Does the clinical outcome of hepatitis C infection vary with the infecting hepatitis C virus type?
Whether differences in the natural history of hepatitis C virus (HCV) can be explained by differences in the infecting HCV type is unknown. The aim of this study was to investigate whether the HCV type might influence the clinical outcome of infection. Study serum samples were assembled from 749 individuals enrolled into the UK HCV National Register from which data on clinical outcomes were extracted. HCV-RNA-positive specimens were genotyped and HCV-RNA-negative specimens serotyped. Logistic regression analysis was used to investigate the independent effect of HCV type on viral clearance by comparing patients who were HCV RNA negative (n = 86) with those who were HCV RNA positive (n = 508). The same method was used to investigate whether HCV type was associated with histological stage of liver disease. The prevalence of HCV type 1 among those who cleared infection was 69% and among those who remained HCV RNA positive was 51%: Type 1 infections were more likely to be HCV RNA negative than non-1 types (OR 0.47, 95% CI 0.29-0.78, P = 0.003). Type 1 infections were also more likely to be associated with histological stage scores above the median when compared with non-1 types (OR 2.03, 95% CI 1.07-3.83, P = 0.03). In conclusion, HCV type 1 infection was more often HCV RNA negative, suggesting that spontaneous clearance may occur more commonly with this type. Among the RNA-positive infections, type 1 infection may be more aggressive than types 2/3.


The meaning of technology for people with chronic renal failure.
The article is based on the findings of a hermeneutic study that focused on the experience of individuals receiving hemodialysis for chronic renal failure. The purpose of the research was to begin to understand the experience and meaning of technology for these individuals. Three themes reflected the dimensions of the participants' individual and collective experiences: coming to terms with loss and limitations, abiding with technology, and enduring the treatment environment. Overall, the participants found themselves struggling to remain embodied while being transformed by a reluctant partnering with technology.


Marine genomics: a clearing-house for genomic and transcriptomic data of marine organisms.
The Marine Genomics project is a functional genomics initiative developed to provide a pipeline for the curation of Expressed Sequence Tags (ESTs) and gene expression microarray data for marine organisms. It provides a unique clearing-house for marine specific EST and microarray data and is currently available at http://www.marinegenomics.org. The Marine Genomics pipeline automates the processing, maintenance, storage and analysis of EST and microarray data for an increasing number of marine species. It currently contains 19 species databases (over 46,000 EST sequences) that are maintained by registered users from local and remote locations in Europe and South America in addition to the USA. A collection of analysis tools are implemented. These include a pipeline upload tool for EST FASTA file, sequence trace file and microarray data, an annotative text search, automated sequence trimming, sequence quality control (QA/QC) editing, sequence BLAST capabilities and a tool for interactive submission to GenBank. Another feature of this resource is the integration with a scientific computing analysis environment implemented by MATLAB. The conglomeration of multiple marine organisms with integrated analysis tools enables users to focus on the comprehensive descriptions of transcriptomic responses to typical marine stresses. This cross species data comparison and integration enables users to contain their research within a marine-oriented data management and analysis environment.


Social relationships and social cognition in nonhuman primates.
Complex social relationships among nonhuman primates appear to contribute to individual reproductive success. Experiments with and behavioral observations of natural populations suggest that sophisticated cognitive mechanisms may underlie primate social relationships. Similar capacities are usually less apparent in the nonsocial realm, supporting the view that at least some aspects of primate intelligence evolved to solve the challenges of interacting with conspecifics.


Turnover of matrix proteins in mammalian mitochondria.
In cultured hepatocytes the turnover of several mitochondrial matrix proteins (e.g. acetyl-CoA acetyltransferase) appears to be initiated by CoA-mediated, sequential transformation into CoA-modified forms. This modification favours the notion that intramitochondrial degradation by a matrix-resident ATP-dependent protease may be preceded by a specific modification by CoA. In a mitochondrial matrix fraction the MgATP-dependent decrease in anti-CoA immunoreactivity coincided with both a decrease in the anti-protein immunoreactivity of acetyl-CoA acetyltransferase and/or of 3-ketoacyl-CoA thiolase, and with the appearance of proteolytic fragments. A closer analysis of the degradation pattern revealed, however, a breakdown of the unmodified acetyl-CoA acetyltransferase and of its CoA-modified form, A1, whereas the form that is more highly modified by CoA, A2, proved to be inaccessible towards an ATP-dependent protease. In mammalian mitochondrial matrix, proteins can be degraded selectively by a matrix-resident ATP-dependent protease. The process of CoA modification results finally in the protection of matrix proteins from degradation. In cultured hepatocytes, leupeptin, an inhibitor of lysosomal proteases, did not affect the steady-state level of the mitochondrial matrix protein acetyl-CoA acetyltransferase. However, leupeptin mediated a specific accumulation of mitochondrial matrix proteins in the cytosolic fractions of hepatocytes cultured over a 24 h period. The levels of acetyl-CoA acetyltransferase, 3-ketoacyl-CoA thiolase and glutamate dehydrogenase proteins increased 1.9-, 2.0- and 2.2-fold respectively. Their status as mature, oligomeric, but enzymically inactive enzymes strongly suggests that they originate from a leakage of autophagosomes, a constituent of the non-selective autophagic/lysosomal pathway for degradation of whole mitochondria.


Endosome/lysosome-detained supramolecular nanogels as an efflux retarder and autophagy inhibitor for repeated photodynamic therapy of multidrug-resistant cancer.
The presence of drug efflux pumps and endo/lysosomal entrapment phenomena in multidrug-resistant cancer cells leads to insufficient and off-target accumulation of anticancer drugs in the cells, which severely reduces the drugs' therapeutic efficacies. Here, we prepare a novel type of photosensitizer (PS)-loaded supramolecular nanogel, which can utilize the endo/lysosomal entrapment for enhanced photodynamic therapy (PDT) of multidrug-resistant cancer. The PS-loaded nanogels can elude the drug efflux pumps, and be markedly internalized by drug-resistant cancer cells through the endocytic pathway. With their pH-sensitive properties, the internalized nanogels can aggregate in the acidic endosomes/lysosomes, thus retarding their exocytosis from the cells. Moreover, the lysosomes of the nanogel-treated cells are severely damaged after irradiation, which inhibits the protective autophagy and improves the photodynamic therapeutic performance of the nanogels. Besides, the in vivo experiments show that the nanogels significantly prolong the tumor retention of the PSs, thus enabling multiple PDT treatments after a single drug injection.


A transdiagnostic approach to understanding eating disorders.
Categorical models dominate the eating disorder field, but the tandem use of categorical and dimensional models has been proposed. A transdiagnostic dimensional model, number of lifetime eating disorder behaviors (LEDB), was examined with respect to (1) its relationship to a variety of indicators of the individual's functioning, (2) the degree to which it was influenced by genetic and environmental risk factors, and (3) exposure to specific environmental risk factors. Data from self-report and interview from 1002 female twins (mean age = 34.91 years, SD = 2.09) were examined. While 15.4% women met criteria for a lifetime eating disorder, 29% had at least one LEDB. The dimensional measure provided an indicator of associated functioning, and was influenced primarily by the nonshared environment. The number of LEDB was associated with the degree of impaired functioning. This impairment was associated with conflict between parents and criticism from parents when growing up.


Cigarette smoke extract induces airway epithelial cell death via repressing PRMT6/AKT signaling.
Chronic obstructive pulmonary disease (COPD) is a severe public health threat world-wide. Cigarette smoke (CS)-induced airway epithelial cell death is a major pathway of pathogenesis in emphysema, a subtype of COPD. Protein arginine methyltransferase 6 (PRMT6) is a type I PRMT that catalyzes mono- and di-methylation on arginine residues within histone and non-histone proteins to modulate a variety of life processes, such as apoptosis. However, its role in CS-induced lung epithelial death has not been fully elucidated. Here we report that PRMT6 was decreased in mouse lung tissues from a cigarette smoke extract (CSE)-mediated experimental emphysematous model and in CSE treated or cigarette smoke exposed lung epithelial cells. Depletion of PRMT6 increased the protein levels of phosphatase PTEN and PI3K regulatory subunit p85 but decreased a downstream kinase PDK1, resulting in AKT dephosphorylation and thereafter, lung epithelial cell death. Knockout of PRMT6 inhibited epithelial survival and promoted CSE-mediated epithelial cell death, while ectopic expression of PRMT6 protein partially reversed epithelial cell death via PI3K/AKT-mediated cell survival signaling in CSE cellular models. These findings demonstrate that PRMT6 plays a crucial role in CS-induced bronchial epithelial cell death that may be a potential therapeutic target against the airway cell death in CS-induced COPD.


[Humoral immune phenomena in acute and chronic viral hepatitis (author's transl)].
During HBAg positive acute viral hepatitis transitory antibodies of a low titer against smooth muscle, vascular endothelium, nuclei, and liver cell membrane antigens (polygonal pattern of immunofluorescence) occur. In HBAg positive chronic aggressive hepatitis, sometimes antibodies against nuclei or smooth muscle are associated with HBAg. Their occurrence heralds an unfavorable prognosis. High titer antibodies against nuclei and smooth muscle - a typical serology finding in lupoid chronic aggressive hepatitis - and mitochondrial antibodies have not been observed in a HBAg positive hepatitis. Subdividing chronic hepatitis in six different groups is possible with HBAg and antibodies. The predominance of histocompatability antigen HLA 8 in lupoid hepatitis and a lack of this leukocyte antigen in HGAg positive chronic aggressive hepatitis suggests that in the various forms of hepatitis, a different susceptability and capability for immune response towards microorganism is reflected. It is postulated that for course and outcome of hepatitis, the type of immune reaction plays a decisive role.


Unmasking the ciliopathies: craniofacial defects and the primary cilium.
Over the past decade, the primary cilium has emerged as a pivotal sensory organelle that acts as a major signaling hub for a number of developmental signaling pathways. In that time, a vast number of proteins involved in trafficking and signaling have been linked to ciliary assembly and/or function, demonstrating the importance of this organelle during embryonic development. Given the central role of the primary cilium in regulating developmental signaling, it is not surprising that its dysfunction results in widespread defects in the embryo, leading to an expanding class of human congenital disorders known as ciliopathies. These disorders are individually rare and phenotypically variable, but together they affect virtually every vertebrate organ system. Features of ciliopathies that are often overlooked, but which are being reported with increasing frequency, are craniofacial abnormalities, ranging from subtle midline defects to full-blown orofacial clefting. The challenge moving forward is to understand the primary mechanism of disease given the link between the primary cilium and a number of developmental signaling pathways (such as hedgehog, platelet-derived growth factor, and WNT signaling) that are essential for craniofacial development. Here, we provide an overview of the diversity of craniofacial abnormalities present in the ciliopathy spectrum, and reveal those defects in common across multiple disorders. Further, we discuss the molecular defects and potential signaling perturbations underlying these anomalies. This provides insight into the mechanisms leading to ciliopathy phenotypes more generally and highlights the prevalence of widespread dysmorphologies resulting from cilia dysfunction.


