Quality of nursing home care assessed by competent nursing home patients.
Interviews were conducted with 60 chronically ill but cognitively competent nursing home patients with a mean age of 80 years, living in 13 nursing homes in the county of Stockholm, Sweden. Quality of nursing home care was assessed through discrepancy between individual priorities (i.e. degree of perceived personal autonomy) and institutional possibility. The results show that there was a high degree of satisfaction with quality of care with regard to meal and shower routines, as well as with the possibilities to watch television, listen to the radio and feel secure. Social relations, on the other hand, was a subject which exposed large discrepancies. Most respondents believed in the importance of social relations whereas results point to a lack of intimacy in the daily living.


Identification of thyroid stimulating hormone receptor-specific T cells in Graves' disease thyroid using autoantigen-transfected Epstein-Barr virus-transformed B cell lines.
The importance of thyrotropin receptor (TSHR) agonist antibodies in the manifestations of Graves' disease (GD) is recognized. There are, however, no convincing reports of TSHR-specific T cells. We have previously cloned T cells specific for thyroglobulin and thyroid peroxidase (TPO) from GD lymphoid infiltrates and used autologous EBV-transformed B cell lines (EBVL) transfected with an expression vector encoding TPO to efficiently detect TPO-specific T cells. Here we used EBVL transfected with TSHR to seek TSHR-specific T cells in the GD infiltrates, after cloning the in vivo activated T cells without antigen. 3 out of 30 clones responded vigorously and reproducibly to EBVL-TSHR, with a mean stimulation index > 7. Their release of IL-2, IL-4, and IL-10 after stimulation with soluble anti-CD3 and phorbol ester was indistinguishable from the other clones from this thyroid. However, they produced relatively little IFN gamma (median IL-4/IFN gamma ratio of 0.80) compared with the other clones (median IL-4/IFN gamma ratio 0.06). Thus, this new potent method of antigen presentation, using autoantigen-transfected EBVL, has permitted the first unequivocal identification of TSHR T cells in GD thyroid, with distinct Th0/Th2 characteristics, unlike previously cloned TPO-responsive cells which have Th1 characteristics.


Expression of neurotrophins and trk receptors in the avian retina.
Using the RNase protection assay, we have found that nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), and neurotrophin-3 (NT-3) are expressed in the avian retina during development. The expression peaks around embryonic days 12-15, with decreasing levels at later stages of development. Abundant levels of NGF and BDNF but low levels of NT-3 mRNA were found in the adult retina. We also found that light/darkness regulated the levels of NGF and BDNF mRNAs but not the levels of NT-3 mRNA in the 5-day-old chicken retina. It was demonstrated that NGF and BDNF mRNA levels were up-regulated by light exposure. The cellular localization of mRNA expression for the neurotrophins and neurotrophin receptors TrkA, TrkB, and TrkC in the retina was studied using in situ hybridization. The patterns of NGF and trkA mRNA expression were very similar and were localized to the external part of the inner nuclear layer on the border with the outer plexiform layer and corresponded to the localization of horizontal cells. NT-3 labeling was also found over the external part of the inner nuclear layer, whereas trkC mRNA was found over all layers in the retina. BDNF labeling was found over all layers in the retina, whereas TrkB labeling was intense over cells in the ganglion cell layer, which is in agreement with the response of ganglion cells to BDNF stimulation. Functional neurotrophin receptors were suggested by the response of retinal explants to neurotrophin stimulation. These data indicate that the neurotrophins play local roles in the retina that involve interactions between specific neuronal populations, which were identified by the localization of the Trk receptor expression. The data also suggest that NGF and BDNF expression is regulated by normal neuron usage in the retina.


Molecular dynamics simulations of phosphonic acid-aluminum oxide self-organization and their evolution into ordered monolayers.
We outline an unprejudiced molecular dynamics simulation approach to study the mechanisms of self-organization encompassing the evolution of surfactant-surface interactions to the growth of self-assembled monolayers (SAMs). Therein, the time-length scale problem is tackled by combining an efficient docking-type procedure for implementing surfactant-by-surfactant association with detailed molecular simulations to explore structural relaxation. For this, nanosecond-scale molecular dynamics simulations unravel ordering processes during the gradual assembly of the monolayer. Along this line, different packing motifs of octadecyl phosphonic acid (ODPA) on the (0001) surface of α-alumina and implications for the final density and ordering of the resulting monolayers are elucidated. Moreover, the role of the solvent is discriminated by comparing SAM formation in 2-propanol, hexane and in a vacuum.


ACOG Committee Opinion No. 494: Sulfonamides, nitrofurantoin, and risk of birth defects.
The evidence regarding an association between the nitrofuran and sulfonamide classes of antibiotics and birth defects is mixed. As with all patients, antibiotics should be prescribed for pregnant women only for appropriate indications and for the shortest effective duration. During the second and third trimesters, sulfonamides and nitrofurantoins may continue to be used as first-line agents for the treatment and prevention of urinary tract infections and other infections caused by susceptible organisms. Prescribing sulfonamides or nitrofurantoin in the first trimester is still considered appropriate when no other suitable alternative antibiotics are available. Pregnant women should not be denied appropriate treatment for infections because untreated infections can commonly lead to serious maternal and fetal complications.


Contextualization and standardization of the supportive leadership behavior questionnaire based on socio- cognitive theory in Iran.
Effective leadership is of prime importance in any organization and it goes through changes based on accepted health promotion and behavior change theory. Although there are many leadership styles, transformational leadership, which emphasizes supportive leadership behaviors, seems to be an appropriate style in many settings particularly in the health care and educational sectors which are pressured by high turnover and safety demands. Iran has been moving rapidly forward and its authorities have understood and recognized the importance of matching leadership styles with effective and competent care for success in health care organizations. This study aimed to develop the Supportive Leadership Behaviors Scale based on accepted health and educational theories and to psychometrically test it in the Iranian context. The instrument was based on items from established questionnaires. A pilot study validated the instrument which was also cross-validated via re-translation. After validation, 731 participants answered the questionnaire. The instrument was finalized and resulted in a 20-item questionnaire using the exploratory factor analysis, which yielded four factors of support for development, integrity, sincerity and recognition and explaining the supportive leadership behaviors (all above 0.6). Mapping these four measures of leadership behaviors can be beneficial to determine whether effective leadership could support innovation and improvements in medical education and health care organizations on the national level. The reliability measured as Cronbach's alpha was 0.84. This new instrument yielded four factors of support for development, integrity, sincerity and recognition and explaining the supportive leadership behaviors which are applicable in health and educational settings and are helpful in improving self -efficacy among health and academic staff.


Recovery facilitation with Montmorency cherries following high-intensity, metabolically challenging exercise.
The impact of Montmorency tart cherry (Prunus cerasus L.) concentrate (MC) on physiological indices and functional performance was examined following a bout of high-intensity stochastic cycling. Trained cyclists (n = 16) were equally divided into 2 groups (MC or isoenergetic placebo (PLA)) and consumed 30 mL of supplement, twice per day for 8 consecutive days. On the fifth day of supplementation, participants completed a 109-min cycling trial designed to replicate road race demands. Functional performance (maximum voluntary isometric contraction (MVIC), cycling efficiency, 6-s peak cycling power) and delayed onset muscle soreness were assessed at baseline, 24, 48, and 72 h post-trial. Blood samples collected at baseline, immediately pre- and post-trial, and at 1, 3, 5, 24, 48, and 72 h post-trial were analysed for indices of inflammation (interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor alpha, high-sensitivity C-reactive protein (hsCRP)), oxidative stress (lipid hydroperoxides), and muscle damage (creatine kinase). MVIC (P < 0.05) did not decline in the MC group (vs. PLA) across the 72-h post-trial period and economy (P < 0.05) was improved in the MC group at 24 h. IL-6 (P < 0.001) and hsCRP (P < 0.05) responses to the trial were attenuated with MC (vs. PLA). No other blood markers were significantly different between MC and PLA groups. The results of the study suggest that Montmorency cherry concentrate can be an efficacious functional food for accelerating recovery and reducing exercise-induced inflammation following strenuous cycling exercise.


Two modes of survival of fission yeast without telomerase.
Deletion of the telomerase catalytic subunit gene trt1+ in Schizosaccharomyces pombe results in death for the majority of cells, but a subpopulation survives. Here it is shown that most survivors have circularized all of their chromosomes, whereas a smaller number maintain their telomeres presumably through recombination. When the telomeric DNA-binding gene taz1+ is also deleted, trt1- taz1- survivors use the recombinational mode more frequently. Moreover, the massive elongation of telomeres in taz1- cells is absent in the double mutant. Thus, Taz1p appears to regulate telomeric recombination as well as telomerase activity in fission yeast.


Immunogenicity of High-Dose MVA-Based MERS Vaccine Candidate in Mice and Camels.
The Middle East respiratory syndrome coronavirus (MERS-CoV) is a zoonotic pathogen that can transmit from dromedary camels to humans, causing severe pneumonia, with a 35% mortality rate. Vaccine candidates have been developed and tested in mice, camels, and humans. Previously, we developed a vaccine based on the modified vaccinia virus Ankara (MVA) viral vector, encoding a full-length spike protein of MERS-CoV, MVA-MERS. Here, we report the immunogenicity of high-dose MVA-MERS in prime-boost vaccinations in mice and camels. Three groups of mice were immunised with MVA wild-type (MVA-wt) and MVA-MERS (MVA-wt/MVA-MERS), MVA-MERS/MVA-wt, or MVA-MERS/MVA-MERS. Camels were immunised with two doses of PBS, MVA-wt, or MVA-MERS. Antibody (Ab) responses were evaluated using ELISA and MERS pseudovirus neutralisation assays. Two high doses of MVA-MERS induced strong Ab responses in both mice and camels, including neutralising antibodies. Anti-MVA Ab responses did not affect the immune responses to the vaccine antigen (MERS-CoV spike). MVA-MERS vaccine, administered in a homologous prime-boost regimen, induced high levels of neutralising anti-MERS-CoV antibodies in mice and camels. This could be considered for further development and evaluation as a dromedary vaccine to reduce MERS-CoV transmission to humans.


