The COVID-19 pandemic: a new challenge for syndromic surveillance.
The COVID-19 pandemic is exerting major pressures on society, health and social care services and science. Understanding the progression and current impact of the pandemic is fundamental to planning, management and mitigation of future impact on the population. Surveillance is the core function of any public health system, and a multi-component surveillance system for COVID-19 is essential to understand the burden across the different strata of any health system and the population. Many countries and public health bodies utilise 'syndromic surveillance' (using real-time, often non-specific symptom/preliminary diagnosis information collected during routine healthcare provision) to supplement public health surveillance programmes. The current COVID-19 pandemic has revealed a series of unprecedented challenges to syndromic surveillance including: the impact of media reporting during early stages of the pandemic; changes in healthcare-seeking behaviour resulting from government guidance on social distancing and accessing healthcare services; and changes in clinical coding and patient management systems. These have impacted on the presentation of syndromic outputs, with changes in denominators creating challenges for the interpretation of surveillance data. Monitoring changes in healthcare utilisation is key to interpreting COVID-19 surveillance data, which can then be used to better understand the impact of the pandemic on the population. Syndromic surveillance systems have had to adapt to encompass these changes, whilst also innovating by taking opportunities to work with data providers to establish new data feeds and develop new COVID-19 indicators. These developments are supporting the current public health response to COVID-19, and will also be instrumental in the continued and future fight against the disease.


Prevalence of Metabolic Syndrome in Women After Maternal Complications of Pregnancy: An Observational Cohort Analysis.
Certain complications of pregnancy, including hypertensive disorders of pregnancy, gestational diabetes mellitus, intrauterine growth restriction, spontaneous preterm birth, and placental abruption, are established independent risk factors for premature cardiovascular disease in women. Metabolic syndrome, which is associated with an increased risk of cardiovascular disease, may be a suitable alternative to traditional cardiovascular risk calculators that underestimate risk in young women. This study aimed to investigate the prevalence of metabolic syndrome in women who experienced a complicated pregnancy 6 months earlier. This observational study investigated the prevalence of metabolic syndrome as defined by the International Diabetes Federation in all eligible participants (n = 247) attending a postpartum lifestyle intervention clinic from August 2018 to June 2021 at the Lyell McEwin Hospital in Adelaide, South Australia. A total of 89 (36%) participants met the criteria for metabolic syndrome at a mean follow up time of 7 months postpartum. Almost 90% of the cohort were abdominally obese, and over two thirds of the total cohort met at least two of the criteria for metabolic syndrome. Women with a prior history of one of the common major pregnancy complications are at high risk of future cardiovascular and metabolic disease, with many showing either metabolic syndrome or multiple risk factors at only 7 months postpartum. The results indicate that follow-up within 1 year postpartum is an appropriate time to commence preventative strategies, as many women are already showing early signs of disease.


Stress fracture of the lateral cuneiform bone: a case report.
Stress fractures are common overuse injuries of the bone that are most often seen in athletes and military personnel. These types of injuries seem to be commonly missed or delayed in diagnosis. Physicians should consider the possibility of such an injury while determining the diagnosis of a long-lasting foot pain. The aim of this paper was to report an isolated stress fracture of the lateral cuneiform bone. A review of the literature failed to find a similar case.


The Role of Immune Responses in HIV Mother-to-Child Transmission.
HIV mother-to-child transmission (MTCT) represents a success story in the HIV/AIDS field given the significant reduction in number of transmission events with the scale-up of antiretroviral treatment and other prevention methods. Nevertheless, MTCT still occurs and better understanding of the basic biology and immunology of transmission will aid in future prevention and treatment efforts. MTCT is a unique setting given that the transmission pair is known and the infant receives passively transferred HIV-specific antibodies from the mother while in utero. Thus, infant exposure to HIV occurs in the face of HIV-specific antibodies, especially during delivery and breastfeeding. This review highlights the immune correlates of protection in HIV MTCT including humoral (neutralizing antibodies, antibody-dependent cellular cytotoxicity, and binding epitopes), cellular, and innate immune factors. We further discuss the future implications of this research as it pertains to opportunities for passive and active vaccination with the ultimate goal of eliminating HIV MTCT.


Dendritic Cell-Inspired Designed Architectures toward Highly Efficient Electrocatalysts for Nitrate Reduction Reaction.
Electrocatalysis for nitrate reduction reaction (NRR) has recently been recognized as a promising technology to convert nitrate to nitrogen. Catalyst support plays an important role in electrocatalytic process. Although porous carbon and metal oxides are considered as common supports for metal-based catalysts, fabrication of such architecture with high electric conductivity, uniform dispersion of nanoparticles, and long-term catalytic stability through a simple and feasible approach still remains a significant challenge. Herein, inspired by the signal transfer mode of dendritic cell, an all-carbon dendritic cell-like (DCL) architecture comprising mesoporous carbon spheres (MCS) connected by tethered carbon nanotubes (CNTs) with CuPd nanoparticles dispersed throughout (CuPd@DCL-MCS/CNTs) is reported. An impressive removal capacity as high as 22 500 mg N g-1 CuPd (≈12 times superior to Fe-based catalysts), high nitrate conversion (>95%) and nitrogen selectivity (>95%) are achieved under a low initial concentration of nitrate (100 mg L-1 ) when using an optimized-NRR electrocatalyst (4CuPd@DCL-MCS/CNTs). Remarkably, nitrate conversion and nitrogen selectivity are both close to 100% in an ultralow concentration of 10 mg L-1 , meeting drinking water standard. The present work not only provides high electrocatalytic performance for NRR but also introduces new inspiration for the preparation of other DCL-based architectures.


Behavioral changes in adult rats after prenatal exposures to complex, weak magnetic fields.
More than 100 adult male and female albino Wistar rats that had been exposed during their entire prenatal development to one of two patterns of magnetic fields and one of four intensities (reference: 5 to 20 nT; low: 30 to 50 nT; medium: 90 to 580 nT; high: 590 nT to 1.2 microT) were tested for their capacity for two forms of classical conditioning. The rats exposed for 10 sec every 50 sec to a field composed of successive 200 msec sequences of several different patterns known to produce physiological effects exhibited significantly more intense conditioned fear and taste aversion than those exposed continuously to a single frequency-modulated pattern. The behavioral differences, relative to the reference group ("controls"), were greatest for rats exposed to the 30 to 50 nT or 90 to 580 nT (low to medium intensities) for both patterns of fields. These results suggest that prenatal exposure to physiologically-patterned magnetic fields within a specific "window" of intensities that overlap with values found in many human habitats may produce long-term changes in behaviors.


Metals and Alzheimer's Disease: How Far Have We Come in the Clinic?
It is estimated that by the year 2050 there will be more than 1.5 billion people globally over the age of 65 years. Aging is associated with changes to a number of different cellular processes which are driven by a variety of factors that contribute to the characteristic decline in function that is seen across multiple physiological domains/tissues in the elderly (including the brain). Importantly, aging is also the primary risk factor for the development of neurodegenerative disorders such as Alzheimer's disease. As such, there is an urgent need to provide a greater understanding of both the pathogenesis and treatment of these devastating neurodegenerative disorders. One of the key cellular processes that becomes dysregulated with age and participates both directly and indirectly in age-related dysfunction, is metal homeostasis and the neurochemistry of metalloproteins, the basic science of which has been extensively reviewed in the past. In this review, we will focus on the human clinical intervention trials that have been conducted over approximately the last four decades that have attempted to establish the efficacy of targeting metal ions in the treatment of AD.


Photobiocatalysis for Abiological Transformations.
Harnessing biocatalysts for novel abiological transformations is a longstanding goal of synthetic chemistry. Combining the merits of biocatalysis and photocatalysis allows for selective transformations fueled by visible light and offers many advantages including new reactivity, high enantioselectivity, greener syntheses, and high yields. Photoinduced electron or energy transfer enables synthetic methodologies that complement conventional two electron processes or offer orthogonal pathways for developing new reactions. Enzymes are well suited and can be tuned by directed evolution to exert control over open-shell intermediates, thereby suppressing undesirable reactions and delivering high chemo- and stereoselectivities. Within the past decade, the combination of biocatalysis and photocatalysis was mainly focused on exploiting light-regenerated cofactors to function native enzymatic activity. However, recent developments have demonstrated that the combination can unlock new-to-nature chemistry. Particularly, the discovery and application of new strategies are well poised to expand the applications of photobiocatalysis.In the past five years, our lab has been studying the combinations of photocatalysis and biocatalysis that can be applied to create new synthetic methodologies and solve challenges in synthetic organic chemistry. Our efforts have expanded the strategies for combining external photocatalysts with enzymes through the construction of a synergistic cooperative stereoconvergent reduction system consisting of photosensitized energy transfer and ene-reductase-catalyzed alkene reduction. Additionally, our efforts have also extended the capability of cofactor-dependent photoenzymatic systems to include enantioselective bimolecular radical hydroalkylations of alkenes by irradiating electron donor-acceptor complexes comprised of enzymatic redox active cofactors and unnatural substrates.In this Account, we highlight strategies developed by our group and others for combining biocatalysis and photocatalysis with the aim of introducing non-natural reactivity to enzymes. Presently, strategies applied to achieve this goal include the repurposing of natural photoenzymes, the elucidation of new photoreactivity within cofactor-dependent enzymes, the combination of external photocatalysts with enzymes, and the construction of artificial photoenzymes. By demonstrating the successful applications of these strategies for achieving selective new-to-nature transformations, we hope to spur interest in expanding the scope of photobiocatalytic systems through the use and extension of these strategies and creation of new strategies. Additionally, we hope to elucidate the intuition in synergizing the unique capabilities of biocatalysis and photocatalysis so that photobiocatalysis can be recognized as a potential solution to difficult challenges in synthetic organic chemistry.


