Biomimicking Leaf-Vein Engraved Soft and Elastic Membrane Promotes Vascular Reconstruction.
Hierarchical vasculature reconstruction is fundamental for tissue regeneration. The regeneration of functional vascular network requires a proper directional guidance, especially in case of large-size defects. To provide the "running track" for vasculature, a leaf-vein mimetic membrane using soft and elastic poly(lactide-co-propylene glycol-co-lactide) dimethacrylate is developed. Engraved with an interconnected and perfusable leaf-vein micropattern, the membrane can guide human umbilical vein endothelial cells (HUVECs) to form vasculature in vitro. In particular, the "running track" upregulates the angiogenesis-related gene expression and promotes the HUVECs to differentiate into tip cells and stalk cells via tuning vascular endothelial growth factor receptor 2 signaling transduction. As a proof of concept, its revascularization capability using a rat calvarial defect model in vivo is evaluated. The in vivo results demonstrate that the leaf-vein engraved membrane accelerates the formation and maturation of vasculature, leading to a hierarchical blood vessel network. With the superior pro-vasculature property, it is believed that the leaf-vein engraved membrane is not only an ideal candidate for the reconstruction of calvarial vasculature but also a promising solution for more complicated vasculature reconstruction, such as muscle, skin, and heart.


Beta-ureidopropionase deficiency presenting with congenital anomalies of the urogenital and colorectal systems.
Beta-ureidopropionase deficiency (McKusick 606673) is an autosomal recessive condition caused by mutations in the UPB1 gene. To date, five patients have been reported, including one putative case detected through newborn screening. Clinical presentation includes neurological and developmental problems. Here, we report another case of beta-ureidopropionase deficiency who presented with congenital anomalies of the urogenital and colorectal systems and with normal neurodevelopmental milestones. Analysis of a urine sample, because of the suspicion of renal stones on ultrasound, showed strongly elevated levels of the characteristic metabolites, N-carbamyl-beta-amino acids. Subsequent analysis of UPB1 identified a novel mutation 209 G>C (R70P) in exon 2 and a previously reported splice receptor mutation IVS1-2A>G. Expression studies of the R70P mutant enzyme showed that the mutant enzyme did not possess any residual activity. Long-term follow-up is required to determine the clinical significance of the beta-ureidopropionase deficiency in our patient.


Insight into Bacterial Community Diversity and Monthly Fluctuations of Medicago sativa Rhizosphere Soil in Response to Hydrogen Gas Using Illumina High-Throughput Sequencing.
The microbial diversity and the monthly fluctuations in Medicago sativa field soil in response to hydrogen gas were investigated. Illumina high-throughput sequencing was used to analyze the bacteria in raw and hydrogen-treated rhizosphere soil. Among the 18 soil samples, the abundance change of the predominant phyla Proteobacteria and Actinobacteria showed opposite trends. The diversity index analysis of the nine leguminous soil samples showed the highest diversity of the microbial community in July. In the other nine soil samples treated with hydrogen, the microbial diversity decreased and the diversity of soil microorganisms in September was higher than that in July, but not significantly so. The heat map analysis revealed that the microbial community composition of the soil samples was different before and after the hydrogen treatment. After the soil samples were treated with hydrogen, the dominant genera were Nocardioide, Pseudomonas, Janibacter, Microbacterium, Microvirga, Streptomyces, and Phenylobacterium in May; Bradyrhizobium, Haliangium, Sphingomonas, Blastocatella, Lysobacter, and Sphingopyxis in July; and Aeromicrobium, Pseudonocardia, Lentzea, and Skermanella in September. This study indicates that time and hydrogen gas have significant effects on the diversity of microbes in M. sativa rhizospheric soil.


The clinical course and outcomes of SARS-CoV-2 virus infection in children: a 24-week follow-up study in Sulaimaniyah, Iraq.
Most children infected with the SARS-CoV-2 virus have asymptomatic or mild disease with a short clinical course and excellent outcome; meanwhile, some children experienced persisting symptoms lasting > 12 weeks from the COVID-19 infection diagnosis. This study aimed to define the acute clinical course of SARS-CoV-2 virus infection and outcomes in children after recovery. This prospective cohort study was conducted on 105 children (aged < 16 years) with confirmed COVID-19 infection at Jamal Ahmed Rashid Teaching Hospital, Sulaimaniyah, Iraq, from July to September 2021. The symptomatic and suspicious cases of COVID-19 infection in children were confirmed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) on nasopharyngeal swabs. About 85.6% of children fully recovered at ≤ 4 weeks from initial COVID-19 infection diagnosis, 42% were hospitalized, while 15.2% reported long COVID-19 infection symptoms. The most commonly reported symptoms were fatigue (7.1%), hair fall (4.0%), lack of concentration (3.0%), and abdominal pain (2.0%). Children aged 11-16 showed a greater risk of long-term COVID-19 infection symptoms. We also observed a higher risk of long COVID infection symptoms in those who reported ongoing symptoms at 4-6 weeks of follow-up assessment (p = 0.01). Despite mild disease and complete recovery in most children, many suffered from long COVID infection symptoms.


Eyelid reconstruction by the semicircle flap technique.
The semicircle flap technique of eyelid reconstruction is a modified lateral advancement-rotation flap. The procedure combines the use of selective lysis of the limbs of the lateral canthal tendon with a semicircular skin-muscle flap confined to the region of the lateral canthus within the boundary established by the lateral eyebrow and the arc it defines. Reconstruction of one half to more than three fourths of the lower or upper eyelid can be accomplished without borrowing tissue from the eyelids, nose, ear, or mouth. Large forehead, brow, or cheek flaps are elininated, as is the need for closure of the palpebral fissure during the early healing course. The procedure has been used in the reconstruction of 36 lower eyelids and five upper eyelids in 40 patients, with a follow-up period of six months to six years. The usual indication for the use of this procedure is reconstruction of a central, marginal lid defect following the excision of a neoplasm. However, it may also be useful in cases of tissue loss caused by trauma, or for severe lid malpositions for which major kid reconstruction is necessary. The early and long-term cosmetic and functional results have been gratifying.


G-CSF-induced myeloid cells stimulated by TLR2 enhance engraftment after allogeneic hematopoietic stem cell transplantation.
A high frequency of G-CSF-mobilized myeloid cells (gMCs) in a donor graft accelerates hematopoietic recovery after peripheral blood stem cell transplantation (PBSCT). However, because of the limited functional efficacy of gMCs, repeated transfusions of gMCs are frequently required. In this study, we investigated a strategy to improve the functional capacity of gMCs during hematopoietic engraftment after allogeneic transplantation. We found that toll-like receptor 2 (TLR2) is constitutively expressed on gMCs. Treating gMCs with the synthetic TLR2 ligand Pam(3)CSK(4) (PAM) dramatically enhanced IL-10 and TNF-α production. However, PAM treatment does not induce substantial cellular maturation. Moreover, PAM treatment significantly improved gMC survival. PAM treated gMCs significantly promoted myeloid differentiation of donor hematopoietic stem cells (HSCs), resulting in accelerated engraftment after allogeneic transplantation. Our data suggest that TLR2-stimulated gMCs may be a novel cellular therapeutic for increasing the efficiency of allogeneic hematopoietic stem cell transplantation (HSCT) by reducing infectious complications associated with delayed engraftment.


Substance use and risky sexual behavior among homeless and runaway youth.
To (a) characterize human immunodeficiency virus (HIV)-related risk behaviors of homeless youth; (b) determine whether substance use is associated with risky sexual behavior in this population; and, if so, (c) explore explanations for this relationship. A purposive sample of 327 homeless youth (ages 14-21 years) in Washington, DC, were surveyed in 1995 and 1996. Survey items were adapted from items used in a national study of adult substance use and sexual behavior and measured global (lifetime) and event-specific (most recent sexual encounter) behaviors. Sexual activity with many partners, "survival" sex, and substance use were common. However, needle use was rare, and consistent condom use was evident in half the sample. Nearly all correlations between global measures of substance use and risky sex were statistically significant, but only a few of the event-specific correlations were significant. Marijuana use during the most recent sexual encounter was associated with nonuse of condoms, but this relationship disappeared in the multivariate model. However, crack use during the last encounter was associated with condom use; this relationship remained significant in the multivariate model. Lack of motivation to use condoms, longer histories of sexual activity and homelessness, symptoms of drug dependency, not discussing HIV risks with partner, and being female were also associated with nonuse of condoms. Homeless youth do use condoms, even within the context of substance use and casual sex. Results suggest that prevention and targeted intervention efforts have had some positive effect on this population, but young homeless women are in need of targeted prevention. Finally, additional research is needed to investigate the observed relationship between crack use and condom use in this sample.


Effect of cholesterol liposomes on calcium mobilization in muscle cells from the rabbit sphincter of Oddi.
To analyze the influence of cholesterol liposome on the Ca2+ mobilization of cultured muscle cells in the rabbit sphincter of Oddi's. New Zealand rabbit was sacrificed and the sphincter of Oddi (SO) segment was obtained aseptically. The SO segment was cut into pieces and cultured in DMEM solution. Then the smooth muscle cells were subcultured, and the 4th-7th passage cells were used for further investigation. The intracellular Ca2+ increase was measured under confocal microscope after the addition of 20 mmol x L(-1) KCl, 10(-7) mol x L(-1) acetylcholine and 10(-7) mol x L(-1) cholecystokinin, and different antagonists were added to analyze the Ca2+ mobilization pathway. After the cells were incubated with 1g x L(-1) cholesterol liposome (CL)(molar ratio was -2:1), the intracellular Ca2+ increase was measured again to determine the effect of CL on cellular Ca(2+) mobilization. The resting cellular calcium concentration of cultured SO cell was 108+/-21 nmol x L(-1).The intracellular Ca2+ increases induced by 20 mmol x L(-1) KCl, 10(-7) mol x L(-1) ACh and 10(-7) mol x L(-1) CCK were 183+/-56% 161+/-52% and 130+/-43%, respectively. When the extracellular Ca2+ was eliminated by 2 mmol x L(-1) EGTA and 5 micromol x L(-1) verapamil, the intracellular Ca2+ increases induced by KCl, ACh and CCK were 20+/-14%,82+/-21% and 104+/-23%, respectively. After the preincubation with heparin, the Ca2+ increases were 62+/-23% and 23+/-19% induced by ACh and CCK, as for preincubation with procaine they were 72+/-28% and 85+/-37% induced by ACh and CCK, respectively. Pretreatment with CL for 18 h, the resting cellular Ca2+ concentration elevated to 152+/-26 nmol x L(-1), however, the cellular Ca2+ increase percentages in response to these agonists were 67+/-32%,56+/-33% and 34+/-15%. KCl elicit the SO cellular Ca2+ increase depends on influx of extracellular Ca2+, ACh evoked the SO cellular Ca2+ increase is through the mobilization of intracellular Ca2+ pool and influx of extracellular Ca2+ as well, CCK excites the SO cells mainly through mobilization of intracellular IP3-sensitive Ca2+ store. After the incorporation with cholesterol liposome, KCl,ACh and CCK induced cellular Ca2+ increase percentages decreased.


