargassum sp. and E. radiata to estuarine sediments to assess responses by macroinvertebrate communities to: (1) changing the identity of the dominant detrital resource; and (2) varying the ratio of input of different macrophytes. Estuarine sediments dosed with P. comosa supported greater abundances of macroinvertebrates than sediments receiving Sargassum sp. or the kelp E. radiata. Whereas plots receiving Sargassum sp. or E. radiata had fewer macroinvertebrates than controls, plots receiving a moderate (120 g dry weight per m(2)) loading of P. comosa had more. Mixtures of detritus dominated by P. comosa supported similar macroinvertebrate communities to monocultures of the alga. Communities in sediments receiving detritus comprised of less than one-third P. comosa were, however, distinctly different. Our study provides evidence that the ecological ramifications of species decline can extend to spatially removed ecosystems, subsidized by allochthonous materials. Even prior to extinction of detrital sources, small changes in their provision of organic matter may alter the structure of subsidized communities.


Effects of different vibration frequencies on muscle strength, bone turnover and walking endurance in chronic stroke.
This randomized controlled trial aimed to evaluate the effects of different whole body vibration (WBV) frequencies on concentric and eccentric leg muscle strength, bone turnover and walking endurance after stroke. The study involved eighty-four individuals with chronic stroke (mean age = 59.7 years, SD = 6.5) with mild to moderate motor impairment (Fugl-Meyer Assessment lower limb motor score: mean = 24.0, SD = 3.5) randomly assigned to either a 20 Hz or 30 Hz WBV intervention program. Both programs involved 3 training sessions per week for 8 weeks. Isokinetic knee concentric and eccentric extension strength, serum level of cross-linked N-telopeptides of type I collagen (NTx), and walking endurance (6-min walk test; 6MWT) were assessed at baseline and post-intervention. An intention-to-treat analysis revealed a significant time effect for all muscle strength outcomes and NTx, but not for 6MWT. The time-by-group interaction was only significant for the paretic eccentric knee extensor work, with a medium effect size (0.44; 95% CI: 0.01, 0.87). Both WBV protocols were effective in improving leg muscle strength and reducing bone resorption. Comparatively greater improvement in paretic eccentric leg strength was observed for the 30 Hz protocol.


Differentiating minimum clinically important difference for primary and revision lumbar fusion surgeries.
Previous studies have reported on the minimum clinically important difference (MCID), a threshold of improvement that is clinically relevant for lumbar degenerative disorders. Recent studies have shown that pre- and postoperative health-related quality of life (HRQOL) measures vary among patients with different diagnostic etiologies. There is also concern that a patient's previous care experience may affect his or her perception of clinical improvement. This study determined if MCID values for the Oswestry Disability Index (ODI), 36-Item Short-Form Health Survey (SF-36), and back and leg pain are different between patients undergoing primary or revision lumbar fusion. Prospectively collected preoperative and 1-year postoperative patient-reported HRQOLs, including the ODI, SF-36 physical component summary (PCS), and numeric rating scales (0-10) for back and leg pain, in patients undergoing lumbar spine fusion were analyzed. Patients were grouped into either the primary surgery or revision group. As the most widely accepted MCID values were calculated from the minimum detectable change, this method was used to determine the MCID. A total of 722 patients underwent primary procedures and 333 patients underwent revisions. There was no statistically significant difference in demographics between the groups. Each group had a statistically significant improvement at 1 year postoperatively compared with baseline. The minimum detectable change-derived MCID values for the primary group were 1.16 for back pain, 1.36 for leg pain, 12.40 for ODI, and 5.21 for SF-36 PCS. The MCID values for the revision group were 1.21 for back pain, 1.28 for leg pain, 11.79 for ODI, and 4.90 for SF-36 PCS. These values are very similar to those previously reported in the literature. The MCID values were similar for the revision and primary lumbar fusion groups, even when subgroup analysis was done for different diagnostic etiologies, simplifying interpretation of clinical improvement. The results of this study further validate the use of patient-reported HRQOLs to measure clinical effectiveness, as a patient's previous experience with care does not seem to substantially alter an individual's perception of clinical improvement.


Protective effects of prepubertal genistein exposure on mammary tumorigenesis are dependent on BRCA1 expression.
This study investigated whether prepubertal dietary exposure to genistein reduces mammary tumorigenesis by upregulating Brca1 expression in mice. Heterozygous Brca1(+/-) mice and their wild-type (WT) littermates were fed control AIN93G diet or 500 ppm genistein-supplemented AIN93G diet from postnatal day (PND) 15 to PND30 and then switched to AIN93G diet. Prepubertal dietary exposure to genistein reduced 7,12-dimethylbenz(a)anthracene (DMBA)-induced mammary incidence (P = 0.029) and aggressiveness of the tumors (P < 0.001) in the WT mice and upregulated the expression of Brca1 in their mammary glands (P = 0.04). In contrast, prepubertal genistein diet neither significantly reduced mammary tumorigenesis or tumor aggressivity nor increased Brca1 mRNA expression in the Brca1(+/-) mice. These results may be related to the opposing effects of prepubertal genistein diet on the expression of Rankl and CK5/CK18 ratio (marker of luminal epithelial cell differentiation) in the mammary gland and estrogen receptor (ER-α) and progesterone receptor (PgR) protein levels in the mammary tumor: these all were reduced in the WT mice or increased in Brca1(+/-) mice. Both the WT and Brca1(+/-) mice exhibited reduced levels of amphiregulin, CK5, and CK18, delayed ductal elongation and a reduction in terminal end bud number in the normal mammary gland, and reduced HER-2 protein levels in the mammary tumors; however, these effects were not sufficient to significantly reduce mammary tumorigenesis in Brca1(+/-) mice. Our results show that upregulation of Brca1 may be required for prepubertal dietary genistein exposure to reduce later mammary tumorigenesis, perhaps because in the absence of this upregulation, mice do not exhibit genistein-induced downregulation of ER-α, PgR, and Rankl.


Emergency department utilization patterns among older adults.
We identified 4-year (2 years before and 2 years after the index [baseline] interview) ED use patterns in older adults and the factors associated with them. A secondary analysis of baseline interview data from the nationally representative Survey on Assets and Health Dynamics Among the Oldest Old linked to Medicare claims data. Participants were 4310 self-respondents 70 years old or older. Current Procedural Terminology (CPT) codes 99281 and 99282 identified low-intensity use, and CPT codes 99283-99285 identified high-intensity use. Exploratory factor analysis and multivariable multinomial logistic regression were used. The majority (56.6%) of participants had no ED visits during the 4-year period. Just 5.7% had only low-intensity ED use patterns, whereas 28.9% used the ED only for high-intensity visits, and 8.7% had a mixture of low-intensity and high-intensity use. Participants with lower immediate word recall scores and those who did not live in major metropolitan areas were more likely to be low-intensity-only ED users. Older individuals, those who did not live in rural counties, had greater morbidity and functional status burdens, and lower immediate word recall scores were more likely to be high-intensity-only ED users. Participants who were older, did not live in major cities, had lower education levels, had greater morbidity and functional status burdens, and lower immediate word recall scores were more likely to have mixed ED use patterns. Nearly half of these older adults used the ED at least once over a 4-year period, with a mean annual ED use percentage of 18.4. Few, however, used the ED only for visits that may have been avoidable. This finding suggests that triaging Medicare patients would not decrease ED overcrowding, although continued surveillance is necessary to detect potential changes in ED use patterns among older adults.


Remote sensing and signaling in kidney proximal tubules stimulates gut microbiome-derived organic anion secretion.
Membrane transporters and receptors are responsible for balancing nutrient and metabolite levels to aid body homeostasis. Here, we report that proximal tubule cells in kidneys sense elevated endogenous, gut microbiome-derived, metabolite levels through EGF receptors and downstream signaling to induce their secretion by up-regulating the organic anion transporter-1 (OAT1). Remote metabolite sensing and signaling was observed in kidneys from healthy volunteers and rats in vivo, leading to induced OAT1 expression and increased removal of indoxyl sulfate, a prototypical microbiome-derived metabolite and uremic toxin. Using 2D and 3D human proximal tubule cell models, we show that indoxyl sulfate induces OAT1 via AhR and EGFR signaling, controlled by miR-223. Concomitantly produced reactive oxygen species (ROS) control OAT1 activity and are balanced by the glutathione pathway, as confirmed by cellular metabolomic profiling. Collectively, we demonstrate remote metabolite sensing and signaling as an effective OAT1 regulation mechanism to maintain plasma metabolite levels by controlling their secretion.