Use of leadless pacemakers in Europe: results of the European Heart Rhythm Association survey.
The purpose of this European Heart Rhythm Association (EHRA) survey is to provide an overview of the current use of leadless pacemakers (LLPM) across a broad range of European centres. An online questionnaire was sent to centres participating in the EHRA Electrophysiology Research Network. Questions dealt with standards of care and policies used for patient management, indications, and techniques of implantation of LLPM. In total, 52 centres participated in the survey. Most (86%) reported using LLPM, although 82% of these centres implanted <30 LLPM devices during the last 12 months. Non-availability (36%), lack of reimbursement (55%), and cost of the device (91%) were factors limiting the use of LLPM. The most commonly reported indications for LLPM were permanent atrial fibrillation (83%), a history of complicated conventional pacemaker (87%), or an anticipated difficult vascular access (91%). Implantation of LLPM is perceived as an easy-to-do and safe procedure by most implanters (64%), while difficult or risky in 28%, and comparable to conventional pacemakers by only a few (8%). Local vascular complications were the most frequently reported major problems (28%), but a significant number of respondents (36%) have never encountered any issue after LLPM implantation. Although cost and reimbursement issues strongly influence the use of LLPM, most respondents (72%) anticipate a significant increase in device utilization within next 2 years.


[A case of von Hippel-Lindau syndrome with optic disc pit and macular hole].
A 69-year-old female patient presented to the ophthalmology department with complaints of blurred vision in the left eye for more than 10 days. Her medical history revealed a history of right renal tumor and left pheochromocytoma, which were treated with surgical resection at an external institution. Ophthalmic examination revealed a temporal superior cup-shaped optic disc pit in the left eye, along with a macular hole approximately 1/5 the size of the optic disc diameter in the macular region. Additionally, peripheral retinal examination at the 6 o'clock and 11 o'clock positions showed vascular tumors, each approximately 1.5 times the size of the optic disc diameter. Based on the patient's medical history, fundus findings, and auxiliary examination results, a diagnosis of macular hole in the left eye, optic disc pit in the left eye, and Von Hippel-Lindau (VHL) syndrome was established. Subsequently, the patient underwent left vitrectomy and macular hole repair surgery, leading to an improvement in visual acuity.


Involvement of the carboxy-terminal residue in the active site of the histidine-containing protein, HPr, of the phosphoenolpyruvate:sugar phosphotransferase system of Escherichia coli.
Histidine-containing protein, HPr, of the Escherichia coli phosphoenolpyruvate:sugar phosphotransferase system has an active site that involves His-15, which is phosphorylated to form a N delta 1-P-histidine, Arg-17, and the carboxy-terminal residue Glu-85. Mutant HPrs with alterations to the three C-terminal residues, Glu-85, Leu-84, and Glu-83, were produced by site-directed mutagenesis. The properties of these mutants were assessed by kinetic analysis of enzyme I, enzyme IImannose, enzyme IIN-acetylglucosamine, and enzyme IImannitol, and the phosphohydrolysis properties of the HPr mutants. The results show that it is the C-terminal alpha-carboxyl of Glu-85 that is involved in the active site, and this involvement may be restricted to the phosphoryl donor action of HPr. The contribution of this alpha-carboxyl group is modest as the deletion of Glu-85 resulted in the reduction of the enzyme II activity (kcat/Km) to about 33%. Removal of both Glu-85 and Leu-84 yields an HPr that is an impaired substrate of both the enzyme I and enzyme II reactions. Glu-83 appears to have no role in the active site.


Characterization of the pathogenicity of clinical Cronobacter malonaticus strains based on the tissue culture investigations.
Cronobacter malonaticus is a member of the genus Cronobacter which is considered an opportunistic pathogen. The significance of C. malonaticus has recently increased since it was documented to be involved in several serious neonatal infections. However, the virulence factors of C. malonaticus including their ability to adhere, invade and overcome host barriers have not been studied before. Unlike previous Cronobacter research, this study is mainly focused on C. malonaticus and is aimed to investigate its virulence characteristics that enable this species to cause adult and neonatal infections. Altogether, 20 strains were included in this study (19 clinical and one environmental strain). Our data showed that the clinical C. malonaticus has an ability to adhere and invade Caco-2, HBMEC, A549 and T24 cell lines. Moreover, the result showed that certain strains of C. malonaticus (including 1827 and 2018) were able to persist well in macrophages. However, ST7 strains 1827 and 2018 proved to be the most invasive strains among all used strains. The CDC strain 1569 (ST307) which was isolated from the blood of a fatal neonatal case showed also significant results in this study as it was able to invade all used human cells and survive and replicate within microphages. Finally, the findings of this study confirm the potential ability of C. malonaticus to cause serious infections in neonates or adults such as necrotising enterocolitis, meningitis, bacteraemia, pneumonia and urinary tract infection.


Molecular basis for the specific and multivariant recognitions of RNA substrates by human hnRNP A2/B1.
Human hnRNP A2/B1 is an RNA-binding protein that plays important roles in many biological processes, including maturation, transport, and metabolism of mRNA, and gene regulation of long noncoding RNAs. hnRNP A2/B1 was reported to control the microRNAs sorting to exosomes and promote primary microRNA processing as a potential m6A "reader." hnRNP A2/B1 contains two RNA recognition motifs that provide sequence-specific recognition of RNA substrates. Here, we determine crystal structures of tandem RRM domains of hnRNP A2/B1 in complex with various RNA substrates, elucidating specific recognitions of AGG and UAG motifs by RRM1 and RRM2 domains, respectively. Further structural and biochemical results demonstrate multivariant binding modes for sequence-diversified RNA substrates, supporting a RNA matchmaker mechanism in hnRNP A2/B1 function. Moreover, our studies in combination with bioinformatic analysis suggest that hnRNP A2/B1 may mediate effects of m6A through a "m6A switch" mechanism, instead of acting as a direct "reader" of m6A modification.


The Mosaic of Rottlerin.
The first total synthesis of rottlerin is described. The methodology allows the development of potential novel protein kinase C δ (PKCδ) analogues for better treatment of various diseases. Kamalachalcone A and dimeric rottlerin were synthesized in a very practical and economical way using FeCl3 as a catalyst.


Boosting with an aerosolized Ad5-nCoV elicited robust immune responses in inactivated COVID-19 vaccines recipients.
The SARS-CoV-2 Omicron variant has become the dominant SARS-CoV-2 variant and exhibits immune escape to current COVID-19 vaccines, the further boosting strategies are required. We have conducted a non-randomized, open-label and parallel-controlled phase 4 trial to evaluate the magnitude and longevity of immune responses to booster vaccination with intramuscular adenovirus vectored vaccine (Ad5-nCoV), aerosolized Ad5-nCoV, a recombinant protein subunit vaccine (ZF2001) or homologous inactivated vaccine (CoronaVac) in those who received two doses of inactivated COVID-19 vaccines. The aerosolized Ad5-nCoV induced the most robust and long-lasting neutralizing activity against Omicron variant and IFNg T-cell response among all the boosters, with a distinct mucosal immune response. SARS-CoV-2-specific mucosal IgA response was substantially generated in subjects boosted with the aerosolized Ad5-nCoV at day 14 post-vaccination. At month 6, participants boosted with the aerosolized Ad5-nCoV had remarkably higher median titer and seroconversion of the Omicron BA.4/5-specific neutralizing antibody than those who received other boosters. Our findings suggest that aerosolized Ad5-nCoV may provide an efficient alternative in response to the spread of the Omicron BA.4/5 variant. https://www.chictr.org.cn/showproj.html?proj=152729, identifier ChiCTR2200057278.


Determinants of Cookstoves and Fuel Choice Among Rural Households in India.
Roughly 2.8 billion people depend on solid fuels for cooking needs, resulting in a tremendous burden of disease from exposure to household air pollution. Despite decades of effort to promote cleaner cooking technologies, displacement of polluting technologies has progressed slowly. This paper describes results of a randomized controlled trial in which eight communities in two regions of rural India were presented with a range of cooking choices including improved solid fuel stoves and clean cooking options like liquefied petroleum gas (LPG) and induction stoves. Using survey data and logistic and multinomial regression, we identify factors associated with two outcomes: (1) pre-intervention ownership of non-solid fuel technologies and (2) household preferences for clean fuels from the range of cooking options offered. The analysis allows us to examine the influence of education, wealth, gender empowerment, stove pricing, and stove exchanges, among other variables. The majority of participants across all communities selected the cleanest options, LPG and induction, irrespective of price, but there is some variation in preferences. Wealth and higher caste stand out as significant predictors of pre-intervention ownership and non-solid fuel cooking options as well as preference for cleaner technologies offered through the intervention. The experimental treatments also influence preferences in some communities. When given the opportunity to exchange, communities in one region are more likely to choose solid fuel stoves (P < 0.05). Giving free stoves had mixed results; households in one region are more likely to select clean options (P < 0.05), but households in the other region prefer solid fuels (P < 0.10).


Characterizing the spatial distributions of soil biota at a legacy base metal mine using environmental DNA.
Characterizing the distribution of biota in response to contaminants is a critical element of site risk assessments. In this study we investigated the spatial distributions of biota and soil chemistry data in surface soil from Sunny Corner, a legacy base metal sulfide mine, Australia. Our results showed that copper (Cu), zinc (Zn), arsenic (As) and lead (Pb) in the surface soil exceeded Australian national soil quality guidelines and posed risks to the environment. Environmental (e)DNA metabarcoding of prokaryote and eukaryote composition confirmed the suggestion of environmental risk posed by these elements collectively explaining 72.9 % and 60.5 % of the total variation in the composition of soil prokaryotes and eukaryotes, respectively. Prokaryotic taxa from the phyla Gemmatimonadetes, Verrucomicrobia and Deinococcus-Thermus showed similar spatial patterns to As and Pb, and were positively correlated. Eukaryotic taxa from the phylum Chlorophyta had similar positive correlations with As and Pb in the soil. In contrast, Amoebozoa and Cercozoa, were sensitive to metals and metalloids, having higher relative abundances in soils with lower concentrations of contaminants. Our study shows that metabarcoding is a promising ecological approach for rapid, large scale assessment of contaminated and potentially impacted sites.


