Cerebral Microbleed Patterns and Cortical Amyloid-β: The ARIC-PET Study.
Cerebral microbleeds (CMBs) are associated with cognitive decline, but their importance outside of cerebral amyloid angiopathy and the mechanisms of their impact on cognition are poorly understood. We evaluated the cross-sectional association between CMB patterns and cerebral Aβ (amyloid-β) deposition, by florbetapir positron emission tomography. The longitudinal ARIC study (Atherosclerosis Risk in Communities) recruited individuals from 4 US communities from 1987 to 1989. From 2012 to 2014, the ARIC-PET (Atherosclerosis Risk in Communities - Positron Emission Tomography) ancillary recruited 322 nondemented ARIC participants who completed 3T brain magnetic resonance imaging with T2*GRE as part of ARIC visit 5 to undergo florbetapir positron emission tomography imaging. Magnetic resonance imaging images were read for CMBs and superficial siderosis; on positron emission tomography, global cortical standardized uptake value ratio >1.2 was considered a positive Aβ scan. Multivariable logistic regression models evaluated CMB characteristics in association with Aβ positivity. Effect modification by sex, race, APOE status, and cognition was evaluated. CMBs were present in 24% of ARIC-PET participants. No significant associations were found between CMBs and Aβ positivity, but a pattern of isolated lobar CMBs or superficial siderosis was associated with over 4-fold higher odds of elevated Aβ when compared with those with no CMBs (odds ratio, 4.72 [95% CI, 1.16-19.16]). A similar elevated risk was not observed in those with isolated subcortical or mixed subcortical and either lobar CMBs or superficial siderosis. Although no significant interactions were found, effect estimates for elevated Aβ were nonsignificantly lower (P>0.10, odds ratio, 0.4-0.6) for a mixed CMB pattern, and odds ratios were nonsignificantly higher for lobar-only CMBs for 4 subgroups: women (versus men); Black participants (versus White participants), APOE ε4 noncarriers (versus carriers), and cognitively normal (versus mild cognitive impairment). In this community-based cohort of nondemented adults, lobar-only pattern of CMBs or superficial siderosis is most strongly associated with brain Aβ, with no elevated risk for a mixed CMB pattern. Further studies are needed to understand differences in CMB patterns and their meaning across subgroups.


Food rationing and the black market in France (1940-1944).
French food rationing was more stringent than that of any other Occupied country in Western Europe in the Second World War, and the nation's resulting aversion to a regime that controlled rations and prices would increase the difficulties of post-war governments. This article investigates the role of French state management in wartime food shortages, assessing the parts played by French policy and German interference in the food shortages, the diversion of supplies to the black market and the inequities in distribution. It finds the French rationing administration to have been poorly organized, but attributes significant responsibility to the German Occupation authorities, whose interference increased the rationing system's dysfunction. French consumers blamed the French state for the problems and relied increasingly on alternate means to supplement inadequate rations. The result was a rationing system that delivered malnourishment, social division and hostility to state management of the food supply.


Cervical Detachment Using Monopolar SupraLoop™ Electrode versus Monopolar Needle in Laparoscopic Supracervical Hysterectomy (LSH): An Interventional, Comparative Cohort Study.
Objective: Currently available monopolar loop electrodes are difficult to handle in laparoscopic supracervical hysterectomy (LSH) and are entirely disposable devices, generating additional operating costs. The aim of this interventional study was the comparison of the efficiency and safety of cervical detachment with a newly developed monopolar loop electrode (SupraLoop™) with a conventional method of cervical detachment in LSH. Material and Methods: Our study sample included 1598 patients; 1070 patients that underwent LSH with cervical detachment using the monopolar SupraLoop™ (study group) and 528 patients that underwent LSH with cervical detachment using the monopolar needle (control group). We also assessed cervical detachment time and total device application and cutting time in a subgroup of 49 patients (23 patients from the study group and 26 patients from the control group). Results: Total operation time for LSH was significantly shorter among SupraLoop™ patients (93 ± 41 minutes) when compared to patients in whom cervical detachment was performed with the needle (105 ± 44 minutes) (p < 0.001). Cervical detachment time and total device application including cutting time was significantly shorter for the SupraLoop™ group (SupraLoop vs. needle; 0.12 ± 0.21 min vs. 5.1 ± 4.4 min [p < 0.001]; 2.3 ± 1.8 min vs. 5.4 ± 2.4 min [p < 0.001]). There were no major or minor complications directly related to the use of the SupraLoop™ device, whereas two intraoperative complications were directly related to the application of the monopolar needle. Conclusion: The newly developed monopolar loop electrode (SupraLoop™) is both an effective and safe instrument for cervical detachment in laparoscopic supracervical hysterectomy, and performed better than the needle, offering a significantly shorter operating time and less complications for the hysterectomy compared to the conventional method.


[Globalization, inequity and Chagas disease].
Chagas disease (American trypanosomiasis) bears a close relationship to multiple social and political aspects involving issues of globalization and inequity. Such relations concern the process of disease production and control in parallel with medical management. Despite the poverty in Latin America and various problems related to inequities and globalization, Chagas disease has been controlled in several areas, a fact that reinforces the countries' self-reliance. Several problems and challenges related to the disease can be expected in the future, mainly concerning medical care for already infected individuals and the sustainability of effective epidemiological surveillance. Both points depend heavily on improved performance by the national health systems, principally in terms of their efficiency and their capacity to overcome inequity. A particularly important role has been attributed to the Latin American scientific and academic community in the implementation and sustainability of efficient control policies. Control activities have now evolved towards internationally shared initiatives, a major new stride forward in the region's political context.


Understanding hydrazine oxidation electrocatalysis on undoped carbon.
Carbons are ubiquitous electrocatalytic supports for various energy-related transformations, especially in fuel cells. Doped carbons such as Fe-N-C materials are particularly active towards the oxidation of hydrazine, an alternative fuel and hydrogen carrier. However, there is little discussion of the electrocatalytic role of the most abundant component - the carbon matrix - towards the hydrazine oxidation reaction (HzOR). We present a systematic investigation of undoped graphitic carbons towards the HzOR in alkaline electrolyte. Using highly oriented pyrolytic graphite electrodes, as well as graphite powders enriched in either basal planes or edge defects, we demonstrate that edge defects are the most active catalytic sites during hydrazine oxidation electrocatalysis. Theoretical DFT calculations support and explain the mechanism of HzOR on carbon edges, identifying unsaturated graphene armchair defects as the most likely active sites. Finally, these findings explain the 'double peak' voltammetric feature observed on many doped carbons during the HzOR.


Pathologizing sexual deviance: a history.
This article provides a historical perspective on how both American and European psychiatrists have conceptualized and categorized sexual deviance throughout the past 150 years. During this time, quite a number of sexual preferences, desires, and behaviors have been pathologized and depathologized at will, thus revealing psychiatry's constant struggle to distinguish mental disorder--in other words, the "perversions," "sexual deviations," or "paraphilias"--from immoral, unethical, or illegal behavior. This struggle is apparent in the works of 19th- and early-20th-century psychiatrists and sexologists, but it is also present in the more recent psychiatric textbooks and diagnostic manuals, such as the consecutive editions of the Diagnostic and Statistical Manual of Mental Disorders (DSM). While much of the historical literature revolves around the controversy over homosexuality, this article also reviews the recent medicohistorical and sociohistorical work on other forms of sexual deviance, including the diagnostic categories listed in the latest edition, the DSM-IV-TR: exhibitionism, voyeurism, fetishism, frotteurism, pedophilia, sexual masochism, sexual sadism, and transvestic fetishism.


[Private home healthcare and its strategies (apparent and hidden)].
This paper analyses the findings of an investigation into private home healthcare. Considered the most visible model of Managed Healthcare, it is being developed through the supply of multiple services. This concept is based on a set of principles - out-of-hospital care, lower infection risks, family-based benefits for patients - all linked to a cost-cutting strategy. Some labor relations aspects are also discussed that underpin the development of this type of care.


The impact of a competitive event and the efficacy of a lactic acid bacteria-fermented soymilk extract on the gut microbiota and urinary metabolites of endurance athletes: An open-label pilot study.
Diet and exercise can alter the gut microbiota, but recent studies have assessed the impact of athletic competition on gut microbiota and host metabolites. We designed an open-label pilot study to investigate the effects of both official competition and a multi-strain lactic acid bacteria-fermented soymilk extract (LEX) on the gut microbiota in Japanese college endurance athletes. The analysis of fecal 16S rRNA metagenome and urinary metabolites was used to identify changes in gut microbiota composition and host metabolism. When the fecal microbiota were investigated before and after a race without using of a supplement (pre-observation period), there was an increase in the phylum Firmicutes and decrease in Bacteroidetes. However, no changes in these phyla were seen before and after a race in those who consumed LEX. Before and after LEX ingestion, changes in urinary metabolites included a significant reduction in yeast and fungal markers, neurotransmitters, and mitochondrial metabolites including the TCA cycle. There were several correlations between urinary metabolites and the composition of fecal microbiota. For example, the level of tricarballylic acid was positively correlated with the composition ratio of phylum Firmicutes (Pearson's r = 0.66; p < 0.01). The bacterial species Parabacteroides distasonis was also found to correlate moderately with several urinary metabolites. These findings suggest two possibilities. First, endurance athletes experience significant fluctuations in gut microbiota after a single competition. Second, LEX ingestion may improve yeast and fungal overgrowth in the gastrointestinal tract and enhancing mitochondrial metabolic function.


Urine ratio of neutrophil gelatinase-associated lipocalin to creatinine as a marker for early detection of cisplatin-associated nephrotoxicity.
Cisplatin is a widely used chemotherapeutic agent with a major side effect of nephrotoxicity. Delayed increase in serum creatinine after cisplatin injection makes serum creatinine not to be an ideal marker for early detection of cisplatin nephrotoxicity. Recently several new biomarkers such as neutrophil gelatinase-associated lipocalin (NGAL) have been proposed for early detection of acute kidney injury (AKI). This study assessed kinetic of urine NGAL-creatinine ratio in patients who received cisplatin-containing chemotherapy. Patients with a glomerular filtration rates greater than 45 mL/min who received cisplatin-containing chemotherapy were included. Urine creatinine and NGAL concentrations were measured before cisplatin infusion and 6, 24, 48, and 72 hours after cisplatin administration. To minimize hydration effects, urine NGAL levels were adjusted according to urine creatinine. Twenty-four patients were assessed. According to the Acute Kidney Injury Network criteria, 2 patients (8%) experienced cisplatin-associated AKI. The median increases in urine NGAL-creatinine ratio were 335% (interquartile range, 320% to 350%) in the patients with AKI and 100% (interquartile range, 73% to 190%) in those without AKI (P = .02) during the first 24 hours after cisplatin administration. A urine NGAL-creatinine ratio greater than 26.9 ng/mg 24 hours after cisplatin infusion had a sensitivity of 86% and a specificity of 50% to detect cisplatin-associated nephrotoxicity. Urine NGAL-creatinine ratio significantly increased in patients with cisplatin-associated AKI. Urine NGAL-creatinine ratio within the first 24 hours after cisplatin infusion may better predict cisplatin-associated nephrotoxicity than serum creatinine level.


