SILAC surrogates: rescue of quantitative information for orphan analytes in spike-in SILAC experiments.
Super-stable isotope labeling by amino acids in cell culture (Super-SILAC) enables the sensitive and accurate analysis of complex biological tissue and tumor samples by comparison of light peptides observed in biological samples to heavy peptides from SILAC cell culture spike-ins. However, despite the use of multiple cell lines for Super-SILAC spike-in standards, the full protein and peptide profiles of biological samples are not completely represented in these internal standards, leading to orphan analytes for which sample to standard ratios cannot be calculated. This problem is exacerbated in some biological systems, such as muscle tissue, which lack adequate cell culture lines to reflect their complex and idiosyncratic protein profiles, resulting in up to 40% of peptide analytes without heavy cognates. Furthermore, these unquantified orphan analytes may be among the most biologically interesting and significant species, since their presence is not common to cell lines cultured in vitro. Here, we report on the development of a surrogate analysis strategy to interpolate quantitative relationships between peptide species, observed across multiple biological samples, which lack representation within the spike-in standards. The precision and accuracy of this method was assessed by replicate experiments in which surrogate-derived ratios from defined mixtures of spike-in SILAC standard and tissue lysate were compared against traditional SILAC ratios for species where both light and heavy peptide cognates were observed. We demonstrate the robustness of our SILAC surrogates strategy across a variety of murine tissues, including liver, spleen, brain, and muscle. Our approach increases the quantitative coverage and precision within a biological sample by rescuing previously intractable peptide species and applying additional evidence to improve the precision of existing quantifications.


Ocular involvement-An unusual initial presentation of chronic myeloid leukemia: A case report.
Chronic myeloid leukemia (CML) patients frequently exhibit systemic symptoms such as fatigue, abdominal discomfort, weight loss, and fever but rarely can have atypical initial presentation in the form of ophthalmic manifestations, which can precede the diagnosis of the primary malignancy. We describe a case of a 29-year-old male who presented in our ophthalmology out-patient department (OPD) with complaints of painless, diminution of vision, which was sudden in onset in right eye (RE) and loss of vision in left eye (LE) for four and seven days, respectively. There had been a history of loss of weight and appetite for the past 2 months. The visual acuity (VA) recorded was finger counting two meters in RE and perception of light in LE with an inaccurate projection of rays in both eyes (BE). The anterior segment evaluation of both eyes (BE) was normal. Fundus revealed multiple elevated yellow subretinal lesions with exudative detachment in the RE and no view in the LE. Ultrasound-Brightness (USG B) scan in the LE revealed multiple hyperreflective echoes likely vitreous hemorrhage. Optical coherence tomography (OCT) showed subretinal hyperreflectivity with surrounding edema in RE suggestive of leukemic infiltrates. On further systemic investigations, chronic myeloid leukemia-chronic phase (CML-CP) was detected; hence, the diagnosis of RE exudative retinal detachment (RD) and LE vitreous hemorrhage with CML-CP was made. Ophthalmic involvement is more often seen in acute than chronic leukemia, which makes the diagnosis challenging. We describe a unique case of a young patient with CML-CP who initially presented with ocular involvement preceding systemic diagnosis. This case report illustrates the importance of a primary care physician or an ophthalmologist in the early diagnosis and prompt management of hematological malignancy, as ophthalmic manifestations may be a rare initial presenting feature in CML-CP. These conditions require urgent referral to a hematologist by a primary care physician in the view of early commencement of therapy.


The prevalence of loneliness across 113 countries: systematic review and meta-analysis.
To identify data availability, gaps, and patterns for population level prevalence of loneliness globally, to summarise prevalence estimates within World Health Organization regions when feasible through meta-analysis, and to examine temporal trends of loneliness in countries where data exist. Systematic review and meta-analysis. Embase, Medline, PsycINFO, and Scopus for peer reviewed literature, and Google Scholar and Open Grey for grey literature, supplemented by backward reference searching (to 1 September 2021) ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Observational studies based on nationally representative samples (n≥292), validated instruments, and prevalence data for 2000-19. Two researchers independently extracted data and assessed the risk of bias using the Joanna Briggs Institute checklist. Random effects meta-analysis was conducted in the subset of studies with relatively homogeneous research methods by measurement instrument, age group, and WHO region. Prevalence data were available for 113 countries or territories, according to official WHO nomenclature for regions, from 57 studies. Data were available for adolescents (12-17 years) in 77 countries or territories, young adults (18-29 years) in 30 countries, middle aged adults (30-59 years) in 32 countries, and older adults (≥60 years) in 40 countries. Data for all age groups except adolescents were lacking outside of Europe. Overall, 212 estimates for 106 countries from 24 studies were included in meta-analyses. The pooled prevalence of loneliness for adolescents ranged from 9.2% (95% confidence interval 6.8% to 12.4%) in South-East Asia to 14.4% (12.2% to 17.1%) in the Eastern Mediterranean region. For adults, meta-analysis was conducted for the European region only, and a consistent geographical pattern was shown for all adult age groups. The lowest prevalence of loneliness was consistently observed in northern European countries (2.9%, 1.8% to 4.5% for young adults; 2.7%, 2.4% to 3.0% for middle aged adults; and 5.2%, 4.2% to 6.5% for older adults) and the highest in eastern European countries (7.5%, 5.9% to 9.4% for young adults; 9.6%, 7.7% to 12.0% for middle aged adults; and 21.3%, 18.7% to 24.2% for older adults). Problematic levels of loneliness are experienced by a substantial proportion of the population in many countries. The substantial difference in data coverage between high income countries (particularly Europe) and low and middle income countries raised an important equity issue. Evidence on the temporal trends of loneliness is insufficient. The findings of this meta-analysis are limited by data scarcity and methodological heterogeneity. Loneliness should be incorporated into general health surveillance with broader geographical and age coverage, using standardised and validated measurement tools. PROSPERO CRD42019131448.


[A study on the thickness of buccal bone in the mandible of different vertical facial type in adults using cone-beam CT].
To provide some references of using micro-implant anchorage in clinical orthodontic treatment, the thickness of buccal bone of mandible of different vertical facial type in adults with cone-beam CT (CBCT) were measured. Initial 3-dimensional images of 45 adult patients (15 men, 30 women)were reoriented by using a standardized protocol, and divided into 3 groups by angle of mandibular plane (G1: high angle, 15 patients; G2: average angle, 15 patients; G3: low angle, 15 patients). After signing the informed consent form, three measurement points were defined at 4, 6, and 8mm from the alveolar crest in each measurement area. Statistical analysis was performed with SPSS11.0 software package. The thickness of buccal bone in mandible was thinner in G1 than in G2, and was thinnest in G3. The cortical bone thickness was thickest at the 8 mm level and thinnest at the 4mm level. The study suggested that the cortical bone thickness at 4mm level from the alveolar crest was safe for implantation. It is more stable when the distance of implants was more away from the alveolar crest. Patients with low mandibular plane angle should use self-tapping micro-implant anchorage. Supported by Nantong Science and Technology Fund (HS2013033).


Increased injection number enhances adenoviral genetic radiotherapy.
Intratumoral injection of an adenoviral vector containing radiation-inducible DNA sequences of the early growth response gene (Egr-1) promoter ligated to a cDNA encoding tumor necrosis factor-alpha (TNF-alpha; Ad.Egr-TNF) increases the radiation killing of a human radioresistant xenograft (SQ-20B). Viral dose-escalation experiments demonstrated that SQ-20B growth inhibition correlated with viral titer. Injection of 5 x 10(8) PFU Ad.Egr-TNF produced regression to a mean volume of 22 +/- 13% of the original tumor volume, 1 x 10(8) PFU to a mean of 62 +/- 24%, and 5 x 10(7) PFU to a mean of 67 +/- 27%. No regression was observed when tumors were injected with 1 x 10(7) PFU Ad.Egr-TNF or with the null viral vector (Ad.null). When two injections of vector (2 x 10(8) PFU Ad.Egr-TNF) were combined with 50 Gy, a significant increase in tumor regression was observed compared with injection of buffer, Ad.Egr-TNF, or 50 Gy. The interactive killing between TNF and radiation was enhanced significantly (P = 0.05) when the number of injections was increased from two to five while maintaining a constant viral titer (2 x 10(8) PFU Ad.Egr-TNF) and a constant radiation dose (50 Gy). Significant TNF-alpha levels were present in irradiated vs. unirradiated tumors following injection with Ad.Egr-TNF. Taken together, these data suggest that the volumetric reduction produced by the combined effects of Ad.Egr-TNF and radiation is enhanced with increasing vector concentration and the number of vector injections.


Vascular endothelial function predicts mortality risk in patients with advanced ischaemic chronic heart failure.
Endothelial function is impaired in advanced chronic heart failure (ACHF) patients. We explored a possible association between endothelial function and subsequent mortality risk in ACHF. We prospectively assessed brachial flow-mediated dilation (FMD) in 82 consecutive New York Heart Association class IV ischaemic ACHF patients with a mean left ventricular ejection fraction (LVEF) of 22 +/- 3%. Following overnight fasting and discontinuation of all medications for > or = 12 h, percent increase in FMD (%FMD) and nitroglycerin-mediated vasodilation were assessed using linear array ultrasound. All patients were followed for 14 +/- 2 months for adverse cardiovascular events, including death, hospitalization for CHF exacerbation, or myocardial infarction. Patients were divided into two groups: those with an FMD lesser than or equal to the median %FMD of 4.6% (n = 41) and those with an FMD above the median (n = 41). Both groups were comparable regarding cardiovascular risk factors, LVEF, and concomitant medications. During follow-up, 22 (53.6%) patients with FMD lesser than or equal to the median had composite adverse cardiovascular events compared with only eight patients (19.5%) with FMD above the median (P < 0.01). Furthermore, fiver deaths (12.1%) occurred in patients with FMD lesser than or equal to the median, compared with no deaths in patients with FMD above the median (P < 0.03). Cox regression analyses revealed that FMD was an independent predictor for these events. Flow-mediated dilation is associated with increased mortality risk in ischaemic ACHF patients.