Determination of pharmaceuticals and related impurities by capillary electrophoresis.
In the first part of this work, the use of capillary electrophoresis (CE) for the separation of two groups of pharmaceuticals, namely a metabolite of tamoxifen and a basic drug substance, DS1 was investigated. The effects of pH and types of modifiers, e.g. surfactant, bile salt, gamma-cyclodextrin and hydroxypropyl-beta-cyclodextrin on selectivity, separation and peak shape were studied. Besides achieving complete separation of the compounds, the CE system was capable of providing separation with significant improvements in overall peak shape of the compounds compared with HPLC. In the case of the basic drug substance DS1, validation of the CE system developed in terms of linearity, selectivity, sensitivity and reproducibility was satisfactorily performed. At the same time, a study of the sample solvent matrix effects on the separation of this group of compounds was examined. The system was successfully applied to the analysis of laboratory-synthesized samples. Good correlation was observed between CE and HPLC, although higher efficiency and faster speed of separation were obtained using the CE system developed. For the tamoxifen metabolite, special emphasis was placed on the use of CE for the separation of the pair of isomers. This was readily achieved through the introduction of gamma-cyclodextrin in the electrolyte. Resolution of at least 1.5 was obtained for the isomers using the CE method.


[Contribution of monogenic hypertension models to understanding of other hypertensions].
Therapeutic control of primary or secondary hypertension remains insufficient because of the presence of individual phenotypic variations of factors acting on sodium excretion and vasoconstriction. The study of monogenic models of hypertension allows to highlight some genetic mutations, mainly responsible of sodium regulation. In some cases, polymorphisms of such genes are found with an increased frequency in hypertensive patients. Each polymorphism by itself is not sufficient to cause hypertension, but their accumulation in a patient increases the hypertensive risk in primary or secondary hypertension. Understanding familial hyperaldosteronism type 1, Liddle or Ulick syndrome, activating mutations of minéralocorticoide receptor or Gordon syndrome give indications on pathophysiology of primary hypertension. Study of some mitochondrial defects or of genes implicated in renal dysplasia also seems interesting area of research. In the future, search for such mechanisms would allow a rational and oriented use of diuretics and antihypertensive therapies.


Fludarabine, cyclophosphamide and anti-thymocyte globulin for alternative donor transplants in acquired severe aplastic anemia: a report from the EBMT-SAA Working Party.
We have developed a reduced-intensity conditioning regimen for patients with severe aplastic anemia (SAA) undergoing alternative donor transplants, which includes fludarabine (120 mg/m(2)), cyclophosphamide (1,200 mg/m(2)) and antithymocyte globulin (7.5 mg/kg). Graft-versus-host disease (GvHD) prophylaxis consisted of cyclosporine and methotrexate. We have enrolled 38 SAA patients in this trial: median age of 14 (3-37) years, transplanted from unrelated (n=33) or family mismatched (n=5) donors, with unmanipulated marrow (n=36) or peripheral blood (n=2). Seven patients (18%) had evidence of graft failure, 11% developed grade II-III acute GvHD and 27% developed chronic GvHD. The actuarial 2-year survival is 73%, with a median follow-up of 621 days. Younger patients (<or=14 years) had a lower risk of rejection (5%) and improved actuarial survival (84%). Causes of death were infections (n=3), graft failure (n=2), Epstein-Barr virus lymphoma (n=2) and hemorrhage (n=2). In conclusion, the actuarial 2-year survival is encouraging in young SAA patients receiving a radiation-free conditioning regimen. The significant risk of graft failure in patients 15 years or older may require modification of the conditioning regimen in adults.


Paclitaxel-induced transcriptional regulation of Fas signaling pathway is antagonized by dexamethasone.
Chemotherapy agents like paclitaxel are often a first line of therapy for triple-negative breast cancer patients and a last line of therapy for other aggressive breast cancers. While such agents are effective pro-apoptotic treatments for breast cancer cells, they produce many unwanted side effects. Synthetic glucocorticoids like dexamethasone are commonly prescribed during chemotherapy treatment of breast cancer patients for anti-emetic and anti-hypersensitivity purposes. Dexamethasone, however, is known to enhance cell survival in solid tumors. The prevalent use of dexamethasone in conjunction with paclitaxel in the treatment of breast cancer patients merits concern. Previous studies demonstrate dexamethasone-mediated survival in a subset of breast cancer cells in the presence of paclitaxel. This work expanded the types of cell lines studied and explored the molecular mechanism driving this phenotype. Human breast cancer cell lines representative of several subtypes of breast cancer including triple-negative breast cancer, luminal, and HER2 were treated in the presence and absence of paclitaxel, dexamethasone, and under co-treatment conditions. Cell survival was monitored under differing conditions. We then manipulated aspects of the nuclear factor kappa B (NFkappaB) signaling pathway to elucidate the importance of this pathway in overcoming chemotherapy treatment. All cell lines tested were sensitive to paclitaxel and showed dexamethasone-mediated rescue from paclitaxel-induced apoptosis, but the rescue of overall cell numbers was most pronounced in triple-negative breast cancer cell lines. Dexamethasone and paclitaxel inversely regulated the activity of NFkappaB, which is essential to both paclitaxel-mediated apoptosis and dexamethasone-mediated rescue. The transcriptional target of NFkappaB, Fas receptor, is inversely regulated by paclitaxel and dexamethasone and is a downstream target of paclitaxel-activated NFkappaB. Dexamethasone antagonizes paclitaxel-mediated apoptosis through inhibition of NFkappaB transcription of Fas receptor. Pre-treatment of breast cancer patients with dexamethasone may greatly reduce patient response to paclitaxel. Our study elucidates a novel mechanism of paclitaxel-induced apoptosis in breast cancer cell lines and explicates dexamethasone's antagonism of paclitaxel.


Radiological risk assessment from the Gamma spectrometry of soil samples in the vicinity of a research centre in Nilore, Pakistan.
Measurements of radionuclides' activities in air, water, and soil give clues about the anthropogenic activities in the region, and imperative to assess the overall radiological risk for individuals. Such an investigation was carried out to characterize the soil activities in the region hosting a research center, and to calculate the associated elements of radiological risk in terms of radiation doses and hazard indices. The soil samples were collected within the radius of 10 km in local area, Nilore, and analysed for activity using a high-purity germanium (HPGe) gamma spectrometric system. In all samples, only the basic nuclides, contributing to terrestrial activity, i.e., 40 K, 232Th, 226Ra, and 137Cs, were observed within the detectable limits of activity. The distribution of the data set and the correlation between the measured activities were studied with the use of the principal component analysis (PCA). The measured average specific activities of 226Ra, 232Th, 40 K, and 137Cs were 40.65 ± 9.84 Bq/kg, 59.31 ± 16.53 Bq/kg, 528.24 ± 131.18 Bq/kg, and 5.16 ± 4.56 Bq/kg respectively. The corresponding dose rate in air was found to be 76.63 ± 18.39 nGy/h, which is slightly higher than the world median value of 51 nGy/h calculated from concentration of terrestrial radionuclides in soil but falls within the world average value range of outdoor external exposure of 18-93 nGy/h obtained through direct measurement, and therefore not harmful for the living species. The standard hazard indices for all soil samples such as radium equivalent activity ([Formula: see text]), external hazard index (Hex), and internal hazard index (Hin) were also found within safe limits for the soil to be used as construction of building material. This investigation led to conclusion that the soil activities are consistent with the usual background level of terrestrial activities, and their associated dose rates are well within the safe limits for public.


The relationship between cadmium exposure and hepatitis B susceptibility and the establishment of its prediction model.
Cadmium, a common metal, is an environmental contaminant that is hepatotoxic and immunotoxic. Cadmium exposure may affect hepatitis B immunity. The purpose of this study was to assess the association between cadmium exposure and hepatitis B serology in the US population and to develop a model to predict susceptibility of hepatitis B. The study included 50,588 individuals in the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. Univariate and multivariate logistic regression and dose-response curves were used to evaluate the relationship between cadmium exposure and hepatitis B serology. Through multivariate logistic regression results, a predictive model was established, and relevant indicators were used to verify the clinical value of the model and evaluate prognostic value of serum cadmium concentration in patients with hepatitis B. We selected 5989 (≥ 6 years old) participants. Univariate logistic regression analysis showed that gender (aOR = 0.7192, 95% CI = 0.6492-0.7968), age (aOR = 1.030, 95% CI = 1.026-1.033), race (aOR = 0.8974, 95% CI = 0.8591-0.9374), poverty ratio (aOR = 1.042, 95% CI = 0.9872-1.101), body mass index (BMI) (aOR = 1.052, 95% CI = 1.044-1.061), hypertension (aOR = 2.017, 95% CI = 1.763-2.306), diabetes (aOR = 2.673, 95% CI = 2.119-3.370), vigorous recreational activities (aOR = 0.6369, 95% CI = 0.5725-0.7085), moderate recreational activity (aOR = 0.7681, 95% CI = 0.6935-0.8574) and cadmium (aOR = 1.295, 95% CI = 1.168-1.436) were closely related to hepatitis B virus (HBV) susceptibility. After adjusting for these confounding factors, multivariate logistic regression analysis showed that the odds ratio of HBV susceptibility was positively correlated with the level of cadmium in serum. The effectiveness of the model was then evaluated by establishing a nomogram, and by calibration curves, ROC curves, and clinical decision curves. Our study shows that cadmium exposure is positively associated with HBV susceptibility risk in the US population, and the constructed model has clinical significance.


Is Universal Health Insurance Superior in Terms of Healthcare Payment? Estimating Financial Burden of Healthcare in Korea: 2009 to 2019.
This study estimates the financial burden of healthcare in Korea using the National Survey of Tax and Benefit panel data from 2009 to 2019. The sum of a household's premium and out-of-pocket medical expenses defines the household financial burden of healthcare. We find that the household financial burden is regressive to income. We also find that the high burden household whose financial burden is over 10% of their household income accounts for about 30% of total household. This result suggests that equity in contribution to healthcare finance does not work well in Korea, which chose the universal health system that emphasizes the progressive contribution by income to medical finance.