Risk factors for primary pulmonary coccidioidomycosis hospitalizations among United States Navy and Marine Corps personnel, 1981-1994.
Recent coccidioidomycosis outbreaks among military personnel have alarmed public health officials. We used computerized hospitalization records to identify risk factors for coccidioidomycosis hospitalizations among active-duty United States Navy and Marine Corps personnel for the years 1981 to 1994. Primary pulmonary disease was the most common form of disease, accounting for 82 (73%) of the 113 first admissions. Crude annual rates of primary pulmonary disease increased markedly in 1992 and 1993 in concert with an epidemic in the United States. Demographic data from the pulmonary admissions were combined with that of a 2% random sample of the entire Navy and Marine Corps population for multivariate risk factor modeling. Persons from junior paygrades, older age groups, and those reporting a race/ethnicity other than Caucasian or Hispanic were most likely to be hospitalized with this disease. These risk factor data should be considered in designing coccidioidomycosis surveillance and prevention programs.


The anticardiolipin assay is required for sensitive screening for antiphospholipid antibodies.
The importance of testing for anticardiolipin antibodies (aCL) in the diagnosis of antiphospholipid syndrome (APS) in patients with thrombosis has recently been challenged (ISTH SSC meeting, Boston 2002). We have analyzed the antiphospholipid serology of 123 patients with persistent antiphospholipid antibodies (aPL) attending our hematology department. The cohort was tested for anti-beta(2)-glycoprotein I (beta(2)-GPI) antibodies and aCL of IgG and IgM class and for lupus anticoagulant (LA). Ninety-six of these patients fulfilled Sapporo clinical criteria for APS and 70 of these patients had venous and/or arterial thrombosis. Patients with LA plus anti-beta(2)-GPI antibodies had significantly higher levels of IgG aCL and anti-beta(2)-GPI antibodies than those exhibiting positivity for only LA or anti-beta(2)-GPI antibodies (P < 0.05). Patients with aCL IgG levels over 60 GPLU were found in all cases to be positive for LA and anti-beta(2)-GPI antibodies; 25.2% (31/123) of all patients and 26.04% (25/96) of patients fulfilling Sapporo clinical criteria for APS were positive for aCL only. The mean IgG aCL level in the Sapporo clinical criteria positive patients who had aCL only was 11.5 GPLU (normal < 5 GPLU). These data indicate that omission of aCL testing from the clinical investigation of APS could lead to a failure to diagnose the syndrome in a proportion of patients.


Development of 3D PVA scaffolds for cardiac tissue engineering and cell screening applications.
The aim of this study was the design of a 3D scaffold composed of poly(vinyl) alcohol (PVA) for cardiac tissue engineering (CTE) applications. The PVA scaffold was fabricated using a combination of gas foaming and freeze-drying processes that did not need any cross-linking agents. We obtained a biocompatible porous matrix with excellent mechanical properties. We measured the stress-strain curves of the PVA scaffolds and we showed that the elastic behavior is similar to that of the extracellular matrix of muscles. The SEM observations revealed that the scaffolds possess micro pores having diameters ranging from 10 μm to 370 μm that fit to the dimensions of the cells. A further purpose of this study was to test scaffolds ability to support human induced pluripotent stem cells growth and differentiation into cardiomyocytes. As the proliferation tests show, the number of live stem cells on the scaffold after 12 days was increased with respect to the initial number of cells, revealing the cytocompatibility of the substrate. In addition, the differentiated cells on the PVA scaffolds expressed anti-troponin T, a marker specific of the cardiac sarcomere. We demonstrated the ability of the cardiomyocytes to pulse within the scaffolds. In conclusion, the developed scaffold show the potential to be used as a biomaterial for CTE applications.


Improving pancreas surgery over time: Performance factors related to transition of care and patient volume.
Pancreas surgery has evolved with better diagnostic imaging, changing indications, and improved patient selection. Outside high-volume tertiary centers, the documented effect of evolution in care and volumes are limited. Thus, we aimed to review indications and outcomes in pancreas surgery during the transition from community-based hospital to a university hospital. All pancreatic surgeries performed between 1986 and 2012 within a well-defined Norwegian population were identified from the hospital's database. Indications and postoperative outcomes, including mortality, were investigated. Of the 219 included patients (54% males; median age, 64 years), 150 (69%) underwent pancreatoduodenectomy; 55 (25%), distal resection; and 5 (2%), enucleation. The annual number of operations increased during the study period (from <10/yr to >20/yr). Most patients (169; 77%) underwent surgery for suspected malignancy. The 30-day mortality decreased significantly over time among patients treated for pancreatic cancer (from 16.1% to 3.5%; p = 0.012). Over time, significant reductions in median hospitalization time (19 versus 12 days; p < 0.001), re-operation rate (37.1% versus 8.4%; p < 0.001), and median ICU stay (3 versus 0 days; p < 0.001) were observed. The transition to university hospital and increase in volume has led to significant improvements in several performance metrics and reduced postoperative mortality. We believe improved perioperative management and focused, multidisciplinary care-bundles to be of importance.


Pediatric Differentiated Thyroid Cancer: When to Perform Conservative and Radical Surgery.
Thyroid tumors affect all age groups, including children and adolescents. Malignant cancer of the thyroid is a relatively uncommon disease in pediatric age. In the recent decades the incidence of paediatric differentiated thyroid carcinoma (DTC) has increased. DTC in paediatric age is rare and has an excellent prognosis. Compared to adult counterpart, DTC in childhood presents some different features as follows: larger volume at the diagnosis, more frequent multicentricity (both mono- and bilateral), earlier local involvement of soft tissue of the neck, earlier lymph node involvement, distant metastases 3-4 times more frequent (most often in the lungs and almost always functional) and more common post-operatory recurrence; nevertheless, the prognosis of DTC in childhood is better and the survival greater than in adult. Because of unusual association between aggressive presentation and good prognosis, the choice about the surgical treatment to perform in DTC is debatable, especially between conservative and radical approach in TNM stage I pediatric patients. To date, total thyroidectomy is the operation most often performed in children with DTC, although recently conservative surgery has been performed in solitary unifocal nodule without evidence distant metastases.


Assessment of benzene-induced hematotoxicity using a human-like hematopoietic lineage in NOD/Shi-scid/IL-2Rγnull mice.
Despite recent advancements, it is still difficult to evaluate in vivo responses to toxicants in humans. Development of a system that can mimic the in vivo responses of human cells will enable more accurate health risk assessments. A surrogate human hematopoietic lineage can be established in NOD/Shi-scid/IL-2Rγ(null) (NOG) mice by transplanting human hematopoietic stem/progenitor cells (Hu-NOG mice). Here, we first evaluated the toxic response of human-like hematopoietic lineage in NOG mice to a representative toxic agent, benzene. Flow cytometric analysis showed that benzene caused a significant decrease in the number of human hematopoietic stem/progenitor cells in the bone marrow and the number of human leukocytes in the peripheral blood and hematopoietic organs. Next, we established chimeric mice by transplanting C57BL/6 mouse-derived bone marrow cells into NOG mice (Mo-NOG mice). A comparison of the degree of benzene-induced hematotoxicity in donor-derived hematopoietic lineage cells within Mo-NOG mice indicated that the toxic response of Hu-NOG mice reflected interspecies differences in susceptibilities to benzene. Responses to the toxic effects of benzene were greater in lymphoid cells than in myeloid cells in Mo-NOG and Hu-NOG mice. These findings suggested that Hu-NOG mice may be a powerful in vivo tool for assessing hematotoxicity in humans, while accounting for interspecies differences.


Reliability of surgeon-specific reporting of complications after colectomy.
We sought to determine the reliability of surgeon-specific postoperative complication rates after colectomy. Conventional measures of surgeon-specific performance fail to acknowledge variation attributed to statistical noise, risking unreliable assessment of quality. We examined all patients who underwent segmental colectomy with anastomosis from 2008 through 2010 participating in the Michigan Surgical Quality Collaborative Colectomy Project. Surgeon-specific complication rates were risk-adjusted according to patient characteristics with multiple logistic regression. Hierarchical modeling techniques were used to determine the reliability of surgeon-specific risk-adjusted complication rates. We then adjusted these rates for reliability. To evaluate the extent to which surgeon-level variation was reduced, surgeons were placed into quartiles based on performance and complication rates were compared before and after reliability adjustment. A total of 5033 patients (n = 345 surgeons) undergoing partial colectomy reported a risk-adjusted complication rate of 24.5%. Approximately 86% of the variability of complication rates across surgeons was explained by measurement noise, whereas the remaining 14% represented true signal. Risk-adjusted complication rates varied from 0% to 55.1% across quartiles before adjusting for reliability. Reliability adjustment greatly diminished this variation, generating a 1.2-fold difference (21.4%-25.6%). A caseload of 168 colectomies across 3 years was required to achieve a reliability of more than 0.7, which is considered a proficient level. Only 1 surgeon surpassed this volume threshold. The vast majority of surgeons do not perform enough colectomies to generate a reliable surgeon-specific complication rate. Risk-adjusted complication rates should be viewed with caution when evaluating surgeons with low operative volume, as statistical noise is a large determinant in estimating their surgeon-specific complication rates.