Influence of breast cancer resistance protein and P-glycoprotein on tissue distribution and excretion of Ko143 assessed with PET imaging in mice.
Ko143 is a reference inhibitor of the adenosine triphosphate-binding cassette (ABC) transporter breast cancer resistance protein (humans: ABCG2, rodents: Abcg2) for in vitro and in vivo use. Previous in vitro data indicate that Ko143 binds specifically to ABCG2/Abcg2, suggesting a potential utility of Ko143 as a positron emission tomography (PET) tracer to assess the density (abundance) of ABCG2 in different tissues. In this work we radiolabeled Ko143 with carbon-11 (11C) and performed small-animal PET experiments with [11C]Ko143 in wild-type, Abcg2(-/-), Abcb1a/b(-/-) and Abcb1a/b(-/-)Abcg2(-/-) mice to assess the influence of Abcg2 and Abcb1a/b on tissue distribution and excretion of [11C]Ko143. [11C]Ko143 was extensively metabolized in vivo and unidentified radiolabeled metabolites were found in all investigated tissues. We detected no significant differences between wild-type and Abcg2(-/-) mice in the distribution of [11C]Ko143-derived radioactivity to Abcg2-expressing organs (brain, liver and kidney). [11C]Ko143 and possibly its radiolabeled metabolites were transported by Abcb1a and not by Abcg2 at the mouse blood-brain barrier. [11C]Ko143-derived radioactivity underwent both hepatobiliary and urinary excretion, with Abcg2 playing a possible role in mediating the transport of radiolabeled metabolites of [11C]Ko143 from the kidney into urine. Experiments in which a pharmacologic dose of unlabeled Ko143 (10 mg/kg) was co-administered with [11C]Ko143 revealed pronounced effects of the vehicle used for Ko143 formulation (containing polyethylene glycol 300 and polysorbate 80) on radioactivity distribution to the brain and the liver, as well as on hepatobiliary and urinary excretion of radioactivity. Our results highlight the challenges associated with the development of PET tracers for ABC transporters and emphasize that inhibitory effects of pharmaceutical excipients on membrane transporters need to be considered when performing in vivo drug-drug interaction studies. Finally, our study illustrates the power of small-animal PET to assess the interaction of drug molecules with membrane transporters on a whole body level.


Long-acting injectable buprenorphine for opioid use disorder: A systematic review of impact of use on social determinants of health.
This systematic review synthesizes evidence on both the effects and perspectives of the use of novel long-acting injectable buprenorphine (LAIB) as part of medication-assisted treatment (MAT) and its impact on social determinants of health (SDH), specifically abstinence, accessibility, employment, forensic matters, and gender and social relationships via a framework approach. The study team searched three databases between January 2010 and June 2020 to identify English-language original research published in peer reviewed journals. This search yielded 9253 papers. A comprehensive search followed by 67 full text publication screenings by two independent reviewers yielded 15 papers meeting inclusion criteria. The study included three randomized control trials, one open label safety study, two case series, and six qualitative papers examining patient perspectives toward the LAIB prior to use. The team assessed the quality of studies via standardized quality assessment tools. The LAIB was positively associated with improvements in abstinence, accessibility, employment, social relationships, and forensic matters. Limited evidence exists on gender equity within the current literature. The qualitative papers highlighted the importance of patients' preferences and individualization of treatment planning to ensure the success of MAT. The quality of evidence was rated as medium or high risk of bias, which does limit interpretation of the results. Overall, the LAIB was positively associated with SDH and should be offered as part of MAT in alignment with the recovery model. Future research should evaluate the implementation and longitudinal impacts of LAI buprenorphine compared to treatment as usual (TAU).


Heterogeneity among human T cell clones recognizing an HLA-DR4,Dw4-restricted epitope from the 18-kDa antigen of Mycobacterium leprae defined by synthetic peptides.
Synthetic peptides have been used to exactly define a T cell epitope region from the immunogenic 18-kDa protein of Mycobacterium leprae. Four M. leprae reactive CD4+ T cell clones, isolated from two healthy individuals vaccinated with killed M. leprae, recognized a determinant initially defined by the peptide (38-50). However, fine mapping of the minimal sequence required for T cell recognition revealed heterogeneity among the T cell clones with regard to the N- and carboxyl-terminal boundaries of the epitopes recognized. MHC restriction analysis showed that the immunogenic peptides were presented to the T cells in an HLA-DR4,Dw4-restricted manner in all cases. The results suggest that a polyclonal T cell response representing different fine specificities is directed toward a possible immunodominant epitope from the M. leprae 18-kDa Ag in individuals carrying this MHC haplotype.


Accessing state-bound memories in the treatment of phobias: two case studies.
Two cases of simple phobia demonstrate the inadequacies of both behavioral and psychodynamic theories. These cases and their treatment outcomes provide support for the state-dependent memory and learning theory. Hypnosis and ideomotor signaling proved to be not only effective treatments but also useful means of illuminating the role and nature of symptom function. Issues of symptom removal and substitution are also discussed in relation to these cases.


The impact of caregiver mental health on child prosocial behavior: A longitudinal analysis of children and caregivers in KwaZulu-Natal, South Africa.
Prosocial behavior has positive social, cognitive, and physical health effects on the individual exhibiting the behavior as well as on society as a whole, and is integral to overall mental and physical wellbeing. The development of prosocial behavior is rooted in early childhood and learned through observation. As such, those spending time with children, especially their caregiver, play a critical role in their prosocial development. The current study investigates the impact of caregiver mental health on the prosocial development of young children over time. This paper presents a secondary analysis of child prosocial development in the Asenze Study, a longitudinal, population-based cohort study based in KwaZulu-Natal, South Africa. Children were followed-up over time from an average age of five to seven years along with their caregivers. Linear GEE regression analysis was used to assess whether a change in presence of a mental health disorder in a caregiver during this 2-year interval (using the Client Diagnostic Questionnaire) impacted the development of their child's prosocial behavior (using the Strengths and Difficulties Questionnaire). After adjusting for early child-care, child HIV status, SDQ child prosocial subscale, SDQ total difficulties score, and household order score (CHAOS), children whose caregivers acquired a mental health disorder had a significantly smaller increase in prosocial behavioral development compared to children whose caregivers never had a mental health disorder. Identifying contextually relevant modifiable factors such as this will help stimulate the development of interventions to promote prosocial development in childhood.


The treatment outcomes of pain survey (TOPS): a clinical monitoring and outcomes instrument for chronic pain practice and research.
The field of health outcomes research has increased the utilization of health-related quality-of-life (HRQoL) instruments to document economic, clinical, and humanistic outcomes (ECHO). The Medical Outcomes Study Short Form 36-item Questionnaire (MOSSF-36, SF-36) has been utilized extensively in many disease states for this purpose, although it is not validated for use in chronic pain patients. The Total Outcomes of Pain Survey (TOPS) incorporates all the domains of the SF-36, and includes additional domains relevant in the management of chronic pain patients. The TOPS is well validated in these patients. In addition to its utility as an outcomes research tool, the TOPS is sensitive enough to document clinical changes in individual patients, making it a useful assessment tool for clinicians.


Tyrosine phosphorylation regulates the partitioning of STAT1 between different dimer conformations.
The activation/inactivation cycle of STAT transcription factors entails their transition between different dimer conformations. Unphosphorylated STATs can dimerize in an antiparallel conformation via extended interfaces of the globular N-domains, whereas STAT activation triggers a parallel dimer conformation with mutual phosphortyrosine:SH2 domain interactions, resulting in DNA-binding and nuclear retention. However, despite the crucial role of STAT tyrosine phosphorylation in cytokine signaling, it has not been determined how this modification affects the stability and the conformational flexibility of STAT dimers. Here, we use analytical ultracentrifugation and electrophoretic mobility shift assay (EMSA) to study the association of STAT1 in solution before and after tyrosine phosphorylation. It is revealed that STAT1 formed high-affinity dimers (K(d) of approximately 50 nM) with estimated half-lives of 20-40 min irrespective of the phosphorylation status. Our results demonstrate that parallel and antiparallel conformations of STAT1 were present simultaneously, supported by mutually exclusive interfaces; and the transition between conformations occurred through affinity-driven dissociation/association reactions. Therefore, tyrosine phosphorylation was dispensable for DNA binding, but the phosphorylation enforced preformed SH2 domain-mediated dimers, thus enhancing the DNA-binding activity of STAT1 >200-fold. Moreover, upon STAT1 activation the N-domains adopted an open conformation and engaged in interdimer interactions, as demonstrated by their participation in tetramerization instead of dimerization. Yet, homotypic N-domain interactions are not conserved in the STAT family, because the N-domain dissociation constants of STAT1, STAT3, and STAT4 differed by more than three orders of magnitude. In conclusion, STAT1 constantly oscillated between different dimer conformations, whereby the abundance of the dimerization interfaces was determined by tyrosine phosphorylation.


A computerized postcoital test sperm motility: comparison with clinical postcoital test and correlations with sperm antibodies.
Sixty-five infertile women had a conventional postcoital test (PCT), a computerized postcoital test (cPCT), and sperm antibody testing. Twenty-four women had good cervical mucus and good PCT sperm motility (group 1), 23 had poor cervical mucus and poor PCT sperm motility (group 2), and 18 had good cervical mucus but poor PCT sperm motility (group 3). The percentage of motile sperm, mean linearity, and the motility index of sperm by cPCT also were decreased in groups 2 and 3 (p less than 0.001) in contrast to group 1. A reduced PCT sperm count was significantly associated with positive titers of antibodies to autologous sperm in the husbands' serum, whereas a reduced PCT motility correlated with high titers of cytotoxic antibodies to husbands' sperm in the wives' serum and cervical mucus. An increased percentage of vibratory sperm at PCT correlated with elevated titers of cytotoxic antibodies to husbands' sperm in the wives' serum and cervical mucus, and hemagglutinating (r = 0.44; p less than 0.001) and immunofluorescent IgA antibodies to husbands' sperm (r = 0.47; p less than 0.001) in the cervical mucus. Mean swimming speed of sperm by cPCT correlated inversely with cytotoxic and hemagglutinating antibody titers to husbands' sperm, and immunobead-binding IgM and immunofluorescent IgG, IgA, and IgM (r = 0.52; p less than 0.001) antibodies to sperm in the seminal plasma. Motility indices correlated inversely with cytotoxic antibody titers to husbands' sperm in the wives' serum, and hemagglutinating antibody titers to husbands' sperm in cervical mucus. The predictive values of PCT and cPCT for the presence of cytotoxic and immunofluorescent IgA antibodies to autoimmune husbands' sperm were 76% and 71%, respectively, in the serum and 85% and 75%, respectively, in the cervical mucus of the wives. The predictive value of PCT and cPCT for immunobead-binding and immunofluorescent IgM antibodies to sperm in the wives' serum was 71%. Computerized PCT measures more sperm characteristics than PCT, although it is in general agreement with PCT.