Evaluation of Culture, Antigen Detection and Polymerase Chain Reaction for Detection of Vaginal Colonization of Group B Streptococcus (GBS) in Pregnant Women.
Group B Streptococcal infection is an important cause of neonatal morbidity and mortality. Early detection of perinatal vagino-rectal (VR) carriage of Group B Streptococcus (GBS) is important in the management of newborn infections. The objective of the study was to evaluate Culture, antigen detection and Polymerase chain reaction for detection of GBS in Pregnant women. Observational descriptive study was done in a tertiary care hospital in Southern India. VR swabs were collected from 50 women at 35 to 37 weeks of gestation. Culture in a selective Lim enrichment broth with subsequent culture on 5% sheep blood agar, Conventional PCR assay and antigen detection method were performed. The performance of antigen detection and PCR methods were compared with culture. STATISTICAL ANALYSIS was performed by Chi-Square test. GBS cultures were positive for 16% of the specimen (8 out of 50). Considering culture as a gold standard, Sensitivity, Specificity, Positive predictive value and Negative predictive value of antigen detection was 100%, 92.86%, 72.73%, 100% and similarly for that of PCR was 100%, 45.23%, 25.80%, 100%, respectively. Antigen detection method was the rapid, sensitive and specific test for the detection of GBS colonizers during pregnancy.


Economic injury level of the psyllid, Agonoscena pistaciae, on Pistachio, Pistacia vera cv. Ohadi.
The pistachio psylla, Agonoscena pistaciae Burckhardt and Lauterer (Hemiptera: Psyllidae) is a major pest of pistachio trees, Pistacia vera L. (Sapindalis: Anacardiaceae) throughout pistachio-producing regions in Iran. Different density levels of A. pistaciae nymphs were maintained on pistachio trees by different insecticide dosages to evaluate the relationship between nymph density and yield loss (weight of 1000 nuts). Psylla nymph densities were monitored weekly by counting nymphs on pistachio terminal leaflets. There was a significant reduction in weight of 1000 nuts as seasonal averages of nymphs increased. Regression analysis was used to determine the relationship between nymph density and weight of 1000 nuts. The economic injury levels varied as a function of market values, management costs, insecticide efficiency and yield loss rate and ranged from 7.7 to 30.7 nymphal days per terminal leaflet, based on weight of 1000 nuts.


Potassium-induced cardioplegia during normothermic cardiac arrest. Morphologic study of the effect of varying concentrations of potassium on myocardial anoxic injury.
Most corrective procedures as well as myocardial revascularization require a period of cardiac arrest, and numerous methods have been proposed to protect the myocardium during this ischemic episode. Potassium-induced cardioplegia is one method that appears to be of benefit in this setting. Since it is recognized that myocardial necrosis may result at very high doses of potassium, we examined the effect of varying concentrations of potassium on myocardial anoxic injury. Using an isolated rat heart preparation, we evaluated anoxic injury occurring with cardioplegic solutions containing various concentrations of K+, ranging from 15 to 200 mEq. per liter, during a 50 minute normothermic arrest followed by 60 minutes of reperfusion. The transverse histologic sections of the left ventricular myocardium were analyzed for contraction band injury by morphometric and qualitative methods. Among the 62 animals studied the least severe anoxic injury was seen with K+ cardioplegia at concentrations of 25 and 30 mEq. per liter. At lower and higher concentrations there was little difference between the hearts exposed to anoxia with or without K+ cardioplegia. Potassium administered in very high doses, i.e., 100 or 200 mEq. of K+ per liter, led to contracture and extensive myocardial cell injury. This study suggests that potassium-induced cardioplegia is effective in reducing cell injury due to anoxia, and in this model an optimal concentration range was 25 to 30 mEq. per liter.


Multi-organ expression profiling uncovers a gene module in coronary artery disease involving transendothelial migration of leukocytes and LIM domain binding 2: the Stockholm Atherosclerosis Gene Expression (STAGE) study.
Environmental exposures filtered through the genetic make-up of each individual alter the transcriptional repertoire in organs central to metabolic homeostasis, thereby affecting arterial lipid accumulation, inflammation, and the development of coronary artery disease (CAD). The primary aim of the Stockholm Atherosclerosis Gene Expression (STAGE) study was to determine whether there are functionally associated genes (rather than individual genes) important for CAD development. To this end, two-way clustering was used on 278 transcriptional profiles of liver, skeletal muscle, and visceral fat (n = 66/tissue) and atherosclerotic and unaffected arterial wall (n = 40/tissue) isolated from CAD patients during coronary artery bypass surgery. The first step, across all mRNA signals (n = 15,042/12,621 RefSeqs/genes) in each tissue, resulted in a total of 60 tissue clusters (n = 3958 genes). In the second step (performed within tissue clusters), one atherosclerotic lesion (n = 49/48) and one visceral fat (n = 59) cluster segregated the patients into two groups that differed in the extent of coronary stenosis (P = 0.008 and P = 0.00015). The associations of these clusters with coronary atherosclerosis were validated by analyzing carotid atherosclerosis expression profiles. Remarkably, in one cluster (n = 55/54) relating to carotid stenosis (P = 0.04), 27 genes in the two clusters relating to coronary stenosis were confirmed (n = 16/17, P<10(-27 and-30)). Genes in the transendothelial migration of leukocytes (TEML) pathway were overrepresented in all three clusters, referred to as the atherosclerosis module (A-module). In a second validation step, using three independent cohorts, the A-module was found to be genetically enriched with CAD risk by 1.8-fold (P<0.004). The transcription co-factor LIM domain binding 2 (LDB2) was identified as a potential high-hierarchy regulator of the A-module, a notion supported by subnetwork analysis, by cellular and lesion expression of LDB2, and by the expression of 13 TEML genes in Ldb2-deficient arterial wall. Thus, the A-module appears to be important for atherosclerosis development and, together with LDB2, merits further attention in CAD research.


Genome-wide association and HLA region fine-mapping studies identify susceptibility loci for multiple common infections.
Infectious diseases have a profound impact on our health and many studies suggest that host genetics play a major role in the pathogenesis of most of them. We perform 23 genome-wide association studies for common infections and infection-associated procedures, including chickenpox, shingles, cold sores, mononucleosis, mumps, hepatitis B, plantar warts, positive tuberculosis test results, strep throat, scarlet fever, pneumonia, bacterial meningitis, yeast infections, urinary tract infections, tonsillectomy, childhood ear infections, myringotomy, measles, hepatitis A, rheumatic fever, common colds, rubella and chronic sinus infection, in over 200,000 individuals of European ancestry. We detect 59 genome-wide significant (P < 5 × 10-8) associations in genes with key roles in immunity and embryonic development. We apply fine-mapping analysis to dissect associations in the human leukocyte antigen region, which suggests important roles of specific amino acid polymorphisms in the antigen-binding clefts. Our findings provide an important step toward dissecting the host genetic architecture of response to common infections.Susceptibility to infectious diseases is, among others, influenced by the genetic landscape of the host. Here, Tian and colleagues perform genome-wide association studies for 23 common infections and find 59 risk loci for 17 of these, both within the HLA region and non-HLA loci.


Is there a relationship between morphokinetic parameters and neonatal sex in fresh embryo transfers?
To investigate whether morphokinetic parameters differ between male and female embryos in IVF embryos resulting in live births, a retrospective cohort study was undertaken. Files of all live births resulting from a single embryo transfer (SET) cultured in time-lapse incubators between 2013 and 2019 in two tertiary care centres were reviewed. The study group consisted of 187 SETs resulted in 187 live births, of which 100 were females (53.5%) and 87 were males (46.5%). Embryo selection for transfer was based on the known implantation data (KID) score provided by the Embryoscope and morphological assessment by experienced embryologists. Neonatal sex was confirmed through live birth documentation. Morphokinetic parameters and day 3 and day 5 KID scores of male and female embryos were compared. Maternal baseline and treatment characteristics were similar between groups. Morphokinetic time-lapse parameters of male and female embryos including: pronuclei fading; cleavage timings (t2-t9); second and third cell cycle durations; synchrony of the second and third cleavages; late morphokinetic parameters and KID scores did not differ between groups. In conclusion, time-lapse morphokinetic parameters and embryo selection methods do not seem to differ between male and female embryos, and their utilization does not bias towards any neonatal sex.


"It just happens": a qualitative study exploring low-income women's perspectives on pregnancy intention and planning.
Unintended pregnancy is common and disproportionately occurs among low-income women. We conducted a qualitative study with low-income women to better typologize pregnancy intention, understand the relationship between pregnancy intention and contraceptive use, and identify the contextual factors that shape pregnancy intention and contraceptive behavior. Semistructured interviews were conducted with low-income, African-American and white women aged 18-45 recruited from reproductive health clinics in Pittsburgh, PA, to explore factors that influence women's pregnancy-related behaviors. Narratives were analyzed using content analysis and the constant comparison method. Among the 66 participants (36 African-American and 30 white), we identified several factors that may impede our public health goal of increasing the proportion of pregnancies that are consciously desired and planned. First, women do not always perceive that they have reproductive control and therefore do not necessarily formulate clear pregnancy intentions. Second, the benefits of a planned pregnancy may not be evident. Third, because preconception intention and planning do not necessarily occur, decisions about the acceptability of a pregnancy are often determined after the pregnancy has already occurred. Finally, even when women express a desire to avoid pregnancy, their contraceptive behaviors are not necessarily congruent with their desires. We also identified several clinically relevant and potentially modifiable factors that help to explain this intention-behavior discrepancy, including women's perceptions of low fecundity and their experiences with male partner contraceptive sabotage. Our findings suggest that the current conceptual framework that views pregnancy-related behaviors from a strict planned behavior perspective may be limited, particularly among low-income populations. This study identified several cognitive and interpersonal pathways to unintended pregnancy among low-income women in Pittsburgh, PA, including perceptions of low reproductive control, perceptions of low fecundity and male partner reproductive coercion.


[Review of cases of zoophilia in patients with Parkinson's disease].
Parkinson's disease (PD) is characterized by motor symptoms such as bradykinesia, rigidity, alteration of postural reflexes and tremor at rest and other non-motor symptoms such as changes in sleep patterns and sexual behavior. However, little is known about paraphilic sexual behaviors. To summarize the number of cases of zoophilic behaviors in patients with PD between January 2000 and December 2017. A review was carried out in PubMed, Scopus and Virtual Health Library. Eleven articles were identified by title; six were excluded because they did not present cases related to zoophilic behavior. We found five cases of men, usually with PD of several years of course, taking dopamine agonists and who presented the zoophilic behaviors followed increasing of the dose. The zoophilic behaviors decreased with reducing doses of dopamine agonists and taking atypical antipsychotic such as clozapine or quetiapine. It is limited the case reports of zoophilic behaviors in patients with PD. The patients reported are men in whom the dose of dopamine agonists was increased. It is important that the clinical follow-up of patients with PD disease includes a careful review of sexual behaviors including those of the paraphilic spectrum.


