Effects of Integrating Family Planning With Maternal, Newborn, and Child Health Services on Uptake of Voluntary Modern Contraceptive Methods in Rural Pakistan: Protocol for a Quasi-experimental Study.
The uptake of modern contraceptive methods (MCMs) remains low, with 25% of women reporting their use in Pakistan. The overarching interventions covering service delivery platforms at facility and community levels necessitate the integration of family planning (FP) with maternal, newborn, and child health (MNCH) services. The main aim of this study is to evaluate the impact of an integrated FP-MNCH service delivery model to increase coverage of MCMs in rural Pakistan. Moreover, we aim to measure the level of effectiveness of interventions regarding the uptake of MCMs. A quasi-experimental, sequential, mixed methods study design with pre- and postevaluation will be adopted to evaluate the impact of integration of FP with MNCH services. The interventions include the following: (1) capacity strengthening of health care providers, including technical trainings; training in counseling of women who attend immunization centers, antenatal care (ANC) clinics, and postnatal care (PNC) clinics; and provision of job aids; (2) counseling of women and girls attending ANC, PNC, and pediatric clinics; (3) ensuring sustained provision of supplies and commodities; (4) community engagement, including establishing adolescent-friendly spaces; and (5) use of District Health Information System data in decision-making. Descriptive statistics will be used to estimate prevalence (ie, proportions) and frequencies of outcome indicators. A univariate difference-in-difference analytical approach will be used to estimate the effect of the interventions. In addition, a Blinder-Oaxaca decomposition analysis will be conducted to identify and quantify determinants of the modern contraceptive prevalence rate. The intervention phase began in July 2021 and will run until June 2022. The impact assessment will be conducted from July to September 2022. This project will evaluate the impact of integrating FP with MNCH services. Furthermore, this study will identify the drivers and barriers in uptake of MCMs and will simultaneously help in modifying the interventional strategies that can be scaled up through existing service delivery platforms within the public and private sectors, according to the local sociocultural and health system context. ClinicalTrials.gov NCT05045599; https://clinicaltrials.gov/ct2/show/NCT05045599. DERR1-10.2196/35291.


The age deficit on photopic counterphase flicker: contrast, spatial frequency, and luminance effects.
This study evaluated the contribution of reduced contrast sensitivity and retinal illuminance to the age-related deficit on the temporal resolution of suprathreshold spatial stimuli. The discrimination of counterphase flicker was measured in optimally refracted young and elderly observers for sinusoidal gratings of three spatial frequencies (1, 4, and 8 cycles per degree) at three contrast levels (0.11, 0.33, and 0.66). Age deficits in flicker discrimination at the two higher contrast levels and at the two lower spatial frequencies were unrelated to observer contrast sensitivity. Flicker discrimination of young observers who carried out the task through .5 ND filters to simulate a two-thirds reduction of retinal illuminance in the older eye, was similar to that of the elderly observers. An age-related reduction in retinal luminance appears to be a major determinant of the age-related spatiotemporal deficit at suprathreshold contrast levels, although neural factors may also be involved.


Efficient CRISPR/Cas9-mediated Targeted Mutagenesis in Populus in the First Generation.
Recently, RNA-guided genome editing using the type II clustered regularly interspaced short palindromic repeats (CRISPR)-associated protein (Cas) system has been applied to edit the plant genome in several herbaceous plant species. However, it remains unknown whether this system can be used for genome editing in woody plants. In this study, we describe the genome editing and targeted gene mutation in a woody species, Populus tomentosa Carr. via the CRISPR/Cas9 system. Four guide RNAs (gRNAs) were designed to target with distinct poplar genomic sites of the phytoene desaturase gene 8 (PtoPDS) which are followed by the protospacer-adjacent motif (PAM). After Agrobacterium-mediated transformation, obvious albino phenotype was observed in transgenic poplar plants. By analyzing the RNA-guided genome-editing events, 30 out of 59 PCR clones were homozygous mutants, 2 out of 59 were heterozygous mutants and the mutation efficiency at these target sites was estimated to be 51.7%. Our data demonstrate that the Cas9/sgRNA system can be exploited to precisely edit genomic sequence and effectively create knockout mutations in woody plants.


The oral health status of Syrian refugee children in Jordan: An exploratory study.
To examine the oral health status and dental treatment needs of children Syrian refugees in Jordan. A convenience sample of Syrian refugee children who aged between 6 and 12 years at al-Zaatari camp was used for the purpose of this study. Examination was performed according to the method proposed by WHO. DMFT and gingival indices were examined and reported by a trained dentist. A total of 125 children were examined. The mean DMFT score was 3.64 ± 9.83, and the mean dmft score was 2.98 ± 4.7. More than half of children (50.4%) were found to have high caries risk according to CAMBRA scale. Most of the DMFT score was contributed by decayed and missing teeth. Nearly, half of children (44.8%) showed fluorosis and almost all children had chronic gingivitis. More than half of the participants (55.2%) reported that they needed dental treatment during their stay at the camp, but only half (52%) received treatment mainly tooth extraction and prescription of medication. Only 6.4% of children received conservative dental treatment. Syrian refugee children in Jordan were found to have high levels of unmet dental needs. Accessibility of dental services was found to be a primary barrier to care.


Assessing the Impact of Data Preprocessing on Analyzing Next Generation Sequencing Data.
Data quality control and preprocessing are often the first step in processing next-generation sequencing (NGS) data of tumors. Not only can it help us evaluate the quality of sequencing data, but it can also help us obtain high-quality data for downstream data analysis. However, by comparing data analysis results of preprocessing with Cutadapt, FastP, Trimmomatic, and raw sequencing data, we found that the frequency of mutation detection had some fluctuations and differences, and human leukocyte antigen (HLA) typing directly resulted in erroneous results. We think that our research had demonstrated the impact of data preprocessing steps on downstream data analysis results. We hope that it can promote the development or optimization of better data preprocessing methods, so that downstream information analysis can be more accurate.


Symmetric ambulatory arterial stiffness index in the young.
The ambulatory arterial stiffness index (AASI) and the symmetric ambulatory arterial stiffness index (s-AASI) have been shown to correlate to arterial stiffness in adults. This study assesses these indices with anthropometric and blood pressure (BP) measures in children. A total of 102 children at a pediatric hypertension clinic who had ambulatory blood pressure monitoring (ABPM) done from 2009 to 2013 were included (75% males, 7-22yo, 47% hypertensive, 24% prehypertensive, and 34% white-coat hypertensives). AASI is 1 minus the regression slope of diastolic BP values on systolic BP values from a 24-hour ambulatory blood pressure monitoring. s-AASI is the symmetric regression of AASI. Obese patients had a significantly higher AASI. s-AASI correlated with systolic BP variability. In multivariable regression, BP variability independently correlated with AASI and s-AASI. s-AASI is related to systolic dipping.AASI and s-AASI are highly dependent on BP variability in children. Further studies are necessary to assess their utility.


Rates of respiratory syncytial virus (RSV)-associated hospitalization among adults with congestive heart failure-United States, 2015-2017.
Respiratory syncytial virus (RSV) can cause severe disease in adults with cardiopulmonary conditions, such as congestive heart failure (CHF). We quantified the rate of RSV-associated hospitalization in adults by CHF status using population-based surveillance in the United States. Population-based surveillance for RSV (RSV-NET) was performed in 35 counties in seven sites during two respiratory seasons (2015-2017) from October 1-April 30. Adults (≥18 years) admitted to a hospital within the surveillance catchment area with laboratory-confirmed RSV identified by clinician-directed testing were included. Presence of underlying CHF was determined by medical chart abstraction. We calculated overall and age-stratified (<65 years and ≥65 years) RSV-associated hospitalization rates by CHF status. Estimates were adjusted for age and the under-detection of RSV. We also report rate differences (RD) and rate ratios (RR) by comparing the rates for those with and without CHF. 2042 hospitalized RSV cases with CHF status recorded were identified. Most (60.2%, n = 1230) were ≥65 years, and 28.3% (n = 577) had CHF. The adjusted RSV hospitalization rate was 26.7 (95% CI: 22.2, 31.8) per 10,000 population in adults with CHF versus 3.3 (95% CI: 3.3, 3.3) per 10,000 in adults without CHF (RR: 8.1, 95% CI: 6.8, 9.7; RD: 23.4, 95% CI: 18.9, 28.5). Adults with CHF had higher rates of RSV-associated hospitalization in both age groups (<65 years and ≥65 years). Adults ≥65 years with CHF had the highest rate (40.5 per 10,000 population, 95% CI: 35.1, 46.6). Adults with CHF had 8 times the rate of RSV-associated hospitalization compared with adults without CHF. Identifying high-risk populations for RSV infection can inform future RSV vaccination policies and recommendations.


[Sleep in fibromyalgia: review of clinical and polysomnographic data].
Fibromyalgia syndrome is a common chronic pain syndrome that is often associated with sleep disturbances characterized by subjective experience of non-restorative sleep. The complaints of sleep disturbances are correlated with polysomnographic features showing clear abnormalities in the continuity of sleep as well as in the sleep architecture. Sleep-recording abnormalities are characterized by a reduced sleep efficiency with increased number of awakenings, a reduced amount of slow wave sleep and an abnormal alpha wave intrusion in non rapid eye movement, termed alpha-delta sleep. These data were confirmed by spectral analysis of sleep showing an increased EEG power density in the higher frequency band and a reduced EEG power density in the lower frequency bands. Moreover, other microstructural aspects of sleep were modified with high frequency of arousals and alpha-K complex reported, both indicators of fragmented sleep. The fibromyalgia symptoms may relate to a non-restorative sleep disorder associated with the alpha-EEG sleep anomalies. However, alpha-EEG sleep anomaly is non-specific for fibrositis, also seen in normal controls during stage 4 sleep deprivation. Moreover, fibromyalgia patients may also experience primary sleep disorder such as sleep apnea or periodic leg movements. The etiology of this common condition is incompletely understood and the existence of a specific entity of fibromyalgia is still a matter of debate. However, several studies have found abnormal brain metabolism of substances such as serotonin implicated in sleep arousal and pain mechanisms and administration of tricyclic antidepressants and selective serotonin reuptake inhibitors may be useful in fibromyalgia. Pain, poor sleep quality and anxiety may contribute to the clinical picture. Several factors such as psychological, environmental, genetic factor, altered serotonin metabolism and altered sleep physiology are involved in the pathogenesis of fibromyalgia.