Lack of pendrin HCO3- transport elevates vestibular endolymphatic [Ca2+] by inhibition of acid-sensitive TRPV5 and TRPV6 channels.
The low Ca(2+) concentration ([Ca(2+)]) of mammalian endolymph in the inner ear is required for normal hearing and balance. We reported (Yamauchi et al., Biochem Biophys Res Commun 331: 1353-1357, 2005) that the epithelial Ca(2+) channels TRPV5 and TRPV6 (transient receptor potential types 5 and 6) are expressed in the vestibular system and that TRPV5 expression is stimulated by 1,25-dihydroxyvitamin D(3), as also reported in kidney. TRPV5/6 channels are known to be inhibited by extracellular acidic pH. Endolymphatic pH, [Ca(2+)], and transepithelial potential of the utricle were measured in Cl(-)/HCO(3)(-) exchanger pendrin (SLC26A4) knockout mice in vivo. Slc26a4(-/-) mice exhibit reduced pH and utricular endolymphatic potential and increased [Ca(2+)]. Monolayers of primary cultures of rat semicircular canal duct cells were grown on permeable supports, and cellular uptake of (45)Ca(2+) was measured individually from the apical and basolateral sides. Net uptake of (45)Ca(2+) was greater after incubation with 1,25-dihydroxyvitamin D(3). Net (45)Ca(2+) absorption was dramatically inhibited by low apical pH and was stimulated by apical alkaline pH. Gadolinium, lanthanum, and ruthenium red reduced apical uptake. These observations support the notion that one aspect of vestibular dysfunction in Pendred syndrome is a pathological elevation of endolymphatic [Ca(2+)] due to luminal acidification and consequent inhibition of TRPV5/6-mediated Ca(2+) absorption.


The analysis of chromosomally aberrant cells based on beta-binomial distribution.
Analysis carried out here generalized on earlier studies of chromosomal aberrations in the populations of Hiroshima and Nagasaki, by allowing extrabinomial variation in aberrant cell counts corresponding to within-subject correlations in cell aberrations. Strong within-subject correlations were detected with corresponding standard errors for the average number of aberrant cells that were often substantially larger than was previously assumed. The extrabinomial variation is accommodated in the analysis in the present report, as described in the section on dose-response models, by using a beta-binomial (beta-B) variance structure. It is emphasized that we have generally satisfactory agreement between the observed and the beta-B fitted frequencies by city-dose category. The chromosomal aberration data considered here are not extensive enough to allow a precise discrimination between competing dose-response models.


Echocardiographic evaluation of left ventricle postnatal growth in newborns and infants.
During intrauterine life is the volume stimulation of the left ventricle low and it's cardiac output in comparison to the right ventricle is about 50%. Before and also after birth the right ventricle is dominant. Postnatally low-resistance placenta is excluded from the systemic circuit, leading to an abrupt pressure elevation and to its further increase. The authors performed echocardiographic evaluation of healthy children from newborn age to 6 month of age. Fifty randomly selected healthy mature infants were included in this study. Echocardiographic examination was performed at the age of 5 days, 1 month and 6 months respectively. Data obtained at the age of 5 days were compared to those at 1 month and 6 months. The authors confirmed a significant increase in the left ventricular volumes (LVESV, LVEDV, SV) developed early newborn in the period to 6 months of age. There was a significant increase in EF in the period age of 5 days to 1 month of age. Mean LVM on the 5th day after birth was 8.13+/-1.50 g. It increased to 11.39+/-2.33 g after 1 month and to 16.61+/-2.75 g after 6 months. They confirmed significant LVMVI decrease to 1.38+/-0.25 g/ml (6 months) from 1.56+/-0.33 (1 month). The authors found significant decrease in RWT values at the age of 6 months compared with the 5th day. Left ventricular parameters confirm postnatal left ventricle growth in healthy infants. The results are useful in interpretation of echocardiographic examinations in newborns and infants.


Phase transitions in the distribution of bipartite entanglement of a random pure state.
Using a Coulomb gas method, we compute analytically the probability distribution of the Renyi entropies (a standard measure of entanglement) for a random pure state of a large bipartite quantum system. We show that, for any order q>1 of the Renyi entropy, there are two critical values at which the entropy's probability distribution changes shape. These critical points correspond to two different transitions in the corresponding charge density of the Coulomb gas: the disappearance of an integrable singularity at the origin and the detachment of a single-charge drop from the continuum sea of all the other charges. These transitions, respectively, control the left and right tails of the entropy's probability distribution, as verified also by Monte Carlo numerical simulations of the Coulomb gas equilibrium dynamics.


Effect of trifluoperazine on in vitro ATP synthesis by Mycobacterium leprae.
The effect of trifluoperazine (TFP), a calmodulin antagonist, was investigated on in vitro ATP levels of human derived Mycobacterium leprae. M. leprae were obtained from biopsies from multi-bacillary forms of leprosy and were incubated in a modified Dubos medium system which supports limited in vitro synthesis of M. leprae. This incubation was carried out in the absence and presence of different concentrations of trifluoperazine. Samples for estimation of bacillary ATP levels were taken at day 0 and at 14 days of incubation. TFP inhibited ATP levels in M. leprae and this inhibitory effect was marginal at 2.5 microg ml(-1) (35% inhibition), highly significant at 5 microg ml(-1) (87% inhibition) and almost total at 10 microg ml(-1) (98.5% inhibition). This compound appears to have potential as an anti-leprotic drug and also as a broad spectrum anti-mycobacterial agent in view of its anti-tubercular activity reported earlier.


Cis-trans signatures of proline-containing tryptic peptides in the gas phase.
High-resolution ion mobility/time-of-flight techniques were used to measure collision cross sections for 968 tryptic digest peptide ions obtained from digestion of common proteins. Here, we report a mobility signature that aids in identifying proline-containing peptides containing 4-10 residues. Of 129 peptides (< or = 10 residues in length) in the database that contain proline residues, 57% show multiple resolved features in the ion mobility distribution for at least one of the [M + H]+ or [M + 2H]2+ ions. These multiple features are attributed to different conformations that arise from populations of cis and trans forms of proline. The number of resolved peaks in the ion mobility distribution appears to be correlated with the peptide ion charge state and the number of proline residues in the peptide.


Dealing with bio- and ecological complexity: Challenges and opportunities.
The complexities of the dynamic processes and their control associated with biological and ecological systems offer many challenges for the control engineer. Over the past decades the application of dynamic modelling and control has aided understanding of their complexities. At the same time using such complex systems as test-beds for new control methods has highlighted their limitations (e.g. in relation to system identification) and has thus acted as a catalyst for methodological advance. This paper continues the theme of exploring opportunities and achievements in applying modelling and control in the bio- and ecological domains.


Disparities in parenting criteria: an exploration of the issues, focusing on adoption and embryo donation.
This paper examines the consistency of parent selection procedures, focusing on adoption and embryo donation. It outlines the current methods of selection and their disparities, and considers reasons for these disparities; namely, the intentionality of the parents, the gestational experience, and the technological imperative. This discussion is followed by an analysis of the ethical validity of these reasons, in terms of their consistency and how well they meet standards of equity and justice. The paper concludes that current approaches to parent selection are unsystematic and inadequate, and discusses the implications of this assessment.


Novel Compound Heterozygous Variants of ETHE1 Causing Ethylmalonic Encephalopathy in a Chinese Patient: A Case Report.
Ethylmalonic encephalopathy (EE) is a very rare autosomal recessive metabolic disorder that primarily affects children. Less than one hundred EE patients have been diagnosed worldwide. The clinical manifestations include chronic diarrhea, petechiae, orthostatic acrocyanosis, psychomotor delay and regression, seizures, and hypotonia. The ETHE1 gene has been shown to be associated with EE, and genetic sequencing provides concrete evidence for diagnosis. To date, only 37 variants of ETHE1 have been reported as disease-causing in EE patients. We identified two novel ETHE1 variants, i.e., c.595+1G>T at the canonical splice site and the missense variant c.586G>C (p. D196H), in a 3-year-old Chinese boy with EE. The patient had mild symptoms with only chronic diarrhea. The typical symptoms, including spontaneous petechiae, acrocyanosis, and hypotonia, were all absent. Herein, we report on the clinical, biochemical, and genetic findings of our patient and review the phenotypes and genotypes of all patients with EE caused by ETHE1 variants with available information. This study supports the early assessment and diagnosis of EE.


Vanishing bile duct syndrome in a HIV patient on HAART therapy.
Vanishing bile duct syndrome refers to a group of disorders characterised by progressive destruction of the intrahepatic bile ducts resulting in cholestasis. It is a final common pathway for many disorders. The diagnoses is mainly made by histological findings. To consider a diagnosis there should be loss of interlobular bile ducts in more than fifty per cent of small portal tracts provided that the specimen contains at least 10 portal tracts. Here the authors present a case of vanishing bile duct syndrome which developed after initiation of highly active antiretroviral treatment therapy.


Activation-induced expression of human programmed death-1 gene in T-lymphocytes.
The Programmed Death-1 (PD-1) gene is a member of the immunoglobulin superfamily of genes. Murine PD-1 mRNA expression has been shown to correlate with activation-induced apoptosis in a mouse T-cell hybridoma cell line and in murine thymocytes. Here we report that expression of the human homolog, hPD-1, seems to correlate with activation of T lymphocytes rather than apoptosis. We observed a time-dependent upregulation of hPD-1 mRNA and protein levels in Jurkat cells during phorbol ester (12-O-tetradecanoylphorbol 13-acetate, TPA)-induced differentiation. Human PD-1 protein was also induced during lectin-stimulated activation of human peripheral blood mononuclear cells. Additionally, TPA stimulation of Jurkat cells induces tyrosine phosphorylation of hPD-1, putatively on its cytoplasmic tail signal transduction motif. These data suggest a role for hPD-1 during activation and differentiation of T-lymphocytes.