Multiple loops of the dihydropyridine receptor pore subunit are required for full-scale excitation-contraction coupling in skeletal muscle.
Understanding which cytosolic domains of the dihydropyridine receptor participate in excitation-contraction (EC) coupling is critical to validate current structural models. Here we quantified the contribution to skeletal-type EC coupling of the alpha1S (CaV1.1) II-III loop when alone or in combination with the rest of the cytosolic domains of alpha1S. Chimeras consisting of alpha1C (CaV1.2) with alpha1S substitutions at each of the interrepeat loops (I-II, II-III, and III-IV loops) and N- and C-terminal domains were evaluated in dysgenic (alpha1S-null) myotubes for phenotypic expression of skeletal-type EC coupling. Myotubes were voltage-clamped, and Ca2+ transients were measured by confocal line-scan imaging of fluo-4 fluorescence. In agreement with previous results, the alpha1C/alpha1S II-III loop chimera, but none of the other single-loop chimeras, recovered a sigmoidal fluorescence-voltage curve indicative of skeletal-type EC coupling. To quantify Ca2+ transients in the absence of inward Ca2+ current, but without changing the external solution, a mutation, E736K, was introduced into the P-loop of repeat II of alpha1C. The Ca2+ transients expressed by the alpha1C(E736K)/alpha1S II-III loop chimera were approximately 70% smaller than those expressed by the Ca2+-conducting alpha1C/alpha1S II-III variant. The low skeletal-type EC coupling expressed by the alpha1C/alpha1S II-III loop chimera was confirmed in the Ca2+-conducting alpha1C/alpha1S II-III loop variant using Cd2+ (10(-4) M) as the Ca2+ current blocker. In contrast to the behavior of the II-III loop chimera, Ca2+ transients expressed by an alpha1C/alpha1S chimera carrying all tested skeletal alpha1S domains (all alpha1S interrepeat loops, N- and C-terminus) were similar in shape and amplitude to wild-type alpha1S, and did not change in the presence of the E736K mutation or in the presence of 10(-4) M Cd2+. Controls indicated that similar dihydropyridine receptor charge movements were expressed by the non-Ca2+ permeant alpha1S(E1014K) variant, the alpha1C(E736K)/alpha1S II-III loop chimera, and the alpha1C(E736K)/alpha1S chimera carrying all tested alpha1S domains. The data indicate that the functional recovery produced by the alpha1S II-III loop is incomplete and that multiple cytosolic domains of alpha1S are necessary for a quantitative recovery of the EC-coupling phenotype of skeletal myotubes. Thus, despite the importance of the II-III loop there may be other critical determinants in alpha1S that influence the efficiency of EC coupling.


Network Together: Node Classification via Cross-Network Deep Network Embedding.
Network embedding is a highly effective method to learn low-dimensional node vector representations with original network structures being well preserved. However, existing network embedding algorithms are mostly developed for a single network, which fails to learn generalized feature representations across different networks. In this article, we study a cross-network node classification problem, which aims at leveraging the abundant labeled information from a source network to help classify the unlabeled nodes in a target network. To succeed in such a task, transferable features should be learned for nodes across different networks. To this end, a novel cross-network deep network embedding (CDNE) model is proposed to incorporate domain adaptation into deep network embedding in order to learn label-discriminative and network-invariant node vector representations. On the one hand, CDNE leverages network structures to capture the proximities between nodes within a network, by mapping more strongly connected nodes to have more similar latent vector representations. On the other hand, node attributes and labels are leveraged to capture the proximities between nodes across different networks by making the same labeled nodes across networks have aligned latent vector representations. Extensive experiments have been conducted, demonstrating that the proposed CDNE model significantly outperforms the state-of-the-art network embedding algorithms in cross-network node classification.


Effect of cytochalasin B on the adhesion of mouse peritoneal macrophages.
The adhesion of normal mouse macrophages to glass surfaces was reduced by nontoxic levels (1-50 mug/ml) of cytochalasin B in combination with a centrifugal force (1,000-8,000 g). Macrophages nonspecifically activated by Corynebacterium acnes were also detached by this treatment, but less effectively. The effects of cytochalasin B treatment on these cells were shown to be reversible. After detachment, the cells reattached to glass, appeared morphologically normal, and behaved like untreated cells as judged by adhesion, acid phosphatase levels, and phagocytosis. The effect of cytochalasin B on several parameters of phagocytosis by normal macrophages was also examined. The results demonstrate that cytochalasin B can be used to detach macrophages from surfaces and suggest a functional relationship between phagocytosis and macrophage adhesion to surfaces. Furthermore, the effect of cytochalasin B on adhesion of phagocytic cells provides a probe for further investigation of the adhesion of cells to surfaces.


Elevated Expression of Kin17 in Cervical Cancer and Its Association With Cancer Cell Proliferation and Invasion.
Cervical cancer is one of the most common cancers in women worldwide. Emerging evidence suggests that kin17 is a tumor-promoting protein in some types of solid tumors. However, whether kin17 contributes to cervical cancer carcinogenesis remains unknown. Kin17 expression in clinical samples from Guangdong Women and Children's Hospital and Health Institute was detected by immunohistochemical staining. A series of functional experiments including 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay, 5-bromo-2'-deoxyuridine assay, colony formation, transwell assay, flow cytometry of apoptosis, and cell cycle were performed to explore the roles of kin17 in cervical cancer cells HeLa. In this study, we showed for the first time that the expression of kin17 was significantly increased in clinical cervical cancer samples, and associated with tumor differentiation, lymph node metastasis, and ki-67 expression in a clinicopathologic characteristics review. Furthermore, silence of kin17 in HeLa cells inhibited cell proliferation, clone formation, cell cycle progression, migration, and invasion, and also promoted cell apoptosis. Our findings demonstrate that kin17 is closely related to the cell proliferation and invasion of cervical cancer and could be a novel diagnostic and therapeutic target for cervical cancer management. The underlying mechanisms should be elucidated in future research.


[A study on the experiences of nurse coroners].
The purpose of this study was to describe the essential structure of the postmortem- examination experiences of nurse career coroners (forensic investigators), to have a profound understanding of their experiences, and ultimately to lay the foundation for nurses' entry into the field of forensic nursing. The subjects in this study were six coroners. After an in-depth interview from January to June 2007, the collected data were analyzed by Colaizzi as qualitative research. Four categories emerged from seven theme clusters. The four categories were: attracted by being dubbed a stabilized public official, a sense of achievement due to having clarified false death, self-confidence after distinguishing the victim and the wrongdoer, eternal developmental potential is seen. It is expected that this study will provide useful information for nurses who are interested in becoming coroners. It will be helpful for career nurses to extend their nursing science into emerging fields like coroners and select a follow-up career.


Case report: term birth after fertility-sparing treatments for stage IB1 small cell neuroendocrine carcinoma of the cervix.
Advances in cervical cancer management for childbearing women have led to less radical approaches. Use of fertility-sparing treatment to treat small cell neuroendocrine carcinoma (SCNEC) is challenging owing to the aggressive nature of the disease, even in early stage disease. A 25-year-old nulligravida woman presented with malodorous vaginal discharge and was diagnosed to have an exophytic cervical SCNEC. A magnetic resonance image scan showed no evidence of parametrial invasion or distant metastasis. Clinical staging allocated her to stage IB1 disease. She underwent radical abdominal trachelectomy for reproductive purpose. Preoperative and postoperative chemotherapy with ifosfamide/etoposide/cisplatin combining gonadotropin-releasing hormone agonist were administered. She had a spontaneous, uneventful pregnancy and successfully delivered a term baby via cesarean section 7 years after treatment. To our knowledge, we describe the first success in offering a fertility-preserving multimodality strategy to present favorable oncologic, reproductive, and obstetric outcomes in a fertile woman of stage I SCNEC. Individualized multimodality therapy may be utilized in specific patients with early-stage cervical cancer to preserve their fertility.


[Motherhood behind bars: the struggle for citizens' rights and health for women inmates and their children in Brazil].
This study analyzes the links between health, rights, legislation, and public policies based on document research on legal safeguards for women and their children residing in prison. The research was conducted at the Federal level and in four States of Brazil: Rio Grande do Sul, Mato Grosso, Paraná, and São Paulo. The study aims to back measures by public agencies to guarantee such rights and to raise awareness of the problem, given the extreme vulnerability of women inmates and their children and the issue's legal and administrative invisibility. The authors identified 33 different legal provisions as points of tension, such as the possibility of house arrest and disparities in the terms and conditions for children to remain inside the prison system. Various provisions cite the Constitutional guarantee of women inmates' right to breastfeed in prison. Meanwhile, the study found gaps in other issues pertaining to motherhood in prison, expressed as dual incarceration (imprisonment arbitrarily extended to their children). It is necessary to expand and enforce the existing legislation to prevent such violations of rights.


Cleavage of fibromodulin in cartilage explants involves removal of the N-terminal tyrosine sulfate-rich region by proteolysis at a site that is sensitive to matrix metalloproteinase-13.
Integrity of cartilage fails in joint disease. The current work aimed to identify candidate active proteinases in joint diseases using an in vitro model for cartilage degradation induced by interleukin-1. A critical event in the process of cartilage destruction in joint disease is the failure of the collagen fiber network to maintain integrity. Proteins binding to the surface of the fibers are likely early points of failure. Fibromodulin, a member of the leucine-rich repeat protein family, is one predominant protein in cartilage and is known for its roles in the formation of collagen fibrils and sustained interaction with these formed fibers. Cleavage removes the tyrosine sulfate-rich region in the N terminus of fibromodulin. Whereas fibromodulin bound to collagen in tissue was digested, purified fibromodulin was not cleaved. In contrast an N-terminal 10-kDa fragment, Gln19-Lys98, of the protein generated by Lys-C digestion contains the cleavage site and was a substrate cleaved by the enzyme in medium from stimulated cultures. In solution, digestion of this substrate with matrix metalloproteinase (MMP)-2, -9, -8, and -13 demonstrated that only MMP-13 was capable to efficiently cleave it. The cleavage product obtained after MMP-13 digestion was identical to that observed in cleaved fibromodulin from cartilage explant cultures stimulated with interleukin-1. MMP-13 treatment of fresh articular cartilage also produced the fragment under study. The elucidation of the enzyme responsible for such cleavage may lead to treatment modalities involving its selective inhibition for patients suffering from arthritis. The known structure of the fragments permits the generation of neo-epitope antibodies to the cleavage site, which can be used to detect ongoing cartilage degradation in patients with arthritic disease, an important adjunct in monitoring disease progression, active disease, and efficacy of treatment.