Eicosanoid production by mouse peritoneal macrophages during Toxoplasma gondii penetration: role of parasite and host cell phospholipases.
The metabolism of endogenous arachidonic acid by mouse resident peritoneal macrophages infected in vitro with Toxoplasma gondii was studied. Prelabeling of macrophages with [5,6,8,9,11,12,14,15-3H]arachidonic acid and challenge with tachyzoites for 15 min resulted in a high mobilization of free labeled arachidonic acid (178%) in the culture medium. The parasites also triggered the synthesis of 6-keto-prostaglandin F1 alpha (47%), prostaglandin E2 (44%), leukotrienes C4 and D4 (33%) and 5-, 12-hydroxyeicosatetraenoic acids (155%). The study indicated that during the intracellular development phase of the parasites, 6-keto-prostaglandin F1 alpha (38%), prostaglandin E2 (31%) leukotrienes C4 and D4 (15%), hydroxyeicosatetraenoic acids (43%), and free arachidonic acid (110%) were secreted into the culture medium. Pretreatment of tachyzoites with phospholipase A2 inhibitors (4-p-bromophenacyl bromide and quinacrine) and no calcium in the culture medium resulted in inhibition of tachyzoite penetration into the macrophages and a decrease of the arachidonic acid metabolism. The triggering of the arachidonic acid cascade by T. gondii was dependent on the active penetration of the parasites into the macrophages, whereas preincubation of the macrophages with phospholipase A2 inhibitors did not affect penetration or free arachidonic acid release, thereby supporting a role for parasite phospholipase in the penetration process and in arachidonic acid mobilization from macrophage membrane phospholipids. Moreover, treatment of macrophages with phospholipase A2 inhibitors decreased the activities of the cyclooxygenase and lipoxygenase pathways, also suggesting an activation of host cell phospholipase A2 by the parasite.


Defining women's health: a dozen messages from more than 150 ethnographies.
Although the women's health research agenda has been largely defined by Western biomedicine and public health, anthropology has much to offer in terms of defining and understanding women's health from the perspective of women themselves. Through the in-depth qualitative tradition of ethnography, anthropologists have documented women's health concerns around the globe, producing a large and constantly expanding literature that is rich and provocative. This article summarizes a dozen major messages about women's health that emerge from the ethnographic literature, now consisting of more than 150 volumes. These volumes are listed in the article, and some primary examples are described as representative of anthropology's contribution to knowledge production in women's health.


Anion-sensitive fluorophore identifies the Drosophila swell-activated chloride channel in a genome-wide RNA interference screen.
When cells swell in hypo-osmotic solutions, chloride-selective ion channels (Cl(swell)) activate to reduce intracellular osmolality and prevent catastrophic cell rupture. Despite intensive efforts to assign a molecular identity to the mammalian Cl(swell) channel, it remains unknown. In an unbiased genome-wide RNA interference (RNAi) screen of Drosophila cells stably expressing an anion-sensitive fluorescent indicator, we identify Bestrophin 1 (dBest1) as the Drosophila Cl(swell) channel. Of the 23 screen hits with mammalian homologs and predicted transmembrane domains, only RNAi specifically targeting dBest1 eliminated the Cl(swell) current (I(Clswell)). We further demonstrate the essential contribution of dBest1 to Drosophila I(Clswell) with the introduction of a human Bestrophin disease-associated mutation (W94C). Overexpression of the W94C construct in Drosophila cells significantly reduced the endogenous I(Clswell). We confirm that exogenous expression of dBest1 alone in human embryonic kidney (HEK293) cells creates a clearly identifiable Drosophila-like I(Clswell). In contrast, activation of mouse Bestrophin 2 (mBest2), the closest mammalian ortholog of dBest1, is swell-insensitive. The first 64 residues of dBest1 conferred swell activation to mBest2. The chimera, however, maintains mBest2-like pore properties, strongly indicating that the Bestrophin protein forms the Cl(swell) channel itself rather than functioning as an essential auxiliary subunit. dBest1 is an anion channel clearly responsive to swell; this activation depends upon its N-terminus.


The effect of imagination on stimulation: the functional specificity of efference copies in speech processing.
The computational role of efference copies is widely appreciated in action and perception research, but their properties for speech processing remain murky. We tested the functional specificity of auditory efference copies using magnetoencephalography recordings in an unconventional pairing: We used a classical cognitive manipulation (mental imagery--to elicit internal simulation and estimation) with a well-established experimental paradigm (one shot repetition--to assess neuronal specificity). Participants performed tasks that differentially implicated internal prediction of sensory consequences (overt speaking, imagined speaking, and imagined hearing) and their modulatory effects on the perception of an auditory (syllable) probe were assessed. Remarkably, the neural responses to overt syllable probes vary systematically, both in terms of directionality (suppression, enhancement) and temporal dynamics (early, late), as a function of the preceding covert mental imagery adaptor. We show, in the context of a dual-pathway model, that internal simulation shapes perception in a context-dependent manner.


The soluble guanylate cyclase stimulator riociguat reduces fibrogenesis and portal pressure in cirrhotic rats.
In cirrhotic patients, portal hypertension (PHT) deteriorates survival, yet treatment options are limited. A major contributor to increased intrahepatic vasoconstriction in PHT is dysfunctional nitric-oxide signaling. Soluble guanylate cyclase (sGC) is the receptor of nitric-oxide and can be stimulated by riociguat. Riociguat is approved for pulmonary hypertension but has not been studied in liver cirrhosis. In this study we assessed the effects of riociguat on PHT and liver fibrosis in cholestatic (bile duct ligation, BDL) and toxic (carbon-tetrachloride, CCl4) rat models. In cirrhotic livers sGC expression was upregulated. In BDL rats, riociguat reduced liver fibrosis and decreased portal pressure without affecting systemic hemodynamics. In an early BDL disease stage, riociguat decreased bile duct proliferation, improved sinusoidal vascular dysfunction and inhibited angiogenesis. In advanced BDL riociguat exhibited anti-inflammatory effects. In CCl4 rats the beneficial effects of riociguat treatment were less pronounced and confined to an early disease stage. Similarly, in patients with cholestatic cirrhosis and PHT nitrates (that induce sGC activity) decreased portal pressure more effectively than in patients with non-cholestatic etiology. We also found an improvement of transaminases in patients with pulmonary hypertension receiving riociguat. Our findings support the clinical development of sGC stimulators in patients with cirrhotic PHT.


Relationship of genetic factors with development of aortic dissection and aneurysm.
This study aims to investigate the relationship between the development of aortic dissections and aneurysms with the polymorphisms of angiotensin converting enzyme gene, methylenetetrahydrofolate reductase gene, plasminogen activator inhibitor-1 gene, and nitric oxide synthase gene. Between April 2009 and July 2014, 38 patients with aortic dissections (28 males, 10 females; mean age 55.1±10.7 years; range, 30 to 78 years) and 67 patients with aortic aneurysms (57 males, 10 females; mean age 63.0±11.4 years; range, 31 to 82 years) were included in this cross-sectional study. The control group consisted of 60 healthy volunteers (41 males, 19 females; mean age 56.3±11.2 years; range, 30 to 82 years) without an aortic aneurysm or dissection, as assessed by thoracoabdominal computed tomography. The prespecified four genes were genotyped with competitive allelespecific polymerase chain reaction. The aortic dissection group had higher nitric oxide synthase-3 (4b/4b) expression levels, compared to the control group. The aortic aneurysm group had also higher nitric oxide synthase-3 (4b/4a) expression levels, compared to the control group. Compared to the control group, a higher rate of angiotensin converting enzyme I/D gene polymorphism was detected in the aneurysm group, while higher D/D polymorphism rates were found in the dissection group; although not statistically significant. Our study results suggest that the nitric oxide synthase-3 intron 4b/4b and nitric oxide synthase-3 intron 4b/4a gene polymorphisms can be used as a predictor of aortic dissection and aneurysm development.


