Responding to the health needs of survivors of human trafficking: a systematic review.
Despite the multiple physical and psychological health consequences associated with human trafficking, there is little evidence-based guidance available for health providers on assessing and meeting the health needs of trafficked people. We aimed to review literature that provided guidance or research on care provision for people who had been trafficked. We conducted a systematic review and qualitative analysis of peer-reviewed and grey literature. Data sources included electronic databases, reference list screening, citation tracking, and expert recommendations. Documents were included if they reported on: 1) male or females (adults or children) who were currently or had previously been trafficked; 2) health interventions or service provision; 3) primary, secondary, tertiary or specialist post-trafficking services; and 4) World Bank high income countries. Two reviewers independently screened and quality appraised documents. Framework analysis was used to analyse extracted data. Forty-four documents were included, 19 of which reported findings of primary studies and nine of which exclusively addressed children. Evidence to inform the identification, referral and care of trafficked people is extremely limited. Within current literature on survivor identification, key indicators included signs of physical and sexual abuse, absence of documentation, and being accompanied by a controlling companion. Findings highlighted the importance of interviewing possible victims in private, using professional interpreters, and building trust. For provision of care, key themes included the importance of comprehensive needs assessments, adhering to principles of trauma-informed care, and cultural sensitivity. Further prominent themes were the necessity of multi-agency working strategies and well-defined referral pathways. Human trafficking survivors require healthcare that is trauma-informed and culturally sensitive to their particular needs. Coordination is needed between health providers and statutory and voluntary organisations. Future research should generate empirical evidence to develop trafficking indicators for use by health providers, alongside validated screening tools, and evaluate the effectiveness of psychological interventions.


Comprehensive analysis of key m5C modification-related genes in type 2 diabetes.
Background: 5-methylcytosine (m5C) RNA methylation plays a significant role in several human diseases. However, the functional role of m5C in type 2 diabetes (T2D) remains unclear. Methods: The merged gene expression profiles from two Gene Expression Omnibus (GEO) datasets were used to identify m5C-related genes and T2D-related differentially expressed genes (DEGs). Least-absolute shrinkage and selection operator (LASSO) regression analysis was performed to identify optimal predictors of T2D. After LASSO regression, we constructed a diagnostic model and validated its accuracy. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to confirm the biological functions of DEGs. Gene Set Enrichment Analysis (GSEA) was used to determine the functional enrichment of molecular subtypes. Weighted gene co-expression network analysis (WGCNA) was used to select the module that correlated with the most pyroptosis-related genes. Protein-protein interaction (PPI) network was established using the STRING database, and hub genes were identified using Cytoscape software. The competitive endogenous RNA (ceRNA) interaction network of the hub genes was obtained. The CIBERSORT algorithm was applied to analyze the interactions between hub gene expression and immune infiltration. Results: m5C-related genes were significantly differentially expressed in T2D and correlated with most T2D-related DEGs. LASSO regression showed that ZBTB4 could be a predictive gene for T2D. GO, KEGG, and GSEA indicated that the enriched modules and pathways were closely related to metabolism-related biological processes and cell death. The top five genes were identified as hub genes in the PPI network. In addition, a ceRNA interaction network of hub genes was obtained. Moreover, the expression levels of the hub genes were significantly correlated with the abundance of various immune cells. Conclusion: Our findings may provide insights into the molecular mechanisms underlying T2D based on its pathophysiology and suggest potential biomarkers and therapeutic targets for T2D.


Reconstructions of individual fish trophic geographies using isotopic analysis of eye-lens amino acids.
Fish eye lenses are a proteinaceous structure that grows by accumulating layers in a chronological manner. Each layer becomes metabolically inert, capturing the ratio of heavy/light carbon and nitrogen isotopes at time of formation. Therefore, eye lenses contain chronological isotopic records and can be used to create a temporal isotopic history throughout an individual's lifetime. We analyzed eye lens amino-acid δ15N to address spatio-temporal baseline variability and to reconstruct trophic histories of 10 individual Red Snapper. Proteins from sequential eye lens laminae were derivatized to measure 10 amino acids, from which glutamic acid (trophic) and phenylalanine (source) were used to estimate trophic positions at different points in life. Best-fitting regressions were generated to represent individual (R2 ≥ 0.89) and generalized (R2 = 0.77) trophic trajectory for Red Snapper. The resulting trophic trajectories indicated an increase in trophic position with increasing length. Until recently, there has not been a lifetime isotopic structure with enough organic nitrogen to recreate geographic histories using compound-specific stable isotope analysis of amino acids (CSIA-AA). This study confirms that eye-lens laminae can be used to reconstruct trophogeographic histories via CSIA-AA.


DNA-based methods for the identification of insect vectors.
Many insect vectors are members of complexes composed of morphologically identical sibling species. The identification of individual species, a requirement of epidemiological studies and control programmes, has traditionally relied upon techniques such as chromosomal analysis or isoenzyme typing. Owing to the limitations of these techniques, the last few years have seen many developments in DNA-based technologies for identification. DNA-based protocols have advantages over the other techniques utilized, in that they may identify all insect stages of both sexes using alcohol-preserved, dried, fresh or frozen specimens. The methods ultimately rely upon either DNA probe hybridization or the polymerase chain reaction (PCR). This review describes a number of approaches taken towards the development of these techniques. The aim of these approaches, whether directed or random, is to produce a methodology that is cheap, accurate and easy to use. In this review, the DNA-based techniques developed for the identification of Anopheles gambiae complex mosquitoes are used to illustrate the power of these methods, although, as the review demonstrates, the technology is directly applicable to many other mosquito or insect vectors. In addition, the methods discussed may be utilized for generating additional epidemiological data, such as identification of parasites within the vector or origin of the bloodmeal. A comprehensive survey of the probe systems available for the identification of insect vectors and the disease-causing organisms they transmit to the human population is therefore included. Given further advances in this technology, it may be anticipated that DNA-based approaches to identification may eventually supersede more traditional methodologies in the fields of tropical medicine and parasitology.


[Effects of zilongjin on proliferation and apoptosis of human breast cancer cell line MCF-7].
To study the effect of Zilongjin (ZLJ, a composite Chinese drug) on proliferation and apoptosis of human breast carcinoma cell line MCF-7. MCF-7 cells were randomly divided into four groups depending on the culture solution used, the control group, cultured with 1640 medium not contained ZLJ; and the three ZJL groups cultured with medium contained low (1.5 mg/mL), moderate (3 mg/mL) and high (6 mg/mL) dosage of ZLJ crude drug respectively. The changes of cell proliferation were assessed by cell growth curve assay and methyl thiazolyl tetrazolium (MTT) assay. And the cell apoptosis was analyzed by flow cytometry, Hoechst 33342 staining and DNA ladder assay. Compared with that in the normal control, the counts of cells in the three ZLJ groups were decreased significantly (P<0.05) at such time point as 24, 48, 72, 96, 120, and 144 h. Furthermore, apart from the comparison of the growth inhibition rate between the low and moderate dosage group at 24 and 72 h which were found to be no significant difference (P>0.05), the comparison f that among the three ZLJ groups appeared to be significant difference (P<0.05). The inhibitory effect of ZLJ on cell proliferation of MCF-7 was time- and dose-dependent; it could retard cells in G0/G1 cell phase; apoptosis of MCF-7 cell was induced by moderate and high dosage of ZLJ with revealing of apoptotic body and DNA ladder formation. ZLJ shows cell proliferation inhibitory and apoptosis inducing effects on human breast cancer cell line MCF-7, and thus to realize its anti-tumor action.


[Assessment of care quality in department of general surgery : usefulness of administrative database].
Administrative database, used previously for control of cost, patient flow and invoicing, offer to researchers a large sample of patients representative of population providing interesting informations in the field of descriptive and analytic epidemiology with less cost. To assess the usefulness of administrative database for quality of care and research. It was a prospective study concerning 4690 hospitalisations in Department B of General Surgery of hôpital Charles Nicolle during a period of 18 months, between June 1st, 2008 and December 31st, 2009. A descriptive analysis followed by a pronostic study with a univariate and multivariate analysis was performed. RÉSULTATS : Our study showed the usefulness of an administrative database in assessing the quality of care, it allowed us to determine postoperative mortality rate (2.7%), deep morbidity (2.5%), parietal morbidity (1.2%), medical complications (6%), nosocomial infections (3.6%) and re intervention (2.7%), with independent predictive factors of these events. To reduce the incidence of these events we should reduce length of pre-operative stay, prevent intra operative accidents, avoid intra operative bleeding in order to reduce intra operative transfusions and avoid as far as possible the stay in ICU Independent predictors of post trauma death are multiple trauma [OR: 6.14, 95% (from 1.68 to 16.94), p = 0.002], a traumatized patient in distress on arrival [OR: 8.74, 95% (3.59 -27.77), p = 0.000] and overall medical complications [OR: 13.18, 95% (from 4.01 to 31.25), p=0.000]. The ISS is a good discriminative indice to assess the severity and life-threatening risk. Administrative databases provide information on the efficiency of care, it helps to realise observational studies on large samples representative of the population at low cost. They are very useful in the research, despite the lack of clinical data.


The development of an Integrated Care Pathway for all patients with advanced life-limiting illness - the Supportive Care Pathway.
To describe the development and implementation of an Integrated Care Pathway for all patients with advanced life-limiting illness who have been admitted to hospital. This pathway, called the Supportive Care Pathway, has been developed not only in response to the national drivers to improve end of life care, but also in recognition of local survey data which demonstrated the need for strategies to support the provision of palliative care. The pathway is aimed primarily at generalist staff who may have a significant number of patients with palliative care needs on their wards, though not necessarily yet in the last days of life. The pathway, which is being piloted on three elderly care wards in the West Midlands, has been developed in line with accepted Integrated Care Pathway methodology and is being evaluated using the Integrated Care Pathways Assessment Tool. The pathway has been well received by staff using it and early evaluation of its effect in improving documentation of care is encouraging. Unacceptable variations in care for those nearing the end of life is recognized. It is believed that the use of the Supportive Care Pathway may help to reduce that variation by identifying and supporting patients thought to be in the last year of their life.