GSEA-SNP identifies genes associated with Johne's disease in cattle.
SNP-based gene-set enrichment analysis from single nucleotide polymorphisms, or GSEA-SNP, is a tool to identify candidate genes based on enrichment analysis of sets of genes rather than single SNP associations. The objective of this study was to identify modest-effect genes associated with Mycobacterium avium subsp. paratuberculosis (Map) tissue infection or fecal shedding using GSEA-SNP applied to KEGG pathways or Gene Ontology (GO) gene sets. The Illumina Bovine SNP50 BeadChip was used to genotype 209 Holstein cows for the GSEA-SNP analyses. For each of 13,744 annotated genes genome-wide located within 50 kb of a Bovine SNP50 SNP, the single SNP with the highest Cochran-Armitage Max statistic was used as a proxy statistic for that gene's strength of affiliation with Map. Gene-set enrichment was tested using a weighted Kolmogorov-Smirnov-like running sum statistic with data permutation to adjust for multiple testing. For tissue infection and fecal shedding, no gene sets in KEGG pathways or in GO sets for molecular function or cellular component were enriched for signal. The GO biological process gene set for positive regulation of cell motion (GO:0051272, q = 0.039, 5/11 genes contributing to the core enrichment) was enriched for Map tissue infection, while no GO biological process gene sets were enriched for fecal shedding. GSEA-SNP complements traditional SNP association approaches to identify genes of modest effects as well as genes with larger effects as demonstrated by the identification of one locus that we previously found to be associated with Map tissue infection using a SNP-by-SNP genome-wide association study.


The Alcohol Use Disorders Identification Test (AUDIT) predicts alcohol withdrawal symptoms during inpatient detoxification.
We evaluated whether the Alcohol Use Disorders Identification Test (AUDIT) predicted clinically meaningful alcohol withdrawal syndrome (AWS) in 118 alcohol dependent patients without a history of seizures. Patients were monitored by serial administration of the revised Clinical Institute Withdrawal Assessment Scale for Alcohol (CIWA-Ar) during inpatient detoxification. Patients (N = 55) who reached threshold level of AWS for receiving medication (CIWA-Ar > 9) scored significantly higher (p <.001) on the AUDIT total score, the dependence sub-scale, and the single item on morning drinking. Sensitivity, specificity, positive and negative predictive power, and screening efficiency showed the value of the AUDIT for identifying patients who developed AWS. The AUDIT should be explored alone and in combination with other parameters to improve screening for clinically meaningful AWS in other settings.


Proteomic analysis of the mammalian mitochondrial ribosome. Identification of protein components in the 28 S small subunit.
The mammalian mitochondrial ribosome (mitoribosome) has a highly protein-rich composition with a small sedimentation coefficient of 55 S, consisting of 39 S large and 28 S small subunits. In the previous study, we analyzed 39 S large subunit proteins from bovine mitoribosome (Suzuki, T., Terasaki, M., Takemoto-Hori, C., Hanada, T., Ueda, T., Wada, A., and Watanabe, K. (2001) J. Biol. Chem. 276, 21724-21736). The results suggested structural compensation for the rRNA deficit through proteins of increased molecular mass in the mitoribosome. We report here the identification of 28 S small subunit proteins. Each protein was separated by radical-free high-reducing two-dimensional polyacrylamide gel electrophoresis and analyzed by liquid chromatography/mass spectrometry/mass spectrometry using electrospray ionization/ion trap mass spectrometer to identify cDNA sequence by expressed sequence tag data base searches in silico. Twenty one proteins from the small subunit were identified, including 11 new proteins along with their complete cDNA sequences from human and mouse. In addition to these proteins, three new proteins were also identified in the 55 S mitoribosome. We have clearly identified a mitochondrial homologue of S12, which is a key regulatory protein of translation fidelity and a candidate for the autosomal dominant deafness gene, DFNA4. The apoptosis-related protein DAP3 was found to be a component of the small subunit, indicating a new function for the mitoribosome in programmed cell death. In summary, we have mapped a total of 55 proteins from the 55 S mitoribosome on the two-dimensional polyacrylamide gels.


Migration of Surgical Clips into the Common Bile Duct after Laparoscopic Cholecystectomy.
Laparoscopic cholecystectomy (LC) is currently the treatment of choice for symptomatic gallstones. Associated complications include bile duct injury, retained common bile duct (CBD) stones, and migration of surgical clips. Clip migration into the CBD can present with recurrent cholangitis over a period of time. Retained CBD stones can be another cause of recurrent cholangitis. A case of two surgical clips migrating into the common bile duct with few retained stones following LC is reported here. The patient had repeated episodes of fever, pain at epigastrium, jaundice, and pruritus 3 months after LC. Liver function tests revealed features of obstructive jaundice. Ultrasonography of the abdomen showed dilated CBD with few stones. In view of acute cholangitis, an urgent endoscopic retrograde cholangiopancreatography was done, which demonstrated few filling defects and 2 linear metallic densities in the CBD. A few retained stones along with 2 surgical clips were removed successfully from the CBD by endoscopic retrograde cholangiopancreatography after papillotomy using a Dormia basket. The patient improved dramatically following the procedure.


The Prenatal Hormone Milieu in Autism Spectrum Disorder.
Though the etiology of autism spectrum disorder (ASD) remains largely unknown, recent findings suggest that hormone dysregulation within the prenatal environment, in conjunction with genetic factors, may alter fetal neurodevelopment. Early emphasis has been placed on the potential role of in utero exposure to androgens, particularly testosterone, to theorize ASD as the manifestation of an "extreme male brain." The relationship between autism risk and obstetric conditions associated with inflammation and steroid dysregulation merits a much broader understanding of the in utero steroid environment and its potential influence on fetal neuroendocrine development. The exploration of hormone dysregulation in the prenatal environment and ASD development builds upon prior research publishing associations with obstetric conditions and ASD risk. The insight gained may be applied to the development of chronic adult metabolic diseases that share prenatal risk factors with ASD. Future research directions will also be discussed.


Evaluation of Visual Information Processing Speed in Depressed People.
Depression disorders are associated with serious dysfunction and depressive symptoms. Cognitive slowing is a clear symptom observed in all depressed people. PVSAT is a measure of cognitive function that specifically assesses visual information processing speed and flexibility, as well as calculation ability. The aim of the present study was to determine whether the Paced Visual Serial Addition Test (PVSAT) might constitute a useful procedure for assessing cognitive functions in depressive disorder. Twenty - eight depressed patients, together with fourteen healthy control (HC) subjects participated in the study. All participants performed the PVSAT and a set of clinical tasks assessing information processing speed, working memory and executive functions. Compared with the HCs, the depressed patients were significantly impaired in their performance of the PVSAT. Significant impairment (compared with controls) was also evidenced by only one of the clinical tasks - the symbol coding task, which assesses information processing speed. Our results demonstrate the high sensitivity of the PVSAT to cognitive impairment. However, correlation analyses showed that the main factor explaining the depressed patients PVSAT impairment was cognitive slowing.


Ultrasensitive Formaldehyde Sensor Based on SnO2 with Rich Adsorbed Oxygen Derived from a Metal Organic Framework.
SnO2 has been a commonly researched gas-sensing material due to its low cost, good performance, and good stability. However, gas sensors based on pure SnO2 usually show a low response or high working temperature. In this work, laminar SnO2 was obtained by using a Sn-based metal organic framework(Sn-MOF)@SnO2 as a precursor. Sn-MOF@SnO2 is prepared at low temperatures using water and dimethylformamide as a solvent, which is simple, low cost, and easily reproducible. After sintering, Sn-MOF@SnO2 is derived to SnO2 with rich adsorbed oxygen, large specific surface area, and unique nanoparticle piled pores, thus showing excellent gas-sensing properties. The prepared SnO2 has an ultrahigh response value of 10,000 to 10 ppm formaldehyde at an optimal working temperature of 120 °C, a fast response/recovery time of 33 s/142 s, and an actual detection limit of lower than 10 ppb as well as high selectivity and high stability. Density functional theory calculations show that the exposed (110) plane of oxygen-rich vacancies in laminar SnO2 can effectively increase the coadsorption capacity of O2 and formaldehyde molecules, thereby improving the formaldehyde gas-sensing performance of the material. The present original approach paves the way to design advanced materials with excellent gas-sensing properties as well as broad application prospects in formaldehyde monitoring.


Role of cholinergic neurons in the cardiovascular responses evoked by central injection of bradykinin or angiotensin II in conscious rats.
Intracerebroventricular (i.c.v.) injection of bradykinin (0.1-10 micrograms) or angiotensin II (0.01-10 micrograms) in conscious, freely moving rats evoked dose-related increases in arterial pressure. The pressor response to bradykinin (BK) was accompanied by an increase in heart rate while angiotensin II (ANG II) decreased heart rate. Pretreatment with hemicholinium-3 to deplete brain acetylcholine levels produced a choline-reversible blockade of the cardiovascular response to BK. In contrast, the pressor response to ANG II was only weakly inhibited by hemicholinium-3 and the bradycardia was unaffected. Central pretreatment with the nicotinic antagonist, hexamethonium (50 micrograms) was more effective than the muscarinic antagonist atropine (20 micrograms) at blocking the cardiovascular responses to i.c.v. injection of BK. Both blocking agents produced a weaker inhibitory effect on the pressor response to ANG II although no anticholinergic pretreatment significantly inhibited the fall in heart rate. These results are consistent with the possibility of a peptidergic-cholinergic interaction in the central cardiovascular actions of BK and perhaps for a component of the pressor response to ANG II.


Biaxial strain distributions in explanted porcine bioprosthetic valves.
Testing whole explanted porcine bioprosthetic valves provides information on changes the valves undergo over time in vivo, and may help elucidate a possible mechanism for bioprosthetic valve failure. The study aim was to measure the static pressure/strain response of whole explanted porcine bioprostheses. Three bioprosthetic valves were explanted prophylactically prior to structural failure. Loading curves (pressure versus strain curves) were generated for these valves using a whole-valve optical strain mapping system. Maximum strain, stiffness, and the occurrence of 'negative compliance' (inverse relationship between cusp strain and applied pressure) were obtained from these curves. All three cusps had very low extensibility (3-10% in the radial direction; 2-4% in the circumferential direction). The non-coronary (NC) cusp was less extensible than the right (RC) or left coronary (LC) cusps in two of the valves. In one valve, the smallest strains were in the RC cusp, where large amounts of calcification were noted. Negative strains were present primarily in one valve. The extensibilities of the three explanted valves were lower than those seen in fresh valves, due to either glutaraldehyde fixation and/or extension of the fibrosal corrugations. Furthermore, the uniqueness of the mechanical properties of the NC cusp previously seen in fresh porcine valves remained through glutaraldehyde fixation and stenting. It is concluded that cusp anisotropy and heterogeneity, as well as the occurrence of negative strains seen in fresh porcine valves, are preserved during the fabrication of porcine bioprostheses.


