Hepatitis B and Hepatitis C in prisons: a prevalence study.
Prisons, which are hazardous places for various contagious diseases, carry additional risks for HBV and HCV because of the communal lifestyle (common use of tools like razor blades, tattoo applications, intravenous drug use and homosexual intercourse). The purpose of this paper is to determine the prevalence of HBV and HCV, and also provide information for prisoners in this respect. This study included 180 prisoners from the Buca F-Type Closed Prison, and 180 prisoners from the Foça Open Prison in Turkey. After the training seminars, serum levels of HBsAg, anti HBs, anti HBc total and anti HCV in the prisoners were assessed using the MICROELISA method. All the prisoners were male. The mean age was 40(21-73) years. According to the results of 360 prisoners from both prisons, 17 (4.7 percent) prisoners were HBsAg positive and were diagnosed as HBV. Isolated anti HBs was positive in 33 (9.1 percent) prisoners who had been previously vaccinated. In 25 (6.9 percent) prisoners isolated Anti HBc total was positive, and in 61 (16.9 percent) prisoners both Anti HBs and Anti HBc total was positive in those who were considered to be recovered from the HBV. Anti HCV was positive in 2 (0.5 percent) prisoners; the process was repeated twice, and found to be repeatedly positive. Coinfection of HBV and HCV was not detected. In this study, the prevalence of HBV and HCV was determined to be similar to those in the normal population. However, it is not expedient to generalize this result and apply it to all prisons. For the sake of public health, prisons should be scanned for infectious diseases, and vaccinations must be applied as necessary, in order to provide protection. It is a study to determine the prevalence of HBV and HCV in the prisoner population, which constitute one of the risk groups because of the communal lifestyle (common use of some tools such as the razor blade, tattoo applications, intravenous drug use and homosexual intercourse), and to compare the results with other groups in Turkey and globally.


Elevating physical activity as a public health priority: establishing core competencies for physical activity practitioners in public health.
Physical activity has emerged as a vital area of public health. This emerging area of public health practice has created a need to develop practitioners who can address physical activity promotion using population-based approaches. Variations in physical activity practitioners' educations and backgrounds warranted the creation of minimal standards to establish the competencies needed to address physical activity as a public health priority. The content knowledge of physical activity practitioners tends to fall into 2 separate areas--population-based community health education and individually focused exercise physiology. Competencies reflect the importance of a comprehensive approach to physical activity promotion, including areas of community health while also understanding the physiologic responses occurring at the individual level. Competencies are organized under the Center for Disease Control and Prevention's 5 benchmarks for physical activity and public health practice. The greatest impact on physical activity levels may be realized from a well-trained workforce of practitioners. Utilization of the competencies will enable the physical activity practitioner to provide technical assistance and leadership to promote, implement, and oversee evaluation of physical activity interventions.


Durable complete responses in metastatic colorectal cancer treated with chemotherapy alone.
The median survival for patients with metastatic colorectal cancer (mCRC) has progressively increased over the past decades. Since the introduction of 5-fluorouracil (5-FU)-based chemotherapy, followed by hepatic resection of metastases, and more recently the adoption of newer chemotherapeutic regimens associated with targeted therapy, the gains are getting more substantial. Despite the recognition of the potential for long-term survival after surgical resection of metastatic disease, long-term survival data to determine the potential curative role of chemotherapy alone is lacking. We performed a retrospective review of 2751 patients who presented with mCRC at The MD Anderson Cancer Center from 1990 through 2003. Patients alive at 5 years who achieved complete response with chemotherapy and were not submitted to any surgical or interventional procedures directed to the metastatic sites were included in the analysis. The 5-year overall survival rate for all patients with mCRC during this period was 10.8%. Among these long-term survivors, 2.2% achieved a sustained complete response after chemotherapy (all 6 with fluoropyrimidines and 2 with irinotecan) as the only treatment modality and were without evidence of disease until the last follow-up visit (median of 10.3 years). This number corresponds to 0.24% (6 of 2541) of all patients with mCRC included in this review. Cure with chemotherapy alone is possible for a very small number of patients with metastatic colorectal cancer. Improved therapies are increasing complete response rates, but the impact of modern chemotherapy on durable complete responses will require additional follow up.


[Arsenic Intake: Impact in Human Nutrition and Health].
Arsenic is an element that is widely distributed throughout the environment. Its compounds are mainly in the state of pentavalent and trivalent oxidation; and in inorganic and organic forms. Arsenical species vary in their degree of toxicity, with inorganic compounds being more toxic than organic and trivalent compounds more toxic than pentavalent compounds. There would be interconversion between the less toxic species and other more toxic species and the cooking and processing methods could affect it. Arsenic is a carcinogenic agent and causes multiple negative effects on human health in the short and long term. Non-occupational human exposure to arsenic occurs mainly through water and food. The regulation is variable for each country and is based on WHO standards, the Codex Alimentarius, and the European Union. Many studies focus on determining the total arsenic content but do not identify arsenical species in foods. Globally, fish and seafood, chicken, meat, rice, and seaweed have high levels of arsenic. In Peru, there are few studies on total arsenic content and arsenical species in food despite the fact that we have areas with high levels of environmental contamination. The objective of this review is to discuss exposure to arsenic through food and water intake, related regulations, toxicity, consequences on human health and main foods that contribute to its intake.


Differences in fatty acid composition of human milk in vegetarian and nonvegetarian women: long-term effect of diet.
The purpose of the current study was to determine whether there were differences in the fatty acid composition of milk from vegetarian mothers compared to nonvegetarian mothers and whether fatty acid composition was related to length of time on a vegetarian diet. Median time on a vegetarian diet was 81 months (range 36-132 months). Milk fat and fatty acids produced de novo in the mammary gland did not differ between diet groups. Milk from vegetarian women (n = 12) contained higher percentages of the precursors of arachidonic acid compared to nonvegetarian women (n = 7). Although there was no difference between diet group in the amount of arachidonic acid present (percent of total), a lower percentage was observed in women the longer they were on a vegetarian diet (r = -0.724, p = 0.008), with a corresponding higher percentage of the sum of precursors of arachidonic acid (r = 0.563, p = 0.056). The percentage of docosahexenoic acid was similar in the milk of vegetarian women compared to nonvegetarian women. The length of time on a vegetarian diet had no effect on these two fatty acids. In summary, differences in fatty acid content were apparent between the two dietary groups and changes with time on a vegetarian diet suggest that not only does current maternal diet affect fatty acid milk composition, but long-term dietary habits may as well.


Association of 5-HT2C (rs3813929) and UCP3 (rs1800849) gene polymorphisms with type 2 diabetes in obese women candidates for bariatric surgery.
Obesity can cause systemic arterial hypertension (SAH) and type 2 diabetes mellitus (DM2) factor that is also influenced by genetic variability. The present study aims to investigate the association between gene polymorphisms related with obesity on the prevalence of SAH and DM2 in the preoperative period and 1 year after Roux-en-Y gastric bypass surgery. In total, 351 obese women in a Brazilian cohort completed the study. The clinical diagnosis of SAH and DM2 was monitored from medical records. Twelve gene polymorphisms (rs26802; rs572169; rs7799039; rs1137101; rs3813929; rs659366; rs660339; rs1800849; rs7498665; rs35874116; rs9701796; and rs9939609) were determined using real-time polymerase chain reaction and TaqMan assay. In the preoperative period, prevalence of SAH and DM2 was 57% and 22%, respectively. One year postoperatively, 86.8% subjects had remission of DM2 and 99.5% had control of SAH. Subjects with T allele from the serotonin receptor gene (5-HT2C, rs3813929) had five times greater chance of DM2, and the CC genotype from uncoupling protein 3 gene (UCP3, rs1800849) had three times greater chance in the preoperative period. These findings indicate that polymorphisms rs3813929 and rs1800849 from 5-HT2C and UCP3 genes were related to DM2 prevalence among the Brazilian obese women candidates for bariatric surgery.


Lipoprotein(a) and Risks of Peripheral Artery Disease, Abdominal Aortic Aneurysm, and Major Adverse Limb Events.
Lp(a) (lipoprotein[a])-lowering therapy to reduce cardiovascular disease is under investigation in phase 3 clinical trials. High Lp(a) may be implicated in peripheral artery disease (PAD), abdominal aortic aneurysms (AAAs), and major adverse limb events (MALE). The authors investigated the association of high Lp(a) levels and corresponding LPA genotypes with risk of PAD, AAA, and MALE. The authors included 108,146 individuals from the Copenhagen General Population Study. During follow-up, 2,450 developed PAD, and 1,251 AAAs. Risk of MALE was assessed in individuals with PAD at baseline and replicated in the Copenhagen City Heart Study. Higher Lp(a) was associated with a stepwise increase in risk of PAD and AAA (P for trend <0.001). For individuals with Lp(a) levels ≥99th (≥143 mg/dL, ≥307 nmol/L) vs <50th percentile (≤9 mg/dL, ≤17 nmol/L), multivariable-adjusted HRs were 2.99 (95% CI: 2.09-4.30) for PAD and 2.22 (95% CI: 1.21-4.07) for AAA. For individuals with PAD, the corresponding incidence rate ratio for MALE was 3.04 (95% CI: 1.55-5.98). Per 50 mg/dL (105 nmol/L) genetically higher Lp(a) risk ratios were 1.39 (95% CI: 1.24-1.56) for PAD and 1.21 (95% CI: 1.01-1.44) for AAA, consistent with observational risk ratios of 1.33 (95% CI: 1.24-1.43) and 1.27 (95% CI: 1.15-1.41), respectively. In women smokers aged 70 to 79 years with Lp(a) <50th and ≥99th percentile, absolute 10-year risks of PAD were 8% and 21%, and equivalent risks in men 11% and 29%, respectively. For AAA, corresponding risks were 2% and 4% in women, and 5% and 12% in men. High Lp(a) levels increased risk of PAD, AAA, and MALE by 2- to 3-fold in the general population, opening opportunities for prevention given future Lp(a)-lowering therapies.