Genetic aetiology of blood pressure relates to aortic stiffness with bi-directional causality: evidence from heritability, blood pressure polymorphisms, and Mendelian randomization.
Haemodynamic determinants of blood pressure (BP) include cardiac output (CO), systemic vascular resistance (SVR), and arterial stiffness. We investigated the heritability of these phenotypes, their association with BP-related single-nucleotide polymorphisms (SNPs), and the causal association between BP and arterial stiffness. We assessed BP, central BP components, and haemodynamic properties (during a single visit) including CO, SVR, and pulse wave velocity (PWV, measure of arterial stiffness) in 3531 (1934 monozygotic, 1586 dizygotic) female TwinsUK participants. Heritability was estimated using structural equation modelling. Association with 984 BP-associated SNP was examined using least absolute shrinkage and selection operator (LASSO) and generalized estimating equation regression. One and two-sample Mendelian randomization (MR) was used to estimate the causal direction between BP and arterial stiffness including data on 436 419 UK Biobank participants. We found high heritability for systolic and pulsatile components of BP (>50%) and PWV (65%) with overlapping genes accounting for >50% of their observed correlation. Environmental factors explained most of the variability of CO and SVR (>80%). Regression identified SNPs (n = 5) known to be associated with BP to also be associated with PWV. One-sample MR showed evidence of bi-directional causal association between BP and PWV in TwinsUK participants. Two-sample MR, confirmed a bi-directional causal effect of PWV on BP (inverse variance weighted (IVW) beta = 0.11, P < 0.02) and BP on arterial stiffness (IVW beta = 0.004, P < 0.0001). The genetic basis of BP is mediated not only by genes regulating BP but also by genes that influence arterial stiffness. Mendelian randomization indicates a bi-directional causal association between BP and arterial stiffness.


[Evaluation of the effects of pulling angle and force on intermittent cervical traction with the Saunder's Halter].
Intermittent cervical traction with proper angle and force is an effective treatment for cervical syndrome. The goals of therapy are effective traction for the affected segments without further damage to the soft tissue. The purposes of this study were to find the traction angle and force which results in the best therapeutic effect. The effect of cervical traction was evaluated by cervical roentgenography, by examining the distance of the posterior margin of the intervertebral space. For a study of the proper angle of traction, intermittent cervical traction was applied to 20 healthy normal volunteers in a supine position with a constant traction force of 15 kgf. The traction lasted for 8 seconds followed by unloading for 4 seconds and the application was alternated after 10 minutes. The elongated gaps of the posterior vertebral margins obtained from the different neck flexion angles of 35, 30, 25, 20 and 15 degrees were compared. Traction of under 30 degrees was longest for the levels of C4- 5 and C5-6. For the C6-7 and C7-T1 levels, traction was longest under 35 degrees. For study of the minimal effective traction force, the same procedures of intermittent cervical traction were applied to another 15 healthy normal volunteers, except the neck was fixed in a flexion of 35 degrees, and the traction force was 9, 12, 15 and 18 kgf. The best results were noted with a traction force of 15 or 18 kgf. However, there were more complaints of neck discomfort after traction with a force of 18 kgf.


Deficient Aeronautical Decision-Making Contributions to Fatal General Aviation Accidents.
INTRODUCTION: General aviation (GA), mainly comprised of light (≤12,500 lb) aircraft, maintains an inferior safety record compared with air carriers. To improve safety, aeronautical decision-making (ADM) practices have been advocated to GA pilots since 1991. Herein, we determined the extent to which GA pilots disregard such practices.METHODS: Fatal accidents (1991-2019) involving private pilots (PPLs) in single-engine airplanes were identified (N = 1481) from the National Transportation Safety Board AccessR database. Of these, deficient go/no-go and in-flight ADM-related mishaps were scored using the PAVE (pilot, aircraft, environment, external pressure)/IMSAFE (illness, medicine, stress, alcohol, fatigue, eating) and PPP (perceive, process, perform) models, respectively. Statistical testing used Poisson distributions, Fisher exact tests, and Mann-Whitney U-tests.RESULTS: Of the 1481 accidents, 846 were identified as deficient ADM-related. Electing to depart into a hazardous environment (PAVE), disregarding wellness (IMSAFE), and poor aircraft familiarity (PAVE) represented the most common categories (54%, 21%, and 20%, respectively) of errant go/no-go ADM. A 64% decline in fatal accidents related to errant go/no-go decisions for the environment category was evident over the 30-yr period, with little decrements in the other domains. Within the errant environment-related category accidents, the decision to depart into forecasted adverse weather (e.g., degraded visibility, icing, thunderstorms) constituted the most prevalent subcategory (56%, N = 195). Surprisingly, of this subcategory, accidents were overrepresented by over nine- and threefold for instrument-rated PPLs disregarding icing and thunderstorm forecasts, respectively.CONCLUSION: With little decrement in ADM-related accidents in the pilot, aircraft, and external pressure domains, new strategies to address such deficiencies for PPLs are warranted.Boyd DD, Scharf MT. Deficient aeronautical decision-making contributions to fatal general aviation accidents. Aerosp Med Hum Perform. 2023; 94(11):807-814.


Association between vaginal washing and vaginal bacterial concentrations.
Vaginal washing is a common practice associated with adverse outcomes including bacterial vaginosis (BV) and HIV infection. Prior studies have not examined the associations between vaginal washing and individual vaginal bacteria, or whether these associations are independent of the effect of vaginal washing on BV. The purpose of this study was to characterize the association between vaginal washing and the presence and concentrations of vaginal bacteria associated with optimal and sub-optimal vaginal states. The analysis utilized data from participants in the placebo arm of the Preventing Vaginal Infections trial, which enrolled HIV-uninfected women from the United States and Kenya. Detection of bacterial taxa associated with BV was compared between visits with versus without reported vaginal washing. The effect of vaginal washing on a number of vaginal bacteria differed substantially (p<0.05) between the US and Kenya, so results were stratified by country. In US women, vaginal washing was associated with a significantly higher likelihood of detection of BV associated bacterium 1 (BVAB1) (relative risk [RR] 1.55, 95% confidence interval [CI] 1.15-2.09, p = 0.004), BVAB2 (RR 1.99, 95%CI 1.46-2.71, p<0.001), Mageeibacillus indolicus (RR 2.08, 95%CI 1.46-2.96, p<0.001), Atopobium vaginae (RR 1.34, 95%CI 1.13-1.59, p = 0.001), Leptotrichia/Sneathia species (RR 1.66, 95% CI 1.33-2.09, p<0.001), Megasphaera species (RR 1.78, 95%CI 1.34-2.37, p<0.001) and Gardnerella vaginalis (RR 1.08, 95%CI 1.01-1.16, p = 0.02). No significant association between vaginal washing and bacterial detection was found in Kenyan women. Adjustment for bacterial vaginosis diagnosed by Gram stain did not alter these results. This study provides evidence that the association between vaginal washing and detection of individual bacterial taxa can vary regionally. For some vaginal bacteria, the association with vaginal washing may be independent of the effect on Gram stain detection of BV. Larger prospective studies in diverse geographic settings should explore whether eliminating vaginal washing impacts the presence and concentrations of key vaginal bacteria.


Acid-Suppressive Therapy and Risk of Infections: Pros and Cons.
This narrative review summarises the benefits, risks and appropriate use of acid-suppressing drugs (ASDs), proton pump inhibitors and histamine-2 receptor antagonists, advocating a rationale balanced and individualised approach aimed to minimise any serious adverse consequences. It focuses on current controversies on the potential of ASDs to contribute to infections-bacterial, parasitic, fungal, protozoan and viral, particularly in the elderly, comprehensively and critically discusses the growing body of observational literature linking ASD use to a variety of enteric, respiratory, skin and systemic infectious diseases and complications (Clostridium difficile diarrhoea, pneumonia, spontaneous bacterial peritonitis, septicaemia and other). The proposed pathogenic mechanisms of ASD-associated infections (related and unrelated to the inhibition of gastric acid secretion, alterations of the gut microbiome and immunity), and drug-drug interactions are also described. Both probiotics use and correcting vitamin D status may have a significant protective effect decreasing the incidence of ASD-associated infections, especially in the elderly. Despite the limitations of the existing data, the importance of individualised therapy and caution in long-term ASD use considering the balance of benefits and potential harms, factors that may predispose to and actions that may prevent/attenuate adverse effects is evident. A six-step practical algorithm for ASD therapy based on the best available evidence is presented.


Diversity of protein carbonylation in allergic airway inflammation.
Oxidative stress is involved in asthma. This study assessed the carbonylation of sputum proteins in 23 uncontrolled adult asthmatic patients and 23 healthy controls. Carbonylated proteins (68 kDa and 53 kDa) were elevated in asthmatics when compared to controls and the 68-kDa carbonylated protein was significantly correlated with sputum eosinophilia. The kinetics of protein carbonylation in bronchoalveolar lavage fluid (BALF) were then examined in a mouse ovalbumin-induced allergic inflammation model. It was found that the carbonylation of various BALF proteins did not uniformly occur after challenge. The appearance of the 53-kDa carbonylated protein was limited within 24 h, while carbonylation of 68-kDa protein peaked at 48 h and was associated with BALF eosinophilia. Thus, it was demonstrated that the 68-kDa and 53-kDa proteins, corresponding to albumin and alpha1-antitrypsin, respectively, were specifically carbonylated in allergic inflammation in humans and in mice and that eosinophils may play a role in mediating carbonylation of albumin.


Transporter-Mediated Solutes Uptake as Drug Target in Plasmodium falciparum.
Malaria remains a public health problem with still more than half a million deaths annually. Despite ongoing efforts of many countries, malaria elimination has been difficult due to emerging resistances against most traditional drugs, including artemisinin compounds - the most potent antimalarials currently available. Therefore, the discovery and development of new drugs with novel mechanisms of action to circumvent resistances is urgently needed. In this sense, one of the most promising areas is the exploration of transport proteins. Transporters mediate solute uptake for intracellular parasite proliferation and survival. Targeting transporters can exploit these processes to eliminate the parasite. Here, we focus on transporters of the Plasmodium falciparum-infected red blood cell studied as potential biological targets and discuss published drugs directed at them.


Visual, kinaesthetic and cross-modal judgments of length by clumsy children: a comparison with young normal children.
In a previous study, clumsy children, when compared to normal children of the same age, were found to be impaired in their ability to match the length of successively presented straight lines within and between the modalities of vision and kinaesthesis. The present study explores this finding further by comparing the clumsy children's performance with that of a group of younger normal children whose skills of movement are comparable to those of the clumsy children. It was found that the clumsy children's performance on the perceptual measures was equivalent to that of the younger normal children.


