Intrauterine inoculation of Mycobacterium paratuberculosis into guinea pigs and cattle.
Mycobacterium paratuberculosis was inoculated intrauterinely into guinea pigs and cattle near the time of insemination to assess the effect and subsequent distribution of the organisms. Guinea pigs inoculated intrauterinely with 1 of 3 concentrations of M paratuberculosis or not inoculated were caged with male guinea pigs for 10 days. Guinea pigs given the largest dose had the lowest rate of pregnancy when examined. At necropsy, tissues were cultured to determine extent of infection. Abortion followed hypersensitivity reactions to johnin in some highly infected animals. Mycobacterium paratuberculosis was recovered in culture from the body and horns of the uterus of cows necropsied 1, 2, 3, and 7 days after inoculation and from 1 of 3 cows necropsied 2 weeks after inoculation. The organisms were not detected in extrauterine organs of any cattle or in uterine specimens taken at 3 or 4 weeks after inoculation. The evidence indicates that the small numbers of M paratuberculosis sometimes found in semen from paratuberculous bulls probably would be destroyed, rather than leading to systemic infection of the dam or to persistent hypersensitivity.


[History, health and its workers: from the international agenda to the Brazilian policies].
This article discusses the agenda for the training and management of the health workforce in Brazil from a historical viewpoint, especially as refers to its relations with the programs in this field developed by the Pan American Health Organization (PAHO) and by the World Health Organization (WHO). In the first section one discusses the role of history in the field of community health. The priority given to the topic health work in the international agenda seems to point to a potential renewal of the relations between history and health. The second section provides a historical examination of the human resources programs of the WHO. In the third section, a similar examination is conducted with respect to the actions of PAHO in the same field. The fourth part of the article discusses--on the basis of the experience called "Program for Strategic Preparation of Health Personnel--PPREPS"--the relations between the national and international policies for the development of human resources in health. Moreover it describes a number of adapted responses and original solutions for facing the health workforce problem proposed by the Brazilian technicians. Finally, some questions are raised for discussion regarding the articulation between history and health workforce policies.


Two-Dimensional Covalent Crystals by Chemical Conversion of Thin van der Waals Materials.
Most of the studied two-dimensional (2D) materials have been obtained by exfoliation of van der Waals crystals. Recently, there has been growing interest in fabricating synthetic 2D crystals which have no layered bulk analogues. These efforts have been focused mainly on the surface growth of molecules in high vacuum. Here, we report an approach to making 2D crystals of covalent solids by chemical conversion of van der Waals layers. As an example, we used 2D indium selenide (InSe) obtained by exfoliation and converted it by direct fluorination into indium fluoride (InF3), which has a nonlayered, rhombohedral structure and therefore cannot possibly be obtained by exfoliation. The conversion of InSe into InF3 is found to be feasible for thicknesses down to three layers of InSe, and the obtained stable InF3 layers are doped with selenium. We study this new 2D material by optical, electron transport, and Raman measurements and show that it is a semiconductor with a direct bandgap of 2.2 eV, exhibiting high optical transparency across the visible and infrared spectral ranges. We also demonstrate the scalability of our approach by chemical conversion of large-area, thin InSe laminates obtained by liquid exfoliation, into InF3 films. The concept of chemical conversion of cleavable thin van der Waals crystals into covalently bonded noncleavable ones opens exciting prospects for synthesizing a wide variety of novel atomically thin covalent crystals.


Reproducibility of resting heart rate variability with short sampling periods.
The purpose of this study was to determine whether resting heart rate variability (HRV) is reproducible with short sampling measurement periods using an office-based personal computer measurement system. Eight healthy active women participated in ECG analyses on 2 days within 1 week under controlled environmental and physiological conditions. After they rested for 10 minutes, a 10-min ECG was recorded. HRV was determined from a 2.5- and 5-min sample period using both time domain variables (meanRR and SDNN) and frequency domain variables (LF, HF, LF:HF). Repeated measures ANOVA found no significant differences between Day 1 and Day 2 for either sampling period (p > or = 0.23). For both the 2.5- and 5-min sampling periods, the intraclass correlations between days for the time domain variables showed good reproducibility (R = 0.86-0.90). The reproducibility of the frequency domain variable was only average (R = 0.67-0.96), with the LF:HF ratio yielding the higher R values.


