The potential of neurosonography in neurological emergency and intensive care medicine: monitoring of increased intracranial pressure, brain death diagnostics, and cerebral autoregulation– part 2.
Transcranial B-mode sonography is an easy to use bedside imaging modality to monitor significant changes of the brain parenchyma such as in malignant middle cerebral infarction or intracerebral hemorrhage. The elevation of intracranial pressure can be followed with various neurosonographical techniques: Measurements of the ventricular width, midline shift, arterial resistance, and optic nerve sheath diameter. They should be viewed as complementary to each other and to other imaging modalities. Repeated cCT and MRI may be avoided in unstable patients by bedside neurosonography in the hands of an experienced physician. Monitoring of evolving hydrocephalus using serial measurements of the third and lateral ventricles can be used to guide therapeutic decisions such as the removal of a ventricular drainage. The cessation of cerebral blood flow in the case of intracranial pressure exceeding systemic arterial pressure is an important part of brain death diagnostics. Early demonstration of a sufficient temporal bone window is needed in patients in whom brain death may be expected. Cerebrovascular autoregulation is an integer component of the brain's blood supply and is compromised in a variety of neurological diseases. In neurological/neurosurgical patients in the intensive care unit, its assessment allows for extended neuromonitoring and control of therapeutic procedures.


[Risk factors associated with lethality on patients with central cord syndrome].
Central Cord Syndrome is the most common incomplete spinal cord injury, and it represents 9% of all spinal injuries of the adult. to determine the risk factors associated with lethality or/and mechanical ventilation (MV) in patients with Central Cord Syndrome (CCS). upon a retrospective cohort with patients with posttraumatic CCS we evaluated at the time of emergency admission and until the hospital discharge. The dependent variable was dead or MV. We calculated incidence, relative risk (RR) with CI95% and a multivariate model for the association of statistically significant variables by means of a risk coefficient model upon the variables that evidenciated tendencies towards risk. From 101 patients with CCS, 85.1% with a severe medullary canal stenosis and 9.9% required MV; the mortality was 13.9%. The only risk factor associated with dead was the use of MV with an RR of 3.6 (CI95% 1.4-9.5); the risk with tendencies towards MV was being older than 60 RR 5.4 (CI95% 0.6-44.2). Other factors demonstrated a tendency towards mortality, but they were not statistically significant. MV is a risk factor associated with mortality, other factors evidenciated tendencies towards mortality; being older than 60, hypertension, diabetes mellitus, narrow spinal canal, more than 20 days of hospital stay and being intervened farther than 10 days from the accident. The incidence of mortality in our sample is greater than thus reported previously on other international articles. To know and identify these and other factors will let us identify patients with a greater risk of complications.


[IgE and IgE-mediated immunoreaction in the pathogenesis of human cysticercosis].
Total IgE, specific IgE and histamine in sera from 35 documented cases of cysticercosis and 30 transfusion donors were measured and mast cell degranulation test was performed. Total IgE levels (730.61 U/ml), the positive rate of specific IgE (85.7%), histamine levels (5.3 micrograms/ml) and the positive rate of mast cell degranulation (42.9%) of the patients were found to be significantly higher than those of the normal group (P less than 0.01). The results suggested that the antigen of Cysticercus cellulosae could induce IgE production and mast cell degranulation, resulting in the release of histamine. It was, therefore, deemed that the IgE and IgE-mediated immunoreaction might be involved in the pathogenesis of human cysticercosis.


Five-loop four-point amplitude of N=4 super-Yang-Mills theory.
Using the method of maximal cuts, we construct the complete D-dimensional integrand of the five-loop four-point amplitude of N=4 super-Yang-Mills theory, including nonplanar contributions. In the critical dimension where this amplitude becomes ultraviolet divergent, we present a compact explicit expression for the nonvanishing ultraviolet divergence in terms of three vacuum integrals. This construction provides a crucial step towards obtaining the corresponding amplitude of N=8 supergravity required to resolve the general ultraviolet behavior of supergravity theories.


A Magnetically Driven Tandem Chip Enables Rapid Isolation and Multiplexed Profiling of Extracellular Vesicles.
The protein phenotypes of extracellular vesicles (EVs) have emerged as promising biomarkers for cancer diagnosis and treatment monitoring. However, the technical challenges in rapid isolation and multiplexed molecular detection of EVs have limited their clinical practice. Herein, we developed a magnetically driven tandem chip to achieve streamlined rapid isolation and multiplexed profiling of surface protein biomarkers of EVs. Driven by magnetic force, the magnetic nanomixers not only act as tiny stir bars to promote mass transfer and enhance reaction efficiency of EVs, but also transport on communicating vessels of the tandem chip continuously and expedite the assay workflow. We designed cyclic surface enhancement of Raman scattering (SERS) tags to bind with target EVs and then release them by exonuclease I, eliminating steric hindrance and amplifying the SERS signal of multiple protein biomarkers on EVs. Due to the excellent assay performance, six breast cancer biomarkers were detected simultaneously on EVs using only 10 μL plasma within 1.5 h. The unweighted SUM signature offers great accuracy in discriminating breast cancer patients from healthy donors. Overall, the dynamic magnetic driving tandem chip offers a new avenue to advance the clinical application of EV-based liquid biopsy.


Family psychiatric morbidity of acute and transient psychotic disorders and their relationship to schizophrenia and bipolar disorder.
Although transient psychotic disorders are currently classified as a category separate from schizophrenia (SZ) and affective disorders, their distinctive features remain uncertain. This study examines the family psychiatric morbidity of the ICD-10 category of 'acute and transient psychotic disorders' (ATPDs), pointing out differences from SZ and bipolar disorder (BD). From a cohort of 2.5 million persons, we identified all patients enrolled in the Danish Psychiatric Register who were ever admitted with ATPDs (n=2537), SZ (n = 10639) and BD disorder (n=5292) between 1996 and 2008. The relative risk (RR) of ATPDs, SZ and BD associated with psychiatric morbidity in first-degree relatives (FDRs) was calculated as the incidence rate ratio using Poisson regression. The RR of ATPDs [1.93, 95% confidence interval (CI) 1.76-2.11] was higher if patients with ATPDs had at least one FDR admitted with any mental disorder than patients without family psychiatric antecedents. An additional risk arose if they had FDRs admitted not only with ATPDs (RR 1.60, 95% CI 1.33-1.92) but also with SZ (RR 2.06, 95% CI 1.70-2.50) and/or BD (RR 1.55, 95% CI 1.23-1.96). Despite some overlap, the risk of SZ (RR 2.80, 95% CI 2.58-3.04) and BD (RR 3.68, 95% CI 3.29-4.12) was markedly higher if patients with SZ and BD had FDRs admitted with the same condition. These findings suggest that family psychiatric predisposition has a relatively modest impact on ATPDs and argue against a sharp differentiation of ATPDs from SZ and BD.


Brazilian guidelines for the clinical management of paracoccidioidomycosis.
Paracoccidioidomycosis is a systemic fungal disease occurring in Latin America that is associated with rural environments and agricultural activities. However, the incidence and prevalence of paracoccidiodomycosis is underestimated because of the lack of compulsory notification. If paracoccidiodomycosis is not diagnosed and treated early and adequately, the endemic fungal infection could result in serious sequelae. While the Paracoccidioides brasiliensis ( P. brasiliensis ) complex has been known to be the causal agent of paracoccidiodomycosis, a new species, Paracoccidioides lutzii ( P. lutzii ), has been reported in Rondônia, where the disease has reached epidemic levels, and in the Central West and Pará. Accurate diagnoses and availability of antigens that are reactive with the patients' sera remain significant challenges. Therefore, the present guidelines aims to update the first Brazilian consensus on paracoccidioidomycosis by providing evidence-based recommendations for bedside patient management. This consensus summarizes etiological, ecoepidemiological, molecular epidemiological, and immunopathological data, with emphasis on clinical, microbiological, and serological diagnosis and management of clinical forms and sequelae, as well as in patients with comorbidities and immunosuppression. The consensus also includes discussion of outpatient treatments, severe disease forms, disease prevalence among special populations and resource-poor settings, a brief review of prevention and control measures, current challenges and recommendations.


IDEPI: rapid prediction of HIV-1 antibody epitopes and other phenotypic features from sequence data using a flexible machine learning platform.
Since its identification in 1983, HIV-1 has been the focus of a research effort unprecedented in scope and difficulty, whose ultimate goals--a cure and a vaccine--remain elusive. One of the fundamental challenges in accomplishing these goals is the tremendous genetic variability of the virus, with some genes differing at as many as 40% of nucleotide positions among circulating strains. Because of this, the genetic bases of many viral phenotypes, most notably the susceptibility to neutralization by a particular antibody, are difficult to identify computationally. Drawing upon open-source general-purpose machine learning algorithms and libraries, we have developed a software package IDEPI (IDentify EPItopes) for learning genotype-to-phenotype predictive models from sequences with known phenotypes. IDEPI can apply learned models to classify sequences of unknown phenotypes, and also identify specific sequence features which contribute to a particular phenotype. We demonstrate that IDEPI achieves performance similar to or better than that of previously published approaches on four well-studied problems: finding the epitopes of broadly neutralizing antibodies (bNab), determining coreceptor tropism of the virus, identifying compartment-specific genetic signatures of the virus, and deducing drug-resistance associated mutations. The cross-platform Python source code (released under the GPL 3.0 license), documentation, issue tracking, and a pre-configured virtual machine for IDEPI can be found at https://github.com/veg/idepi.


A tissue-specific, naturally occurring human SNF2L variant inactivates chromatin remodeling.
Mammalian genomes encode two imitation switch family chromatin remodeling proteins, SNF2H and SNF2L. In the mouse, SNF2H is expressed ubiquitously, whereas SNF2L expression is limited to the brain and gonadal tissue. This pattern of SNF2L expression suggests a critical role for SNF2L in neuronal physiology. Indeed, SNF2L was shown to promote neurite outgrowth as well as regulate the human engrailed homeotic genes, important regulators of brain development. Here we identify a novel splice variant of human SNF2L we call SNF2L+13, which contains a nonconserved in-frame exon within the conserved catalytic core domain of SNF2L. SNF2L+13 retains the ability to incorporate into multiprotein complexes; however, it is devoid of enzymatic activity. Most interestingly, unlike mouse SNF2L, human SNF2L is expressed ubiquitously, and regulation is mediated by isoform variation. The human SNF2L+13 null variant is predominant in non-neuronal tissue, whereas the human wild type active SNF2L isoform is expressed in neurons. Thus, like the mouse, active human SNF2L is limited to neurons and a few other tissues.