Determination of type in capsulated transformants on pneumococcus by the genome of non-capsulated donor and recipient strains.
Capsulated transformants producing type II polysaccharide have been obtained by reactions between a number of R mutants of type II pneumococcus. All the IIR strains except II-R36 yielded extracts which transformed 2 VIIIR strains to VIIIS. Two of the IIR strains were transformed to VIIIS by an extract of 1 VIIIR strain. The most striking result was the production of both IIS and VIIIS transformants by the action of extracts of both VIIIR strains applied to cells of II-RB. This suggests that the determination of capsular type in pneumococcus does not depend on single allelomorphic genes; it seems more likely that a number of genes may be required to determine type specificity, and that some genes may be common to different types, possibly in connection with common biochemical pathways for some stages of polysaccharide synthesis. This is further indicated by the finding that extracts of capsulated strains of each of the types I, II, III, VII, VIII, XIV, and XVIII are capable of giving IIS transformants with 1 or more of the IIR strains in addition to the expected donor-type transformants. Strain II-R36 was transformed by extracts of all S types except type VII, but the only transformants found were of the donor type. It appears that II-R36 may have multiple genetic deficiencies for type II capsulation, possibly in the form of a deletion. This may be the case also with IIIS strains since only IIIS transformants were found when IIIS extract was applied to any of the IIR strains.


Intense Activity of the Raphe Spinal Pathway Depresses Motor Activity via a Serotonin Dependent Mechanism.
Motor fatigue occurring during prolonged physical activity has both peripheral and central origins. It was previously demonstrated that the excitability of motoneurons was decreased when a spillover of serotonin could activate extrasynaptic 5-HT1A receptors at the axon initial segment (AIS) of motoneurons. Here we investigated the impact of massive synaptic release of serotonin on motor behavior in an integrated preparation of the adult turtle performing fictive scratching behaviors. We found that a prolonged electrical stimulation of the raphe spinal pathway induced a reversible inhibition of the motor behavior that lasted several tens of seconds. The effect disappeared when the spinal cord was perfused with an antagonist for 5-HT1A receptors. By demonstrating a direct impact of serotonin on motor behavior, we suggest a central role of this monoamine behind central fatigue.


Evaluation of the ARI program: a health facility survey in Simbu, Papua, New Guinea.
The purpose of this health facility survey was to evaluate how the ARI (Acute Respiratory Infection) Program actually works in an everyday, non-research setting. We surveyed 33 clinics and aid posts, including 223 children with ARI and 104 health workers. In this primary health care setting, health workers diagnosed 37% of ARI cases as pneumonia, compared to 69% in the same children assessed independently by trained ARI surveyors using Papua New Guinea case management, which defines fast breathing as > or = 40 per minute for children 1 month to 5 years of age. Agreement between health workers and surveyors was reasonably good (kappa > or = 0.6) for the history of symptoms, but was poor (kappa < 0.3) for diagnoses, treatments and signs such as respiratory rate (RR) and chest indrawing. Health workers counted the RR in only 14% of cases in the survey. In essence, we found that health workers in Simbu are not practising ARI case management. We conclude that case management guidelines which define fast breathing as a rate of > or = 40 per minute classify too many obviously well children as pneumonia. Furthermore, we encountered difficulties in measuring RR accurately, and documented marked inter-observer variation in this setting. Consequently, we are concerned about the ARI Program's excessive reliance on RR and rigid protocols at the expense of clinical sense. Case management guidelines developed for aid post orderlies or village health workers may need to be modified, or used differently by experienced nurses at health centres, who recognize sick children better than by following a standardized protocol. Despite better overall ARI knowledge and practice by nurses, we could demonstrate an impact of the ARI Training Program only on community health workers (CHWs). In order to improve ARI clinical practice, we recommend that the ARI Program in PNG initiates regular on-site clinical supervision of nurses and CHWs at health centres.


Gentiopicroside-Loaded Chitosan Nanoparticles Inhibit TNF-α-Induced Proliferation and Inflammatory Response in HaCaT Keratinocytes and Ameliorate Imiquimod-Induced Dermatitis Lesions in Mice.
In this study, we aimed to report the biological characteristics of the first successful synthesis of gentiopicroside-loaded chitosan nanoparticles and to evaluate the therapeutic effects and preliminary mechanisms of gentiopicrin-loaded chitosan on psoriasis-like cell and mouse models. Gentiopicroside-loaded chitosan nanoparticles (CHI-GEN) were prepared, and their biological characteristics were evaluated. HaCaT keratinocytes were stimulated with TNF-α to establish a psoriatic keratinocyte model. MTT assay and flow cytometry were used to measure cell viability and apoptosis, respectively. mRNA levels of K17, VEGF A, and IL-6 and IL-23A were detected using qRT-PCR. These tests were used to preliminarily assess the effects of CHI-GEN on keratinocyte proliferation and inflammation. Imiquimod was used to construct a psoriasis-like mice model. The severity of psoriasis was scored based on the psoriasis area severity index (PASI), H&E staining was used to observe the histological changes and the level of inflammation and cell proliferation of skin lesions was evaluated by measuring the mRNA levels of K17, IL-23A, and IL-17A using qRT-PCR. The average particle size of CHI-GEN nanoparticles was approximately 100 nm, and the zeta potential was 2.69 ± 0.87 mV. The cumulative release was 67.2% in solutions of pH 5.5 at 24 h. GEN reduced TNF-α-induced excessive proliferation of HaCaT keratinocytes and downregulated mRNA levels of K17, VEGF A, and inflammatory cytokines IL-6 and IL-23A, which was more obvious in the CHI-GEN treatment group. Additionally, CHI-GEN significantly improved the severity of skin lesions in psoriasis-like mice and downregulated the mRNA expressions of IL-6, IL-23A, and IL-17A in mice skin lesions. In conclusion, we successfully prepared gentiopicrin-chitosan nanoparticles. Our results show that these nanoparticles have anti-psoriasis activity, inhibits keratinocyte proliferation and improves symptoms in psoriasis model mice and can be used to develop an effective strategy for the treatment of psoriasis.


[The effect of radiation on malignant cells].
Mechanisms of death following irradiation of malignant cells are incompletely understood. Radiation-induced lesions and their consequences on the cancer cell are described. Factors conditioning malignant cell response to radiation are discussed, as well as the mechanisms of radiation-induced carcinogenesis. Finally, the recent molecular biology contributions to gene regulation during cell growth are presented.


Cementodentinal Tear Associated with a Periodontal- Endodontic Combined Lesion: A Case Report with a 14-Month Follow-up.
This case report describes the diagnosis and multidisciplinary treatment of a clinically indiscoverable cementodentinal tear associated with a periodontal-endodontic combined lesion. The tear site was located at the palatal root surface of the maxillary left canine. Due to its position and concomitant periapical periodontitis, it was not noticed at the initial visit until a 3D CBCT examination was conducted. Through combined endodontic-periodontal therapy (which included root canal therapy, root debridement, and periodontal flap surgery), the tear fragment was removed, and the periapical lesion healed gradually. A histologic examination confirmed the definitive diagnosis of a cementodentinal tear. After 14 months, the periodontal and endodontic status of the maxillary left canine were stable. According to these results, CBCT examination and multidisciplinary cooperation seem to be effective and necessary for the diagnosis and treatment of such clinically indiscoverable cementodentinal/cemental tears.


An external fixation method and device to study fracture healing in rats.
We wished to establish a reproducible model for fracture fixation to be used in fracture healing research and therefore developed an external fixation construct and surgical procedure adapted to Sprague-Dawley rats. We evaluated the mechanical properties of the construct in brass rods and rat bone, in an Instron test machine with axial and transverse loading, and the in vivo performance. We found that the mechanical properties of the construct in brass rods were predictable and could be repeated in rat femora. In all tests, the axial load was about 10 times the transverse for the same degree of deformation. The stiffness among fixators was uniform. 1 mm pins caused about 50% less stiffness than 1.2 mm pins in axial loading of rat bone (p < 0.001) and brass rods (p < 0.001) as well as in transverse loading of brass rods (p < 0.001). Loosening of 1 or 2 screws that lock the pins to the fixator reduced stiffness by about 50% in axial loading of rat bone (p = 0.009) and brass rods (p = 0.05). A change in the distance between the bone surface and the fixator was linearly related to the stiffness in axial loading of rat bone (p < 0.001) and brass rods (p < 0.001) and in transverse loading of brass rods (p < 0.001). If the bone ends touched each other, the axial stiffness of the construct increased almost 10 times (265 N/mm), as compared to a fracture gap size of 2 mm (31 N/mm). In vivo experiments had a complication rate of less than 10% when we used 1.2 mm pins, 6 mm offset and rats weighing 350-450 g. Our method and device for experimental external fixation of rat femora are reliable and the findings are reproducible. These can be used in bone repair and fracture healing research.


Indicators for serious kidney complications associated with toxic exposures: an analysis of the National Poison Data System.
Over two million poisoning exposures are reported to U.S. poison control centers annually. A broad population-based survey of toxic exposures and the correlated patterns of reported kidney injury (acute or chronic) have not been systematically characterized. Our objective was to study the demographic and exposure patterns associated with indicators for serious kidney complications (ISKC), as defined by the variables in the NPDS. This was a retrospective, case-control study using the data elements available in the NPDS. We assessed data related to patient characteristics, substance exposure, and management. Cases and controls were derived from adult and pediatric exposures documented in NPDS (2001-2007) as having "renal effects." For substance-specific analyses, cases were restricted to those involving single substances or single entity pharmaceutical preparations. ISKC cases presented with one or more of the following NPDS codes: increased creatinine, and/or oliguria/anuria, and/or renal failure. Controls were subjects with "renal effects" but did not have increased creatinine, nor anuria/oliguria, nor renal failure. Univariate and multivariate logistic regression analyses identified factors associated with ISKC and determined the relationship between these factors. From the approximate 16.8 million exposures reported to the NPDS within the study timeframe, there were 16,444 single substance exposures with renal effects of which 9,074 cases experienced ISKC (55.2%) compared to 7,370 controls without ISKC. Cases with ISKC tended to be males, adults, and reported to involve intentional exposures. Cases with ISKC had higher rates of reported hemodialysis/hemofiltration (27.7%; N = 2,517) and death (10.9%; N = 990) compared to controls, respectively, (2.1%; N = 155) and (0.8%; N = 60), p < 0.001. Substances considered a priori to be nephrotoxic were associated with a higher risk of ISKC. The NPDS provided insight into the subjects and types of exposures that associate with ISKC. Subjects with ISKC experienced higher rates of morbidity and mortality compared to subjects without ISKC. We identified subject characteristics and classes of compounds associated with ISKC. We hope that the hypotheses generated from this study of the NPDS will raise awareness of the possible risk factors and complications associated with ISKC.