Bidirectional electron transfer in molecular tetrads.
Two-color excitation of a molecular tetrad leads to directed electron transfer in opposite directions along the molecular axis according to which chromophore is illuminated and gives a 40,000-fold disparity in the lifetimes of the resultant charge-separated states.


Twelve per cent of 6142 eyes treated for neovascular age-related macular degeneration (nAMD) presented with low visual outcome within 2 years. Analysis from the Swedish Macula Registry (SMR).
To analyse characteristics from the SMR to explore the risk factors for visual acuity (VA) below ≤ 35 letters of the Early Treatment Diabetic Retinopathy Study (ETDRS) due to nAMD during a two-year follow-up. This study evaluates 6142 treatment-naïve eyes, with focus on a subgroup of 780 eyes with final VA outcome of ≤ 35 letters, regarding differences of baseline characteristics, change of VA, number of injections and choice of drug to predict visual outcome. Patients with final VA ≤ 35 letters were older; p < 0.0001, and received fewer injections, 6.2 ± 3.8 vs. 8.7 ± 5.4; p < 0.00001. Only 4% of all patients with ≥ 70 letters baseline VA decreased to a final VA of ≤ 35 letters. The two groups with a final VA of ≤ 35 letters and VA > 35 letters presented the following baseline lesion locations; p = 0.001; 61% vs. 57% subfoveal, 18% vs. 21% juxtafoveal and 4% vs. 6% extrafoveal. Lesion size, in the group with final VA ≤ 35 letters, was 2805 ± 2093 μm vs. 2440 ± 1637 μm in the group with a VA of > 35 letters; p = 0.005. A logistic regression analysis including baseline VA, best- or worse-seeing eye, age, membrane size, membrane location, symptom duration showed VA; p = < 0.0001, best- or worse-seeing eye; p = 0.026, age; p = < 0.0001, and membrane size; p = 0.002 to predict a decline of VA within 2 years. In eyes treated for wet AMD and studied for 2 years, 12.7% of eyes declined to a final VA of ≤ 35 letters. Visual acuity, worse-seeing eye treated, age and membrane size turned out as the baseline characteristics that had significantly influenced visual decline to ≤ 35 letters during the two-year follow-up.


Can alcohol hand rubs increase compliance with hand hygiene?
A review of the literature indicates that alcohol hand rubs reduce microbial load, are less irritant to the skin of healthcare workers, and are more easily accessible than conventional methods of hand hygiene. The review also indicates that using alcohol hand rub increases compliance to hand hygiene guideline rates by 25%. This study examines whether making alcohol hand rubs readily available to healthcare workers will increase and maintain compliance with hand hygiene protocols and guidelines, thereby reducing nosocomial infection, or whether the methods of staff education on the use and benefits of products and other interventions need to be examined.


Periodic acid-Schiff staining abnormality in microvillous atrophy: photometric and ultrastructural studies.
The accumulation of periodic acid Schiff (PAS)-positive material in the epithelium in microvillous atrophy (MVA) is diagnostic but unexplained. It occurs earlier in the epithelial life cycle than the formation of microvillous inclusions and warrants further investigation. Scanning photometry was used to assess the distribution of the PAS-positive material within epithelial cells and to assess how this changed with position on the crypt-villus axis. Thiery staining was applied to test the PAS positivity of the secretory granules, and quantitative ultrastructural morphometry was used to study secretory granule distribution in the epithelium. The PAS abnormality arose in upper crypt epithelium in congenital and late-onset MVA and continued up the villus. Thiery staining demonstrated that the secretory granules were PAS positive. Quantitative morphometry showed that secretory granules in congenital MVA were predominantly present in upper crypt and declined in the low villus. In late-onset MVA, secretory granules arose in the upper crypt but predominated in the low villus region. No evidence of secretory granule coalescence with the apical membrane was seen, although evidence of crinophagy was observed. Secretory granule profiles were seen, indicating that they formed part of a membrane-bound vesicular network within the cell, rather than existing simply as discrete bodies. The Golgi complex appeared normal. The secretory granules are responsible for the PAS-positive staining in upper crypt and low villus regions in MVA. They appear to form an intracytoplasmic vesicular network, undergo crinophagy, and decline in prominence in the low to midvillous region. The absence of evidence of coalescence with the apical membrane indicates that the secretory granules arise from a post-Golgi block in exocytosis rather than from endocytosis of gut luminal contents. Periodic acid-Schiff positivity in upper villous regions arises from microvillous inclusions and lysosomal bodies.


Ten self-inflicted intracranial penetrating nail gun injuries.
Penetrating craniocerebral injuries from nail gun use are rare. We describe a case of 10 self-inflicted nail gun injuries with intracranial penetrations. We also review the literature and discuss management strategies of such craniocerebral trauma. A 33-year-old male with a long-standing history of severe depression took a nail gun and sustained 10 penetrating intracranial injuries. Initial neuroimaging revealed 10 penetrating nails, all sparing the major cerebral vasculature. Immediate surgical removal was undertaken in the surgical suite using a combination of craniotomies, craniectomies, and blind removal. Intracranial injuries from self-inflicted nail gun misuse is becoming increasingly more frequent. Initial appropriate clinical decision-making are critical in preventing further cortical or vascular damage.


Anandamide receptors.
Anandamide (N -arachidonoyl-ethanolamine, AEA) was the first endogenous ligand of cannabinoid receptors to be discovered. Yet, since early studies, AEA appeared to exhibit also some effects that were not mediated by cannabinoid CB(1) or CB(2) receptors. Indeed, AEA exerts some behavioral actions also in mice with genetically disrupted CB(1) receptors, whereas in vitro it is usually a partial agonist at these receptors and a weak activator of CB(2) receptors. Nevertheless, several pharmacological effects of AEA are mediated by CB(1) receptors, which, by being coupled to G-proteins, can be seen as AEA "metabotropic" receptors. Furthermore, at least two different, and as yet uncharacterized, G-protein-coupled AEA receptors have been suggested to exist in the brain and vascular endothelium, respectively. AEA is also capable of directly inhibiting ion currents mediated by L-type Ca(2+) channels and TASK-1 K(+) channels. However, to date the only reasonably well characterized, non-cannabinoid site of action for AEA is the vanilloid receptor type 1 (VR1), a non-selective cation channel gated also by capsaicin, protons and heat. VR1 might be considered as an AEA "ionotropic" receptor and, under certain conditions, mediates effects ranging from vasodilation, broncho-constriction, smooth muscle tone modulation and nociception to stimulation of hippocampal pair-pulse depression, inhibition of tumor cell growth and induction of apoptosis.


Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer.
Normal cells explore multiple states to survive stresses encountered during development and self-renewal as well as environmental stresses such as starvation, DNA damage, toxins or infection. Cancer cells co-opt normal stress mitigation pathways to survive stresses that accompany tumour initiation, progression, metastasis and immune evasion. Cancer therapies accentuate cancer cell stresses and invoke rapid non-genomic stress mitigation processes that maintain cell viability and thus represent key targetable resistance mechanisms. In this Review, we describe mechanisms by which tumour ecosystems, including cancer cells, immune cells and stroma, adapt to therapeutic stresses and describe three different approaches to exploit stress mitigation processes: (1) interdict stress mitigation to induce cell death; (2) increase stress to induce cellular catastrophe; and (3) exploit emergent vulnerabilities in cancer cells and cells of the tumour microenvironment. We review challenges associated with tumour heterogeneity, prioritizing actionable adaptive responses for optimal therapeutic outcomes, and development of an integrative framework to identify and target vulnerabilities that arise from adaptive responses and engagement of stress mitigation pathways. Finally, we discuss the need to monitor adaptive responses across multiple scales and translation of combination therapies designed to take advantage of adaptive responses and stress mitigation pathways to the clinic.


Robust Matrix Factorization With Spectral Embedding.
Nonnegative matrix factorization (NMF) and spectral clustering are two of the most widely used clustering techniques. However, NMF cannot deal with the nonlinear data, and spectral clustering relies on the postprocessing. In this article, we propose a Robust Matrix factorization with Spectral embedding (RMS) approach for data clustering, which inherits the advantages of NMF and spectral clustering, while avoiding their shortcomings. In addition, to cluster the data represented by multiple views, we present the multiview version of RMS (M-RMS), and the weights of different views are self-tuned. The main contributions of this research are threefold: 1) by integrating spectral clustering and matrix factorization, the proposed methods are able to capture the nonlinear data structure and obtain the cluster indicator directly; 2) instead of using the squared Frobenius-norm, the objectives are developed with the l2,1 -norm, such that the effects of the outliers are alleviated; and 3) the proposed methods are totally parameter-free, which increases the applicability for various real-world problems. Extensive experiments on several single-view/multiview data sets demonstrate the effectiveness of our methods and verify their superior clustering performance over the state of the arts.


Nanofibrous rutile-titania/graphite composite derived from natural cellulose substance.
Calcination and carbonization of ultrathin titania gel film pre-coated cellulose nanofibers of ordinary laboratory filter paper at 1300 degrees C under argon atmosphere yielded a hierarchical nanofibrous rutile-titania/carbon composite material. The carbon fibers derived from the initial cellulose nanofibers possess a core-shell structure with amorphous carbon at the inner part and graphite state carbon at the outer part. The initial titania gel films were converted into rutile phase titania nanoparticles with sizes of 20-50 nm anchored on the surface of the carbon fibers. The resulting composite possesses considerable electric conductivity as well as decolorization activity towards dye-bearing wastewater.