The effect of Section 1557 of the Affordable Care Act on surgical outcomes in non-English primary language speakers.
In 2016, Section 1557 mandated use of qualified language interpreter services. We examined the effect of Section 1557 on surgical outcomes. Utilizing the Healthcare Cost and Utilization Project State Inpatient Database (2013-2020), we performed a difference-in-differences analysis of adult surgical patients (Maryland, New Jersey). The exposure was implementation of Section 1557 (pre-period: 2013-2015; post-period: 2017-2020). The treatment group was non-English primary language speakers (n-EPL). The comparison group was English primary language speakers (EPL). Outcomes included length-of-stay, postoperative complications, mortality, discharge disposition, and readmissions. Among 2,298,584 patients, 198,385 (8.6%) were n-EPL. After implementation of Section 1557, n-EPL saw no difference in readmission rates but did experience significantly higher rates of mortality (+0.43%, p = 0.049) and non-routine discharges (+1.81%, p = 0.031) in Maryland, and higher rates of post-operative complications (+0.31%, p = 0.001) in both states, compared to pre-Section 1557. Contrary to our hypothesis, Section 1557 did not improve surgical outcomes for n-EPL.


HiChIP: efficient and sensitive analysis of protein-directed genome architecture.
Genome conformation is central to gene control but challenging to interrogate. Here we present HiChIP, a protein-centric chromatin conformation method. HiChIP improves the yield of conformation-informative reads by over 10-fold and lowers the input requirement over 100-fold relative to that of ChIA-PET. HiChIP of cohesin reveals multiscale genome architecture with greater signal-to-background ratios than those of in situ Hi-C.


Eigenvalue problem of the Schrödinger equation via the finite-difference time-domain method.
We present a very efficient scheme to calculate the eigenvalue problem of the time-independent Schrödinger equation. The eigenvalue problem can be solved via an initial-value procedure of the time-dependent Schrödinger equation. First, the time evolution of the wave function is calculated by the finite-difference time-domain method. Then the eigenenergies of the electron system can be obtained through a fast Fourier transformation along the time axis of the wave function after some point. The computing effort for this scheme is roughly proportional to the total grid points involved in the structure and it is suitable for large scale quantum systems. We have applied this approach to the three-dimensional GaN quantum dot system involving one million grid points. It takes only 7 h to calculate the confined energies and the wave functions on a standard 2-GHz Pentium 4 computer. The proposed approach can be implemented in a parallel computer system to study more complex systems.


Formulation and in Vitro, ex Vivo and in Vivo Evaluation of Elastic Liposomes for Transdermal Delivery of Ketorolac Tromethamine.
The objective of the current study was to formulate ketorolac tromethamine-loaded elastic liposomes and evaluate their in vitro drug release and their ex vivo and in vivo transdermal delivery. Ketorolac tromethamine (KT), which is a potent analgesic, was formulated in elastic liposomes using Tween 80 as an edge activator. The elastic vesicles were prepared by film hydration after optimizing the sonication time and number of extrusions. The vesicles exhibited an entrapment efficiency of 73 ± 11%, vesicle size of 127.8 ± 3.4 nm and a zeta potential of -12 mV. In vitro drug release was analyzed from liposomes and an aqueous solution, using Franz diffusion cells and a cellophane dialysis membrane with molecular weight cut-off of 8000 Da. Ex vivo permeation of KT across pig ear skin was studied using a Franz diffusion cell, with phosphate buffer (pH 7.4) at 32 °C as receptor solution. An in vivo drug permeation study was conducted on healthy human volunteers using a tape-stripping technique. The in vitro results showed (i) a delayed release when KT was included in elastic liposomes, compared to an aqueous solution of the drug; (ii) a flux of 0.278 mg/cm2h and a lag time of about 10 h for ex vivo permeation studies, which may indicate that KT remains in the skin (with the possibility of exerting a local effect) before reaching the receptor medium; (iii) a good correlation between the total amount permeated, the penetration distance (both determined by tape stripping) and transepidermal water loss (TEWL) measured during the in vivo permeation studies. Elastic liposomes have the potential to transport the drug through the skin, keep their size and drug charge, and release the drug into deep skin layers. Therefore, elastic liposomes hold promise for the effective topical delivery of KT.