Access to public drinking water fountains in Berkeley, California: a geospatial analysis.
In January 2015, Berkeley, California became the first city in the Unites States to impose a tax on sugar-sweetened beverages. The tax is intended to discourage purchase of sugary beverages and promote consumption of healthier alternatives such as tap water. The goal of the study was to assess the condition of public drinking water fountains and determine if there is a difference in access to clean, functioning fountains based on race or socio-economic status. A mobile-GIS App was created to locate and collect data on existing drinking water fountains in Berkeley, CA. Demographic variables related to race and socio-economic status (SES) were acquired from the US Census - American Community Survey database. Disparities in access to, or condition of drinking water fountains relative to demographics was explored using spatial analyses. Spatial statistical-analysis was performed to estimate demographic characteristics of communities near the water fountains and logistic regression was used to examine the relationship between household median income or race and condition of fountain. Although most fountains were classified as functioning, some were dirty, clogged, or both dirty and clogged. No spatial relationships between demographic characteristics and fountain conditions were observed. All geo-located data and a series of maps were provided to the City of Berkeley and the public. The geo-database created as an outcome of this study is useful for prioritizing maintenance of existing fountains and planning the locations of future fountains. The methodologies used for this study could be applied to a wide variety of asset inventory and assessment projects such as clinics or pharmaceutical dispensaries, both in developed and developing countries.


Biofuels from microbes.
Today, biomass covers about 10% of the world's primary energy demand. Against a backdrop of rising crude oil prices, depletion of resources, political instability in producing countries and environmental challenges, besides efficiency and intelligent use, only biomass has the potential to replace the supply of an energy hungry civilisation. Plant biomass is an abundant and renewable source of energy-rich carbohydrates which can be efficiently converted by microbes into biofuels, of which, only bioethanol is produced on an industrial scale today. Biomethane is produced on a large scale, but is not yet utilised for transportation. Biobutanol is on the agenda of several companies and may be used in the near future as a supplement for gasoline, diesel and kerosene, as well as contributing to the partially biological production of butyl-t-butylether, BTBE as does bioethanol today with ETBE. Biohydrogen, biomethanol and microbially made biodiesel still require further development. This paper reviews microbially made biofuels which have potential to replace our present day fuels, either alone, by blending, or by chemical conversion. It also summarises the history of biofuels and provides insight into the actual production in various countries, reviewing their policies and adaptivity to the energy challenges of foreseeable future.


How explicit and implicit test instructions in an implicit learning task affect performance.
Typically developing children aged 5 to 8 years were exposed to artificial grammar learning. Following an implicit exposure phase, half of the participants received neutral instructions at test while the other half received instructions making a direct, explicit reference to the training phase. We first aimed to assess whether implicit learning operated in the two test conditions. We then evaluated the differential impact of age on learning performances as a function of test instructions. The results showed that performance did not vary as a function of age in the implicit instructions condition, while age effects emerged when explicit instructions were employed at test. However, performance was affected differently by age and the instructions given at test, depending on whether the implicit learning of short or long units was assessed. These results suggest that the claim that the implicit learning process is independent of age needs to be revised.


The Neuroprotective Effect of Byu d Mar 25 in LPS-Induced Alzheimer's Disease Mice Model.
Inflammatory factors play an important role in the pathogenesis of Alzheimer's disease (AD). Byu d Mar 25 (BM25) has been suggested to have protective effects in the central nervous system. However, the effect of BM25 on AD has not been determined. This study aims to investigate the neuroprotective effect of BM25 in AD. A total of 40 AD model mice were randomly assigned to the following five groups (n = 8 per group): the AD + NS group, the AD + donepezil group, and three AD + BM25 groups treated with either 58.39 mg/kg (AD + BM25-L), 116.77 mg/kg (AD + BM25-M), or 233.54 mg/kg BM25 (AD + BM25-H). The Morris water maze test was performed to assess alterations in spatial learning and memory deficits. Nissl staining was performed to detect Nissl bodies and neuronal damage. The expression of IL-1β and TNF-α was evaluated by ELISA. The protein expression of P-P38, P38, P-IκBα, caspase 1, COX2, and iNOS was determined by western blotting. The expression of Aβ, p-Tau, and CD11b was measured by immunohistochemistry. The mRNA expression levels of IL-1β, TNF-α, COX2, and iNOS were measured by qRT-PCR. Spatial memory significantly improved in the AD + BM25-M and AD + BM25-H groups compared with the AD + NS group (p < 0.05). The expression of Aβ and p-Tau significantly decreased in the AD + BM25-M and AD + BM25-H groups (p < 0.05). The neuron density and hierarchy and number of pyramidal neurons significantly increased in the AD + BM25-M and AD + BM25-H groups (p < 0.05). In addition, the expression levels of CD11b, IL-1β, TNF-α, COX2, iNOS, caspase 1, p-IκBα, and p-P38 significantly decreased in the AD + BM25-M and AD + BM25-H groups (p < 0.05). In conclusion, our findings suggest that BM25 may exert anti-inflammatory and neuroprotective effects in AD model mice by suppressing the activity of microglia and inhibiting the phosphorylation of IκBα and p38 MAPK.


Metastatic oligodendroglioma. Case report.
We report a case of remote metastasis of oligodendroglioma. Similar cases are reported in the literature for malignant cerebral tumors. Our case seems rather different because of low grade histology. Potential malignancy was evidenced only by further investigations with labeling indexes.


[Substance abuse : a men's disease ?]
For biological and social reasons, men have to face pressure and incentives towards competivity, performance and risk seeking behaviours. These put them at risk for substance use, abuse and dependence, also in a recreational context, to improve their performances. Men's substance use is therefore significantly higher compared to women (2/3 of the global prevalence). The purpose of this paper is a description of gender differences in substance use and advice to provide state of the art screening and care of male patients. Recommendations for a « men-friendly » consultation include : provide a space where men feel comfortable ; if possible, give the choice between a male or a female practitioner ; use other communication media then language only ; discuss and put in perspective the traditional male image ; and collaborate with the patient.


Fluorinated Boronic Acid-Appended Pyridinium Salts and 19F NMR Spectroscopy for Diol Sensing.
The identification and discrimination of diols is of fundamental importance in medical diagnostics, such as measuring the contents of glucose in the urine of diabetes patients. Diol sensors are often based on fluorophore-appended boronic acids, but these severely lack discriminatory power and their response is one-dimensional. As an alternative strategy, we present the use of fluorinated boronic acid-appended pyridinium salts in combination with 19F NMR spectroscopy. A pool of 59 (bio)analytes was screened, containing monosaccharides, phosphorylated and N-acetylated sugars, polyols, carboxylic acids, nucleotides, and amines. The majority of analytes could be clearly detected and discriminated. In addition, glucose and fructose could be distinguished up to 1:9 molar ratio in mixtures. Crucially, the receptors feature high sensitivity and selectivity and are water-soluble, and their 19F-NMR analyte fingerprint is pH-robust, thereby making them particularly well-suited for medical application. Finally, to demonstrate this applicability, glucose could be detected in synthetic urine samples down to 1 mM using merely a 188 MHz NMR spectrometer.


Influence of NKG2D Genetic Variants on Response to Anti-TNF Agents in Patients with Rheumatoid Arthritis.
A natural killer group 2 member D (NKG2D) acts as a powerful activating and co-stimulatory receptor on immune effector cells including NK and T cells. Disruptions within the NKG2D signalling pathway may trigger an exacerbated immune response and promote autoimmune reactions. The objective of the study was to evaluate a plausible role of polymorphisms within the NKG2D gene as a predictor of how effective anti-tumor necrosis factor (TNF) therapy is in rheumatoid arthritis (RA) patients. A total of 280 RA patients receiving anti-TNF therapy were genotyped for NKG2D rs2255336 (A > G), rs1049174 (C > G), and rs1154831 (C > A). Clinical response was evaluated according to the European League against Rheumatism (EULAR) criteria at the 12th and 24th week. Both the NKG2D rs225336 and rs1049174 polymorphisms were significantly associated with efficacy of TNF inhibitors. Inefficient therapy was more frequently observed in patients with rs2255336 GG or rs1049174 CC genotype as compared to other genotypes (p-value = 0.003 and p-value = 0.004, respectively). The presence of the rs2255336 G or the rs1049174 C allele correlated with a worse EULAR response (p-value = 0.002, p-value = 0.031, respectively). Moreover, patients carrying the rs2255336 or rs1049174 heterozygous genotype achieved better EULAR responses than patients with homozygous genotypes (p-value = 0.010 and p-value = 0.002, respectively). Data from the present study provides evidence that NKG2D polymorphisms may affect response to anti-TNF inhibitors in RA patients.


Structure-activity relations of the cardiac gap junction channel.
Cardiac gap junction channels play the important roles of synchronizing pacemaker cells and allowing impulse propagation along the conduction system and throughout the ventricular myocardium. These channels, which support current flow in both longitudinal and tranverse directions, are permeable to anions and cations with radii less than approximately 0.5 nm and in rat heart have unitary conductances on the order of 50 pS. This unitary conductance is consistent with channel geometry described by a right cylindrical pore with diameter large enough for the brilliantly fluorescent dye molecule lucifer yellow to pass between cells. These channels, like others in biological systems, are opened and closed by various treatments, a process termed gating. Cytoplasmic acidification reduces junctional conductance (gj), an effect that is apparently potentiated by elevated myoplasmic Ca ions. Reduced gj also occurs in response to a variety of lipophilic molecules, including halothane, heptanol, and unsaturated fatty acids; the mechanism of action may involve disruption of the protein-lipid microenvironment of the gap junction channel. Arachidonic acid uncouples, and this effect is partially, but incompletely, blocked by an inhibitor of the lipoxygenase metabolic pathways. Cyclooxygenase inhibitors have no protective effects. Certain cyclic nucleotides can rapidly increase gj [adenosine 3',5'-cyclic monophosphate (cAMP)] or slightly decrease it [guanosine 3',5'-cyclic monophosphate (cGMP)], and agents that use these cyclic nucleotides as second messengers (isoproterenol and perhaps carbachol, respectively) produce consistent effects. Agents expected to cause protein kinase C activation (tumor-promoting phorbol esters and diacylglycerol) increase gj rapidly. The gap junction protein from rat heart has been cloned and sequenced. From the primary sequence for the protein, plausible sites of action within the putative cytoplasmic domains are proposed for each of these treatments. In response to gating stimuli that close the channel (halothane, CO2, heptanol), unitary channel conductance is unchanged, suggesting that these agents act by reducing open time probability. Together, these properties constitute the beginnings of our endeavor to define pharmacological agents that are potentially useful in therapeutic manipulation of synchronous discharge, conduction velocity, and isochronous wavefront propagation in cardiac tissue.