Early experience with stentless versus stented valves.
The Toronto stentless porcine valve (SPV) was designed to improve hemodynamics after aortic valve replacement by maximizing available flow area in comparison to stented valves (STD). To assess possible hemodynamic differences between STD and SPV, 59 patients undergoing isolated aortic valve replacement (+/-coronary artery bypass graft) were prospectively evaluated by preoperative and 3- to 6-month postoperative echocardiography. Among these, 23 patients received a STD, whereas 36 received the Toronto SPV. The mean size (mm) of SPV implanted was larger (SPV, 26.6+/-2.1; STD, 24.0+/-2.9; P=0.0002). Patients receiving STD valves were older and had a higher prevalence of coronary artery disease and congestive heart failure. There were no preoperative differences in left ventricular mass index (g/mo2), peak or mean pressure gradients (mmHg), effective orifice area (cm2), extent of fractional shortening (%), or velocity of circumferential shortening (cf/sec). ANOVA demonstrated a significant reduction in left ventricular mass index at 3 to 6 months (P=.0001) but no differences in left ventricular mass index regression between groups (STD, -28.8+/-37.5; SPV, -31.2+/-32.4; P=.36). Effective orafice area was increased postoperatively (P=.0001), particularly among SPV cases (STD, 1.5+/-0.4; SPV, 1.9+/-0.7; P=.01). Postoperative left ventricular mass index and mean pressure gradient were reduced (P=.0001) but did not differ between groups. Fractional shortening and velocity of circumferential shortening were greater in the SPV patients at 3 to 6 months after aortic valve replacement (P=.0004 and .0001, respectively), and an interactive effect was seen between time and prosthetic group (P=.0028 and .032, respectively). In a consecutive series of patients, we identified no hemodynamic differences between STD and SPV, although ventricular function improved after SPV. Because of the nonrandomized nature of the study, selection bias may have accounted for some of the observed results. A prospective, randomized trial is necessary to determine the hemodynamic advantages, if any, of the SPV valve.


A quantitative model of population pressure and its potential use in development planning.
An attempt is made to develop a quantitative model of the concept of population pressure, using the example of population pressure on land resources in agricultural societies. "The model shows that environmental quality is tied to population growth and that population pressure does not bear relationship with population density." The implications of the findings for development planning are considered. (summary in IND)


The false positive troponin results: case studies of analytical interference.
Cardiac troponin I and T are particularly sensitive and specific markers for cardiomyocyte damage. Myocardial injury can occur due to a discrepancy between oxygen supply and demand (eg coronary artery occlusion and arrhythmias), other cardiac causes (eg pericarditis, myocarditis, cardiac surgery, cardioversion etc) or systemic conditions (eg sepsis, stroke and chronic renal disease). The latest European Society of Cardiology guidelines help to guide clinicians through these different causes. Occasionally troponin concentrations may not fit the clinical presentation and, therefore, other aetiologies should be considered. An under-appreciated basis of a high troponin concentration is a false positive result, which can be attributable to analytical interference from components in the patient's blood. Uncovering this interference can be pivotal to avoid unnecessary and potentially harmful investigations or treatment for patients. We present two cases of false positive troponin results caused by analytical interference. The normal reference range for the assay (Access; Beckman Coulter, High Wycombe, UK) used at our organisation is 0-18 ng/L.


General antimutators are improbable.
Antimutator mutations reduce spontaneous mutation rates, at least at some sites and along some pathways. Antimutators have been found in several microbial systems since their initial discovery in bacteriophage T4, where they occur mainly among mutations of gene 43 (which encodes the viral DNA polymerase). The phage T4 antimutators are highly specific, often strongly reducing mutations rates but only along specific pathways, usually A.T-->G.C. They may fail to affect other pathways, such as G.C-->A.T, and may even accelerate mutation at yet other pathways, such as transversions (R.Y-->Y.R). Both enzymatic and evolutionary considerations suggest that it should be difficult to isolate strong, general antimutator mutations, that is, mutations that substantially lower the total spontaneous mutation rate over the entire genome without producing strongly deleterious side effects. This notion has been tested by measuring mutation rates over a target comprising several kilobases in a set of phage T4 antimutators. In each case, this rate was indistinguishable from or greater than the wild-type rate. A survey of reports describing antimutators in other microbes reveals that none are yet demonstrated to be general antimutators.


Color-tunable upconversion photoluminescence and highly performed optical temperature sensing in Er3+/Yb3+ co-doped ZnWO4.
Er3+/Yb3+ co-doped ZnWO4 phosphors were synthesized by a solid state reaction method and their structure, photoluminescence and temperature sensing properties were characterized. The color-tunable upconversion emissions (from green to red) were observed by increasing the doped Er3+/Yb3+ concentration. The temperature sensing properties were studied by using the fluorescence intensity ratio technique in the temperature range of 83-583 K, and high performance was obtained. The maximum sensitivity is found to be 0.0099 K-1 at 583 K. The XRD Rietveld refinement revealed that the phosphors crystallized in monoclinic structure with the space group P2/c (13) at room temperature. The results suggest that the phosphors could be an exceptional choice for next generation luminescence-based temperature sensing devices as well as in multiple biolabels.


A comparison of two class 10 pathogenesis-related genes from alfalfa and their activation by multiple stresses and stress-related signaling molecules.
A collection of 29 pathogenesis-related 10 (PR10) genes of Medicago sativa and Medicago truncatula showed that they were almost all obtained from cDNA libraries of tissues undergoing abiotic or biotic stresses. The predicted proteins could be divided into two subclasses, PR10.1 and PR10.2, but in silico predicted models of their three-dimensional structures revealed that they could be further divided based on size of the hydrophobic internal cavity and number of β-bulges. A comparison of the expression of two highly similar M. sativa subclass PR10.1 genes, MsPR10.1A and MsPR10.1B, predicted to have similar sized hydrophobic internal cavities, but a different number of β-bulges revealed differences in their expression patterns. MsPR10.1A was induced faster than MsPR10.1B by ABA, ethylene, and X. campestris pv. alfalfae, but slower than MsPR10.1B by harvesting and wounding. Unlike MsPR10.1A, MsPR10.1B expression was induced in non-harvested tissues following harvesting, but was not induced by heat treatment. Histochemical observations of Nicotiana benthamiana transformed with 657 bp of the MsPR10.1A promoter fused to the β-glucuronidase (GUS) gene showed that GUS expression was wound-inducible in leaves, which was consistent with MsPR10.1A expression in alfalfa leaves. GUS expression in stems and leaves was mostly in vascular tissue. The MsPR10.1A promoter may be valuable in controlling the expression in vascular tissues and disease resistance.


Annexin II-binding immunoglobulins in patients with lupus nephritis and their correlation with disease manifestations.
Annexin II on mesangial cell surface mediates the binding of anti-dsDNA antibodies and consequent downstream inflammatory and fibrotic processes. We investigated the clinical relevance of circulating annexin II-binding immunoglobulins (Igs) in patients with severe proliferative lupus nephritis, and renal annexin II expression in relation to progression of nephritis in New Zealand Black and White F1 mice (NZBWF1/J) mice. Annexin II-binding Igs in serum were measured by ELISA. Ultrastructural localization of annexin II was determined by electron microscopy. Seropositivity rates for annexin II-binding IgG and IgM in patients with active lupus nephritis were significantly higher compared with controls (8.9%, 1.3% and 0.9% for annexin II-binding IgG and 11.1%, 4.0% and 1.9% for annexin II-binding IgM for patients with active lupus nephritis, patients with non-lupus renal disease and healthy subjects respectively). In lupus patients, annexin II-binding IgM level was higher at disease flare compared with remission. Annexin II-binding IgG and IgM levels were associated with that of anti-dsDNA and disease activity. Annexin II-binding IgG and IgM levels correlated with histological activity index in lupus nephritis biopsy samples. In NZBWF1/J mice, serum annexin II-binding IgG and IgM levels and glomerular annexin II and p11 expression increased with progression of active nephritis. Annexin II expression was present on mesangial cell surface and in the mesangial matrix, and co-localized with electron-dense deposits along the glomerular basement membrane. Our results show that circulating annexin II-binding IgG and IgM levels are associated with clinical and histological disease activity in proliferative lupus nephritis. The co-localization of annexin II and p11 expression with immune deposition in the kidney suggests pathogenic relevance.


[Use of isothiobarbamin in the correction of disorders of the vital activities of the brain in intracerebral hemorrhage].
Isothiobarbamin injected intravenously to cats in the phase of circulatory hypoxia 1-2 days after intracerebral hemorrhage improves the functional activity, blood supply, oxygen supply to the brain, prevents excessive accumulation of lactate in the brain tissue. The drug exerts the stimulating effect on the disordered local blood flow: the blood supply to the ischemic areas increases, and that of the hyperemic ones decreases. The mechanism of the vasodilative effect of isothiobarbamin is due to inhibition of Ca2+ delivery through the potential-dependent and serotonin-activated channels of the smooth muscle plasmic membrane. The drug activity increases with a rise of the initial vascular tone.


Efficacy of Acellular Dermal Matrix Type in Treatment of Capsular Contracture in Breast Augmentation: A Systematic Review and Meta-Analysis.
Capsular contracture is a known complication of breast augmentation and is among the top reasons for revisional breast augmentation procedures. The use of acellular dermal matrix (ADM) has been shown to reduce the rate of capsular contracture in breast reconstruction and augmentation, theorizing that it acts as a protective barrier between the implant capsule and inflammatory process responsible for capsular contracture. The role of ADM in treatment of capsular contracture has been investigated in numerous studies, with a variety of ADMs. The aim of this study was to perform a systematic review of existing literature on the use of ADM for treatment of capsular contracture in aesthetic breast augmentation patients to investigate differences in efficacy of ADM types. The PubMed, Embase, and CINAHL databases were systematically reviewed for articles pertaining to capsular contracture, acellular dermal matrices, and breast augmentation. Number of patients, type of ADM, Baker grade, follow-up time, complication rate, and capsular contracture rate were recorded from identified articles. Data was pooled from studies to calculate a capsular contracture rate for each ADM type, with a chi-squared test performed for analysis. Identified studies with a comparative group were included in a meta-analysis utilizing risk ratio (RR) to assess the efficacy of ADM. Nine articles including ADM for treatment of capsular contracture in breast augmentation met criteria for inclusion, with a total of 481 breasts. Strattice was the most commonly utilized ADM (n = 391), followed by AlloDerm (n = 57). There was a statistically significant difference in efficacy of ADM among the studied ADM types (P < .001). AlloDerm, FlexHD, and DermaMatrix had the lowest capsular contracture rates (0%). NeoForm and SurgiMend had the highest capsular contracture rates (each 25%, but with n = 4 and n = 8, respectively). Strattice had a capsular contracture rate of 1.53% in the pooled data, and meta-analysis showed that Strattice reduced the risk of capsular contracture (RR 0.14 [95% CI 0.06, 0.31]) compared with conventional treatment. Acellular dermal matrices appear to be effective at treating capsular contracture after breast augmentation while maintaining a low complication rate. Overall capsular contracture rates are low with the use of ADM. There is a statistically significant difference in efficacy among ADM types. Meta-analysis shows that Strattice is effective at reducing the risk of capsular contracture in breast augmentation patients when compared to conventional treatment. Future research, especially in the form of randomized controlled trials, is needed to further investigate the efficacy of various ADMs in the treatment of capsular contracture.