Disparate exposure to physically demanding working conditions in France.
Our study was aimed at examining disparate exposure to physically demanding working conditions in France, a key objective being to identify the types of employees/jobs requiring high-priority preventive actions. We analyzed the data from the 2017 French nationwide cross-sectional survey (SUMER) on occupational hazards to which French employees in various sectors were subjected. The prevalence of several types of physically demanding working conditions (lifting of heavy loads, awkward body postures, vibrations, noise, and extreme temperatures) was explored. Potential associations of individual and job characteristics with these factors of hardship at work were studied by multivariate logistic regression. In total, 48% of employees were exposed to at least one physically demanding working condition and 24.8% were exposed to multiple constraints. While managers and intellectual professionals were exposed relatively infrequently to physical constraints, blue-collar workers experienced the highest frequency of exposure. On the one hand, the role of company size depended on the factor of hardship at work considered; on the other hand, employees in large-scale companies were generally less exposed. As expected, employees in the construction industry were the most exposed to physical constraints; that said, our results also show that some activities in the services sector (e.g., personal care, administrative and support services) were quite significantly affected by a wide array of physically demanding working conditions. Notwithstanding the establishment in France of Plans de Santé au travail (preventive workplace health and safety plans), occupational risks were found to be high, and above all, they were unevenly distributed among the various socio-professional categories, and strongly contributed to social inequalities in health. Our results identify the types of publics to be designated as high-priority targets for preventive measures aimed at reducing the adverse impacts of physically demanding working conditions and the incidence of associated musculoskeletal disorders.


Expansion of bronchial epithelial cell populations by in vitro culture of explants from dysplastic and histologically normal sites.
The genetic and phenotypic properties of cells which ultimately give rise to carcinoma of the lung are not well defined in part because of unavailability of preneoplastic cells from well-characterized dysplastic sites. In order to expand bronchial epithelial cell populations from patients at high risk for lung cancer, endobronchial biopsy specimens were explanted onto collagen- and fibronectin-coated dishes and cultured in serum-free, chemically defined media. One hundred forty-nine biopsy pairs were obtained from smokers and from healthy volunteers for culture and histologic evaluation. The histologic appearances of mucosa adjacent to the site of the cultured biopsies ranged from normal through varying degrees of noninvasive squamous dysplasia to invasive carcinoma. Confluent monolayers of pure epithelial cells were obtained from 68% of the cultured explants. Sites exhibiting high-grade dysplasia were 51% more likely to yield successful cultures than sites exhibiting normal histology (13 of 14 cultures successful versus 52 of 83 cultures successful, P < 0.02). Cultures had a maximum proliferative life span of 81 days and none of the cultures spontaneously became immortalized. Immunolabeling studies revealed that all cultured epithelial cells, regardless of the in situ histologic appearances of the mucosa at the biopsy site, strongly expressed keratin and epidermal growth factor receptor, weakly expressed transferrin receptor and human folate receptor, and were negative for neural cell adhesion molecule and human leukocyte antigen DR (HLADR). Ploidy and karyotypic analyses were performed in a limited number of explants from normal and dysplastic sites and all were found to be diploid without karyotypic abnormality. We conclude that pure bronchial epithelial cell populations can be routinely expanded from histologically normal and dysplastic sites by tissue culture of biopsy explants and that the expanded cell populations may represent a library of normal and preneoplastic cells which are suitable for immunophenotypic, ploidy, genetic, or functional analyses.


Lentivirus-mediated knockdown of TSP50 suppresses the growth of non-small cell lung cancer cells via G0/G1 phase arrest.
Non-small cell lung cancer (NSCLC) as the most frequently diagnosed lethal cancer remains the major cause of overall cancer-related death worldwide. Testes-specific protease 50 (TSP50) has been proved as a critical biomarker in various cancers, and we previously reported that TSP50 protein expression is overexpressed in clinical resected NSCLC tumor tissues and related to poor prognosis in NSCLC patients. Hence, the present study was designed to further investigate the potential oncogenesis mechanism of TSP50 in NSCLC cells. Real-time quantitative PCR, immunohistochemical assay and western blot analysis were used to analyze the TSP50 mRNA and protein expression in 20 NSCLC cases, and TSP50 expression was observed to have high levels in the NSCLC specimens and paired metastatic lymph node tissues when compared to the levels in corresponding normal lung tissues and normal lymph nodes. In the experiments in NSCLC cell lines, lentiviral short hairpin RNA (shRNA) delivery system was applied to knock down TSP50 in 95D cells, and the following investigations revealed that downregulation of TSP50 expression markedly reduced cell proliferation, colony formation and migration ability in vitro. Furthermore, the inhibition of TSP50 induced G0/G1-phase arrest and decreased expression levels of cell cycle relative markers CDK4, CDK6, and CyclinD1 and increased expression of p21 and p53 in 95D cells. In conclusion, this study indicates that TSP50 plays a significant role in NSCLC cell proliferation and may act as a novel oncogene in the development and progression of NSCLC, offering a potential cancer therapeutic target for the treatment of NSCLC.


Meta-analyses of human gut microbes associated with obesity and IBD.
Recent studies have linked human gut microbes to obesity and inflammatory bowel disease, but consistent signals have been difficult to identify. Here we test for indicator taxa and general features of the microbiota that are generally consistent across studies of obesity and of IBD, focusing on studies involving high-throughput sequencing of the 16S rRNA gene (which we could process using a common computational pipeline). We find that IBD has a consistent signature across studies and allows high classification accuracy of IBD from non-IBD subjects, but that although subjects can be classified as lean or obese within each individual study with statistically significant accuracy, consistent with the ability of the microbiota to experimentally transfer this phenotype, signatures of obesity are not consistent between studies even when the data are analyzed with consistent methods. The results suggest that correlations between microbes and clinical conditions with different effect sizes (e.g. the large effect size of IBD versus the small effect size of obesity) may require different cohort selection and analysis strategies.


A Comparative Study of Birdcage RF Coil Configurations for Ultra-High Field Magnetic Resonance Imaging.
Improvements in transmission and reception sensitivities of radiofrequency (RF) coils used in ultra-high field (UHF) magnetic resonance imaging (MRI) are needed to reduce specific absorption rates (SAR) and RF power deposition, albeit without applying high-power RF. Here, we propose a method to simultaneously improve transmission efficiency and reception sensitivity of a band-pass birdcage RF coil (BP-BC RF coil) by combining a multi-channel wireless RF element (MCWE) with a high permittivity material (HPM) in a 7.0 T MRI. Electromagnetic field (EM-field) simulations, performed using two types of phantoms, viz., a cylindrical phantom filled with oil and a human head model, were used to compare the effects of MCWE and HPM on BP-BC RF coils. EM-fields were calculated using the finite difference time-domain (FDTD) method and analyzed using Matlab software. Next, to improve RF transmission efficiency, we compared two HPM structures, namely, a hollow cylinder shape HPM (hcHPM) and segmented cylinder shape HPM (scHPM). The scHPM and MCWE model comprised 16 elements (16-rad BP-BC RF coil) and this coil configuration demonstrated superior RF transmission efficiency and reception sensitivity along with an acceptable SAR. We expect wider clinical application of this combination in 7.0 T MRIs, which were recently approved by the United States Food and Drug Administration.


A Comprehensive Prognostic and Immune Analysis of SLC41A3 in Pan-Cancer.
SLC41A3, as a member of the 41st family of solute carriers, participates in the transport of magnesium. The role of SLC41A3 in cancer prognosis and immune regulation has rarely been reported. This study was designed to analyze the expression status and prognostic significance of SLC41A3 in pan-cancers. The mRNA expression profiles of SLC41A3 were obtained from The Cancer Genome Atlas (TCGA), the Genotype-Tissue Expression (GTEx), the Broad Institute Cancer Cell Line Encyclopedia (CCLE), and the International Cancer Genome Consortium (ICGC). The Cox regression and Kaplan-Meier analyses were used to evaluate the prognostic value of SLC41A3 in pan-cancer. Furthermore, the correlation between SLC41A3 expression and immune cells infiltration, immune checkpoint, mismatch repair (MMR), DNA methyltransferase (DNMT), tumor mutation burden (TMB), and microsatellite instability (MSI) were calculated using data form TCGA database. The results showed that the expression of SLC41A3 was down-regulated in kidney renal clear cell carcinoma (KIRC), and was associated with poor overall survival and tumor-specific mortality. Whereas, the expression of SLC41A3 was up-regulated in liver hepatocellular carcinoma (LIHC), and the results of Cox regression analysis revealed that SLC41A3 was an independent factor for LIHC prognosis. Meanwhile, a nomogram including SLC41A3 and stage was built and exhibited good predictive power for the overall survival of LIHC patients. Additionally, correlation analysis suggested a significant correlation between SLC41A3 and TMB, MSI, MMR, DNMT, and immune cells infiltration in various cancers. The overall survival and disease-specific survival analysis revealed that the combined SLC41A3 expression and immune cell score, TMB, and MSI were significantly associated with clinical outcomes in ACC, LIHC, and UVM patients. Therefore, we proposed that SLC41A3 may serve as a potential prognostic biomarker for cancer.


National survey of the status of infection surveillance and control programs in acute care hospitals with more than 300 beds in the Republic of Korea.
This study was conducted to assess the status of infection surveillance and control programs (ISCPs) and to analyze the trends associated with ISCP implementation since the first program was established in Korea in 1991. A questionnaire modified from the Study on the Efficacy of Nosocomial Infection Control was mailed 4 times nationwide to acute care hospitals (n = 164) with more than 300 beds between June and October 2003. Eighty-five hospitals participated (52%). The mean number of beds (649) in the responding hospitals was significantly greater than in nonresponding hospitals. Of the participating hospitals, 92% had educational functions, 40% to 90% used hand hygiene resources, and 100% had infection control committees; 86% had infection control doctors, 98% had infection control nurses (ICNs), 89% employed only 1 ICN, and 59% employed an ICN only part-time; 68% performed surveillance, undertaking 2.7 epidemic investigations per year and 8.4 teaching programs per year; 88% undertook needlestick prevention programs; 58% performed regular air culture; and 64% discarded ineffective ISCPs. Annual trends analysis of ISCPs indicated that accreditation and legislation impact strongly on Korean ISCPs. The figures for ISCPs in this study indicate that improvements have been made since the 1990s. Legislation and accreditation have strongly influenced ISCPs. Much consideration should be given to the weaknesses in Korean ISCPs: surveillance, insufficient hand hygiene resources, and shortage of ICNs.


Prevalence of major depression in preschool children.
The prevalence of preschool major depressive disorder (MDD) was studied in the community. The whole population of children between 3 and 6 years attending preschool nurseries in three areas (one urban, one rural and one suburban) in Spain (n = 1,427) were contacted. Selection was by a two-stage procedure. At stage I, the ESDM 3-6, a screening measure for preschool depression, was used to identify a sample for more intensive interviewing. Sensitivity and specificity of the cut-off point of the ESDM 3-6 had been previously tested in a pilot study (n = 229). During the first stage, 222 preschool children (15.6%) were found to be probable depressives, because they scored 27 or more, the cut-off used. At stage II, the children were interviewed and diagnosed by the consensus of two clinicians, blind to the ESDM 3-6 results. DSM-IV diagnostic criteria were used to define caseness. A total of 16 children (1.12%) met the MDD criteria. The prevalence by areas was urban 0.87%, rural 0.88%, suburban 1.43%. Sex distribution prevalence was 1:1. This study is a contribution to the scarce epidemiology of preschool depression in the community.