Blockade of alpha v beta3 and alpha v beta5 integrins by RGD mimetics induces anoikis and not integrin-mediated death in human endothelial cells.
Alpha v integrins are thought to play an important role in tumor angiogenesis. However, discrepancies between findings with Arg-Gly-Asp (RGD) mimetics, which block angiogenesis in animal models, and knockout mice, in which loss of some alpha v integrins enhances tumor angiogenesis, raise questions concerning the function of these integrins and the precise role of alpha v substrate mimetics in antiangiogenic therapies. We have examined the effects of a novel non-peptide RGD mimetic, S 36578-2, on human endothelial cells to elucidate its antagonist activity and to identify possible agonist functions. S 36578-2 is highly selective for alpha v beta3 and alpha v beta5 integrins and induces detachment, caspase-8 activation, and apoptosis in human umbilical endothelial cells (HUVECs) plated on vitronectin. Importantly, the compound has no effect on the morphology or survival of cells plated on interstitial matrix components such as fibronectin, and it does not potentiate the apoptotic process in suspended cells. Identical results were obtained with a cyclic RGD peptide with similar target specificity. In microvascular endothelial cells, S 36578-2-induced death was also linked to its antiadhesive effect, with established lines markedly more resistant than primary cultures to the antiadhesive and proapoptotic effects. Altogether, these findings have important implications for the development of this class of antiangiogenics.


An evaluation of ICD-11 PTSD and complex PTSD criteria in a sample of adult survivors of childhood institutional abuse.
The WHO recently launched the proposal for the 11th version of the International Classification of Diseases (ICD-11) that also includes two diagnoses related to traumatic stress. In contrast to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), ICD-11 will probably, in addition to posttraumatic stress disorder (PTSD), also define a new diagnosis termed "complex posttraumatic stress disorder" (CPTSD). We aimed to apply the proposed ICD-11 criteria for PTSD and CPTSD and to compare their prevalence to the ICD-10 (International Classification of Diseases [10th revision]) PTSD prevalence. In addition, we compiled a list of symptoms for CPTSD based on subthreshold PTSD so as to include a wider group of individuals. To evaluate the appropriateness of the WHO ICD-11 proposal compared to the criteria of ICD-10, we applied the newly introduced criteria for PTSD and CPTSD deriving from the Posttraumatic Stress Disorder Checklist - Civilian Version (PCL-C) and the Brief Symptom Inventory (BSI) scales, to a sample of adult survivors (N=229) of childhood institutional abuse. We evaluated the construct validity of CPTSD using confirmatory factor analysis (CFA). More individuals fulfilled the criteria for PTSD according to ICD-10 (52.8%) than the ICD-11 proposal (17% for PTSD only; 38.4% if combined with complex PTSD). The new version of PTSD neutralized the gender effects. The prevalence of CPTSD was 21.4%, and women had a significantly higher rate of CPTSD than men (40.4 and 15.8%, respectively). Those survivors who were diagnosed with CPTSD experienced institutional abuse for a longer time. CFA showed a strong model fit. CPTSD is a highly relevant classification for individuals with complex trauma history, but surprisingly, effects of gender were apparent. Further research should thus address gender effects.


Both the concentration and redox state of glutathione and ascorbate influence the sensitivity of arabidopsis to cadmium.
Cadmium (Cd) is a non-essential trace element that elicits oxidative stress. Plants respond to Cd toxicity via increasing their Cd-chelating and antioxidative capacities. They predominantly chelate Cd via glutathione (GSH) and phytochelatins (PCs), while antioxidative defence is mainly based on the use and recycling of both GSH and ascorbate (AsA), complemented by superoxide dismutase (SOD) and catalase (CAT). In addition, both metabolites act as a substrate for the regeneration of other essential antioxidants, which neutralize and regulate reactive oxygen species (ROS). Together, these functions influence the concentration and cellular redox state of GSH and AsA. In this study, these two parameters were examined in plants of Arabidopsis thaliana exposed to sub-lethal Cd concentrations. Wild-type plants and mutant arabidopsis plants containing 30-45 % of wild-type levels of GSH (cad2-1) or 40-50 % of AsA (vtc1-1), together with the double-mutant (cad2-1 vtc1-1) were cultivated in a hydroponic system and exposed to sub-lethal Cd concentrations. Cadmium detoxification was investigated at different levels including gene expression and metabolite concentrations. In comparison with wild-type plants, elevated basal thiol levels and enhanced PC synthesis upon exposure to Cd efficiently compensated AsA deficiency in vtc1-1 plants and contributed to decreased sensitivity towards Cd. Glutathione-deficient (cad2-1 and cad2-1 vtc1-1) mutants, however, showed a more oxidized GSH redox state, resulting in initial oxidative stress and a higher sensitivity to Cd. In order to cope with the Cd stress to which they were exposed, GSH-deficient mutants activated multiple alternative pathways. Our observations indicate that GSH and AsA deficiency differentially alter plant GSH homeostasis, resulting in opposite Cd sensitivities relative to wild-type plants. Upon Cd exposure, GSH-deficient mutants were hampered in chelation. They experienced phenotypic disturbances and even more oxidative stress, and therefore activated multiple alternative pathways such as SOD, CAT and ascorbate peroxidase, indicating a higher Cd sensitivity. Ascorbate deficiency, however, was associated with enhanced PC synthesis in comparison with wild-type plants after Cd exposure, which contributed to decreased sensitivity towards Cd.