Melt movement through the Icelandic crust.
We use both seismology and geobarometry to investigate the movement of melt through the volcanic crust of Iceland. We have captured melt in the act of moving within or through a series of sills ranging from the upper mantle to the shallow crust by the clusters of small earthquakes it produces as it forces its way upward. The melt is injected not just beneath the central volcanoes, but also at discrete locations along the rift zones and above the centre of the underlying mantle plume. We suggest that the high strain rates required to produce seismicity at depths of 10-25 km in a normally ductile part of the Icelandic crust are linked to the exsolution of carbon dioxide from the basaltic melts. The seismicity and geobarometry provide complementary information on the way that the melt moves through the crust, stalling and fractionating, and often freezing in one or more melt lenses on its way upwards: the seismicity shows what is happening instantaneously today, while the geobarometry gives constraints averaged over longer time scales on the depths of residence in the crust of melts prior to their eruption. This article is part of the Theo Murphy meeting issue 'Magma reservoir architecture and dynamics'.


Biophysical Characterization of the Leukemic Bone Marrow Vasculature Reveals Benefits of Neoadjuvant Low-Dose Radiation Therapy.
Although vascular alterations in solid tumor malignancies are known to decrease therapeutic delivery, the effects of leukemia-induced bone marrow vasculature (BMV) alterations on therapeutic delivery are not well known. Additionally, functional quantitative measurements of the leukemic BMV during chemotherapy and radiation therapy are limited, largely due to a lack of high-resolution imaging techniques available preclinically. This study develops a murine model using compartmental modeling for quantitative multiphoton microscopy (QMPM) to characterize the malignant BMV before and during treatment. Using QMPM, live time-lapsed images of dextran leakage from the local BMV to the surrounding bone marrow of mice bearing acute lymphoblastic leukemia (ALL) were taken and fit to a 2-compartment model to measure the transfer rate (Ktrans), fractional extracellular extravascular space (νec), and vascular permeability parameters, as well as functional single-vessel characteristics. In response to leukemia-induced BMV alterations, the effects of 2 to 4 Gy low-dose radiation therapy (LDRT) on the BMV, drug delivery, and mouse survival were assessed post-treatment to determine whether neoadjuvant LDRT before chemotherapy improves treatment outcome. Mice bearing ALL had significantly altered Ktrans, increased νec, and increased permeability compared with healthy mice. Angiogenesis, decreased single-vessel perfusion, and decreased vessel diameter were observed. BMV alterations resulted in disease-dependent reductions in cellular uptake of Hoechst dye. LDRT to mice bearing ALL dilated BMV, increased single-vessel perfusion, and increased daunorubicin uptake by ALL cells. Consequently, LDRT administered to mice before receiving nilotinib significantly increased survival compared with mice receiving LDRT after nilotinib, demonstrating the importance of LDRT conditioning before therapeutic administration. The developed QMPM enables single-platform assessments of the pharmacokinetics of fluorescent agents and characterization of the BMV. Initial results suggest BMV alterations after neoadjuvant LDRT may contribute to enhanced drug delivery and increased treatment efficacy for ALL. The developed QMPM enables observations of the BMV for use in ALL treatment optimization.


Intensive intravenous infusion of insulin in diabetic cats.
Remission occurs in 10-50% of cats with diabetes mellitus (DM). It is assumed that intensive treatment improves β-cell function and increases remission rates. Initial intravenous infusion of insulin that achieves tight glycemic control decreases subsequent insulin requirements and increases remission rate in diabetic cats. Thirty cats with newly diagnosed DM. Prospective study. Cats were randomly assigned to one of 2 groups. Cats in group 1 (n = 15) received intravenous infusion of insulin with the goal of maintaining blood glucose concentrations at 90-180 mg/dL, for 6 days. Cats in group 2 (n = 15) received subcutaneous injections of insulin glargine (cats ≤4 kg: 0.5-1.0 IU, q12h; >4 kg 1.5-2.0 IU, q12h), for 6 days. Thereafter, all cats were treated with subcutaneous injections of insulin glargine and followed up for 6 months. Cats were considered in remission when euglycemia occurred for ≥4 weeks without the administration of insulin. Nonparametric tests were used for statistical analysis. In groups 1 and 2, remission was achieved in 10/15 and in 7/14 cats (P = .46), and good metabolic control was achieved in 3/5 and in 1/7 cats (P = .22), respectively. Overall, good metabolic control or remission occurred in 13/15 cats of group 1 and in 8/14 cats of group 2. In group 1, the median insulin dosage given during the 6-month follow-up was significantly lower than in group 2 (group 1: 0.32 IU/kg/day, group 2: 0.51 IU/kg/day; P = .013). Initial intravenous infusion of insulin for tight glycemic control in cats with DM decreases insulin requirements during the subsequent 6 months.


Regulation of nuclear envelope assembly/disassembly by MAP kinase.
Mouse eggs arrested in metaphase II display high levels of cdc2/cyclin B1 and MAP protein kinase activities. Following fertilization there is a time-dependent decrease in the activity of each of these protein kinases. The decline in cdc2/cyclin B1 protein kinase correlates with the resumption of meiosis and the emission of the second polar body and precedes the decline in MAP kinase activity, which correlates temporally with the formation of the male and female pronuclear envelopes. These results suggest that high levels of MAP kinase activity are incompatible with the presence of a pronuclear envelope. To test this possibility, we expressed in mouse eggs a constitutively active form of MAP kinase kinase (MEK) whose only known target is p42/p44 MAP kinase. We show that following fertilization cdc2/cyclin B1 kinase activity declines and a second polar body is emitted. The endogenous MAP kinase remains active, however, and no pronuclear envelopes form. Thus, high levels of MAP kinase activity by itself in mouse eggs appear incompatible with the presence of a pronuclear envelope.


Recipient screening prior to solid-organ transplantation.
Screening a potential transplant recipient for infectious diseases is an important component of the transplantation process. Such screening may lead to the discovery and treatment of occult active infection, may help determine posttransplant prophylactic strategies, or may disqualify the recipient from receiving a transplant. The pretransplant period also affords an opportunity for updating vaccination status and providing education regarding the reduction of posttransplant infectious risks. The present brief review will outline the investigation of preexisting active infection, as well as latent bacterial, mycobacterial, fungal, parasitic, and viral infections. Recommendations for pretransplant immunization and education are provided.


Trends of Healthy Life Expectancy of the Elderly in China in 1994-2015: Revisiting From the Perspective of Morbidity Transition.
Research on healthy life expectancy (HLE) in China has been fueled by a spate of new data sources and studies, yet no consensus is reached on the pattern of HLE changes and the underlying mechanism. This study examined the change of HLE in China over 20 years with long term national data. Health status, measured by activities of daily living, is combined with mortality to calculate the disability-free life expectancy by the Sullivan method. The results show that the HLE rose slower than life expectancy (LE) in 1994-2004, indicating morbidity expansion. However, in 2010-2015, the proportion of HLE to LE increased, manifesting morbidity compression. A counterfactual analysis further shows that health improvement has been increasingly important in increasing HLE in 2010-2015, despite the dominance of mortality decline. The findings suggest that morbidity can transition between compression, expansion and dynamic equilibrium over a long period due to different combinations of mortality and health improvements. Given the limited data in this study, whether and how morbidity transitions unfold in the future remains open and requires further research.


Multi-scale approach for the rheological characteristics of emulsions using molecular dynamics and lattice Boltzmann method.
An emulsion system was simulated under simple shear rates to analyze its rheological characteristics using a hierarchical multi-scale approach. The molecular dynamics (MD) simulation was used to describe the interface of droplets in an emulsion. The equations derived from the MD simulation relative to interfacial tension, temperature, and surfactant concentration were applied as input parameters within lattice Boltzmann method (LBM) calculations. In the LBM simulation, we calculated the relative viscosity of an emulsion under a simple shear rate along with changes in temperature, shear rate, and surfactant concentration. The equations from the MD simulation showed that the interfacial tension of the droplets tended to decrease with an increase in temperature and surfactant concentration. The relative viscosity from the LBM simulation decreased with an increase in temperature. The shear thinning phenomena explaining the inverse proportion between shear rate and viscosity were observed. An increase in the surfactant concentration caused an increase in the relative viscosity for a decane-in-water emulsion, because the increased deformation caused by the decreased interfacial tension significantly influenced the wall shear stress.


Pharmacological mechanisms of clinically favorable properties of a selective beta1-adrenoceptor antagonist, nebivolol.
Nebivolol is a racemic mixture of d- and l-enantiomers. The drug is characterized by beta(1)-adrenoceptor selectivity and long-acting beta-blockade exerted predominantly by d-enantiomer. Nebivolol is devoid of intrinsic sympathomimetic activity and has no relevant membrane stabilizing action. Antiproliferative properties of nebivolol were demonstrated in endothelial and smooth muscle cell cultures. Infusion of nebivolol causes a vasodilation in all vascular beds by endothelial-dependent mechanism involving stimulation of beta(3)-adrenoceptors as well as by endothelial-independent mechanism. Nebivolol possesses not only direct vasodilator properties but also augments the action of endothelium-dependent vasodilators. The antioxidant property of nebivolol can at least in part explain why treatment with this drug enhances eNOS activity and minimizes the reperfusion-induced myocardial injury. The systemic effects of nebivolol in humans have an unusual hemodynamic profile. In contrast to traditional beta-adrenoceptor antagonists, nebivolol reduces preload and afterload due to systemic vasodilation and improves arterial distensibility. At 5 mg daily nebivolol effectively reduces systolic and diastolic blood pressure over a 24-h period. During treatment with nebivolol arterial pressure follows the natural circadian rhythm. Trough-to-peak ratio for nebivolol is 0.9. It has been demonstrated in numerous placebo-controlled studies that exercise tolerance is not reduced during nebivolol therapy. By chronic administration to patients with left ventricular dysfunction nebivolol increases myocardial contractility. Nebivolol produced no significant changes in lipid levels, insulin sensitivity or glucose tolerance. These findings make nebivolol a promising therapeutic tool for the treatment of arterial hypertension and chronic heart failure.