Kinetics and stoichiometry of growth of plant cell cultures of Catharanthus roseus and Nicotiana tabacum in batch and continuous fermentors.
Plant cell suspension cultures of Catharanthus roseus and Nicotiana tabacum were grown in stirred tank bioreactors operated in batch and continuous mode. The stoichiometry of growth of both species in steady-state glucose limited chemostats was studied at a range of different dilution rates. A linear relation was applied to describe specific glucose uptake, oxygen consumption, and carbon dioxide production as a function of the growth rate. Specific respiration deviated greatly from the linear relation. An unstructured mathematical model, based on the observed stoichiometry in the glucose limited chemostats, was applied to describe the growth in batch culture. From a comparison between the observed growth pattern in batch fermentors and computer simulations it appeared that the stoichiometry of growth of the C. roseus culture was different under steady-state and dynamic conditions. It was concluded that a mathematical model for the growth of suspension culture plant cells in which the biomass is considered to be a single compound with an average chemical composition is of limited value because large changes in the composition of the biomass may occur.


[Type 2 diabetes and cognitive functions in patients with chronic cerebrovascular diseases].
Type 2 diabetes (Т2DM) both directly and indirectly impacts the development of morphological and functional changes of the central nervous system. The study was to determine clinical and neurophysiological patterns of cognitive impairment (CI) in patients with chronic cerebrovascular diseases (CCD) and Т2DM. We examined 132 patients with CCD. First group included 58 patients without Т2DM aged 64.5 [58; 72], second group 74 patients with CCD and Т2DM 63 [57; 70]. Clinical, neurological, neuropsychological, neurophysiological (cognitive evoked potentials (EP) and neurovisualisation (brain MRI) examination was carried out to all patients. Somatic and neurological characteristics of the patients were similar in both groups with the exception of more distinct metabolic changes in Т2DM patients. Neurovisualisation study of the brain MRI in Т2DM patients revealed more distinct changes in the form of white matter hyperintensity and subarachnoidal spaces enlargement. Neuropsychological examination in patients revealed the reduction of intellectual flexibility, constructive praxis disruption, optical spatial dysfunction and deteoration of delayed word recall. Significant disorders in the way of overall cognitive impairment, lobar dysfunction and impaired verbal associative productivity, proved by statistically lower amplitude and higher latency of P300 EP peak were noted in Т2DM patients. Correlation links were detected: for P300 amplitude and direct and inverse number listing test (r=0.366 and r=0.520; p=0.006 and p0.001 respectively); P300 latency and HbA1c (r=0.32; р0.05) in group 2 and glucose levels in both groups (r=0.30; p0.05); inverse relationship of latency with control functions evaluation (r=-0.34; p=0.008). CCD especially with Т2DM manifests with neurocognitive imbalance, including control functions disruption and are accompanied by neurophysiological and neurovisualistion changes.


Radio-labeling of the PstI restriction fragments and improvement in the sequencing procedure.
A new and simple method has been developed for efficient labeling of the protruding 3' ends of DNA fragments generated by class-II restriction enzymes. This new method utilizes a synthetic oligodeoxynucleotide 5'-GTGCA-3', which is complementary to the protruding 3' end of the fragment and hybridizes with it in such a manner that the end of the restriction fragment will now have a protruding, one-nucleotide (nt)-long 5' end. This then serves as a template to incorporate just one nt at the 3' end of the restriction fragment. This procedure is easy to use, highly efficient (labeling at 80% of the theoretical incorporation) and generates labeled fragments that are suitable for sequencing. We have also improved the nt sequencing procedure of Bencini et al. [Biotechniques 2 (1984) 4-5] by replacing 'A greater than C' reaction with 'G' and 'C' specific reactions and employing butanol precipitation of DNA.


Reduction of beta-amyloid-induced neurotoxicity on hippocampal cell cultures by moderate acidosis is mediated by transforming growth factor beta.
Progression of Alzheimer's disease (AD) is associated with chronic inflammation and microvascular alterations, which can induce impairment of brain perfusion because of vascular pathology and local acidosis. Acidosis can promote amyloidogenesis, which could further contribute to neurodegenerative changes. Nevertheless, there is also evidence that acidosis has neuroprotective effects in hypoxia models. Here we studied the effect of moderate acidosis on beta-amyloid (Abeta)-mediated neurotoxicity. We evaluated morphological changes, cell death, nitrite production and reductive metabolism of hippocampal cultures from Sprague-Dawley rats exposed to Abeta under physiological (pH 7.4) or moderate acidosis (pH 7.15-7.05). In addition, because transforming growth factor beta (TGFbeta) 1 is neuroprotective and is induced by several pathophysiological conditions, we assessed its presence at the different pHs. The exposure of hippocampal cells to Abeta induced a conspicuous reduction of neurites' arborization, as well as increased neuronal death and nitric oxide production. However, Abeta neurotoxicity was significantly attenuated when hippocampal cultures were kept at pH 7.15-7.05, showing a 68% reduction on lactate dehydrogenase release compared with cultures exposed to Abeta at pH 7.4 (P<0.01). Similarly, 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide reduction increased 3.5-fold (P<0.05), and Abeta-induced nitrite production was reduced by 65% when exposed to moderate acidosis compared with basal pH media (P<0.05). At the same time, moderate acidosis decreased intracellular TGFbeta1 precursor (latency associated protein-TGFbeta1) and increased up to fourfold TGFbeta1 bioactivity, detecting a 43% increase in the active TGFbeta levels in cultures exposed to Abeta and moderate acidosis. Inhibition of TGFbeta signaling abolished the neuroprotective effect of moderate acidosis. Our results show that moderate acidosis protected hippocampal cells from Abeta-mediated neurotoxicity through the increased activation and signaling potentiation of TGFbeta.


Stroke in women: risk and prevention throughout the lifespan.
Women have a one in five chance of having a stroke during their lifetime. Although the majority of strokes occur in the oldest age groups, younger women have unique risks during their childbearing years because of pregnancy, preeclampsia, and the use of oral contraceptives. Fortunately, the absolute risk of stroke in these young women is low, but a history of preeclampsia during pregnancy or postpartum may be an indication of risk that carries over into later years after childbearing. In addition, menopause represents a risk because of the potential for increasing blood pressure, low-density lipoprotein cholesterol, abdominal obesity, insulin resistance, and decreasing high-density lipoprotein cholesterol. Early identification of stroke risk in women will help to minimize the effect of the stroke epidemic in older women.


Improved Sweetpotato Whitefly and Potato Psyllid Control in Tomato by Combining the Mirid Dicyphus hesperus (Heteroptera: Miridae) With Specialist Parasitic Wasps.
Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae) and Bactericera cockerelli Sulcer (Hemiptera: Psyllidae) are important pests in tomato, and the mirid Dicyphus hesperus Knight (Heteroptera: Miridae) has been shown as an effective predator of both pests. Although the predator was able to suppress populations of both pests, the remaining levels could still exceed tolerable levels. Thus, we here hypothesized whether the combination of D. hesperus with the specialist parasitoids Eretmocerus eremicus Rose y Zolnerowich (Hymenoptera: Aphelinidae) (whitefly) and Tamarixia triozae (Burks) (Hymenoptera: Eulophidae) (psyllid) would result in better pest control on a greenhouse scale. For that, we conducted a trial in which we compared the results against B. tabaci and B. cockerelli in greenhouses treated with D. hesperus alone or the predator in combination with the specialist parasitoids. The results showed that the predator was able to establish and suppress B. tabaci and B. cockerelli in tomato, but the addition of the specialist parasitoids resulted in better and more cost-effective pest control. Implementation of this method would therefore increase the robustness and reliability of biocontrol-based integrated pest management programmes for tomato crops, over methods based exclusively on D. hesperus release.


Excretion of total and muscular N tau-methylhistidine and creatinine in muscle diseases.
The daily urinary excretions of N tau-methylhistidine and creatinine from 52 adult patients were measured under standardized conditions. The ratio of N tau-methylhistidine to creatinine excretion was calculated on the basis of the total and muscle-specific excretion rates and correlated to the clinical status of the patients. In patients with muscular diseases and in those with diseases of the central nervous system, the total daily excretion of both metabolites was about 30% lower than in controls. The muscle-specific ratio in patients with diseases of the central nervous system and patients with muscular diseases was not different from that observed in controls. Only in patients with neurogenic atrophies was the ratio elevated, so that it was more than twice the control value. The ratio of excreted N tau-methylhistidine/creatinine is only valid as an indicator of myofibrillar protein breakdown after correction for the contribution of nonskeletal muscle tissues to the urinary excretion.


Radiology on Board the PLA(N) Peace Ark Hospital Ship During a Humanitarian Medical Relief Mission to the Philippines.
From November 24 to December 10, 2013, the Chinese People's Liberation Army Navy [PLA(N)] hospital ship Peace Ark was deployed to the Leyte Gulf in the Philippines to provide humanitarian medical relief in Tacloban after Typhoon Haiyan. The purpose of this study was to assess the radiological services aboard the ship to provide guidance for future missions. A retrospective review was performed on a cohort of 109 patients who underwent digital radiography (DR) and 59 patients who underwent computed tomography (CT) scans during a 16-day period during a humanitarian medical relief mission to the Philippines. Patient demographics, DR findings, and CT findings were analyzed. The mean age of the 109 DR patients was 39.7 years for the 64 males and 43.7 years for the 45 females. A total of 148 DR examinations were performed of the chest (n=109), extremities (n=35), and spine (n=4). The mean age of the 59 CT patients was 43.8 years for the 32 males and 49.1 years for the 27 females. A total of 72 CT scans were performed of the head and neck (n=36), thorax (n=24), abdomen (n=5), spine (n=4), and extremities (n=3). The imaging findings mainly included disaster-related and non-disaster-related fractures, pulmonary tuberculosis, pulmonary infection, acute brain infarction, intracranial hematoma, and occupying lesions. Analysis of radiological services during a humanitarian medical relief mission to the Philippines provided meaningful information for future humanitarian medical relief missions.