An Overview of Cleaning Agents' Health Hazards and Occupational Injuries and Diseases Attributed to Them in Sweden.
Using data from the Swedish Products Register, hosted by the Swedish Chemicals Agency (KemI), national occupational injury and disease statistics, and call records from the Swedish Poisons Information Centre (PIC) we characterize health hazards of marketed cleaning products and recorded injuries, disease, and incidents linked to cleaning or disinfection agents. The results show that cleaning agents pose many kinds of health hazards, although corrosion and irritation hazards dominate, in particular for the eyes (54% of all included products). Few products were recognized as inhalation hazards. The nature of the health hazards is reflected in the occupational disease and injury statistics and PIC records for eyes and skin but not for the respiratory tract. Among occupational disease cases attributed to cleaning or disinfection agents, 61% concern skin and 26% the respiratory tract. Among occupational injury cases 64% concern chemical burns. However, only a small part (<0.5%) of all reported diseases and injuries were explicitly attributed to cleaning or disinfection agents. On average, there were 11 cases of disease attributed to cleaning or disinfection agents per million workers and year. For occupational injuries the corresponding number was 8. The data concern a broad range of sectors and occupations, but notable sectors were healthcare, accommodation and food service, and manufacturing. Women were more likely to suffer from disease, men and women equally likely to suffer from injury. PIC cases were evenly distributed between men and women, but the clear risk cases more frequently involved men. Occupational diseases increased many-fold in 2020 while injuries decreased, which could be due to COVID-19 changing use patterns of cleaning and disinfection agents at work. We conclude that cleaning agents pose a variety of risks to a large part of the workforce, although particular attention for preventive efforts may need to be directed to the healthcare, accommodation and food service, and manufacturing sectors.


Spatially restricted G protein-coupled receptor activity via divergent endocytic compartments.
Postendocytic sorting of G protein-coupled receptors (GPCRs) is driven by their interactions between highly diverse receptor sequence motifs with their interacting proteins, such as postsynaptic density protein (PSD95), Drosophila disc large tumor suppressor (Dlg1), zonula occludens-1 protein (zo-1) (PDZ) domain proteins. However, whether these diverse interactions provide an underlying functional specificity, in addition to driving sorting, is unknown. Here we identify GPCRs that recycle via distinct PDZ ligand/PDZ protein pairs that exploit their recycling machinery primarily for targeted endosomal localization and signaling specificity. The luteinizing hormone receptor (LHR) and β2-adrenergic receptor (B2AR), two GPCRs sorted to the regulated recycling pathway, underwent divergent trafficking to distinct endosomal compartments. Unlike B2AR, which traffics to early endosomes (EE), LHR internalizes to distinct pre-early endosomes (pre-EEs) for its recycling. Pre-EE localization required interactions of the LHR C-terminal tail with the PDZ protein GAIP-interacting protein C terminus, inhibiting its traffic to EEs. Rerouting the LHR to EEs, or EE-localized GPCRs to pre-EEs, spatially reprograms MAPK signaling. Furthermore, LHR-mediated activation of MAPK signaling requires internalization and is maintained upon loss of the EE compartment. We propose that combinatorial specificity between GPCR sorting sequences and interacting proteins dictates an unprecedented spatiotemporal control in GPCR signal activity.


Abundance and temporal distribution of Ornithonyssus sylviarum Canestrini and Fanzago (Acarina: Mesostigmata) in gray catbird (Dumatella carolinensis) nests.
The northern fowl mite, Ornithonyssus sylviarum Canestrini and Fanzago, is a common ectoparasite of wild birds. Despite its ability to transmit eastern equine encephalitis (EEE) virus under laboratory conditions and potential for involvement in the natural EEE virus cycle, we know little about its abundance or temporal distribution in nature. From June to August 2000, we studied the abundance of O. sylviarum in the nests of gray catbirds (Dumatella carolinensis), a reservoir host for EEE virus, at Killbuck Marsh Wildlife Area (KMWA), a known EEE virus focus in Wayne County, Ohio. A total of 7,883 O. sylviarum, including 1,910 adults and 5,973 protonymphs, were recovered from 23 of 26 gray catbird nests collected during various phases of the nesting cycle. We found no association between mite abundance and number of catbird nestlings in successful nests. However, mite abundance increased significantly with date of nest collection and peaked in late July when transmission of EEE virus is likely to occur at KMWA. We therefore suggest that O. sylviarum may contribute to the transmission of EEE virus among gray catbirds at KMWA.


Parallel on-line detection of a methylbismuth species by hyphenated GC/EI-MS/ICP-MS technique as evidence for bismuth methylation by human hepatic cells.
Methylation of metal(loid)s by bacteria or even mammals is a well known process that can lead to increased toxicity for humans. Nevertheless, reliable analytical techniques and tools are indispensable in speciation analysis of trace elements, especially since environmental or biological samples are usually characterised by complex matrices. Here the methylating capability of hepatic cells was observed in vitro. HepG2 cells were incubated with colloidal bismuth subcitrate, bismuth cysteine and bismuth glutathione, respectively for a period of 24 h. For identification the cell lysate was ethylated by sodium tetraethyl borate under neutral conditions. After cryo focussing by purge and trap, the bismuth speciation was carried out via GC/EI-MS/ICP-MS. Colloidal bismuth subcitrate and bismuth cysteine were methylated by HepG2 cells, while no methylated bismuth species was detected after incubation with bismuth glutathione.


Nuclear phosphoproteome analysis of 3T3-L1 preadipocyte differentiation reveals system-wide phosphorylation of transcriptional regulators.
Adipocytes (fat cells) are important endocrine and metabolic cells critical for systemic insulin sensitivity. Both adipose excess and insufficiency are associated with adverse metabolic function. Adipogenesis is the process whereby preadipocyte precursor cells differentiate into lipid-laden mature adipocytes. This process is driven by a network of transcriptional regulators (TRs). We hypothesized that protein PTMs, in particular phosphorylation, play a major role in activating and propagating signals within TR networks upon induction of adipogenesis by extracellular stimulus. We applied MS-based quantitative proteomics and phosphoproteomics to monitor the alteration of nuclear proteins during the early stages (4 h) of preadipocyte differentiation. We identified a total of 4072 proteins including 2434 phosphorylated proteins, a majority of which were assigned as regulators of gene expression. Our results demonstrate that adipogenic stimuli increase the nuclear abundance and/or the phosphorylation levels of proteins involved in gene expression, cell organization, and oxidation-reduction pathways. Furthermore, proteins acting as negative modulators involved in negative regulation of gene expression, insulin stimulated glucose uptake, and cytoskeletal organization showed a decrease in their nuclear abundance and/or phosphorylation levels during the first 4 h of adipogenesis. Among 288 identified TRs, 49 were regulated within 4 h of adipogenic stimulation including several known and many novel potential adipogenic regulators. We created a kinase-substrate database for 3T3-L1 preadipocytes by investigating the relationship between protein kinases and protein phosphorylation sites identified in our dataset. A majority of the putative protein kinases belong to the cyclin-dependent kinase family and the mitogen-activated protein kinase family including P38 and c-Jun N-terminal kinases, suggesting that these kinases act as orchestrators of early adipogenesis.


Perceptions of parenting: individual differences and the effect of community.
Neighborhood norms are an important determinant of beliefs and attitudes about parenting, and measuring changes in community norms is an important component of evaluating community-based programs for improving child outcomes. The purpose of this study was to determine whether or not a survey of community residents' perceptions of parenting could be used to measure community parenting norms and whether these perceptions differed by individual or community characteristics. Two community surveys with 870 and 914 respondents, respectively, were conducted in 3 low-income neighborhoods. Results indicated that perceptions of parenting could be measured reliably at the community level although it is important to consider the presence of multiple norms when using such measures. Furthermore, differences in perceptions of parenting associated with individual characteristics were markedly decreased when neighborhood characteristics were considered, suggesting that the association of individual characteristics with perceptions of parenting is confounded by neighborhood characteristics.


Gut Microbiota Profile in Adults Undergoing Bariatric Surgery: A Systematic Review.
Gut microbiota (GM) after bariatric surgery (BS) has been considered as a factor associated with metabolic improvements and weight loss. In this systematic review, we evaluate changes in the GM, characterized by 16S rRNA and metagenomics techniques, in obese adults who received BS. The PubMed, Scopus, Web of Science, and LILACS databases were searched. Two independent reviewers analyzed articles published in the last ten years, using Rayyan QCRI. The initial search resulted in 1275 documents, and 18 clinical trials were included after the exclusion criteria were applied. The predominance of intestinal bacteria phyla varied among studies; however, most of them reported a greater amount of Bacteroidetes (B), Proteobacteria (P), and diversity (D) after BS. Firmicutes (F), B, and the (F/B) ratio was inconsistent, increasing or decreasing after Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) were conducted, compared to before surgery. There was a reduction in the relative proportion of F. Moreover, a higher proportion of Actinobacteria (A) was observed after RYGB was conducted. However, the same was not identified when SG procedures were applied. Genera abundance and bacteria predominance varied according to the surgical procedure, with limited data regarding the impact on phyla. The present study was approved by PROSPERO, under registration number CRD42020209509.