Birds and anthropogenic noise: are urban songs adaptive?
In cities with intense low-frequency traffic noise, birds have been observed to sing louder and at a higher pitch. Several studies argue that higher song pitch is an adaptation to reduce masking from noise, and it has even been suggested that the song divergence between urban and nonurban songs might lead to reproductive isolation. Here we present models of signal transmission to compare the benefits of raised song amplitude and song pitch in terms of sound transmission. We chose two bird species that sing with higher pitch in urban areas, the great tit (Parus major) and the blackbird (Turdus merula). For both species, we calculated communication distances in response to different levels of urban noise and in their natural forest habitats. We found that an increase in vocal pitch increased communication distance only marginally. In contrast, vocal amplitude adjustments had a strong and significantly larger effect. Our results indicate that frequency changes of urban songs are not very effective in mitigating masking from traffic noise. Increased song pitch might not be an adaptation to reduce signal masking but a physiological side effect of singing at high amplitudes or an epiphenomenon of urbanization that is not related to signal transmission.


Lung Cancer Associated with Sarcoidosis - A case report -.
Sarcoidosis is a somewhat common pulmonary disease, but the concurrence of lung cancer and sarcoidosis in the same patient is very rare. Because sarcoidosis usually presents as mediastinal lymphadenopathies, this concurrence in a lung cancer patient detected radiologically is apt to be misunderstood to be mediastinal metastases, and it is thus considered to be an unresectable disease. We report a case of lung cancer associated with sarcoidosis that developed in a 65-year-old woman who underwent surgery. Radiological studies revealed a 1.9×1.7 cm mass in the left upper lobe with multiple enlarged bilateral mediastinal lymph nodes (2R, 3a, 4R, 4L, 5, 6, 7, 8R). Pathologic findings showed that the mass was a well-differentiated adenocarcinoma and all of the enlarged mediastinal lymph nodes were granulomas without cancer metastasis. We report this case with a review of the literature.


RAPTA-Decorated Polyacrylamide Nanoparticles: Exploring their Synthesis, Physical Properties and Effect on Cell Viability.
In this study, we report the first successful immobilisation of a known cytoactive [Ru(η6 -arene)(C2 O4 )PTA] (RAPTA) complex to a biologically inert polyacrylamide nanoparticle support. The nanoparticles have been characterised by zetasizer analysis, UV/Vis, ATR-FTIR, TGA and ICP-MS to qualitatively and quantitatively confirm the presence of the metallodrug on the surface of the carrier. The native RAPTA complex required a concentration of 50 μM to produce a cell viability of 47.1±2.1 % when incubated with human Caucasian colorectal adenocarcinoma cells for 72 h. Under similar conditions a cell viability of 45.1±1.9 % was obtained with 0.5 μM of RAPTA complex in its immobilised form. Therefore, conjugation of the RAPTA metallodrug to our nanoparticle carriers resulted in a significant 100-fold decrease in effective concentration of ruthenium required for a near identical biological effect on cell viability.


Metabolic Changes in Tumor Microenvironment: How Could They Affect γδ T Cells Functions?
The metabolic changes that occur in tumor microenvironment (TME) can influence not only the biological activity of tumor cells, which become more aggressive and auto sustained, but also the immune response against tumor cells, either producing ineffective responses or polarizing the response toward protumor activity. γδ T cells are a subset of T cells characterized by a plasticity that confers them the ability to differentiate towards different cell subsets according to the microenvironment conditions. On this basis, we here review the more recent studies focused on altered tumor metabolism and γδ T cells, considering their already known antitumor role and the possibility of manipulating their effector functions by in vitro and in vivo approaches. γδ T cells, thanks to their unique features, are themselves a valid alternative to overcome the limits associated with the use of conventional T cells, such as major histocompatibility complex (MHC) restriction, costimulatory signal and specific tumor-associated antigen recognition. Lipids, amino acids, hypoxia, prostaglandins and other metabolic changes inside the tumor microenvironment could reduce the efficacy of this important immune population and polarize γδ T cells toward IL17 producing cells that play a pro tumoral role. A deeper knowledge of this phenomenon could be helpful to formulate new immunotherapeutic approaches that target tumor metabolisms.


Structural analysis of unstable norbixin isomers guided by pure shift nuclear magnetic resonance.
We report the analysis of complex samples obtained during the microwave irradiation/heating of norbixin, which has been identified as a potential therapeutic target for age-related macular degeneration (AMD). In this context, identifying the different isomers that are obtained during its degradation is of primary importance. However, this characterization is challenging because, on the one hand, some of these isomers are unstable, and on the other hand, the 1 H spectra of these isomeric mixtures are poorly resolved. We could successfully apply 1D pure shift experiments to obtain ultrahigh-resolution 1 H nuclear magnetic resonance (NMR) spectra of the norbixin isomer samples and exploit their information content to analyze complementary 2D NMR data and describe accurately their isomeric composition.


Use of topical tranexamic acid or aminocaproic acid to prevent bleeding after major surgical procedures.
To evaluate the literature describing topical use of tranexamic acid or aminocaproic acid for prevention of postoperative bleeding after major surgical procedures. Literature was retrieved through MEDLINE (1946-September 2011) and International Pharmaceutical Abstracts (1970-September 2011) using the terms tranexamic acid, aminocaproic acid, antifibrinolytic, topical, and surgical. In addition, reference citations from publications identified were reviewed. All identified articles in English were evaluated. Clinical trials, case reports, and meta-analyses describing topical use of tranexamic acid or aminocaproic acid to prevent postoperative bleeding were included. A total of 16 publications in the setting of major surgical procedures were included; the majority of data were for tranexamic acid. For cardiac surgery, 4 trials used solutions containing tranexamic acid (1-2.5 g in 100-250 mL of 0.9% NaCl), and 1 trial assessed a solution containing aminocaproic acid (24 g in 250 mL of 0.9% NaCl). These solutions were poured into the chest cavity before sternotomy closure. For orthopedic procedures, all of the data were for topical irrigation solutions containing tranexamic acid (500 mg-3 g in 50-100 mL of 0.9% NaCl) or for intraarticular injections of tranexamic acid (250 mg to 2 g in 20-50 mL of 0.9% sodium chloride, with or without carbazochrome sodium sulfate). Overall, use of topical tranexamic acid or aminocaproic acid reduced postoperative blood loss; however, few studies reported a significant reduction in the number of packed red blood cell transfusions or units given, intensive care unit stay, or length of hospitalization. Topical application of tranexamic acid and aminocaproic acid to decrease postsurgical bleeding after major surgical procedures is a promising strategy. Further data are needed regarding the safety of this hemostatic approach.


[Metabonomics study of lung cancer cells based on liquid l chromatography-mass spectrometry].
The metabolic profiles of the polar metabolites and the non-polar metabolites in lung tumor cell lines H358, A549, HCC827, H1299, Calu-3, Calu-l, PC-9 and normal cell line MRC-5 were analyzed separately using high performance liquid chromatography-quadrupole time-of flight mass spectrometry (HPLC-Q-TOF/MS). Partial least square discriminant analysis ( PLS-DA) was used to process the metabolic data. The results showed that the metabolites of the lung cancer cell lines and normal cell line have significant differences. Further, 10 polar metabolites and 21 non-polar metabolites which had a significant contribution to classification were selected and preliminarily identified due to the accurate mass. Comparing with the normal cell line, the lung tumor cell lines present an abnormal metabolism in protein, fatty acid, and phospholipids. These results may provide important information for the early diagnosis of lung cancer.


Review of the evidence base for treatment of childhood psychopathology: internalizing disorders.
This article reviews the empirical literature on psychosocial, psychopharmacological, and adjunctive treatments for children between the ages of 6 and 12 with internalizing disorders. The aim of this review was to identify interventions that have potential to prevent substance use disorders in adolescence by treating internalizing disorders in childhood. Results suggest that a variety of behavioral, cognitive-behavioral, and pharmacological interventions are effective in reducing symptoms of childhood depression, phobias, and anxiety disorders. None of the studies reviewed included substance abuse outcomes. Thus, little can be said about the relationship between early treatment and the prevention of later substance use. The importance of evaluating the generalizability of research-supported interventions to community settings is highlighted and recommendations for future research are offered.


Augmented β-Cell Function and Mass in Glucocorticoid-Treated Rodents Are Associated with Increased Islet Ir-β /AKT/mTOR and Decreased AMPK/ACC and AS160 Signaling.
Glucocorticoid (GC) therapies may adversely cause insulin resistance (IR) that lead to a compensatory hyperinsulinemia due to insulin hypersecretion. The increased β-cell function is associated with increased insulin signaling that has the protein kinase B (AKT) substrate with 160 kDa (AS160) as an important downstream AKT effector. In muscle, both insulin and AMP-activated protein kinase (AMPK) signaling phosphorylate and inactivate AS160, which favors the glucose transporter (GLUT)-4 translocation to plasma membrane. Whether AS160 phosphorylation is modulated in islets from GC-treated subjects is unknown. For this, two animal models, Swiss mice and Wistar rats, were treated with dexamethasone (DEX) (1 mg/kg body weight) for 5 consecutive days. DEX treatment induced IR, hyperinsulinemia, and dyslipidemia in both species, but glucose intolerance and hyperglycemia only in rats. DEX treatment caused increased insulin secretion in response to glucose and augmented β-cell mass in both species that were associated with increased islet content and increased phosphorylation of the AS160 protein. Protein AKT phosphorylation, but not AMPK phosphorylation, was found significantly enhanced in islets from DEX-treated animals. We conclude that the augmented β-cell function developed in response to the GC-induced IR involves inhibition of the islet AS160 protein activity.


The influence of client's ethnicity on psychotropic medication management in community mental health services.
The aim of this study was to investigate whether people born in non-English-speaking countries differed from clients born in Australia on quality of medication management, measured by mean neuroleptic dose, method of administration, use of atypical antipsychotics and perceived compliance with medication, and to investigate the influence of matching the client with a case manager from the same ethnic background on these measures. Information about medication and perceived compliance was provided for 168 clients of five community mental health services in Melbourne. Chlorpromazine equivalent doses (CPZe) were calculated, and average dose, route of administration, percentage receiving atypical antipsychotics and perceived compliance with medication were analysed by country of birth and preferred language. Each analysis was repeated for clients matched to a case manager from the same ethno-linguistic background compared to those with 'unmatched' case managers. While non-English-speaking background (NESB) clients generally did not receive different dose sizes, those born in Vietnam had a lower mean dose. People born in a non-English-speaking country tended to be more likely than the Australian born to receive a depot injection, although this was not quite statistically significant. Twenty-seven percent of clients received an atypical neuroleptic; age was a significant factor, with older clients less likely to receive an atypical. There was no difference in receipt of atypicals or perceived compliance by country of birth, language or gender. Matching for a case manager of the same background had no effect except for route of administration, with matched clients less likely to receive depot medication than unmatched. Generally, the ethnic background of clients had little influence on the quality of medication management they received from community mental health services.


