Oxygen diffusion: an enzyme-controlled variable parameter.
Previous oxygen microelectrode studies have shown that the oxygen diffusion coefficient (DO₂) increases during extracellular PO₂ decreases, while intracellular PO₂ remained unchanged and thus cell function (spike activity of neurons). Oxygen dependency of complex multicellular organisms requires a stable and adequate oxygen supply to the cells, while toxic concentrations have to be avoided. Oxygen brought to the tissue by convection diffuses through the intercellular and cell membranes, which are potential barriers to diffusion. In gerbil brain cortex, PO₂ and DO₂ were measured by membrane-covered and by bare gold microelectrodes, as were also spike potentials. Moderate respiratory hypoxia was followed by a primary sharp drop of tissue PO₂ that recovered to higher values concomitant with an increase of DO₂. A drop in intracellular PO₂ recovered immediately. Studies on the abdominal ganglion of aplysia californica showed similar results.Heterogeneity is a feature of both normal oxygen supply to tissue and supply due to a wide range of disturbances in oxygen supply. Oxygen diffusion through membranes is variable thereby ensuring adequate intracellular PO₂. Cell-derived glucosamine oxidase seems to regulate the polymerization/depolymerisation ratio of membrane mucopolysaccharides and thus oxygen diffusion.Variability of oxygen diffusion is a decisive parameter for regulating the supply/demand ratio of oxygen supply to the cell; this occurs in highly developed animals as well as in species of a less sophisticated nature. Autoregulation of oxygen diffusion is as important as the distribution/perfusion ratio of the capillary meshwork and as the oxygen extraction ratio in relation to oxygen consumption of the cell. Oxygen diffusion resistance is the cellular protection against luxury oxygen supply (which can result in toxic oxidative species leading to mutagenesis).


Nonresponse on the Center for Epidemiological Studies-Depression Scale in Chinese Americans.
This paper examines the phenomenon of nonresponse on the CES-D in a group of Chinese-American. Of the 403 respondents, 43 missed 1 to 4 CES-D items and 43 missed more than 4 items. The completers were likely to be younger and better educated men. Those who missed up to four items were likely to be middle-aged men, and missed the positive items most frequently. This was discussed within the context of Chinese cultural values. The group who missed more than four items were likely to be older women. For them, nonresponse may be a result of unfamiliarity with survey research and reluctance to share personal experiences with strangers. Implications of this investigation are discussed.


Sample size and power calculations based on generalized linear mixed models with correlated binary outcomes.
The generalized linear mixed model (GLIMMIX) provides a powerful technique to model correlated outcomes with different types of distributions. The model can now be easily implemented with SAS PROC GLIMMIX in version 9.1. For binary outcomes, linearization methods of penalized quasi-likelihood (PQL) or marginal quasi-likelihood (MQL) provide relatively accurate variance estimates for fixed effects. Using GLIMMIX based on these linearization methods, we derived formulas for power and sample size calculations for longitudinal designs with attrition over time. We found that the power and sample size estimates depend on the within-subject correlation and the size of random effects. In this article, we present tables of minimum sample sizes commonly used to test hypotheses for longitudinal studies. A simulation study was used to compare the results. We also provide a Web link to the SAS macro that we developed to compute power and sample sizes for correlated binary outcomes.


Tetrakis(trifluoromethanesulfonyl)propane: highly effective Brønsted acid catalyst for vinylogous Mukaiyama-Michael reaction of alpha,beta-enones with silyloxyfurans.
1,1,3,3-Tetrakis(trifluoromethanesulfonyl)propane was found as an excellent Brønsted acid catalyst for the Mukaiyama-Michael reaction of alpha,beta-enones with 2-silyloxyfurans; using beta,beta-disubstituted enones as a Michael acceptor, an excellent yield construction of quaternary carbon centers could be achieved; in addition, very low catalyst loading of Brønsted acid was used in a range from 0.05 to 1.0 mol%.


NIR-responsive polydopamine-based calcium carbonate hybrid nanoparticles delivering artesunate for cancer chemo-photothermal therapy.
Artesunate (AS), the first-line treatment of malaria with a satisfactory safety profile, has been repurposed as a potential anticancer candidate as it mainly generates reactive oxygen species (ROS) through its intrinsic endoperoxide bridge reacting with ferrous-based catalysts to suppress cancer cell growth. However, further clinical translation of AS is hindered by the attenuated anticancer efficacy due to insufficient ROS generation. Herein, we rationally integrated hydrophobic-modified AS (hAS) with biomimetic polydopamine (PDA) and biomineral calcium carbonate to fabricate high AS-loaded nanomedicine (Ca-PDA/hAS@PEG) for cancer chemo-photothermal therapy, which exerted anticancer effects in the following ways: (1) the heat was generated when PDA was irradiated by near-infrared (NIR) light for photothermal therapy. Meanwhile, the increased temperature accelerated the production of ROS from hAS, thus enhancing the anticancer efficacy of hAS-based chemotherapy; (2) hAS-mediated chemotherapy boosted the cancer inhibition effect of photothermal therapy by arousing the intracellular ROS levels in the presence of endogenous ferrous ions and sensitizing cancer cells to thermal ablation; (3) the integration of calcium carbonate into the nanoparticle facilitated the pH-responsive drug release for precise treatment. Such hybrid nanoparticles exhibited a combinational antitumor effect of photothermal therapy and chemotherapy in vivo with no systemic toxicity. Taken together, our work presents a facile strategy to improve the anticancer efficacy of AS by combining chemical modification and photothermal therapy-assisted endoperoxide bridge cleavage, which may offer opportunities to pave the way for clinical translation of AS-based nanomedicines. STATEMENT OF SIGNIFICANCE: The clinical translation of artesunate (AS) is hindered by the attenuated anticancer efficacy due to insufficient ROS generation. Herein, we rationally integrated hydrophobic-modified AS (hAS) with biomimetic polydopamine (PDA) and biomineral calcium carbonate to fabricate high AS-loaded nanomedicine (Ca-PDA/hAS@PEG) for improved cancer chemo-photothermal therapy. The heat generated from PDA in response to near-infrared light irradiation could locally ablate tumor as well as accelerate the production of ROS by hAS, thus enhancing the anticancer efficacy of hAS-based chemotherapy. On the other hand, hAS-based chemotherapy amplified the intracellular oxidative stress, sensitizing cancer cells to thermal ablation. Our work presents a facile strategy to improve the anticancer efficacy of AS by combining chemical modification and photothermal therapy-assisted endoperoxide bridge cleavage.


Mapping gut parasitism patterns in a cohort of Egyptians.
In developing countries, the prevalence of intestinal parasitic infection is still significant, particularly due to geographical and socioeconomic variables. The objective of this study was to map the distribution pattern of intestinal parasitic infection in a cohort of the Egyptian population, as well as to assess associated risk factors. A cross-sectional hospital-based study was conducted on 386 patients. A single fecal specimen was collected from the study individual and examined microscopically for the detection of parasitic infection. DNA was extracted from all samples and utilized to amplify Entamoeba histolytica complex species, Cryptosporidium species, Giardia intestinalis assemblages, and Blastocystis species using PCRs. Typing of Cryptosporidium species and Giardia intestinalis assemblages was performed using restriction enzymes RasI and HaeIII respectively. While Blastocystis spp. subtypes (ST) were identified through sequencing of PCR products and phylogenetic analysis. 59.6% (230/386) of the study patients were infected with one or more intestinal parasites, 87.4%; 201/230 of patients had mono-parasitic infections, and 12.6%; 29/230 had multiple-parasitic infections (P < 0.0001). The predominant protozoa were Blastocystis, followed by Entamoeba histolytica complex, and Giardia intestinalis both as mono-parasites and as part of multiple parasites. Molecular assays showed that Blastocystis ST3, Entamoeba dispar, Giardia intestinalis assemblage B, and Cryptosporidium hominis were the most prevalent species. Intestinal parasitic infection was significantly associated with age, gender, residence, and water source. Multi-parasitism showed that residency in a rural area was a risk factor (OR 4.49; 95% CI 1.51-13.37; P = 0.007). Egyptians residing in rural areas have a high prevalence of intestinal multi-parasitism. Therefore, to lessen the prevalence and effects of these infections in this group, effective and sustainable control methods, providing health education focusing on good personal hygiene habits, and providing a safe drinking water supply should be implemented.


Mighty bugs: leprosy bacteria turn schwann cells into stem cells.
For intracellular parasites that strongly prefer infecting a particular cell type, systemic spread is challenging. Masaki et al. show that the leprosy bacterium cleverly expands its repertoire by driving dedifferentiation of Schwann cells, their preferred host, to cells with stem cell properties that can subsequently redifferentiate into mesodermal lineages.


Correlation between hypo-osmotic swelling test and 'water test' to assess human sperm membrane integrity.
Fifty-nine men who requested vasectomy and 43 infertile patients had a semen analysis performed prior to surgery or during evaluation. A hypo-osmotic swelling test (HOS) and a new 'Water test' were performed simultaneously, in order to assess correlation between these two procedures. Our results showed that values obtained with the 'Water test' were significantly higher than those obtained with the HOS test (P < 0.001). These findings suggest that it is necessary to determine normal values for this new test before introducing it in the routine semen analysis.


Effects of a high-intensity interval training session and chocolate milk on appetite and cognitive performance in youth aged 9-13 years.
To investigate the separate and combined effects of a single session of high intensity interval training (HIIT) and chocolate milk on appetite and cognitive performance in youth aged 9-13 years. Blood glucose, salivary cortisol, and subjective emotions were measured to evaluate potential underlying mechanisms contributing to changes in appetite and cognitive performance. Using a 2 × 2 repeated measures design, 20 youth (n = 12 girls and n = 8 boys; age = 11.4 ± 0.3 years) performed HIIT on a cycle ergometer (7 × 60 s bouts, interspersed by 60 s active recovery) or sitting, followed by consumption of 163 kcal chocolate milk or water. Capillary blood glucose, salivary cortisol, cognitive performance, and subjective appetite and emotions were assessed at baseline and at several time points post-treatment. Subjective appetite decreased from baseline following chocolate milk consumption compared water (p = 0.04), and increased from baseline after HIIT compared to sitting (p = 0.01). Participants recalled more words during a short-term memory task and had faster reaction times during an attention task following HIIT compared to sitting (Δ = 1.1 ± 0.02 words, p = 0.03; and Δ = 117.9 ± 23.1 ms, p = 0.01, respectively). Blood glucose increased from baseline following chocolate milk consumption compared to water (at 10 min: Δ = 1.0 ± 0.33 vs. Δ = 0.29 ± 0.060 mmol/L; p < 0.0001). Our findings that HIIT may have a positive effect on aspects of cognitive performance suggest that youth should engage in HIIT-like exercise during recesses and lunch at school to attenuate declines in cognitive performance throughout the day. Registered at https://clinicaltrials.gov (NCT03305107).