Pathogenesis of myelofibrosis with myeloid metaplasia: lessons from mouse models of the disease.
The primary genetic lesion(s), as well as the biological processes responsible for the typical structural changes of the bone marrow microenvironment in idiopathic myelofibrosis, are still poorly understood, although a central role in disease pathogenesis has been attributed to the clonal proliferation and defective maturation of megakaryocytes. Two animal models of the disease have been described, that in the last few years significantly contributed to the elucidation of some of the pathogenetic steps of the human disease; these are represented by mice genetically modified to overexpress thrombopoietin and by knock-down mice with defective GATA-1 expression in megakaryocytes (GATA-1(low) mice). This review will outline these murine models, both characterized by extensive accumulation of megakaryocytes in hematopoietic tissues, and illustrate how they provided insights into the identification of some of the molecules and mechanisms responsible for the development of fibrosis and osteosclerosis that present major similarities with those observed in patients with idiopathic myelofibrosis.


Postconcussive symptoms are associated with compensatory cortical recruitment during a working memory task.
The severity of sports-related concussion is often characterized by the number and severity of postconcussive symptoms (eg, headache, dizziness, difficulty concentrating). Although the level of postconcussive symptoms after injury is believed to index the severity of the neurological insult sustained, studies examining the relationship between symptom severity and neural functioning in concussed athletes remain rare. This exploratory study examined the association between self-reported symptom severity and functional activation on a working memory task in a group of 16 recently concussed student athletes. Functional magnetic resonance imaging was used to examine the relationship of symptom severity to brain activation during a working memory task in 16 concussed subjects. Findings indicated that symptom severity was associated with regionally specific hyperactivation during a working memory task, even though symptom severity was not significantly related to task accuracy. The results add to a growing body of literature that demonstrates that functional neuroimaging may have the potential to serve as a sensitive biomarker of the severity of concussion and mild traumatic brain injury.


Role of parathyroid hormone in the glucose intolerance of chronic renal failure.
Evidence has accumulated suggesting that the state of secondary hyperparathyroidism and the elevated blood levels of parathyroid hormone (PTH) in uremia participate in the genesis of many uremic manifestations. The present study examined the role of PTH in glucose intolerance of chronic renal failure (CRF). Intravenous glucose tolerance tests (IVGTT) and euglycemic and hyperglycemic clamp studies were performed in dogs with CRF with (NPX) and without parathyroid glands (NPX-PTX). There were no significant differences among the plasma concentrations of electrolytes, degree of CRF, and its duration. The serum levels of PTH were elevated in NPX and undetectable in NPX-PTX. The NPX dogs displayed glucose intolerance after CRF and blood glucose concentrations during IVGTT were significantly (P less than 0.01) higher than corresponding values before CRF. In contrast, blood glucose levels after IVGTT in NPX-PTX before and after CRF were not different. K-g rate fell after CRF from 2.86 +/- 0.48 to 1.23 +/- 0.18%/min (P less than 0.01) in NPX but remained unchanged in NPX-PTX (from 2.41 +/- 0.43 to 2.86 +/- 0.86%/min) dogs. Blood insulin levels after IVGTT in NPX-PTX were more than twice higher than in NPX animals (P less than 0.01) and for any given level of blood glucose concentration, the insulin levels were higher in NPX-PTX than NPX dogs. Clamp studies showed that the total amount of glucose utilized was significantly lower (P less than 0.025) in NPX (6.64 +/- 1.13 mg/kg X min) than in NPX-PTX (10.74 +/- 1.1 mg/kg X min) dogs. The early, late, and total insulin responses were significantly (P less than 0.025) greater in the NPX-PTX than NPX animals. The values for the total response were 143 +/- 28 vs. 71 +/- 10 microU/ml, P less than 0.01. There was no significant difference in the ratio of glucose metabolized to the total insulin response, a measure of tissue sensitivity to insulin, between the two groups. The glucose metabolized to total insulin response ratio in NPX (5.12 +/- 0.76 mg/kg X min per microU/ml) and NPX-PTX (5.18 +/- 0.57 mg/kg X min per microU/ml) dogs was not different but significantly (P less than 0.01) lower than in normal animals (9.98 +/- 1.26 mg/kg X min per microU/ml). The metabolic clearance rate of insulin was significantly (P less than 0.02) reduced in both NPX (12.1 +/- 0.7 ml/kg X min) and NPX-PTX (12.1 +/- 0.9 ml/kg X min) dogs, as compared with normal animals (17.4 +/- 1.8 ml/kg X min). The basal hepatic glucose production was similar in both groups of animals and nor different from normal dogs; both the time course and the magnitude of suppression of hepatic glucose production by insulin were similar in both in groups. There were no differences in the binding affinity, binding sites concentration, and binding capacity of monocytes to insulin among NPX, NPX-PTX, and normal dogs. The data show that (a) glucose intolerance does not develop with CRF in the absence of PTH, (b) PTH does not affect metabolic clearance of insulin or tissue resistance to insulin in CRF, and (c) the normalization of metabolism in CRF in the absence of PTH is due to increased insulin secretion. The results indicate that excess PTH in CRF interferes with the ability of the beta-cells to augment insulin secretion appropriately in response to the insulin-resistant state.


Acupuncture and acupressure and massage health outcomes for patients with anorexia nervosa: findings from a pilot randomized controlled trial and patient interviews.
This study examined the feasibility of conducting a randomized controlled trial of acupuncture compared with an active control in an inpatient setting, to examine individuals' experience of the interventions, clinical outcomes from the trial, and to integrate data to explain the trial findings. This was a pilot randomized controlled trial with in-depth interviews with trial participants. The study was conducted at a private medical facility in Sydney, Australia. Twenty-six (26) patients with anorexia nervosa who were medically stable were the subjects. Treatment as usual was administered, and the intervention was delivered twice a week for the first 3 weeks, followed by weekly treatment for three weeks. The acupuncture group received acupuncture at the points Hegu (LI4), Zusanli (ST36), Neiguan (PC6), Taichong (LR3), Yanglingquan (GB34), and additional points based on the Traditional Chinese Medicine diagnosis. The control group received acupressure and massage. Acupressure involved consciously and gradually directing pressure to the center of the point being worked on. Clinical outcomes were measured at baseline and at 6 weeks following completion of the intervention. The primary outcome measure was body-mass index (BMI), and secondary outcomes included eating disorder psychopathology, anxiety, and depression. A semistructured interview was conducted asking questions about their interaction with the practitioner, what happened, how they felt, whether it made them feel differently, and what they attributed any change to. We found timely recruitment with the population recruited within a 5-month period. Study dropouts were 23% and treatment compliance was moderate, but acceptable for this challenging population. Participants in the control group demonstrated reduced eating concerns. Participants described both interventions positively, and experienced a sense of calmness and relaxation. Acupuncture and acupressure and massage may improve the patient's subjective sense of wellbeing, and further research is needed.


Enhanced chondrogenic differentiation of murine embryonic stem cells in hydrogels with glucosamine.
Differentiation of embryonic stem (ES) cells generally occurs after formation of three-dimensional cell aggregates, known as embryoid bodies (EBs). We have previously reported that hydrogels provide EBs a supportive environment for in vitro chondrogenic differentiation and three dimensional tissue formation [Hwang NS, et al. The Effects of three dimensional culture and growth factors on the chondrogenic differentiation of murine ES cells. Stem Cells 2006;24:284-91]. In this study, we report chondrogenic differentiation of murine ES cells encapsulated in photopolymerizing poly(ethylene-glycol)-based (PEG) hydrogels in the presence of glucosamine (GlcN), an amino monosaccharide found in chitin, glycoproteins and glycosaminoglycans such as hyaluronic acid, chondroitin sulfate and heparin sulfate. We examined the growth and differentiation of encapsulated EBs in standard chondrogenic differentiation medium containing 0-, 2-, and 10-mm GlcN. Morphometric analysis and examination of gene and protein expression indicated that treatment of hydrogel cultures with 2-mm GlcN for 21 days significantly increased EB size, levels of aggrecan mRNA, and tissue-specific extracellular matrix accumulation. GlcN can induce multiple aspects of cell behavior and optimal GlcN concentrations can be beneficial for directing the differentiation and tissue formation of ES cells.