Injection treatments for patellar tendinopathy.
Injection treatments are increasingly used as treatment for patellar tendinopathy. The aim of this systematic review is to describe the different injection treatments, their rationales and the effectiveness of treating patellar tendinopathy. A computerised search of the Medline, Embase, CINAHL and Web of Knowledge databases was conducted on 1 May 2010 to identify studies on injection treatments for patellar tendinopathy. 11 articles on seven different injection treatments (dry needling, autologous blood, high-volume, platelet-rich plasma, sclerosis, steroids and aprotinin injections) were found: 4 randomised controlled trials (RCTs), 1 non-RCT, 4 prospective cohort studies and 2 retrospective cohort studies. All studies reported positive results. The Delphi scores of the four RCTs ranged from 5 to 8 out of 9. Different and sometimes contradictory rationales were used for the injection treatments. All seven different injection treatments seem promising for treating patellar tendinopathy. Unlike the other injection treatments, steroid treatment often shows a relapse of symptoms in the long term. Results should be interpreted with caution as the number of studies is low, few high-quality studies have been conducted and the studies are hard to compare due to different methodology. More high-quality studies using the same cross-cultural reliable and valid outcome measure are needed, as well as further research into the pathophysiology. Finally, some implications are provided for clinicians who want to use injection treatments as a part of their treatment for patellar tendinopathy, distinguishing between reactive and degenerative phase of patellar tendinopathy.


Predictors of Neurological Outcome Following Infant Cardiac Surgery Without Deep Hypothermic Circulatory Arrest.
The aim of this study is to describe the clinical characteristics, perioperative course and neuroimaging abnormalities of infants with congenital heart disease (CHD) undergoing heart surgery without deep hypothermic circulatory arrest (DHCA) and identify variables associated with neurological outcome. Infants with CHD undergoing open-heart surgery without DHCA between 2009 and 2017 were identified from a cardiac surgery database. Full-term infants < 10 weeks of age at the time of surgery who had both a pre- and postoperative brain magnetic resonance imaging exam (MRI) were included. Clinical characteristics and perioperative variables were collected from the electronic medical record. Brain Injury Scores (BIS) were assigned to pre- and postoperative brain MRIs. Variables were examined for association with neurological outcome at 12 months of age or greater. Forty-two infants were enrolled in the study, of whom 69% (n = 29) had a neurological assessment ≥ to 12 months of age. Adverse neurological outcome was associated with longer intensive care unit (ICU) stay (P = 0.003), lengthier mechanical ventilation (P = 0.031), modified Blalock-Taussig (MBT) shunt procedure (P = 0.005) and postoperative seizures (P = 0.005). Total BIS scores did not predict outcome but postoperative infarction and/or intraparenchymal hemorrhage (IPH) was associated with worse outcome by multivariable analysis (P = 0.018). Infants with CHD undergoing open-heart surgery without DHCA are at increased risk of worse neurological outcome when their ICU stay is prolonged, mechanical ventilation is extended, MBT shunt is performed or when postoperative seizures are present. Cerebral infarctions and IPH on postoperative MRI are also associated with worse outcome.


High-energy breakfast with low-energy dinner decreases overall daily hyperglycaemia in type 2 diabetic patients: a randomised clinical trial.
High-energy breakfast and reduced-energy dinner (Bdiet) significantly reduces postprandial glycaemia in obese non-diabetic individuals. Our objective was to test whether this meal schedule reduces postprandial hyperglycaemia (PPHG) in patients with type 2 diabetes by enhancing incretin and insulin levels when compared with high-energy dinner and reduced-energy breakfast (Ddiet). In a randomised, open label, crossover design performed in a clinic setting, 18 individuals (aged 30-70 years with BMI 22-35 kg/m(2)) with type 2 diabetes (<10 years duration) treated with metformin and/or diet were given either Bdiet or Ddiet for 7 days. Participants were randomised by a person not involved in the study using a coin flip. Postprandial levels of plasma glucose, insulin, C-peptide and intact and total glucagon-like peptide-1 (iGLP-1 and tGLP-1) were assessed. The Bdiet included 2,946 kJ breakfast, 2,523 kJ lunch and 858 kJ dinner. The Ddiet comprised 858 kJ breakfast, 2,523 kJ lunch and 2,946 kJ dinner. Twenty-two individuals were randomised and 18 analysed. The AUC for glucose (AUCglucose) throughout the day was 20% lower, whereas AUCinsulin, AUCC-peptide and AUCtGLP-1 were 20% higher for the Bdiet than the Ddiet. Glucose AUC0-180min and its peak were both lower by 24%, whereas insulin AUC0-180min was 11% higher after the Bdiet than the Ddiet. This was accompanied by 30% higher tGLP-1 and 16% higher iGLP-1 levels. Despite the diets being isoenergetic, lunch resulted in lower glucose (by 21-25%) and higher insulin (by 23%) with the Bdiet vs Ddiet. High energy intake at breakfast is associated with significant reduction in overall PPHG in diabetic patients over the entire day. This dietary adjustment may have a therapeutic advantage for the achievement of optimal metabolic control and may have the potential for being preventive for cardiovascular and other complications of type 2 diabetes. Trial registration ClinicalTrials.gov NCT01977833 Funding No specific funding was received for the study.


Pancreatic KCa3.1 channels in health and disease.
Ion channels play an important role for regulation of the exocrine and the endocrine pancreas. This review focuses on the Ca2+-regulated K+ channel KCa3.1, encoded by the KCNN4 gene, which is present in both parts of the pancreas. In the islets of Langerhans, KCa3.1 channels are involved in the regulation of membrane potential oscillations characterizing nutrient-stimulated islet activity. Channel upregulation is induced by gluco- or lipotoxic conditions and might contribute to micro-inflammation and impaired insulin release in type 2 diabetes mellitus as well as to diabetes-associated renal and vascular complications. In the exocrine pancreas KCa3.1 channels are expressed in acinar and ductal cells. They are thought to play a role for anion secretion during digestion but their physiological role has not been fully elucidated yet. Pancreatic carcinoma, especially pancreatic ductal adenocarcinoma (PDAC), is associated with drastic overexpression of KCa3.1. For pharmacological targeting of KCa3.1 channels, we are discussing the possible benefits KCa3.1 channel inhibitors might provide in the context of diabetes mellitus and pancreatic cancer, respectively. We are also giving a perspective for the use of a fluorescently labeled derivative of the KCa3.1 blocker senicapoc as a tool to monitor channel distribution in pancreatic tissue. In summary, modulating KCa3.1 channel activity is a useful strategy for exo-and endocrine pancreatic disease but further studies are needed to evaluate its clinical suitability.


Butyl Acrylate/Vinyl Acetate Copolymer Latex Synthesis Using Ultrasound As an Initiator
The polymerization of oil-in-water (o/w) emulsions of monomeric species has been performed at 30°C (±5°C) under ultrasonic irradiation, in the absence of any added chemical initiators. Emulsions of butyl acrylate and vinyl acetate as well as emulsified mixtures of the two monomers have been reacted in this way. In all cases, the radicals formed as a result of the ultrasonic cavitation were sufficient to cause polymerization. Stable blue-white or white dispersions of polymer latex particles were obtained. The kinetics of the copolymerization process were monitored. The data obtained here show that the polymerization rate depends strongly upon the monomer concentration dissolved in the aqueous phase and on its vapor pressure. The more volatile of the monomers examined, vinyl acetate, was seen to have a markedly lower polymerization rate at equivalent monomer concentrations when compared to the butyl acrylate. This was attributed to monomer evaporation into the cavities formed by the ultrasound, causing a dampening of the cavitation process and hence a lower radical density. Data of particle sizes and polymer molecular weights for the latex samples support this hypothesis.


Suppressing recombination in polymer photovoltaic devices via energy-level cascades.
An energy cascading structure is designed in a polymer photovoltaic device to suppress recombination and improve quantum yields. By the insertion of a thin polymer interlayer with intermediate energy levels, electrons and holes can effectively shuttle away from each other while being spatially separated from recombination. An increase in open-circuit voltage and short-circuit current are observed in modified devices.


Fractures of the distal phalanx and associated soft tissue and osseous abnormalities in 22 horses with ossified sclerotic ungual cartilages diagnosed with magnetic resonance imaging.
Ungual cartilage ossification in the forelimb is a common finding in horses. Subtle abnormalities associated with the ungual cartilages can be difficult to identify on radiographs. Magnetic resonance (MR) imaging findings of 22 horses (23 forelimbs) with a fracture of the distal phalanx and ossified ungual cartilage were characterized and graded. All horses had a forelimb fracture. Eleven involved a left forelimb (seven medial; four lateral), and 12 involved a right forelimb (five medial; seven lateral). All fractures were nonarticular, simple in configuration, and nondisplaced. The fractures were oriented in an axial proximal to abaxial distal and palmar to dorsal direction, and extended from the base of the ossified ungual cartilage into the distal phalanx. The fracture involved the fossa of the collateral ligament on the distal phalanx in 17 of 23 limbs. The palmar process and ossified ungual cartilage was abnormally mineralized in all horses. Ligaments and soft tissues adjacent to the ossified ungual cartilages were affected in all horses. The routine site of fracture in this study at the base of the ossified ungual cartilage extending into the distal phalanx suggests a biomechanical cause or focal stress point from cycling. The ligamentous structures associated with the ungual cartilages were often affected, showed altered signal intensity as well as enlargement and were thought to be contributing to the lameness. In conclusion, ossified ungual cartilages may lead to fracture of the palmar process of the distal phalanx and injury of the ungual cartilage ligaments.


