Short communication: Relationship between the efficiency of utilization of feed nitrogen and 15N enrichment in casein from lactating dairy cows.
The objective of the present study was to evaluate the relationship between the efficiency of conversion of feed N into milk N [N-use efficiency (NUE)] and (15)N enrichment of milk casein from lactating cows fed corn silage-based diets. Samples of feeds and milk were obtained from 3 experiments with lactating dairy cows. All diets were based on corn silage and were designed to evaluate the effects of (1) diets with different ratios of effective rumen-degradable protein to fermentable metabolizable energy (experiment 1), (2) different proportions of quickly and slowly rumen-degradable protein (experiment 2), and (3) synchronizing the availability of fermentable metabolizable energy and effective rumen-degradable protein in the rumen (experiment 3). Although no significant effect of diet on casein δ(15)N values was detected, casein was more enriched than the diet in each of the experiments. Nitrogen-use efficiency was negatively related to adjusted Δ(15)N (casein δ(15)N--diet δ(15)N) for experiments 1 and 2 individually and when combining data from all 3 experiments. The relatively low values for Δ(15)N suggest that these productive animals were using dietary N efficiently, with a high proportion of N going to milk protein and less to urea. The weak, although significant, relationship between NUE and adjusted Δ(15)N, is consistent with relatively little variation in hepatic deamination and transamination, with variation in rumen efficiency having the predominant effect on NUE. The present study confirms the lower (15)N enrichment in protein when NUE is high and the potential to use N-isotope fractionation as a marker of NUE.


Protection and expression of human motor memories.
When we adapt our movements to a perturbation, and then adapt to another perturbation, is the initial memory destroyed, or is it protected? Despite decades of experiments, this question remains unresolved. The confusion, in our view, is due to the fact that in every instance the approach has been to assay contents of motor memory by retesting with the same perturbations. When performance in retesting is the same as naive, this is usually interpreted as the memory being destroyed. However, it is also possible that the initial memory is simply masked by the competing memory. We trained humans in a reaching task in field B and then in field A (or washout) over an equal number of trials. To assay contents of motor memory, we used a new tool: after completion of training in A, we withheld reinforcement (i.e., reward) for a brief block of trials and then clamped movement errors to zero over a long block of trials. We found that this led to spontaneous recovery of B. That is, withholding reinforcement for the current motor output resulted in the expression of the competing memory. Therefore, adaptation followed by washout or reverse adaptation produced competing motor memories. The protection from unlearning was unrelated to sudden changes in performance errors that might signal a contextual change, as competing memories formed even when the perturbations were introduced gradually. Rather, reinforcement appears to be a critical signal that affords protection to motor memories, and lack of reinforcement encourages retrieval of a competing memory.


Transient elastography accurately predicts presence of significant portal hypertension in patients with chronic liver disease.
Hepatic venous pressure gradient (HVPG) is a prognostic marker in patients with cirrhosis. Transient elastography measures liver stiffness (LS). To assess the correlation between LS and HVPG and to investigate the performance of transient elastography for the diagnosis of significant portal hypertension (PHT). Liver stiffness was measured by Fibroscan in 150 consecutive patients who underwent a liver biopsy with haemodynamic measurements. Usual clinical and biological data were collected. Significant PHT was defined as a HVPG > or = 10 mmHg. Hepatic venous pressure gradient was found to be > or = 10 mmHg in 76 patients. Cirrhosis was diagnosed in 89 patients. HVPG was found to be correlated with: LS (rho = 0.858; P < 0.001) and inversely correlated with prothrombin index (rho = -0.718; P < 0.001). Regarding significant PHT, AUROC for LS and prothrombin index were 0.945 [0.904-0.987] and 0.892 [0.837-0.947] respectively. The cut-off value of 21 kPa accurately predicted significant PHT in 92% of the 144 patients for whom LS was successful. Liver stiffness measurement is correlated with HVPG and transient elastography identifies patients with significant PHT.


Tapetal cell fate, lineage and proliferation in the Arabidopsis anther.
The four microsporangia of the flowering plant anther develop from archesporial cells in the L2 of the primordium. Within each microsporangium, developing microsporocytes are surrounded by concentric monolayers of tapetal, middle layer and endothecial cells. How this intricate array of tissues, each containing relatively few cells, is established in an organ possessing no formal meristems is poorly understood. We describe here the pivotal role of the LRR receptor kinase EXCESS MICROSPOROCYTES 1 (EMS1) in forming the monolayer of tapetal nurse cells in Arabidopsis. Unusually for plants, tapetal cells are specified very early in development, and are subsequently stimulated to proliferate by a receptor-like kinase (RLK) complex that includes EMS1. Mutations in members of this EMS1 signalling complex and its putative ligand result in male-sterile plants in which tapetal initials fail to proliferate. Surprisingly, these cells continue to develop, isolated at the locular periphery. Mutant and wild-type microsporangia expand at similar rates and the 'tapetal' space at the periphery of mutant locules becomes occupied by microsporocytes. However, induction of late expression of EMS1 in the few tapetal initials in ems1 plants results in their proliferation to generate a functional tapetum, and this proliferation suppresses microsporocyte number. Our experiments also show that integrity of the tapetal monolayer is crucial for the maintenance of the polarity of divisions within it. This unexpected autonomy of the tapetal 'lineage' is discussed in the context of tissue development in complex plant organs, where constancy in size, shape and cell number is crucial.


Skewed distribution of irradiance predicted by the second-order Rytov approximation.
The first-order Rytov approximation predicts that the probability-density function for intensity fluctuations in a random medium should be a log normal distribution. Here the corrections to this prediction that arise from the second term in the Rytov series are explored. The primary effect is to skew the distribution so as to favor values that are less than the average. This effect is controlled by the Rytov variance beta0(2) alone, and the predicted distribution contains no adjustable parameters. The theoretical result is compared with numerical simulations for weak scattering of plane and spherical waves. The agreement is quite good unless the intensity fluctuations are very large or very small relative to the mean irradiance. In those ranges, the predictions require additional terms in the Rytov expansion.


Inhibition mechanism and hot-spot prediction of nine potential drugs for SARS-CoV-2 Mpro by large-scale molecular dynamic simulations combined with accurate binding free energy calculations.
Coronavirus disease 2019 (COVID-19), which is caused by a new coronavirus known as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is spreading around the world. However, a universally effective treatment regimen has not been developed to date. The main protease (Mpro), a key enzyme of SARS-CoV-2, plays a crucial role in the replication and transcription of this virus in cells and has become the ideal target for rational antiviral drug design. In this study, we performed molecular dynamics simulations three times for these complexes of Mpro (monomeric and dimeric) and nine potential drugs that have a certain effect on the treatment of COVID-19 to explore their binding mechanism. In addition, a total of 12 methods for calculating binding free energy were employed to determine the optimal drug. Ritonavir, Arbidol, and Chloroquine consistently showed an outstanding binding ability to monomeric Mpro under various methods. Ritonavir, Arbidol, and Saquinavir presented the best performance when binding to a dimer, which was independent of the protonated state of Hie41 (protonated at Nε) and Hid41 (protonated at Nδ), and these findings suggest that Chloroquine may not effectively inhibit the activity of dimeric Mproin vivo. Furthermore, three common hot-spot residues of Met165, Hie41, and Gln189 of monomeric Mpro systems dominated the binding of Ritonavir, Arbidol, and Chloroquine. In dimeric Mpro, Gln189, Met165, and Met49 contributed significantly to binding with Ritonavir, Arbidol, and Saquinavir; therefore, Gln189 and Met165 might serve as the focus in the discovery and development of anti-COVID-19 drugs. In addition, the van der Waals interaction played a significant role in the binding process, and the benzene ring of the drugs showed an apparent inhibitory effect on the normal function of Mpro. The binding cavity had great flexibility to accommodate these different drugs. The results would be notably helpful for enabling a detailed understanding of the binding mechanisms for these important drug-Mpro interactions and provide valuable guidance for the design of potent inhibitors.


Quantitative measurement of cAMP concentration using an exchange protein directly activated by a cAMP-based FRET-sensor.
Förster resonance energy transfer (FRET)-based biosensors for the quantitative analysis of intracellular signaling, including sensors for monitoring cyclic adenosine monophosphate (cAMP), are of increasing interest. The measurement of the donor/acceptor emission ratio in tandem biosensors excited at the donor excitation wavelength is a commonly used technique. A general problem, however, is that this ratio varies not only with the changes in cAMP concentration but also with the changes of the ionic environment or other factors affecting the folding probability of the fluorophores. Here, we use a spectral FRET analysis on the basis of two excitation wavelengths to obtain a reliable measure of the absolute cAMP concentrations with high temporal and spatial resolution by using an "exchange protein directly activated by cAMP". In this approach, FRET analysis is simplified and does not require additional calibration routines. The change in FRET efficiency (E) of the biosensor caused by [cAMP] changes was determined as DeltaE = 15%, whereas E varies between 35% at low and 20% at high [cAMP], allowing quantitative measurement of cAMP concentration in the range from 150 nM to 15 microM. The method described is also suitable for other FRET-based biosensors with a 1:1 donor/acceptor stoichiometry. As a proof of principle, we measured the specially resolved cAMP concentration within living cells and determined the dynamic changes of cAMP levels after stimulation of the Gs-coupled serotonin receptor subtype 7 (5-HT7).


Health Complaints Attributed to Dental Amalgam: A Retrospective Survey Exploring Perceived Health Changes Related to Amalgam Removal.
Many patients have complex health complaints they attribute to dental amalgam. There is some evidence of symptom relief after removal of amalgam. The aims of this study were to assess the total symptom load in patients with all their amalgam fillings removed, and to investigate the self-reported improvement of health with regard to precautions taken under amalgam removal and time since removal. The survey was distributed to all members (n=999) of the Norwegian Dental patients association in 2011. The study participants returned the questionnaires anonymously by means of a pre-stamped envelope. The questionnaire asked for sociodemographic data, subjectively perceived health status, complaints persisting after amalgam removal and self-reported changes in symptoms after amalgam removal. A total of 324 participants were included in the study. The majority of the participants reported improved health after amalgam removal, even though the mean degree of severity of complaints was still high. Exhaustion and musculoskeletal complaints were most severe, and reflects the fact that 38% of the participants reported poor to very poor current health. With regard to amalgam removal, associations between improved health, number of precautions applied, and time since removal were found. Most of the participants in this study reported improvement of health after amalgam removal even though they still suffered a high complaint load. Since absolute symptom load is a robust predictor for general health outcome and socioeconomic burden for society, a possible intervention, which enables patients to further improve their health status is desirable.


