Circadian regulation of DNA excision repair: implications for chrono-chemotherapy.
The mammalian circadian system synchronizes organisms' daily cyclical physiology from gene expression to gross behavioral patterns. A new study from our group suggests that DNA repair is also intimately linked to circadian rhythm. Since the repair of DNA lesions contributes to the resistance of chemotherapy with DNA damaging agents such as cisplatin, understanding the fundamental molecular mechanism regulating DNA repair pathways is important for cancer therapy. Here we review the significance of the connection linking the circadian clock with nucleotide excision repair and discuss potential implications for chemotherapy.


Superior Hypogastric Plexus Neurolysis to Manage Metastatic Pelvic Pain in a Forty-Five-Year-Old Spina Bifida Patient: A Case Report.
A 45-year-old patient with spina bifida and adenocarcinoma of the rectum was treated with a superior hypogastric plexus (SHP) ablation for pain control. The procedure enabled her to reduce opioid consumption, being more clear-headed and functional to be discharged to her residence. The case is presented to highlight the options of neurolytic interventions to manage pain in terminally ill cancer patients. We discuss the options of SHP ablation and justify our choice of approach and the use of a neurolytic agent.


Mammals and Mutations, Life Span, Cancer Risk.
Findings from the Wellcome Sanger Institute in Hinxton, UK, indicate that across 16 mammalian species, somatic mutation rates per year appear to strongly influence life span. Another study of 191 mammalian species, led by the University of Montpellier in France, shows that cancer mortality risk is associated with diet but independent of body mass and life span, confirming the validity of Peto's paradox.


Digital measures of freezing of gait across the spectrum of normal, non-freezers, possible freezers and definite freezers.
Over the course of the disease, freezing of gait (FoG) will gradually impact over 80% of people with Parkinson's disease (PD). Clinical decision-making and research design are often based on classification of patients as 'freezers' or 'non-freezers'. We derived an objective measure of FoG severity from inertial sensors on the legs to examine the continuum of FoG from absent to possible and severe in people with PD and in healthy controls. One hundred and forty-seven people with PD (Off-medication) and 83 healthy control subjects turned 360° in-place for 1 minute while wearing three wearable sensors used to calculate a novel Freezing Index. People with PD were classified as: 'definite freezers', new FoG questionnaire (NFOGQ) score > 0 and clinically observed FoG; 'non-freezers', NFOGQ = 0 and no clinically observed FoG; and 'possible freezers', either NFOGQ > 0 but no FoG observed or NFOGQ = 0 but FoG observed. Linear mixed models were used to investigate differences in participant characteristics among groups. The Freezing Index significantly increased from healthy controls to non-freezers to possible freezers and to definite freezers and showed, in average, excellent test-retest reliability (ICC = 0.89). Unlike the Freezing Index, sway, gait and turning impairments were similar across non-freezers, possible and definite freezers. The Freezing Index was significantly related to NFOG-Q, disease duration, severity, balance confidence, and the SCOPA-Cog (p < 0.01). An increase in the Freezing Index, objectively assessed with wearable sensors during a turning- in-place test, may help identify prodromal FoG in people with PD prior to clinically-observable or patient-perceived freezing. Future work should follow objective measures of FoG longitudinally.


Pachytene arrest and other meiotic effects of the start mutations in Saccharomyces cerevisiae.
Mutations in the Start class of cell division cycle genes (CDC28, CDC36 and CDC39) define the point in the G1 phase of the vegetative cycle at which the cell becomes committed to completing another round of cell division. Genetic, cytological and biochemical data demonstrate that these mutations cause meiotic cells to become arrested at pachytene following completion of both chromosomal DNA replication and spindle pole body (SPB) duplication. In contrast these mutations have previously been found to cause arrest of the mitotic cell cycle prior to either of these landmark events, so the role of the Start genes in these events during vegetative growth must be indirect. Our observations are consistent with the hypothesis that CDC28, CDC36 and CDC39 are required for irreversible commitment to nuclear division in both the mitotic and meiotic pathways. CDC28 was additionally found to be required for the SPB separation that precedes spindle formation in preparation for the second meiotic division. Cytological and genetic analyses of this requirement revealed both that such separation may fail independently at either SPB and that ascospore formation can proceed independently of SPB separation.


How Social Determinants of Health of Individuals Living or Working in U.S. Department of Veterans Affairs Home-Based Long-Term Care Programs in Puerto Rico Influenced Recovery after Hurricane Maria.
In September 2017, Hurricane Maria devastated Puerto Rico, causing extensive infrastructure damage and a significant number of deaths. In the months and years since, recovery from Maria has been slow, hampered by delayed delivery of fiscal aid, corruption, economic hardships, and Puerto Rico's colonial status. Simultaneously, Puerto Rico's population is rapidly aging and hundreds of thousands of mostly younger Puerto Ricans are migrating out of Puerto Rico for more opportunities. Many Puerto Ricans who are older or disabled and need long-term care receive this care in home-based environments, as Puerto Rico has minimal institutionalized long-term care infrastructure and limited funding to expand it. The Department of Veterans Affairs (VA) offers several home-based long-term care options for Veterans in Puerto Rico. In this qualitative case study, veterans, VA staff, veterans' caregivers, caregivers' family members, and veterans' family members receiving or involved with providing this care were interviewed regarding their experiences during and after Hurricane Maria. Specifically, this study highlights how social determinants of health of those residing in or involved with VA home-based long-term care programs influenced recovery from Hurricane Maria, and how findings can inform disaster recovery and provision of home-based long-term care going forward.


Regulation of Sertoli cell differentiation by the testicular paracrine factor PModS: analysis of common signal transduction pathways.
In the testis the mesenchymally derived peritubular cells produce a paracrine factor, PModS, that mediates mesenchymal-epithelial interactions and modulates Sertoli cell functions essential for the process of spermatogenesis. PModS has a more dramatic effect on Sertoli cell differentiated functions in vitro than any regulatory agent previously shown to influence the cells, including FSH. The current study initiates an investigation of the pharmacology of PModS through an analysis of several common signal transduction pathways. PModS was found to stimulate cGMP levels in Sertoli cells and maintain elevated levels for up to 5 days in culture. PModS had no influence on cAMP levels. In contrast, FSH stimulated cAMP, but had no influence on cGMP levels. For comparison, an agent known to influence cGMP levels, atrial naturetic factor (ANF), was used to treat Sertoli cells. ANF caused a dramatic increase in Sertoli cell cGMP levels within minutes of treatment, but did not maintain elevated cGMP levels after a 72-h treatment. Although ANF increased guanylate cyclase in whole Sertoli cell homogenates and particulate fractions, PModS did not directly influence guanylate cyclase activity. As previously shown, PModS stimulates transferrin expression as a marker of Sertoli cell differentiated function. Agents that elevate cellular cGMP, including ANF, sodium nitroprusside, and 8-bromo-cGMP, did not influence Sertoli cell transferrin expression. In addition, these agents did not influence the actions of PModS or FSH. Therefore, cGMP does not appear to directly mediate the actions of PModS. As an alternative signal transduction pathway, calcium mobilization and inositol phosphate (IP) metabolism were examined. PModS did not alter calcium uptake or intracellular calcium mobilization. PModS also did not influence the levels of inositol mono-, bis-, or trisphosphates, whereas calf serum did stimulate levels of all three IP metabolites in Sertoli cells. Therefore, PModS does not appear to act through a mobilization of calcium or increased metabolism of IP. A final signal transduction pathway involving phosphorylation was also examined. PModS treatment was found to increase tyrosine phosphorylation of specific proteins in a crude Sertoli cell cytosol preparation. Genistein is an inhibitor of tyrosine kinases and was found to reduce PModS actions at a 3.7-microM concentration of genistein and inhibit PModS actions at a 37-microM concentration of genistein. Therefore, PModS may act through a tyrosine phosphorylation event that remains to be elucidated. Combined observations indicate that PModS does not use cyclic nucleotides, calcium mobilization, or IP metabolism as a signal transduction pathway.(ABSTRACT TRUNCATED AT 400 WORDS)


Higher House Dust Mite-Specific IgE Levels among Chronic Spontaneous Urticaria Patients May Implicate Higher Basophil Reactivity.
Allergen-specific IgE (sIgE) sensitization exists in a considerable fraction of chronic spontaneous urticaria (CSU) patients. Basophils have been implicated in the pathogenesis of CSU. This paper aimed to explore the relationship between allergic sensitization and basophil reactivity in CSU and the possible underlying mechanism. Basophil-enriched leukocytes were isolated from the peripheral blood of 76 CSU patients and 9 healthy controls. Basophil CD63 and FcεRIα (the alpha subunit of the high-affinity IgE receptor) expression in the blood samples with various house dust mite (HDM)-sIgE levels were determined by flow cytometry. Basophil reactivity and SHIP-1 (a molecule related to the IgE/FcεRI signaling pathway) expression were analyzed after stimulation with an HDM allergen or other stimuli. HDM-sIgEstrong positive (≥3.5 kU/L) CSU patients had a significantly higher mean percentage of basophil CD63 and higher baseline levels of FcεRIα expressed by basophils than HDM-sIgEnormal (<0.35 kU/L) CSU patients and healthy controls; the same went for total serum IgE. After stimulation with Dermatophagoides pteronyssinus peptidase 1 (Derp1) alone or together with Derp1-sIgE, the stimulation index of CD63 and levels of FcεRIα expressed by basophils in HDM-sIgEstrong positive CSU patients were significantly higher than those in HDM-sIgEnormal CSU patients and healthy controls. Significantly more SHIP-1 mRNA expression in HDM-sIgEstrong positive CSU patients was induced after the combined stimulation in comparison to other subjects. CSU patients with higher HDM-sIgE levels (≥3.5 kU/L) may have higher CD63 and FcεRIα expression on peripheral blood basophils. Peripheral blood basophils in these CSU patients are more responsive to HDM allergen stimulation. Higher HDM-sIgE levels among CSU patients may implicate higher basophil reactivity.