Counterion adsorption theory of dilute polyelectrolyte solutions: apparent molecular weight, second virial coefficient, and intermolecular structure factor.
Polyelectrolyte chains are well known to be strongly correlated even in extremely dilute solutions in the absence of additional strong electrolytes. Such correlations result in severe difficulties in interpreting light scattering measurements in the determination of the molecular weight, radius of gyration, and the second virial coefficient of charged macromolecules at lower ionic strengths from added strong electrolytes. By accounting for charge-regularization of the polyelectrolyte by the counterions, we present a theory of the apparent molecular weight, second virial coefficient, and the intermolecular structure factor in dilute polyelectrolyte solutions in terms of concentrations of the polymer and the added strong electrolyte. The counterion adsorption of the polyelectrolyte chains to differing levels at different concentrations of the strong electrolyte can lead to even an order of magnitude discrepancy in the molecular weight inferred from light scattering measurements. Based on counterion-mediated charge regularization, the second virial coefficient of the polyelectrolyte and the interchain structure factor are derived self-consistently. The effect of the interchain correlations, dominating at lower salt concentrations, on the inference of the radius of gyration and on molecular weight is derived. Conditions for the onset of nonmonotonic scattering wave vector dependence of scattered intensity upon lowering the electrolyte concentration and interpretation of the apparent radius of gyration are derived in terms of the counterion adsorption mechanism.


Implementing smokeless tobacco control policy in Pakistan: a qualitative study among Naswar supply chain actors.
To obtain insights into the perceptions of barriers and facilitators to implementation of the WHO Framework Convention on Tobacco Control (FCTC) among smokeless tobacco (SLT) supply chain actors in the Khyber Pakhtunkhwa province of Pakistan. We conducted a qualitative study to investigate the perceptions about SLT control policy formulation and implementation among exclusive Naswar sellers and point of sale vendors. We conducted five focus group discussions in three districts of Khyber Pakhtunkhwa using combined deductive-inductive thematic analyses. We identified three central themes that potentially impact policy formulation, its implementation and application. The first theme examines the role of children in the Naswar business: as potential customers, and as potential heirs to a Naswar-selling business. A second theme targets the 'business of Naswar', which includes a specific identity of Naswar sellers, its potential to generate profits and the special case of Naswar regulation as a socially accepted and culturally rooted product. The third theme addresses the unusual ingredients of Naswar and its production process, making Naswar a health risk for consumers and producers. We also report conflicting views regarding SLT control among the supply chain actors. This study provides insights into the perceptions of important SLT supply-side stakeholders regarding various SLT control policy options based on the FCTC. While there is some opposition to policy approaches like taxation and switching of business, implementing a ban on selling SLT to minors may be a viable option for policymakers in the short term.


Evaluation of the in vitro activity of tobramycin as compared with that of gentamicin sulfate.
The in vitro activity of tobramycin was quantitatively compared with that of gentamicin sulfate against 195 bacterial isolates from clinical material. Tobramycin was found to be twice as active as gentamicin against isolates of Pseudomonas aeruginosa. Conversely, gentamicin proved fourfold more active than tobramycin against isolates of Serratia marcescens. Both drugs were of comparable activity against isolates of Staphylococcus aureus and the majority of the enterobacterial isolates other than S. marcescens. On the basis of the obtained data, the following criteria are proposed for the interpretation of diffusion susceptibility tests with 10-mug discs of gentamicin and tobramycin. Enterobacteriaceae and isolates of S. aureus are designated as susceptible to gentamicin and tobramycin if the zones of inhibition measure 15 mm or more in diameter; zones of 14 mm or less are indicative of resistance. Pseudomonadaceae are interpreted as sensitive to tobramycin and gentamicin if the inhibition zones measure at least 15 and 12 mm in diameter, respectively.


A comparative study of efficacy and safety of arformoterol and salbutamol nebulization as rescue therapy in acute non-severe asthma.
Arformoterol, a long-acting beta-2 agonist, has a rapid onset and long duration of action. Its role as rescue medication in acute asthma attack is undetermined. To compare the efficacy and tolerability of arformoterol with salbutamol nebulization, a study was conducted among 50 patients with acute non-severe asthma. Patients were randomly assigned to group 1 (n = 25) and group 2 (n = 25) who received three doses of salbutamol and arformoterol nebulization, respectively, at 20-min intervals. The peak expiratory flow rate (PEFR) was measured at the baseline and 5 min after each dose. The demographics and baseline characteristics were comparable between the two groups. The mean PEFR significantly increased in both these groups when compared with the baseline. The increases in the PEFR in two groups were similar after the third dose. The adverse effects in both these groups were minor. Arformoterol was as effective and safe as salbutamol in acute non-severe asthma.


The ADAMTS5 Metzincin Regulates Zebrafish Somite Differentiation.
The ADAMTS5 metzincin, a secreted zinc-dependent metalloproteinase, modulates the extracellular matrix (ECM) during limb morphogenesis and other developmental processes. Here, the role of ADAMTS5 was investigated by knockdown of zebrafish adamts5 during embryogenesis. This revealed impaired Sonic Hedgehog (Shh) signaling during somite patterning and early myogenesis. Notably, synergistic regulation of myod expression by ADAMTS5 and Shh during somite differentiation was observed. These roles were not dependent upon the catalytic activity of ADAMTS5. These data identify a non-enzymatic function for ADAMTS5 in regulating an important cell signaling pathway that impacts on muscle development, with implications for musculoskeletal diseases in which ADAMTS5 and Shh have been associated.


NH3-dependent NAD+ synthetase from Bacillus subtilis at 1 A resolution.
The final step of NAD+ biosynthesis includes an amide transfer to nicotinic acid adenine dinucleotide (NaAD) catalyzed by NAD+ synthetase. This enzyme was co-crystallized in microgravity with natural substrates NaAD and ATP at pH 8.5. The crystal was exposed to ammonium ions, synchrotron diffraction data were collected and the atomic model was refined anisotropically at 1 A resolution to R = 11.63%. Both binding sites are occupied by the NAD-adenylate intermediate, pyrophosphate and two magnesium ions. The atomic resolution of the structure allows better definition of non-planar peptide groups, reveals a low mean anisotropy of protein and substrate atoms and indicates the H-atom positions of the phosphoester group of the reaction intermediate. The phosphoester group is protonated at the carbonyl O atom O7N, suggesting a carbenium-ion structure stabilized by interactions with two solvent sites presumably occupied by ammonia and a water molecule. A mechanism is proposed for the second catalytic step, which includes a nucleophilic attack by the ammonia molecule on the intermediate.


Breast implant-associated anaplastic large cell lymphoma: review of a distinct clinicopathologic entity.
Primary breast anaplastic large cell lymphoma (ALCL) is rare but is more commonly seen in patients with implants; fewer than 50 cases of breast implant-associated ALCL have been reported in the English language literature. Breast implant-associated ALCL is not a disease of the breast parenchyma, but instead is a disease of the fibrous capsule surrounding the implant. The patients usually present with an effusion around the implant and, rarely, with a solid mass. Morphologically, the neoplastic cells are large, epithelioid, and pleomorphic, with abundant cytoplasm, vesicular irregular nuclei, and frequent mitoses. Occasional "hallmark" cells may be present. The lesional cells typically show strong and diffuse immunoreactivity for CD30 and often express T-cell markers, cytotoxic-associated antigens, and epithelial membrane antigen. Almost all reported cases are negative for anaplastic lymphoma kinase. Molecular genetic analyses have demonstrated T-cell receptor gene rearrangements. The differential diagnosis essentially includes poorly differentiated carcinoma, other lymphomas, and chronic inflammation. Once a diagnosis of lymphoma is established, it is important to exclude systemic anaplastic lymphoma kinase-negative ALCL involving the breast, primary cutaneous ALCL, and other CD30(+) lymphoproliferative disorders. The patients with effusion-associated ALCL often have an indolent course and excellent prognosis, responding well to excision of the fibrous capsule around the implant (capsulectomy) and implant removal. In contrast, patients who present with a distinct mass may have a more aggressive course and poor prognosis, requiring chemotherapy and/or radiation therapy.


A peroxidase-coupled method for the colorimetric determination of serum triglycerides.
We describe an enzymatic method for rapid, precise measurement of serum triglycerides with use of sample:reagent ratios as large as 1:200. Hydrolysis of triglycerides is catalyzed by lipase to produce glycerol and free fatty acids. The glycerol generated is then phosphorylated by adenosine 5'-triphosphate in the presence of glycerol kinase. Oxidation of the resulting glycerol 3-phosphate to produce hydrogen peroxide is catalyzed by L-alpha-glycerophosphate oxidase. An intense red chromogen is produced by the peroxidase-catalyzed coupling of 4-aminoantipyrene and sodium 2-hydroxy-3,5-dichlorobenzenesulfonate with hydrogen peroxide. This sensitive chromogen system not only permits use of unusually small sample volumes, it also facilitates a linear response to serum triglyceride concentrations up to at least 10 g/L while displaying good Ringbom (measure of accuracy) characteristics.


Serum biomarkers from cell-based assays for AhRL and MIS strongly predicted the future development of diabetes in a large community-based prospective study in Korea.
Exposure to environment-polluting chemicals (EPC) is associated with the development of diabetes. Many EPCs exert toxic effects via aryl hydrocarbon receptor (AhR) and/or mitochondrial inhibition. Here we investigated if the levels of human exposure to a mixture of EPC and/or mitochondrial inhibitors could predict the development of diabetes in a prospective study, the Korean Genome and Epidemiological Study (KoGES). We analysed AhR ligands (AhRL) and mitochondria-inhibiting substances (MIS) in serum samples (n = 1,537), collected during the 2008 Ansung KoGES survey with a 4-year-follow-up. Serum AhRL, determined by the AhR-dependent luciferase reporter assay, represents the contamination level of AhR ligand mixture in serum. Serum levels of MIS, analysed indirectly by MIS-ATP or MIS-ROS, are the serum MIS-induced mitochondria inhibiting effects on ATP content or reactive oxygen species (ROS) production in the cultured cells. Among 919 normal subjects at baseline, 7.1% developed impaired glucose tolerance (IGT) and 1.6% diabetes after 4 years. At the baseline, diabetic and IGT sera displayed higher AhRL and MIS than normal sera, which correlated with indices of insulin resistance. When the subjects were classified according to ROC cut-off values, fully adjusted relative risks of diabetes development within 4 years were 7.60 (95% CI, 4.23-13.64), 4.27 (95% CI, 2.38-7.64), and 21.11 (95% CI, 8.46-52.67) for AhRL ≥ 2.70 pM, MIS-ATP ≤ 88.1%, and both, respectively. Gender analysis revealed that male subjects with AhRL ≥ 2.70 pM or MIS-ATP ≤ 88.1% showed higher risk than female subjects. High serum levels of AhRL and/or MIS strongly predict the future development of diabetes, suggesting that the accumulation of AhR ligands and/or mitochondrial inhibitors in body may play an important role in the pathogenesis of diabetes.