Loss of systemic endothelial function post-PCI.
Loss of endothelial function (LEF) post-PCI may contribute to both acute and long-term complications. A protective effect of BNP on endothelium was suggested previously. Flow-mediated vasodilation (FMD) of the brachial artery, as well as plasma levels of endothelin, BNP, Pro BNP and corin were measured before and following routine PCI. 49 patients with normal baseline endothelial function were recruited. 30 patients developed LEF and were randomized to i.v. nesiritide (the commercially available recombinant form of human BNP) or saline infusion for 3 h. Patients who developed LEF post-PCI had reduced baseline plasma corin levels and their BNP/ProBNP ratio was reduced after the procedure. Nesiritide infusion significantly improved FMD both immediately (Nesiritide versus saline: 2.87+/-0.78% versus 0.51+/-0.25%, P=0.007) and 24 h after the treatment (2.52+/-0.69% versus 0.72+/-0.32%, P=0.025). The elevated plasma ET-1 was reduced by Nesiritide (0.38+/-0.11 fmol/ml 24 h post-PCI versus 0.16+/-0.02 fmol/ml 24 h post BNP, P=0.047), but remained unchanged in saline group (0.39+/-0.21 fmol/ml versus 0.42+/-0.23 fmol/ml, P=0.749). Systemic LEF post-PCI is a frequent event. It may be related to impaired cleavage of ProBNP to BNP. Short-term i.v. nesiritide improves systemic LEF post-PCI.


Dietary modulation of gut functional ecology studied by fecal metabonomics.
A major source of intestinal metabolites results from both host and microbial processing of dietary nutrients. (1)H NMR-based metabolic profiling of mouse feces was carried out over time in different microbiome mouse models, including conventional (n = 9), conventionalized (n = 10), and "humanized" gnotobiotic mice inoculated with a model of human baby microbiota (HBM, n = 17). HBM mice were supplemented with Lactobacillus paracasei with (n = 10) and without (n = 7) prebiotics. Animals not supplemented with prebiotics received a diet enriched in glucose and lactose as placebo. In conventionalized animals, microbial populations and activities converged in term of multivariate mapping toward conventional mice. Both groups decreased bacterial processing of dietary proteins when switching to a diet enriched in glucose and lactose, as described with low levels of 5-aminovalerate, acetate, and propionate and high levels of lysine and arginine. The HBM model differs from conventional and conventionalized microbiota in terms of type, proportion, and metabolic activity of gut bacteria (lower short chain fatty acids (SCFAs), lactate, 5-aminovalerate, and oligosaccharides, higher bile acids and choline). The probiotics supplementation of HBM mice was associated with a specific amino acid pattern that can be linked to L. paracasei proteolytic activities. The combination of L. paracasei with the galactosyl-oligosaccharide prebiotics was related to the enhanced growth of bifidobacteria and lactobacilli, and a specific metabolism of carbohydrates, proteins, and SCFAs. The present study describes how the assessment of metabolic changes in feces may provide information for studying nutrient-microbiota relationships in different microbiome mouse models.


Organometallic chemistry of amidate complexes. accelerating effect of bidentate ligands on the reductive elimination of N-aryl amidates from palladium(II).
We report a series of arylpalladium complexes of acetamidate, sulfonamidate, and deprotonated oxazolidinone ligands that undergo reductive elimination with rates and yields that depend on the binding mode of the ancillary and amidate ligands. Complexes of the acetamidate ligands containing the bidentate phosphines DPPF and Xantphos as ancillary ligands undergo reductive elimination. The rate and yield were higher from the complex ligated by Xantphos, which contains a larger bite angle. In contrast, the analogous amidate complex containing a single sterically hindered monodentate ligand and a kappa2-bound amidate ligand does not undergo reductive elimination. This trend of faster reductive elimination from complexes containing bidentate ancillary ligands than from a complex with a single monodentate ancillary ligand is unusual and is consistent with an effect of the denticity of the ancillary ligand on the binding mode of the amidate. Complexes of sulfonamidate ligands underwent reductive elimination faster than complexes of acetamidates, and reductive elimination occurred from complexes containing both bidentate and monodentate ancillary ligands. Like reductive elimination from the acetamidate complexes, reductive eliminations from the sulfonamidate complexes were faster when the complexes possessed bidentate Xantphos and kappa1-sulfonamidate ligands.


Assessment of Vascular Patency and Inflammation with Intravascular Optical Coherence Tomography in Patients with Superficial Femoral Artery Disease Treated with Zilver PTX Stents.
Zilver PTX nitinol self-expanding drug-eluting stent with paclitaxel coating is effective for treatment of superficial femoral artery (SFA) disease. However, as with any stent, it induces a measure of vascular inflammatory response. The current clinical trial (NCT02734836) aimed to assess vascular patency, remodeling, and inflammatory markers with intravascular optical coherence tomography (OCT) in patients with SFA disease treated with Zilver PTX stents. Serial OCT examinations were performed in 13 patients at baseline and 12-month follow-up. Variables evaluated included neointimal area, luminal narrowing, thrombus area, stent expansion as well as measures of inflammation including, peri-strut low-intensity area (PLIA), macrophage arc, neovascularization, stent strut apposition and coverage. Percentage of malapposed struts decreased from 10.3 ± 7.9% post-intervention to 1.1 ± 2.2% at 12-month follow-up, but one patient showed late-acquired stent malapposition (LASM). The percent of uncovered struts at follow-up was 3.0 ± 4.5%. Average expansion of stent cross-sectional area from baseline to follow-up was 35 ± 19%. The average neointimal area was 7.8 ± 3.8 mm2. Maximal luminal narrowing was 61.1 ± 25.0%, and average luminal narrowing was 35.4 ± 18.2%. Average peri-strut low-intensity area (PLIA) per strut was 0.017 ± 0.018 mm2. Average number of neovessels per mm of stent was 0.138 ± 0.181. Average macrophage angle per frame at follow-up was 7 ± 11°. Average thrombus area at follow-up was 0.0093 ± 0.0184 mm2. At 12-month follow-up, OCT analysis of Zilver PTX stent shows outward remodeling and minimal neointimal growth, but evidence of inflammation including PLIA, neovessels, thrombus and macrophages. Thirteen patients with PAD had paclitaxel-coated stents implanted in their SFAs and were then imaged with OCT at baseline and 12-month follow-up. OCT proxy metrics of inflammation were quantified.


Meal pattern analysis to investigate the satiating potential of fat, carbohydrate, and protein in rats.
We examined meal patterns after isocaloric duodenal infusions of fat, carbohydrate (CHO), and protein by measuring meal size, intermeal interval (IMI) and total food intake (TFI). Wistar rats were adapted to normal feeding 6 h/day, with continuous computer monitoring of feeding patterns. One of five solutions (10 ml of 1 kcal/ml at 0.45 ml/min; 0, 20, 50, 80, or 100% of energy from fat) or saline (control) was infused 10 min after initiation of eating. Separate rats received casein or casein hydrolysate at 18.5 or 37% energy. Equivalent energy loads varying in fat, CHO, and protein content compared with saline resulted in similar reductions in first meal intakes. The second meal did not differ among fat and CHO treatments including saline; however, infusion with a protein-containing solution increased the size of meal 2. The IMI was doubled by protein infusion independently of dose or source but extended dose dependently by fat. TFI was lower after high fat and higher after protein than after saline infusion. The results indicate that the concentrations of fat, CHO, and protein differentially affect the qualitative and quantitative aspects of feeding in rats.


A Role for Salivary Peptides in the Innate Defense Against Enterotoxigenic Escherichia coli.
Diarrheal disease from enterotoxigenic Escherichia coli (ETEC) causes significant worldwide morbidity and mortality in young children residing in endemic countries and is the leading cause of traveler's diarrhea. As ETEC enters the body through the oral cavity and cotransits the digestive tract with salivary components, we hypothesized that the antimicrobial activity of salivary proteins might extend beyond the oropharynx into the proximal digestive tract. Here, we show that the salivary peptide histatin-5 binds colonization factor antigen I pili, thereby blocking adhesion of ETEC to intestinal epithelial cells. Mechanistically, we demonstrate that histatin-5 stiffens the typically dynamic pili, abolishing their ability to function as spring-like shock absorbers, thereby inhibiting colonization within the turbulent vortices of chyme in the gastrointestinal tract. Our data represent the first report of a salivary component exerting specific antimicrobial activity against an enteric pathogen and suggest that histatin-5 and related peptides might be exploited for prophylactic and/or therapeutic uses. Numerous viruses, bacteria, and fungi traverse the oropharynx to cause disease, so there is considerable opportunity for various salivary components to neutralize these pathogens prior to arrival at their target organ. Identification of additional salivary components with unexpectedly broad antimicrobial spectra should be a priority.


