Unique folding of precursor microRNAs: quantitative evidence and implications for de novo identification.
MicroRNAs (miRNAs) participate in diverse cellular and physiological processes through the post-transcriptional gene regulatory pathway. Hairpin is a crucial structural feature for the computational identification of precursor miRNAs (pre-miRs), as its formation is critically associated with the early stages of the mature miRNA biogenesis. Our incomplete knowledge about the number of miRNAs present in the genomes of vertebrates, worms, plants, and even viruses necessitates thorough understanding of their sequence motifs, hairpin structural characteristics, and topological descriptors. In this in-depth study, we investigate a comprehensive and heterogeneous collection of 2241 published (nonredundant) pre-miRs across 41 species (miRBase 8.2), 8494 pseudohairpins extracted from the human RefSeq genes, 12,387 (nonredundant) ncRNAs spanning 457 types (Rfam 7.0), 31 full-length mRNAs randomly selected from GenBank, and four sets of synthetically generated genomic background corresponding to each of the native RNA sequence. Our large-scale characterization analysis reveals that pre-miRs are significantly different from other types of ncRNAs, pseudohairpins, mRNAs, and genomic background according to the nonparametric Kruskal-Wallis ANOVA (p<0.001). We examine the intrinsic and global features at the sequence, structural, and topological levels including %G+C content, normalized base-pairing propensity P(S), normalized minimum free energy of folding MFE(s), normalized Shannon entropy Q(s), normalized base-pair distance D(s), and degree of compactness F(S), as well as their corresponding Z scores of P(S), MFE(s), Q(s), D(s), and F(S). The findings will promote more accurate guidelines and distinctive criteria for the prediction of novel pre-miRs with improved performance.


Universal health coverage for strengthening prevention and control of noncommunicable diseases in COVID-19 era.
The novel coronavirus disease (COVID-19) pandemic has been exhausting the entire global economy. As the greatest challenge to sustainable development in all societies and health systems, noncommunicable diseases (NCDs) and their relevant risk factors are the main causes of illness and death during the 21st century in high, middle, and low-income countries (LMICs). NCDs are also among the main underlying causes of death among COVID-19 patients in many countries. People living with or affected by NCDs (PLWANCDs) are more vulnerable to becoming severely ill with COVID-19. Although the ongoing pandemic will be a fundamental game-changer for prioritization and resource allocation in many countries in years to come, ample evidence indicates that NCDs will remain the main killer of people and the costliest barrier to sustainable societies. Looking through the lenses of universal health coverage (UHC), this paper advocates rebuilding our world during COVID-19 aftermath, in a way to harmonize efforts to live with pandemics and make our health systems resilient, balanced, and comprehensive enough to accommodate all threats to humanity, including both communicable and noncommuincable diseases.


Effects of PslG on the Surface Movement of Pseudomonas aeruginosa.
PslG attracted a lot of attention recently due to its great potential abilities in inhibiting biofilms of Pseudomonas aeruginosa However, how PslG affects biofilm development still remains largely unexplored. Here, we focused on the surface motility of bacterial cells, which is critical for biofilm development. We studied the effects of PslG on bacterial surface movement in early biofilm development at a single-cell resolution by using a high-throughput bacterial tracking technique. The results showed that compared with no exogenous PslG addition, when PslG was added to the medium, bacterial surface movement was significantly (4 to 5 times) faster and proceeded in a more random way with no clear preferred direction. A further study revealed that the fraction of walking mode increased when PslG was added, which then resulted in an elevated average speed. The differences of motility due to PslG addition led to a clear distinction in patterns of bacterial surface movement and retarded microcolony formation greatly. Our results provide insight into developing new PslG-based biofilm control techniques.IMPORTANCE Biofilms of Pseudomonas aeruginosa are a major cause for hospital-acquired infections. They are notoriously difficult to eradicate and pose serious health hazards to human society. So, finding new ways to control biofilms is urgently needed. Recent work on PslG showed that PslG might be a good candidate for inhibiting/disassembling biofilms of Pseudomonas aeruginosa through Psl-based regulation. However, to fully explore PslG functions in biofilm control, a better understanding of PslG-Psl interactions is needed. Toward this end, we examined the effects of PslG on the surface movement of Pseudomonas aeruginosa in this work. The significance of our work is in greatly enhancing our understanding of the inhibiting mechanism of PslG on biofilms by providing a detailed picture of bacterial surface movement at a single-cell level, which will allow a full understanding of PslG abilities in biofilm control and thus present potential applications in biomedical fields.


Serum anti-Müllerian hormone levels: a novel measure of ovarian reserve.
Anti-Müllerian hormone (AMH) is produced by the granulosa cells of preantral and small antral follicles and its levels can be assessed in serum. Since the number of ovarian follicles declines with increasing age, AMH levels might be used as a marker for ovarian ageing. Therefore, we studied the relationship between AMH levels and ovarian response during ovarian stimulation for IVF. A total of 130 patients undergoing their first IVF treatment cycle using a long protocol with GnRH agonist was prospectively included. Blood withdrawal was performed and the number of antral follicles was assessed by ultrasound on day 3 of a spontaneous cycle. Poor response and the number of oocytes were used as primary outcome measures. In a random subset of 23 patients a GnRH agonist stimulation test was performed to investigate whether a rise in FSH and LH would affect AMH levels. The data of 119 patients were analysed. Serum AMH levels were highly correlated with the number of antral follicles (r = 0.77; P < 0.01) and the number of oocytes retrieved (r = 0.57, P < 0.01). A negative association was found between AMH levels and poor ovarian response (fewer than 4 oocytes or cycle cancellation; OR 0.82, 95% CI 0.75-0.90, P < 0.01). Inclusion of inhibin B and FSH concentrations to AMH in a multivariate model improved the prediction of ovarian response. The post GnRH agonist rise in FSH and LH levels did not influence AMH values. Poor response in IVF, indicative of a diminished ovarian reserve, is associated with reduced baseline serum AMH concentrations. In line with recent observations it appears that AMH can be used as a marker for ovarian ageing.


Respiratory viral infections in infants: causes, clinical symptoms, virology, and immunology.
In global terms, respiratory viral infection is a major cause of morbidity and mortality. Infancy, in particular, is a time of increased disease susceptibility and severity. Early-life viral infection causes acute illness and can be associated with the development of wheezing and asthma in later life. The most commonly detected viruses are respiratory syncytial virus (RSV), rhinovirus (RV), and influenza virus. In this review we explore the complete picture from epidemiology and virology to clinical impact and immunology. Three striking aspects emerge. The first is the degree of similarity: although the infecting viruses are all different, the clinical outcome, viral evasion strategies, immune response, and long-term sequelae share many common features. The second is the interplay between the infant immune system and viral infection: the immaturity of the infant immune system alters the outcome of viral infection, but at the same time, viral infection shapes the development of the infant immune system and its future responses. Finally, both the virus and the immune response contribute to damage to the lungs and subsequent disease, and therefore, any prevention or treatment needs to address both of these factors.


Dynamic challenges inhibiting optimal adoption of kidney paired donation: findings of a consensus conference.
While kidney paired donation (KPD) enables the utilization of living donor kidneys from healthy and willing donors incompatible with their intended recipients, the strategy poses complex challenges that have limited its adoption in United States and Canada. A consensus conference was convened March 29-30, 2012 to address the dynamic challenges and complexities of KPD that inhibit optimal implementation. Stakeholders considered donor evaluation and care, histocompatibility testing, allocation algorithms, financing, geographic challenges and implementation strategies with the goal to safely maximize KPD at every transplant center. Best practices, knowledge gaps and research goals were identified and summarized in this document.


Oridonin inhibits the proliferation of human colon cancer cells by upregulating BMP7 to activate p38 MAPK.
Oridonin (ORI), a diterpenoid purified from Rabdosia rubescens, has been reported as a promising chemotherapy drug for colon cancer treatment; yet, the precise mechanisms underlying this anticancer activity remain unclear. In the present study, we investigated the anticancer effect of ORI in HCT116 cells, and dissected the possible molecular mechanisms underlying this activity. With crystal violet staining, flow cytometry and western blot assay, we found that ORI effectively inhibited the proliferation and induced the apoptosis of HCT116 cells. Further analysis of the results indicated that BMP7 was greatly upregulated by ORI in the HCT116 cells, but its endogenous expression in FHC cells was apparently lower than that in the colon cancer cell lines. Exogenous expression of BMP7 inhibited the proliferation of the HCT116 cells, and substantially potentiated the anticancer effect of ORI. However, the specific antibody of BMP7 nearly abolished this anticancer activity of ORI in the HCT116 cells. Meanwhile, ORI exerted no significant effect on the level of phosphorylated Smad1/5/8 or total p38 MAPK, but greatly increased the level of phosphorylated p38 MAPK in the HCT116 cells. A p38 MAPK-specific inhibitor partly reversed the antiproliferative effect of BMP7 in the HCT116 cells, but prominently promoted the effect of the BMP7 antibody on proliferation. Exogenous expression of BMP7 increased the ORI-induced phosphorylation of p38 MAPK, while the BMP7 antibody almost abolished the ORI-elevated p38 MAPK phosphorylation. Our findings suggest that ORI may be an efficacious drug for colon cancer treatment. This anticancer activity of ORI may be mediated by upregulating BMP7 at least to increase the activation of p38 MAPK.


Action-induced clonus mimicking tremor.
Action tremor has been described in cerebellar, task-specific, dystonic, or Holmes tremor. We report 2 patients who developed unilateral kinetic or isometric action tremor of the upper extremity, following cervical spondylotic myelopathy and capsular ischemic stroke. Slight motor weakness and spasticity with exaggerated tendon jerks and passive stretch-induced clonus were present on the same limb. The central motor pathways lesions might have been responsible for a hyperexcitability of the stretch-reflex arc and an enhancement of the coactivation of skeletal muscles through a loss of the descending or segmental control of the spinal reflexes. The unusual topography of the symptoms, their occurrence during motion, and the similar frequency of the passive clonus and the action tremor, led us to hypothesize that both patients had prolonged action-induced clonus, mimicking action tremor. Lesions of the central motor pathways lesions might be responsible for action tremor under certain conditions.


NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain.
Nck, an adaptor protein composed of one SH2 and three SH3 domains, is a common target for a variety of cell surface receptors. We have identified a novel mammalian serine/threonine kinase that interacts with the SH3 domains of Nck, termed Nck Interacting Kinase (NIK). This kinase is most homologous to the Sterile 20 (Ste20) family of protein kinases. Of the members of this family, GCK and MSST1 are most similar to NIK in that they bind neither Cdc42 nor Rac and contain an N-terminal kinase domain with a putative C-terminal regulatory domain. Transient overexpression of NIK specifically activates the stress-activated protein kinase (SAPK) pathway. Both the kinase domain and C-terminal regulatory region of NIK are required for full activation of SAPK. NIK likely functions upstream of MEKK1 to activate this pathway; a dominant-negative MEK kinase 1 (MEKK1) blocks activation of SAPK by NIK. MEKK1 and NIK also associate in cells and this interaction is mediated by regulatory domains on both proteins. Two other members of this kinase family, GCK and HPK1, contain C-terminal regulatory domains with homology to that of NIK. These findings indicate that the C-terminal domain of these proteins encodes a new protein domain family and suggests that this domain couples these kinases to the SAPK pathway, possibly by interacting with MEKK1 or related kinases.


Increased risk of colorectal adenomas in Italian subjects carrying the p53 PIN3 A2-Pro72 haplotype.
Few reports have investigated the association of two p53 polymorphisms (Arg72Pro and PIN3-A2) with colorectal cancer (CRC) risk, and no previous study has analyzed their role as susceptibility alleles for colorectal adenoma. To explore the impact of the p53 PIN3-Arg72Pro haplotype on colorectal adenoma formation and progression to cancer. One hundred and eighty-four colorectal tumor patients (124 with adenomas and 60 with adenocarcinoma) and 188 controls (42 subjects with a clean colon, 54 hospital controls and 92 blood donors) from the Italian population were tested for PIN3-Arg72Pro haplotype status. A significantly increased risk of colorectal adenomas was observed in patients carrying the PIN3 A2-Pro72 haplotype (OR = 2.02, 95% CI: 1.17-3.48; p = 0.01), while those carrying the PIN3 A1-Pro72 haplotype had a significantly increased risk of developing CRC (OR = 3.33; 95% CI: 1.40-7.89; p = 0.006). Comparisons of cases with the clean colon control group provided stronger evidence of the associations. A family history of CRC did not affect the risk estimates. No association was observed between the pathologic features of adenomas, the Arg72Pro and PIN3 polymorphisms, and the PIN3-Arg72Pro haplotype. Our finding that two different p53 haplotypes are associated with colorectal adenoma and cancer, respectively, suggests that each of these haplotypes may independently impact on p53 function(s) within different genetic pathways of colorectal carcinogenesis.


High Prevalence of Tobacco Product and E-Cigarette Use among Electronic Dance Music Party Attendees.
Background: Electronic dance music (EDM) party attendees are at high risk for use of various illegal drugs; however, little is known about their tobacco use. Understanding tobacco use patterns in this population at high risk for illegal drug use can inform multi-product interventions. Objectives: 954 EDM party attendees (ages 18-40) were surveyed in New York City in 2017. We estimated prevalence of use of cigarettes, hookah, cigars, other tobacco, and e-cigarettes and delineated correlates of current (past-month) use using bivariable and multivariable models. Results: Past-month use of cigarettes (36.2%), e-cigarettes (15.6%), cigars (12.5%), and hookah (11.7%) in particular was prevalent. In multivariable models, females were less likely to use e-cigarettes than males (adjusted prevalence ratio [aPR] = 0.63, p = .030), and those who attended graduate school were less likely to use cigarettes (aPR = 0.55, p = .003) and/or e-cigarettes (aPR = 0.33, p = .026). Past-year ecstasy/MDMA/Molly use was a risk factor for past-month use of cigarettes (aPR = 1.38, p = .013) and/or cigars (aPR = 1.61, p = .032), and past-year cocaine use was a risk factor for past-month use of cigarettes (aPR = 1.80, p < .001), cigars (aPR = 1.80, p = .013), other tobacco products (aPR = 3.05, p = .003), and/or e-cigarettes (aPR = 2.39, p = .003). 55.4% of ecstasy users and 60.3% of cocaine users were current cigarette smokers, but use of other products among users of these drugs was less prevalent (9.8-27.9%). Conclusions: Results suggest that current tobacco use is prevalent in this population who is also at high risk for use of drugs such as ecstasy and cocaine. Prevention and cessation efforts need to target tobacco users in this scene while incorporating components addressing illegal drug use.


Pharmaco-metabonomic phenotyping and personalized drug treatment.
There is a clear case for drug treatments to be selected according to the characteristics of an individual patient, in order to improve efficacy and reduce the number and severity of adverse drug reactions. However, such personalization of drug treatments requires the ability to predict how different individuals will respond to a particular drug/dose combination. After initial optimism, there is increasing recognition of the limitations of the pharmacogenomic approach, which does not take account of important environmental influences on drug absorption, distribution, metabolism and excretion. For instance, a major factor underlying inter-individual variation in drug effects is variation in metabolic phenotype, which is influenced not only by genotype but also by environmental factors such as nutritional status, the gut microbiota, age, disease and the co- or pre-administration of other drugs. Thus, although genetic variation is clearly important, it seems unlikely that personalized drug therapy will be enabled for a wide range of major diseases using genomic knowledge alone. Here we describe an alternative and conceptually new 'pharmaco-metabonomic' approach to personalizing drug treatment, which uses a combination of pre-dose metabolite profiling and chemometrics to model and predict the responses of individual subjects. We provide proof-of-principle for this new approach, which is sensitive to both genetic and environmental influences, with a study of paracetamol (acetaminophen) administered to rats. We show pre-dose prediction of an aspect of the urinary drug metabolite profile and an association between pre-dose urinary composition and the extent of liver damage sustained after paracetamol administration.


Correlation of increased mortality with the suppression of radiation-inducible microsomal epoxide hydrolase and glutathione S-transferase gene expression by dexamethasone: effects on vitamin C and E-induced radioprotection.
Previous studies in this laboratory have shown that gamma-ray ionizing radiation in combination with oltipraz, a radioprotective agent, enhances hepatic microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST) expression. The present study was designed to investigate the effects of dexamethasone on the radiation-inducible expression of mEH and rGST genes and on the vitamin C and E-induced radioprotective effects in association with the expression of the genes. Treatment of rats with a single dose of dexamethasone (0.01-1 mg/kg, p.o.) caused a dose-dependent decrease in the constitutive mEH gene expression at 24 hr. The radiation-inducible mEH mRNA level (threefold increase after 3 Gy gamma-irradiation) was decreased by 21% and 88% by dexamethasone at the doses of 0.1 and 1 mg/kg, respectively. Although dexamethasone alone caused 2- to 5-fold increases in the hepatic rGSTA2 mRNA level, rats treated with dexamethasone prior to 3 Gy irradiation exhibited 80%-93% suppression in the radiation-inducible increases in the rGSTA2 mRNA level. The inducible rGSTA3 and rGSTA5 mRNA levels were also significantly decreased by dexamethasone, whereas the rGSTM1 mRNA level was reduced to a lesser extent. Vitamin C and/or E, however, failed to enhance the radiation-inducible increases in hepatic mEH and rGST mRNA levels. Whereas rats exposed to 3 Gy irradiation with or without vitamin C treatment (30 or 200 mg/kg/day, p.o., 2 days) exhibited approximately threefold increases in the mEH and rGSTA2/3/5 mRNA levels relative to untreated animals, dexamethasone treatment (1 mg/kg, p.o.) resulted in 64%-96% decreases in the mRNA levels at 24 hr. The inducible rGSTM1/2 mRNA levels in the vitamin C/E-treated rats were approximately 50% suppressed by dexamethasone. Although vitamin C and/or E treatment (200 mg/kg/day, p.o., 2 days) improved the 30-day survival rates of the 8 Gy gamma-irradiated mice from 39% up to 74%, the improved survival rate of gamma-irradiated animals was reduced to 30% by dexamethasone pretreatment (1 mg/kg/day, 2 days). The mean survival time of dexamethasone-treated animals was reduced to approximately 2 days from 14 days in the animals with total body irradiation alone. No significant hematologic changes were observed in mice at 10 days after dexamethasone plus gamma-irradiation, as compared with irradiation alone. These results demonstrate that: dexamethasone substantially suppresses radiation-inducible mEH, rGSTA and rGSTM expression in the liver; vitamins C/E exhibit radioprotective effects without enhancing radiation-inducible mEH and GST gene expression; and inhibition of radiation-inducible mEH and rGST gene expression in the vitamin C- and E-treated animals by dexamethasone was highly correlated with reduction in the survival rate and the mean survival time of gamma-irradiated animals.


How does routinely delivered cognitive-behavioural therapy for gambling disorder compare to "gold standard" clinical trial?
Currently, it is unknown whether treatment outcomes derived from randomized controlled trials (RCTs) of cognitive-behavioural therapy (CBT) for problem gamblers still hold when applied to patients seen in routine practice. Thus, data from an RCT of cognitive therapy versus exposure therapy for problem gambling versus patients of a gambling help service were compared. Assessments of problem gambling severity, psychosocial impairment, and alcohol use were undertaken at baseline and post-treatment and evaluated within a counterfactual framework. Findings showed that the contrast between routine CBT for pokies and horse betting had a significant effect, indicative of a 62% lower gambling urge score if routine CBT recipients had all been horse/track betters opposed to gambling with "pokies." However, the majority of contrasts indicated therapeutic outcomes achieved in routine CBT treatments were of equivalent robustness relative to RCT conditions. The present findings infer routine practice treatment outcomes are as efficacious as those generated in RCT contexts.


Haemophilus b conjugate vaccines for prevention of Haemophilus influenzae type b disease among infants and children two months of age and older. Recommendations of the immunization practices advisory committee (ACIP).
These recommendations include information on use of two vaccines recently licensed for use with infants: Haemophilus b Conjugate Vaccine (Diphtheria CRM197 Protein Conjugate) (HbOC), manufactured by Praxis Biologics, Inc., and Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) (PRP-OMP), manufactured by Merck Sharp and Dohme, newly licensed for use with infants. This statement also updates recommendations for use of these and other Haemophilus b conjugate vaccines with older children and adults.


