Extraction of 11-Keto-β -Boswellic Acid from Indian Olibanum by Contemporary Extraction Modes: Optimization and Validation of HPTLC.
Boswellic acids are the main constituents of Boswellia serrata gum. These comprise of four pentacyclic triterpenes, 11-keto-β-boswellic acid (KBA) being one of them. Comparing the extraction efficiency of KBA through microwave-assisted extraction (MAE) and ultrasound-assisted extraction (UAE) followed by optimizing the extraction process using response surface methodology (RSM) and validation of HPTLC. UAE and MAE of KBA were carried out employing methanol as an extracting solvent. To figure out the better mode of extraction, single factorial experiments were conducted for further optimization. Design expert software was used for optimization purposes where solvent to drug ratio, extraction temperature and extraction time were taken as input variables. Quantification of KBA in each extract was done through High-Performance Thin Layer Chromatography (HPTLC), and the method was validated as per International Council for Harmonization (ICH) guidelines. UAE stood out to be a better mode of extraction for KBA. Solvent to drug ratio of 20.42 mL/gram, extraction temperature of 44.01°C and extraction time of 11.54 minutes were established as optimum conditions, which yielded 8.44%w/w of KBA. Regarding HPTLC, the Rf value of KBA was measured, and the correlation coefficient was calculated from the standard curve. Accuracy, precision and recovery were found within limits. From this study, it was concluded that a non-thermal method is a better choice of extraction for KBA. All the input variables significantly affected KBA content, which was confirmed by model fitting. Moreover, the HPTLC method was developed for the quantification of KBA, which was found to be accurate, reliable and highly sensitive.


Efficient co-production of xylooligosaccharides, furfural and reducing sugars from yellow bamboo via the pretreatment with biochar-based catalyst.
The research on the efficient use of biomass to produce chemical products has received extensive attention. In this work, a novel heterogeneous biocarbon-based heterogeneous catalyst AT-Sn-YB was prepared using yellow bamboo (YB) as a carrier, and its physical properties were proved to be good by various characterization and stability experiments. In the γ-valerolactone/water (3:1, v/v) medium containing 100 mM CuCl2, the use of AT-Sn-YB (3.6 wt%) under 170 °C for 20 min was applied to catalyze YB into furfural (80.3% yield), accompanied with 2.8 g/L xylooligosaccharides. The YB solid residue obtained from treatment was efficiently saccharified to reducing sugars (17.2 g/L). Accordingly, comprehensive understanding of efficiently co-producing xylooligosaccharides, furfural and reducing sugars from YB was demonstrated via the pretreatment with biochar-based catalyst. This study innovatively used a new type of solid acid to complete the efficient co-production of chemical products, and realized the value-added utilization of yellow bamboo.


Diversity of tomato-infecting begomoviruses and spatiotemporal dynamics of an endemic viral species of the Brazilian Atlantic rain forest biome.
Yield losses induced by a complex of begomoviruses are observed across all major tomato-producing areas in Brazil. Tomato severe rugose virus (ToSRV) is the most widespread begomovirus in the country. Conversely, tomato common mosaic virus (ToCmMV) displays a more restricted geographical distribution to areas associated with the Atlantic Rain Forest (ARF) biome, encompassing the States of Espírito Santo-ES, Minas Gerais-MG, and Rio de Janeiro-RJ. Here, we characterized 277 tomato-infecting isolates collected in fields located within the ARF biome from 2006 to 2018. ToSRV displayed the highest prevalence (n = 157), followed by ToCmMV (n = 95) and tomato interveinal chlorosis virus (n = 14). Four other begomoviruses were also detected, but with very low incidences. ToCmMV was the predominant begomovirus in the ARF biome up to 2014-2015 with very low ToSRV incidence. Subsequently, ToSRV became the most prevalent species in ES and RJ, but ToCmMV was still predominating in the "Zona da Mata" meso-region in MG. Due to the remarkable endemic distribution of ToCmMV, we carried out phylogeographical studies of this virus using information from all 28 available isolates with complete DNA-A sequences. The closest common ancestor of ToCmMV was more likely originated around Coimbra-MG area ≈ 25 years before the formal report of this viral species. So far, all surveys indicated tomatoes as the only natural hosts of ToCmMV with outbreaks occurring mainly (but not exclusively) in highland areas. ToSRV shows a more widespread incidence across both highland and lowland areas of the ARF biome.


Protein synthesis in skin and bone of the young rat.
Fractional rates of protein synthesis in tissues of young growing rats were estimated by injection of flooding amounts (1.5 mmol/kg body-weight) of [3H]phenylalanine. Rates of 63.6%/d and 90.4%/d respectively were obtained in the skin and bone (tibia) of fed animals. These rates were comparable to that in liver (86.3%/d) but considerably higher than in muscle (16.9%/d). Absolute amounts of protein synthesized in tissues of fed rats were estimated. Together the skin and bones accounted for 25% of whole-body synthesis, a value similar to the contribution of liver (15%) and muscle (25%). In fed rats the ratio, RNA:protein in skin and bone was lower than in liver, but much higher than in muscle. However, the amounts of protein synthesized per unit RNA in skin and bone were higher than in both liver and muscle. After 2 d of starvation the fractional rates of protein synthesis in skin and bone fell by 26% and 31% respectively. This was greater than the fall in liver (17%) but less than in muscle (66%). In bone the fall in synthesis was accompanied by decreases in both RNA:protein and synthesis per unit RNA, but in skin there was a fall in RNA:protein which was partially countered by an increase in the rate of synthesis per unit RNA.


Can artificial neural replicators be useful for studying RNA replicators?
Here, I discuss the usefulness of the application of special artificial neural systems - neural replicators - to study viroids - small pathogens that are short replicating RNA sequences. Using special representations of nucleotide sequences in the form of two sequences with binary components - these two sequences are incomplete representations of the same nucleotide sequence - I show that these neural systems of different sizes are replicated in a special way on them. This allows us to extract some useful information about viroids and their structure, motifs, and relationships. This study is only the first attempt to use neural replicators to analyze genetic data.


Fonsecaea pedrosoi skin infection in a dog.
Fonsecaea pedrosoi is the most common fungal agent associated with human chromoblastomycosis. In the current study, a phaeohyphomycotic condition of the skin caused by Fonsecaea pedrosoi is described in a dog.


The relationships between clinical teaching behaviour and transition shock in newly graduated nurses.
To explore the relationships between clinical teaching behaviour and transition shock in newly graduated nurses and significant differences in the northwest and northeast China. A cross-sectional design. A total of 211 (nurses) and 925 (preceptors) were recruited in six Third-class different hospitals from July to August 2019. The transition shock is negatively correlated with the clinical teaching behaviour in northwest and northeast China, while the transition shock in the northwest is higher than that in the northeast for the behindhand economy and natural limit. The transition process of newly graduated nurses in northeast China with ethnic minorities and the behindhand economy is more difficult. For newly graduated nurses, personal health and a supportive environment need further improvement. Teaching strategies for preceptors need to be enhanced. Two-way feedback is more useful for both the newly graduated nurses and preceptors to improve quality care, and holistic care.


[The human fetal development time table of the major limb bones-ultrasonic bone age].
B-ultrasonic technique was used to examine 297 Chinese fetuses in normal pregnancy woman of completed week age from 12 to 38 weeks. The lengths of the major limb bones were measured and statistical analysis showed that the positive linear correlation between the development of fetuses' limb bones and the completed fetal age is significant.


Pathology of ilioinguinal neuropathy produced by mesh entrapment: case report and literature review.
Ilioinguinal neuropathy is a well-described complication of mesh inguinal herniorrhaphy. We report the first human case, to our knowledge, of ilioinguinal nerve mesh entrapment with neuropathological changes that suggest an inflammatory cause for this chronic pain syndrome.


Alpha CTX as a biomarker of skeletal invasion of breast cancer: immunolocalization and the load dependency of urinary excretion.
We recently showed that increased urinary excretion of the cross-linked, nonisomerized form of the C-telopeptide of collagen type I (alphaalphaCTX) could be a sensitive indicator of the presence of bone metastases in breast cancer patients. The present study was sought to investigate (a) the localization of alphaCTX epitopes in the proximity of a bone metastasis and (b) the relationship between number of metastases and the urinary excretion of alphaalphaCTX. Adjacent bone sections from breast cancer patients were stained for the presence of tumor cells (anti-cytokeratin antibody), osteoclasts (TRAcP activity), and alphaCTX (anti-alphaCTX antibody). The association between the extent of metastatic bone disease and urinary excretion of alphaalphaCTX measured with ELISA was assessed in 90 breast cancer patients (45 with bone metastasis and 45 without bone metastasis). Immunohistochemistry revealed accumulation of TRAcP-positive osteoclasts and intense staining for alphaCTX epitopes in the proximity of cytokeratin-positive bone metastasis. Areas of alphaCTX staining showed unstructured bone tissue under polarized light. In addition, there was a significant linear association between the number of bone metastases and the urinary levels of alphaalphaCTX in breast cancer patients with metastatic bone disease, independent of age and body mass index (r = 0.56, P < 0.001). The estimated relative increases in alphaalphaCTX associated with the presence of one, two, or three metastases are 38%, 57%, and 81%, respectively. Taken into account the 17% intraindividual variation of the assay, alphaalphaCTX could be a sensitive biochemical marker for the close monitoring of cancer patients aiming the facilitation of early metastasis detection.


A new class of rat glutathione S-transferase Yrs-Yrs inactivating reactive sulfate esters as metabolites of carcinogenic arylmethanols.
A glutathione (GSH) S-transferase (GST), catalyzing the inactivation of reactive sulfate esters as metabolites of carcinogenic arylmethanols, was isolated from the male Sprague-Dawley rat liver cytosol and purified to homogeneity in 12% yield with a purification factor of 901-fold. The purified GST was a homo-dimeric enzyme protein with subunit Mr 26,000 and pI 7.9 and designated as Yrs-Yrs because of its enzyme activity toward "reactive sulfate esters." GST Yrs-Yrs could neither be retained on the S-hexylglutathione gel column nor showed any activity toward 1,2-dichloro-4-nitrobenzene, 4-nitrobenzyl chloride, and 1,2-epoxy-3-(4'-nitrophenoxy)propane. 1-Chloro-2,4-dinitro-benzene was a very poor substrate for this GST. 1-Menaphthyl sulfate was the best substrate for GST Yrs-Yrs among the examined mutagenic arylmethyl sulfates. The enzyme had higher activities toward ethacrynic acid and cumene hydroperoxide. N-terminal amino acid sequence of subunit Yrs, analyzed up to the 25th amino acid, had no homology with any of the known class alpha, mu, and pi enzymes of the Sprague-Dawley rat. Anti-Yrs-IgG raised against GST Yrs-Yrs showed no cross-reactivity with any of subunits Ya, Yc, Yb1, Yb2, and Yp. Anti-IgGs raised against Ya, Yc, Yb1, Yb2, and Yp also showed no cross-reactivity with GST Yrs-Yrs. The purified enzyme proved to differ evidently from the 12 known cytosolic GSTs in various tissues of the rat in all respects. Immunoblot analysis of various tissue cytosols of the male rat indicated that apparent concentrations of the GST Yrs-Yrs protein were in order of liver greater than testis greater than adrenal greater than kidney greater than lung greater than brain greater than skeletal muscle congruent to heart congruent to small intestine congruent to spleen congruent to skin congruent to 0.