Chemometrics-Based Aroma Discrimination of 14 Egyptian Mango Fruits of Different Cultivars and Origins, and Their Response to Probiotics Analyzed via SPME Coupled to GC-MS.
The present study investigated the volatile organic compounds (VOCs) in 14 Egyptian mango specimens collected from three different regions and of different cultivars (cvs). VOCs were extracted via solid-phase microextraction, followed by gas chromatography-mass spectrometry analysis. The results obtained for sesquiterpene hydrocarbons' qualitative abundance were represented by 28 peaks, whereas monoterpene hydrocarbons amounted for the highest levels in most of the mango cvs. Multivariate data analyses were employed for sample classification and identification of markers. Unsupervised principal component analysis revealed that "zebdia" cv from the three origins combined together being enriched in terpinolene. Moreover, supervised orthogonal partial least square-discriminant analysis identified β-terpinene and (Z)-geranylacetone in the premium "awees" cv. The impact of probiotic bacteria on mango juice aroma was further assessed revealing no potential changes in the composition. This study provides the first comprehensive insights into Egyptian mango aroma and reveals that the cv type overcomes the geographical origin in their aroma profile.


Genetic polymorphisms of xeroderma pigmentosum group D and prostate cancer risk: a meta-analysis.
The Xeroderma pigmentosum group D (XPD, also referred to as excision repair cross complementing gene 2, ERCC2) is one of key genes involved in nucleotide excision repair and two potentially functional polymorphisms of XPD (Asp312Asn and Lys751Gln) have been widely investigated in various cancers including prostate cancer. However, the results were conflicting rather than conclusive. Thus, we conducted a meta-analysis to evaluate the associations between these two polymorphisms of XPD and the risk of prostate cancer. An electronic search of PubMed and Embase was conducted to select relevant studies. Studies containing available genotype frequencies of XPD Asp312Asn and Lys751Gln were chosen, and the associations were assessed by pooled odds ratios with 95% confidence intervals. According to PubMed and Embase databases, we identified seven eligible studies from six articles, including 2641 cases and 3259 controls for Asp312Asn and nine eligible studies from eight articles, including 3255 cases and 3654 controls for Lys751Gln. The meta-analysis showed that no overall association was observed between XPD Asp312Asn and prostate cancer risk. However, the significantly increased risk of 312Asp allele was found among Asians and Africans, but it seemed to be protective in Caucasians when stratified by ethnicity. For XPD Lys751Gln, overall findings had implicated null effects. These findings indicated that the Asn allele of XPD Asp312Asn might be a risk-factor for developing prostate cancer among Asian and African men but protective for Caucasian population.


Accelerated intermittent theta burst stimulation in major depressive disorder: A systematic review.
Major depressive disorder [MDD] is expected to be the leading cause of overall global burden of disease by the year 2030 [WHO]. Non-response to first line pharmacological and psychotherapeutic antidepressive treatments is substantial, with treatment-resistant depression [TRD] affecting approximately one third of depressed patients. There is an urgent need for rapid acting and effective treatments in this population. Repetitive Transcranial Magnetic Stimulation [rTMS] is an non-invasive treatment option for patients with MDD or TRD. Recent studies have proposed new paradigms of TMS, one paradigm is accelerated intermittent Theta Burst Stimulation [aiTBS]. This systematic review assesses the efficacy, safety and tolerability of aiTBS in patients with MDD. This review was registered with PROSPERO [ID number: 366556]. A systematic literature review was performed using Pubmed, Web of Science and PsycINFO. Case reports/series, open-label and randomized controlled trials [RCTs] were eligible for inclusion if they met the following criteria; full text publication available in English describing a form of aiTBS for MDD or TRD. aiTBS was defined as at least three iTBS treatments sessions per day, during at least four days for one week. 32 studies were identified describing aiTBS in MDD, 13 studies described overlapping samples. Six articles from five unique studies met eligibility criteria; two open-label studies and three RCTs [two double blind and one quadruple blind]. Response rates directly after treatment ranged from 20.0% to 86.4% and remission rates ranged from 10.0 to 86.4%. Four weeks after treatment response rates ranged from 0.0% to 66.7% and remission rates ranged from 0.0% to 57.1%. Three articles described a significant reduction in suicidality scores. aiTBS was well tolerated and safe, with no serious adverse events reported. aiTBS is a promising form of non-invasive brain stimulation [NIBS] with rapid antidepressant and antisuicidal effects in MDD. Additionally, aiTBS was well tolerated and safe. However, the included studies had small samples sizes and differed in frequency, intersession interval, neuro localization and stimulation intensity. Replication studies and larger RCTs are warranted to establish efficacy, safety and long term effects.


Recovery heart rate: an indicator of cardiovascular risk among middle school children.
Recovery heart rate (RHR) has been used in adults to evaluate cardiovascular (CV) fitness, but less is known about RHR in children. Data from 1,276 participants in Project Healthy Schools, a school-based intervention in southeast Michigan, were collected. In addition, to demographic characteristics, physiologic factors examined included body mass index (BMI), lipid and glucose levels, blood pressure, and HR. Information on diet, physical activity, and sedentary behavior was collected through self-report. RHR was determined by measurement of HR after a 3-minute step test. Using quartiles of RHR as a marker of fitness, associations with demographic, physiologic, and behavioral factors were explored using χ(2) and Student t tests. Compared with children in the lowest quartile of RHR (i.e., most fit), those in the upper quartile of RHR (i.e., least fit) had greater mean LDL cholesterol (93.0 vs. 86.7 mg/dL; P = 0.02) and lower mean HDL cholesterol (50.9 vs. 55.9 mg/dL; P < 0.001). Children in the upper 95 % of BMI had greater mean RHR compared with those in the normal BMI range (116.6 vs. 100.3 kg/m(2)). Children in the upper quartile of RHR reported fewer days of vigorous to moderate exercise per week compared with children in the lowest quartile of RHR [4.8 vs. 4.1 (P < 0.001) for moderate exercise and 3.6 vs. 3.0 (P = 0.001) for vigorous exercise]. Among middle school children, RHR appears to be associated with physiologic parameters and health behaviors. RHR may be useful for identifying children at increased risk for developing CV risk factors.


Effect of water activity on enterotoxin B production and growth of Staphylococcus aureus.
Staphylococcus aureus C-243, an enterotoxin B-producing strain, was cultured on media adjusted to various water activity (a(w)) levels by means of two different solute systems. Total numbers and rate of growth were diminished at low a(w) levels, and enterotoxin synthesis was extremely sensitive to reduction in a(w). A reduction of a(w) from 0.99 to 0.98 in one medium and from 0.99 to 0.97 in the other medium resulted in extremely low levels of enterotoxin in spent culture media despite the attainment of high numbers of staphylococci.


Lean in messages increase attributions of women's responsibility for gender inequality.
Although women's underrepresentation in senior-level positions in the workplace has multiple causes, women's self-improvement or "empowerment" at work has recently attracted cultural attention as a solution. For example, the bestselling book Lean In states that women can tackle gender inequality themselves by overcoming the "internal barriers" (e.g., lack of confidence and ambition) that prevent success. We sought to explore the consequences of this type of women's empowerment ideology. Study 1 found that perceptions of women's ability to solve inequality were associated with attributions of women's responsibility to do so. Studies 2, 3, 5a, and 5b experimentally manipulated exposure to women's empowerment messages, finding that while such messages increase perceptions that women are empowered to solve workplace gender inequality, they also lead to attributions that women are more responsible both for creating and solving the problem. Study 4 found a similar pattern in the context of a specific workplace problem, and found that such messages also lead to a preference for interventions focused on changing women rather than changing the system. Studies 5a and 5b sought to replicate prior studies and document the weakened effects of messages that explicitly explain that women's "internal barriers" are the products of "external barriers" obstructing women's progress. This research suggests that self-improvement messages intended to empower women to take charge of gender inequality may also yield potentially harmful societal beliefs. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Carceral-community epidemiology, structural racism, and COVID-19 disparities.
Black and Hispanic communities are disproportionately affected by both incarceration and COVID-19. The epidemiological relationship between carceral facilities and community health during the COVID-19 pandemic, however, remains largely unexamined. Using data from Cook County Jail, we examine temporal patterns in the relationship between jail cycling (i.e., arrest and processing of individuals through jails before release) and community cases of COVID-19 in Chicago ZIP codes. We use multivariate regression analyses and a machine-learning tool, elastic regression, with 1,706 demographic control variables. We find that for each arrested individual cycled through Cook County Jail in March 2020, five additional cases of COVID-19 in their ZIP code of residence are independently attributable to the jail as of August. A total 86% of this additional disease burden is borne by majority-Black and/or -Hispanic ZIPs, accounting for 17% of cumulative COVID-19 cases in these ZIPs, 6% in majority-White ZIPs, and 13% across all ZIPs. Jail cycling in March alone can independently account for 21% of racial COVID-19 disparities in Chicago as of August 2020. Relative to all demographic variables in our analysis, jail cycling is the strongest predictor of COVID-19 rates, considerably exceeding poverty, race, and population density, for example. Arrest and incarceration policies appear to be increasing COVID-19 incidence in communities. Our data suggest that jails function as infectious disease multipliers and epidemiological pumps that are especially affecting marginalized communities. Given disproportionate policing and incarceration of racialized residents nationally, the criminal punishment system may explain a large proportion of racial COVID-19 disparities noted across the United States.


Evaluation of an endoscopic suturing device for transoral outlet reduction in patients with weight regain following Roux-en-Y gastric bypass.
A dilated gastrojejunal anastomosis (GJA) is thought to be associated with weight regain in patients with Roux-en-Y gastric bypass (RYGB). Due to a high rate of perioperative morbidity, surgical revision is not generally performed. The aim of this study was to assess the technical feasibility, safety, and early outcomes of a procedure using a commercially available endoscopic suturing device to reduce the diameter of the GJA. This was a retrospective analysis of 25 consecutive patients who underwent transoral outlet reduction (TORe) for dilated GJA and weight regain. An endoscopic suturing device was used to place sutures at the margin of the GJA in order to reduce its aperture. On chart review, clinical data were available at 3, 6, and 12 months. Patients had regained a mean of 24 kg from their weight loss nadir and had a mean body mass index of 43 kg/m2 at the time of endoscopic revision. Average anastomosis diameter was 26.4 mm. Technical success was achieved in all patients (100 %) with a mean reduction in anastomosis diameter to 6 mm (range 3 - 10 mm), representing a 77.3 % reduction. The mean weight loss in successful cases was 11.5 kg, 11.7 kg, and 10.8 kg at 3, 6, and 12 months, respectively. There were no major complications. This case series demonstrated the technical feasibility, safety, and efficacy of performing gastrojejunostomy reduction using a commercially available endoscopic suturing device. This technique may represent an effective and minimally invasive option for the management of weight regain in patients with RYGB.


