The vasorelaxant effect of hydrogen sulfide is enhanced in streptozotocin-induced diabetic rats.
Hydrogen sulfide (H₂S) is an endogenous gas which has potent relaxant effect in vascular and nonvascular smooth muscles. In the present study, we have investigated how streptozotocin (STZ)-induced diabetes affected the relaxant effect of H₂S in rat isolated thoracic aorta and mesenteric and pulmonary arteries. Diabetes was induced by IV injection of STZ (35 mg/kg). Insulin treatment was applied by using insulin implants. At the end of 4 and 12 weeks, the thoracic aorta and mesenteric and pulmonary arteries were isolated, and the relaxation responses to sodium hydrogen sulfide (NaHS), diazoxide, and acetylcholine were evaluated. The mRNA and protein levels of H₂S-synthesizing enzymes were also examined by RT-PCR and Western Blot. The relaxation response to NaHS in the arteries isolated from both 4 and 12 week-diabetic rats was increased when compared with that obtained from the control group. Glibenclamide inhibited the relaxation response to NaHS in the arteries isolated from either diabetic or non-diabetic group of rats. Concurrent treatment of insulin to STZ-injected rats prevented the potentiation of the relaxant effect of NaHS in the arteries. However, acetylcholine and diazoxide-induced relaxation responses were not altered in diabetic group of rats. The mRNA and protein levels of H₂S-synthesizing enzymes were also not altered in diabetic rats. STZ-induced experimental diabetes in rats resulted in the potentiation of the relaxation response to H₂S in vascular tissues. The potentiated relaxation to H₂S in diabetic arteries may play a role in vascular complications frequently seen in severe diabetes.


Biocide resistant and antibiotic cross-resistant potential pathogens from sewage and river water from a wastewater treatment facility in the North-West, Potchefstroom, South Africa.
Exposure to antibiotics, biocides, chemical preservatives, and heavy metals in different settings such as wastewater treatment plants (WWTPs) may apply selective pressure resulting in the enrichment of multiple resistant, co- and cross-resistant strains of bacteria. The purpose of this study was to identify and characterize potentially pathogenic triclosan (TCS) - and/or, chloroxylenol (PCMX) tolerant bacteria from sewage and river water in the North-West, Potchefstroom, South Africa. Several potential pathogens were identified, with Aeromonas isolates being most abundant. Clonal relationships between Aeromonas isolates found at various sampling points were elucidated using ERIC-PCR. Selected isolates were characterized for their minimum inhibitory concentrations against the biocides, as well as antibiotic resistance profiles, followed by an evaluation of synergistic and antagonistic interactions between various antimicrobials. Isolates were also screened for the presence of extracellular enzymes associated with virulence. High-performance liquid chromatography revealed the presence of both biocides in the wastewater, but fingerprinting methods did not reveal whether the WWTP is the source from which these organisms enter the environment. Isolates exhibited various levels of resistance to antimicrobials as well as several occurrences of synergy and antagonisms between the biocides and select antibiotics. Several isolates had a very high potential for virulence but further study is required to identify the specific virulence and resistance genes associated with the isolates in question.


Are there young carers in oncology? A systematic review.
This systematic review aims to investigate the support children provide in the case of a relative's cancer. Searches were performed on four electronic databases (Embase, PsycINFO, PubMed and ScienceDirect) to identify studies that report on the support provided by children to a relative diagnosed with cancer. Two researchers independently evaluated the eligibility of the studies and cross-checked them for accuracy. The Crowe Critical Appraisal Tool (CCAT) was used to assess the quality of the studies included. Out of the 10948 articles screened, 30 were included in this review. Results highlighted that cancer provokes changes in families, such as shifts in roles and increased responsibilities for the youth. Children often provided significant support to their sick relative and family members, including practical, emotional, and medical support such as household duties, medical assistance, companionship, and distraction. However, they were designated as young carers in only one study. The support provided was associated with negative effects such as stress and fatigue, and with positive effects such as increased empathy and independence. Children wished to support their family but also named several needs, such as time for themselves and the opportunity to enjoy their childhood. The results of this systematic review highlight the importance of taking into account the support provided by young people facing the cancer of a relative and designating them as young carers. Much remains to be accomplished to officially recognize their role and to support them properly.


Rape prevention with college men: evaluating risk status.
This study evaluates the effectiveness of a theoretically based rape prevention intervention with college men who were at high or low risk to perpetrate sexually coercive behavior. Participants (N = 146) are randomly assigned to the intervention or control group. Outcomes include rape myth acceptance, victim empathy, attraction to sexual aggression, sex-related alcohol expectancies, and behavioral indicators, measured across three time points. Positive effects are found for rape myth acceptance, victim empathy, attraction to sexual aggression, and behavioral intentions to rape. Only rape myth acceptance and victim empathy effects sustain at the 5-week follow-up. High-risk men are generally unaffected by the intervention although low-risk men produced larger effects than the entire sample. Results suggest rape prevention studies must assess risk status moderation effects to maximize prevention for high-risk men. More research is needed to develop effective rape prevention with men who are at high risk to rape.


Effect of in-feed administration and withdrawal of tylosin phosphate on antibiotic resistance in enterococci isolated from feedlot steers.
Tylosin phosphate is a macrolide commonly administered to cattle in North America for the control of liver abscesses. This study investigated the effect of in-feed administration of tylosin phosphate to cattle at subtherapeutic levels and its subsequent withdrawal on macrolide resistance using enterococci as an indicator bacterium. Fecal samples were collected from steers that received no antibiotics and steers administered tylosin phosphate (11 ppm) in-feed for 197 days and withdrawn 28 days before slaughter. Enterococcus species isolated from fecal samples were identified through sequencing the groES-EL intergenic spacer region and subject to antimicrobial susceptibility testing, identification of resistance determinants and pulsed-field gel electrophoresis profiling. Tylosin increased (P < 0.05) the proportion of ery(R) and tyl(R) enterococci within the population. Just prior to its removal, the proportion of ery(R) and tyl(R) resistant enterococci began decreasing and continued to decrease after tylosin was withdrawn from the diet until there was no difference (P > 0.05) between treatments on d 225. This suggests that antibiotic withdrawal prior to slaughter contributes to a reduction in the proportion of macrolide resistant enterococci entering the food chain. Among the 504 enterococci isolates characterized, Enterococcus hirae was found to predominate (n = 431), followed by Enterococcus villorum (n = 32), Enterococcus faecium (n = 21), Enterococcus durans (n = 7), Enterococcus casseliflavus (n = 4), Enterococcus mundtii (n = 4), Enterococcus gallinarum (n = 3), Enterococcus faecalis (n = 1), and Enterococcus thailandicus (n = 1). The diversity of enterococci was greater in steers at arrival than at exit from the feedlot. Erythromycin resistant isolates harbored the erm(B) and/or msrC gene. Similar PFGE profiles of ery(R) E. hirae pre- and post-antibiotic treatment suggest that increased abundance of ery(R) enterococci after administration of tylosin phosphate reflects selection for strains that were already present within the gastrointestinal tract of cattle at arrival.


Elevated Atmospheric CO2 Concentration Has Limited Effect on Wheat Grain Quality Regardless of Nitrogen Supply.
Elevated atmospheric CO2 concentrations (e[CO2]) can decrease the grain quality of wheat. However, little information exists concerning interactions between e[CO2] and nitrogen fertilization on important grain quality traits. To investigate this, a 2-year free air CO2 enrichment (FACE) experiment was conducted with two CO2 (393 and 600 ppm) and three (deficiency, adequate, and excess) nitrogen levels. Concentrations of flour proteins (albumins/globulins, gliadins, and glutenins) and key minerals (iron, zinc, and sulfur) and baking quality (loaf volume) were markedly increased by increasing nitrogen levels and varied between years. e[CO2] resulted in slightly decreased albumin/globulin and total gluten concentration under all nitrogen conditions, whereas loaf volume and mineral concentrations remained unaffected. Two-dimensional gel electrophoresis revealed strong effects of nitrogen supply and year on the grain proteome. Under adequate nitrogen, the grain proteome was affected by e[CO2] with 19 downregulated and 17 upregulated protein spots. The downregulated proteins comprised globulins but no gluten proteins. e[CO2] resulted in decreased crude protein concentration at maximum loaf volume. The present study contrasts with other FACE studies showing markedly stronger negative impacts of e[CO2] on chemical grain quality, and the reasons for that might be differences between genotypes, soil conditions, or the extent of growth stimulation by e[CO2].


Characterization of the interaction between p100, a novel G-protein-related protein, and rat liver endosomes.
p100 is a recently identified 100 kDa protein which shares a putative receptor-binding sequence with the signal transducing G-proteins Gt and Gi. In liver, p100 immunoreactivity is distributed between the cytosolic and the microsomal fractions [Traub, Evans & Sagi-Eisenberg (1990) Biochem. J. 272, 453-458; Udrisar & Rodbell (1990) Proc. Natl. Acad. Sci. U.S.A. 87, 6321-6325]. More specifically, we have localized the membrane-associated form of p100 to an endosomal subfraction of rat liver microsomes. In this study we have investigated the nature of the interaction between p100 and microsomal membranes. p100 was located on the cytoplasmic surface of the microsomal vesicles, and could be released by treatment with 0.5 M-NaCl or 0.5 M-Tris/HCl, pH 7.0. However, p100 was not released by non-ionic detergents, such as Triton X-100. Binding of p100 to the membrane was reversible, as both membrane-released and cytosolic p100 could re-bind stripped (Tris-washed) microsomes. Soluble p100 could not, however, bind to untreated microsomes. Binding to stripped microsomes approached saturation and was inhibited by up to 60% by either heat treatment or mild trypsin treatment of the vesicles. This implies that the interaction between p100 and the microsomal vesicles involves the direct binding of p100 to vesicular proteins. This binding was regulated by both adenine and guanine nucleotides. As p100 contains a region similar to the C-terminal decapeptide of alpha i, (the alpha-subunit of Gi) and has a localization that is restricted to an endosomal subfraction, we propose that cytosolic p100 may bind to cytoplasmically exposed domains of internalized receptors. Thus, like the adaptins, p100 may be involved in the process of sorting and receptor trafficking through the endosomal compartment of the cells.