Correlation of E protein binding with cell susceptibility to dengue 4 virus infection.
Supernatant culture fluids from dengue virus type 4 (DEN-4)-infected cultures of monkey kidney Vero cells and Aedes albopictus C6/36 cells contained the virion structural proteins; secreted NS1 was found only in supernatants from infected Vero cells. Using supernatant culture fluids from [35S]methionine-labelled, virus-infected Vero and C6/36 cells, binding of radiolabelled viral proteins was examined with various cell lines varying in susceptibility to DEN-4 infection. Binding of viral E protein was observed with the highly infectible Vero and LLC-MK2 cell lines, whereas a very small degree of binding was seen with four other cell lines (mouse fibroblast L929, bovine kidney MDBK, human hepatoma Hep G2 and primary human endothelial cells) which are less susceptible to DEN-4 infection. The results suggest that cell susceptibility to DEN-4 may be determined largely at the stage of virus binding, i.e. by the presence of a cell receptor capable of binding viral E protein.


A third vesicular glutamate transporter expressed by cholinergic and serotoninergic neurons.
Two proteins previously known as Na(+)-dependent phosphate transporters have been identified recently as vesicular glutamate transporters (VGLUT1 and VGLUT2). Together, VGLUT1 and VGLUT2 are operating at most central glutamatergic synapses. In this study, we characterized a third vesicular glutamate transporter (VGLUT3), highly homologous to VGLUT1 and VGLUT2. Vesicles isolated from endocrine cells expressing recombinant VGLUT3 accumulated l-glutamate with bioenergetic and pharmacological characteristics similar, but not identical, to those displayed by the type-1 and type-2 isoforms. Interestingly, the distribution of VGLUT3 mRNA was restricted to a small number of neurons scattered in the striatum, hippocampus, cerebral cortex, and raphe nuclei, in contrast to VGLUT1 and VGLUT2 transcripts, which are massively expressed in cortical and deep structures of the brain, respectively. At the ultrastructural level, VGLUT3 immunoreactivity was concentrated over synaptic vesicle clusters present in nerve endings forming asymmetrical as well as symmetrical synapses. Finally, VGLUT3-positive neurons of the striatum and raphe nuclei were shown to coexpress acetylcholine and serotonin transporters, respectively. Our study reveals a novel class of glutamatergic nerve terminals and suggests that cholinergic striatal interneurons and serotoninergic neurons from the brainstem may store and release glutamate.


Redox state of cytochrome aa3 in isolated perfused rat kidney.
Optical spectroscopy was used to evaluate mitochondrial anoxia in the isolated perfused rat kidney by determining the percentage of cytochrome aa3 in the reduced state. Despite high levels of plasma flow (greater than 20 ml . g-1 . min-1) and venous PO2 (greater than 300 mmHg), 25--40% of cytochrome aa3 appeared to be in its reduced form. Agents that alter metabolism or transport primarily in renal cortex had little or no effect on the redox state of cytochrome aa3. These included 3-mercaptopicolinate, an inhibitor of gluconeogenesis; 2-tetradecylglycidic acid, an inhibitor of fat metabolism via carnitine-fatty acyltransferase, and acetazolamide. In contrast, a decrease in medullary transport induced by the loop diuretics bumetanide or furosemide produced an increase in cytochrome aa3 oxidation consistent with a decrease in transport-related oxygen consumption in the hypoxic area. The results suggest that substantial portions of the kidney, particularly in the renal medulla, may normally operate on the brink of anoxia despite high PO2 in artery and vein.


[FUNCTIONING OF THE INSTITUTIONS FOR ASSESSING QUALIFICATIONS OF MEDICAL SPECIALISTS IN OUTPATIENT AND INPATIENT SETTINGS].
The study of the level of appropriateness of the institutions for assessing qualifications of medical specialists with regard to their purpose is relevant due to a number of manifestations of the dysfunction of these institutions and the need to eliminate them. It is advisable to analyze these phenomena not only in general, but also from individual angles, including in the context of their functioning in outpatient and inpatient conditions. This perspective allows us to identify additional aspects of the dysfunction. The study was carried out on the basis of statistics of the Moscow Healthcare Department and materials of two surveys of medical specialists conducted in 2019 and 2022 by the Department. Opinions of medical personnel in polyclinics and hospitals about advantages and disadvantages of the work of institutions of accreditation and certification to get a qualification category were studied. The shortcomings were associated with the dysfunction factors. It is established that these shortcomings are ranked according to the level of significance. The most significant out of them (high workload and lessened incentives for advancement in skills) are characteristic of both types of medical institutions and their divisions, but more pronounced in outpatient settings. It is shown that a number of shortcomings were eliminated by legislation and due to the development of the infrastructure for continuing medical education. However, some shortcomings cannot be eliminated within the institutions themselves, and further reforming of the healthcare system is required.


TRACK EVENT THEORY: A CELL SURVIVAL and RBE MODEL CONSISTENT WITH NANODOSIMETRY.
A simple model for cell survival which is valid also at high dose has been developed. The model parameters can be traced back to measurable quantities from nanodosimetry. It is assumed that a cell is killed by an event which is defined by two or more double strand breaks in differently sized lethal interaction volumes (LIVs). Two different mechanisms can produce events, one-track events by one-particle track and two-track events by two. One- and two-track events are statistically independent. From the stochastic nature of cell killing which is described by the Poisson distribution, the cell survival probability was derived. The ratio of the number of one- and two-track events can be directly expressed in terms of nanodosimetry by the probability F2 that at least two ionizations are produced in a basic interaction volume (5-10 base pairs). From the model, relative biological effectiveness (RBE) can be derived which depends only on F2 and the size of the LIV. The expression for RBE fits experimental data with satisfying quality.


Examining Links Between Infant Parasympathetic Regulation during the Still-Face Paradigm and Later Callous-Unemotional Traits.
Although research suggests that callous-unemotional (CU) traits are underpinned by deficits in social affiliation and reduced sensitivity to threat, there has been little investigation of the biophysiological regulatory mechanisms underlying these processes in infancy. The current study uses data from the Durham Child Health and Development Study (DCHD; n = 206) to examine whether and how the combination of infants' behavioral reactivity and levels of respiratory sinus arrhythmia (RSA), an indicator of parasympathetic nervous system functioning, during the still-face episode of the still-face paradigm at 6 months differentiates risk for CU traits and oppositional defiant behaviors (ODD) at age 3 years, as well as whether these relations vary by children's attachment security. Results indicate that reduced negative affect during the still-face episode at 6 months predicts higher CU traits (B = -0.28, β = -0.27, p = 0.003) and ODD (B = -0.35, β = -0.24, p = 0.007) at 3 years. Results also show that comparatively lower RSA, i.e. engaged parasympathetic system, predicts higher CU traits (B = -0.10, β = -0.34, p = 0.013), but not ODD. Tests of moderation suggest the combination of blunted negative affect but comparatively lower RSA levels during a social stressor constitutes risk for later CU traits for children who are also insecurely attached (simple slope = -0.70, t = 2.88, p = 0.006 at -1 SD). Findings contribute to our understanding of the complex and interactive risk processes which precede the development of CU traits.


Photocurrent generation from thylakoid membranes on osmium-redox-polymer-modified electrodes.
Thylakoid membranes (TMs) are uniquely suited for photosynthesis owing to their distinctive structure and composition. Substantial efforts have been directed towards use of isolated photosynthetic reaction centers (PRCs) for solar energy harvesting, however, few studies investigate the communication between whole TMs and electrode surfaces, due to their complex structure. Here we report on a promising approach to generate photosynthesis-derived bioelectricity upon illumination of TMs wired with an osmium-redox-polymer modified graphite electrode, and generate a photocurrent density of 42.4 μA cm(-2).


Conventional Aortic Valve Replacement after Displacement of a Percutaneously Implanted Aortic Prosthesis: Case Report.
A case is described of aortic stenosis that was initially treated with transcatheter aortic valve implantation (TAVI) due to a high-risk profile. Following dysfunction of the TAVI prosthesis, conventional aortic valve replacement (AVR) was successfully performed; the subsequent postoperative course was uneventful. In conclusion, the target population for TAVI must be more accurately specified, with further research helping to define whether AVR or TAVI is the best treatment option for 'intermediate-risk' patients.


Further characterization of glycine-containing microcystins from the McMurdo dry Valleys of Antarctica.
Microcystins are hepatotoxic cyclic peptides produced by several cyanobacterial genera worldwide. In 2008, our research group identified eight new glycine-containing microcystin congeners in two hydro-terrestrial mat samples from the McMurdo Dry Valleys of Eastern Antarctica. During the present study, high-resolution mass spectrometry, amino acid analysis and micro-scale thiol derivatization were used to further elucidate their structures. The Antarctic microcystin congeners contained the rare substitution of the position-1 ᴅ-alanine for glycine, as well as the acetyl desmethyl modification of the position-5 Adda moiety (3S-amino-9S-methoxy-2S,6,8S-trimethyl-10-phenyldeca-4E,6E-dienoic acid). Amino acid analysis was used to determine the stereochemistry of several of the amino acids and conclusively demonstrated the presence of glycine in the microcystins. A recently developed thiol derivatization technique showed that each microcystin contained dehydrobutyrine in position-7 instead of the commonly observed N-methyl dehydroalanine.


Broadening the approach to youth violence prevention through public health.
Violence is a critical cause of death and nonfatal injuries among youth, and even those who witness violence can suffer serious health and mental health consequences. This highlights the need for prevention programs and policies aimed at reducing risks, promoting prosocial behavior, strengthening families, and creating communities in which youth are safe from violence. The Centers for Disease Control and Prevention's Injury Center is developing a National Public Health Strategy to Prevent Youth Violence. The strategy will establish a full application of the public health approach, ranging from research to practice. It also spotlights what is working, as a way to mobilize community leaders in supporting evidence-based initiatives. With the empirical guidance of articles such as those in this special issue, a shared strategy to prevent youth violence will help focus efforts and resources on solutions that show the most promise, and ensure that American communities undertake more comprehensive and coordinated prevention efforts to protect our nation's youth.


[The effect of cholesterol on the function of staphylotoxin channels].
Bilayer lipid membrane (BLM) formed from lecithin and lecithin-cholesterol mixtures by Mueller and Montal were used. It was found that the parameters of ST-channel functioning did not depend on the presence of the carbohydrate solvent. The 0.5 molar cholesterol in BLM markedly influenced the characteristic relaxation time depending on the electric field vector direction through the membrane, and increasing them only when the potential from the side of added channel-former was negative.