Modulation in gene expression and enzyme activity suggested the roles of monodehydroascorbate reductase in development and stress response in bread wheat.
Monodehydroascorbate reductase (MDHAR) is a crucial enzymatic antioxidant of the ascorbate-glutathione pathway involved in reactive oxygen species scavenging. Herein, we identified 15 TaMDHAR genes in bread wheat. Phylogenetic analysis revealed their clustering into three groups, which are also related to the subcellular localization in the peroxisome matrix, peroxisome membrane, and chloroplast. Each TaMDHAR protein consisted of two conserved domains; Pyr_redox and Pyr_redox_2 of the pyridine nucleotide disulfide oxidoreductase family. The occurrence of diverse groups of cis-regulatory elements in the promoter region and their interaction with numerous transcription factors suggest assorted functions of TaMDHARs in growth and development and in light, phytohormones, and stress responses. Expression analysis in various tissues further revealed their importance in vegetative and reproductive development. In addition, the differential gene expression and enhanced enzyme activity during drought, heat, and salt treatments exposed their role in abiotic stress response. Interaction of MDHARs with various antioxidant enzymes and biochemicals related to the ascorbate-glutathione cycle exposed their synchronized functioning. Interaction with auxin indicated the probability of cross-talk between antioxidants and auxin signaling. The miR168a, miR169, miR172 and others interaction with various TaMDHARs further directed their association with developmental processes and stress responses. The current study provides extensive information about the importance of TaMDHARs, moreover, the precise role of each gene needs to be established in future studies.


A distinct autosomal recessive disorder of limb development with preaxial brachydactyly, phalangeal duplication, symphalangism and hyperphalangism.
We describe four children from two consanguineous families with distinctive hand and foot anomalies including preaxial brachydactyly, together with phalangeal duplication, symphalangism and hyperphalangism of fingers I-III. These anomalies are remarkably similar to those described in a previous case report. Additional features were noted both in this case and, to variable degrees, in the four children reported here. These included sensorineural deafness, optic atrophy, mild facial dysmorphism, orodental anomalies and developmental delay. Autosomal recessive inheritance was previously suggested as the patient had a similarly affected brother and his parents were consanguineous. These four cases provide additional evidence for a novel, autosomal recessive disorder involving limb and other associated anomalies.


Cardiac malignant pheochromocytoma with bone metastases.
A patient with malignant cardiac pheochromocytoma with bone metastases is described. The primary tumor was located between the pulmonary trunk and the left atrium, while metastatic lesions were found in the iliac bones. Treatments with antihypertensive agents, alpha-methylparatyrosine, and combination chemotherapy with cyclophosphamide, vincristine, and dacarbazine partially improved the patient's symptoms, catecholamine levels, and the metastatic lesion of the iliac bones. However, the primary tumor in the heart progressively increased in size and the patient died of disseminated intravascular coagulation and other various complications about 4 years after the diagnosis of the disease.


Lessons from everyday lives: a moral justification for acute care research.
Progress in emergency and critical care requires that clinical research be performed on patients who are incapable of granting consent for research participation. Analyses of the ethics of such research have left some questions incompletely answered. Why should we be permitted to expose vulnerable patients to research risks without their consent? In particular, how do we justify research interventions that have no potential benefit for participants (nontherapeutic interventions)? This article presents a moral justification for nontherapeutic interventions in emergency research. By relying on a framework for assessing research risks, and by drawing on the example of pediatric research, this justification is founded in how institutional review boards, and society in general, analyze risk. Our justification for emergency research also suggests additional protections for emergency research participants, including a stringent threshold for research risk, that still permit important research to proceed.


Person-centred maternity care in low-income and middle-income countries: analysis of data from Kenya, Ghana, and India.
Several qualitative studies have described disrespectful, abusive, and neglectful treatment of women during facility-based childbirth, but few studies document the extent of person-centred maternity care (PCMC)-ie, responsive and respectful maternity care-in low-income and middle-income countries. In this Article, we present descriptive statistics on PCMC in four settings across three low-income and middle-income countries, and we examine key factors associated with PCMC in each setting. We examined data from four cross-sectional surveys with 3625 women aged 15-49 years who had recently given birth in Kenya, Ghana, and India (surveys were done from August, 2016, to October, 2017). The Kenya data were collected from a rural county (n=877) and from seven health facilities in two urban counties (n=530); the Ghana data were from five rural health facilities in the northern region (n=200); and the India data were from 40 health facilities in Uttar Pradesh (n=2018). The PCMC measure used was a previously validated scale with subscales for dignity and respect, communication and autonomy, and supportive care. We analysed the data using descriptive statistics and bivariate and multivariate regressions to examine predictors of PCMC. The highest mean PCMC score was found in urban Kenya (60·2 [SD 12·3] out of 90), and the lowest in rural Ghana (46·5 [6·9]). Across sites, the lowest scores were in communication and autonomy (from 8·3 [3.3] out of 27 in Ghana to 15·1 [5·9] in urban Kenya). 3280 (90%) of the total 3625 women across all countries reported that providers never introduced themselves, and 2076 (57%) women (1475 [73%] of 1980 in India) reported providers never asked permission before performing medical procedures. 120 (60%) of 200 women in Ghana and 1393 (69%) of 1980 women in India reported that providers did not explain the purpose of examinations or procedures, and 116 (58%) women in Ghana and 1162 (58%) in India reported they did not receive explanations on medications they were given; additionally, 104 (52%) women in Ghana did not feel able to ask questions. Overall, 576 (16%) women across all countries reported verbal abuse, and 108 (3%) reported physical abuse. PCMC varied by socioeconomic status and type of facility in three settings (ie, rural and urban Kenya, and India). Regardless of the setting, women are not getting adequate PCMC. Efforts are needed to improve the quality of facility-based maternity care. Bill & Melinda Gates Foundation, Marc and Lynne Benioff, and USAID Systems for Health.


Nootropic efficacy of Satvavajaya Chikitsa and Ayurvedic drug therapy: A comparative clinical exposition.
Ayurveda is known for philosophical basis, and its approach to psychological ailments is quite different from conventional system of management. Satvavajaya Chikitsa (Ayurvedic psychotherapy) is a nonpharmacological approach aimed at control of mind and restraining it from unwholesome Artha (objects) or stressors. Withdrawal of the mind from unwholesome objects is known as Sattvavajaya Chikitsa or it is a treatment by Self Control. Charaka defines it as a mind controlling therapy in which a stress has been laid on restraining of mind from unwholesome objects. Thus, it includes all the methods of Manonigraha and Astanga Yoga (Yogic techniques) too. Indian philosophy portrays Astanga Yoga as a primary tool to control mind; hence it can be used as Satvavajaya Chikitsa. To evaluate efficacy of Satvavajaya Chikitsa and Aushadhiya Medhya Chikitsa for improving Smriti in young healthy volunteers. Totally, 102 physically healthy volunteers between age group 16 and 25 years were divided into two groups. In Group A, Satvavajaya Chikitsa was adopted in form of Yogic procedures such as Asana, Pranayama, Chanting etc., with counseling and placebo. Group B was Shankhapushpi tablets made with whole part of Shankhpushpi plant was used as standard control. The Weschler's memory scale (WMS) was adopted to collect data before and after intervention period of 2 months. Paired and Unpaired t-test were used for analysis the data in Sigmastat Software. Group A (Satvavajaya + placebo) with counseling showed statistically highly significant result (P < 0.001) in verbal retention for similar pair, verbal retention for dissimilar pair and visual immediate tests; while Group B (Shankhapushpi tablets) showed significant result (P < 0.01) in auditory delayed, visual delayed, auditory recognition and visual recognition tests. Satvavajaya Chikitsa shows better results in immediate recollection in terms of short-term memory; while Shankhapushpi found much better in long-term memory enhancement on various tests of WMS.


The significance of an integrated management mode of prenatal diagnosis-postnatal treatment for critical congenital heart disease in newborns.
Congenital heart disease (CHD) is the most common congenital defect in human beings. The purpose of this article is to investigate impact of an integrated management mode of 'prenatal diagnosis-postnatal treatment' on birth, surgery, prognosis and complications associated with critical CHD (CCHD) in newborns. A retrospective analysis of the medical records of newborns diagnosed with CCHD were divided into two groups: prenatal diagnosis and postnatal diagnosis. The demographics, clinical characteristics, surgical status, prognosis and complications of the two groups were compared and the differences identified. Among the 290 newborns with CCHD, 97 (33.4%) were prenatally diagnosed and 193 (66.6%) were postnatally diagnosed. Newborns in the prenatal diagnostic group were hospitalized immediately after birth, whereas the median age of admission was 6.00 (3.00-12.00) days in postnatal diagnostic group, P=0.000. In terms of postnatal symptoms and signs, the incidence of anhelation, cyanosis and cardiac murmur was higher in the postnatal diagnostic group. The rates of preoperative intubation, postoperative open chest exploration and treatment abandonment were higher in the postnatal diagnostic group. The postnatal diagnostic group was more prone to postoperative complications, such as pneumonia and hypoxic-ischemic brain damage. The preoperative mortality [0 (0.0%) vs. 12 (6.2%), P=0.028] in the prenatal diagnostic group was lower than that in the postnatal diagnostic group. And the one-year survival rate of the prenatal diagnostic group was higher (log-rank test P=0.034). The integrated management mode of prenatal diagnosis-postnatal treatment can improve postnatal symptoms, reduces complications, reduces preoperative mortality and increases one-year survival rates in newborns with CCHD.


Vincristine-induced vocal cord palsy: case report and review of the literature.
Vincristine-induced vocal cord paralysis is a rare but serious complication. We report 2 patients with acute lymphoblastic leukemia who developed progressive stridor during induction chemotherapy. There were no clinical features of peripheral or autonomic neuropathy. Flexible laryngoscopy confirmed the diagnosis of bilateral vocal cord palsy; interestingly, the nerve conduction test revealed axonal motor neuropathy involving the median and common peroneal nerves in both patients. The first patient required prolonged ventilatory support necessitating unilateral cordectomy before extubation, whereas the second only required supplemental oxygen therapy. There was resolution of stridor in the first patient after cordectomy and gradual clinical improvement in the second. These cases illustrate that a high index of suspicion of vincristine-induced vocal cord palsy with prompt otolaryngology consultation for laryngoscopy is required in the diagnostic evaluation of a patient who has received vincristine.