Gaps in Receipt of Clinically Indicated Genetic Counseling After Diagnosis of Breast Cancer.
Purpose Little is known about the extent to which genetic counseling is integrated into community practices for patients newly diagnosed with breast cancer. We examined the receipt of clinically indicated genetic counseling in these patients. Patients and Methods We surveyed 5,080 patients between the ages of 20 and 79 years, diagnosed from July 2013 to August 2015 with early-stage breast cancer and reported to the SEER registries of Georgia and Los Angeles County. Surveys were linked to SEER clinical data and genetic test results. The study sample (N = 1,711) comprised patients with indications for formal genetic risk evaluation. Results Overall, 47.4% did not get tested, 40.7% tested negative, 7.4% had a variant of uncertain significance only, and 4.5% had a pathogenic mutation. Three quarters (74.6%) received some form of genetic counseling (43.5%, formal counseling and 31.1%, physician-directed discussion). Virtually all tested patients (96.1%) reported some form of genetic discussion (62.2%, formal counseling and 33.9%, physician-directed discussion). However, only one half (50.6%) of those not tested received any discussion about genetics. Younger women were more likely to report some type of counseling, controlling for other factors: odds ratio, 4.5 (95% CI, 2.6 to 8.0); 1.9 (95% CI, 1.1 to 3.3); and 1.5 (95% CI, 1.0 to 2.3) for women younger than 50 years of age, 50 to 59 years of age, and 60 to 69 years of age versus those 70 years of age and older. Patients' assessments of the amount of information they received about whether to get tested were similarly high whether they were counseled by a genetics expert or by a physician only (80.8% v 79.4% stated information was just right, P = .59). Conclusion Less than one half (43.5%) of patients with clinical indications received formal genetic counseling. There is a large gap between mandates for timely pretest formal genetic counseling in higher-risk patients and the reality of practice today.


Syncope associated with swallowing in two British Bulldogs with unilateral carotid body tumours.
Carotid body tumours were diagnosed in two British Bulldogs that each had a history of syncopal episodes induced by eating, drinking or pulling on the leash. In both dogs, a cervical mass was identified using computed tomography (CT) or magnetic resonance imaging, with carotid body tumour (CBT) being the histopathological diagnosis. A heart base mass was also identified in one dog by both CT and echocardiography. Swallowing syncope has been reported in the human literature in association with cervical mass lesions, but this is the first report in dogs. The present cases emphasise the value of advanced imaging of the head and neck in dogs presenting with clinical signs of syncope associated with swallowing and the importance of careful manipulation of the neck in patients with CBTs.


[Men's health care in the scope of the Family Health Strategy].
The National Policy of Comprehensive Care for Men's Health created the guidelines for the strategies and actions based on comprehensive care, seeking the promotion of health and the prevention of disease duly focused as core issues of the Family Health Strategy (FHS). This article describes the specificities of men's health care in the context of the FHS from the standpoint of the manager, the demands of the men linked to the health units assessed and the practices adopted by the teams. Men's health care was evaluated by interviews with 43 FHS team managers (FHST), systematically selected considering the geographical region, city size and FHS coverage; and by interviewing 86 adult men of the respective FHS coverage area. It was seen that the strategy of the FHST is to address the health-disease process in the family and environmental context. However, in men's health there are still several gaps, from the adaptation of the structure of primary health care through to the motivation and development of actions against the most common health problems of this population group. This situation sometimes limits men's access to health services thereby negating the goal of the Policy.


The Relationship Between The Electromyographic Activity Of Rectus And Oblique Abdominal Muscles And Bioimpedance Body Composition Analysis - A Pilot Observational Study.
Measurements using surface electromyography (sEMG) may be more complicated when the different thickness of the subcutaneous tissue layer is observed, therefore it is important to show the influence of fat tissue on the results of sEMG measurements. The main aim of the study was to assess the relationship between the sEMG RMS value of rectus and external oblique muscles of the abdomen and the composition of the body, which was assessed using bioelectrical impedance analysis. The target group was made up of healthy people aged 20-30-year-old. The study visit protocol of the participants was as follows: a medical history, instructions on the purpose of measurements and examination procedures, obtaining consent for participation in the research, an analysis of the body weight composition by the electrical bioimpedance method, a fat tissue thickness measurement using body fat calipers, preparation of the subject for sEMG measurements (sEMG RMS value of rectus and external oblique abdominal muscles). Twenty-nine people were qualified for the study according to the inclusion and exclusion criteria. sEMG amplitudes decreased when the person had a higher fat content and had less water in the body. These results were related to the rectus abdominal muscle (mainly its upper part) during the active contraction of this muscle. In addition, it was observed that when actively bent their torsos forward people with a higher BMI and with a greater thickness of fat tissue had a lower sEMG RMS value of the rectus abdominal muscle. In order to conduct reliable examinations using sEMG, parameters concerning the amount of fat tissue, the thickness of fat tissue, BMI and amount of water in the body should be taken into account.


Intrarenal renin inhibition increases renal function by an angiotensin II-dependent mechanism.
ACRIP is a competitive inhibitor of renin in which an analogue of statine, (3R,4S)-4-amino-3-hydroxy-6-methylheptanoic acid, is incorporated into analogues of porcine renin substrate. ACRIP inhibits the enzymatic activity of renin, thus blocking the initiation of the angiotensin cascade. We studied the intrarenal action of ACRIP in small quantities without measurable systemic effects on renal function. In the first experiment, ACRIP was administered intrarenally at 0.02, 0.2, and 2 micrograms.kg-1.min-1 to uninephrectomized conscious dogs (n = 6) in metabolic balance at sodium intake of 10 meq/day. ACRIP, in doses of 0.02 and 0.2 micrograms.kg-1.min-1, markedly increased urine sodium excretion (UNaV) from 5.8 +/- 1.4 to 15.1 +/- 5.1 and 19.9 +/- 3.2 mu eq/min, respectively. Urinary flow rate (UV) underwent a similar increase and glomerular filtration rate (GFR) increased from 25.7 +/- 2.5 to 35.6 +/- 2.5 at 0.02 micrograms.kg-1.min-1 of ACRIP. Renal plasma flow (RPF), plasma renin activity (PRA), and plasma aldosterone concentration (PAC) were not affected. At 2 micrograms.kg-1.min-1, ACRIP traversed the kidney in quantities large enough to produce a reduction in systemic PRA and mean arterial pressure and caused natriuresis, diuresis, and increased GFR. In a second experiment, ACRIP was administered intrarenally at 0.2 micrograms.kg-1.min-1 in a separate group (n = 4) under identical conditions. ACRIP-induced increases in UV and UNaV were completely blocked by concurrent intrarenal administration of angiotensin II. The results indicate that intrarenal angiotensin II acts as a physiological regulator of renal sodium and fluid homeostasis.


Trends in antipsychotic prescribing practices in an urban community mental health clinic.
Availability of new psychotropic agents, and formulations, as well as expanded indications for previously available agents, has had an impact on prescribing patterns in community psychiatric practice. This study tracked changes in patient diagnostic profiles and compared antipsychotic prescribing patterns for patients managed by a continuing care team over a 2.25-year period. Data pertaining to patient diagnoses and psychotropic medications was obtained from sequential cross-sectional file review and the pharmacy database. Data were collected in late 2004 (n = 224) and early 2007 (n = 294). The majority of patients suffered from DSM-IV schizophrenia, schizoaffective and related disorders (68% in 2004, 71% in 2007). Second generation antipsychotic (SGA) medications (79% in 2004, 99% in 2007 of all antipsychotics) were the most widely used agents. Use of quetiapine as a proportion of all oral SGAs increased (8% to 17%) as did that of long-acting risperidone (<1% to 17% of all antipsychotics) paralleled by a decline in long-acting first generation antipsychotic agents (15% to <1%). Significant changes in the prescription of non-benzodiazepine hypnotics and mood stabilizers were also noted. Statistically significant changes in prescribing patterns of antipsychotics during the study period were noted. Likely causes are discussed.


Does the number of levels affect lumbar fusion outcome?
Retrospective outcome measurement after circumferential reconstructive surgery with lumbar fusion in patients with chronic discogenic low back pain. To examine the effect of the number of fusion levels on surgical outcomes in patients with chronic discogenic low back pain using provocative pressure-controlled diskography as a primary diagnostic tool. Although there is general agreement that construct length adversely affects arthrodesis success rates, the effect of the number of levels on lumbar fusion surgery outcome has not been reported. Previous fusion outcome studies have generally relied on magnetic resonance imaging or conventional diskography for diagnosis. From 1994 through 2000, prospectively collected medical records of patients who underwent reconstructive lumbar spine surgery with confirmation of the pain generator by pressure-controlled diskography were retrospectively analyzed. Data were subdivided into 2 groups of patients. The first group, designated the short segment group, contained patients who underwent fusion at 1 or 2 levels. The second group, designated the long segment group, contained patients who underwent fusion at 3-5 levels. Surgical methods included circumferential reconstruction of the lumbar spine by either posterior or combined anterior and posterior approach. Surgeries included posterior decompression necessary to relieve documented regions of neural compression, combined with interbody arthrodesis at selective levels, augmented by posterior segmental spinal instrumentation and posterolateral arthrodesis. All patients completed a preoperative aquatic-conditioning program. Whenever possible, coexisting medical conditions were corrected or stabilized before surgery. A preoperative Short Form RAND 36-Item Health Survey (SF-36) was completed, and repeated at 1 and 2 years after surgery. The short and long segment groups contained 142 and 82 patients, respectively, who completed the preoperative SF-36 questionnaire completely. One hundred patients in the short segment group (vide infra) were available for 1-year follow-up, and68 were available for 2-year follow-up. In the long segment group, 81 patients were available for 1-year follow-up, and 49 were available for 2-year follow-up. Mean ages were 41.0 and 47.6 years in the short and the long segment groups, respectively. The 2 groups did not differ significantly in gender, smoking habits, workers' compensation, or litigation (P > 0.05). In the short segment group, postoperative 1-year mean Physical Component Summary (PCS) and Mental Component Summary scores significantly improved (P < 0.001 and P = 0.002, respectively). Domains other than general health perceptions showed significantly improved 1-year follow-up scores (P <or= 0.001). Two-year follow-up scores showed significant improvement (P < 0.001 for physical function [PF], role function as limited by physical problems [RP], bodily pain [BP], social function [SF], and PCS). The vitality (VT) and role function as limited by emotional problems (RE) also improved (P = 0.005 and P < 0.05, respectively). In the long segment group, postoperative 1-year mean PCS scores improved significantly (P < 0.001), with some improvement in Mental Component Summary score (P < 0.05). The long segment group also showed significantly improved PF, RP, BP, and SF scores (P < 0.001). The VT and RE scores gave P = 0.002 and P < 0.05, respectively. Comparing preoperative and 2-year follow-up scores, PCS, PF, RP, BP, and SF showed significant improvement (P < 0.001), and the VT score gave P < 0.01. Mean difference in postoperative and preoperative scores for both groups did not show significant differences (P > 0.05), although the PF score showed differences in 1 and 2-year follow-up scores (P = 0.048 and P = 0.068, respectively). When using strict patient selection criteria that include independent determination of pain generators via pressure-controlled diskography and completion of a preoperative conditioning program for improving general health status, the number of levels in reconstructive lumbar surgery may not significantly impact overall clinical outcome.