Primate model of parkinsonism: selective lesion of nigrostriatal neurons by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine produces an extrapyramidal syndrome in rhesus monkeys.
Systemic administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to rhesus monkeys (1.0-2.5 mg/kg i.v.) produces irreversible damage to nigrostriatal neurons. Dopaminergic neurons in the dorsolateral part of striatum were the most vulnerable. The major clinical signs of an extrapyramidal syndrome, but not resting tremor, appeared only in MPTP-treated monkeys suffering from more than 80% reduction in striatal dopamine. No chronic changes in the mesolimbic dopaminergic system were observed. Immunocytochemical staining of the mid-brain with a tyrosine hydroxylase antiserum indicated that MPTP produced a significant decrease of dopaminergic cell bodies in the A9, but not in the A10 ventrotegmental area. Despite greater than 80% decrease in A9 nigral cell bodies, the dopamine content decreased only by 50%. Sprouting of the surviving nigral A9 neurons was observed histologically and neurochemically in the area above substantia nigra. The present behavioral, neurochemical and histological results indicate that MPTP produces an ideal primate model for studying parkinsonism. Selective lesion of more than 80% of the nigrostrial neurons by MPTP is sufficient to produce the major clinical signs of the extrapyramidal syndrome in idiopathic parkinsonism.


Effects of methotrexate on serum testosterone level in sleep deprived male Wistar rats.
Sleep deprivation has been reported to decrease testosterone levels but the mechanism remains unclear. Studies have shown that sleep deprivation increases interleukin 1 beta (IL-1β), a pro-inflammatory cytokine and that increased IL-1β levels cause reductions in Leydig cell production of testosterone. This study was therefore designed to determine the effects of methotrexate, an IL-1β blocker on serum testosterone levels in sleep deprived male Wistar rats. Twenty male Wistar rats were randomly assigned into four groups (n = 5); group I (Control) received the vehicle (1% tween 80 solution); group II (methotrexate) received 0.5 mg/kg body weight methotrexate; group III (SD) was sleep deprived and received the vehicle; group IV (SD+Methotrexate) was sleep deprived and received 0.5 mg/kg body weight methotrexate. Sleep deprivation was induced using the modified multiple platform technique for 14 days. Treatments were administered twice weekly by oral gavage for 14 days. Blood was collected on day 14 and serum was obtained for analyses of testosterone, LH and FSH levels. IL-1β level and histology of the testis were also determined. Data were expressed as Mean ± SEM and analysed using ANOVA. p < 0.05 was considered significant. Serum testosterone levels were significantly decreased while testicular IL-1β was increased in SD and SD+Methotrexate compared with Control. FSH and LH levels were not significantly different among the groups. Results of this study suggest that reduction in serum testosterone level in sleep deprived rats is not dependent on increased level of IL-1β.


Characterization of a β-D-mannosidase from a marine gastropod, Aplysia kurodai.
A β-D-mannosidase (EC 220.127.116.11) with a molecular mass of approximately 100 kDa was purified from the digestive fluid of a marine gastropod Aplysia kurodai by ammonium sulfate fractionation followed by column chromatographies on TOYOPEARL Butyl-650 M, TOYOPEARL DEAE-650 M, and Superdex 200 10/300 GL. This enzyme, named AkMnsd in the present study, showed optimal activities at pH 4.5 and 40 °C and was stable at the acidic pH range from 2.0 to 6.7 and the temperature below 38 °C. The Km and Vmax values for AkMnsd determined at pH 6.0 and 30 °C with p-nitrophenyl β-d-mannopyranoside were 0.10 mM and 3.75 μmol/min/mg, respectively. AkMnsd degraded various polymer mannans as well as mannooligosaccharides liberating mannose as a major degradation product. Linear mannan from green alga Codium fragile was completely depolymerized by AkMnsd in the presence of AkMan, an endolytic β-mannanase, which we previously isolated from the same animal (Zahura et al., Comp. Biochem. Physiol. B 157, 137-148 (2010)). A cDNA encoding AkMnsd was amplified from the Aplysia hepatopancreas cDNA by the PCR using degenerated primers designed on the basis of N-terminal and internal amino-acid sequences of AkMnsd. The cloned AkMnsd cDNA consisted of 2985 bp and encoded an amino-acid sequence of 931 residues with the calculated molecular mass of 101,970 Da. The deduced sequence of AkMnsd showed 20-43% amino-acid identity to those of glycoside-hydrolase-family 2 (GHF2) β-mannosidases. The catalytically important amino-acid residues determined in GHF2 enzymes were completely conserved in AkMnsd. Thus, AkMnsd is regarded as a new member of GHF2 mannosidase from marine gastropod.


Conformational changes in ornithine decarboxylase enable recognition by antizyme.
Rapid, polyamine-induced degradation of mammalian ornithine decarboxylase (L-ornithine carboxy-lyase, EC 18.104.22.168) (ODC) is though to be controlled by the availability of a small, ODC-binding protein termed antizyme. In this study we have investigated the ability of antizyme to bind ODC protein in various altered physiological states. In particular, cold, NaCl, spermidine and deprivation of coenzyme and substrate enhance enzyme-antizyme complex formation and are all found to promote ODC homodimer dissociation. Conversely, conditions that maintain the active ODC homodimer state prevent antizyme binding and inactivation of ODC. Further, covalent modification of ODC near its active site by difluoromethylornithine or phosphate also increases its sensitivity to antizyme. These results suggest that the initial signal in ODC degradation may actually be a subtle conformational change in the enzyme that enables antizyme to bind to the enzyme and may subsequently facilitate its degradation.


Hemorrhagic endovasculitis-like lesion induced in placental organ culture.
In organ culture, human chorionic villi develop vascular changes that resemble so-called hemorrhagic endovasculitis. The latter is a morphologic finding more prevalent in placentas of stillborn infants but seen also in those of liveborn infants, in whom the lesion is localized rather than generalized. We compared the histologic vascular changes in short-term organ cultures of 15 placentas (10 term, 5 preterm) with the naturally occurring vascular lesion in 6 placentas (2 liveborn, 4 stillborn). All organ cultures of placentas from liveborn infants developed hemorrhagic endovasculitis-like lesions in the fetal stem arteries; these lesions were present as early as 1 day and persisted for 7 days in culture. A mechanism common to both the in vivo and in vitro systems depending on hypoxia and vascular smooth muscle contraction may explain both the naturally occurring and tissue culture-induced lesions.


Adsorption of soluble Pb(II) by a photocrosslinked polysaccharide hybrid: A swelling-adsorption correlation study.
A biosorbent for adsorption of soluble, inorganic Pb(II) was prepared through a photocrosslinking of a mixture of xanthan gum and guar gum at various mass ratios. The polysaccharide mixes were irradiated using UV A in presence of benzophenone. Chemical crosslinks were formed which led to a controlled swelling of the polysaccharide mix (swelling ratio <20%), referred as crosslinked hybrid in the text. The hybrids were characterized for microstructure, rheology, surface area and surface charge behavior. Interesting changes in crystallographic pattern, both in the pre and the post adsorption stages, was investigated using x-ray diffraction technique. Adsorption efficiency was estimated in respect of blend composition, adsorbate-adsorbent concentration and pH under competitive and non-competitive conditions. A correlation between the swelling of the crosslinked hybrid and the metal adsorption was drawn at various pH to elucidate an interaction between the two phenomena.


Improvement in the biological standard of living in 20th century Korea: Evidence from age at menarche.
We used age at menarche to understand improvement in the biological standard of living in South Korea during the 20th century. The main dataset, the Korean National Health and Nutrition Examination Survey, provided a consistent source of nationally representative data with a large number of observations over a long period of time. We calculated mean ages at menarche by birth year and estimated the rate of decrease in age at menarche, while avoiding survival bias. The mean age at menarche decreased from 16.64 for the birth year 1941 to 12.68 for the birth year 1992, decreasing 0.78 (or 0.81 in a regression) years per decade for the period. Comparisons with other populations demonstrate that this is the fastest rate of decline ever known. In contrast to other developed countries, the decreasing rate in Korea does not appear to slow. We also compared the trend in age at menarche to that of height and found that the rate of increase in height is also the fastest in history. Age at menarche is an appropriate index of change in the general standard of living in South Korea over the 20th century. Am. J. Hum. Biol. 29:e22882, 2017. © 2016 Wiley Periodicals, Inc.


The influence of pedestrian countdown signals on children's crossing behavior at school intersections.
Previous studies have shown that pedestrian countdown signals had different influences on pedestrian crossing behavior. The purpose of this study was to examine the effects of the installation of countdown signals at school intersections on children's crossing behavior. A comparison analysis was carried out on the basis of observations at two different school intersections with or without pedestrian countdown signals in the city of Jinan, China. Four types of children's crossing behavior and child pedestrian-vehicle conflicts were analyzed in detail. The analysis results showed that using pedestrian countdown timers during the Red Man phase led to more children's violation and running behavior. Theses violators created more conflicts with vehicles. However, pedestrian countdown signals were effective at helping child pedestrian to complete crossing before the red light onset, avoid getting caught in the middle of crosswalk. No significant difference was found in children who started crossing during Flashing Green Man phase between the two types of pedestrian signals. Moreover, analysis results indicated that children who crossed the road alone had more violation and adventure crossing behavior than those had companions. Boys were found more likely to run crossing than girls, but there was no significant gender difference in other crossing behavior. Finally, it's recommended to remove countdown at the end of the Red Man phase to improve children's crossing behavior and reduce the conflicts with vehicles. Meanwhile other measures are proposed to improve children safety at school intersections.