Substance P induces plasticity and synaptic tagging/capture in rat hippocampal area CA2.
The hippocampal area Cornu Ammonis (CA) CA2 is important for social interaction and is innervated by Substance P (SP)-expressing supramammillary (SuM) nucleus neurons. SP exerts neuromodulatory effects on pain processing and central synaptic transmission. Here we provide evidence that SP can induce a slowly developing NMDA receptor- and protein synthesis-dependent potentiation of synaptic transmission that can be induced not only at entorhinal cortical (EC)-CA2 synapses but also at long-term potentiation (LTP)-resistant Schaffer collateral (SC)-CA2 synapses. In addition, SP-induced potentiation of SC-CA2 synapses transforms a short-term potentiation of EC-CA2 synaptic transmission into LTP, consistent with the synaptic tagging and capture hypothesis. Interestingly, this SP-induced potentiation and associative interaction between the EC and SC inputs of CA2 neurons is independent of the GABAergic system. In addition, CaMKIV and PKMζ play a critical role in the SP-induced effects on SC-CA2 and EC-CA2 synapses. Thus, afferents from SuM neurons are ideally situated to prime CA2 synapses for the formation of long-lasting plasticity and associativity.


Liver parenchymal changes detected by MR elastography and diffusion-weighted imaging after stereotactic body radiotherapy for hepatocellular carcinoma.
Stereotactic body radiotherapy (SBRT) is a local treatment option for hepatocellular carcinoma (HCC). SBRT-induced focal reactions on the liver parenchyma have not been thoroughly evaluated using quantitative magnetic resonance imaging (MRI). To quantitatively evaluate liver parenchymal changes caused by SBRT for HCC using magnetic resonance elastography (MRE) and diffusion-weighted imaging (DWI). We retrospectively evaluated 22 adult patients who received SBRT for HCC and 27 who received locoregional therapy other than SBRT (controls). Liver stiffness by MRE and apparent diffusion coefficient (ADC) values by DWI of the liver parenchyma were measured before and after SBRT. Regions of interest (ROIs) were drawn on the two areas of radiation dose distribution levels, > 30 Gy and ≤ 30 Gy; a ROI was drawn in the control group. The two indices were compared before and after SBRT using a Wilcoxon matched-pairs signed-rank test. Liver stiffness and ADC values were significantly increased after SBRT in the dose areas of > 30 Gy compared with those before SBRT (4.05 vs 4.85 kPa; p < 0.05 in liver stiffness, and 1.10 vs 1.40 ×10-3 s/mm2; p < 0.05 in ADC values). In the dose area of ≦ 30 Gy, liver stiffness showed a significant increase in one reader (p = 0.033) but not in another reader (p = 0.085); ADC value showed no significant difference before and after SBRT as per both readers (p > 0.05). The control group demonstrated no significant differences before and after treatment (p > 0.05). MRE and DWI can be used to detect SBRT-induced liver parenchymal changes.


Photophysical, photochemical, and thermodynamic properties of shikimic acid derivatives: calycin and rhizocarpic acid (lichens).
Photophysical and photochemical parameters of the lichen metabolites calycin and rhizocarpic acid were determined. Experiments were carried out in micellar solutions of 3% Brij 35, at pH 2 and 12, and in acetonitrile. Both metabolites absorb in the UV-A and UV-B regions, and emit fluorescence in the visible region of the solar spectrum. Shifts were not observed in the absorption spectra, at pH 2 and 12. The low phi(c), between 10(-5) and 10(-2), shows that both compounds are photostable in the experimental conditions. For rhizocarpic acid, two values of pK(a) were obtained: 5.1 corresponding to the hydroxyl group, and 9.0 corresponding to the protonated nitrogen. Calycin presents only one value of pK(a): 4.9, that is attributed to the hydroxyl group. L-(+)-Gluconic-gamma-lactonic acid was used as a reference model; the compound showed greater photoinstability, demonstrating that the photodegradation observed occurs mainly in the oxolane carbonylic ring.


Cognitions, emotions, and sexual response: analysis of the relationship among automatic thoughts, emotional responses, and sexual arousal.
The relationship between automatic thoughts and emotions presented during sexual activity and their correlation with sexual arousal was investigated. A total of 491 individuals (163 women and 232 men without sexual problems and 47 women and 49 men with a DSM-IV diagnosis of sexual dysfunction) completed the Sexual Modes Questionnaire (SMQ; Nobre and Pinto-Gouveia, Journal of Sex Research, 40, 368-382, 2003). Results indicated several significant correlations among automatic thoughts, emotions, and sexual arousal. Erection concern thoughts in the men and failure/disengagement thoughts and lack of erotic thoughts in the women presented the most significant negative correlations with sexual arousal. Additionally, sadness and disillusion were positively related to these negative cognitions and negatively associated with sexual arousal in both sexes. On the other hand, pleasure and satisfaction were negatively associated with the above-mentioned negative cognitions and positively associated with subjective sexual arousal in both men and women. Overall, findings support the hypothesis that cognitive, emotional, and behavioral dimensions are closely linked and suggest a mode typical of sexual dysfunction composed of negative automatic thoughts, depressive affect, and low subjective sexual arousal.


Methamphetamine induces oligodendroglial cell death in vitro.
We investigated whether the psychostimulant methamphetamine (METH) has a cytotoxic effect on oligodendrocytes and which cell-death pathways are involved in the cytotoxic process. METH caused concentration- and time-dependent cytotoxicity in rat oligodendrocyte cultures. METH induced apoptotic cell death and mRNA expression of pro-apoptotic proteins (bax and DP5), but not anti-apoptotic proteins (bcl-2 and bcl-XL). These results suggest that METH induces cytotoxicity in rat oligodendrocytes via the differential regulation of the expression of genes involved in the apoptotic process.


Histopathological evaluation of pulpotomy with Er,Cr:YSGG laser vs formocresol.
The purpose of this study was to histologically investigate whether pulpotomy with Er,Cr:YSGG laser is an acceptable alternative for formocresol. Pulpotomy of 48 dog's primary canine teeth was performed with formocresol or Er,Cr:YSGG laser. Histological evaluations on hematoxylin and eosin-stained pulp tissues were made by an optical microscope 7 or 60 days later. Statistical analysis was performed with Fisher's exact test, Mann-Whitney U test, and Student's t test. Seven days after pulpotomy, samples treated with laser had significantly favorable histological features in the following measures: continuity of odontoblastic layer (P<0.001), presence of hemorrhage (P<0.008), amount of inflammation (P<0.002), tissue necrosis (P<0.001), internal resorption (P<0.002), level of vascularization (P<0.002), and size of abscess (P<0.041). Similar results were observed 60 days after pulpotomy, except that the differences were not mostly significant due to natural exfoliation of 16 teeth. In conclusion, Er,Cr:YSGG laser system is an acceptable alternative for formocresol in pulpotomy of deciduous teeth.


A beginner's guide to phylogenetics.
Metagenomics and the development of high throughput next generation sequencing capabilities have forced significant development in the field of phylogenetics: the study of the evolutionary relatedness of the planet's inhabitants. Herein, I review the major tree-building strategies, challenges and opportunities which exist in this rapidly expanding field of evolutionary biology.


Severe neurological impairment in hereditary methaemoglobinaemia type 2.
Recessive congenital methaemoglobinaemia (RCM) due to NADH-cytochrome b5 reductase (cytb5r) deficiency is a very rare disorder. We report on two unrelated patients (4 and 2.5 years old) with RCM type 2. Developmental delay was obvious at the age of 4 months. On follow-up, both children showed severe tetraspastic cerebral palsy, profound cognitive impairment, strabismus, impressive secondary microcephaly and failure to thrive. One novel mutation in the DIA1gene was identified. Prenatal diagnosis was successfully done in both families by mutation analysis in chorionic villi or measurement of cytb5r in fetal amniotic cells. Due to the severity of this disease and its 25% recurrence risk, prenatal diagnosis should be made available to all affected families.


Three dimensional engineered models to study hypoxia biology in breast cancer.
Breast cancer is the second leading cause of mortality among women worldwide. Despite the available therapeutic regimes, variable treatment response is reported among different breast cancer subtypes. Recently, the effects of the tumor microenvironment on tumor progression as well as treatment responses have been widely recognized. Hypoxia and hypoxia inducible factors in the tumor microenvironment have long been known as major players in tumor progression and survival. However, the majority of our understanding of hypoxia biology has been derived from two dimensional (2D) models. Although many hypoxia-targeted therapies have elicited promising results in vitro and in vivo, these results have not been successfully translated into clinical trials. These limitations of 2D models underscore the need to develop and integrate three dimensional (3D) models that recapitulate the complex tumor-stroma interactions in vivo. This review summarizes role of hypoxia in various hallmarks of cancer progression. We then compare traditional 2D experimental systems with novel 3D tissue-engineered models giving accounts of different bioengineering platforms available to develop 3D models and how these 3D models are being exploited to understand the role of hypoxia in breast cancer progression.


Scabies and Pediculosis in Penitentiary Institutions in Poland-A Study of Ectoparasitoses in Confinement Conditions.
Scabies (caused by Sarcoptes scabiei var. hominis) and pediculosis (caused by Pediculus humanus) are infectious diseases common in educational institutions and long-term care centres. The aim of the study was to assess the scale of the phenomenon in confinement conditions favouring the spread of these parasitoses. Data on the prevalence of scabies (2001-2015) and pediculosis (2008-2015) in Polish prisoners were provided by the Central Board of Prison Service. The information for the period between 2010 and 2015 in the Lublin Province was obtained from the District Inspectorate of the Prison Service in Lublin. Correlations between the prevalence of scabies and pediculosis and the number of prisoners were analysed, as well as correlations between the number of passes granted to prisoners and the prevalence of scabies and pediculosis in incarcerated individuals. The prevalence of scabies and pediculosis in Polish prisoners has been estimated at 2.3% and 1.9%, respectively. Pediculosis and scabies are still current issues in Polish prisons. Convicts returning from passes and new prisoners should be carefully examined and monitored for the presence of S. scabiei var. hominis and P. humanus invasion. Education of prisoners could be a promising tool in prevention of scabies and pediculosis in correctional settings.