Differences in static- and dynamic-balance task performance after 4 weeks of intrinsic-foot-muscle training: the short-foot exercise versus the towel-curl exercise.
Proper functioning of the intrinsic foot musculature (IFM) is essential in maintaining the integrity of the medial longitudinal arch (MLA). Improper functioning of the IFM leads to excessive pronation of the foot, which has been linked to various pathologies. Therefore, training the IFM to avoid excessive pronation may help prevent some of these pathologies; however, it is not clear how to train these muscles optimally. To investigate the effects of 2 different types of IFM training on the height of the MLA and static- and dynamic-balance task performance. Randomized controlled trial, repeated-measures mixed-model design. University biomechanics laboratory for testing and a home-based training program. 24 healthy, university-age volunteers (3 groups of 8) with no history of major lower limb pathology or balance impairment. One experimental group performed 4 wk of the short-foot exercise (SFE) and the other performed 4 wk of the towel-curl exercise (TCE). Participants were asked to perform 100 repetitions of their exercise per day. Navicular height during weight bearing, the total range of movement of the center of pressure (COP) in the mediolateral (ML) direction for a static-balance test and a dynamic-balance test. There were no differences in the navicular height or static-balance tests. For the dynamic-balance test, all groups decreased the ML COP movement on the dominant limb by a small amount (~5 mm); however, the SFE group was able to decrease COP movement much more than the TCE group in the nondominant limb. The SFE appeared to train the IFM more effectively than the TCE; however, there were differing results between the dominant and nondominant legs. These imbalances need to be taken into consideration by clinicians.


In the Age of Social Media, How Does the Public Choose a Plastic Surgeon? A Crowdsourcing Analysis of Major Deciding Factors.
Patients consider many factors when selecting a plastic surgeon. Previous studies have demonstrated the importance of board certification and reputation in this decision. Despite this, there is a paucity of knowledge on the role that cost of procedure, social media, and surgeon training have on the decision-making process. The authors' study used a population-based survey administered by Amazon Mechanical Turk. Adults 18 years and older and residing in the United States were asked to rank the importance of 36 factors from 0 (least important) to 10 (most important) when selecting a plastic surgeon. A total of 369 responses were analyzed. The mean age of respondents was 36.9 years (SD, 10.9 years), and 174 participants (47.2%) were female. Of those surveyed, 216 (55.0%) had previously undergone plastic surgery, and all respondents were considering plastic surgery either at the time of survey or in the future. The most common first step for respondents in identifying a plastic surgeon was a web-based search (32.2%). The top three most important factors in selecting a plastic surgeon were surgeon's experience with the desired procedure (7.48), surgeon's board certification (7.38), and surgeon's years in practice (7.36). The three least important factors were the surgeon's race (5.43), number of social media posts (5.62), and television appearances (5.64). The authors' survey provides insight into the role that different elements play in the decision of selecting a plastic surgeon in the United States. Understanding how patients select a plastic surgeon can help surgeons optimize these elements in their practices.


Open plains are not a level playing field for hominid consonant-like versus vowel-like calls.
Africa's paleo-climate change represents an "ecological black-box" along the evolutionary timeline of spoken language; a vocal hominid went in and, millions of years later, out came a verbal human. It is unknown whether or how a shift from forested, dense habitats towards drier, open ones affected hominid vocal communication, potentially setting stage for speech evolution. To recreate how arboreal proto-vowels and proto-consonants would have interacted with a new ecology at ground level, we assessed how a series of orangutan voiceless consonant-like and voiced vowel-like calls travelled across the savannah. Vowel-like calls performed poorly in comparison to their counterparts. Only consonant-like calls afforded effective perceptibility beyond 100 m distance without requiring repetition, as is characteristic of loud calling behaviour in nonhuman primates, typically composed by vowel-like calls. Results show that proto-consonants in human ancestors may have enhanced reliability of distance vocal communication across a canopy-to-ground ecotone. The ecological settings and soundscapes experienced by human ancestors may have had a more profound impact on the emergence and shape of spoken language than previously recognized.


Semiclassical methods in chemical physics.
Semiclassical theory finds use in chemical physics both as a computational method and as a conceptual framework for interpreting quantum features in experiments and in numerical quantum calculations. The semiclassical description of one-dimensional dynamical systems is essentially a solved problem for eigenvalue and scattering situations and for general topologies of potential functions (simple potential wells, multiple wells, multiple barriers, and so forth). Considerable progress has also been made in generalizing semiclassical theory to multidimensional dynamical systems (such as inelastic and reactive scattering of atoms and molecules and vibrational energy levels of polyatomic molecules), and here, too, it provides a useful picture of quantum features (interference in product state distribution, generalized tunneling phenomena, and others) in these more complex systems.


Theoretical studies of the effects of heterogeneity in the parasite population on the transmission dynamics of malaria.
Periodicity in malaria transmission has generally been ascribed to seasonal fluctuations in mosquito population density or spatial heterogeneity with periodic migration. In this paper we demonstrate that simple models of strain heterogeneity can generate periodic behaviour as a consequence of the interaction between parasite strains and host immunological defences. As the degree of cross-immunity between strains increases, the system moves from a régime of independent strain transmission and coexistence, through increasingly coupled behaviour, to the displacement of the strain of lower transmissibility by the strain with a higher basic reproductive rate (R0). Cross-immunity thus serves both to bring the strains into competition, and also to couple the dynamics. We find analytical and numerical results on strain coexistence to show how the range of possible outcomes may be read as an effect of the tension between these two effects of cross-protection.


LOSS OF GROUP CARBOHYDRATE DURING MOUSE PASSAGES OF A GROUP A HEMOLYTIC STREPTOCOCCUS.
In the course of rapid passages through mice a strain of group A type 27 hemolytic streptococcus was found to have lost its group carbohydrate without the loss of type-specific precipitinogens, agglutinogens, or its capacity to induce protective antibodies in rabbits, and without the acquisition of the carbohydrate of another group. The loss of group carbohydrate was shown to be complete, within the limits of the methods for its detection. Extracts of the anomalous strain did not react with group A antisera; and antisera prepared with organisms of this anomalous strain did not contain demonstrable antibodies for the group carbohydrate. Bacterial suspension of the anomalous strain failed to absorb any appreciable amount of group-specific antibody. The fact that the anomalous strain lacking group-specific carbohydrate, C, was derived from the original was established by the demonstration of persistence of its other characteristics, in particular the precipitinogens, agglutinogens, and antigens responsible for protective antibodies of type 27.


[Physico-chemical characteristics of highly purified ceruloplasmin mRNA from rat liver].
Highly purified preparations of mRNA coding for ceruloplasmin (CP) ere isolated from rat liver polyribosomes using indirect immunoprecipitation of CP polysomes and poly(U)-sepharose chromatography of polysomal RNA. The homogeneity of CP mRNA was as high as 86--90%. The molecular weight of CP mRNA is 1.3 . 10(6) daltons which is in excess when compared to the minimal size of mRNA necessary to code for CP precursor (about 700 amino acid residues). The base composition of CP mRNA is of AU-type. The experiments on end-labeling with [3H]borohydride after periodate oxidation whowed that CP mRNA contains 3'-terminal poly(A). Poly(U)-sepharose chromatography with stepwise temperature elution revealed length heterogeneity of poly(A) consisting of particular, different thermal subfractions of CP mRNA contain poly(A) consisting of 38, 90 and 165 adenylate residue. 5'-end of CP mRNA is block with inverted 7-methylguanosine (m7G) which is reducible with [3H]borohydride after periodate oxidation. This m7G residue is a component of RNAse- and alkali-resistant oligonucleotide, which structure according to net charge value and its shifts after various enzymatic treatments, is m7G5'ppp5'XmpAp.


Improved Diagnosis and Care for Rare Diseases through Implementation of Precision Public Health Framework.
Public health relies on technologies to produce and analyse data, as well as effectively develop and implement policies and practices. An example is the public health practice of epidemiology, which relies on computational technology to monitor the health status of populations, identify disadvantaged or at risk population groups and thereby inform health policy and priority setting. Critical to achieving health improvements for the underserved population of people living with rare diseases is early diagnosis and best care. In the rare diseases field, the vast majority of diseases are caused by destructive but previously difficult to identify protein-coding gene mutations. The reduction in cost of genetic testing and advances in the clinical use of genome sequencing, data science and imaging are converging to provide more precise understandings of the 'person-time-place' triad. That is: who is affected (people); when the disease is occurring (time); and where the disease is occurring (place). Consequently we are witnessing a paradigm shift in public health policy and practice towards 'precision public health'.Patient and stakeholder engagement has informed the need for a national public health policy framework for rare diseases. The engagement approach in different countries has produced highly comparable outcomes and objectives. Knowledge and experience sharing across the international rare diseases networks and partnerships has informed the development of the Western Australian Rare Diseases Strategic Framework 2015-2018 (RD Framework) and Australian government health briefings on the need for a National plan.The RD Framework is guiding the translation of genomic and other technologies into the Western Australian health system, leading to greater precision in diagnostic pathways and care, and is an example of how a precision public health framework can improve health outcomes for the rare diseases population.Five vignettes are used to illustrate how policy decisions provide the scaffolding for translation of new genomics knowledge, and catalyze transformative change in delivery of clinical services. The vignettes presented here are from an Australian perspective and are not intended to be comprehensive, but rather to provide insights into how a new and emerging 'precision public health' paradigm can improve the experiences of patients living with rare diseases, their caregivers and families.The conclusion is that genomic public health is informed by the individual and family needs, and the population health imperatives of an early and accurate diagnosis; which is the portal to best practice care. Knowledge sharing is critical for public health policy development and improving the lives of people living with rare diseases.


Immunoglobulin heavy chain constant region variants in rheumatoid arthritis.
Polymorphisms within the immunoglobulin heavy chain constant region at switch (S)mu and S alpha 1 loci were studied in patients with rheumatoid arthritis (RA) and controls in parallel with Gm and A2m allotyping. S mu and S alpha 1 restriction fragment length polymorphisms were defined using a S mu probe which was hybridised to SstI digests of DNA extracted from circulating white cells. There were no differences in S mu and S alpha 1 gene or phenotype frequencies between RA and control groups nor within the RA population between DR4 positive and negative subjects. The Gm allotype G1m(x), coded for by genes at the gamma-1 locus, was found in 29/92 (32%) of DR4 positive and 5/52 (10%) of DR4 negative subjects with RA, as compared with 25/115 (22%) cf controls. The A2m allotype A2m(2), coded for by the alpha 2 locus, was found in 11/92 (12%) of DR4 positive subjects with RA, zero of 52 DR4 negative subjects, and 5/115 (4%) of controls. These results exclude a major effect of genes within the heavy chain constant region linked to mu or alpha 1 loci on susceptibility to RA, but suggest that further study of variants closely linked to the alpha 2 locus is indicated.