Pulmonary homograft implantation for ventricular outflow tract reconstruction: early phase results.
The pulmonary valve homograft (PH) has been reported to have potential advantages over the aortic valve homograft, including a larger diameter, a thinner wall, and decreased intrinsic calcification. From January 16, 1986, to July 14, 1987, eight consecutive patients underwent repair of congenital cardiac anomalies using a cryopreserved PH. Patients ranged in age from 18 months to 32 years. Diagnoses included tetralogy of Fallot with pulmonary atresia (3 patients); tetralogy with absent pulmonary valve (1 patient); corrected transposition with pulmonic stenosis (1 patient); transposition of the great arteries, ventricular septal defect, and pulmonic stenosis (2 patients); and double-outlet right ventricle with pulmonic stenosis (1 patient). The PH was implanted orthotopically in the patient with absent pulmonary valve, and in the other 7 it was placed as a valved extracardiac conduit. Two of the tetralogy patients with severe bifurcational pulmonary stenosis and another with nonconfluent pulmonary arteries and origin of the left pulmonary artery from a patent ductus arteriosus had their repairs facilitated using the branching pulmonary arterial portion of the PH. There were no hospital or posthospital deaths. Postrepair right ventricular to left ventricular systolic pressure ratios were a mean of 0.35 at 18 hours postoperatively (range, 0.21-0.61). All patients were studied with Doppler and echocardiography after repair. The mean gradient across the PH was 9 mm Hg (range, 2-27 mm Hg), and no pulmonary valve incompetence was present. One patient (12.5%) required reoperation seven months after repair for conduit revision due to compression by the sternum and is now well.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of pemafibrate on fatty acid levels and liver enzymes in non-alcoholic fatty liver disease patients with dyslipidemia: A single-arm, pilot study.
Dyslipidemia (DL) is commonly associated with non-alcoholic fatty liver disease (NAFLD). Pemafibrate, a selective peroxisome proliferator activated receptor α modulator (SPPARMα), has been shown to improve liver function among patients with DL. The aim of this single-arm prospective study is to evaluate the efficacy of pemafibrate in NAFLD patients with DL. Twenty NAFLD patients with DL who received pemafibrate (0.1 mg) twice a day for 12 weeks were prospectively enrolled in this study. The primary end-point was change in serum alanine aminotransferase (ALT) levels from baseline to week 12. Serum ALT levels decreased from 75.1 IU/L at baseline to 43.6 IU/L at week 12 (P = 0.001). Significant improvements in triglyceride, high-density lipoprotein cholesterol, total fatty acid, saturated fatty acid (SFA), and unsaturated fatty acid were also noted. The serum level of remnant-like protein cholesterol, SFA, and polyunsaturated / saturated fatty acid ratio (PUFA / SFA ratio) at baseline were correlated with change in ALT level (r = -0.53, r = -0.57, and r = 0.46, respectively). Change in PUFA and change in PUFA / SFA ratio were negatively correlated with change in ALT level (r = -0.49 and r = -0.53). No hepatic or renal adverse events were reported. Selective peroxisome proliferator activated receptor α could be a promising novel agent for treatment of NAFLD patients with DL by regulating fatty acid composition. A further long-term large-scale trial is warranted to confirm the efficacy of SPPARMα on NAFLD with DL.


Concurrent Chemo-Proton Therapy Using Adaptive Planning for Unresectable Stage 3 Non-Small Cell Lung Cancer: A Phase 2 Study.
This study prospectively evaluated the efficacy and safety of concurrent chemo-proton therapy (CCPT) using adaptive planning for unresectable stage III non-small cell lung cancer (NSCLC). The primary endpoint was overall survival (OS). Secondary endpoints were local control rate (LCR), progression-free survival (PFS), incidence of grade 3 or higher adverse events, and changes in quality of life (QOL). Patients received cisplatin (60 mg/m2) on day 1 and S-1 (∼40 mg/m2 twice daily) on days 1 to 14, q4w, for up to 4 cycles, plus concurrent proton therapy at a total dose of 70 GyRBE for the primary lesion and 66 GyRBE for lymph node metastasis with 2 GyRBE per day. Proton therapy was performed using respiratory-gated and image guided techniques, and adaptive plans were implemented. Forty-seven patients were enrolled between August 2013 and August 2018. Four cycles of cisplatin plus S-1 were completed in 34 patients. The mean number of cycles was 4 (range, 1-4). The median follow-up of all and surviving patients was 37 (range, 4-84) and 52 months (range, 26-84), respectively. The mean number of replanning sessions was 2.5 (range, 1-4). The 2- and 5-year OS, LCR, and PFS were 77% (95% confidence interval 64%-89%) and 59% (43%-76%), 84% (73%-95%) and 61% (44%-78%), and 43% (28%-57%) and 37% (22%-51%), respectively. The median OS was not reached. No grade 3 or higher radiation pneumonitis was observed. There was no significant deterioration in the QOL scores after 24 months except for alopecia. CCPT with adaptive planning was well tolerated and yielded remarkable OS for unresectable stage III NSCLC.


Technical aspects and utility of fMRI using BOLD and ASL.
Functional magnetic resonance imaging (fMRI) is an emerging methodology which provides various approaches to visualizing regional brain activity non-invasively. Although the exact mechanisms underlying the coupling between neural function and fMRI signal changes remain unclear, fMRI studies have been successful in confirming task-specific activation in a variety of brain regions, providing converging evidence for functional localization. In particular, fMRI methods based on blood oxygenation level dependent (BOLD) contrast and arterial spin labeling (ASL) perfusion contrast have enabled imaging of changes in blood oxygenation and cerebral blood flow (CBF). While BOLD contrast has been widely used as the surrogate marker for neural activation and can provide reliable information on the neuroanatomy underlying transient sensorimotor and cognitive functions, recent evidence suggests perfusion contrast is suitable for studying relatively long term effects on CBF both at rest or during activation. New developments in combining or simultaneously measuring the electrophysiological and fMRI signals allow a new class of studies that capitalize on dynamic imaging with high spatiotemporal resolution. This article reviews the biophysical bases and methodologies of fMRI and its applications to the clinical neurosciences, with emphasis on the spatiotemporal resolution of fMRI and its coupling with neurophysiology under both normal and pathophysiological conditions.


Guinea pig liver 3-hydroxyhexobarbital dehydrogenase. Purification and properties.
3-Hydroxyhexobarbital dehydrogenase, which catalyzes the reversible oxidation of 3-hydroxyhexobarbital to 3-oxohexobarbital, has been purified 470-fold from the soluble fraction of guinea pig liver with a yield of 47%. The specific activity of the purified enzyme is 9.4 units/mg of protein. Results of polyacrylamide gel disc electrophoresis and isoelectric focusing indicated that the purified enzyme preparation is a single and homogeneous protein. NADP+ served as preferred co-factor, but NAD+ is also utilized in the presence of phosphate ion. The guinea pig liver enzyme possessed a relatively narrow substrate specificity in comparison with the rabbit liver enzyme. It is very distinctive that guinea pig liver 3-hydroxyhexobarbital dehydrogenase catalyzes the dehydrogenation of 17beta-hydroxysteroids such as testosterone, 4-androstene-3beta,17beta-diol, 5alpha-androstane-3alpha,17beta-diol, 5alpha-androstane-3beta,17beta-diol, 5alpha-androstan-17beta-ol-3-one, and 5beta-androstane-3alpha,17beta-diol.


Radiation-induced meningeal sarcoma. A case report with a review of the literature.
A case is reported of a 21 month old boy from whom a 357 g ependymona was removed. Postoperatively, radiation therapy (Co60) was administered, and the central dosage was estimated to be 4,350 r given over 46 days. Seven and a half years later craniotomy was again performed because of a supposed recurrence. However, a meningeal sarcoma weighing 370 g was found. Tumour induction by radiotherapy is discussed on the basis of published reports, and the need of estimating tumour dose in relationship to the age of the patient is stressed.


Phosphoenolpyruvate carboxykinase in experimental intrauterine growth retardation in rats.
This study examines the role of impaired gluconeogenesis in the pathogenesis of neonatal hypoglycemia in intrauterine growth retardation (IUGR). IUGR was produced experimentally in eight pregnant rats by ligation of uterine arteries at the 17th day of gestation. Delivery occurred spontaneously at term. Sham operations were performed in five pregnant rats at the same gestational age and the fetuses delivered at term served as controls. The body weights of newborn rats with IUGR were significantly lower than the controls (5.32 +/- 0.12 vs. 6.22 +/- 0.06 g, mean +/- SE, P less than 0.001). The fetal liver weights were also significantly smaller in IUGR than in the control animals (0.224 +/- 0.14 vs. 0.340 +/- 0.12 g, P less than 0.001). The activity of phosphoenolpyruvate carboxykinase (PEPCK) (the rate-limiting enzyme of gluconeogenesis) in liver cytosols was significantly lower in rats with IUGR (0.06 +/- 0.01 vs. 0.11 +/- 0.02 microM phosphoenolpyruvate/g liver/min when compared with controls (P less than 0.05). A direct relationship between this enzyme and the birth weight was observed, suggesting a close relationship between intrauterine nutrition and the status of gluconeogenesis. The blood glucose level was also lower in growth-retarted fetuses (36.6 +/- 4.7 vs. 69.6 +/- 4.3 mg/dl, p less than 0.001) when compared with controls. The data suggest that gluconeogenesis is impaired in IUGR and is partly responsible for the increase in the incidence of neonatal hypoglycemia in this group of subjects.


Unique changes in the retinal microvasculature reveal subclinical retinal impairment in patients with systemic lupus erythematosus.
To determine the changes of the microvasculature and microstructure in the inner intra-retinal layers in systemic lupus erythematosus (SLE) patients without lupus retinopathy (LR). Thirty-two SLE patients (58 eyes) without LR (NLR), 14 patients (22 eyes) with LR and 50 healthy subjects (50 eyes) were enrolled. Spectral domain optical coherence tomography equipped with Angiovue was used to obtain three-dimensional retinal thickness maps and microvascular images of the superficial and deep retinal capillary plexuses (SRCP/DRCP) around the macula. Quantitative analyses were performed using a custom automated algorithm. Disease activity of patients was assessed using the SLE disease activity index (SLEDAI). Retinal capillary skeleton density of the SRCP in SLE patients without LR was significantly lower than the controls in almost all regions, which further decreased in the LR group (P < .05). No significant changes were evident in DRCP of the NLR group (P > .05). The inner retina in the LR group was significantly thinner than the controls in most regions, though there were only a few regions that were different between the NLR and the control groups (P < .05). There were significant differences of the SLEDAI scores between the two SLE groups. Significantly lower density in SRCP and regional thinning in inner retina were observed in the SLE patients without clinical fundus changes. OCT equipped with Angiovue might be useful in evaluating the microvascular and microstructural disorders of the inner retinal layers in SLE patients, which may contribute a quantitative approach to the early diagnosis and progression of LR.