Long-term evolution of stents implanted in branch pulmonary arteries.
Branch pulmonary artery stenosis complicates the management of congenital heart diseases. Surgical branch pulmonary artery angioplasty is associated with a high reintervention rate. As an alternative, percutaneous or intraoperative branch pulmonary artery stents have been implanted to improve efficiency, but long-term evaluations are limited. To describe the long-term evolution of branch pulmonary artery stents. We conducted a retrospective cohort study at Tours University Hospital. All stents implanted by surgery or catheterization in branch pulmonary arteries with a minimum follow-up of 12 months and at least one catheterization control were included. The primary endpoint combined cardiovascular mortality, surgical or percutaneous reintervention for stent complication or new stent implantation. Between 2007 and 2017, 76 stents in 51 patients were included (62 stents implanted by surgery, 14 by catheterization). At implantation, the patients' mean age and weight were 4.7years (interquartile range 4.2years) and 17.3kg (interquartile range 11.0kg), respectively. Mean branch pulmonary artery minimum diameter was 4.1±2.1mm (mean Z-score-4.9±2.9), and mean initial stent diameter was 9.1±3.1mm. During a follow-up of 5.3years (range 0-11.2 years), freedom from primary endpoint was 86.8% (95% confidence interval 79.6-94.8%) at 1 year, 71.5% (95% confidence interval 61.9-82.7%) at 5years and 69.6% (95% confidence interval 59.6-81.2%) at 10 years. We did not identify any factors associated with major adverse cardiovascular events. Among stents without major adverse cardiovascular events, the mean branch pulmonary artery diameter Z-score at last evaluation had increased by +4.8±3.2 compared with the initial diameter (P<0.001). After stent implantation, a median of 2 re-expansions were performed for each stent (range 0-7). Stent implantation should offer a good long-term solution for branch pulmonary artery stenosis, although iterative re-expansions are required.


Altered tissue content of trace metals in diabetic hyperinsulinaemic sand rats (Psammomys obesus).
The concentrations of zinc, copper, and chromium in liver, kidney, muscle, bone and serum from control normoinsulinaemic and hyperinsulinaemic sand rats (Psammomys obesus) and from untreated spontaneously hyperinsulinaemic-hyperglycaemic sand rats were compared. A chronic hyperinsulinaemic-hyperglycaemic state was associated with a significant reduction (p less than 0.01) of zinc concentration in the liver, kidney and muscle but an elevation of zinc content in bone and of chromium in the liver. A hyperinsulinaemic-nor-moglycaemic state was not associated with similar changes in zinc concentration in the liver, kidney, muscle and bone. We conclude that in hyperinsulinaemic-hyperglycaemic sand rats there is a tendency to zinc depletion in several tissues. This depletion is not solely the result of a hyperinsulinaemic state but may be related to accompanying hyperglycaemia.


Electronically driven spin-reorientation transition of the correlated polar metal Ca3Ru2O7.
The interplay between spin-orbit coupling and structural inversion symmetry breaking in solids has generated much interest due to the nontrivial spin and magnetic textures which can result. Such studies are typically focused on systems where large atomic number elements lead to strong spin-orbit coupling, in turn rendering electronic correlations weak. In contrast, here we investigate the temperature-dependent electronic structure of [Formula: see text], a [Formula: see text] oxide metal for which both correlations and spin-orbit coupling are pronounced and in which octahedral tilts and rotations combine to mediate both global and local inversion symmetry-breaking polar distortions. Our angle-resolved photoemission measurements reveal the destruction of a large hole-like Fermi surface upon cooling through a coupled structural and spin-reorientation transition at 48 K, accompanied by a sudden onset of quasiparticle coherence. We demonstrate how these result from band hybridization mediated by a hidden Rashba-type spin-orbit coupling. This is enabled by the bulk structural distortions and unlocked when the spin reorients perpendicular to the local symmetry-breaking potential at the Ru sites. We argue that the electronic energy gain associated with the band hybridization is actually the key driver for the phase transition, reflecting a delicate interplay between spin-orbit coupling and strong electronic correlations and revealing a route to control magnetic ordering in solids.


Lipoprotein (a)-mediated vascular calcification: population-based and in vitro studies.
Lipoprotein (a) [Lp(a)] is a causal risk factor for cardiovascular diseases, while its role in vascular calcification has not been well-established. Here, we investigated an association of Lp(a) with vascular calcification using population-based and in vitro study designs. A total of 2806 patients who received coronary computed tomography were enrolled to assess the correlation of Lp(a) with the severity of coronary artery calcification (CAC). Human aortic smooth muscle cells (HASMCs) were used to explore mechanisms of Lp(a)-induced vascular calcification. In the population study, Lp(a) was independently correlated with the presence and severity of CAC (all p < 0.05). In vitro study showed that cell calcific depositions and alkaline phosphatase (ALP) activity were increased and the expression of pro-calcific proteins, including bone morphogenetic protein-2 (BMP2) and osteopontin (OPN), were up-regulated by Lp(a) stimulation. Interestingly, Lp(a) activated Notch1 signaling, resulting in cell calcification, which was inhibited by the Notch1 signaling inhibitor, DAPT. Lp(a)-induced Notch1 activation up-regulated BMP2-Smad1/5/9 pathway. In contrast, Noggin, an inhibitor of BMP2-Smad1/5/9 pathway, significantly blocked Lp(a)-induced HASMC calcification. Notch1 activation also induced translocation of nuclear factor-κB (NF-κB) accompanied by OPN overexpression and elevated inflammatory cytokines production, while NF-κB silencing alleviated Lp(a)-induced vascular calcification. Elevated Lp(a) concentrations are independently associated with the presence and severity of CAC and the impact of Lp(a) on vascular calcification is involved in the activation of Notch1-NF-κB and Notch1-BMP2-Smad1/5/9 pathways, thus implicating Lp(a) as a potential novel therapeutic target for vascular calcification.


Ultrastructural alterations in ovaries from nifurtimox or benznidazole-treated rats: their relation to ovarian nitroreductive biotransformation of both drugs.
Chagas' disease is a parasitic chronic condition affecting several million people in Latin America. Two drugs are used in the chemotherapy of Chagas' disease: nifurtimox (Nfx) and benznidazole (Bz). Both are nitroderivatives whose deleterious effects are related to their reductive biotransformation. In this work we report that rat ovaries exhibited Bz and Nfx nitroreductase activity. The Bz nitroreductase was only found in the mitochondrial fraction and was partially inhibited by CO. The Nfx nitroreductase activity was maximal in ovarian mitochondria but was also present in microsomes and in the cytosol. The microsomal enzyme was completely inhibited by CO while that in mitochondria was only partially inhibited by CO. The cytosolic activity only proceeded using hypoxanthine as substrate and was inhibited by allopurinol. The cytosolic activity was able to proceed in part under oxygen. All the other Bz or Nfx nitroreductases were completely inhibited by atmospheric oxygen. The potential participation of cytochrome P450, flavoenzymes, iron-sulfur-protein, and xanthinooxidase in both nitroreductive processes is discussed. The administration of either Nfx or Bz to female rats produced ultrastructural degenerative effects in the different cell types of ovaries. Specific alterations such as swelling, disruption, disorganization, and loss of matrix components were observed in ovarian mitochondria. These alterations occurred irrespectively of the ovarian cycle stage. The potential reproductive toxicological consequences of Bz or Nfx administration are analyzed.


Extracellular phosphomannan as a phosphate reserve in the yeast Kuraishia capsulata.
We have found that extracellular phosphomannan is the main phosphate reserve in the yeast Kuraishia capsulata, in contrast to other yeast species effectively absorbing Pi. Under nitrogen starvation, K. capsulata absorbed essentially all Pi from the medium containing 240 mM glucose, 2.5 mM MgSO4, and 11 mM KH2PO4. Inorganic polyphosphate level in the cells was about 14% of the Pi absorbed. Most of the Pi (~60%) was found in the fraction of extracellular phosphomannan that can be used as a carbon and phosphorus source by this yeast in deficient media.


The correlation between carbamazepine and valproic acid monotherapy with serum adiponectin and carnitine.
Antiepileptic drugs may cause systemic and metabolic side effects. The aim of our study was to investigate the effects of valproic acid and carbamazepine monotherapy used in the treatment of epilepsy patients on serum adiponectin and carnitine levels. The study included 60 patients, of which 30 patients receiving valproic acid monotherapy and 30 patients receiving carbamazepine monotherapy, who were followed up by the epilepsy outpatient clinic with the diagnosis of idiopathic epilepsy, and 30 healthy volunteers. Patients, who used drugs for at least 6 months, were selected. Venous blood samples were collected from the patients and healthy volunteers after their consent was obtained. Serum carnitine and adiponectin levels in the collected samples were measured using the ELISA method. Serum carnitine levels were 5166.55 ng/ml (± 1954.92) in patients receiving carbamazepine, 4224.56 ng/ml (± 2055.54) in patients using valproic acid, and 5802.64 ng/ml (± 3422.57) in the control group. Serum adiponectin levels were 13,606.51 ng/ml (± 5915.92) in patients using carbamazepine, 11,986.58 ng/ml (± 5367.82) in patients receiving valproic acid, and 14,033.43 ng/ml (± 5646.34) in the control group. In both groups, both serum carnitine and serum adiponectin levels were lower than the control group. There was a negative but insignificant correlation between the duration and dose of carbamazepine and valproic acid drug use and serum adiponectin and carnitine levels. There is a need for more extensive studies with larger sample size to investigate the effect of antiepileptic drugs used on serum adiponectin and carnitine levels.


Pitfalls in diagnosing PFO: characteristics of false-negative contrast injections during transesophageal echocardiography in patients with patent foramen ovales.
Contrast injections during transesophageal echocardiography for patent foramen ovale (PFO) detection may be false negative. The characteristics of false-negative injections were studied retrospectively. Contrast transesophageal echocardiography was analyzed for the presence or absence of two characteristics: leftward bulging of the interatrial septum and dense contrast filling of the region of the right atrium adjacent to the interatrial septum. Two hundred forty-seven injections were administered to 14 patients with PFOs, and 130 (53%) were false negative. The absence of either characteristic during a single injection resulted in low sensitivity for PFO detection of 7%. When the two characteristics were present at the same time, the sensitivity for PFO detection after a single injection was as high as 95%. The simultaneous presence of both leftward bulging of the interatrial septum and dense contrast filling of the region in the right atrium, adjacent to the interatrial septum, is a prerequisite for PFO detection, and if either characteristic is missing, the injection is inconclusive.


Immunizations and infectious disease screening for internationally adopted children.
Health care professionals play a critical role in providing age-appropriate immunizations and assessing newly arrived internationally adopted children for infectious diseases. A systematic approach to screening for infectious diseases combined with assessment of signs and symptoms that could be related to diseases prevalent in the child's country of origin supports children's long-term health and that of their new families.


Iatrogenic Cushing syndrome after intra-articular triamcinolone in a patient receiving ritonavir-boosted darunavir.
Drug interactions involving human immunodeficiency virus protease inhibitors are common due to their inhibition of the cytochrome P450 3A4 isoenzyme. We describe the case of an HIV-infected patient treated with ritonavir-boosted darunavir who developed cushingoid features following an intra-articular injection of triamcinolone acetate. We review the probable mechanism for this interaction and describe similar cases of Cushing syndrome in patients receiving concomitant ritonavir and triamcinolone.