Surveillance and vaccine effectiveness of an influenza epidemic predominated by vaccine-mismatched influenza B/Yamagata-lineage viruses in Taiwan, 2011-12 season.
The 2011-12 trivalent influenza vaccine contains a strain of influenza B/Victoria-lineage viruses. Despite free provision of influenza vaccine among target populations, an epidemic predominated by influenza B/Yamagata-lineage viruses occurred during the 2011-12 season in Taiwan. We characterized this vaccine-mismatched epidemic and estimated influenza vaccine effectiveness (VE). Influenza activity was monitored through sentinel viral surveillance, emergency department (ED) and outpatient influenza-like illness (ILI) syndromic surveillance, and case-based surveillance of influenza with complications and deaths. VE against laboratory-confirmed influenza was evaluated through a case-control study on ILI patients enrolled into sentinel viral surveillance. Logistic regression was used to estimate VE adjusted for confounding factors. During July 2011-June 2012, influenza B accounted for 2,382 (72.5%) of 3,285 influenza-positive respiratory specimens. Of 329 influenza B viral isolates with antigen characterization, 287 (87.2%) were B/Yamagata-lineage viruses. Proportions of ED and outpatient visits being ILI-related increased from November 2011 to January 2012. Of 1,704 confirmed cases of influenza with complications, including 154 (9.0%) deaths, influenza B accounted for 1,034 (60.7%) of the confirmed cases and 103 (66.9%) of the deaths. Reporting rates of confirmed influenza with complications and deaths were 73.5 and 6.6 per 1,000,000, respectively, highest among those aged ≥65 years, 50-64 years, 3-6 years, and 0-2 years. Adjusted VE was -31% (95% CI: -80, 4) against all influenza, 54% (95% CI: 3, 78) against influenza A, and -66% (95% CI: -132, -18) against influenza B. This influenza epidemic in Taiwan was predominated by B/Yamagata-lineage viruses unprotected by the 2011-12 trivalent vaccine. The morbidity and mortality of this vaccine-mismatched epidemic warrants careful consideration of introducing a quadrivalent influenza vaccine that includes strains of both B lineages.


Geographic variation in cardiovascular procedure use among Medicare fee-for-service vs Medicare Advantage beneficiaries.
Little is known about how different financial incentives between Medicare Advantage and Medicare fee-for-service (FFS) reimbursement structures influence use of cardiovascular procedures. To compare regional cardiovascular procedure rates between Medicare Advantage and Medicare FFS beneficiaries. Cross-sectional study of Medicare beneficiaries older than 65 years between 2003-2007 comparing rates of coronary angiography, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) surgery across 32 hospital referral regions in 12 states. Rates of coronary angiography, PCI, and CABG surgery. We evaluated a total of 878,339 Medicare Advantage patients and 5,013,650 Medicare FFS patients. Compared with Medicare FFS patients, Medicare Advantage patients had lower age-, sex-, race-, and income-adjusted procedure rates per 1000 person-years for angiography (16.5 [95% CI, 14.8-18.2] vs 25.9 [95% CI, 24.0-27.9]; P < .001) and PCI (6.8 [95% CI, 6.0-7.6] vs 9.8 [95% CI, 9.0-10.6]; P < .001) but similar rates for CABG surgery (3.1 [95% CI, 2.8-3.5] vs 3.4 [95% CI, 3.1-3.7]; P = .33). There were no significant differences between Medicare Advantage and Medicare FFS patients in the rates per 1000 person-years of urgent angiography (3.9 [95% CI, 3.6-4.2] vs 4.3 [95% CI, 4.0-4.6]; P = .24) or PCI (2.4 [95% CI, 2.2-2.7] vs 2.7 [95% CI, 2.5-2.9]; P = .16). Procedure rates varied widely across hospital referral regions among Medicare Advantage and Medicare FFS patients. For angiography, the rates per 1000 person-years ranged from 9.8 to 40.6 for Medicare Advantage beneficiaries and from 15.7 to 44.3 for Medicare FFS beneficiaries. For PCI, the rates ranged from 3.5 to 16.8 for Medicare Advantage and from 4.7 to 16.1 for Medicare FFS. The rates for CABG surgery ranged from 1.5 to 6.1 for Medicare Advantage and from 2.5 to 6.0 for Medicare FFS. Across regions, we found no statistically significant correlation between Medicare Advantage and Medicare FFS beneficiary utilization for angiography (Spearman r = 0.19, P = .29) and modest correlations for PCI (Spearman r = 0.33, P = .06) and CABG surgery (Spearman r = 0.35, P = .05). Among Medicare Advantage beneficiaries, adjustment for additional cardiac risk factors had little influence on procedure rates. Although Medicare beneficiaries enrolled in capitated Medicare Advantage programs had lower angiography and PCI procedure rates than those enrolled in Medicare FFS, the degree of geographic variation in procedure rates was substantial among Medicare Advantage beneficiaries and was similar in magnitude to that observed among Medicare FFS beneficiaries.


Assessment of causal link between psychological factors and symptom exacerbation in inflammatory bowel disease: a protocol for systematic review of prospective cohort studies.
Inflammatory bowel disease is an idiopathic chronic disease that affects around 28 million people worldwide. Symptoms are distressing and have a detrimental effect on patients' quality of life. A possible link between exacerbation of symptoms and psychological factors has been suspected but not established. Previous reviews concerned with this link had conceptual and methodological limitations. In this paper we set out a protocol that lays the foundations for a systematic review that will address these shortcomings. The aim of this review is to provide researchers and clinicians with clarity on the role of psychological factors in inflammatory bowel disease symptom exacerbation. We will identify all original, published, peer reviewed studies relevant to the topic and published in English from inception to November 2012. The databases MEDLINE, EMBASE, CINAHL and PsychINFO will be systematically searched. The search terms will include: inflammatory bowel disease, Crohn's disease, ulcerative colitis, psychological stress, mental stress, life stress, family stress, hassles, social stress, coping, mood disorders, anxiety and depression in sequential combinations.Studies will be screened according to predetermined inclusion and exclusion criteria by two reviewers. We will include clinical prospective cohort studies of all human participants aged 18 years or over with a diagnosis of inflammatory bowel disease. All eligible papers will be independently and critically appraised using the Critical Appraisal Skills Programme (CASP) tool by two reviewers. Two reviewers will independently extract and synthesise data from the studies using a predefined data extraction sheet. Disagreements will be resolved by discussion between reviewers and a third party will be consulted if agreement is not reached. Synthesised data will be analysed using Bradford Hill criterion for causality. If data permits, meta-analysis will be performed. This study will provide the most comprehensive review and synthesis of current evidence around the link between psychological factors and symptom exacerbation in inflammatory bowel disease. Results will inform clinicians in appropriate intervention development for this patient group that would reduce symptom exacerbation and therefore improve patients' quality of life.


Impingement-Free Hip Flexion in Asymptomatic Young Adult Women.
Ultrasound-assisted measurement of hip flexion has demonstrated that hip flexion has been historically overestimated in men. To our knowledge, assessment of hip flexion in women using similar methods has not been reported. Establishing normative values for hip flexion is vital to aid diagnosis, management, and future research. Therefore, we asked 2 questions: (1) At what range of midsagittal hip flexion do soft-tissue impingement and femoroacetabular abutment occur in asymptomatic young adult women? (2) Do radiographic findings on a supine anteroposterior pelvic radiograph correlate with ultrasound-assisted measurements of hip flexion? Fifty-five asymptomatic adult women volunteers (107 hips) underwent ultrasound-assisted assessment of hip flexion. Hip flexion was recorded at the initiation of labral contact and at bone-on-bone contact. Recorded motion was correlated with common radiographic measurements of hip morphology as observed on a supine anteroposterior pelvic radiograph. The mean age of the subjects was 26 ± 3 years (range, 21 to 35 years), and the mean body mass index was 23 ± 3 kg/m (range, 17 to 31.6 kg/m). Mean impingement-free and maximum midsagittal passive flexion were 72° ± 8° (95% confidence interval [CI], 70° to 74°) and 101° ± 11° (95% CI, 99° to 103°), respectively. There were no significant correlations between radiographic measurements of hip morphology and ultrasound-measured hip range of motion. Observed hip flexion in the asymptomatic hips of young women is substantially less than has been historically reported. Morphologic features that are measurable on anteroposterior pelvic radiographs do not correlate with ultrasound-measured hip flexion. Diagnosis of hip disorders and treatments that are designed to alter hip range of motion should be based on normative data. Future studies regarding surgical restoration and/or preservation of hip flexion should be based on an understanding of normal hip range of motion. Ultrasound-assisted hip flexion measurement established normative values to guide surgical restoration and/or preservation of hip flexion.


Induced Pluripotent Stem Cells for Inherited Optic Neuropathies-Disease Modeling and Therapeutic Development.
Inherited optic neuropathies (IONs) cause progressive irreversible visual loss in children and young adults. There are limited disease-modifying treatments, and most patients progress to become severely visually impaired, fulfilling the legal criteria for blind registration. The seminal discovery of the technique for reprogramming somatic nondividing cells into induced pluripotent stem cells (iPSCs) has opened several exciting opportunities in the field of ION research and treatment. A systematic review of the literature was conducted with PubMed using the following search terms: autosomal dominant optic atrophy, ADOA, dominant optic atrophy, DOA, Leber hereditary optic neuropathy, LHON, optic atrophy, induced pluripotent stem cell, iPSC, iPSC derived, iPS, stem cell, retinal ganglion cell, and RGC. Clinical trials were identified on the ClinicalTrials.gov website. This review article is focused on disease modeling and the therapeutic strategies being explored with iPSC technologies for the 2 most common IONs, namely, dominant optic atrophy and Leber hereditary optic neuropathy. The rationale and translational advances for cell-based and gene-based therapies are explored, as well as opportunities for neuroprotection and drug screening. iPSCs offer an elegant, patient-focused solution to the investigation of the genetic defects and disease mechanisms underpinning IONs. Furthermore, this group of disorders is uniquely amenable to both the disease modeling capability and the therapeutic potential that iPSCs offer. This fast-moving area will remain at the forefront of both basic and translational ION research in the coming years, with the potential to accelerate the development of effective therapies for patients affected with these blinding diseases.