Relationships Between Telomere Length, Plasma Glucagon-like Peptide 1, and Insulin in Early-Life Stress-Exposed Nonhuman Primates.
Early-life stress is associated with alterations in telomere length, a marker of accumulated stress and aging, and a risk factor for psychiatric disorders. Nonhuman primate maternal variable foraging demand (VFD) is a validated early-life stress model, resulting in anxiety- and depressive-like symptoms in offspring. Previous studies reported increased plasma glucagon-like peptide 1 (pGLP-1) along with insulin resistance in this model. We investigated whether VFD rearing related to adult telomere length and to these neuroendocrine markers. Adult leukocyte telomere length was measured in VFD-reared (12 males, 13 females) and non-VFD-reared (9 males, 26 females) bonnet macaques. Associations between adult telomere length and adolescent fasting pGLP-1 or insulin resistance in VFD-reared versus non-VFD-reared groups were examined using regression modeling, controlling for sex, weight, and age. VFD subjects had relatively longer telomeres than non-VFD subjects (p = .017), and females relatively longer than males (p = .0004). Telomere length was positively associated with pGLP-1 (p = .0009) and with reduced insulin sensitivity (p < .0001) in both sexes, but not as a function of rearing group. Unexpectedly, VFD was associated with longer adult telomere length. Insulin resistance may lead to higher pGLP-1 levels in adolescence, which could protect telomere length in VFD offspring as adults. Associations between adult telomere length and adolescent insulin resistance and high pGLP-1 may reflect an adaptive, compensatory response after early-life stress exposure.


Identification of key microRNAs and hub genes in non-small-cell lung cancer using integrative bioinformatics and functional analyses.
Non-small-cell lung cancer (NSCLC) is an extremely debilitating respiratory malignancy. However, the pathogenesis of NSCLC has not been fully clarified. The main objective of our study was to identify potential microRNAs (miRNAs) and their regulatory mechanism in NSCLC. Using a systematic review, two NSCLC-associated miRNA data sets (GSE102286 and GSE56036) were obtained from Gene Expression Omnibus, and the differentially expressed miRNAs (DE-miRNAs) were accessed by GEO2R. Survival analysis of candidate DE-miRNAs was conducted using the Kaplan-Meier plotter database. To further illustrate the roles of DE-miRNAs in NSCLC, their potential target genes were predicted by miRNet and were annotated by the Database for Annotation, Visualization and Integrated Discovery (DAVID) program. Moreover, the protein-protein interaction (PPI) and miRNA-hub gene regulatory network were established using the STRING database and Cytoscape software. The function of DE-miRNAs in NSCLC cells was evaluated by transwell assay. Compared with normal tissues, a total of eight DE-miRNAs was commonly changed in two data sets. The survival analysis showed that six miRNAs (miR-21-5p, miR-31-5p, miR-708-5p, miR-30a-5p, miR-451a, and miR-126-3p) were significantly correlated with overall survival. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that target genes of upregulated miRNAs were enriched in pathways in cancer, microRNAs in cancer and proteoglycans in cancer, while the target genes of downregulated miRNAs were mainly associated with pathways in cancer, the PI3K-Akt signaling pathway and HTLV-I infection. Based on the miRNA-hub gene network and expression analysis, PTEN, EGFR, STAT3, RHOA, VEGFA, TP53, CTNNB1, and KRAS were identified as potential target genes. Furthermore, all six miRNAs exhibited significant effects on NSCLC cell invasion. These findings indicate that six DE-miRNAs and their target genes may play important roles in the pathogenesis of NSCLC, which will provide novel information for NSCLC treatments.


Structure and Magnetic Properties of Thermodynamically Predicted Rapidly Quenched Fe85-xCuxB15 Alloys.
In this work, based on the thermodynamic prediction, the comprehensive studies of the influence of Cu for Fe substitution on the crystal structure and magnetic properties of the rapidly quenched Fe85B15 alloy in the ribbon form are performed. Using thermodynamic calculations, the parabolic shape dependence of the ΔGamoprh with a minimum value at 0.6% of Cu was predicted. The ΔGamoprh from the Cu content dependence shape is also asymmetric, and, for Cu = 0% and Cu = 1.5%, the same ΔGamoprh value is observed. The heat treatment optimization process of all alloys showed that the least lossy (with a minimum value of core power losses) is the nanocomposite state of nanocrystals immersed in an amorphous matrix obtained by annealing in the temperature range of 300-330 °C for 20 min. The minimum value of core power losses P10/50 (core power losses at 1T@50Hz) of optimally annealed Fe85-xCuxB15 x = 0,0.6,1.2% alloys come from completely different crystallization states of nanocomposite materials, but it strongly correlates with Cu content and, thus, a number of nucleation sites. The TEM observations showed that, for the Cu-free alloy, the least lossy crystal structure is related to 2-3 nm short-ordered clusters; for the Cu = 0.6% alloy, only the limited value of several α-Fe nanograins are found, while for the Cu-rich alloy with Cu = 1.2%, the average diameter of nanograins is about 26 nm, and they are randomly distributed in the amorphous matrix. The only high number of nucleation sites in the Cu = 1.2% alloy allows for a sufficient level of grains' coarsening of the α-Fe phase that strongly enhances the ferromagnetic exchange between the α-Fe nanocrystals, which is clearly seen with the increasing value of saturation induction up to 1.7T. The air-annealing process tested on studied alloys for optimal annealing conditions proves the possibility of its use for this type of material.


Platelet activation during exercise-induced myocardial ischaemia.
Twenty-six normal subjects (aged 18-52) and eighteen patients with ischaemic heart disease (aged 36-67) underwent maximal 12 lead ECG treadmill exercise testing. Coronary angiography was performed on sixteen of the patients. In-vivo platelet activation was assessed by measuring plasma levels of the platelet specific protein beta-thromboglobulin (beta-tg). The mean beta-tg levels pre- and post-exercise in the normal subjects were 47 (SD: 42- 26-85) ng/ml and 48 (29-78) ng/ml respectively, and in the patient group 68 (43-107) ng/ml and 70 (45-109) ng/ml. There was a significant difference between the two groups at rest (p less than 0.05), but there was no change in either following exercise. Post exercise beta-tg levels showed no correlation with the degree of induced ischaemia as judged by ST segment depression and the number of leads involved. Resting beta-tg levels, however, were positively correlated with the presence and extent of angiographically demonstrable coronary disease (r = 0.53, p less than 0.05). We conclude that in vivo platelet activation is present at rest in patients with coronary artery disease, and whilst related to the presence and extent of such disease is unrelated to induced ischaemia.


Right upper lobe intrapulmonary mature cystic teratoma. An unusual location with unusual associations and a review of the literature.
Teratomas are rare neoplasms made up of mature embryonic germ cell layers. Extra-gonadal teratomas are rare and primarily in the mediastinum. Mature cystic teratomas (MCT) are slow-growing benign tumors accounting for a small number of mediastinal germ cell tumors. Patients with MCT are often asymptomatic, and even most symptomatic intrapulmonary teratomas present with vague and non-specific symptoms such as cough, hemoptysis, and chest pain. A Yemeni patient presented for two years with dry cough, shortness of breath, and stitching right-sided chest pain. Plain X-ray showed pleural thickening associated with two opacities in the right lung- one located centrally in the upper lobe and another peripherally- which were confirmed with a CT scan. During right-sided decortication with resection of the two masses, extensive adhesions were found between the right pleura and the chest wall. The adhesions were released, and right-sided decortication led to the removal of the peripheral cystic mass attached to the pleura. Histopathology reported the presence of squamous epithelium lining with ectodermal components such as hair follicles, sebaceous glands, keratin debris, fatty, and fibromuscular tissue. Intrapulmonary teratomas are rare tumors, with less than 100 cases reported in the past few years. All the reported cases are in the left lung lobes, yet our case is on the right side. Although the right-sided mature cystic teratoma is even scarcer, physicians should have a high index of suspicion for teratoma when encountering abnormal lesion in the right side of the lung confirming it either by CT or MRI.


Novel yeasts with potential probiotic characteristics isolated from the endogenous ferment of artisanal Minas cheese.
Artisanal Minas cheese (QMA) is traditionally elaborate using raw milk and endogenous ferment (pingo - whey or rala - grated ripened cheese). In the present study, 91 yeast strains were isolated and identified from pingo and rala. Eight yeast species were identified by the MALDI-TOF mass spectrometry and confirmed by sequencing of the ITS region. The yeasts' protease and lipase activities were evaluated in addition to probiotic properties such as tolerance to low pH and bile salts, hydrophobicity, autoaggregation, co-aggregation with pathogens, and antimicrobial susceptibility. The rala ferment showed a greater variety of species. Yarrowia lipolytica was the dominant specie (52.7% of isolates), followed by the Kluyveromyces lactis and Kodamaea ohmeri (9.9 and 6.6%, respectively). From the total yeasts evaluated, 74 strains showed positive enzymatic activity: 52 strains showed lipolytic (51 Y. lipolytica and one Trichosporon japonicum) and 44 proteolytic activities (18 Y. lipolytica, 13 K. ohmeri, 11 K. lactis, and 2 Wickerhamiella sp.). All evaluated isolates demonstrated tolerance to pH 2.0, and 69 isolates supported the presence of bile salts. From them, 12 isolates showed the capacity of autoaggregation (> 30%) and hydrophobicity (> 90.0%) and were then selected for co-aggregation and antibiotic resistance assays. All selected isolates showed co-aggregation with Salmonella Enteritidis, Escherichia coli, and Listeria monocytogenes greater than 30%. None of the yeast showed sensibility to the evaluated antibiotics and antagonistic activity against the evaluated pathogens. The results demonstrated that pingo and rala have different yeast composition with different enzymatic activity, which may affect the characteristics of the cheese. Furthermore, some yeast strains: Y. lipolytica (9 strains isolated from rala) and K. ohmeri (3 strains isolated from pingo) demonstrated attractive probiotic potential.