Proliferative events experimentally induced by transient cold shock in the brain of adult terrestrial heterothermic vertebrates: preliminary analysis of PCNA expression in Triturus carnifex.
Experimental procedures used to investigate the persistence, location and abundance of scattered ("matrix cells") and/or clustered ("matrix areas") stem cells in the brain, responsible for proliferation in adult terrestrial heterothermic vertebrates have included an induced transient drop in body temperature in specimens subsequently deprived of encephalic areas. In a set of coordinated investigations focused on the influence of an exposure to a drastic thermally environment on these activities, we gave priority to Triturus carnifex, since there is a much larger amount of detailed, unequivocal experimental evidence available for this species than for other vertebrates of the same evolutionary level. In the present study, cold-shocked newts were examined after a stay at external temperature (the most suitable one based on previous experience) to allow the maximal expression of cerebral proliferation. In a qualitative evaluation, the brain of experimental specimens compared with that of normal individuals seemed not to show, contrary to expectations, more pronounced cell proliferation as assessed by Proliferating Cell Nuclear Antigen immunolabelling of neural-like cells in the S phase of cell cycle. This discrepancy with previous reports from other authors may depend on having used cold stress alone, while other traumatic stimuli (operatory shock, encephalic injury) administered by the previous authors might have induced a greater number of cells to move from a stand-by condition to proliferation, allowing for reparative and/or regenerative phenomena.


Pathological Renal Findings of Chronic Renal Failure in a Patient with the E66Q Mutation in the α-galactosidase A Gene.
A 66-year-old Japanese man was diagnosed with interstitial nephritis on a renal biopsy at 45 years of age and began to receive hemodialysis at 65 years of age. He was suspected of having Fabry disease as a result of a screening study for Fabry disease performed in hemodialysis patients. He had an E66Q mutation in the α-galactosidase A gene. We conducted an electron microscopic examination of a renal biopsy specimen obtained when the patient was diagnosed with chronic renal failure at 45 years of age in order to elucidate the pathogenicity of the E66Q mutation. Interestingly, an electron microscopic examination of the renal biopsy specimen indicated no characteristic findings of Fabry disease.


Prediction of significant fibrosis in HBeAg-positive patients with chronic hepatitis B by a noninvasive model.
A model was constructed consisting of clinical and serum variables to discriminate between hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with and without significant fibrosis (stages 2-4 vs. stages 0-1). Consecutive treatment-naive CHB patients who underwent liver biopsy were divided into 2 sequential groups: a training group (n = 200) and a validation group (n = 172). Multivariate analysis identified alpha2-macroglobulin, age, gamma glutamyl transpeptidase, and hyaluronic acid as independent predictors of fibrosis. The area under the receiver operating characteristic curve was 0.84 for the training group and 0.77 for the validation group. Using a cutoff score of <3.0, the presence of significant fibrosis (F2 to F4) could be excluded with high accuracy (86.1% negative predictive value [NPV], 70.1% positive predictive value [PPV], and 94.8% sensitivity) in 43 (21.5%) of 200 patients in the training group, and with the same certainty (90.9% NPV, 64.7% PPV, and 98.0% sensitivity) in 22 (12.8%) of 172 patients in the validation group. Similarly, applying a cutoff score of >8.7, the presence of significant fibrosis could be correctly identified with high accuracy (91.1% PPV, 51.6% NPV, and 95.2% specificity) in 41 (20.5%) of 200 patients in the training group, and with the same certainty (84.8% PPV, 52.4% NPV, and 90.4% specificity) in 39 (22.7%) of 172 patients of the validation group. In conclusion, a predictive model with a combination of easily accessible variables identified HBeAg-positive CHB patients with and without significant fibrosis with a high degree of accuracy. Application of this model may decrease the need for liver biopsy in staging of 35.5% CHB.


Congenital heart disease in adults and adolescents: comparative value of transthoracic and transesophageal echocardiography and MR imaging.
To compare the diagnostic value of transesophageal echocardiography and magnetic resonance (MR) imaging with that of transthoracic echocardiography in the evaluation of congenital heart disease in adults and adolescents. Corresponding transesophageal echocardiographic and MR images obtained in 61 patients (aged 14-74 years; 28 female, 33 male) with congenital cardiac abnormalities were analyzed retrospectively. Results were compared with those of transthoracic echocardiography in all patients and were confirmed by using cardiac catheterization (n = 41) and/or surgery (n = 41). of the 344 abnormalities detected with at least one imaging technique, 259 were demonstrated with transthoracic echocardiography. Transesophageal echocardiography depicted the atrioventricular junction and atrial structures the best. MR imaging was the only technique to fully depict 31 extracardiac abnormalities. In complex cardiac defects, the combination of all three imaging techniques was best. Transesophageal echocardiography and MR imaging are beneficial complementary imaging techniques in adults or adolescents with congenital heart disease.


Structure and sequence based functional annotation of Zika virus NS2b protein: Computational insights.
While Zika virus (ZIKV) outbreaks are a growing concern for global health, a deep understanding about the virus is lacking. Here we report a contribution to the basic science on the virus- a detailed computational analysis of the non structural protein NS2b. This protein acts as a cofactor for the NS3 protease (NS3Pro) domain that is important on the viral life cycle, and is an interesting target for drug development. We found that ZIKV NS2b cofactor is highly similar to other virus within the Flavivirus genus, especially to West Nile Virus, suggesting that it is completely necessary for the protease complex activity. Furthermore, the ZIKV NS2b has an important role to the function and stability of the ZIKV NS3 protease domain even when presents a low conservation score. In addition, ZIKV NS2b is mostly rigid, which could imply a non dynamic nature in substrate recognition. Finally, by performing a computational alanine scanning mutagenesis, we found that residues Gly 52 and Asp 83 in the NS2b could be important in substrate recognition.


C-reactive protein binds to both oxidized LDL and apoptotic cells through recognition of a common ligand: Phosphorylcholine of oxidized phospholipids.
C-reactive protein (CRP) is an acute-phase protein that binds specifically to phosphorylcholine (PC) as a component of microbial capsular polysaccharide and participates in the innate immune response against microorganisms. CRP elevation also is a major risk factor for cardiovascular disease. We previously demonstrated that EO6, an antioxidized LDL autoantibody, was a T15 clono-specific anti-PC antibody and specifically binds to PC on oxidized phosphatidylcholine (PtC) but not on native PtC. Similarly, EO6 binds apoptotic cells but not viable cells. In addition, such oxidized phospholipids are recognized by macrophage scavenger receptors, implying that these innate immune responses participate in the clearance because of their proinflammatory properties. We now report that CRP binds to oxidized LDL (OxLDL) and oxidized PtC (OxPtC), but does not bind to native, nonoxidized LDL nor to nonoxidized PtC, and its binding is mediated through the recognition of a PC moiety. Reciprocally, CRP binds to PC, which can be competed for by OxLDL and OxPtC but not by native LDL, nonoxidized PtC, or by oxidized phospholipids without the PC headgroup. CRP also binds to apoptotic cells, and this binding is competed for by OxLDL, OxPtC, and PC. These data suggest that CRP binds OxLDL and apoptotic cells by recognition of a PC moiety that becomes accessible as a result of oxidation of PtC molecule. We propose that, analogous to EO6 and scavenger receptors, CRP is a part of the innate immune response to oxidized PC-bearing phospholipids within OxLDL and on the plasma membranes of apoptotic cells.


Involvement of the NLRP3 inflammasome in innate and humoral adaptive immune responses to fungal beta-glucan.
Fungal beta-glucan, such as curdlan, triggers antifungal innate immune responses as well as shaping adaptive immune responses. In this study, we identified a key pathway that couples curdlan to immune responses. Curdlan promoted the production of the proinflammatory cytokine IL-1beta by dendritic cells and macrophages through the NLRP3 inflammasome. Stimulation with Candida albicans and Saccharomyces cerevisiae also triggered the NLRP3 inflammasome-mediated IL-1beta production. In vivo, NLRP3 was required for efficient Ag-specific Ab production when curdlan was used as an adjuvant, whereas it was dispensable for the induction of Th1 and Th17 cell differentiation. Furthermore, stimulation of purified B cells with curdlan-induced CD69 up-regulation and IgM production while stimulation with other NLRP3 inflammasome activators, such as silica and aluminum salt, did not. Notably, this induction required NLRP3 but was independent of Toll-like receptor and IL-1 receptor family signaling, suggesting the presence of NLRP3-dependent and IL-1 receptor family independent mechanisms in B cells responsible for Ab responses. Collectively, these findings reveal a critical role for the NLRP3 inflammasome in the regulation of antifungal innate immune responses as well as B cell activation.


Preparation of Magnetic Iron Oxide Nanoparticles (MIONs) with Improved Saturation Magnetization Using Multifunctional Polymer Ligand.
This paper describes the preparation of ultra-small magnetic iron oxide (Fe₃O₄) nanoparticles (MIONs) coated with water-soluble thioether end-functionalized polymer ligand pentaerythritol tetrakis 3-mercaptopropionate-polymethacrylic acid (PTMP-PMAA). The MIONs were prepared by co-precipitation of aqueous iron precursor solution at a high temperature. The polymer modified MIONs were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), thermogravimetric analysis (TGA), and vibrating sample magnetometery (VSM). It was found that these MIONs were successfully modified by this water-soluble polymer ligand with a fairly uniform size and narrow size distribution. The dried powder of MIONs could be stored for a long time and re-dispersed well in water without any significant change. Additionally, the polymer concentration showed a significant effect on size and magnetic properties of the MIONs. The saturation magnetization was increased by optimizing the polymer concentration. Furthermore, the 3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide (MTT)-assay demonstrated that these MIONs were highly biocompatible and they could be successfully coupled with fluorescent dye Rhodamine due to the formation of amide bond between carboxylic acid groups of MIONs and amine groups of dye. The obtained results indicated that these multifunctional MIONs with rich surface chemistry exhibit admirable potential in biomedical applications.


Adolescent Psychosis and Rectal Prolapse.
Psychosis is a constellation of symptoms that present with a disconnect from reality. The duration, severity, and presentation of symptoms can present on a wide spectrum, and etiologies can vary from patient to patient. Psychosis is also associated with self-injurious thinking, behavior, and suicidality. Long-term treatment of psychosis with antipsychotics can often result in side effects like constipation, sedation, dry mouth, and metabolic syndrome. Though rectal prolapse is uncommon in adolescent patients, there was a noted correlation with rectal prolapse in adult patients that were treated for chronic psychiatric disease. We report a case of a 17-year-old female with psychosis and rectal prolapse, who was admitted for inpatient treatment.