Biomechanical analyses of overlap and mesh dislocation in an incisional hernia model in vitro.
Incisional hernia repair is one of the most common surgical complications. Despite the introduction of mesh techniques of repair, recurrences are still prevalent. The aim of the current study was to evaluate the dependence of mesh dislocation on defect size, facial overlap, mesh-position, and orientation of the mesh in cases of anisotropic stretchability. An in vitro incisional hernia model was used, which consisted of a pressure chamber, an elastic silicone pad representing the peritoneal sac, and a silicone mat with bovine muscle tissue representing the abdominal wall. Intrinsic pressure (up to 200 mm Hg) was generated within the pressure chamber by continuous inflation with CO(2). A slit-like or flap-like defect was created in the silicone mat to simulate small or large hernia defects, respectively. The implanted mesh was arranged in both onlay and sublay configurations. A large pore polypropylene mesh with significant anisotropic stretchability was investigated, whereas overlaps of 2, 3, and 4 cm were applied. Despite the application of pressures up to 200 mm Hg, no mesh ruptures occurred. In the slit-like defect model, the minimal overlap required to prevent dislocation at 200 mm Hg was 3 cm using the sublay technique provided that the mesh was positioned with its most stretchable axis parallel to the largest slit dehiscence. Perpendicular rotation of the mesh resulted in dislocation at 160 mm Hg, despite using an overlap of 3 cm. Mesh reinforcement showed less stability in both the onlay position and the flap-like defect. An overlap of 3 cm is sufficient to prevent early mesh dislocation. Meshes with anisotropic stretchability should be orientated with the most stretchable axis in the direction of least overlap.


Developmental programming: Adipose depot-specific transcriptional regulation by prenatal testosterone excess in a sheep model of PCOS.
Prenatal testosterone (T)-treated female sheep manifest adipose depot-specific disruptions in inflammatory/oxidative state, adipocyte differentiation and thermogenic adipocyte distribution. The objective of this study was to identify common and divergent gene pathways underlying prenatal T excess-induced adipose depot-specific disruptions. RNA sequencing and network analyses were undertaken with visceral (VAT), subcutaneous (SAT), epicardiac (ECAT) and perirenal (PRAT) adipose tissues from control and prenatal T-treated (100 mg T propionate twice a week from days 30-90 of gestation) female sheep at 21 months of age. Increased expression of adiposity and inflammation-related genes in VAT and genes that promote differentiation of white adipocytes in SAT were congruous with their metabolic roles with SAT favoring uptake/storage of free fatty acids and triglycerides and VAT favoring higher rate of fatty acid turnover and lipolysis. Selective upregulation of cardiac muscle and renoprotection genes in ECAT and PRAT respectively are suggestive of protective paracrine actions. Expression profile in prenatal T-treated sheep paralleled depot-specific dysfunctions with increased proinflammatory genes in VAT, reduced adipocyte differentiation genes in VAT and SAT and increased vascular related gene expression in PRAT. The high expression of genes involved in cardiomyocyte function in ECAT is suggestive of cardioprotective function being maintained to overcome the prenatal T-induced cardiac dysfunction and hypertension. These findings coupled with changes in gene pathways and networks involved in chromatin modification, extracellular matrix, immune and mitochondrial function, and endoplasmic reticulum to Golgi transport suggest that dysregulation in gene expression underlie prenatal T-treatment induced functional differences among adipose depots and manifestation of metabolic dysfunction.


Religiosity as Mediator in Reducing Misconduct of Adolescents-at-Risk.
In dealing with adolescents-at-risk who are involved in misconduct, the religious factor can be an effective approach. The objective of this research is to study the religious factor as a mediator in dealing with misconduct of adolescents-at-risk. This research is a survey study by design. The method used is quantitative through questionnaire using Likert scale. A study was done on 556 respondents comprising of adolescents within the range of ages 13 to 24 years. Factor analysis finds two main domains in misconduct of adolescents-at-risk, that is, family dysfunction and lack of religiosity. Mediation analysis is used to determine whether the religious factor may become the mediator for adolescent misconduct. Results of regression analysis show that the factor of family dysfunction contributes higher to the misconduct of adolescent-at-risk in comparison with the factor of religiosity. However, the issue of dysfunctional family itself is related with the lack of religiosity within family. A family which is concerned about religious education and practice will reduce the opportunity for adolescents to be involved in misconduct. Hence, to further empower the role of the religious factor in dealing with adolescents-at-risk, the family plays an important role in applying religious aspects in order for adolescents to be able to control themselves from any misconduct. Thus, results of mediation analysis show that 0.275 states the religious factor is a mediator for misconduct of adolescents-at-risk. This research will also focus on the relationship between lack of religiosity among adolescents, how it is related to dysfunctional family and how religiosity can be a mediator to reduce misconduct of adolescent-at-risk.


Hypoglycemia induced behavioural deficit and decreased GABA receptor, CREB expression in the cerebellum of streptozoticin induced diabetic rats.
Intensive glycemic control during diabetes is associated with an increased incidence of hypoglycemia, which is the major barrier in blood glucose homeostasis during diabetes therapy. The CNS neurotransmitters play an important role in the regulation of glucose homeostasis. In the present study, we showed the effects of hypoglycemia in diabetic and non- diabetic rats on motor functions and alterations of GABA receptor and CREB expression in the cerebellum. Cerebellar dysfunction is associated with seizure generation, motor deficits and memory impairment. Scatchard analysis of [(3)H]GABA binding in the cerebellum of diabetic hypoglycemic and control hypoglycemic rats showed significant (P<0.01) decrease in B(max) and K(d) compared to diabetic and control rats. Real-time PCR amplification of GABA receptor subunit GABA(Aα1) and GAD showed significant (P<0.001) down-regulation in the cerebellum of hypoglycemic rats compared to diabetic and control rats. Confocal imaging study confirmed the decreased GABA receptors in hypoglycemic rats. CREB mRNA expression was down-regulated during recurrent hypoglycemia. Both diabetic and non-diabetic hypoglycemic rats showed impaired performance in grid walk test compared to diabetic and control. Impaired GABA receptor and CREB expression along with motor function deficit were more prominent in hypoglycemic rats than hyperglycemic which showed that hypoglycemia is causing more neuronal damage at molecular level. These molecular changes observed during hypo/hyperglycemia contribute to motor and learning deficits which has clinical significance in diabetes treatment.


Inactivation of human cells cultivated in vitro by the new mitotic inhibitors NY 4137 and NY 4138.
The effect of the two closely related drugs, the sulfone 2-(2-thenyl)sulfonyl-5-bromopyrimidine (NY 4137), and the sulfoxide 2-(2-thenyl)sulfinyl-5-bromopyrimidine (NY 4138), a sulfoxide, on the survival of cells of the human line NHIK 3025 was investigated. Cell survival was measured as the ability of single cells to form macroscopic colonies. Two-hour treatment with 0.012 mM NY 4137 resulted in 50% inactivation. The drug concentration of NY 4138 had to be adjusted about 10 times higher than that of NY 4137 for treatment periods of 2 or 24 h to obtain similar surviving fraction after treatment of asynchronous cells. Treatment of synchronized NHIK 3025 cells with NY 4137 showed that survival varied little with cell age. Following treatment with NY 4138, however, cells were particularly sensitive in G2 and in mitosis. As the survival curves for both drugs display a plateau region, where increasing the drug dose has little or no effect on cell inactivation, the presence of resistant subpopulations of cells is considered. High-performance liquid chromatography of drug solutions in cell culture medium showed that both NY 4137 and NY 4138 bound to, or were metabolized by, medium and/or cell components. The concentration of NY 4137 in cell culture medium, however, was reduced at a higher rate than NY 4138. The half-life of NY 4137 was on the order of 5 h, while the half-life of NY 4138 was over 24 h. These observations correlate well with the relative chemical reactivities for these drugs in nucleophilic displacement reactions.


Health-related quality of life after spontaneous subarachnoid hemorrhage measured in a recent patient population.
This study sought to determine the impact of spontaneous subarachnoid hemorrhage (SAH) on health-related quality of life (HRQOL). Data were taken retrospectively from 601 patients (219 male, 382 female) treated between 1998 and 2008. Questionnaires concerning HRQOL were circulated prospectively, and the responses from 253 patients (81 male, 172 female) were analyzed. The questionnaires comprised the standardized Short-Form 36 (SF-36) and Short-Form 12 (SF-12) Health Surveys, a number of nonstandardized questions, and visual analogue scales. Statistical analysis of the results was exploratory, using unifactorial ANOVA (Scheffe), multivariate analyses of variance. The HRQOL is reduced considerably by SAH and remains so for a period of 10 years. Physical and emotional domains are primarily affected, but also cognitive functions, including memory and concentration in particular. Similarly, certain roles are affected that prove difficult to rehabilitate after acute care and cause serious debility in the long term. The Hunt and Hess Scale, Glasgow Outcome Scale, and seizures were found to have the greatest impact on HRQOL. Documentation of HRQOL after 6 to 12 months is useful because patients are often found to have a diminished HRQOL in the absence of a clear physical impairment. Because psychological, emotional, cognitive, and social functioning influence HRQOL in the long term, efforts at rehabilitation should focus in particular on improving such factors. Documentation of HRQOL is a useful, additive tool for consolidating and evaluating the outcome, and a treatment end point after SAH, respectively.


White matter microstructural alterations in migraine: a diffusion-weighted MRI study.
Migraine is a common and disabling neurological disease. The pathomechanism that underlies the disorder is not entirely understood, and reliable biomarkers are missing. In the current analysis we looked for microstructural alterations of the brain white matter in migraine patients by means of diffusion-weighted magnetic resonance imaging. The measurements were carried out with a novel approach based on fine-tuned nonlinear registration and nonparametric permutation test in an alignment-invariant tract representation (Tract-Based Spatial Statistics). We found reduced fractional anisotropy in the right frontal white matter cluster of migraine patients. In the same region we also found increased mean diffusivity and increased radial diffusivity. The probabilistic tractography showed connection of this cluster to other parts of the pain network (orbitofrontal cortex, insula, thalamus, dorsal midbrain). We speculate that these findings reflect maladaptive plastic changes or white matter disintegration.


A model for the classification of specimens containing random proportions of abnormal cells.
The effect of abnormal cell proportion on the performance of an automated cervical prescreening system is discussed in K.R. Castleman and B.S. White, Cytometry 2:155-18. The model employed assumes fixed proportions of abnormal cells, both in the design stage and in the test stage. In the present paper, an extended model is developed that allows for random variability of this proportion. It is shown, that there is a fundamental, non-zero lower limit to the false-negative specimen error rate, which depends only on the coefficient of variation. This limit may be reached even for moderate values of the coefficient of variation, which implies that a satisfactory prescreening system may not be feasible.


How well do UK assistantships equip medical students for graduate practice? Think EPAs.
The goal of better medical student preparation for clinical practice drives curricular initiatives worldwide. Learning theory underpins Entrustable Professional Activities (EPAs) as a means of safe transition to independent practice. Regulators mandate senior assistantships to improve practice readiness. It is important to know whether meaningful EPAs occur in assistantships, and with what impact. Final year students at one UK medical school kept learning logs and audio-diaries for six one-week periods during a year-long assistantship. Further data were also obtained through interviewing participants when students and after three months as junior doctors. This was combined with data from new doctors from 17 other UK schools. Realist methods explored what worked for whom and why. 32 medical students and 70 junior doctors participated. All assistantship students reported engaging with EPAs but gaps in the types of EPAs undertaken exist, with level of entrustment and frequency of access depending on the context. Engagement is enhanced by integration into the team and shared understanding of what constitutes legitimate activities. Improving the shared understanding between student and supervisor of what constitutes important assistantship activity may result in an increase in the amount and/or quality of EPAs achieved.