Characterisation of germinating and non-germinating wheat seeds by nuclear magnetic resonance (NMR) spectroscopy.
Experiments were conducted to characterise the changes, especially of water status in germinating and non-germinating wheat seeds by nuclear magnetic resonance (NMR) spectroscopy. NMR relaxation time ( T(2)) measurements showed tri-phasic or bi-phasic characteristics during different stages of hydration, depending on the seed's ability to germinate. Component analysis of T(2) data revealed the existence of only two components, bound and bulk water, in dry seeds. In contrast, both the germinating and non-germinating wheat seeds had a three-component water proton system (bound, bulk and free water) in phase I of hydration. During the lag phase (phase II) of hydration, bulk water component of non-germinating seeds disappeared completely, resulting in a two component water proton system. Nevertheless, the three component water proton system was observed in the germinating seeds in phase II. Following phase II, rapid hydration (phase III) was observed in germinating seeds only. Water protons were re-organised and there were increases in bulk and free water but decreases in bound water concomitantly. Comparison of the physical state of water in these seeds by NMR spectroscopy with that of tissue leachate conductivity measurement suggests that the seed membrane system was affected more evidently in non-germinating seeds, leading to the disorganised cell structure. The present study provides evidence that the reorganisation of physical state of water in germinating wheat seeds during hydration is essential for its subsequent event of germination.


Selection of bionic Co-former improves the dissolution of Neohesperidin via Co-amorphous solid dispersion with Naringin.
The co-amorphous solid dispersion (c-ASD) is a useful method to enhance water solubility of poorly soluble drugs. The objective of this study was to improve the dissolution of Neohesperidin (NE) via binary c-ASD which, to the best of our knowledge, has not yet been reported. Since NE and Naringin (NA) co-exist abundantly in Chinese herbal medicine Fructus Aurantii Immaturus, it was hypothesised that NA served as a co-former of NE-NA c-ASD to improve the dissolution profile of NE. Hence, NA was selected to prepare c-ASD with NE at a weight ratio of 4:10, 10:10, 10:4 by lyophilisation. They were characterised according to thermal properties, molecular interactions, dissolution properties and physical stability. We found that the 10:10 ratio was the most potent in enhancing the dissolution behaviour of NE; whereby NE and NA are highly synchronous in pair-wise solvation process. A molecular mixture was achieved through the intermolecular H-bond and pi-pi stacking force formed between NE and NA and was stable for 7 -months. We concluded that the NE-NA co-amorphous binary system is a promising strategy to improve the dissolution behaviour and stabilise the amorphous state of NE. Bionic co-former selection may be an innovative and effective way to accurately determine the appropriate co-former of poorly water soluble substances.


Gene dosage effect for human triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase in partial trisomy 12p13 and trisomy 18p.
An 8-year-old girl with profound mental retardation and a neurologic syndrome associated with morphologic abnormalities was found to have a supernumerary small submetacentric chromosome. Several members of her family carried a balanced translocation t(12;18)(p12;q11), and the child's karyotype could be explained by 3:1 maternal segregation (tertiary trisomy). The proband was trisomic for 12p13 and 18p. A gene dosage effect was demonstrated for triosephosphate isomerase and glyceraldehyde-3-phosphate in erythrocytes and leukocytes allowing us to assign the corresponding loci to the tip of the chromosome 12 short arm.


Skilled maternal healthcare and good essential newborn care practice in rural Bangladesh: A cross-sectional study.
Essential newborn care (ENC) practices play an important role in reducing the risk of infant mortality and morbidity. Therefore, more studies are needed on ENC practices. Skilled maternal healthcare can be a good strategy to increase the practice. Learn about the independent and joint effects of skilled maternal healthcare during pregnancy and childbirth on newborn care practices. The study used a cross-sectional data obtained from Bangladesh Multiple Indicator Cluster Survey, 2019. To investigate the association between maternal healthcare utilization and good ENC practice (cord care, delayed bathing, and immediate breast-feeding), χ 2 test and t-test in bivariate and binary logistic regression analysis, respectively have been performed after taking into account complex survey design. Only about 24% (95% confidence interval [CI]: 22.95%-25.89%) women given birth at home in rural Bangladesh followed good newborn care practice. The results obtained from adjusted regression analysis showed that a woman was 24%, 49%, and 75% more likely of having good ENC practice if she received four or more skilled checkups during antenatal period only (adjusted odds ratios [AOR]: 1.24, 95% CI: 0.97, 1.60), received assistance from SBA during delivery only (AOR: 1.49, 95% CI 1.12, 1.97) and received skilled healthcare in both pregnancy and delivery (AOR: 1.75, 95% CI 1.13, 2.71), respectively compared to a woman who did not get an opportunity to receive skilled healthcare during pregnancy and delivery. Among the selected confounders, maternal age at birth, birth order, education of household heads and religion showed a significant association with good ENC practice. The study revealed that proper maternal healthcare during pregnancy and childbirth from skilled health personnel can improve the rate of ENC practices. For this, more training programs should be started, especially at the community level, and health promotion activities are needed to create awareness about efficient maternal healthcare practices.


Enhanced mirroring upon mutual gaze: multimodal evidence from TMS-assessed corticospinal excitability and the EEG mu rhythm.
Previous research has demonstrated that eye contact between actor and observer specifically enhances the 'mirroring' of others' actions, as measured by transcranial magnetic stimulation (TMS)-induced motor evoked potentials (MEPs). However, it remains unknown whether other markers of mirror system activation, such as suppression of the EEG mu rhythm (8-13 Hz) over the sensorimotor strip, are also susceptible to perceived eye contact. Here, both TMS-induced MEPs and EEG mu suppression indices were assessed (in separate sessions) while 32 participants (mean age: 24y; 8m) observed a simple hand movement combined with direct or averted gaze from the actor. Both measures were significantly modulated by perceived eye gaze during action observation; showing an increase in MEP amplitude and an attenuation of the mu rhythm during direct vs. averted gaze. Importantly, while absolute MEP and mu suppression scores were not related, a significant association was identified between gaze-related changes in MEPs and mu suppression, indicating that both measures are similarly affected by the modulatory impact of gaze cues. Our results suggest that although the neural substrates underlying TMS-induced MEPs and the EEG mu rhythm may differ, both are sensitive to the social relevance of the observed actions, which might reflect a similar neural gating mechanism.


Socio-economic inequality and healthcare costs over the life course - A dynamic microsimulation approach.
Although there is well-established evidence for the existence of socio-economic inequalities in virtually all dimensions of health, little is known about the implications of these socio-economic disparities for healthcare costs from a cumulative life course perspective. Accounting for differentials in healthcare use patterns and mortality, we assess how lifetime costs differ between socio-economic groups. This study used dynamic microsimulation modelling. Combining price weights for healthcare services with information on healthcare consumption from the 2014 Austrian Health Interview Survey (n = 15,771), we calculated average cost profiles by gender, age and education consistent with aggregate System of Health Accounts. A dynamic microsimulation model was used to project cumulative healthcare costs over the entire lifecycle for the 2019 birth cohort in four different scenarios to illustrate the influence of the different cost determinants on lifetime costs. Before considering social inequalities in mortality, men with compulsory education have close to 66% higher lifetime costs than men with tertiary education; for women, the difference is close to 20%. Accounting for longevity differentials reduces this gap to approximately 40% for men and 10% for women. Closing the gap in healthcare use and in longevity between socio-economic groups would reduce lifetime healthcare expenditure by 4.1% in the 2019 birth cohort and by 19% in the whole population. Accounting for mortality differentials between socio-economic groups has a large impact on estimated lifetime healthcare costs. Reducing social inequalities in health can contribute to containing healthcare expenditures against the backdrop of rising life expectancy.


Basics of compounding: United States pharmacapeia general chapter 797 pharmaceutical compounding-sterile preparations, part 10: first revision: the main changes, events, and rationale.
From 2005 to 2007, the United States Pharmacopeia's Sterile Compounding Committee revolutionized sterile preparation practices with a thorough revision to a monumental standard. By revising United States Pharmacopeia General Chapter 797, they defined safe procedures for compounded sterile preparations in profound detail. From proper hygiene to air quality control, the revised Chapter 797 aims to reduce complications related to treatment with compounded sterile preparations, offers invaluable information to those involved in the compounding process, and establishes standards to improve the quality of the compounding process. The vast intellect, innovative review process, and dedicated research incorporated into this revision have assisted those involved with compounding pharmacy around the world.


Understanding residents' behaviour intention of recycling plastic waste in a densely populated megacity of emerging economy.
Plastic waste is choking our planet, but the recycling rate is still universally low. Understanding factors affecting recycling behaviours can help address this pressing issue. Taking Dhaka as an example, this study explores the determinants of the intentions to recycle plastic waste. We employed the Theory of Planned Behaviour (TPB) and extended it with two additional variables: Moral Norms, and Perceived sufficiency of knowledge and policy support. Survey data of 577 were collected and analysed using PLS-SEM. The findings suggest attitude, perceived behavioural control, moral norms and subjective norms significantly impact recycling intention, among which moral norms (β = 0.148, p < 0.05) acts even more strongly than subjective norms (β = 0.12, p < 0.05). Moreover, low level perception of knowledge and policy support makes people perceive less control over recycling behaviour (β = 0.188, p < 0.05), but actually reinforce their recycling intention (β = -0.091, p < 0.1). This study enriches the theoretical discussion of TPB, and contributes to the efforts of encouraging plastic recycling in populated megacity of emerging economy.


Cluster of late preterm and term neonates with necrotizing enterocolitis symptomatology: descriptive and case-control study.
To investigate a necrotizing enterocolitis (NEC) cluster of late preterm and term neonates (gestational age ≥34 weeks). We conducted a descriptive and a case-control study. Medical records of neonates with modified Bell stage ≥ IB NEC and matched controls were reviewed, in addition to microbiological and environmental investigation. Study variables included maternal/delivery and neonatal factors, medications, procedures and feeding practices. Univariable/multivariable logistic regression analyses were performed for all and for stage ≥ II cases. Out of 1841 late preterm and term neonates, 10 stage IB and 10 stage ≥ II [mean(SD) birthweight 2529.3 (493.04) g, gestational age 36.96 (1.48) weeks] presented with NEC symptomatology at mean 4.6 (range 2-8) days. Nearly all (19/20) resulted from high-risk pregnancies and received postpartum intermediate care. All were exclusively or partly formula fed. Most (14/20) were born by cesarean delivery. Eight underwent surgery, with no fatality. Intermediate care (p = 0.006), transient tachypnea (p = 0.049), not receiving breast milk (p = 0.019) and in addition intrauterine growth restriction (IUGR) (p = 0.017) for stage ≥ II cases were independently associated with NEC. Late preterm and term neonates in need of intermediate care, with IUGR and transient tachypnea were susceptible to NEC; feeding with breast milk was an important protective factor.