Activation of human neutrophils by the anti-inflammatory mediator Esenbeckia leiocarpa leads to atypical apoptosis.
Despite the fact that Esenbeckia leiocarpa, a Brazilian plant, possesses potential anti-inflammatory properties, its effect in neutrophils, key players in inflammation, has never been investigated. In this study, a crude hydroalcoholic extract (CHE) was used to evaluate the potential toxic or agonistic effect of E. leiocarpa in human neutrophils. At a noncytotoxic concentration of 500 μg/mL, CHE increased actin polymerization and cell signaling events, especially p38 MAPK. Its modulatory activity on neutrophil cell apoptosis was investigated by cytology and by flow cytometry and, although CHE increased the apoptotic rate (by cytology) and increased annexin-V binding, it did not, unexpectedly, increase CD16 shedding. CHE increased the degradation of the cytoskeletal proteins gelsolin and paxillin but, surprisingly, not of vimentin. The proapoptotic activity of CHE was reversed by a pan-caspase inhibitor but not by a p38 inhibitor. We conclude that CHE is a novel human neutrophil agonist that induces apoptosis by a caspase-dependent and p38-independent mechanism in an atypical fashion based on its lack of effect on CD16 shedding and vimentin degradation. Since the resolution of inflammation occurs by elimination of apoptotic neutrophils, the ability of CHE to induce neutrophil apoptosis correlates well with its anti-inflammatory properties, as previously reported.


Can we use the pharmacy data to estimate the prevalence of chronic conditions? a comparison of multiple data sources.
The estimate of the prevalence of the most common chronic conditions (CCs) is calculated using direct methods such as prevalence surveys but also indirect methods using health administrative databases.The aim of this study is to provide estimates prevalence of CCs in Lazio region of Italy (including Rome), using the drug prescription's database and to compare these estimates with those obtained using other health administrative databases. Prevalence of CCs was estimated using pharmacy data (PD) using the Anathomical Therapeutic Chemical Classification System (ATC).Prevalences estimate were compared with those estimated by hospital information system (HIS) using list of ICD9-CM diagnosis coding, registry of exempt patients from health care cost for pathology (REP) and national health survey performed by the Italian bureau of census (ISTAT). From the PD we identified 20 CCs. About one fourth of the population received a drug for treating a cardiovascular disease, 9% for treating a rheumatologic conditions.The estimated prevalences using the PD were usually higher that those obtained with one of the other sources. Regarding the comparison with the ISTAT survey there was a good agreement for cardiovascular disease, diabetes and thyroid disorder whereas for rheumatologic conditions, chronic respiratory illnesses, migraine and Alzheimer's disease, the prevalence estimates were lower than those estimated by ISTAT survey. Estimates of prevalences derived by the HIS and by the REP were usually lower than those of the PD (but malignancies, chronic renal diseases). Our study showed that PD can be used to provide reliable prevalence estimates of several CCs in the general population.


[The miR-148a alleviates hepatic ischemia/reperfusion injury in mice via targeting CaMKIIα].
Objective To evaluate the impact of miR-148a on hepatic ischemia/reperfusion (I/R) injury via inhibiting Ca(2+)/calmodulin-dependent protein kinase IIα (CaMKIIα), and analyze the potential mechanism. Methods Liver I/R model was built in mice. Expression of CaMKIIα was detected in the hepatic tissues by Western blotting. The mRNA levels of miR-148a, CaMKIIα, tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were analyzed by quantitative real-time PCR (qRT-PCR). HE staining was performed to observe morphological changes of the livers in each group. TUNEL was used to evaluate the degree of hepatocellular apoptosis in each group. Results After hepatic I/R injury, the expression of miR-148a increased, and it was negatively correlated with CaMKIIα. After therapy with exogenous miR-148a mimics, the protein expression of CaMKIIα, the mRNA levels of TNF-α and IL-1β, the degree of inflammatory cell infiltration and liver cell necrosis, and the level of hepatocellular apoptosis were all downregulated. Conclusion The miR-148a may alleviate hepatic I/R injury in mouse by inhibiting CaMKIIα.


Prevalence of attention-deficit/hyperactivity disorder and intellectual disability among children with hydrocephalus.
Little is known about the prevalence of attention-deficit/hyperactivity disorder (ADHD) in children with hydrocephalus. In this study, the authors assessed the prevalence of ADHD and its association with clinical and demographic factors, including intellectual disability (ID), a potential factor that can confound the diagnosis of ADHD. The authors conducted a cross-sectional study of children 6-12 years of age with hydrocephalus using parent telephone surveys. The Child and Adolescent Intellectual Disability Screening Questionnaire (CAIDS-Q) and the National Institute for Children's Health Quality (NICHQ) Vanderbilt Assessment Scale were used to screen for ID and ADHD, respectively. Among children without ID, the authors identified those with ADHD and calculated a prevalence estimate and 95% confidence interval (Wald method). Logistic regression analysis was conducted to compare children with ADHD with those without ADHD based on demographics, family income, parental educational, etiology of hydrocephalus, and primary treatment. As a secondary analysis, the authors compared subjects with ID with those without using the same variables. Multivariable analysis was used to identify factors with independent association with ADHD and ID. A total of 147 primary caregivers responded to the telephone questionnaire. Seventy-two children (49%) met the cutoff score for ID (CAIDS-Q). The presence of ID was significantly associated with lower family income (p < 0.001). Hydrocephalus etiology (p = 0.051) and initial treatment (p = 0.06) approached significance. Of children without ID (n = 75), 25 demonstrated a likely diagnosis of ADHD on the NICHQ, yielding a prevalence estimate of 0.33 (95% CI 0.22-0.44). No clinical or demographic variable showed significant association with ADHD. These data indicate that the prevalence of ADHD among children with hydrocephalus (33%) is higher than among the general population (estimated prevalence in Alabama is 12.5%). ID is also common (49%). Routine screening for ADHD and ID in children with hydrocephalus may help to ensure that adequate resources are provided to optimize functional outcomes across development.


Restriction of dietary energy intake has a greater impact on bone integrity than does restriction of calcium in exercising female rats.
We sought to elucidate the effects of restricting calcium, energy, or food on the skeletal integrity of exercising female rats. Female Sprague-Dawley rats (4 mo old) were randomly assigned to 5 groups (n = 10/group): ad libitum intake of an AIN-93M diet (Research Diets D10012M, Research Diets, Inc.) with no exercise (AL-S) or with exercise (AL-EX) or to 1 of 3 exercising restriction groups [40% restriction of calcium only (CAR-EX), energy only (ER-EX), or food (FR-EX)]. All EX rats were treadmill trained 3 d/wk, 45 min/d for 12 wk at ~60% maximal oxygen consumption. After 12 wk, total body bone mineral content (by DXA) and body mass, but not lean mass, were lower in ER-EX (-17%) and FR-EX rats (-13%) compared with the AL-EX group. CAR-EX had few negative effects on bone geometry (by peripheral quantitative computed tomography) or histomorphometry. However, declines in total volumetric bone mineral density at the proximal tibia metaphysic (PTM) were observed in ER-EX (-6%) and FR-EX (-8%) groups; only FR-EX rats exhibited increased osteoclast surface and decreased mineral apposition rate in PTM cancellous bone. Decrements in serum estradiol, uterine weights, or both in these 2 groups implicate altered estrogen status as contributory. Urine pH declined significantly by 12 wk in all restricted groups, but net acid excretion increased only in CAR-EX rats. These findings, when compared with published data on sedentary rats, suggest that treadmill running exercise may mitigate some, but not all, deleterious effects on bone after chronic energy or food restriction but is more protective during calcium restriction.


Microfluidic sorting with blinking optical traps.
It is shown that by appropriately choosing the periodicity of a blinking optical trap only larger sized colloidal spheres can be selectively trapped out of a mixed population. This happens because smaller sized, more agile, spheres escape out of the trap volume during the off period of the trap beam. Therefore, by scanning an array of blinking traps over a mixed sample, bigger spheres can be forced to move with the traps and eventually could be taken to the output side. Experimental demonstration of sorting between 1 µm and 2 µm diameter silica spheres is presented.


Plasma membrane-bound tissue inhibitor of metalloproteinases (TIMP)-2 specifically inhibits matrix metalloproteinase 2 (gelatinase A) activated on the cell surface.
The cell-surface activation of pro-matrix metalloproteinase 2 (pro-MMP-2) is considered to be critical for cell migration and invasion. Treatment of human uterine cervical fibroblasts with concanavalin A activates pro-MMP-2 on the cell surface by converting it to the 65-kDa form with a minor form of 45 kDa. However, the 65-kDa MMP-2 was inactivated by tissue inhibitor of metalloproteinases (TIMP)-2 that was bound to the plasma membrane upon concanavalin A treatment. TIMP-2 binds to the plasma membrane through its N-terminal domain by two different modes of interaction as follows: one is sensitive to a hydroxamate (HXM) inhibitor of MMPs and the other is HXM-insensitive. TIMP-2 bound to the membrane in a HXM-insensitive manner, comprising about 40-50% of TIMP-2 on the membrane, is the inhibitor of the cell surface-activated MMP-2. It, however, does not inhibit MMP-3, MMP-9, and the 45-kDa MMP-2 lacking the C-terminal domain. The inhibition of the 65-kDa MMP-2 by TIMP-2 is initiated by the interaction of their C-terminal domains. Subsequently, the MMP-2.TIMP-2 complex is released from the membrane, and the activity of MMP-2 is blocked by TIMP-2. In the presence of collagen types I, II, III, V, or gelatin, the rate of inhibition of the 65-kDa MMP-2 by the membrane-bound TIMP-2 decreased considerably. These results suggest that the pericellular activity of MMP-2 is tightly regulated by membrane-bound TIMP-2 and surrounding extracellular matrix components.


Perceptions and acceptability of some stakeholders about the bovine tuberculosis surveillance system for wildlife (Sylvatub) in France.
Bovine tuberculosis (bTB) is a common disease of cattle and wildlife, with economic repercussions and implications for animal and human health. The surveillance of bTB in wildlife is particularly important, to shed light on the epidemiological role of wild species and for the adaptation of control measures. In France, a bTB surveillance system for free-ranging wildlife, the Sylvatub system, was launched in 2011 on wild boars, red deer, roe deer and badgers. It relies on active and passive surveillance activities, constrained by practical difficulties, such as the accessibility of wild animals, and regulatory rules for the trapping of badgers, for example. We report here the first assessment of stakeholders' perceptions of the Sylvatub system and its acceptability, based on 20 individual semi-structured interviews with three types of stakeholder (collectors, coordinators, officers) in areas with different rates of bTB infection. With the caveat that these findings cannot be assumed to be representative of the national situation, we found that the Sylvatub system was considered useful by all the stakeholders interviewed. Those from the world of hunting participate in surveillance mostly to help livestock farmers, who are not systematically involved in bTB surveillance in wildlife. Many practical and regulatory constraints were raised, which could be offset by recognition of the work done by the "hunting community", to maintain the willingness of these individuals to participate. We also identified a need for improvements in communication and information. Qualitative information, such as that collected here, is essential to improve our understanding of the reasons favoring and disfavoring participation in surveillance, and should be taken into account in the evaluation process. These results are relevant to hunters and to veterinary authorities wishing to identify the determinants of participation in the Sylvatub system. They could provide support for decision-making processes to improve surveillance strategies.