[Relative indicators for disease outcome in breast carcinoma].
Tumor size, axillary nodal status, histologic grading and the hormonal receptor status are the established prognostic factors for breast carcinoma. Concurrent to these factors the clinical validation of the new innovative tumor characteristics from molecular biology is difficult to achieve. Clinicians are more and more interested in indicators of response to particular treatments (predictive factors) and less in prognostic factors relevant for the natural course. The hormonal receptor status is the best known predictive factor with regard to the response to hormonal treatment. Among the innovative parameters the tumor suppressor gene p53 and the oncogene Her2/neu show a good correlation to sensitivity to cytostatic treatment. The detection of more and more molecular mechanisms of tumor growth and tumor spread raise hopes that innovative treatment approaches will lead to an antineoplastic effect. The molecular tumor parameters then may play the role of predictive factors for a specific treatment. For the present the established tumor factors should be used as the base for a treatment plan and the available already known predictive factors should be taken into consideration.


[Use of the ORIM-1 microscope for determining the thickness of paraffin sections].
On measuring the thickness of paraffin sections with the help of the "OPIM-1" microscope the error for sections of optimal thickness 5--10 mkm was no more than 3%.


Feeding and the development of enteroinsular hormone secretion in the preterm infant: effects of continuous gastric infusions of human milk compared with intermittent boluses.
Preterm infants receive gastric milk feeds as continuous infusions or intermittent boluses. It is not known whether these feeding methods have different effects on the development of digestive metabolism. We have measured plasma levels of insulin, pancreatic polypeptide (PP), gastric inhibitory polypeptide (GIP), gastrin, motilin, enteroglucagon (EG) and neurotensin (NT) in 19 preterm infants (28-34 weeks gestation) tolerating full enteral feeding from birth. 7 infants received human milk by continuous infusion, 12 infants were bolus fed. Hormones were measured in cord blood and at 6 and 13 days of age; samples were drawn preprandially in bolus fed infants. Both groups showed similar significant increases in plasma motilin, PP, NT and EG levels. At 13 days infusion fed infants had higher insulin. GIP and gastrin levels. No difference in rate of weight gain was seen in the two groups of infants. We conclude that both methods of feeding induce progressive changes in circulating enteroinsular hormone levels. However, the endocrine milieu is different in the two groups, particularly since bolus-fed infants experience marked cyclical surges in hormones after boluses of milk by 13 days of age. These differences in hormone release may affect metabolic homeostasis.


Inhibition of airway smooth muscle tone by a phorbol ester in the guinea pig trachea: role of epithelium and receptor reserve of the contractile agent.
Bronchial hyperresponsiveness in patients with asthma may be associated with a damaged or dysfunctional epithelium. Also, changes in the activities of protein kinase C have been implicated in the pathogenesis of asthma. This study examined the role of protein kinase C in the modulation of airway smooth muscle tone and the influence of the epithelium on this function. Phorbol-12,13-diacetate (PDA) (10(-8) to 10(-5) M) induced concentration-dependent and epithelium-independent relaxations of guinea pig tracheal rings. PDA (10(-8) to 10(-5) M) induced significantly greater relaxations of tracheal rings contracted with 5-hydroxytryptamine (10(-5) M) than in tissues contracted to an equivalent degree with acetylcholine (10(-6) M). In experiments using phenoxybenzamine (10(-7) M and 10(-5) M), the dissociation constant (KA) for acetylcholine was significantly greater than that for 5-hydroxytryptamine. The fraction of active receptors (q) calculated for acetylcholine was significantly smaller than that calculated for an equieffective concentration of 5-hydroxytryptamine. Relaxations to PDA in tissues contracted with acetylcholine (2 x 10(-6) M) or 5-hydroxytryptamine (10(-5) M) were significantly augmented by phenoxybenzamine (10(-5) M and 10(-7) M, respectively). PDA did not affect contractions to acetylcholine (10(-8) to 10(-3) M) in the presence of epithelium but caused a significant right-ward displacement of the acetylcholine concentration-contraction curve in the absence of epithelium. The concentration-contraction curves for 5-hydroxytryptamine (10(-8) to 10(-5) M) were significantly displaced to the right by PDA in the presence or absence of epithelium. This effect was greater in the absence of epithelium.(ABSTRACT TRUNCATED AT 250 WORDS)


Novel lactone-layered double hydroxide ionomer powders for bone tissue repair.
This article describes the use of a novel lactone-layered double hydroxide polymer network (PN), derived from a poly(lactide-co-caprolactone) copolymer, as a controlled ion-release agent for artificial bone tissue regeneration. The osteogenic cell culture Saos-2 is used as a test culture to investigate the PN's performance as an extracellular ion-release agent. The compelling performance of this PN is demonstrated in both growth and osteogenic media compared with a control of cells grown on tissue culture plastic (TCP) without PN. Firstly, the PNs released concentration of magnesium ions over time ranging from 10 to 60 mM after 24 hr, depending on the PN sample. After incubation of Saos-2 with the PN, while no difference was seen in cell number, there was significant upregulation of bone-related gene expression at 14 days-~5fold increase in Bone Morphogenetic Protein 2, ~3fold increase in osteopontin and ~2fold increase in collagen Type I. In addition, normalized alkaline phosphatase activity was seen to significantly increase by ~2fold with PN presence. A ~4fold increase in collagen Type I protein expression (via Gomori Trichrome Stain) was observed with PN presence. In addition, a ~4fold increase in phosphate deposits (as seen with Von Kossa staining analysis) was seen with PN presence. It is found that this novel PN material has a significant potential for bone tissue regeneration.


Clinical service organisation for heart failure.
Chronic heart failure (CHF) is a serious, common condition associated with frequent hospitalisation. Several different disease management interventions (clinical service organisation interventions) for patients with CHF have been proposed. To assess the effectiveness of disease management interventions for patients with CHF. We searched: Cochrane CENTRAL Register of Controlled Trials (to June 2003); MEDLINE (January 1966 to July 2003); EMBASE (January 1980 to July 2003); CINAHL (January 1982 to July 2003); AMED (January 1985 to July 2003); Science Citation Index Expanded (searched January 1981 to March 2001); SIGLE (January 1980 to July 2003); DARE (July 2003); National Research Register (July 2003); NHS Economic Evaluations Database (March 2001); reference lists of articles and asked experts in the field. Randomised controlled trials comparing disease management interventions specifically directed at patients with CHF to usual care. At least two reviewers independently extracted data information and assessed study quality. Study authors were contacted for further information where necessary. Sixteen trials involving 1,627 people were included. We classified the interventions into three models: multidisciplinary interventions (a holistic approach bridging the gap between hospital admission and discharge home delivered by a team); case management interventions (intense monitoring of patients following discharge often involving telephone follow up and home visits); and clinic interventions (follow up in a CHF clinic). There was considerable overlap within these categories, however the components, intensity and duration of the interventions varied. Case management interventions tended to be associated with reduced all cause mortality but these findings were not statistically significant (odds ratio 0.86, 95% confidence interval 0.67 to 1.10, P = 0.23), although the evidence was stronger when analysis was limited to the better quality studies (odds ratio 0.68, 95% confidence interval 0.46 to 0.98, P = 0.04). There was weak evidence that case management interventions may be associated with a reduction in admissions for heart failure. It is unclear what the effective components of the case management interventions are. The single RCT of a multidisciplinary intervention showed reduced heart-failure related re-admissions in the short term. At present there is little available evidence to support clinic based interventions. The data from this review are insufficient for forming recommendations. Further research should include adequately powered, multi-centre studies. Future studies should also investigate the effect of interventions on patients' and carers' quality of life, their satisfaction with the interventions and cost effectiveness.


Risk Factors for the Development of Clostridium difficile-associated Colitis after Colorectal Cancer Surgery.
Clostridium difficile (C. difficile)-associated colitis, a known complication of colon and rectal surgery, can increase perioperative morbidity and mortality, leading to increased hospital stay and costs. Several contributing factors, including advanced age, mechanical bowel preparation, and antibiotics, have been implicated in this condition. The purpose of this study was to determine the clinical features of and factors responsible for C. difficile-associated colitis after colorectal cancer surgery. The medical records of patients who had undergone elective resection for colorectal cancer from January 2008 to April 2010 were reviewed. Cases that involved procedures such as transanal excision, stoma creation, or emergency operation were excluded from the analysis. Resection with primary anastomosis was performed in 219 patients with colorectal cancer. The rate of postoperative C. difficile-associated colitis was 6.8% in the entire study population. Preoperative metallic stent insertion (P = 0.017) and aged sixty and older (≥ 60, P = 0.025) were identified as risk factors for postoperative C. difficile-associated colitis. There were no significant differences in variables such as preoperative oral non-absorbable antibiotics, site of operation, operation procedure, and duration of prophylactic antibiotics. Among the potential causative factors of postoperative C. difficile-associated colitis, preoperative metallic stent insertion and aged sixty and older were identified as risk factors on the basis of our data. Strategies to prevent C. difficile infection should be carried out in patients who have undergone preoperative insertion of a metallic stent and are aged sixty and older years.


Professional nursing issues in the administration of investigational antiarrhythmic medications.
This article examined the trepidation that is often present with the use of investigational antiarrhythmic medications. It specifically addressed the professional and legal responsibilities to which coinvestigator nurses are accountable in the administration of these drugs. In addition, recommendations were given on how the coinvestigator nurse can assess the special needs, particularly the socioeconomic needs, of the patient who receives investigational antiarrhythmic medication so that appropriate interventions may be provided.