The Internalized Homophobia Scale for Vietnamese Sexual Minority Women: Conceptualization, Factor Structure, Reliability, and Associations With Hypothesized Correlates.
We developed the first Vietnamese Internalized Homophobia (IH) scale for use with Vietnamese sexual minority women (SMW). Drawing from existing IH scales in the international literature and based on prior qualitative research about SMW in the Viet Nam context, the scale covers two domains: self-stigma (negative attitudes toward oneself as a sexual minority person) and sexual prejudice (negative attitudes toward homosexuality/same-sex relations in general). Scale items, including items borrowed from existing scales and items based on local expressions, were reviewed and confirmed by members of the target population. Quantitative evaluation used data from an anonymous web-based survey of Vietnamese SMW, including those who identified as lesbian (n = 1187), or as bisexual (n = 641) and those who were unsure about their sexual identity (n = 353). The scale was found to consist of two highly correlated factors reflecting self-stigma (not normal/wholesome and self-reproach and wishing away same-sex sexuality) and one factor reflecting sexual prejudice, and to have excellent internal consistency. Construct validity was evidenced by subscale associations with a wide range of hypothesized correlates, including perceived sexual stigma, outness, social support, connection to other SMW, relationship quality, psychological well-being, anticipation of heterosexual marriage, and endorsement of same-sex marriage legalization. Self-stigma was more strongly associated with psychosocial correlates, and sexual prejudice was more associated with endorsement of legal same-sex marriage. The variations in these associations across the hypothesized correlates and across sexual identity groups were consistent with the minority stress model and the IH literature, and exhibited context-specific features, which are discussed.


Differential macular morphology in patients with RPE65-, CEP290-, GUCY2D-, and AIPL1-related Leber congenital amaurosis.
To evaluate genotypic and macular morphologic correlations in patients with RPE65-, CEP290-, GUCY2D-, or AIPL1-related Leber congenital amaurosis (LCA) using spectral-domain optical coherence tomography (SD-OCT). SD-OCT macular scans were performed in 21 patients, including 10 with RPE65, 7 with CEP290, 3 with GUCY2D, and 1 with AIPL1 mutations. An image processing software was used to manually draw segmentation lines by three observers. Lamellar structure was evaluated based on the number of retinal layers on segmented images. Total retinal thickness was measured at the central macular and perifoveal areas by using an automated algorithm. All three patients with GUCY2D mutations (age range, 20-53 years) retained six retinal layers with visible photoreceptor inner/outer segment juncture (PSJ). However, the preservation of lamellar structures did not parallel better visual acuity. Patients with other mutations had poorly defined PSJ and disorganized retinal lamellar structures, where only one to three retinal layers could be observed. Patients with CEP290 mutations trended to have retention of the outer nuclear layer at the fovea and macular thickening, especially at younger ages. In patients with RPE65 (age range, 20-71 years) and AIPL1 mutations (age, 22 years), macular thickness was markedly decreased. Disorganization of retinal lamellar structures in the RPE65 group trended toward a worsening with increasing age. Variations of macular microstructures were observed among LCA patients with different genotypes. Disorganization of retinal lamellar structure was generally age related. Preservation of retinal microanatomic structures may not be associated with better visual acuity.


One-antigen mismatched related versus HLA-matched unrelated donor hematopoietic stem cell transplantation in adults with acute leukemia: Center for International Blood and Marrow Transplant Research results in the era of molecular HLA typing.
Approximately 13% of patients lacking an HLA-identical sibling have a one-antigen-mismatched related donor (MMRD). Historically, outcomes from the use of a one-antigen MMRD were considered equivalent to those from the use of a matched unrelated donor (UD). Recent improvements in UD stem cell transplantation (SCT) resulting from better molecular HLA matching justifies investigating whether UD should be preferred over MMRD in adult patients with acute leukemia. Here, we compared the outcomes of MMRD (n = 89) and HLA-A, -B, -C, and -DRB1 allele-matched UD (n = 700) SCT reported to the Center for International Blood and Marrow Transplant Research between 1995 and 2005. The patients underwent transplantation for acute myelogenous leukemia or acute lymphoblastic leukemia in first or second complete remission. Donor type was not associated with hematologic recovery. Univariate and multivariate comparisons of MMRD versus HLA-matched UD transplants showed no statistically significant differences in overall survival, disease-free survival, treatment-related mortality, relapse, or 100-day grade III-IV acute graft-versus-host disease (GVHD). MMRD SCT was associated with a lower rate of chronic GVHD at 1 year (35% vs 47%; P = .03), which was confirmed by multivariate analysis (relative risk, 0.58; 95% confidence interval, 0.39-0.85; P < .01). According to our data, HLA-matched UD and MMRD SCT are associated with comparable survival. Given that less chronic GVHD was observed in the MMRD transplantations, this option, when available, remains the first choice in patients with acute leukemia without an HLA-identical sibling in need of allogeneic SCT.


Expression of anti-Müllerian hormone (AMH) in the equine testis.
Anti-Müllerian hormone (AMH) induces regression of Müllerian ducts during male fetal development; in the human male, it is expressed in Sertoli cells during fetal development (and through puberty). The objective was to characterize expression of AMH in the fetal, neonatal, prepubertal, and adult equine testis, as well as in equine cryptorchid testes, in select testicular neoplasms, and in intersex gonads, based upon immunohistochemistry (IHC). Testes were removed from equine fetuses at 5.5, 10, and 11 months of gestation, at 12 months of age, and from adult stallions. In addition, cryptorchid testes, testis tumors (teratomas, seminomas, Sertoli cell tumors), and male intersex gonads were examined by IHC for expression of AMH using a goat polyclonal primary antibody (alpha-AMH) directed against a C-terminal peptide antigen from human AMH. Immunolabeling with alpha-AMH was localized to Sertoli cells within the developing seminiferous tubules of fetal, neonatal and prepubertal equine testes, with no expression detected in Sertoli cells from normal adult equine testes. Furthermore, expression was detected in cryptorchid testes (in animals up to 3-4 years of age) and in Sertoli cell tumors and male intersex gonads. In conclusion, AMH was strongly expressed by Sertoli cells in fetal, neonatal and prepubertal equine testes, but not in normal adult testes. That AMH was expressed in cryptorchid testes may provide a useful biomarker for detection of cryptorchid testes, as well as for immunohistochemical characterization of testicular tumors and intersex gonads in the horse.


Toxicity of eosinophil MBP is repressed by intracellular crystallization and promoted by extracellular aggregation.
Eosinophils are white blood cells that function in innate immunity and participate in the pathogenesis of various inflammatory and neoplastic disorders. Their secretory granules contain four cytotoxic proteins, including the eosinophil major basic protein (MBP-1). How MBP-1 toxicity is controlled within the eosinophil itself and activated upon extracellular release is unknown. Here we show how intragranular MBP-1 nanocrystals restrain toxicity, enabling its safe storage, and characterize them with an X-ray-free electron laser. Following eosinophil activation, MBP-1 toxicity is triggered by granule acidification, followed by extracellular aggregation, which mediates the damage to pathogens and host cells. Larger non-toxic amyloid plaques are also present in tissues of eosinophilic patients in a feedback mechanism that likely limits tissue damage under pathological conditions of MBP-1 oversecretion. Our results suggest that MBP-1 aggregation is important for innate immunity and immunopathology mediated by eosinophils and clarify how its polymorphic self-association pathways regulate toxicity intra- and extracellularly.


(Eye-)tracking the escape from the self: guilt proneness moderates the effect of failure on self-avoidance.
Failure increases the motivation to escape self-awareness. To date, however, the role of self-conscious emotions (shame and guilt) in triggering escape responses after failure has not been sufficiently addressed. In this pre-registered study (N = 156 undergraduates), we adapted a classic paradigm (avoidance of one's image in a mirror) to a modern eye-tracking technology to test the hypothesis that shame proneness moderates the effect of failure on self-awareness avoidance. Individual differences in guilt and shame proneness were assessed before priming thoughts of failure or success. Then, an eye-tracking paradigm was used to monitor gaze avoidance of one's screen-reflected face during a neutral, unrelated task. Unexpectedly, results showed that guilt but not shame proneness exacerbated self-avoidance after failure. The present findings challenge the dominant view that shame fosters avoidance more so than guilt.


Fingerprinting black tea: When spectroscopy meets machine learning a novel workflow for geographical origin identification.
Food fraud, along with many challenges to the integrity and sustainability, threatens the prosperity of businesses and society as a whole. Tea is the second most commonly consumed non-alcoholic beverage globally. Challenges to tea authenticity require the development of highly efficient and rapid solutions to improve supply chain transparency. This study has produced an innovative workflow for black tea geographical indications (GI) discrimination based on non-targeted spectroscopic fingerprinting techniques. A total of 360 samples originating from nine GI regions worldwide were analysed by Fourier Transform Infrared (FTIR) and Near Infrared spectroscopy. Machine learning algorithms (k-nearest neighbours and support vector machine models) applied to the test data greatly improved the GI identification achieving 100% accuracy using FTIR. This workflow will provide a low-cost and user-friendly solution for on-site and real-time determination of black tea geographical origin along supply chains.


Leucocyte sodium content and sodium pump activity in overweight and lean hypertensives.
Leucocyte sodium content and sodium pump activity was studied in overweight and lean hypertensive subjects and normotensive controls, all in the fasting state. In lean subjects (body mass index less than 27 kg m-2), hypertensives did not have altered leucocyte sodium content or pump activity. In the overweight (mostly obese) subjects, the leucocyte sodium content was higher in hypertensive than in normotensive subjects (median (range) 56.1 (42.0-84.1) vs 32.0 (18.2-59.4) mmol kg-1, P less than 0.001). This raised sodium content in overweight hypertensives was associated with a lower (ouabain-sensitive) 22Na efflux rate constant (2.25 (1.15-3.01) vs 2.64 (1.98-3.61) h-1, P less than 0.05) and a higher passive (or ouabain-insensitive) 22Na efflux rate constant (0.90(0.53-1.18) vs 0.63 (0.21-1.09) h-1, P less than 0.01). The systolic and diastolic blood pressures were significantly correlated to intracellular Na+ in the overweight group (r = 0.41 and 0.56, P less than 0.02 and 0.001 respectively). Thus, hypertension in the overweight subjects is associated with accumulation of intracellular sodium that may be due to abnormalities of the active sodium pump, though changes in ouabain-insensitive mechanisms also occur.