Understanding quantitative research: part 1.
This article, which is the first in a two-part series, provides an introduction to understanding quantitative research, basic statistics and terminology used in research articles. Critical appraisal of research articles is essential to ensure that nurses remain up to date with evidence-based practice to provide consistent and high-quality nursing care. This article focuses on developing critical appraisal skills and understanding the use and implications of different quantitative approaches to research. Part two of this article will focus on explaining common statistical terms and the presentation of statistical data in quantitative research.


Southeastern European Health Network (SEEHN) Communicable Diseases Surveillance: a decade of bridging trust and collaboration.
The communicable disease threats and changes that began emerging in south-east Europe in the early 1990s - after a decade of war and while political and health systems region-wide were undergoing dramatic changes - demanded a novel approach to infectious disease surveillance. Specifically, they called for an approach that was focused on cross-border collaboration and aligned with European Union standards and requirements. Thus, the Southeastern European Health network (SEEHN) was established in 2001 as a cooperative effort among the governments of Albania, Bosnia and Herzegovina, Bulgaria, Croatia, Moldova, Montenegro, Romania, Serbia, and the former Yugoslav Republic of Macedonia. In 2002, SEEHN initiated a communicable diseases project aimed at strengthening both national and regional surveillance systems with a focus on cross-border collaboration. Over time, SEEHN has nurtured growth of a regional fabric of SEE experts in communicable diseases surveillance and response who are able to discuss emerging issues and best practices at any time and without being constrained by the rigidity of traditional or existing systems. Main achievements to date include joint preparation of influenza pandemic preparedness plans at both national and regional levels and the introduction of molecular techniques into influenza surveillance laboratories region-wide. Here, we describe the history of the SEEHN communicable disease project; major activities and accomplishments; and future sustainability of the regional infectious disease surveillance network that has emerged and grown over the past decade.


Histone deacetylase 3 promotes RCAN1 stability and nuclear translocation.
Regulator of calcineurin 1 (RCAN1; also referred as DSCR1 or MCIP1) is located in close proximity to a Down syndrome critical region of human chromosome 21. Although RCAN1 is an endogenous inhibitor of calcineurin signaling that controls lymphocyte activation, apoptosis, heart development, skeletal muscle differentiation, and cardiac function, it is not yet clear whether RCAN1 might be involved in other cellular activities. In this study, we explored the extra-functional roles of RCAN1 by searching for novel RCAN1-binding partners. Using a yeast two-hybrid assay, we found that RCAN1 (RCAN1-1S) interacts with histone deacetylase 3 (HDAC3) in mammalian cells. We also demonstrate that HDAC3 deacetylates RCAN1. In addition, HDAC3 increases RCAN1 protein stability by inhibiting its poly-ubiquitination. Furthermore, HDAC3 promotes RCAN1 nuclear translocation. These data suggest that HDAC3, a new binding regulator of RCAN1, affects the protein stability and intracellular localization of RCAN1.


Reducing contrast-induced acute kidney injury using a regional multicenter quality improvement intervention.
Contrast-induced acute kidney injury (CI-AKI) is associated with increased morbidity and mortality after percutaneous coronary interventions and is a patient safety objective of the National Quality Forum. However, no formal quality improvement program to prevent CI-AKI has been conducted. Therefore, we sought to determine whether a 6-year regional multicenter quality improvement intervention could reduce CI-AKI after percutaneous coronary interventions. We conducted a prospective multicenter quality improvement study to prevent CI-AKI (serum creatinine increase ≥0.3 mg/dL within 48 hours or ≥50% during hospitalization) among 21 067 nonemergent patients undergoing percutaneous coronary interventions at 10 hospitals between 2007 and 2012. Six intervention hospitals participated in the quality improvement intervention. Two hospitals with significantly lower baseline rates of CI-AKI, which served as benchmark sites and were used to develop the intervention, and 2 hospitals not receiving the intervention were used as controls. Using time series analysis and multilevel poisson regression clustering to the hospital level, we calculated adjusted risk ratios for CI-AKI comparing the intervention period to baseline. Adjusted rates of CI-AKI were significantly reduced in hospitals receiving the intervention by 21% (risk ratio, 0.79; 95% confidence interval: 0.67-0.93; P=0.005) for all patients and by 28% in patients with baseline estimated glomerular filtration rate <60 mL/min per 1.73 m(2) (risk ratio, 0.72; 95% confidence interval: 0.56-0.91; P=0.007). Benchmark hospitals had no significant changes in CI-AKI. Key qualitative system factors associated with improvement included multidisciplinary teams, limiting contrast volume, standardized fluid orders, intravenous fluid bolus, and patient education about oral hydration. Simple cost-effective quality improvement interventions can prevent ≤1 in 5 CI-AKI events in patients with undergoing nonemergent percutaneous coronary interventions.


Early retinal neurodegeneration and impaired Ran-mediated nuclear import of TDP-43 in progranulin-deficient FTLD.
Frontotemporal dementia (FTD) is the most common cause of dementia in people under 60 yr of age and is pathologically associated with mislocalization of TAR DNA/RNA binding protein 43 (TDP-43) in approximately half of cases (FLTD-TDP). Mutations in the gene encoding progranulin (GRN), which lead to reduced progranulin levels, are a significant cause of familial FTLD-TDP. Grn-KO mice were developed as an FTLD model, but lack cortical TDP-43 mislocalization and neurodegeneration. Here, we report retinal thinning as an early disease phenotype in humans with GRN mutations that precedes dementia onset and an age-dependent retinal neurodegenerative phenotype in Grn-KO mice. Retinal neuron loss in Grn-KO mice is preceded by nuclear depletion of TDP-43 and accompanied by reduced expression of the small GTPase Ran, which is a master regulator of nuclear import required for nuclear localization of TDP-43. In addition, TDP-43 regulates Ran expression, likely via binding to its 3'-UTR. Augmented expression of Ran in progranulin-deficient neurons restores nuclear TDP-43 levels and improves their survival. Our findings establish retinal neurodegeneration as a new phenotype in progranulin-deficient FTLD, and suggest a pathological loop involving reciprocal loss of Ran and nuclear TDP-43 as an underlying mechanism.


Recent Studies on Berry Bioactives and Their Health-Promoting Roles.
Along with the increased knowledge about the positive health effects of food bioactives, the eating habits of many individuals have changed to obtain higher nutritional benefits from foods. Fruits are among the most preferred food materials in this regard. In particular, berry fruits are important sources in the diet in terms of their high nutritional content including vitamins, minerals, and phenolic compounds. Berry fruits have remedial effects on several diseases and these health-promoting impacts are associated with their phenolic compounds which may vary depending on the type and variety of the fruit coupled with other factors including climate, agricultural conditions, etc. Most of the berries have outstanding beneficial roles in many body systems of humans such as gastrointestinal, cardiovascular, immune, and nervous systems. Furthermore, they are effective on some metabolic disorders and several types of cancer. In this review, the health-promoting effects of bioactive compounds in berry fruits are presented and the most recent in vivo, in vitro, and clinical studies are discussed from a food science and nutrition point of view.


Entry or exit? A transition-probability approach to explaining the high prevalence of single motherhood among black women.
I analyze the prevalence of single motherhood among black and non-Hispanic white women in terms of differences in entry and exit. Higher initial entry rates among black women, especially through unpartnered childbearing, account for slightly more than half the difference between blacks and whites in the prevalence of single motherhood. The remainder of the difference is due to black single mothers' much lower rates of exit through union formation and to their very high rates of reentry through dissolution of these later unions. Entry and exit rates through the 1990s imply a widening racial gap.


Achievement of more stringent disease control is associated with reduced burden on workplace and household productivity: results from long-term certolizumab pegol treatment in patients with psoriatic arthritis.
Psoriatic arthritis (PsA) impacts the physical health and functional ability of patients, leading to reduced productivity. High unemployment rates and absence due to sickness have been reported in patients with PsA. This post hoc study investigated certolizumab pegol treatment impact on workplace and household productivity in patients with PsA, and assessed whether achievement of more stringent disease control was associated with greater improvements in productivity. RAPID-PsA was a 216-week phase III trial. This post hoc study used a generalised estimating equations (GEE) model to examine the disease activity association, measured using American College of Rheumatology (ACR) and Disease Activity in PSoriatic Arthritis (DAPSA), and workplace and household productivity, assessed using an arthritis-specific Work Productivity Survey (WPS). The GEE model estimated the mean cumulative number of days patients meeting different disease control criteria were affected by absenteeism or presenteeism in the workplace and household. In all, 273 patients were randomised to certolizumab pegol and 183 (67.0%) completed Week 216. At baseline, 60.8% of patients were employed outside the home. Improved disease control, measured using ACR and DAPSA criteria, was associated with fewer cumulative days affected by workplace absenteeism through Week 216: ACR70: 4.1 days, ACR50 to <70: 7.7, ACR20 to <50: 20.9, <ACR20: 35.7; DAPSA remission (REM): 3.3, low disease activity (LDA): 9.8, moderate disease activity (MoDA): 22.4, high disease activity (HDA): 54.0. Improved disease control was also associated with fewer days affected by workplace presenteeism: ACR70: 5.6, ACR50 to <70: 19.3, ACR20 to <50: 71.2, < ACR20: 141.2; DAPSA REM: 5.7, LDA: 25.8, MoDA: 77.2, HDA: 223.6. Similar associations between greater disease control and improved productivity were observed for household absenteeism and presenteeism. This post hoc study demonstrates the cumulative workplace and household work productivity benefits for patients with PsA when achieving more stringent thresholds of disease control with certolizumab pegol treatment.