Uric acid and left ventricular hypertrophy in Japanese men.
Experimental studies have reported that allopurinol protects hypertensive rats from left ventricular hypertrophy (LVH) with negligible effects on blood pressure (BP). Uric acid (UA) was thought to induce cardiomyocyte growth and interstitial fibrosis of the heart, partly via activation of the renin-angiotensin system. In the present study, the relationship between serum UA levels and electrocardiographically-diagnosed LVH (ECG-LVH) was examined in Japanese men not taking medication for hypertension (HTN), which could confound the association. A total of 3,305 male workers aged 35-66 years (mean age+/-SD, 48.0+/-7.1) were studied. LVH was defined as meeting the ECG criteria (ie, Sokolow-Lyon voltage and/or Cornell voltage QRS duration product). Subjects were divided into 3 groups by tertile of serum UA level. The highest tertile (UA range 0.39-0.65 mmol/L or 6.6-11.0 mg/dl) had a significantly increased prevalence of LVH compared with the lowest tertile independent of age, body mass index, serum creatinine level, HTN, diabetes and hyperlipidemia (odds ratio 1.58, 95% confidence interval 1.23-2.02, P<0.001). Similar results were obtained in both the normal and high BP subgroups. UA concentration independently and positively associated with ECG-LVH in Japanese men.


Fibromyalgia: mechanisms, current treatment and animal models.
Fibromyalgia syndrome (FMS) is a chronic pain syndrome characterized by diffuse musculoskeletal pain. In quantitative sensory testing studies, FMS patients display alterations in heat, cold, and mechanical sensitivity. Genetic studies support a key role for the biogenic amine system, and single nucleotide polymorphisms have been identified in serotonin and dopamine transporter and receptor genes of FMS patients. The pathophysiology of fibromyalgia includes contributions from both the ascending and descending somatosensory systems, and decreased central nervous system inhibition of peripheral nociceptive signalling. Three drugs have been approved for the treatment of FMS: Lyrica® (pregablin), Cymbalta® (duloxetine), and Savella® (milnacipran). These drugs were originally developed for indications other than FMS, and were later approved for FMS after successful clinical trials. One hurdle in the development of drugs specifically for FMS is the availability of preclinical animal models of the disease. Recently, several rodent models have been described with potential for translation to the human pain syndrome. In this review, we discuss recent developments toward understanding the pathophysiology of FMS, currently available pharmacologic therapy, ongoing clinical trials, and potential animal models of FMS.


Crl stimulates RpoS activity during stationary phase.
RpoS, an alternative primary sigma factor, has been shown to be regulated at multiple levels, including transcription, translation and protein stability. Here, we present evidence that suggests that RpoS is regulated at yet another level by the product of the crl gene. The crl gene was first thought to encode the major curlin subunit of curli (curli are surface structures that are induced by growth into stationary phase under conditions of low osmolarity and low temperature). Later, it was determined that crl actually contributes in a positive fashion to stimulate transcription of csgBA, the true locus encoding for the major subunit of curli. RpoS is also required for normal stationary-phase induction of csgBA. We found that lesions in crl, like lesions in rpoS, cause increased transcription of ompF during stationary phase. Taken together, these observations prompted us to analyse the effects of crl on an additional RpoS-regulated phenomenon. We found that a crl null allele influences expression of RpoS-regulated genes in a fashion similar to an rpoS null allele. Genetic evidence suggests that crl and rpoS function in a single pathway and that Crl functions upstream, or in concert with, RpoS. Although the effects of Crl on RpoS-regulated genes is entirely dependent on the integrity of RpoS, the presence of a crl null allele does not decrease the level of RpoS protein. Thus, we propose that Crl stimulates the activity of the RpoS regulon by stimulating RpoS activity during stationary phase.


Interleukin-1 receptor-associated kinase 2 is critical for lipopolysaccharide-mediated post-transcriptional control.
IRAK2, a member of the interleukin-1 receptor-associated kinase (IRAK) family, has been implicated in Toll-like receptor (TLR)-mediated signaling. We generated IRAK2-deficient mice to examine its function in detail. These mice are resistant to lipopolysaccharide-induced septic shock, because of impaired TLR4-mediated induction of pro-inflammatory cytokines and chemokines. Although IRAK2 deficiency did not affect TLR4-mediated NFkappaB activation, a reduction of lipopolysaccharide (LPS)-mediated mRNA stabilization contributed to the reduced cytokine and chemokine production observed in bone marrow-derived macrophages from IRAK2-deficient mice. Furthermore, the ratios of LPS-induced cytokine and chemokine mRNAs in translation-active (polysomal) versus translation-inactive (free ribosomes) pools were reduced in IRAK2-deficient macrophages compared with wild type macrophages. Importantly, LPS-induced phosphorylation of MKK3/6, MNK1, and eIF4E was significantly reduced in IRAK2-deficient macrophages compared with wild type macrophages. Moreover, LPS stimulation induced an interaction of IRAK2 with TRAF6, MKK3/6, and MK2, implicating a critical role for mitogen-activated protein kinase signaling in LPS-induced IRAK2-mediated post-transcriptional control. These results reveal that IRAK2 is required for LPS-mediated post-transcriptional control of cytokine and chemokine expression, which plays an essential role in TLR4-induced septic shock.


Cal MediConnect Enrollment: Why Are Dual-Eligible Consumers in Los Angeles County Opting Out?
Los Angeles County has the state's lowest rate of consumer enrollment in Cal MediConnect, a program that is responsible for the delivery and coordination of medical, behavioral health, and long-term services and support benefits for individuals who are dually eligible for Medicare and Medi-Cal. This policy brief examines the factors that influence consumer decisions and may contribute to low enrollment rates. Influential factors include consumer knowledge of health care options, perception of choice, and disruption of existing care. Differences in decision making by age, complexity of health care needs, race/ethnicity, immigration status, and primary language are also noted. Policy recommendations include engaging consumers in the planning and dissemination of information about their health care options, optimizing consumer choice and implementing the least disruptive pathway to enrollment, and recognizing and responding to the great diversity of dual-eligible consumers in Los Angeles County.


Going beyond the Millennium Ecosystem Assessment: an index system of human well-being.
Understanding the linkages between ecosystem services (ES) and human well-being (HWB) is crucial to sustain the flow of ES for HWB. The Millennium Ecosystem Assessment (MA) provided a state-of-the-art synthesis of such knowledge. However, due to the complexity of the linkages between ES and HWB, there are still many knowledge gaps, and in particular a lack of quantitative indicators and integrated models based on the MA framework. To fill some of these research needs, we developed a quantitative index system to measure HWB, and assessed the impacts of an external driver--the 2008 Wenchuan Earthquake--on HWB. Our results suggest that our proposed index system of HWB is well-designed, valid and could be useful for better understanding the linkages between ES and HWB. The earthquake significantly affected households' well-being in our demonstration sites. Such impacts differed across space and across the five dimensions of the sub-index (i.e., the basic material for good life, security, health, good social relations, and freedom of choice and action). Since the conceptual framework is based on the generalizable MA framework, our methods should also be applicable to other study areas.


Mechanism of opioid-induced pupillary effects.
This study tested the hypothesis that increased activity in the pupilloconstrictor nucleus by the addition of ambient light and by the administration of fentanyl, sufficient to block pupillary reflex dilation, constricts the pupil of anesthetized patients. Pupil diameter was measured in 10 anesthetized patients during noxious stimulation above an epidural block level, in darkness and then with light directed into the left eye. Two measurements were taken from the right eye separated by 5 min. Following the second measurement, fentanyl (1 mcg/kg) was administered and the measures in light and dark were repeated. The effect of light and fentanyl on pupil size and pupillary reflex dilation were analyzed. An increase in light directed into the left eye constricted the pupil from 2.15+/-0.38 to 1.87+/-0.40 mm before fentanyl. Fentanyl did not constrict the pupil either in darkness or light but it did decrease pupillary reflex dilation by 49%. The miotic pupil during general anesthesia is not maximally constricted. Increased excitation of the pupilloconstrictor nucleus does not account for blockade of pupillary reflex dilation after fentanyl administration during desflurane anesthesia. This study does not support the hypothesis that opioid effects on the human pupil are brought about by a direct excitatory action on the pupilloconstrictor nucleus.


Hyperandrogenemia reduces endothelium-derived hyperpolarizing factor-mediated relaxation in mesenteric artery of female rats.
Women with polycystic ovary syndrome (PCOS) are often presented with hyperandrogenemia along with vascular dysfunction and elevated blood pressure. In animal models of PCOS, anti-androgen treatment decreased blood pressure, indicating a key role for androgens in the development of hypertension. However, the underlying androgen-mediated mechanism that contributes to increased blood pressure is not known. This study determined whether elevated androgens affect endothelium-derived hyperpolarizing factor (EDHF)-mediated vascular relaxation responses through alteration in function of gap junctional proteins. Female rats were implanted with placebo or dihydrotestosterone (DHT) pellets (7.5 mg, 90-day release). After 12 weeks of DHT exposure, blood pressure was assessed through carotid arterial catheter and endothelium-dependent mesenteric arterial EDHF relaxation using wire myograph. Connexin expression in mesenteric arteries was also examined. Elevated DHT significantly increased mean arterial pressure and decreased endothelium-dependent EDHF-mediated acetylcholine relaxation. Inhibition of Cx40 did not have any effect, while inhibition of Cx37 decreased EDHF relaxation to a similar magnitude in both controls and DHT females. On the other hand, inhibition of Cx43 significantly attenuated EDHF relaxation in mesenteric arteries of controls but not DHT females. Elevated DHT did not alter Cx37 or Cx40, but decreased Cx43 mRNA and protein levels in mesenteric arteries. In vitro exposure of DHT to cultured mesenteric artery smooth muscle cells dose-dependently downregulated Cx43 expression. In conclusion, increased blood pressure in hyperandrogenic females is due, at least in part, to decreased EDHF-mediated vascular relaxation responses. Decreased Cx43 expression and activity may play a role in contributing to androgen-induced decrease in EDHF function.