Integrating Cardiac MRI Imaging and Multidisciplinary Clinical Care is Associated With Improved Outcomes in Patients With Fabry Disease.
Given the inherent complexities of Fabry disease (FD) and evolving landscape of cardiovascular clinical management, there is no established ideal clinical care model for these patients. We identified clinical factors predictive of increased risk of major adverse cardiac events (MACE) in patients with FD targeted to improve clinical outcomes. Ninety-five patients studied over a median follow-up time of 6.3 years, and 26 patients reached the composite endpoint with a high prevalence of heart failure and cerebrovascular events and no cardiac-related mortality. Patients with MACE had worse health-related quality of life scores. Hypertrophy and presence of myocardial fibrosis increase risk of MACE by 4-5 times, and dyslipidemia increases risk of MACE by 3 times. Early Fabry-specific treatment and close monitoring of comorbidities reduce cardiac complications and mortality. These findings highlight the importance of comprehensive multidisciplinary management to help improve outcomes in FD patients.


[Clinical observation on aplastic anemia treated by Spatholobus suberectus Composita].
To investigate the pharmaceutical effect of Spatholobus Suberectus Composita (SEC) on bone marrow hematopoiesis and microenvironment of aplastic anemia. One hundred and six cases of aplastic anemia patients were treated by SEC and the pathological change of bone marrow were observed before and after treatment for 24 months, and compared with 17 cases of normal volunteers as control. The total effective rate was 77.4%. The degree of marrow hyperplasia (15.7 +/- 10.2 vol% vs 39.2 +/- 13.9 vol%), the percentage of the granulocytes (31.4 +/- 12.4% vs 39.9 +/- 10.4%), the erythroblastes (19.8 +/- 15.9% vs 36.7 +/- 13.5%), megakaryocytes (1.4 +/- 2.3 cell/section vs 24.0 +/- 24.6 cells/section), and the microvessel number (40.0 +/- 23.4 ves/100 mm2 vs 201.0 +/- 141.0 ves/100 mm2) ascended significantly (P < 0.01 or P < 0.05). SEC could not only irritate the hematopoiesis, but also exert reconstructive action to marrow microenvironment.


Various Properties of Silicone Breast Implant Surfaces and Multimodal Techniques for the Functional Surface Modification.
"Silicone breast implants are the most widely used medical devices for breast reconstruction and augmentation, and revision, but even after more than 60 years of use they are associated with multiple continued complications. Using advancement in current technologies, researchers are attempting to create an optimal implant surface for patients. Through these efforts, plastic surgeons and material researchers have made great progress in the field of implant research. Multimodal techniques for the functional modification of implant surfaces will contribute to further the development of ideal biomaterials useful in breast implants.


Autologous serum therapy in chronic urticaria.
Autologous serum therapy is a promising therapy for treatment resistant urticaria. This is useful in developing countries as this is economical option. Minimum instruments like centrifuge, syringe and needles are required for the procedure.


Optical comparison between micro-CT and OCT in imaging of marginal composite adaptation: Observational study.
Dental composite is the most used aesthetic restorative biomaterial worldwide. However, it undergoes polymerisation shrinkage that could lead to loss of the interfacial seal between tooth and resin in some circumstances. This demands high-resolution imaging technologies to detect these defects. This study carried out a comparison between microcomputed tomography (micro-CT; Shimadzu, Japan) and swept-source optical coherence tomography (SS-OCT; Santec, Japan) in the detection of marginal adaptation defects at the tooth-resin interface. Unlike in micro-CT, it was possible to outline interfacial gaps along with tooth-resin interfaces with SS-OCT, which was attributed to the Fresnel diffraction of light. This in vitro comparison demonstrates SS-OCT has great potential in dental imaging to effectively assess dental composite adaptation and marginal defects when high resolution is desired in real time. LAY DESCRIPTION: Detection of tooth-colored restoration defects had been assessed by different radiographic methods. However, most of these methods are either invasive or suffer from low-resolution. In this study, a comparison has been carried out between two different high-resolution imaging systems; microcomputed tomography and optical coherence tomography, to explore their potentials in detecting restorations defects. The results showed optical coherence tomography has a great accuracy in locating the underlying defects when the obtained images were validated against confocal laser scanning microscopy images.


Interpersonal youth violence perpetration and victimization in a diverse Asian American and Pacific Islander adolescent sample.
This study was the first to examine ethnic, sex, and ethnicity-by-sex differences for under-researched, Asian American and Pacific Islander, adolescent groups on youth violence outcomes other than cyberbullying. This effort included the less researched, emotional violence, and included socioeconomic status (SES) measures as covariates. The sample size from 2 high schools in spring 2007 was 881, using an epidemiologic survey design. The pattern of results was higher rates of violence victimization for ethnic groups, with lower representation in the 2 schools' population, and ethnic groups that more recently moved or immigrated to Hawai'i. For emotional victimization, girls of European American and "other", ethnicities self-reported higher rates than boys. Several implications (e.g., need for ethnically and gender-based approaches) and further research (e.g., ethnocultural identity) are discussed.


Surface immobilization of active vascular endothelial growth factor via a cysteine-containing tag.
Developing tissue engineering scaffolds with immobilized growth factors requires facile and reliable methods for the covalent attachment of functionally active proteins. We describe here a new approach to immobilize recombinant proteins based on expression of the protein of interest with a 15-aa long fusion tag (Cys-tag), which avails a free sulfhydryl group for site-specific conjugation. To validate this approach, we conjugated a single-chain vascular endothelial growth factor expressed with an N-terminal Cys-tag (scVEGF) to fibronectin (FN) using a common thiol-directed bi-functional cross-linking agent. We found that the FN-scVEGF conjugate retains VEGF activity similar to that of free scVEGF when used as a soluble ligand. Cells expressing VEGF receptor VEGFR-2 grown on plates coated with FN-scVEGF displayed morphological phenotypes similar to those observed for cells grown on FN in the presence of equivalent amounts of free scVEGF. In addition, 293/KDR cell growth stimulation was observed in the same concentration range with either immobilized or free scVEGF. The effects of immobilized scVEGF, and soluble scVEGF were blocked by NVP-AAD777-NX, a VEGF receptor tyrosine kinase inhibitor. These data indicate that site-specific immobilization via Cys-tag provides a facile and reliable method for permanent deposition of functionally active growth factors on synthetic or protein scaffolds with applications for advanced tissue engineering.


Management of distal humeral fractures in the elderly.
Although relatively uncommon, fractures of the distal humerus in the elderly patient population are significant injuries of which optimal management is a subject of debate in orthopaedic literature. The combination of complex anatomy, poor bone quality and extensive comminution often seen with these fractures makes successful treatment difficult. Currently, most surgeons support surgical fixation of distal humeral fractures with the belief that restoration of the patient's native elbow joint provides the best opportunity for a good functional outcome. Others have proposed the use of total elbow arthroplasty as a primary treatment method for geriatric distal humeral fractures based on the difficulties associated with ORIF and the relatively low demands of this patient population. To date, there have been no prospective randomised trials comparing these two treatment alternatives, and a comparison of available outcome data shows good functional outcome for both forms of fracture management. With the aging of the population and an associated increase in the incidence of distal humeral fractures, the debate over the optimal treatment regime will undoubtedly continue.


Developing population health scientists: Findings from an evaluation of the Robert Wood Johnson Foundation Health & Society Scholars Program.
•RWJF Health & Society Scholars (HSS) program outcomes evaluated.•HSS alumni have higher scholarly productivity and impact than control group.•HSS alumni are more engaged in population health research than controls.•HSS alumni and controls are similar on other outcome measures.•Training programs can be evaluated with adequate attention to selection bias.


Adverse cardiac remodeling augments adipose tissue ß-adrenergic signaling and lipolysis counteracting diet-induced obesity.
Cardiac triacylglycerol accumulation is a common characteristic of obesity and type 2 diabetes and strongly correlates with heart morbidity and mortality. We have previously shown that cardiomyocyte-specific perilipin 5 overexpression (Plin5-Tg) provokes significant cardiac steatosis via lowering cardiac lipolysis and fatty acid (FA) oxidation. In strong contrast to cardiac steatosis and lethal heart dysfunction in adipose triglyceride lipase deficiency, Plin5-Tg mice do not develop heart dysfunction and show a normal life span on chow diet. This finding prompted us to study heart function and energy metabolism in Plin5-Tg mice fed high-fat diet (HFD). Plin5-Tg mice showed adverse cardiac remodeling on HFD with heart function only being compromised in one-year-old mice, likely due to reduced cardiac FA uptake, thereby delaying deleterious cardiac lipotoxicity. Notably, Plin5-Tg mice were less obese and protected from glucose intolerance on HFD. Changes in cardiac energy catabolism in Plin5-Tg mice increased ß-adrenergic signaling, lipolytic, and thermogenic protein expression in adipose tissue ultimately counteracting HFD-induced obesity. Acute cold exposure further augmented ß-adrenergic signaling in Plin5-Tg mice, whereas housing at thermoneutrality did not protect Plin5-Tg mice from HFD-induced obesity albeit blood glucose and insulin levels remained low in transgenic mice. Overall, our data suggest that the limited capacity for myocardial FA oxidation on HFD increases cardiac stress in Plin5-Tg mice, thereby stimulating adipose tissue ß-adrenergic signaling, triacylglycerol catabolism, and thermogenesis. However, long-term HFD-mediated metabolic stress causes contractile dysfunction in Plin5-Tg mice, which emphasizes the importance of a carefully controlled dietary regime in patients with cardiac steatosis and hypertrophy.