Comprehensive machine learning analysis of Hydra behavior reveals a stable basal behavioral repertoire.
Animal behavior has been studied for centuries, but few efficient methods are available to automatically identify and classify it. Quantitative behavioral studies have been hindered by the subjective and imprecise nature of human observation, and the slow speed of annotating behavioral data. Here, we developed an automatic behavior analysis pipeline for the cnidarian Hydra vulgaris using machine learning. We imaged freely behaving Hydra, extracted motion and shape features from the videos, and constructed a dictionary of visual features to classify pre-defined behaviors. We also identified unannotated behaviors with unsupervised methods. Using this analysis pipeline, we quantified 6 basic behaviors and found surprisingly similar behavior statistics across animals within the same species, regardless of experimental conditions. Our analysis indicates that the fundamental behavioral repertoire of Hydra is stable. This robustness could reflect a homeostatic neural control of "housekeeping" behaviors which could have been already present in the earliest nervous systems.


Principal components of hand kinematics and neurophysiological signals in motor cortex during reach to grasp movements.
A few kinematic synergies identified by principal component analysis (PCA) account for most of the variance in the coordinated joint rotations of the fingers and wrist used for a wide variety of hand movements. To examine the possibility that motor cortex might control the hand through such synergies, we collected simultaneous kinematic and neurophysiological data from monkeys performing a reach-to-grasp task. We used PCA, jPCA and isomap to extract kinematic synergies from 18 joint angles in the fingers and wrist and analyzed the relationships of both single-unit and multiunit spike recordings, as well as local field potentials (LFPs), to these synergies. For most spike recordings, the maximal absolute cross-correlations of firing rates were somewhat stronger with an individual joint angle than with any principal component (PC), any jPC or any isomap dimension. In decoding analyses, where spikes and LFP power in the 100- to 170-Hz band each provided better decoding than other LFP-based signals, the first PC was decoded as well as the best decoded joint angle. But the remaining PCs and jPCs were predicted with lower accuracy than individual joint angles. Although PCs, jPCs or isomap dimensions might provide a more parsimonious description of kinematics, our findings indicate that the kinematic synergies identified with these techniques are not represented in motor cortex more strongly than the original joint angles. We suggest that the motor cortex might act to sculpt the synergies generated by subcortical centers, superimposing an ability to individuate finger movements and adapt the hand to grasp a wide variety of objects.


Exploring the mechanisms of macrolides in cystic fibrosis.
Several studies have reported clinical improvements in cystic fibrosis (CF) patients on macrolide antibiotics although the mechanism of action remains unclear. We conducted an open-label study of azithromycin (500 mg daily for 2 weeks) in 9 adult CF patients to explore 3 possible mechanisms: up-regulation of the multi-drug resistance (MDR) or cystic fibrosis transmembrane regulator (CFTR) proteins, correction of epithelial ion transport and reduced bacterial adherence. End-points included nasal potential difference (PD) measurements, nasal epithelial MDR and CFTR mRNA levels and Pseudomonas aeruginosa adherence to nasal epithelium. Forced expiratory volume in the 1st second (FEV(1)) increased significantly after 2 weeks of azithromycin (pre- 41.1 [5.0]%; post- 44.6 [5.8]%; P<0.05), although improvements in forced vital capacity (FVC) did not reach significance (pre- 61.3 [4.0]%; post- 67.1 [5.4]%, NS). Before treatment all subjects had nasal PD measurements characteristic of CF. Treatment led to no significant group differences in any measures of either sodium absorption or chloride secretion. Neither CFTR nor MDR mRNA levels had altered significantly and the adherence of P. aeruginosa did not decrease. We conclude that these are unlikely to be significant contributing mechanisms accounting for the consistent beneficial results observed in clinical trials of macrolides in CF.


Specific and effective detection of anammox bacteria using PCR primers targeting the 16S rRNA gene and functional genes.
Anaerobic ammonium-oxidizing (anammox) bacteria play an important role in the nitrogen cycle by coupling ammonium and nitrite to produce dinitrogen gas (N2). Polymerase chain reaction (PCR) is a fast, simple, and sensitive method that is widely used to assess the diversity, abundance, and activity of the slow-growing bacteria. In this review, we summarize and evaluate the wide variety of PCR primers targeting the 16S rRNA gene and functional genes (hzo, nir, and hzs) of anammox bacteria for their effectiveness and efficiencies in detecting this group of bacteria in different sample types. Furthermore, the efficiencies of different universal high-throughput sequencing 16S rRNA gene primers in anammox bacteria investigations were also evaluated to provide a reference for primer selection. Based on our in silico evaluation results, none of the 16S rRNA gene primers could recover all of the known anammox bacteria, but multiple hzo and hzs gene primers could accomplish this task. However, uncertain copies (1-3 copies) of hzo genes were identified in the genomes, and the hydrazine oxidation reaction catalyzed by hydrazine oxidoreductases (HZOs) can also be catalyzed by other hydroxylamine oxidoreductases (HAOs) in anammox bacteria, which can potentially result in large deviations in hzo-based qPCR and RT-qPCR analyses and results. Therefore, the use of optimal primers targeting unique hzs genes are recommended, although the efficiencies of these newly designed primers need further verification in practical applications. This article provides comprehensive information for the effective and specific detection of anammox bacteria using specific primers targeting the 16S rRNA gene and functional genes and serves as a basis for future high-quality primer design.


Clinical outcomes of seasonal influenza and pandemic influenza A (H1N1) in pediatric inpatients.
In April 2009, a novel influenza A H1N1 (nH1N1) virus emerged and spread rapidly worldwide. News of the pandemic led to a heightened awareness of the consequences of influenza and generally resulted in enhanced infection control practices and strengthened vaccination efforts for both healthcare workers and the general population. Seasonal influenza (SI) illness in the pediatric population has been previously shown to result in significant morbidity, mortality, and substantial hospital resource utilization. Although influenza pandemics have the possibility of resulting in considerable illness, we must not ignore the impact that we can experience annually with SI. We compared the outcomes of pediatric patients ≤18 years of age at a large urban hospital with laboratory confirmed influenza and an influenza-like illness (ILI) during the 2009 pandemic and two prior influenza seasons. The primary outcome measure was hospital length of stay (LOS). All variables potentially associated with LOS based on univariable analysis, previous studies, or hypothesized relationships were included in the regression models to ensure adjustment for their effects. There were 133 pediatric cases of nH1N1 admitted during 2009 and 133 cases of SI admitted during the prior 2 influenza seasons (2007-8 and 2008-9). Thirty-six percent of children with SI and 18% of children with nH1N1 had no preexisting medical conditions (p = 0.14). Children admitted with SI had 1.73 times longer adjusted LOS than children admitted for nH1N1 (95% CI 1.35 - 2.13). There was a trend towards more children with SI requiring mechanical ventilation compared with nH1N1 (16 vs.7, p = 0.08). This study strengthens the growing body of evidence demonstrating that SI results in significant morbidity in the pediatric population. Pandemic H1N1 received considerable attention with strong media messages urging people to undergo vaccination and encouraging improved infection control efforts. We believe that this attention should become an annual effort for SI. Strong unified messages from health care providers and the media encouraging influenza vaccination will likely prove very useful in averting some of the morbidity related to influenza for future epidemics.


Memory of cell shape biases stochastic fate decision-making despite mitotic rounding.
Cell shape influences function, and the current model suggests that such shape effect is transient. However, cells dynamically change their shapes, thus, the critical question is whether shape information remains influential on future cell function even after the original shape is lost. We address this question by integrating experimental and computational approaches. Quantitative live imaging of asymmetric cell-fate decision-making and their live shape manipulation demonstrates that cellular eccentricity of progenitor cell indeed biases stochastic fate decisions of daughter cells despite mitotic rounding. Modelling and simulation indicates that polarized localization of Delta protein instructs by the progenitor eccentricity is an origin of the bias. Simulation with varying parameters predicts that diffusion rate and abundance of Delta molecules quantitatively influence the bias. These predictions are experimentally validated by physical and genetic methods, showing that cells exploit a mechanism reported herein to influence their future fates based on their past shape despite dynamic shape changes.