Genetic Variants Involved in Bipolar Disorder, a Rough Road Ahead.
Bipolar Disorder (BD), along with depression and schizophrenia, is one of the most serious mental illnesses, and one of the top 20 causes of severe impairment in everyday life. Recent molecular studies, using both traditional approaches and new procedures such as Whole-Genome Sequencing (WGS), have suggested that genetic factors could significantly contribute to the development of BD, with heritability estimates of up to 85%. However, it is assumed that BD is a multigenic and multifactorial illness with environmental factors that strongly contribute to disease development/progression, which means that progress in genetic knowledge of BD might be difficult to interpret in clinical practice. The aim of this study is to provide a synthetic description of the main SNPs variants identified/confirmed by recent extensive WGS analysis as well as by reconstruction in an in vitro mechanism or by amygdala activation protocol in vivo. Bibliographic data, genomic and protein Data Banks were consulted so as to carry out a cross genomic study for mutations, SNPs and chromosomal alterations described in these studies in BD patients. Fifty-five different mutations have been described in 30 research papers by different genetic analyses including recent WGS analysis. Many of these studies have led to the discovery of the most probable susceptibility genes for BD, including ANK3, CACNA1C, NCAN, ODZ4, SYNE1, and TRANK1. Exploration has started the role of several of these mutations in BD pathophysiology using in vitro and animal models. Although new genomic research technology in BD opens up new possibilities, the current results for common variants are still controversial because of four broad conditions: analytical validity, clinical validity, clinical utility and a reasonable cost for genetic analysis are not yet accessible.


Immune mobilising T cell receptors redirect polyclonal CD8+ T cells in chronic HIV infection to form immunological synapses.
T cell exhaustion develops in human immunodeficiency virus (HIV) infection due to chronic viral antigenic stimulation. This adaptive response primarily affects virus-specific CD8+ T cells, which may remain dysfunctional despite viral load-reducing antiretroviral therapy; however, abnormalities may also be evident in non-HIV-specific populations. Both could limit the efficacy of cell therapies against viral reservoirs. Here, we show that bulk (polyclonal) CD8+ T cells from people living with HIV (PLWH) express proposed markers of dysfunctional HIV-specific T cells at high levels yet form lytic immunological synapses (IS) and eliminate primary resting infected (HIV Gaglo) CD4+ T cells, when redirected by potent bispecific T cell-retargeting molecules, Immune mobilising monoclonal T cell receptors (TCR) Against Virus (ImmTAV). While PLWH CD8+ T cells are functionally impaired when compared to CD8+ T cells from HIV-naïve donors, ImmTAV redirection enables them to eliminate Gaglo CD4+ T cells that are insensitive to autologous HIV-specific cytolytic T cells. ImmTAV molecules may therefore be able to target HIV reservoirs, which represent a major barrier to a cure.


Beyond structural insight: a deep neural network for the prediction of Pt L2/3-edge X-ray absorption spectra.
X-ray absorption spectroscopy at the L2/3 edge can be used to obtain detailed information about the local electronic and geometric structure of transition metal complexes. By virtue of the dipole selection rules, the transition metal L2/3 edge usually exhibits two distinct spectral regions: (i) the "white line", which is dominated by bound electronic transitions from metal-centred 2p orbitals into unoccupied orbitals with d character; the intensity and shape of this band consequently reflects the d density of states (d-DOS), which is strongly modulated by mixing with ligand orbitals involved in chemical bonding, and (ii) the post-edge, where oscillations encode the local geometric structure around the X-ray absorption site. In this Article, we extend our recently-developed XANESNET deep neural network (DNN) beyond the K-edge to predict X-ray absorption spectra at the Pt L2/3 edge. We demonstrate that XANESNET is able to predict Pt L2/3 -edge X-ray absorption spectra, including both the parts containing electronic and geometric structural information. The performance of our DNN in practical situations is demonstrated by application to two Pt complexes, and by simulating the transient spectrum of a photoexcited dimeric Pt complex. Our discussion includes an analysis of the feature importance in our DNN which demonstrates the role of key features and assists with interpreting the performance of the network.


The association between birthweight and current blood pressure: a cross-sectional study in an Australian Aboriginal community.
To study the relationship of blood pressure to birthweight and current body mass index in a population with high rates of low birthweight (< 2.5 kg). A cross-sectional population screening program conducted between 1992 and 1998, with retrospective retrieval of birthweights. A remote coastal Australian Aboriginal community with a high prevalence of diabetes, cardiovascular and renal disease. Eighty-two per cent of the community members (1473/1805) were screened. Birthweights were available for 767 (71%) of the screened participants aged 7-43 years. The association between birthweight and current blood pressure, accounting for current body mass index. Mean birthweights were low, and 18% of children and 35% of adults had been low-birthweight babies. In children (7-17 years), blood pressure was not correlated with birthweight, but in adults there was an inverse correlation - a 1 kg increase in birthweight was associated with a 2.9 mmHg (95% CI, 0.3-5.5 mmHg) decrease in systolic blood pressure, after adjusting for age, sex and current weight. Overweight adults with low birthweight had the highest blood pressures. Low birthweight is significantly associated with higher blood pressure in adult life, and the effect is amplified by higher current weight. Given the high rates of low birthweight in Aboriginal people in remote areas, and the detrimental effect of higher blood pressures on chronic diseases (currently present in epidemic proportions), interventions should focus on improving birthweights and on weight control in adolescents and adults. Special attention should be paid to children with low birthweight to avoid their becoming overweight in adult life.


A single dose of ChAdOx1 Chik vaccine induces neutralizing antibodies against four chikungunya virus lineages in a phase 1 clinical trial.
Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18-50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and T-cell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT50 seroconversion after a single dose.


A non-invasive biomarker of type III collagen degradation reflects ischaemia reperfusion injury in rats.
Maintenance of kidney function in kidney allografts remains a challenge, as the allograft often progressively develops fibrosis after kidney transplantation. Fibrosis is caused by the accumulation of extracellular matrix proteins like type I and III collagen (COL I and III) that replace the functional tissue. We assessed the concentrations of a neo-epitope fragment of COL III generated by matrix metalloproteinase-9 cleavage (C3M) in two rat models resembling the ischaemic injury taking place following kidney transplantation. We measured C3M in urine (U-C3M) and plasma (P-C3M) samples of rats subjected to unilateral nephrectomy followed by sham operation (NTx) or ischaemia reperfusion injury (NTxIRI) as well as in rats subjected to bilateral ischaemia reperfusion injury (BiIRI). Levels of U-C3M were normalized to urinary creatinine and were correlated to plasma creatinine, blood urea nitrogen, messenger ribonucleic acid (mRNA) of markers of kidney injury, and mRNA and protein levels of markers of tissue repair and fibrosis. Levels of U-C3M were significantly elevated 7 days after ischaemia reperfusion in the NTxIRI. BiIRI animals showed higher levels of U-C3M after 7 and 14 days of reperfusion but not at 21 days. P-C3M did not change in any of the models. There was a significant correlation between U-C3M and mRNA levels of fibronectin, COL I alpha 1 chain (COL Ia1) and neutrophil gelatinase-associated lipocalin (NGAL), and protein levels of alpha smooth muscle actin (αSMA), fibronectin and COL III in NTxIRI but not in NTx animals. Levels of U-C3M increased significantly in the BiIRI animals subsequent to reperfusion, and mirrored the histological alterations. Furthermore, U-C3M was associated with the extent of fibrosis, and remained elevated even after plasma creatinine levels decreased. These results demonstrate that degradation of COL III increases after ischaemia reperfusion injury, and that U-C3M may be a non-invasive marker of tissue repair and fibrosis in the ischaemic kidney.


Dysregulated cytokine production by dendritic cells modulates B cell responses in the NZM2410 mouse model of lupus.
The breakdown in tolerance of autoreactive B cells in the lupus-prone NZM2410-derived B6.Sle1.Sle2.Sle3 (TC) mice results in the secretion of autoantibodies. TC dendritic cells (DCs) enhance B cell proliferation and antibody secretion in a cytokine-dependent manner. However, the specific cytokine milieu by which TC DCs activate B cells was not known. In this study, we compared TC and C57BL/6 (B6) control for the distribution of DC subsets and for their production of cytokines affecting B cell responses. We show that TC DCs enhanced B cell proliferation through the production of IL-6 and IFN-γ, while antibody secretion was only dependent on IL-6. Pre-disease TC mice showed an expanded PDCA1(+) cells prior to disease onset that was localized to the marginal zone and further expanded with age. The presence of PDCA1(+) cells in the marginal zone correlated with a Type I Interferon (IFN) signature in marginal zone B cells, and this response was higher in TC than B6 mice. In vivo administration of anti-chromatin immune complexes upregulated IL-6 and IFN-γ production by splenic DCs from TC but not B6 mice. The production of BAFF and APRIL was decreased upon TC DC stimulation both in vitro and in vivo, indicating that these B cell survival factors do not play a role in B cell modulation by TC DCs. Finally, TC B cells were defective at downregulating IL-6 expression in response to anti-inflammatory apoptotic cell exposure. Overall, these results show that the TC autoimmune genetic background induces the production of B cell-modulating inflammatory cytokines by DCs, which are regulated by the microenvironment as well as the interplay between DC.


The BVM Effect. An overview of studies assessing airway management in out-of-hospital cardiac arrest.
Numerous studies addressing airway management in OHCA have shown a strong association between improved survival with treatment using BVM alone rather than with advanced airways. This BVM effect appears to persist despite variations in geographical region, patient population, and CPR quality. The underlying cause of this phenomenon remains to be determined. Of note, the survival benefit with BVM alone vs. advanced airways doesn't appear in the pediatric population in the papers reviewed by the authors. The authors recommend that a prospective randomized study be conducted in order to explore this finding and to attempt to determine its causation.


Optical coherence tomography shows progressive local nerve fiber loss after disc hemorrhages in glaucoma patients.
The aim of this work is to investigate whether optic disc hemorrhages (ODH) lead to significant loss of nerve fibers at the lesion site over time and whether such a loss is reflected by visual field defects corresponding to the affected nerve fiber bundle. In this retrospective study of ten sequential glaucoma patients (ten eyes) with ODH, we used high-resolution OCT circular scans (Spectralis HRA + OCT, Heidelberg Engineering, Heidelberg, Germany) to determine peripapillary retinal nerve fiber layer (RNFL) thickness at the time of ODH presentation and at follow-up visit between 3 and 6 months. Corresponding perimetric data were analyzed for global (mean defect, MD) and localized progression of visual field defects. ODH were mostly located in the inferior quadrant as determined clinically and from fundus photographs. Iterative OCT imaging revealed a significant RNFL reduction in the affected quadrant relative to the respective quadrant in the fellow eye (RNFL change = -2.25 ± 2.69 μm vs. 0.75 ± 2.78 μm, p = 0.01) within 120 ± 43 days. However, only three cases presented with new/progressive nerve fiber bundle defects corresponding to the lesion site within the given follow-up period. ODH lead to a significantly higher RNFL loss at the lesion site relative to the overall structural progression in glaucoma patients. However, this focal change is not generally reflected by respective nerve fiber bundle defects in the time frame investigated.