Skeletal muscle - A bystander or influencer of metabolic syndrome?
Metabolic syndrome is the concurrent presentation of multiple cardiovascular risk factors, including obesity, insulin resistance, hyperglycemia, dyslipidemia and hypertension. It has been suggested that some of these risk factors can have detrimental effects on the skeletal muscle while others can be a direct result of skeletal muscle abnormalities, showing a two-way directionality in the pathogenesis of the condition. This review aims to explore this bidirectional correlation by discussing the impact of metabolic syndrome on skeletal muscle tissue in general and will also discuss ways in which skeletal muscle alterations may contribute to the pathogenesis of metabolic syndrome. Literature searches were conducted with key words (e.g. metabolic syndrome, skeletal muscle, hyperglycemia) using PubMed, EBSCOhost, Science Direct and Google Scholar. All article types were included in the search. The pathological mechanisms associated with metabolic syndrome, such as hyperglycemia and inflammation, have been associated with changes in skeletal muscle fiber composition, metabolism, insulin sensitivity, mitochondrial function, and strength. Additionally, some skeletal muscle alterations, particularly mitochondrial dysfunction and insulin resistance, are suggested to contribute to the development of metabolic syndrome. For example, the suggested underlying mechanisms of sarcopenia development are also contributors to metabolic syndrome pathogenesis. Whilst numerous studies have identified a relationship between metabolic syndrome and skeletal muscle abnormalities, further investigation into the underlying mechanisms is needed to elucidate the best prevention and management strategies for these conditions.


Histochemical and ultrastructural changes in locally gamma-irradiated rabbit intestine.
The effect of local irradiation of a 50-cm long intestinal segment outside the abdominal cavity in rabbits has been studied. The rabbits were killed at 12, 24, 48 and 72 hours after irradiation. Activities of succinate and lactate dehydrogenase, acid and alkaline phosphatase and thiamine pyrophosphatase were studied histochemically in the irradiated intestinal segment and in the part of the intestine remaining in the abdominal cavity. The same material was studied electron-microscopically. Changes in enterocytes of the intestinal crypts were observed mainly in the mitochondria and in the form of a chaotic distribution of endoplasmic membranes and densely scattered ribosomes. In intestinal crypt cells, irradiation was followed by a depression in the activities of succinate and lactate dehydrogenases and alkaline phosphatase. These changes were related to postradiation damage, not to recovery.


Extracellular Vesicle-Mediated Bilateral Communication between Glioblastoma and Astrocytes.
Glioblastoma the most aggressive form of brain cancer, comprises a complex mixture of tumor cells and nonmalignant stromal cells, including neurons, astrocytes, microglia, infiltrating monocytes/macrophages, lymphocytes, and other cell types. All nonmalignant cells within and surrounding the tumor are affected by the presence of glioblastoma. Astrocytes use multiple modes of communication to interact with neighboring cells. Extracellular vesicle-directed intercellular communication has been found to be an important component of signaling between astrocytes and glioblastoma in tumor progression. In this review, we focus on recent findings on extracellular vesicle-mediated bilateral crosstalk, between glioblastoma cells and astrocytes, highlighting the protumor and antitumor roles of astrocytes in glioblastoma development.


2,3,5,4'-Tetrahydroxy stilbene-2-Ο-β-D-glucoside, a mechanism-based inactivator of CYP2C19 and CYP3A4, potentiates hepatic protein adduction and hepatotoxicity induced by emodin in vivo.
2,3,5,4'-Tetrahydroxy stilbene-2-Ο-β-D-glucoside (TSG) and emodin (EMD) are two main components of Polygonum multiflorum Thunb. (PMT). Its root is widely used as herbal medicine and supplement. However, PMT-induced liver injury has drawn increasing attention. The purpose of this study was to investigate the interaction of TSG with EMD in the aspects of enzymology, pharmacokinetics, and hepatotoxicity. Co-administration with TSG increased internal exposure of EMD, EMD-derived hepatic protein adduction, and EMD-induced liver injury in mice. Mouse and human liver microsomal incubation study demonstrated that co-incubation with TSG decreased the formation of hydroxylation metabolites of EMD. Human recombinant cytochrome P450 enzyme incubation study showed that TSG induced time-, concentration-, NADPH-dependent and irreversible inhibition of CYP2C19 and CYP3A4. An epoxide metabolite derived from TSG was responsible for the observed enzyme inactivations. The findings allow us to better understand the mechanisms by which herbal processing detoxifies raw PMT.


Quantification of pulmonary microcirculation by dynamic contrast-enhanced magnetic resonance imaging: comparison of four regularization methods.
Tissue microcirculation can be quantified by a deconvolution analysis of concentration-time curves measured by dynamic contrast-enhanced magnetic resonance imaging. However, deconvolution is an ill-posed problem, which requires regularization of the solutions. In this work, four algebraic deconvolution/regularization methods were evaluated: truncated singular value decomposition and generalized Tikhonov regularization (GTR) in combination with the L-curve criterion, a modified LCC (GTR-MLCC), and a response function model that takes a-priori knowledge into account. To this end, dynamic contrast-enhanced magnetic resonance imaging data sets were simulated by an established physiologically reference model for different signal-to-noise ratios and measured on a 1.5-T system in the lung of 10 healthy volunteers and 20 patients. Analysis of both the simulated and measured dynamic contrast-enhanced magnetic resonance imaging datasets revealed that GTR in combination with the L-curve criterion does not yield reliable and clinically useful results. The three other deconvolution/regularization algorithms resulted in almost identical microcirculatory parameter estimates for signal-to-noise ratios > 10. At low signal-to-noise ratios levels (<10) typically occurring in pathological lung regions, GTR in combination with a modified L-curve criterion approximates the true response function much more accurately than truncated singular value decomposition and GTR in combination with response function model with a difference in accuracy of up to 76%. In conclusion, GTR in combination with a modified L-curve criterion is recommended for the deconvolution of dynamic contrast-enhanced magnetic resonance imaging curves measured in the lung parenchyma of patients with highly heterogeneous signal-to-noise ratios.


COVID-19 anxiety scale (CAS): Development and psychometric properties.
The objective of the present research is to develop and validate the COVID-19 Anxiety Scale (CAS). We conducted three studies to gather evidence regarding content and construct validity, as well to evaluate the reliability of the measure. Study 1 is subdivided into two studies. In Study 1a, we analyze the content validity of the new measure through content expert analysis (N = 10 expert raters). In Study 1b (N = 30), we perform a pilot study with a sample from the target population. In Study 2 (N = 352), we explored the unifactorial structure of the measure, and analyzed its internal consistency verified. Finally, in Study 3 (N = 200), we assess the adequacy of the factor structure and gather evidence on convergent-discriminant validity and gender-scale invariance. In summary, our results demonstrate that CAS is a reliable and adequate instrument to assess COVID-19 related anxiety.


Double balloon catheters: A promising tool for induction of labor in multiparous women with unfavorable cervices
To compare the effectiveness and safety of oxytocin and a cervical ripening balloon in women with unfavorable cervices for inducing labor. A total of eighty pregnant women between 37-41 gestational weeks having singleton pregnancies and intact membranes with unfavorable cervices were randomized into two groups, cervical ripening balloon (n=40) and oxytocin infusion (n=40). The primary outcomes were the labor time and the route of delivery. Secondary outcomes were the effect of parity on time of labor, and obstetric and perinatal outcomes. The median time to delivery was 9.45 hours in cervical ripening balloon group and 13.2 hours in the oxytocin group in multiparous women. The differences were statistically significant (p<0.001). The median time until delivery was 11.48 hours in cervical ripening balloon group and 13.46 hours in the oxytocin group; the differences were statistically significant (p<0.001). Cesarean delivery ratios were similar in both groups (p=0.431). The results of the present study are promising for balloon use, especially in multiparous women. It is beneficial to support these data with wide ranging population-based studies.


Cognitive-emotion processing in psychogenic nonepileptic seizures.
Previous literature suggests that cognitive-emotion processing contributes to the pathogenesis of psychogenic nonepileptic seizures (PNES). Characterization of alterations in cognitive-emotion processing in PNES could inform treatment. In this descriptive, cross-sectional study, 143 patients with video electroencephalogram (EEG) confirmed PNES were prospectively recruited. Patients completed self-report questionnaires on emotion perception (Trait Meta-Mood Scale (TMMS) attention and clarity subscales) and coping style (Affective Styles Questionnaire [ASQ] concealing, adjusting, and tolerating subscales) at the time of their initial evaluation for PNES. Demographic, clinical data and measures of psychopathology severity were also obtained. The TMMS and ASQ subscale scores were compared to available normative data and between PNES subgroups (based on presence of trauma-related factors). Correlation coefficients were obtained to evaluate associations between subscale scores and measures of psychopathology. Mean scores on both TMMS subscales (attention 47.0 [SD 7.4] and clarity 37.5 [SD 8.0]) and the ASQ adjusting subscale (22.2 [SD 6.3]) were significantly lower than available normative data (p < .001). Among patients with PNES, those with a history of childhood abuse or active posttraumatic stress disorder (PTSD) were found to have significantly lower scores on emotion clarity, adjustment, and tolerance subscales than those without such histories (p < .05). Degree of clarity of emotions correlated negatively with severity of depression, anxiety, stress, and illness perception (p ≤ .001). Adjustment to and tolerance of emotional states correlated negatively with severity of depression and stress (p < .01). Patients with PNES, especially those with active PTSD and childhood trauma, have lower clarity of their emotions and lower ability to adjust to emotional states than healthy individuals. These cognitive-emotion processing deficits are more pronounced in patients with more severe depression and reported stress. This study characterizes alterations in cognitive-emotion processing in PNES that are well-suited therapeutic targets and can therefore inform treatment interventions.


Gas-liquid chromatographic method for the routine estimation of disopyramide in plasma or serum.
A rapid, sensitive and specific gas-liquid chromatographic method is presented for the routine monitoring of plasma concentrations of the anti-arrhythmic compound, disopyramide. The procedure involves extraction of the drug from alkaline plasma into ether, purification of the extract and gas chromatographic analysis using OV-101 liquid phase and flame ionization detection. The results demonstrate the accuracy and reproducibility of the method. Contrary to a previous report, it has been shown that delay in separating plasma from erythrocytes does not affect the disopyramide level in plasma.


Applications for nitric oxide in halting proliferation of tumor cells.
Tumor resistance to cytotoxic therapeutics coupled with dose-limiting toxicity is a serious hurdle in the field of medical oncology. In the face of this obstacle, nitric oxide has emerged as a powerful adjuvant for the hypersensitization of tumors to more traditional chemo- and radio-therapeutics. Furthermore, emerging evidence indicates that nitric oxide donors have the potential to function independently in the clinical management of cancer. Herein, we discuss the role of nitric oxide in cancer and the potential for nitric oxide donors to support conventional therapeutics.