Experimental study of shape transitions and energy scaling in thin non-Euclidean plates.
We present the first quantitative measurements of shape and energy variation in non-Euclidean plates. Using environmentally responsive gel, we construct non-Euclidean disks of constant imposed Gaussian curvature, K(tar). We vary the disks' thickness t(0) and measure the dependence of configurations, surface curvature, and energy content on t(0). For K(tar)<0, configurations are of a single wavy mode and undergo a set of bifurcations that leads to their refinement with decreasing thickness. This leads to sharp increase in the amount of surface bending as t(0)→0, and to a slow decay of both bending and stretching energies. Both vary like t(0)(2), compared with t(0)(3) of the bending energy in disks with K(tar)>0.


Long-distance dispersal suppresses introgression of local alleles during range expansions.
During range expansions, even low levels of interbreeding can lead to massive introgression of local alleles into an invader's genome. Nonetheless, this pattern is not always observed in human populations. For instance, European Americans in North America are barely introgressed by Amerindian genes in spite of known contact and admixture. With coalescent spatially explicit simulations, we examined the impact of long-distance dispersal (LDD) events on introgression of local alleles into the invading population using a set of different demographic scenarios applicable to a diverse range of natural populations and species. More specifically, we consider two distinct LDD models: one where LDD events originate in the range core and targets only the expansion front and a second one where LDD events can occur from any area to any other. We find that LDD generally prevents introgression, but that LDD events specifically targeting the expansion front are most efficient in suppressing introgression. This is likely due to the fact that LDD allows for the presence of a larger number of invader alleles at the wave front, where effective population size is thus increased and local introgressed alleles are rapidly outnumbered. We postulate that the documented settlement of pioneers directly on the wave front in North America has contributed to low levels of Amerindian admixture observed in European Americans and that this phenomenon may well explain the lack of introgression after a range expansion in natural populations without the need to evoke other mechanisms such as natural selection.


Important role of β1-integrin in fucoidan-induced apoptosis via caspase-8 activation.
Fucoidan induces apoptosis by activating caspase-8 in human MCF-7 breast cancer cells, but the detailed mechanism for this is not understood. We demonstrate here that fucoidan interacted with the cell surface, and silencing the β1-integrin gene expression inhibited fucoidan-induced apoptosis accompanied by caspase-8 activation. Fucoidan induced formation of the β1-integrin-caspase-8 complex. These data indicate that β1-integrin is an important factor for the cell-surface binding of fucoidan and plays an important role in fucoidan-induced apoptosis. Fucoidan also induced recruitment of caspase-8 to the β1-integrin intracellular domain, cleaved it into the activated protein by direct combination with β1-integrin, and induced apoptosis via the caspase cascade in MCF-7 cells.


Maternal pregnancy C-reactive protein predicts offspring birth size and body composition in metropolitan Cebu, Philippines.
The gestational milieu is an important influence on fetal development and long-term disease risk. Here we assess relationships between maternal pregnancy inflammation, indicated by C-reactive protein (CRP), and offspring anthropometric outcomes measured soon after birth. Data come from female participants (n=327, age 24.4-30.2 years) in a longitudinal study located in Metropolitan Cebu, Philippines. Between 2009 and 2014, pregnancy interviews (n=429) were conducted during which questionnaire and anthropometric data were obtained along with dried blood spot cards for CRP measurement. Offspring body weight, length, head circumference and five skinfold thickness measures were obtained soon after birth. Maternal pregnancy CRP was borderline (-1.11±0.64 days/log-mg/l; P<0.1) inversely related to gestational age at delivery, but did not increase the likelihood of preterm delivery. After adjusting for maternal pre-pregnancy body mass index, height, pregnancy adiposity, age, parity and other covariates, CRP was significantly, inversely related to offspring body weight (-0.047±0.017 kg/log-mg/l), length (-0.259±0.092 cm/log-mg/l) and sum of skinfolds (-0.520±0.190 mm/log-mg/l) (all P<0.05), and borderline inversely related to offspring head circumference (-0.102±0.068 cm/log-mg/l; P<0.1). Notably, relationships were continuous across the full CRP range, and not limited to unusually high levels of inflammation. These findings point to an important role of maternal non-specific immune activation as a predictor of offspring birth outcomes. In light of evidence that early life microbial, nutritional and stress experiences influence adult inflammatory regulation, these findings point to inflammation as a potential pathway for the intergenerational transmission of maternal experience to offspring health.


Development of automated text-message reminder system to improve uptake of child vaccination in Ethiopia.
Non-attendance and delay for vaccination schedules remains a big challenge to healthcare workers. Among the frequently mentioned reasons for missed vaccination in children is forgetfulness of caretakers to show up in vaccination schedules. This necessitates developing an automated reminder system with integration of mobile technologies. This paper aimed to develop and test an automated mobile text message reminder system in the local context of Ethiopia. This system is developed using iterative development process through phases of requirement analysis, design, development, testing and refinement. Requirement gathering was done before development of the system. Front end application was developed using java technologies while back end applications were developed with oracle database. Finally, pilot testing of the automated reminder system was done on 30 participants. The automated system has been developed based on requirements. The text message reminder system has two components: 1. Web based application for client registration and automatic reminder scheduling; 2. SMS application for automatic SMS text messaging. In the pilot testing, all the text messages (100%) were dispatched from the automated system to the respective participants. Finally, the system has shown a notification that the text messages have been sent successfully. Text message reminder system has been developed for routine childhood immunization program in Ethiopian context. Text message based mHealth interventions should be carefully designed, developed, tested and refined before actual implementation.


Australian nursing and midwifery student beliefs and attitudes about domestic violence: A multi-site, cross-sectional study.
Nurses and midwives have a professional responsibility to identify and provide effective care to those experiencing domestic violence. Pre-registration preparation may develop this capability. In order to inform curriculum development, this study explored Australian nursing and midwifery students' attitudes and beliefs about domestic violence. Data were collected between June and October 2017. Descriptive statistics were calculated and comparative analysis performed on independent variables. Thematic analysis was performed on open-ended qualitative responses. Participants included 1076 students from nine Australian universities. The majority were enrolled in nursing programs (88.4%), followed by midwifery (8.6%), and combined nursing/midwifery (2.4%) programs. There was no statistically significant difference in scores by year level across all subscales, suggesting there was no developmental change in beliefs and attitudes toward domestic violence over the course of study. Nursing students held views that were more violence-tolerant than midwifery students. Australian and Chinese-born males were more likely to refute that domestic violence is more common against women. Students had a limited understanding of domestic violence suggesting a critical need to address undergraduate nursing and midwifery curricula.


[Changes in body composition in adult patients with hypopituitarism after substitutive treatment with growth hormone].
Adult growth hormone (GH) deficiency is associated with changes in body composition, with lower total body water (TBW) and fat free mass (FFM) and higher fat mass (FM). These changes can be modified after sustitutive treatment with GH. We studied 20 patients, 14 males and 6 females with hypopituitarism and GH deficiency, the mean age was 40.3 years, as well as 20 comparable controls. The diagnosis of GH deficiency was based on the lack of GH response after an hypoglycemic test. We determined body composition by bioelectrical impedance. An initial 6 month double-blind placebo controlled phase was followed by an open treatment phase ending when the patients had received GH for 18 or 24 months. The initial dose was 0.125 U/kg/week during the first month and after 0.25 U/kg/week. The patients showed lower TWB and FFM and higher BF in relation to controls and after 3 months of GH treatment an increase of the TBW, FFM and a decrease in BF and waist/hip ratio was observed with a steady state in the changes of body composition after 3 months that continued 6 months after the GH treatment withdraw. Two patients presented maleolar oedema, 4 arterial hypertension that was settled with GH dose reduction and in the fourth patient the treatment had to be withdraw. Three patients presented carpal tunnel syndrome. In 4 patients the treatment was withdrawn. In patients with adult GH deficiency, we can observe differences in the body composition that can be significantly modified by GH treatment.


[Study of interaction between contrast media and human serum albumin by the fluorescence method].
Structural changes in the human serumal albumin under the effect of roentgen-contrast media, viz. bilignost, triiotrast, endografine, iodamide, triombrine and cardiotrast, were investigated by the method of fluorescence. The complex-formation of albumin with triiodotrast, bilignost and endografine was shown to call forth a short-wave shift of the fluorescence peak by approximately 20 nm. The binding section for these substances is characterized by an association constant equalling 1.2-10(5) M-1. The authors presume that triiodotrast, bilignost and endografine cause changes in the microstructure of the aqueo-protein layer in the area of the tryptophan residue localization. As to triombine, iodamide and cardiotrast fluorescence failed to disclose their combination with the human serumal albumin.


Role of the C terminus in neuropeptide Y Y1 receptor desensitization and internalization.
We have studied truncation mutants of the rat neuropeptide Y (NPY) Y1 receptor lacking four (Thr361stop, Y1T361*) or eight (Ser352stop, Y1S352*) potential serine/threonine C-terminal phosphorylation sites. NPY-stimulated hemagglutinin-tagged Y1, Y1T361*, and Y1S352* receptors all efficiently activated G proteins in Chinese hamster ovary (CHO) cell membranes, but desensitization after NPY pretreatment was only prevented in the HAY1S352* clone. In transfected colonic carcinoma epithelial layers, functional Y1 and Y1T361* peptide YY responses became more transient as the agonist concentration increased, whereas those mediated by the Y1S352* receptor remained sustained. NPY-stimulated HAY1 receptor phosphorylation was increased by transient overexpression of G protein-coupled receptor kinase 2, and only Ser352stop truncation abolished this response in CHO or human embryonic kidney (HEK) 293 cells. Rapid internalization of cell-surface HAY1 receptors in HEK293 cells was observed in response to agonist, resulting in partial colocalization with transferrin, a marker for clathrin-mediated endocytosis and recycling. It is surprising that both truncated receptors were constitutively internalized, predominantly in transferrin-positive compartments. NPY increased cell-surface localization of HAY1S352* receptors, whereas the distribution of both mutants was unaltered by BIBO3304. Recruitment of green fluorescent protein-tagged beta-arrestin2 to punctate endosomes was observed only for HAY1 and HAY1T361* receptors and solely under NPY-stimulated conditions. Thus, the key C-terminal sequence between Ser352 and Lys360 is a major site for Y1 receptor phosphorylation, is critical for its desensitization, and contributes to the association between the receptor and beta-arrestin proteins. However, additional beta-arrestin-independent mechanisms control Y1 receptor trafficking under basal conditions.