Paid work, unpaid work and social support: a study of the health of male and female nurses.
Paid work, unpaid work in the home and social support are important elements of the social production of health and illness, though their combined effects on both women and men have only recently become a focus of research. This paper examines their association with the health problems of nurses, presenting data from a survey of a proportional random sample of 2285 male and female nurses registered in the Province of Ontario. The data are first analysed for the full sample and then multiple regression analyses are run separately for male and female Registered Nurses. The demands of paid work (overload, exposure to hazards), unpaid work (time pressures, caring for a dependent adult) and overall stress in life are associated with greater health problems. There is also evidence of significant links between social support and health. A poor relationship with a supervisor is associated with health problems. On the other hand, enjoying a confiding relationship with a friend and having up to 4 children reduces the likelihood of experiencing health problems. The features of nursing associated with fewer health problems are challenge, statisfaction with work and working under 20 hours a week. Several common themes emerge in the analyses of women and men: overload, hazard exposure, satisfaction with work, having 3-4 children and level of overall stress in life. Yet the models are also very different and point to the need for further analyses of the social production of health problems in relation to gender. They also suggest that female nurses, in particular, may suffer the effects of restructuring in the health care sector. Workload issues are especially important for women. Younger women, those reporting time pressures and caring for a dependent adult are more likely to report health problems. Having a confiding relationship with a friend is associated with fewer health problems for women. Among men, those who dislike housework are more likely to experience health problems. Satisfaction with work and overall stress in life were associated with health problems for both men and women, though there may be gender differences in what generates satisfaction and stress.


Modulation of cerebral somatosensory evoked potentials arising from tibial and sural nerve stimulation during rhythmic active and passive movements of the human lower limb.
The magnitudes of cerebral somatosensory evoked potentials (SEPs), following stimulation of cutaneous or muscle afferents in the upper limb, are reduced during active and passive movements of the fingers. The generalizability of such a movement effect was tested for lower limb events. We measured SEP magnitudes following activation of cutaneous (sural) and mixed (tibial) nerves during the flexion phase of active and passive rhythmic movements of the human lower limb. In eight volunteers, 150 SEPs per condition were recorded from Cz' referenced to Fpz'. Compared to stationary controls, both active and passive movements significantly depressed the early SEP components (P1-N1) [mean values, to 12.8%, 9.9% respectively for tibial nerve and to 29.6%, 25.6% for sural nerve stimulation, p < 0.05]. The attenuation was still observed when only one leg was moved and with stimulation at an earlier point in the flexion phase of movement. Visual fixation did not significantly affect P1-N1 amplitudes, compared to eyes closed. As previously shown, soleus H reflexes with stable M waves were significantly depressed during the movements (p < 0.05). The general construct may be that centripetal flow initiated from somatosensory receptors during limb movement leads to modulation of both spinal and cortical responses following large diameter cutaneous or muscle afferent activation.


Histologic characterization of experimental cutaneous leishmaniasis in mice infected with Leishmania braziliensis in the presence or absence of sand fly vector salivary gland lysate.
Leishmania braziliensis is the causative agent of human cutaneous leishmaniasis in parts of the New World. In the murine model of infection, L. braziliensis does not produce severe or lasting cutaneous lesions in either BALB/c or C3H mice. However, when the parasites are injected into BALB/c mice with salivary gland lysate of the sand fly vector for the parasite, infection is significantly enhanced, as measured by lesion size, parasite burden, and the outcome of infection. Histologic examination of these cutaneous lesions showed that initially, nodular and diffuse dermal infiltrates of neutrophils, eosinophils, and histiocytes occurred in all mice. Over time, the saliva-free lesions progressed to small organized granulomas of epithelioid macrophages that contained few parasites, with eventual resolution of inflammation and mild dermal fibrosis. The saliva-associated lesions progressed to extensive, poorly organized accumulations of heavily parasitized epithelioid macrophages, with persistent neutrophils and eosinophils, and minimal fibroplasia. These results indicate that sand fly salivary gland lysate markedly modifies the inflammatory response to infection with L. braziliensis.


Regulatory role of Piezo1 channel in endothelium-dependent hyperpolarization-mediated vasorelaxation of small resistance vessels and its anti-inflammatory action.
Although endothelial Piezo1 channel is known to induce NO-mediated vasorelaxation of conduit vessels, it remains largely unknown if it can induce endothelial-dependent hyperpolarization (EDH)-mediated vasorelaxation of resistance vessels. Therefore, the present study aims to investigate Piezo1/EDH-mediated vasorelaxation in health and its involvement in ulcerative colitis (UC) and sepsis, two intractable and deadly inflammatory diseases. The tension of the second-order branch of mouse mesenteric artery was measured via the Danish DMT600M microvascular measurement system. The changes in cytoplasmic calcium ([Ca2+]cyt) signaling in vascular endothelial cells were detected by fluorescent calcium assay, and the membrane potential changes were monitored by patch clamp. Experimental murine models of UC and sepsis were induced by dextran sulfate sodium (DSS) and lipopolysaccharides (LPS), respectively. A selective activator of Piezo1 channel, Yoda1, dose-dependently induced vasorelaxation of the second-order branch of mouse mesenteric artery in an endothelium-dependent manner. The endothelial Piezo1 channel mediated the vasorelaxation through EDH mechanism by a functional coupling of Piezo1 and TRPV4 channels. Their function and coupling were verified by [Ca2+]cyt imaging and patch clamp study in single endothelial cells. Moreover, while ACh-induced vasorelaxation played a major role in health, it was significantly impaired in the pathogenesis of UC and sepsis; however, Piezo1/EDH-mediated vasorelaxation remained intact. Finally, Piezo1/EDH-mediated vasorelaxation recovered ACh-induced vasorelaxation impaired in UC and sepsis. Piezo1/TRPV4/EDH-mediated vasorelaxation rescues the impaired ACh-induced vasorelaxation to likely recover hemoperfusion to organs, leading to organ protection against UC and sepsis. Our study not only suggests that endothelial Piezo1, TRPV4 and KCa channels are the potential therapeutic targets, but also implies that Piezo1 activators may benefit to prevent/treat UC and sepsis.


Renal transport of urate during diuretic-induced hypouricemia.
The effect of two weeks administration of a uricosuric diuretic (SKF-62698) on renal urate handling has been examined in 11 normal men. Plasma urate concentrations had declined by more than 60 per cent after two weeks. Urate excretion per unit of glomerular filtration rate and urate clearance (Curate) per unit of glomerular filtration rate were increased after the administration of SKF-62698. The importance of intact tubular secretion of urate in producing these changes was assessed by administering pyrazinamide, an agent that curtails urate secretion, to each participant. The decrements in urate excretion and clearance produced by pyrazinamide both increased significantly, whereas the residual urate excretion rates and clearances not suppressible by pyrazinamide were only minimally altered by SKF-62698 treatment. These results suggest that the excretion of secreted urate was enhanced by prolonged administration of SKF-62698, probably secondary to the inhibition of postsecretory urate reabsorption. In addition, because the nonsuppressible urate excretion did not decline despite a 63 per cent reduction in the plasma urate, it is likely that the reabsorption of filtered urate also was impaired by SKF-62698.


Antimicrobial stewardship capacity and manpower needs in the Asia Pacific.
Antimicrobial stewardship is a strategy to combat antimicrobial resistance in hospitals. Given the burden and impact of antimicrobial resistance in the Asia Pacific, it is important to document capacity and gaps in antimicrobial stewardship programmes (ASP). We aimed to understand existing capacities and practices, and define the resources needed to establish antimicrobial stewardship where it is lacking. An anonymous online survey, consisting of questions on antimicrobial control at country, hospital and programme levels, was circulated to healthcare providers in the field of infectious diseases and microbiology through Asian Network for Surveillance of Resistant Pathogens, ReAct Group and the Australasian Society for infectious Diseases. 139 participants from 16 countries or regions completed the survey. The majority of participants were adult infectious diseases physicians (61/139, 43.9%) and microbiologists (31/139, 22.3%). Participants from 7 countries reported that antimicrobials can be obtained without prescriptions. Despite the high percentage (75.5%) of respondents working in large hospitals, only 22/139 participants (15.8%) from Australia, China, Singapore, Taiwan, Thailand and Vietnam reported having more than 10 infectious diseases physicians. Hospital empiric antimicrobial guidelines for common infections were available according to 110/139 (79.1%) participants. Pre-authorisation of antimicrobials was reported by 88/113 (77.9%) respondents while prospective audit and feedback was reported by 93/114 (81.6%). Automatic stop orders and culture-guided de-escalation were reported by only 52/113 (46.0%) and 27/112 (24.1%) respectively. The survey reveals a wide range of ASP development in Asia Pacific. Establishing national workgroups and guidelines will help advance antimicrobial stewardship in this diverse region.


MRI Derived Simulations of Flow Patterns in the Stomach.
A framework to simulate the flow in the stomach using subject-specific motility patterns and geometries was developed. Dynamic 2D magnetic resonance images (MRIs) were obtained. Motility parameters such as contraction speed and occlusion were quantified, and 3D stomach geometries were reconstructed using a semi-automated approach. Computational fluid dynamics (CFD) simulations were performed, and flow patterns were investigated. The stomach of both subjects had distinct anatomical features with computed volumes of 789 mL and 619 mL. For the one subject, the occlusion (i.e., normalized contraction size) was 12% while it was around 25% for the other subject. Contraction speeds were also different (1.9-2.8 mm/s vs 3.0-5.1 mm/s) for each subject. CFD simulations resulted in unsteady laminar flow for both subjects with average velocities of 2.1 and 3.2 mm/s. While antegrade flow was mainly observed in the simulations, a retropulsive jet was also present in both stomachs. The versatile framework developed within this study would allow the generation of CFD models of gastric motility from dynamic MRIs.Clinical Relevance- Subject-specific models of flow patterns informed by gastric motility features can elucidate the impact of contractions and anatomical variations on digestion. Such models can inform therapies to treat gastric dysfunctions and improve their efficacy.


Factors influencing nearshore hypoxia in the southeastern Arabian Sea: A sensor-based study.
Seasonal upwelling and the associated incursion of hypoxic waters into the coastal zone is a widely studied topic over different upwelling zones. However, its persistence or variations over short time scales are poorly addressed. The present study, therefore, brings out a first report on hourly variations in the temperature, salinity and dissolved oxygen recorded by an environmental data buoy equipped with sensors, deployed in the nearshore waters of Alappuzha (southeastern Arabian Sea) from April to August 2022. The characteristic feature of the Alappuzha coast is the development of mud banks during the southwest monsoon, providing a tranquil environment suitable for continuous sensor-based measurements when the sea remains turbulent elsewhere. The results showed that despite an advance in the upwelling intensity, there is a significant variation in the oxygen concentration in the study domain on a diurnal scale. In general, the nearshore region was under hypoxia during the first half of the day (00:00 to 12:00 h), which increased steadily to reach normoxic and supersaturated levels during the rest of the day (12:00 to 24:00 h). Statistical analysis showed that winds significantly correlate to the coastal environment's subsurface oxygen concentration. During the morning hours, the wind was weak, and the water column remained stratified over the subsurface hypoxic water layer. The situation changed in the afternoon (12:00 h onwards), as there was a steady increase in the local wind speed (>5 m/s), which was sustained during the rest of the day. A local wind speed >5 m/s can disturb the stratification and enhance the mixing process from 12:00 to 24:00 h. The total kinetic energy of 11.5 J/m3 is the threshold for this oxygen supersaturation. These findings emphasize the role of wind-induced mixing in alleviating coastal hypoxia, highlighting the need for further biogeochemical and ecological investigations into the impacts of alternating oxic-hypoxic conditions in nearshore waters.