Study protocol for a randomised controlled trial evaluating the clinical effect of antibiotic prophylaxis in children with recurrent respiratory tract infections: the Approach study.
Respiratory tract infections (RTIs) affect children all over the world and are associated with significant morbidity and mortality. In particular, recurrent RTIs cause a high burden of disease and lead to frequent doctor visits. Children with recurrent RTIs generally have no significant alterations or deficits in systemic immunity. In an attempt to treat the assumed bacterial component involved, they are often treated with prolonged courses of prophylactic antibiotics taken on a daily basis. Despite its common use, there is no evidence that this is beneficial. Studies assessing the clinical effectiveness of antibiotic prophylaxis as well as potential adverse effects and antibiotic resistance development, are therefore urgently needed. We present a protocol for a randomised double-blind placebo-controlled trial comparing co-trimoxazole with placebo treatment in children with recurrent RTIs. A total of 158 children (aged 6 months-10 years) with recurrent RTIs without significant comorbidity will be enrolled from a minimum of 10 Dutch hospitals. One group receives co-trimoxazole 18 mg/kg two times per day (36 mg/kg/day) and the other group receives a placebo two times per day for a period of 3 months. The main objective is to determine whether antibiotic prophylaxis is more effective than placebo to prevent/reduce respiratory symptoms in children with recurrent RTIs. Respiratory symptoms will be scored by parents on a daily basis in both study arms by the use of a mobile phone application. Our primary outcome will be the number of days with at least two respiratory symptoms during the treatment. Ethics approval was obtained from the Medical Ethics Research Committee Zuidwest Holland/LDD. A manuscript with the study results will be submitted to a peer-reviewed journal. All participants will be informed about the study results. The results of the study will inform clinical guidelines regarding the prophylactic treatment of children with recurrent RTIs. NL7044.


Perceived and Ideal Body Image in Young Women in South Western Saudi Arabia.
The aim of this study was to investigate perceived and ideal body image (BI) and associated factors among female university students in Saudi Arabia. This cross-sectional study included 663 university female students. Anthropometric measurements including weight, height, BMI, and BI perception (the 9-figure silhouette) were obtained. Descriptive and logistic regression analysis were conducted. An agreement between actual, perceived, and ideal BI was found in 23% of the participants. Behavioral (activity levels), social (presence of obese parents and fathers' level of education), and economic factors (households' monthly income, number of cars in the household, and kind of residence) were positively and significantly associated with the desire to be thinner. Similarly, socioeconomic associations (number of sisters and number of cars in the household) correlated positively and significantly with the desire to be heavier. The whole family should rather be considered in interventions related to appearance concerns and BI discrepancies. Furthermore, campaigns targeting improvement of adolescents' physical self-image should be a major priority of the public health sector.


Dietary effects on body composition, glucose metabolism, and longevity are modulated by skeletal muscle mitochondrial uncoupling in mice.
Little is known about how diet and energy metabolism interact in determination of lifespan under ad libitum feeding. From 12 weeks of age until death, male and female wild-type (WT) and transgenic (TG) mice with increased skeletal muscle mitochondrial uncoupling (HSA-mUCP1 mice) were fed one of three different semisynthetic diets differing in macronutrient ratio: control (high-carbohydrate/low-fat-HCLF) and two high-fat diets: high-carbohydrate/high-fat (HCHF), and low-carbohydrate/high-fat (LCHF). Compared to control and LCHF, HCHF feeding rapidly and significantly increased body fat content in WT. Median lifespan of WT was decreased by 33% (HCHF) and 7% (LCHF) compared to HCLF. HCHF significantly increased insulin resistance (HOMA) of WT from 24 weeks on compared to control. TG mice had lower lean body mass and increased energy expenditure, insulin sensitivity, and maximum lifespan (+10%) compared to WT. They showed a delayed development of obesity on HCHF but reached similar maximum adiposity as WT. TG median lifespan was only slightly reduced by HCHF (-7%) and unaffected by LCHF compared to control. Correlation analyses showed that decreased longevity was more strongly linked to a high rate of fat gain than to adiposity itself. Furthermore, insulin resistance was negatively and weight-specific energy expenditure was positively correlated with longevity. We conclude that (i) dietary macronutrient ratios strongly affected obesity development, glucose homeostasis, and longevity, (ii) that skeletal muscle mitochondrial uncoupling alleviated the detrimental effects of high-fat diets, and (iii) that early imbalances in energy homeostasis leading to increased insulin resistance are predictive for a decreased lifespan.


Isolation of a new virus, HBLV, in patients with lymphoproliferative disorders.
A novel human B-lymphotropic virus (HBLV) was isolated from the peripheral blood leukocytes of six individuals: two HTLV-III seropositive patients from the United States (one with AIDS-related lymphoma and one with dermatopathic lymphadenopathy), three HTLV-III seronegative patients from the United States (one with angioimmunoblastic lymphadenopathy, one with cutaneous T-cell lymphoma, and one with immunoblastic lymphoma), and one HTLV-III seronegative patient with acute lymphocytic leukemia from Jamaica. All six isolates were closely related by antigenic analysis, and sera from all six virus-positive patients reacted immunologically with each virus isolate. In contrast, only four sera from 220 randomly selected healthy donors and none from 12 AIDS patients without associated lymphoma were seropositive. The virus selectively infected freshly isolated human B cells and converted them into large, refractile mono- or binucleated cells with nuclear and cytoplasmic inclusion bodies. HBLV is morphologically similar to viruses of the herpesvirus family but is readily distinguishable from the known human and nonhuman primate herpesviruses by host range, in vitro biological effects, and antigenic features.


Patellar tendon ACL reconstruction and rehabilitation practices and opinions (autograft versus allograft): orthopaedic sports medicine fellowship program survey.
We wanted to determine the bone-patellar tendon-bone (BPTB) anterior cruciate ligament (ACL) reconstruction practices of accredited orthopaedic sports medicine fellowship programs and their opinions about whether differences should exist in rehabilitation protocol, bracing, and timing of release to cutting/agility sports between autogeneic and allogeneic grafts. Our survey showed most programs did 51 to 100 BPTB ACL reconstructions during the 12 months before survey completion. Standard rehabilitation protocols were used without differences based on BPTB graft type or fixation concerns. Programs were equally divided regarding whether BPTB graft type should be a timing of release to cutting/agility sports factor. Programs were almost equally divided regarding routinely prescribed derotation braces. More programs used autograft rather than allograft BPTB tissue for ACL reconstruction, without rehabilitation protocol differences based on graft type or fixation concerns. Conflicting results regarding protocol and timing of release to cutting/agility sports indicate that several factors may contribute to the clinical decision-making process. Equivocal results regarding derotation brace prescription raises concerns regarding their necessity.


Anaesthetic morbidity at the University Hospital of the West Indies.
There is little information on adverse anaesthetic outcomes from the Caribbean. The aim of this study was to investigate the occurrence of anaesthetic morbidity and mortality at the University Hospital of the West Indies (UHWI) and to identify possible risk factors. All anaesthetic procedures at the UHWI were monitored for adverse events and patient outcomes for the 12-month period from March 2004 to February 2005. Possible risk factors for these adverse events were assessed using logistic regression. Of 3185 anaesthetic procedures, the incidence of intra-operative events was 201 per 1000 (95% CI 187, 215); 151 per 1000 being cardiovascular and 26 per 1000 respiratory. Others included excess blood loss and equipment failure, hyperglycaemia, nausea and vomiting. Patients with intraoperative complications were three times more likely to have complications during recovery (OR = 3.35; 95% CI 2.59, 4.33, p < 0.001). The incidence of complications among paediatric patients was 139 per 1000 (95% CI 104, 174) intra-operatively and 58 per 1000 (95% CI 34, 81) during recovery. Risk factors for developing complications (p < 0.05) included age > 50 years, ASA status > or = II, prolonged anaesthesia, high surgical risk, general or combined anaesthetic techniques, senior anaesthetist, intubated patients and co-morbidities. There were 14 operative mortalities, none of which was anaesthesia-related Anaesthetic complication rates at the UHWI are comparable to those in developed countries, except for higher paediatric complication rates and ICU admissions and lower rates of postoperative nausea and vomiting.


Mechanism of protection afforded by polyaspartic acid against gentamicin-induced phospholipidosis. II. Comparative in vitro and in vivo studies with poly-L-aspartic, poly-L-glutamic and poly-D-glutamic acids.
Poly-L-aspartic acid (poly-L-Asp) protects rats against gentamicin (GM)-induced nephrotoxicity (functional and pathological changes) and early cortical alterations (phospholipidosis and increase in cell turnover) without decreasing, but actually increasing, the renal accumulation of the drug. We suggested that this protection occurs through the complexation of GM by poly-L-Asp, after their pinocytosis and accumulation in the lysosomes of the renal cortex (Kishore et al., J. Pharmacol. Exp. Ther. 867-874, 1990). Here we examine further our proposal by comparatively assessing poly-L-Asp (as provided by the Sigma Chemical Co., St. Louis, MO; MW 9-11,000), with two other polyanionic peptides, viz, poly-L-glutamic (poly-L-Glu; MW 14,300) and poly-D-glutamic (poly-D-Glu; MW 20,000) acids obtained from the same supplier. In vitro, all three polyanions showed a similar capacity to bind GM, to displace it from anionic phospholipids at acid pH and thereby to decrease the inhibitory potency of GM toward lysosomal phospholipase A1. In vivo, however, only poly-L-Asp and poly-D-Glu were able to prevent the development of GM-induced renal lysosomal phospholipidosis as assessed by key biochemical criteria (increase in lipid phosphorus and decrease of acid sphingomyelinase activity) and by examination of the lysosomal content in the electron microscope (accumulation of myeloid bodies). Based on these criteria, poly-L-Glu completely failed to protect. In vitro, poly-L-Glu was 13- to 17-fold more susceptible to hydrolysis by liver lysosomal extracts at pH 5.4 after 48 hr incubation, as compared to poly-L-Asp and poly-D-Glu, respectively. Assuming that all three polyanions tested are transported and accumulated in lysosomes of renal cortex to the same extent and that their respective rates of hydrolysis therein compare to that measured in vitro, these results suggest that stability of polyanions in lysosomes is an essential requisite for protection against GM-induced phospholipidosis and thus strengthens our earlier proposal that the site of action of poly-L-Asp must be in lysosomes. Although protecting from phospholipidosis, poly-D-Glu, however, caused a so far undescribed lysosomal storage disorder consisting of the accumulation of osmiophilic, nonlamellar material. This study, therefore, also demonstrates that not all polyanions resistant to lysosomal enzymes can be used as nephroprotectants, inasmuch as these, as is the case for poly-D-Glu, may cause renal alterations on their own.