Exploring Memory Care Clinics in Minnesota: A Qualitative Analysis.
We explored memory clinic care provision in Minnesota, examining diversity and similarities of services provided and challenges faced. We also considered how well their services and care philosophies aligned with national dementia care practice recommendations. We created a 53-question interview guide and interviewed 11 memory clinics across Minnesota in late 2019. Interview transcripts were analyzed using Braun and Clarke's thematic analyses in NVivo 12. We identified 6 themes regarding financial issues, staffing, appointment logistics, care provision during and after the memory evaluation as well as features of an ideal clinic. Memory evaluation and care provision were very different across clinics, primarily due to team make-up, particularly team size and specialty. However, memory care providers shared a passion for providing patient-centered memory care, emphasizing family and patient education and partnership. Their care was largely aligned with national memory care recommendations. Common challenges, including maintaining financial stability and clinic efficiency, exerted significant influence on clinic functioning and survival.


Trachomatous Scar Ranking: A Novel Outcome for Trachoma Studies.
AbstractWe evaluated a new trachoma scarring ranking system with potential use in clinical research. The upper right tarsal conjunctivas of 427 individuals from Ethiopian villages with hyperendemic trachoma were photographed. An expert grader first assigned a scar grade to each photograph using the 1981 World Health Organization (WHO) grading system. Then, all photographs were ranked from least (rank = 1) to most scarring (rank = 427). Photographic grading found 79 (18.5%) conjunctivae without scarring (C0), 191 (44.7%) with minimal scarring (C1), 105 (24.6%) with moderate scarring (C2), and 52 (12.2%) with severe scarring (C3). The ranking method demonstrated good internal validity, exhibiting a monotonic increase in the median rank across the levels of the 1981 WHO grading system. Intrarater repeatability was better for the ranking method (intraclass correlation coefficient = 0.84, 95% CI = 0.74-0.94). Exhibiting better internal and external validity, this ranking method may be useful for evaluating the difference in scarring between groups of individuals.


Clinical application of 18F-fluorodeoxyglucose positron emission tomography/computed tomography radiomics-based machine learning analyses in the field of oncology.
Machine learning (ML) analyses using 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)/computed tomography (CT) radiomics features have been applied in the field of oncology. The current review aimed to summarize the current clinical articles about 18F-FDG PET/CT radiomics-based ML analyses to solve issues in classifying or constructing prediction models for several types of tumors. In these studies, lung and mediastinal tumors were the most commonly evaluated lesions, followed by lymphatic, abdominal, head and neck, breast, gynecological, and other types of tumors. Previous studies have commonly shown that 18F-FDG PET radiomics-based ML analysis has good performance in differentiating benign from malignant tumors, predicting tumor characteristics and stage, therapeutic response, and prognosis by examining significant differences in the area under the receiver operating characteristic curves, accuracies, or concordance indices (> 0.70). However, these studies have reported several ML algorithms. Moreover, different ML models have been applied for the same purpose. Thus, various procedures were used in 18F-FDG PET/CT radiomics-based ML analysis in oncology, and 18F-FDG PET/CT radiomics-based ML models, which are easy and universally applied in clinical practice, would be expected to be established.


Regulation of miRNA expression during neural cell specification.
MicroRNA (miRNA) are a newly recognized class of small, noncoding RNA molecules that participate in the developmental control of gene expression. We have studied the regulation of a set of highly expressed neural miRNA during mouse brain development. Temporal control is a characteristic of miRNA regulation in C. elegans and Drosophila, and is also prominent in the embryonic brain. We observed significant differences in the onset and magnitude of induction for individual miRNAs. Comparing expression in cultures of embryonic neurons and astrocytes we found marked lineage specificity for each of the miRNA in our study. Two of the most highly expressed miRNA in adult brain were preferentially expressed in neurons (mir-124, mir-128). In contrast, mir-23, a miRNA previously implicated in neural specification, was restricted to astrocytes. mir-26 and mir-29 were more strongly expressed in astrocytes than neurons, others were more evenly distributed (mir-9, mir-125). Lineage specificity was further explored using reporter constructs for two miRNA of particular interest (mir-125 and mir-128). miRNA-mediated suppression of both reporters was observed after transfection of the reporters into neurons but not astrocytes. miRNA were strongly induced during neural differentiation of embryonic stem cells, suggesting the validity of the stem cell model for studying miRNA regulation in neural development.


Factors influencing the motor development of prematurely born school-aged children in Brazil.
Despite technological advances in neonatology, premature children are still susceptible to disruptions in neurological development. The current study aimed to analyze the factors that influence motor development in prematurely born school-aged children in Brazil. This cross-sectional study involved 100 "apparently normal" children, aged 8-10 years, born at less than 35 weeks of gestation or with birth weight< 1500 g. Their motor development was assessed using the Movement Assessment Battery for Children (MABC-2). The children's neuropsychological and academic performance was assessed with the Token Test (TT) and Teste de Desempenho Escolar (TDE), respectively. Parents answered questions regarding the child's clinical history and behavior using the Strengths and Difficulties Questionnaire (SDQ) and family environment resources (RAF). Hierarchical multivariate analyses revealed that 39% of the children scored lower on the MABC-2, as compared to that expected for their age (manual dexterity: 49%; balance: 35%; throwing/catching a ball: 26%). Multivariate analysis indicated that the lower the birth weight, the maternal age at childbirth, and the RAF score, the greater was the chance of impairment on the MABC-2 scores. The probability of having an impairment MABC-2 scores was four times higher when the mother was not employed. We also found associations between MABC-2 scores and the tasks of tying shoes and opening/closing zippers and buttons. Factors related to children's home environments and birth weight are associated with deficient motor performance in prematurely born Brazilian school-aged children. Deficient motor skills were also associated with difficulty in performing functional tasks requiring greater manual dexterity.


In situ synthesis of polyaniline/carbon nanotube composites in a carbonized wood scaffold for high performance supercapacitors.
Carbonized and activated wood scraps are appealing scaffolds upon which to host active materials for supercapacitors, realizing the transformation of waste into a valuable device. However, the active material when loaded on the inner walls of the wood tracheids can be easily peeled off, resulting in poor cycling stability of the capacitor and low energy density. Here, we designed a novel composite electrode material for high-performance supercapacitors based on a polyaniline/carbon nanotube composite material with a core-shell structure synthesized in situ in a carbonized wood scaffold. Carbon nanotubes with excellent conductivity were first synthesized in situ on the inner walls of the tracheids via chemical vapor deposition, which were stably embedded in the wood tracheids to increase the specific surface area and active material loading active sites. Then, a layer of polyaniline was deposited on the outer surface of each carbon nanotube via electrochemical deposition to form a core-shell nanostructure. The composite material as a single electrode has high specific capacitances of 240.0 F cm-3 and 1019.5 F g-1 at 10 mA cm-2. Finally, the asymmetric supercapacitor based on the carbon nanotubes/carbonized wood scaffold as the anode and polyaniline/carbon nanotubes/carbonized wood scaffold as the cathode exhibited a high energy density of 40.5 W h kg-1 at 162.5 W kg-1 and a high capacity retention rate of 93.74% after 10 000 charge and discharge cycles at a current density of 20 mA cm-2.


Nutritional Ketosis for Weight Management and Reversal of Metabolic Syndrome.
The goal of this paper is to review current literature on nutritional ketosis within the context of weight management and metabolic syndrome, namely, insulin resistance, lipid profile, cardiovascular disease risk, and development of non-alcoholic fatty liver disease. We provide background on the mechanism of ketogenesis and describe nutritional ketosis. Nutritional ketosis has been found to improve metabolic and inflammatory markers, including lipids, HbA1c, high-sensitivity CRP, fasting insulin and glucose levels, and aid in weight management. We discuss these findings and elaborate on potential mechanisms of ketones for promoting weight loss, decreasing hunger, and increasing satiety. Humans have evolved with the capacity for metabolic flexibility and the ability to use ketones for fuel. During states of low dietary carbohydrate intake, insulin levels remain low and ketogenesis takes place. These conditions promote breakdown of excess fat stores, sparing of lean muscle, and improvement in insulin sensitivity.


Anti-TNF treatment reduces rat skeletal muscle wasting in monocrotaline-induced cardiac cachexia.
The aim was to explore efficacy of tumor necrosis factor (TNF) inhibitors in attenuating increases in anorexia and ubiquitin proteasome pathway transcripts in cardiac cachexia, a potentially lethal condition that responds poorly to current treatments. Cardiac cachexia was rapidly induced with monocrotaline in Sprague-Dawley rats. Either soluble TNF receptor-1 or the general inhibitor of TNF production, pentoxifylline, was given to diminish TNF action on the first indication of cachexia. Animals were anesthetized with a ketamine-xylazine-acepromazine cocktail, and then skeletal muscles were removed for subsequent measurements including ubiquitin proteasome pathway transcripts and Western blots. Both soluble TNF receptor-1 and pentoxifylline attenuated losses in both body and skeletal muscle masses and also reduced increases in selected ubiquitin proteasome pathway transcripts. The action of soluble TNF receptor-1 was partly through reversal of reduced food consumption, while the effects of pentoxifylline were independent of food intake. Here we demonstrate, for the first time, that attenuation of anorexia by soluble TNF receptor-1 treatment in monocrotaline-induced cardiac cachexia is responsible for attenuating increases in some ubiquitin proteasome pathway transcripts as well as preserving body mass and attenuating loss of skeletal muscle mass.


Decompressing Stoma a s Bridge to Elective Surgery is an Effective Strategy for Left-sided Obstructive Colon Cancer: A National, Propensity-score Matched Study.
The purpose of this population-based study was to compare decompressing stoma (DS) as bridge to surgery (BTS) with emergency resection (ER) for left-sided obstructive colon cancer (LSOCC) using propensity-score matching. Recently, an increased use of DS as BTS for LSOCC has been observed in the Netherlands. Unfortunately, good quality comparative analyses with ER are scarce. Patients diagnosed with nonlocally advanced LSOCC between 2009 and 2016 in 75 Dutch hospitals, who underwent DS or ER in the curative setting, were propensity-score matched in a 1:2 ratio. The primary outcome measure was 90-day mortality, and main secondary outcomes were 3-year overall survival and permanent stoma rate. Of 2048 eligible patients, 236 patients who underwent DS were matched with 472 patients undergoing ER. After DS, more laparoscopic resections were performed (56.8% vs 9.2%, P < 0.001) and more primary anastomoses were constructed (88.5% vs 40.7%, P < 0.001). DS resulted in significantly lower 90-day mortality compared to ER (1.7% vs 7.2%, P = 0.006), and this effect could be mainly attributed to the subgroup of patients over 70 years (3.5% vs 13.7%, P = 0.027). Patients treated with DS as BTS had better 3-year overall survival (79.4% vs 73.3%, hazard ratio 0.36, 95% confidence interval 0.20-0.65) and fewer permanent stomas (23.4% vs 42.4%, P < 0.001). In this nationwide propensity-score matched study, DS as a BTS for LSOCC was associated with lower 90-day mortality and better 3-year overall survival compared to ER, especially in patients over 70 years of age.