The effects of a single night of complete and partial sleep deprivation on physical and cognitive performance: A Bayesian analysis.
This study investigated the effects of complete and partial sleep deprivation on multiple aspects of athletic performance. Ten males completed a cognitive function test, maximal handgrip strength, countermovement jump (CMJ) and a 15 min all out cycling test to assess aerobic performance. These tests were performed following 3 different sleep conditions; normal sleep (CON), a 4 hr sleep opportunity (PART) and complete sleep deprivation (DEP). Data were analysed using a Bayesian multi-level regression model to provide probabilities of impairment (p = %). Aerobic performance, CMJ and handgrip strength were impaired by 11.4% (p = 100%), 10.9% (p = 100%) and 6% (p = 97%) following DEP, while aerobic performance and CMJ were highly likely impaired by 4.1% (p = 90%) and 5.2% (p = 94%) following PART. Cognitive reaction time was not impacted by PART or DEP. In contrast the accuracy of responses was highly likely impaired by 2% (91) following DEP, while there was less certainty of impaired accuracy following PART (-1%, p = 73). Multiple aspects of physical and cognitive performance were impacted by sleep deprivation. The greatest detrimental effects were seen for aerobic performance and CMJ. Partial sleep deprivation equating to 4 hrs of sleep causes subtle, but potentially important negative impairments on athletic performance.


Pituitary incidentaloma: an endocrine society clinical practice guideline.
The aim was to formulate practice guidelines for endocrine evaluation and treatment of pituitary incidentalomas. Consensus was guided by systematic reviews of evidence and discussions through a series of conference calls and e-mails and one in-person meeting. We recommend that patients with a pituitary incidentaloma undergo a complete history and physical examination, laboratory evaluations screening for hormone hypersecretion and for hypopituitarism, and a visual field examination if the lesion abuts the optic nerves or chiasm. We recommend that patients with incidentalomas not meeting criteria for surgical removal be followed with clinical assessments, neuroimaging (magnetic resonance imaging at 6 months for macroincidentalomas, 1 yr for a microincidentaloma, and thereafter progressively less frequently if unchanged in size), visual field examinations for incidentalomas that abut or compress the optic nerve and chiasm (6 months and yearly), and endocrine testing for macroincidentalomas (6 months and yearly) after the initial evaluations. We recommend that patients with a pituitary incidentaloma be referred for surgery if they have a visual field deficit; signs of compression by the tumor leading to other visual abnormalities, such as ophthalmoplegia, or neurological compromise due to compression by the lesion; a lesion abutting the optic nerves or chiasm; pituitary apoplexy with visual disturbance; or if the incidentaloma is a hypersecreting tumor other than a prolactinoma.


Spectrum of high-resolution MRI findings in diabetic neuropathy.
Diabetes is the most common cause of neuropathy. Focal diabetic neuropathy, although less common than entrapment neuropathy, clinically mimics entrapment neuropathy. This article depicts the spectrum of MR abnormalities in diabetic subjects- from abnormal T2 hyperintensity and fascicular enlargement in the acute and subacute stages to atrophic-appearing fascicles with intraepineurial fat deposition in the chronic stage-on high-resolution high-field (3-T) MRI. A spectrum of imaging abnormalities is observed in diabetic neuropathy. It is important for radiologists to understand the pathophysiology and recognize high-resolution MR appearances of these lesions and of related entities in the differential diagnosis for appropriate diagnosis and patient treatment.


Ten simple rules for reporting voxel-based morphometry studies.
Voxel-based morphometry [Ashburner, J. and Friston, K.J., 2000. Voxel-based morphometry-the methods. NeuroImage 11(6 Pt 1), 805-821] is a commonly used tool for studying patterns of brain change in development or disease and neuroanatomical correlates of subject characteristics. In performing a VBM study, many methodological options are available; if the study is to be easily interpretable and repeatable, the processing steps and decisions must be clearly described. Similarly, unusual methods and parameter choices should be justified in order to aid readers in judging the importance of such options or in comparing the work with other studies. This editorial suggests core principles that should be followed and information that should be included when reporting a VBM study in order to make it transparent, replicable and useful.


Comparative activities of the beta-lactamase inhibitors YTR 830, clavulanate, and sulbactam combined with ampicillin and broad-spectrum penicillins against defined beta-lactamase-producing aerobic gram-negative bacilli.
The in vitro synergistic activities of the beta-lactamase inhibitors YTR 830, clavulanate, and sulbactam, combined with ampicillin, ticarcillin, mezlocillin, azlocillin, piperacillin, and apalcillin, were determined against 34 strains of members of the Enterobacteriaceae family, Pseudomonas aeruginosa, Aeromonas hydrophila, and Haemophilus influenzae with characterized plasmid or chromosomal beta-lactamases or both. Strains were tested against fixed concentrations of beta-lactamase inhibitors (8 micrograms/ml) combined with doubling dilutions of beta-lactams. Synergy was defined as a fourfold or greater decrease in the MIC of the beta-lactam. Against Enterobacteriaceae producing Richmond and Sykes class III and V plasmid-mediated beta-lactamases, synergy was obtained against most strains with YTR 830- and clavulanate-beta-lactam combinations, with sulbactam being less effective. Against Enterobacteriaceae producing class I chromosomal beta-lactamases, combinations containing YTR 830 or sulbactam were more synergistic than combinations containing clavulanate. Against strains producing class V PSE enzymes, all three inhibitors were synergistic with piperacillin and apalcillin against strains producing PSE-1, -3, and -4 enzymes, while the PSE-2-producing strain was resistant to all inhibitors. YTR 830-beta-lactam combinations were also synergistic against strains producing the novel beta-lactamases OHIO-1, TLE-1, AER-1, and ROB-1. Overall, YTR 830 with piperacillin or apalcillin was the most effective combination.


Expression of an N-terminal fragment of COP1 confers a dominant-negative effect on light-regulated seedling development in Arabidopsis.
CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) is an essential regulatory gene that plays a role in light control of seedling development in Arabidopsis. The COP1 protein possesses three recognizable structural domains: a RING finger zinc binding domain near the N terminus, followed by a coiled-coll domain and a domain with WD-40 repeats in the C-terminal half. To determine whether COP1 acts specifically as a light-inactivable repressor of photomorphogenic development and to elucidate the functional roles of the specific structural domains, mutant cDNAs encoding the N-terminal 282 amino acids (N282) of COP1 were expressed and analyzed in transgenic plants. High-level expression of the N282 fragment caused a dominant-negative phenotype similar to that of the loss-of-function cop1 mutants. The phenotypic characteristics include hypersensitivity of hypocotyl elongation to inhibition by white, blue, red, and far-red light stimuli. In the dark, N282 expression led to pleiotropic photomorphogenic cotyledon development, including cellular differentiation, plastid development, and gene expression, although it has no significant effect on the hypocotyl elongation. However, N282 expression had a minimal effect on the expression of stress- and pathogen-inducible genes. These observations support the hypothesis that COP1 is directly involved in the light control of seedling development and that it acts as a repressor of photomorphogenesis. Further, the results imply that the N282 COP1 fragment, which contains the zinc binding and colled-coil domains, is capable of interacting with either downstream targets or with the endogenous wild-type COP1, thus interfering with normal regulatory processes. The fact the N282 is able to interact with N282 and full-length COP1 in yeast provided evidence for the latter possibility.


Sex hormones play a role in vulnerability to sleep loss on emotion processing tasks.
The central aim of this study was to investigate hormones as a predictor of individual vulnerability or resiliency on emotion processing tasks following one night of sleep restriction. The restriction group was instructed to sleep 3 a.m.-7 a.m. (13 men, 13 women in follicular phase, 10 women in luteal phase of menstrual cycle), and a control group slept 11 p.m.-7 a.m. (12 men, 12 follicular women, 12 luteal women). Sleep from home was verified with actigraphy. Saliva samples were collected on the evening prior to restriction, and in the morning and afternoon following restriction, to measure testosterone, estradiol, and progesterone. In the laboratory, event-related potentials (ERPs) were recorded during presentation of images and faces to index neural processing of emotional stimuli. Compared to controls, sleep-restricted participants had a larger amplitude Late Positive Potential (LPP) ERP to positive vs neutral images, reflecting greater motivated attention towards positive stimuli. Sleep-restricted participants were also less accurate categorizing sad faces and exhibited a larger N170 to sad faces, reflecting greater neural reactivity. Sleep-restricted luteal women were less accurate categorizing all images compared to control luteal women, and progesterone was related to several outcomes. Morning testosterone in men was lower in the sleep-restricted group compared to controls; lower testosterone was associated with lower accuracy to positive images, a greater difference between positive vs neutral LPP amplitude, and lower accuracy to sad and fearful faces. In summary, women higher in progesterone and men lower in testosterone were more vulnerable to the effects of sleep restriction on emotion processing tasks. This study highlights a role for sex and sex hormones in understanding individual differences in vulnerability to sleep loss.