Non-suicidal self-injury among first-year college students and its association with mental disorders: results from the World Mental Health International College Student (WMH-ICS) initiative.
Although non-suicidal self-injury (NSSI) is an issue of major concern to colleges worldwide, we lack detailed information about the epidemiology of NSSI among college students. The objectives of this study were to present the first cross-national data on the prevalence of NSSI and NSSI disorder among first-year college students and its association with mental disorders. Data come from a survey of the entering class in 24 colleges across nine countries participating in the World Mental Health International College Student (WMH-ICS) initiative assessed in web-based self-report surveys (20 842 first-year students). Using retrospective age-of-onset reports, we investigated time-ordered associations between NSSI and Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-IV) mood (major depressive and bipolar disorder), anxiety (generalized anxiety and panic disorder), and substance use disorders (alcohol and drug use disorder). NSSI lifetime and 12-month prevalence were 17.7% and 8.4%. A positive screen of 12-month DSM-5 NSSI disorder was 2.3%. Of those with lifetime NSSI, 59.6% met the criteria for at least one mental disorder. Temporally primary lifetime mental disorders predicted subsequent onset of NSSI [median odds ratio (OR) 2.4], but these primary lifetime disorders did not consistently predict 12-month NSSI among respondents with lifetime NSSI. Conversely, even after controlling for pre-existing mental disorders, NSSI consistently predicted later onset of mental disorders (median OR 1.8) as well as 12-month persistence of mental disorders among students with a generalized anxiety disorder (OR 1.6) and bipolar disorder (OR 4.6). NSSI is common among first-year college students and is a behavioral marker of various common mental disorders.


D-dimer is not elevated in asymptomatic high altitude climbers after descent to 5340 m: the Mount Everest Deep Venous Thrombosis Study (Ev-DVT).
We performed this study to determine the prevalence of elevated D-dimer, a marker for deep venous thrombosis (DVT), in asymptomatic high altitude climbers. On-site personnel enrolled a convenience sample of climbers at Mt. Everest Base Camp (Nepal), elevation 5340 m (17,500 ft), during a single spring climbing season. Subjects were enrolled after descent to base camp from higher elevation. The subjects completed a questionnaire to evaluate their risk factors for DVT. We then performed a D-dimer test in asymptomatic individuals. If the D-dimer test was negative, DVT was considered ruled out. Ultrasound was available to perform lower-extremity compression ultrasounds to evaluate for DVT in case the D-dimer was positive. We enrolled 76 high altitude climbers. None had a positive D-dimer test. The absence of positive D-dimer tests suggests a low prevalence of DVT in asymptomatic high altitude climbers.


A General Strategy for Fabricating Isolated Single Metal Atomic Site Catalysts in Y Zeolite.
Exploring high-performance zeolite-supported metal catalysts is of great significance. Herein, we develop a strategy for fabricating isolated single metal atomic site catalysts in Y zeolite (M-ISAS@Y, M = Pt, Pd, Ru, Rh, Co, Ni, Cu) by in situ separating and confining a metal-ethanediamine complex into β-cages during the crystallization process followed by thermal treatment. The M-ISAS are stabilized by skeletal oxygens of Y zeolite, and the crystallinity, porosity, and large surface area are well inherited in M-ISAS@Y. As a demonstration, acidic Pt-ISAS@Y is used for n-hexane isomerization involving consecutive catalytic dehydrogenation/hydrogenation on Pt-ISAS and isomerization on Brønsted acid sites. The turnover frequency value of Pt-ISAS reaches 727 h-1, 5 times more than Pt nanoparticles (∼3.5 nm), with a total isomer selectivity of more than 98%. This strategy provides a convenient route to fabricate promising zeolite-based M-ISAS catalysts for industrial applications.


Interrogation technique for TFBG-SPR refractometers based on differential orthogonal light states.
The generation of near-IR surface plasmon resonance in gold-coated tilted fiber Bragg gratings is strongly dependent on both the polarization state of the transmission light and the property of confining materials (including the coating materials and surrounding media). These dependencies can be advantageously used to demodulate the amplitude spectrum and retrieve the surrounding refractive index. In this paper, we present an automated demodulation technique that measures the surrounding refractive index by comparing the differential amplitude of resonance peaks near the plasmon attenuation for two orthogonal amplitude spectra recorded in the same operating conditions. A mean sensitivity of more than 500 nm per refractive index unit is reported. This new refractive index measurement method is shown to be accurate to 5×10(-5) over a full range of 0.01 in water solutions.


Saccade kinematics modulate perisaccadic perception.
Around the time of execution of an eye movement, participants systematically misperceive the spatial location of briefly flashed visual stimuli. This phenomenon, known as perisaccadic mislocalization, is thought to involve an active process that takes into account the motor plan (efference copy) of the upcoming saccade. While it has been proposed that the motor system anticipates and informs the visual system about the upcoming eye movements, at present the type and detail of information carried by this motor signal remains unclear. Some authors have argued that the efference copy conveys only coarse information about the direction of the eye movement, while a second theoretical view proposes that it provides specific details about the direction, amplitude, and velocity of the saccade to come. To test between these alternatives, we investigated the influence of saccade parameters on a perisaccadic unmasking task in which performance in discriminating the identity of a target (face or house) followed by a trailing mask is dramatically improved around the time of saccade onset. We found that the amplitude and peak velocity of the upcoming saccade modulated target perception, even for stimuli presented well before saccadic onset. We developed a predictive model for the generation of the efference copy that incorporates both saccade amplitude and saccade velocity planning prior to saccade execution. Overall, these results suggest that the efference copy stores specific information about the parameters of upcoming eye movement and that these parameters influence perception even prior to saccade onset.


The evolutionary history of holometabolous insects inferred from transcriptome-based phylogeny and comprehensive morphological data.
Despite considerable progress in systematics, a comprehensive scenario of the evolution of phenotypic characters in the mega-diverse Holometabola based on a solid phylogenetic hypothesis was still missing. We addressed this issue by de novo sequencing transcriptome libraries of representatives of all orders of holometabolan insects (13 species in total) and by using a previously published extensive morphological dataset. We tested competing phylogenetic hypotheses by analyzing various specifically designed sets of amino acid sequence data, using maximum likelihood (ML) based tree inference and Four-cluster Likelihood Mapping (FcLM). By maximum parsimony-based mapping of the morphological data on the phylogenetic relationships we traced evolutionary transformations at the phenotypic level and reconstructed the groundplan of Holometabola and of selected subgroups. In our analysis of the amino acid sequence data of 1,343 single-copy orthologous genes, Hymenoptera are placed as sister group to all remaining holometabolan orders, i.e., to a clade Aparaglossata, comprising two monophyletic subunits Mecopterida (Amphiesmenoptera + Antliophora) and Neuropteroidea (Neuropterida + Coleopterida). The monophyly of Coleopterida (Coleoptera and Strepsiptera) remains ambiguous in the analyses of the transcriptome data, but appears likely based on the morphological data. Highly supported relationships within Neuropterida and Antliophora are Raphidioptera + (Neuroptera + monophyletic Megaloptera), and Diptera + (Siphonaptera + Mecoptera). ML tree inference and FcLM yielded largely congruent results. However, FcLM, which was applied here for the first time to large phylogenomic supermatrices, displayed additional signal in the datasets that was not identified in the ML trees. Our phylogenetic results imply that an orthognathous larva belongs to the groundplan of Holometabola, with compound eyes and well-developed thoracic legs, externally feeding on plants or fungi. Ancestral larvae of Aparaglossata were prognathous, equipped with single larval eyes (stemmata), and possibly agile and predacious. Ancestral holometabolan adults likely resembled in their morphology the groundplan of adult neopteran insects. Within Aparaglossata, the adult's flight apparatus and ovipositor underwent strong modifications. We show that the combination of well-resolved phylogenies obtained by phylogenomic analyses and well-documented extensive morphological datasets is an appropriate basis for reconstructing complex morphological transformations and for the inference of evolutionary histories.


Algal control and enhanced removal in drinking waters in Cairo, Egypt.
Algal blooms at the major water treatment plants in Egypt have been reported since 2006. While previous studies focused on algal types and their correlation with disinfection by-products, correlation between raw water quality and algal blooms were not explored. Therefore, a survey of Nile water quality parameters at a major water intake in the Greater Cairo Urban Region was conducted from December 2011 to November 2012. Bench-scale experiments were conducted to evaluate the effectiveness of the conventional chloride/alum treatment compared with combined Cl/permanganate pre-oxidation with Al and Fe coagulants during the outbreak period. Addition of permanganate (0.5 mg/L) significantly reduced the chlorine demand from 5.5 to 2.7 mg/L. The applied alum coagulant dose was slightly reduced while residual Al was reduced by 27% and the algal count by 50% in the final treated waters. Applying ferric chloride and ferric sulfate as coagulants to waters treated with the combined pre-oxidation procedure effectively reduced algal count by 60% and better the total organic carbon reduction and residual aluminum in the treated water. Multivariate statistical analysis was used to identify the relationship between water quality parameters and occurrence of algae and to explain the impact of coagulants on the final water quality.