Nrf2-Mediated System xc- Activation in Astroglial Cells Is Involved in HIV-1 Tat-Induced Neurotoxicity.
HIV-associated neurocognitive disorders (HANDs) affect a large part of HIV-infected patients, despite highly active antiretroviral therapy. HANDs occur in the absence of a direct infection of neurons. Nevertheless, viral proteins (e.g., Tat) are capable to cause neuronal dysfunction via oxidative stress, but the cellular pathways leading to HANDs are not yet fully defined. Here, we investigated the effects of Tat on Nrf2-mediated antioxidant response and system xc- expression in U373 human astroglial cells. Moreover, the effect of Tat-producing astrocytes on neuronal cell viability was assessed using SH-SY5Y cells as a culture model. We demonstrated that Tat produced by astrocytes was able to induce Nrf2 activation and system xc- expression in astrocytes, thus reducing cell viability of co-cultured neuronal cells. Furthermore, sulfasalazine, a specific system xc- inhibitor, was able to reduce extracellular glutamate and to prevent the reduction of neuronal viability, thus demonstrating that the neurotoxic effect was dependent on an increased glutamate release through the transporter. Our findings provide evidence of the involvement of astroglial Nrf2/system xc- pathway in the neurotoxicity induced by HIV-1 Tat protein, thereby suggesting how astrocytes may exacerbate neurodegeneration through the conversion of an antioxidant response to excitotoxicity.


Stachyose increases intestinal barrier through Akkermansia muciniphila and reduces gut inflammation in germ-free mice after human fecal transplantation.
Early life is a crucial period for the development of the intestinal microbiota and is related to the body's immunity. Yet research is lacking regarding the effect of stachyose on infants gut microbiomes at this stage and the mechanism is not clear. Therefore, in this experiment, feces samples collected from infants were transplanted into germ-free mice, to explore the effect of stachyose on the intestinal microbiota and host gut barrier. We found that stachyose promoted the relative abundance of A. muciniphila in human feces; enhanced the symbiotic relationships of A. muciniphila; increased the short-chain fatty acid level, and secretory immunoglobulin A level; reduced the levels of lipopolysaccharide, IL-1, IL-17 and TNF-α through downregulated the expression of NF-κB; increased expression of tight junction proteins (occludin and ZO-1) and goblet cell through A. muciniphila. The intake of stachyose is conducive to promoting the proliferation of beneficial bacteria and enhancing the intestinal barrier in germ-free mice. This research provides a theoretical basis for the use of prebiotics to improve intestinal microbiota and barrier in humans.


The effect of knowledge levels of intensive care nurses about pressure injuries on their attitude toward preventing pressure injuries.
The aim of this study was to determine the current knowledge levels of intensive care nurses about pressure injuries and their attitudes toward preventing pressure injuries, and to reveal the relationship between these variables. This descriptive cross-sectional study was conducted with 152 nurses, working in the Adult Intensive Care Units of a Training and Research Hospital. Data were collected between 10.08.2021 and 31.11.2021 with the Patient Information Form, Modified Pieper Pressure Ulcer Knowledge Test and Attitude toward Pressure Injury Prevention Scale. Frequency analysis, descriptive statistics, multiple logistic regression analysis and the structural equation modeling technique were used in the analysis of the study data. The mean age of the nurses was 25.82 ± 3.42 years, 86.2% of them were female and 67.1% of them had a bachelor's degree. Total mean score of the Modified Pieper Pressure Ulcer Knowledge Test of the intensive care nurses was found to be 32.58 ± 6.58. The knowledge score of 113 out of 152 nurses was ≥60% or above. The total mean score of the Attitude toward Pressure Injury Prevention Scale was 42.00 ± 5.70 and a total of 76.97% (117 participants) of them were found to score 75% or above on the scale. The results of the regression analysis showed that educational degree, and status of having training about pressure injuries did not affect the total mean score of the Knowledge Test and the Attitude Scale. However, it revealed that the frequency of encountering a patient with pressure injuries in the unit where they work has affected the total mean score of the scales significantly (p < 0.05). As per the results of the structural equation model, the Modified Pieper Pressure Ulcer Knowledge Test scores of the nurses were found to have a statistically significant effect on the scores of the Attitude toward Pressure Injury Prevention Scale (p < 0.05). This study revealed that intensive care unit nurses had a positive attitude toward Pressure Injury Prevention and their knowledge was sufficient and that as the Modified Pieper Pressure Ulcer Knowledge Test scores increase, their positive attitude toward Pressure Injury Prevention also increases.


Effect of CCL4-induced cirrhosis on the pathophysiologic course of acute myocardial infarction in nonarteriosclerotic vs arteriosclerotic male rats.
Arteriosclerotic and nonarteriosclerotic rats were treated with carbon tetrachloride (CCL4) to induce cirrhosis of the liver. Massive myocardial infarction was then induced in intact and CCL4-treated animals. During acute necrosis (Days 1 thru 3), animals were killed at 4, 8, 12 and 24 h on Days 1 and 2, and during myocardial repair on Days 4, 5 and 8. During the induction of cirrhosis, animals developed polydypsia, polyuria, and hyperglycemia; during myocardial infarction, the arteriosclerotic + cirrhotic animals developed severe and persistent congestive heart failure, i.e., hydrothorax. Adrenal and thymus gland weights and corticosterone levels indicated that cirrhosis per se increased pituitary--adrenal activity, particularly in arteriosclerotic animals. Enzyme levels of SGOT and SGPT demonstrated severe hepatic damage due to cirrhosis and acute myocardial infarction. Blood triglycerides and cholesterol responded abnormally in cirrhotic animals during acute myocardial ischemia due to their entrapment within hepatic cells. The cirrhotic animals manifested poor myocardial repair with persistent foci of necrosis, calcification, and a high incidence of large, occlusive, atrial thrombi. It is suggested that cirrhosis interferes with lipid metabolism and adrenal steroid conjugation leading to abnormal levels of mineralocorticoids which favor congestive heart failure, poor myocardial repair, and atrial thrombosis.


On-line electro-oculography.
The design and use of an on-line PDP 11/40-based system for quantitative study of ocular kinetics are described. The system can be used in neurophysiological or ophthalmological applications. Two different techniques are presented. In one, horizontal, vertical or oblique eye motion can be studied, in the other horizontal eye motion only. Several parameters of eye motion can be measured including saccadic velocity, eye movement latency and accuracy of refixation. For ophthalmological EOG applications the system allows measurement of the absolute voltage excursion corresponding to a horizontal eye movement of a specific amplitude. The system consists of five software programs and supporting signal processing equipment. The software package runs under the RSX11M executive.


Use of the fascial stapler in proctopexy for rectal prolapse.
Proctopexy using synthetic mesh is a popular method of treating rectal prolapse. Suturing the graft to the presacral fascia is time-consuming and can lead to complications. With the fascial stapler, two parallel rows of three staples are used to quickly and securely anchor the Marlex sling to the sacrum, thus avoiding hemorrhage from the presacral veins. Fourteen patients have been treated with no complications.


Decreased acetylation of isoniazid in chronic renal failure.
Pharmacokinetic parameters of isoniazid obtained from 37 normal subjects were compared with parameters obtained from 14 patients with chronic renal failure. In the 29 normal rapid acetylators and eight normal slow acetylators, the mean plasma half-life values of isoniazid were 1.54 +/- 0.31 and 3.68 +/- 0.59 hours, respectively. The plasma half-life values of isoniazid in patients with chronic renal failure varied widely from 1.30 to 10.13 hours, but the values were significantly longer than those of normal subjects. Because isoniazid clearance is governed mainly by hepatic metabolism, such a significant prolongation of plasma half-life of isoniazid was unexpected; thus the pharmacokinetics of isoniazid were reevaluated in the same patients with chronic renal failure after the kidney transplantation. After successful kidney transplantation, the shortening of isoniazid half-life was pronounced and the nonrenal clearance was markedly increased. These findings indicate that decreased isoniazid clearance in chronic renal failure is caused in minor part by the decreased renal excretion of isoniazid and in major part by the depressed hepatic N-acetylation of isoniazid.


Fabrication of mechanical robust keratin film by mesoscopic molecular network reconstruction and its performance for dye removal.
Regenerated keratin-based adsorbents have attracted much attention in environmental pollution remediation. However, fabricating keratin-based adsorbents with excellent adsorption performance is still a challenging issue due to its weak mechanical property. In this study, mechanical robust keratin composite films were designed and engineered at mesoscopic scale by molecular network reconstruction strategy. It was found that the β-crystallites structure of silk fibroin template could induce the transformation of free unfolded molecular chains of keratin to β-sheet conformation and further resulted in the controllable manipulating of the mechanical properties of keratin films. This mechanical reinforced composite film showed high adsorption efficiency and capacity for dyes as well as ideal regeneration and recycling performance. Adsorption behavior of reactive brilliant blue KN-R by keratin composite films was comprehensively studied. The adsorption capacity (qe) and removal efficiency for KN-R by the adsorbent could reach as high as 190.84 mg/g and 98.52%, respectively. The adsorbent exhibited excellent regeneration and recycling performance due to its mechanical robustness. The molecular network reconstruction strategy is both straightforward and effective for fabricating mechanical robust adsorbent for pollutant remediation.


[Train-the-Trainer: Professionalisation of Didactics in Daily Clinical Routine - the Personal Perception of Clinical Teaching Staff with Respect to Didactic Competence and the Framework Conditions of Teaching].
Teaching training programs contribute to improving the quality of medical education. In a course of the Train-the-Trainer (TTT) concept of the Surgical Working Group for Teaching, teachers (TN) from different medical professions and career levels were taught together. Assessments of teaching activities in everyday clinical practice of residents (AÄ), senior staff (OÄ) and nurses (KP), their perception of teaching obstacles and requirements to improve teaching. Prior to the beginning of the course, biographical data, previous teaching experiences, teaching obstacles as well as their notions to improve teaching in the daily clinical routine were requested. Upon completion, the participants were asked to rate the course. The answers to the closed and open questions were evaluated quantitatively and qualitatively. From 2014 to 2017, six basic courses (TTT-A) were conducted at three locations. 97 participants participated in the surveys (AÄ n = 44, OÄ n = 19, KP n = 17). More than two-thirds declared previously acquired teaching knowledge. There were no significant differences between medical and nursing staff. While AÄ and KP primarily taught at the bedside, OÄ taught mainly in the context of lectures, electives and seminars. Only a small proportion of all occupational groups felt well prepared for teaching in everyday clinical practice. The main drawbacks were lack of time and staff, too many students per group and too little teaching knowledge. Nearly two-thirds of the AÄ found teaching in general as a strong or moderate burden, compared to about 50% of the OÄ and 60% KP. Aspirations for improvement of teaching included more precise characterisation of the learning objectives, greater appreciation of teaching as a whole, and regular measures to make teaching professional. Occupational group-related differences in everyday clinical practice and individual career progression, impact type, implementation and perception of the teaching activity. By focusing on learning objectives and essential teaching methods and examination formats relevant to teaching at the bedside, teacher training programs across professional groups can contribute to knowledge and expertise growth. Indications of a sustainable effect encourage the continuation and further development of the TTT concept.