Chronic unpredictable early-life stress (CUELS) protocol: Early-life stress changes anxiety levels of adult zebrafish.
Early-life stress can lead to two different behavioral responses: (1) increased susceptibility to psychiatric disorders or (2) resilience. Here, we created a chronic unpredictable early-life stress (CUELS) protocol to assess the effects of early experiences in adult zebrafish. Animals were exposed to mild stressors twice a day and the duration was varied between groups (0, 1, 3, 7 and 14 days of stress). The stressor consisted of light/dark cycle changes; social isolation; overcrowding; water changes; water cooling; mechanical stirring; water heating; and immersion in shallow water. Behavior was assessed at young stages (21 days post-fertilization - open field analysis) and adulthood (4-months-old - novel tank diving test, light/dark task, shoaling, free movement pattern Y-maze and Pavlovian fear conditioning). Cortisol levels were assessed to evaluate the impact of CUELS in the HPI axis. Zebrafish exposed to 7 days of CUELS showed a decreased anxiety-like phenotype in two behavioral tasks, presenting increased time spent in top and decreased time spent in the dark area. Animals exposed to 14 days of CUELS showed an opposite anxious phenotype compared to 3 and 7 days of CUELS. No significant changes were observed in memory and cognition, social behavior and cortisol levels. In general, 7 days of CUELS protocol decreased anxiety in young and adult zebrafish, and could be used to understand the mechanisms underlying early-life experiences-derived alterations in neural circuits of anxiety.


Attitudes of nurses toward perinatal bereavement: findings from a study in Hong Kong.
Nurses' attitudes toward perinatal bereavement care are explored by identifying profiles of nurses working in 2 obstetrics and gynecology units in Hong Kong. Relationships between nurses' attitudes toward bereavement supports, need for bereavement education, and hospital policy are explored. A descriptive, correlational survey design was used, and 169 nurses recruited from an obstetric and gynecology (ob-gyn) unit at 2 local public hospitals in Hong Kong completed a structured questionnaire. Attitudes toward perinatal bereavement support; required support and education needs for nurses on bereavement care. Two-step cluster analysis yielded 2 clusters. Cluster 1 consisted of 55.6% (n = 94) and cluster 2 consisted of 44.3% (n = 75) of nurses. Cluster 2 nurses were younger and had less ob-gyn experience, more junior ranking, and less education than cluster 1 nurses. Cluster 1 nurses had additional midwifery and bereavement care education, personal grieving experiences, and experience handling grieving clients. The majority held positive bereavement care attitudes, but only 29.6% (n = 50) had bereavement-related education. Attitudes toward bereavement care were positively correlated with educational needs (r(s) = 0.52) and hospital policy support (r(s) = 0.56). Hong Kong nurses emphasized the need for increased bereavement care knowledge and experience, improved communication skills, and greater hospital and team members' support. Findings may be used to improve support of nurses, to ensure sensitive bereavement care in perinatal settings, and to enhance nursing curricula. The desire of Hong Kong nurses for bereavement education highlights the universality of grief for a lost infant, regardless of cultural differences in approaching emotional topics. This study may help nurses in the United States and elsewhere gain a broader perspective in this area.


The impact of electrical stimulation techniques on behavior.
Low-intensity transcranial electrical stimulation (tES) methods are a group of noninvasive brain stimulation techniques, whereby currents are applied with intensities typically ranging between 1 and 2 mA, through the human scalp. These techniques have been shown to induce changes in cortical excitability and activity during and after the stimulation in a reversible manner. They include transcranial direct current simulation (tDCS), transcranial alternating current simulation (tACS), and transcranial random noise stimulation (tRNS). Currently, an increasing number of studies have been published regarding the effects of tES on cognitive performance and behavior. Processes of learning and increases in cognitive performance are accompanied by changes in cortical plasticity. tES can impact upon these processes and is able to affect task execution. Many studies have been based on the accepted idea that by increasing cortical excitability (e.g., by applying anodal tDCS) or coherence of oscillatory activity (e.g., by applying tACS) an increase in performance should be detected; however, a number of studies now suggest that the basic knowledge of the mechanisms of action is insufficient to predict the outcome of applied stimulation on the execution of a cognitive or behavioral task, and so far no standard paradigms for increasing cortical plasticity changes during learning or cognitive tasks have been established. The aim of this review is to summarize recent findings with regard to the effects of tES on behavior concentrating on the motor and visual areas. WIREs Cogn Sci 2014, 5:649-659. doi: 10.1002/wcs.1319 For further resources related to this article, please visit the WIREs website. The authors have declared no conflicts of interest for this article.


The effect of the layer-interlayer chemistry of LDHs on developing high temperature carbon capture materials.
The layer-interlayer chemistry of layered double hydroxides (LDHs) offers a vast opportunity to develop mixed metal oxides (MMOs) as novel sorbents for high temperature CO2 capture. Here, we report the synthesis of adamantanecarboxylate intercalated Ca-Al LDH by employing a co-hydration method. Thermal decomposition under a controlled atmosphere converts the layered metal hydroxides to MMOs and an intercalated anion into a carbonaceous support. The higher thermal stability and polymeric nature of the intercalated adamantanecarboxylate ion act as a thermal/mechanical support for the layered MMOs. The resultant hybrid solid sorbent shows excellent high temperature CO2 capture and cycling performance under both CO2 rich and lean (industrial flue gas) conditions. The hybrid sample shows almost 100% carbonation of all the active phase present, leading to maximum atom efficiency. The hybrid sorbent also shows rapid kinetics for both the carbonation and regeneration steps. The employed synthetic strategy offers a new approach to develop improved novel sorbents based on LDHs for high temperature CO2 capture.


Nanoparticle-plant interaction: Implications in energy, environment, and agriculture.
In the recent techno-scientific revolution, nanotechnology has gained popularity at a rapid pace in different sectors and disciplines, specifically environmental, sensing, bioenergy, and agricultural systems. Controlled, easy, economical, and safe synthesis of nanomaterials is desired for the development of new-age nanotechnology. In general, nanomaterial synthesis techniques, such as chemical synthesis, are not completely safe or environmentally friendly due to harmful chemicals used or to toxic by-products produced. Moreover, a few nanomaterials are present as by-product during washing process, which may accumulate in water, air, and soil system to pose serious threats to plants, animals, and microbes. In contrast, using plants for nanomaterial (especially nanoparticle) synthesis has proven to be environmentally safe and economical. The role of plants as a source of nanoparticles is also likely to expand the number of options for sustainable green renewable energy, especially in biorefineries. Despite several advantages of nanotechnology, the nano-revolution has aroused concerns in terms of the fate of nanoparticles in the environment because of the potential health impacts caused by nanotoxicity upon their release. In the present panoramic review, we discuss the possibility that a multitudinous array of nanoparticles may find applications convergent with human welfare based on the synthesis of diverse nanoparticles from plants and their extracts. The significance of plant-nanoparticle interactions has been elucidated further for nanoparticle synthesis, applications of nanoparticles, and the disadvantages of using plants for synthesizing nanoparticles. Finally, we discuss future prospects of plant-nanoparticle interactions in relation to the environment, energy, and agriculture with implications in nanotechnology.


Effect of Zinc Supplementation on Early Outcome of Neonatal Sepsis--A Randomized Controlled Trial.
To find the effect of zinc supplementation on the outcome of neonatal sepsis at one month of age. This randomized controlled trial was conducted in a tertiary care neonatal unit, enrolling neonates with clinical features of sepsis and positive blood culture or positive sepsis screening tests. The treatment group received 3 mg/kg/twice a day of zinc sulfate monohydrate orally for 10 d along with standard antibiotic therapy. The control group received standard antibiotic treatment without zinc. Samples were collected from both the groups before and after the treatment. Babies were monitored till discharge and followed up as out-patients till one month of age. Demographic characteristics were similar between the cases and controls. After 10 d of treatment, the mean serum zinc level between the two groups was 737.09 ± 219.97 vs. 801.26 ± 405.56, (p = 0.20). Outcome measures like days of hospital stay (15 vs. 15; p = 0.69) and mortality rate (4.5% vs. 13.6%; p = 0.27) were not found to be significantly different between the groups. At one month of age, more number of control neonates had abnormal neurological findings as compared to the zinc supplemented group [(P = 0.02); RR (95%CI) = 0.28 (0.11-0.73)]. Zinc supplementation in neonates with sepsis improves the neurological status at one month of age although the mortality reduction was not statistically significant.