Future expenditure risk of silent members: a statistical analysis.
Silent-members are members of a medical health plan who submit no claims for healthcare services in a benefit year despite 12 months of continuous-enrollment. This study was conducted to evaluate the future expenditure risk of commercial-insured members who avoid all medical care despite coverage. In order to determine if the silent-members were at greater risk, we compared them to members who received care in the anchor year (2009) but had low-expenditures. The low-expenditure members were assumed to represent persons without significant medical conditions and without care-avoidance behaviors. We examined the claims experience of a cohort of silent members in the 2 years after the silent year (2009) and compared it with the corresponding claims experience for a cohort of low-expenditure members from the same anchor year (2009). Members of commercial health plans (BCBS of Texas) were selected based on continuous-enrollment in 2009. Two sub-groups were identified based on annual claims expenditure: Care avoiders were members with 12 months continuous-enrollment and no medical claims, and are thus referred to as "silent members" in the insurance industry. Low-Expenditure members were those with 12 months continuous-enrollment and total PMPY (per member per year) annual medical claims expenditure in the lowest 10th percentile of members with claims experience. "Low-expenditure" members served as a comparison group to the "silent members", under the assumption that such claimants were using benefits for minor healthcare issues as needed. Key variables were enrollment and expenditures. Enrollment data identified demographics and continuous-enrollment. Medical claims data were used to calculate utilization and expenditures. All claims data were de-identified and no consent was required, as approved by the Institutional Review Board. No research involved human subjects. Multivariate logistic regression models were applied. Silent members who seek care in subsequent years have a greater probability of becoming high-expenditure claimants than those with low-expenditure experience. For silent members who subsequently seek treatment, the probability of becoming high-expenditure is significantly greater than low-expenditure members from the anchor year. The implications of future high costs for silent members who become claimants may support the need for additional research to address the risks of care avoidance behaviors.


Shape control in seed-mediated synthesis of non-elongated Cu nanoparticles and their optical properties.
Shape and surface chemistry control in copper nanoparticle synthesis is an important research area due to a wide range of developing applications of this material in catalysis, energy conversion, sensing and many others. In addition to being an inexpensive and abundant metal, copper is an attractive photocatalyst due to its optical properties in the visible range. Here, we report a facile, tunable and sustainable methodology for synthesizing Pd-seeded Cu nanoparticles with various shapes, including cubes, spheres, raspberry-like particles and cages stabilized with a bilayer of a cationic surfactant in aqueous media. The experimental and theoretical examination of the optical response in the series of synthesized nanoparticles revealed that the low-energy extinction peak is associated with electronic interband transitions in the metal, in contrast to a widely spread attribution of this peak to a plasmonic response in Cu nanoparticles.


Prophylactic oxytocin for the third stage of labour to prevent postpartum haemorrhage.
Active management of the third stage of labour reduces the risk of postpartum blood loss (postpartum haemorrhage (PPH)), and is defined as administration of a prophylactic uterotonic, early umbilical cord clamping and controlled cord traction to facilitate placental delivery. The choice of uterotonic varies across the globe and may have an impact on maternal outcomes. This is an update of a review first published in 2001 and last updated in 2013. To determine the effectiveness of prophylactic oxytocin to prevent PPH and other adverse maternal outcomes in the third stage of labour. For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, WHO International Clinical Trials Registry Platform (ICTRP) (6 March 2019) and reference lists of retrieved studies. Randomised, quasi- or cluster-randomised trials including women undergoing vaginal delivery who received prophylactic oxytocin during management of the third stage of labour. Primary outcomes were blood loss 500 mL or more after delivery, need for additional uterotonics, and maternal all-cause mortality. Two review authors independently assessed trials for inclusion, extracted data, and assessed trial quality. Data were checked for accuracy. We assessed the quality of the evidence using the GRADE approach. This review includes 24 trials, with 23 trials involving 10,018 women contributing data. Due to many trials assessed at high risk of bias, evidence grade ranged from very low to moderate quality.Prophylactic oxytocin versus no uterotonics or placebo (nine trials)Prophylactic oxytocin compared with no uterotonics or placebo may reduce the risk of blood loss of 500 mL after delivery (average risk ratio (RR) 0.51, 95% confidence interval (C) 0.37 to 0.72; 4162 women; 6 studies; Tau² = 0.10, I² = 75%; low-quality evidence), and blood loss 1000 mL after delivery (RR 0.59, 95% CI 0.42 to 0.83; 4123 women; 5 studies; low-quality evidence). Prophylactic oxytocin probably reduces the need for additional uterotonics (average RR 0.54, 95% CI 0.36 to 0.80; 3135 women; 4 studies; Tau² = 0.07, I² = 44%; moderate-quality evidence). There may be no difference in the risk of needing a blood transfusion in women receiving oxytocin compared to no uterotonics or placebo (RR 0.88, 95% CI 0.44 to 1.78; 3081 women; 3 studies; low-quality evidence). Oxytocin may be associated with an increased risk of a third stage greater than 30 minutes (RR 2.55, 95% CI 0.88 to 7.44; 1947 women; 1 study; moderate-quality evidence), however the confidence interval is wide and includes 1.0, indicating that there may be little or no difference.Prophylactic oxytocin versus ergot alkaloids (15 trials)It is uncertain whether oxytocin reduces the likelihood of blood loss 500 mL (average RR 0.84, 95% CI 0.56 to 1.25; 3082 women; 10 studies; Tau² = 0.14, I² = 49%; very low-quality evidence) or the need for additional uterotonics compared to ergot alkaloids (average RR 0.89, 95% CI 0.43 to 1.81; 2178 women; 8 studies; Tau² = 0.76, I² = 79%; very low-quality evidence), because the quality of this evidence is very low. The quality of evidence was very low for blood loss of 1000 mL (RR 1.13, 95% CI 0.63 to 2.01; 1577 women; 3 studies; very low-quality evidence), and need for blood transfusion (average RR 1.37, 95% CI 0.34 to 5.51; 1578 women; 7 studies; Tau² = 1.34, I² = 45%; very low-quality evidence), making benefit of oxytocin over ergot alkaloids uncertain. Oxytocin probably increases the risk of a prolonged third stage greater than 30 minutes (RR 4.69, 95% CI 1.63 to 13.45; 450 women; 2 studies; moderate-quality evidence), although it is uncertain if this translates into increased risk of manual placental removal (average RR 1.10, 95% CI 0.39 to 3.10; 3127 women; 8 studies; Tau² = 1.07, I² = 76%; very low-quality evidence). Oxytocin may make little or no difference to risk of diastolic blood pressure > 100 mm Hg (average RR 0.28, 95% CI 0.04 to 2.05; 960 women; 3 studies; Tau² = 1.23, I² = 50%; low-quality evidence), and is probably associated with a lower risk of vomiting (RR 0.09, 95% CI 0.05 to 0.14; 1991 women; 7 studies; moderate-quality evidence), although the impact of oxytocin on headaches is uncertain (average RR 0.19, 95% CI 0.03 to 1.02; 1543 women; 5 studies; Tau² = 2.54, I² = 72%; very low-quality evidence).Prophylactic oxytocin-ergometrine versus ergot alkaloids (four trials)Oxytocin-ergometrine may slightly reduce the risk of blood loss greater than 500 mL after delivery compared to ergot alkaloids (RR 0.44, 95% CI 0.20 to 0.94; 1168 women; 3 studies; low-quality evidence), based on outcomes from quasi-randomised trials with a high risk of bias. There were no maternal deaths reported in either treatment group in the one trial that reported this outcome (RR not estimable; 1 trial, 807 women; moderate-quality evidence). Need for additional uterotonics was not reported.No subgroup differences were observed between active or expectant management, or different routes or doses of oxytocin for any of our comparisons. Prophylactic oxytocin compared with no uterotonics may reduce blood loss and the need for additional uterotonics. The effect of oxytocin compared to ergot alkaloids is uncertain with regards to blood loss, need for additional uterotonics, and blood transfusion. Oxytocin may increase the risk of a prolonged third stage compared to ergot alkaloids, although whether this translates into increased risk of manual placental removal is uncertain. This potential risk must be weighed against the possible increased risk of side effects associated with ergot alkaloids. Oxytocin-ergometrine may reduce blood loss compared to ergot alkaloids, however the certainty of this conclusion is low. More high-quality trials are needed to assess optimal dosing and route of oxytocin administration, with inclusion of important outcomes such as maternal mortality, shock, and transfer to a higher level of care. A network meta-analysis of uterotonics for PPH prevention plans to address issues around optimal dosing and routes of oxytocin and other uterotonics.


Stimulation of the human motor cortex alters generalization patterns of motor learning.
It has been hypothesized that the generalization patterns that accompany learning carry the signatures of the neural systems that are engaged in that learning. Reach adaptation in force fields has generalization patterns that suggest primary engagement of a neural system that encodes movements in the intrinsic coordinates of joints and muscles, and lesser engagement of a neural system that encodes movements in the extrinsic coordinates of the task. Among the cortical motor areas, the intrinsic coordinate system is most prominently represented in the primary sensorimotor cortices. Here, we used transcranial direct current stimulation (tDCS) to alter mechanisms of synaptic plasticity and found that when it was applied to the motor cortex, it increased generalization in intrinsic coordinates but not extrinsic coordinates. However, when tDCS was applied to the posterior parietal cortex, it had no effects on learning or generalization in the force field task. The results suggest that during force field adaptation, the component of learning that produces generalization in intrinsic coordinates depends on the plasticity in the sensorimotor cortex.


Index-guided arrays with a large index step.
The mode-selection mechanism operative in a new class of large-index-step index-guided arrays is elucidated, and it is shown that such arrays may be designed to operate stably in the fundamental mode at high power levels. In contrast to evanescently coupled arrays, these devices operate in a new set of so-called leaky modes. The calculations demonstrate a significant discrimination between the fundamental and high-order leaky modes that is sensitive to the widths of the high-index coupling regions but insensitive to the drive current. This resulting mode discrimination combined with the inherently large index step present in these devices should allow them to operate stably under cw conditions and/or at high drive currents.


Improving disaster risk reduction capacity of District Civil Protection Units in managing veld fires: A case of Mangwe District in Matabeleland South Province, Zimbabwe.
This article analysed disaster risk reduction capacity of District Civil Protection Units (DCPUs) in managing veld fires in Mangwe District of Matabeleland South Province, Zimbabwe. Veld fires have resulted in unnecessary material, environmental and economic losses. Communities' livelihoods and property have been destroyed, and the natural environment depleted. The research sought to improve disaster risk reduction capacity of DCPUs in managing veld fires, through new intervention strategies and a new model. The objectives of the study were to investigate the main causes of veld fires; to analyse their impacts; to examine the effectiveness of the current intervention strategies; and to identify challenges in implementing these interventions. Furthermore, the study sought to recommend new possible intervention strategies. This mainly qualitative study employed self-administered questionnaires, interviews and focus-group discussions. Questionnaires were used to investigate members of the DCPU's ideas, views and experiences, interviews solicited perceptions of community leaders and their subjects, whilst focus-group discussions assisted with information from members of the District Civil Protection Planning Committee. Veld fires in the district are mainly caused by human activities, and they are prevalent during the months of September and October. They affect livelihoods and the natural environment the most. This study found that DCPUs are not prepared to manage veld fires and therefore recommended new strategies and adoption of the community-based disaster risk reduction model. The new strategies include involving community leaders and members of the communities in DCPUs; regular training and workshops to members of DCPUs on veld fire management; creation of fire protection associations; regular campaigns and rehearsal of emergency drills by the DCPU personnel; the introduction of competitions and incentives in veld fire management; vigorous public education on the erection of proper fireguards around homes, cattle pens, crop fields and vegetable gardens; and the imposition of stiffer penalties for carelessly or deliberately causing veld fires. Policy-makers, governments and stakeholders would benefit from the new intervention strategies. The community-based disaster risk reduction model would benefit researchers and disaster risk reduction practitioners.