Wilson disease: high prevalence in a mountainous area of Crete.
Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The disorder is caused by mutations in the ATP7B gene, encoding a copper transporting P-type ATPase. The worldwide incidence is in the order of 30 cases per million, with a gene frequency of 0.56% and a carrier frequency of 1 in 90. The increased number of Wilson disease patients in the island of Crete led us to study the spectrum of mutations in a small village close to the city of Heraklion, from where many patients have been referred during the last 25 years. In order to estimate the frequency of the disease, we firstly investigated the number of births and the number of WD patients in the village since 1978. Six out of 90 births were diagnosed as WD patients, presenting the highest prevalence of WD reported so far. Analysis of the whole gene in three Wilson disease patients, and relatives of a boy who died from WD, led to the detection of 4 different point mutations. Two of them were missense (p.I1148T and p.G1176R) and cosegregated in cis in the same patient; the other allele of this patient carried a nonsense mutation (p.Q289X). This is the first report in the literature of three mutations co-segregating in the same WD patient. The fourth mutation identified was a novel frameshift mutation (c.398delT) with documented cosegregation. When screening 200 inhabitants originating from the same area, 18 were found to be carriers of one of these mutations. These findings indicate the need for health education intervention, genetic counselling and newborn screening for the Wilson disease.


Opinions on early-age marriage and marriage customs among Kurdish-speaking women in southeast Turkey.
For women, marriage before the age of 18 years has adverse consequences for physical, mental and emotional well-being and constitutes a barrier for continued education. According to a national survey, about 50% of all women in Eastern Turkey were aged under 18 years at first marriage. This study explored women's opinions and experiences of early marriage and culture-specific marriage customs in the province of Diyarbakir, a region of Turkey populated mostly by people of Kurdish ethnicity. A random sample of 966 women aged 15 years or older living in urban and rural areas of the province completed a questionnaire on age at marriage and social status. Qualitative data on women's opinions and experiences were also collected through focus group interviews with 90 women. The frequency of early marriage ranged from 19% in the youngest age group to 63% in women aged 60 years or older. Analysis of focus group interviews through a qualitative modified content method showed that girls were considered marriageable some years after the menarche and considerations regarding the protection of family honour were key factors leading parents to arrange the early marriage of their daughters, sometimes without their consent. Some culture-specific marriage customs included cradle betrothal, cousin marriage and berdel (exchange of brides between two families). There is a need for public health and family planning workers to create greater awareness of the adverse consequences of early marriage through parental arrangements.


Technological Challenges in the Development of Optogenetic Closed-Loop Therapy Approaches in Epilepsy and Related Network Disorders of the Brain.
Epilepsy is a chronic, neurological disorder affecting millions of people every year. The current available pharmacological and surgical treatments are lacking in overall efficacy and cause side-effects like cognitive impairment, depression, tremor, abnormal liver and kidney function. In recent years, the application of optogenetic implants have shown promise to target aberrant neuronal circuits in epilepsy with the advantage of both high spatial and temporal resolution and high cell-specificity, a feature that could tackle both the efficacy and side-effect problems in epilepsy treatment. Optrodes consist of electrodes to record local field potentials and an optical component to modulate neurons via activation of opsin expressed by these neurons. The goal of optogenetics in epilepsy is to interrupt seizure activity in its earliest state, providing a so-called closed-loop therapeutic intervention. The chronic implantation in vivo poses specific demands for the engineering of therapeutic optrodes. Enzymatic degradation and glial encapsulation of implants may compromise long-term recording and sufficient illumination of the opsin-expressing neural tissue. Engineering efforts for optimal optrode design have to be directed towards limitation of the foreign body reaction by reducing the implant's elastic modulus and overall size, while still providing stable long-term recording and large-area illumination, and guaranteeing successful intracerebral implantation. This paper presents an overview of the challenges and recent advances in the field of electrode design, neural-tissue illumination, and neural-probe implantation, with the goal of identifying a suitable candidate to be incorporated in a therapeutic approach for long-term treatment of epilepsy patients.


Central Nervous System Involvement as Relapse in Undiagnosed Whipple's Disease with Atypical Symptoms at Onset.
Whipple's disease (WD) is a rare systemic disease caused by the gram-positive bacillus Tropheryma Whipplei and mostly characterized by arthralgias, chronic diarrhea, weight loss, fever and abdominal pain. Central Nervous System involvement is not uncommon and it may precede other disease manifestations, appear after treatment and improvement of gastrointestinal signs or rarely be the only WD symptom. We report a case in a middle-aged male with unexplained neurological signs and symptoms which were presented as relapse of previously undiagnosed WD with atypical symptoms at onset. After diagnosis confirmation, the patient was appropriately treated which resulted in improvement of major symptoms.


Activity of synthetic enzymes of tetrahydrobiopterin in the human placenta.
Tetrahydrobiopterin (BH4) is an essential co-factor for nitric oxide (NO) synthase (NOS) and regulates the production of NO, or endothelium-derived relaxation factor. Although NOS is highly expressed in the placenta and NO plays a critical role in the regulation of feto-placental circulation, the mechanism maintaining the level of BH4 is not known. To investigate the de novo synthesis of BH4 in the human placenta, the activity of guanosine triphosphate cyclohydrolase I (GTPCH), 6-pyruvoyltetrahydropterin synthase (PTPS), and sepiapterin reductase (SR) in the chorionic tissue during the first, second and third trimester of pregnancy was analyzed. GTPCH activity was the lowest of the three enzymes and became negligible after the second trimester. There was no significant change in PTPS activity throughout pregnancy. Although SR activity decreased significantly after the second trimester, the levels remained abundant throughout pregnancy. These results showed that GTPCH is a rate-limiting enzyme and the total activity of the de novo synthesis of BH4 is negligible in the mature placenta after the second trimester when fetal growth is accelerated. The present study suggests that the level of BH4 in the placenta depends principally on the system other than de novo synthesis. The salvage pathway is considered the most potent system, which is formed by the transfer of the substrates from the fetus and their enzymatic conversion to BH4 in the placenta.


An efficient computational approach to characterize DSC-MRI signals arising from three-dimensional heterogeneous tissue structures.
The systematic investigation of susceptibility-induced contrast in MRI is important to better interpret the influence of microvascular and microcellular morphology on DSC-MRI derived perfusion data. Recently, a novel computational approach called the Finite Perturber Method (FPM), which enables the study of susceptibility-induced contrast in MRI arising from arbitrary microvascular morphologies in 3D has been developed. However, the FPM has lower efficiency in simulating water diffusion especially for complex tissues. In this work, an improved computational approach that combines the FPM with a matrix-based finite difference method (FDM), which we call the Finite Perturber the Finite Difference Method (FPFDM), has been developed in order to efficiently investigate the influence of vascular and extravascular morphological features on susceptibility-induced transverse relaxation. The current work provides a framework for better interpreting how DSC-MRI data depend on various phenomena, including contrast agent leakage in cancerous tissues and water diffusion rates. In addition, we illustrate using simulated and micro-CT extracted tissue structures the improved FPFDM along with its potential applications and limitations.


[Ultrasonographic findings in hepatoblastoma].
At de National Institute of Pediatrics in Mexico City, the ultrasonographic findings of hepatoblastomas were analyzed in order to establish the echographic pattern of this malignant liver tumor. The ultrasonic images of patient's livers dating back six years were retrospectively reviewed. The hyperrecognisance of the hepatoblastoma as a solid, poorly limited mass, with or without the presence of calcifications, with the displacement of the portal vein and frequently found in the right lobe, were considered as the most relevant echographic characteristics of the hepatoblastoma. The echographic characteristics found of the hepatoblastoma can aid in the sonographic diagnosis of the disease. The leukemic liver infiltrations, the primary liver lymphoma and the metastasis, due to their hyperrecognisance, can be confused with the diagnosis of hepatoblastoma.


Forward masking: adaptation or integration?
The aim of this study was to attempt to distinguish between neural adaptation and persistence (or temporal integration) as possible explanations of forward masking. Thresholds were measured for a sinusoidal signal as a function of signal duration for conditions where the delay between the masker offset and the signal offset (the offset-offset interval) was fixed. The masker was a 200-ms broadband noise, presented at a spectrum level of 40 dB (re: 20 microPa), and the signal was a 4-kHz sinusoid, gated with 2-ms ramps. The offset-offset interval was fixed at various durations between 4 and 102 ms and signal thresholds were measured for a range of signal durations at each interval. A substantial decrease in thresholds was observed with increasing duration for signal durations up to about 20 ms. At short offset-offset intervals, the amount of temporal integration exceeded that normally found in quiet. The results were simulated using models of temporal integration (the temporal-window model) and adaptation. For both models, the inclusion of a peripheral nonlinearity, similar to that observed physiologically in studies of the basilar membrane, was essential in producing a good fit to the data. Both models were about equally successful in accounting for the present data. However, the temporal-window model provided a somewhat better account of similar data from a simultaneous-masking experiment, using the same parameters. This suggests that the linear, time-invariant properties of the temporal-window approach are appropriate for modeling forward masking. Overall the results confirm that forward masking can be described in terms of peripheral nonlinearity followed by linear temporal integration at higher levels in the auditory system. However, the difference in predictions between the adaptation and integration models is relatively small, meaning that influence of adaptation cannot be ruled out.


Nanoparticle generation: the concept of a stagnation size region for condensation growth.
We demonstrate that the critical size cluster concept, commonly used in a nucleation theory, should be given some further attention. It has been implied that the supercritical cluster (size larger than critical) can grow via condensation. However, as we show, there is a size range, where the arrival of a vapor molecule onto a cluster surface leads to such a heating of the supercritical cluster that, due to possible evaporation, makes it unstable and, therefore, disables its condensation growth. The described phenomenon leads to substantial accumulation of certain size clusters in the system, which is clearly evident from our experimental investigation. The found suppression of the nucleus growth within the certain size range (exceeding critical) has fundamental implications for many systems where the generation of nanoparticles occur at high temperatures.