[Effect of nitroglycerin on the calcium mechanism regulating the tonus of large and small coronary arteries].
It has been established in experiments on isolated ring-shaped strips of large and small coronary artery of the dog that nitroglycerin produces a more pronounced and prolonged relaxation of the myocytes of large coronary arteries at the expense of the inhibition of transmembranous transport and intracellular exchange of calcium ions. In small coronary arteries, nitroglycerin inhibits transmembranous transport of calcium ions, exerting no antagonistic effect on the exchange of intracellular calcium ions. Thus, the different effect of nitroglycerin on the tone of large and small coronary arteries is accounted for by different sensitivity to the drug action of the depot of intracellular calcium ions in the myocytes of these objects.


Dynamics of neuronal interactions: relation to behavior, firing rates, and distance between neurons.
This report describes exploration of the hypothesis that cortical function is mediated by dynamic modulation of coherent firing in groups of neurons. We recorded neuronal activity in the frontal cortex of behaving monkeys and found that correlation between neurons changed frequently within a fraction of a second and in relation to behavior. Those modulations can happen without modulation of firing rates. When firing rates are modulated, the modulation of correlation is not related to it in a simple way. Moreover, the dynamic patterns of correlation depend on the distance between neurons. These findings support the notion that, in order to perform a computational task, neurons can associate rapidly into a functional group, while dissociating from concurrently activated competing groups.


Gamma irradiation of animal sera for inactivation of viruses and mollicutes--a review.
Animal-derived materials such as animal sera represent a low, but finite, risk for introduction of an adventitious agent (virus or mollicute) into a biological bulk harvest during upstream manufacturing processes involving mammalian cell substrates. Viral and mollicute (Mycoplasma sp. and Acholeplasma sp.) contamination events have been relatively rare, but many of those that have been reported have been attributed to use of infected animal sera in growth media during cell expansion. The risk of introduction of viruses and mollicutes may be mitigated by elimination of the use of animal sera and implementation instead of chemically defined or serum- and animal-derived material-free cell culture media. When use of animal sera is unavoidable, however, mitigation of the risk of introducing an adventitious contaminant may involve treatment of the sera to inactivate potential contaminants. Gamma irradiation is one of the most widely employed methods for viral and mollicute inactivation in animal sera. In this article, we review the inactivation results reported for viral and mollicute inactivation in frozen serum. Studies performed to assess the impact of gamma irradiation on serum quality and performance are also discussed. The available data indicate that inactivation of mollicutes in serum is essentially complete at the gamma radiation doses normally employed (25-40 kGy), while the efficacy and kinetics for viral inactivation in serum by gamma irradiation appear to be dependent in part upon the size of the target virus.


Muscle atrophy in intensive care unit patients.
The muscle atrophy is one of the most important and frequent problems observed in patients in Intensive Care Units. The term describes the disorder in the structure and in the function of the muscle while incidence rates range from 25-90 % in patients with prolonged hospitalization. This is a review containing all data related to the issue of muscle atrophy and is especially referred to its causes and risk factors. The importance of early diagnosis and early mobilization are also highlighted in the study. a literature review was performed on valid databases such as Scopus, PubMed, Cinhal for the period 2000-2013 in English language. The following keywords were used: loss of muscle mass, ICU patients, immobilization, bed rest. From the review is concluded that bed rest and immobilization in order to reduce total energy costs, are the main causes for the appearance of the problem. The results of the reduction of the muscle mass mainly affect the musculoskeletal, cardiovascular and respiratory system. The administration of the cortisone, the immobility, the sepsis and hyperglycemia are included in the risk factors. The prevention is the primary therapeutic agent and this is achieved due to the early mobilization of the patients, the use of neuromuscular electrical stimulation and the avoidance of exposure to risk factors. The prevention of muscle atrophy is a primary goal of treatment for the patients in the ICU, because it reduces the incidence of the disease, reduces the time spent in ICU and finally improves the quality of patients' life.


Prediction of alpha factor values for fine pore aeration systems.
The objective of this work was to analyse the impact of different geometric and operating parameters on the alpha factor value for fine bubble aeration systems equipped with EPDM membrane diffusers. Measurements have been performed on nitrifying plants operating under extended aeration and treating mainly domestic wastewater. Measurements performed on 14 nitrifying plants showed that, for domestic wastewater treatment under very low F/M ratios, the alpha factor is comprised between 0.44 and 0.98. A new composite variable (the Equivalent Contact Time, ECT) has been defined and makes it possible for a given aeration tank, knowing the MCRT, the clean water oxygen transfer coefficient and the supplied air flow rate, to predict the alpha factor value. ECT combines the effect on mass transfer of all generally accepted factors affecting oxygen transfer performances (air flow rate, diffuser submergence, horizontal flow).


Semantic interoperability of Health Risk Assessments.
The health insurance and benefits industry has administered Health Risk Assessments (HRAs) at an increasing rate. These are used to collect data on modifiable health risk factors for wellness and disease management programs. However, there is significant variability in the semantics of these assessments, making it difficult to compare data sets from the output of 2 different HRAs. There is also an increasing need to exchange this data with Health Information Exchanges and Electronic Medical Records. To standardize the data and concepts from these tools, we outline a process to determine presence of certain common elements of modifiable health risk extracted from these surveys. This information is coded using concept identifiers, which allows cross-survey comparison and analysis. We propose that using LOINC codes or other universal coding schema may allow semantic interoperability of a variety of HRA tools across the industry, research, and clinical settings.


Glanzmann's thrombasthenia (defective platelet integrin alphaIIb-beta3): proposals for management between evidence and open issues.
Glanzmann's Thrombasthenia (GT) is a rare autosomal recessive bleeding disorder, characterized by a quantitative or qualitative defect of platelet surface alpha(IIb)-beta(3) integrin. Presently, no specific guideline/algorithm for clinical management for GT is available. Due to the rarity and heterogeneity of inherited platelet abnormalities, recommendations and guidelines are based on reports from opinions and clinical experience of panel of experts, and refer to the general management of platelet disorders. Based on the limited evidence in the area and on the strategies in clinical settings of inherited/acquired platelet defects, proposals for management of minor bleeding, moderate/major bleeding unresponsive to conservative management, major surgery, minor surgery and dental procedures for GT patients without, or with anti-platelet isoantibodies are reported. In addition to life-style advices and continuous patient education programs, when and how to employ/combine local measures, antifibrinolytic agents, hormone treatment, platelet transfusions and recombinant activated Factor VII is described. The prospective collection of treatments in GT patients recently established (Glanzmann's Thrombasthenia Registry, GTR), based on a careful definition of clinical settings and outcomes, is likely to provide newer insight for optimising clinical management in GT.


Does Age-Adjusted Charlson Comorbidity Score Impact Survival Endpoints in Women with Federation of Gynecology and Obstetrics-Stage III Endometrial Cancer?
We sought to evaluate the impact of age-adjusted Charlson comorbidity index (AACCI) score on survival endpoints for women with advanced stage endometrial carcinoma (EC). We identified 238 women with stage III EC. AACCI score was calculated and 3 groups were created accordingly; group 1 with a score of 0-2, group 2 with score 3-4, and group 3 with score ≥5. Significant predictors of recurrence-free (RFS), disease-specific (DSS) and overall survival (OS) were analyzed. Median follow-up was 54 months and median age was 65 years. Stage IIIC was the most common stage (69%). The 3 groups were well-balanced except for less utilization of adjuvant chemotherapy in group 3 (p = 0.01). Five-year OS was significantly lower in group 3 compared to groups 1 and 2 (23 vs. 65 and 51%, respectively). Similarly, 5-year RFS was 54, 41, and 33% and DSS was 65, 54, and 35% for groups 1, 2, and 3 respectively. On multivariate analyses, AACCI group 3, cervical stromal involvement, positive peritoneal cytology, and higher tumor grade were predictors for shorter OS. Cervical stromal involvement and higher grade were independent predictors for worse RFS and DSS. Additionally, positive cytology, lymphovascular space invasion, and stage IIIC2 were significantly detrimental for RFS. Our study suggests that comorbidity burden is a strong predictor of worse OS in women with stage III EC. Women with higher AACCI are less likely to receive adjuvant chemotherapy. Comorbidity score can significantly impact survival endpoints for women with advanced EC.


Effects of whole-body vibration or resistive-vibration exercise on blood clotting and related biomarkers: a systematic review.
Whole-body vibration (WBV) and resistive vibration exercise (RVE) are utilized as countermeasures against bone loss, muscle wasting, and physical deconditioning. The safety of the interventions, in terms of the risk of inducing undesired blood clotting and venous thrombosis, is not clear. We therefore performed the present systematic review of the available scientific literature on the issue. The review was conducted following the guidelines by the Space Biomedicine Systematic Review Group, based on Cochrane review guidelines. The relevant context or environment of the studies was "ground-based environment"; space analogs or diseased conditions were not included. The search retrieved 801 studies; 77 articles were selected for further consideration after an initial screening. Thirty-three studies met the inclusion criteria. The main variables related to blood markers involved angiogenic and endothelial factors, fibrinolysis and coagulation markers, cytokine levels, inflammatory and plasma oxidative stress markers. Functional and hemodynamic markers involved blood pressure measurements, systemic vascular resistance, blood flow and microvascular and endothelial functions. The available evidence suggests neutral or potentially positive effects of short- and long-term interventions with WBV and RVE on variables related to blood coagulation, fibrinolysis, inflammatory status, oxidative stress, cardiovascular, microvascular and endothelial functions. No significant warning signs towards an increased risk of undesired clotting and venous thrombosis were identified. If confirmed by further studies, WBV and RVE could be part of the countermeasures aimed at preventing or attenuating the muscular and cardiovascular deconditioning associated with spaceflights, permanence on planetary habitats and ground-based simulations of microgravity.