DBS and electrical neuro-network modulation to treat neurological disorders.
The use of neuromodulatory techniques in the treatment of neurological disorders is expanding and now includes devices targeting the motor cortex, basal ganglia, spinal cord, peripheral nervous system, and autonomic nervous system. In this chapter, we review and discuss the current and past literature as well as review indications for each of these devices in the ongoing management of many common neurological diseases including chronic pain, Parkinson's disease, tremor, dystonia, and epilepsy. We also discuss and update mechanisms of deep brain stimulation and electrical neuro-network modulation.


Deformation of the human brain induced by mild acceleration.
Rapid deformation of brain matter caused by skull acceleration is most likely the cause of concussion, as well as more severe traumatic brain injury (TBI). The inability to measure deformation directly has led to disagreement and confusion about the biomechanics of concussion and TBI. In the present study, brain deformation in human volunteers was measured directly during mild, but rapid, deceleration of the head (20-30 m/sec2 peak, approximately 40 msec duration), using an imaging technique originally developed to measure cardiac deformation. Magnetic resonance image sequences with imposed "tag" lines were obtained at high frame rates by repeating the deceleration and acquiring a subset of image data each repetition. Displacements of points on tag lines were used to estimate the Lagrangian strain tensor field. Qualitative (visual) and quantitative (strain) results illustrate clearly the deformation of brain matter due to occipital deceleration. Strains of 0.02-0.05 were typical during these events (0.05 strain corresponds roughly to a 5% change in the dimension of a local tissue element). Notably, compression in frontal regions and stretching in posterior regions were observed. The motion of the brain appears constrained by structures at the frontal base of the skull; it must pull away from such constraints before it can compress against the occipital bone. This mechanism is consistent with observations of contrecoup injury in occipital impact.


Assessment of wastewater-irrigated soil containing heavy metals and establishment of specific biomarkers.
Irrigation with treated wastewater (TWW) is a vital alternative for arid and semi-arid lands but it poses pollution-risk to soil, vegetation and groundwater. Therefore, in the present study, in vitro bioassays were used to evaluate the adverse effects of TWW and irrigated-soil extract sample, on mammalian cells, with respect to heavy metal--Ni, Cd, Pb, Fe, Al-content. The heat shock protein (HSP) 47, E-screen, and transepithelial electrical resistance (TEER) assays served to investigate the stress response of treated-HSP47-transfected Chinese hamster ovary (CHO) cells, the estrogenic activity of the samples in MCF-7 breast cancer cells, and the barrier function (BF) of Caco-2 cells. Furthermore, proteomics analyses were performed to shed light on involved mechanisms and to establish pollution biomarkers. Results showed that the TWW elicited a stress response on HSP cells from 0.1% concentration while soil extract samples exhibited a stress at 1%. TWW induced an estrogenic activity at 10%; up-regulating cell proliferation and tumor-related proteins. Soil extract triggered the enhanced expression of HSP70 family proteins as survival mechanisms against their cytotoxicity toward MCF-7 cells. Moreover, depending on the concentration, 1% of soil extract from 20 cm depth (T20) resulted in a disruption of BF in Caco-2 cells involving cell metabolism, protein synthesis and tumor marker proteins, whereas, 5% of T20 induced the expression of BF-related proteins associated to heat shock, oxidative stress, cell proliferation and glycolytic metabolic pathway. These biological techniques were found to be extremely useful to evaluate the impact of wastewater reuse and to establish specific biomarkers that are common proteins for humans, other mammals and plants. Future studies should focus on exposure quantifications.


Effect of GINS2 on proliferation and apoptosis in leukemic cell line.
Although previous researches have demonstrated that GINS2 express abundantly and abnormally in many malignant solid tumors, such as breast cancer, melanoma and hepatic carcinoma. However, the role and precise molecular mechanism in acute promyelocytic leukemia (APL) are rarely reported. In this current study, we investigated the possible effect and particular mechanism of GINS2 in occurrence and development of APL. We synthesized interference plasmid targeted GINS2 successfully in vitro and also constructed recombinant adenovirus vector carrying GINS2 gene in order to down-regulate or up-regulate GINS2 expression from two aspects of positive and negative in APL. After siRNA were transfected into HL60 cells, both GINS2 expression level of mRNA and protein in interfering group were down-regulated when compared with control groups. Together, MTT and flow cytometry technology showed that cell growth was significantly inhibited. Moreover, the expression lever of Bax was distinctly increased whereas Bcl2 was dramatically decreased in transfected group. Further experiments revealed that down-regulation of GINS2 expression inhibited DNA replication and had a G2/M phase block in HL60 cells. What's more, ATM, CHK2, and P53 gene could involve in the pathogenic signaling pathways of HL60 cells when GINS2 gene was down-regulated. On the contrary, after HL60 cells were infected by recombinant adenovirus vector which contained GINS2 gene, we observed that over-expression of GINS2 could promote HL-60 cell proliferation. What's more, GINS2 might implicate a potential target for leukemia gene therapy.


Chiropractic treatment of older adults with neck pain with or without headache or dizziness: analysis of 288 Australian chiropractors' self-reported views.
Neck pain is a leading cause of individual and societal burden worldwide, affecting an estimated 1 in 5 people aged 70 years and older. The nature and outcomes of chiropractic care for older adults with neck pain, particularly those with co-morbid headaches, remains poorly understood. Therefore, we sought to ascertain: What proportion of Australian chiropractors' caseload comprises older adults with neck pain (with or without headache); How are these conditions treated; What are the reported outcomes? An online survey examining practitioner and practice characteristics, clinical patient presentations, chiropractic treatment methods and outcomes, and other health service use, was distributed to a random nationally representative sample of 800 Australian chiropractors. Quantitative methods were used to analyze the data. Two hundred eighty-eight chiropractors (response rate = 36%) completed the survey between August and November 2017. Approximately one-third (M 28.5%, SD 14.2) of the chiropractors' patients were older adults (i.e. aged ≥65 years), of which 45.5% (SD 20.6) presented with neck pain and 31.3% (SD 20.3) had co-morbid headache. Chiropractors reported to combine a range of physical and manual therapy treatments, exercises and self-management practices in their care of these patients particularly: manipulation of the thoracic spine (82.0%); activator adjustment of the neck (77.3%); and massage of the neck (76.5%). The average number of visits required to resolve headache symptoms was reported to be highest among those with migraine (M 11.2, SD 8.8). The majority of chiropractors (57.3%) reported a moderate response to treatment in reported dizziness amongst older adults with neck pain. Approximately 82% of older adult patients were estimated to use at least one other health service concurrently to chiropractic care to manage their neck pain. This is the first known study to investigate chiropractic care of older adults living with neck pain. Chiropractors report using well-established conservative techniques to manage neck pain in older adults. Our findings also indicate that this target group of patients may frequently integrate chiropractic care with other health services in order to manage their neck pain. Further research should provide in-depth investigation of older patients' experience and other patient-reported outcomes of chiropractic treatment.


Hand-sewn cystogastrostomy using the novel single-incision laparoscopy with flexible-tip laparoscope.
Laparoscopy performed through a single incision has been increasingly reported as a novel technique implemented in a wide variety of surgical procedures. We report what we believe to be the first case of cystogastrostomy for treatment of a pancreatic pseudocyst using this technique. Patient developed pancreatic pseudocyst after severe biliary pancreatitis. The cyst was noted to increase in size on follow-up computed tomography scans. In addition, patient developed symptoms requiring intervention.


Can we distinguish anxiety from depression?
It is becoming increasingly apparent that although anxiety and depression are separate syndromes and can be identified as such, there is considerable overlap of clinical symptoms and pathophysiological processes. Data indicate that comorbid anxiety and depression is more common than either disorder alone. A large US study found that 58% of individuals with a history of depression also had an anxiety disorder, and a study by the World Health Organization showed that anxiety and depression were the most common coexisting psychological problems in primary care. Generalized anxiety disorder in particular is strongly comorbid with, and commonly precedes, major depression. The implications of comorbid anxiety and depression are significant, with increased social and psychological impairment, and poorer clinical outcomes and prognosis. Anxiety and depression coexist at much higher rates than would be expected by chance alone, suggesting that the two disorders are closely related and may have a common cause. Disturbances of serotonin and norepinephrine neurotransmission are both implicated in anxiety and depression, and new evidence suggests that these systems may provide a mechanistic link between the two disorders, with changes in one system being reflected in the other. Abnormal homeostasis of these two systems may result in anxiety and depression. New theories hypothesize a continuum of illness, with anxiety and depression possibly being different phenotypic expressions of a common neurobiological origin. There is still uncertainty regarding the neurobiological cause, but it is probably linked to dysregulation in the serotonergic and noradrenergic systems.


A dual function for chaperones SSB-RAC and the NAC nascent polypeptide-associated complex on ribosomes.
The yeast Hsp70/40 system SSB-RAC (stress 70 B-ribosome-associated complex) binds to ribosomes and contacts nascent polypeptides to assist cotranslational folding. In this study, we demonstrate that nascent polypeptide-associated complex (NAC), another ribosome-tethered system, is functionally connected to SSB-RAC and the cytosolic Hsp70 network. Simultaneous deletions of genes encoding NAC and SSB caused conditional loss of cell viability under protein-folding stress conditions. Furthermore, NAC mutations revealed genetic interaction with a deletion of Sse1, a nucleotide exchange factor regulating the cytosolic Hsp70 network. Cells lacking SSB or Sse1 showed protein aggregation, which is enhanced by additional loss of NAC; however, these mutants differ in their potential client repertoire. Aggregation of ribosomal proteins and biogenesis factors accompanied by a pronounced deficiency in ribosomal particles and translating ribosomes only occurs in ssbDelta and nacDeltassbDelta cells, suggesting that SSB and NAC control ribosome biogenesis. Thus, SSB-RAC and NAC assist protein folding and likewise have important functions for regulation of ribosome levels. These findings emphasize the concept that ribosome production is coordinated with the protein-folding capacity of ribosome-associated chaperones.