Alcohol intake and risk of erectile dysfunction: a dose-response meta-analysis of observational studies.
The purpose of the present study was to conduct a meta-analysis of cross-sectional studies assessing the relationship between alcohol consumption and the risk of erectile dysfunction (ED). To identify relevant studies, databases such as Pubmed, Medline, Embase, and the Cochrane Library were searched from the inception of the present study to March 2016. Finally, 24 studies (154,295 patients) were included. We combined a study-specific odds ratio (OR) estimated by using a random effects meta-analysis. The results of our meta-analysis indicated that light to moderate alcohol consumption (<21 drinks/week) was correlated with a decreased risk of erectile dysfunction (OR = 0.71; 95% CI: 0.59-0.86; P = 0.000). However, regular (ever vs. never) and high alcohol consumption (>21 drinks/week) had no significant influence on the prevalence of ED (regular: OR = 0.87; 95% CI: 0.75-1.07; P = 0.062; high: OR = 0.99; 95% CI: 0.80-1.22; P = 0.893). In a dose-response meta-analysis, a non-linear relationship was observed between alcohol consumption and risk of ED (P for non-linearity = 0.0000). In conclusion, moderate intake of alcohol exhibited a beneficial effect on the risk of ED, whereas regular and high consumption did not.


Effects of the Ten Percent Cap in Medicare Home Health Care on Treatment Intensity and Patient Discharge Status.
To estimate the effect of the 10 percent cap introduced to Medicare home health care on treatment intensity and patient discharge status. Medicare Denominator, Medicare Home Health Claims, and Medicare Provider of Services Files from 2008 through 2010. We used agency-level variation in the proportion of outlier payments prior to the implementation of the 10 percent cap to identify how home health agencies adjusted the number of home health visits and patient discharge status under the new law. Under the 10 percent cap, agencies dramatically decreased the number of service visits. Agencies also dropped relatively healthy patients and sent sicker patients to nursing homes. The drastic reduction in the number of service visits and discontinuation of relatively healthy patients from home health care suggest that the 10 percent cap improved the efficiency of home health services as intended. However, the 10 percent cap increased other types of health care expenditures by pushing sicker patients to use more expensive health services.


In-vitro Antimycoplasmal Activity of Triclosan in Combination with Fluoroquinolones against Five mycoplasma Species.
Mycoplasmosis caused by mycoplasma has immensely reduced the performance of commercial animal husbandry, along with prevalence and increase of drug resistance in mycoplasma, thus new agents and therapies are urgently needed. Triclosan is a broad spectrum antimicrobial agent with a favorable safety profile. In the present study, we tested the antimycoplasmal activity of triclosan alone, as well as the in-vitro interaction of triclosan and the fluoroquinolones, gatifloxacin (GAT), moxifloxacin (MXF), levofloxacin (LVX), sparfloxacin (SPX), ciprofloxacin (CIP), enrofloxacin (EFX), and norfloxacin (NOR), against five mycoplasma species. This study demonstrated that triclosan had antimycoplasmal activity against both fluoroquinolones-sensitive species and a fluoroquinolones-resistant species isolated from clinic, with minimum inhibitory concentrations (MICs) of 16.0-64.0 μg/mL and 64.0 μg/ mL, respectively. A synergistic antimycoplasmal effect between triclosan and GAT, MFX or EFX against the five mycoplasma species was observed, with modulation factors (MFs) of 4-8, 4-16, 8-32, respectively, and fractional inhibitory concentration indexes (FICIs) of 0.375- 0.500, 0.350-0.500, 0.281-0.375, respectively. The combination of triclosan with LVX, SPX, CIP or NOR displayed either synergistic activity or indifference against the same mycoplasma species with MFs of 2-64, 4-16, 2-16, 2-64, respectively, while FICI values range from 0.516- 0.750, 0.500-0.625, 0.306-0.750, and 0.615-0.750, respectively. No antagonism was observed for any drug combination against any of the species tested. To the best of our knowledge, this is the first report that triclosan has synergistic activity with fluoroquinolones against mycoplasma species.