Use of in vitro methaemoglobin generation to study antioxidant status in the diabetic erythrocyte.
Poor glycaemic control in diabetes and a combination of oxidative, metabolic, and carbonyl stresses are thought to lead to widespread non-enzymatic glycation and eventually to diabetic complications. Diabetic tissues can suffer both restriction in their supply of reducing power and excessive demand for reducing power. This contributes to compromised antioxidant status, particularly in the essential glutathione maintenance system. To study and ultimately correct deficiencies in diabetic glutathione maintenance, an experimental model would be desirable, which would provide in vitro a rapid, convenient, and dynamic reflection of the performance of diabetic GSH antioxidant capacity compared with that of non-diabetics. Xenobiotic-mediated in vitro methaemoglobin formation in erythrocytes drawn from diabetic volunteers is significantly lower than that in erythrocytes of non-diabetics. Aromatic hydroxylamine-mediated methaemoglobin formation is GSH-dependent and is indicative of the ability of an erythrocyte to maintain GSH levels during rapid thiol consumption. Although nitrite forms methaemoglobin through a complex GSH-independent pathway, it also reveals deficiencies in diabetic detoxification and antioxidant performance compared with non-diabetics. Together with efficient glycaemic monitoring, future therapy of diabetes may include trials of different antiglycation agents and antioxidant combinations. Equalization in vitro of diabetic methaemoglobin generation with that of age/sex-matched non-diabetic subjects might provide an early indication of diabetic antioxidant status improvement in these studies.


Inhaled corticosteroids and bone health.
Inhaled corticosteroids (ICS) are the cornerstones in the management of bronchial asthma and some cases of chronic obstructive pulmonary disease. Although ICS are claimed to have low side effect profiles, at high doses they can cause systemic adverse effects including bone diseases such as osteopenia, osteoporosis and osteonecrosis. Corticosteroids have detrimental effects on function and survival of osteoblasts and osteocytes, and with the prolongation of osteoclast survival, induce metabolic bone disease. Glucocorticoid-induced osteoporosis (GIO) can be associated with major complications such as vertebral and neck of femur fractures. The American College of Rheumatology (ACR) published criteria in 2010 for the management of GIO. ACR recommends bisphosphonates along with calcium and vitamin D supplements as the first-line agents for GIO management. ACR recommendations can be applied to manage patients on ICS with a high risk of developing metabolic bone disease. This review outlines the mechanisms and management of ICS-induced bone disease.


Aligning Microtomography Analysis with Traditional Anatomy for a 3D Understanding of the Host-Parasite Interface - Phoradendron spp. Case Study.
The complex endophytic structure formed by parasitic plant species often represents a challenge in the study of the host-parasite interface. Even with the large amounts of anatomical slides, a three-dimensional comprehension of the structure may still be difficult to obtain. In the present study we applied the High Resolution X-ray Computed Tomography (HRXCT) analysis along with usual plant anatomy techniques in order to compare the infestation pattern of two mistletoe species of the genus Phoradendron. Additionally, we tested the use of contrasting solutions in order to improve the detection of the parasite's endophytic tissue. To our knowledge, this is the first study to show the three-dimensional structure of host-mistletoe interface by using HRXCT technique. Results showed that Phoradendron perrottetii growing on the host Tapirira guianensis forms small woody galls with a restricted endophytic system. The sinkers were short and eventually grouped creating a continuous interface with the host wood. On the other hand, the long sinkers of P. bathyoryctum penetrate deeply into the wood of Cedrela fissilis branching in all directions throughout the woody gall area, forming a spread-out infestation pattern. The results indicate that the HRXCT is indeed a powerful approach to understand the endophytic system of parasitic plants. The combination of three-dimensional models of the infestation with anatomical analysis provided a broader understanding of the host-parasite connection. Unique anatomic features are reported for the sinkes of P. perrottetii, while the endophytic tissue of P. bathyoryctum conformed to general anatomy observed for other species of this genus. These differences are hypothesized to be related to the three-dimensional structure of each endophytic system and the communication stablished with the host.


High density data storage on ultraviolet sensitive tape.
A novel recording material for optical data storage has been developed. On this material information can be recorded permanently by means of ultraviolet light and read out by visible light, and no developing or fixation process is required. Immediate control reading is possible. With a tape of this material, experimental investigations were performed concerning the design of a bit-by-bit storage system. The results confirm that excellent specifications are attainable by using a simple way of light deflection and tape guidance and a new principle of readout: Storage density of at least some Mbits/cm(2) at transfer rates for recording and reading up to at least some Mbits/sec and immediate control readout.


Stability of Arsenic Species During Bioaccessibility Assessment Using the In Vitro UBM and HPLC-ICP-MS Detection.
The stability of four major arsenic (As) species during application of the BARGE (Bioaccessibility Research Group of Europe) unified bioaccessibility method (UBM) has been assessed. The concentrations of As species in the UBM gastric and gastro-intestinal (gastric + intestinal) phases were determined using HPLC-ICP-MS whilst the total As content in the samples was determined using ICP-MS alone. The arsenic species studied were arsenite As(III), arsenate As(V), dimethylarsinic acid (DMA) and monomethylarsonic acid (MMA). These species were separated in 10 min using an anion exchange column (Hamilton PRP-X100) with a mobile phase containing 20 mmol L-1 NH4H2PO4/1% methanol (pH 6.0). The recoveries of arsenic species spiked into the gastric and gastro-intestinal fluids were in the range 90-108%. No interconversion between As species was observed as a result of applying the BARGE UBM, which is a particularly important finding for the reliability of As(III) measurements. The accuracy of the BARGE UBM for in vitro extractable As(V) was verified using British Geological Survey (BGS) guidance material 102 (an ironstone soil). For a commercial rice sample, the bioaccessibility sequence of As was DMA > As(III) > As(V) for the gastric phase and As(III) > DMA > As(V) for the gastro-intestinal phase.


Signaling through CD38 induces NK cell activation.
Human CD38 is a signal transduction molecule, and, concurrently, an ectoenzyme catalyzing the synthesis and degradation of cyclic ADP-ribose (cADPR), a potent Ca2+ mobilizer. One facet of CD38 that has not yet been addressed is its role in NK cells. To this end, the events triggered by CD38 ligation with agonistic mAb were analyzed on freshly purified human NK cells. Ligation was followed by (i) a significant rise in the intracellular level of Ca2+, (ii) increased expression of HLA class II and CD25, and (iii) tyrosine phosphorylation of discrete cytoplasmic substrates. The phosphorylation cascade involved CD3-zeta and FcepsilonRIgamma chains, zeta-associated protein (ZAP)-70 and the proto-oncogene product c-Cbl. NK effector functions were then analyzed: CD38 signaling was able (iv) to induce release of IFN-gamma and, more prominently, of granulocyte macrophage colony stimulating factor, as assessed by measuring both mRNA and protein products; and, lastly, (v) to induce cytolytic effector functions on target cells after IL-2 activation, as shown both by cytotoxicity assays and ultrastructural changes. The tyrosine-phosphorylated substrates and all the effects mediated by CD38 were similar to those observed following triggering via CD16 (FcgammaRIIIA); moreover, Ca2+ mobilization via CD38 no longer operated in NK-derived cell lines lacking CD16. These results suggest that the activation signals transduced by CD38 in NK cells elicit relevant cellular events. The effects are similar to those elicited via CD16 and possibly rely on common signaling pathways.


Association between exposure to second-hand smoke and telomere length: cross-sectional study of 1303 non-smokers.
Both active smoking and second-hand smoke (SHS) are important risk factors for many age-related diseases. Active smoking is associated with shortened telomere length. However, whether SHS accelerates telomere attrition with age is uncertain. The aim of this study was to examine the association between SHS exposure and shortening by age of leukocyte telomere length among adult non-smokers. We undertook a cross-sectional study of the association between self-reported levels of SHS exposure and telomere length shortening per annum on a subgroup of participants from the Scottish Family Health Study. Inclusion was restricted to non-smokers aged ≥ 18 years, who had provided self-reported overall usual SHS exposure (total hours per week) and blood samples for telomere analysis. Linear regression models were used to compare the ratio of telomere repeat copy number to single copy gene number (T/S)by age according to SHS exposure. Of the 1303 eligible participants, 779 (59.8%) reported no SHS exposure, 495 (38.0%) low exposure (1-19 h per week) and 29 (2.2%) high exposure (≥20 h per week). In the univariate linear regression analyses, relative T/S ratio declined with increasing age in all exposure groups. Telomere length decreased more rapidly with increasing age among those with high exposure to SHS [adjusted coefficient -0.019, 95% confidence interval (CI) -0.031- -0.007) when compared with both those with no exposure to SHS (adjusted coefficient -0.006, 95% CI -0.008- -0.004) (high vs no SHS: P = 0.010) and those with low exposure to SHS (adjusted coefficient -0.005, 95% CI -0.007- -0.003) (high vs low SHS: P = 0.005). Our findings suggest that high SHS exposure may accelerate normal biological ageing, and support efforts to protect the public from SHS exposure. Further studies on relevant mechanisms should be conducted.


Trans-national conservation and infrastructure development in the Heart of Borneo.
The Heart of Borneo initiative has promoted the integration of protected areas and sustainably-managed forests across Malaysia, Indonesia, and Brunei. Recently, however, member states of the Heart of Borneo have begun pursuing ambitious unilateral infrastructure-development schemes to accelerate economic growth, jeopardizing the underlying goal of trans-boundary integrated conservation. Focusing on Sabah, Malaysia, we highlight conflicts between its Pan-Borneo Highway scheme and the regional integration of protected areas, unprotected intact forests, and conservation-priority forests. Road developments in southern Sabah in particular would drastically reduce protected-area integration across the northern Heart of Borneo region. Such developments would separate two major clusters of protected areas that account for one-quarter of all protected areas within the Heart of Borneo complex. Sabah has proposed forest corridors and highway underpasses as means of retaining ecological connectivity in this context. Connectivity modelling identified numerous overlooked areas for connectivity rehabilitation among intact forest patches following planned road development. While such 'linear-conservation planning' might theoretically retain up to 85% of intact-forest connectivity and integrate half of the conservation-priority forests across Sabah, in reality it is very unlikely to achieve meaningful ecological integration. Moreover, such measure would be exceedingly costly if properly implemented-apparently beyond the operating budget of relevant Malaysian authorities. Unless critical road segments are cancelled, planned infrastructure will fragment important conservation landscapes with little recourse for mitigation. This likelihood reinforces earlier calls for the legal recognition of the Heart of Borneo region for conservation planning as well as for enhanced tri-lateral coordination of both conservation and development.