Oxygenated End-Hypothermic Machine Perfusion in Expanded Criteria Donor Kidney Transplant: A Randomized Clinical Trial.
Continuous hypothermic machine perfusion during organ preservation has a beneficial effect on graft function and survival in kidney transplant when compared with static cold storage (SCS). To compare the effect of short-term oxygenated hypothermic machine perfusion preservation (end-HMPo2) after SCS vs SCS alone on 1-year graft survival in expanded criteria donor kidneys from donors who are brain dead. In a prospective, randomized, multicenter trial, kidneys from expanded criteria donors were randomized to either SCS alone or SCS followed by end-HMPo2 prior to implantation with a minimum machine perfusion time of 120 minutes. Kidneys were randomized between January 2015 and May 2018, and analysis began May 2019. Analysis was intention to treat. On randomization and before implantation, deceased donor kidneys were either kept on SCS or placed on HMPo2. Primary end point was 1-year graft survival, with delayed graft function, primary nonfunction, acute rejection, estimated glomerular filtration rate, and patient survival as secondary end points. Centers in 5 European countries randomized 305 kidneys (median [range] donor age, 64 [50-84] years), of which 262 kidneys (127 [48.5%] in the end-HMPo2 group vs 135 [51.5%] in the SCS group) were successfully transplanted. Median (range) cold ischemia time was 13.2 (5.1-28.7) hours in the end-HMPo2 group and 12.9 (4-29.2) hours in the SCS group; median (range) duration in the end-HMPo2 group was 4.7 (0.8-17.1) hours. One-year graft survival was 92.1% (n = 117) in the end-HMPo2 group vs 93.3% (n = 126) in the SCS group (95% CI, -7.5 to 5.1; P = .71). The secondary end point analysis showed no significant between-group differences for delayed graft function, primary nonfunction, estimated glomerular filtration rate, and acute rejection. Reconditioning of expanded criteria donor kidneys from donors who are brain dead using end-HMPo2 after SCS does not improve graft survival or function compared with SCS alone. This study is underpowered owing to the high overall graft survival rate, limiting interpretation. isrctn.org Identifier: ISRCTN63852508.


Keratinocyte growth factor and the transcription factors C/EBP alpha, C/EBP delta, and SREBP-1c regulate fatty acid synthesis in alveolar type II cells.
Strategies to stimulate endogenous surfactant production require a detailed understanding of the regulation of lipogenesis in alveolar type II cells. We developed culture conditions in which keratinocyte growth factor (KGF) stimulates fatty acid and phospholipid synthesis. KGF stimulated acetate incorporation into phosphatidylcholine, disaturated phosphatidylcholine, and phosphatidylglycerol more than 5% rat serum alone. To determine the mRNA levels of lipogenic enzymes and transport proteins, we analyzed gene expression by oligonucleotide microarrays. KGF increased the mRNA levels for fatty acid synthase, stearoyl-CoA desaturase-1 (SCD-1), and epidermal fatty acid-binding protein more than rat serum alone. In addition, KGF increased the mRNA levels of the transcription factors CCAAT/enhancer-binding protein alpha (C/EBPalpha) and C/EBPdelta as well as SREBP-1c (ADD-1), but not PPARgamma. These changes in C/EBPalpha and C/EBPdelta were confirmed by in situ hybridization. SCD-1 was also found to be highly expressed in alveolar type II cells in vivo. Furthermore, KGF increased protein levels of fatty acid synthase, C/EBPalpha, C/EBPdelta, SREBP-1, epidermal fatty acid-binding protein, and SCD. Finally, the liver X receptor agonist T0901317 increased acetate incorporation and SREBP-1 but not SREBP-2 protein levels. In summary, KGF stimulates lipogenesis in type II cells by a coordinated expression of lipogenic enzymes and transport proteins regulated by C/EBP isoforms and SREBP-1c.


Beamforming in noninvasive brain-computer interfaces.
Spatial filtering (SF) constitutes an integral part of building EEG-based brain-computer interfaces (BCIs). Algorithms frequently used for SF, such as common spatial patterns (CSPs) and independent component analysis, require labeled training data for identifying filters that provide information on a subject's intention, which renders these algorithms susceptible to overfitting on artifactual EEG components. In this study, beamforming is employed to construct spatial filters that extract EEG sources originating within predefined regions of interest within the brain. In this way, neurophysiological knowledge on which brain regions are relevant for a certain experimental paradigm can be utilized to construct unsupervised spatial filters that are robust against artifactual EEG components. Beamforming is experimentally compared with CSP and Laplacian spatial filtering (LP) in a two-class motor-imagery paradigm. It is demonstrated that beamforming outperforms CSP and LP on noisy datasets, while CSP and beamforming perform almost equally well on datasets with few artifactual trials. It is concluded that beamforming constitutes an alternative method for SF that might be particularly useful for BCIs used in clinical settings, i.e., in an environment where artifact-free datasets are difficult to obtain.


A time-varying effect model for examining group differences in trajectories of zero-inflated count outcomes with applications in substance abuse research.
This study proposes a time-varying effect model for examining group differences in trajectories of zero-inflated count outcomes. The motivating example demonstrates that this zero-inflated Poisson model allows investigators to study group differences in different aspects of substance use (e.g., the probability of abstinence and the quantity of alcohol use) simultaneously. The simulation study shows that the accuracy of estimation of trajectory functions improves as the sample size increases; the accuracy under equal group sizes is only higher when the sample size is small (100). In terms of the performance of the hypothesis testing, the type I error rates are close to their corresponding significance levels under all settings. Furthermore, the power increases as the alternative hypothesis deviates more from the null hypothesis, and the rate of this increasing trend is higher when the sample size is larger. Moreover, the hypothesis test for the group difference in the zero component tends to be less powerful than the test for the group difference in the Poisson component. Copyright © 2016 John Wiley & Sons, Ltd.


Each small antral follicle in ovaries of women with polycystic ovary syndrome produces more antimüllerian hormone than its counterpart in a normal ovary: an observational cross-sectional study.
To ascertain if subfertile women with polycystic ovary syndrome (PCOS) secrete more antimüllerian hormone (AMH) per antral follicle than control women. Observational cross-sectional study. Fertility clinic. A total of 438 women attending the fertility clinic over a period of 13 months from September 2012 to September 2013. Serum concentrations of AMH and the total antral follicle count (AFC) were obtained from women attending the fertility clinic. The ratio of AMH/AFC for each subject was calculated. Women were categorized into three groups: PCOS, polycystic ovarian morphology (PCOM), and control. PCOS and PCOM were defined based on the European Society for Human Reproduction and Embryology/American Society for Reproductive Medicine Rotterdam consensus criteria. The ratio of AMH/AFC for each subject in the three groups: PCOS, PCOM, and control. The median AMH/AFC ratios in the PCOS, PCOM, and control groups were 1.92, 1.13, and 1.00, respectively. The AMH/AFC ratio was significantly higher in the PCOS group compared with the PCOM and control groups (F[2,152] = 21.82). Women in the three groups were not statistically different regarding age, body mass index, earlier ovarian surgery, and smoking status. Subfertile women with PCOS secrete significantly more AMH per antral follicle than women with PCOM only and control women.


Pressure Injury Progression and Factors Associated With Different End-Points in a Home Palliative Care Setting: A Retrospective Chart Review Study.
Patients with advanced illnesses show the highest prevalence for pressure injuries. In the palliative care setting, the ultimate goal is injury healing, but equally important is wound maintenance, wound palliation (wound-related pain and symptom management), and primary and secondary wound prevention. To describe the course of healing for pressure injuries in a home palliative care setting according to different end-points, and to explore patient and caregiver characteristics and specific care activities associated with their achievement. Four-year retrospective chart review of 669 patients cared for in a home palliative care service, of those 124 patients (18.5%) had at least one pressure injury with a survival rate less than or equal to six months. The proportion of healed pressure injuries was 24.4%. Of the injuries not healed, 34.0% were in a maintenance phase, whereas 63.6% were in a process of deterioration. Body mass index (P = 0.0014), artificial nutrition (P = 0.002), and age <70 years (P = 0.022) emerged as predictive factors of pressure injury complete healing. Artificial nutrition, age, male caregiver (P = 0.034), and spouse (P = 0.036) were factors significantly associated with a more rapid pressure injury healing. Continuous deep sedation was a predictive factor for pressure injury deterioration and significantly associated with a more rapid worsening. Pressure injury healing is a realistic aim in home palliative care, particularly for injuries not exceeding Stage II occurring at least two weeks before death. When assessing pressure injuries, our results highlight the need to also pay attention to artificial nutrition, continuous deep sedation, and the caregiver's role and gender.


Exogenous and locally synthesized angiotensin II and glomerulosa cell functions.
We conducted this study to examine the effects of exogenous and locally synthesized angiotensin II (Ang II) on cultured bovine glomerulosa cell functions (i.e., aldosterone secretion and cell proliferation measured by [3H] thymidine incorporation into the deoxyribonucleic acids (DNA) after the arresting cell growth). The effects of Ang II were found to depend on the culture conditions. After 72 hours of serum-free culture, the differentiated function of cultured cells such as Ang II-induced aldosterone secretion was suppressed, and DNA synthesis was stimulated by Ang II. After 24 hours of serum-free culture, the cells showed a good steroidogenic response and DNA synthesis was inhibited after Ang II was added in a concentration-dependent manner (10(-11) to 10(-7) M). Ang II was detected in 24 hours of culture grown in a serum-free medium by a specific Ang II radioimmunoassay. Ion-exchange high-performance liquid chromatography indicated that this immunoreactive (ir) Ang II was composed mainly of Ang II with small amounts of angiotensin III (Ang III). The concentration of irAng II in the cultured medium was significantly reduced by the addition of captopril, indicating de novo generation and secretion of Ang II. Captopril (10(-5) to 10(-3) M) reduced aldosterone secretion and reciprocally increased DNA synthesis. Ang II antagonist, [Sar1, Ile8] Ang II, increased DNA synthesis presumably by competitive blockade of locally synthesized Ang II. In summary, Ang II inhibited cell proliferation. In addition to exogenous (circulating) Ang II, Ang II was generated and secreted by the glomerulosa cells themselves, and this locally synthesized Ang II appeared to work as an autocrine factor to stimulate aldosterone secretion and to suppress cell proliferation.