Construction and validation of a novel prognostic signature for cutaneous melanoma based on ferroptosis-related genes.
Ferroptosis, a recently uncovered iron-dependent, non-apoptotic cell death process, has been increasingly linked to cancer development. In this study, our objective was to develop a prognostic model centered on ferroptosis-related genes (FRGs) and assess its efficacy as an overall survival (OS) prediction biomarker. We conducted a systematic analysis of cutaneous melanoma (CM) and devised a novel ferroptosis-related prognostic signature (FRGSig) using the TCGA database. An independent dataset from GSE65904 was employed to corroborate the validity of the FRGSig. Both univariate and multivariate Cox proportional hazard regression analyses were utilized to construct a FRGSig composed of five FRGs. mRNA expression and immunohistochemistry (IHC) analysis demonstrated that the expression of FRGSig genes varied between tumor and normal tissues. According to Kaplan-Meier analysis, patients with elevated FRGsig scores faced a worse prognosis. The predictive accuracy of FRGSig was evaluated using the time-dependent receiver operating characteristic curve (ROC), with the area under the curve (AUC) values for 1, 3, and 5 OS at 0.682, 0.711, 0.735 in the TCGA cohort, and 0.662, 0.695, 0.712 in the validation dataset, respectively. Univariate and multivariate Cox regression analyses demonstrated that FRGSig served as an independent prognostic factor. Further analysis revealed a significant relationship between FRGSig and Tumor Mutational Burden (TMB) as well as immune infiltration levels. Gene set enrichment analysis (GSEA) disclosed functional disparities between high- and low-risk groups, suggesting that immune checkpoint-related pathways could be instrumental in the improved prognosis of the low-risk group. Taken together, the FRGSig has potential guidance for prognosis prediction and clinical treatment of CM.


Sex-related differences in cardiovascular stress reactivity in healthy and hypertensive rats.
In healthy females the chronotropic effects of stress are more pronounced, while the hypertensive effects are weakened compared to males. Hemodynamic parameters in females returned to normal more rapidly than in males. Renovascular hypertension in males is more pronounced than in females and is associated with increased cardiovascular stress reactivity (in females it is associated with decreased cardiovascular stress reactivity), which increase the risk of cardiovascular complications in males.


Simulation of pulsed ELF magnetic fields generated by GSM mobile phone handsets for human electromagnetic bioeffects research.
Human provocation studies that investigate the effects of Global System for Mobiles (GSM) communication systems on the brain have focused on Radio Frequency (RF) exposure. We wish to further extend such study by investigating the effect of both RF and Extremely Low Frequency (ELF) field exposure, the latter generated by the GSM handset's battery switching. The use of a commercial handset as an exposure source for such investigations is problematic for a number of reasons and therefore a simulated exposure source, capable of producing both RF and ELF components of exposure, is desirable. As a first step in developing such a source, we have quantified and characterized the ELF field from several commercial handsets (the RF characteristics being already well understood). Through experimental measurement we deduce that these fields can be sufficiently simulated by a 9 mm radius loop residing 10 mm beneath the front surface of the handset device and carrying enough current to generate peak fields of 25 microT at the surface of the handset.


Fungal air-borne spores as health risk factors among workers in alimentary industries.
A survey to evaluate the occurrence of air-borne fungal spores in two different food industries, dairies and bakeries, was conducted. Our data revealed considerable fungal pollution in the environments of both industries, as well as some differences in the distribution of the genera of fungi recovered. Noteworthy was the frequent finding of numerous fungi frequently responsible for allergic rhinitis, asthma and other diseases, or well-known for their production of mycotoxins in foods or characterized by their degradative activity against various substances. Aspergillus, Candida, Fusarium, Geotrichum, Mucor and Penicillium were the most common genera identified in dairies while Alternaria, Aspergillus, Botrytis, Candida, Cladosporium, Penicillium and Saccharomyces occurred more frequently in bakeries. The survey showed that fungi can play a significant role in allergic and non-allergic diseases in modern working environments.


The effects of footbath on sleep among the older adults in nursing home: A quasi-experimental study.
To examine the long-term effects of foot-bathing therapy, using different water temperatures, on the sleep quality of older adults living in nursing homes. A quasi-experimental study design with non-equivalent control group. Thirty participants were recruited from a nursing home in Gyeong-gi Province, South Korea. The participants were randomly assigned to experimental, placebo, and control groups. The foot-bathing therapy was performed for 30min daily for four weeks. Water at 40°C was used for the experimental group, while water at 36.5°C was used for the placebo group. The control group did not receive any intervention. The participants' sleep patterns (total sleep amount, sleep efficiency, and sleep latency) and sleep-disturbed behaviors were compared based on group, using actigraphy and a sleep disorder inventory. The total amount of sleep and sleep efficiency were significantly different for the experimental group, especially those with poor sleep quality. There were no differences in sleep latency or sleep-disturbed behaviors among the groups. The long-term effect of the therapy decreased in the third week of the therapy. Daily, 30-min foot-bathing therapy sessions with water at 40°C were effective in improving sleep quality for older adults. The therapy was more effective for participants with poor sleep quality at baseline assessment than those with relatively good sleep quality. The long-term effects of foot-bathing therapy decreased three weeks after initiation; therefore, it might be desirable to deliver the therapy for two weeks, pause it for a week, and then resume it.


Distribution of corticotropin-releasing-factor-like immunoreactivity in brainstem of two monkey species (Saimiri sciureus and Macaca fascicularis): an immunohistochemical study.
Immunohistochemical methods were utilized to systematically map the distribution of corticotropin-releasing-factor-like immunoreactivity (CRF-LI) in the diencephalon, mesencephalon, and rhombencephalon of two monkey species (Saimiri sciureus and Macaca fascicularis). A primary antiserum directed against the human form of the peptide was utilized. Immunoreactive neuronal perikarya and processes were evident in numerous areas, and the distributions of these elements were similar for the two species. As previously reported for rats, monkeys, and human, intense immunoreactivity was evident in putative hypophyseal neurons in the parvicellular component of the paraventricular nucleus of the hypothalamus and in fibers extending from this area into the median eminence. The results for other brainstem regions, most of which have been previously examined for CRF-LI only in rats, indicate that many similarities exist between rats and monkeys in the distribution of this peptide in brainstem extrahypophyseal neuronal circuits, although substantial differences are also evident. For example, immunoreactive perikarya previously observed in other hypothalamic nuclei in rats were not evident in monkeys. Conversely, in monkeys, unlike rats, labeled perikarya were evident in several thalamic nuclei, especially in the intralaminar complex. Also, two large groups of immunoreactive neurons which have generally not been observed in rat studies were present in the mesencephalon and rhombencephalon. In the mesencephalon this consisted of a group of neurons just lateral to the mesencephalic tegmentum, extending throughout the rostral-caudal extent of the midbrain. In the rhombencephalon, labeled perikarya were observed throughout the inferior olive. Some of the differences between rats and monkeys in the locations of labeled perikarya may be due to differences in antiserum specificity and/or sensitivity, or they may result from the fact that colchicine pretreatment was not utilized in the present study. The distributions of immunoreactive fibers also exhibited similarities and differences between monkeys and rats. The most striking terminal fields observed in the present study which have not been previously described are a moderate-to-dense field within and adjacent to presumed dopamine-containing neurons in the substantia nigra pars compacta, a dense innervation of certain subdivisions of the interpeduncular nucleus, and a regionally and parasagittally organized distribution of fibers in the Purkinje cell and molecular layers of the cerebellar cortex.(ABSTRACT TRUNCATED AT 400 WORDS)


Prolongation of cardiac refractory times in man by clofilium phosphate, a new antiarrhythmic agent.
The electrophysiologic effects of clofilium phosphate, a new quaternary ammonium antiarrhythmic agent, were evaluated in 15 patients with a variety of cardiac dysrhythmias. Ten patients had ventricular dysrhythmias and five patients had supraventricular dysrhythmias. Clofilium was administered as a single bolus intravenously in doses ranging from 60 to 300 micrograms/kg during electrophysiologic testing. Blood pressure and heart rate were unchanged, and there were no significant side effects. Conduction time was unchanged in atrial tissue, ventricular tissue, atrioventricular node, and in the His-Purkinje system. QT intervals lengthened, atrial effective refractory period increased, and ventricular effective refractory period increased. The effective refractory period of the AV node was unchanged. Refractoriness of the bundle branches or His-Purkinje system was increased in eight patients. Inducible supraventricular arrhythmias were improved in four of four patients, and inducible ventricular arrhythmias were improved in at least five of nine patients. Clofilium is a model for an antiarrhythmic drug which should be useful in interrupting or suppressing reentrant arrhythmias because it increases refractoriness without major changes in conduction time.


Species richness alone does not predict cultural ecosystem service value.
Many biodiversity-ecosystem services studies omit cultural ecosystem services (CES) or use species richness as a proxy and assume that more species confer greater CES value. We studied wildflower viewing, a key biodiversity-based CES in amenity-based landscapes, in Southern Appalachian Mountain forests and asked (i) How do aesthetic preferences for wildflower communities vary with components of biodiversity, including species richness?; (ii) How do aesthetic preferences for wildflower communities vary across psychographic groups?; and (iii) How well does species richness perform as an indicator of CES value compared with revealed social preferences for wildflower communities? Public forest visitors (n = 293) were surveyed during the summer of 2015 and asked to choose among images of wildflower communities in which flower species richness, flower abundance, species evenness, color diversity, and presence of charismatic species had been digitally manipulated. Aesthetic preferences among images were unrelated to species richness but increased with more abundant flowers, greater species evenness, and greater color diversity. Aesthetic preferences were consistent across psychographic groups and unaffected by knowledge of local flora or value placed on wildflower viewing. When actual wildflower communities (n = 54) were ranked based on empirically measured flower species richness or wildflower viewing utility based on multinomial logit models of revealed preferences, rankings were broadly similar. However, designation of hotspots (CES values above the median) based on species richness alone missed 27% of wildflower viewing utility hotspots. Thus, conservation priorities for sustaining CES should incorporate social preferences and consider multiple dimensions of biodiversity that underpin CES supply.


Genomic and epigenetic aberrations of chromosome 1p36.13 have prognostic implications in malignancies.
Deletions of chromosome 1p36 are common in malignancies; however, there is limited information regarding the biological and prognostic implications of 1p36 in cancer. Steroid Receptor-Associated and Regulated Protein (SRARP) is a tumor suppressor on chromosome 1p36.13 that its inactivation predicts poor cancer outcome, indicating that the 1p36.13 segment requires further studies. Therefore, a comprehensive multi-omics analysis of The Cancer Genome Atlas (TCGA), the Pan-Cancer Analysis of Whole Genomes (PCAWD), the International Cancer Genome Consortium (ICGC), and the Genomic Data Commons (GDC) Pan-Cancer datasets was conducted to investigate the prognostic implications of 1p36.13 in malignancies. This study revealed that expression and DNA methylation of multiple genes on 1p36.13 are significantly associated with survival in primary tumors and normal adjacent tissues. In addition, copy-number loss in every gene on 1p36.13 predicts poor cancer outcome. Importantly, copy-number loss and somatic mutations of chromosome 1p36.13 segment are associated with worse survival in primary tumors, and DNA hypermethylation of 1p36.13 predicts poor outcome in normal adjacent tissues. Therefore, genomic and epigenetic aberrations of chromosome 1p36.13 have promising prognostic implications in cancer.