Prevention of peritendinous adhesions using an electrospun DegraPol polymer tube: a histological, ultrasonographic, and biomechanical study in rabbits.
One of the great challenges in surgical tendon rupture repair is to minimize peritendinous adhesions. In order to reduce adhesion formation, a physical barrier was applied to a sutured rabbit Achilles tendon, with two different immobilization protocols used postoperatively. Thirty New Zealand white rabbits received a laceration on the Achilles tendon, sutured with a 4-strand Becker suture, and half of the rabbits got a DegraPol tube at the repair site. While fifteen rabbits had their treated hind leg in a 180° stretched position during 6 weeks (adhesion provoking immobilization), the other fifteen rabbits were recasted with a 150° position after 3 weeks (adhesion inhibiting immobilization). Adhesion extent was analysed macroscopically, via ultrasound and histology. Inflammation was determined histologically. Biomechanical properties were analysed. Application of a DegraPol tube reduced adhesion formation by approximately 20%--independently of the immobilization protocol. Biomechanical properties of extracted specimen were not affected by the tube application. There was no serious inflammatory reaction towards the implant material. Implantation of a DegraPol tube tightly set around a sutured tendon acts as a beneficial physical barrier and prevents adhesion formation significantly--without affecting the tendon healing process.


Does the sagittal alignment of the cervical spine have an impact on disk degeneration? Minimum 10-year follow-up of asymptomatic volunteers.
There have been few studies that investigated and clarified the relationships between progression of degenerative changes and sagittal alignment of the cervical spine. The objective of the study was to longitudinally evaluate the relationships among progression of degenerative changes of the cervical spine with age, the development of clinical symptoms and sagittal alignment of the cervical spine in healthy subjects. Out of 497 symptom-free volunteers who underwent MRI and plain radiography of the cervical spine between 1994 and 1996, 113 subjects (45 males and 68 females) who responded to our contacts were enrolled. All subjects underwent another MRI at an average of 11.3 years after the initial study. Their mean age at the time of the initial imaging was 36.6 +/- 14.5 years (11-65 years). The items evaluated on MRI were (1) decrease in signal intensity of the intervertebral disks, (2) posterior disk protrusion, and (3) disk space narrowing. Each item was evaluated using a numerical grading system. The subjects were divided into four groups according to the age and sagittal alignment of the cervical spine, i.e., subjects under or over the age of 40 years, and subjects with the lordosis or non-lordosis type of sagittal alignment of the cervical spine. During the 10-year period, progression of decrease in signal intensity of the disk, posterior disk protrusion, and disk space narrowing were recognized in 64.6, 65.5, and 28.3% of the subjects, respectively. Progression of posterior disk protrusion was significantly more frequent in subjects over 40 years of age with non-lordosis type of sagittal alignment. Logistic regression analysis revealed that stiff shoulder was closely correlated with females (P = 0.001), and that numbness of the upper extremity was closely correlated with age (P = 0.030) and male (P = 0.038). However, no significant correlation between the sagittal alignment of the cervical spine and clinical symptoms was detected. Sagittal alignment of the cervical spine had some impact on the progression of degenerative changes of the cervical spine with aging; however, it had no correlation with the occurrence of future clinical symptoms.


Cross-validation of the Care Dependency Scale in intensive care unit (ICU-CDS).
The Care Dependency Scale is a theory-based, comprehensive tool widely used in low-intensity care settings to evaluate patients' dependency. This study aimed to test the psychometric properties of the Care Dependency Scale in intensive care units. A multicentre cross-sectional validation study was conducted. Exploratory factor analysis and confirmatory factor analysis were performed using a Maximum Likelihood robust estimator with Geomin oblique rotation. Adult patients admitted to intensive care units of four Italian hospitals. The sample included 453 patients (mean age = 68 years, 62% male). The exploratory factor analysis, conducted on a subsample of 227 patients, revealed a two-factor structure (Physical care dependency and Psychosocial care dependency) with good fit indexes. The confirmatory factor analysis was conducted on another subsample of 226 patients and a second-order factor was specified. The model tested yielded adequate fit indexes. Concurrent and known-groups validity, and reliability, were also adequate. The Care Dependency Scale is a multidimensional, valid and reliable tool able to assess the care dependency of critically ill patients. It can help to distinguish between physical and psychosocial needs and to create a base for patient-customised and holistic care.


Anti-Müllerian hormone trend after laparoscopic surgery in women with ovarian endometrioma.
Operative laparoscopy is the gold standard in the treatment of endometriotic ovarian cysts. Excisional surgery is the best technique to prevent recurrences and improve symptoms but it may result in ovarian reserve damage due to the removal of healthy ovarian cortex. The aim of this study was to investigate the extent of the ovarian reserve damage after stripping technique of unilateral endometriomas, by dosing the Anti-Müllerian Hormone (AMH). This prospective study was conducted at the Center of Minimally Invasive Pelvic Surgery of the Department of Health of Woman and Child, University of Padua, from October 2010 to June 2012. Twenty-five women underwent excision of monolateral endometriosis ovarian cyst by stripping without accessing a bipolar coagulation and performing an intracortical suture. The AMH serum levels were estimated in the early proliferative phase of the cycle, before surgery (time 0), 24 h after surgery (time 1), the first menstrual cycle after surgery (time 2) and the third menstrual cycle after surgery (time 3). We found a nonstatistically significant decreases in serum AMH levels after surgical excision of the cysts. Our results suggest that an appropriate surgical technique, without the use of the bipolar coagulation of ovarian border, does not determine a significant reduction of ovarian reserve.


Spanish adaptation and validation of the Child Food Security Survey Module (CFSSM-S).
The present study aimed to assess the: (i) internal structure of the Spanish Child Food Security Survey Module (CFSSM-S) with exploratory and confirmatory factor analysis (EFA and CFA); (ii) measurement invariance by gender, grade, weight status, socio-economic status (SES) and family affluence; and (iii) relationships with these external variables. A cross-sectional study was conducted. The CFSSM-S and other tools were employed to assess food insecurity, weight status, SES and family affluence, respectively. A secondary school (grades 7-10) in the city of Terrassa in Catalonia, Spain. Participants included adolescent boys and girls (n 426) aged 12-17 years. The cross-validation design with EFA and CFA captured a single factor, 'food insecurity'. The goodness-of-fit for the one-factor model with CFA (root-mean-square error of approximation=0·038, comparative fit index=0·984, Tucker-Lewis index=0·979) and internal consistency (ω=0·95) were excellent. The measurement invariance indicated that CFSSM-S could be used across genders, grades, weight status, SES and family affluence. Only mean differences for SES and family affluence were found which showed a linear trend, indicating higher CFSSM-S scores for participants with lower SES and family affluence. Of participants, 1·9 % experienced very low food security, 16·4 % low food security and 81·7 % were food secure. The CFSSM-S is the first validated instrument to assess food insecurity with psychometric guarantees in Spanish adolescents. Researchers and health practitioners in Spain could use this self-reported questionnaire to gain more information about adolescent health in relation to food insecurity.


Antipsychotics in the treatment of delirium: a systematic review.
Antipsychotics are frequently used in the management of delirium, although there is limited information regarding the safety and efficacy of antipsychotics in treating delirium. The purpose of this study was to systematically evaluate the evidence for the efficacy and safety of antipsychotics in treating delirium. MEDLINE (July 1980 to July 2005) and Cochrane databases were searched for English language articles using keywords. Prospective studies with standardized criteria for diagnosing delirium and evaluating its severity. In total, 14 studies (9 single agent studies and 5 comparison trials) met inclusion criteria. Study medications included haloperidol, chlorpromazine, olanzapine, risperidone, and quetiapine. Improvements in delirium severity were reported with all of these antipsychotic medications. No study included a placebo comparison to account for spontaneous improvements in delirium. Other methodological limitations included inadequate blinding, randomization, and handling of participant withdrawals. The improvements in delirium tended to occur soon after initiation of treatment, and most of the studies examined used relatively low doses of antipsychotic medication. Serious adverse events attributable to antipsychotic medication were uncommon in studies, although side effects were not evaluated systematically in most studies. To date, there are no published double-blind, randomized, placebo-controlled trials to establish the efficacy or safety of any antipsychotic medication in the management of delirium. There is limited evidence from uncontrolled studies that supports the use of low-dose, short-term treatment of delirium with some antipsychotics. Further study with well-designed clinical trials is required in this area.


ANORECTAL MANOMETRY STANDARD OF A BRAZILIAN POPULATION AT PRODUCTIVE AGE WITHOUT PELVIC FLOOR DISORDERS: A PROSPECTIVE VOLUNTEERED STUDY.
Due to the lack of normal standards of anorectal manometry in Brazil, data used are subject to normality patterns described at different nationalities. To determine the values and range of the parameters evaluated at anorectal manometry in people, at productive age, without pelvic floor disorders comparing the parameters obtained between male and female. Prospective analysis of clinical data, such as gender, age, race, body mass index (BMI) and anorectal manometry, of volunteers from a Brazilian university reference in pelvic floor disorders. Forty patients were included, with a mean age of 45.5 years in males and 37.2 females (p=0.43). According to male and female, respectively in mmHg, resting pressures were similar (78.28 vs. 63.51, p=0.40); squeeze pressures (153.89 vs. 79.78, p=0.007) and total squeeze pressures (231.27 vs. 145.63, p=0.002). Men presented significantly higher values of anorectal squeeze pressures, as well as the average length of the functional anal canal (2.85 cm in male vs. 2.45 cm in female, p=0.003). Normal sphincter pressure levels in Brazilians differ from those used until now as normal literature standards. Male gender has higher external anal sphincter tonus as compared to female, in addition a greater extension of the functional anal canal.