The role of nutrients in modulating disease.
The role of nutrition in the management of diseases has often centred on correcting apparent nutrient deficiencies or meeting estimated nutritional requirements of patients. Nutrition has traditionally been considered a supportive measure akin to fluid therapy and rarely it has been considered a primary means of ameliorating diseases. Recently, however, further understanding of the underlying mechanisms of various disease processes and how certain nutrients possess pharmacological properties have fuelled an interest in exploring how nutritional therapies themselves could modify the behaviour of various conditions. Nutrients such as omega-3 fatty acids, antioxidants and certain amino acids such as arginine and glutamine have all been demonstrated to have at least the potential to modulate diseases. Developments in the area of critical care nutrition have been particularly exciting as nutritional therapies utilising a combination of approaches have been shown to positively impact outcome beyond simply proving substrate for synthesis and energy. Application of certain nutrients for the modulation of diseases in veterinary patients is still in early stages, but apparent successes have already been demonstrated, and future studies are warranted to establish optimal approaches. This review describes the rationale of many of these approaches and discusses findings both in human beings and in animals, which may guide future therapy.


Sexual and Contraceptive Practices among Female Undergraduates in a Nigerian Tertiary Institution.
The reproductive health of adolescents and young women is integral to the wellbeing of a society. This study was carried out to determine current sexual practices and contraceptive usage among female undergraduate students in a Southwest Nigerian tertiary institution. It was a cross-sectional questionnaire based survey of female university undergraduates. Pre-tested questionnaire was used to elicit information on socio-demographic variables and sexual and contraceptive practices. Frequency tables were generated and univariate and multivariate logistic regressions were used to determine factors that influenced sexual and contraceptive practices. SPSS software version 16.0 was used for analysis. Of 350 students sampled, 306 completed the questionnaire. One hundred and eighty six (60.8%) students were currently sexually active. The mean age of sexual debut was 19.11 years. Sixty-six (35.5%) had more than one sexual partners. Contraceptive knowledge was 100%, but consistent use was 34.4%. A third of the respondents had sex for material rewards and/or under the influence of alcohol and recreational drugs. Students who were less than 20 years old (Adjusted OR: 3.52; 95%CI=2.10-6.82) were more likely to be sexually active while those from polygamous/separated families (Adjusted OR: 0.32; 95% CI=0.18-0.58) were less likely to be sexually active. There is a high level of sexual activity and low contraceptive use among female undergraduate students in Southwest Nigeria. More reproductive health education and promotion is necessary to safeguard their sexual health.


Molecular epidemiology of malaria in Cameroon. XVI. Longitudinal surveillance of in vitro pyrimethamine resistance in Plasmodium falciparum.
Clinical observations have shown that pyrimethamine resistance develops rapidly in endemic countries where antifolate drugs are used massively for the treatment of Plasmodium falciparum infections. To analyze this phenomenon, the in vitro response of clinical isolates to pyrimethamine and the dihydrofolate reductase (dhfr) gene sequence were analyzed in 2000-2001 and compared with the results obtained since 1994 in Yaounde, Cameroon. Of 139 samples obtained in 2000-2001, 10 (7.2%) isolates were of the wild-type, 116 had pure mutant alleles (2 [1.4%] with a single mutation, 11 [7.9%] with double mutations, and 103 [74.1%] with triple mutations), and 13 (9.4%) had mixed alleles. With the exception of a single isolate with triple mutations (50% inhibitory concentration [IC50] = 84.3 nM), all isolates with pure wild-type dhfr alleles (IC50 < 100 nM) and those with pure mutant dhfr alleles (between 1 and 3 point mutations; IC50 > or = 100 nM) were clearly distinguished by in vitro drug sensitivity assays. The results of the two methods are highly correlated, and both methodologic approaches indicate an increasing proportion of pyrimethamine-resistant isolates in Yaounde over the past eight years (42-45% in 1994-1995, 63-67% in 1997-1998, and 88-92% in 2000-2001). At present, clinical isolates carrying triple dhfr mutations predominate in Yaounde. This situation calls for a regular surveillance of the efficacy of antifolate drugs by all available means, including clinical evaluation, in vitro drug sensitivity assays, molecular markers, and pharmacologic studies.


An exploratory study on the impact of daily activities on the pleasure and physical activity of older adults.
Pleasure is one determinant of intrinsic motivation and yet a dimension often forgotten when promoting physical activity among the older population. In this study we investigate the relation between daily activities and physical activity, experience of pleasure, and the interaction between pleasure and physical activity in the daily lives of community-dwelling older adults. Participants carried a hip-worn accelerometer during 30 consecutive days resulting in a total of 320 days of data collection. Current activity, location, companion and experience of pleasure during each activity were assessed through experience sampling on a smartphone every 1-2 h. Between- and within-individual differences were analysed with multi-level models and 10xN = 1 regression analysis. Outdoor activities were associated with higher physical activity than indoor activities (p < 0.001). Performing leisure activities, outdoors and not alone significantly predicted pleasure in daily life (all p's < 0.05). Being more active while performing leisure activities resulted in higher experiences of pleasure (p < 0.001). However, when performing basic activities of daily living (e.g. commuting or households) this relation was inverted. Results provide meaningful indication for individual variance. The 30 days of data collected from each participant allow for identification of individual differences. Daily activities and their contexts do influence the experience of pleasure and physical activity of older adults in daily life of older adults, although similar research with larger population is recommended. Results are in accordance with the literature, indicating that the method adopted (accelerometry combined with experience sampling) provides reliable representation of daily life. Identification of individual differences can eventually be automatically performed through data mining techniques. Further research could look at innovative approaches to promote Active Ageing using mobile technology in the daily life, by promoting physical activity through recommendation of pleasurable activities, and thus likely to increase the intrinsic motivation to become physically active.


Pre-attentive spectro-temporal feature processing in the human auditory system.
In the present study, we investigated the pre-attentive processing of low-level acoustic properties and the impact of this mechanism on functional lateralization in the human auditory system. Mismatch negativity (MMN) of the event-related potentials (ERP) were recorded in 19 adult humans who passively listened to a standard stimulus and spectrally and temporally deviant sounds. We predicted modulations of the MMN amplitude in response to spectrally and temporally graded deviants. Based on recent models of functional hemispheric lateralisation, we further hypothesized a left-lateralized source of the MMN in response to temporal deviants and, in contrast, a right-lateralized source of the MMN in response to spectral deviants. In agreement with our hypothesis, we showed that spectrally and temporally deviant sounds lead to robust MMNs recorded from frontocentral scalp electrodes. The amplitudes of the MMNs were modulated by the grade of spectral and temporal deviation from the standard sound. Furthermore, by using an assumption-free source localization approach (LORETA) we demonstrated functionally lateralized activations with dominance of the right hemisphere for the processing of spectral characteristics and of the left hemisphere for the processing of temporal acoustic properties. Results of our study further contribute to the ongoing debate on the role of low-level acoustic feature perception in functional hemispheric lateralization in the context of auditory and speech processing. Our data indicate that the pre-attentive feature-specific deviant processing is mediated by partly distinct neural subsystems for temporal and spectral information.


An efficient method-of-lines simulation procedure for organic semiconductor devices.
We describe an adaptive grid method-of-lines (MOL) solution procedure for modelling charge transport and recombination in organic semiconductor devices. The procedure we describe offers an efficient, robust and versatile means of simulating semiconductor devices that allows for much simpler coding of the underlying equations than alternative simulation procedures. The MOL technique is especially well-suited to modelling the extremely stiff (and hence difficult to solve) equations that arise during the simulation of organic-and some inorganic-semiconductor devices. It also has wider applications in other areas, including reaction kinetics, combustion and aero- and fluid dynamics, where its ease of implementation also makes it an attractive choice. The MOL procedure we use converts the underlying semiconductor equations into a series of coupled ordinary differential equations (ODEs) that can be integrated forward in time using an appropriate ODE solver. The time integration is periodically interrupted, the numerical solution is interpolated onto a new grid that is better matched to the solution profile, and the time integration is then resumed on the new grid. The efficacy of the simulation procedure is assessed by considering a single layer device structure, for which exact analytical solutions are available for the electric potential, the charge distributions and the current-voltage characteristics. Two separate state-of-the-art ODE solvers are tested: the single-step Runge-Kutta solver Radau5 and the multi-step solver ODE15s, which is included as part of the Matlab ODE suite. In both cases, the numerical solutions show excellent agreement with the exact analytical solutions, yielding results that are accurate to one part in 1 x 10(4). The single-step Radau5 solver, however, is found to provide faster convergence since its efficiency is not compromised by the periodic interruption of the time integration when the grid is updated.


CD24hiCD38hi and CD24hiCD27+ Human Regulatory B Cells Display Common and Distinct Functional Characteristics.
Although IL-10-producing regulatory B cells (Bregs) play important roles in immune regulation, their surface phenotypes and functional characteristics have not been fully investigated. In this study, we report that the frequency of IL-10-producing Bregs in human peripheral blood, spleens, and tonsils is similar, but they display heterogenous surface phenotypes. Nonetheless, CD24hiCD38hi transitional B cells (TBs) and CD24hiCD27+ B cells (human equivalent of murine B10 cells) are the major IL-10-producing B cells. They both suppress CD4+ T cell proliferation as well as IFN-γ/IL-17 expression. However, CD24hiCD27+ B cells were more efficient than TBs at suppressing CD4+ T cell proliferation and IFN-γ/IL-17 expression, whereas they both coexpress IL-10 and TNF-α. TGF-β1 and granzyme B expression were also enriched within CD24hiCD27+ B cells, when compared with TBs. Additionally, CD24hiCD27+ B cells expressed increased levels of surface integrins (CD11a, CD11b, α1, α4, and β1) and CD39 (an ecto-ATPase), suggesting that the in vivo mechanisms of action of the two Breg subsets are not the same. Lastly, we also report that liver allograft recipients with plasma cell hepatitis had significant decreases of both Breg subsets.