Bronchoscopy induces intestinal mucosal barrier dysfunction: a possible role for nitric oxide.
This study investigates the effect of bronchoscopy on intestinal mucosal barrier function and its association with intestinal nitric oxide production. 30 rats were used. The study group (n=15) underwent rigid bronchoscopy. At 24 h following bronchoscopy, ileal nitrite/nitrate levels were evaluated. The ileum was also examined for mucosal damage, and graded according Chiu's histologic injury scale. In the bronchoscopy group, the ileal nitrite/nitrate levels were significantly higher than those of controls (398.5 +/- 85.1 and 44.5 +/- 6.6 nmol/g tissue, respectively, P=0.001). In the bronchoscopy group, the mucosal damage was significant, compared with those of controls (mean ranks, 22.8 and 8.2, P<0.0001). The changes varied from denuded villi and dilated capillaries to significant architectural distortion, lamina propria disintegration, ulceration and hemorrhage. Significant correlation was found between ileal nitrite/nitrate levels and mucosal damage in the bronchoscopy group (rs=0.56, P=0.03). This study suggests that bronchoscopy induces intestinal mucosal barrier dysfunction in association with excess intestinal nitric oxide production. These events may be involved in mechanisms responsible for bacterial translocation after bronchoscopy.


Relationship between cell ploidy and glucocorticoid induced death in human lymphoid cell lines.
We have found a relationship between sensitivity to glucocorticoid induced cell death (at 10 microM glucocorticoid) and ploidy in the human lymphoid cell line CCRF/CEM-C7. Most sensitive clones are diploid, whilst resistant clones and the resistant parent line CCRF/CEM are tetraploid. Diploid sensitive clones have a tendency to become aneuploid within a few months of isolation, with alterations in their kinetic responses to glucocorticoids. This is followed by a doubling in DNA content which results in reversion to the tetraploid glucocorticoid resistant state of the parent line CCRF/CEM. A few sensitive clones have been found to be tetraploid but with different kinetic responses to glucocorticoids as compared to diploid clones. The principal difference being an extended lag period (48-72 h) prior to lethal response. The relationship between ploidy and glucocorticoid sensitivity does not appear to extend to other human lymphoid cell lines.


Effects of adequacy of gender reassignment surgery on psychological adjustment: a follow-up of fourteen male-to-female patients.
The relationship between the adequacy of surgical result and postoperative psychopathology was examined in 14 male-to-female transsexuals selected for the absence of preoperative psychopathology. Data indicated that the best predictors of postoperative psychopathology as rated on Hunt and Hampson's (1980) Standardized Rating Format were breast scarring, erectile urethral meatus, current social supports, family reaction, urinary incontinence, and need for extra surgery. Together, these accounted for 98% of the variance in postoperative psychopathology. These data suggest that factors which make it difficult for postoperative transsexuals to "pass" or which continue to remind them of their gender-reassigned status are associated with adjustment difficulties. Surgical results may be a major determinant of postoperative psychopathology.


Association between SARS-CoV-2 RNAemia and dysregulated immune response in acutely ill hospitalized COVID-19 patients.
Severe/critical COVID-19 is associated with immune dysregulation and plasmatic SARS-CoV-2 detection (i.e. RNAemia). We detailed the association of SARS-CoV-2 RNAemia with immune responses in COVID-19 patients at the end of the first week of disease. We enrolled patients hospitalized in acute phase of ascertained SARS-CoV-2 pneumonia, and evaluated SARS-CoV-2 RNAemia, plasmatic cytokines, activated/pro-cytolytic T-cells phenotypes, SARS-CoV-2-specific cytokine-producing T-cells (IL-2, IFN-γ, TNF-α, IL-4, IL-17A), simultaneous Th1-cytokines production (polyfunctionality) and amount (iMFI). The humoral responses were assessed with anti-S1/S2 IgG, anti-RBD total-Ig, IgM, IgA, IgG1 and IgG3, neutralization and antibody-dependent cellular cytotoxicity (ADCC). Out of 54 patients, 27 had detectable viremia (viremic). Albeit comparable age and co-morbidities, viremic more frequently required ventilatory support, with a trend to higher death. Viremic displayed higher pro-inflammatory cytokines (IFN-α, IL-6), lower activated T-cells (HLA-DR+CD38+), lower functional SARS-CoV-2-specific T-cells (IFN-γ+CD4+, TNF-α+CD8+, IL-4+CD8+, IL-2+TNF-α+CD4+, and IL-2+TNF-α+CD4+ iMFI) and SARS-CoV-2-specific Abs (anti-S IgG, anti-RBD total-Ig, IgM, IgG1, IgG3; ID50, %ADCC). These data suggest a link between SARS-CoV-2 RNAemia at the end of the first stage of disease and immune dysregulation. Whether high ab initium viral burden and/or intrinsic host factors contribute to immune dysregulation in severe COVID-19 remains to be elucidated, to further inform strategies of targeted therapeutic interventions.


Analysis of major congeners of polybromobiphenyls and polybromodiphenyl ethers in office dust using high resolution gas chromatography-mass spectrometry.
The study focused on analysis of polybromobiphenyls (PBBs) and polybromodiphenyl ethers (PBDEs) congeners in office dust obtained in Pretoria, South Africa. Of the 32 congeners considered for identification, (BB-1, 2, 4, 10, 15, 26, 29, 30, 31, 38, 49, 80, 103, 153, 155, 209 and BDE-3, 15, 17, 28, 47, 66, 77, 85, 99, 100, 126, 138, 153, 154, 183, 209) only BB-2, 4, 30, 153, 209 and BDE-47, 66, 85, 99, 153 and 209 congeners were detected. The sum of PBBs concentration detected in office dust ranged from <dl-196 ng g(-1) dry weight (dw) with a median and mean of 11.4 and 38.2 ng g(-1), respectively. On the other hand, the sum of PBDEs concentration detected ranged from 21.6 to 578.6 ng g(-1)dw with a median and mean of 162 and 169 ng g(-1)dw, respectively. A Spearman rank correlation between ∑(5)PBBs and ∑(6)PBDEs (r(s)=0.55, p=0.003), indicated a statistical significant positive correlation for the similarity of pollution sources for both compound classes. However, no correlation was observed between the number of electronic materials and summation of concentrations of PBBs and PBDEs congeners detected. Concentrations of PBDEs detected in this study are substantially lower than reported in office dust in developed countries.


Evaluation of ambient air concentrations of polycyclic aromatic hydrocarbons in Germany from 1990 to 1998.
All available polycyclic aromatic hydrocarbon (PAH) concentration data in ambient air obtained over the past 10 years in Germany were evaluated to clarify whether it is justified to use benzo(a)pyrene (BaP) as a marker compound for the total PAH exposure. The data basis comprises annual mean concentrations from 1990 to 1998 supplied by the emission protection authorities of the federal states with additional information on the region, year and site of measurement. The data are very heterogeneous with respect to sample size, the number of individual PAHs analyzed, place of origin and year. Nine of 25 individual compounds with sufficient sample size (74<N<518) were submitted to an explorative descriptive analysis and multiple regression analysis. Six compounds were selected for factor analysis to evaluate whether associations can be related to one or several background determinants. The concentration data of BaA, BeP, BaP, DBA, BghiP, COR, BbF, BkF and INP are not normally distributed and demonstrate great variability. Location, East-West differences persisting after the German reunion and time characterize the distributive patterns, e.g., from 1991 to 1997, a significant decrease in BaP could be determined based on the data from North Rhine-Westphalia (1991, N=51, median 1.6 ng/m(3); 1997, N=45, median 0.7 ng/m(3); P<or=0.0001). The BaP concentrations in the new federal states in the East (N=80, median 2.2 ng/m(3)) are about twice as high compared to the ones in the old federal states in the West (N=438, median 1.1 ng/m(3); P<or=0.0001). BaP measurements taken at sites characterized by traffic (1.8 ng/m(3)), industrial (1.3 ng/m(3)) or urban environment (1.3 ng/m(3)) rank significantly higher compared to measurements taken at rural sites (0.92 ng/m(3); P<or=0.0001). Factor analysis of the intercorrelation matrix of BaA, BeP, BaP, DBA, BghiP and COR yields one factor to explain 92% of the variability of the six individual PAHs. BaP shows the highest factor loading. These results confirm the common practice to use BaP as marker compound for the PAH exposure in ambient air.


Release of gonadotropin alpha subunit from rat pituitary cultures in response to GnRH.
Gonadotropin releasing hormone (GnRH)-stimulated release of the alpha subunit common to the gonadotropins and to thyrotropin was studied in rat pituitary cell cultures. In these studies we took advantage of a recently prepared antiserum specific for the alpha subunit. We show that pituitary cells treated with GnRH released alpha subunit in a similar pattern to intact luteinizing hormone (LH) during short-term incubations (0-12 h); during prolonged incubations (12-48 h), however, release of alpha subunit did not desensitize in response to the releasing hormone and the pattern became different from that measured for intact LH. Further, we assessed the relative requirement for Ca2+ in the release of LH and alpha subunit. When pituitary cells were treated with 10(-8) M GnRH in the presence of a range of concentrations of the Ca2+ ion channel antagonist, methoxyverapamil (D-600), release of both LH and alpha subunit was inhibited in a similar and dose-dependent manner; 10(-4) M D-600 showed maximum inhibitory efficacy (IC50 = 10(-5) M). The calmodulin antagonist, pimozide, also inhibited both GnRH-stimulated LH and alpha subunit release (IC50 = 0.75 microM). These data suggested that although the Ca2+/calmodulin system appears to mediate both the release of LH and alpha subunit in response to GnRH, these processes appear differentially regulated during long-term exposure to the releasing hormone.


Low Pretreatment Viral Loads in Infants With HIV in an Era of High-maternal Antiretroviral Therapy Coverage.
With expansion of antiretroviral therapy (ART) programs, transmission rates are low but new infant infections still occur. We investigated predictors of pre-ART viral load (VL) and CD4+ T-cell counts and percentages in infants diagnosed with HIV at birth in a setting with high coverage of maternal ART and infant prophylaxis. As part of an early treatment study, 97 infants with confirmed HIV-infection were identified at a hospital in Johannesburg, South Africa. Infant VL and CD4+ T-cell parameters were measured before ART initiation. Data were collected on maternal characteristics, including VL, CD4+ T-cell counts and ART, and infant characteristics, including sex, birth weight, and mode of delivery. Pre-ART, median infant VL was 28,405 copies/mL [interquartile range (IQR): 2515-218,150], CD4+ T-cell count 1914 cells/mm (IQR: 1474-2639) and percentage 40.8% (IQR: 32.2-51.2). Most (80.4%) infants were born to mothers who received ART during pregnancy and 97.9% of infants received daily nevirapine prophylaxis until ART initiation at median of 2 days of age (IQR: 1-7). Infant pre-ART VL was more likely to be ≥1000 copies/mL when their mothers had VL ≥1000 copies/mL [Odds Ratio (OR): 6.88, 95% confidence interval (CI): 2.32-20.41] and was higher in boys than girls (OR: 3.29, 95% CI: 1.07-9.95). Lower maternal CD4+ T-cell count (<350 cells/mm) was associated with lower infant CD4+ T-cell count (<1500 cells/mm) (OR: 3.59, 95% CI: 1.24-10.43). Pre-ART VL and CD4+ T-cell parameters of intrauterine-infected infants were associated with VL and CD4+ T-cell counts of their mothers. Maternal ART during pregnancy may begin treatment of intrauterine infection and may mask the severity of disease in infected infants identified in the current era with high-maternal ART coverage.