Lysophosphatidic acid inhibits gap-junctional communication and stimulates phosphorylation of connexin-43 in WB cells: possible involvement of the mitogen-activated protein kinase cascade.
Lysophosphatidic acid (LPA) was shown to be a powerful inhibitor of gap-junctional communication between cultured rat liver WB cells, as determined by the transfer of Lucifer Yellow, with 50% inhibition obtained at about 0.3 microM LPA. Inhibition of communication was rapid (5 min) and was maintained for at least 80 min. After incubation for 3 h with LPA, communication competence was partially restored and dye transfer was refractory to further addition of LPA. Communication in LPA-refractory cells retained sensitivity to inhibition by phorbol ester and by epidermal growth factor (EGF). LPA-induced inhibition was associated with phosphorylation of connexin-43 protein, as detected by slower migration of the protein detected on Western blots, which could be eliminated by incubation of samples with alkaline phosphatase. A close correspondence was observed between the time- and dose-dependency of LPA effects on communication and the induction of mitogen-activated protein kinase (MAP kinase). Activation of both the 42 kDa and 44 kDa subspecies were confirmed by mobility shifts on Western blots using an anti-(MAP kinase R1) (erk 1-III) antibody and by fractionation on Mono Q columns. Cells pretreated with phorbol ester for 24 h were insensitive to phorbol ester inhibition of communication or activation of MAP kinase, but retained their sensitivity to LPA. The results indicate that LPA initiates the activation of protein kinase cascades in WB cells that are probably independent of protein kinase C and identifies connexin-43 as one substrate for the activated kinases.


Socioeconomic, Rural-Urban, and Racial Inequalities in US Cancer Mortality: Part I-All Cancers and Lung Cancer and Part II-Colorectal, Prostate, Breast, and Cervical Cancers.
We analyzed socioeconomic, rural-urban, and racial inequalities in US mortality from all cancers, lung, colorectal, prostate, breast, and cervical cancers. A deprivation index and rural-urban continuum were linked to the 2003-2007 county-level mortality data. Mortality rates and risk ratios were calculated for each socioeconomic, rural-urban, and racial group. Weighted linear regression yielded relative impacts of deprivation and rural-urban residence. Those in more deprived groups and rural areas had higher cancer mortality than more affluent and urban residents, with excess risk being marked for lung, colorectal, prostate, and cervical cancers. Deprivation and rural-urban continuum were independently related to cancer mortality, with deprivation showing stronger impacts. Socioeconomic inequalities existed for both whites and blacks, with blacks experiencing higher mortality from each cancer than whites within each deprivation group. Socioeconomic gradients in mortality were steeper in nonmetropolitan than in metropolitan areas. Mortality disparities may reflect inequalities in smoking and other cancer-risk factors, screening, and treatment.


Preparation of diclofenac-imprinted polymer beads for selective molecular separation in water.
Molecular imprinting technique is an attractive strategy to prepare materials for target recognition and rapid separation. In this work, a new type of diclofenac (DFC)-imprinted polymer beads was synthesized by Pickering emulsion polymerization using 2-(dimethylamino)ethyl methacrylate as the functional monomer. The selectivity and capacity of the molecularly imprinted polymers (MIPs) were investigated in aqueous solution. Equilibrium binding results show that the MIPs have a high selectivity to bind DFC in a wide range of pH values. Moreover, in liquid chromatography experiment, the imprinted polymer beads were packed into column to investigate the binding selectivity under nonequilibrium conditions. The retention time of DFC on the MIP column is significantly longer than its structural analogues. Also, retention of DFC on the MIP column was significantly longer than on the nonimprinted polymer column under aqueous condition. As the new MIP beads can be used to achieve direct separation of DFC from water, the synthetic method and the affinity beads developed in this work opened new possibilities for removing toxic chemicals from environmental and drinking water.


Seroprevalence of COVID-19 infection in the Emirate of Abu Dhabi, United Arab Emirates: a population-based cross-sectional study.
The United Arab Emirates (UAE) was the first country in the Middle East to report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Serosurveys are essential to understanding the extent of virus transmission. This cross-sectional study aims to assess the seroprevalence of SARS-CoV-2 infection in the Emirate of Abu Dhabi. Between 19 July and 14 August 2020, 4487 households were selected using a random sample stratified by region and citizenship of the head of household (UAE citizen or non-citizen). A cluster sample of 40 labour camps was selected. Data on socio-demographic characteristics, risk factors and symptoms compatible with coronavirus disease 2019 (COVID-19) were collected. Each participant was first tested by Roche Elecsys® Anti-SARS-CoV-2 assay, followed, when reactive, by the LIAISON® SARS-CoV-2 S1/S2 IgG assay. Among 8831 individuals from households, seroprevalence was 10·4% [95% confidence intervals (CIs) 9·5-11·4], with higher seroprevalence in Abu Dhabi and Al Ain regions compared with those in Al Dhafra. In households, we found no sex difference and UAE citizens had lower seroprevalence compared with those of other nationalities. Among 4855 workers residing in labour camps, seroprevalence was 68·6% (95% CI 61·7-74·7), with higher seroprevalence among workers from Southeast Asia. In households, individuals with higher body mass indexes demonstrated higher seroprevalences than individuals with normal weight. Anosmia and ageusia were strongly associated with seropositivity. The majority of household populations in the Emirate of Abu Dhabi remained unexposed to SARS-CoV-2. In labour camps, SARS-CoV-2 transmission was high. Effective public health measures should be maintained.


Contextual consideration of the emergence of alexithymia: A case study highlighting cross-cultural client factors and limited English proficiency.
Alexithymia, characterized by deficits in recognition or expression of emotional experiences, has been demonstrated to be associated with depressive symptoms. In psychotherapy, alexithymia can partly manifest as stunted, disfluent speech when an individual attempts to describe his or her subjective experiences. However, similarly stunted, disfluent speech can be observed in individuals with limited English proficiency who are not diagnosed with a depressive disorder. For individuals who present with both symptoms of depression and limited English proficiency, it can be difficult to determine if disfluent speech is a clinical symptom secondary to depression or simply a byproduct of a language barrier. Determining the underlying cause of speech disfluency is necessary to inform case conceptualization and treatment planning. The following case study describes a Spanish-speaking woman who presented for outpatient psychotherapy to treat major depressive disorder and generalized anxiety disorder. Challenges to the therapy are described; recommendations for English-speaking psychotherapists in similar clinical situations are also provided. (PsycINFO Database Record


Identification of urinary Gc-globulin as a novel biomarker for bladder cancer by two-dimensional fluorescent differential gel electrophoresis (2D-DIGE).
Improving the early detection rate and surveillance of bladder cancer remains a great challenge in medicine. Here, we identified sixteen proteins including Gc-globulin (GC) in urine from bladder cancer patients and normal controls by two-dimensional fluorescent differential gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF/TOF MS). Bioinformatics analyses indicated GC played important roles in the regulation of growth, apoptosis, death and epidermal growth factor receptor activity. The GC expression patterns in urine or tissue from cases and controls were further quantified by western blotting, immunohistochemical staining and enzyme-linked immunosorbent assay (ELISA). ELISA quantification by correcting for creatinine expression showed GC-Cr was significantly increased in bladder cancer patients than in benign bladder damages cases and normal controls (1013.70±851.25 versus 99.34±55.87, 105.32±47.81 ng/mg, respectively). Receiver operating characteristic (ROC) analysis suggested that at 161.086 ng/mg urinary GC, bladder cancer could be detected with 92.31% sensitivity and 83.02% specificity, and 1407.481 ng/mg with 82.61% sensitivity and 88.24% specificity could be used for the detection of infiltrating urothelial carcinoma of bladder cancer. Taken together, we identified GC as a potential novel urinary biomarker for the early detection and surveillance of bladder cancer.


Sequential testing in a high stakes OSCE: Determining number of screening tests.
The sequential objective structured clinical exam (OSCE) is a stand-alone variation of the traditional OSCE whereby all students sit a screening test. Those who pass this initial assessment undergo no further testing while weakly performing students sit an additional (sequential) test to determine their overall pass/fail status. Our aim was to determine outcomes of adopting a sequential OSCE approach using different numbers of screening stations and pass marks. We carried out a retrospective, observational study of anonymised databases of two cohorts of student outcomes from the final OSCE examination at the University of Aberdeen Medical School. Data were accessed for students (n = 388) who sat the exam in the years 2013-2014. We used Stata simulate program to compare outcomes - in terms of sensitivity and specificity - across 5000 random selections of 6-14 OSCE stations using random selections of groups of 100 students (with different screening test pass marks) versus those obtained across 15 stations. Across 6-14 stations, the sensitivity was ≥87% in 2013 and ≥84% in 2014 while the specificity ranged from 60% to 100% in both years. Specificity generally increased as the number of screening stations increased (with concomitant narrowing of the 95% confidence interval), while sensitivity varied between 84 and 98%. Similar sensitivities and specificities were found with screening pass marks of +1, +2 and +3 standard errors of measurement (SEM). Eight stations as a screening test appeared to be a reasonable compromise in terms of high sensitivity (88-89%) and specificity (83-86%). This research extends current sequential OSCE literature using a novel and robust approach to identify the "ideal" in terms of number of screening stations and pass mark. We discuss the educational and resource implications of our findings and make recommendations for the use of the sequential OSCE in medical education.