[Agreement among observers in the classification of acute leukemias].
This study was carried out to establish the level of concordance between two observers from two different health institutions in Mexico City, in the diagnosis of acute leukemias and their different varieties. We studied 73 consecutive cases of adults with these diseases. Each one of the two observers established their diagnosis on two occasions at least 15 days apart. They first made their diagnosis taking as a base the neoplastic cells morphology in bone marrow smears, and after that, with morphology plus specific cytochemistry. The outcomes of the two observers were also compared with the official diagnosis. Kappa test was performed to know interobserver and intraobserver concordance. The kappa values for the diagnosis myeloid/lymphoid were found among the highest (51 to 91). Weighted kappa was also applied to know the level of concordance in the diagnosis of the different varieties of acute leukemia, myeloid and lymphoid. In these cases the weighted kappa values were lower compared with the previous values (lymphoid, from 47 to 82; myeloid, from 30 to 66). Cytochemistry paradoxically was a confusing factor when it was used: in these cases the kappa values were lower (32 to 84) than morphology alone (39 to 91). The outcomes showed the subjective level in the diagnosis of the myeloid subtypes was more important in them than in the lymphoid subtypes.


The influence of relative humidity and temperature on stability of moexipril hydrochloride in solid phase.
Kinetic and thermodynamic parameters of the decomposition of moexipril hydrochloride in solid phase in the absence and presence of humidity were calculated. The evaluation of stability of moexipril hydrochloride was followed by the HPLC method. The applied method was validated (evaluation of the following parameters: selectivity, linearity, precision, limit of detection (LOD), limit of quantification (LOQ) and repeatability). The effect of humidity on the stability of MHCl in solid phase at 363 K was described by the equation: In ki = ax + b = (0.0676 +/- 0.016) . RH% - (15.53+/-0.78). Identification of degradation products of MHCl were carried out by the HPLC-MS method.


Specificity of DNA sequences recognized by the zinc-finger homeodomain protein, GmZF-HD1 in soybean.
Zinc finger-homeodomain proteins (ZF-HDs) have been identified in many plant species. In soybean (Glycine max), GmZF-HD1 functions as a transcription factor that activates the soybean calmodulin isoform-4 (GmCaM-4) gene in response to pathogens. Recently, we reported specific binding of GmZF-HD1 to a 30-nt A/T-rich cis-element which constitutes two repeats of a conserved homeodomain binding site, ATTA, within -1207 to -1128bp of the GmCaM-4 promoter. Herein, homeodomain sequences of the GmZF-HD1 protein were compared to those of other homeodomain proteins and characterized the specificity of DNA sequences in the interaction of the GmCaM-4 promoter with GmZF-HD1 protein. Considering the conservation of homeodomains in plants, the AG sequence within a 30-nt A/T-rich cis-element is required for binding of the GmZF-HD1 protein. Approximately 25-bp of A/T-rich DNA sequences containing an AG sequence is necessary for effective binding to the GmZF-HD1 protein. Taken together, the results support the notion that the GmZF-HD1 protein specifically functions in plant stress signalling by interacting with the promoter of GmCaM-4.


Rationalizing Perovskite Data for Machine Learning and Materials Design.
Machine learning has been recently used for novel perovskite designs owing to the availability of a large amount of perovskite formability data. Trustworthy results should be based on the valid and reliable data that can reveal the nature of materials as much as possible. In this study, a procedure has been developed to identify the formability of perovskites for all of the compounds with the stoichiometry of ABX3 and (A'A″)(B'B'')X6 that exist in experiments and are stored in the Materials Projects database. Our results have enriched the data of perovskite formability to a large extent and corrected the possible errors of previous data in ABO3 compounds. Furthermore, machine learning with a multiple models approach has identified the A2B'B″O6 compounds that have suspicious formability results in the current experimental data. Therefore, further experimental validation experiments are called for. This work paves a way for cleaning perovskite formability data for reliable machine-learning work in future.


[Susceptibility of clinical isolates to aztreonam].
Aztreonam (AZT), which has a newly developed and synthetic structure belonging to the group of monobactams, possesses excellent antibacterial activity against a broad range of Gram-negative bacteria (including the beta-lactamase producing strains). Antibacterial activities of AZT were examined and compared with those of 5 antibiotics (cefoperazone (CPZ), latamoxef (LMOX), cefotaxime (CTX), cefmetazole (CMZ) and cefsulodin (CFS) against 296 strains of clinical isolates. The evaluation of antibacterial activities was determined with the inhibition zone diameter obtained by the single disc method. The results can be summarized by three categories as follows: 1. Susceptibility of clinical isolates to AZT and other antibiotics AZT and other 3rd-generation antibiotics (CPZ, LMOX, CTX) showed excellent antibacterial activities against most strains. Especially AZT was more active against Enterobacter cloacae and Serratia marcescens than reference drugs. Against Pseudomonas aeruginosa, the activity of AZT was similar to that of CFS. AZT showed as excellent activity against P. aeruginosa as CFS. 2. Susceptibility of strains isolated from different clinical materials and different clinics AZT showed the highest antibacterial activity against the clinical isolates from sputum, pharynx, urine, pus, bile, puncture fluid, blood and others. AZT exhibited the most potent activity against isolates in the 7 clinics we tested. 3. Susceptibility of strains isolated from inpatients and outpatients AZT demonstrated the highest antibacterial activity (the rate of susceptibility: 87.0%) against strains obtained from inpatients (except for P. aeruginosa). The activity of AZT (81.4%) against P. aeruginosa was as active as that of CFS (81.4%), and it was the highest in all drugs. Antibacterial activity of these antibiotics against bacteria was rated as follows: AZT greater than LMOX greater than CPZ greater than CTX greater than CMZ AZT showed the highest antibacterial activity (100%) against strains isolated in all the materials and at all the clinics tested of outpatients. Antibacterial activity of these antibiotics against isolates from outpatients was rated as follows: AZT greater than CPZ greater than LMOX greater than CTX greater than CMZ.


[Surgical margin to direct the treatment and predict the prognosis of laryngeal carcinoma after partial laryngectomy].
The surgical margin is very important for laryngeal carcinoma treatment. To preserve more laryngeal tissue can give patients good function, however, which increase the rate of positive surgical margin and recurrence. The correct surgical margin is benefit for laryngeal carcinoma patients' prognosis. This study was designed to investigate the value of surgical margin to direct the treatment of laryngeal carcinoma after partial laryngectomy and to evaluate the prognosis of laryngeal carcinoma. The authors studied 115 cases of laryngeal carcinoma in which surgical margin samples were harvested during partial laryngectomy. The recurrence rate and survival curve of the positive and negative margin group were compared; The survival curve between the groups with and without postoperative radiotherapy both in negative margin group and positive margin group were also compared. The results of the negative group were better than that of the positive group: recurrence rate was higher (28.0% Vs 7.8% P = 0.006), the survival curve was better(P = 0.0241); The survival curve of those with positive surgical margin, at the same time, treated by postoperative radiotherapy was better than that of those without postoperative radiotherapy (P = 0.0046); but in negative group, the survival curve of those who treated with or without postoperative radiotherapy or not was different insignificantly (P = 0.0829). The prognosis of the positive margin group of laryngeal carcinoma was waster than that of the negative group, but it can be improved partially by postoperative radiotherapy. The best way to improve the prognosis was dissect entirely; There is not necessary to treat negative group by postoperative radiotherapy.


Relationship between intracranial pressure and antifungal agents levels in the CSF of patients with cryptococcal meningitis.
The purpose of this study was to evaluate the influence of intracranial hypertension in the cerebrospinal fluid (CSF) levels of amphotericin B and fluconazole levels of patients with cryptococcal meningitis. CSF samples and intracranial pressure were obtained by means of routine punctures performed at days 1, 7, and 14 of therapy, respectively. Amphotericin B and fluconazole CSF levels were measured by HPLC method as previously described. The minimum inhibitory concentration for amphotericin B, fluconazole, 5΄flucytosine, and voriconazole of each Cryptococcus isolate was performed according to CLSI. The predominant Cryptococcus species found was C. neoformans, and the major underlying condition was AIDS. Only one CSF sample had a detectable level for amphotericin B during the 14 days of therapy. Fluconazole CSF levels progressively increased from day 1 to day 14 of therapy for most cases. Fluconazole levels in the CSF were above the minimum inhibitory concentrations (MICs) for Cryptococcus during the initial 14 days of antifungal therapy. Variations of intracranial pressure did not affect amphotericin B and fluconazole levels in the CSF. The generalized estimating correlation (GEE) and Spearman correlation test (SCT) showed no significant correlation between the amphotericin B or fluconazole concentrations in the CSF and intracranial pressure (P = .953 and P = .093, respectively for GEE test and P = .477 and P = .847, respectively, for SCT). Combination therapy of amphotericin B with fluconazole was effective in 60% of the patients considering CSF cultures were negative in 9 of 15 patients after 14 days of therapy. Further studies are necessary to evaluate the role of intracranial hypertension on the therapeutic efficacy of different antifungal agents in patients with cryptococcal meningitis.


[Evidence-based medicine and the validation of quality-of-life questionnaires: the Spanish version of the MOS-HIV questionnaire for the evaluation of the quality of life in patients infected by HIV].
To validate the Spanish version of the MOS-HIV questionnaire for measuring quality of life in HIV-infected patients. 275 HIV-infected patients distributed in three diagnostic categories (asymptomatic, symptomatic and AIDS) and 40 blood donors as healthy controls were recruited from 23 Spanish hospitals and answered the MOS-HIV. Feasibility was assessed by analysing the mean time of administration and the percentage of patients with missing response. Internal consistency was assessed using Cronbach's alpha. A subsample of 48 stable patients completed the questionnaire on two occasions to assess test-retest reliability using the Intraclass Correlation Coefficient. Validity was assessed by calculating the area under the Receiver's Operating Characteristics (ROC) curve between patients and controls, and by correlating MOS-HIV scores with the VAS of Euroqol, the number of symptoms, the CD4+ count and viral load. The mean time of administration was 16 minutes and 18.9% of patients did answer the MOS-HIV with some missing response. All the scales showed high internal consistency (Cronbach's alpha = 0.78-0.89). Test-retest reliability of Physical Health (PHS) and Mental Health (MHS) Summary Scores was 0.58 y 0.85, respectively. The MOS-HIV discriminated between patients and controls (ROC = 0.77, CI = 0.69-0.85 and ROC = 0.80, CI = 0.72-0.88, for the PHS and MHS, respectively). The correlation of the scales of the MOS-HIV with the CD4+ count and viral load was low (r = -0.26 to 0.3), and with the number of symptoms and the VAS of Euroqol were moderate (r = -0.28 to -0.49 and r = 0.4 to 0.66, respectively). Considering evidence-based medicine principles, the Spanish version of the MOS-HIV has shown adequate feasibility, reliability and validity for its use in clinical research, but their use in clinical practice is limited because of their time of administration, the low reproducibility of some scales and the features of their scoring system.