Eisosomes Regulate Phosphatidylinositol 4,5-Bisphosphate (PI(4,5)P2) Cortical Clusters and Mitogen-activated Protein (MAP) Kinase Signaling upon Osmotic Stress.
Eisosomes are multiprotein structures that generate linear invaginations at the plasma membrane of yeast cells. The core component of eisosomes, the BAR domain protein Pil1, generates these invaginations through direct binding to lipids including phosphoinositides. Eisosomes promote hydrolysis of phosphatidylinositol 4,5 bisphosphate (PI(4,5)P2) by functioning with synaptojanin, but the cellular processes regulated by this pathway have been unknown. Here, we found that PI(4,5)P2 regulation by eisosomes inhibits the cell integrity pathway, a conserved MAPK signal transduction cascade. This pathway is activated by multiple environmental conditions including osmotic stress in the fission yeast Schizosaccharomyces pombe. Activation of the MAPK Pmk1 was impaired by mutations in the phosphatidylinositol (PI) 5-kinase Its3, but this defect was suppressed by removal of eisosomes. Using fluorescent biosensors, we found that osmotic stress induced the formation of PI(4,5)P2 clusters that were spatially organized by eisosomes in both fission yeast and budding yeast cells. These cortical clusters contained the PI 5-kinase Its3 and did not assemble in the its3-1 mutant. The GTPase Rho2, an upstream activator of Pmk1, also co-localized with PI(4,5)P2 clusters under osmotic stress, providing a molecular link between these novel clusters and MAPK activation. Our findings have revealed that eisosomes regulate activation of MAPK signal transduction through the organization of cortical lipid-based microdomains.


Frequency and synchrony of tetanically-induced, gamma-frequency population discharges in the rat hippocampal slice: the effect of diazepam and propofol.
Fast, rhythmic discharges, at gamma frequencies, have been evoked in the CA1 region of the hippocampus by tetanic stimulation applied via pairs of electrodes placed close to the pyramidal layer. The discharges had a latency of 65-225 ms and a frequency of 60-100 Hz; they were synchronous (phase lag < 2 ms) when recorded from sites 0.4-0.8 mm apart. Diazepam (5-15 microM) and propofol (5 microM) reduced the frequency by 15-26%, but had no significant effect on synchrony or phase lag, suggesting that the generation and synchrony of this rhythm are pharmacologically distinct. 10 microM propofol had a more marked effect and, when frequency fell by approximately 50%, synchrony was also reduced.


Inhibition of DNA damage response at telomeres improves the detrimental phenotypes of Hutchinson-Gilford Progeria Syndrome.
Hutchinson-Gilford progeria syndrome (HGPS) is a genetic disorder characterized by premature aging features. Cells from HGPS patients express progerin, a truncated form of Lamin A, which perturbs cellular homeostasis leading to nuclear shape alterations, genome instability, heterochromatin loss, telomere dysfunction and premature entry into cellular senescence. Recently, we reported that telomere dysfunction induces the transcription of telomeric non-coding RNAs (tncRNAs) which control the DNA damage response (DDR) at dysfunctional telomeres. Here we show that progerin-induced telomere dysfunction induces the transcription of tncRNAs. Their functional inhibition by sequence-specific telomeric antisense oligonucleotides (tASOs) prevents full DDR activation and premature cellular senescence in various HGPS cell systems, including HGPS patient fibroblasts. We also show in vivo that tASO treatment significantly enhances skin homeostasis and lifespan in a transgenic HGPS mouse model. In summary, our results demonstrate an important role for telomeric DDR activation in HGPS progeroid detrimental phenotypes in vitro and in vivo.


[What is inflammatory bowel disease?].
Inflammatory bowel diseases are chronic conditions of unknown origin that result from continuous or intermittent inflammation of a part of the intestinal wall. The main classic types of IBD are ulcerative colitis, Crohn's disease and indeterminate colitis that cannot be classified accurately as ulcerative colitis or Crohn's disease with pure colonic involvement. The two main subtypes of microscopic colitis, namely lymphocytic and collagenous colitis, fulfill the criteria that define IBD and should be considered as true IBD.


Aortic aneurysm after patch aortoplasty repair of coarctation: a prospective analysis of prevalence, screening tests and risks.
Twenty-nine children were evaluated prospectively for the presence of an aortic aneurysm at the repair site 1 to 19 years after patch aortoplasty repair of coarctation of the aorta. In each child, noninvasive evaluation included a chest X-ray film, computed tomography of the chest and two-dimensional echocardiography. The presence and size of an aortic aneurysm were determined quantitatively by measuring the ratio of the diameter of the thoracic aorta at the repair site to the diameter of the aorta at the diaphragm (aortic ratio). An aortic ratio of greater than or equal to 1.5 was judged abnormal and was shown to be significantly greater than the aortic ratio of a normal control group. An aortogram was obtained in each child if any noninvasive screening test was found to be abnormal. As assessed by the aortogram, the prevalence of aortic aneurysm was 24% in this patient group. The sensitivity of echocardiography and chest computed tomography for detecting an aneurysm was 71% and 66%, and the specificity 76% and 85%, respectively. The chest X-ray film was 100% sensitive and 68% specific in determining the presence of an aneurysm. Although the data are not statistically significant, they suggest that children undergoing patch aortoplasty as the primary procedure (rather than a reoperation after earlier resection), and children in whom a Dacron patch is utilized may be at increased risk for aneurysm formation.(ABSTRACT TRUNCATED AT 250 WORDS)


Association of circulating FGF-21 levels in the first week of life and postnatal growth in hospitalized preterm infants.
The role of fetal and neonatal growth in the development of adult-onset diseases such as obesity and metabolic syndrome has become increasingly appreciated. Fibroblast growth factor-21 (FGF-21) is known as a regulator of glucose and lipid metabolism. FGF-21 levels are elevated in obese adults and children. The role of FGF-21 in neonatal growth in preterm infants is not known. We aimed to evaluate the association of circulating FGF-21 levels in the first week of life and neonatal growth parameters at the time of discharge from NICU. We performed a longitudinal study of 25 preterm neonates admitted to NICU. Blood samples were collected at two time points: within 24 h of life (T1), and 24-96 h after the first blood draw (T2). FGF-21 levels were measured in plasma by ELISA. Weight, length, BMI and their Z-scores were measured at the time of birth and discharge. The FGF-21 levels were significantly higher at T2 than at T1 (p < 0.001). FGF-21 levels at both time points were positively correlated with gestational age (r = 0.43, p = 0.03). FGF-21 at T1 was positively associated with weight Z-score (β = 0.19, p = 0.001) and length Z-score at discharge (β = 0.21, p = 0.03). Circulating FGF-21 levels increase significantly in the first week, and the FGF-21 levels within the first 24 h are positively associated with weight and length Z-scores at discharge in preterm infants. These results suggest that FGF-21 may be involved in growth and developmental maturation.


Exposure to per- and polyfluoroalkyl substances through the consumption of fish from lakes affected by aqueous film-forming foam emissions - A combined epidemiological and exposure modeling approach. The SAMINOR 2 Clinical Study.
Releases of aqueous film-forming foams (AFFFs) from airport firefighting activities have been identified as important local point sources of per- and polyfluoroalkyl substances (PFASs) in nearby waterways. PFASs can be taken up by fish, and in turn by the humans that consume them. Despite the global extent of AFFF emissions, few studies exist on related impacts on humans. We aimed to investigate the associations between the consumption of fish from AFFF-affected waters and serum PFAS concentrations in humans using a combination of statistical tools, empirical data, and toxicokinetic modeling. Participants of the SAMINOR 2 Clinical Study were the basis for this study sample, which comprised 74 persons. Fifty-nine participants who reported consuming fish from AFFF-affected waters and 15 nonconsumers completed a questionnaire and gave serum samples. Participants were classified based on their consumption of trout and char: high (n=16), moderate (n=16), low (n=27), and nonconsumers (n=15); and serum samples were tested for the presence of 15 PFASs. Perfluorooctane sulfonic acid (PFOS) was found in all participants, with the highest concentrations detected in the high consumption group (geometric means, 28ng/mL) compared to the low consumption group and nonconsumers (10 and 11ng/mL, respectively). In an analysis of variance contrast model, a significant, positive increasing trend was seen for fish consumption and PFOS, perfluorohexane sulfonic acid (PFHxS), and perfluorononanoic acid (PFNA). Toxicokinetic modeling allowed us to predict the median increases in serum concentrations of PFOS, PFHxS, and PFNA among high consumers within a factor of 2.2. The combination of statistical evaluation and toxicokinetic modeling clearly demonstrated a positive relationship between consumption of fish from AFFF-affected waters and serum PFAS concentrations. Further studies on dietary exposure to other PFASs present in AFFF and its consequences on human health are warranted.


Evaluation of DNA binding with some selected hydrazide and semicarbazide derivatives.
A group of hydrazide and semicarbazide derivatives containing isopropylidene, benzylidene, cyclohexylidene, and phospholidene groups was synthesized and characterized by spectroscopic techniques. These compounds were tested for DNA interaction studies monitored by UV-Vis and IR data as well as molecular docking. Investigations on interactions of these compounds with DNA revealed an intercalative mode of binding between them. It is interesting to note that semicarbazide derivatives with aliphatic substituents showed better DNA binding than the aromatic substituents.