The effect of nicardipine on neuronal function following ischemia.
In cerebral ischemia, it has been proposed that calcium influx into neurons results in irreversible cellular injury during reperfusion. We administered nicardipine, a dihydropyridine calcium entry blocker, by continuous subcutaneous infusion to twenty five rats beginning before (PR) or following (PO) ischemia, and compared somatosensory evoked potentials (SEPs) to twenty eight ischemic control animals. Comparable ischemic cellular changes were seen in the hippocampi of all animals. SEP amplitude was higher in both the PR (p less than .005) and PO (p less than .0005) groups compared to controls. This effect was found in all three components (P1, N1, P2) of the evoked response. Plasma nicardipine levels of 6-10 ng/ml were associated with mild hypotension. We conclude that nicardipine improved neuronal function as measured by SEPs when administered before or after ischemia, most likely by interrupting the cytotoxic events occurring in cortical neurons during reperfusion.


Use of computational fluid dynamics to estimate hemodynamic effects of respiration on hypoplastic left heart syndrome surgery: total cavopulmonary connection treatments.
Total cavopulmonary connection (TCPC), a typical kind of Fontan procedure, is commonly used in the treatment of a functional single ventricle. The palliative cardiothoracic procedure is performed by connecting the superior vena cava and the inferior vena cava to the pulmonary arteries. Due to the difficulty of direct study in vivo, in this paper, computational fluid dynamics (CFD) was introduced to estimate the outcomes of patient-specific TCPC configuration. We mainly focused on the influence of blood pulsation and respiration. Fast Fourier transforms method was employed to separate the measured flow conditions into the rate of breath and heart beat. Blood flow performance around the TCPC connection was investigated by analyzing the results of time-varying energy losses, blood flow distribution rate, local pressure, and wall shear stress distributions. It was found that the value of energy loss including the influence of respiration was 1.5 times higher than the value of energy loss disregarding respiratory influences. The results indicated that the hemodynamic outcomes of TCPC treatment are obviously influenced by respiration. The influence of respiration plays an important role in estimating the results of TCPC treatment and thus should be included as one of the important conditions of computational haemodynamic analysis.


Effect of area poverty rate on cancer screening across US communities.
To analyse the contextual effect of area poverty rate on never having been screened for breast, cervical, and colorectal cancer by (1) describing the extent of the variation in screening behaviours among 98 US metropolitan areas; (2) determining if the variation in lack of screening can be explained by differences in the characteristics of the persons who resided in these areas; and (3) determining if living in a metropolitan area with a higher poverty rate increased the likelihood of never having been screened for cancer over and above individual characteristics. Cross sectional survey using data from the 2002 Behavioral Risk Factor Surveillance System. Multilevel logistic regression included both individual level factors as well as area poverty rate. Ninety eight areas across the USA. Over 118 000 persons residing in 98 areas; a sample aimed at estimating 48.3% of the US population age 18 or older. After adjustment for individual level factors, increasing area level poverty rate (per 5%) remained associated with never having had a mammogram (odds ratio (OR) = 1.28, 95% confidence interval (CI): 1.03 to 1.37); clinical breast examination (OR = 1.28, 95% CI: 1.11 to 1.48), colonoscopy/sigmoidoscopy (OR = 1.10, 95% CI: 1.01 to 1.19), and a faecal occult blood test (OR = 1.19, 95% CI: 1.12 to 1.27). Poverty rate was not independently associated with never having had a Pap smear (OR = 1.12; 95% CI: 0.90 to 1.41). The size of the variance among metropolitan or micropolitan statistical areas (MMSAs) varied by type of screening test, with intraclass correlation coefficients ranging from 4.9% (never having had a Pap smear) to 1.2% (never having had a colonoscopy/sigmoidoscopy). Area poverty rate was independently associated with never having been screened for breast and colorectal cancer, but not cervical cancer. The size of the variance among MMSAs was modest at best.


[Developments in pharmacotherapy: personalised pharmacotherapy?].
Effect-sizes of pharmacological treatments for addictive disorders are limited and a substantial number of patients do not derive any benefit from these treatments. To develop strategies that will enhance the effectivity of pharmacotherapy in the future. We reviewed the literature using a model of staging and profiling which matches pharmacological interventions to specific stages of addiction. Pharmacological interventions can be tailored to the specific stage of the disease. In the early stages of a disease, pharmacotherapy can be directed towards reducing impulsivity, craving and compulsive behaviour and controlling substance abuse. In later stages the aim is to reduce negative effects, craving and compulsive behaviour and bring the patient to the stage of total abstinence. Furthermore, if therapists opt for pharmacotherapy they must take specific characteristics of the patient into consideration. Currently, phenotypical (clinical) characteristics do not provide a firm enough basis for pharmacological interventions. Endophenotypical or genetic characteristics seem to be very promising. However, most findings still need to be replicated and validated. The era of truly personalised medication for addiction has not yet arrived, but there are some very promising developments. In the short term, the prospects for pharmacogenetics seem to be the most favourable. A model of staging and profiling can provide a valuable framework for new developments in pharmacotherapy.


Validation of the Brazilian Version of the Voice Disability Coping Questionnaire.
To perform the validation of the Brazilian version of the Voice Disability Coping Questionnaire (B-VDCQ) using procedures according to the Scientific Advisory Committee of Medical Outcomes Trust and psychometric analyses to determine the scales validity and reliability. In the preliminary procedures, the VDCQ was administered to 14 patients to determine if items were culturally valid and propose possible adaptations for a B-VDCQ. The sample of this study consisted of a data set of 178 individuals, 87 with vocal complaint, comprising 19 men and 68 women, with mean age of 34.1 years and 91 without vocal complaint, comprising 29 men and 62 women, with mean age of 32.4 years. To demonstrate validity, the B-VDCQ scores were compared to vocal self-assessment and perceptual analysis. To determine the reliability and test-retest reproducibility, 14 voice patients repeated the measurement between 3 and 14 days after the first administration. Principal component analyses of the patients with vocal complaint yielded four coping strategies: venting, support seeking, minimisation, and avoidant acceptance. Subscales of the questionnaire showed acceptable internal consistency and reproducibility values, apart from the minimisation subscale. B-VDCQ validity was demonstrated through relationships with perceptual analyses and vocal self-assessment and subscale score differences between the two groups. The B-VDCQ has been submitted to essential steps necessary for cultural adaptation and validation. It is a simple instrument to administer and shows to be specific for evaluating patients with voice problems. The B-VDCQ can be an important addition to the voice evaluation of patients with dysphonia.


Attitudes towards unions through a generational cohort lens.
Studying a large American union, we report on findings from two studies investigating perceptions of and attitudes towards unions through a generational cohort lens. Study one explores the link between generational cohort and members' perceptions of unions, employing qualitative analysis of 100 interviews: 30 Millennials, 35 Gen X, and 35 Baby Boomers. Analysis determined that union members focus on either ideological or instrumental explanations to support perceptions that their generation was either pro-union or anti-union. Themes identified in study one were further explored in a quantitative study which involved statistical analysis of survey data (n = 4717) to identify possible differences in pro and anti-union attitudes across three generational cohorts: baby boomer (n = 2857), Gen X (n = 1256), and millennials (n = 304). Data from both studies support the idea that pro-union perceptions and attitudes are more prevalent among those in the baby boomer cohort than Gen Xers, and millennials.


Electron correlation effects in third-order densities.
The electronic energy of a system of fermions can be obtained from the second-order reduced density matrix through the contracted Schrödinger equation or its anti-Hermitian counterpart. Both energy expressions depend on the third-order reduced density matrix (3-RDM) which is usually approximated from lower-order densities. The accuracy of these methods depends critically on the set of N-representability conditions enforced in the calculation and the quality of the approximate 3-RDM. There are no benchmark studies including most 3-RDM approximations and, thus far, no assessment of the deterioration of the approximations with correlation effects has been performed. In this paper we introduce a series of tests to assess the performance of 3-RDM approximations in a model system with varying electron correlation effects, the three-electron harmonium atom. The results of this work put forward several limitations of the currently most used 3-RDM approximations for systems with important electron correlation effects.


Ambra1 regulates autophagy and development of the nervous system.
Autophagy is a self-degradative process involved both in basal turnover of cellular components and in response to nutrient starvation or organelle damage in a wide range of eukaryotes. During autophagy, portions of the cytoplasm are sequestered by double-membraned vesicles called autophagosomes, and are degraded after fusion with lysosomes for subsequent recycling. In vertebrates, this process acts as a pro-survival or pro-death mechanism in different physiological and pathological conditions, such as neurodegeneration and cancer; however, the roles of autophagy during embryonic development are still largely uncharacterized. Beclin1 (Becn1; coiled-coil, myosin-like BCL2-interacting protein) is a principal regulator in autophagosome formation, and its deficiency results in early embryonic lethality. Here we show that Ambra1 (activating molecule in Beclin1-regulated autophagy), a large, previously unknown protein bearing a WD40 domain at its amino terminus, regulates autophagy and has a crucial role in embryogenesis. We found that Ambra1 is a positive regulator of the Becn1-dependent programme of autophagy, as revealed by its overexpression and by RNA interference experiments in vitro. Notably, Ambra1 functional deficiency in mouse embryos leads to severe neural tube defects associated with autophagy impairment, accumulation of ubiquitinated proteins, unbalanced cell proliferation and excessive apoptotic cell death. In addition to identifying a new and essential element regulating the autophagy programme, our results provide in vivo evidence supporting the existence of a complex interplay between autophagy, cell growth and cell death required for neural development in mammals.


Insertional inactivation of the lpxA gene involved in the biosynthesis of lipid A in Neisseria meningitidis resulted in lpxA/lpxA::aph-3' heterodiploids.
The lpxA gene is known to be involved in the biosynthesis of lipid A in Gram-negative bacteria and thought to be an essential gene. However, viable meningococcal lpxA mutants devoid of detectable endotoxin (lipooligosaccharide) have been reported. We characterised such mutants in strains of Neisseria meningitidis belonging to serogroups B and C using molecular and biochemical analysis. While lpxA mutants with no detectable or a low level of lipooligosaccharide could be obtained in N. meningitidis, the simple insertional inactivation of lpxA was not possible. In all mutants, we obtained lpxA/lpxA::aph-3' heterodiploids harbouring one copy of the wild-type lpxA gene and one copy of the inactivated lpxA gene by insertion of the kanamycin resistance cassette, aph-3'. The absence of lipooligosaccharide in these mutants may result from a negative transdominance effect of a truncated LpxA protein on the wild-type LpxA protein.