Genetically engineered human pulmonary surfactant.
Pulmonary surfactant is a complex array of phospholipids and proteins that specifically interact to lower the surface tension in the alveoli of the lungs. This article reviews pulmonary surfactant proteins A, B, and C. Also surfactant replacement in animal studies is discussed.


Termination and post-termination events in eukaryotic translation.
Translation termination in eukaryotes occurs in response to a stop codon in the ribosomal A-site and requires two release factors (RFs), eRF1 and eRF3, which bind to the A-site as an eRF1/eRF3/GTP complex with eRF1 responsible for codon recognition. After GTP hydrolysis by eRF3, eRF1 triggers hydrolysis of the polypeptidyl-tRNA, releasing the completed protein product. This leaves an 80S ribosome still bound to the mRNA, with deacylated tRNA in its P-site and at least eRF1 in its A-site, which needs to be disassembled and released from the mRNA to allow further rounds of translation. The first step in recycling is dissociation of the 60S ribosomal subunit, leaving a 40S/deacylated tRNA complex bound to the mRNA. This is mediated by ABCE1, which is a somewhat unusual member of the ATP-binding cassette family of proteins with no membrane-spanning domain but two essential iron-sulfur clusters. Two distinct pathways have been identified for subsequent ejection of the deacylated tRNA followed by dissociation of the 40S subunit from the mRNA, one executed by a subset of the canonical initiation factors (which therefore starts the process of preparing the 40S subunit for the next round of translation) and the other by Ligatin or homologous proteins. However, although this is the normal sequence of events, there are exceptions where the termination reaction is followed by reinitiation on the same mRNA (usually) at a site downstream of the stop codon. The overwhelming majority of such reinitiation events occur when the 5'-proximal open reading frame (ORF) is short and can result in significant regulation of translation of the protein-coding ORF, but there are also rare examples, mainly bicistronic viral RNAs, of reinitiation after a long ORF. Here, we review our current understanding of the mechanisms of termination, ribosome recycling, and reinitiation after translation of short and long ORFs.


Hemisphere contributions to the composition of the pattern-evoked potential waveform.
The transverse distribution of scalp-recorded potentials evoked by pattern reversal stimulation was studied in 50 healthy subjects. In most individuals the full-field responses were symmetrical over the occipital scalp, but important variations in distribution, symmetry and waveform were recorded in some cases. Asymmetrical responses were similar for each eye (i.e., they were "uncrossed" or homonymous asymmetries). Full-field peak latencies and amplitudes in the lateral channels were more variable than those at midline electrodes. Half-field responses were markedly asymmetric with well-lateralised components widespread over occipital-parietal scalp. In contrast to the full-field responses, component values measured near the midline were less consistent than those from lateral channels due to waveform distortions in this area ("transitional zone"). Upper field stimulation is particularly likely to produce such midline waveform distortions. Activity recorded from the scalp contralateral to the half-field stimulated shows more inter-individual and inter-hemispheric variation than that recorded from ipsilateral electrodes. Variants in the full-field waveform can be accounted for by relative differences in amplitude and distribution of the ipsilateral and contralateral components from each half field. The algebraic sum of these half-field components does not differ significantly from the components of the separately recorded full-field response. Furthermore, responses from the surviving half-field in patients after total hemispherectomy contain all the ipsilateral and contralateral half-field components seen in healthy subjects.


Bladder outlet obstruction and inguinal hernia: incidence in males over fifty years of age.
Increased intra-abdominal pressure secondary to prostatic obstruction of the bladder outlet is frequently cited as an important factor in the formation of inguinal hernias in middle-aged and elderly males. However, as far as can be determined, the correlation of these two conditions has never been evaluated. Twenty-five male patients, aged fifty years or older, presenting for repair of inguinal hernia, were evaluated urologically, and the results are presented.


Bone turnover in asthmatic children treated with oral prednisolone or inhaled budesonide.
Biochemical markers of bone turnover were studied in prepubertal school children with asthma in two randomized double-blind crossover trials with run-in, treatment, and wash-out periods of 2 weeks. One group (n = 11) was treated with 2.5 and 5.0 mg prednisolone, the other (n = 14) with 200 and 800 micrograms inhaled budesonide per day. Serum osteocalcin, serum total alkaline phosphatase, fasting urinary excretion of hydroxyproline and calcium, serum 25-hydroxyvitamin D, and 1,25 dihydroxyvitamin D were assessed. A dose-related reduction of serum osteocalcin (Page's test for trend: P = 0.04; z = -2.3) and of the fasting urinary hydroxyproline:creatinine ratio (Page's test for trend: P = 0.05; z = -2.0) was found in the children who were treated with prednisolone. Inhaled budesonide was not associated with statistically significant effects on any of the biochemical markers. Short-term treatment with low daily doses of prednisolone may cause a suppression of bone turnover in children with asthma. To reduce the risk of adverse effects on bone turnover, doses of inhaled budesonide up to 800 micrograms daily may be preferable to low doses of prednisolone. Bone turnover remains to be evaluated during long-term treatment.


The effects of air pollution on the respiratory health of children: a cross-sectional study.
To investigate the effects of air pollution on the respiratory health of children, a subject of some controversy, a comparative study was undertaken of 2,385 school children who lived in central urban, peripheral urban, and suburban areas. Daily monitoring of sulphur dioxide and total suspended particle concentrations in all areas showed that pollutant concentrations in central and peripheral urban areas were above commonly accepted safety levels for respiratory health, while concentrations in the suburban area were within acceptable limits. A questionnaire administered to each mother assessed environmental exposure to pollutants in the household, the occurrence of respiratory symptoms as well as lung diseases as diagnosed by a physician, and general information. Children were interviewed about smoking habits and any acute respiratory symptoms. Children also performed standard lung function tests. Results showed that children from both urban areas had lessened pulmonary function and a higher prevalence of bronchial secretion with common colds than did those from the suburban area. These differences persisted after corrections for exposure to indoor pollutants, active or passive smoking, socioeconomic status, and sex. Parental cigarette smoking was related to a fall in forced expiratory volume in 1 second and an increased incidence of acute respiratory illnesses and chronic cough in children. Although boys had higher lung volumes and lower air flow, regression analysis showed no significant influence of the interactions "sex-geographic area" and "sex-smoking" on lung function. It was concluded that air pollution has a significant effect on the respiratory health of children.


An analysis of concanavalin A-mediated agglutination in two Chinese hamster ovary subclones whose surface phenotypes respond to maintenance in medium supplemented with dibutyryl cyclic AMP. V. Biochemical composition of the plasma membrane.
We have used two Chinese hamster ovary subclones whose surface phenotype has been extensively investigated with regard concanavalin A-mediated cell-cell agglutination and concanavalin A-induced receptor site clustering to investigate what changes in membrane composition, if any, can be correlated with the concanavalin A-detected changes in surface phenotype. These cell clones are uniquely disposed for this purpose since maintenance of the cells under different growth conditions produces changes in agglutinability and receptor site mobility in one cell clone (H-7W) but not the other (K-1). After extensive characterization of the surface membranes of these two subclones we have been unable to identify any change in the membrane peptides, glycopeptide, cholesterol, or fatty acid composition which can be directly correlated with the concanavalin A-detected surface phenotypes. It is of particular interest to note that we have been unable to correlate the presence or absence of the large external transformation-sensitive glycoprotein with the relative mobility of the lectin receptors or with the degree of concanavalin A-mediated cell agglutination. Furthermore we have been unable, in this system, to corroborate earlier data suggesting a role for cholesterol in determining the relative mobility of the lectin receptors. Thus using a cell system consisting of genetically matched cell clones, we have been unable to identify any changes in the biochemical composition of the plasma membrane which might be associated with the surface phenotypes detected by concanavalin A.


Magnetic resonance imaging findings of the mass-forming type of autoimmune pancreatitis: comparison with pancreatic adenocarcinoma.
To determine the characteristic magnetic resonance imaging (MRI) features of mass-forming autoimmune pancreatitis (AIP), which allow its differentiation from pancreatic adenocarcinoma (PAC). MR images of 37 patients with either pathologically proven, mass-forming AIPs (n = 9) or PACs (n = 28) were retrospectively reviewed. The pancreatic MR protocol included unenhanced images, contrast-enhanced dynamic images, diffusion-weighted imaging (DWI), and MR-cholangiopancreatography (MRCP). Two reviewers analyzed the MR images regarding the number, location, morphologic features, and enhancement degree and pattern of the lesions as well as secondary changes of the pancreatic parenchyma, the biliary and pancreatic ducts. The size and apparent diffusion coefficient (ADC) values of the lesions were measured. Although sensitivities were low (28.6%-44.4%), specificities of multiplicity, capsule-like rim enhancement, and skipped stricture of the biliary or pancreatic duct in mass-forming AIP were high (100%). Sensitivities and specificities of irregular or geographic shape, delayed enhancement, and a low ADC value <1.26 × 10(-3) mm(2) /s in mass-forming AIP were favorable (71.4%-83.3% and 78.5%-89.3%). Although to differentiate mass-forming AIP from pancreatic cancer is difficult, the combination of MRI findings including contrast-enhanced dynamic images, MRCP, and DWI can be a help.


Dark-adapted oscillatory potentials in preterm infants with and without retinopathy of prematurity.
To describe the appearance and maturation of dark-adapted oscillatory potentials (OPs) in electroretinograms (ERGs) recorded from preterm infants, and to determine any effect of retinopathy of prematurity (ROP). Dark-adapted ERGs were recorded in conjunction with screening for ROP and at outpatient follow-up, using a flash luminance of 11.3 scot cd s m(-2) (4.06 phot cd s m(-2)). Eligible infants were born before 31 weeks' gestation and/or weighed ≤1,250 grams at birth. Presence or absence of OPs was established for 68 ERG recordings from 38 infants at maturities ranging from 30 weeks' postmenstrual age (PMA) to 28 weeks' post-term corrected age. 20 infants did not develop ROP, eight developed stage 1, one stage 2 and one stage 3 disease which regressed spontaneously. Eight infants received treatment for threshold ROP. OPs were present in 50 % of infants at 36 weeks' PMA and in all by 50 weeks' PMA. The earliest appearance of OPs was at 30+5 weeks' PMA. Individual OP amplitudes increased and peak time of individual OPs decreased with increasing maturity. For infants with threshold ROP summed OP amplitudes tended to be smaller prior to treatment (6.5 vs 9.9μV, P = 0.09) and were significantly smaller by 50 weeks' PMA (14 vs 30μV, P = 0.007). OP1 was less likely to be present in infants who developed stage 3 or worse ROP (P = 0.000). Dark-adapted OPs are recordable in some preterm infants from 30 weeks' PMA. Relative suppression of early OPs is a potential marker for developing ROP.