The Pseudomonas aeruginosa rhlAB operon is not expressed during the logarithmic phase of growth even in the presence of its activator RhlR and the autoinducer N-butyryl-homoserine lactone.
The Pseudomonas aeruginosa rhlAB operon encodes the enzyme rhamnosyltransferase 1, which produces the biosurfactant mono-rhamnolipid; rhlAB induction is dependent on the quorum-sensing transcription activator RhlR complexed with the autoinducer N-butyryl-homoserine lactone (C(4)-HSL). In this work we studied rhlAB induction in a P. aeruginosa and Escherichia coli background. We found that, in both bacteria, its expression is not induced during the logarithmic phase of growth even in the presence of RhlR and C(4)-HSL. Additionally, we found that rhlAB expression is partially sigma(s) dependent.


A Computational Approach towards Visual Object Recognition at Taxonomic Levels of Concepts.
It has been argued that concepts can be perceived at three main levels of abstraction. Generally, in a recognition system, object categories can be viewed at three levels of taxonomic hierarchy which are known as superordinate, basic, and subordinate levels. For instance, "horse" is a member of subordinate level which belongs to basic level of "animal" and superordinate level of "natural objects." Our purpose in this study is to take an investigation into visual features at each taxonomic level. We first present a recognition tree which is more general in terms of inclusiveness with respect to visual representation of objects. Then we focus on visual feature definition, that is, how objects from the same conceptual category can be visually represented at each taxonomic level. For the first level we define global features based on frequency patterns to illustrate visual distinctions among artificial and natural. In contrast, our approach for the second level is based on shape descriptors which are defined by recruiting moment based representation. Finally, we show how conceptual knowledge can be utilized for visual feature definition in order to enhance recognition of subordinate categories.


Spontaneous pneumothorax: time to rethink management?
There are substantial differences in international guidelines for the management of pneumothorax and much geographical variation in clinical practice. These discrepancies have, in part, been driven by a paucity of high-quality evidence. Advances in diagnostic techniques have increasingly allowed the identification of lung abnormalities in patients previously labelled as having primary spontaneous pneumothorax, a group in whom recommended management differs from those with clinically apparent lung disease. Pathophysiological mechanisms underlying pneumothorax are now better understood and this may have implications for clinical management. Risk stratification of patients at baseline could help to identify subgroups at higher risk of recurrent pneumothorax who would benefit from early intervention to prevent recurrence. Further research into the roles of conservative management, Heimlich valves, digital air-leak monitoring, and pleurodesis at first presentation might lead to an increase in their use in the future.


The plant nucleoplasmin AtFKBP43 needs its extended arms for histone interaction.
The nucleoplasmin family of histone chaperones is a key player in governing the dynamic architecture of chromatin, thereby regulating various DNA-templated processes. The crystal structure of the N-terminal domain of Arabidopsis thaliana FKBP43 (AtFKBP43), an FK506-binding immunophilin protein, revealed a characteristic nucleoplasmin fold, thus confirming it to be a member of the FKBP nucleoplasmin class. Small-Angle X-ray Scattering (SAXS) analyses confirmed its pentameric nature in solution, and additional studies confirmed the nucleoplasmin fold to be highly stable. Unlike its homolog AtFKBP53, the AtFKBP43 nucleoplasmin core domain could not interact with histones and required the acidic arms, C-terminal to the core, for histone association. However, SAXS generated low-resolution envelope structure, ITC, and AUC results revealed that an AtFKBP43 pentamer with C-terminal extensions interacts with H2A/H2B dimer and H3/H4 tetramer in an equimolar ratio, like AtFKBP53. Put together, AtFKBP43 belongs to a hitherto unreported subclass of FKBP nucleoplasmins that requires the C-terminal acidic stretches emanating from the core domain for histone interaction.


Posterior spinal dysraphism with lumbocostovertebral syndrome.
We report a 5-year-old male child with absent rib, hemivertebra, superior lumbar hernia (features of lumbocostovertebral syndrome) and posterior spinal dysraphism, which is the second case in the English literature with such a combination of defects. Radiology and management of the case is discussed.


[Minor malformation score in congenital cleft of the lip and palate].
The authors analyzed minor malformation score in 63 children (36 boys and 27 girls) with congenital cleft of the lip and palate in order to evaluate purposefulness of its application as a screening method in detecting various major malformations. The results obtained revealed extremely increased minor malformation score in our patients and confirmed that an increased minor malformation score is associated with major malformation, i.e. clefts of the lip and palate. Therefore, it could be used as a screening method for detection of major malformations.


Update on perioperative systemic therapy for urothelial carcinoma.
Level 1 evidence supports cisplatin-based neoadjuvant chemotherapy (NAC) in muscle-invasive urothelial bladder cancer (MIUBC). Recent data from small prospective trials with neoadjuvant immune checkpoint inhibitors are encouraging, but long-term follow-up is required. Randomized trials have failed to accrue a sufficient number of patients and have not demonstrated a survival benefit with adjuvant chemotherapy in MIUBC, but for those with high-risk features at surgery, adjuvant cisplatin-based therapy is appropriate. In upper tract urothelial carcinoma, several retrospective trials and one recent phase 2 prospective trial support the use of NAC, and a randomized trial with adjuvant chemotherapy demonstrated improved disease- and metastasis-free survival and a trend toward improved overall survival.


High-resolution CT evaluation of bronchial lumen to vertebral body, pulmonary artery to vertebral body and bronchial lumen to pulmonary artery ratios in Dirofilaria immitis-infected cats with and without selamectin administration.
Objectives The bronchial lumen to pulmonary artery (BA) ratio is utilized to evaluate pulmonary pathology on CT images. The BA ratio may be unreliable when changes are present in bronchial and pulmonary arteries concurrently. Bronchial lumen to vertebral body (BV) and pulmonary artery to vertebral body (AV) ratios have been established in normal cats and may serve as an alternative. This study aimed to evaluate the BV, AV and BA ratios in cats before and after infection with Dirofilaria immitis, with and without selamectin administration, and to characterize the distribution of disease. Methods Archived CT images were reviewed from three groups of cats: D immitis-infected untreated (n = 6); infected pretreated with selamectin (n = 6); and uninfected untreated (n = 5). The BV, AV and BA ratios were calculated for all lung lobes for baseline (D0) and day 240 (D240) postinfection. Ratios and percentage change from baseline were compared between lobes and between groups. Results BV and AV ratios were more consistent in identifying abnormalities when disease was present in bronchial and arteries concurrently than BA ratios. Infected untreated cats had significant changes in both BV and AV ratios and percentage change from baseline. Abnormal BV and AV ratios were noted in the infected selamectin group, although less widely distributed. Conclusions and relevance The BV and AV ratios more accurately identified bronchial and pulmonary artery abnormalities in D immitis-infected cats. Both bronchial and pulmonary artery changes were present in infected cats, decreasing the diagnostic application of the BA ratio. Pulmonary artery changes were more widely distributed than bronchial changes in the lung. Heartworm-infected cats receiving selamectin had bronchial and pulmonary artery changes but to a lesser extent than untreated heartworm-infected cats. The CT-derived BV and AV ratios are a useful measure to evaluate lung disease of cats.


Clinical impact of altered immunoglobulin levels in Henoch-Schönlein purpura.
The aim of the present study was the identification of immunological features, present at the time of diagnosis, that would predict the severity of Henoch-Schönlein purpura and its outcome. A cohort study was carried out in a tertiary pediatric hospital of 69 children with Henoch-Schönlein purpura, in whom serum complement components C3, C4 and IgA, IgM, IgG were repeatedly determined. During the acute phase of the disease in 54/69 patients (78.3%) immunological imbalances were observed. In 24/54 cases (44.4%) certain complications involving the kidneys and the gastrointestinal tract were noted as opposed to in 3/15 children (20%) without immunologic abnormalities. In 50/69 children (72.5%), elevated serum IgA was detected and 16 of them (32%) developed renal involvement while only 1/19 children (5.3%) with normal IgA concentration had renal involvement. Considering separately the group of 9/69 children (13%) with increased IgM and those with normal IgM levels (53/69; 76.8%), irrespective of IgA and IgG concentration, we found a comparable percentage of children who had both renal and intestinal involvement without, however, developing severe complications, which were exclusively seen in patients with increased IgA (5/7 children) and reduced IgM levels. Serum C3 fraction was elevated in 26 children (37.7%) and in 73% of cases it was associated with increased serum IgA values. Renal involvement was seen in 32% of children with increased IgA values. Most importantly, elevated IgA concentration along with reduced IgM levels was associated with higher prevalence of severe complications.


Specific anti-Bordetella pertussis activities in human blood examined by enzyme-linked immunoassay and biological assay.
Enzyme-linked immunoassays have been employed in this work to measure antibodies against either pertussigen or filamentous hemagglutinin, using a urease-conjugated second antibody system. Pertussigen and filamentous hemagglutinin were obtained from the supernatants of Bordetella pertussis cultures by chromatographic procedures, and were shown to be essentially free of other proteins. Further checks have established the specificity of the enzyme-linked immunoassay-systems. Anti-pertussigen and anti-filamentous hemagglutinin antibody titers, in a pilot study of sera from normal adults, showed little correlation with the donors' pertussis contact, infection or vaccination histories. Nevertheless, the titers did correlate with the ability of the sera to neutralize the biological actions of pertussigen in mice and the haemagglutinating activity of filamentous haemagglutinin, respectively. Antibody titers of sera from patients with suspected or confirmed pertussis infection fell within the range covered by sera from normal adults. Sera from unvaccinated children (less than two months old) also showed some anti-pertussis activity that was probably maternal in origin. Further selected adult plasma samples have been compared for anti-pertussis activity by enzyme-linked immunoassays and agglutination. These samples also have been evaluated for their abilities to protect mice passively against intra-nasal and intra-cerebral challenge with Bordetella pertussis.