T cell induction of membrane IL 1 on macrophages.
We have studied the role of T cells in the induction of a membrane-associated form of interleukin 1 (mIL 1) in murine macrophages. T helper cell clones and a T cell hybridoma induced macrophages to express mIL 1 after an antigen-specific, Ia-restricted interaction. Induction of mIL 1 was proportional to antigen concentration and was increased in the early course of the response in macrophages pretreated in culture with interferon-gamma. mIL 1 activity was detectable 4 hr after interaction with T cells. mIL 1 induction was inhibited by antibodies to either class II molecules or the T cell receptor. Two pathways of T cell-mediated mIL 1 induction could be defined. In the first, T cells, whose protein synthesizing capacity was completely eliminated by pretreatment with the irreversible protein synthesis inhibitor emetine, induced levels of mIL 1 expression indistinguishable from controls. In the second, T cells stimulated by paraformaldehyde-fixed macrophages in the presence of concanavalin A or antigen secreted a soluble factor that induced macrophage mIL 1 expression. Thus, it appears that T cells may induce macrophages to express mIL 1 both by direct cell-cell contact mediated through binding of T cell receptor to the Ia/antigen complex, and through the release of a lymphokine after activation. This lymphokine does not appear to be IL 2, IFN-gamma, BSF-1, or CSF-1.


[Positive developments for patients with breast cancer as a result of the sentinel node biopsy procedure].
As an increasing number of large prospective studies show a high accuracy of the sentinel node for the staging of the axilla in women with invasive breast cancer, there is no need to test the value of this new technique in a randomised trial. Much more emphasis should be given to a reliable implementation of the technique in general practice, requiring a closely co-operating multidisciplinary team meticulously performing the different steps of the technique. The guidelines designed by the Dutch Working Group on the Sentinel Node in Breast Cancer include a learning phase of--arbitrarily--50 procedures in patients also undergoing a complete axillary dissection. What remains is the need for a treatment trial aimed at reducing the morbidity of the treatment of axillary metastases while retaining equal regional tumour control and patient survival. As the indication for adjuvant systemic treatment has shifted from the N-stage to T-stage parameters (size, grade, mitotic activity), the axillary nodal status has become less important as a staging tool. Thus, comparison of surgery or radiotherapy of sentinel node positive patients in a randomised trial appears to be a logical next step.


[Cigarette smoking and mortality in the Korean Multi-center Cancer Cohort (KMCC) study].
The aim of this study was to evaluate the association between cigarette smoking and total mortality, cancer mortality and other disease mortalities in Korean adults. A total of 14,161 subjects of the Korean Multi-center Cancer Cohort who were over 40 years of age and who were cancer-free at baseline enrollment reported their lifestyle factors, including the smoking status. The median follow-up time was 6.6 years. During the follow-up period from 1993 to 2005, we identified 1159 cases of mortality, including 260 cancer mortality cases with a total of 91,987 person-years, by the national death certificate. Cox proportional hazard regression model was used to estimate the hazard ratio (HR) of cigarette smoking for total mortality, cancer mortality and disease-specific mortality, as adjusted for age, gender, the geographic area and year of enrollment, the alcohol consumption status, the education level and the body mass index (BMI). Cigarette smoking was significantly associated with an increased risk of total mortality, all-cancer mortality and lung cancer mortality (p-trend, <0.01, <0.01, <0.01, respectively). Compared to non-smoking, current smokers were at a higher risk for mortality [HR (95% CI)=1.3 (1.1-1.5) for total mortality; HR (95% CI)=1.6 (1.1-2.2) for all-cancer mortality; HR (95% CI)=3.9 (1.9-7.7) for lung cancer mortality]. This study's results suggest that cigarette smoking might be associated with total mortality, all-cancer mortality and especially lung cancer mortality among Korean adults.


PAPIN. A novel multiple PSD-95/Dlg-A/ZO-1 protein interacting with neural plakophilin-related armadillo repeat protein/delta-catenin and p0071.
A neural plakophilin-related armadillo repeat protein (NPRAP)/delta-catenin interacts with one of Alzheimer disease-related gene products, presenilin 1. We have previously reported the interaction of NPRAP/delta-catenin with synaptic scaffolding molecule, which is involved in the assembly of synaptic components. NPRAP/delta-catenin also interacts with E-cadherin and beta-catenin and is implicated in the organization of cell-cell junctions. p0071, a ubiquitous isoform of NPRAP/delta-catenin, is localized at desmosomes in HeLa and A431 cells and at adherens junctions in Madin-Darby bovine kidney cells. We have identified here a novel protein interacting with NPRAP/delta-catenin and p0071 and named this protein plakophilin-related armadillo repeat protein-interacting PSD-95/Dlg-A/ZO-1 (PDZ) protein (PAPIN). PAPIN has six PDZ domains and binds to NPRAP/delta-catenin and p0071 via the second PDZ domain. PAPIN and p0071 are ubiquitously expressed in various tissues and are localized at cell-cell junctions in normal rat kidney cells and bronchial epithelial cells. PAPIN may be a scaffolding protein connecting components of epithelial junctions with p0071.


Oncogenic ras results in increased cell kill due to defective thermoprotection in lung cancer cells.
The survival response of normal cells to heat stress is an upregulation of heat shock proteins and ras protein activation. We hypothesized that in lung cancer cells the presence of oncogenic ras interferes with thermoprotective mechanisms resulting in cell death. An equal number of lung tissue culture cells (normal and cancerous) were subjected to either heat stress and then recovery (43 degrees C for 180 minutes, 37 degrees C for 180 minutes) or recovery alone (37 degrees C for 360 minutes). End points were surviving number of cells, cell-death time course, heat shock protein (HSP70, HSC70, HSP27) expression before and after heat stress, and time course for HSP70 expression during heat stress and recovery. Heated cells were compared with unheated control cells, then this difference was compared between cell types. Heat stress in normal cells caused an 8% decrease in cell number versus a 78% +/- 5% decrease in cancer cells (p < 0.05). In normal cells, heat stress caused a 4.4-fold increase in HSP70, no change in HSC70, and a 1.7-fold increase in HSP27. In contrast, cancer cells initially contained significantly less HSP70 (p < 0.05), and there was a 27-fold increase in HSP70 and a 2-fold increase in HSC70 with no HSP27 detected (comparison significant, p < 0.05). HSP70 time course in normal cells showed that HSP70 increased 100-fold, reaching a vertex at 2 hours and remaining elevated for 24 hours; in cancer cells, HSP70 maximum expression (100-fold) peaked at 5 hours,,then decreased to slightly elevated at 24 hours. Cancer cells with oncogenic ras have defective thermoprotective mechanism(s) causing increased in vitro cell death, which provides an opportunity for thermal treatment of lung cancer.


An insight into the contributions of self-shielding and lamp reflectors to patient exposure in phototherapy units.
Calibration of phototherapy equipment can prove to be difficult. One problem is that the self-shielding produced by a patient reduces the irradiance relative to that determined when the cabinet is empty. A model has been developed to determine the factor to apply to the irradiance measured with the cabinet empty to give the irradiance with the patient present, i.e. the self-shielding correction factor. The model assumes that the cabinet consists of a number of discrete infinite line sources backed by perfect mirrors. The patient is treated as a barrier that prevents some of these sources being seen by the detector in the mirror it faces. The model was tested using a Waldmann 8001 K unit and three UV meters for UVA and UVB sources. The measurements suggested some modifications to the model--for UVA multiple reflections were important and for UVB the reflectors were only 30% efficient. The correction factors obtained were 0.87 for UVA and 0.96 for UVB.


Recombination and population mosaic of a multifunctional viral gene, adeno-associated virus cap.
Homologous recombination is a dominant force in evolution and results in genetic mosaics. To detect evidence of recombination events and assess the biological significance of genetic mosaics, genome sequences for various viral populations of reasonably large size are now available in the GenBank. We studied a multi-functional viral gene, the adeno-associated virus (AAV) cap gene, which codes for three capsid proteins, VP1, VP2 and VP3. VP1-3 share a common C-terminal domain corresponding to VP3, which forms the viral core structure, while the VP1 unique N-terminal part contains an enzymatic domain with phospholipase A2 activity. Our recombinant detection program (RecI) revealed five novel recombination events, four of which have their cross-over points in the N-terminal, VP1 and VP2 unique region. Comparison of phylogenetic trees for different cap gene regions confirmed discordant phylogenies for the recombinant sequences. Furthermore, differences in the phylogenetic tree structures for the VP1 unique (VP1u) region and the rest of cap highlighted the mosaic nature of cap gene in the AAV population: two dominant forms of VP1u sequences were identified and these forms are linked to diverse sequences in the rest of cap gene. This observation together with the finding of frequent recombination in the VP1 and 2 unique regions suggests that this region is a recombination hot spot. Recombination events in this region preserve protein blocks of distinctive functions and contribute to convergence in VP1u and divergence of the rest of cap. Additionally the possible biological significance of two dominant VP1u forms is inferred.


Drug-induced hematologic syndromes.
Objective. Drugs can induce almost the entire spectrum of hematologic disorders, affecting white cells, red cells, platelets, and the coagulation system. This paper aims to emphasize the broad range of drug-induced hematological syndromes and to highlight some of the newer drugs and syndromes. Methods. Medline literature on drug-induced hematologic syndromes was reviewed. Most reports and reviews focus on individual drugs or cytopenias. Results. Drug-induced syndromes include hemolytic anemias, methemoglobinemia, red cell aplasia, sideroblastic anemia, megaloblastic anemia, polycythemia, aplastic anemia, leukocytosis, neutropenia, eosinophilia, immune thrombocytopenia, microangiopathic syndromes, hypercoagulability, hypoprothrombinemia, circulating anticoagulants, myelodysplasia, and acute leukemia. Some of the classic drugs known to cause hematologic abnormalities have been replaced by newer drugs, including biologics, accompanied by their own syndromes and unintended side effects. Conclusions. Drugs can induce toxicities spanning many hematologic syndromes, mediated by a variety of mechanisms. Physicians need to be alert to the potential for iatrogenic drug-induced hematologic complications.