Effect of directly observed therapy for highly active antiretroviral therapy on virologic, immunologic, and adherence outcomes: a meta-analysis and systematic review.
Directly observed therapy of highly active antiretroviral therapy (DOT-HAART) is a feasible adherence intervention. Prospective DOT-HAART studies have shown mixed results, and optimal target groups have yet to be defined. We performed a meta-analysis and systematic review to assess the effect of DOT-HAART on adherence and virologic and immunologic response. We performed a comprehensive search through August 2009 to identify peer-reviewed controlled studies that involved outpatient DOT-HAART among adults and reported at least 1 outcome assessed in this meta-analysis. Random-effects meta-analyses were performed; differences in effect on virologic suppression were examined using stratified meta-analyses and meta-regression on several study characteristics. Seventeen studies met inclusion criteria. Compared with control groups, DOT-HAART recipients were more likely to achieve an undetectable viral load (random effects risk ratio 1.24, 95% confidence interval (CI): 1.08 to 1.41), a greater increase in CD4 cell count (random effects weighted mean difference 43 cells/microL, 95% CI: 12 to 74 cells/microL), and HAART adherence of > or =95% (random effects risk ratio 1.17, 95% CI: 1.03 to 1.32). Results varied with respect to virologic response. DOT-HAART did not have a significant effect on virologic suppression when restricted to randomized controlled studies. Post-treatment effect was not observed in a limited number of studies. DOT-HAART had a significant effect on virologic, immunologic, and adherence outcomes, although its efficacy was not supported when restricting analysis to randomized controlled trials. DOT-HAART shows greatest treatment effect when targeting individuals with greater risk of nonadherence and when delivering the intervention that maximizes participant convenience and provides enhanced adherence support. Further investigation is needed to assess the postintervention effect and cost-effectiveness of DOT-HAART.


Toward Low-Temperature Solid-Source Synthesis of Monolayer MoS2.
Two-dimensional (2D) semiconductors have been proposed for heterogeneous integration with existing silicon technology; however, their chemical vapor deposition (CVD) growth temperatures are often too high. Here, we demonstrate direct CVD solid-source precursor synthesis of continuous monolayer (1L) MoS2 films at 560 °C in 50 min, within the 450-to-600 °C, 2 h thermal budget window required for back-end-of-the-line compatibility with modern silicon technology. Transistor measurements reveal on-state current up to ∼140 μA/μm at 1 V drain-to-source voltage for 100 nm channel lengths, the highest reported to date for 1L MoS2 grown below 600 °C using solid-source precursors. The effective mobility from transfer length method test structures is 29 ± 5 cm2 V-1 s-1 at 6.1 × 1012 cm-2 electron density, which is comparable to mobilities reported from films grown at higher temperatures. The results of this work provide a path toward the realization of high-quality, thermal-budget-compatible 2D semiconductors for heterogeneous integration with silicon manufacturing.


The development of adopted children after institutional care: a follow-up study.
Research suggests that institutional care has long-lasting effects on children. However, no study has longitudinally studied infants in an institution and their subsequent development at age four. Sixty-one adopted children aged four years who had spent their first two years of life in an institution were compared to 39 children reared in their own two-parent families. Cognitive development, security of attachment, shyness, children's emotional understanding and behavioural problems were examined in both groups. Parental health and stress were also assessed. At four years adopted children still had lower scores on cognitive development, were less secure, and less able to understand emotions than family-reared children. Children with a secure attachment type in infancy were found to be less secure at age four, compared with those who were classified in infancy as having an insecure attachment type. Their physical development had recovered, they were less shy, had no behavioural problems and no problems in the relationship with their teacher. Early residential group care has long-lasting effects on important socio-emotional and cognitive aspects of preschool children's development.


Non-accidental injuries found in necropsies of domestic cats: a review of 191 cases.
Animal cruelty is defined as a deliberate action that causes pain and suffering to an animal. In Brazil, legislation known as the Environmental Crimes Law states that cruelty toward all animal species is criminal in nature. From 644 domestic cats necropsied between January 1998 and December 2009, 191 (29.66%) presented lesions highly suggestive of animal cruelty. The main necroscopic finding was exogenous carbamate poisoning (75.39%) followed by blunt-force trauma (21.99%). Cats from 7 months to 2 years of age were the most affected (50.79%). In Brazil, violence is a public health problem and there is a high prevalence of domestic violence. Therefore, even if laws provide for animal welfare and protection, animals are common targets for violent acts. Within a context of social violence, cruelty toward animals is an important parameter to be considered, and the non-accidental lesions that were found are evidence of malicious actions.


[Emergent Caesarean Section in a Patient with a Mediastinal Tumor and Von Recklinghausen Disease: A Case Report].
It is rare to encounter a pregnant patient with a mediastinal tumor, and if the tumor size increases as the pregnancy progresses, this increase can cause complications such as airway constriction and vascular occlusion. We report a case of a pregnant patient diagnosed with von Recklinghausen disease at the age of seven and diagnosed with a mediastinal tumors just after her present admission. The impending suffocation progressed and fetal heart rate decreased during her hospitalization. Her trachea was intubated and she was moved to an operating room for an emergent cesarean section under general anesthesia. With this rapid response, we could rescue both patient and infant. If the size of mediastinal tumor increases as pregnancy progresses, the tumor will cause suffocation by airway compression from the outside, in addition to specific airway edema on the inward side. The present case demonstrates that appropriate desisoins must be made for airway manegement and initiation of surgery.


Activation of phospholipase Cgamma2 by tyrosine phosphorylation.
Phospholipase Cgamma2 (PLCgamma2) has been implicated in collagen-induced signal transduction in platelets and antigen-dependent signaling in B-lymphocytes. It has been suggested that tyrosine kinases activate PLCgamma2. We expressed the full-length cDNA for human PLCgamma2 in bacteria and purified the recombinant enzyme. The recombinant enzyme was Ca(2+)-dependent with optimal activity in the range of 1 to 10 microM Ca(2+). In vitro phosphorylation experiments with recombinant PLCgamma2 and recombinant Lck, Fyn, and Lyn tyrosine kinases showed that phosphorylation of PLCgamma2 led to activation of the recombinant enzyme. Using site-directed mutagenesis, we investigated the role of specific tyrosine residues in activation of PLCgamma2. A mutant form of PLCgamma2, in which all three tyrosines at positions 743, 753, and 759 in the SH2-SH3 linker region were replaced by phenylalanines, exhibited decreased Lck-induced phosphorylation and completely abolished the Lck-dependent activation of PLCgamma2. Individual mutations of these tyrosine residues demonstrated that tyrosines 753 and 759, but not 743, were responsible for Lck-induced activation of PLCgamma2. To confirm these results, we procured a phosphospecific antibody to a peptide containing phosphorylated tyrosines corresponding to residues 753 and 759. This antibody recognized phosphorylated wild-type PLCgamma2 on Western blots but did not interact with unphosphorylated PLCgamma2 or with PLCgamma2 containing mutated tyrosine residues at 753 and 759. Using this antibody, we showed in intact platelets that collagen, a PLCgamma2-dependent agonist, induces phosphorylation of PLCgamma2 at Y753 and Y759. These studies demonstrate the importance of these two tyrosine residues in regulating the activity of PLCgamma2.


Stirred bioreactors for the expansion of adult pancreatic stem cells.
Adult pluripotent stem cells are a cellular resource representing unprecedented potential for cell therapy and tissue engineering. Complementary to this promise, there is a need for efficient bioprocesses for their large scale expansion and/or differentiation. With this goal in mind, our work focused on the development of three-dimensional (3-D) culture systems for controlled expansion of adult pancreatic stem cells (PSCs). For this purpose, two different culturing strategies were evaluated, using spinner vessels: cell aggregated cultures versus microcarrier technology. The use of microcarrier supports (Cytodex 1 and Cytodex 3) rendered expanded cell populations which retained their self-renewal ability, cell marker, and the potential to differentiate into adipocytes. This strategy surmounted the drawbacks of aggregates in culture which were demonstrably unfeasible as cells clumped together did not proliferate and lost PSC marker expression. Furthermore, the results obtained showed that although both microcarriers tested here were suitable for sustaining cell expansion, Cytodex 3 provided a better substrate for the promotion of cell adherence and growth. For the latter approach, the potential of bioreactor technology was combined with the efficient Cytodex 3 strategy under controlled environmental conditions (pH-7.2, pO2-30% and temperature-37 degrees C); cell growth was more efficient, as shown by faster doubling time, higher growth rate and higher fold increase in cell concentration, when compared to spinner cultures. This study describes a robust bioprocess for the controlled expansion of adult PSC, representing an efficient starting point for the development of novel technologies for cell therapy.


Toward the Long-Term Stability of Cobalt Benzoate Confined Highly Dispersed PtCo Alloy Supported on a Nitrogen-Doped Carbon Nanosheet/Fe3C Nanoparticle Hybrid as a Multifunctional Catalyst for Zinc-Air Batteries.
This work reports a new type of platinum-based heterostructural electrode catalyst that highly dispersed PtCo alloy nanoparticles (NPs) confined in cobalt benzoate (Co-BA) nanowires are supported on a nitrogen-doped ultra-thin carbon nanosheet/Fe3C hybrid (PtCo@Co-BA-Fe3C/NC) to show high electrochemical activity and long-term stability. One-dimensional Co-BA nanowires could alleviate the shedding and agglomeration of PtCo alloy NPs during the reaction so as to achieve satisfactory long-term durability. Moreover, the synergistic effect at the interface optimizes the surface electronic structure and prominently accelerates the electrochemical kinetics. The oxygen reduction reaction half-wave potential is 0.923 V, and the oxygen evolution reaction under the condition of 10 mA•cm-2 is 1.48 V. Higher power density (263.12 mW•cm-2), narrowed voltage gap (0.49 V), and specific capacity (808.5 mAh•g-1) for PtCo@Co-BA-Fe3C/NC in Zn-air batteries are achieved with long-term cycling measurements over 776 h, which is obviously better than the Pt/C + RuO2 catalyst. The interfacial electronic interaction of PtCo@Co-BA-Fe3C/NC is investigated, which can accelerate electron transfer from Fe to Pt. Density functional theory calculations also indicate that the interfacial potential regulates the binding energies of the intermediates to achieve the best performance.


A light microscopic and ultrastructural study of spindle-shaped hepatocellular carcinoma.
Spindle-cell hepatocellular carcinoma is an unusual morphologic variant of hepatocellular carcinoma with a typical sarcomatous appearance. The exact diagnosis of this tumor may be difficult when only small biopsies are available and in the absence of ultrastructural studies. We describe two cases of hepatocellular carcinoma: one was entirely composed of spindle-shaped cells, and the other was a typical hepatocellular carcinoma with only a small area of sarcomatous, fusiform cells. In the first case, ultrastructural studies demonstrated desmosomes and many Mallory bodies and confirmed the epithelial nature of the neoplasm. In the second case, no ultrastructural studies were available, but the presence of gradual transition from liver cell carcinoma to spindle-cell carcinoma excluded the diagnosis of carcino-sarcoma.