Is it pathological to believe conspiracy theories?
According to a naturalist conception of what counts as a disorder, conspiracy beliefs are pathological beliefs if they are the outcome of a cognitive dysfunction. In this article, I take issue with the view that it is pathological to believe a conspiracy theory. After reviewing several approaches to the aetiology of conspiracy beliefs, I find that no approach compels us to view conspiracy beliefs as the outcome of a dysfunction: a speaker's conspiracy beliefs can appear as implausible and unshakeable to an interpreter, but in a naturalist framework it is not pathological for the speaker to adopt and maintain such beliefs.


A European survey on the conservative surgical management of endometriotic cysts on behalf of the European Society for Gynaecological Endoscopy (ESGE) Special Interest Group (SIG) on Endometriosis.
The mainstay of endometrioma management, when treatment is required, is surgical. Although laparoscopy is considered to be the gold standard for endometriosis surgery, there is no clarity on the preferred laparoscopic technique, which may depend on whether the primary goalis treatment of infertility or pelvic pain, prevention of recurrence or preservation of ovarian reserve. The aim of this survey to assess the surgical practice of the members of the European Society for Gynaecological Endoscopy (ESGE) on the conservative management of endometiotic cysts in women of reproductive age. The current survey showed that practice for the conservative management of endometriotic cysts was that laparoscopy accounted for 84.9% of the cases, expectant management for 12.1%, and laparotomy for 3%. The preferred surgical approach was cystectomy in 69% of the cases, while the parameters that determined the preferred surgical method were the diameter of the cyst (62%) and the bilaterality or non-location (53%). The type of energy used was in most cases bipolar (83%), 71.4% of surgeons did not reconstitute the ovary and 41% of responses included the administration of adhesion barrier agents. The primary surgical end-point was ovarian reserve (50%), which was tested preoperatively in 51.8%, mainly with an anti-mullerian hormone. In case of an incidentally deep-infiltrating endometriosis, 55.4% of the responses included concomitant treatment thereof, while 71% of the participants considered that a "pelvic surgeon", who could more effectively treat co- existing pelvic and intestinal disease, should be the ideal one to effectively manage endometriosis. The majority of participants (74%) in this survey consider that there is insufficient scientific evidence regarding the conservative management of endometriotic cysts. The treatment of ovarian endometrioma should be individualised, taking into consideration not only the relief of symptoms, pregnancy rates or recurrence rates, but also ovarian function and reserve after surgery.


ACE2-based decoy receptors for SARS coronavirus 2.
SARS coronavirus 2 is neutralized by proteins that block receptor-binding sites on spikes that project from the viral envelope. In particular, substantial research investment has advanced monoclonal antibody therapies to the clinic where they have shown partial efficacy in reducing viral burden and hospitalization. An alternative is to use the host entry receptor, angiotensin-converting enzyme 2 (ACE2), as a soluble decoy that broadly blocks SARS-associated coronaviruses with limited potential for viral escape. Here, we summarize efforts to engineer higher affinity variants of soluble ACE2 that rival the potency of affinity-matured antibodies. Strategies have also been used to increase the valency of ACE2 decoys for avid spike interactions and to improve pharmacokinetics via IgG fusions. Finally, the intrinsic catalytic activity of ACE2 for the turnover of the vasoconstrictor angiotensin II may directly address COVID-19 symptoms and protect against lung and cardiovascular injury, conferring dual mechanisms of action unachievable by monoclonal antibodies. Soluble ACE2 derivatives therefore have the potential to be next generation therapeutics for addressing the immediate needs of the current pandemic and possible future outbreaks.


Association between Psychological Status and Functional Outcome in Surgically Managed Fractures around Hip in Geriatric Patients - A Prospective Study.
Fractures around the hip in the geriatric population not only lead to functional but also psychological impairment. Psychiatric disturbances can be associated with poor participation in rehabilitation, increased risk of falling again, and higher rates of mortality. The present study was undertaken to assess the association between the psychological status and functional outcome of surgically managed elderly Indian patients who had sustained fractures around the hip. The present study was a hospital based prospective, single centre study. One hundred and two geriatric patients who had sustained hip fracture and had been managed surgically, having no cognitive dysfunction, living independently, having unhindered walking capability before the fracture, were included in the study. They were called for follow-up at 3rd, 6th, and 12th month after the hip surgery. Psychological assessment was done by the Hospital Anxiety and Depression Scale (HADS) and functional outcome by using the Harris hip score (HHS). Our study did not show association between psychological status and functional outcome except in one sub-group. Significant correlation was observed between the psychological status and functional outcome in most of the patients in the extra-capsular group. We have identified improvement in the depression, anxiety and functional scores during the follow-up. We conclude that psychiatric disturbances in a geriatric patient after undergoing a surgery for hip fracture may lead to poor recovery. We recommend that all such geriatric patients should undergo a psychological assessment and proper therapy should be instituted to achieve good functional recovery.


[Early surgical treatment of new restrictive forms of pulmonary tuberculosis].
The outcomes of surgical treatment were analyzed in 264 new cases of restrictive pulmonary tuberculosis subjected to pulmonectomy without pretreatment with drugs in the preoperative period. Sixty one patients who had refused to have surgery or operated on after treatment were as a control. Indications for such policy were defined. These included limited tuberculomas and cavernous tuberculosis without local seeding, perifocal infiltration, exacerbations and preserved cellular and humoral immunity and non-specific protection factors. The outcomes of surgical interventions in the experimental group were slightly better. They had fewer complications, rapid recovery of working capacity, low per cent of disability than patients operated on after preoperative chemotherapy. There was no increase in the incidence of relapses.


Decidual, amniotic fluid, maternal and fetal prolactin in normal and abnormal pregnancies.
In the present studies, the content and the in vitro production of prolactin by decidua as well as the concentrations of prolactin in amniotic fluid, maternal and fetal serum in normal term pregnancies, induced abortions at various gestational ages, and in pregnancies complicated by diabetes mellitus, preeclampsia, chronic hypertension, and polyhydramnios were measured. Maternal and fetal prolactin levels varied considerably throughout gestation, but at term did not differ significantly between normal and abnormal pregnancies. Prolactin levels in amniotic fluid as well as decidual prolactin content and production were significantly lower only in pregnancies complicated by either hypertension or polyhydramnios. In both normal and abnormal pregnancies, decidual prolactin production correlated strongly with amniotic fluid concentrations. The present data suggest that 1) maternal and fetal prolactin levels do not differ significantly between normal and abnormal pregnancies, 2) the decidua is the principal source of amniotic fluid prolactin, and 3) the significantly lower levels of prolactin in amniotic fluid of pregnancies complicated by hypertension or polyhydramnios are probably due to adverse effects of these conditions on the synthesis and release of prolactin by decidua.


Alternative medicine in atrial fibrillation treatment-Yoga, acupuncture, biofeedback and more.
The last decade has seen a significant improvement in the management of atrial fibrillation (AF) with the development of newer medications and improvement in catheter ablation techniques. Recurrence of AF remains a significant problem in these patients and medications offer limited supportive role. Complementary and alternative treatment strategies therefore remain a viable option for these AF patients. Several studies have shown improvement in AF symptoms with yoga therapy, acupuncture and biofeedback. There are also several herbal medicine and supplements such as omega-3 fatty acids, antioxidant vitamins, barberry, motherwort, cinchona, Shensongyangxin, hawthorn, Kella and Wenxin Keli that have been evaluated as potential therapeutic options in AF. These studies are however limited by small sample sizes with mixed results. Besides the pharmacological action, metabolism, interactions with other medications and the adverse effects of the herbal medications and supplements remain poorly understood. In spite of the above limitations, complementary therapies remain a promising option in the management of AF and further studies are necessary to validate their safety and efficacy.


Free Recall Episodic Memory Performance Predicts Dementia Ten Years prior to Clinical Diagnosis: Findings from the Betula Longitudinal Study.
Early dementia diagnosis is a considerable challenge. The present study examined the predictive value of cognitive performance for a future clinical diagnosis of late-onset Alzheimer's disease or vascular dementia in a random population sample. Cognitive performance was retrospectively compared between three groups of participants from the Betula longitudinal cohort. Group 1 developed dementia 11-22 years after baseline testing (n = 111) and group 2 after 1-10 years (n = 280); group 3 showed no deterioration towards dementia during the study period (n = 2,855). Multinomial logistic regression analysis was used to investigate the predictive value of tests reflecting episodic memory performance, semantic memory performance, visuospatial ability, and prospective memory performance. Age- and education-corrected performance on two free recall episodic memory tests significantly predicted dementia 10 years prior to clinical diagnosis. Free recall performance also predicted dementia 11-22 years prior to diagnosis when controlling for education, but not when age was added to the model. The present results support the suggestion that two free recall-based tests of episodic memory function may be useful for detecting individuals at risk of developing dementia 10 years prior to clinical diagnosis.


Hazardous children's products on the Australian and US market 2011-2017: an empirical analysis of child-related product safety recalls.
While there is evidence that unsafe children's products are entering the Australian market, with increasing product safety recalls, no research has examined the nature of recalls or their trends over time. This research analyses Australian and US child-related product safety recall data to better understand the frequency and nature of unsafe children's products, emerging hazard trends and cross-jurisdictional similarities and differences. Results can inform improved childhood injury prevention policy and regulation strategies in Australia. Empirical analysis of child-related product safety recalls in Australia and the USA over the period 2011-2017. Cross-jurisdictional comparison revealed similarities in Australia and the USA, with over 80% of recalled products occurring in four industry segments (toys/games, household furniture/furnishings, clothing and sports equipment) and a common leading hazard of choking. Australia and the USA also had a similar number of child-related recalls over the study period (Australia: 652, USA: 668). Disparate trends included a 21% decrease in US child-related recalls over the study period, with most recalled products still complying with mandated safety requirements. In contrast, Australian child-related recalls increased by 88% over the study period, with the majority of recalled products failing to comply with mandated safety requirements. Based on US child-related recall data, the leading cause of injuries was the child falling, the most severe injuries related to furniture/furnishings and the most frequent injuries related to sports equipment. Analysing recall data provides new insights into hazardous children's products. Cross-jurisdictional comparison of data on recalls highlights disparities and indicates a need for reforms to improve regulation of children's products in Australia.