A conceptual framework for Hispanic oral health care.
The need to study the health and health care determinants of US Hispanics is mandated by their rapid population growth. Nonetheless, it is challenging to study such a diverse population that incorporates many similarities and differences in values and experiences. This paper aims to highlight the factors that should be considered in Hispanic oral health research in the United States, and presents, in a theoretical framework, the relationships between these factors. The proposed ecological framework is supported by an extensive literature review, with an emphasis on the factors that are reported to differ among ethnic groups. It has a foundation in social science and is based on existing models from different fields of knowledge. To be comprehensive, the framework simultaneously addresses individual and environmental constructs. Within these, antecedent factors shape the intention to seek oral health care, while empowerment factors play a mediating role between intention and actual receipt of care. Individual antecedent factors incorporate risk markers, need, and predisposing factors. Environmental antecedent factors are represented by social constructs that allude to the population's health culture. Empowerment factors explain the level of control that a person perceives or the environment provides in receiving care. A thorough consideration of the factors that drive Hispanics' oral health care usage will aid US researchers and practitioners in improving this population's health and access to care.


A Retrospective Study on the Incidence of Seizures among Neurosurgical Patients Who Treated with Imipenem/Cilastatin or Meropenem.
We sought to evaluate the safety of imipenem and meropenem in the treatment of infections in neurosurgical patients. An observational retrospective study was conducted of consecutive cases treated with imipenem from Sept. 2007 to Sept. 2009 and meropenem within 1 year from Sept. 2008 in Beijing Tiantan Hospital, China. Data including the dosage and duration of the drug use, occurrence of seizures and mortality outcome was collected from the electronic pharmacy records. The incidence of epilepsy, epileptic standardized morbidity rate (SMR) were reported. Attention was paid to the relationship between the use of imipenem/meropenem and the incidence of epilepsy. The imipenem patients within two years amounted to 71, with mean age 45.9±20.2 years, male to female ratio 46/25. The incidence of epilepsy was 11.3% (8 cases). Among them, 1 case occurred during treatment (1/633, 1.6/1000 patient-days), and the remaining 7 cases occurred before treatment (7/2819, 2.5/1000 patient-days), with the standardized incidence rate 0.64, 95% CI (0.08-5.18).The meropenem patients within one year amounted to 92, mean age 45.1±19.4 years, male to female ratio 51/41. The incidence of epilepsy was 6.5% (6 cases). 2 occurred during treatment (2/582, 2.0/1000 patients-hospital days) and 4 before treatment (4/2047, 3.4/1000 patients-inpatient days), standardized incidence rate 1.76, 95% CI (0.32-9.63). Despite many other epileptogenic factors, imipenem or meropenem did not increase the risk of seizures in neurosurgical patients. There was not further risk for patients with pre-existing seizures or creatinine clearance abnormalities when dosed appropriate.


Detection of papillomavirus in equine periocular and penile squamous cell carcinoma.
Squamous cell carcinoma (SCC) is the most common tumor arising in the periocular and penile areas of horses. Both ultraviolet radiation and papillomaviruses have been implicated in the pathogenesis of SCC in various species, including the horse. This retrospective study used polymerase chain reaction (PCR) to detect papillomavirus DNA in archival biopsy samples from equine periocular and penile SCC from 3 different geographic areas (northeast, southeast, and central United States). Forty-two periocular SCCs were tested; none contained papillomavirus DNA. Twenty-two penile SCCs were tested, and papillomavirus DNA was identified in 10 (43%) cases. Sequencing of the PCR products revealed homology with Equus caballus papillomavirus 2 (EcPV-2). No geographic distribution in the detection of papillomavirus was identified. Penile SCCs were significantly more likely to be papillomavirus positive than the periocular SCCs (P < 0.001). The role of papillomavirus in the development of penile SCC requires further investigation. The differing pathogeneses of periocular and penile SCC suggest that the tumors may respond differently to treatment.


Tamm-Horsfall urinary glycoprotein. The subunit structure.
1. Subunit molecular weights of 76000-82000 were obtained for native and alkylated Tamm-Horsfall glycoprotein by gel filtration on Sephadex G-200 in the presence of sodium dodecyl sulphate. 2. A further estimate of the subunit molecular weight of 79000+/-4000 was obtained by disc gel electrophoresis in sodium dodecyl sulphate. 3. A minimum value of the chemical molecular weight of 79000+/-6000 was obtained from the number of N-terminal amino acids released by cyanogen bromide cleavage of the glycoprotein. 4. Similar values were obtained for the subunit molecular weight of Tamm-Horsfall glycoprotein from patients with cystic fibrosis. 5. On ultracentrifugation both in 1.0% sodium dodecyl sulphate and in 70% formic acid, Tamm-Horsfall glycoprotein sedimented as a single component, slightly faster than serum albumin. 6. On reduction of the disulphide bonds the same subunit molecular weight was obtained, which suggested that these bonds are intrachain.


Native DNA electronics: is it a matter of nanoscale assembly?
The genomic DNA is enveloped by nanotubes formed by the nuclear aggregates of polyamines (NAPs) that induce DNA conformational changes and provide protection and increased interaction abilities for the double strands. In a physiological environment, the nanotube arrangement is initiated by spontaneous interaction among the terminal amino groups of the polyamines and the phosphate ions, with the consequent formation of cyclic monomers that hook at the DNA grooves. The polymer thus formed has the morphological features of an organic semiconductor and therefore, it can be considered to be able to conduct electric charges. Phosphate ions positioned on the NAP external surface could regulate, as in a physical electric circuit, both linear and rotational (histones) protein motion, in accordance with the basilar principles of the electronics. A model of a carrier system for protein motion along the polymer wrapping the DNA strands, based on the phosphate-phosphate complexation, is proposed.


The Leapfrog standards: ready to jump from marketplace to courtroom?
The Leapfrog Group, a consortium of large employers, aims to use its collective purchasing power to motivate hospitals to implement particular measures designed to improve patient safety and the quality of care. While these criteria are meant to be purely aspirational, and while Leapfrog's effort is praiseworthy, we caution that the articulation of these standards of care may have unintended legal consequences. Efforts by aggressive medical malpractice attorneys could rapidly transform Leapfrog's standards from marketplace advantages for compliant hospitals to performance expectations required by law. This undesirable potential outcome compounds the importance of selecting these standards with the utmost care.


[Diabetic angiopathies and ketoacidosis].
The role of ketoacidotic conditions in the occurrence of diabetic angiopathies and influence of the latter on the occurrence and development of ketoacidosis in patients with diabetic vascular lesions was studied. Altogether 1152 diabetes mellitus patients were examined. It was established that abrupt fluctuations of glycemia in labile forms of diabetes with a tendency toward ketoacidosis resulted in a more noticeable vascular lesion. Diabetic nephropathy was shown to cause the development of ketoacidotic conditions as was demonstrated by a higher frequency of ketoacidosis in persons with diabetic nephropathies. The period of disease made a decisive effect on the gravity and progression of vascular lesion in diabetes mellitus.


Transforming growth factor beta-induced cell cycle arrest of human hematopoietic cells requires p57KIP2 up-regulation.
Transforming growth factor beta (TGFbeta) is one of few known negative regulators of hematopoiesis, yet the mechanisms by which it affects cell cycle arrest and stem cell quiescence are poorly understood. Induction of the cyclin-dependent kinase inhibitors, p15INK4b (p15) and p21WAF1 (p21) is important for TGFbeta-mediated cytostasis in epithelial cells but not in hematopoietic cells. Using primary human hematopoietic cells and microarray analysis, we identified p57KIP2 (p57) as the only cyclin-dependent kinase inhibitor induced by TGFbeta. Up-regulation of p57 mRNA and protein occurs before TGFbeta-induced G1 cell cycle arrest, requires transcription, and is mediated via a highly conserved region of the proximal p57 promoter. The up-regulation of p57 is essential for TGFbeta-induced cell cycle arrest in these cells, because two different small interfering RNAs that prevent p57 up-regulation block the cytostatic effects of TGFbeta on human hematopoietic cells. Reduction of basal p57 expression by this approach also allows hematopoietic cells to proliferate more readily in the absence of TGFbeta. p57 is a putative tumor suppressor gene whose expression is frequently silenced by promoter hypermethylation in hematologic malignancies. Our studies identify a molecular pathway by which TGFbeta mediates its cytostatic effects on human hematopoietic cells and suggests an explanation for the frequent silencing of p57 expression.


Community-Level HIV Stigma as a Driver for HIV Transmission Risk Behaviors and Sexually Transmitted Diseases in Sierra Leone: A Population-Based Study.
Although HIV stigma has been identified as an important risk factor for HIV transmission risk behaviors, little is known about the contribution of community-level HIV stigma to HIV transmission risk behaviors and self-reported sexually transmitted diseases (STDs) or how gender may modify associations. We pooled data from the 2008 and 2013 Sierra Leone Demographic and Health Surveys. For HIV stigma, we examined HIV stigmatizing attitudes and HIV disclosure concerns at both individual and community levels. Outcomes of HIV transmission risk behaviors were recent condom usage, consistent condom usage, and self-reported STDs. We assessed associations with multivariable logistic regressions. We also analyzed gender as an effect modifier of these associations. Of 34,574 respondents, 24,030 (69.5%) who had heard of HIV were included in this analysis. Community-level HIV stigmatizing attitudes and disclosure concerns were associated with higher odds of self-reported STDs (adjusted odds ratio = 2.07; 95% confidence interval: 1.55 to 2.77; adjusted odds ratio = 2.95; 95% confidence interval: 1.51 to 5.58). Compared with men, community-level HIV stigmatizing attitudes among women were a stronger driver of self-reported STDs (interaction P = 0.07). Gender modified the association between community-level HIV disclosure concerns and both recent and consistent condom usage (interaction P = 0.03 and P = 0.002, respectively). Community-level HIV disclosure concerns among women were observed to be a driver of risky sex and self-reported STDs. This study shows that community-level HIV stigma may be a driver for risky sex and self-reported STDs, particularly among women. Our findings suggest that community-held stigmatizing beliefs and HIV disclosure concerns among women might be important targets for HIV stigma reduction interventions.