Responding to the signal and the noise: behavior of planktonic gastropod larvae in turbulence.
Swimming organisms may actively adjust their behavior in response to the flow around them. Ocean flows are typically turbulent and are therefore characterized by chaotic velocity fluctuations. While some studies have observed planktonic larvae altering their behavior in response to turbulence, it is not always clear whether a plankter is responding to an individual turbulence fluctuation or to the time-averaged flow. To distinguish between these two paradigms, we conducted laboratory experiments with larvae in turbulence. We observed veliger larvae of the gastropod Crepidula fornicata in a jet-stirred turbulence tank while simultaneously measuring two components of the fluid and larval velocity. Larvae were studied at two different stages of development, early and late, and their behavior was analyzed in response to different characteristics of turbulence: acceleration, dissipation and vorticity. Our analysis considered the effects of both the time-averaged flow and the instantaneous flow, around the larvae. Overall, we found that both stages of larvae increased their upward swimming speeds in response to increasing turbulence. However, we found that the early-stage larvae tended to respond to the time-averaged flow, whereas the late-stage larvae tended to respond to the instantaneous flow around them. These observations indicate that larvae can integrate flow information over time and that their behavioral responses to turbulence can depend on both their present and past flow environments.


A state-of-the-art review of the experience of care coordination interventions for people living with multimorbidity.
To explore recent research on care coordination interventions for people living with multimorbidity, from the perspective of the person receiving care. Care coordination interventions for people living with multimorbidity show some effectiveness in improving management of their health and reducing potentially preventable hospitalisations. The experience of people enrolled in care coordination interventions requires further exploration. State-of-the-art review. A review was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist where five databases (The Cochrane Library, PsycINFO, Scopus, CINAHL and MEDLINE) were searched for qualitative sources published from January 2008-March 2019. Two additional databases focused on multimorbidity and integrated care were included in the search. Titles, abstracts and full texts were screened using inclusion criteria. Reference lists of the included articles were hand-searched. Summary tables were developed for data extraction, and the data were mapped to the research question. Eighteen primary research articles were included. Three themes of participant experience were identified: (a) relationships built on trust, (b), a sense of safety and security and (c) feeling cared for and respected. The contribution of qualitative approaches to evaluating the experiences of care for people living with multimorbidity is growing. Participants' describe a focus on relationships formed with healthcare professionals during care coordination. Further research incorporating lived experiences of participants could illuminate these concepts further. People living with multimorbidity who require assistance via care coordination value trusting relationships with healthcare professionals, who respect their needs and provide a sense of security. Understanding participant experiences is important to shape care coordination interventions that incorporate person-centred approaches.


Evaluation of a Decision Tree for Efficient Antenatal Red Blood Cell Antibody Screening.
Hemolytic disease of the fetus and newborn due to maternal red blood cell alloimmunization can have serious consequences. Because early detection enables careful monitoring of affected pregnancies, programs to routinely screen all pregnant women have been widely adopted. Due to the low prevalence of alloimmunization, these require large investments of resources to detect a small number of cases. We conducted a validation study of a decision tree developed in the Netherlands for determining whether to screen for alloimmunization. In a Swedish cohort, we compared the performance of that decision tree to two alternative models that used maternal characteristics, obstetric history, and transfusion history to identify high-risk women for screening or low-risk women who might be exempt from screening. The models were compared for predictive ability and potential reduction in the volume of screening. The decision tree applied to our study population identified 89% of alloimmunized women with a negative predictive value (NPV) of 99.7% by screening 62% of the population. To achieve the same NPV, our model exempting low-risk women captured 90% of alloimmunizations by screening 63% of the population. In contrast, the model identifying high-risk women for screening while maintaining a similar NPV captured 63% of alloimmunized women by screening 20% of the population. We validated that an existing decision tree for selecting women for maternal screening performed well in our population, identifying a large proportion of women who became alloimmunized, with a predictive performance almost identical to that of a more elaborate model.


Obesity, lipid profiles and oxidative stress in children after liver transplantation.
In adult liver transplant recipients, coronary artery disease and congestive heart failure are significant cause of morbidity and mortality. This may be attributed to the long-term immunosuppressive treatment, mostly with calcineurin inhibitors and steroids, which in long-term may be associated with hyperlipidemia, oxidative stress and cardiovascular complications. Since such data for children is sparse, the aim of this study was to assess the lipid and oxidative stress markers after pediatric liver transplantation (LTx). We performed prospective analysis of 74 children, at the median age of 7.9 (2.8-11.6) years, 3.2 (1.2-4.3) years after LTx. We assessed the BMI Z-scores, cholesterol fractions (LDLc, HDLc, VLDLc), triglicerides, apolipoproteins (ApoAI, ApoB, ApoE), LCAT, insulin resistance by HOMA-IR and markers of oxidative stress and atherosclerosis: glutathione (GSH), glutathione peroxidase (GPx), asymmetrical dimethyl arginine (ADMA) and oxidized low-density lipoprotein (oxyLDL). At baseline, the results were compared with a healthy age-and-sex matched control group. After 3.1±0.3 year follow-up we repeated all investigations and compared them with the baseline results. At the baseline, we investigated 74 patients 3.2 (1.2-4.3) years after LTx, at the median age of 7.9 (2.8-11.6) years. The prevalence of overweight or obesity (BMI >85th percentile) was 23% and was more common in girls (24% vs 20%). Fourteen patients had TCH >200 mg%, 9 patients had LDLc >130 mg% and TG were at normal levels in all patients. Compared to the controls, there were no significant differences in lipid profiles but we found decreased GSH (p<0.001) and GPx (p<0.001) which play role as an antioxidant defense. OS markers were higher in the study group: ADMA (p<0.001), and oxyLDL (p<0.0001). Insulin resistance by HOMA-IR was increased in the study group (p=0.0002) but fasting glucose remained within normal ranges in all patients. After 3.1-year follow-up, the BMI >95th and >85Th percentile was present in 8% and 14% respectively. ADMA and oxyLDL decreased, whilst GSH and GPx increased when compared to the baseline. There was also significant decrease in apoB and Lp(a). Children after LTx had normal lipid profiles when compared to controls, however there is a tendency for hypercholesterolemia and obesity, which may play a role in cardiovascular complications in the future. Some markers of oxidative stress were increased after LTx, however further investigations are required to establish its clinical significance.


Which patients with myelofibrosis should receive ruxolitinib therapy? ELN-SIE evidence-based recommendations.
Ruxolitinib is an oral Janus-activated kinase 1 (JAK1)/JAK2 inhibitor approved for the treatment of patients with myelofibrosis based on the results of two randomized clinical trials. However, discordant indications were provided by regulatory agencies and scientific societies for selecting the most appropriate candidates to this drug. The European LeukemiaNet and the Italian Society of Hematology shared the aim of building evidence-based recommendations for the use of ruxolitinib according to the GRADE methodology. Eighteen patient-intervention-comparator-outcome profiles were listed, each of them comparing ruxolitinib to other therapies with the aim of improving one of the three clinical outcomes: (a) splenomegaly, (b) disease-related symptoms, and (c) survival. Ruxolitinib was strongly recommended for improving symptomatic or severe (>15 cm below the costal margin) splenomegaly in patients with an International Prognostic Scoring System (IPSS)/dynamic IPSS risk intermediate 2 or high. Ruxolitinib was also strongly recommended for improving systemic symptoms in patients with an MPN10 score >44, refractory severe itching, unintended weight loss not attributable to other causes or unexplained fever. Because of weak evidence, the panel does not recommend ruxolitinib therapy for improving survival. Also, the recommendations given above do not necessarily apply to patients who are candidates for allogeneic stem cell transplant.


Sexual harassment: the experience of out-of-school teenagers in Benin City, Nigeria.
Out-of-school teenage sexual harassment is a problem for both boys and girls in our society today, and the effects of this experience can affect their lives negatively in later adult life. The data on sexual harassment, particularly those on the out-of-school teenage population in Nigeria are very scanty, as a result of the sensitive nature of, and the stigma attached to the subject. This study sought to investigate the experiences of out-of-school teenagers with regards to sexual harassment in Benin City, Edo State, Nigeria. A survey method was used whereby a questionnaire was employed since most of the teenagers could not read. A total of 650 youths (293 males and 357 females) participated in the study. The findings indicate that sexual harassment is common out there in the streets, to the extent that it was viewed as the norm in the society by the youths. For example, 296 (83%) of all females and 152 (62%) of all males had experienced one or more forms of sexual harassment. It was also found that more females (82%) compared to 48% males experienced harassment and that anger was the most common response to the experience. The majority of the victims considered their assailants as abnormal and for the most part did not know how to handle the situation. The implications of these findings both for social/legal action and for health/sex education are discussed.


Nano-clustering of ligands on surrogate antigen presenting cells modulates T cell membrane adhesion and organization.
We investigate the adhesion and molecular organization of the plasma membrane of T lymphocytes interacting with a surrogate antigen presenting cell comprising glass supported ordered arrays of antibody (α-CD3) nano-dots dispersed in a non-adhesive matrix of polyethylene glycol (PEG). The local membrane adhesion and topography, as well as the distribution of the T cell receptors (TCRs) and the kinase ZAP-70, are influenced by dot-geometry, whereas the cell spreading area is determined by the overall average density of the ligands rather than specific characteristics of the dots. TCR clusters are recruited preferentially to the nano-dots and the TCR cluster size distribution has a weak dot-size dependence. On the patterns, the clusters are larger, more numerous, and more enriched in TCRs, as compared to the homogeneously distributed ligands at comparable concentrations. These observations support the idea that non-ligated TCRs residing in the non-adhered parts of the proximal membrane are able to diffuse and enrich the existing clusters at the ligand dots. However, long distance transport is impaired and cluster centralization in the form of a central supramolecular cluster (cSMAC) is not observed. Time-lapse imaging of early cell-surface contacts indicates that the ZAP-70 microclusters are directly recruited to the site of the antibody dots and this process is concomitant with membrane adhesion. These results together point to a complex interplay of adhesion, molecular organization and activation in response to spatially modulated stimulation.