Dynamic documentation of the evolution of retinopathy of prematurity in video format.
Serial digital photographic examinations have been combined into a video format, which shows development and evolution of the disease over time. This dynamic format has changed the teaching of retinopathy of prematurity (ROP) by illustrating the subtle changes in the temporal arcade angle and choroidal vascular pattern, which can be observed over time in these videos. Consecutive weekly or biweekly images were obtained on the same infant and were captured using digital retinal photography (RetCam 120) and then archived on compact discs. Those infants that were most photographic and demonstrative of the evolution of ROP were selected for animation. The optic nerve vessels were aligned and image border blended into the previous image using a layer mask, thus creating an animation of consecutive images. The videos highlight the evolving features of ROP, such as development of arborized vessels posterior to the ridge, development of Stage 3 lesions, progression of plus disease, choroidal vascular changes accompanying the progression of ROP, dynamic changes in the temporal arcade angle, and regression of disease following last photocoagulation. The documentation of this disease as it evolves and its presentation in video format, using digital retinal photographic technology, has allowed subtle anatomical changes to be visualized and potentially studied. This process highlights a new dimension of the dynamic nature of the disease for those involved in the care of an infant with ROP.


Theoretical study on efficient HF gas sensing by functionalized, decorated, and doped nanocone strategy.
Hydrogen fluoride (HF) is a highly dangerous and corrosive gas that can cause severe burns and respiratory damage. The density functional theory method (DFT) used to study the interaction between the HF gas and the surface of a carbon nanocone (CNC) doped with gallium atom as a chemical sensor. The results showed that CNC wasn't a good candidate to sense the HF gas and consequently its electrical properties are changed insignificant. To improve the properties of the CNC, several strategies were tried: functionalizing by pyridinol (Pyr) and pyridinol oxide (PyrO), decorated with metals (M = B, Al, and Ga), and doped with element of third group (M = B, Al, and Ga). The obtained data demonstrated that the promising results were obtained by doping the CNC with Ga atom. After full optimization, we achieved one stable configuration between the HF gas and CNC-Ga structure (S15 configuration) with Eads = -19.86 kcal/mol. The electronic properties of the CNC-Ga structure is sensible changed after the HF molecule is adsorbed. According to calculated the energy gap between HOMO and LUMO orbitals of S15 configuration are increased which could be applied a chemical signal. Eventually, one could propose that the CNC-Ga has the ability to act as a Φ-type sensor based on its physical adsorption energy and quick recovery time and doped with gallium atom is a promising strategy.


Infant stroke and beta-2-glycoprotein 1 antibodies: six cases.
The binding of autoimmune anticardiolipin antibodies to phospholipid has been shown to require a plasma cofactor, beta-2-glycoprotein 1 (beta2-GPI). Antibodies against beta2-GPI are associated with both venous and arterial thrombosis in adults and have been suggested as a new antiphospholipid syndrome marker. We present six children with cerebral thrombosis at the age of 0-12 months, who had IgG antibodies to beta2-GPI (titers 26, 29, 31, 39, 101 and 109 SGU, when 20 SGU was the cut-off). In at least four patients, the conventional antiphospholipid markers (lupus anticoagulant and IgG and IgM anticardiolipin) were negative. All six children had normal results in the other routine thrombophilia assays (thrombin time, antithrombin, protein C, protein S, factor V Leiden mutation, prothrombin mutation). the anti-beta-2 glycoprotein 1 assay, requiring only 5 microl serum, may be a useful addition to antiphospholipid-antibody diagnostics in cases of paediatric stroke.


Study on enhanced serum protein protecting and anti-cathepsin activities of various curcumin formulations containing traditional excipients and bio-enhancers.
Cathepsins have emerged out as significant targets in variety of tissue degenerative disorders such as inflammation, alzeimers, tumerogenesis including metastasis and invasion. Elevated levels of cathepsins and reduced cellular inhibitors at the site of these diseased conditions suggest the exploration of novel inhibitors of cathepsins. In the search of effective novel inhibitors as anti-cathepsin agents different natural products are also screened. One such molecule, curcumin has been reported as potential anti-cathepsin agent in recent past. Low solubility of curcumin makes it an important subject for screening effect of different pharmaceutical excipients toward enhanced solubility. In the present work we report serum protein protecting and anti-cathepsin activities of 28 different formulations of curcumin. The formulations have been prepared using four ingredients used in traditional medicinal system. Milk has been found to enhance solubility to a significant level. Cow milk fat, sucrose and piperine exhibited positive cooperation. The results have been explained on the basis of chemical behavior of different ingredients.


Microbial risk assessment: dose-response relations and risk characterization.
Characterizations of the risks associated with foodborne pathogens are dependent on the availability of information on the population's exposure to the biological agents. However, by itself, exposure data are insufficient to assess the public health impact of pathogenic microorganisms. This requires the availability of effective dose-response models. Successful development of models that describe dose-response relations for enteric pathogens is dependent on a sound understanding of the mechanisms of pathogenicity associated with individual pathogens. This includes knowledge of how the various pathogen, host, and food matrix factors influence pathogenicity. Currently, a group of sigmoidal mathematical equations are used to empirically describe dose-response relations. While these have proven to be highly useful, advances in microbial food safety risk assessment will likely require the development of mechanistic models that more effectively consider the range of factors that influence the frequency and severity of foodborne infections in a population.


Prevalence, Morphological Classification, And Factors Associated With Anemia Among Pregnant Women Accessing Antenatal Clinic At Itojo Hospital, South Western Uganda.
The study aimed to determine the prevalence, morphological classification, and risk factors of anemia among pregnant mothers attending antenatal clinic at Itojo hospital, Ntungamo district, southwestern Uganda. After obtaining an informed consent, 5mL of blood was collected from the vein of each participant for complete blood count (CBC) and peripheral film report. The CBC was performed using HumaCount 80 hematology analyzer (HUMAN Gesellschaft für Biochemica und Diagnostica mbH Max-Planck-Ring 21 65,205 Wiesbaden Germany). Peripheral blood smears were made and stained using Wright's Romanowsky stain and examined under ×1000 magnification for morphological classification of anemia. Structured questionnaires were administered to each participant to collect information on patients' demography and risk factors of anaemia in pregnancy. The data generated were prepared in EXCEL and later transferred to SPSS version 20 for analysis. Univariate logistic regression and multivariate logistic regression were used to evaluate the association of socio-demographic characteristics of the participants with anemia. A 95% confidence level was used and statistical significance was reached at p<0.05. One hundred and sixty-three participants (n=163) were recruited for the study with the median age of 25 years and range of (17 to 40 years). The overall prevalence of anemia was 12 (7.4%), the morphological classification was 1 (8.3%) normocytic normochromic anemia, 6 (50%) microcytic hypochromic anemia, and 5 (41.7%) macrocytic anemia. Spouse occupation (p=0.03), household income (p=0.04), use of insecticide-treated mosquito nets (p=0.001), history of urinary tract infection (p=0.002), use of haematinics (p≤0.001), and history of postpartum hemorrhage (p=0.03) were significantly associated with anemia in pregnancy. Despite the reported high prevalence of anemia in pregnancy in other areas within the country, anemia prevalence was low in this study. Routine screening for anemia at all antenatal care clinics countrywide is recommended.


Spectrophotometric study of the effects of surfactants and ethanol on the acidity constants of fluorescein.
In the present paper, a sensitive, fast and suitable method for the calculation of pK(a) values of fluorescein is proposed. The effects of sodium dodecyl sulfate (SDS) and Triton X-100 (TX-100) as a surface-active agent on the acidic and basic forms, and the spectral properties of fluorescein were studied by the spectrophotometric method. The study was performed in sub-micelle surfactant concentration, and absorption spectra at 300-550 nm intervals were recorded. Stepwise acidity constants of fluorescein at pH range 1.50-10.00 and at constant ionic strength 0.1M and 25 degrees C were determined using DATAN program using pH-spectrophotometric titration data. The method is efficient, however the component spectra showed intensive overlapping. The calculated acidity constants of fluorescein in water at ionic strength 0.1 are pK(a1)=2.20, pK(a2)=4.30 and pK(a3)=6.43. The acidity constants of the dye in ethanol-water solution were studied by the same procedure. Effect of surfactants and ethanol on acidity constants and pure spectrum of each component are also discussed.


Delayed myotoxicity in snake envenoming by the tiger snake group.
Snakebite on the North Coast of New South Wales is not an uncommon cause of envenoming. We report a case of a young woman who presented after a snake bite and did not develop fulminant signs and symptoms of envenoming until 32 h after the bite.


Oxidative metabolism is associated with physiological disorders in fruits stored under multiple environmental stresses.
In combination with low temperature, controlled atmosphere storage and 1-methylcyclopropene (ethylene antagonist) application are used to delay senescence of many fruits and vegetables. Controlled atmosphere consists of low O2 and elevated CO2. When sub-optimal partial pressures are used, these practices represent multiple abiotic stresses that can promote the development of physiological disorders in pome fruit, including flesh browning and cavities, although there is some evidence for genetic differences in susceptibility. In the absence of surface disorders, fruit with flesh injuries are not easily distinguished from asymptomatic fruit until these are consumed. Oxidative stress metabolites tend to accumulate (e.g., γ-aminobutyrate) or rapidly decline (e.g., ascorbate and glutathione) in vegetative tissues exposed to hypoxic and/or elevated CO2 environments. Moreover, these phenomena can be associated with altered energy and redox status. Biochemical investigations of Arabidopsis and tomato plants with genetically-altered levels of enzymes associated with the γ-aminobutyrate shunt and the ascorbate-glutathione pathway indicate that these metabolic processes are functionally related and critical for dampening the oxidative burst in vegetative and fruit tissues, respectively. Here, we hypothesize that γ-aminobutyrate accumulation, as well energy and antioxidant depletion are associated with the development of physiological injury in pome fruit under multiple environmental stresses. An improved understanding of this relationship could assist in maintaining the quality of stored fruit.


Phylum Nematoda: feeding habits for all valid genera using a new, universal scheme encompassing the entire phylum, with descriptions of morphological characteristics of the stoma, a key, and discussion of the evidence for trophic relationships.
This paper details a system for classifying the trophic relationships of the entire Phylum Nematoda, together with a table specifying the categories of every valid genus. This system encompasses both the diets of nematodes and how the food is obtained. The types of evidence used to evaluate trophic relationships and the inferences that can be drawn from each are evaluated. The general morphological and ecological characteristics of each trophic type are detailed, and a morphological key is presented. This information will enable the trophic relationships of any valid genus of nematodes to be assessed, along with currently undescribed genera, provided their affinities to existing genera can be ascertained. The system and list can add value to ecological, environmental and biodiversity studies where there is no morphological information, for example in environmental sequencing or metabarcoding studies.