Pseudomonas aeruginosa Bloodstream Infections in Patients with Cancer: Differences between Patients with Hematological Malignancies and Solid Tumors.
Objectives: To assess the clinical features and outcomes of Pseudomonas aeruginosa bloodstream infection (PA BSI) in neutropenic patients with hematological malignancies (HM) and with solid tumors (ST), and identify the risk factors for 30-day mortality. Methods: We performed a large multicenter, retrospective cohort study including onco-hematological neutropenic patients with PA BSI conducted across 34 centers in 12 countries (January 2006−May 2018). Episodes occurring in hematologic patients were compared to those developing in patients with ST. Risk factors associated with 30-day mortality were investigated in both groups. Results: Of 1217 episodes of PA BSI, 917 occurred in patients with HM and 300 in patients with ST. Hematological patients had more commonly profound neutropenia (0.1 × 109 cells/mm) (67% vs. 44.6%; p < 0.001), and a high risk Multinational Association for Supportive Care in Cancer (MASCC) index score (32.2% vs. 26.7%; p = 0.05). Catheter-infection (10.7% vs. 4.7%; p = 0.001), mucositis (2.4% vs. 0.7%; p = 0.042), and perianal infection (3.6% vs. 0.3%; p = 0.001) predominated as BSI sources in the hematological patients, whereas pneumonia (22.9% vs. 33.7%; p < 0.001) and other abdominal sites (2.8% vs. 6.3%; p = 0.006) were more common in patients with ST. Hematological patients had more frequent BSI due to multidrug-resistant P. aeruginosa (MDRPA) (23.2% vs. 7.7%; p < 0.001), and were more likely to receive inadequate initial antibiotic therapy (IEAT) (20.1% vs. 12%; p < 0.001). Patients with ST presented more frequently with septic shock (45.8% vs. 30%; p < 0.001), and presented worse outcomes, with increased 7-day (38% vs. 24.2%; p < 0.001) and 30-day (49% vs. 37.3%; p < 0.001) case-fatality rates. Risk factors for 30-day mortality in hematologic patients were high risk MASCC index score, IEAT, pneumonia, infection due to MDRPA, and septic shock. Risk factors for 30-day mortality in patients with ST were high risk MASCC index score, IEAT, persistent BSI, and septic shock. Therapy with granulocyte colony-stimulating factor was associated with survival in both groups. Conclusions: The clinical features and outcomes of PA BSI in neutropenic cancer patients showed some differences depending on the underlying malignancy. Considering these differences and the risk factors for mortality may be useful to optimize their therapeutic management. Among the risk factors associated with overall mortality, IEAT and the administration of granulocyte colony-stimulating factor were the only modifiable variables.


[The efficiency of Rhadinopsylla rothschildi and R. dahurica fleas as vectors of the causative agent of plague in a Transbaikal natural focus].
Experiments have shown that a block of proventriculus arises in 2.1 to 12.5% of infected fleas of R. rothschildi and in 7.2 to 10.5% of R. dahurica. These fleas transmit the plague agent to different animals (Brandt's vole, narrow-skulled vole, Dahurian suslik). The plague microbe is preserved in the organism of infected insects till the end of the experiment, 74 and 24 days respectively. Therefore, the fleas can play a part in the maintenance of plague epizootics in the Transbaikal natural nidus.


Identifying Fatigue Indicators Using Gait Variability Measures: A Longitudinal Study on Elderly Brisk Walking.
Real-time detection of fatigue in the elderly during physical exercises can help identify the stability and thus falling risks which are commonly achieved by the investigation of kinematic parameters. In this study, we aimed to identify the change in gait variability parameters from inertial measurement units (IMU) during a course of 60 min brisk walking which could lay the foundation for the development of fatigue-detecting wearable sensors. Eighteen elderly people were invited to participate in the brisk walking trials for 60 min with a single IMU attached to the posterior heel region of the dominant side. Nine sets of signals, including the accelerations, angular velocities, and rotation angles of the heel in three anatomical axes, were measured and extracted at the three walking times (baseline, 30th min, and 60th min) of the trial for analysis. Sixteen of eighteen participants reported fatigue after walking, and there were significant differences in the median acceleration (p = 0.001), variability of angular velocity (p = 0.025), and range of angle rotation (p = 0.0011), in the medial-lateral direction. In addition, there were also significant differences in the heel pronation angle (p = 0.005) and variability and energy consumption of the angles in the anterior-posterior axis (p = 0.028, p = 0.028), medial-lateral axis (p = 0.014, p = 0.014), and vertical axis (p = 0.002, p < 0.001). Our study demonstrated that a single IMU on the posterior heel of the dominant side can address the variability of kinematics parameters for elderly performing prolonged brisk walking and could serve as an indicator for walking instability, and thus fatigue.


Two-dimensional solitons in nonlinear lattices.
We address the existence and stability of two-dimensional solitons in optical or matter-wave media, which are supported by purely nonlinear lattices in the form of a periodic array of cylinders with self-focusing nonlinearity, embedded into a linear material. We show that such lattices can stabilize two-dimensional solitons against collapse. We also found that stable multipoles and vortex solitons are also supported by nonlinear lattices, provided that the nonlinearity exhibits saturation.


Accelerometer-measured daily steps and subjective cognitive ability in older adults: A two-year follow-up study.
There is still a paucity of longitudinal studies examining the relationships between objectively-assessed daily steps and cognitive performance in older adults. The current study aimed to explore whether there is a dose-response relationship between accelerometer-measured daily steps and subjective cognitive decline rate after 2 years in older adults. A total of 285 community-dwelling older adults (age = 74.52 ± 6.12 years, female = 55.4%) wore accelerometers for 7 consecutive days measuring daily steps in 2012. Subjective cognitive ability was measured using a Chinese version of the Ascertain Dementia 8-item Questionnaire (AD8). In total 274 (96.1%) participants completed the follow-up study in 2014. Multivariable negative binomial regression adjusted for confounders was undertaken. Daily steps were linearly related to a reduced decline rate in subjective cognitive ability after 2 years. When daily steps were categorized into groups (<3500, 3500-6999, and ≥7000 steps/day), taking approximately 3500-6999 steps/day was associated with a reduced subjective cognitive decline rate (RR = 0.57, 95% CI = 0.37-0.89) after 2 years compared with <3500 steps/day. When accruing ≥7000 steps/day, the decline rate progressively decreased further (RR = 0.43, 95% CI = 0.23-0.82). Sensitivity analyses supported the stability of these findings. These results suggest that there is an inverse dose-response association of daily steps with subjective cognitive decline rate. Even as few as 3500-6999 steps/day was associated with a lower subjective cognitive decline rate after 2 years. Accumulating ≥7000 steps/day could provide greater protection for subjective cognitive ability.


Spatial-Resolution Cell Type Proteome Profiling of Cancer Tissue by Fully Integrated Proteomics Technology.
Increasing attention has been focused on cell type proteome profiling for understanding the heterogeneous multicellular microenvironment in tissue samples. However, current cell type proteome profiling methods need large amounts of starting materials which preclude their application to clinical tumor specimens with limited access. Here, by seamlessly combining laser capture microdissection and integrated proteomics sample preparation technology SISPROT, specific cell types in tumor samples could be precisely dissected with single cell resolution and processed for high-sensitivity proteome profiling. Sample loss and contamination due to the multiple transfer steps are significantly reduced by the full integration and noncontact design. H&E staining dyes which are necessary for cell type investigation could be selectively removed by the unique two-stage design of the spintip device. This easy-to-use proteome profiling technology achieved high sensitivity with the identification of more than 500 proteins from only 0.1 mm2 and 10 μm thickness colon cancer tissue section. The first cell type proteome profiling of four cell types from one colon tumor and surrounding normal tissue, including cancer cells, enterocytes, lymphocytes, and smooth muscle cells, was obtained. 5271, 4691, 4876, and 2140 protein groups were identified, respectively, from tissue section of only 5 mm2 and 10 μm thickness. Furthermore, spatially resolved proteome distribution profiles of enterocytes, lymphocytes, and smooth muscle cells on the same tissue slices and across four consecutive sections with micrometer distance were successfully achieved. This fully integrated proteomics technology, termed LCM-SISPROT, is therefore promising for spatial-resolution cell type proteome profiling of tumor microenvironment with a minute amount of clinical starting materials.


Descending aortic translocation for left aortic arch with right descending aorta and coarctation of the aorta.
Left aortic arch with right descending aorta associated with coarctation of the aorta is a rare congenital cardiac anomaly. Conventional aortic arch repair in this condition may cause airway compression by the abnormally coursing descending aorta. We present the case of a neonate with this anomaly who underwent successful descending aortic translocation to prevent postoperative left main bronchial stenosis.


Climatic controls on West Nile virus and Sindbis virus transmission and outbreaks in South Africa.
The processes influencing the magnitude of West Nile virus (WNV) transmission from 1 year to the next require thorough investigation. The intensity of WNV transmission is related to the dynamics and interactions between the pathogen, vector, vertebrate hosts, and environment. Climatic variability is one process that can influence interannual disease transmission. South Africa has a long WNV and Sindbis virus (SINV) record where consistent climate and disease relationships can be identified. We relate climate conditions to historic mosquito infection rates. Next, we detect similar associations with reported human outbreaks dating back to 1941. Both concurrent summer precipitation and the change in summer precipitation from the previous to the current summer were strongly associated with WNV and SINV transmission and recorded human outbreaks. Each 100 mm interannual summer precipitation change increased WNV infection rates by 0.39 WNV-positive Culex univittatus/1000 tested Cx. univittatus. An improved understanding of biotic and abiotic disease transmission dynamics may help anticipate and mitigate future outbreaks.


Thermogenesis following meal feeding, isoproterenol, and cold in rats with LH lesions.
Responses to several thermogenic stimuli were measured in rats maintaining stable but reduced body weights following lateral hypothalamic (LH) lesions. Oxygen consumption was monitored in open-circuit respirometers before and after exposure to cold (16.5 degrees C), intubation of a meal, and isoproterenol injection (40 micrograms/kg 0.75). Observations were made in both warm- (28 degrees C) and cold-acclimated (9 degrees C) LH-lesioned rats. Cold exposure, intubation, and drug injection each caused marked increases in heat production in sham- and LH-lesioned rats. This thermogenic response was similar in magnitude and form for both groups. Acclimation to 9 degrees C caused increased baseline levels of heat production when measured at 28 degrees C. Subsequent exposure to thermogenic stimuli revealed an exaggerated response to isoproterenol but not intubation in cold-acclimated groups. The LH-lesioned cold-acclimated rats responded in the same manner as sham-lesioned cold-acclimated rats. These findings are in contrast to the immediate postlesion period when rats show enhanced thermogenic activity. At reduced body weights LH-lesioned rats show normal rates of heat production and make normal responses to thermogenic stimuli. Enhanced thermogenesis does not appear to play a role in the maintenance of chronically reduced body mass in LH-lesioned rats.


Cattle Manure Enhances Methanogens Diversity and Methane Emissions Compared to Swine Manure under Rice Paddy.
Livestock manures are broadly used in agriculture to improve soil quality. However, manure application can increase the availability of organic carbon, thereby facilitating methane (CH4) production. Cattle and swine manures are expected to have different CH4 emission characteristics in rice paddy soil due to the inherent differences in composition as a result of contrasting diets and digestive physiology between the two livestock types. To compare the effect of ruminant and non-ruminant animal manure applications on CH4 emissions and methanogenic archaeal diversity during rice cultivation (June to September, 2009), fresh cattle and swine manures were applied into experimental pots at 0, 20 and 40 Mg fresh weight (FW) ha-1 in a greenhouse. Applications of manures significantly enhanced total CH4 emissions as compared to chemical fertilization, with cattle manure leading to higher emissions than swine manure. Total organic C contents in cattle (466 g kg-1) and swine (460 g kg-1) manures were of comparable results. Soil organic C (SOC) contents were also similar between the two manure treatments, but dissolved organic C (DOC) was significantly higher in cattle than swine manure. The mcrA gene copy numbers were significantly higher in cattle than swine manure. Diverse groups of methanogens which belong to Methanomicrobiaceae were detected only in cattle-manured but not in swine-manured soil. Methanogens were transferred from cattle manure to rice paddy soils through fresh excrement. In conclusion, cattle manure application can significantly increase CH4 emissions in rice paddy soil during cultivation, and its pretreatment to suppress methanogenic activity without decreasing rice productivity should be considered.