The use of tapered implants in the maxillae of periodontally susceptible patients: 10-year outcomes.
This study is a retrospective assessment of the long-term efficacy of dental implant therapy in periodontally susceptible patients. A private-practice chart review was conducted to identify partially dentate subjects treated with implant-supported restorations that had been monitored annually for at least 9.5 years. Subjects were assigned to either a periodontal group or a control group according to their health histories. Data were entered into spreadsheets on a personal computer and analyzed statistically with dedicated software. Thirty periodontal subjects were treated with 138 implants and 45 prostheses, and 16 control subjects were treated with 35 implants and 21 prostheses. The mean follow-up was 130 months. One implant failed before loading in the periodontal group. Cumulative 10-year survival rates were 99.3% (n = 137/138) for periodontal implants and 100% (n = 35/35) for control implants. Most surviving implants had no bone loss (n = 109/172, 63.4%). Most of the surviving implants with bone loss (n = 63/172, 36.6%) were concentrated in the periodontal cohort (90%, n = 57/63) and among women (60%, n = 15/25) regardless of cohort. Prosthesis failure was 25.2% (n = 16/66), with 12 porcelain fractures, 2 cement failures, and 2 framework fractures. In all cases, failed prostheses were immediately replaced and patients continued to function. Periodontal susceptibility resulted in increased bone loss but did not affect implant survival. The cause of greater bone loss in women could not be determined from the data but may have been related to the postmenopausal status of the subject population (mean age = 54 years).


Promoting Community and Population Health in Public Health and Medicine: A Stepwise Guide to Initiating and Conducting Community-engaged Research.
Various methods, approaches, and strategies designed to understand and reduce health disparities, increase health equity, and promote community and population health have emerged within public health and medicine. One such approach is community-engaged research. While the literature describing the theory, principles, and rationale underlying community engagement is broad, few models or frameworks exist to guide its implementation. We abstracted, analyzed, and interpreted data from existing project documentation including proposal documents, project-specific logic models, research team and partnership meeting notes, and other materials from 24 funded community-engaged research projects conducted over the past 17 years. We developed a 15-step process designed to guide the community-engaged research process. The process includes steps such as: networking and partnership establishment and expansion; building and maintaining trust; identifying health priorities; conducting background research, prioritizing "what to take on"; building consensus, identifying research goals, and developing research questions; developing a conceptual model; formulating a study design; developing an analysis plan; implementing the study; collecting and analyzing data; reviewing and interpreting results; and disseminating and translating findings broadly through multiple channels. Here, we outline and describe each of these steps.


Monoterpenes as regulators of malignant cell proliferation.
Limonene and related monoterpenes display compelling anticarcinogenic activity. The mechanism(s) that underline this activity is/are as yet unknown. One attractive possibility is that the monoterpenes interact with the RAS signal transduction pathway. The monoterpenes have been shown to impair incorporation of mevalonic acid-derived isoprene compounds, that is farnesyl pyrophosphate, into RAS and RAS-related proteins. As farnesylation is critical for RAS's membrane localization and function, the isoprenylation pathways have received attention as potential targets of anti-RAS pharmacological maneuvers. We have expanded on prior studies and demonstrate that one of limonene's metabolic derivatives, perillyl alcohol, decreases the levels of antigenic RAS in the human-derived myeloid THP-1 and lymphoid RPMI-8402 leukemia cell lines. Both limonene and perillyl alcohol decrease levels of 35[S] methionine labeled RAS proteins in cells that have been pulsed with radiolabeled methionine for four hours. In contrast, lovastatin, which inhibits hydroxymethylglutaryl coenzyme A reductase and thus depletes cells of farnesyl pyrophosphate, does not diminish levels of total antigenic RAS but rather results in a shift in the RAS protein; levels of farnesylated RAS decrease whereas levels of unmodified/unfarnesylated RAS increase. As limonene and perillyl alcohol do not induce such a shift we conclude that these monoterpenes decrease farnesylated RAS protein levels by a mechanism that is clearly distinct from that of either depleting cells of farnesyl pyrophosphate or inhibiting the enzyme farnesyl protein transferase that catalyzes the posttranslational farnesylation of RAS. These findings are discussed with respect to implications for the monoterpenes to alter RAS protein synthesis and degradation. The results of these studies will likely impact the inclusion of the monoterpenes in clinical anticancer trials.


Testing the effectiveness of a Fatigue and Activity Management Education for Work (FAME-W) intervention for individuals with inflammatory arthritis: Study protocol for a randomized control trial.
A work-focused fatigue management intervention, Fatigue and Activity Management Education for Work (FAME-W) programme was developed for individuals with inflammatory arthritis (IA) to manage fatigue in order to maintain demands of their work activities and tasks. This paper presents the protocol for a randomized control trial that will test the effectiveness and acceptability of FAME-W in improving work performance. This protocol presents a multisite randomized control trial and mixed methods process evaluation. Eligible participants will be aged 18-65 years with a diagnosis of inflammatory arthritis and will be in paid employment. The primary outcome of the study will be Work Role Functioning (WRF) questionnaire, and the secondary outcomes will be fatigue, mood, health-related quality of life (HRQOL) and pain. Data will be collected immediately pre- and post-intervention and at 3 months of follow-up. The process evaluation will consist of focus groups and individual interviews to explore participants' experiences of FAME-W. Occupational therapists delivering the programme will complete a facilitator log to assess the fidelity and quality of intervention implementations. Facilitators will participate in individual interviews to explore intervention delivery and acceptability. Results will be expected to show that FAME-W will improve work performance by helping participants gain self-management strategies around managing fatigue and other symptoms related to fatigue. It is hoped that FAME-W will be an effective and acceptable intervention for individuals with IA in improving work performance by helping them manage their symptoms. ClinicalTrials.gov: NCT05138445, Registered on 30 November 2021.


Partial hepatectomy and subsequent radiation facilitates engraftment of mouse embryonic stem cells in the liver.
For liver-targeted regenerative medicine, embryonic stem (ES) cell-derived hepatocyte-like cells proffer great expectation. In vitro exposure to a combination of various growth factors, such as hepatocyte growth factor and fibroblast growth factor-4, as well as cytokines, leads to differentiation of ES cells into hepatocyte-like cells. We sought to determine the in vivo environment that allowed engraftment of ES cells transplanted to the liver. Thus, we examined the effect of partial hepatectomy (50%) (PHT) and subsequent radiation (RT) of the male Balb/c mouse host liver on ES cell engraftment. ES cells (5 x 10(6)) derived from 129Sv mice were transplanted into the residual liver. The controls were ES cells transplanted into a normal liver. Bromo-deoxy-residine (BrdU)-uptake was performed to evaluate the effect of hepatectomy and RT on hepatocyte regeneration. Mouse ES cells engrafted, forming teratomas in the normal liver without showing any mononuclear infiltration. A liver modified by PHT and RT facilitated engraftment of mouse ES cells compared with a normal liver. Hepatic RT significantly suppressed hepatocytic uptake of BrdU.


Semiquantitative assessment of cytomorphologic features can predict mutation status of thyroid nodules with indeterminate cytologic diagnosis.
Molecular diagnostics increasingly direct the management of thyroid nodules with an indeterminate cytologic diagnosis. This study was undertaken to correlate cytomorphologic features with the molecular profiles in an effort to identify features predictive of molecular aberrations. One hundred eighty-nine thyroid nodules with an indeterminate thyroid cytology diagnosis (atypia of undetermined significance, suspicious for follicular lesion, and suspicious for malignancy) with an adequate sample submitted for targeted mutation detection by polymerase chain reaction or next-generation sequencing were assessed semiquantitatively for the following cytomorphologic parameters: cellularity, Hurthle cell changes, microfollicles, nuclear elongation, nuclear grooves, nuclear enlargement, nuclear atypia, extent of atypia, and colloid. Based on this evaluation, a cumulative cytomorphologic score (CCS) and a more simplified overall atypia score (OAS) were assigned to each case. Associations among mutational status and each of the aforementioned parameters, CCS, and OAS were determined. Of the 189 nodules with indeterminate cytology, 63 (33.3%) harbored at least 1 mutation. RAS and BRAF were the most common mutations, found in 34 (18.0%) and 13 (6.9%) cases, respectively. Both CCS and OAS were highly associated with the presence of all mutations (P < .0001) and with the presence of BRAF and RAS mutations in particular (all P < .01). Semiquantitative assessment of various cytomorphologic features in indeterminate thyroid cytology cases showed a strong association of higher OAS and CCS and incidence of BRAF and RAS mutations. Using a more objective approach to thyroid cytology can potentially decrease the overall number of indeterminate diagnoses, leading to fewer repeat procedures and unnecessary surgical procedures.


High prevalence of abnormal menstruation among women living with HIV in Canada.
To measure the prevalence and correlates of abnormal menstruation among women living with HIV (WLWH) in Canada. We used cross-sectional questionnaire data from the community-based Canadian HIV Women's Sexual and Reproductive Health Cohort Study (CHIWOS), which enrolled WLWH aged ≥16 from British Columbia (BC), Ontario, and Quebec. For this analysis, we excluded women >45 years, who had primary amenorrhea, were pregnant, on hormonal contraception, or who reported history of endometrial cancer, last menstrual period >12 months ago, or premature ovarian failure. The primary outcome was abnormal menstruation (Yes vs No) based on responses to five questions about menstrual regularity, frequency, volume, duration, and intermenstrual bleeding in the six months prior to interview. An exploratory multivariable logistic regression analysis examined independent correlates of abnormal menstruation. Of 1422 women enrolled, 521 (37%) met eligibility criteria. Overall, 55.9% (95% CI:52%-60%) reported abnormal menstruation. In adjusted analyses, abnormal menstruation was associated with having a biologic sister/mother who entered menopause before age 40 (AOR 5.01, 95%CI 1.39-18.03), Hepatitis B co-infection (AOR 6.97, 95%CI 1.52-31.88), current smoking (AOR 1.69, 95%CI 1.55-3.41); and currently taking antiretroviral therapy (ART) (AOR 2.36, 95%CI 1.25-4.45) compared to being ART-naïve. Women in BC had higher adjusted odds of abnormal menstruation (AOR 2.95, 95%CI 1.61-5.39), relative to women in Ontario and Quebec. Over half of WLWH in this analysis had abnormal menstruation. Correlates of abnormal menstruation include genetic, socio-behavioural factors (province of residence, smoking), Hepatitis B co-infection, and current ART use.