Microscopic and macroscopic infarct complicating pediatric epilepsy surgery.
There is some suggestion that microscopic infarct could be associated with invasive monitoring, but it is unclear if the microscopic infarct is also visible on imaging and associated with neurologic deficits. The aims of this study were to assess the rates of microscopic and macroscopic infarct and other major complications of pediatric epilepsy surgery, and to determine if these complications were higher following invasive monitoring. We reviewed the epilepsy surgery data from a tertiary pediatric center, and collected data on microscopic infarct on histology and macroscopic infarct on postoperative computed tomography (CT) or magnetic resonance imaging (MRI) done one day after surgery and major complications. Three hundred fifty-two patients underwent surgical resection and there was one death. Forty-two percent had invasive monitoring. Thirty patients (9%) had microscopic infarct. Univariable analyses showed that microscopic infarct was higher among patients with invasive monitoring relative to no invasive monitoring (20% vs. 0.5%, respectively, p < 0.001). Eighteen patients (5%) had macroscopic infarct on CT or MRI. Univariable analysis showed no significant difference in macroscopic infarct between invasive monitoring and no invasive monitoring (8% vs. 3%, respectively, p = 0.085). One patient with microscopic infarct had transient right hemiparesis, and two with both macroscopic and microscopic infarct had unexpected persistent neurologic deficits. Thirty-two major complications (9.1%) were reported, with no difference in major complications between invasive monitoring and no invasive monitoring (10% vs. 7%, p = 0.446). In the multivariable analysis, invasive monitoring increased the odds of microscopic infarct (odds ratio [OR] 15.87, p = 0.009), but not macroscopic infarct (OR 2.6, p = 0.173) or major complications (OR 1.4, p = 0.500), after adjusting for age at surgery, sex, age at seizure onset, operative type, and operative location. Microscopic infarct was associated with invasive monitoring, and none of the patients had permanent neurologic deficits. Macroscopic infarct was not associated with invasive monitoring, and two patients with macroscopic infarct had persistent neurologic deficits.


The Non-Legume Parasponia andersonii Mediates the Fitness of Nitrogen-Fixing Rhizobial Symbionts Under High Nitrogen Conditions.
Organisms rely on symbiotic associations for metabolism, protection, and energy. However, these intimate partnerships can be vulnerable to exploitation. What prevents microbial mutualists from parasitizing their hosts? In legumes, there is evidence that hosts have evolved sophisticated mechanisms to manage their symbiotic rhizobia, but the generality and evolutionary origins of these control mechanisms are under debate. Here, we focused on the symbiosis between Parasponia hosts and N2-fixing rhizobium bacteria. Parasponia is the only non-legume lineage to have evolved a rhizobial symbiosis and thus provides an evolutionary replicate to test how rhizobial exploitation is controlled. A key question is whether Parasponia hosts can prevent colonization of rhizobia under high nitrogen conditions, when the contribution of the symbiont becomes nonessential. We grew Parasponia andersonii inoculated with Bradyrhizobium elkanii under four ammonium nitrate concentrations in a controlled growth chamber. We measured shoot and root dry weight, nodule number, nodule fresh weight, nodule volume. To quantify viable rhizobial populations in planta, we crushed nodules and determined colony forming units (CFU), as a rhizobia fitness proxy. We show that, like legumes and actinorhizal plants, P. andersonii is able to control nodule symbiosis in response to exogenous nitrogen. While the relative host growth benefits of inoculation decreased with nitrogen fertilization, our highest ammonium nitrate concentration (3.75 mM) was sufficient to prevent nodule formation on inoculated roots. Rhizobial populations were highest in nitrogen free medium. While we do not yet know the mechanism, our results suggest that control mechanisms over rhizobia are not exclusive to the legume clade.


Screening for cytotoxic compounds in poor-prognostic chronic lymphocytic leukemia.
For chronic lymphocytic leukemia (CLL) patients with poor-prognostic genomic aberrations the therapeutic options are limited. We used the Spectrum Collection library to identify compounds with anti-leukemia activity in high-risk CLL. We identified substances with equal high cytotoxic activity in vitro in samples from poor-prognostic CLL (11q-/17p-, n=3) as compared to those from favourable-prognostic CLL (13q-, n=3). Cell survival was measured by fluorometric microculture cytotoxicity assay. Out of 2,000 compounds, 65 had a similar effect in both prognostic groups. Fifteen compounds were selected for dose-response experiments in 16 additional CLL samples. Of these compounds, 12 continued to have similar cytotoxicity between prognostic subgroups. Additional experiments demonstrated that in CLL cells with 11q or 17p deletion, 5-azacytidine induced apoptosis in a dose-dependent manner and lipoprotein lipase expression was reduced following orlistat treatment. Using primary cultures of cells from high-risk CLL patients for compound screening is a feasible approach and that 5-azacytidine and orlistat exemplify substances that exhibit cytotoxicity in poor-risk CLL.


PLCδ1 Plays Central Roles in the Osmotic Activation of ΔN-TRPV1 Channels in Mouse Supraoptic Neurons and in Murine Osmoregulation.
The magnocellular neurosecretory cells (MNCs) of the hypothalamus play a vital role in osmoregulation, but the mechanisms underlying MNC osmosensitivity are not fully understood. We showed previously that high osmolality activates phospholipase C (PLC) in rat MNCs in a Ca2+-dependent manner and that PLC activation is necessary for full osmotic activation of an N-terminal variant of the TRPV1 (ΔN-TRPV1) channel. We therefore hypothesized that the Ca2+-dependent δ1 isoform of PLC contributes to ΔN-TRPV1 activation and tested whether MNC function is defective in a transgenic PLCδ1 KO mouse. Water deprivation for 24 h caused greater increases in serum osmolality and losses in body weight in PLCδ1 KO mice than it did in control mice. Action potentials and ΔN-TRPV1 currents were measured in acutely isolated mouse MNCs using whole-cell patch clamp before and after exposure to hypertonic solutions. This treatment elicited a significant activation of ΔN-TRPV1 currents and an increase in firing rate in MNCs isolated from control mice, but not from PLCδ1 KO mice. Submembranous filamentous actin was measured in isolated MNCs before and after treatment with angiotensin II and hypertonic solution. Both treatments caused an increase in filamentous actin fluorescence in MNCs isolated from control mice, but both responses were significantly attenuated in MNCs from PLCδ1 KO mice. Our data demonstrate that the PLCδ1 isoform plays a key role in the activation of ΔN-TRPV1 channels and in osmosensory transduction in MNCs. This study advances our understanding of the molecular mechanisms underlying mammalian osmoregulation.SIGNIFICANCE STATEMENT Magnocellular neurosecretory cells (MNCs) of the hypothalamus play a central role in osmoregulation. We have identified a key role for the PLCδ1 isoform in the activation of ΔN-TRPV1 channels and osmosensory transduction in MNCs. The data indicate that the PLCδ1 isoform is activated by the Ca2+ influx occurring during MNC action potentials and exerts a positive feedback on ΔN-TRPV1 channels to enhance MNC excitability. This study provides evidence that PLCδ1 is a key molecule underlying osmosensory transduction, the regulation of VP release, and osmoregulation.


Transplantation of fetal suprachiasmatic nuclei into middle-aged rats restores diurnal Fos expression in host.
In young animals, the suprachiasmatic nuclei (SCN) of the hypothalamus, which are critical circadian pacemakers, exhibit a light-induced diurnal rhythm in Fos expression. The expression of this immediate-early gene has been used as an index of the activity of the SCN and their ability to respond to external cues that entrain them, such as light. In the present study, we show that by the time rats reach middle age baseline Fos expression increases prematurely during the dark and that light-induced Fos expression is blunted and delayed. We also demonstrate that transplantation of fetal tissue containing the SCN into the third cerebral ventricle of middle-aged rats enables aged hosts to regain the ability to exhibit diurnal patterns of Fos expression that are strikingly similar to those observed in young animals. Our findings lead to the following conclusions: 1) the diurnal pattern of activity of SCN cells is blunted in middle-aged rats, and 2) SCN transplants provide unique signals that enable the cellular systems of the host to regain rhythmic functional capabilities. These results provide new insights into the critical active role that the host plays in restoration of function evoked by the presence of a transplant.


The next green movement: Plant biology for the environment and sustainability.
From domestication and breeding to the genetic engineering of crops, plants provide food, fuel, fibers, and feedstocks for our civilization. New research and discoveries aim to reduce the inputs needed to grow crops and to develop plants for environmental and sustainability applications. Faced with population growth and changing climate, the next wave of innovation in plant biology integrates technologies and approaches that span from molecular to ecosystem scales. Recent efforts to engineer plants for better nitrogen and phosphorus use, enhanced carbon fixation, and environmental remediation and to understand plant-microbiome interactions showcase exciting future directions for translational plant biology. These advances promise new strategies for the reduction of inputs to limit environmental impacts and improve agricultural sustainability.


An investigation of the challenges to coordination at the interface of primary and specialized palliative care services in Switzerland: A qualitative interview study.
Good coordination of healthcare services is vital for ensuring health cost efficiency and high-quality care for patients. It is especially important in the context of palliative care as services are often highly fragmented due to a combination of diverse professional groups, organizations, and approaches to care. However, the coordination of services in this field is often evaluated as insufficient. Little is known about the challenges to coordination in this sector in Switzerland. The present study addresses this gap in research by investigating the challenges to coordination at the interface of palliative care services in Switzerland. Interviews (n = 24) with 38 healthcare practitioners working in palliative care in four cantons (Basel-City, Lucerne, Ticino, and Vaud) form the basis for this investigation. The selected cantons not only represent French, Italian, and German language regions of Switzerland but also represent diverse rural, urban, and historical contexts. Expert interviews are analyzed using structural content analysis. Three clusters of challenges to coordination were identified in the data: (1) organizational challenges to coordination, which relate to explicit forms of coordination; (2) relational challenges to coordination; and (3) structural challenges to coordination, which relate to implicit forms of coordination. The study reveals a need for better financial support for coordination in palliative care and a stronger focus on interprofessional coordination in educating professionals in palliative care. Future research on how to further foster good team coordination practices between primary and specialized palliative services merits further investigation. Since these findings are indicative of areas for improvement for coordination at the interface of Swiss palliative care services, they are of particular interest for healthcare practitioners, policymakers, and researchers involved in the evolution of coordinative practice.