The expression of sex steroid synthesis and inactivation enzymes in subcutaneous adipose tissue of PCOS patients.
Modulation of sex steroid pre-receptor in adipose tissue is important for the development of metabolic diseases, but its roles in the pathogenesis of polycystic ovary syndrome (PCOS) has not been fully characterized. Herein we compared the expression of key sex steroid converting enzymes in the subcutaneous adipose tissue (SAT) between patients with PCOS and the matched controls. Most of the sex steroid converting enzymes were highly expressed in the SAT, except 17α-hydroxylase (CYP17A1). Compared with the controls, PCOS patients showed significantly higher levels of 3β-hydroxysteroid dehydrogenase1-2 (3β-HSD1-2), aldo-keto reductase 1C 1-3 (AKR1C1-3) and leptin, but lower level of P450 aromatase and 5α-reductase 1. Interestingly, leptin was positively correlated to AKR1C2 expression and negatively to 5α-reductase1 as well as peroxisome proliferator-activated receptor γ (PPARγ). In summary, the expression of enzymes synthesizing testosterone and enzymes inactivating DHT and progesterone was higher in SAT of PCOS patients compared to controls. Correlation analysis indicated that increased leptin expression may be negatively related to local DHT level. These data suggested that sex steroid converting enzymes expression was different in SAT of PCOS patients that might contribute to abnormal testosterone and leptin level of PCOS patients.


The relationship between the BMI-adjusted weight loss grading system and quality of life in patients with incurable cancer.
Weight loss (WL) has long been recognized as an important factor associated with reduced quality of life (QoL) and reduced survival in patients with cancer. The body mass index (BMI)-adjusted weight loss grading system (WLGS) has been shown to be associated with reduced survival. However, its impact on QoL has not been established. The aim of this study was to assess the relationship between this WLGS and QoL in patients with advanced cancer. A biobank analysis was undertaken of adult patients with advanced cancer. Data collected included patient demographics, Eastern Cooperative Oncology Group performance status, and anthropometric parameters (BMI and %WL). Patients were categorized according to the BMI-adjusted WLGS into one of five distinct WL grades (grades 0-4). QoL was collected using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-C30. The Kruskal-Wallis test and multivariate logistic regression analyses were used to assess the relationship between the WLGS and QoL scores. Overall survival was assessed using Kaplan-Meier curve and Cox proportional hazard models. A total of 1027 patients were assessed (51% male, median age: 66 years). Gastrointestinal cancer was most prevalent (40%), and 87% of patients had metastatic disease. Half (58%) of patients had a WL grade of 0-1, while 12%, 20%, and 10% had WL grades of 2, 3, and 4, respectively. Increasing WL grades were significantly associated with poorer QoL functioning and symptoms scales (all P < 0.05). Physical, role, and emotional functioning decreased by a median of >20 points between WL grade 0 and WL grade 4, while appetite loss, pain, dyspnoea, and fatigue increased by a median score >20 points, indicative of a large clinical significant difference. Increasing WL grades were associated with deteriorating QoL summary score. WL grades 2, 3, and 4 were independently associated with a QoL summary score below the median (<77.7) [odds ratio (OR) 1.69, P = 0.034; OR 2.06, P = 0.001; OR 4.29, P < 0.001, respectively]. WL grades 3 and 4 were independently associated with reduced overall survival [hazard ratio 1.54 (95% confidence interval: 1.22-1.93), P < 0.001 and hazard ratio 1.87 (95% confidence interval: 1.42-2.45), P < 0.001, respectively]. Our findings support that the WLGS is useful in identifying patients at risk of poor QoL that deteriorates with increasing WL grades. WL grade 4 is independently associated with a particularly worse prognosis and increased symptom burden. Identification and early referral to palliative care services may benefit these patients.


Pulmonary manifestations in a group of patients with Behcet's disease.
In this study we investigated the frequency and characteristics of pulmonary manifestations in a group of patients with Behcet's disease (BD) who were admitted to Cairo University Hospital. Fifteen patients were included in our study, 14 men (93.3%) and one woman (6.66%).Their mean age was 30.06 ± 9.8 years and the mean age of onset of BD was 23.7 ± 5.54 years. All patients were subjected to full history taking, clinical examination, plain chest X-ray and helical computed tomography (CT) study of the chest. Pulmonary involvements were detected in 11 patients with BD, 73.3% of cases: 10 men (90.9%) and one woman (9.09%).Their mean age was 28.8 ± 8.07, the mean age of onset of BD was 23.2 ± 5.59 years and the mean disease duration until lung manifestations appear was 3.7 ± 4.8 years. The main pulmonary and constitutional symptoms in these 11 patients were as follows: dyspnea 81.8%, cough 63.6%, weight loss 63.6%, chest tightness 54.5%, hemoptysis 45%, massive hemoptysis 27.2%, fever 36.3% and expectoration 36.3. Analysis of both vascular and parenchymal lung lesions in helical CT scan in the 11 patients with BD were as follows: pulmonary artery aneurysm (PAA) occurred in 5/11 patients (45.4%), pulmonary nodules occurred in 3/11 patients (27.2%), pleural effusion occurred in 3/11 patients (27.2%), pulmonary embolism and infarction occurred in 1/11 patients (9.09%) and pneumonitis occurred in 1/11 patients (9.09%). The higher frequency of pulmonary manifestations in our patients (73.3%) and the higher frequency of PAA (33.3%) could be related to the fact that this study was conducted on a group of patients who were admitted to the hospital with more severe illnesses.


Bronchial hyperresponsiveness, atopy, and bronchoalveolar lavage eosinophils in persistent middle lobe syndrome.
Most cases of middle lobe syndrome (MLS) in children are considered to be due to asthma and may recover spontaneously; however, in persistent MLS, repeated episodes of infection often institute a vicious cycle that may lead to persistent symptoms and bronchial hyperresponsiveness (BHR). The present study was undertaken to investigate whether asthma, as an underlying diagnosis, is predictive of a favorable outcome of children with persistent MLS. We evaluated 53 children with MLS who underwent an aggressive management protocol that included fiberoptic bronchoscopy (FOB) and bronchoalveolar lavage (BAL). These patients were compared to two other groups: one consisting of children with current asthma but no evidence of MLS (N = 40) and another of non-asthmatic controls (N = 42), matched for age and sex. Prevalence of sensitization (>or=1 aeroallergen) did not differ between patients with MLS and "non-asthmatics" but was significantly lower than that of "current asthmatics." A positive response to methacholine bronchial challenge was observed with increased frequency among children with MLS when compared to "current asthmatic" and non-asthmatic children. Multivariate logistic regression analysis revealed a positive correlation between an increased number of eosinophils in the BAL fluid (BALF) and a favorable outcome, whereas no correlation was detected between sensitization or BHR and BAL cellular components. In conclusion, children with MLS have an increased prevalence of BHR, even when compared to asthmatics, but exhibit prevalence of atopy similar to that of non-asthmatics. An increased eosinophilic BALF count is predictive of symptomatic but not radiographic improvement of MLS patients after aggressive anti-asthma management.


EM-Gaze: eye context correlation and metric learning for gaze estimation.
In recent years, deep learning techniques have been used to estimate gaze-a significant task in computer vision and human-computer interaction. Previous studies have made significant achievements in predicting 2D or 3D gazes from monocular face images. This study presents a deep neural network for 2D gaze estimation on mobile devices. It achieves state-of-the-art 2D gaze point regression error, while significantly improving gaze classification error on quadrant divisions of the display. To this end, an efficient attention-based module that correlates and fuses the left and right eye contextual features is first proposed to improve gaze point regression performance. Subsequently, through a unified perspective for gaze estimation, metric learning for gaze classification on quadrant divisions is incorporated as additional supervision. Consequently, both gaze point regression and quadrant classification performances are improved. The experiments demonstrate that the proposed method outperforms existing gaze-estimation methods on the GazeCapture and MPIIFaceGaze datasets.


Adaptive immunity increases the pace and predictability of evolutionary change in commensal gut bacteria.
Co-evolution between the mammalian immune system and the gut microbiota is believed to have shaped the microbiota's astonishing diversity. Here we test the corollary hypothesis that the adaptive immune system, directly or indirectly, influences the evolution of commensal species. We compare the evolution of Escherichia coli upon colonization of the gut of wild-type and Rag2(-/-) mice, which lack lymphocytes. We show that bacterial adaptation is slower in immune-compromised animals, a phenomenon explained by differences in the action of natural selection within each host. Emerging mutations exhibit strong beneficial effects in healthy hosts but substantial antagonistic pleiotropy in immune-deficient mice. This feature is due to changes in the composition of the gut microbiota, which differs according to the immune status of the host. Our results indicate that the adaptive immune system influences the tempo and predictability of E. coli adaptation to the mouse gut.


Monoclonal antibodies against leucoagglutinin-reactive human T-lymphocyte surface components. II. Studies on the mechanism of K46M-induced activation and determination of the frequency of responding cells.
A monoclonal antibody, K46M (IgM kappa), obtained after immunization with leucoagglutinin (La)-reactive T-cell surface components, stimulated human lymphocytes to proliferate. It induced maximal proliferation at greater than 20 micrograms IgM/ml after 3-4 days of culture. Cells stimulated by K46M produced interleukin 2 (IL-2) and gamma interferon (IFN-gamma) and expressed receptors for IL-2 and transferrin. The majority of the activated cells were phenotypically T cells as defined by monoclonal antibodies against CD3 and CD2, and an increase in the K46M-positive cells was also observed during the activation period. K46M-activated cells display major histocompatibility complex (MHC)-unrestricted cytotoxicity against several cultured target cells. The frequencies of the cytotoxic and of the proliferative precursor cells were determined using a limiting dilution assay. K46M seems to activate a larger fraction of cytotoxic precursor cells against Molt 4 than against K562, but the statistical significance of these observations requires further exploration. Both K46M or La activated 40% of PBL to proliferate, whereas 70% of PBL were induced by OKT3. However, the frequency of K46M-activated cells was 40% only when the lymphocytes were plated at low cell densities, i.e. less than 0.5 cells per well. At higher densities an inhibition of proliferation was seen that resulted in a biphasic response curve, indicating that the activation of PBL by K46M was not a single hit event. This was not found with either La or OKT3. Whether K46M, in contrast to OKT3 and La, activates a subpopulation with suppressor activity remains to be established.