Magnesium availability regulates the development of root hairs in Arabidopsis thaliana (L.) Heynh.
Root hairs are reported to be plastic in response to nutrient supply, but relatively little is known about their development in response to magnesium (Mg) availability. Here, we showed that development of root hairs of Arabidopsis decreased progressively with increasing Mg supply, which was related to the initiation of new trichoblast files and likelihood of trichoblasts to form hairs. Tip-focused reactive oxygen species (ROS) and cytosolic Ca(2+) concentrations [(Ca(2+) )c] during elongation of root hairs were enhanced under low Mg but decreased under high Mg. Under low Mg, application of diphenylene iodonium (DPI) or BAPTA [1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid] blocked the enhanced development of root hairs and the opposite was true when the plants under high Mg were treated with phenazine methosulphate (PMS), methyl viologen (MV) or CaCl2 . Furthermore, Mg availability did not alter root hair growth in rhd2-1 mutant that contains lower levels of ROS and cytosolic [Ca(2+) ]c. Transcriptome data and qPCR results revealed a greater fraction of morphogenetic H-genes, and cell wall organization genes were up-regulated by low Mg but down-regulated by high Mg. Our data suggest a profound effect of Mg supply on the development of root hairs in Arabidopsis, through the characterized Ca(2+) and ROS signals that modulate the elongation of root hairs and the expression of root-hair morphogenetic genes.


Effects of one year treatment of vildagliptin added to pioglitazone or glimepiride in poorly controlled type 2 diabetic patients.
The aim of the study was to compare the effects of vildagliptin added to pioglitazone or glimepiride on metabolic and insulin resistance related-indices in poorly controlled type 2 diabetic patients (T2DM). 168 patients with T2DM were randomized to take either pioglitazone 30 mg once a day plus vildagliptin 50 mg twice a day or glimepiride 2 mg 3 times a day plus vildagliptin 50 mg twice a day. We evaluated body weight, body mass index (BMI), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), homeostasis model assessment beta-cell function index (HOMA-beta), fasting plasma proinsulin (FPPr), proinsulin/fasting plasma insulin ratio (Pr/FPI ratio), adiponectin (ADN), resistin (R), tumor necrosis factor-alpha (TNF-alpha), and high sensitivity C-reactive protein (Hs-CRP) at their baseline values, and after 3, 6, 9, and 12 months of treatment. We observed a similar improvement of HbA1c, FPG, PPG, and Hs-CRP compared to baseline in the 2 groups. Fasting plasma insulin, FPPr, Pr/FPI ratio, R, and TNF-alpha were significantly decreased and ADN was significantly increased with pioglitazone plus vildagliptin, but not with glimepiride plus vildagliptin. HOMA-IR, and HOMA-beta values obtained with pioglitazone plus vildagliptin were significantly better than the values obtained with glimepiride plus vildagliptin. Pioglitazone plus vildagliptin were found to be more effective in preserving beta-cell function, and in reducing insulin resistance, and inflammatory state parameters.


Genetic variability in Hanoverian warmblood horses using pedigree analysis.
A data set constituting a total of 310,109 Hanoverian warmblood horses was analyzed to ascertain the genetic variability, coefficients of inbreeding, and gene contributions of foreign populations. The reference population contained all Hanoverian horses born from 1980 to 2000. In addition, Hanoverian stallions born from 1980 to 1995 and Hanoverian breeding mares from the birth years 1980 to 1995 with registered foals were analyzed for the same genetic parameters. The average complete generation equivalent was approximately 8.43 for the reference population. The mean coefficient of inbreeding was 1.33, 1.19, and 1.29% for the reference population, stallions, and breeding mares, respectively. The effective number of founders was largest in stallions (364.3) and smallest in the reference population (244.9). The ratio between the effective number of founders and the effective number of ancestors was 3.15 for the reference population, 3.25 for the stallions, and 3.06 for the breeding mares. The effective population size in the Hanoverian warmblood reference population was 372.34. English Thoroughbreds contributed nearly 35% of the genes to the Hanoverian reference population and even slightly greater contributions (39%) to the stallions. Trakehner and Arab horses contributed approximately 8 and 2.7%, respectively, to the Hanoverian gene pool. The most important male ancestors were Aldermann I from the A/E line, Fling from the F/W line, and Absatz from the Trakehner line, whereas the breeding mare Costane had the greatest contribution to the reference population, stallions, and breeding mares. From 1996 onward, the stallions Weltmeyer and Donnerhall had the largest genetic impact on the Hanoverian horse population.


[Transposition of great arteries. Understanding its pathogenesis].
Transposition of the great arteries (TGA) is a frequent and severe cardiac defect. In patients with this malformation, diagnostic and surgical results and the long-term prognosis significantly improved in the last years. From the embryological point of view there are two main theories: 1) the anomalous infundibular rotation, and 2) the anomaly of the aortico-pulmonary septum. Both of them still present important limits. Moreover, TGA is difficult to reproduce by animal experiments, but interesting data, using retinoid acid in pregnant rats, are nowadays available, as well as there are interesting data from the epidemiologic studies on human teratologic agents. TGA is rarely associated with genetic syndromes and with additional extracardiac anomalies. A few cases are in relation with DiGeorge syndrome with deletion of chromosome 22q11. On the contrary TGA is significantly prevalent, in association with other cardiac and extracardiac anomalies, in children with lateralization defects, heterotaxy and asplenia syndrome (right isomerism). However in patients with heterotaxy and polysplenia syndrome (left isomerism) TGA is significantly more rare. In mice with mutation of Smad2 and NODAL, two genes involved in the lateralization process, some cases of TGA, with or without right isomerism of the lungs, were reported. Moreover, in families with heterotaxy some cases with congenitally corrected TGA were reported and a new gene associated with heterotaxy, CRYPTIC, can present mutations in patients with "isolated" TGA. A recent study on familiar recurrence of TGA shows in the same family some cases of TGA and of corrected TGA so that a monogenic inheritance (autosomic dominant or recessive) with variable phenotypic expression can be suggested. The normal righthand spiralization of the heart is genetically determined in cases of situs solitus and d-loop of the ventricles. This pattern is not present in cases of TGA presenting a parallel position of the great arteries. On the basis of these observations and according to new epidemiologic and genetic data some cases of TGA should be classified in the group of the anomalies of lateralization and ventricular loop. The mystery is still present but perhaps some gleams of light are appearing.


Effect of culture medium and cryoprotectants on the growth and survival of probiotic lactobacilli during freeze drying.
To investigate the effects of the medium and cryoprotective agents used on the growth and survival of Lactobacillus plantarum and Lactobacillus rhamnosus GG during freeze drying. A complex medium was developed consisting primarily of glucose, yeast extract and vegetable-derived peptone. Trehalose, sucrose and sorbitol were examined for their ability to protect the cells during freeze drying. Using standardized amount of cells and the optimized freeze drying media, the effect of the growth medium on cell survival during freeze drying was investigated. The results showed that glucose and yeast extract were the most important growth factors, while sucrose offered better protection than trehalose and sorbitol during freeze drying. When the cells were grown under carbon limiting conditions, their survival during freeze drying was significantly decreased. A clear relationship was observed between cell growth and the ability of the cells to survive during the freeze drying process. The survival of probiotic strains during freeze drying was shown to be dependent on the cryoprotectant used and the growth medium.


Carcinoma of the large intestine and nontraumatic, metastatic, clostridial myonecrosis.
Traumatic, clostridial myonecrosis is a rare and serious complication of wounds. Nontraumatic, metastatic, clostridial myonecrosis may be caused by carcinoma of the large intestine. Nontraumatic myonecrosis becomes evident with localized pain, generalized toxicity, local signs of inflammation, and crepitation. Serum creatine kinase determinations may be of help in diagnosing patients suspected of having acute myonecrosis. Immediate heroic surgical intervention, usually with demonstration of Clostridium septicum, is mandatory to control the myonecrosis. Appropriate antibiotic therapy is a valuable adjunct to surgical intervention, and penicillin in massive doses appears to be the agent of choice for the clostridia. Hyperbaric oxygen therapy may help in the optimal control. General supportive measures, including frequent blood transfusions, are most important. To save the life of the patient with nontraumatic, metastatic, clostridial myonecrosis, it is necessary, as soon as the patient's general condition permits, to diagnose and eliminate the cause of the myonecrosis. In addition to the case reported, 16 cases have been reported in the literature, making a total of 17. Five patients have survived (survival rate, 29 percent).


Siltuximab (CNTO 328): a promising option for human malignancies.
Siltuximab (CNTO 328) is a promising antibody-drug conjugate targeting cytokine interleukin-6 (IL-6). It is highly binding to IL-6 and thus neutralizing IL-6 bioactivity and promoting death of tumor cell. In this review, we mainly focus on the mechanisms, clinical studies, and adverse effect of siltuximab in the treatment of human malignancies. We also provide our recommendations for siltuximab treatment in the future.


The effect of flow equalisation and prefermentation on the sludge production and sludge characteristics in a BNR plant.
A full-scale study investigated the influence of diurnal flow equalisation and prefermentation on the characteristics of sludge. The diurnal variations in the sludge concentration and the level of sludge blanket in the secondary clarifiers were evened out significantly with the use of an equalization basin. Stable conditions in the aeration basin and in the secondary clarifiers contributed to the improvements in the performance of the BNR plant. A decrease in the waste activated sludge production and an improvement in the settleability were also observed. The low WAS yield was attributed to the low yield COD compounds produced by the prefermentation, longer sludge age and constant conditions obtained by the flow equalisation. Some evidence was found that good settling properties would be related to the amount of suspended solids fed to the biological process as well as to the good performance of the biological process.


[Pelvic ostheomyelitis: diagnostics and treatment].
Results of treatment of 223 patients with ostheomyelitis of various etiology and localization were analyzed. Such aspects as diagnostic difficulties, polifocal type of the disease, sepsis development on the background of pelvic ostheomyelitis were discussed. Ostheoscintygraphy, magnetic resonance imaging and computed tomography proved to be of highest diagnostic value by pelvic ostheomyelitis. The original method of surgical treatment of purulent sacroileitis with the use of combined (pelvic and extrapelvic) access was represented.