Transfusion of red blood cells in patients with a prehospital Glasgow Coma Scale score of 8 or less and no evidence of shock is associated with worse outcomes.
Red blood cell transfusion practices vary, and the optimal hemoglobin for patients with traumatic brain injury has not been established. A retrospective review of data collected prospectively as part of a randomized, controlled trial involving emergency medical service agencies within the Resuscitation Outcomes Consortium was conducted. In patients with a Glasgow Coma Scale (GCS) score of 8 or less without evidence of shock (defined by a systolic blood pressure [SBP] < 70 or SBP of 70 to 90 with a heart rate ≥108), the association of red blood cell transfusion with 28-day survival, adult respiratory distress syndrome-free survival, Multiple Organ Dysfunction Score (MODs), and 6-month Extended Glasgow Outcome Scale (GOSE) score was modeled using multivariable logistic regression with robust SEs adjusting for age, sex, injury severity (Injury Severity Score [ISS]), initial GCS score, initial SBP, highest field heart rate, penetrating injury, fluid use, study site, and hemoglobin (Hgb) level. A total of 1,158 patients had a mean age of 40, 76% were male, and 98% experienced blunt trauma. The initial mean GCS score was 5, and the initial mean SBP was 134. The mean head Abbreviated Injury Scale (AIS) score was 3.5. A categorical interaction of red blood cell transfusion stratified by initial Hgb showed that when the first Hgb was greater than 10 g/dL, volume of packed red blood cell was associated with a decreased 28-day survival (odds ratio, 0.83; 95% confidence interval [CI], 0.74-0.93; p < 0.01) and decreased adult respiratory distress syndrome-free survival (odds ratio, 0.82; 95% CI, 0.74-0.92; p < 0.01). When the initial Hgb was greater than 10, each unit of blood transfused increased the MODs by 0.45 (coefficient 95% CI, 0.19-0.70; p < 0.01). In patients with a suspected traumatic brain injury and no evidence of shock, transfusion of red blood cells was associated with worse outcomes when the initial Hgb was greater than 10. Therapeutic study, level III.


Investigating factors related to the effects of time-out on stuttering in adults.
Response-contingent time-out has been shown to be an effective technique for enhancing fluency in people who stutter. However, the factors that determine individual responsiveness to time-out are not well understood. The study investigated the effectiveness of using response-contingent time-out to reduce stuttering frequency in adults who stutter. In addition, it investigated the predictive value of participants' stutter severity, age, previous treatment history, and type of stutter on the responsiveness to time-out conditioning. Sixty people who stutter participated in the study. Half were exposed to time-out following each moment of stuttering over a 40-min period, the remaining participants acted as controls. Results showed that individuals who stutter are highly responsive to time-out, and that the participants with a more severe stutter responded better than those with a mild stutter. To a lesser degree, previous treatment and speech rate also influenced treatment success. Age and type of stutter did not, although the proportion of repetition types of stutters increased over the experiment conditions, with prolongations and blocks decreasing, for the treatment group. This simple operant conditioning treatment method is effective in reducing stuttering. Individuals respond to time-out regardless of their age, type of stutter, stuttering severity or treatment history, thus it is a treatment methodology potentially suitable for all clients. This study investigated initial responsiveness to time-out; therefore, further research is necessary to determine the durability of fluency over time.


The antimicrobial sensitivity of Streptococcus mutans to nanoparticles of silver, zinc oxide, and gold.
Dental caries is a worldwide public health problem for which Streptococcus mutans has been identified as the possible infectious etiology. In recent years nanotechnology has permitted the development of new properties of materials. The objective of this study was to compare the bactericidal and bacteriostatic effects of nanoparticles of silver, zinc oxide, and gold on S. mutans. We used the liquid dilution method to find the minimum inhibitory concentrations (MICs) and with subcultures obtained the minimum bactericidal concentrations (MBCs). For silver the results showed an average MIC of 4.86 +/- 2.71 microg/mL and MBC of 6.25 microg/mL; for zinc the MIC was 500 +/- 306.18 muicrog/mL and MBC of 500 microg/mL; the gold nanoparticles demonstrated an effect only at an initial concentration of 197 mug/mL. We established a higher antimicrobial effect against S. mutans of silver nanoparticles at lower concentrations than gold or zinc, which would allow achieving important clinical effects with a reduced toxicity.


The changing epidemiology of invasive Haemophilus influenzae disease, especially in persons > or = 65 years old.
Few studies have reported the epidemiological characteristics of Haemophilus influenzae disease among adults. Public health surveillance and hospital discharge data from Illinois were examined to determine the descriptive epidemiological characteristics and trends of invasive H. influenzae disease, and mortality data from Illinois were compared with data from several other states. During January 1996-December 2004, 770 cases of invasive H. influenzae disease were reported to the Illinois Department of Public Health (Springfield). The incidence of disease increased from 0.4 to 1.0 cases per 100,000 persons, including an increase of incidence in adults aged > or = 65 years from 1.1 to 3.9 cases per 100,000 persons. Nontypeable H. influenzae disease accounted for the greatest proportion of cases (35.8%-61.5%) in all but 1 age group. The number of cases of invasive nontypeable H. influenzae disease increased by 657%, from a low of 7 cases in 1996 to a high of 53 cases in 2004; as a proportion of annual cases, nontypeable H. influenzae disease increased from 17.5% in 1996 to 70.7% in 2004. Overall, the case-fatality rate was 12.7%, with the highest rate observed in persons aged > or = 65 years (20.6%). The case-fatality rate was similar for the hospital discharge database and for Indiana, Maryland, Oregon, and Wisconsin (range, 12.9%-18.2%). In Illinois, the incidence of invasive H. influenzae disease increased from 1996 to 2004, and its epidemiological characteristics changed from a disease predominantly found in children and dominated by serotype b to a disease predominantly found in adults and dominated by nontypeable strains.


Calcium and vitamin D supplementation through fortified dairy products counterbalances seasonal variations of bone metabolism indices: the Postmenopausal Health Study.
To assess the effectiveness of a dietary intervention combined with fortified dairy products on bone metabolism and bone mass indices in postmenopausal women. Forty postmenopausal women (55-65 years old) were equally randomized into a dietary group (DG), receiving daily and for 30 months, 1,200 mg of calcium and 7.5 μg of vitamin D(3) for the first 12 months that increased to 22.5 μg for the remaining 18 months of intervention through fortified dairy products; and a control group (CG). Differences in the changes of bone metabolism and bone mass indices were examined with repeated measures ANOVA. A significant increase was observed for PTH levels only in the CG during the first six winter months of intervention (p = 0.049). After 30 months of intervention, during winter, serum 25(OH)D significantly decreased in the CG while remained in the same high levels as in the summer period in the DG. Serum RANKL levels decreased significantly in the DG compared with the increase in the CG during the 30-month intervention period (p = 0.005). Serum CTx decreased significantly in the DG after six (-0.08; -0.12 to -0.03) and 12 (-0.03; -0.08 to -0.02) months of intervention. Finally, the DG had more favorable changes in total body BMD than the CG (p < 0.001). Increasing dietary intake of calcium and vitamin D in osteopenic postmenopausal women appears to be effective in producing favorable changes in several bone metabolism and bone mass indices and in counterbalancing seasonal variations in hormonal and biochemical molecules.


No evidence of an increased mortality risk associated with low levels of glycated haemoglobin in a non-diabetic UK population.
There is debate about increased mortality risk associated with low levels of glycaemia. To address this issue, we examined the shape of the risk relationship between glycated haemoglobin and mortality in a UK population. In 17,196 men and women aged 39-82 years participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) Study in Norfolk without known diabetes or cardiovascular disease, we estimated HRs for total and cause-specific mortality comparing categories of glycated haemoglobin (<4.5%, 4.5% to <5.0%, 5.0% to <5.5% [reference], 5.5% to <6.0%, 6.0% to <6.5%, and ≥6.5%) using Cox regression. During a mean (±SD) follow-up of 11.2 (±2.1) years 1,953 participants died. The HR for all-cause mortality increased with categories of increasing glycated haemoglobin in adjusted analyses (HR 0.94 [95% CI 0.72-1.22], 0.99 [0.86-1.13], 1.00 [0.92-1.08], 1.10 [1.02-1.19], 1.29 [1.14-1.46] and 1.45 [1.16-1.80]). Spline regression suggested no increased risk at the low end of the distribution. Indeed, the HR for all-cause mortality was virtually constant in the low range and only started to rise when the level was approximately 5.5%. There were similar associations of glycated haemoglobin with cause-specific mortality, with the strongest association being seen for cardiovascular mortality. Our findings in a large non-diabetic population do not support the concern about increased mortality risk with low glycated haemoglobin. Differences in population characteristics might explain contrary results of earlier studies and need further exploration.


Exogenous Nitric Oxide Alleviates Water Deficit and Increases the Seed Production of an Endemic Amazonian Canga Grass.
Open pit mining can cause loss in different ecosystems, including damage to habitats of rare and endemic species. Understanding the biology of these species is fundamental for their conservation, and to assist in decision-making. Sporobolus multiramosus is an annual grass endemic to the Amazon canga ecosystems, which comprise rocky outcrop vegetation covering one of the world's largest iron ore reserves. Here, we evaluated whether nitric oxide aids S. multiramosus in coping with water shortages and examined the physiological processes behind these adaptations. nitric oxide application improved the water status, photosynthetic efficiency, biomass production, and seed production and germination of S. multiramosus under water deficit conditions. These enhancements were accompanied by adjustments in leaf and root anatomy, including changes in stomata density and size and root endodermis thickness and vascular cylinder diameter. Proteomic analysis revealed that nitric oxide promoted the activation of several proteins involved in the response to environmental stress and flower and fruit development. Overall, the results suggest that exogenous nitric oxide has the potential to enhance the growth and productivity of S. multiramosus. Enhancements in seed productivity have significant implications for conservation initiatives and can be applied to seed production areas, particularly for the restoration of native ecosystems.


COVID-19 Vaccination and Related Determinants of Hesitancy among Pregnant Women: A Systematic Review and Meta-Analysis.
Mass vaccination against COVID-19 is necessary to control the pandemic. COVID-19 vaccines are now recommended during pregnancy to prevent the disease. A systematic review of the literature in the electronic databases PubMed and EMBASE was performed and we aimed to investigate the attitude of documents towards COVID-19 vaccination and the prognostic factors of vaccination hesitation. A meta-analysis was also conducted to estimate the overall percentage of pregnant women who were willing to be vaccinated or had been vaccinated against COVID-19. A total of 18 studies were included in the review and meta-analysis. The acceptance rate of vaccination against COVID-19 among pregnant women ranged from 17.6% to 84.5%. The pooled proportion of acceptance of vaccination against COVID-19 in pregnant women was 0.53 (95% CI: 0.44-0.61). Predictors of acceptance of COVID-19 vaccination were older age, White race, occupational status, higher level of education, comorbidities, third trimester of pregnancy, influenza vaccination, knowledge about COVID-19, and confidence that vaccines for COVID-19 are safe and effective. The prevalence of COVID-19 vaccination in pregnant women is low. Targeted information campaigns are needed to increase vaccine education in this population.