Political violence exposure, adolescent school violence, and drug use: The mediating role of school support and posttraumatic stress.
Adolescents may engage in risk behaviors to cope with the negative psychological impacts resulting from exposure to political violence. Guided by the Deterioration Deterrence Model and General Strain Theory, the present study assessed the mediating role of school support and posttraumatic stress (PTS) on two adolescent risk behaviors (i.e., school violence and drug use) among Arab and Jewish Israeli adolescents. We analyzed data from a nationally representative survey that consisted of 4,733 Israeli high school students (54.5% females; 63.2% Jewish) following the Second Lebanon War. Structural equation modeling using weighted data bootstrapped with 2,000 iterations evaluated the mediated effects of school support and PTS. The results showed that both school support and PTS mediated the pathways from political violence exposure to school violence and drug use. However, although school support and PTS fully mediated the relationship between political violence exposure and these risk behaviors for Jewish students, school support and PTS only partially mediated the relationships for Arab students. While school support can help decrease the detrimental effect of exposure to terrorism and war, Israeli adolescents exposed to more political violence may perceive receiving less school support than those experiencing less exposure. Findings of this study provide evidence for the theorized mediated pathways between political violence exposure and adolescent risk behaviors by PTS and school support. The study serves as a basis for future research that can unpack the relationship between exposure to political violence and adolescent risk-taking behaviors. (PsycINFO Database Record


Influence of chloroplast development on the activation of the diphenyl ether herbicide acifluorfen-methyl.
The activity of acifluorfen-methyl (AFM); methyl 5-(2-chloro-4-[trifluoromethyl] phenoxy)-2-nitrobenzoate in excised cucumber cotyledons (Cucumis sativus L.) was examined. AFM induced membrane disruption, was significantly greater when etiolated cotyledons were illuminated 16 hours at 150 microeinsteins per square meter per second photosynthetically active radiation versus incubation under illumination of 4-fold greater intensity. These results were unexpected since the loss of membrane integrity is initiated by photodynamic reactions. Untreated, etiolated cotyledons were not able to accumulate chlorophyll under the higher light intensity while control and herbicide treated cotyledons greened significantly under the lower intensity illumination suggesting that some process associated with greening stimulated AFM activity. Inhibition of greening by cycloheximide also reduced AFM activity. Intermittent lighting induced greening in AFM treated cotyledons without causing any detectable loss of plasmalemma integrity. Utilization of this system for pretreatment of cotyledons prior to continuous illumination revealed that activity was greater when tissue was greened in the presence of AFM than when herbicide treatments were made after a greening period of the same duration. The results indicate that the pigments in situ in etiolated tissue are sufficient, without greening, to initiate membrane disruption by AFM. However, greening increases the herbicidal efficacy greatly. Furthermore, the stimulation appears to be due to specific interactions between AFM and the developing plastid and is not attributable solely to an increase in endogenous photosensitizers.


Boron compartmentation in roots of sunflower plants of different boron status: A study using the stable isotopes 10B and 11B adopting two independent approaches.
The intracellular compartmentation of boron (B) in roots of sunflower plants precultured with 100 &mgr;M B (high B) or 1 &mgr;M B (low B) was studied using two independent approaches. In the first approach, short-term efflux studies using the stable isotopes 11B and 10B were carried out. In roots of high B plants, the calculated concentrations of B (nmol gFW -1) were 52.6 in the cell wall, 7.5 in the vacuole, 27.1 in the cytosol and 48.0 in the free space. In roots of low B plants, the concentrations of B (nmol gFW -1) were 43.4 in the cell wall, 2.8 in the vacuole, 17.9 in the cytosol and almost zero in the free space. Although the B supply differed by a factor 100, the B concentrations in the cytosol and the vacuole of low B plants were 66 and 37% of the respective concentrations in high B plants. This suggests an additional role for B in plant metabolism, besides its function in the cell wall. In the second approach, root B pools (cell sap and water-insoluble residue) were determined for comparison, and found to be in good agreement with the results from the efflux study.


Research on the synchronous detection of neuronal signals under a nerve stimulation system control.
Deep brain stimulation (DBS) provides a recognized research intervention for neurological disease currently. However, there is a lack of traditional electrical stimulator to observe neuronal firing activity synchronously. The aim of the present study was to realize concurrent detection of neuronal signals better under a nerve stimulation system control. Herein, we designed an integrated software, which could control not only neuro-stimulator but also detection instrument at the same time. Moreover, the actual stimulation signals applied to the experiment object could be collected back to data acquisition card and in consistent with the electrophysiological signals. As to basic performance of self-building stimulator, the accuracy of output square signal was verified to be greater than 99.05 % with the change of voltage amplitude. Practicably, combined with homemade microelectrode array (MEA) detecting device, medial forebrain bundle (MFB) DBS effects were observed significantly through the changes of electrophysiological signals in caudate putamen (CPu) of Sprague-Dawley (SD) rat, and the signal-to-noise ratio (SNR) was 5:1 after stimulation. Therefore, the comprehensive nerve stimulation system, which consists of neuro-stimulator and integrated software, could be widely used in the field of neuroscience research with high precision and synchronization.


Non-simple conformal loop ensembles on Liouville quantum gravity and the law of CLE percolation interfaces.
We study the structure of the Liouville quantum gravity (LQG) surfaces that are cut out as one explores a conformal loop-ensemble CLE κ ' for κ ' in (4, 8) that is drawn on an independent γ -LQG surface for γ 2 = 16 / κ ' . The results are similar in flavor to the ones from our companion paper dealing with CLE κ for κ in (8/3, 4), where the loops of the CLE are disjoint and simple. In particular, we encode the combined structure of the LQG surface and the CLE κ ' in terms of stable growth-fragmentation trees or their variants, which also appear in the asymptotic study of peeling processes on decorated planar maps. This has consequences for questions that do a priori not involve LQG surfaces: In our paper entitled "CLE Percolations" described the law of interfaces obtained when coloring the loops of a CLE κ ' independently into two colors with respective probabilities p and 1 - p . This description was complete up to one missing parameter ρ . The results of the present paper about CLE on LQG allow us to determine its value in terms of p and κ ' . It shows in particular that CLE κ ' and CLE 16 / κ ' are related via a continuum analog of the Edwards-Sokal coupling between FK q percolation and the q-state Potts model (which makes sense even for non-integer q between 1 and 4) if and only if q = 4 cos 2 ( 4 π / κ ' ) . This provides further evidence for the long-standing belief that CLE κ ' and CLE 16 / κ ' represent the scaling limits of FK q percolation and the q-Potts model when q and κ ' are related in this way. Another consequence of the formula for ρ ( p , κ ' ) is the value of half-plane arm exponents for such divide-and-color models (a.k.a. fuzzy Potts models) that turn out to take a somewhat different form than the usual critical exponents for two-dimensional models.


Prenatal diagnosis of unilateral pulmonary dysplasia.
Pulmonary hypoplasia is a rare congenital disorder; most cases occur in association with other congenital abnormalities, including congenital diaphragmatic hernia, oligohydramnios, and/or skeletal deformities. The authors report a case of unilateral pulmonary hypoplasia diagnosed prenatally and confirmed at autopsy.


Acteoside attenuates RSV-induced lung injury by suppressing necroptosis and regulating metabolism.
Background: Necroptosis and inflammation are closely related to the pathogenesis of respiratory syncytial virus (RSV). Acteoside (AC), a natural phenylpropanoid glycoside from Kuding Tea, has significant anti-RSV effect. However, the roles of AC on RSV-induced lung necroptosis and inflammation are yet to be elucidated. Methods: The effects of AC were investigated in BALB/c mice and A549 cells. Lung histopathology was observed through H&E staining. The viral titer was assessed via plaque assay. The RSV-F expression was determined by RT-qPCR and immunohistochemistry assay. The levels of cytokines were detected by ELISA and RT-qPCR. The necroptosis rate and mitochondrial membrane potential were evaluated via flow cytometry. The expressions of HMGB1/NF-κB and RIP1/RIP3/MLKL/PGAM5/DRP1 were detected by western blot. Additionally, untargeted metabolomics was conducted to investigate the metabolic profiles and related metabolic pathways via Gas Chromatography-Mass Spectrometry. Results: The results showed that compared with the RSV-infected group, AC treatment significantly attenuated lung pathological damage, virus replication, and cytokines levels. AC also alleviated RSV-induced necroptosis and mitochondrial dysfunction in vitro and in vivo. Moreover, AC treatment down-regulated the expression of HMGB1, p-Iκbα/Iκbα, p-p65/p65, RIP1, RIP3, MLKL, PGAM5, and DRP1. Furthermore, metabolomic analyses suggested that the perturbations in major metabolites of AC therapy were related to variations in amino acid and energy metabolism. Conclusion: Our findings validated the beneficial effects of AC in suppressing necroptosis and regulating metabolism, suggesting AC may be a new drug candidate for RSV infection.


Ca(2+)-activated K(+) channels modulate basal and E(2)beta-induced rises in uterine blood flow in ovine pregnancy.
Uterine blood flow (UBF) increases >30-fold during ovine pregnancy. During the last trimester, this reflects vasodilation, which may be due to placentally derived estrogens. In nonpregnant ewes, estradiol-17 beta (E(2)beta) increases UBF >10-fold by activating nitric oxide synthase and large conductance calcium-dependent potassium channels (BK(Ca)). To determine whether BK(Ca) channels modulate basal and E(2)beta-induced increases in UBF, studies were performed in near-term pregnant ewes with uterine artery flow probes and catheters for intra-arterial infusions of tetraethylammonium (TEA), a selective BK(Ca) channel antagonist at <1 mM, in the absence or presence of E(2)beta (1 microg/kg iv). Uterine arteries were collected to measure BK(Ca) channel mRNA. TEA (0.15 mM) decreased basal UBF (P < 0.0001) 40 +/- 8% and 55 +/- 7% (n = 11) at 60 and 90 min, respectively, and increased resistance 175 +/- 48% without affecting (P > 0.1) mean arterial pressure (MAP), heart rate, or contralateral UBF. Systemic E(2)beta increased UBF 30 +/- 6% and heart rate 13 +/- 1% (P < or = 0.0001, n = 13) without altering MAP. Local TEA (0.15 mM) inhibited E(2)beta-induced increases in UBF without affecting increases in heart rate (10 +/- 4%; P = 0.006). BK(Ca) channel mRNA was present in uterine artery myocytes from pregnant and nonpregnant ewes. Exponential increases in ovine UBF in late pregnancy may reflect BK(Ca) channel activation, which may be mediated by placentally derived estrogens.