Integrated biohydrogen production via lignocellulosic waste: Opportunity, challenges & future prospects.
Hydrogen production through biological route is the cleanest, renewable and potential way to sustainable energy generation. Productions of hydrogen via dark and photo fermentations are considered to be more sustainable and economical approach over numerous existing biological modes. Nevertheless, both the biological modes suffer from certain limitations like low yield and production rate, and because of these practical implementations are still far away. Therefore, the present review provides an assessment and feasibility of integrated biohydrogen production strategy by combining dark and photo-fermentation as an advanced biochemical processing while using lignocellulosics biomass to improve and accelerate the biohydrogen production technology in a sustainable manner. This review also evaluates practical viability of the integrated approach for biohydrogen production along with the analysis of the key factors which significantly influence to elevate this technology on commercial ground with the implementation of various environment friendly and innovative approaches.


Neighborhood physical disorder, social cohesion, and insomnia: results from participants over age 50 in the Health and Retirement Study.
ABSTRACT Background: We determined the association between neighborhood socio-environmental factors and insomnia symptoms in a nationally representative sample of US adults aged >50 years. Methods: Data were analyzed from two waves (2006 and 2010) of the Health and Retirement Study using 7,231 community-dwelling participants (3,054 men and 4,177 women) in the United States. Primary predictors were neighborhood physical disorder (e.g. vandalism/graffiti, feeling safe alone after dark, and cleanliness) and social cohesion (e.g. friendliness of people, availability of help when needed, etc.); outcomes were insomnia symptoms (trouble falling asleep, night awakenings, waking too early, and feeling unrested). Results: After adjustment for age, income, race, education, sex, chronic diseases, body mass index, depressive symptoms, smoking, and alcohol consumption, each one-unit increase in neighborhood physical disorder was associated with a greater odds of trouble falling asleep (odds ratio (OR) = 1.09, 95% confidence interval (CI): 1.04-1.14), waking too early (OR = 1.05, 95% CI: 1.00-1.10), and, in adults aged ≥69 years (adjusting for all variables above except age), feeling unrested in the morning (OR = 1.11, 95% CI: 1.02-1.22 in 2006). Each one-unit increase in lower social cohesion was associated with a greater odds of trouble falling asleep (OR = 1.06, 95% CI: 1.01-1.11) and feeling unrested (OR = 1.09, 95% CI: 1.04-1.15). Conclusions: Neighborhood-level factors of physical disorder and social cohesion are associated with insomnia symptoms in middle-aged and older adults. Neighborhood-level factors may affect sleep, and consequently health, in our aging population.


Reactions catalyzed by 5-aminoimidazole ribonucleotide carboxylases from Escherichia coli and Gallus gallus: a case for divergent catalytic mechanisms.
A comparative investigation of the substrate requirements for the enzyme 5-aminoimidazole ribonucleotide (AIR) carboxylase from E. coli and G. gallus has been conducted using in vivo and in vitro studies. In Escherichia coli, two enzymes PurK and PurE are required for the transformation of AIR to 4-carboxy-5-aminoimidazole ribonucleotide (CAIR). The Gallus gallus PurCE is a bifunctional enzyme containing AIR carboxylase and 4-[(N-succinylamino)carbonyl]-5-aminoimidazole ribonucleotide (SAICAR) synthetase. The E. coli PurE and the C-terminal domain of the G. gallus PurCE protein maintain a significant degree of amino acid sequence identity and also share CAIR as a product of their enzymatic activities. The substrate requirements of AIR carboxylases from E. coli and G. gallus have been compared by a series of in vitro experiments. The carbamic acid, N5-carboxyaminoimidazole ribonucleotide (N5-CAIR) is a substrate for the E. coli PurE (Mueller et al., 1994) but not for the G. gallus AIR carboxylase. In contrast, AIR and CO2 are substrates for the G. gallus AIR carboxylase. The recognition properties of the two proteins were also compared using inhibition studies with 4-nitro-5- aminoimidazole ribonucleotide (NAIR). NAIR is a tight-binding inhibitor of the G. gallus AIR carboxylase (K(i) = 0.34 nM) but only a steady-state inhibitor (K(i) = 0.5 microM) of the E. coli PurE. These data suggest significant differences in the transition states for the reactions catalyzed by these two evolutionarily related enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)


Atrial natriuretic peptide stimulates lipid mobilization during repeated bouts of endurance exercise.
Atrial natriuretic peptide (ANP) controls lipolysis in human adipocytes. Lipid mobilization is increased during repeated bouts of exercise, but the underlying mechanisms involved in this process have not yet been delineated. The relative involvement of catecholamine- and ANP-dependent pathways in the control of lipid mobilization during repeated bouts of exercise was thus investigated in subcutaneous adipose tissue (SCAT) by microdialysis. The study was performed in healthy males. Subjects performed two 45-min exercise bouts (E1 and E2) at 50% of their maximal oxygen uptake separated by a 60-min rest period. Extracellular glycerol concentration (EGC), reflecting SCAT lipolysis, was measured in a control probe perfused with Ringer solution and in two other probes perfused with either Ringer plus phentolamine (alpha(1/2)-AR antagonist) or Ringer plus both phentolamine and propranolol (beta-AR antagonist). Plasma epinephrine, plasma glycerol, and EGC were 1.7-, 1.6-, and 1.2-fold higher in E2 than in E1, respectively. Phentolamine potentiated exercise-induced EGC increase during E2 only. Propranolol reduced the lipolytic rate during both E1 and E2 compared with the probe with phentolamine. Plasma ANP concentration increased more during E2 than during E1 and was correlated with the increase in EGC in the probe containing phentolamine plus propranolol. The results suggest that ANP is involved in the control of lipolysis during exercise and that it contributes to stimulation of lipolysis during repeated bouts of exercise.


Polymyxin-Induced Lipid A Deacylation in Pseudomonas aeruginosa Perturbs Polymyxin Penetration and Confers High-Level Resistance.
Polymyxins are last-line antibiotics against life-threatening multidrug-resistant Gram-negative bacteria. Unfortunately, polymyxin resistance is increasingly reported, leaving a total lack of therapies. Using lipidomics and transcriptomics, we discovered that polymyxin B induced lipid A deacylation via pagL in both polymyxin-resistant and -susceptible Pseudomonas aeruginosa. Our results demonstrated that the deacylation of lipid A is an "innate immunity" response to polymyxins and a key compensatory mechanism to the aminoarabinose modification to confer high-level polymyxin resistance in P. aeruginosa. Furthermore, cutting-edge neutron reflectometry studies revealed that an assembled outer membrane (OM) with the less hydrophobic penta-acylated lipid A decreased polymyxin B penetration, compared to the hexa-acylated form. Polymyxin analogues with enhanced hydrophobicity displayed superior penetration into the tail regions of the penta-acylated lipid A OM. Our findings reveal a previously undiscovered mechanism of polymyxin resistance, wherein polymyxin-induced lipid A remodeling affects the OM packing and hydrophobicity, perturbs polymyxin penetration, and thereby confers high-level resistance.


Patterns and sources of personality development in old age.
Despite abundant evidence that personality development continues in adulthood, little is known about the patterns and sources of personality development in old age. We thus investigated mean-level trends and individual differences in change as well as the genetic and environmental sources of rank-order continuity and change in several personality traits (neuroticism, extraversion, openness, agreeableness, conscientiousness, perceived control, and affect intensity) and well-being. In addition, we analyzed the interrelation between perceived control and change in other personality traits as well as between change in personality traits and change in well-being. We analyzed data from older adult twins, aged 64-85 years at Time 1 (N = 410; 135 males and 275 females; 134 monozygotic and 63 dizygotic twin pairs), collected at 2 different time points about 5 years apart. On average, neuroticism increased, whereas extraversion, conscientiousness, and perceived control significantly decreased over time. Change in perceived control was associated with change in neuroticism and conscientiousness, pointing to particular adaptation mechanisms specific to old age. Whereas individual differences in personality traits were fairly stable due to both genetic and environmental sources, individual differences in change were primarily due to environmental sources (beyond random error) indicating plasticity in old age. Even though the average level of well-being did not significantly change over time, individual well-being tended to decrease with strongly increasing levels of neuroticism as well as decreasing extraversion, conscientiousness, and perceived control, indicating that personality traits predict well-being but not vice versa. We discuss implications for theory on personality development across the lifespan.


[Synthetic DNA-bindings ligands containing reaction centers specific for AT- and GC-pairs in DNA].
In the present communication design, synthesis and DNA binding activities of three bis-netropsins and two netropsin analogs containing two N-propylpyrrolecarboxamide fragments linked covalently to peptides Gly-Gly-(analog I) and Val-Val-Val-Gly-Gly-(analog II) are reported. Each bis-netropsin consists of two netropsin-like fragments attached to peptides -Gly-Cys-Gly-NH2 (compound IIIa), H-Gly-Cys-Gly-Gly-Gly-(compound IV) or Gly-Cys-Sar-NH2 (compound IIIb) which are linked symmetrically via S-S bonds. Physico-chemical studies show that each bis-netropsin carries 6 AT-specific reaction centers and covers approximately 10 base pairs upon binding to poly(dA).poly(dT). This indicates that two netropsin-like fragments of the bis-netropsin molecule are implicated in specific interaction with DNA base pairs. The peptide fragments of bis-netropsins IIIa and IV form small beta-sheets containing two-GC-specific reaction centers. The DNase I cleavage patterns of bis-netropsin-DNA complexes visualized by high resolution gel electrophoresis show that the preferred binding sites for bis-netropsins IIIa and IV are identical and contain two runs of three or more AT pairs separated by two GC pairs. Specificity determinants of netropsin analog II binding in the beta-associated dimeric form are identical to those of bis-netropsin IIIa thereby indicating that there is a similarity in the structure of complexes formed by these ligands with DNA. In the monomeric form analog II exhibits binding specificity identical to that of analog I. Replacement of C-terminal glycine residues by sarcosines in the peptide fragments of bis-netropsin IIIa leads to a decrease in the affinity of ligand for DNA.