Clinical outcomes of acute myocardial infarction arising from non-lipid-rich plaque determined by NIRS-IVUS.
Acute myocardial infarction (AMI) can rarely arise from non-lipid-rich coronary plaques. This study sought to compare the clinical outcomes after percutaneous coronary intervention (PCI) between AMI showing maximum lipid-core burden index in 4 mm (maxLCBI4mm) < 400 and ≥ 400 in the infarct-related lesions assessed by near-infrared spectroscopy-intravascular ultrasound (NIRS-IVUS). We investigated 426 AMI patients who underwent NIRS-IVUS in the infarct-related lesions before PCI. Major adverse cardiovascular events (MACE) were defined as the composite of cardiac death, non-fatal MI, clinically driven target lesion revascularization (TLR), clinically driven non-TLR, and congestive heart failure requiring hospitalization. 107 (25%) patients had infarct-related lesions of maxLCBI4mm < 400, and 319 (75%) patients had those of maxLCBI4mm ≥ 400. The maxLCBI4mm < 400 group had a younger median age at onset (68 years [IQR: 57-78 years] vs. 73 years [IQR: 64-80 years], P = 0.007), less frequent multivessel disease (39% vs. 51%, P = 0.029), less frequent TIMI flow grade 0 or 1 before PCI (62% vs. 75%, P = 0.007), and less frequent no-reflow immediately after PCI (5% vs. 11%, P = 0.039). During a median follow-up period of 31 months [IQR: 19-48 months], the frequency of MACE was significantly lower in the maxLCBI4mm < 400 group compared with the maxLCBI4mm ≥ 400 group (4.7% vs. 17.2%, P = 0.001). MaxLCBI4mm < 400 was an independent predictor of MACE-free survival at multivariable analysis (hazard ratio: 0.36 [confidence interval: 0.13-0.98], P = 0.046). MaxLCBI4mm < 400 measured by NIRS in the infract-related lesions before PCI was associated with better long-term clinical outcomes in AMI patients.


Regulation of starch biosynthesis in plant leaves: activation and inhibition of ADPglucose pyrophosphorylase.
The ADPglucose pyrophosphorylases of 7 plant-leaf tissues were partially purified and characterized. In all cases the enzymes showed stability to heat treatment at 65 degrees for 5 minutes in the presence of 0.02 m phosphate buffer, pH 7.0. The leaf ADPglucose pyrophosphorylases were activated 5 to 15-fold by 3-phosphoglycerate. Fructose-6-phosphate and fructose 1, 6-diphosphate stimulated ADPglucose pyrophosphorylase to lesser extents. The A(0.5) (conc of activator required to give 50% of the observed maximal activation) of 3-phosphoglycerate for the barley enzyme was 7 x 10(-6)m while for the sorghum enzyme it was 3.7 x 10(-4)m. Inorganic phosphate proved to be an effective inhibitor of ADPglucose synthesis. The I(0.5) (conc of inhibitor that gave 50% inhibition of activity for the various leaf enzymes varied from 2 x 10(-5)m (barley) to 1.9 x 10(-4)m (sorghum). This inhibition was reversed or antagonized by the activator 3-phosphoglycerate. These results form the basis for an hypothesis of the regulation of leaf starch biosynthesis.


[Effects of lead acetate on expression of brain-derived neurotropic factor and P75NTR in rat brain].
To study the effects of lead acetate on the expression of brain-derived neurotropic factor (BDNF) and its receptor P75NTR in rat brain. Lead acetate was given to SD rats by intraperitoneal injection (ip) for 5 days at the dosage of 25, 50 and 100mg/kg body weight respectively. The contents of lead in serum, cerebral cortex and hippocampus were measured by atomic absorption spectrophotochemistry. The levels of BDNF mRNA and protein expression in cerebral cortex and hippocampus were observed by RT-PCR and immunohistochemistry, respectively. The levels of P75NTR protein expression in rat brain were measured by immunohistochemistry. Compared with the control, the contents of lead were significantly increased in serum, cerebral cortex and hippocampus in the treatment groups respectively (P < 0.01, P < 0.05). The BDNF mRNA expression in the cerebral cortex (0.52 +/- 0.05, 0.33 +/- 0.03) and hippocampus (0.77 +/- 0.10, 0.92 +/- 0.08) of 50, 100 mg/kg treated groups was significantly higher than that of the control group (0.52 +/- 0.05, 0.33 +/- 0.03), respectively (P < 0.05). The results of immunohistochemistry showed that the area density of BDNF protein in cerebral cortex of every treatment group (0.040 +/- 0.027, 0.048 +/- 0.027, 0.086 +/- 0.040) was significantly increased whereas the average gray value (187.11 +/- 11.15, 180.53 +/- 5.82, 180.15 +/- 8.01) was significantly lower than that of the control (0.026 +/- 0.005, 204.98 +/- 3.45) (P < 0.05, P < 0.01). The area density of BDNF protein in hippocampus of every treatment group was 0.040 +/- 0.027, 0.048 +/- 0.027, 0.086 +/- 0.040, respectively, which was significantly increased compared with the control (0.045 +/- 0.019, P < 0.05). The average gray value of BDNF protein in hippocampus (181.03 +/- 5.16, 171.25 +/- 12.65) of 50, 100 mg/kg were significantly lower than that of the control (198.98 +/- 6.40, P < 0.01). There was no positive expression of P75NTR protein in the control and 25 mg/kg body weight groups. The positive expression of P75NTR protein was detected in 50 and 100 mg/kg body weight groups. Lead can increase the BDNF and P75NTR expression in rat brain which might play an important role in the neural damage and repair.


Public health and precision medicine share a goal.
The advances made in genomics and molecular tools aid public health programs in the investigation of outbreaks and control of diseases by taking advantage of the precision medicine. Precision medicine means "segregating the individuals into subpopulations who vary in their disease susceptibility and response to a precise treatment" and not merely designing of drugs or creation of medical devices. By 2017, the United Kingdom 100,000 Genomes Project is expected to sequence 100,000 genomes from 70,000 patients. Similarly, the Precision Medicine Initiative of the United States plans to increase population-based genome sequencing and link it with clinical data. A national cohort of around 1 million people is to be established in the long term, to investigate the genetic and environmental determinants of health and disease, and further integrated to their electronic health records that are optional. Precision public health can be seen as administering the right intervention to the needy population at an appropriate time. Precision medicine originates from a wet-lab while evidence-based medicine is nurtured in a clinic. Linking the quintessential basic science research and clinical practice is necessary. In addition, new technologies to employ and analyze data in an integrated and dynamic way are essential for public health and precision medicine. The transition from evidence-based approach in public health to genomic approach to individuals with a paradigm shift of a "reactive" medicine to a more "proactive" and personalized health care may sound exceptional. However, a population perspective is needed for the precision medicine to succeed.


An update on the impact of Staphylococcus aureus enterotoxins in chronic sinusitis with nasal polyposis.
Nasal polyps in adults, characterized by abundant eosinophils, local overproduction of immunoglobulin E, and often associated with asthma, have been appreciated as an eosinophilic inflammation, potentially of allergic origin, but unrelated to a bacterial impact. Evidence accumulates, however, that Staphylococcus aureus colonizes chronic rhinosinusitis with, but not without polyps, with significantly increased prevalence. The germs release enterotoxins, which act as superantigens and induce a topical multiclonal IgE-formation as well as a severe, possibly steroid-insensitive eosinophilic inflammation. Recently, S. aureus could be demonstrated to reside intraepithelially, and potentially to release superantigens into the tissue from within the epithelial cells. An immune defect, either in the innate or adaptive immunity, might be responsible for this phenomenon. Follicle-like structures and lymphocyte accumulations, specifically binding enterotoxins, can be found within the polyp tissues, giving rise to local IgE formation. The superantigen-induced immune response also leads to a modulation of the severity of the eosinophilic inflammation, and may be linked to lower airway co-morbidity in polyp patients. Interestingly, IgE antibodies to enterotoxins can be found in the majority of aspirin-sensitive polyp tissues, associated with a substantial increase in ECP and IL-5. The possible role of S. aureus enterotoxins in polyp disease in Europe, the US and Asia has meanwhile been supported by several studies, demonstrating the presence of IgE antibodies to enterotoxins and inflammatory consequences in nasal polyp tissue. First studies also point to an involvement of S. aureus derived enterotoxins in lower airway disease, such as severe asthma and exacerbated COPD, clearly suggesting a clinical need for diagnosis and treatment of the germ and its related effects. Therapeutic approaches are so far empirical, and need further study, also serving to proof the clinical relevance of the concept.


Top-down mass spectrometry of integral membrane proteins.
Top-down mass spectrometry focuses on intact proteins, thereby avoiding loss of information accompanying 'shotgun' protocols that reduce the proteome to a collection of peptides. A suite of liquid-chromatography technologies has been developed for purification of intact integral membrane proteins in aqueous/organic solvent mixtures compatible with biological 'soft-ionization' mass spectrometry, preserving covalent structure into the gas phase. Multiply charged protein ions are fragmented in the gas phase, using either collision-activated or electron-capture dissociation, thus yielding complex spectra of sequence-dependent product ions that collectively define the original native covalent state of an intact protein. Top down offers a more detail-orientated approach to post-transcriptional and post-translational diversity allowing an enhanced insight beyond genomic translation, which has now extended into the bilayer proteome.


Incidence of haematological malignancies in Kosovo-A post "uranium war" concern.
During the Kosovo War (1998-99) approximately 31,000 rounds with Depleted Uranium (DU) were fired on 85 targets in Kosovo. The number of haematological malignancies (HM) increased after the war and the concern was the use of DU during the war. The aim of this study was to analyse the incidence rates of HM in Kosovo throughout a 20-year that includes pre- and post- war period (1995-2015); and to examine if there is any association between the use of DU rounds and incidence rates of HM in different regions of Kosovo. In this retrospective register-based study, 1,798 new patients diagnosed with leukaemia, Hodgkin lymphoma, non-Hodgkin lymphoma and Multiple myeloma were analysed over a 20 year period. Incidence rates were calculated focusing on specific time periods, regions and age-groups. In addition, the correlation between the use of DU in different regions and their incidence of HM was analysed. The average annual crude rate of all HM in Kosovo was 5.02 cases per 100,000 persons. Incidence rates of HM in first post-war period (2000-2003) increased by 0.37 cases/100,000 persons (9.51%) compared to the pre-war period (1995-1998) whereas in the last post-war period (2012-2015), incidence of HM increased by 3.19/100,000 persons (82%). Gjakova and Peja, the first and third most exposed regions to DU ordnance ranked first and second in difference in HM. Prishtina, Gjilan and Ferizaj, regions with the least number of rounds/km2, were characterized by a decline of incidence rates. After the war, the increase in incidence rate of HM was higher in two regions with most DU rounds/km2 expended Despite these findings, this study warrants further investigation and does not lead us to a conclusive finding on the existence of a causal relationship between the use of DU during the war and the rise in incidence of HM in Kosovo.