Modeling and state-space identification of deformable mirrors.
To develop high-performance controllers for adaptive optics (AO) systems, it is essential to first derive sufficiently accurate state-space models of deformable mirrors (DMs). However, it is often challenging to develop realistic large-scale finite element (FE) state-space models that take into account the system damping, actuator dynamics, boundary conditions, and multi-physics phenomena affecting the system dynamics. Furthermore, it is challenging to establish a modeling framework capable of the automated and quick derivation of state-space models for different actuator configurations and system geometries. On the other hand, for accurate model-based control and system monitoring, it is often necessary to estimate state-space models from the experimental data. However, this is a challenging problem since the DM dynamics is inherently infinite-dimensional and it is characterized by a large number of eigenmodes and eigenfrequencies. In this paper, we provide modeling and estimation frameworks that address these challenges. We develop an FE state-space model of a faceplate DM that incorporates damping and actuator dynamics. We investigate the frequency and time domain responses for different model parameters. The state-space modeling process is completely automated using the LiveLink for MATLAB toolbox that is incorporated into the COMSOL Multiphysics software package. The developed state-space model is used to generate the estimation data. This data, together with a subspace identification algorithm, is used to estimate reduced-order DM models. We address the model-order selection and model validation problems. The results of this paper provide essential modeling and estimation tools to broad AO and mechatronics scientific communities. The developed Python, MATLAB, and COMSOL Multiphysics codes are available online.


Bayesian models: the structure of the world, uncertainty, behavior, and the brain.
Experiments on humans and other animals have shown that uncertainty due to unreliable or incomplete information affects behavior. Recent studies have formalized uncertainty and asked which behaviors would minimize its effect. This formalization results in a wide range of Bayesian models that derive from assumptions about the world, and it often seems unclear how these models relate to one another. In this review, we use the concept of graphical models to analyze differences and commonalities across Bayesian approaches to the modeling of behavioral and neural data. We review behavioral and neural data associated with each type of Bayesian model and explain how these models can be related. We finish with an overview of different theories that propose possible ways in which the brain can represent uncertainty.


Acute and subacute symptoms among workers in the printing industry.
The study population comprised 52 male printers and 52 controls. Each person was interviewed about job history, general health, and work-related symptoms. Symptoms from eyes and airways, neurological symptoms, and general symptoms were recorded. A lung function test and a measurement of the sense of smell were also carried out. The printers had significantly more eye, airway, and neurological symptoms than the controls; the main complaints being irritation of eyes, nose, throat, and a reduced sense of taste. The neurological symptoms were disorders of vision, vertigo, feeling of intoxication, and headache. Furthermore, abdominal pain and flatulence occurred more often among the printers. The symptoms showed no relation to age or job seniority, but neurological and general symptoms were related to shift work. No difference in lung function was found between the two groups. The printers had a slightly lower threshold of smell than the controls. Although the total load due to organic solvents and dust in the air was far below legal limits, the number of magnitude of symptoms experienced by the printers exceeded what is supposed when norms for workroom exposure are set. It is suggested that either the irritative effects of solvents are underestimated or the assumption of additive effects when great numbers of solvents are found does not hold true. A reduction of the number of solvents by eliminating the most toxic solvents or by using dyes without solvents is suggested.


Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials.
Faricimab is a bispecific antibody that acts through dual inhibition of both angiopoietin-2 and vascular endothelial growth factor A. We report primary results of two phase 3 trials evaluating intravitreal faricimab with extension up to every 16 weeks for neovascular age-related macular degeneration (nAMD). TENAYA and LUCERNE were randomised, double-masked, non-inferiority trials across 271 sites worldwide. Treatment-naive patients with nAMD aged 50 years or older were randomly assigned (1:1) to intravitreal faricimab 6·0 mg up to every 16 weeks, based on protocol-defined disease activity assessments at weeks 20 and 24, or aflibercept 2·0 mg every 8 weeks. Randomisation was performed through an interactive voice or web-based response system using a stratified permuted block randomisation method. Patients, investigators, those assessing outcomes, and the funder were masked to group assignments. The primary endpoint was mean change in best-corrected visual acuity (BCVA) from baseline averaged over weeks 40, 44, and 48 (prespecified non-inferiority margin of four letters), in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. These trials are registered with ClinicalTrials.gov (TENAYA NCT03823287 and LUCERNE NCT03823300). Across the two trials, 1329 patients were randomly assigned between Feb 19 and Nov 19, 2019 (TENAYA n=334 faricimab and n=337 aflibercept), and between March 11 and Nov 1, 2019 (LUCERNE n=331 faricimab and n=327 aflibercept). BCVA change from baseline with faricimab was non-inferior to aflibercept in both TENAYA (adjusted mean change 5·8 letters [95% CI 4·6 to 7·1] and 5·1 letters [3·9 to 6·4]; treatment difference 0·7 letters [-1·1 to 2·5]) and LUCERNE (6·6 letters [5·3 to 7·8] and 6·6 letters [5·3 to 7·8]; treatment difference 0·0 letters [-1·7 to 1·8]). Rates of ocular adverse events were comparable between faricimab and aflibercept (TENAYA n=121 [36·3%] vs n=128 [38·1%], and LUCERNE n=133 [40·2%] vs n=118 [36·2%]). Visual benefits with faricimab given at up to 16-week intervals demonstrates its potential to meaningfully extend the time between treatments with sustained efficacy, thereby reducing treatment burden in patients with nAMD. F Hoffmann-La Roche.


Skin barrier lipid enzyme activity in Netherton patients is associated with protease activity and ceramide abnormalities.
Individuals with Netherton syndrome (NTS) have increased serine protease activity, which strongly impacts the barrier function of the skin epidermis and leads to skin inflammation. Here, we investigated how serine protease activity in NTS correlates with changes in the stratum corneum (SC) ceramides, which are crucial components of the skin barrier. We examined two key enzymes involved in epidermal ceramide biosynthesis, β-glucocerebrosidase (GBA) and acid-sphingomyelinase (ASM). We compared in situ expression levels and activities of GBA and ASM between NTS patients and controls and correlated the expression and activities with i) SC ceramide profiles, ii) in situ serine protease activity, and iii) clinical presentation of patients. Using activity-based probe labeling, we visualized and localized active epidermal GBA, and a newly developed in situ zymography method enabled us to visualize and localize active ASM. Reduction in active GBA in NTS patients coincided with increased ASM activity, particularly in areas with increased serine protease activity. NTS patients with scaly erythroderma exhibited more pronounced anomalies in GBA and ASM activities than patients with ichthyosis linearis circumflexa. They also displayed a stronger increase in SC ceramides processed via ASM. We conclude that changes in the localization of active GBA and ASM correlate with i) altered SC ceramide composition in NTS patients, ii) local serine protease activity, and iii) the clinical manifestation of NTS.


The association of maternal serum uric acid with the risk of small for gestational age newborn: a retrospective cohort study.
Prior results on the association between serum uric acid (UA) levels in the early trimester and the risk of small for gestational age (SGA) remain unclear. This study evaluated the association of maternal first-, second-, and third-trimester UA levels with the risk of SGA infants. A total of 23, 194 singleton mothers from the International Peace Maternity and Child Health Hospital between January 2014 and January 2017 were included. Maternal UA levels were measured at 12.1 ± 1.08th (UA1) and 32.2 ± 1.03th (UA2) gestational weeks. △UA was calculated as the difference between UA2 and UA1. Logistic regression and restricted cubic spline (RCS) were performed to evaluate the association between maternal UA and △UA during pregnancy and SGA. Receiver operating characteristic (ROC) analysis was employed to assess the serum uric acid prediction value. Women in the higher quartiles of UA1 had a significantly higher risk of SGA. A clear increased risk for SGA was observed with higher quartiles for UA2 (p for trend <0.05). An approximately "J-shaped" relationship was observed between UA2 and △UA, and the risk of SGA was observed. When compared with those with a lower level of UA in the first trimester, those with a higher level of UA1, the more increase in the later UA levels were associated with a higher risk of SGA [adjusted odds ratio (aOR) = 1.67, 95% CI:1.37-2.05]. The ROC curve areas were 0.525 for UA1, 0.582 for UA2 and 0.576 for △UA. The findings suggested that non-preeclamptic and non-hypertensive women who experienced early pregnancy with high UA levels had an elevated risk of SGA. Moreover, a high maternal UA level in the earlier trimester may be an early predictor of SGA.


Association between schizophrenia and an autoimmune bullous skin disease-pemphigus: a population-based large-scale study.
Immunological hypotheses have become increasingly prominent suggesting that autoimmunity may be involved in the pathogenesis of schizophrenia. Schizophrenia was found to be associated with a wide range of autoimmune diseases. However, the association between pemphigus and schizophrenia has not been established yet. We aimed to estimate the association between pemphigus and schizophrenia using a large-scale real-life computerised database. This study was conducted as a cross-sectional study utilising the database of Clalit Health Services. The proportion of schizophrenia was compared between patients diagnosed with pemphigus and age-, gender- and ethnicity-matched control subjects. Univariate analysis was performed using χ2 and Student's t-test and a multivariate analysis was performed using a logistic regression model. A total of 1985 pemphigus patients and 9874 controls were included in the study. The prevalence of schizophrenia was greater in patients with pemphigus as compared to the control group (2.0% v. 1.3%, respectively; p = 0.019). In a multivariate analysis, pemphigus was significantly associated with schizophrenia (OR, 1.5; 95% CI, 1.1-2.2). The association was more prominent among females, patients older than 60 years, and Jews. Pemphigus is significantly associated with schizophrenia. Physicians treating patients with pemphigus should be aware of this possible association. Patients with pemphigus should be carefully assessed for comorbid schizophrenia and be treated appropriately.


Comparison and validation of novel pyrogen tests based on the human fever reaction.
The absence of pyrogens (fever-inducing contamination) in injectable drugs is a crucial safety control because pyrogens can pose a life-threatening risk to the patient. The field of applications for pyrogen-testing is expanding and becoming more diverse due to innovative high-tech products such as medical devices, cellular therapies and species-specific agents (e.g. recombinant proteins). The overall aim of the consortium is to develop, evaluate and validate a method based on the human fever reaction to replace the rabbit pyrogen test and the Limulus assay. The network brings together the six most prominent test systems developed recently in Europe for trans-national comparison and subsequent validation of the most promising models. This pre-competitive development will initiate further applications and exploitations for new fields of pyrogen testing such as cellular therapies, medical devices and pyrogen pollution control in the work place. A method for introduction into the European Pharmacopoeia will be developed as a replacement for the rabbit pyrogen test for end-product control.


A comparison of approaches to modeling the relationship between ergonomic exposures and upper extremity disorders.
For a study of upper extremity musculoskeletal disorders among automobile manufacturing workers, an ergonomic exposure index was constructed by summing ten psychophysical (interview) items. Here we explore the sensitivity of the exposure-response relationship to the formulation of that index. Five alternative exposure indices were constructed: three a priori weighting schemes and two sets of weights derived from multivariate regression coefficients. In addition, structural equation modeling was performed with LISREL. The original index and a priori weighting schemes had similar associations with upper extremity disorders, adjusted for nonoccupational covariates. A reasonable model fit was achieved in LISREL after two modifications; the standardized solution showed that nonneutral postures were significantly related to upper extremity signs and symptoms. In this large population, with adequate range of exposures, the exposure-response relationship appeared generally robust to the mathematical formulation of the exposure index. Among the available exposure variables, postural strain had the strongest association.