Tocolytic treatment for the management of preterm labour: a systematic review.
Spontaneous preterm labour and delivery accounts for approximately one-third of preterm births, which is the predominant cause of perinatal mortality and morbidity. This review aims to evaluate the evidence on the benefits and harms of five classes of tocolytic therapy, namely: betamimetics, calcium channel blockers, magnesium, non-steroidal anti-inflammatory agents, and atosiban. We performed a systematic review of the effectiveness of tocolytics to stop uterine contractions (first-line therapy). Reports of randomised controlled trials from searches of MEDLINE, bibliographies of review articles, Cochrane Collaboration and its Pregnancy and Childbirth Review Group between 1966 and 2003 were identified, using the search terms "randomised controlled trial" (RCT), "preterm labor", "tocolysis", "betamimetics", "ritodrine", "prostaglandin synthetase inhibitors", "indomethacin", "calcium channel blockers", "nifedipine", "oxytocin receptor blockers", "atosiban", and "magnesium sulphate". Studies on women with preterm labour comparing the effects of a tocolytic with a placebo or no treatment that met our inclusion criteria, were included. To our knowledge, the trials were conducted mainly before 1999 and there were no placebo-controlled trials after that. Of the 86 articles identified and evaluated, 14 first-line studies met more stringent requirements for meta-analyses. Tocolytics were associated with significant decreases in the odds of delivery within 24 hours (odds-ratio [OR] 0.54, 95 percent confidence interval [CI] 0.32-0.91) and 48 hours (OR 0.47, 95 percent CI 0.30-0.75). These effects were significant for beta-agonists, atosiban and indomethacin, but not magnesium sulphate. Maternal side-effects significantly associated with betamimetics were pulmonary oedema, cardiac arrhthymias and hypokalaemia. Although calcium antagonists have not been evaluated against placebo, comparative trials with beta-agonists have shown more favourable neonatal outcomes and better prolongation of gestation. In conclusion, the management of threatened preterm labour with first-line tocolytic therapy can prolong gestation. However, the time gained in-utero need to be optimised. There is no clear first-line tocolytic agent. The use of tocolytic agents should be individualised and based on maternal condition, potential side-effects and gestational age.


Retracted Publications in Orthopaedics: Prevalence, Characteristics, and Trends.
Retracted publications are a crucial, yet overlooked, issue in the scientific community. The purpose of our study was to assess the prevalence, characteristics, and trends of retracted publications in the field of orthopaedics. Five databases were utilized to identify retracted publications in orthopaedics. The cited articles were assessed for various characteristics, including reason for retraction, based on the Committee on Publication Ethics (COPE) guidelines and trends over time. From 1984 to June 4, 2016, 59 of 229,502 orthopaedic publications were retracted (3 per 10,000 articles). There was a spike in the prevalence (22 of 59) of retracted articles in 2015. When compared with the total number of retracted publications identified through PubMed, the field of orthopaedics represented 1.4% of all retracted publications. The original version of 47 of these 59 retracted publications was still available on the respective journal's web site; 14 (30%) of these were not noted as having been retracted. The mean time from electronic publication to retraction was 19.4 ± 23.3 months. The mean number of citations of a retracted publication after the date of retraction was 9.3 ± 19.3. Reasons for retraction included plagiarism (32%), misconduct (27%), redundant publication (22%), miscalculation or experimental error (8%), and unethical research (0%); the reason for retraction was not stated for 10% of the publications. There was no correlation between a journal's impact factor and the mean number of months to retraction (p = 0.564). While uncommon, the retraction of publications within the field of orthopaedics may be increasing. The most often cited reasons for retraction were plagiarism, misconduct, and redundant publication. Retracted articles continue to be cited in the literature after retraction. Greater awareness of the COPE guidelines within the orthopaedic community and more efficient means to prevent the citation of retracted articles are needed.


Identifying differential trajectories and predictors for depressive symptoms in adolescents using latent class growth analysis: A population-based cohort study.
This study investigated the differential trajectories and relevant determinants of depressive symptoms in adolescents by following cohorts that included junior, senior, and vocational high school adolescents, over a 3-year period in Taiwan. Longitudinal data were obtained from 575 adolescents who participated in the Taiwan Adolescent to Adult Longitudinal Study. Data analysis included latent class growth with time-varying covariate, univariate, and multivariate analysis. A three-class ("low but increasing trajectory," "moderate and stable trajectory," and "high but decreasing trajectory") model fit the data of the cohort. Our findings indicated that 29%, 38%, and 33% of the adolescents were in the low but increasing, moderate and stable, and high but decreasing trajectories, respectively. After confounders were controlled for, bullying experiences were identified as a risk factor for depressive symptoms. The protective factors against depressive symptoms included resilience and peer and social support. The transitions between different educational stages critically influence the depressive symptoms of adolescents, and the adolescents follow different depressive trajectories, that have different etiology. Therefore, identifying adolescents at high risk for depression and designing student-centered intervention programs through individualized and multidimensional assessment of depressive symptoms are crucial for adolescents.


Diffuse Pediatric-type High-grade Glioma Arising in an Ovarian Mature Cystic Teratoma.
Immature neuroectodermal tissue can be found in the ovary as part of an immature teratoma or as part of a teratoma with malignant neuroectodermal transformation. Such lesions may closely resemble central nervous system tumors, but their biologic similarity is unclear. We describe an 18-yr-old female who presented with abdominal pain caused by an ovarian mass with widespread metastases. Histology showed a primitive, high-grade tumor arising in the background of a mature teratoma. The tumor was SOX10 positive, with focal expression of GFAP, S100, NSE, and synaptophysin. Molecular analysis demonstrated co-amplification of PDGFRA and KIT , alterations common in high-grade gliomas. By whole-genome methylation profiling, it clustered into the "diffuse pediatric-type high-grade glioma, RTK1 subtype, subclass c" group. Despite progressing through 2 lines of chemotherapy with widespread metastatic disease, she achieved an excellent response to chemotherapy directed toward aggressive germ cell tumors. This case emphasizes the importance of immunohistochemical, genomic, and epigenetic analyses to accurately classify these exceedingly rare tumors and determine the optimal therapy.


Power series solution of the inhomogeneous exclusion process.
We develop a power series method for the nonequilibrium steady state of the inhomogeneous one-dimensional totally asymmetric simple exclusion process (TASEP) in contact with two particle reservoirs and with site-dependent hopping rates in the bulk. The power series is performed in the entrance or exit rates governing particle exchange with the reservoirs, and the corresponding particle current is computed analytically up to the cubic term in the entry or exit rate, respectively. We also show how to compute higher-order terms using combinatorial objects known as Young tableaux. Our results address the long outstanding problem of finding the exact nonequilibrium steady state of the inhomogeneous TASEP. The findings are particularly relevant to the modeling of mRNA translation in which the rate of translation initiation, corresponding to the entrance rate in the TASEP, is typically small.


Comparison of nucleotide and deduced amino acid sequence of the 5' non-coding region and structural protein genes of the wild-type Japanese encephalitis virus strain SA14 and its attenuated vaccine derivatives.
Nucleotide sequences of the 5' non-coding region and the structural protein genes of the live, attenuated Japanese encephalitis vaccine virus strains SA14-2-8 and SA14-5-3 and the wild-type parental strain SA14/USA were determined. SA14-2-8 differed from SA14/USA by 13 nucleotides and eight amino acids whereas SA14-5-3 differed from SA14/USA by 15 nucleotides and eight amino acids. A comparison of the 5' non-coding region and amino acid sequences of the structural proteins of these two attenuated vaccine strains and of vaccine strains SA14-14-2/PHK and SA14-14-2/PDK with three sequences of their wild-type parent SA14 virus was performed. This revealed only two common amino acid substitutions at positions 138 and 176 in the envelope (E) protein. The substitution at E138 was predicted to cause a change in the secondary structure of the E protein. These two amino acid substitutions in the E protein may contribute to attenuation of the Japanese encephalitis vaccine viruses.


Alloy CsCd x Pb1-x Br3 Perovskite Nanocrystals: The Role of Surface Passivation in Preserving Composition and Blue Emission.
Various strategies have been proposed to engineer the band gap of metal halide perovskite nanocrystals (NCs) while preserving their structure and composition and thus ensuring spectral stability of the emission color. An aspect that has only been marginally investigated is how the type of surface passivation influences the structural/color stability of AMX3 perovskite NCs composed of two different M2+ cations. Here, we report the synthesis of blue-emitting Cs-oleate capped CsCd x Pb1-x Br3 NCs, which exhibit a cubic perovskite phase containing Cd-rich domains of Ruddlesden-Popper phases (RP phases). The RP domains spontaneously transform into pure orthorhombic perovskite ones upon NC aging, and the emission color of the NCs shifts from blue to green over days. On the other hand, postsynthesis ligand exchange with various Cs-carboxylate or ammonium bromide salts, right after NC synthesis, provides monocrystalline NCs with cubic phase, highlighting the metastability of RP domains. When NCs are treated with Cs-carboxylates (including Cs-oleate), most of the Cd2+ ions are expelled from NCs upon aging, and the NCs phase evolves from cubic to orthorhombic and their emission color changes from blue to green. Instead, when NCs are coated with ammonium bromides, the loss of Cd2+ ions is suppressed and the NCs tend to retain their blue emission (both in colloidal dispersions and in electroluminescent devices), as well as their cubic phase, over time. The improved compositional and structural stability in the latter cases is ascribed to the saturation of surface vacancies, which may act as channels for the expulsion of Cd2+ ions from NCs.