Tau Phosphorylation Rates Measured by Mass Spectrometry Differ in the Intracellular Brain vs. Extracellular Cerebrospinal Fluid Compartments and Are Differentially Affected by Alzheimer's Disease.
Tau protein aggregation into neurofibrillary tangles in the central nervous system contributes to the etiology of certain neurodegenerative disorders, including Alzheimer's disease (AD). Though the mechanism of tau destabilization is not fully understood yet, tau protein has been found to be hyperphosphorylated in tau aggregates. To investigate this further, we developed a highly sensitive and specific mass spectrometry (MS) method using parallel reaction monitoring (PRM) to identify tau phosphorylation sites. This method enables us to compare the abundance of phosphorylation sites in tau proteins in the brain and cerebrospinal fluid (CSF) in humans with and without AD. We detected 29 distinct phosphorylated tau (p-tau) sites in full-length tau from soluble human brain lysate and 12 sites on truncated tau in CSF, mainly in the mid-domain. Brain soluble tau phosphorylation sites are localized on three domains including a proline-rich mid-domain, the C-terminus, and a cluster on the N-terminal projection domain not previously characterized. Some phosphorylation sites increased in CSF, while others decreased compared to brain. Notably, phosphorylation on T205 and S208, recognized by AT8 antibody defining Braak stages of brain tau aggregation, were not detected in normal brain soluble tau but were found in the CSF. Comparison of the p-tau rates from the brain and the CSF indicated that the abundance of phosphorylated sites varied in a site-specific manner. CSF tau proteins from non-AD participants were significantly hyperphosphorylated on T111, T205, S208, T217 and T231. In AD CSF, hyperphosphorylation on these sites was exacerbated, and phosphorylation on T153 and T175 specifically were detected. This supports the hypothesis that tau hyperphosphorylation could be a physiological process amplified by AD pathology. Conversely, we found that S202 was hypophosphorylated in CSF and was not hyperphosphorylated in AD, demonstrating that p-tau isoforms could have different metabolisms depending on which sites are phosphorylated. These site-specific p-tau rates are independent of tau concentration and distinct of current CSF tau and p-tau assays measuring tau isoforms levels. Targeted MS multiplexing ability and high-throughput capacity lets us envision the use of these new p-tau measurements as promising biomarkers for AD diagnosis and tracking therapeutic responses.


New Treatment Algorithms in Hodgkin Lymphoma: Too Much or Too Little?
Hodgkin lymphoma treatment continues to evolve as new means of assessing response to treatment, new appreciation of important risk factors, and more effective therapeutic agents become available. Treatment algorithms integrating functional imaging now provide the opportunity to modify therapy during its delivery, allowing adjustment of duration and intensity of chemotherapy and rationale identification of patients who may benefit from the addition of therapeutic irradiation. Novel agents, including the antibody drug conjugate brentuximab vedotin and checkpoint inhibitors such as nivolumab and pembrolizumab can improve the effectiveness of treatment while keeping toxicity within acceptable limits. Carefully designed clinical trials permit the identification of superior approaches in which efficacy is enhanced and toxicity minimized. Clinicians treating patients with Hodgkin lymphoma now have access to novel treatment approaches, which will require detailed assessment of each patient and careful discussion of the goals and risks of treatment at the time of planning primary treatment, again during delivery of that treatment as data indicating ongoing effectiveness become available, at the conclusion of initial intervention, and, when the need arises, at the time of recurrence of disease.


The psychoactive effects of antidepressants and their association with suicidality.
Although antidepressants are known to produce some adverse mental effects, their full range of psychoactive effects has not been systematically described. It has been suggested that some antidepressants are associated with increased suicidal thoughts and actions, but the issue remains controversial, and the mechanism of association, if any, is unclear. In the current study we examined descriptions of the major psychoactive and physical effects experienced by users of two commonly used antidepressants, fluoxetine and venlafaxine, as reported on a patient-oriented web site. We categorised responses into common psychoactive effects and explored associations among those effects, including reported increases in suicidal ideation. In the 468 descriptions we examined, the most commonly reported drug-induced psychoactive effects were sedation, impaired cognition, reduced libido, emotional blunting, activation (feelings of arousal, insomnia and agitation) and emotional instability. There were no differences between the two drugs in the prevalence of reporting of these effects. Activation effects were associated with involuntary movements, suggesting a physical basis. Emotional blunting was associated with cognitive impairment, reduced libido and sedation. Emotional instability, which included the reported side effects of increased anxiety, anger, aggression and mood swings, was related to activation effects and was more commonly reported by younger respondents. Increased suicidal thoughts were rare but were associated with both types of emotional effect. The effects identified are consistent with other data, and suggest that some antidepressants may induce emotional effects that are experienced as unpleasant, may impact on the symptoms of mental disorders, and may account for the suggested occurrence of increased suicidal impulses in some users.


Efficient screening of 2D molecular polymorphs at the solution-solid interface.
Formation of multiple polymorphs during two-dimensional (2D) crystallization of organic molecules is more of a routine occurrence than rarity. Although such diverse crystalline structures provide exciting possibilities for studying crystal engineering in 2D, predicting the occurrence of polymorphs for a given building block is often non-trivial. Moreover, there is scarcity of methods that can experimentally verify the presence of such crystalline polymorphs in a straightforward fashion. Here we demonstrate a relatively simple experimental approach for screening of 2D polymorphs formed at the solution-solid interface. The strategy involves use of solution flow produced by contacting a piece of tissue paper to the sample to generate a lateral density gradient along the substrate surface. In situ generation of such gradient allows rapid discovery and nanoscale separation of multiple 2D polymorphs in a single experiment. The concept is demonstrated using three structurally different building blocks that differ in terms of intermolecular interactions responsible for 2D crystal formation. The method described here represents a powerful tool for efficient screening of 2D polymorphs formed at the solution-solid interface.


The therapeutic potential of neuronal KCNQ channel modulators.
Neuronal KCNQ (Kv7) channels (KCNQ2-5 or Kv7.2-7.5, disclosed to date) were discovered by virtue of their homology with a known cardiac channel involved in long QT syndrome (KvLQT or KCNQ1, Kv7.1) and first disclosed in 1998. The involvement of KCNQ2 (Kv7.2) and KCNQ3 (Kv7.3) in a benign idiopathic neonatal epilepsy, KCNQ4 (Kv7.4) in a form of congenital deafness, and the discovery that neuronal KCNQ heteromultimers were among the molecular substrates of M-channels, resulted in a high level of interest for potential drug development strategies. A number of small-molecule modulators were quickly identified, including openers or activators such as the antiepileptic drug candidate retigabine and the structurally-related analgesic drug flupirtine (Katadolon trade mark Asta Medica), and a group of KCNQ channel inhibitors/blockers originally developed for cognition enhancement. All of these data have suggested a rich target profile for modulators of neuronal KCNQ channels, including a variety of neuronal hyperexcitability disorders and conditions for openers, such as the epilepsies, acute pain, neuropathic pain, migraine pain and some neurodegenerative and psychiatric disorders. KCNQ blockers could likewise have utility in disorders characterised by neuronal hypoactivity, including cognition enhancement and perhaps disorders of mood. Emerging patent literature suggests significant interest in neuronal KCNQ modulation in the pharmaceutical industry and significant chemical diversity concerning KCNQ modulation.


Molecular characterization of swine leucocyte antigen class II genes in outbred pig populations.
The highly polymorphic swine leucocyte antigen (SLA) genes are among the most important determinants of swine immune responses to disease and vaccines. Accurate and effective SLA genotyping methods are required to understand how SLA gene polymorphisms affect immunity, especially in outbred pigs with diverse genetic backgrounds. In this study, we present a simple and rapid molecular-based typing system for characterizing SLA class II alleles of the DRB1, DQB1 and DQA loci. This system utilizes a set of 47 sequence-specific PCR primers developed to differentiate alleles by groups that share similar sequence motifs. We applied this typing method to investigate the SLA class II diversity in four populations of outbred pigs (n = 206) and characterized a total of 19 SLA class II haplotypes, six of which were shared by at least three of the sampled pig populations. We found that Lr-0.1 (DRB1*01XX-DQB1*01XX-DQA*01XX) was the most prevalent haplotype with a combined frequency of 16.0%, followed by Lr-0.2 (DRB1*02XX-DQB1*02XX-DQA*02XX) with 14.6% and Lr-0.15b (DRB1*04XX-DQB1*0202-DQA*02XX) with 14.1%. Over 70% of the pigs (n = 147) had at least one copy of one of these three haplotypes. The PCR-based typing system described in this study demonstrates a reliable and unambiguous detection method for SLA class II alleles. It will be a valuable tool for studying the influence of SLA diversity on various immunological, pathological and physiological traits in outbred pigs.


Oxidant and Antioxidant Effects of Gentisic Acid in a 177Lu-Labelled Methionine-Containing Minigastrin Analogue.
The radiolabelling of receptor-binding peptides for therapy is a challenge since the peptide itself is exposed (during labelling, storage and transport) to radiation-induced damage, directly or indirectly, in aqueous solution. Hence, the use of radiostabilizers seems to be mandatory, especially in peptide molecules that contain radiation-sensitive amino acids. The aim of this study was to investigate the effect of two stabilizers, gentisic acid and methionine, to delve into how each of them affects the radiolabelling and stability of the minigastrin analogue [177Lu]Lu-DOTA-His-His-Glu-Ala-Tyr-Gly-Trp-Met-Asp-Phe-NH2 through the analysis of the 22 species distinguished over time by an optimized HPLC system. The stabilizers, in different combinations, were present from the beginning of the labelling process carried out at 96 °C for 15 min. The stability was studied for up to 7 days. The unexpected selective oxidation of the methionine residue of the radiolabelled peptide, promoted by gentisic acid, led to studying the effect of pH, from 3.5 to 6.0, in the presence of only this stabilizer. A pH-dependent antioxidant behaviour was revealed, showing a decrease in peptide impurities but an increase in the selective oxidation as the pH was increased. The selective oxidation of the methionine residue could be induced by oxidizing species probably produced in the reaction between gentisic acid and free radicals of water, during the protection of the radiolabelled peptide from the attack of these harmful species. Therefore, the addition of methionine becomes necessary to effectively decrease this selective oxidation in the methioninecontaining peptide.


[Multiple myeloma as a treatable cause of stroke: clinical case and review of the literature].
Monoclonal and polyclonal immunoglobulinemia, including lymphoma, Waldenström's macroglobulinemia and less commonly multiple myeloma (MM), are considered as infrequent causes of ischemic stroke. Hyperviscosity states, as well as procoagulant disturbances, both potentially treatable, have been implicated in its etiopathogenesis. The so-called "hyperviscosity syndrome" is a clinical syndrome consisting of headache, visual, auditory and vestibular disturbances, confusion and decreased level of consciousness, and is caused by extreme hypervolemia with a high degree of erythrocyte aggregation caused by paraproteinemia. However, in addition to this global cerebral ischemia syndrome, increase in blood viscosity (BV) can also be a cause of focal ischemia. We report a case of a patient diagnosed with IgG type MM, who suffered multiple vertebrobasilar transient ischemic attacks and minor ischemic strokes concurrent with a reactivation of his hematological disease. He became completely asymptomatic after specific treatment with dexamethasone of the paraproteinemia associated with MM. We discuss its pathophysiology in this report.