Atypical fibroxanthoma in an HIV-infected individual.
Atypical fibroxanthoma is a neoplasm primarily occurring in older patients, with a predilection for photo-damaged skin of the head and neck. Compared to the immunocompetent population, patients infected with HIV have a higher risk of certain malignancies including non-Hodgkin lymphoma, Kaposi's sarcoma and skin cancer. Although atypical fibroxanthoma has been reported in another immunocompromised group, namely organ transplant recipients, there are no previous reports in the published literature of this tumour arising in patients infected with HIV. We report a case of an atypical fibroxanthoma arising in a 71- year old HIV-positive male.


[Haitians in Montreal: demographic and spatial evolution].
"Analysing demographic characteristics over a given period may be useful in explaining the spatial distribution of ethnic groups in an urban environment. This paper first presents the main aspects of the demographic evolution of Quebec's Haitian population during the 1971-1981 period. It then analyses the evolution of the spatial distribution of this population in the Montreal region. It finally tries to show the interrelations between both evolutions." (SUMMARY IN ENG AND SPA)


[Drug resistance analysis of staphylococcus infection in our hospital from 2003 to 2005].
To explore the change in mobility of staphylococcus and its drug resistance etiology investigation and clinical treatment. The routine biochemical identification was used for staphylococcus differentiation. Minimal inhibitory concentrations was used for drug-resistance determination. Some drug-resistance determination were detected by K-B method. The inducible resistance of erythromycin to clindamycin was checked by D-test. Staphylococcus was in the first place in the hospital infection. The rates of methicillin-resistant staphylococcus were 54.1%. The drug-resistance rates of staphylococcus to penicillin, oxacillin, erythromycin, tetracycline, ciprofloxacin, gentamicin, clindamycin, SMZCO, chloramphenicol, vancomycin, teicoplanin antibacterials were 93.2%, 54.1%, 85.1%, 56.7%, 45.9%, 48.6%, 58.1%. 45.9%, 31.1%, 0%, 0%. D-test positive rate was 37.9%. The results are helpful in study of pathogenic bacteria and drug resistance characteristics in staphylococcus infection.


Decarboxylative-coupling of allyl acetate catalyzed by group 10 organometallics, [(phen)M(CH3)]+.
Gas-phase carbon-carbon bond forming reactions, catalyzed by group 10 metal acetate cations [(phen)M(O2CCH3)](+) (where M = Ni, Pd or Pt) formed via electrospray ionization of metal acetate complexes [(phen)M(O2CCH3)2], were examined using an ion trap mass spectrometer and density functional theory (DFT) calculations. In step 1 of the catalytic cycle, collision induced dissociation (CID) of [(phen)M(O2CCH3)](+) yields the organometallic complex, [(phen)M(CH3)](+), via decarboxylation. [(phen)M(CH3)](+) reacts with allyl acetate via three competing reactions, with reactivity orders (% reaction efficiencies) established via kinetic modeling. In step 2a, allylic alkylation occurs to give 1-butene and reform metal acetate, [(phen)M(O2CCH3)](+), with Ni (36%) > Pd (28%) > Pt (2%). Adduct formation, [(phen)M(C6H11O2)](+), occurs with Pt (24%) > Pd (21%) > Ni(11%). The major losses upon CID on the adduct, [(phen)M(C6H11O2)](+), are 1-butene for M = Ni and Pd and methane for Pt. Loss of methane only occurs for Pt (10%) to give [(phen)Pt(C5H7O2)](+). The sequences of steps 1 and 2a close a catalytic cycle for decarboxylative carbon-carbon bond coupling. DFT calculations suggest that carbon-carbon bond formation occurs via alkene insertion as the initial step for all three metals, without involving higher oxidation states for the metal centers.


Structural diversity and biological significance of glycosphingolipids in pathogenic and opportunistic fungi.
Glycosphingolipids (GSLs) are ubiquitous membrane components and have key roles in biological systems, acting as second messengers or modulators of signal transduction by affecting several events, ranging from cell adhesion, cell growth, cell motility, regulation of apoptosis and cell cycle. Over the last 20 years our laboratory and other research groups determined the glycan and ceramide structures of more than 20 GSLs from several pathogenic/opportunistic fungi, using a combination of gas chromatography, mass spectrometry, nuclear magnetic resonance as well as other immunochemical and biochemical techniques. Fungal GSLs can be divided in two major classes: neutral GSLs, galactosyl- and glucosylceramide (GlcCer), and acidic GSLs, the glycosylinositol-phosphorylceramides (GIPCs). Glycosyl structures in fungal GIPCs exhibited significant structural diversity and distinct composition when compared to mammalian GSLs, e.g., the expression of inositol-mannose and inositol-glucosamine cores and the terminal residue of β-D-galactofuranose which are absent in mammalian cells. Studies performed by our group demonstrated that GIPC (Galfβ 6[Manα3]Manα2InsPCer) elicited in patients with paracoccidioidomycosis an immune response with production of antibodies directed to the terminal residue of β-D-galactofuranose. Further studies also showed that inhibition of GlcCer biosynthetic pathways affects fungal colony formation, spore germination and hyphal growth, indicating that enzymes involved in GlcCer biosynthesis may represent promising targets for the therapy of fungal infections. Recently, it was shown that GlcCer and GIPCs are preferentially localized in membrane microdomains and monoclonal antibodies directed to these GSLs interfere in several fungal biological processes such as growth and morphological transition. This review focuses on glycan structures carried on sphingolipids of pathogenic/opportunistic fungi, and aspects of their biological significance are discussed.


Dermoscopic features of nevoid melanoma: a retrospective study.
Nevoid melanoma (NeM) is a rare variant of melanoma resembling melanocytic nevus. The aim of the study was to systematically review the dermoscopic features of NeM. A hospital-based retrospective study was conducted. Dermoscopic features of NeMs diagnosed through excisional biopsy between January 2015 1, and March 1, 2021, were compared to superficial spreading melanomas (SSMs) matched by Breslow's thickness. Then, a literature search was performed. Electronic searches on PubMed database via Medline were conducted to retrieve any manuscript reporting detailed dermoscopic features of histopathologically confirmed NeM. A total of 60 malignant melanomas (MM) comprising 20 NeM and 40 SSM were collected. Twelve out of 20 (60%) NeM showed a nevus-like appearance, including reticular and globular patterns, and in 35% of these cases it was detected because of dermoscopic changes. Then, a total of seven original manuscripts were retrieved from the literature review, comprising 56 cases overall. NeM showed nevus-like pattern in 53% of the cases, multicomponent pattern in 21% and amelanotic in 9%. Enlargement, irregularly distributed dots/globules, irregular pigmentation, and atypical vascular pattern were found in NeM with nevus-like appearance. NeM with multicomponent pattern were characterized by irregular pigmentation, blue-white veil, irregular dots and atypical vascular pattern. Amelanotic NeM is rare and show atypical vascular pattern and milia-like cysts. Dermoscopy of NeM is challenging as it frequently shows a nevus-like pattern, but clues and detection of dermoscopic changes may help to identify it.


Relating Advanced Electrospun Fiber Architectures to the Temporal Release of Active Agents to Meet the Needs of Next-Generation Intravaginal Delivery Applications.
Electrospun fibers have emerged as a relatively new delivery platform to improve active agent retention and delivery for intravaginal applications. While uniaxial fibers have been explored in a variety of applications including intravaginal delivery, the consideration of more advanced fiber architectures may offer new options to improve delivery to the female reproductive tract. In this review, we summarize the advancements of electrospun coaxial, multilayered, and nanoparticle-fiber architectures utilized in other applications and discuss how different material combinations within these architectures provide varied durations of release, here categorized as either transient (within 24 h), short-term (24 h to one week), or sustained (beyond one week). We seek to systematically relate material type and fiber architecture to active agent release kinetics. Last, we explore how lessons derived from these architectures may be applied to address the needs of future intravaginal delivery platforms for a given prophylactic or therapeutic application. The overall goal of this review is to provide a summary of different fiber architectures that have been useful for active agent delivery and to provide guidelines for the development of new formulations that exhibit release kinetics relevant to the time frames and the diversity of active agents needed in next-generation multipurpose applications.


Different preservation of myocardial capillary endothelial cells and cardiomyocytes during and after cardioplegic ischemia (25 degrees C) of canine hearts.
Complete resumption of cardiac function after cardioplegic arrest presupposes a well-preserved myocardial ultrastructure during and after ischemia. Therefore, we determined ischemia-induced ultrastructural alterations in the myocardium during and after reversible cardioplegic ischemia using stereological methods. Cardiac arrest was induced with St. Thomas' Hospital- or Custodiol (HTK) solution. Reperfusion with Tyrode's solution followed after reversible cardioplegic ischemia in situ. Samples were taken 1) from beating hearts, 2) from cardioplegically arrested hearts immediately after the end of coronary perfusion, 3) from ischemic hearts incubated in the cardioplegic solution at 25 degrees C, and 4) from reperfused beating hearts after ischemia in situ at 22 degrees C. Cellular swelling was determined as the barrier thickness of capillary endothelium and as the sum of cardiomyocyte volume fractions of free sarcoplasm and mitochondria. In St. Thomas'-arrested hearts, intraischemic volume increase was significantly more pronounced in endothelial cells than in cardiomyocytes. Reperfusion at the intraischemic practical limit of resuscitability (ATP levels of 4 micromol/gww) significantly reduced intraischemic swelling of cardiomyocytes, but not of capillary endothelial cells. Mitochondrial damage was more pronounced in capillary endothelial cells during ischemia and after reperfusion. Thus, after reversible cardioplegic arrest, structural recovery of cardiomyocytes is better than that of capillary endothelial cells. An incomplete structural protection of capillary endothelial cells may predominantly contribute to postischemic dysfunction in the reperfused heart.


The tannin-osmium conductive staining after dehydration: an attempt to observe the chromosome structure by SEM without metal coating.
The tannin-osmium conductive staining method was modified in order to observe chromosomal structures without metal coating. The treatment with tannic acid and OsO4, which has been used in aqueous solution in the original method, was performed in acetone solution after dehydration in the present study. The usefulness of this method is discussed showing ultrastructural images of chromosomes of Drosophila and Tradescantia, which can be achieved by the method.