Anemia in general medical inpatients prolongs length of stay and increases 30-day unplanned readmission rate.
Anemia, either chronic or newly developed in the hospital as a result of underlying disease and/or phlebotomy, is seen commonly among general medical inpatients, and its impact on the quality and efficiency of care is unknown. This study investigated the relation among hemoglobin level, length of stay, and 30-day unplanned readmission rates in a cohort of 314 general medical inpatients 18 years old and older admitted to a teaching hospital during a period of 4 months in a large urban academic medical center, using retrospective chart review of the electronic health record. Anemia was common among this cohort of general medical inpatients (44.6%), and there was a statistically significant decrease in hemoglobin levels during their hospitalization. Anemic patients, as compared with nonanemic patients, had significantly longer mean and median length of stay. More important, the admission hemoglobin level and its change during hospitalization were significant predictors of increased length of stay. For every 1-U increase in admission hemoglobin level, the median length of stay was reduced by 0.5 days. For every 1-U increase in the level of hemoglobin change, the median length of stay was extended by 1.5 days. Likewise, the discharge hemoglobin level predicted the rate of 30-day unplanned readmission. For every 1-U decrease in discharge hemoglobin level, the readmission rate increased by nearly 4%. These relations remained after adjusting for common demographic and clinical variables, including age, sex, nutritional status, and number of comorbidities. Anemia is common among general medical inpatients and adversely affects their length of stay and 30-day unplanned readmission rate.


Relationship between left atrial function and plasma level of atrial natriuretic peptide in patients with heart disease.
To investigate the relationship between left atrial function and secretion of atrial natriuretic peptide (ANP), we analyzed left ventricular inflow and pulmonary venous flow, left atrial dynamics, intracardiac pressures, and plasma ANP level in 92 patients with various cardiac diseases. From the apical four-chamber view, maximal left atrial volume and percent fractional change of the left atrial area during atrial systole (LA-%AC) were calculated. The ratio of peak early filling velocity to peak atrial systolic velocity (E/A) in the left ventricular inflow and the ratio of peak systolic velocity to peak diastolic velocity (S/D) in the pulmonary venous flow were measured with the pulsed Doppler method. A significant linear correlation was found between plasma ANP levels and pulmonary capillary wedge pressure. Significant linear correlations were also found between left ventricular end-diastolic pressure and both maximal left atrial volume and LA-%AC. Plasma ANP level was significantly correlated with maximal left atrial volume, LA-%AC, E/A, and S/D. A multivariate analysis revealed that only LA-%AC was significantly correlated with the plasma ANP level. These results suggest that left atrial systolic dysfunction associated with a left atrial afterload mismatch is closely related to the ANP secretion.


Conserved biosynthetic pathways for phosalacine, bialaphos and newly discovered phosphonic acid natural products.
Natural products containing phosphonic or phosphinic acid functionalities often display potent biological activities with applications in medicine and agriculture. The herbicide phosphinothricin-tripeptide (PTT) was the first phosphinate natural product discovered, yet despite numerous studies, questions remain surrounding key transformations required for its biosynthesis. In particular, the enzymology required to convert phosphonoformate to carboxyphosphonoenolpyruvate and the mechanisms underlying phosphorus methylation remain poorly understood. In addition, the model for non-ribosomal peptide synthetase assembly of the intact tripeptide product has undergone numerous revisions that have yet to be experimentally tested. To further investigate the biosynthesis of this unusual natural product, we completely sequenced the PTT biosynthetic locus from Streptomyces hygroscopicus and compared it with the orthologous cluster from Streptomyces viridochromogenes. We also sequenced and analyzed the closely related phosalacine (PAL) biosynthetic locus from Kitasatospora phosalacinea. Using data drawn from the comparative analysis of the PTT and PAL pathways, we also evaluate three related recently discovered phosphonate biosynthetic loci from Streptomyces sviceus, Streptomyces sp. WM6386 and Frankia alni. Our observations address long-standing biosynthetic questions related to PTT and PAL production and suggest that additional members of this pharmacologically important class await discovery.


[Effect of exogenous α-naphthaleneacetic acid on carbon metabolism of soybean under drought stress at flowering stage].
With pot experiment, two soybean (Glycine max) varieties, Jindou 21 (drought-tole-rant) and Xudou 22 (drought-sensitive), were used to examine the effects of α-naphthaleneacetic acid (NAA) on carbon metabolism of soybean under drought stress at flowering stage. The results showed that under drought stress, compared to Xudou 22, Jindou 21 had smaller decrease in net photosynthetic rate (Pn), smaller increase in photorespiration rate (Pr) and soluble sugar content of leaves, while a greater increase in the activities of sucrose phosphate synthase (SPS) and sucrose synthetase (SS) (synthesis) of leaves and sucrose content of roots. NAA treatment increased Pn and decreased Pr under drought stress, and thus obviously alleviated the growth inhibition of drought stress on plants. NAA treatment reduced the activities of starch-degrading enzymes, acid invertase (AI) and SS (cleavage), thereby inhibited the accumulation of soluble sugar induced by drought stress. In addition, NAA treatment increased SPS and SS (synthesis) activities of leaves, sucrose content of roots and shoot-root ratio, indicating that NAA treatment improved the transportation of sucrose from leaf blade to root under drought stress. In conclusion, exogenous NAA could enhance drought tolerance in soybean by regulating carbon metabolism.


Nd:YAG single-crystal fiber as high peak power amplifier of pulses below one nanosecond.
We explore the potential of Nd:YAG single-crystal fibers for the amplification of passively Q-switched microlasers operating below 1 ns. Different regimes are tested in single or double pass configurations. For high gain and high power amplification this novel gain medium provided average powers up to 20 W at high repetition rate (over 40 kHz) for a pulse duration of 1 ns. As an energy amplifier, Nd:YAG single-crystal fiber delivered 2.7 mJ, 6 MW 450 ps pulses at 1 kHz. The extraction efficiencies vary from 8% to 32.7% following the configurations.


Prostate-specific antigen: concepts for staging prostate cancer and monitoring response to therapy.
The prostate-specific antigen (PSA) level alone does not facilitate precise pathologic staging on an individual basis, although advanced stage tends to correlate with an increased PSA level. The staging accuracy of PSA, however, can be enhanced by considering the variables of tumor grade and clinical stage. Staging radionuclide bone scans in asymptomatic, untreated patients with clinically localized prostate cancer and a PSA value of less than 10.0 ng/mL are unnecessary. After radical prostatectomy, the serum PSA level is exquisitely sensitive to recurrent or residual disease. Ultrasensitive PSA assays can increase the sensitivity of PSA as a tumor marker after surgical removal of the prostate. Currently, however, the clinical usefulness of PSA concentrations detected in the ultrasensitive range after radical prostatectomy is unknown. Serum PSA values aid in monitoring patients who have received definitive radiation therapy for prostate cancer. Patients in whom the serum PSA level decreases to the reference range have a favorable prognosis. An increasing serum PSA concentration after radiation therapy heralds progressive prostate cancer. The serum PSA level after androgen deprivation therapy (ADT) also has prognostic importance in that a decrease to the normal range predicts a prolonged remission in most patients. Because expression of PSA is under direct hormonal influence, however, ADT can decrease the serum PSA value independent of antitumorigenic activity. Patients who have received ADT must be closely monitored for signs of clinical progression because, in some patients, a serum PSA concentration within the reference range may underestimate actual tumor burden and activity. PSA is the most useful and accurate tumor marker for staging and monitoring prostate cancer after therapy.


Geriatric syndromes: new frontiers in HIV and sarcopenia.
: HIV infection, in many circumstances, can now be managed as a chronic disease due to the marked increase in life expectancy since the introduction of combination antiretroviral therapy (ART). As the patients who first had access to combination ART age into their 50s and 60s, the effects of chronic HIV infection on health have become an important research focus in HIV infection. People living with HIV appear to exhibit an earlier occurrence of some aging-related conditions compared to people without HIV, in part due to higher rates of comorbidities, high-risk behaviors (e.g. smoking, substance use), chronic immune activation, inflammation, and ART-specific factors. Some studies have even suggested an earlier-than-expected appearance of the 'geriatric syndromes,' which are complex medical syndromes of older adults that are associated with morbidity and mortality. The geriatric syndromes include a wide variety of disease processes ranging from incontinence and dementia to impairments in physical function. This review will focus on one geriatric syndrome, sarcopenia, in older HIV-infected populations, and its relation to other aging syndromes, including frailty and falls. The contribution of HIV itself, ART exposure, and specific comorbidities, and the importance of early recognition and prevention of these aging syndromes will be highlighted.


Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors.
Tumor progression is facilitated by regulatory T cells (Treg) and restricted by effector T cells. In this study, we document parallel regulation of CD8(+) T cells and Foxp3(+) Tregs by programmed death-1 (PD-1, PDCD1). In addition, we identify an additional role of CTL antigen-4 (CTLA-4) inhibitory receptor in further promoting dysfunction of CD8(+) T effector cells in tumor models (CT26 colon carcinoma and ID8-VEGF ovarian carcinoma). Two thirds of CD8(+) tumor-infiltrating lymphocytes (TIL) expressed PD-1, whereas one third to half of CD8(+) TIL coexpressed PD-1 and CTLA-4. Double-positive (PD-1(+)CTLA-4(+)) CD8(+) TIL had characteristics of more severe dysfunction than single-positive (PD-1(+) or CTLA-4(+)) TIL, including an inability to proliferate and secrete effector cytokines. Blockade of both PD-1 and CTLA-4 resulted in reversal of CD8(+) TIL dysfunction and led to tumor rejection in two thirds of mice. Double blockade was associated with increased proliferation of antigen-specific effector CD8(+) and CD4(+) T cells, antigen-specific cytokine release, inhibition of suppressive functions of Tregs, and upregulation of key signaling molecules critical for T-cell function. When used in combination with GVAX vaccination (consisting of granulocyte macrophage colony-stimulating factor-expressing irradiated tumor cells), inhibitory pathway blockade induced rejection of CT26 tumors in 100% of mice and ID8-VEGF tumors in 75% of mice. Our study indicates that PD-1 signaling in tumors is required for both suppressing effector T cells and maintaining tumor Tregs, and that PD-1/PD-L1 pathway (CD274) blockade augments tumor inhibition by increasing effector T-cell activity, thereby attenuating Treg suppression.