Production of low molecular weight cadmium-binding proteins in rabbit lung following exposure to cadmium chloride.
Low molecular weight cadmium-binding proteins were studed in lung tissue from rabbits exposed to aerosols of CdCl2. Lungs obtained from animals exposed by inhalation to aerosols of 800 or 1600 micrograms/m3 CdCl2 for 2-hr periods/day, every other day for a 5-day period, were found to contain at least three low molecular weight cadmium-binding proteins, two of which were similar electrophoretically and spectrally to rabbit liver metallothionein. The third protein(s), which accounted for the majority of the cadmium in the soluble fraction of the tissue, did not bind to an anionic exchange gel and did not appear to be a polymerized form of metallothionein. Translocation studies of lung cadmium suggest a long half-life for cadmium in lung tissue following inhalation exposure, due perhaps to the high affinity of cadmium for specific lung cadmium-binding proteins. A small but significant redistribution of lung cadmium did occur to both kidney and liver tissue with time.


Expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases define the migratory characteristics of human monocyte-derived dendritic cells.
Dendritic cells (DCs) have an essential role in the initiation of immune responses as they deliver antigen/epitope and the appropriate signals to activate naïve T cells and thus start an immune response. In order to fulfil their function, DCs have to patrol different part of the body, thus migrating through the extracellular matrix to sample the local 'antigenic' environment. In the present study, we have investigated which enzymes might be involved in this process using the Matrigel trans-well migration assay, an in vitro model of extracellular matrix migration. In this assay we analysed the migratory ability of interleukin-4 (IL-4)/granulocyte macrophage-colony-stimulating factor (GM-CSF)-derived immature DCs as well as mature DCs, induced by tumour necrosis factor-alpha (TNF-alpha) and modified vaccinia virus Ankara (MVA). The 'mature' DCs showed an increased migration through Matrigel, which was significantly inhibited by inhibitors of matrix metalloproteinases (MMP). We also observed that the dominant MMP involved in this process was MMP-9, and a concomitant decrease of the endogenous tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 was also observed. Collectively these data suggest that the balance between MMP/TIMP determines the net migratory capacity of human DCs. Surprisingly, TIMP-3 was significantly increased in mature DC. Our data thus indicate that MMP and TIMP play a role in the migratory ability of human DCs. Our results also suggest that TIMP-3 expression might represent a new marker of maturation of human DCs.


AMPK at the nexus of energetics and aging.
When energy supply is low, organisms respond by slowing aging and increasing resistance to diverse age-related pathologies. Targeting the mechanisms underpinning this response may therefore treat multiple disorders through a single intervention. Here, we discuss AMP-activated protein kinase (AMPK) as an integrator and mediator of several pathways and processes linking energetics to longevity. Activated by low energy, AMPK is both prolongevity and druggable, but its role in some pathologies may not be beneficial. As such, activating AMPK may modulate multiple longevity pathways to promote healthy aging, but unlocking its full potential may require selective targeting toward substrates involved in longevity assurance.


Prevalence of submandibular gland involvement in neck dissection specimens of patients with oral cavity carcinoma.
The submandibular gland is commonly removed during neck dissection in patients with head and neck cancer. The patient experiences various complications due to the removal of the submandibular gland. Therefore, the necessity of submandibular gland removal should be evaluated. This study aimed to was to determine the frequency of submandibular gland (SMG) involvement in patients with oral cavity squamous cell carcinoma (SCC). In this retrospective study, medical records of patients with oral cavity cancer who were referred to Amir Alam Hospital between 2015 and 2020 were reviewed. Patient data includes surgical report, histopathology report (tumor size, number of lymph nodes involved, and SMG tumor involvement), Tumor Location, History of Smoking, History of Opium, and Alcohol consumption was extracted from patients' medical records and statistically analyzed using SPSS software version 20. Of the total 60 patients, 24 (40%) were female and 36 (60%) were male. Smoking was reported in 55% of patients with a mean of 4.11 pack-year. Alcohol and opium use was observed in 18.3% and 26% of patients. The majority of patients (78.3%) had tongue cancer. More than half of the patients (53.3%) reported tumors of 2 cm or smaller, and 16.7% of patients had tumors larger than 4 cm. The majority of patients (80.3%) did not have cervical lymph node metastasis, 13.1% had 1-2 involved lymph nodes and 4.9% had 3 to 6 involved lymph nodes and there were no cases of metastasis to more than 6 lymph nodes. Finally, no individual had submandibular gland involvement, ie 100% of patients had no submandibular gland metastasis. The results confirmed that SMG involvement is very rare in patients with oral SCC and therefore it is not necessary to remove the gland as part of treatment. Preservation of the submandibular gland prevents complications related to the removal of this gland and reduces morbidity and increases the quality of life of patients after surgery.


Systematic study of imidazoles inhibiting IDO1 via the integration of molecular mechanics and quantum mechanics calculations.
Indoleamine 2,3-dioxygenase 1 (IDO1) is regarded as an attractive target for cancer immunotherapy. To rationalize the detailed interactions between IDO1 and its inhibitors at the atomic level, an integrated computational approach by combining molecular mechanics and quantum mechanics methods was employed in this report. Specifically, the binding modes of 20 inhibitors was initially investigated using the induced fit docking (IFD) protocol, which outperformed other two docking protocols in terms of correctly predicting ligand conformations. Secondly, molecular dynamics (MD) simulations and MM/PBSA free energy calculations were employed to determine the dynamic binding process and crucial residues were confirmed through close contact analysis, hydrogen-bond analysis and binding free energy decomposition calculations. Subsequent quantum mechanics and nonbonding interaction analysis were carried out to provide in-depth explanations on the critical role of those key residues, and Arg231 and 7-propionate of the heme group were major contributors to ligand binding, which lowed a great amount of interaction energy. We anticipate that these findings will be valuable for enzymatic studies and rational drug design.


Fermentative hydrogen production from soybean protein processing wastewater in an anaerobic baffled reactor (ABR) using anaerobic mixed consortia.
Fermentative H(2) production from soybean protein processing wastewater (SPPW) was investigated in a four-compartment anaerobic baffled reactor (ABR) using anaerobic mixed cultures under continuous flow condition in the present study. After being inoculated with aerobic activated sludge and operated at the inoculants of 5.98 gVSS L(-1), COD of 5000 mg L(-1), HRT of 16 h and temperature of (35 ± 1) °C for 22 days, the ABR achieved stable ethanol-type fermentation. The specific hydrogen production rate of anaerobic activated sludge was 165 LH(2)kg MLVSS(-1) day(-1), the substrate conversion rate was 600.83 LH(2)kg COD(-1)and the COD removal efficiency was 44.73% at the stable operation status. The ABR system exhibited a better stability and higher hydrogen yields than continuous stirring tank reactor under the same operational condition. The experimental data documented the feasibility of substrate degradation along with molecular H(2) generation utilizing SPPW as primary carbon source in the ABR system.


Fissures in the anterior arch of the atlas diagnosed by careful study of the lateral radiographs.
Fissures in the anterior arch of the atlas are rare. The defect can properly be diagnosed on axial radiographs and can be suspected in studying carefully the lateral x-ray. The developmental cause of the split anterior arch and its clinical significance are discussed. A median cleft, analogous to a fissure in the anterior arch of the atlas, may also occur in the proatlas, as shown in one case.


Association between equine temperament and polymorphisms in dopamine D4 receptor gene.
The variable number of tandem repeats (VNTR) polymorphism of the dopamine D4 receptor (DRD4) gene has been reported to be associated with the personality trait of novelty-seeking in humans. In the genus Equus, this region includes an 18-bp repeat unit and there are inter- and intraspecies differences in the number of repetitions. Because horses are unique among livestock species in that their temperament is considered important, we investigated the possible role of this region on equine temperament in thoroughbred horses. We simultaneously determined the sequences of this polymorphic region and administered a questionnaire survey to horse caretakers with questions about 20 different traits of their horses' temperament. Although there was no difference in the number of repeats among the 136 thoroughbred horses studied, two single nucleotide polymorphisms (SNPs), one of which might cause an amino acid change (A-G substitution), existed. By analyzing the association between these SNPs and temperament scores, a significant association was revealed between two temperament traits (Curiosity and Vigilance) and the A-G substitution. Horses without the A allele had significantly higher Curiosity and lower Vigilance scores than those with the A allele at the A-G substitution. In addition, similar associations between both temperament scores and each genotype of the A-G substitution were observed in two subgroups divided according to the time of their introduction to the farm. These results suggested that the SNP in the VNTR region of the equine DRD4 gene might be related to individual differences in equine temperament.


Mobilizing male opinion leaders' support for family planning to improve maternal health: a theory-based qualitative study from Pakistan.
Pakistan is a patriarchal society in which male opinion leaders play an important role in determining health-seeking behaviors pertaining to family planning (FP) among their respective communities. This research focuses on cataloguing the perceptions of opinion leaders (clergymen, health professionals, and social workers) about the barriers for using services and practical solutions for promoting FP in the slums of Karachi, Pakistan. A qualitative study using an open-ended, semistructured interview schedule with hypothetical scenarios and in-depth interviews with a purposive sample of 45 opinion leaders (25 mosque imams/clergymen, 12 nonallopathic health professionals, and eight social workers/activists) was conducted in 2006-2007 in Karachi, Pakistan. Transcripts were coded thematically utilizing NVivo by using an adapted constant comparison analysis process as described by Strauss and Corbin. Seven key themes were derived from the in-depth interviews. Five themes provide insight into the opinion leaders' perceptions of barriers to FP and modern contraception methods. Among the barriers religious taboos and cultural pressures were particularly note-worthy. Two themes offered opportunities for more effective development and implementation of FP programs. It is evident from the study that opinion leaders in the community and the clergy lack the understanding of the importance of birth spacing. However, because they have a great deal of influence on the community at large, it is imperative to interact with them to build their capacity in order to propagate the messages of FP and improve maternal health and reproductive health in general.


Periodontal diseases in Thai schoolchildren. Clinical and microbiological observations.
The prevalence of periodontitis among Thai schoolchildren is unknown. In a cross-sectional study, the prevalence and severity of periodontal diseases, in a group of Thai schoolchildren, along with the presence and numbers of bacterial species commonly associated with periodontitis were investigated. A consent form was sent out to 192 schoolchildren in one school (Chanachanupathom School) in Chana, Southern Thailand (in the age range of 12-18 years) and 119 attended for a clinical and microbiological examination. Clinical recordings included number of teeth present, DMFT, plaque index, bleeding index, clinical attachment loss (CAL), and probing pocket depth (PPD). Pooled plaque samples were analyzed with culture and qPCR against bacteria associated with periodontitis. The children had low caries experience (DMFT = 3.2 ± 2.3), poor oral hygiene, high bleeding scores, and 67 (56.3%) had at least one interproximal site with CAL ≥ 1 mm. Thirty-seven (31.1%) of the children were diagnosed with periodontitis stage I, and sixteen (13.4%) were classified as periodontitis Stage II. Aggregatibacter actinomycetemcomitans was sparsely found in all but the healthy clinical groups (gingivitis, periodontitis Stage I and II), while the groups showed a high prevalence of Fusobacterium spp., Prevotella intermedia/nigrescens, and Campylobacter species as well as of the periodontitis-associated species Porphyromonas gingivalis, Treponema denticola, and Tannerella forsythia. Thai schoolchildren have poor oral hygiene with abundant amounts of plaque and high presence of bleeding. Early onset periodontitis is common but mostly in its mild form and is not associated with the presence of A. actinomycetemcomitans.