Surface enhanced Raman spectroscopy as a novel tool for rapid quantification of heroin and metabolites in saliva
Heroin can be detected and quantified by certain analytical methods, however, forensic professionals and criminal laboratories study for cheaper and faster detection tools. Surface-enhanced Raman spectroscopy (SERS) rises as a possible alternative tool with its widening application spectra. There are few studies regarding Raman and SERS spectra of heroin and its metabolites, which are unfortunately controversial. In this study, we compared five different surfaces in order to find out more efficient Raman-active substrate for opiate detection and rapid quantification of heroin and its metabolites in saliva. Morphine standard material was used to identify proper surface for SERS analysis of opiates. Heroin and its metabolites (morphine, morphine-3-ß-glucuronide and 6-monoacetyl morphine) were calibrated between 50 ppb and 500 ppm and quantified on AuNRs with signal enhancement of silver colloids in saliva. Raman microscope with a 785-nm laser source was used. Obtained results showed that heroin and its metabolites can be detected and quantified in saliva samples using a SERS-based system. Additionally, the present study revealed that synergetic effect of a specific gold nano-surface with ability controlling liquid motion and silver nanoparticles increase band numbers and intensities. Therefore, we suggest a fast, accurate and cost-effective method to detect and quantify heroin in biological fluids


Global Estimates of Dietary Intake of Docosahexaenoic Acid and Arachidonic Acid in Developing and Developed Countries.
For international recommendations on docosahexaenoic acid (DHA) and arachidonic acid (ARA) dietary intake to be valid, there needs to be a greater understanding of dietary patterns across both the developed and developing world. The aim of this investigation was to provide a global overview of dietary intake of DHA and ARA. Food balance sheets from the Food and Agriculture Organisation Statistics Division and fatty acid composition data from Australian food composition tables in Nutrient Tables 2010 were utilised to generate median per capita intake estimates for DHA and ARA in 175 countries worldwide. Estimated dietary intake per capita for DHA and ARA in 47 developed and 128 developing countries demonstrated that 48% of the 175 countries have an ARA intake of <150 mg/day and 64% have a dietary DHA intake of <200 mg/day. There was a direct relationship between dietary ARA and DHA intake and the per capita gross national income of the country. Regional analysis showed the lowest ARA and DHA dietary intake in Sub-Saharan Africa and Central and Southern Asian populations. This study demonstrates there are many populations worldwide that have ARA and DHA intake that do not reflect current international recommendations, and the public health consequences of this global inadequacy need to be urgently considered.


Characterization of a DNA-binding nuclear autoantigen mainly associated with S phase and G2 cells.
During analysis of autoimmune sera showing reactivity to nuclear antigens a serum producing a previously undescribed cell cycle-specific nuclear immunofluorescence pattern was observed. By indirect immunofluorescence the serum generated a densely speckled nucleoplasmic staining pattern of varying intensity with relative sparing of the nucleoli. The staining pattern could be abolished by treating cells with DNase but was not affected by RNase treatment. By flow cytometric dual parameter analysis the antigen expression was shown to increase during S phase with a maximum in G2 cells, whereas G1 and M cells expressed low levels. The cell cycle-specific expression of the target antigen was similar in some aspects to the expression of cyclin A but clearly not identical. The serum recognized a 68/60 kDa doublet in immunoblotting of soluble MOLT-4 cell extract. Antibodies eluted separately from either of the two bands produced the cell cycle-specific staining pattern as well as the doublet in immunoblotting. DNA-cellulose was used for analysis of DNA-binding property and the higher band was found to be DNA-binding, whereas the lower band was not. In summary, this serum reacts with a DNA-binding and cell cycle-specific nuclear antigen which might be a novel protein involved in cell cycle progression.


A new ephrin-A1 isoform (ephrin-A1b) with altered receptor binding properties abrogates the cleavage of ephrin-A1a.
Ephrins are ligands for the Eph receptor tyrosine kinases, which play important roles in patterning nervous and vascular systems. Ephrin-A1 is a glycosylphosphatidylinositol-anchored ligand that binds to the EphA receptor tyrosine kinases. In the present study, we have identified a new ephrin-A1 isoform, denoted ephrin-A1b (ephrin-A1 isoform b). Compared with the originally described ephrin-A1 sequence, ephrin-A1a [Holzman, Marks and Dixit (1990) Mol. Cell. Biol. 10, 5830-5838], ephrin-A1b lacks a segment of 22 amino acids (residues 131-152). At the transcript level, exon 3 is spliced out in the transcript encoding ephrin-A1b. Transfection of HEK-293T cells (human embryonic kidney 293 cells) with an ephrin-A1b-expressing plasmid resulted in a significant expression of the protein on the cell surface. However, soluble EphA2 receptor (EphA2-Fc) bound weakly to ephrin-A1b-expressing transfectants, but bound strongly to ephrin-A1a-expressing transfectants. Ephrins have been shown to undergo regulated cleavage after interaction with their receptors. This process is inhibited by co-expression of ephrin-A1a and ephrin-A1b, indicating that ephrin-A1b influences the cleavage process. Taken together, these findings indicate that this newly described isoform may regulate the function of its ephrin-A1a counterpart.


Normothermic rapid volume replacement in traumatic hypovolemia. A prospective analysis using a new device.
Inadequate infusion flow rates and hypothermia are significant problems encountered in managing traumatic hemorrhagic shock. The Rapid Solution Administration Set (RSAS) allows normothermic volume restoration at flow rates of up to 2200 mL/min via a single peripheral venipuncture. The RSAS was utilized in 33 consecutive multiple-trauma patients with a mean trauma score (TS) of 6.8. Admission systolic blood pressure averaged 66.9 mm Hg. A mean of 5692 mL of packed red blood cells, 5515 mL of blood products, and 12,052 mL of crystalloid solution per patient was infused within 24 hours of admission mostly via the RSAS. Mortality was 45% at 24 hours following arrival and 61% overall. The mortality was 93.8% (15/16) in patients with a TS of 5 or less and 29.4% (5/17) in patients with a TS over 5. The initial postinfusion patient temperatures averaged 35.2 degrees C. All abnormal preinfusion coagulation values normalized within 24 hours in the survivors, and no significant complications occurred with the use of the RSAS. The RSAS seems to provide an uncomplicated means of normothermic volume replacement. The 24-hour survival in potentially salvageable patients may be improved. Its use in patients with lethal injuries (TS less than or equal to 3) requires further evaluation.


Modulation of NFκB signalling pathway by tocotrienol: A systematic review.
Tocotrienols have been reported to exert anticancer, anti-inflammatory, antioxidant, cardio-protective and boneprotective effects through modulation of NFκB signalling pathway. The objective of this systematic review is to evaluate available literature showing the effect of tocotrienols on NFκB signalling pathway and identify the potential mechanisms involved. A comprehensive search was conducted using PubMed and SCOPUS databases using the keywords "tocotrienol" and "NFκB" or "nuclear factor kappa b". Main inclusion criteria were English language original articles showing the effect of tocotrienol on NFκB signalling pathway. Fifty-nine articles were selected from the total of 117 articles initially retrieved from the literature search. Modulation of regulatory proteins and genes such as inhibition of farnesyl prenyl transferase were found to be the mechanisms underlying the tocotrienol-induced suppression of NFκB activation.


Outcomes in 1096 patients with severe thrombotic thrombocytopenic purpura before the Caplacizumab era.
Thrombotic thrombocytopenic purpura (TTP) is a diagnostic and therapeutic emergency. Therapeutic plasma exchange (TPE) combined with immunosuppression has been the cornerstone of the initial management. To produce optimal benefits, emerging treatments must be used against a background of best standard of care. Clarifying current uncertainties is therefore crucial. The objective of this study was to analyze a large high-quality database (Marketscan) of TTP patients managed between 2005 and 2014, in the pre-caplacizumab era, in order to assess the impact of time to first TPE and use of first-line rituximab on mortality, and whether mortality declines over time. Among the 1096 included patients (median age 46 [IQR 35-55], 70% female), 28.8% received TPE before day 2 in the ICU. Hospital mortality was 7.6% (83 deaths). Mortality was independently associated with older age (hazard ratio [HR], 1.024/year; 95% confidence interval [95%CI], [1.009-1.040]), diagnosis of sepsis (HR, 2.360; 95%CI [1.552-3.588]), and the need for mechanical ventilation (HR, 4.103; 95%CI, [2.749-6.126]). Factors independently associated with lower mortality were TPE at ICU admission (HR, 0.284; 95%CI, [0.112-0.717]), TPE within one day after ICU admission (HR, 0.449; 95%CI, [0.275-0.907]), and early rituximab therapy (HR, 0.229; 95% CI, [0.111-0.471]). Delayed TPE was associated with significantly higher costs. Immediate TPE and early rituximab are associated with improved survival in TTP patients. Improved treatments have led to a decline in mortality over time, and alternate outcome variables such as the use of hospital resources or longer term outcomes therefore need to be considered.


Selected polyclonal antibodies and ADH challenge in frog urinary bladder: a label-fracture study.
It is clearly established that the changes induced by antidiuretic hormone (ADH) in its target epithelial cells result from the insertion in the apical membrane of new components that contain channels for water. We have already undertaken an initial study of these channels by raising polyclonal antibodies against Triton X-100 apical extracts from ADH-treated bladders and approached their purification by different adsorption steps. In the present study, we used the label-fracture technique to investigate the localization of the binding sites of the obtained polyclonal antibodies on the apical membrane of ADH-stimulated frog urinary bladder. The results obtained clearly demonstrated a preferential labeling by the selected antibodies of morphological structures such as the groove arrays and the fusion images that are generally accepted as being involved in ADH-induced changes in water permeability of the apical membrane.