Poly(methylidene malonate 2.1.2) nanoparticles: a biocompatible polymer that enhances peri-adventitial adenoviral gene delivery.
Vascular gene therapy is currently limited by low and transient levels of gene transfection. The objectives of this study were to determine whether peri-adventitial delivery of adenovirus coupled to nanoparticles could improve transfection efficiency and duration. Adenovirus was absorbed to the surface of nanoparticles that were made from poly(methylidene malonate)2.1.2 (PMM2.1.2). These complexes were found to have good adhesive properties to both cultured vascular smooth muscle cells and to the luminal and adventitial layers of excised rabbit carotid arteries. Adenovirus encoding to beta-galactosidase coupled to PMM2.1.2 nanoparticles or adenovirus alone were delivered locally to the adventitia of rabbit carotid arteries. Transfection rate was assessed histologically by the percentage of beta-galactosidase positive cells in the vessel wall at 1 and at 2 weeks. There was significantly higher transfection rate when adenovirus was complexed with nanoparticles as compared to free adenovirus (At 1 week: 10+/-3.9% beta-gal positive cells vs. 2.4+/-0.3% and at 2 weeks: 4.3+/-4.1% vs. 0%, P<0.005 for all). This difference was present in both the medial and adventitial layers. In conclusion, adenoviral mediated gene therapy was significantly enhanced by adsorbing the virus to PMM2.1.2 nanoparticles. This delivery method may be a good therapeutic strategy for the treatment of various vascular diseases.


Quantifying microbial growth and carbon use efficiency in dry soil environments via 18 O water vapor equilibration.
Soil microbial physiology controls large fluxes of C to the atmosphere, thus, improving our ability to accurately quantify microbial physiology in soil is essential. However, current methods to determine microbial C metabolism require liquid water addition, which makes it practically impossible to measure microbial physiology in dry soil samples without stimulating microbial growth and respiration (namely, the "Birch effect"). We developed a new method based on in vivo 18 O-water vapor equilibration to minimize soil rewetting effects. This method allows the isotopic labeling of soil water without direct liquid water addition. This was compared to the main current method (direct 18 O-liquid water addition) in moist and air-dry soils. We determined the time kinetics and calculated the average 18 O enrichment of soil water over incubation time, which is necessary to calculate microbial growth from 18 O incorporation in genomic DNA. We tested isotopic equilibration patterns in three natural and six artificially constructed soils covering a wide range of soil texture and soil organic matter content. We then measured microbial growth, respiration and carbon use efficiency (CUE) in three natural soils (either air-dry or moist). The proposed 18 O-vapor equilibration method provided similar results as the current method of liquid 18 O-water addition when used for moist soils. However, when applied to air-dry soils the liquid 18 O-water addition method overestimated growth by up to 250%, respiration by up to 500%, and underestimated CUE by up to 40%. We finally describe the new insights into biogeochemical cycling of C that the new method can help uncover, and we consider a range of questions regarding microbial physiology and its response to global change that can now be addressed.


In vitro cleavage by asbestos fibers of the fifth component of human complement through free-radical generation and kallikrein activation.
Chrysotile and crocidolite fibers incubated in normal human plasma (NHP) generated from the C5 component of complement C5a-type fragments that stimulated polymorphonuclear leukocyte (PMN) chemotaxis. Absorption of NHP with antiserum against C5a totally abolished neutrophil chemotactic activity. Asbestos fibers also produced C5a small peptides in the presence of ethylene glycol bis(beta-aminoethyl ether) N,N,N'N'-tetraacetic acid (EGTA) but not ethylene diamine tetraacetic acid (EDTA). Activation of C5 was significantly inhibited when asbestos fibers were pretreated with iron chelators such as sodium dithionite (DTN), deferoxamine (DFX), or ascorbate (AA). Concentration-related inhibition of C5 activation was also observed when asbestos fibers were added concurrently to plasma in the presence of DFX, 1,3-dimethyl-2-thiourea (DMTU), a strong hydroxyl scavenger, or aprotinin (APR), a specific protease inhibitor. Further, chrysotile and crocidolite significantly increased plasma kallikrein activity. Data demonstrate that asbestos-induced C5 activation plays a role in inflammatory reactions characteristic of asbestosis through mechanisms involving iron ions, hydroxyl radicals, and oxidized C5-ike fragments. The ferrous ions present at the asbestos fiber surface trigger this activation and catalyze, via Fenton reaction, the production of hydroxyl radicals, which in turn convert native C5 to an oxidized C5-like form. This product is then cleaved by kallikrein, activated by the same asbestos fibers, yielding an oxidized C5a with the same functional properties as C5a.


Medical complications of self-induced vomiting.
Bulimia nervosa, often characterized by self-induced vomiting, is complicated by medical manifestations that affect nearly every organ system in the body. Effects range from superficial skin and dental findings to esophageal pathology, electrolyte abnormalities, cardiac arrhythmias, and in extreme cases, death. Ultimately, cessation of vomiting is necessary to cure most associated medical complications. Improper management of medical complications may lead to significant psychological distress to the patient. Fortunately, efficacious treatments do exist both to ease symptoms and ideally help the patient make a smooth transition to cessation of self-induced vomiting behavior.


Nuclear factor-1-X regulates astrocyte-specific expression of the alpha1-antichymotrypsin and glial fibrillary acidic protein genes.
Discrete tissue-specific changes in chromatin structure of the distal serpin subcluster on human chromosome 14q32.1 allow a single gene encoding alpha1-antichymotrypsin (ACT) to be expressed in astrocytes and glioma cells. This astrocyte-specific regulation involves activatory protein-1 (AP-1) because overexpression of dominant-negative c-jun(TAM67) abolishes ACT expression in glioma cells. Here we identify a new regulatory element, located within the -13-kb enhancer of the ACT gene, that binds nuclear factor-1 (NFI) and is indispensable for the full basal transcriptional activity of the ACT gene. Furthermore, down-regulation of NFI expression by siRNA abolishes basal ACT expression in glioma cells. However, NFI does not mediate astrocyte-specific expression by itself, but likely cooperates with AP-1. A detailed analysis of the 14-kb long 5'-flanking region of the ACT gene indicated the presence of adjacent NFI and AP-1 elements that colocalized with DNase I-hypersensitive sites found in astrocytes and glioma cells. Interestingly, knock-down of NFI expression also specifically abrogates the expression of glial acidic fibrillary protein (GFAP), which is an astrocyte-specific marker protein. Mutations introduced into putative NFI and AP-1 elements within the 5'-flanking region of the GFAP gene also diminished basal expression of the reporter. In addition, we found, using isoform-specific siRNAs, that NFI-X regulates the astrocyte-specific expression of ACT and GFAP. We propose that NFI-X cooperates with AP-1 by an unknown mechanism in astrocytes, which results in the expression of a subset of astrocyte-specific genes.


Serum ferritin and iron status in 'healthy' elderly individuals.
Iron status, including S-ferritin, S-iron, S-transferrin, transferrin saturation and haemoglobin, was assessed in 267 selected elderly subjects (128 male, 139 female) with a median age of 79 years (range 60-93 years) not suffering from diseases connected with inappropriately high S-ferritin. In both sexes, S-ferritin levels were practically constant over the examined age range. Males had a geometric mean ferritin of 75 micrograms/l and females a value of 60 micrograms/l (p less than 0.001). Levels of S-ferritin less than 15 micrograms/l (i.e. depleted iron stores) were found in 7.8% of males and in 10.1% of females. An S-ferritin level less than 15 micrograms/l and transferrin saturation less than 15% (i.e. latent iron deficiency) was observed in 2.3% of males and in 2.2% of females. None had iron deficiency anaemia. In subjects (n = 232) without iron deficiency [i.e. S-ferritin greater than or equal to 15 micrograms/l, mean red cell volume greater than or equal to 79 fl and haemoglobin greater than or equal to 121 g/l (7.5 mmol/l)], the arithmetic mean of S-iron was 18 mumol/l. S-transferrin 28 mumol/l and transferrin saturation 33%. The levels of S-iron, S-transferrin and transferrin saturation were not significantly different in males and females.


Stabilization of LKB1 and Akt by neddylation regulates energy metabolism in liver cancer.
The current view of cancer progression highlights that cancer cells must undergo through a post-translational regulation and metabolic reprogramming to progress in an unfriendly environment. In here, the importance of neddylation modification in liver cancer was investigated. We found that hepatic neddylation was specifically enriched in liver cancer patients with bad prognosis. In addition, the treatment with the neddylation inhibitor MLN4924 in Phb1-KO mice, an animal model of hepatocellular carcinoma showing elevated neddylation, reverted the malignant phenotype. Tumor cell death in vivo translating into liver tumor regression was associated with augmented phosphatidylcholine synthesis by the PEMT pathway, known as a liver-specific tumor suppressor, and restored mitochondrial function and TCA cycle flux. Otherwise, in protumoral hepatocytes, neddylation inhibition resulted in metabolic reprogramming rendering a decrease in oxidative phosphorylation and concomitant tumor cell apoptosis. Moreover, Akt and LKB1, hallmarks of proliferative metabolism, were altered in liver cancer being new targets of neddylation. Importantly, we show that neddylation-induced metabolic reprogramming and apoptosis were dependent on LKB1 and Akt stabilization. Overall, our results implicate neddylation/signaling/metabolism, partly mediated by LKB1 and Akt, in the development of liver cancer, paving the way for novel therapeutic approaches targeting neddylation in hepatocellular carcinoma.


More reliable protein NMR peak assignment via improved 2-interval scheduling.
Protein NMR peak assignment refers to the process of assigning a group of "spin systems" obtained experimentally to a protein sequence of amino acids. The automation of this process is still an unsolved and challenging problem in NMR protein structure determination. Recently, protein NMR peak assignment has been formulated as an interval scheduling problem (ISP), where a protein sequence P of amino acids is viewed as a discrete time interval I (the amino acids on P one-to-one correspond to the time units of I), each subset S of spin systems that are known to originate from consecutive amino acids from P is viewed as a "job" j(s), the preference of assigning S to a subsequence P of consecutive amino acids on P is viewed as the profit of executing job j(s) in the subinterval of I corresponding to P, and the goal is to maximize the total profit of executing the jobs (on a single machine) during I. The interval scheduling problem is max SNP-hard in general; but in the real practice of protein NMR peak assignment, each job j(s) usually requires at most 10 consecutive time units, and typically the jobs that require one or two consecutive time units are the most difficult to assign/schedule. In order to solve these most difficult assignments, we present an efficient 13/7-approximation algorithm for the special case of the interval scheduling problem where each job takes one or two consecutive time units. Combining this algorithm with a greedy filtering strategy for handling long jobs (i.e., jobs that need more than two consecutive time units), we obtain a new efficient heuristic for protein NMR peak assignment. Our experimental study shows that the new heuristic produces the best peak assignment in most of the cases, compared with the NMR peak assignment algorithms in the recent literature. The above algorithm is also the first approximation algorithm for a nontrivial case of the well-known interval scheduling problem that breaks the ratio 2 barrier.