Degradation of swept-parameter VEP responses by neutral density filters in amblyopic and normal subjects.
To determine whether objective visual function, measured by swept-parameter visual evoked potential (sVEP), is preferentially degraded by neutral density filtration (NDF) in normal control and fellow eyes compared to amblyopic eyes, and to determine whether the response to NDF is a function of stimulus type, using grating and vernier stimuli. Monocular Snellen acuity and both grating and vernier sVEP responses were measured in each eye of 23 children or adolescents with amblyopia and 21 visually and neurologically normal children or adolescents. Acuity and sVEP responses were measured with and without a 2.0 log unit neutral density filter before the viewing eye. Suprathreshold sVEP grating responses were more sensitive than vernier to degradation by amblyopia in the unfiltered state and to NDF-induced preferential degradation of responses from fellow and normal control eyes. For threshold measurements, on the other hand, vernier responses were more sensitive to degradation by amblyopia in the unfiltered state and to NDF-induced preferential depression. Threshold vernier responses of amblyopic eyes were paradoxically enhanced by NDF. Neutral density filtration causes preferential degradation of both threshold and suprathreshold sVEP responses in normal control eyes and fellow eyes of amblyopes, compared to amblyopic eyes. The degradation is stimulus specific and dependent upon whether threshold or suprathreshold responses are measured. Grating responses are more likely to identify suprathreshold abnormalities, while vernier stimuli are more likely to detect threshold abnormalities. These findings may be used to optimize the stimulus parameters and design of future studies utilizing evoked potential techniques in amblyopic subjects.


Optimal pedalling rate in prolonged bouts of cycle ergometry.
This study was designed to investigate the variables which contribute to the determination of optimal pedalling rate in cycling. Five trained bicycle racers were used as subjects for the study. The experiment consisted of five 20- to 30-min tests at about 85% of each subject's pre-determined VO2max. Pedal rates of 40, 60, 80, 100, and 120 rpm were used. In the experiment, efficiency, heart rate, and perceived exertion measures were obtained at 10 and 20 min of exercise. Blood lactate concentration and plasma levels of epinephrine and norepinephrine were measured at rest, during the exercise sampling periods, and at 5 min of recovery following the exercise bout. When compared across pedal rates, gross efficiency, heart rate, and perceived exertion all were minimal at 60 or 80 rpm for each sampling period. Blood lactate showed the same relationship to pedal rate as the preceding variables at 10 min of exercise but not late in the test. The catecholamine values appeared to follow a similar trend but not significantly. The experiment showed that for this group of cyclists an optimal pedal rate existed for a prolonged period of exercise and was evident in measures of both efficiency and perceived exertion. The experiment indicates that, for researchers and for cyclists who use high power outputs, the choice of pedal rate is an important one.


4-(9-fluorenylmethyloxycarbonyl)phenylhydrazine (FmPH): a new chromophoric reagent for quantitative monitoring of solid-phase aldehydes(1-3).
A direct method for quantifying solid-phase aldehydes has been developed, using a new reagent, 4-(9-fluorenylmethyloxycarbonyl)phenylhydrazine (FmPH). The FmPH reagent was synthesized in three steps (24% overall yield) from commercially available p-hydrazinobenzoic acid. Resin-bound aldehydes reacted quantitatively with FmPH, in the presence of trimethylorthoformate (TMOF) as a dehydrating agent, to form a highly conjugated, immobilized FmPH-hydrazone. Next, mild treatment of the hydrazone with an excess of piperidine-N,N-dimethylformamide (1:1) released the piperidine-dibenzofulvene adduct chromophore (epsilon(301nm) = 7800 M(-1) cm(-1)) from the support. FmPH quantitation of aldehydes proved to be a straightforward, sensitive, and reproducible technique for monitoring resin-bound aldehydes [albeit insufficiently reactive to allow reliable quantification of ketones]. The FmPH aldehyde assay is applicable to a range of solid supports, as demonstrated specifically for poly(ethylene glycol)-polystyrene (PEG-PS), aminomethylpolystyrene (AMP), and cross-linked ethoxylate acrylate resin (CLEAR).


Resistance artery mechanics and composition in angiotensin II-infused mice: effects of cyclooxygenase-1 inhibition.
The aim of this study was to investigate the role of cyclooxygenase (COX)-1 on vascular alterations in structure, mechanics, and extracellular matrix (ECM) components induced by angiotensin (Ang) II in mesenteric arteries from wild-type (WT) and COX-1 knockout (COX-1(-/-)) mice. Animals were infused with vehicle or Ang II (400 ng/kg/min, s.c.) ± SC-560 (COX-1 inhibitor), DFU (COX-2 inhibitor), or SQ-29548 (TP receptor antagonist). After 2 weeks, vessels were isolated and exposed to intraluminal pressures (3-140 mmHg, pressurized myograph) to determine mechanical properties. Angiotensin II-induced vascular hypertrophic remodelling in WT was reversed by SC-560 or SQ-29548, but unaffected by DFU. Angiotensin II increased vessel stiffness (P< 0.01), this effect being ameliorated by SC-560 or SQ-29548, but unmodified by DFU. Angiotensin II failed to modify vessel elasticity in COX-1(-/-) mice. In WT vessels, Ang II enhanced COX-1 immunostaining, induced collagen and fibronectin depositions and decreased elastin content (P< 0.01). These effects were reversed by SC-560 or SQ-29548, but unaffected by DFU. In COX-1(-/-) mice, Ang II did not affect ECM contents. In WT, Ang II increased COX-1 and decreased COX-2 expression, and enhanced the vascular release of 6-keto-PGF1α which was prevented by COX-1 blockade. Human coronary artery smooth muscle cells, incubated with Ang II, showed an increased expression of procollagen I, which was abrogated by SC-560 or SQ-29548. Angiotensin II-induced alterations of resistance arteries in structure, mechanics, and ECM composition were prevented by COX-1 inhibition and TP receptor antagonism, indicating that Ang II-mediated vascular damage is mediated by COX-1-derived prostanoid prostacyclin, activating TP receptors.


'Is there any point in me doing this?' Views and experiences of women in the Diabetes and Antenatal Milk Expressing (DAME) trial.
The Diabetes and Antenatal Milk Expressing (DAME) randomised controlled trial (RCT) was conducted in 2011-2015, at six sites in Melbourne, Australia to explore the effect of advising women with diabetes in pregnancy to express breast milk from 36 weeks gestation. Infants whose mothers were randomised to express in pregnancy were more likely to be exclusively breast milk fed during their hospital stay, and there was no evidence of harm. This paper explores women's views and experiences of antenatal expressing. In this two-arm RCT, 635 women with diabetes in pregnancy who were otherwise of low medical risk were randomised at 36-37 weeks gestation to usual care (not expressing, n = 316), or the intervention, where women were advised to hand express for 10 min twice daily until birth (n = 319). Semistructured face-to-face interviews were conducted with 10 women who expressed antenatally. They were asked about their experiences of antenatal expressing, including how they felt about the overall experience, the amount of breast milk they expressed, making time to express, and their experience of breastfeeding. Thematic analysis of the in-depth interviews identified six themes: (1) learning and adapting expressing, (2) feelings and sensations associated with expressing, (3) support, (4) dis/empowerment, (5) health, and (6) the value of breast milk. Women had both positive and negative experiences of antenatal expressing. If health professionals are advising antenatal expressing to women, it is important they understand the range of outcomes and experiences.


Exacerbating factors induce different gene expression profiles in peripheral blood mononuclear cells from asthmatics, patients with chronic obstructive pulmonary disease and healthy subjects.
Despite several common phenotypic features, chronic obstructive pulmonary disease (COPD) and severe asthma differ with regard to their causative factors and pathophysiology. Both diseases may be exacerbated by environmental factors, however, the molecular profiles of disease episodes have not been comprehensively studied. We identified differences in gene and protein expression profiles expressed by peripheral blood mononuclear cells (PBMC) of COPD patients, patients with atopic asthma and healthy subjects when challenged with exacerbating factors in vitro: lipopolysaccharide (LPS), house dust mite (HDM) and cat allergen. PBMC isolated from patients with severe atopic asthma and COPD, as well as healthy subjects were stimulated with rDer p 1 DG, rFel d 1 DG and LPS. The changes in the expression of 47 genes belonging to five groups (phospholipase A2, eicosanoids, transcription factors, cytokines and airway remodeling) were studied using TaqMan low density array cards. Immunoblotting was used to study relative protein expression. rDer p 1 significantly up-regulated the expression of PLA2G4A, PLA2G6, PLA2G15, CYSLTR1, LB4R2, PTGS1, PTGS2, FOXP1, GATA3, HDAC2, IREB2, PPARG, STAT4, TSLP and CHI3L1 genes in asthmatics in comparison to healthy subjects. LPS induced significant expression of ANXA1 and LTA4H in asthmatics when compared to COPD patients and healthy subjects. SOX6,STAT4 and IL1RL1 were induced in COPD after LPS stimulation. Analysis of protein expression revealed a pattern similar to mRNA expression. LPS-induced exacerbation of asthma and COPD is characterized by differential expression of selected genes in PBMC. HDM allergen changed the expression profile of inflammatory genes between patients with asthma of atopic origin and healthy controls.


Constant chemical potential cycles for capacitive deionization.
The primary energy consuming operations which occur within a Capacitive Deionization (CDI) cell, are the ion removal (electrosorption), ion concentrating (electrodesorption), and solution switching processes. In theory the maximum system performance for a CDI system arises when solution switching occurs while maintaining a fixed number of ions (N), and when electrosorption/desorption occurs while maintaining a fixed chemical potential (μ). These fixed state variable based operations are analogous to the Carnot cycle, where heat transfer occurs at constant temperature and compression and expansion occur while maintaining constant entropy. In reality, maintaining a constant number of ions during switching is not practically feasible, thus here we investigate two alternative cycles where switching instead occurs while maintaining constant charge or voltage. Unlike constant number of ions, maintaining charge and voltage constant is feasible using a potentiostat. These theoretical cycles were chosen as they are analogues or ideal-like (Stirling and Ericsson) cycles, which are also practically feasible. The thermodynamic analysis reveals that these alternative cycles provide an avenue to approach the theoretical limit with low saline feed water; however, they are not capable of approximating ideal operations at elevated feed-water concentrations.


Symbol-Level Selective Channel Estimation in Packet-Based OFDM Systems.
Wireless access in vehicular environments to support wireless communication between vehicles has been developed to provide road safety and infotainment services. In vehicular environments where the channel changes rapidly, channel estimation is very important in improving the reliability of wireless communication. Therefore, numerous channel estimation schemes have been proposed; however, none of the schemes proposed so far can perform well over the entire signal-to-noise ratio (SNR) region. In this paper, we propose a novel channel estimation scheme that selectively uses the better scheme between two channel estimation schemes on a symbol-by-symbol basis. The results show that the proposed scheme performs symbol-by-symbol selection of the better channel estimation scheme within a packet, and thus shows excellent performance over the entire SNR region in vehicular environments in terms of the bit error rate and packet error rate.