The footprint of recent and strong demographic decline in the genomes of Mangalitza pigs.
The Mangalitza pig breed has suffered strong population reductions due to competition with more productive cosmopolitan breeds. In the current work, we aimed to investigate the effects of this sustained demographic recession on the genomic diversity of Mangalitza pigs. By using the Porcine Single Nucleotid Polymorphism BeadChip, we have characterized the genome-wide diversity of 350 individuals including 45 Red Mangalitza (number of samples; n=20 from Hungary and n=25 from Romania), 37 Blond Mangalitza, 26 Swallow-belly Mangalitza, 48 Blond Mangalitza × Duroc crossbreds, 5 Bazna swine, 143 pigs from the Hampshire, Duroc, Landrace, Large White and Pietrain breeds and 46 wild boars from Romania (n=18) and Hungary (n=28). Performance of a multidimensional scaling plot showed that Landrace, Large White and Pietrain pigs clustered independently from Mangalitza pigs and Romanian and Hungarian wild boars. The number and total length of ROH (runs of homozygosity), as well as FROH coefficients (proportion of the autosomal genome covered ROH) did not show major differences between Mangalitza pigs and other wild and domestic pig populations. However, Romanian and Hungarian Red Mangalitza pigs displayed an increased frequency of very long ROH (>30 Mb) when compared with other porcine breeds. These results indicate that Red Mangalitza pigs underwent recent and strong inbreeding probably as a consequence of severe reductions in census size.


Improved port film quality with six megavolt linear accelerator.
This article introduces a new technique for accurate verification of therapy treatment sites with radiographs. It can be used not only on most linear accelerators, but also on cobalt treatment units, with slight variation in exposure technique. It can eliminate the poor image detail presently seen and accepted at various therapy instiutions with a new method of quality control.


Effective electronic-only Kohn-Sham equations for the muonic molecules.
A set of effective electronic-only Kohn-Sham (EKS) equations are derived for the muonic molecules (containing a positively charged muon), which are completely equivalent to the coupled electronic-muonic Kohn-Sham equations derived previously within the framework of the nuclear-electronic orbital density functional theory (NEO-DFT). The EKS equations contain effective non-coulombic external potentials depending on parameters describing the muon's vibration, which are optimized during the solution of the EKS equations making the muon's KS orbital reproducible. It is demonstrated that the EKS equations are derivable from a certain class of effective electronic Hamiltonians through applying the usual Hohenberg-Kohn theorems revealing a "duality" between the NEO-DFT and the effective electronic-only DFT methodologies. The EKS equations are computationally applied to a small set of muoniated organic radicals and it is demonstrated that a mean effective potential may be derived for this class of muonic species while an electronic basis set is also designed for the muon. These computational ingredients are then applied to muoniated ferrocenyl radicals, which had been previously detected experimentally through adding a muonium atom to ferrocene. In line with previous computational studies, from the six possible species, the staggered conformer, where the muon is attached to the exo position of the cyclopentadienyl ring, is deduced to be the most stable ferrocenyl radical.


[Therapeutic approach to non-complicated non-parasitic hepatic cysts].
Results of treatment of 378 patients with non-complicated non-parasitic hepatic cysts during the last 15 years are presented. Diagnostics was based on the developed algorithm of diagnostics and treatment of space-occupying lesions of liver. Therapeutic approach to non-parasitic hepatic cysts was defined on the basis of their sizes. At case of small cysts monitoring was carried out. During the period of supervision the authors didn't observe any complications. Increasing of the cyst sices was signed only in 7.94% of cases. Puncture and sclerotherapy under ultrasound control were carried out in medium cysts with 96.70% of efficacy. If the authors didn't deny the parasitic or tumorous nature of liver lesions carry out the surgical treatment, which was also considered to be indicated at case of sizcable enlargement of the non-parasitic hepatic cysts and inefficiency of mini-invasive treatment.


Metals in the lungs of Ontario hardrock miners.
The objective of this study was to determine the concentration of nickel, cadmium, and lead in the autopsied lungs of 29 hardrock miners. It involved chemical analysis of the lungs, where each lung was divided horizontally into 3 sections and analyzed by an atomic absorption spectrophotometer equipped with a graphite furnace. The grand mean levels of nickel, cadmium, and lead were found to be 1.84, 1.74, and 2.75 μg/g of dry tissue, respectively. The effect of smoking was also examined. The ratios using the mean values between smoker and nonsmoker for nickel, cadmium, and lead were found to be 0.7, 5.4, and 1.4, respectively. The level of cadmium in smokers was significantly higher than nonsmokers. This study provides an estimate of retained metals in the lungs of the Ontario hardrock miners as a result of occupational exposure to hardrock mining environment.


[Comparative evaluation of the effectiveness of radiotherapy, surgery and combined treatment of stage I-II laryngeal cancer (T1-2NoMo) based on the data of a cooperative randomized study].
During 1979-1987 269 patients with laryngeal cancer stage I-II were included into a cooperative randomized study: 111 patients had T1 and 158 patients, T2 tumor; 13% of patients showed cancer of the vestibular cord and 87% of them of the true vocal cord. 76 patients underwent surgery, 129 patients--radiotherapy, and 64 patients received combined treatment, i.e. radio- and chemotherapy (prospidine). The rate of relapses and regional metastases was 11.8 +/- 3.7% and 2.6 +/- 1.8% after surgery, 21.4 +/- 3.8% and 1.6 +/- 1.1% after radiotherapy, and 23.4 +/- 5.3% and 6.3 +/- 3.0% after combined treatment. In terms of the recurrence-free time surgical intervention showed the highest efficacy. With respect to the 5-year survival, measured in the above patients plus 42 patients operated on because of relapses and regional metastases, surgery of vocal cord cancer was effective in 100% in case of stage I, 97.4% in case of stage II; radiotherapy was effective in 91.7% in case of stage I, 88.8% in case of stage II, and combined treatment was effective in 100% in case of stage I and 70.3% in case of stage II; surgery of vestibular cord cancer stage II was effective in 100%, combined treatment in 88.9%, and radiotherapy in 68.6%. When vocal cord cancer involves the anterior commissure, ventricle, and space, preference should be given to surgery because relapses after radiotherapy were seen in 38-42%. Combined radio- and chemotherapy did not reduce the recurrence rate and therefore cannot be recommended for practical purposes.


Recognition of gene acceptor site based on multi-objective optimization.
A new method for predicting the gene acceptor site based on multi-objective optimization is introduced in this paper. The models for the acceptor, branch and distance between acceptor site and branch site were constructed according to the characteristics of the sequences from the exon-intron database and using common biological knowledge. The acceptor function, branch function and distance function were defined respectively, and the multi-objective optimization model was constructed to recognize the splice site. The test results show that the algorithm used in this study performs better than the SplicePredictor, which is one of the leading acceptor site detectors.


Renal Transcriptome Analysis of Programmed Hypertension Induced by Maternal Nutritional Insults.
Maternal nutrition can affect development, leading to long-term effects on the health of offspring. The most common outcome is programmed hypertension. We examined whether alterations in renal transcriptome are responsible for generating programmed hypertension among four different models using next-generation RNA sequencing (NGS) technology. Pregnant Sprague-Dawley rats received 50% caloric restriction (CR), intraperitoneal injection of 45 mg/kg streptozotocin, 60% high-fructose (HF) diet, or 1% NaCl in drinking water to conduct CR, diabetes, HF, or high-salt models, respectively. All four models induced programmed hypertension in adult male offspring. We observed 16 shared genes in a two-week-old kidney among four different models. The identified differential expressed genes (DEGs) that are related to the regulation of blood pressure included Adrb3, Alb, Apoe, Calca, Kng1, Adm2, Guca2b, Hba2, Hba-a2, and Ppara. The peroxisome proliferator-activated receptor (PPAR) signaling pathway and glutathione metabolism pathway were shared by the CR, diabetes, and HF models. Conclusively, a variety of maternal nutritional insults induced the same phenotype-programmed hypertension with differential alterations of renal transcriptome in adult male offspring. The roles of DEGs identified by the NGS in this study deserve further clarification to develop ideal maternal dietary interventions and thus spare the next generations from the burden of hypertension.


Comparing dedicated and designated models of integrating mental health into chronic disease care: study protocol for a cluster randomized controlled trial.
In low- and middle-income countries (LMIC), it is uncertain whether a "dedicated" approach to integrating mental health care (wherein a community health worker (CHW) has the sole responsibility of delivering mental health care) or a "designated" approach (wherein a CHW provides this service in addition to usual responsibilities) is most effective and cost-effective. This study aims to compare the effectiveness and cost-effectiveness of these two models of service integration relative to treatment as usual (TAU) for improving mental health and chronic disease outcomes among patients with HIV or diabetes. This is a cluster randomised trial. We will randomise 24 primary health care facilities in the Western Cape Province of South Africa to one of three study arms. Within each cluster, we will recruit 25 patients from HIV and 25 from diabetes services for a total sample of 1200 participants. Eligible patients will be aged 18 years or older, take medication for HIV or diabetes, and screen positive on the Alcohol Use Disorder Identification Test for hazardous/harmful alcohol use or depression on the Centre for Epidemiology Scale on Depression. Participants recruited in clinics assigned to the designated or dedicated approach will receive three sessions of motivational interviewing and problem-solving therapy, while those recruited at TAU-assigned clinics will be referred for further assessment. Participants will complete an interviewer-administered questionnaire at baseline, and at 6 and 12 months post-enrolment to assess change in self-reported outcomes. At these end points, we will test HIV RNA viral load for participants with HIV and HbA1c levels for participants with diabetes. Primary outcomes are reductions in self-reported hazardous/harmful alcohol use and risk of depression. Secondary outcomes are improvements in adherence to chronic disease treatment, biomarkers of chronic disease outcomes, and health-related quality of life. Mixed-effect linear regression models will model the effect of the interventions on primary and secondary outcomes. The cost-effectiveness of each approach will be assessed using incremental cost-effectiveness ratios. Study findings will guide decision-making around how best to integrate mental health counselling into chronic disease care in a LMIC setting. Pan African Clinical Trials Registry, Trial registration number: ACTR201610001825403 . Registered 17 October 2016.


Report of the National Cancer Institute-sponsored workshop on definitions of diagnosis and response in acute myeloid leukemia.
The National Cancer Institute (NCI) sponsored a workshop to develop a set of standardized diagnostic and response criteria for acute myeloid leukemia (AML) clinical trials. The French-American-British (FAB) classification was retained for diagnosing AML, with the addition of patients with bone marrow morphologic features of a myelodysplastic syndrome and less than 30% bone marrow blasts, but with greater than or equal to 30% blasts in the peripheral blood. In this report, there are four important subgroups of AML not defined in the FAB classification that are discussed: undifferentiated acute leukemia, MO (AML lacking definitive myeloid differentiation by morphology or conventional cytochemistry but with ultrastructural or immunophenotypic evidence for AML), mixed lineage leukemia, and hypocellular AML. Definitions of response for clinical trials are presented to facilitate comparisons among different studies. Complete remission is considered the only response worth reporting in phase III trials, since lesser responses do not improve survival. Partial remissions may be of interest to identify active new agents in phase I and II studies. Monoclonal antibodies and cytogenetic studies are not part of the routine assessment of remission or reassessment at relapse, and their role in the evaluation of patients with AML is currently being evaluated in clinical trials. Although we recognize that some of the definitions in this report are arbitrary, generalized use of these guidelines will make results of clinical trials more comparable and interpretable.