Survival after parathyroidectomy in chronic hemodialysis patients with severe secondary hyperparathyroidism.
The life for end-stage renal disease patients has remarkably improved in the last years. Although mineral and bone disorders remain as unsolved complication, in severe secondary hyperparathyroidism (sHPT), the ultimate treatment is parathyroidectomy (PTX). It is an old treatment, but there are still insufficient data regarding survival after PTX. The study goals were to compare 2-year mortality and morbidity after PTX in surgically versus medically treated sHPT and to compare the efficacy and safety in subtotal versus total PTX in a cohort of patients receiving hemodialysis (HD). This prospective, longitudinal study was carried out on a cohort of chronic HD patients with severe sHPT (iPTH over 700 pg/ml). Among the overall HD population, 26 patients underwent PTX. This group was compared to a control group treated with specific drugs. Laboratory parameters, specific symptoms and mortality were registered after 24 months of follow-up for each group. The subgroups of subtotal and total PTX patients were also compared. All average values of mineral markers were significantly reduced after PTX, as a proof that surgical treatment was effective. The reduction in mineral markers and the improvement in symptoms and mortality rates were similar after total and subtotal PTX. Bone pain was significantly lower in patients after PTX than in those drug treated (p = 0.0005), but not muscle weakness and itching. Survival at 2 years was better in patients surgically treated (PTX) despite significantly higher mean baseline values of iPTH, Ca and ALP compared to patients medically treated (p = 0.03). We compared clinical and laboratory outcomes in HD patients with severe sHPT. Mortality, bone pain and mineral markers were improved by PTX. Total and subtotal PTX had similar clinical outcomes.


Crystal structure of the bacterial YhcH protein indicates a role in sialic acid catabolism.
The yhcH gene is part of the nan operon in bacteria that encodes proteins involved in sialic acid catabolism. Determination of the crystal structure of YhcH from Haemophilus influenzae was undertaken as part of a structural genomics effort in order to assist with the functional assignment of the protein. The structure was determined at 2.2-A resolution by multiple-wavelength anomalous diffraction. The protein fold is a variation of the double-stranded beta-helix. Two antiparallel beta-sheets form a funnel opened at one side, where a putative active site contains a copper ion coordinated to the side chains of two histidine and two carboxylic acid residues. A comparison to other proteins with a similar fold and analysis of the genomic context suggested that YhcH may be a sugar isomerase involved in processing of exogenous sialic acid.


¹H, ¹³C, and ¹⁵N NMR resonance assignments of reduced full length and shortened forms of the Grx domain of Mus musculus TGR.
Two forms of the glutaredoxin (Grx) domain (full length Grx domain and short Grx lacking the N-terminal region) of Mus musculus thioredoxin glutathione reductase (TGR) were isotopically labelled with (15)N and (13)C isotopes, expressed and purified to homogeneity. We report here the (1)H, (13)C and (15)N NMR assignment for both Grx forms of this mouse TGR. This investigation represents the first NMR analysis of a mammalian TGR.


Conventional and amended bioretention soil media for targeted pollutant treatment: A critical review to guide the state of the practice.
Bioretention systems are widely used green infrastructure elements that utilize engineered bioretention soil media (BSM) for stormwater capture and treatment. Conventional bioretention soil media, which typically consists of sand, sandy loam, loamy sand or topsoil amended with compost, has limited capacity to remove and may leach some stormwater pollutants. Alternative engineered amendments, both organic and inorganic, have been tested to supplement BSM. Yet, municipalities and regulatory agencies have been slow to adopt these alternative amendments into their design specifications, partly because of a lack of clear guidance on how to select the right amendment to treat a target stormwater contaminant under highly variable climatic conditions. This article aims to provide that guidance by: (1) summarizing the current design BSM specifications adopted by jurisdictions worldwide, (2) comparing the performance of conventional and amended BSM, (3) highlighting advantages and limitations of BSM amendments, and (4) identifying challenges for implementing amendments in field conditions. The analysis not only informs the research community of the barriers faced by stormwater managers in implementing BSM amendments but also provides guidelines for their adoption by interested agencies to comply with existing regulations and meet design needs. This feedback loop could catalyze further innovation in the development of sustainable stormwater treatment technologies.


Constitutive interferon expression from retroviral vector.
A genomic fragment with the human beta-interferon gene was cloned into a pL3-4, a defective Moloney murine leukemia virus (M-MuLV) vector. Here we show that clones selected after viral infection of mouse NIH 3T3 cells constitutively produced 128 IU/ml of human beta-interferon. Constitutive synthesis of retroviral RNA was confirmed by dot blot hybridization of RNA isolated from two of the selected clones. Poly(I) x poly(C) and cycloheximide induction resulted in an increased RNA level, but this was not reflected in an increased production of biologically active interferon.


Catecholamines, oxytocin and milk removal in dairy cows.
Experiments were designed to study the effects of catecholamines on oxytocin responses and milk removal in dairy cows. Adrenalin, noradrenalin, dopamine, isoproterenol (a beta-adrenoceptor agonist), phentolamine (an alpha-adrenergic blocker) and propranolol (a beta-adrenergic blocker) were infused intravenously. In addition, adrenalin was infused together with phentolamine and/or propranolol. Infusions started 8 min before milking and lasted until the end of milking. In some cases electroshocks (for 5 s) were applied immediately before milking in the absence and presence of phentolamine and propranolol. Adrenalin, noradrenalin and dopamine reduced milk removal, but only if administered in supraphysiological amounts. The effect of adrenalin and electroshocks on milk removal could be inhibited only partly by phentolamine. Inhibition of milk removal was not mediated by reduced oxytocin responses. Enhanced local release of catecholamines from sympathetic nerves was presumably responsible for lowered milk removal in response to electroshocks. Milk removal was facilitated during alpha-adrenergic blockade and during beta-adrenoceptor stimulation.


Sexuality in the puerperium: a review.
Pregnancy and the puerperium herald dramatic and complex physiological, psychological, interpersonal, and sexual changes in a woman and in the marital process. Pregnancy tends to have an increasingly negative effect on sexual desire, expression, and satisfaction as term approaches. Clinical variables discussed include anatomic and physiological changes, puerperal sexual response patterns, marital adjustment, body image, dyspareunia related to episiotomy, lactation, and traditional taboos and cautions regarding coitus for the new mother. Most research respondents reported gradual return to prepregnancy levels of sexual desire, enjoyment, and coital frequency, with a minority in most cited studies indicating sexual interest and coitus levels below prepregnancy levels up to 1 year after delivery. The most frequently listed reasons for poor postpartum sexual adjustment include episiotomy discomfort, fatigue, vaginal bleeding or discharge, dyspareunia, insufficient lubrication, fears of awakening the infant or not hearing him/her, fear of injury, and decreased sense of attractiveness. Postpartum counseling should be offered prior to hospital discharge.


Compassion for animals in the laboratory: impairment or refinement of research methodology?
There are now signs in the United States as well as in Europe that the importance of a positive human-nonhuman animal relationship in research laboratories is appreciated more seriously. In addition to knowledge and skills, primary attributes of animal research personnel must be feelings of compassion and sensitivity toward animals to safeguard the reliability of scientific research data.


[Pedagogic reflexions on the evidence-based medicine curriculum of the German Central Agency for Quality in Medicine and the German Network for Evidence-Based Medicine].
The German Agency for Quality in Medicine (AQuMed) and the Network for Evidence-based Medicine (EbM) have recently published the draft of an EbM Curriculum for continuing medical education. This standardised concept might lead to an improvement of the quality of EbM courses for physicians. Critical appraisal of the curriculum from a didactic point of view reveals both a substantial lack of teaching methods and teaching aids, and a lack of appropriate tools for the evaluation of the actual increase in professional competence. This includes specialised subject knowledge, methodological considerations as well as highly developed communication and social skills. We recommend incorporation of these components into the curriculum design to facilitate its successful implementation.


Dielectric behavior of gelatine-glycosaminoglycans blends: an impedance analysis.
The dielectric behavior of the gelatine-GAGs based blend systems has been studied to understand the dynamic behavior of the water at the protein-GAGs interfaces which are relevant for tissue engineering application. Impedance (Z) and phase have been measured as a function of frequencies from 0.01 Hz to 100 kHz. GAGs tunes the ionic charge drift which initiates polarization mechanisms through charge accumulation at structural interfaces and creates conduction currents. The admittance results showed that at high frequency, the conductivity increases with increasing GAGs concentration indicating changes in hydration shell of the gelatine by the GAGs.


Feasibility of measuring pericoronary fat from precontrast scans: Effect of iodinated contrast on pericoronary fat attenuation.
Pericoronary adipose tissue (PCAT) attenuation has been identified as a marker for cardiovascular risk. The effect of contrast enhancement on fat attenuation is unknown. We aim to compare precontrast coronary scans to postcontrast CCTA for quantification of pericoronary fat volume and attenuation. Thin slice pre- and post-contrast studies obtained at 120 kVp, heart rate <60, with no plaque or artifact in the right coronary artery (RCA) were selected. Analysis was limited to pixels -30 Hounsfield units (HU) to -190 HU and from 10 mm to 50 mm distal to the RCA origin at a radial distance equal to the vessel diameter. A subgroup with no plaque across all coronaries was also analyzed. Of 119 study pairs, the average RCA diameter was highly correlated at 3.85 mm (postcontrast) and 3.84 mm (precontrast), r = 0.97, p < 0.0001. The mean attenuation of pre- and postcontrast images was also highly correlated at -87.02 ± 7.15 HU and -82.74 ± 6.54 HU, respectively (r = 0.65, p < 0.0001). Pericoronary fat volume in the -190 to -30 HU range was 396 mm³ lower in the post contrast versus pre-contrast, consistent with higher attenuation (less negative) voxels postcontrast (p < 0.0001). Inter- and intra-reader agreement ranged 95-100% and 90% for precontrast and 85-90% for postcontrast studies, respectively. Subgroup analysis revealed precontrast attenuation -85.59 ± 7.53 HU and postcontrast -82.21 ± 7.15 HU were highly correlated r = 0.67, p < 0.0001. Pericoronary fat enhances with iodinated contrast, potentially explaining some of its risk-predictive capabilities. Fat attenuation and volume can be reliably measured from precontrast calcium scans, with volume quantification showing particularly strong correlation. Excellent inter- and intra-reader agreement is also demonstrated.


Retinal arteriovenous malformation with fluctuating vision and ischemic central retinal vein occlusion and its sequelae: 25-year follow-up of a case.
A patient with a retinal arteriovenous malformation (AVM) had experienced episodic visual loss with spontaneous recovery for many years, followed by permanent visual loss secondary to central retinal vein occlusion. She subsequently progressed to development of retinal neovascularization extending onto the posterior vitreous face with recurrent vitreous hemorrhage requiring vitrectomy. A brief review of the literature is presented, and the cause of the fluctuations in vision and central retinal vein occlusion are discussed.