Transversus Abdominis Plane Blocks with Single-Dose Liposomal Bupivacaine in Conjunction with a Nonnarcotic Pain Regimen Help Reduce Length of Stay following Abdominally Based Microsurgical Breast Reconstruction.
Side effects associated with use of postoperative narcotics for pain control can delay recovery after abdominally based microsurgical breast reconstruction. The authors evaluated a nonnarcotic pain control regimen in conjunction with bilateral transversus abdominis plane blocks on facilitating early hospital discharge. A retrospective analysis was performed of consecutive patients who underwent breast reconstruction using abdominally based free flaps, with or without being included in a nonnarcotic protocol using intraoperative transversus abdominis plane blockade. During this period, the use of locoregional analgesia evolved from none (control), to continuous bupivacaine infusion transversus abdominis plane and catheters, to single-dose transversus abdominis plane blockade with liposomal bupivacaine solution. Demographic factors, length of stay, inpatient opioid consumption, and complications were reported for all three groups. One hundred twenty-eight consecutive patients (182 flaps) were identified. Forty patients (62 flaps) were in the infusion-liposomal bupivacaine group, 48 (66 flaps) were in the single-dose blockade-catheter group, and 40 (54 flaps) were in the control group. The infusion-liposomal bupivacaine patients had a significantly shorter hospital stay compared with the single-dose blockade-catheter group (2.65 ± 0.66 versus 3.52 ± 0.92 days; p < 0.0001) and the control group (2.65 ± 0.66 versus 4.05 ± 1.26 days; p < 0.0001). There was no significant difference in flap loss or major complications among groups. When used as part of a nonnarcotic postoperative pain regimen, transversus abdominis plane blocks performed with single injections of liposomal bupivacaine help facilitate early hospital discharge after abdominally based microsurgical breast reconstruction. A trend toward consistent discharge by postoperative day 2 was seen. This could result in significant cost savings for health care systems. Therapeutic, III.


Urinary pyrethroid and chlorpyrifos metabolite concentrations in Northern California families and their relationship to indoor residential insecticide levels, part of the Study of Use of Products and Exposure Related Behavior (SUPERB).
Since the 2001 U.S. federally mandated phase-out of residential uses of organophosphates (OPs), use of and potential for human exposure to pyrethroids in the indoor residential environment has increased. We report concentrations of common pyrethroids, pyrethroid metabolites, and chlorpyrifos in floor wipes, and urinary concentrations of pyrethroid metabolites and 3,5,6-trichloro-2-pyridinol (TCPy) in samples collected in 2007-2009 from 90 northern California families as part of the Study of Use of Products and Exposure Related Behavior (SUPERB). Correlation and regression analyses examined associations between floor wipe and urine sample concentrations. The most frequently detected urinary metabolites were TCPy (64.7%, median concentration of 1.47 ng/mL) and 3-phenoxybenzoic acid (3PBA) (62.4%, 0.79 ng/mL). Compared to the National Health and Nutrition Examination Survey (NHANES) 2001-2002 general U.S. population, this population had substantially higher pyrethroid metabolite and lower TCPy urinary concentrations. This may be related to the increased residential use of pyrethroids after the phase-out of OPs. Chlorpyrifos (98.7%), cis- and trans-permethrin (97.5%), bifenthrin (59.3%), and 3PBA (98.7%) were frequently detected in the floor wipes. Floor wipe concentrations for pyrethroid insecticides were found to be significant predictors of child creatinine-adjusted urinary metabolite concentrations (log-log regression coefficients ranging from 0.26 to 0.29; p < 0.05) suggesting that indoor residential exposure to pyrethroid insecticides is an important exposure route for children.


The SMARTER pilot study: Testing feasibility of real-time feedback for dietary self-monitoring.
Self-monitoring (SM) of food intake is central to weight loss treatment. Technology makes it possible to reinforce this behavior change strategy by providing real-time feedback (FB) tailored to the diary entry. To test the feasibility of providing 1-4 daily FB messages tailored to dietary recordings via a smartphone, we conducted a 12-week pilot randomized clinical trial in Pittsburgh, PA in US in 2015. We compared 3 groups: SM using the Lose It! smartphone app (Group 1); SM + FB (Group 2); and SM + FB + attending three in-person group sessions (Group 3). The sample (N = 39) was mostly white and female with a mean body mass index of 33.76 kg/m2. Adherence to dietary SM was recorded daily, weight was assessed at baseline and 12 weeks. The mean percentage of days adherent to dietary SM was similar among Groups 1, 2, and 3 (p = 0.66) at 53.50% vs. 55.86% vs. 65.33%, respectively. At 12 weeks, all groups had a significant percent weight loss (p < 0.05), with no differences among groups (- 2.85% vs. - 3.14% vs. - 3.37%) (p = 0.95); 26% of the participants lost ≥ 5% of their baseline weight. Mean retention was 74% with no differences among groups (p = 0.37). All groups adhered to SM at levels comparable to or better than other weight loss studies and lost acceptable amounts of weight, with minimal intervention contact over 12 weeks. These preliminary findings suggest this 3-group approach testing SM alone vs. SM with real-time FB messages alone or supplemented with limited in-person group sessions warrants further testing in a larger, more diverse sample and for a longer intervention period.


Safety and immunogenicity of two different doses of a Vero cell-derived, whole virus clade 2 H5N1 (A/Indonesia/05/2005) influenza vaccine.
A successful vaccine development strategy for areas with clustered H5N1 events requires conduct of vaccine trials in potentially non-naïve subjects and evaluation of post-vaccination responsiveness. An open-label, randomized, phase I/II study therefore assessed the immunogenicity and safety of two different dose levels of an inactivated, non-adjuvanted, whole virus clade 2.1 (A/Indonesia/05/2005) H5N1 Vero cell-derived influenza vaccine in healthy adults (21-45 years) from a region where the virus has been circulating (Hong Kong) as well as Singapore. Subjects (N=110) were randomized 1:1 to receive two vaccinations with either 3.75 μg or 7.5 μg H5N1 haemagglutinin antigen 21 days apart. Safety, immunogenicity (microneutralization [MN] and single radial haemolysis [SRH] at baseline and post-vaccination) and cross-reactivity against a heterologous clade 1 strain (A/Vietnam/1203/2004) of the vaccine were assessed. Pre-existing immunity to the vaccine strain was 14% which is higher than previously reported for these regions. Two vaccinations with either vaccine formulation induced high seroprotection rates (MN titre ≥ 1:20) against the vaccine strain A/Indonesia/05/2005: 82.7% and 86.5% in the 3.75 μg and 7.5 μg dose groups. Seroconversion rates and fold increase exceeded the CPMP criterion of >40% and >2.5 for MN and SRH in both dose groups after the second vaccination, while the seroprotection rate in the 7.5 μg dose group determined by SRH was only marginally lower (69.2%) than the CPMP criterion of >70%. Thus, 11 of 12 CHMP criteria were fulfilled. A cross-reactive antibody response against the heterologous A/Vietnam/1203/2004 strain was demonstrated after the second vaccination (>21% by MN and ≥ 25% by SRH). Persistence of antibodies against the vaccine strain was also demonstrated 6 months after the first vaccination, indicating that a booster vaccination would be effective in those who have received two priming doses. No serious adverse events were reported. The H5N1 influenza vaccine against clade 2.1 strain A/Indonesia/05/2005 was well tolerated and immunogenic after two vaccinations, and induced a cross-neutralizing antibody response, with no dose effect.


Beta2 integrin phosphorylation on Thr758 acts as a molecular switch to regulate 14-3-3 and filamin binding.
Leukocyte integrins of the beta2 family are essential for immune cell-cell adhesion. In activated cells, beta2 integrins are phosphorylated on the cytoplasmic Thr758, leading to 14-3-3 protein recruitment to the beta2 integrin. The mutation of this phosphorylation site impairs cell adhesion, actin reorganization, and cell spreading. Thr758 is contained in a Thr triplet of beta2 that also mediates binding to filamin. Here, we investigated the binding of filamin, talin, and 14-3-3 proteins to phosphorylated and unphosphorylated beta2 integrins by biochemical methods and x-ray crystallography. 14-3-3 proteins bound only to the phosphorylated integrin cytoplasmic peptide, with a high affinity (K(d), 261 nM), whereas filamin bound only the unphosphorylated integrin cytoplasmic peptide (K(d), 0.5 mM). Phosphorylation did not regulate talin binding to beta2 directly, but 14-3-3 was able to outcompete talin for the binding to phosphorylated beta2 integrin. X-ray crystallographic data clearly explained how phosphorylation eliminated filamin binding and induced 14-3-3 protein binding. Filamin knockdown in T cells led to an increase in stimulated cell adhesion to ICAM-1-coated surfaces. Our results suggest that the phosphorylation of beta2 integrins on Thr758 acts as a molecular switch to inhibit filamin binding and allow 14-3-3 protein binding to the integrin cytoplasmic domain, thereby modulating T-cell adhesion.


Enablers and Barriers Related to Preconception Physical Activity: Insights from Women of Reproductive Age Using Mixed Methods.
Engaging in regular preconception physical activity (PA) is associated with benefits, including improved cardiovascular health and mental well-being. However, most women do not meet PA recommendations in the preconception period. This study aimed to investigate enablers and barriers related to PA in preconception women using a sequential mixed method design. An online survey was followed by Zoom interviews with women of reproductive age (aged 18-45 years). A weaving approach and the Capability Opportunity Motivation Behaviour (COM-B) model were used to integrate and present the data. Seven hundred and eighty-eight non-pregnant women from Australia, India, and the US completed the quantitative survey, and 13 Australian-based women participated in a qualitative interview. Physical activity levels were associated with having social support, a desire to improve body image, and becoming a healthier person. Women encountered barriers such as misconceptions about PA, competing priorities, financial constraints, and a lack of accessibility. Enablers for participation in PA included knowledge of its importance, a desire to be healthier, weight loss, social support, and having goals. The multifaceted and intricate nature of enablers and barriers for preconception PA lays the groundwork for developing tailored interventions and policies aimed at promoting preconception PA among women.