A three-dimensional computational model of collagen network mechanics.
Extracellular matrix (ECM) strongly influences cellular behaviors, including cell proliferation, adhesion, and particularly migration. In cancer, the rigidity of the stromal collagen environment is thought to control tumor aggressiveness, and collagen alignment has been linked to tumor cell invasion. While the mechanical properties of collagen at both the single fiber scale and the bulk gel scale are quite well studied, how the fiber network responds to local stress or deformation, both structurally and mechanically, is poorly understood. This intermediate scale knowledge is important to understanding cell-ECM interactions and is the focus of this study. We have developed a three-dimensional elastic collagen fiber network model (bead-and-spring model) and studied fiber network behaviors for various biophysical conditions: collagen density, crosslinker strength, crosslinker density, and fiber orientation (random vs. prealigned). We found the best-fit crosslinker parameter values using shear simulation tests in a small strain region. Using this calibrated collagen model, we simulated both shear and tensile tests in a large linear strain region for different network geometry conditions. The results suggest that network geometry is a key determinant of the mechanical properties of the fiber network. We further demonstrated how the fiber network structure and mechanics evolves with a local formation, mimicking the effect of pulling by a pseudopod during cell migration. Our computational fiber network model is a step toward a full biomechanical model of cellular behaviors in various ECM conditions.


Dynamics of the HIV-1 variability in adults from Bucharest, 1992-1998.
Variability is a hallmark of HIV viruses both at the genetic and the phenotypic level. Viral sequencing and phylogenetic analysis of many isolates revealed specific distribution of HIV-1 subtypes according to the geographic location and route of transmission. In Romania, the currently available data coming from the study of pediatric HIV infection suggest the predominance of subtype F. However, there are few data concerning the distribution of HIV-1 subtypes among adults. We investigated the changes in the distribution of different HIV-1 subtypes among HIV-1 infected adult patients from Bucharest over a 6 years period (1992-1998) by means of V3 binding assays. The analysis of the relative incidence of different HIV-1 serotypes revealed the steady predominance of serotype F (50-75%) among the adults from Bucharest and a small but constant increase of the number of samples with serotype B- from 5% in 1994 to 14% in 1998. In contrast, the serotype E is either absent or weakly represented (4%) during the period of the study. All over the years there was a relatively high proportion (6-30%) of non-reactive samples. This could be an indication for the possible emergence of new or recombinant HIV-1 subtypes.


Fat augmentation for nonparalytic glottic insufficiency.
While autogenous fat augmentation for glottic insufficiency has been used before, relatively little information is currently available on the effectiveness of fat injection in patients with nonparalytic glottic insufficiency resulting from problems such as various defects of vocal atrophy or sulcus vocalis. This paper compares retrospectively the efficiency of fat injection after surgery in patients with vocal atrophy (n = 16) and sulcus vocalis (n = 8). The perceptual acoustic and phonatory functions and videolaryngostroboscopic data were evaluated before and after fat augmentation in 24 patients. The mean follow-up time was 19.5 months. Fifteen patients displayed excellent results; 1 showed some improvement; 6 experienced postprocedure failure, and 2 were not available for follow-up analysis. Perceptual rating showed significant improvement in grade, roughness and breathiness (p < 0.05). The videolaryngostroboscopic rating showed significant improvements in vocal fold edge linearity, vocal fold vibration amplitude and mucosal wave excursion (p < 0.05). More improvement in vocal atrophy was observed compared with sulcus vocalis following fat injection procedures. Our research showed that middle defects improved more compared to those in the anterior and posterior area. Fat injection is an effective autogenous implant and may be considered as an option in the treatment of patients with vocal atrophy or sulcus vocalis. Although fat reabsorption was a problem, repeating the procedure could be considered.


The importance of nanoscale confinement to electrocatalytic performance.
Electrocatalytic nanoparticles that mimic the three-dimensional geometric architecture of enzymes where the reaction occurs down a substrate channel isolated from bulk solution, referred to herein as nanozymes, were used to explore the impact of nano-confinement on electrocatalytic reactions. Surfactant covered Pt-Ni nanozyme nanoparticles, with Ni etched from the nanoparticles, possess a nanoscale channel in which the active sites for electrocatalysis of oxygen reduction are located. Different particle compositions and etching parameters allowed synthesis of nanoparticles with different average substrate channel diameters that have varying amounts of nano-confinement. The results showed that in the kinetically limited regime at low overpotentials, the smaller the substrate channels the higher the specific activity of the electrocatalyst. This is attributed to higher concentrations of protons, relative to bulk solution, required to balance the potential inside the nano-confined channel. However, at higher overpotentials where limitation by mass transport of oxygen becomes important, the nanozymes with larger substrate channels showed higher electrocatalytic activity. A reaction-diffusion model revealed that the higher electrocatalytic activity at low overpotentials with smaller substrate channels can be explained by the higher concentration of protons. The model suggests that the dominant mode of mass transport to achieve these high concentrations is by migration, exemplifying how nano-confinement can be used to enhance reaction rates. Experimental and theoretical data show that under mass transport limiting potentials, the nano-confinement has no effect and the reaction only occurs at the entrance of the substrate channel at the nanoparticle surface.


A cross sectional study of the association between walnut consumption and cognitive function among adult US populations represented in NHANES.
To examine the association between walnut consumption and measures of cognitive function in the US population. Nationally representative cross sectional study using 24 hour dietary recalls of intakes to assess walnut and other nut consumption as compared to the group reporting no nut consumption. 1988-1994 and 1999-2002 rounds of the National Health and Nutrition Examination Survey (NHANES). Representative weighted sample of US adults 20 to 90 years of age. The Neurobehavioral Evaluation System 2 (NES2), consisting of simple reaction time (SRTT), symbol digit substitution (SDST), the single digit learning (SDLT), Story Recall (SRT) and digit-symbol substitution (DSST) tests. Adults 20-59 years old reporting walnut consumption of an average of 10.3 g/d required 16.4ms less time to respond on the SRTT, P=0.03, and 0.39s less for the SDST, P=0.01. SDLT scores were also significantly lower by 2.38s (P=0.05). Similar results were obtained when tertiles of walnut consumption were examined in trend analyses. Significantly better outcomes were noted in all cognitive test scores among those with higher walnut consumption (P < 0.01). Among adults 60 years and older, walnut consumers averaged 13.1 g/d, scored 7.1 percentile points higher, P=0.03 on the SRT and 7.3 percentile points higher on the DSST, P=0.05. Here also trend analyses indicate significant improvements in all cognitive test scores (P < 0.01) except for SRTT (P = 0.06) in the fully adjusted models. These significant, positive associations between walnut consumption and cognitive functions among all adults, regardless of age, gender or ethnicity suggest that daily walnut intake may be a simple beneficial dietary behavior.


Long-term outcomes of percutaneous retrogasserian glycerol rhizotomy in 3370 patients with trigeminal neuralgia.
To assess the long-term outcomes of percutaneous retrogasserian glycerol rhizotomy (PRGR) in patients with medically unresponsive idiopathic trigeminal neuralgia. A total of 3370 patients undergoing PRGR between 1983 and 2003 in our hospital were followed up for 13.1 years (range 3-23 years), and the outcomes were investigated. Of the 3370 patients, 99.58% had complete initial pain relief. A total of 2750 patients were followed up when 112 died of unrelated causes and 508 were lost to follow up. Of the 2750 patients, 962 (35%) had pain recurrence at various intervals: 0.3% in 1 year; 21% in 1 to 5 years; 7% in 5 to 10 years; 4% in 10 to 15 years and 3% in 15 to 23 years. The major complication was facial numbness, among which hypesthesia outweighed hypalgesia. Most patients recovered within half a year, although 109 patients (3.96%) developed permanent mild hypesthesia. There was no anesthesia dolorosa or surgery related mortality in this series. PRGR is a minimally invasive and simple procedure yielding a favorable outcome for trigeminal neuralgia. The major complications of this procedure are reversible within various time intervals. It may serve as a first-line surgical modality for patients unresponsive to pharmacotherapy.


DNA is a co-factor for its own replication in Xenopus egg extracts.
Soluble Xenopus egg extracts efficiently replicate added plasmids using a physiological mechanism, and thus represent a powerful system to understand vertebrate DNA replication. Surprisingly, DNA replication in this system is highly sensitive to plasmid concentration, being undetectable below ∼10 pM and highly efficient above ∼75 pM. DNA replication at the high plasmid concentration does not require plasmid-plasmid contacts, since replication is not inhibited when plasmids are immobilized in agarose prior to addition of egg extract. The absence of replication at low plasmid concentration is due to a defect in the assembly of pre-replication complexes (pre-RCs). pre-RC assembly requires contact-independent communication between plasmids. Our results show that in Xenopus egg extracts, aggregation of multiple replication forks is not required for efficient replication of plasmid DNA, and they suggest that DNA functions as a co-factor for its own duplication.


Bactericidal activity of lemon juice and lemon derivatives against Vibrio cholerae.
Food products can be possible vectors of the agent responsible for cholera epidemics, because some of these products allow Vibrio cholerae O1 to develop to concentrations above the dangerous level. This study deals with the behaviour of essential oils, natural and concentrated lemon juice and fresh and dehydrated lemon peel against V. cholerae O1 biotype Eltor serotype Inaba tox+. Our aim was to evaluate whether these products, used at different dilutions, exhibit bactericidal or bacteriostatic activity against the microorganism, when present at concentrations of 10(2), 10(4), 10(6) and 10(8) colony forming units (CFU) ml(-1), and after different exposure times. 10(8) CFU ml(-1) was considered an infectious dose. Concentrated lemon juice and essential oils inhibited V. cholerae completely at all studied dilutions and exposure times. Fresh lemon peel and dehydrated lemon peel partially inhibited growth of V. cholerae. Freshly squeezed lemon juice, diluted to 10(-2), showed complete inhibition of V. cholerae at a concentration of 10(8) CFU ml(-1) after 5 min of exposure time; a dilution of 2 x 10(-3) produced inhibition after 15 min and a dilution of 10(-3) after 30 min. It can be concluded that lemon, a natural product which is easily obtained, acts as a biocide against V. cholerae, and is, therefore, an efficient decontaminant, harmless to humans.