Safety and efficacy of non-vitamin K antagonist oral anticoagulants compared with well-controlled warfarin in Thai patients with atrial fibrillation.
In trials of patients with atrial fibrillation (AF), non-vitamin K antagonist oral anticoagulants (NOACs) were not inferior to warfarin for thromboembolic and bleeding events. However, there are scant data comparing the efficacy and safety of NOACs in patients with AF with that of well-controlled warfarin treatment in such patients. To compare total bleeding and thromboembolic events in patients with AF who received NOACs, with the same events in those who received well-controlled warfarin treatment. We used retrospective data from patients with AF who received NOACs or well-controlled warfarin at the Central Chest Institute of Thailand from January 2017 to December 2019. The primary outcome was total bleeding or thromboembolic events or both. The secondary outcome was all-cause mortality, total bleeding events including major or minor bleeding, and thromboembolic events including ischemic stroke or systemic embolization. We included data from 180 patients with AF, 90 who received NOACs and 90 who received well-controlled warfarin. The average time in the therapeutic range for those who received warfarin was 84.9% ± 9.8%. The patients who received well-controlled warfarin had more frequent thromboembolic or total bleeding events or both than those who received NOACs (odds ratio [OR] 3.17; 95% confidence interval [CI] 2.27-4.07; P = 0.01). There were more minor bleeding events in those who received well-controlled warfarin (OR 3.75; 95% CI 2.79-4.71; P = 0.01). However, there was no significant difference in thromboembolic events, major bleeding, or all-cause mortality between the 2 groups. Thai patients with AF who received NOACs had less thromboembolic or total bleeding events than those who received well-controlled warfarin treatment.


Periodontal status and IOTN interventions among young hemophiliacs.
Fifty-two young individuals suffering from severe haemophilia A and B volunteered to be compared with school- and college-going students for oral health status description and subsequent management. A total of 244 students (84.42% boys and 15.58% girls) with the age group of 13-23 years were divided into two groups, A and B (controls). The purpose of this study was to increase awareness about evidence-based dental practices by oral examinations followed by comparisons of periodontal health and prevalence of malocclusions among medically compromised students and healthy controls. Results described the oral health in severe haemophilic population to be compromised with combined simplified health index score of 0.50 and Decayed/Modified/Filled Teeth (DMFT) index score of 2.07 when compared with 0.42 and 0.95, respectively, among group B. Although prevalence of malocclusion and orthodontic treatment needs among group A were higher, yet it was not confirmed as a reason for degraded dental and periodontal status. However, spontaneous and/or toothbrush (trauma)-induced gingival bleeding episodes among group A could be explained as factors discouraging oral hygiene maintenance, particularly self-administered measures. Four haemophiliacs presented with symptoms of Temporomandibular Joint Dysfunction Syndrome (TMPDS). Evidence-based oral medicine and clinical practices need to be encouraged and applied to enhance the quality of life among haemophiliacs, particularly in developing world. Dental treatment needs of haemophilic population appear to be greater and maybe incorporated in routine dental practices, at institutional and individual levels.


[Clinical trial of domestic drug polyoxidonium in secondary immunodeficiency].
To test clinical efficiency and immunocorrectives characteristics of polyoxidonium in patients with chronic bronchitis (CB) and chronic recurrent furunculosis. 56 patients entered the trial; 13 with CB in remission, 22 with CB in exacerbation and 21 with chronic recurrent furunculosis. Clinical examinations and tests were made before polyoxidonium therapy and 2-3 days after it. Immunological tests consisted of determination of sub-population composition of peripheral blood lymphocytes, serum immunoglobulins and phagocytic activity of neutrophils. Polyoxidonium is an effective and safe immunocorrector. It has a strong influence on functional activity of blood phagocytic cells. Polyoxidonium treatment of CB and chronic recurrent furunculosis results in positive shifts in hematological and immunological indices. This allows to recommend it for treatment of acute and chronic infections.


Beyond topographic mapping: towards functional-anatomical imaging with 124-channel EEGs and 3-D MRIs.
A functional-anatomical brain scanner that has a temporal resolution of less than a hundred milliseconds is needed to measure the neural substrate of higher cognitive functions in healthy people and neurological and psychiatric patients. Electrophysiological techniques have the requisite temporal resolution but their potential spatial resolution has been not realized. Here we briefly review progress in increasing the spatial detail of scalp-recorded EEGs and in registering this functional information with anatomical models of a person's brain. We describe methods and systems for 124-channel EEGs and magnetic resonance image (MRI) modeling, and present first results of the integration of equivalent-dipole EEG models of somatosensory stimulation with 3-D MRI brain models.


Evaluating models of remember-know judgments: complexity, mimicry, and discriminability.
Remember-know judgments provide additional information in recognition memory tests, but the nature of this information and the attendant decision process are in dispute. Competing models have proposed that remember judgments reflect a sum of familiarity and recollective information (the one-dimensional model), are based on a difference between these strengths (STREAK), or are purely recollective (the dual-process model). A choice among these accounts is sometimes made by comparing the precision of their fits to data, but this strategy may be muddied by differences in model complexity: Some models that appear to provide good fits may simply be better able to mimic the data produced by other models. To evaluate this possibility, we simulated data with each of the models in each of three popular remember-know paradigms, then fit those data to each of the models. We found that the one-dimensional model is generally less complex than the others, but despite this handicap, it dominates the others as the best-fitting model. For both reasons, the one-dimensional model should be preferred. In addition, we found that some empirical paradigms are ill-suited for distinguishing among models. For example, data collected by soliciting remember/know/new judgments--that is, the trinary task--provide a particularly weak ground for distinguishing models. Additional tables and figures may be downloaded from the Psychonomic Society's Archive of Norms, Stimuli, and Data, at www.psychonomic.org/archive.


Simulation of alcohol action upon a detailed Purkinje neuron model and a simpler surrogate model that runs >400 times faster.
An approach to investigate brain function/dysfunction is to simulate neuron circuits on a computer. A problem, however, is that detailed neuron descriptions are computationally expensive and this handicaps the pursuit of realistic network investigations, where many neurons need to be simulated. We confront this issue; we employ a novel reduction algorithm to produce a 2 compartment model of the cerebellar Purkinje neuron from a previously published, 1089 compartment model. It runs more than 400 times faster and retains the electrical behavior of the full model. So, it is more suitable for inclusion in large network models, where computational power is a limiting issue. We show the utility of this reduced model by demonstrating that it can replicate the full model's response to alcohol, which can in turn reproduce experimental recordings from Purkinje neurons following alcohol application. We show that alcohol may modulate Purkinje neuron firing by an inhibition of their sodium-potassium pumps. We suggest that this action, upon cerebellar Purkinje neurons, is how alcohol ingestion can corrupt motor co-ordination. In this way, we relate events on the molecular scale to the level of behavior.


Increased apoptotic neuronal cell death and cognitive impairment at early phase after traumatic brain injury in aged rats.
Progressive age-associated increases in cerebral dysfunction have been shown to occur following traumatic brain injury (TBI). Moreover, levels of neuronal mitochondrial antioxidant enzymes in the aged brain are reduced, resulting in free radical-induced cell death. It was hypothesized that cognitive impairment after TBI in the aged progresses to a greater degree than in younger individuals, and that damage involves neuronal degeneration and death by free radicals. In this study, we investigated the effects of free radicals on neuronal degeneration, cell death, and cognitive impairment in 10-week-old (young group) and 24-month-old rats (aged group) subjected to TBI. Young and aged rats received TBI with a pneumatic controlled injury device. At 1, 3 and 7 days after TBI, immunohistochemistry, lipid peroxidation and behavioral studies were performed. At 1, 3 and 7 days post-TBI, the number of 8-hydroxy-2'-deoxyguanosine-, 4-hydroxy-2-nonenal- and single-stranded DNA (ssDNA)-positive cells, and the levels of malondialdehyde around the damaged area after TBI significantly increased in the aged group when compared with the young group (P < 0.05). In addition, the majority of ssDNA-positive cells in both groups co-localized with neuronal cells around the damaged area. There was a significant decrease in the number of surviving neurons and an increase in cognitive impairment after TBI in the aged group when compared with the young group (P < 0.05). These results indicate that following TBI, high levels of free radicals are produced in the aged rat brain, which induces neuronal degeneration and apoptotic cell death around the damaged area, resulting in cognitive impairment.


Tamoxifen resistance in MCF7 cells promotes EMT-like behaviour and involves modulation of beta-catenin phosphorylation.
We have previously demonstrated that, following acquisition of endocrine resistance, breast cancer cells display an altered growth rate together with increased aggressive behaviour in vitro. Since dysfunctional cell-cell adhesive interactions can promote an aggressive phenotype, we investigated the integrity of this protein complex in our breast cancer model of tamoxifen resistance. In culture, tamoxifen-resistant MCF7 (TamR) cells grew as loosely packed colonies with loss of cell-cell junctions and demonstrated altered morphology characteristic of cells undergoing epithelial-to-mesenchymal transition (EMT). Neutralising E-cadherin function promoted the invasion and inhibited the aggregation of endocrine-sensitive MCF7 cells, whilst having little effect on the behaviour of TamR cells. Additionally, TamR cells had increased levels of tyrosine-phosphorylated beta-catenin, whilst serine/threonine-phosphorylated beta-catenin was decreased. These cells also displayed loss of association between beta-catenin and E-cadherin, increased cytoplasmic and nuclear beta-catenin and elevated transcription of beta-catenin target genes known to be involved in tumour progression and EMT. Inhibition of EGFR kinase activity in TamR cells reduced beta-catenin tyrosine phosphorylation, increased beta-catenin-E-cadherin association and promoted cell-cell adhesion. In such treated cells, the association of beta-catenin with Lef-1 and the transcription of c-myc, cyclin-D1, CD44 and COX-2 were also reduced. These results suggest that homotypic adhesion in tamoxifen-resistant breast cancer cells is dysfunctional due to EGFR-driven modulation of the phosphorylation status of beta-catenin and may contribute to an enhanced aggressive phenotype and transition towards a mesenchymal phenotype in vitro.