An evaluation of the New Roche Diagnostics Kit for the rapid identification of clinically important non-dextrose, non-fastidious gram-negative rods.
The evaluation of the new Roche Diagnostics Commercial kit (Roche Diagnostics, 1975) for the identification of non-dextrose fermenting, non-fastidious gram-negative rods has been compared with conventional methods in the recognition and identification of these non-dextrose, non-fastidious gram-negative bacteria. This new kit has definite advantages over and above the conventional methods in a number of ways. It is cheaper to run, and above all it is less cumbersome, less time consuming and it is accurate. Apart from all these, the new method makes use of the odour test (Roche Diagnostics, 1975) and other additional conventional tests recommended by the Oxi/ferm manufacturer.


Uterine and embryonic metabolism after diapause in the tammar wallaby, Macropus eugenii.
Pouch young were removed from lactating tammars to terminate embryonic diapause. Uterine metabolism was assessed at periods afterwards by incubating endometrial explants with [3H]leucine, and measuring the incorporation into acid-soluble material. Blastocysts were incubated with [3H]uridine to assess uptake and incorporation into acid-soluble material. Uterine reactivation, shown by an increase in the rate of leucine incorporation into secreted protein, was evident by Day 4 after removal of pouch young and was significantly more in both secreted and tissue protein by Day 6. Both continued to increase in gravid and non-gravid uteri up to Day 12. By the end of pregnancy (Day 26) uterine metabolism in the gravid uterus produced 2-3 times more secreted protein than in the non-gravid uterus, demonstrating a local feto-placental influence on the uterus. Tissue incorporation had declined in endometrium of gravid and non-gravid uteri by Day 26. Day 5 embryos were metabolically more active than in quiescence, although expansion of the embryos was not seen until Day 9. The early reactivation of the uterus and embryo from diapause suggests that it is not triggered by the previously described peaks of progesterone and oestradiol in plasma at Day 5, although there may be an earlier, increased sensitivity to these steroids which allows uterine reactivation to precede changes in peripheral plasma concentration.


Phosphatidylcholine liposomes as carriers to improve topical ascorbic acid treatment of skin disorders.
Liposomes have been intensively investigated as carriers for different applications in dermatology and cosmetics. Ascorbic acid has potent antioxidant and anti-inflammatory properties preventing photodamage of keratinocytes; however, due to its instability and low skin penetration, an appropriate carrier is mandatory to obtain desirable efficacy. The present work investigates the ability of a specific ascorbate phosphatidylcholine (PC) liposome to overcome the barrier of the stratum corneum and deliver the active agent into the dermis to prevent photodamage. Abdominal skin from ten patients was used. Penetration of PC liposomes was tested ex vivo in whole skin, epidermis, and dermis by means of fluorescein and sodium ascorbate. Histology and Franz diffusion cells were used to monitor the percutaneous absorption. Ultraviolet (UV)-high performance liquid chromatography was used to analyze diffusion of sodium ascorbate through the different skin layers, while spectrofluorimetry and fluorescent microscopy were used for fluorescein monitoring. UVA/UVB irradiation of whole skin was applied to analyze the antioxidant capacity by Trolox assay and anti-inflammatory effects by tumor necrosis factor alpha and interleukin 1 beta enzyme-linked immunoassay. PC liposomal formulation improved skin penetration of fluorescein and ascorbate. Fluorescein PC liposomes showed better diffusion through epidermis than dermis while ascorbate liposomes showed better diffusion through the dermis than the epidermis. Ascorbate PC liposomes showed preventive antioxidant and anti-inflammatory properties on whole human skin irradiated with UVA/UVB. In summary, ascorbate PC liposomes penetrate through the epidermis and allow nonstable hydrophilic active ingredients reach epidermis and dermis preventing skin photodamage.


High-pressure elasticity of alpha-quartz: instability and ferroelastic transition
The single-crystal elastic moduli of alpha-quartz were measured to above 20 GPa in a diamond-anvil cell by Brillouin spectroscopy. The behavior of the elastic moduli indicates that the high-pressure phase transition in quartz is ferroelastic in nature and is driven by softening of C44 through one of the Born stability criteria. The trends in elastic moduli confirm theoretical predictions, but there are important differences, particularly with respect to the magnitudes of the B(i). The quartz I-II transition occurs prior to complete softening of the mode and amorphization.


Expression of coproporphyrinogen oxidase is associated with detection of upper gastrointestinal carcinomas by 5-aminolevulinic acid-mediated photodynamic diagnosis.
5-Aminolevulinic acid is a precursor of photosensitizing protoporphyrin IX and has been applied for photodynamic diagnosis of brain and bladder tumors with few side effects. Although most upper gastrointestinal tumors can be detected during photodynamic diagnosis, some tumors containing signet-ring cells cannot be visualized. Here, we aimed to assess whether proteins involved in the absorbance, activation, and turnover of protoporphyrin IX altered the fluorescence signal in gastric cancer. Aminolevulinic acid-mediated photodynamic diagnosis was performed in 23 lesions from 20 patients using an endoscope equipped with a blue laser light that caused red fluorescence emission of photosensitizing protoporphyrin IX. Red fluorescence signal and intensity was assessed during photodynamic diagnosis procedures. Lesions were resected by endoscopic and/or laparoscopic surgery, and specimens were immunostained and assessed for the expression of ATP-binding cassette sub-family G member 2, oligopeptide transporter-1, and coproporphyrinogen oxidase. Photodynamic diagnosis was negative in four cases (17.4%). Three cases of photodynamic diagnosis-negative lesions were signet-ring cell carcinomas, and only one case was differentiated adenocarcinoma (intestinal type). Twenty intestinal type, photodynamic diagnosis-positive lesions showed high expression of coproporphyrinogen oxidase, whereas signet-ring cell carcinomas were all negative. Oligopeptide transporter-1 immunoreactivity was significantly higher in tumors of intestinal type. ATP-binding cassette sub-family G member 2 expression tended to be higher in luminal surface tumors than in intestinal type tumors. Aminolevulinic acid-mediated photodynamic diagnosis provided good detection of upper gastrointestinal tumors of intestinal type but not diffuse type tumors, such as signet-ring cell carcinomas, possibly owing to coproporphyrinogen oxidase expression.


In Vivo Nematicidal Potential of Camel Milk on Heligmosomoides Polygyrus Gastro-intestinal Nematode of Rodents.
Following our previous findings on the in vitro anthelmintic effect of camel milk on Haemonchus contortus, the current study aimed at investigating its in vivo effect. Investigations were carried out using mice infected with Heligmosomoides polygyrus which is a parasite commonly used to test the efficacy of anthelmintics. Thirty six Swiss white mice of both sexes aged 5 - 6 weeks old, and weighing between 20 and 25 g were orally infected with 0.5 ml dose of 100, 1-week-old H. polygyrus infective larvae (L3). After the pre-patent period, infected animals were randomly divided into 6 groups of 6 animals each. The nematicidal efficacy of camel milk was monitored through faecal egg count reduction (FECR) and total worm count reduction (TWCR). Four doses (8.25; 16.5; 33.0; 66.0 ml/kg body weight (bw)) for fresh camel milk and 22 mg/kg bw for albendazole were studied using a bioassay. Albendazole and 4 % dimethylsulfoxide were included in the protocol as reference drug and placebo, respectively. For all tested doses except 8.25 ml/kg bw, camel milk was effective in vivo against H. polygyrus reducing both faecal egg count and worm count (p < 0.05). The dose 66 ml/kg bw showed the highest nematicidal activity causing a 76.75 % FECR and a 69.62 % TWCR 7 day after initiating the treatment. These results support the possible use of camel milk in the control of gastro-intestinal helminthiasis.


The blood platelets contribution to innate host defense - what they have learned from their big brothers.
Bactericidal effects of blood platelets have been known for more than 120 years, but the underlying mechanisms are largely obscure. Keeping in mind structural and functional analogies of platelets to neutrophils, three different mechanisms are thinkable: Engulfment of pathogens, release of microbicidal proteins, and production of reactive oxygen species (ROS). Here, we focus on the release of ROS and a possible contribution of blood plasma and thrombin to the bactericidal effects. Killing of bacteria was evaluated by DNA fluorescence labeling and electron microscopy. Release of ROS by platelets was measured photometrically by cytochrome C and phenol red/peroxidase assays and was further evaluated by topological methods. We found that (i) platelets produce 1500 times less O(2) (-) and 4000 times less H(2)O(2) compared to neutrophils, (ii) ROS do not affect the killing rates, and (iii) no local enrichment of ROS was detectable. On the other hand, thrombin and plasma proteins with a molecular mass of >100 kDa are essential for bactericidal effects. We suggest that platelets contribute to the innate host defense by providing a catalytical surface for synthesis of thrombin. In the presence of a heat-instable plasma protein, thrombin may generate a strong bactericidal complex, which is only effective in close vicinity to the platelet membrane.


Early, intermediate, and late acute stages in Chagas' disease: a study combining anti-galactose IgG, specific serodiagnosis, and polymerase chain reaction analysis.
The acute phase of Chagas' disease was classified as early, intermediate, and late based on the levels of anti-Galalpha, 3Gal IgG (Gal) and specific IgM (M) and IgG (G) anti-T. cruzi reactivity. While the early phase was M+G-Gal-, the intermediate phase was M+G-Gal+, M+G+Gal-, or M+G+Gal+, and the late phase was M-G+Gal+. This sequence of stages was consistent with our previous studies on acute-phase proteins. Analysis by the polymerase chain reaction (PCR) of parasite DNA in 65 blood samples of children living in Cochabamba, Bolivia showed a significant correlation (90.8%) between ELISA and PCR positivity. A lower correlation was observed between indirect hemagglutination, PCR (58%), and ELISA. Electrocardiographic analysis of 43 children studied by the PCR did not show any alteration typical of acute chagasic myocarditis. The PCR positivity was observed in eight samples where only Gal was increased, suggesting a very early T. cruzi infection, when specific antibodies were not yet present. By associating anti-Gal IgG with specific serology, early T. cruzi infection can be detected with greater precision. We suggest the use of anti-Gal antibody reactivity as an aid for the detection of recent T. cruzi infections, at least in endemic areas where diseases caused by other trypanosomatids do not overlap.