Rate responses of auditory nerve fibers to tones in noise near masked threshold.
The rate responses of auditory nerve fibers were measured for best frequency (BF) tone bursts in the presence of continuous background noise. Rate functions for BF tones were constructed over a 32-dB range of levels, centered on the behavioral masked thresholds of cats. The tone level at which noticeable rate changes are evoked by the tones corresponds closely to behavioral masked threshold at all noise levels used (-10- to 30-dB spectrum level). As the noise level increases, the response rate to the background noise approaches saturation, and the incremental rate response to tones decreases. At high noise levels, the rate responses to tones of low and medium spontaneous rate fibers are larger than those of high spontaneous rate fibers. Empirical statistics of auditory nerve fiber spike counts are reported; these differ from those expected of a Poisson process in that the variance is smaller than the mean. A new measure of discharge rate is described that allows rate changes to be expressed in units of a standard deviation. This measure allows tone-evoked responses to be interpreted in terms of their detectability in a signal detection task. Rate responses of low and medium spontaneous rate fibers are more detectable than those of high spontaneous rate fibers, especially at high noise levels. There appears to be sufficient information in the rate response of a small number of auditory nerve fibers to support behaviorally observed levels of detection performance.


Effect of temperature on transmembrane potential of mouse liver cells.
Mouse liver transmembrane potential (Vm), measured under steady-state conditions with conventional microelectrodes, was -40 +/- 0.6 mV, and intracellular Na+ and K+ activities, measured with liquid ion-exchanger ion-sensitive microelectrodes, were 17 +/- 2 and 104 +/- 4 mM, respectively. The corresponding K+ and Na+ equilibrium potentials (EK and ENa) were -88 and 48 mV. Vm also varied as a linear function of temperature. In the range of 37-27 degrees C, the temperature coefficient (Q10) of 1.61 was greater than the Q10 of 1.033 predicted for a direct proportion of absolute temperature. A decrease in hepatocyte EK accounted for only a small portion of the total decrease in Vm resulting due to cooling from 37 to 25 degrees C. In contrast, slopes of the linear portion of Vm versus log10 external K+ activity were -24 and -14 mV/10-fold change in external K+ activity at 37 and 25 degrees C, respectively. This is consistent with an increase of membrane Na+- to -K+ permeability ratio (PNa/PK) with cooling. Ba2+ and quinine, which block membrane K+ channels, reversibly inhibited increases in hepatocyte Vm resulting due to heating from 37 to 40 degrees C. This suggests that membrane PK varies directly with temperature. We postulate that effects of temperature on liver Vm result from temperature effects on membrane K+ channel conductance and on the Na+-K+ pump. The results also are consistent with temperature effects on kinetic parameters for opening and closing of membrane K+ channels.


Remodeling of peripheral nerve ensheathment during the larval-to-adult transition in Drosophila.
Over the course of a 4-day period of metamorphosis, the Drosophila larval nervous system is remodeled to prepare for adult-specific behaviors. One example is the reorganization of peripheral nerves in the abdomen, where five pairs of abdominal nerves (A4-A8) fuse to form the terminal nerve trunk. This reorganization is associated with selective remodeling of four layers that ensheath each peripheral nerve. The neural lamella (NL), is the first to dismantle; its breakdown is initiated by 6 hours after puparium formation, and is completely removed by the end of the first day. This layer begins to re-appear on the third day of metamorphosis. Perineurial glial (PG) cells situated just underneath the NL, undergo significant proliferation on the first day of metamorphosis, and at that stage contribute to 95% of the glial cell population. Cells of the two inner layers, Sub-Perineurial Glia (SPG) and Wrapping Glia (WG) increase in number on the second half of metamorphosis. Induction of cell death in perineurial glia via the cell death gene reaper and the Diptheria toxin (DT-1) gene, results in abnormal bundling of the peripheral nerves, suggesting that perineurial glial cells play a role in the process. A significant number of animals fail to eclose in both reaper and DT-1 targeted animals, suggesting that disruption of PG also impacts eclosion behavior. The studies will help to establish the groundwork for further work on cellular and molecular processes that underlie the co-ordinated remodeling of glia and the peripheral nerves they ensheath. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1144-1160, 2017.


Comparing the ethical challenges of forgoing tube feeding in American and Hong Kong patients with advanced dementia.
To develop a cross-cultural dialogue for enriching our understanding of how an ethical environment can be constructed in fostering tube-feeding decisions in patients with advanced dementia (AD). Drawing on the findings of two prospective case studies conducted in Boston and Hong Kong, this paper compares the decision-making patterns of forgoing tube feeding for AD patients and their emergent ethical dilemmas typified in a special dementia care unit in Boston (BCU) and a long-term care unit in Hong Kong (HKCU). Differences in forgoing tube feeding decision are delineated in the two places. No-tube-feeding practice was sustained in BCU in two ways: advance decision-making with respect paid to the patient's wishes and advance proxy decision-making focused on patient comfort. With life preservation as the prevailing value in the Hong Kong medical system, only strong family request coupled with medical evidence of patient's ability to continue hand-feeding that tube feeding would be discontinued. All patients died with some form of artificial feeding. A paradigm shift of values underpinning the practice of forgoing tube feeding in the context of palliative care is observed in three aspects. First, the emphasis on prognostication based on biomedical markers in predicting the length of survival is shifted to a focus on the "diagnosis of dying". Second, the overriding concern in conventional medical practice with preserving life is shifting to an overriding concern of "what is best for the patient." Third, in the last days of life, the conventional approach of "trying to do everything for the patient" had shifted from a technological to a relational one. Palliative measures for relieving discomfort and providing a peaceful and dignified environment in which the patient could die are the primary concern. Although the predominant medical culture in Hong Kong is biomedical, voices from the patients and family members challenge this conventional practice, and suggest that the alternative model may be a better choice.


Hydroxamic Acid and Benzoic Acid-Based STAT3 Inhibitors Suppress Human Glioma and Breast Cancer Phenotypes In Vitro and In Vivo.
STAT3 offers an attractive target for cancer therapy, but small-molecule inhibitors with appealing pharmacologic properties have been elusive. Here, we report hydroxamic acid-based and benzoic acid-based inhibitors (SH5-07 and SH4-54, respectively) with robust bioactivity. Both inhibitors blocked STAT3 DNA-binding activity in vitro and in human glioma, breast, and prostate cancer cells and in v-Src-transformed murine fibroblasts. STAT3-dependent gene transcription was blocked along with Bcl-2, Bcl-xL, Mcl-1, cyclin D1, c-Myc, and survivin expression. Nuclear magnetic resonance analysis of STAT3-inhibitor complexes defined interactions with the SH2 and DNA-binding domains of STAT3. Ectopic expression of the SH2 domain in cells was sufficient to counter the STAT3-inhibitory effects of SH4-54. Neither compound appreciably affected STAT1 or STAT5 DNA-binding activities, STAT3-independent gene transcription, or activation of a panel of oncogenic kinases in malignant cells. Each compound decreased the proliferation and viability of glioma, breast, and prostate cancer cells and v-Src-transformed murine fibroblasts harboring constitutively active STAT3. Further, in mouse xenograft models of glioma and breast cancer, administration of SH5-07 or SH4-54 effectively inhibited tumor growth. Our results offer preclinical proof of concept for SH5-07 and SH4-54 as candidates for further development as cancer therapeutics.


Revisiting the body-schema concept in the context of whole-body postural-focal dynamics.
The body-schema concept is revisited in the context of embodied cognition, further developing the theory formulated by Marc Jeannerod that the motor system is part of a simulation network related to action, whose function is not only to shape the motor system for preparing an action (either overt or covert) but also to provide the self with information on the feasibility and the meaning of potential actions. The proposed computational formulation is based on a dynamical system approach, which is linked to an extension of the equilibrium-point hypothesis, called Passive Motor Paradigm: this dynamical system generates goal-oriented, spatio-temporal, sensorimotor patterns, integrating a direct and inverse internal model in a multi-referential framework. The purpose of such computational model is to operate at the same time as a general synergy formation machinery for planning whole-body actions in humanoid robots and/or for predicting coordinated sensory-motor patterns in human movements. In order to illustrate the computational approach, the integration of simultaneous, even partially conflicting tasks will be analyzed in some detail with regard to postural-focal dynamics, which can be defined as the fusion of a focal task, namely reaching a target with the whole-body, and a postural task, namely maintaining overall stability.


A randomized control trial of Internet-delivered HIV prevention targeting rural MSM.
The Internet may be important for delivering human immunodeficiency virus (HIV) risk reduction to men who have sex with men (MSM) in rural areas. This randomized control trial (RCT) tested the acceptability and efficacy of an Internet-delivered HIV risk-reduction intervention. Two modules include a conversation between an HIV-negative man and an HIV-positive man, with interactive graphics. Ninety men were randomly assigned to intervention or wait-list control and 79% completed the study. An 'intent-to-treat' model was used. HIV/acquired immune deficiency syndrome (AIDS) knowledge, self-efficacy and outcome expectancies increased after participating in the intervention, and changes were maintained at 1-week follow-up. Participants said they would participate again. This RCT provides support for the acceptability and efficacy of the Internet for delivering HIV prevention messages to rural MSM.


Gender Differences in Risks of Suicide and Suicidal Behaviors in the USA: A Narrative Review.
We review recent research (2018-2023) on gender differences in suicidal behaviors (i.e., suicidal ideations and attempts, death by suicide). We examine research studies in the following areas: developmental period, substance use, and special populations (Veterans, sexual and gender minorities). Novel results were found in these different areas. For example, suicide rates for female youth are increasing at a faster rate relative to male youth. Further, some evidence suggests that heavy alcohol use/binge drinking is a significant and growing risk factor for suicidal behaviors in women. Military service may be a more significant risk factor for suicidal behaviors among male Veterans compared to female Veterans. Additionally, suicide rates are rising for gender minority youth/young adults. Recent research on gender differences in suicide outcomes demonstrates findings that align with previous research, as well as new insights on this important topic.