Waves of Maturation and Senescence in Micro-structural MRI Markers of Human Cortical Myelination over the Lifespan.
Seminal human brain histology work has demonstrated developmental waves of myelination. Here, using a micro-structural magnetic resonance imaging (MRI) marker linked to myelin, we studied fine-grained age differences to deduce waves of growth, stability, and decline of cortical myelination over the life-cycle. In 484 participants, aged 8-85 years, we fitted smooth growth curves to T1- to T2-weighted ratio in each of 360 regions from one of seven cytoarchitectonic classes. From the first derivatives of these generally inverted-U trajectories, we defined three milestones: the age at peak growth; the age at onset of a stable plateau; and the age at the onset of decline. Age at peak growth had a bimodal distribution comprising an early (pre-pubertal) wave of primary sensory and motor cortices and a later (post-pubertal) wave of association, insular and limbic cortices. Most regions reached stability in the 30-s but there was a second wave reaching stability in the 50-s. Age at onset of decline was also bimodal: in some right hemisphere regions, the curve declined from the 60-s, but in other left hemisphere regions, there was no significant decline from the stable plateau. These results are consistent with regionally heterogeneous waves of intracortical myelinogenesis and age-related demyelination.


Randomised trial of methods of extubation in acute and chronic respiratory distress.
Sixty infants (median gestational age 29 weeks) with acute and 60 infants (median gestational age 25 weeks) with chronic respiratory distress were randomised to be extubated either directly into a headbox or onto 3 cm H2O nasal continuous positive airway pressure (CPAP). Our aim was to test the hypothesis that extubation onto nasal CPAP rather than directly into a headbox was more likely to be associated with successful extubation in infants with acute rather than chronic respiratory distress. Overall the failure rate of extubation was approximately 33%, with no significant difference between the infants with acute and chronic respiratory distress. There was no significant difference in the failure rate of extubation among infants randomised to receive nasal CPAP or headbox oxygen in either the acute or chronic respiratory distress groups.


Impact of the Alkyne Substitution Pattern and Metalation on the Photoisomerization of Azobenzene-Based Platinum(II) Diynes and Polyynes.
Trimethylsilyl-protected dialkynes incorporating azobenzene linker groups, Me3SiC≡CRC≡CSiMe3 (R = azobenzene-3,3'-diyl, azobenzene-4,4'-diyl, 2,5-dioctylazobenzene-4,4'-diyl), and the corresponding terminal dialkynes, HC≡CRC≡CH, have been synthesized and characterized. The CuI-catalyzed dehydrohalogenation reaction between trans-[Ph(Et3P)2PtCl] and the deprotected dialkynes in a 2:1 ratio in iPr2NH/CH2Cl2 gives the platinum(II) diynes trans-[Ph(Et3P)2PtC≡CRC≡CPt(PEt3)2Ph], while the dehydrohalogenation polycondensation reaction between trans-[(nBu3P)2PtCl2] and the dialkynes in a 1:1 molar ratio under similar reaction conditions affords the platinum(II) polyynes, [-Pt(PnBu3)2-C≡CRC≡C-]n. The materials have been characterized spectroscopically, with the diynes also studied using single-crystal X-ray diffraction. The platinum(II) diynes and polyynes are all soluble in common organic solvents. Optical-absorption measurements show that the compounds incorporating the para-alkynylazobenzene spacers have a higher degree of electronic delocalisation than their meta-alkynylazobenzene counterparts. Reversible photoisomerization in solution was observed spectroscopically for the alkynyl-functionalized azobenzene ligands and, to a lesser extent, for the platinum(II) complexes. Complementary quantum-chemical modeling was also used to analyze the optical properties and isomerization energetics.


Long-term musical experience and auditory and visual perceptual abilities under adverse conditions.
Musicians have been shown to have enhanced speech perception in noise skills. It is unclear whether these improvements are limited to the auditory modality, as no research has examined musicians' visual perceptual abilities under degraded conditions. The current study examined associations between long-term musical experience and visual perception under noisy or degraded conditions. The performance of 11 musicians and 11 age-matched nonmusicians was compared on several auditory and visual perceptions in noise measures. Auditory perception tests included speech-in-noise tests and an environmental sound in noise test. Visual perception tasks included a fragmented sentences task, an object recognition task, and a lip-reading measure. Participants' vocabulary knowledge and nonverbal reasoning abilities were also assessed. Musicians outperformed nonmusicians on the speech perception in noise measures as well as the visual fragmented sentences task. Musicians also displayed better vocabulary knowledge in comparison to nonmusicians. Associations were found between perception of speech and visually degraded text. The findings show that long-term musical experience is associated with modality-general improvements in perceptual abilities. Possible systems supporting musicians' perceptual abilities are discussed.


More assortative mating in US compared to European parents and spouses of patients with bipolar disorder: implications for psychiatric illness in the offspring.
The effect of assortative mating on offspring is often not considered. Here, we present data on illness in the spouse and the parents of patients with bipolar disorder as they affect illness in the offspring. A history of psychiatric illness (depression, bipolar disorder, suicide attempt, alcohol abuse, drug abuse, and "other" illness) was elicited for the parents, spouse, and the offspring of 968 patients with bipolar disorder (540 of whom had children) who gave informed consent for participation in a treatment outcome network. Assortative mating for a mood disorder in the spouse and parents in those from the United States (US) was compared to those from the Netherlands and Germany and related to illnesses in the offspring. There was more illness and assortative mating for a mood disorder in both the spouse and patient's parents from the US compared to Europe. In the parents of the US patients, assortative mating for a mood disorder was associated with more depression, bipolar disorder, alcohol, and "other" illness in the offspring. Compared to the Europeans, there was more assortative mating for mood and other disorders in two generations of those from the US. This bilineal positivity for a parental mood disorder was related to more depression a second generation later in the patients' offspring. In clinical assessment of risk of illness in the offspring, the history of psychiatric illness in the spouse and patient's parents might provide additional information.


Treatment options for alcoholic and non-alcoholic fatty liver disease: A review.
Alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD) are serious health problems worldwide. These two diseases have similar pathological spectra, ranging from simple steatosis to hepatitis to cirrhosis and hepatocellular carcinoma. Although most people with excessive alcohol or calorie intake display abnormal fat accumulation in the liver (simple steatosis), a small percentage develops progressive liver disease. Despite extensive research on understanding the pathophysiology of both these diseases there are still no targeted therapies available. The treatment for ALD remains as it was 50 years ago: abstinence, nutritional support and corticosteroids (or pentoxifylline as an alternative if steroids are contraindicated). As for NAFLD, the treatment modality is mainly directed toward weight loss and co-morbidity management. Therefore, new pathophysiology directed therapies are urgently needed. However, the involvement of several inter-related pathways in the pathogenesis of these diseases suggests that a single therapeutic agent is unlikely to be an effective treatment strategy. Hence, a combination therapy towards multiple targets would eventually be required. In this review, we delineate the treatment options in ALD and NAFLD, including various new targeted therapies that are currently under investigation. We hope that soon we will be having an effective multi-therapeutic regimen for each disease.


Renal accumulation of biglycan and lipid retention accelerates diabetic nephropathy.
Hyperlipidemia worsens diabetic nephropathy, although the mechanism by which renal lipids accumulate is unknown. We previously demonstrated that renal proteoglycans have high low-density lipoprotein (LDL) binding affinity, suggesting that proteoglycan-mediated LDL retention may contribute to renal lipid accumulation. The aim of this study was to determine the relative effect of diabetes and hyperlipidemia on renal proteoglycan content. Diabetic and non-diabetic LDL receptor-deficient mice were fed diets containing 0% or 0.12% cholesterol for 26 weeks, and then kidneys were analyzed for renal lipid and proteoglycan content. Diabetic mice on the high-cholesterol diet had accelerated development of diabetic nephropathy with elevations in urine albumin excretion, glomerular and renal hypertrophy, and mesangial matrix expansion. Renal lipid accumulation was significantly increased by consumption of the 0.12% cholesterol diet, diabetes, and especially by both. The renal proteoglycans biglycan and decorin were detectable in glomeruli, with a significant increase in renal biglycan content in diabetic mice on the high-cholesterol diet. Renal biglycan and renal apolipoprotein B were colocalized, and regression analyses showed a significant relation between renal biglycan and renal apolipoprotein B content. The increased renal biglycan content in diabetic nephropathy probably contributes to renal lipid accumulation and the development of diabetic nephropathy.


Exertional dyspnea and cough as preludes to acute attacks of bronchial asthma.
Although wheezing is believed to be a cardinal manifestation of asthma, some patients with this disorder may not present with wheezing, but rather with either exertional dyspnea or cough. In 14 such patients with dyspnea, there was peripheral airway dysfunction with markedly elevated residual volumes, frequency dependence of dynamic compliance and depressed flow rates in the middle-vital-capacity range, whereas specific conductance and one-second forced expiratory volumes were normal. Circumstantial evidence suggests that mucosal edema or mucous secretions may have been responsible. In seven patients with cough, studies revealed a more severe obstructive pattern that appeared to be the result of increased large-airway resistance, and the patients' response to isoproterenol indicated that contraction of bronchial smooth muscle may have been principally responsible. Thus, intermittent episodes of cough or breathlessness may represent variant aspects of asthmatic attacks.


Activation of V(D)J recombination at the IgH chain JH locus occurs within a 6-kilobase chromatin domain and is associated with nucleosomal remodeling.
IgH genes are assembled during early B cell development by a series of regulated DNA recombination reactions in which DH and JH segments are first joined followed by V(H) to DJH rearrangement. Recent studies have highlighted the role of chromatin structure in the control of V(D)J recombination. In this study, we show that, in murine pro-B cell precursors, the JH segments are located within a 6-kb DNase I-sensitive chromatin domain containing acetylated histones H3 and H4, which is delimited 5' by the DQ52 promoter element and 3' by the intronic enhancer. Within this domain, the JH segments are covered by phased nucleosomes. High-resolution mapping of nucleosomes reveals that, in pro-B cells, unlike recombination refractory nonlymphoid cells, the recombination signal sequences flanking the four JH segments are located in regions of enhanced micrococcal nuclease and restriction enzyme accessibility, corresponding to either nucleosome-free regions or DNA rendered accessible within a nucleosome. These results support the idea that nucleosome remodeling provides an additional level of control in the regulation of Ig locus accessibility to recombination factors in B cell precursors.