Health system costs of falls of older adults in Western Australia.
The aim of this study was to determine the health system costs associated with falls in older adults who had attended an emergency department (ED) in Western Australia. The data relating to the ED presentations and hospital admissions were obtained from population-based hospital administrative records for 2001-2002. The type of other health services (eg, outpatient, medical, community, ancillary and residential care), the quantity, and their cost were estimated from the literature. In adults aged 65 years and above, there were 18 706 ED presentations and 6222 hospital admissions for fall-related injuries. The estimated cost of falls to the health system was $86.4 million, with more than half of this attributable to hospital inpatient treatment. Assuming the current rate of falls remains constant for each age group and gender, the projected health system costs of falls in older adults will increase to $181 million in 2021 (expressed in 2001-02 Australian dollars). The economic burden to the health services imposed by falls in older adults is substantial, and a long-term strategic approach to falls prevention needs to be adopted. Policy in this area should be targeted at both reducing the current rate of falls through preventing injury in people from high-risk groups and reducing the future rate of falls through reducing population risk.


Evaluation of spin-flip scattering in chirality-induced spin selectivity using the Riccati equation.
The chirality-induced spin selectivity (CISS) in layers of helical molecules has gained considerable attention in the emerging field of spintronics, because the effect enables spin-filter devices under ambient conditions. Several theoretical studies have been carried out to explain this effect on a microscopic scale, but the origin of the effect is still controversial. In particular, the role of spin-flip scattering during electron transport is an open issue. In this study, we describe the electron and spin transport by macroscopic rate equations including spin-dependent losses and spin-flip scattering. We reduce the problem to the solution of the Riccati differential equation to obtain analytical expressions. The results allow the strength and scalability of CISS based spin-filters to be determined and interpreted from experimental data or quantum mechanical models. For the helical systems studied experimentally so far, it turns out that spin-flip scattering plays a minor role.


Structural Preservation Does Not Ensure Function at Sensory Ia-Motoneuron Synapses following Peripheral Nerve Injury and Repair.
Injury that severs peripheral nerves often results in long-lasting motor behavioral deficits and in reorganization of related spinal motor circuitry, neither of which reverse even after nerve regeneration. Stretch areflexia and gait ataxia, for example, emerge from a combination of factors including degeneration of Ia-motoneuron synapses between peripherally damaged Ia muscle spindle afferents and motoneurons. Based on evidence that nerve injury acts via immune responses to induce synapse degeneration, we hypothesized that suppressing inflammatory responses would preserve Ia-motoneuron connectivity and aid in restoring normal function. We tested our hypothesis by administering the anti-inflammatory agent minocycline in male and female rats following axotomy of a peripheral nerve. The connectivity of Ia-motoneuron synapses was then assessed both structurally and functionally at different time points. We found that minocycline treatment overcame the physical loss of Ia contacts on motoneurons which are otherwise lost after axotomy. While necessary for functional recovery, synaptic preservation was not sufficient to overcome functional decline expressed as smaller than normal stretch-evoked synaptic potentials evoked monosynaptically at Ia-motoneuron connections and an absence of the stretch reflex. These findings demonstrate a limited capacity of minocycline to rescue normal sensorimotor behavior, illustrating that structural preservation of synaptic connectivity does not ensure normal synaptic function.SIGNIFICANCE STATEMENT Here we demonstrate that acute treatment with the semisynthetic tetracycline anti-inflammatory agent minocycline permanently prevents the comprehensive loss of synaptic contacts made between sensory neurons and spinal motoneurons following peripheral nerve injury and eventual regeneration. Treatment failed, however, to rescue normal function of those synapses or the reflex circuit they mediate. These findings demonstrate that preventing synaptic disconnection alone is not sufficient to restore neural circuit operation and associated sensorimotor behaviors.


A review of genus-group names in Diptera (Insecta) that J.C. Fabricius <br />"borrowed" from other dipterists and proposed as new in his systematic works from 1775 to 1805.
It is shown that a total of eight pre-existing genus-group names in Diptera were "borrowed" and deliberately given new identities in the systematic works of J.C. Fabricius: Bibio Fabricius, 1775, Ceria Fabricius, 1794, Hirtea Fabricius, 1798, Mulio Fabricius, 1798, Scatophaga Fabricius, 1805, Sicus Fabricius, 1798, Thereva Fabricius, 1798 and Voluccella Fabricius, 1794. These names are reviewed from the standpoint that they are nomenclaturally available as intentional homonymous proposals of names for new genus-group taxa. New type-species designations are made for Bibio Fabricius, Mulio Fabricius, and Scatophaga Fabricius. Bibio Fabricius, 1775 is recognized as a senior synonym of Thereva Latreille, 1797, syn. n., but is invalid as it is a junior homonym of Bibio Geoffroy, 1762. Scatophaga Fabricius, 1805 is recognized as a junior synonym of Psila Meigen, 1803, syn. n. The nominal species Musca suilla Fabricius, 1794 has been misinterpreted as a species of Scathophaga Meigen, 1803 by subsequent authors. Scathophaga spurca Meigen, 1826 is revived as the valid name for Scathophaga suilla auct. nec (Fabricius, 1794), stat. rev. A lectotype is designated for Musca suilla Fabricius and it is shown to belong to the scathophagid Norellisoma spinimanum (Fallén, 1819), syn. n. In order to maintain stability of nomenclature and prevailing usage, reversal of precedence is invoked to declare Cordylura spinimana Fallén, 1819 as a nomen protectum and Musca suilla Fabricius, 1794 as a nomen oblitum.


Hemifacial microsomia and the branchio-oto-renal syndrome.
Hemifacial microsomia (HFM) and the branchio-oto-renal syndrome (BOR) are both associated with malformations of the external ears; preauricular tags, pits, or sinuses; and conductive or mixed hearing loss. Other overlapping features have been described, including cervical appendages containing cartilage in HFM, and facial paresis in BOR; however, the significance of these findings has not been discussed by previous authors. The purpose of this paper is to describe four additional propositi with overlapping features of BOR and HFM. In two cases there is a positive family history of either first and second branchial arch anomalies or malformation of the kidney. Two cases appear to be sporadic. The overlapping clinical features suggest that in some families HFM may constitute a component toward the severe end of the spectrum of the autosomal dominant BOR syndrome. The empiric recurrence risk for HFM was 3% in one study. If our interpretation of these reported cases is correct, genetic recurrence risks for individuals in these families may fall in the range of an autosomal dominant condition. Since expression of both conditions varies widely, and minor manifestations may be overlooked, the importance of careful evaluation of first- and second-degree relatives is emphasized.


Genomewide Stabilization of mRNA during a "Feast-to-Famine" Growth Transition in Escherichia coli.
Bacteria have to continuously adjust to nutrient fluctuations from favorable to less-favorable conditions and in response to carbon starvation. The glucose-acetate transition followed by carbon starvation is representative of such carbon fluctuations observed in Escherichia coli in many environments. Regulation of gene expression through fine-tuning of mRNA pools constitutes one of the regulation levels required for such a metabolic adaptation. It results from both mRNA transcription and degradation controls. However, the contribution of transcript stability regulation in gene expression is poorly characterized. Using combined transcriptome and mRNA decay analyses, we investigated (i) how transcript stability changes in E. coli during the glucose-acetate-starvation transition and (ii) if these changes contribute to gene expression changes. Our work highlights that transcript stability increases with carbon depletion. Most of the stabilization occurs at the glucose-acetate transition when glucose is exhausted, and then stabilized mRNAs remain stable during acetate consumption and carbon starvation. Meanwhile, expression of most genes is downregulated and we observed three times less gene expression upregulation. Using control analysis theory on 375 genes, we show that most of gene expression regulation is driven by changes in transcription. Although mRNA stabilization is not the controlling phenomenon, it contributes to the emphasis or attenuation of transcriptional regulation. Moreover, upregulation of 18 genes (33% of our studied upregulated set) is governed mainly by transcript stabilization. Because these genes are associated with responses to nutrient changes and stress, this underscores a potentially important role of posttranscriptional regulation in bacterial responses to nutrient starvation.IMPORTANCE The ability to rapidly respond to changing nutrients is crucial for E. coli to survive in many environments, including the gut. Reorganization of gene expression is the first step used by bacteria to adjust their metabolism accordingly. It involves fine-tuning of both transcription (transcriptional regulation) and mRNA stability (posttranscriptional regulation). While the forms of transcriptional regulation have been extensively studied, the role of mRNA stability during a metabolic switch is poorly understood. Investigating E. coli genomewide transcriptome and mRNA stability during metabolic transitions representative of the carbon source fluctuations in many environments, we have documented the role of mRNA stability in the response to nutrient changes. mRNAs are globally stabilized during carbon depletion. For a few genes, this leads directly to expression upregulation. As these genes are regulators of stress responses and metabolism, our work sheds new light on the likely importance of posttranscriptional regulations in response to environmental stress.


Second hits exacerbate alcohol-related organ damage: an update.
Chronic and excessive alcohol abuse cause direct and indirect detrimental effects on a wide range of body organs and systems and accounts for ~4% of deaths worldwide. Many factors influence the harmful effects of alcohol. This concise review presents newer insights into the role of select second hits in influencing the progression of alcohol-induced organ damage by synergistically acting to generate a more dramatic downstream biological defect. This review specifically addresses on how a lifestyle factor of high fat intake exacerbates alcoholic liver injury and its progression. This review also provides the mechanistic insights into how increasing matrix stiffness during liver injury promotes alcohol-induced fibrogenesis. It also discusses how hepatotropic viral (HCV, HBV) infections as well as HIV (which is traditionally not known to be hepatotropic), are potentiated by alcohol exposure to promote hepatotoxicity and fibrosis progression. Finally, this review highlights the impact of reactive aldehydes generated during alcohol and cigarette smoke coexposure impair innate antimicrobial defense and increased susceptibility to infections. This review was inspired by the symposium held at the 17th Congress of the European Society for Biomedical research on Alcoholism in Lille, France entitled 'Second hits in alcohol-related organ damage'.