Early diagnosis of Meckel's syndrome.
Meckel's syndrome is a disorder of polygenic origin inherited as an autosomal recessive. The main features are microcephaly, occipital encephalocoele with associated midline facial defects, renal and limb anomalies. The diagnosis has previously been made ultrasonically by the repeated demonstration of small head size. In this instance a renal anomaly was demonstrated and use to confirm the diagnosis.


Uncommon Side Effects of COVID-19 Vaccination in the Pediatric Population.
Introduction The rapid development of vaccines followed the Coronavirus disease 2019 (COVID-19) pandemic. There is still significant vaccine hesitancy, especially among parents. Large-scale pediatric population-based studies or reviews about vaccine side effects are limited. Data sources and methods The Centers for Disease Control and Prevention (CDC) recommends recipients or their providers notify possible adverse events to the Vaccine Adverse Event Reporting System (VAERS). We evaluated Delaware state data from the VAERS system for the pediatric age group. Results A total of 111 reports were reviewed, with summaries of the reported key side effects discussed, including seizures, myocarditis, stroke, multisystem inflammatory syndrome in children (MIS-C), chest pain, hematuria, menstrual disorder, appendicitis, behavioral and otological side effects, etc. Conclusions We noted the approximate prevalence of reported adverse events to be <0.2%. Further studies with larger sample sizes or those focused on each key side effect are needed to evaluate these side effects in detail. An open discussion about the possible side effects and reinforcing the individual, family, and community benefits are key to promoting COVID-19 vaccine acceptance.


Stabilizing the heterologously expressed uric acid-xanthine transporter UapA from the lower eukaryote Aspergillus nidulans.
Despite detailed genetic and mutagenic analysis and a recent high-resolution structure of a bacterial member of the nucleobase-ascorbate transporter (NAT) family, understanding of the mechanism of action of eukaryotic NATs is limited. Preliminary studies successfully expressed and purified wild-type UapA to high homogeneity; however, the protein was extremely unstable, degrading almost completely after 48 h at 4°C. In an attempt to increase UapA stability we generated a number of single point mutants (E356D, E356Q, N409A, N409D, Q408E and G411V) previously shown to have reduced or no transport activity, but correct targeting to the membrane. The mutant UapA constructs expressed well as GFP fusions in Saccharomyces cerevisiae and exhibited similar fluorescent size exclusion chromatography (FSEC) profiles to the wild-type protein, following solubilization in 1% DDM, LDAO or OM + 1 mM xanthine. In order to assess the relative stabilities of the mutants, solubilized fractions prepared in 1% DDM + 1 mM xanthine were heated at 45°C for 10 min prior to FSEC. The Q408E and G411V mutants gave markedly better profiles than either wild-type or the other mutants. Further FSEC analysis following solubilization of the mutants in 1% NG ± xanthine confirmed that G411V is more stable than the other mutants, but showed that Q408E is unstable under these conditions. G411V and an N-terminally truncated construct G411VΔ1-11 were submitted to large-scale expression and purification. Long-term stability analysis revealed that G411VΔ1-11 was the most stable construct and the most suited to downstream structural studies.


Effects of Angiotensin II Receptor Blockers and ACE (Angiotensin-Converting Enzyme) Inhibitors on Virus Infection, Inflammatory Status, and Clinical Outcomes in Patients With COVID-19 and Hypertension: A Single-Center Retrospective Study.
With the capability of inducing elevated expression of ACE2 (angiotensin-converting enzyme 2), the cellular receptor for severe acute respiratory syndrome coronavirus 2, angiotensin II receptor blockers (ARBs) or ACE inhibitors treatment may have a controversial role in both facilitating virus infection and reducing pathogenic inflammation. We aimed to evaluate the effects of ARBs/ACE inhibitors on coronavirus disease 2019 (COVID-19) in a retrospective, single-center study. One hundred twenty-six patients with COVID-19 and preexisting hypertension at Hubei Provincial Hospital of Traditional Chinese Medicine in Wuhan from January 5 to February 22, 2020, were retrospectively allocated to ARBs/ACE inhibitors group (n=43) and non-ARBs/ACE inhibitors group (n=83) according to their antihypertensive medication. One hundred twenty-five age- and sex-matched patients with COVID-19 without hypertension were randomly selected as nonhypertension controls. In addition, the medication history of 1942 patients with hypertension that were admitted to Hubei Provincial Hospital of Traditional Chinese Medicine from November 1 to December 31, 2019, before the COVID-19 outbreak were also reviewed for external comparison. Epidemiological, demographic, clinical, and laboratory data were collected, analyzed, and compared between these groups. The frequency of ARBs/ACE inhibitors usage in patients with hypertension with or without COVID-19 were comparable. Among patients with COVID-19 and hypertension, those received either ARBs/ACE inhibitors or non-ARBs/ACE inhibitors had comparable blood pressure. However, ARBs/ACE inhibitors group had significantly lower concentrations of hs-CRP (high-sensitivity C-reactive protein; P=0.049) and PCT (procalcitonin, P=0.008). Furthermore, a lower proportion of critical patients (9.3% versus 22.9%; P=0.061) and a lower death rate (4.7% versus 13.3%; P=0.216) were observed in ARBs/ACE inhibitors group than non-ARBs/ACE inhibitors group, although these differences failed to reach statistical significance. Our findings thus support the use of ARBs/ACE inhibitors in patients with COVID-19 and preexisting hypertension.


Modulation of the neurotransmitter systems through the anti-inflammatory and antidepressant-like effects of squalene from Aurantiochytrium sp.
Although algae have been the focal point of biofuel research, studies on their biological activities have been limited. In recent years, however, the importance of algae as sources of functional ingredients has been recognized due to their health beneficial effects. In this study, we evaluated the antidepressant-like activities of ethanol extract of Aurantiochytrium sp. (EEA) in the forced swimming test (FST)-induced depression in ICR mice. Imipramine, a commercially available tricyclic antidepressant drug, was used as positive control. Animals were administered EEA orally for 14 consecutive days and were subjected to the locomotor activity testing. Additionally, changes in gene expression in mice brain were assessed by real-time PCR and microarray assays to understand the molecular mechanisms underlying the effect of EEA. We found that the immobility time in FST was significantly reduced in the EEA-treated mice compared to that of in the control mice. Microarray and real-time PCR results revealed that EEA treatment induced changes in several genes in mice brain associated with pro-inflammation and dopaminergic, cholinergic, glutamatergic, and serotonergic synapses. It has previously been reported that several cytokines, such as IL-6 and TNF-α, which mediate neuroinflammation, are also responsible for indirectly altering brain neurotransmitter levels in neuropsychiatric disorders. Therefore, the regulation of the expression of pro-inflammatory genes in EEA-administered mice brain is considered to contribute to the enhancement of neurotransmitter systems-related gene expression in our study. Moreover, our in vitro study suggested that squalene, a component produced by Aurantiochytrium, was one of the active substances in EEA. In conclusion, our study provides the first evidence that Aurantiochytrium sp. can reduce neuroinflammation that may contribute to the modulation of the neurotransmitter systems, which could underlie its antistress and antidepressant effects.


Thyroid function in pulmonary tuberculosis.
To evaluate the thyroid hormone economy in pulmonary tuberculosis (PTB). Cohort comparative study. Multan Institute of Radiotherapy and Nuclear Medicine (MINAR) from January 2003 to June 2005. The study included 266 confirmed cases of pulmonary tuberculosis (PTB), aged between 11 and 65 years, who had completed short course of chemotherapy. Two samples were collected from each patient, first after final diagnosis and second after completion of the treatment. Initial analysis of samples showed that 31 samples had both T3 (triiodothyronine) and T4 (thyroxine) in lower than normal range. One more sample in the middle of treatment was collected for these patients. Radioimmunoassays and immunoradiometeric assays were applied to estimate mean TT3, TT4 and TSH (thyroid stimulating hormone) levels. Students t-test was used to compare patient and normal values derived from 713 volunteers. The age had no effect on levels of T3, T4 and TSH in normal persons. Mean T3 and T4 values (0.74 nmol/l and 91.9 nmol/l) in PTB patients were significantly decreased (p < 0.001) with 50% and 11.6 % cases in lower than normal range respectively. Follow-up data on subgroup of 31 patients showed that both T3 and T4 levels improved after chemotherapy. TSH levels remained unaffected throughout. Both T3 and T4 levels were decreased in PTB but T4 levels were less affected. TSH was found unaffected by the disease. This confirms that PTB produces euthyroid sick syndrome (SES) i.e., decreased T3 and T4, and no change affected by 5'deiodinase (an enzyme that causes deiodination of T4). The levels improved after chemotherapy.


Identification of three internal feeders from Korla fragrant pears by quantitative real-time polymerase chain reaction.
Cydia pomonella, Euzophera pyriella Yang, and Grapholitha molesta are destructive pest species of Korla fragrant pears in Xinjiang. They are also quarantine pests of concern in a number of countries. Identification of these small pest larvae by morphological characters is difficult, and misidentifications will influence appropriate quarantine decisions. Here, a 520 bp fragment of mitochondrial cytochrome oxidase subunit I (COI) was first amplified and sequenced from each species, and a diagnostic region was observed. Subsequently, the species-specific primer and probe sets of quantitative real-time PCR (qPCR) were designed, which amplified a 114-116 bp fragment of COI genes. This method was validated by amplification DNA extracted from single, multiple, and mixed pest samples. Results indicated that this method allows rapid discrimination and reliable identification of larvae, pupae, and adult specimens of all three species, which could help the international export trading of Korla fragrant pears and related products.