Differences in Immune Defense Evasion of Selected Inbred Lines of Heterorhabditis Bacteriophora in Two White Grub Species.
We determined virulence of seven Heterorhabditis bacteriophora strain GPS11 inbred lines possessing superior infective juvenile longevity, and heat and ultra violet radiation tolerance against white grubs Popillia japonica and Cyclocephala borealis. At 1 and 2 weeks after treatment, inbred line A2 was significantly more virulent towards P. japonica compared to the parent strain GPS11 and inbred lines A7, A8, A12 and A21; and line A2 caused significantly higher C. borealis mortality than lines A6 and A12. Penetration, encapsulation and survival of two inbred lines, A2 and A12, that showed the highest and lowest virulence against both grub species were then assessed. There were no differences between the two lines for the total number of nematodes penetrated in either P. japonica or C. borealis within the first 24 h, but a significantly higher percentage of penetrated nematodes were alive in line A2 compared to the line A12 in both grub species. P. japonica immune response over time to hemocoel-injected nematodes of A2, A12 and the parent strain was further investigated. While all injected nematodes were encapsulated at 6 h post injection, non-encapsulated living nematodes were detected at 12 and 24 h post injection, showing the breakage out of encapsulation. A higher percentage of non-encapsulated living nematodes and a lower percentage of dead nematodes were found in line A2 as compared to the line A12 after 12 h post injection. These data suggest that virulence differences in the studied H. bacteriophora inbred lines are not due to differences in nematode penetration or recognition by the grub immune system, but are related to the ability of the infective juveniles to break out of encapsulation.


Isolated tricuspid stenosis and heart failure: a focus on carcinoid heart disease.
A rare clinical occurrence, heart failure in the setting of tricuspid stenosis should immediately trigger a search for underlying systemic carcinoid disease. Carcinoid tumor cells can secrete a variety of vasoactive substances that result in skin erythema, excretory diarrhea, bronchospasm, and hemodynamic instability, but these manifestations are noted only in a few patients. Right heart valvular disease is common since the vasoactive noxious substances pass through the right heart unaffected and undergo metabolism in the pulmonary circulation, thereby decreasing involvement of the left-sided valves. Localization of the carcinoid tumor followed by surgically directed valvular treatment is mandatory for relief of symptoms. In nonoperative candidates, cytotoxic chemotherapy or long-term symptomatic drug treatment with somatostatin is indicated.


Inhibition of growth hormone signaling by the fasting-induced hormone FGF21.
Starvation blocks the actions of growth hormone (GH) and inhibits growth through mechanisms that are not well understood. In this report, we demonstrate that fibroblast growth factor 21 (FGF21), a hormone induced by fasting, causes GH resistance. In liver, FGF21 reduces concentrations of the active form of signal transducer and activator of transcription 5 (STAT5), a major mediator of GH actions, and causes corresponding decreases in the expression of its target genes, including insulin-like growth factor 1 (IGF-1). FGF21 also induces hepatic expression of IGF-1 binding protein 1 and suppressor of cytokine signaling 2, which blunt GH signaling. Chronic exposure to FGF21 markedly inhibits growth in mice. These data suggest a central role for FGF21 in inhibiting growth as part of its broader role in inducing the adaptive response to starvation.


Phylogenic analysis of human bocavirus detected in children with acute respiratory infection in Yaounde, Cameroon.
Human Bocavirus (HBoV) was first identified in 2005 and has been shown to be a common cause of respiratory infections and gastroenteritis in children. In a recent study, we found that 10.7% of children with acute respiratory infections (ARI) were infected by HBoV. Genetic characterization of this virus remains unknown in Central Africa, particularly in Cameroon Leeding us to evaluate the molecular characteristics of HBoV strains in Cameroonian children with ARI. Phylogenetic analysis of partial HBoV VP1/2 sequences showed a low level of nucleotide variation and the circulation of HBoV genotype 1 (HBoV-1) only. Three clades were obtained, two clustering with each of the reference strains ST1 and ST2, and a third group consisting of only Cameroon strains. By comparing with the Swedish reference sequences, ST1 and ST2, Cameroon sequences showed nucleotide and amino acid similarities of respectively 97.36-100% and 98.35-100%. These results could help improve strategies for monitoring and control of respiratory infections in Cameroon.


Peptide Cross-linkers: Immobilization of Platinum Nanoparticles Highly Dispersed on Graphene Oxide Nanosheets with Enhanced Photocatalytic Activities.
For exerting potential catalytic and photocatalytic activities of metal nanoparticles (MNPs), immobilization of MNPs on a support medium in highly dispersed state is desired. In this Research Article, we demonstrated that surfactant-free platinum nanoparticles (PtNPs) were efficiently immobilized on graphene oxide (GO) nanosheets in a highly dispersed state by utilizing oligopeptide β-sheets as a cross-linker. The fluorenyl-substituted peptides were designed to form β-sheets, where metal-binding thiol groups and protonated and positively charged amino groups are integrated on the opposite sides of the surface of a β-sheet, which efficiently bridge PtNPs and GO nanosheet. In comparison to PtNP/GO composite without the peptide linker, the PtNP/peptide/GO ternary complex exhibited excellent photocatalytic dye degradation activity via electron transfer from GO to PtNP and simultaneous hole transfer from oxidized GO to the dye. Furthermore, the ternary complex showed photoinduced hydrogen evolution upon visible light irradiation using a hole scavenger. This research provides a new methodology for the development of photocatalytic materials by a bottom-up strategy on the basis of self-assembling features of biomolecules.


Electrical stimulation over muscle tendons in humans. Evidence favouring presynaptic inhibition of Ia fibres due to the activation of group III tendon afferents.
Electrical stimulation over muscle tendons produces a transient suppression of voluntary EMG activity; its onset latency is approximately 55 ms in the forearm extensor muscles. This phenomenon has been attributed to the activation of a polysynaptic inhibitory pathway originating from Ib afferent fibres. To clarify its origin we conducted several experiments in 10 normal healthy subjects. The EMG silence after tendon stimulation appeared at relatively high stimulus intensities (> 50 mA); conditioning cutaneous stimulation left it unchanged, and the inhibition had a short recovery cycle (50 ms). Tendon stimulation still evoked EMG suppression during an ischaemic block of fast-conducting afferents. The motor potentials evoked by transcranial magnetic stimulation of the motor cortex during the EMG silence remained almost unchanged, whereas the H reflex was strongly inhibited. Hence we conclude that tendon stimulation activates slow-conducting tendon afferents, possibly group III fibres, connected not through a polysynaptic pathway originating from Ib afferents but through an oligo- or disynaptic inhibitory circuit. The EMG suppression after tendon stimulation probably represents a dysfacilitation of the alpha-motor neurons due to presynaptic inhibition of Ia fibres produced by tendon afferent input to the spinal cord.


Muon spin relaxation measurements of NaxCoO2.yH2O.
Using the transverse field muon spin relaxation technique, we measure the temperature dependence of the magnetic field penetration depth lambda, in the NaxCoO2.yH(2)O system. We find that lambda, which is determined by the superfluid density n(s) and the effective mass m*, is very small and on the edge of the TF-microSR sensitivity. Nevertheless, the results indicate that this system obeys the Uemura relation. By comparing lambda with the normal state electron density, we conclude that m* of the superconductivity carrier is 70 times larger than the mass of bare electrons. Finally, the order parameter in this system cannot be described by a complete gap over the entire Fermi surface.


Magnesium sulphate in patients with thrombotic thrombocytopenic purpura (MAGMAT): a randomised, double-blind, superiority trial.
Studies have suggested benefits from magnesium sulphate in thrombotic thrombocytopenic purpura (TTP). We aimed to measure the effects of magnesium sulphate supplementation on TTP recovery. In this multicenter, randomised, double-blind, controlled, superiority study, we enrolled adults with a clinical diagnosis of TTP. Patients were randomly allocated to receive magnesium sulphate (6 g intravenously followed by a continuous infusion of 6 g/24 h for 3 days) or placebo, in addition to the standard treatment. The primary outcome was the median time to platelet normalisation (defined as a platelet count ≥ 150 G/L). Efficacy and safety were assessed by intention-to-treat. Overall, we enrolled 74 participants, including one who withdrew his/her consent. Seventy-three patients were further analyzed, 35 (48%) allocated to magnesium sulphate and 38 (52%) to placebo. The median time to platelet normalisation was 4 days (95% confidence interval [CI], 3-4) in the magnesium sulphate group and 4 days (95% CI 3-5) in the placebo group. The cause-specific hazard ratio of response was 0.93 (95% CI 0.58-1.48, p = 0.75). The number of patients with ≥ 1 serious adverse reactions was similar in the two groups. By day 90, four patients in the magnesium sulphate group and two patients in the placebo group had died (p = 0.42). The most frequent adverse event was low blood pressure occurring in 34% in the magnesium sulphate group and 29% in the placebo group (p = 0.80). Among patients with TTP, the addition of magnesium sulphate to the standard of care did not result in a significant improvement in time to platelet normalisation.


Postsclerotherapy hyperpigmentations. Chromated glycerin as a screen for patients at risk (a retrospective study).
Chromated glycerin reportedly causes less post-sclerotherapy hyperpigmentations than polidocanol. To investigate whether replacing polidocanol with chromated glycerin lowers the incidence of postsclerotherapy hyperpigmentation. Retrospective study of 134 records of patients treated for leg telangiectasia. At the first session only chromated glycerin was injected. From the second session on treatment was continued--according to the response--either with chromated glycerin or with the stronger polidocanol. Chromated glycerin caused strong sclero-inflammatory reaction in 27% of patients, who were therefore treated with chromated glycerin only; in the remaining 73%, chromated glycerin was replaced with polidocanol, because of mild (or absent) reaction. Postsclerotherapy hyperpigmentation developed in three patients, all treated with chromated glycerin, while no postsclerotherapy hyperpigmentation developed in the patients treated with polidocanol. Single "trial" session with chromated glycerin permits to select patients at risk of developing postsclerotherapy hyperpigmentation, and treat these with a milder sclerosant. This approach also reduced the incidence of early postsclerotherapy hyperpigmentation compared with similar series treated with polidocanol alone.