Detecting conserved protein complexes using a dividing-and-matching algorithm and unequally lenient criteria for network comparison.
The increase of protein-protein interaction (PPI) data of different species makes it possible to identify common subnetworks (conserved protein complexes) across species via local alignment of their PPI networks, which benefits us to study biological evolution. Local alignment algorithms compare PPI network of different species at both protein sequence and network structure levels. For computational and biological reasons, it is hard to find common subnetworks with strict similar topology from two input PPI networks. Consequently some methods introduce less strict criteria for topological similarity. However those methods fail to consider the differences of the two input networks and adopt equally lenient criteria on them. In this work, a new dividing-and-matching-based method, namely UEDAMAlign is proposed to detect conserved protein complexes. This method firstly uses known protein complexes or computational methods to divide one of the two input PPI networks into subnetworks and then maps the proteins in these subnetworks to the other PPI network to get their homologous proteins. After that, UEDAMAlign conducts unequally lenient criteria on the two input networks to find common connected components from the proteins in the subnetworks and their homologous proteins in the other network. We carry out network alignments between S. cerevisiae and D. melanogaster, H. sapiens and D. melanogaster, respectively. Comparisons are made between other six existing methods and UEDAMAlign. The experimental results show that UEDAMAlign outperforms other existing methods in recovering conserved protein complexes that both match well with known protein complexes and have similar functions.


Regional distribution of adult rheumatologists.
To analyze the distribution of rheumatology practices in the US and factors associated with that distribution, in order to better understand the supply of the rheumatology workforce. Using the American College of Rheumatology membership database, all practicing adult rheumatologist office addresses were mapped with ArcView software. The number of rheumatologists per Core Based Statistical Area (CBSA) was calculated. To investigate whether sociodemographic factors correlated with clustering of rheumatologists, covariates from the 2010 US Census for each CBSA, including age, sex, race/ethnicity, and median household income, were modeled. Many CBSAs, predominantly smaller micropolitan areas, did not have a practicing rheumatologist. For some of these smaller micropolitan areas (with populations of at least 40,000), the closest practicing rheumatologist was more than 200 miles away. However, we also identified several more-populous areas (populations of 200,000 or more) without a practicing rheumatologist. Greater numbers of rheumatologists were more likely to practice in areas with higher population densities and higher median incomes. More rheumatologists were also found in CBSAs in which there were rheumatology training programs. These findings demonstrate that many smaller regions of the country have no or few practicing adult rheumatologists. Patients with chronic rheumatic conditions in these areas likely have limited access to rheumatology care. Policy changes could address potential regional rheumatology workforce shortages, but limitations of the current data would need to be addressed prior to implementation of such changes.


Insights into the Mutational Burden of Human Induced Pluripotent Stem Cells from an Integrative Multi-Omics Approach.
To understand the mutational burden of human induced pluripotent stem cells (iPSCs), we sequenced genomes of 18 fibroblast-derived iPSC lines and identified different classes of somatic mutations based on structure, origin, and frequency. Copy-number alterations affected 295 kb in each sample and strongly impacted gene expression. UV-damage mutations were present in ∼45% of the iPSCs and accounted for most of the observed heterogeneity in mutation rates across lines. Subclonal mutations (not present in all iPSCs within a line) composed 10% of point mutations and, compared with clonal variants, showed an enrichment in active promoters and increased association with altered gene expression. Our study shows that, by combining WGS, transcriptome, and epigenome data, we can understand the mutational burden of each iPSC line on an individual basis and suggests that this information could be used to prioritize iPSC lines for models of specific human diseases and/or transplantation therapy.


Tailoring dielectric resonator geometries for directional scattering and Huygens' metasurfaces.
In this paper we describe a methodology for tailoring the design of metamaterial dielectric resonators, which represent a promising path toward low-loss metamaterials at optical frequencies. We first describe a procedure to decompose the far field scattered by subwavelength resonators in terms of multipolar field components, providing explicit expressions for the multipolar far fields. We apply this formulation to confirm that an isolated high-permittivity dielectric cube resonator possesses frequency separated electric and magnetic dipole resonances, as well as a magnetic quadrupole resonance in close proximity to the electric dipole resonance. We then introduce multiple dielectric gaps to the resonator geometry in a manner suggested by perturbation theory, and demonstrate the ability to overlap the electric and magnetic dipole resonances, thereby enabling directional scattering by satisfying the first Kerker condition. We further demonstrate the ability to push the quadrupole resonance away from the degenerate dipole resonances to achieve local behavior. These properties are confirmed through the multipolar expansion and show that the use of geometries suggested by perturbation theory is a viable route to achieve purely dipole resonances for metamaterial applications such as wave-front manipulation with Huygens' metasurfaces. Our results are fully scalable across any frequency bands where high-permittivity dielectric materials are available, including microwave, THz, and infrared frequencies.


Transmission of O-band wavelength-division-multiplexed heralded photons over a noise-corrupted optical fiber channel.
We transmitted O-band heralded photons over 10 km of optical fiber in a proof-of-concept experiment demonstrating the feasibility of using heralded photons to improve the noise tolerance of quantum key distribution. In our experiment, the optical fiber channel was corrupted by noise photons to the extent that if we had used an attenuated laser as the photon source, a photon signal-to-noise ratio of < 4.0 at the receiver, corresponding to a quantum bit-error rate of > 10.0%, would have prevented the effective generation of secure keys. Using a photon heralding scheme, the photon signal-to-noise ratio in our experiment was shown to be > 7.8. This corresponds to a quantum bit-error rate of < 5.7%, which is good enough for distilling secure keys. In addition, we showed that it is possible to incorporate wavelength-division-multiplexing into the photon heralding scheme to improve overall key rate. We discussed and clarified the prospects and limitations of the photon heralding scheme for noise-tolerant quantum key distribution.


[Effect of naftidrofuryl oxalate (LS-121) on experimental amnesia model in rats].
Effects of naftidrofuryl oxalate (LS-121) on experimental amnesia models, which were induced by cycloheximide (CXM), scopolamine (SCOP) and basal-forebrain (BF) lesion, were investigated using the step-through passive avoidance response in rats. In the retention test, a cut-off time of 600 sec was employed for the measurement of step-through latency (STL). The animals, that showed over 300 sec of STL was regarded as having the criterion of memory retention (% of retention). Increase in both parameters of STL and % of retention was regarded to indicate that the drug was able to improve the amnesia. If only one of the two parameters was increased, we considered that the drug had a tendency to improve the amnesia. Pretraining, post-training and pre-retention treatment of LS-121 (25 mg/kg) improved CXM- and SCOP-induced amnesia. Post-training treatment of LS-121 (25 mg/kg) showed a tendency to improve the BF lesion-induced amnesia. These results suggest that the antiamnesic action of LS-121 may be produced through an activation of the acetylcholinergic neuronal system. Since it improved the amnesia when administered in the pre-retention test, there is a possibility that LS-121 has not only a protective effect, but also a therapeutic effect. Furthermore, it is suggested that LS-121 may also have a therapeutic effect on Alzheimer's disease, since it showed a tendency to improve the BF lesion-induced amnesia.


Sex-biased miRNA expression in Atlantic halibut (Hippoglossus hippoglossus) brain and gonads.
The role of miRNA in fish sexual development is not elucidated yet. We profiled miRNAs in gonads and brains of Atlantic halibut using SOLiD sequencing technology. We found tissue- and sexually dimorphic expression of several miRNAs, including miR-29a, miR-34, miR-143, miR-145, miR-202-3p, miR-451, and miR-2188. miR-9 and miR-202 were abundant in brain and gonads, respectively. In the next step, we selected some miRNAs showing differential expression patterns between sexes and performed RT-qPCR on 3 age groups: juveniles, 3-year-, and 5-year-olds. In brains, miR-451 was significantly down-regulated in juveniles compared to adults. let-7a, miR-143, and miR-202-3p were up-regulated in gonads of mature males compared to immature females at the same age. We investigated the effect of suppressing aromatase cytochrome P450 enzyme on miRNA expression at the onset of sex differentiation through masculinization with Fadrozole or 17-α-methyltestosterone. We found significant differences in miRNA expression between masculinized individuals and untreated controls. miR-202-3p was significantly down-regulated in female juveniles compared to male juveniles. The expression levels of let-7a and miR-451 were restored after termination of the masculinization treatment. Our data give a first insight into miRNA involvement in sexual development in teleosts.


Pathology of asymptomatic, prenatally diagnosed cystic lung malformations.
The management of asymptomatic congenital cystic lung malformations is controversial. Arguments for excision of asymptomatic lesions are the potential for infection and malignancy. Following antenatal detection, our institute performs a CT at 1month, clinic follow-up by 3months to discuss the controversial management, and offers surgery by 6months of age. We investigated the histopathology of asymptomatic lesions to determine whether there was evidence of subclinical infection or malignancy. A retrospective review of prospectively collected antenatal congenital cystic lung malformations more than a 10year period (2005-2014) was conducted. Information was gathered from the antenatal registry and histopathology reports. Infection was defined by the presence of microabscesses or neutrophil/macrophage infiltration, as per histopathological criteria. From the cohort of 99 patients, the study focused on 69 asymptomatic lesions. These cases comprised 34 congenital pulmonary airway malformations (CPAM), 15 pulmonary sequestrations (PS), and 20 hybrid lesions. Eighteen cases (26%) had microscopic disease - 16 cases of infection and 2 tumors. The infectious cases comprised 7 with microabscesses and 9 with neutrophil/macrophage infiltration. There were two cases of tumors, namely pleuropulmonary blastoma. These tumors were followed up by the oncology team with regular imaging until 3years of age and clinical review thereafter. Twenty-six percent of antenatally detected, asymptomatic cystic lung malformations demonstrated either subclinical infection or malignancy. This information can be used for counseling parents and determining the method of treatment.