A comprehensive analysis of Aurora A; transcript levels are the most reliable in association with proliferation and prognosis in breast cancer.
Aurora A kinase, a centrosomal serine/threonine kinase which plays an essential role in chromosome segregation during cell division, is commonly amplified and/or over expressed in human malignancies. Aurora A is suggested to be one of the proliferation parameters which is an independent prognostic factor for early invasive breast cancer patients; however the individual clinical or prognostic relevance of this gene has been a matter of debate. A comprehensive analysis of Aurora A at the levels of gene expression, gene copy number and protein expression was performed for 278 primary invasive breast cancer patients; and the correlation with clinical outcomes were investigated. Aurora A gene expression level not only correlated with gene amplification, but was also significantly associated with several clinicopathological parameters and patient prognosis. Patients with higher nuclear grade, negative progesterone receptor status and higher Ki67 expressed higher levels of Aurora A mRNA, which was associated not only with poor relapse-free survival (RFS) but was also found to be a significant multivariate parameter for RFS. Aurora A protein expression was also significantly associated with clinicopathological characteristics; lymph node status, nuclear grade, estrogen receptor status and Ki67, but not with prognosis. By contrast, Aurora A gene amplification correlated with tumor size, nuclear grade and Ki67, and had no prognostic value. Our data indicate that Aurora A gene expression is an effective tool, which defines both tumor proliferation potency and patient prognosis.


Glyceraldehyde as an Efficient Chemical Crosslinker Agent for the Formation of Chitosan Hydrogels.
The rheological changes that occur during the chemical gelation of semidilute solutions of chitosan in the presence of the low-toxicity agent glyceraldehyde (GCA) are presented and discussed in detail. The entanglement concentration for chitosan solutions was found to be approximately 0.2 wt.% and the rheological experiments were carried out on 1 wt.% chitosan solutions with various amounts of GCA at different temperatures (25 °C and 40 °C) and pH values (4.8 and 5.8). High crosslinker concentration, as well as elevated temperature and pH close to the pKa value (pH ≈ 6.3-7) of chitosan are three parameters that all accelerate the gelation process. These conditions also promote a faster solid-like response of the gel-network in the post-gel region after long curing times. The mesh size of the gel-network after a very long (18 h) curing time was found to contract with increasing level of crosslinker addition and elevated temperature. The gelation of chitosan in the presence of other chemical crosslinker agents (glutaraldehyde and genipin) is discussed and a comparison with GCA is made. Small angle neutron scattering (SANS) results reveal structural changes between chitosan solutions, incipient gels, and mature gels.


The value of informal care in the context of option B+ in Malawi: a contingent valuation approach.
Informal care, the health care provided by the patient's social network is important in low income settings although its monetary value is rarely estimated. The lack of estimates of the value of informal care has led to its omission in economic evaluations but this can result in incorrect decisions about cost effectiveness of an intervention. We explore the use of contingent valuation methods of willingness to pay (WTP) and willingness to accept (WTA) to estimate the value of informal care provided to HIV infected women that are accessing antiretroviral therapy (ART) under the Option B+ approach to prevention of mother-to-child transmission (PMTCT) of HIV in Malawi. We collected cross sectional data from 93 caregivers of women that received ART care from six health facilities in Malawi. Caregivers of women that reported for ART care on the survey day and consented to participate in the survey were included until the targeted sample size for the facility was reached. We estimated the value of informal care by using the willingness to accept (WTA) and willingness to pay (WTP) approaches. Medians were used to summarize the values and these were compared by the Wilcoxon signed-rank test. The median WTA to provide informal care in a month was US$30 and the median WTP for informal care was US$13 and the two were statistically different (p < 0.000). Median WTP was higher in the urban areas than in the rural areas (US$21 vs. US$13, p < 0.001) and for caregivers from households from higher wealth quintile than in the lower quintile (US$15 vs. US$13, p < 0.0462). Informal caregivers place substantial value on informal care giving. In low income settings where most caregivers are not formally employed, WTP and WTA approaches can be used to value informal care. NCT02005835.


Inhibition of Salmonalla enterica by a novel strain of Bacillus subtilis isolated from the faeces of healthy chickens.
1. The objective of the study was to demonstrate that Bacillus subtilis strain VL28 (BS-VL28), a novel strain isolated from faeces of healthy chicken, has potential as a probiotic.2. The study evaluated the probiotic properties of BS-VL28 and the effects of dietary supplementation of this strain on growth performance and mortality in chickens challenged with Salmonella enterica CT01.3. BS-VL28 exhibited a specific inhibitory activity against Escherichia coli CT11, Salmonella enterica CT01, Staphylococcus spp. CT21 and Streptococcus spp. CT31.4. BS-VL28 also showed an auto-aggregation percentage of 82%, co-aggregation activity greater than 60%, high tolerance to low pH (<2.0) under the presence of 0.05% bile salts. However, the results from the antibiotic susceptibility tests demonstrated that this strain was sensitive to erythromycin, gentamycin, doxycycline, norfloxacin, oxytetracycline, trimethoprim-sulfamethoxazole, enrofloxacin but was intermediate to neomycin.5. Inclusion of probiotic (5 g BS-VL28 (107 CFU/g) per kg of feed to diet of challenged chickens showed better performance and feed conversion rates (FCR). There was a significant decrease (p < 0.05) in mortality in the probiotic-treated group compared to the control and antibiotic-treated groups.6. From these results, BS-VL28 could potentially function as a probiotic for broilers.


Reaction force analysis of solvent effects in the addition of HCl to propene.
We have investigated computationally, via reaction force analyses, the addition of HCl to propene, both Markovnikov and anti-Markovnikov, in the gas phase and in chloroform solution. The calculations were carried out at the CCSD(T)/aug-pVTZ//B3LYP/aug-cc-pVDZ level. A particular interest was in the magnitudes of the two components of the activation energies that are defined by the minimum of the reaction force for each process. The total activation energies for Markovnikov and anti-Markovnikov addition are found to be, respectively, 39.7 and 45.9 kcal/mol in the gas phase and 27.1 and 34.9 kcal/mol in chloroform solution. In solution, the first portion of the reaction (prior to the reaction force minimum) involves substantial stretching of the H-Cl bond, which makes that contribution to the total activation energy greater than in the gas phase. However the second part of the activation is much less energy demanding in solution for both the Markovnikov and anti-Markovnikov additions. The overall preference for Markovnikov addition is due to the electrostatic potential of propene favoring the initial approach of the HCl hydrogen to the terminal carbon.


Anodic Oxidation of Aminotetrazoles: A Mild and Safe Route to Isocyanides.
A new electrochemical method for the preparation of isocyanides from easily accessible aminotetrazole derivatives has been developed, which tolerates an unprecedented range of functional groups. The use of chemical, rather than electrochemical, oxidation to afford isocyanides was also demonstrated, which provides access to these compounds for those without electrosynthesis equipment. The practicality of scale-up using flow electrochemistry has been demonstrated, in addition to the possibility of using electrochemically generated isocyanides in further reactions.


Enrofloxacin and its major metabolite ciprofloxacin in green sea turtles (Chelonia mydas): An explorative pharmacokinetic study.
The present study aimed to assess the pharmacokinetic features of enrofloxacin (ENR) and its major metabolite, ciprofloxacin (CIP) in green sea turtles (Chelonia mydas) after single intravenous (i.v.) and intramuscular (i.m.) administration at two dosages of 5 and 7.5 mg/kg body weight (b.w.). The study used 10 animals randomly divided into equal groups. Blood samples were collected at assigned times up to 168 hr. The concentrations of ENR and CIP in turtle plasma were quantified by a validated high-performance liquid chromatography equipped with fluorescence detector (HPLC-FLD). The concentration of ENR in the experimental turtles with respect to time was pharmacokinetically analyzed using a noncompartment model. The concentrations of ENR in the plasma were quantified up to 144 hr after i.v. and i.m. administrations at dosages of 5 and 7.5 mg/kg b.w., whereas CIP was quantified up to 96 and 144 hr, respectively. The elimination half-life values of ENR were 38.7 and 50.4 hr at dose rates of 5 and 7.5 mg/kg b.w. after i.v. administration, whereas CIP was 33.6 and 22.6 hr, respectively. The maximum concentration (Cmax ) values of ENR were 2.07 and 2.59 μg/ml at dose rates of 5 and 7.5 mg/kg b.w., respectively. The value of area under the curve from 0 to 24 hr (AUC0-24 )/minimum inhibitory concentration (MIC) ratio of ENR was >125 for bacteria with MIC of 0.12 and 0.13 μg/ml after the administration of 5 mg/kg by i.m. and i.v. administration, respectively. Based on the pharmacokinetic data, susceptibility break-point and pharmacokinetic (PK)/pharmacodynamic (PD) indices, i.m. single administration of ENR at a dosage of 5 mg/kg b.w. might be clinically appropriate for treatment of susceptible bacteria in green sea turtles (Chelonia mydas).


Antibody in host defense against mouse pneumonitis agent (murine Chlamydia trachomatis).
In a murine model of chlamydial pneumonia employing murine Chlamydia trachomatis, immune serum given intranasally delayed death in nude (nu/nu) mice and prevented death in nu/+ mice. Serum-derived immunoglobulin G and A fractions and immune lavage fluid fractions containing immunoglobulins G and A were effective in producing protection when used to opsonize the murine C. trachomatis inoculum. In hyperclean mice (previously made germfree and then colonized with a limited flora nonpathogenic to mice) antibody given intravenously was ineffective. The effects of antibody and nonspecific stimulation of cell-mediated immunity (after previous infection with Histoplasma capsulatum) were additive in increasing host resistance to murine C. trachomatis.


Hepatocyte growth factor may accelerate healing in chronic leg ulcers: a pilot study.
Hepatocyte growth factor (HGF) is a heparin-binding protein with mitogenic, motogenic and morphogenic activities for various cell types. The regenerative properties of HGF have been the object of several animal and in vitro studies in recent years. To investigate the physiological and therapeutic effects of HGF on chronic leg ulcers. HGF in gel form was locally applied, once daily for 7 days, to 15 of 19 chronic leg ulcers in 11 elderly patients. All patients had previously been treated by conventional methods and their leg ulcers had been in stable conditions for between 1 and 14 years. Any signs of allergy, discomfort or pain were reported daily. Microcirculation perfusion in the ulcers, compared to the intact contiguous skin, was determined by laser Doppler at the beginning of the study, after 1 week and again after 3 months (in seven patients). Ulcer size and characteristics were also documented. It was observed that microcirculatory perfusion, which might reflect the angiogenic effect of HGF, was statistically significantly correlated (r = 0.94, p < 0.002) to ulcer area reduction in the treated ulcers. Excellent (84-100% area reduction) or partial healing (58-59%) was seen in eight out of 11 patients. No control group was included in this pilot study, which must be completed by proper control studies. This study suggests that HGF may heal chronic leg ulcers, possibly by improving the microcirculation. Proper control studies need to be performed.