Effects of treatments and distribution on microbiome and antibiotic resistome from source to tap water in three Chinese geographical regions based on metagenome assembly.
Antibiotic resistance genes (ARGs) represent emerging environmental pollutants that present health risks. Drinking water supply systems (DWSSs), including sources to tap water, play crucial roles in the dissemination and propagation of ARGs. However, there was a paucity of knowledge on the relative abundance, diversity, mobility, and pathogenic hosts of ARGs in DWSSs from source to tap. Therefore, the effects of treatments and distributions on the microbial community and ARGs from three geographical regions (downstream areas of the Yellow, Yangtze, and Pearl Rivers) were elucidated in the present study. Treatment processes lowered the complexity of the microbial community network, whereas transportation increased it. The assembly mechanisms of the microbial community and antibiotic resistome were primarily driven by stochastic processes. Distribution greatly increased the contribution of stochastic processes. Multidrug ARGs (for example, multidrug transporter and adeJ) and bacitracin ARG (bacA) were the primary mobile ARGs in drinking water, as identified by the metagenomic assembly. Achromobacter xylosoxidans, Acinetobacter calcoaceticus, and Acinetobacter junii harbored diverse multidrug ARGs and mobile genetic elements (MGEs) (recombinases, integrases, and transposases) as potential pathogens and were abundant in the disinfected water. Environmental factors, including pH, chlorine, latitude, longitude, and temperature, influenced the ARG abundance by directly regulating the MGEs and microbial community diversity. This study provides critical information on the fate, mobility, host pathogenicity, and driving factors of ARGs in drinking water, which is conducive to ARG risk assessment and management to provide high-quality drinking water to consumers.


Diagnostic efficacy of cell block immunohistochemistry, smear cytology, and liquid-based cytology in endoscopic ultrasound-guided fine-needle aspiration of pancreatic lesions: a single-institution experience.
The diagnostic efficiency of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) cytology varies widely depending on the treatment method of the specimens. The present study aimed to evaluate the diagnostic efficacy of cell block (CB) immunohistochemistry, smear cytology (SC), and liquid-based cytology (LBC) in patients with pancreatic lesions without consulting an on-site cytopathologist. This study prospectively enrolled 72 patients with pancreatic lesions. The EUS-FNA specimens were examined by SC, LBC, and CB immunohistochemistry. The diagnostic efficacy of the 3 methods was then compared. Patients' final diagnosis was confirmed by surgical resection specimens, diagnostic imaging, and clinical follow-up. Our results included 60 malignant and 12 benign pancreatic lesions. The diagnostic sensitivity (90%), negative predictive value (66.7%), and accuracy (91.7%) of CB immunohistochemistry were significantly higher than those of SC (70.0%, 30.0%, and 75.0%, respectively) and LBC (73.3%, 31.6%, and 77.8%, respectively) (all P<0.05). The combination of CB and SC, or CB and LBC, did not significantly increase the efficacy compared to CB immunohistochemistry alone. Our findings suggest that in the absence of an on-site cytopathologist, CB immunohistochemistry on EUS-FNA specimens offers a higher diagnostic efficacy in patients with pancreatic lesions than does SC and LBC.


Biomechanics of pollen pellet removal by the honey bee.
Honey bees (Apis mellifera) carry pollen back to their hive by mixing it with nectar and forming it into a pellet. The pellet must be firmly attached to their legs during flight, but also easily removable when deposited in the hive. How does the honey bee achieve these contrary aims? In this experimental study, we film honey bees removing pollen pellets and find they peel them off at speeds 2-10 times slower than their typical grooming speeds. Using a self-built pollen scraper, we find that slow removal speeds reduce the force and work required to remove the pellet under shear stress. Creep tests on individual pollen pellets revealed that pollen pellets are viscoelastic materials characterized by a Maxwell model with long relaxation times. The relaxation time enables the pellet to remain a solid during both transport and removal. We hope that this work inspires further research into viscoelastic materials in nature.


Natural history and mechanisms of COPD.
The natural history of COPD is complex, and the disease is best understood as a syndrome resulting from numerous interacting factors throughout the life cycle with smoking being the strongest inciting feature. Unfortunately, diagnosis is often delayed with several longitudinal cohort studies shedding light on the long 'preclinical' period of COPD. It is now accepted that individuals presenting with different COPD phenotypes may experience varying natural history of their disease. This includes its inception, early stages and progression to established disease. Several scenarios regarding lung function course are possible, but it may conceptually be helpful to distinguish between individuals with normal maximally attained lung function in their early adulthood who thereafter experience faster than normal FEV1 decline, and those who may achieve a lower than normal maximally attained lung function. This may be the main mechanism behind COPD in the latter group, as the decline in FEV1 during their adult life may be normal or only slightly faster than normal. Regardless of the FEV1 trajectory, continuous smoking is strongly associated with disease progression, development of structural lung disease and poor prognosis. In developing countries, factors such as exposure to biomass and sequelae after tuberculosis may lead to a more airway-centred COPD phenotype than seen in smokers. Mechanistically, COPD is characterized by a combination of structural and inflammatory changes. It is unlikely that all patients share the same individual or combined mechanisms given the heterogeneity of resultant phenotypes. Lung explants, bronchial biopsies and other tissue studies have revealed important features. At the small airway level, progression of COPD is clinically imperceptible, and the pathological course of the disease is poorly described. Asthmatic features can further add confusion. However, the small airway epithelium is likely to represent a key focus of the disease, combining impaired subepithelial crosstalk and structural/inflammatory changes. Insufficient resolution of inflammatory processes may facilitate these changes. Pathologically, epithelial metaplasia, inversion of the goblet to ciliated cell ratio, enlargement of the submucosal glands and neutrophil and CD8-T-cell infiltration can be detected. Evidence of type 2 inflammation is gaining interest in the light of new therapeutic agents. Alarmin biology is a promising area that may permit control of inflammation and partial reversal of structural changes in COPD. Here, we review the latest work describing the development and progression of COPD with a focus on lung function trajectories, exacerbations and survival. We also review mechanisms focusing on epithelial changes associated with COPD and lack of resolution characterizing the underlying inflammatory processes.


Nonparametric discriminant analysis.
A nonparametric method of discriminant analysis is proposed. It is based on nonparametric extensions of commonly used scatter matrices. Two advantages result from the use of the proposed nonparametric scatter matrices. First, they are generally of full rank. This provides the ability to specify the number of extracted features desired. This is in contrast to parametric discriminant analysis, which for an L class problem typically can determine at most L 1 features. Second, the nonparametric nature of the scatter matrices allows the procedure to work well even for non-Gaussian data sets. Using the same basic framework, a procedure is proposed to test the structural similarity of two distributions. The procedure works in high-dimensional space. It specifies a linear decomposition of the original data space in which a relative indication of dissimilarity along each new basis vector is provided. The nonparametric scatter matrices are also used to derive a clustering procedure, which is recognized as a k-nearest neighbor version of the nonparametric valley seeking algorithm. The form which results provides a unified view of the parametric nearest mean reclassification algorithm and the nonparametric valley seeking algorithm.


Functional Analysis of Ectodysplasin-A Mutations in X-Linked Nonsyndromic Hypodontia and Possible Involvement of X-Chromosome Inactivation.
Mutations of the Ectodysplasin-A (EDA) gene are generally associated with syndrome hypohidrotic ectodermal dysplasia or nonsyndromic tooth agenesis. The influence of EDA mutations on dentinogenesis and odontoblast differentiation has not been reported. The aim of this study was to identify genetic clues for the causes of familial nonsyndromic oligodontia and explore the underlying mechanisms involved, while focusing on the role of human dental pulp stem cells (hDPSCs). Candidate gene sequences were obtained by PCR amplification and Sanger sequencing. Functional analysis was conducted, and the pathogenesis associated with EDA mutations in hDPSCs was investigated to explore the impact of the identified mutation on the phenotype. Capillary electrophoresis (CE) was used to detect X-chromosome inactivation (XCI) in the blood of female carriers. In this study, we identified an EDA mutation in a Chinese family: the missense mutation c.1013C>T (Thr338Met). Transfection of hDPSCs with a mutant EDA lentivirus decreased the expression of EDA and dentin sialophosphoprotein (DSPP) compared with transfection of control EDA lentivirus. Mechanistically, mutant EDA inhibited the activation of the NF-κB pathway. The CE results showed that symptomatic female carriers had a skewed XCI with a preferential inactivation of the X chromosome that carried the normal allele. In summary, we demonstrated that EDA mutations result in nonsyndromic tooth agenesis in heterozygous females and that, mechanistically, EDA regulates odontogenesis through the NF-κB signalling pathway in hDPSCs. Due to the large heterogeneity of tooth agenesis, this study provided a genetic basis for individuals who exhibit similar clinical phenotypes.


IL-7 coordinates proliferation, differentiation and Tcra recombination during thymocyte β-selection.
Signaling via the pre-T cell antigen receptor (pre-TCR) and the receptor Notch1 induces transient self-renewal (β-selection) of TCRβ(+) CD4(-)CD8(-) double-negative stage 3 (DN3) and DN4 progenitor cells that differentiate into CD4(+)CD8(+) double-positive (DP) thymocytes, which then rearrange the locus encoding the TCR α-chain (Tcra). Interleukin 7 (IL-7) promotes the survival of TCRβ(-) DN thymocytes by inducing expression of the pro-survival molecule Bcl-2, but the functions of IL-7 during β-selection have remained unclear. Here we found that IL-7 signaled TCRβ(+) DN3 and DN4 thymocytes to upregulate genes encoding molecules involved in cell growth and repressed the gene encoding the transcriptional repressor Bcl-6. Accordingly, IL-7-deficient DN4 cells lacked trophic receptors and did not proliferate but rearranged Tcra prematurely and differentiated rapidly. Deletion of Bcl6 partially restored the self-renewal of DN4 cells in the absence of IL-7, but overexpression of BCL2 did not. Thus, IL-7 critically acts cooperatively with signaling via the pre-TCR and Notch1 to coordinate proliferation, differentiation and Tcra recombination during β-selection.