Timing of maternal isoniazid preventive therapy on tuberculosis infection among infants exposed to HIV in low-income and middle-income settings: a secondary analysis of the TB APPRISE trial.
Infants born to women with HIV in settings with a high tuberculosis burden are at risk of tuberculosis infection and rapid progression to active disease. Maternal isoniazid preventive therapy might mitigate this risk, but optimal timing of therapy remains unclear. The TB APPRISE trial showed that initiation of isoniazid during pregnancy resulted in more frequent adverse pregnancy outcomes than when initiated postpartum. We aimed to determine the proportion of infants testing positive for tuberculosis infection born to mothers who initiated isoniazid therapy antepartum compared with postpartum using two commonly used tests, the test agreement, and predictors of test positivity. TB APPRISE was a randomised, double-blind, placebo-controlled, non-inferiority trial done at 13 study sites across eight countries (Botswana, Haiti, India, South Africa, Tanzania, Thailand, Uganda, and Zimbabwe). Pregnant women with HIV on antiretroviral therapy were randomly assigned to receive immediate isoniazid preventive therapy (28 weeks isoniazid [300 mg daily], then placebo until week 40 after delivery) or deferred treatment (placebo until week 12 after delivery, then isoniazid [300 mg daily] for 28 weeks). Mother-infant pairs were followed up until 48 weeks after delivery. We included all liveborn infants with a tuberculin skin test or interferon-γ release assay (IGRA) at 44 weeks. The outcomes assessed in this secondary analysis were tuberculosis test positivity by study group, test agreement, and predictors of test positivity. This study was registered with ClinicalTrials.gov, NCT01494038. Between Aug 19, 2014, and April 4, 2016, 956 mothers were randomly assigned, and 749 mother-child pairs were included in this secondary analysis. Of 749 infants, 694 (93%) received Bacille Calmette-Guérin (BCG) vaccination, 675 (90%) were born to mothers who had completed isoniazid treatment, 20 (3%) were exposed to tuberculosis, seven (1%) became HIV positive, and one (<1%) developed probable tuberculosis. 43 (6%; 95% CI 4-8]) of 732 infants had a positive IGRA test result and 55 (8%; 6-10) of 727 infants had a positive tuberculin skin test result. Test positivity did not differ by study group (p=0·88 for IGRA; p=0·44 for tuberculin skin test). Test agreement was poor (κ=0·107 [95% CI 0·002-0·212]). Infant tuberculin skin test positivity was associated with breastfeeding (adjusted odds ratio 6·63 [95% CI 1·57-27·9]), BCG vaccination (4·97 [1·50-16·43]), and maternal tuberculin skin test positivity at delivery (3·28 [1·70-6·33]); IGRA positivity was associated with female sex (2·09 [1·06-4·14]). Deferral of maternal isoniazid preventive therapy to early postpartum had no effect on infant tuberculosis acquisition in our trial population, regardless of the diagnostic test used; however, tuberculosis test agreement is poor during infancy. US National Institutes of Health.


[Respiratory disorders during sleep in patients with cardiovascular diseases at the stage of rehabilitation].
High prevalence of cardiovascular and cerebrovascular diseases dictates the necessity of enhancing the efficacy of preventive and rehabilitative programs, elaboration and implementation of innovative medical technologies. Sleep disturbances and especially associated respiratory disorders are important risk factors of arterial hypertension, cardiac insufficiency, abnormal heart rhythms, cerebrovascular pathology, insulin resistance, and type 2 diabetes mellitus. Introduction of the methods for diagnostics and correction of sleep disturbances into rehabilitative programs improves immediate and long-term results of the treatment.


Dietary habits and prevalence of allergic rhinitis in 6 to 7-year-old schoolchildren in Turkey.
The prevalence of allergic rhinitis and other allergies has risen worldwide. Dietary habits are considered to be among the potential risk factors. The aim of this study was to evaluate the prevalence of allergic rhinitis and its relationship with dietary habits and other risk factors among 6 to 7-year-old Turkish schoolchildren. In this cross-sectional study, a total of 11483 children aged 6-7 years were surveyed. The prevalence of symptoms of allergic rhinitis was assessed using the ISAAC protocol. Dietary information was collected using a food frequency questionnaire. Of them, 9875 (50.7% M 49.3% F) questionnaires were appropriately completed. The prevalence rates of lifetime rhinitis, current rhinitis, current rhinoconjunctivitis and physician-diagnosed allergic rhinitis, were 44.3%, 29.2%, 8.5% and 8.1%, respectively. Consumption of rice, and cereals ≥3 times per week showed protective effect on physician-diagnosed allergic rhinitis (aOR = 0.53, 95% CI = 0.32-0.87 and aOR = 0.58, 95% CI = 0.36-0.92). Eating pasta, and chocolates ≥3 times per week showed protective effect on current rhinoconjunctivitis (aOR = 0.45, 95% CI = 0.25-0.79 and aOR = 0.50, 95% CI = 0.29-0.86). Eating lollipops, candies and animal fats ≥3 times per week was positively associated with current rhinoconjunctivitis (aOR = 1.47, 95% CI = 1.00-2.17 and aOR = 2.25, 95% CI = 1.11-4.56). Protective effect of the Mediterranean diet was not significant. Frequent consumption of cereals, rice, pasta and chocolates may have beneficial effect on symptoms of rhinoconjunctivitis. Although dietary habits may affect the prevalence of symptoms of current rhinoconjunctivitis, the Mediterranean diet alone may not be protective against rhinoconjunctivitis.


Simplified partial digest problem: enumerative and dynamic programming algorithms.
We study the Simplified Partial Digest Problem (SPDP), which is a mathematical model for a new simplified partial digest method of genome mapping. This method is easy for laboratory implementation and robust with respect to the experimental errors. SPDP is NP-hard in the strong sense. We present an $O(n2;n)$ time enumerative algorithm and an O(n(2q)) time dynamic programming algorithm for the error-free SPDP, where $n$ is the number of restriction sites and n is the number of distinct intersite distances. We also give examples of the problem, in which there are 2(n+2)/(3)-1 non-congruent solutions. These examples partially answer a question recently posed in the literature about the number of solutions of SPDP. We adapt our enumerative algorithm for handling SPDP with imprecise input data. Finally, we describe and discuss the results of the computer experiments with our algorithms.


A cleavage map of bacteriophage phiX174 genome.
Restriction endonucleases isolated from Hemophilus influenzae, Hemophilus parainfluenzae, and Hemophilus aegyptius were used to cleave varphiX174 replicative form DNA into three sets of specific DNA fragments. The order of these fragments in the varphiX replicative form molecule was determined by (1) analysis of partial digest products, (2) analysis of overlapping sets of fragments produced by two different restrictive enzymes. On the basis of these results, a detailed physical map of the varphiX174 genome has been constructed with respect to the cleavage sites of all three enzymes.


The mechanism of rhythmic ethylene production in sorghum. The role of phytochrome B and simulated shading.
Mutant sorghum (Sorghum bicolor [L.] Moench) deficient in functional phytochrome B exhibits reduced photoperiodic sensitivity and constitutively expresses a shade-avoidance phenotype. Under relatively bright, high red:far-red light, ethylene production by seedlings of wild-type and phytochrome B-mutant cultivars progresses through cycles in a circadian rhythm; however, the phytochrome B mutant produces ethylene peaks with approximately 10 times the amplitude of the wild type. Time-course northern blots show that the mutant's abundance of the 1-aminocyclopropane-1-carboxylic acid (ACC) oxidase mRNA SbACO2 is cyclic and is commensurate with ethylene production, and that ACC oxidase activity follows the same pattern. Both SbACO2 abundance and ACC oxidase activity in the wild-type plant are very low under this regimen. ACC levels in the two cultivars did not demonstrate fluctuations coincident with the ethylene produced. Simulated shading caused the wild-type plant to mimic the phenotype of the mutant and to produce high amplitude rhythms of ethylene evolution. The circadian feature of the ethylene cycle is conditionally present in the mutant and absent in the wild-type plant under simulated shading. SbACO2 abundance in both cultivars demonstrates a high-amplitude diurnal cycle under these conditions; however, ACC oxidase activity, although elevated, does not exhibit a clear rhythm correlated with ethylene production. ACC levels in both cultivars show fluctuations corresponding to the ethylene rhythm previously observed. It appears that at least two separate mechanisms may be involved in generating high-amplitude ethylene rhythms in sorghum, one in response to the loss of phytochrome B function and another in response to shading.


Business opportunities in transforming health care: an interview with William W. McGuire.
After a spate of high-profile acquisitions including Oxford Health Plans, UnitedHealth Group (UHG) covers twenty-two million Americans in insured and self-insured health plans and tens of millions more through specialty products. Bill McGuire describes his strategy of growth through acquisition and through diversification into Medicaid managed care, the individual insurance market, and services for the elderly under the Medicare Modernization Act of 2003. He sees business and public policy opportunities in the unjustifiable variation in cost and quality across the health care spectrum and proposes a framework of basic insurance benefits for all Americans, with options for people to purchase additional benefits with their own money.


[Immune-mediated neuropathy].
Guillain-Barré syndrome (GBS) has two types; acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). Recently, a nation-wide retrospective study showed that the rate of AMAN is higher in Japan than in western countries. A prospective study is now in progress. Elevated titers of serum anti-ganglioside antibodies are characteristic of GBS. Complement system has been shown to be involved in the anti-ganglioside antibody-mediated pathogenetic mechanisms. Some GBS patients have antibodies specific to a conformational epitope formed by two different gangliosides. Among such anti-ganglioside complex antibodies, anti-GD1a/GD1b IgG antibodies are shown to be associated with severe GBS requiring artificial ventilation. In contrast, antibodies highly specific to GD1b are associated with GBS with ataxia. Sensory ataxic neuropathy is induced by sensitization of rabbits with GD1b. An apoptotic mechanism has recently been shown to be involved in the pathogenesis of this animal model. Most of the patients with Fisher syndrome have anti-GQ1b IgG antibodies. Recent investigation on anti-ganglioside complex antibody showed that antibodies in Fisher syndrome can be subdivided into the three groups; GQ1b-specific, GQ1b/GM1-specific, and GQ1b/GD1a-specific. Research on antibodies to gangliosides and ganglioside complexes will provide us with a clue to develop a novel treatment of GBS.