The WRKY45-2 WRKY13 WRKY42 transcriptional regulatory cascade is required for rice resistance to fungal pathogen.
Blast caused by fungal Magnaporthe oryzae is a devastating disease of rice (Oryza sativa) worldwide, and this fungus also infects barley (Hordeum vulgare). At least 11 rice WRKY transcription factors have been reported to regulate rice response to M. oryzae either positively or negatively. However, the relationships of these WRKYs in the rice defense signaling pathway against M. oryzae are unknown. Previous studies have revealed that rice WRKY13 (as a transcriptional repressor) and WRKY45-2 enhance resistance to M. oryzae. Here, we show that rice WRKY42, functioning as a transcriptional repressor, suppresses resistance to M. oryzae. WRKY42-RNA interference (RNAi) and WRKY42-overexpressing (oe) plants showed increased resistance and susceptibility to M. oryzae, accompanied by increased or reduced jasmonic acid (JA) content, respectively, compared with wild-type plants. JA pretreatment enhanced the resistance of WRKY42-oe plants to M. oryzae. WRKY13 directly suppressed WRKY42. WRKY45-2, functioning as a transcriptional activator, directly activated WRKY13. In addition, WRKY13 directly suppressed WRKY45-2 by feedback regulation. The WRKY13-RNAi WRKY45-2-oe and WRKY13-oe WRKY42-oe double transgenic lines showed increased susceptibility to M. oryzae compared with WRKY45-2-oe and WRKY13-oe plants, respectively. These results suggest that the three WRKYs form a sequential transcriptional regulatory cascade. WRKY42 may negatively regulate rice response to M. oryzae by suppressing JA signaling-related genes, and WRKY45-2 transcriptionally activates WRKY13, whose encoding protein in turn transcriptionally suppresses WRKY42 to regulate rice resistance to M. oryzae.


Electrochemical generation of hydroxyl radicals for examining protein structure.
The use of hydroxyl radicals to covalently label the solvent-exposed surface of proteins has been shown to be a powerful tool to examine the structure of proteins and intermolecular interfaces. Current methods to generate hydroxyl radicals for footprinting experiments rely on the laser photolysis of H2O2 or the synchrotron radiolysis of water, which adds significant costs and/or complexity to the experiments. In this work, we develop the electro-Fenton reaction as a means to generate hydroxyl radicals for structural footprinting mass spectrometry experiments to complement current laser and synchrotron-based methods, while reducing the costs and complexity of initiating such experiments. The use of an electrochemical flow cell also enables control of the timing and extent of the radical generation process, while reducing the complexity typically associated with radical footprinting experiments. Ubiquitin, a model protein, was labeled with electro-Fenton generated hydroxyl radicals and top-down proteomics was used to verify oxidation sites on the protein surface.


Hand-assisted Approach as a Model to Teach Complex Laparoscopic Hepatectomies: Preliminary Results.
Currently, there are limited and scarce models to teach complex liver resections by laparoscopy. The aim of this study is to present a hand-assisted technique to teach complex laparoscopic hepatectomies for fellows in liver surgery. Laparoscopic hand-assisted approach for resections of liver lesions located in posterosuperior segments (7, 6/7, 7/8, 8) was performed by the trainees with guidance and intermittent intervention of a senior surgeon. Data as: (1) percentage of time that the senior surgeon takes the surgery as main surgeon, (2) need for the senior surgeon to finish the procedure, (3) necessity of conversion, (4) bleeding with hemodynamic instability, (5) need for transfusion, (6) oncological surgical margins, were evaluated. In total, 12 cases of complex laparoscopic liver resections were performed by the trainee. All cases included deep lesions situated on liver segments 7 or 8. The senior surgeon intervention occurred in a mean of 20% of the total surgical time (range, 0% to 50%). A senior intervention >20% was necessary in 2 cases. There was no need for conversion or reoperation. Neither major bleeding nor complications resulted from the teaching program. All surgical margins were clear. This preliminary report shows that hand-assistance is a safe way to teach complex liver resections without compromising patient safety or oncological results. More cases are still necessary to draw definitive conclusions about this teaching method.