Apoptosis-like cell death in experimentally-induced cryptorchidism in adult mice.
In order to elucidate the mechanism of germ cell degeneration in experimental cryptorchidism, we examined the testes of adult mice from a morphological standpoint. Adult ICR mice were made cryptorchid either unilaterally or bilaterally. In some mice, testes were surgically replaced back into the scrotum at 2 months after induction of cryptorchidism to observe the regenerative process. Morphological changes of cryptorchid and replaced testes have been studied by light and electron microscopy. Testes were also examined by the TUNEL (TdT-mediated dUTP-biotin nick end labelling) method to evaluate whether the degenerative cells, spermatocytes and spermatids, were dying by apoptosis or by any other process(es). At 8 weeks after the induction of cryptorchidism, the seminiferous epithelium consisted only of Sertoli cells, spermatogonia, and some spermatocytes of early meiotic stages. Soon after the replacement of testes to the scrotum, most of the seminiferous tubules resumed spermatogenic processes. Many degenerating cells, especially the spermatocytes, showed condensation of the nucleus and cytoplasm in cryptorchid testes. Although the cytoplasm was markedly eosinophilic under a light microscope to imply condensation of the cytoplasm, the extent of the condensation was not as pronounced under an electron microscope as reported in previous publications. The cytoplasm showed no expansion. By the TUNEL method, many of the degenerating cells, mainly the spermatocytes, have been shown as undergoing apoptosis. These data provide evidence that at least some of the cells die by apoptosis, or by a process similar to apoptosis.


Impairment of blood-brain barrier integrity during carotid surgery as assessed by serum S-100B protein concentrations.
During carotid endarterectomy (CEA) the internal carotid artery is cross-clamped for a period of several minutes. This maneuver may cause cerebral hypoperfusion and/or impairment of the blood-brain barrier (BBB) even in cases where clinical signs are absent. The aim of the present study was to examine whether such alterations could be detected by monitoring the cerebral marker S-100B protein concentrations during and after CEA in the serum. Twenty-five consecutive patients (17 M/8 F, mean age: 64.2 years, range 47-79 years) undergoing elective CEA at our department were studied. All of these patients were without perioperative neurological deficit. Intraoperative samples were collected from internal jugular and peripheral venous blood: 1) before carotid cross-clamping; 2) immediately before declamping; 3) after clamp release. Postoperative samples were taken from peripheral blood at 6 and 24 h, respectively. S-100B was assayed in sera using an immunoluminometric technique. During carotid cross-clamping, S-100B protein concentrations in the ipsilateral jugular serum significantly (p < 0.02) increased to pre-clamp values. After declamping, however, S-100B returned to the baseline level. No differences were seen between the responses of hypertensive and normotensive patients. There was no correlation between carotid occlusion time and S-100B protein concentrations. In the peripheral venous serum no significant changes in S-100B concentrations were detected during or after CEA. We presume that the elevation of S-100B protein concentration during CEA in patients with no neurological deficits indicates the transient opening of the BBB elicited by carotid cross-clamping.


Comprehending the impact of low vision on the lives of children and adolescents: a qualitative approach.
To develop a comprehensive, conceptual model detailing the aspects of a child's life (<18 years) that are affected by low vision. Three stakeholders were involved in the developmental process of the conceptual model: children and adolescents with a visual impairment (n = 40), parents of children with a visual impairment (n = 25) and professionals of multidisciplinary rehabilitation centres and specialised schools (n = 25). Qualitative methods including focus groups, online and face-to-face brainstorming sessions and concept mapping were used to investigate the impact of visual impairment on the lives of children and adolescents and to create the conceptual model. To aid interpretation of the large age range, four age-bands were formed. For each age-band (0-2, 3-6, 7-12 and 13-17 years), a total of 153, 200, 297 and 306 statements were generated by all stakeholders, respectively. The conceptual models show that low vision affects the sensorial development as well as the physical, psychological and social well-being of children and adolescents. In addition, identified external factors (i.e. education/employment and parental influence) can either facilitate or hinder participation. The developed model shows which life aspects of children are affected by low vision. The needs identified by children and adolescents correspond not entirely to the perspective of parents and low vision professionals. Future research should focus on developing and validating a new questionnaire based on the conceptual model. This will aid goal setting, rehabilitation referral and the accomplishment of developmental milestones and life transitions of children and adolescents with a visual impairment, ultimately improving their participation and quality of life.


The influence of polymerization conditions on color stability of three indirect composite materials.
The aim of the present study was to evaluate color change and color stability against aqueous media of three indirect composite materials (Epricord, Estenia, and Twiny) that were polymerized with different systems. Disk-shaped specimens were prepared with their proprietary polymerization systems or with a metal halide light polymerization unit (Twinkle X). The specimens were then immersed in water or tea. Change in color from baseline (24 h) to 4 weeks was determined with a chromameter (ShadeEye NCC) using a white background. The L*, a*, and b* values for both states were determined, and ΔE*(ab) values were calculated. The Estenia specimens immersed in tea had significantly lower ΔL* (-7.0 to -5.6) and significantly higher ΔE*(ab) values (6.5 to 8.6) than did the Epricord and Twiny specimens, under all polymerization conditions. The results indicate that after tea immersion the Estenia material was less stable against color change than were the other two materials. The Twinkle X metal halide unit was suitable for polymerization of the three composite materials, using an exposure period of 60 s or longer.


Opportunistic feeding behaviour and Leishmania infantum detection in Phlebotomus perniciosus females collected in the human leishmaniasis focus of Madrid, Spain (2012-2018).
An outbreak of human leishmaniasis due to Leishmania infantum has been registered in an urban area of southwestern Madrid, Spain, since 2010. Entomological surveys carried out in the municipalities of Fuenlabrada, Leganés, Getafe and Humanes de Madrid showed that Phlebotomus perniciosus is the only potential vector. In this work, an intensive molecular surveillance was performed in P. perniciosus females captured in the region between 2012 and 2018. A total of 1805 P. perniciosus females were analyzed for Leishmania infection, and 1189 of them also for bloodmeal identification. Eleven different species of vertebrate were detected by amplification and subsequent sequencing of the 359 bp cytb fragment. The most prevalent blood source identified was hare (n = 553, 46.51%), followed by rabbit (n = 262, 21.95%). Less frequent were cat (n = 45, 3.80%), human (n = 34, 2.90%), pig (n = 14, 1.20%), horse (n = 11, 0.93%), sheep (n = 3, 0.25%), rhea (n = 3, 0.25%), partridge (n = 1, 0.09%) and chicken (n = 1, 0.09%). The distribution of the blood meal sources varied between the different locations. Regarding L. infantum detection, PCR amplification of a fragment of kDNA, cpb gene and ITS1 region showed 162 positive specimens (8.97%). The highest infection rate was found in the municipality of Leganés (15.17%). The results of this molecular survey in P. perniciosus, the only leishmaniasis vector in the outbreak occurred in southwestern Madrid region, showed its opportunistic blood-feeding behaviour, high infection rates and the differences between the different points. This study was an essential part of the intensive surveillance plan in the area and the results obtained have supported the implementation of control measures in the outbreak.


Synthesis of di-, tri- and tetracyclopropylhydrazines.
Previously unknown 1,1-dicyclopropylhydrazine was obtained in two steps starting from dicyclopropylamine. It serves as a convenient starting material to tri- and tetracyclopropylhydrazines, which have not been described in the literature either. Tricyclopropylhydrazine was prepared in an overall four-step sequence featuring the de Meijere-Chaplinski modification of the Kulinkovich reaction as a key step. Tetracyclopropylhydrazine was obtained by the reductive amination of the cyclopropanone ethyl trimethylsilyl acetal with 1,1-dicyclopropylhydrazine or with the parent hydrazine. Synthetic utility of these cyclopropylhydrazine building blocks is presented as well.


Neuropeptides as therapeutic approach to autoimmune diseases.
Because there are no particular molecular signatures of self, autoimmunity is the inevitable evolutionary price of being able to make effective responses against a wide variety of pathogens by the immune system. Without the various phenomena referred to as immune tolerance, the organism would surely self-destruct. Considerable evidence suggests that various endogenous neuropeptides play a major role in the education of our immune system to be self-tolerant. The fact that neuropeptides regulate various layers involved in maintenance of tolerance, including regulation of the balance between pro-inflammatory and anti-inflammatory responses and between self-reactive Th1/Th17 cells and regulatory T cells, makes them attractive candidates for the development of new therapies for the treatment of autoimmune disorders. Here we use the vasoactive intestinal peptide of a prototype of immunomodulatory neuropeptide to review the most relevant data found for other neuropeptides with similar characteristics, including melanocyte-stimulating hormone, urocortin, adrenomedullin, neuropeptide Y, cortistatin and ghrelin. We also evaluate the challenges that must be overcome before achieving their clinical application and offer our opinion on how a physiologically functional neuropeptide system contributes to general health.


Functional Outcome and Quality of Life After Nonoperative Treatment of Posterior Process Fractures of the Talus.
Fractures of the posterior process of the talus are frequently overlooked, possibly leading to nonunion, arthritis, and chronic pain. Given the rare occurrence, previous case series have been small and without functional outcome scores. Therefore, we aimed to provide evidence on outcomes after nonoperative and operative management of posterior process fractures of the talus. All patients treated at a level 1 trauma center between 2012 and 2018 were retrospectively evaluated. Patient, fracture, and treatment characteristics were collected, and functional outcome as well as quality of life were assessed. Twenty-nine patients with posterior process fractures of the talus were identified in our database. The most frequently seen mechanism of trauma was fall from height in 13 patients (44.8%). Twenty-two patients underwent primary arthrodesis or operative reduction and fixation of the fracture (75.9%). Eighty-two percent of the patients returned the questionnaires with a mean follow-up of 6 years. The 2 patients with primary arthrodesis were excluded from outcome analysis. The mean Foot Function Index score was 1.8 (range 0.0-10). The mean American Orthopaedic Foot & Ankle Society (AOFAS) score was 78.7 points (range 0-100). The mean quality of life EuroQol-5D (EQ-5D) index score was 0.78 (range -0.26 to 1). The mean visual analog scale (VAS) on overall patient satisfaction was 8.2 (range 1-10). Operative management of extended posterior talar fractures was found to provide good functional outcome, quality of life, and patient satisfaction. Although the patients treated nonoperatively were found to have less severe injuries, they demonstrated worse overall outcome, which is supportive of surgical management. Nonoperative treatment is therefore only justified in selected patients. Level IV, retrospective case series.