Peer Influence, Peer Selection and Adolescent Alcohol Use: a Simulation Study Using a Dynamic Network Model of Friendship Ties and Alcohol Use.
While studies suggest that peer influence can in some cases encourage adolescent substance use, recent work demonstrates that peer influence may be on average protective for cigarette smoking, raising questions about whether this effect occurs for other substance use behaviors. Herein, we focus on adolescent drinking, which may follow different social dynamics than smoking. We use a data-calibrated Stochastic Actor-Based (SAB) Model of adolescent friendship tie choice and drinking behavior to explore the impact of manipulating the size of peer influence and selection effects on drinking in two school-based networks. We first fit a SAB Model to data on friendship tie choice and adolescent drinking behavior within two large schools (n = 2178 and n = 976) over three time points using data from the National Longitudinal Study of Adolescent to Adult Health. We then alter the size of the peer influence and selection parameters with all other effects fixed at their estimated values and simulate the social systems forward 1000 times under varying conditions. Whereas peer selection appears to contribute to drinking behavior similarity among adolescents, there is no evidence that it leads to higher levels of drinking at the school level. A stronger peer influence effect lowers the overall level of drinking in both schools. There are many similarities in the patterning of findings between this study of drinking and previous work on smoking, suggesting that peer influence and selection may function similarly with respect to these substances.


Karyoptosis: A novel type of cell death caused by chronic autophagy inhibition.
Macroautophagy/autophagy influences onset and progression of several human neurodegenerative diseases, because of its critical role as a regulator of neuronal proteostasis and organelle quality control. In many neurodegenerative diseases, impairment in autophagy is thought to play a fundamental part in the terminal phases of cellular degeneration and death. However, the ultimate mechanism of neuronal cell death remains elusive. In a recent study we have identified a new form of regulated cell death, which arises upon autophagy inhibition.


A controlled clinical trial on the effects of motor intervention on balance and cognition in institutionalized elderly patients with dementia.
To analyse the effects of two interventions on the cognition and balance of institutionalized elderly people with mixed dementia. Fifty-four participants were allocated into three groups. Group 1 was assisted by an interdisciplinary programme comprising physiotherapy, occupational therapy and physical education. A physiotherapist alone carried out the intervention in group 2. Group 3 was considered as control. Assessors were blinded to guarantee the absence of bias. Cognitive functions were analysed with the Mini-Mental State Examination and the Brief Cognitive Screening Battery. Balance was assessed with the Berg Balance Scale and the Timed Get-Up-and-Go Test. Multiple analysis of variance (MANOVA) was used to test possible main effects of the interventions. The results showed benefits on the balance of subjects in both groups 1 (F=3.9, P<0.05) and 2 (F=3.1, P<0.05), compared with group 3. MANOVA did not indicate benefits on the cognitive functions between groups 1 and 3 (F=1.1, P>0.05) and groups 2 and 3 (F=1.6, P>0.05). However, univariate analysis indicated some benefits of the interdisciplinary intervention on two specific domains measured by the Brief Cognitive Screening Battery (F=26.5, P<0.05; F=4.4, P<0.05). Six months of multidisciplinary or physiotherapeutic intervention were able to improve a person's balance. Although global cognition did not improve through treatment, when the intervention was carried out on a multidisciplinary basis we observed an attenuation in the decline of global cognition on two specific cognitive domains. Exercises applied in different contexts may have positive outcomes for people with dementia.


Controlling prescription drug costs: regulation and the role of interest groups in Medicare and the Veterans Health Administration.
Medicare and the Veterans Health Administration (VA) both finance large outpatient prescription drug programs, though in very different ways. In the ongoing debate on how to control Medicare spending, some suggest that Medicare should negotiate directly with drug manufacturers, as the VA does. In this article we relate the role of interest groups to policy differences between Medicare and the VA and, in doing so, explain why such a large change to the Medicare drug program is unlikely. We argue that key policy differences are attributable to stable differences in interest group involvement. While this stability makes major changes in Medicare unlikely, it suggests the possibility of leveraging VA drug purchasing to achieve savings in Medicare. This could be done through a VA-administered drug-only benefit for Medicare-enrolled veterans. Such a partnership could incorporate key elements of both programs: capacity to accept large numbers of enrollees (like Medicare) and leverage to negotiate prescription drug prices (like the VA). Moreover, it could be implemented at no cost to the VA while achieving savings for Medicare and beneficiaries.


Development of Oral Health Impacts on Daily Living Questionnaire Items - a Qualitative Study.
To develop an instrument to measure Oral Health-related Quality of Life (OHQoL) and the changes after dental treatment among older adults in Hong Kong, in order to understand their views on the influences of oral health problems and generate relevant items to design the instrument. A qualitative study was conducted among adults aged 55 and over. Information on their perceived oral health impacts was collected during semi-structured interviews. A framework approach was used to identify the oral health impacts and to understand the meaning of those impacts on the perception of life satisfaction. A total of 39 participants (average age 72 years) underwent the semi-structured interviews; 20 were seeking dental treatment and 19 had already received dental treatment for 1 to 3 months. In total, 308 statements on oral health impacts were drawn from the participants' descriptions. After four steps of item reduction and refinement, a list of 20 items was generated before being classified into eight domains: Cleansing, Eating, Speaking, Appearance, Social, Psychological, Awareness, and Health and Finance. Older adults in Hong Kong perceive that oral health impacts on different aspects of life. The face validity and content validity of the developed Oral Health Impact on Daily Living (OHIDL) was proved through qualitative study.


Circadian Rhythms and Acute Coronary Syndrome in the Elderly.
Ischemic heart disease is the leading cause of death in Western countries. The incidence, prevalence and mortality rate of acute cardiac events increase with age. Circadian rhythms allow organisms to prepare for their daily fluctuations brought on by day-night cycles, thus playing an important role in the cardiovascular physiology. This can be sometimes a double-edged sword, since exaggerated responses may not be beneficial or may be even harmful in individuals susceptible to adverse acute cardiovascular events. Remarkably, occurrence of such events has been related to a circadian pattern with a peak in the morning hours. Of interest, elderly patients seem to have an increased risk of acute coronary events, especially in the morning, though a bimodal distribution has also been observed. Further studies are required to get more insights on age-related differential circadian patterns in acute coronary syndromes patients.


Multiple equilibria in complex chemical reaction networks: extensions to entrapped species models.
In two earlier papers, means were provided to decide the capacity of complex chemical reaction networks, taken with mass-action kinetics, to admit multiple equilibria in the context of the isothermal homogeneous continuous flow stirred tank reactor (CFSTR). In such a reactor, all species are deemed to be in the outflow, a fact which has an important bearing on the nature of the governing equations. In contrast, one can imagine CFSTR-like models of the cell in which certain large molecules (e.g., enzymes) remain entrapped within the cell, whereas smaller ones (e.g., metabolites) are free to diffuse through the cell boundary. Although such models bear a strong physical resemblance to the classical CFSTR picture, there are substantive differences in the corresponding mathematics. Without a presumption of mass-action kinetics, this research is intended to indicate a general way in which results about uniqueness of equilibria in the classical CFSTR context extend to entrapped species models.


Percutaneous transtracheal ventilation.
PTV is an adjunct to airway management that can prove helpful in selected cases. Its speed and ease of performance are offset by the need for specialized equipment to accomplish it. This difficulty, combined with infrequent indications, makes PTV a rarely performed procedure. Nevertheless, it remains a viable airway management alternative whose applications may be broadened in the future.


Management of acute aortic dissection in critical care.
Aortic dissections are associated with significant mortality and morbidity, with rapid treatment paramount. They are caused by a tear in the intimal lining of the aorta that extends into the media of the wall. Blood flow through this tear leads to the formation of a false passage bordered by the inner and outer layers of the media. Their diagnosis is challenging, with most deaths caused by aortic dissection diagnosed at post-mortem. Aortic dissections are classified by location and chronicity, with management strategies depending on the nature of the dissection. The Stanford method splits aortic dissections into type A and B, with type A dissections involving the ascending aorta. De Bakey classifies dissections into I, II or III depending on their origin and involvement and degree of extension. The key to diagnosis is early suspicion, appropriate imaging and rapid initiation of treatment. Treatment focuses on initial resuscitation, transfer (if possible and required) to a suitable specialist centre, strict blood pressure and heart rate control and potentially surgical intervention depending on the type and complexity of the dissection. Effective post-operative care is extremely important, with awareness of potential post-operative complications and a multi-disciplinary rehabilitation approach required. In this review article we will discuss the aetiology and classifications of aortic dissection, their diagnosis and treatment principles relevant to critical care. Critical care clinicians play a key part in all these steps, from diagnosis through to post-operative care, and thus a thorough understanding is vital.


Coupled waveguide-surface plasmon resonance biosensor with subwavelength grating.
This study develops a coupled waveguide-surface plasmon resonance (CWSPR) biosensor with a subwavelength grating structure for the real-time analysis of biomolecular interactions. In the proposed optical metrology system, normally incident white light is coupled into the waveguide layer through the subwavelength grating structure thereby enhancing the wave vector which excites the surface plasmons on the metal sensing surface. The proposed CWSPR biosensor not only retains the same sensing sensitivity as that of a conventional surface plasmon resonance device, but also yields a sharper dip in the reflectivity spectrum and therefore provides an improved measurement precision. Moreover, the metrology setup overcomes the limitations of the conventional Kretschmann attenuated total reflection approach and is less sensitive to slight variations in the angle of the incident light. The experimental results confirm that the current CWSPR biosensor provides a straightforward yet powerful technique for real-time biomolecular interaction analysis.