Up-regulation of miR-182 by β-catenin in breast cancer increases tumorigenicity and invasiveness by targeting the matrix metalloproteinase inhibitor RECK.
MiR-182 is a member of the miR-183 cluster located at human chromosome 7q32 region and is up-regulated in human cancers. We study the regulation of miR-182 expression and its oncogenic role. MiR-182 level was investigated by real-time reverse transcription-PCR. Chromatin immunoprecipitation assay was used to confirm promoter binding of transcription factors. The correlation between miR-182 and RECK was analyzed by Western blotting, real-time RT-PCR and 3(')-untranslated region reporter assay. Zymography, matrix metalloproteinase activity, invasion and colony formation were used to study the tumorigenic activity. MiR-182 is over-expressed in human breast tumor tissues and cell lines. Inhibition or knockdown of β-catenin reduced miR-182 level in MDA-MB-231 cells. ChIP assay confirmed the binding of β-catenin on miR-182 promoter. Anti-miR-182 increased the MMP inhibitor RECK protein in MDA-MB-231 cells while pre-miR-182 reduced RECK protein but not mRNA in normal mammary epithelial H184B5F5/M10 cells. Restoration of RECK protein by anti-miR-182 attenuated MMP-9 activity, cell invasion and colony formation. Ectopic expression of miR-182 inhibited restoration of RECK protein by β-catenin inhibitor indicating miR-182 is important for β-catenin-induced down-regulation of RECK. An inverse association between miR-182 and RECK was demonstrated in breast tumor tissues. We provide evidence that miR-182 is up-regulated by β-catenin signaling pathway in breast cancer and its up-regulation increases tumorigenicity and invasiveness by repressing RECK. Our data demonstrate for the first time that miR-182 expression is controlled by β-catenin. In addition, we identify a new miR-182 target RECK which is important for miR-182-induced tumorigenesis.


[The "petit papier": a clinical sign that should not be underestimated].
The Authors report two cases in which the sign of the "petit-papier" gives interesting question for a correct management of the patients in which the somatoform disorders is often the bulklt background of an organic illness.


Caregivers' experiences and perspectives of factors associated with relapse in Iranian people living with schizophrenia: A qualitative study.
Relapse in People Living with Schizophrenia (PLS) has several reasons and recognizing these can increase the effectiveness of treatment interventions. Formal and informal caregivers are an informed source to reduce relapse in PLS. This study explores the caregivers' perspective in Iran on the factors affecting relapse in PLS. A total of 28 caregivers (16 formal caregivers and 12 informal caregivers) of PLS were enrolled in our qualitative study. A content analysis was conducted using individual and group, semi-structured in-depth interviews with informal and formal caregivers of PLS. This study was conducted in a hospital, three universities, and a non-governmental organization in Tehran, Iran. The majority (69%) of the participants were females. About half of the informal caregivers were over 60 years old and about 40% of the formal caregivers were in the age range of 30 to 40 years. The average number of years of work for informal caregivers was 17.6 years and the average of work experience among the formal caregivers was 14.1 years. Seven key dual themes were identified from data: 'awareness-stigma', 'social support-social exclusion', 'treatment adherence-treatment discontinuation', 'holistic approach - one-dimensional approach', 'supported employment-social dysfunction', 'emotional management in family - family with high emotional expression', and 'access to treatment-treatment gap'. The results of this research can help practitioners and policymakers to enable evidence-based practices to reduce relapse in PLS by emphasizing and acting on factors identified in our analyses.


Perineoplasty compared with vestibuloplasty for severe vulvar vestibulitis.
To evaluate the efficacy of vestibuloplasty (vestibular undercutting without excision) to treat severe vulvar vestibulitis. Prospective randomisation of patients scheduled for surgery to undergo either perineoplasty or vestibuloplasty. Differences in outcome between groups were analysed using Fisher's exact test. The Vulvar Clinic and referral centre for vestibulitis, Kupath Holim Health System, Department of Obstetrics and Gynaecology, Carmel Medical Centre, Rapapport Faculty of Medicine, Hatechnion, Haifa, Israel. Twenty-one women with vulvar vestibulitis. Vestibuloplasty failed to relieve symptoms in 10 women, while perineoplasty resulted in complete resolution of symptoms in 9/11 women (P < 0.002). The poor outcome of vestibuloplasty, if also reported by other centres, may render it an unacceptable treatment for vulvar vestibulitis. Vestibuloplasty aims to denervate sensitive vestibular tissue, and its failure may suggest that innervation disturbances are not the main cause of the syndrome.


Transforming grief into peace: The normal grieving mind-Memory construction, deconstruction, and reconsolidation.
On the 19th of September 2020 Ernest Rossi, my husband, professional partner, and best friend of 30 years left this mortal world. His passing was a comparatively rapid process of dissipation extended over a period of approximately six days. In addition to the complex of emotions and physical responses, I experienced grief. This grief affected me more than any prior loss or sadness in my life as my consciousness was altered into fluctuating quantum trance states characteristic of hypnosis while dancing on the spacetime continuum. As I transformed grief to peace, I utilized established "Rossi" principles as guidelines for effective therapeutic hypnosis and developing a satisfying life. In the tradition of our life together, I was the "operator" who had a subjective experience and yet, at the same time, I was also the "observer" who would watch, learn, and discover new knowledge. This paper is the emergent outpouring of the dynamic interplay between the observer and the operator, which is, therefore experiential, revealing, revelational, and numinous.


Genetic heterogeneity for autosomal recessive pyridoxine-dependent seizures.
Pyridoxine-dependent seizure (PDS) is a rare autosomal recessive intractable seizure disorder only controlled by a daily supplementation of pharmacological doses of pyridoxine (Vitamin B6). Although glutamate decarboxylase utilizes pyridoxal phosphate as a cofactor during conversion of the excitatory amino acid, glutamate, to the inhibitory neurotransmitter, gamma-amino butyric acid (GABA), several studies have failed to demonstrate a linkage to either of the glutamate-decarboxylase-encoding genes (GAD1 and GAD2) and PDS excluding involvement of this functional candidate. However, in 2000, a locus for PDS was mapped to a 5 cM interval at chromosome 5q31 in four consanguineous and one multisib pedigree (Z(max)=8.43 at theta=0 for marker D5S2017) [Cormier-Daire et al. in Am J Hum Genet 67(4):991-993 2000]. We undertook molecular genetic studies of six nonconsanguineous North American families, using up to ten microsatellite markers to perform haplotype segregation analysis of the 5q31 locus. Assignment to the chromosome 5q PDS locus was excluded in one of the six North American PDS pedigrees, as chromosome 5q31 haplotypes were incompatible with linkage to this locus. The remaining five PDS pedigrees showed haplotype segregation consistent with linkage to 5q31, generating a maximum combined lod score of 1.87 (theta=0) at marker D5S2011. In this study, we establish genetic heterogeneity for PDS, catalog 21 genes within the originally defined PDS interval, and identify additional recombinations that indicate a higher priority interval, containing just 11 genes.


Differences in responses to English and Korean versions of the Caregiver Priorities & Child Health Index of Life with Disabilities (CPCHILD).
The purpose of this study was to identify differences in caregiver responses to Korean-language and English-language versions of the Caregiver Priorities & Child Health Index of Life with Disabilities (CPCHILD) questionnaire. Patient data were acquired from the Cerebral Palsy Hip Outcomes Project database, which was established to run a large international multicenter prospective cohort study of the outcomes of hip interventions in cerebral palsy. Thirty-three children whose caregivers had completed the Korean version of CPCHILD were matched by propensity scoring with 33 children whose parents completed the English version. Matching was performed on the basis of 12 covariates: age, gender, gross motor function classification system level, migration percentage of right and hip, seizure status, feeding method, tracheostomy status, pelvic obliquity, spinal deformity, parental report of hip pain and contracture interfering with care. There were no significant differences in CPCHILD scores for section 4 (Communication and Social Interaction), and section 5 (Health) between two groups. Korean-language CPCHILD scores were significantly lower than English-language CPCHILD scores for section 1 (Personal Care/Activities of Daily Living), section 2 (Positioning, Transferring and Mobility), section 3 (Comfort and Emotions) and section 6 (Overall Quality of Life) as well as in terms of total score. Cultural influences, and the community or social environment may impact the caregivers' perception of the health-related quality of life of their children. Therefore, physicians should consider these differences when interpreting the study outcomes across different countries.


NMR observability of ATP: preferential depletion of cytosolic ATP during ischemia in perfused rat liver.
The extent to which cellular metabolites are NMR observable is of fundamental importance in the interpretation of in vivo NMR studies. Analysis of ischemic rat liver shows that ATP resonances measured by 31P NMR decrease considerably faster than total tissue ATP measured in extracts. This discrepancy demonstrates that, in liver, ATP is not 100% observable. Furthermore, the data are consistent with the supposition that in situ mitochondrial ATP resonances are not normally observable by in vivo NMR techniques. The specificity of the NMR measurement for cytosolic ATP indicates that 31P NMR can be a valuable tool for the specific measurement of ATP in this compartment.


Structural features and antioxidant activity of a new galactoglucan from edible mushroom Pleurotus djamor.
A new water soluble galactoglucan with apparent molecular weight ~1.61 × 105 Da, was isolated from the edible mushroom Pleurotus djamor by hot water extraction followed by purification through dialysis tubing cellulose membrane and sepharose 6B column chromatography. The sugar analysis showed the presence of glucose and galactose in a molar ratio of nearly 3:1 respectively. The structure of the repeating unit in the polysaccharide was determined through chemical and NMR experiments as: In vitro antioxidant studies showed that the PDPS exhibited hydroxyl radical scavenging activity (EC50 = 1.681 ± 0.034 mg/mL), DPPH radical scavenging activity (EC50 = 3.83 ± 0.427 mg/mL), reducing power (EC50 = 4.258 ± 0.095 mg/mL), and ABTS radical quenching activity (EC50 = 0.816 ± 0.077 mg/mL). So, PDPS should be explored as a natural antioxidant.


Usefulness of prolonged video-EEG monitoring and provocative procedure with saline injection for the diagnosis of non epileptic seizures of psychogenic origin.
To assess the usefulness of long term video-EEG monitoring (VEEGM) and intravenous injection of saline solution (IVISS) for the diagnosis of non epileptic seizures of psychogenic origin (PNES). PNES are common among patients referred to an epilepsy center. Long term VEEGM remains the gold standard method for assessing the correct diagnosis. However, spontaneous PNES do not always occur during VEEGM, and a provocative test is often required. Although IVISS is the most commonly performed method, its usefulness is still debated. We performed a long term VEEGM and an IVISS test the last day of the monitoring to each patient admitted to the Epilepsy Monitoring Unit of Erasme Hospital, Brussels, between October 2001 and February 2005 for suspicion of PNES. Patient charts were retrospectively reviewed. Of a total of 138 patients admitted to our center, 28 (20.3%) were referred for suspicion of PNES. There were 7 men and 21 women with a mean age of 35 years. Twenty-one patients (75%) had PNES during the VEEGM. Ten patients (36 %) had spontaneous PNES and positive IVISS. Nine patients (32 %) had no spontaneous PNES but a positive IVISS. Two patients (7 %) had spontaneous PNES and a negative IVISS. Among patients with PNES, 8 had also epileptic findings. IVISS is a useful diagnostic tool since it was the only way to confirm the diagnosis of PNES in 32% of our patients. We suggest that investigation for the diagnosis of PNES should always include both a prolonged VEEGM and an IVISS test.