Correlation Analysis between Gut Microbiota Alterations and the Cytokine Response in Patients with Coronavirus Disease during Hospitalization.
The role of the intestinal microbiota in coronavirus disease 2019 (COVID-19) is being elucidated. Here, we analyzed the temporal changes in microbiota composition and the correlation between inflammation biomarkers/cytokines and microbiota in hospitalized COVID-19 patients. We obtained stool specimens, blood samples, and patient records from 22 hospitalized COVID-19 patients and performed 16S rRNA metagenomic analysis of stool samples over the course of disease onset compared to 40 healthy individual stool samples. We analyzed the correlation between the changes in the gut microbiota and plasma proinflammatory cytokine levels. Immediately after admission, differences in the gut microbiota were observed between COVID-19 patients and healthy subjects, mainly including enrichment of the classes Bacilli and Coriobacteriia and decrease in abundance of the class Clostridia. The bacterial profile continued to change throughout the hospitalization, with a decrease in short-chain fatty acid-producing bacteria including Faecalibacterium and an increase in the facultatively anaerobic bacteria Escherichia-Shigella. A consistent increase in Eggerthella belonging to the class Coriobacteriia was observed. The abundance of the class Clostridia was inversely correlated with interferon-γ level and that of the phylum Actinobacteria, which was enriched in COVID-19, and was positively correlated with gp130/sIL-6Rb levels. Dysbiosis was continued even after 21 days from onset. The intestines tended to be an aerobic environment in hospitalized COVID-19 patients. Because the composition of the gut microbiota correlates with the levels of proinflammatory cytokines, this finding emphasizes the need to understand how pathology is related to the temporal changes in the specific gut microbiota observed in COVID-19 patients. IMPORTANCE There is growing evidence that the commensal microbiota of the gastrointestinal and respiratory tracts regulates local and systemic inflammation (gut-lung axis). COVID-19 is primarily a respiratory disease, but the involvement of microbiota changes in the pathogenesis of this disease remains unclear. The composition of the gut microbiota of patients with COVID-19 changed over time during hospitalization, and the intestines tended to be an aerobic environment in hospitalized COVID-19 patients. These changes in gut microbiota may induce increased intestinal permeability, called leaky gut, allowing bacteria and toxins to enter the circulatory system and further aggravate the systemic inflammatory response. Since gut microbiota composition correlates with levels of proinflammatory cytokines, this finding highlights the need to understand how pathology relates to the gut environment, including the temporal changes in specific gut microbiota observed in COVID-19 patients.


Incidence of Pseudomonas aeruginosa in recreational and hydrotherapy pools.
Pseudomonas aeruginosa remains an important agent of opportunistic infection in patients, particularly those with respiratory complications and burns. One natural niche of this organism is water and water-associated facilities, hence the aim of this study was to examine specimens from recreational and hydrotherapy pools in Northern Ireland over a two-year period. Water specimens (n = 3,510) were obtained from three amenity categories, namely, 13 hydrotherapy pools (specimen number [n] = 323), 51 Jacuzzis/spas (n = 1,397) and 68 swimming pools (n = 1,790). Specimens (100 ml) were filtered through a cellulose acetate (0.45 micron pore size) gridded filter and the membrane was placed on Pseudomonas CFC agar (Oxoid CM559 + SR103) and incubated at 37 degrees C for 48 +/- 2 h. Colonies that clearly showed pyocyanin production or met other identification criteria were considered P. aeruginosa. Of the amenities examined 4/13 hydrotherapy pools (30.8%), 37/51 Jacuzzis/spas (72.5%) and 26/68 swimming pools (38.2%) were positive for P. aeruginosa. The most heavily contaminated amenity category was the Jacuzzi/spa, where 34.7% and 12% of private and public sites respectively were positive for P. aeruginosa at a level of greater than 1,000 cfu 100 ml-1. Approximately twice as many samples were positive in private Jacuzzis/spas compared to publicly operated facilities. There was a similar trend with respect to public and private hydrotherapy pools, though bacterial counts did not exceed 1,000 cfu 100 ml-1. Recreational and therapeutic amenities involving the use of water may be a potential source of P. aeruginosa for susceptible patient groups, including patients with cystic fibrosis and bronchiectasis. This may vary depending on amenity type and public/private ownership of such amenities.


Efficiency at maximum power of a quantum heat engine based on two coupled oscillators.
We propose and theoretically investigate a system of two coupled harmonic oscillators as a heat engine. We show how these two coupled oscillators within undamped regime can be controlled to realize an Otto cycle that consists of two adiabatic and two isochoric processes. During the two isochores the harmonic system is embedded in two heat reservoirs at constant temperatures T(h) and T(c)(<T(h)), respectively, and it is tuned slowly along a protocol to realize an adiabatic process. To illustrate the performance in finite time of the quantum heat engine, we adopt the semigroup approach to model the thermal relaxation dynamics along the two isochoric processes, and we find the upper bound of efficiency at maximum power (EMP) η* to be a function of the Carnot efficiency η(C)(=1-T(c)/T(h)): η*≤η(+)≡η(C)(2)/[η(C)-(1-η(C))ln(1-η(C))], identical to those previously derived from ideal (noninteracting) microscopic, mesoscopic, and macroscopic systems.


[On the roller coaster: An abridged history of mental health planning in Spain. SESPAS Report 2020].
Effective mental health change in Spain started in 1985 with the Report of the Ministerial Commission for the Psychiatric Reform that recommended integrating psychiatric care into the general health system, providing care in the patient's context and for specific diagnoses. The SESPAS 2002 Report carried out an analysis of this reform and recommended the creation of a permanent ministerial commission, the design of a national map of socio-sanitary mental health services, the creation of a coordination and promotion agency for and carrying out a financial analysis of resource provision and research. Since 2004, the Technical Committee for the Mental Health Strategy boosted the elaboration of a theoretical and normative framework that unfortunately did not lead to a road map for the improvement of the system. After 2011, during the financial crisis, the Ministry of Health lost the opportunity to lead a second phase of change of the mental health care, which was evidence-based: no key technical reports were published nor was an action plan based on data developed. Currently, the 1985 community mental health model is still the general framework of mental health care with the addition of aspects related to the recovery model and the balance of care model. Significant progress has been made in developing care systems assessment methods and data-based models that could advance mental health planning. The gap between general health attention and mental health care has increased and the expected reform of the mental health system will not take place in the near future.


HMGN proteins modulate chromatin regulatory sites and gene expression during activation of naïve B cells.
The activation of naïve B lymphocyte involves rapid and major changes in chromatin organization and gene expression; however, the complete repertoire of nuclear factors affecting these genomic changes is not known. We report that HMGN proteins, which bind to nucleosomes and affect chromatin structure and function, co-localize with, and maintain the intensity of DNase I hypersensitive sites genome wide, in resting but not in activated B cells. Transcription analyses of resting and activated B cells from wild-type and Hmgn(-/-) mice, show that loss of HMGNs dampens the magnitude of the transcriptional response and alters the pattern of gene expression during the course of B-cell activation; defense response genes are most affected at the onset of activation. Our study provides insights into the biological function of the ubiquitous HMGN chromatin binding proteins and into epigenetic processes that affect the fidelity of the transcriptional response during the activation of B cell lymphocytes.


Diagnostic Performance of a Novel Multiplex PCR Assay for Candidemia among ICU Patients.
Candidemia poses a major threat to ICU patients and is routinely diagnosed by blood culture, which is known for its low sensitivity and long turnaround times. We compared the performance of a novel, Candida-specific multiplex real-time PCR assay (Fungiplex® Candida IVD Real-Time PCR Kit) with blood culture and another established diagnostic real-time PCR assay (LightCycler SeptiFast Test) with respect to Candida detection from whole blood samples. Clinical samples from 58 patients were analyzed by standard blood culture (BC) and simultaneously tested with the Fungiplex Candida PCR (FP) and the SeptiFast test (SF) for molecular detection of Candida spp. Compared to BC, the FP test showed high diagnostic power, with a sensitivity of 100% and a specificity of 94.1%. Overall diagnostic accuracy reached 94.6%. Using SF, we found a sensitivity of 60%, a specificity of 96.1%, and an overall diagnostic accuracy of 92.9%. The Fungiplex Candida PCR has shown good sensitivity and specificity on clinical samples of high-risk patients for direct detection of Candida species in whole blood samples. Together with conventional diagnostics (BC and antigen testing), this new multiplex PCR assay may contribute to a rapid and accurate diagnosis of candidiasis.


Prognostic factors for survival in advanced non-small cell lung cancer.
To determine the prognostic value for survival of various pretreatment characteristics and treatments in advanced non-small cell lung cancer (NSCLC) patients. The retrospective study was conducted by reviewing the 81 files of advanced NSCLC patients treated with chemotherapy at the Oncology Unit, Rajavithi Hospital. Eighteen clinical variables were investigated and analysed as prognostic factors for survival. The first chemotherapy regimens for the 81 patients included: etoposide plus platinum derivatives (41), new drugs (taxanes or gemcitabine) plus platinum derivatives (39) and one other platinum based regimen (1). The overall survival time for all patients was 39.4 weeks with a 95% confidence interval of 30 to 49 weeks. In the multivariate analysis, male gender; bone metastasis and liver metastasis are poor prognostic factors. Receiving palliative surgery and achieving objective response to first regimen chemotherapy are good prognostic factors. Patients who received either old or new drug combinations showed no difference in their survival as determined by univariate or multivariate analyses which could be due to limitations in the present retrospective study. However; this may show that regimens consisting of older, less expensive drug combinations still provide survival advantages in advanced NSCLC and should be considered in limited financial circumstances.


Sino-orbital aspergillosis in a diabetic patient.
Sino-orbital aspergillosis in a 61-year-old male with uncontrolled non-insulin dependent diabetes mellitus presented with three months history of left ear pain, left side headache with mucopurulent nasal discharge and one week history of progressive swelling and pain with difficulty in opening of the left eye and sudden loss of vision. In spite of surgical debridement and medical management with amphotericin B and itraconazole his visual outcome was poor and the infection was unabated at one month follow up.


Addition-Elimination or Nucleophilic Substitution? Understanding the Energy Profiles for the Reaction of Chalcogenolates with Dichalcogenides.
We have quantum chemically explored the mechanism of the substitution reaction between CH3X(-) and the homo- and heterodichalcogenides CH3X'X″CH3 (X, X', X″ = S, Se, Te) using relativistic density functional theory at ZORA-OLYP/TZ2P and COSMO for simulating the effect of aqueous solvation. In the gas phase, all substitution reactions proceed via a triple-well addition-elimination mechanism that involves a stable three-center intermediate. Aqueous solvation, in some cases, switches the character of the mechanism to double-well SN2 in which the stable three-center intermediate has become a labile transition state. We rationalize reactivity trends and some puzzling aspects of these elementary reactions, in particular, vanishing activation energies and ghost three-center intermediates, using the activation strain model (ASM).