Urgently listed lung transplant patients have outcomes similar to those of electively listed patients.
To (1) determine outcomes after urgent listing compared with elective listing for lung transplant and (2) compare in-hospital morbidity and mortality, survival, and allograft function in these 2 groups. From January 2006 to September 2017, 201 patients were urgently and 1423 electively listed. Among urgently listed patients, 130 subsequently underwent primary lung transplant as did 995 electively listed patients. Competing-risks analysis for death and transplant after listing and weighted balancing score matching (76 pairs) were used to compare in-hospital morbidity and survival. Mixed-effect longitudinal modeling was used to compare allograft function to 8 years post-transplant. At 1 month, mortality was 26% in urgently listed patients, and 58% were transplanted. Risk factors for death included older age, higher bilirubin, and transfer from an outside hospital. At transplantation, urgently listed transplant patients were younger (53 ± 13 vs 55 ± 12 years), had more ventilator and extracorporeal membrane oxygenation support (32/25% vs 20/2.0%), more restrictive lung disease (95/73% vs 509/51%), and a higher lung allocation score (82 ± 13 vs 47 ± 17). In-hospital morbidity and mortality, time-related survival, and longitudinal allograft function were similar between matched groups. Urgent listing more often than not leads to transplantation. Although urgently listed patients are sicker overall, after transplant their perioperative morbidity and mortality, overall survival, and allograft function are similar to those of electively listed patients. Appropriate patient selection and aggressive supportive care allow urgently listed lung transplant patients to achieve these similar post-transplant outcomes.


High historical variability weakens the effects of current climate differentiation on microbial community dissimilarity and assembly.
Understanding the influences of global climate change on soil microbial communities is essential in evaluating the terrestrial biosphere's feedback to this alarming anthropogenic disturbance. However, little is known about how intra-site historical climate variability can mediate the influences of current climate differences on community dissimilarity and assembly. To fill this gap, we examined and disentangled the interactive effects of historical climate variability and current climate differences on the soil bacterial community dissimilarity and stochasticity of community assembly among 143 sites from 28 forests across eastern China. We hypothesize that the relative importance of stochasticity and community dissimilarity are related to historical climate variability and that an increasing sum of intra-site historical variability enhances stochasticity while reduces dissimilarity between two communities. To test our hypothesis, we statistically controlled for covariates between sites including differences in soil chemistry, plant diversity, spatial distance, and seasonal climate variations at annual timescales. We observed that an increase in inter-site current climate differences led to a reduced impact of stochasticity in community assembly and a pronounced divergence between communities. In stark contrast, when communities were subjected to a high level of intra-site historical climate fluctuation, the observed impact incurred from current climate differences was substantially weakened. Moreover, the influence of increased historical variability was consistent along the gradient of current temperature differences between sites. However, effects induced by historical fluctuation in precipitation were disproportional and only evident when small inter-site differences were observed. Consequently, if the prior climate variability is ignored, especially regarding environmental factors like temperature, we assert that the influence current climate differentiation has on regulating community dissimilarity and assembly stochasticity will be underestimated. Together, our findings highlight the importance and need of explicitly controlling the mean and the historical variability of climate factors for the next "generation" of climate change experiments to come.


The solitary schwannoma of the eighth cranial nerve. An immunohistochemical study of the cochlear nerve-tumor interface.
Given recent controversy concerning hearing preservation surgery of the acoustic neurinoma, an immunohistochemical study was undertaken to investigate the cochlear nerve-tumor interface. Ten intact medium-sized acoustic neurinomas were studied by means of classic staining procedures and an immunohistochemical technique using monoclonal mouse antibodies to human neurofilaments. Our observations indicate that the cochlear nerve is histologically involved in the tumoral process in those cases in which macroscopically visible adherences between the cochlear nerve and the tumor are present. We were not able to discern a clear cleavage plane. Six of the 10 specimens showed tumoral invasion of the cochlear nerve. Several therapeutic attitudes are discussed in view of these observations and reports from the international literature. In conclusion, the principle of hearing preservation surgery is rejected in favor of total tumor removal in every case in which surgery is indicated.


Factors influencing compliance with antiepileptic drug regimes.
Failure to comply with drug regimes is prevalent amongst patients with epilepsy and the consequence of this is often an increased risk of further seizures. This paper describes the level of, and influences upon, non-compliance with antiepileptic drug (AED) treatment. A postal questionnaire was sent to an unselected, community-based population of patients with epilepsy. This instrument included questions about patients' AED treatment, any related side-effects, and AED-taking behaviour. Univariate analysis showed that factors associated with compliance were patient age, how important patients felt it was to take drugs as prescribed, whether patients reported feelings of stigma, whether on mono- or polytherapy, whether they were experiencing any side-effects because of AEDs, whether patients had a regular arrangement to see their GP about epilepsy and how easy they found their GP to talk to. Multivariate analysis showed that the strongest predictors of non-compliance were feeling it was not very or not at all important to take AEDs as prescribed, being a teenager, being aged under 60 and being on monotherapy. Further implementation of educational programmes for people with epilepsy would help to improve levels of compliance thereby reducing the risk of unnecessary seizures.


Statins Are Associated With a Decreased Risk of Decompensation and Death in Veterans With Hepatitis C-Related Compensated Cirrhosis.
Statins decrease portal pressure in patients with cirrhosis and increase survival times of patients who have bled from varices. However, statins can be hepatotoxic. It is important to determine whether long-term statin use will be beneficial or detrimental for patients with cirrhosis because physicians are reluctant to prescribe statins to patients with liver disease. We investigated the effects of statins on decompensation and survival times in patients with compensated cirrhosis. We performed a retrospective cohort using the Veteran Affairs Clinical Case Registry, which contains nationwide data from veterans infected with the hepatitis C virus (HCV). We identified patients with compensated cirrhosis from January 1996 through December 2009. Statin use was according to filled prescriptions. Cirrhosis and decompensation were determined from International Classification of Diseases, 9th revision codes, using a validated algorithm. Among 40,512 patients with HCV compensated cirrhosis (98% male; median age, 56 y), 2802 statin users were identified. We developed a propensity score model using variables associated with statin prescription, and new statin users were matched with up to 5 nonusers; 685 statin users were matched with 2062 nonusers. Discrimination of the propensity score model was 0.92. Statin users had a lower risk of decompensation (hazard ratio [HR], 0.55; 95% confidence interval [CI], 0.39-0.77) and death (HR, 0.56; 95% CI, 0.46-0.69), compared with nonusers. Findings persisted after adjustment for age, FIB-4 index score, serum level of albumin, model for end-stage liver disease and Child-Turcotte-Pugh scores (HR for decompensation, 0.55; 95% CI, 0.39-0.78), and death (HR, 0.55; 95% CI, 0.45-0.68). Based on data from the Veteran Affairs Clinical Case Registry, statin use among patients with HCV and compensated cirrhosis is associated with a more than 40% lower risk of cirrhosis decompensation and death. Although statins cannot yet be recommended widely for these patients, their use should not be avoided.


I-like R plasmids promote degradation of stable ribonucleic acid in Escherichia coli.
Some I-like R plasmids, R483, R144, R64drd-11 and R621a, belonging to compatibility groups IncI alpha and I gamma promoted degradation of stable RNA in the srnA1 cells of Escherichia coli after addition of rifampin at 42 degrees C. R16 and R834 plasmids of compatibility group IncB also promoted the degradation of RNA. However, other many kinds of plasmids did not. The promotion of RNA degradation was delayed by the addition of chloramphenicol with rifampin.


MDA-Lymphatic Filariasis.
Lymphatic filariasis is one of the neglected tropical diseases. It is estimated that 120 million people are currently infected in 73 countries where filariasis is endemic. Lymphatic filariasis is a leading cause of chronic disability worldwide, including of 15 million people who have lymphoedema (elephantiasis) and 25 million men who have hydrocoele.


Difficult Access and Poor Productivity: Mammography Screening in Brazil.
Background: Factors that may hamper access to mammographic screening in any given region include socioeconomic limitations and the geographical distribution and quality of the mammography machines. This study evaluated access to breast cancer screening within the Brazilian National Health Service (SUS), the geographical distribution of mammography equipment and the number of mammograms performed in Brazil. Methods: This ecological study evaluated the availability of mammography machines within the SUS, those available for Brazil as a whole, its macroregions, states and the Federal District in 2016. The number of mammography machines required for breast cancer screening was calculated and compared to the number of machines available. The expected number of mammograms was compared with the actual number performed. Machines were georeferenced based on their location and the municipal seat, according to healthcare region, with 60 km being defined as the maximum distance for an individual to travel for a mammogram. Results: In 2016, there were 4,628 mammography machines in Brazil. Of these, 4,492 were in use and 2,113 (47%) were available to the SUS. Considering the number of mammograms required as a function of the number clinically indicated, 2,068 machines would be required for breast cancer screening in Brazil. The network of machines available would be capable of producing 14,279,654 exams; however, only 4,073,079 exams were performed, representing 29% of the total capacity of production in the country in 2016. Regarding the maximum distance of 60 km to access a mammogram, only relatively small areas of Brazil were found not to meet this indicator. Conclusion: These results suggest that the difficulty of the Brazilian population in accessing breast cancer screening through the SUS is not associated with the number of machines available or with the geographical location of the equipment but rather with the insufficient number of mammograms performed.


A resonance suppression method in platform style inertial reference unit via particle swarm optimization notch filter.
With the development of laser communication, remote sensing imaging, and other technologies, an inertial reference unit (IRU) plays an essential part in the line-of-sight (LOS) stabilization system used for acquiring, pointing, and tracking targets. The IRU provides a stable reference beam to realize accurate LOS pointing under external disturbances. Compared with the frame style IRU, the platform style IRU (PIRU) can achieve a higher bandwidth and better precision. However, mechanical resonance is introduced by a flexure hinge inevitably in the PIRU, which affects the performance of the LOS stabilization system. In this paper, an open-loop dynamic model of PIRU is established. Identification experiments are carried out with results indicating a 28.7 dB resonance peak at 27.07 Hz in the x axis and a 30.3 dB resonance peak at 26.59 Hz in the y axis. An asymmetric notch filter is used to suppress the resonance peak to achieve a higher control bandwidth. A fitness function is designed to represent the effect of resonance suppression. A particle swarm optimization algorithm is used to search for an optimal solution of the fitness function to obtain the parameters of the asymmetric notch filter. Experimental results show that the resonance peak is reduced by 97.88% and the system bandwidth reaches 159.31 Hz.


The problems of aggression and violence for health-care staff.
Nurses frequently face violent and aggressive behaviour in the course of their daily work. Staff working in accident and emergency departments report the highest incidence of verbal and physical aggression and actual violence. This literature review examines the problem and highlights advice available on defusing potentially dangerous situations at work.