Thioredoxin reductase-dependent insulin disulfide reduction by phage T7 DNA polymerase reflects dissociation of the enzyme into subunits.
Phage T7 DNA polymerase contains Escherichia coli thioredoxin as a subunit and is a 1:1 complex with T7 gene 5 protein. The enzyme showed high thioredoxin activity in assays at 37 degrees C using reduction of insulin disulfides with NADPH and thioredoxin reductase, leading Randahl (Randahl, H. (1982) FEBS Lett. 150, 109-113) to propose that the thioredoxin dithiol active site is exposed in T7 DNA polymerase. However, T7 DNA polymerase and free thioredoxin differ in reactivity with iodoacetic acid after preincubation with dithiothreitol or incubation with insulin. Insulin reduction assays work at low temperatures even at 0 degrees C. The time and temperature dependence of the thioredoxin activity of T7 DNA polymerase demonstrated that dissociation into subunits at 25 or 37 degrees C accounts for the previously observed activity. Thus, T7 DNA polymerase contains the reduced form of thioredoxin with its active site SH groups masked by the subunit contact with the gene 5 protein in agreement with the results of Adler and Modrich (Adler, S., and Modrich, P. (1983) J. Biol. Chem. 258, 6956-6962). The subunit interaction of thioredoxin and gene 5 protein is salt-insensitive, but markedly temperature-dependent consistent with involvement of a hydrophobic surface area in reduced thioredoxin.


[Formula: see text]Selecting measures for the neurodevelopmental assessment of children in low- and middle-income countries.
Diseases affecting millions of children in low- and middle-income countries (LMICs), such as malnutrition, micronutrient deficiency, malaria, and HIV, can lead to adverse neurodevelopmental outcomes. Thus, a key health outcome in children is neurodevelopmental status. In this paper, the neurodevelopmental screening and testing measures most commonly utilized in LMICs are reviewed, and a matrix is presented to help researchers and clinicians determine which measures may be most useful for various LMIC inquiries. The matrix is based on an Internet literature review of 114 publications for the period January 1998 to February 2016, reporting the psychometric properties of instruments tested in LMIC children. The measures are classified as screening tests or more detailed tests that include both comprehensive batteries of general development and tests of specific domains. For completeness, two experts have reviewed this paper, as well as the authors. An overview of the tests used to date is presented, including the benefits and drawbacks of each test, in order to provide researchers and developmental clinicians with a way to decide which tests may be best suited to their developmental assessment goals. Remarkable progress has been made in neurodevelopmental testing in children in LMICs over the past two decades but there remains a need for additional research in this area to develop new tests, better evaluate and adapt current tests, and assess test validity and reliability across cultures.


Watching neutral and threatening movies: subjective experience and autonomic responses in subjects with different hypnotizability levels.
Subjects with high hypnotizability scores (Highs) have been considered more prone to experience negative affect and more vulnerable to its autonomic effects with respect to low hypnotizable individuals (Lows). The aim of the study was to analyze the subjective experience, tonic skin conductance (SC), respiratory frequency (RF), heart rate (HR) and heart rate variability (HRV) of healthy Highs and Lows during a long-lasting, emotionally neutral task (Session R, 46 subjects) and a moderately threatening one (Session T, 35 subjects). At the end of the relaxing Session R, all participants reported an increased relaxation. At the end of the threatening Session T, only 20 subjects reported a decreased relaxation (effective T: eT subsample). Highs and Lows of this subsample reported a similarly reduced relaxation and showed a similarly increased skin conductance. HR and HRV did not differ between the two sessions and between Highs and Lows. Among the subjects not reporting decreased relaxation at the end of Session T (ineffective T: iT subsample, n=15), relaxation was deeper and associated with lower skin conductance in Highs, although HR and HRV did not differ between Highs and Lows. All together, the results do not support the hypothesis of higher proneness of Highs to experience negative affect and to exhibit the autonomic correlates of negative emotion.


Stable non-mutator stocks of maize have sequences homologous to the Mu1 transposable element.
Mutator stocks of maize produce mutants at many loci at rates 20- to 50-fold above spontaneous levels. Current evidence suggests that this high mutation rate is mediated by an active transposable element system, Mu. Members of this transposable element family are found in approximately 10-60 copies in Mutator stocks. We report here an initial characterization of previously undetected sequences homologous to Mu elements in eight non-Mutator inbred lines and varieties of maize that have a normal low mutation rate. All stocks have approximately 40 copies of sequences homologous only to the terminal repeat and show weak homology to an internal probe. In addition, several of the stocks contain an intact Mu element. One intact Mu element and two terminal-specific clones have been isolated from one non-Mutator line, B37. The cloned sequences have been used to demonstrate that in genomic DNA the intact element, termed Mu1.4B37, is modified, such that restriction sites in its termini are not accessible to cleavage by the HinfI restriction enzyme. This modification is similar to that observed in Mutator lines that have lost activity. We hypothesize that the DNA modification of the Mu-like element may contribute to the lack of Mutator activity in B37.


Evaluation of Annuloaortic Ectasia by Angioscopy and IVUS "Report of 2 cases".
We attempted combined use of angioscopy and intravascular ultrasonography (IVUS) to localize the coronary ostia and determine the aortic segment to be replaced in patients with annuloaortic ectasia, because these preoperative informations are important for selection of an appropriate technique for reconstructing the coronary artery, to prevent complications, and also to postoperative follow-up. Two cases with annuloaortic ectasia underwent angioscopy and IVUS both pre- and post-operatively. Structure of aortic cusps, position of coronary ostia, the extent of ectasia with very thin wall were clearly observed by IVUS. Angioscopy showed milky white luminal surface of the ectasic segment. After Cabrol's operation, the sutured portion of native aorta and graft was clearly identified by IVUS and mural thrombus and naked surface of graft were observed by angioscopy. Complications were observed in none. The results indicate feasibility of combined use of angioscopy and IVUS for determination of surgical approach and follow-up in patients with AAE.


A Structured Literature Review of the Epidemiology and Disease Burden of Non-Alcoholic Steatohepatitis (NASH).
Non-Alcoholic Steatohepatitis (NASH) is a chronic, progressive disease characterized by fatty liver and liver cell injury, advancing to fibrosis, cirrhosis and hepatocellular carcinoma (HCC). Diagnosis involves liver biopsy; however, as a result of its high cost and invasiveness, NASH remains underdiagnosed, and accurate burden of disease (BoD) data are lacking. Our aim was to understand the epidemiological and BoD landscape in NASH and identify knowledge gaps. The Ovid search engine was used to conduct a structured review, following quality systematic principles. It included publications that reported on epidemiology, quality of life (QoL) and BoD outcomes in NASH adults. Searches were limited to English language studies published between January 2007 and September 2017. Additional grey literature searches were conducted. A total of 53 references were selected; 38 were peer-reviewed and 15 were grey literature sources. NASH is estimated to affect 3-5% of the global population, most suffering from several comorbidities. Advancing fibrosis drives clinical outcomes, with approximately 20% of patients developing cirrhosis and/or HCC, the latter being a leading cause of death in NASH. A recent model predicted the 15-year survival of advanced fibrosis patients at F3 and F4 as 51.0% and 28.4%, respectively. The limited data consistently show that NASH patients experience significantly poorer QoL and higher costs compared to non-NASH patients. This first broad-ranging examination of NASH literature revealed a paucity of evidence, with poor-quality, small studies found. The overwhelming impact of NASH and its patient and healthcare burden is evident. Further evidence is needed to improve our understanding of NASH, especially as fibrosis stages advance. Gilead Science Inc.


Comparative study on some systemic humoral and cellular immune markers in only HIV or HIV and hepatitis B infected children.
Three different groups of asymptomatic children, aged from 12 to 24 months (30 subjects per each group), i.e. controls, only HIV, or HIV/hepatitis B virus (HBV) double infected, were studied, as concerned the following systemic immune parameters: immunoglobulin (IgG, IgM, IgA, IgD) levels; absolute numbers of blood CD+4, CD+8, CD+16 and CD+19 cells; phytohaemagglutinin (PHA)-blast responsiveness of T lymphocytes; natural killer (NK) cell activity--as tested by means of cytotoxicity assays; per cent suppression of PHA-dependent T cell blastogenesis in the presence of concanavalin A (Con A) selected T suppressor (Ts) cells. On the other hand, in 15 ARC-shifting cases belonging to HIV, and HIV/HBV groups, respectively, a second serum sample was collected and searched comparatively with the corresponding first serum sample, as regarded: presence of total and anti-p24 HIV antibodies, patterns of Western Blot (WB), as well as amounts of free p24-HIV antigen. In asymptomatic double HIV/HBV infected subjects, some immune disorders occurred, at a more significant degree, as compared to only HIV-infected. Once the shift toward ARC being installed, in both infected groups a decrease of anti-p24 HIV antibody presence, disappearance of corresponding band in WB confirmation test, as well as presence of free p24 antigen in serum, were noticed. However, greater amounts of p24 antigen in HIV/HBV infected, as compared to only HIV infected patients, were found. Some considerations about diagnostic and predictive value of presented data are discussed.


Long noncoding RNA FAM225B facilitates proliferation and metastasis of nasopharyngeal carcinoma cells by regulating miR-613/CCND2 axis.
Growing evidence has suggested that abnormally expressed long non-coding RNAs (lncRNAs) play critical regulatory roles in nasopharyngeal carcinoma (NPC) pathogenesis. Family with sequence similarity 225 member B (FAM225B) is a novel lncRNA that has been implicated in several human cancers, yet its role in the context of NPC remains largely unclear. The aim of this study was to determine the expression level of FAM225B and its clinical significance in NPC patients. We observed a remarkable increase of FAM225B in NPC tissues and cell lines compared with controls. Also, highly expressed FAM225B was closely correlated with advanced TNM stage, distant metastasis, and poor overall survival. Interestingly, loss-of-function analysis revealed that FAM225B knockdown significantly inhibited tumor growth in vitro and in vivo, and decreased the migratory and invasive capacity of NPC cells. Mechanically, FAM225B functioned as an endogenous sponge by competing for miR-613 binding to up-regulate CCND2 expression. More importantly, rescue experiments further demonstrated that the suppressive impacts of FAM225B knockdown on cell proliferation, migration and invasion were significantly reversed after CCND2 overexpression. Taken all together, these findings highlight FAM225B as an oncogene that promotes NPC proliferation and metastasis through miR-613/CCND2 axis.


Low-temperature urine collection apparatus for laboratory rodents.
An apparatus for the collection of urine at -19 degrees C from unrestrained small laboratory animals was developed. The cooling unit accommodated five rodent metabolism cages for the collection of urine volumes up to 50 ml per collection period. The unit operated continuously for 5--6 weeks with no maintenance other than removal of the urine specimens, cleaning of the cages and collection dishes, and provision of feed and water.