The use of missing birth record data as a marker for adverse reproductive outcomes: a geocoded analysis of birth record data.
Adverse reproductive outcomes (AROs) disproportionately affect black American infants and significantly contribute to the U.S. infant mortality rate. Without accurate understanding of AROs, there remains little hope of ameliorating infant mortality rates or eliminating infant health disparities. However, despite the importance of monitoring infant mortality rates and health disparities, birth record data quality is not assured. Racial disparities in the reporting of birth record data have been documented, and missing birth record data for AROs appears to be disproportionate. Due to the extent of missing birth record data, innovative strategies have been developed to evaluate relationships between maternal socioeconomic status (SES) and community-based ARO rates. Because addresses convey aggregate information about income level, education and occupation, ZIP codes, census tracts and census block-groups have been applied to geocoding efforts. The goals of this study are to: 1) analyze the extent of missing birth record data for New Jersey areas with high rates of an ARO (preterm birth), 2) evaluate associations between the extent of missing birth record data and other AROs, and 3) consider how geocoding strategies could be applied to provide a basis for understanding maternal SES risk factors and ARO resource allocation for at-risk communities.


Development of Dual TaqMan Based One-Step rRT-PCR Assay Panel for Rapid and Accurate Diagnostic Test of MERS-CoV: A Novel Human Coronavirus, Ahead of Hajj Pilgrimage.
Coronaviruses (CoVs) are large ribonucleic acid (RNA) viruses causing primarily respiratory disease in humans. A novel human coronavirus, subsequently named middle east respiratory syndrome coronavirus (MERS-CoV), was first reported in Saudi Arabia in September of 2012. With increasing numbers of infections and deaths from MERS-CoV, development of a rapid and reliable kit was crucial to prevent further spread of MERS-CoV. In this study, we present two real-time reverse-transcription polymerase chain reaction (rRT-PCR) assays for in-house rapid and sensitive diagnostic testing of MERS-CoV, detecting the regions upstream of the envelope gene (upE) and open reading frame (ORF) 1b, respectively, for initial screening and final confirmation of MERS-CoV infection, as recommended by the world health organization (WHO). In this experimental study, acquiring patient samples was difficult; thus, according to WHO recommendations and standard protocols, we synthesized RNA sequences of upE and ORF1b genes as the template signatures and TaqMan based-diagnostic rRT-PCR assays were carried out using these synthetic genes for detection of MERS-CoV. In this research, we also inaugurated a cell-free system to transcribe these RNA sequences using the DNA templates synthesized. The upE and ORF1b based one-step rRT-PCR assays were optimized by testing several times via different synthetic RNAs, and validation results were highly successful. The sensitivity obtained for upE was fewer than ten copies of RNA template per reaction and for ORF1b was 50 or fewer copies per reaction. This study showed that the developed rRT-PCR assays are rapid, reliable, reproducible, specific, sensitive, and simple tools for detection of MERS-CoV. Finally, a kit consisting of two assay signatures and controls was assembled, which can be distributed to public health laboratories in Iran to support international MERS-CoV surveillance and public health response.


Evaluation of KIR3DL1/KIR3DS1 allelic polymorphisms in Kenyan children with endemic Burkitt lymphoma.
Endemic Burkitt lymphoma (eBL) is a fast-growing germinal center B cell lymphoma, affecting 5-10 per 100,000 children annually, in the equatorial belt of Africa. We hypothesize that co-infections with Plasmodium falciparum (Pf) malaria and Epstein-Barr virus (EBV) impair host natural killer (NK) and T cell responses to tumor cells, and thus increase the risk of eBL pathogenesis. NK cell education is partially controlled by killer immunoglobulin-like receptors and variable expression of KIR3DL1 has been associated with other malignancies. Here, we investigated whether KIR3D-mediated mechanisms contribute to eBL, by testing for an association of KIR3DL1/KIR3DS1 genotypes with the disease in 108 eBL patients and 99 healthy Kenyan children. KIR3DL1 allelic typing and EBV loads were assessed by PCR. We inferred previously observed phenotypes from the genotypes. The frequencies of KIR3DL1/KIR3DL1 and KIR3DL1/KIR3DS1 did not differ significantly between cases and controls. Additionally, none of the study participants was homozygous for KIR3DS1 alleles. EBV loads did not differ by the KIR3DL1 genotypes nor were they different between eBL survivors and non-survivors. Our results suggest that eBL pathogenesis may not simply involve variations in KIR3DL1 and KIR3DS1 genotypes. However, considering the complexity of the KIR3DL1 locus, this study could not exclude a role for copy number variation in eBL pathogenesis.


Instructed reappraisal and cardiovascular habituation to recurrent stress.
Instructed reappraisal has previously been associated with a challenge-oriented cardiovascular response profile, indexed by greater cardiac output (CO) and lower total peripheral resistance (TPR), in response to a single stress exposure. The present study builds on this research by employing a stress habituation paradigm where participants completed a speech task twice; in which prior to the second task participants heard reappraisal instructions (i.e., view feelings of stress arousal as something that is beneficial) or control instructions. This paradigm allowed us to (a) test if reappraisal aids cardiovascular habituation to recurrent stress, and (b) examine if reappraisal leads to a within-participant change in CO/TPR responding from an uninstructed task to an instructed reappraisal task. Habitual use of reappraisal was assessed using the Emotion Regulation Questionnaire. The analyses report upon 173 young adults (121 women, 52 men). Cardiovascular parameters were measured continuously using the Finometer Pro. All participants demonstrated similar cardiovascular habituation during the second stress exposure (lower SBP, CO, and HR); suggesting that reappraisal did not aid cardiovascular habituation to recurrent stress. Reappraisal instructions did not lead to a challenge-oriented response compared to both the control group and responses to the uninstructed task. This study is the first to examine the relationship between instructed reappraisal and cardiovascular habituation and identifies that habitual use of reappraisal does not interact with reappraisal instructions to influence cardiovascular responses to stress.


[Applying decision trees to establish risk rating model of breast cancer incidence based on non-genetic factors among Southwest China females].
Objective: To estimate incident probability and establish risk rating model of breast cancer incidence under different combinations of non-genetic factors among Southwest China females, applying the decision trees. Methods: From 2014 to 2015, a total of 783 cases, which were pathologically diagnosed as primary breast cancer, were sequentially collected from West China Hospital of Sichuan University, Sichuan Cancer Hospital and Sichuan Province People's Hospital. 3, 879(excluding 36 samples with missing data) controls were randomly selected and matched by area of residence and age. Classification and regression tree (CART) algorithm was applied to construct breast cancer risk rating model according to non-genetic factors. 5 test sets were randomly selected for model validation. Results: BI-RADS classes, menopausal status, age, history of benign breast disease, menarche age, age of first delivery and number of live births were identified as risk factors and included in the risk rating model of breast cancer incidence. Among these factors, BI-RADS classes, menopausal status and age were the most important. The risk rating model developed were vitrificated by 5 test sets, and the average sensitivity, positive predictive value, accuracy were 95.60%, 92.26%, 97.93%, respectively. Conclusions: Breast cancer risk rating model constructed by decision trees was valid and reliable. The model could be used as the basic tool of breast cancer risk assessment among Southwest China females.


Assessment of the genetic diversity of Xylella fastidiosa isolated from citrus in Brazil by PCR-RFLP of the 16S rDNA and 16S-23S intergenic spacer and rep-PCR fingerprinting.
The genetic diversity among twenty three strains of Xylella fastidiosa, isolated from sweet orange citrus, was assessed by RFLP analysis of the 16S rDNA and 16S-23S intergenic spacer and by rep-PCR fingerprinting together with strains isolated from coffee, grapevine, plum and pear. The PCR products obtained by amplification of the 16S rDNA and 16S-23S spacer region were digested with restriction enzymes and a low level of polymorphism was detected. In rep-PCR fingerprinting, a relationship between the strains and their hosts was observed by using the BOX, ERIC and REP primers. Two major groups were obtained within the citrus cluster and relationships to the geographic origin of the strains revealed. Citrus strains isolated from the States of São Paulo and Sergipe formed one group and strains from the Southern States formed another group. Distinct origins of X. fastidiosa in the Southern and Southeastern States is postulated. The pear isolate was distantly related to all of the other X. fastidiosa strains.


Clinical significance of double staining of MIB-1 and AgNORs in primary breast carcinoma.
Argyrophilic nucleolar organizer regions (AgNORs) and MIB-1 as proliferating activities have been applied separately to assess the malignant potential of cancer cells. We conducted staining of AgNORs and MIB-1 in 42 surgically-resected invasive breast carcinomas. Paraffin-embedded sections were used for double staining and the mean AgNOR counts in 100 MIB-1-positive and -negative cells were calculated. The mean AgNOR count in MIB-1-positive cells was significantly higher than in MIB-1-negative ones. AgNOR counts in MIB-1-positive tumors were significantly higher in tumors > or =2 cm and those with positive nodes. Multivariate analysis identified the AgNOR count in MIB-1-positive tumors as the only independent factor related to node metastasis. Survival of patients with lower counts of AgNORs in MIB-1-positive tumors was significantly better compared to those with higher counts. Double staining of MIB-1 and AgNORs is useful for predicting lymph node metastasis and prognosis of patients with breast carcinoma.


Posttraumatic stress disorder with amnesia following asphyxiation.
We describe five cases of traumatic asphyxiation injury, each meeting diagnostic criteria for posttraumatic stress disorder (PTSD) and characterized by a range of postinjury cognitive impairment. Four patients exhibited dense retrograde amnesia, including absence of conscious memory for the traumatic event. Appreciation of these asphyxiation cases, which involve temporally extended trauma exposure, may help resolve arguments regarding the possibility of co-occurrence of PTSD and neurological amnesia based exclusively on observations of much briefer duration events (specifically, motor vehicle crashes). These five cases also provide evidence that cognitive symptoms of PTSD can develop in the absence of conscious memory for the event.


In vitro elution of daptomycin by a synthetic crystallic semihydrate form of calcium sulfate, stimulan.
A synthetic crystallic semihydrate form of calcium sulfate, Stimulan, was evaluated as a biodegradable carrier for the daily in vitro elution of daptomycin. Daptomycin and Stimulan were admixed at a ratio of 95:5. Elution lasted for 28 days. Eluted concentrations peaked on days 1 and 11, when the mean values were 1,320.1 and 949.2 microg/ml, respectively. The lowest eluted concentration was detected on day 28. These results support the application of the system described in experimental models of osteomyelitis.