Effect of isolation techniques on the characteristics of pigeon pea (Cajanus cajan) protein isolates.
In this study, the effect of different isolation techniques on the isolated proteins from pigeon pea was investigated. Water, methanol, ammonium sulfate, and acetone were used for the precipitation of proteins from pigeon pea. Proximate composition, and antinutritional and functional properties of the pigeon pea flour and the isolated proteins were measured. Data generated were statistically analyzed. The proximate composition of the water-extracted protein isolate was moisture 8.30%, protein 91.83%, fat 0.25%, ash 0.05%, and crude fiber 0.05%. The methanol-extracted protein isolate composition was moisture 7.87%, protein 91.83%, fat 0.17%, and ash 0.13%, while crude fiber and carbohydrates were not detected. The composition of the ammonium sulfate-extracted protein isolate was moisture 7.73%, protein 91.73%, fat 0.36, ash 0.13%, and crude fiber 0.67%. The acetone-extracted protein isolate composition was moisture 8.03%, protein 91.50%, ash 0.67%, and fat 0.30%, but crude fiber and carbohydrates were not detected. The isolate precipitated with ammonium sulfate displayed the highest foaming capacity (37.63%) and foaming stability (55.75%). Isolates precipitated with methanol and acetone had the highest water absorption capacity (160%). Pigeon pea protein isolates extracted with methanol and ammonium sulfate had the highest oil absorption capacity of 145%. Protein isolates recovered through acetone and methanol had the highest emulsifying capacity of 2.23% and emulsifying stability of 91.47%, respectively. The proximate composition of the recovered protein isolates were of high purity. This shows the efficiency of the extraction techniques. The isolates had desirable solubility index. All the isolation techniques brought significant impact on the characteristics of the isolated pigeon pea protein.


Mechanisms and consequences of leukocyte-endothelial interaction.
Leukocyte adhesion to endothelium is a critical event in host defense against microorganisms and in the repair of tissue damage. Under some circumstances, however, altered leukocyte-endothelial interactions may contribute to the pathogenesis of inflammatory and immune diseases. In a number of experimental models, the inhibition of leukocyte adherence to endothelium substantially reduces vascular and tissue injury. Antiadhesion therapy may represent a novel approach to the treatment of a wide spectrum of clinical disorders.


Controlling the rate of Type I error over a large set of statistical tests.
When many tests of significance are examined in a research investigation with procedures that limit the probability of making at least one Type I error--the so-called familywise techniques of control--the likelihood of detecting effects can be very low. That is, when familywise error controlling methods are adopted to assess statistical significance, the size of the critical value that must be exceeded in order to obtain statistical significance can be extremely large when the number of tests to be examined is also very large. In our investigation we examined three methods for increasing the sensitivity to detect effects when family size is large: the false discovery rate of error control presented by Benjamini and Hochberg (1995), a modified false discovery rate presented by Benjamini and Hochberg (2000) which estimates the number of true null hypotheses prior to adopting false discovery rate control, and a familywise method modified to control the probability of committing two or more Type I errors in the family of tests examined--not one, as is the case with the usual familywise techniques. Our results indicated that the level of significance for the two or more familywise method of Type I error control varied with the testing scenario and needed to be set on occasion at values in excess of 0.15 in order to control the two or more rate at a reasonable value of 0.01. In addition, the false discovery rate methods typically resulted in substantially greater power to detect non-null effects even though their levels of significance were set at the standard 0.05 value. Accordingly, we recommend the Benjamini and Hochberg (1995, 2000) methods of Type I error control when the number of tests in the family is large.


Novel screening for transthyretin amyloidosis by using fat ultrasonography.
We aimed to assess the possibility of using a noninvasive screening method for hereditary transthyretin amyloidosis by means of abdominal fat ultrasonography. Quantitative analysis of ultrasound B-mode images demonstrated a significant increase in mean echogenicity and a loss of the normal structure of the layers of fat tissue in patients with hereditary transthyretin amyloidosis (n = 19). The ultrasound features of the fat tissue and the degree of amyloid deposition seen histopathologically showed a significant correlation. These results suggest that abdominal fat ultrasonography may be a valuable method for screening for hereditary transthyretin amyloidosis. Ann Neurol 2017;81:604-608.


Ribulose-1,5-bisphosphate carboxylase/oxygenase from thermophilic red algae with a strong specificity for CO2 fixation.
Strongly carboxylase-specific ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) was found in Galdieria partita and Cyanidium caldarium (Cyanidiophyceae). The relative specificity, VcKo/VoKc, of Galdieria and Cyanidium RuBisCO was 238 and 222, respectively; 2.4 to 2.5-fold that of higher plant RuBisCOs. The apparent Km of RuBisCO from the thermophilic red algae for CO2 was 6 to 7 microM and the smallest of the values reported so far for other RuBisCOs. The pre-rhodophyte Porphiridium purpureum, which lives at moderate temperatures, had RuBisCO with the relative specificity value of 144. A large difference (5.2 kcal x mol(-1)) in the activation energies between the carboxylase and oxygenase activities in Galdieria RuBisCO was a cause of the strong specificity for the carboxylase activity.


Vascular Endothelial Growth Factor Receptor Family in Ascidians, Halocynthia roretzi (Sea Squirt). Its High Expression in Circulatory System-Containing Tissues.
The vascular endothelial growth factor (VEGF)-VEGF Receptor (VEGFR) system is an important pathway for regulation of angiogenesis. However, its evolutionary development, particularly the step from invertebrates to vertebrates, is still largely unknown. Here, we molecularly cloned the VEGFR-like gene from Halocynthia roretzi, a species belonging to the Tunicata, the chordate subphylum recently considered the sister group of vertebrates. The cDNA encoded a homolog of human VEGFR, including the transmembrane domain, and the tyrosine kinase domain with a kinase-insert region, which was designated S. sq VEGFR (GenBank AB374180). Similar to Tunicates including ascidians in the phylogenetic tree, the Amphioxus, another chordate, is located close to vertebrates. However, S. sq VEGFR has a higher homology than the Amphioxus VEGFR-like molecule (GenBank AB025557) to human VEGFR in the kinase domain-2 region. The S. sq VEGFR mRNA was expressed at highest levels in circulatory system-containing tissues, suggesting that S. sq VEGFR plays an important role in the formation or maintenance of circulatory system in Tunicates, Halocynthia roretzi.


Updated recommendations for managing the care of patients receiving oral bisphosphonate therapy: an advisory statement from the American Dental Association Council on Scientific Affairs.
and Overview. In 2005, the American Dental Association (ADA) Council on Scientific Affairs convened an expert panel to develop clinical recommendations for dentists treating patients who are receiving oral bisphosphonate therapy. The Journal of the American Dental Association published the resulting report in 2006. This 2008 advisory statement is the first of projected periodic updates of the 2006 clinical recommendations. This 2008 advisory statement concludes, on the basis of a review of the current literature, that for patients receiving bisphosphonate therapy, the risk of developing bisphosphonate-associated osteonecrosis (BON) of the jaw apparently remains low. It also newly concludes that current screening and diagnostic tests are unreliable for predicting a patient's risk of developing the condition. This statement updates the 2006 recommendations regarding general dentistry, management of periodontal diseases, implant placement and maintenance, oral and maxillofacial surgery, endodontics, restorative dentistry and prosthodontics, and orthodontics.


Serum 5-Methyltetrahydrofolate Status Is Associated with One-Carbon Metabolism-Related Metabolite Concentrations and Enzyme Activity Indicators in Young Women.
Maintaining optimal one-carbon metabolism (OCM) is essential for health and pregnancy. In this cross-sectional study, folate status was assessed based on 5-methyltetrahydrofolate (5-MTHF) levels, and the association between 5-MTHF and OCM-related metabolites was investigated in 227 female Japanese university students aged 18-25 years. The participants were divided into high and low 5-MTHF groups based on their folate status. Serum samples of the participants were collected while they were fasting, and 18 OCM-related metabolites were measured using stable-isotope dilution liquid chromatography-electrospray tandem mass spectrometry. The association between serum 5-MTHF and OCM-related metabolite concentrations was assessed using Spearman's rank correlation coefficient. Serum 5-MTHF concentrations were negatively correlated with total homocysteine (tHcy) concentrations and positively correlated with S-adenosylmethionine (SAM) and total cysteine (tCys) concentrations. Serum 5-MTHF concentrations demonstrated a stronger negative correlation with tHcy/tCys than with tHcy alone. The negative correlation between betaine and tHcy concentrations was stronger in the low 5-MTHF group than in the high 5-MTHF group. The 5-MTHF status could be linked to Hcy flux into the transsulfuration pathway via SAM. Therefore, the tHcy/tCys ratio may be a more sensitive indicator of the 5-MTHF status than tHcy alone. Furthermore, a low 5-MTHF status can enhance Hcy metabolism via betaine.


A novel haemoplasma species identified in archived primate blood smears.
In order to confirm a microscopic diagnosis of 'eperythrozoonosis' made over 40 years ago in a captive owl monkey (Aotus trivirgatus), DNA was extracted from archived fixed and stained blood smears and subjected to generic haemotropic mycoplasma (haemoplasma) quantitative real-time PCR (qPCR) and a human glyceraldehyde-3-phosphate dehydrogenase qPCR as an amplification control. The qPCRs confirmed the extraction of host DNA from the samples and the presence of a haemoplasma species. Partial 16S rRNA and ribonuclease P ribosomal gene fragments were amplified by PCR, cloned and sequenced. Sequence data and phylogeny showed the owl monkey haemoplasma to lie in the haemominutum clade of haemoplasmas, most closely related to 'Candidatus Mycoplasma kahaneii'. This study confirms the use of generic haemoplasma qPCRs to successfully amplify haemoplasma DNA from fixed, stained and archived blood smears from the early 1970s and provides molecular confirmation of the existence of a novel haemoplasma species in an owl monkey, for which the name 'Candidatus Mycoplasma aoti' sp. nov. is proposed.


Water-Soluble Organic Composition of the Arctic Sea Surface Microlayer and Association with Ice Nucleation Ability.
Organic matter in the sea surface microlayer (SML) may be transferred to the atmosphere as sea spray and hence influence the composition and properties of marine aerosol. Recent work has demonstrated that the SML contains material capable of heterogeneously nucleating ice, but the nature of this material remains largely unknown. Water-soluble organic matter was extracted from SML and underlying seawater from the Arctic and analyzed using a combination of mass spectrometric approaches. High performance liquid chromatography-ion trap mass spectrometry (LC-IT-MS), and Fourier transform ion cyclotron resonance MS (FT-ICR-MS), showed seawater extracts to be compositionally similar across all stations, whereas microlayer extracts had a different and more variable composition. LC-IT-MS demonstrated the enrichment of particular ions in the microlayer. Ice nucleation ability (defined as the median droplet freezing temperature) appeared to be related to the relative abundances of some ions, although the extracts themselves did not retain this property. Molecular formulas were assigned using LC-quadrupole time-of-flight MS (LC-TOF-MS2) and FT-ICR-MS. The ice nucleation tracer ions were associated with elevated biogenic trace gases, and were also observed in atmospheric aerosol collected during the summer, but not early spring suggesting a biogenic source of ice nuclei in the Arctic microlayer.