The use of antifibrinolytics in pediatric patients with hypoproliferative thrombocytopenia.
Despite the use of evidence-based platelet transfusion therapy during periods of hypoproliferative thrombocytopenia, a large proportion of pediatric hematology/oncology patients continue to suffer from clinically significant bleeding. Antifibrinolytic (AF) drugs have been shown in certain surgical and trauma settings to decrease bleeding, blood transfusion, and improve survival. We conducted a retrospective assessment of the safety of using AF drugs in pediatric patients with hypoproliferative thrombocytopenia at our center as well as the impact on bleeding occurrence and severity.


Enhanced early sensory outcome after nerve repair as a result of immediate post-operative re-learning: a randomized controlled trial.
We assessed the use of guided plasticity training to improve the outcome in the first 6 months after nerve repair. In a multicentre randomized controlled trial, 37 adults with median or ulnar nerve repair at the distal forearm were randomized to intervention, starting the first week after surgery with sensory and motor re-learning using mirror visual feedback and observation of touch, or to a control group with re-learning starting when reinnervation could be detected. The primary outcome at 3 and 6 months post-operatively was discriminative touch (shape texture identification test, part of the Rosen score). At 6 months, discriminative touch was significantly better in the early intervention group. Improvement of discriminative touch between 3 and 6 months was also significantly greater in that group. There were no significant differences in motor function, pain or in the total score. We conclude that early re-learning using guided plasticity may have a potential to improve the outcomes after nerve repair. LEVEL OF EVIDENCE II.


Effect of Lactobacillus acidophilus & epidermal growth factor on experimentally induced Clostridium difficile infection.
Clostridium difficile-associated disease (CDAD) remains an important nosocomial ailment. Antimicrobial therapy used for CDAD gives inconsistent results. This experimental study was planned to investigate the beneficial effects of Lactobacillus acidophilus and epidermal growth factor (EGF) for CDAD management. Among 10 groups of BALB/c mice (6 in each), group 1 served as controls receiving no inoculum. Animals in groups 2-10 received C. difficile, those in groups 3, 6 and 9 received L. acidophilus and those in groups 4, 7 and 10 received EGF after C. difficile inoculation. Animals in groups 5-7 were pre-treated with ampicillin and those in groups 8-10 with lansoprazole prior to C. difficile. The animals were killed and investigated for colonisation by C. difficile and toxin production, myeloperoxidase (MPO) activity and histopathology. Colonisation by C. difficile was found to be significantly different (P<0.001) in the various groups. C. difficile toxin titres and MPO activity were significantly lower in animals given L. acidophilus and EGF after ampicillin (groups 6 and 7) and lansoprazole (groups 9 and 10). The severity of acute inflammation was also significantly less (P<0.05) in caecal and colonic segments of animals in groups 6 and 7 compared to those in group 5. Although the severity of acute inflammation was less in the caecal and colonic segment of animals in groups 9 and 10, the reduction was not significant compared to group 8. Our findings showed that the administration of L. acidophilus and EGF reduced the severity of C. difficile infection in the experimental animals.


Bochdalek hernia in an adult female with intrathoracic left kidney and splenic flexure of the colon: a rare case report with literature review.
Congenital diaphragmatic hernia (CDH) is extremely rare in adults. Bochdalek hernia (BH) is the most common one among all congenital diaphragmatic hernias. This is due to incomplete fusion of pleuroperitoneal folds during early fetal development. It remains asymptomatic in many adults. It usually occurs on the left side and is common in males (62%). Open or laparoscopic surgical repair is the treatment of choice. We reported on a rare case of BH in an adult female with intra-thoracic left kidney and splenic flexure of the colon, who presented with non-specific abdominal symptoms. Key message: BH in adults is usually present with vague abdominal symptoms. We advocate the use of the CECT scan of the abdomen in the management of all cases with non-specific abdominal symptoms.


Search for new particles in two-jet final states in 7 TeV proton-proton collisions with the ATLAS detector at the LHC.
A search for new heavy particles manifested as resonances in two-jet final states is presented. The data were produced in 7 TeV proton-proton collisions by the LHC and correspond to an integrated luminosity of 315 nb⁻¹ collected by the ATLAS detector. No resonances were observed. Upper limits were set on the product of cross section and signal acceptance for excited-quark (q*) production as a function of q* mass. These exclude at the 95% C.L. the q* mass interval 0.30<m(q*)<1.26 TeV, extending the reach of previous experiments.


Differential Expression of Multiple Disease-Related Protein Groups Induced by Valproic Acid in Human SH-SY5Y Neuroblastoma Cells.
Valproic acid (VPA) is a multifunctional medication used for the treatment of epilepsy, mania associated with bipolar disorder, and migraine. The pharmacological effects of VPA involve a variety of neurotransmitter and cell signaling systems, but the molecular mechanisms underlying its clinical efficacy is to date largely unknown. In this study, we used the isobaric tags for relative and absolute quantitation shotgun proteomic analysis to screen differentially expressed proteins in VPA-treated SH-SY5Y cells. We identified changes in the expression levels of multiple proteins involved in Alzheimer's disease, Parkinson's disease, chromatin remodeling, controlling gene expression via the vitamin D receptor, ribosome biogenesis, ubiquitin-mediated proteolysis, and the mitochondrial oxidative phosphorylation and electron transport chain. Our data indicate that VPA may modulate the differential expression of proteins involved in mitochondrial function and vitamin D receptor-mediated chromatin transcriptional regulation and proteins implicated in the pathogenesis of neurodegenerative diseases.


Liposome-tethered supported lipid bilayer platform for capture and release of heterogeneous populations of circulating tumor cells.
Because of scarcity, vulnerability, and heterogeneity in the population of circulating tumor cells (CTCs), the CTC isolation system relying on immunoaffinity interaction exhibits inconsistent efficiencies for all types of cancers and even CTCs with different phenotypes in individuals. Moreover, releasing viable CTCs from an isolation system is of importance for molecular analysis and drug screening in precision medicine, which remains a challenge for current systems. In this work, a new CTC isolation microfluidic platform was developed and contains a coating of the antibody-conjugated liposome-tethered-supported lipid bilayer in a developed chaotic-mixing microfluidic system, referred to as the "LIPO-SLB" platform. The biocompatible, soft, laterally fluidic, and antifouling properties of the LIPO-SLB platform offer high CTC capture efficiency, viability, and selectivity. We successfully demonstrated the capability of the LIPO-SLB platform to recapitulate different cancer cell lines with different antigen expression levels. In addition, the captured CTCs in the LIPO-SLB platform can be detached by air foam to destabilize the physically assembled bilayer structures due to a large water/air interfacial area and strong surface tension. More importantly, the LIPO-SLB platform was constructed and used for the verification of clinical samples from 161 patients with different primary cancer types. The mean values of both single CTCs and CTC clusters correlated well with the cancer stages. Moreover, a considerable number of CTCs were isolated from patients' blood samples in the early/localized stages. The clinical validation demonstrated the enormous potential of the universal LIPO-SLB platform as a tool for prognostic and predictive purposes in precision medicine.


Microhydration effects on the encapsulation of potassium ion by dibenzo-18-crown-6.
We have measured electronic and conformer-specific vibrational spectra of hydrated dibenzo-18-crown-6 (DB18C6) complexes with potassium ion, K(+)•DB18C6•(H2O)n (n = 1-5), in a cold, 22-pole ion trap. We also present for comparison spectra of Rb(+)•DB18C6•(H2O)3 and Cs(+)•DB18C6•(H2O)3 complexes. We determine the number and the structure of conformers by analyzing the spectra with the aid of quantum chemical calculations. The K(+)•DB18C6•(H2O)1 complex has only one conformer under the conditions of our experiment. For K(+)•DB18C6•(H2O)n with n = 2 and 3, there are at least two conformers even under the cold conditions, whereas Rb(+)•DB18C6•(H2O)3 and Cs(+)•DB18C6•(H2O)3 each exhibit only one isomer. The difference can be explained by the optimum matching in size between the K(+) ion and the crown cavity; because the K(+) ion can be deeply encapsulated by DB18C6 and the interaction between the K(+) ion and the H2O molecules becomes weak, different kinds of hydration geometries can occur for the K(+)•DB18C6 complex, giving multiple conformations in the experiment. For K(+)•DB18C6•(H2O)n (n = 4 and 5) complexes, only a single isomer is found. This is attributed to a cooperative effect of the H2O molecules on the hydration of K(+)•DB18C6; the H2O molecules form a ring, which is bound on top of the K(+)•DB18C6 complex. According to the stable structure determined in this study, the K(+) ion in the K(+)•DB18C6•(H2O)n complexes tends to be pulled largely out from the crown cavity by the H2O molecules with increasing n. Multiple conformations observed for the K(+) complexes will have an advantage for the effective capture of the K(+) ion over the other alkali metal ions by DB18C6 because of entropic effects on the formation of hydrated complexes.


Can monkeys (Macaca mulatta) represent invisible displacement?
Four experiments were conducted to assess whether or not rhesus macaques (Macaca mulatta) could represent the unperceived movements of a stimulus. Subjects were tested on 2 computerized tasks, HOLE (monkeys) and LASER (humans and monkeys), in which subjects needed to chase or shoot at, respectively, a moving target that either remained visible or became invisible for a portion of its path of movement. Response patterns were analyzed and compared between target-visible and target-invisible conditions. Results of Experiments 1, 2, and 3 demonstrated that the monkeys are capable of extrapolating movement. That this extrapolation involved internal representation of the target's invisible movement was suggested but not confirmed. Experiment 4, however, demonstrated that the monkeys are capable of representing the invisible displacements of a stimulus.


Developmental perturbation induced by maternal asthma during pregnancy: the short- and long-term impacts on offspring.
Maternal asthma is a common disease to complicate human pregnancy. Epidemiological studies have identified that asthma during pregnancy increases the risk of a number of poor outcomes for the neonate including growth restriction, lower birthweight, preterm delivery, neonatal resuscitation, and stillbirth. Asthma therefore represents a significant health burden to society and could have an impact on the lifelong health of the children of women with asthma. Our research has identified that maternal asthma in pregnancy induces placental dysfunction and developmental perturbation in the fetus in a sex specific manner. These alterations in development could increase the risk of metabolic disease in adulthood of children of asthmatic mothers, especially females. In this paper, we will discuss the evidence currently available that supports the hypothesis that children of mothers with asthma may be at risk of lifelong health complications which include diabetes and hypertension.