[Medical Methods: What Makes them Necessary? Part I: Medical Methods, medical Necessity and its Main Criteria].
"Medical necessity" (MedN) is a fuzzy term. Our project aims at concretising the concept between medical ethics, social law, and social medicine to support health care regulation, primarily within Germany's statutory health insurance system. In a previous publication we identified MedN as a tripartite predicate: A specific clinical condition requires a specific medical intervention to reach a specific medical goal. Our two-part text searches for and discusses criteria to classify medical methods as generally medically necessary (medn), provided a non-trivial clinical condition and a relevant, legitimate, and reachable goal actually exist. In this paper we present the first part of our results. Based on an extensive ethical, sociolegal and sociomedical body of literature, and starting with an non-controversial case vignette (thrombolysis in acute stroke), we generally followed a critical reconstructive approach. First we defined the term "medical method". In several interdisciplinary rounds, we then collected and discussed criteria from three sources: methods to develop clinical practice guidelines as compendia of indication rules, the National Model of Prioritisation in Swedish Health Care, and the HTA Core Model of the European Network for Health Technology Assessment as an instrument of political counselling. We identified general clinical efficacy and benefit as the 2 main "medical" criteria of MedN. As a third - epistemic - criterion, the corresponding bodies of evidence are always to be considered. Since clinical and prioritising guidelines grade their recommendations, the question arises whether MedN should be conceptualised as a dichotomous or finer graded predicate. In accord with German social law we advocate for the binary form. Further discussions focused on multifactorial MedN-configurations, the range of the term, and the variability of evidence requirements. No matter how the content of MedN is conceptualised, it seems impossible to include its criteria in an algorithm. So deliberative effort is indispensable at any stage of developing a programme to classify medical methods as medically necessary.


Human herpes virus 8 replication during disseminated tuberculosis in a man with human immunodeficiency virus: a case report.
Human herpes virus 8 (HHV-8) is mainly responsible for the development of Kaposi's sarcoma and multicentric Castleman's disease in immunocompromised patients with untreated human immunodeficiency virus. Positive viral loads have been described in cases of Kaposi's sarcoma and multicentric Castleman's disease, with higher values found in the latter. We describe the case of a patient with HIV in whom a high level of HHV-8 replication was detected and who contracted an opportunistic disease other than multicentric Castleman's disease or Kaposi's sarcoma. A 25-year-old man of West African origin with HIV complained of asthenia, weight loss, fever, and abdominal pain. Physical examination revealed that the patient had adenopathies and hepatosplenomegaly, but no skin or mucosal lesions were seen. Our first presumptive diagnosis was disseminated tuberculosis. However, since the cultures (sputum, bronchoalveolar lavage, blood, urine and lymph node biopsies) for mycobacteria were negative, the diagnosis was expanded to include multicentric Castleman's disease which was supported by high HHV-8 viral loads in the patient's blood: 196,000 copies/ml in whole blood, 39,400 copies/ml in plasma and 260 copies/10E5 in peripheral blood mononuclear cells. However, the histology and positive polymerase chain reaction assay for Mycobacterium tuberculosis complex of a second lymph node biopsy enabled us to conclude that the patient had disseminated tuberculosis and we started the patient on antituberculosis treatment. We analyzed the HHV-8 deoxyribonucleic acid in two other plasma samples (one from six months earlier and the other was 10 days after the positive test) and both yielded negative results. A search for latent and lytic HHV-8 antibodies confirmed that the patient was seropositive for HHV-8 before this episode. We describe the case of a patient with HIV who tested positive for asymptomatic HHV-8 replication during an opportunistic disease suggestive of multicentric Castleman's disease. The initial analysis was nullified by the diagnosis of a disease that was unrelated to HHV-8. This case report underlines the need to clarify the full clinical meaning and implication of a positive HHV-8 viral load in patients with AIDS. The diagnosis of multicentric Castleman's disease needs to be studied further to determine its sensitivity and specificity. Finally, when faced with the dilemma of urgently starting chemotherapy on a patient whose condition is deteriorating and whose clinical presentation suggests multicentric Castleman's disease, high HHV-8 viral loads should be interpreted with caution and histological analysis of lymph nodes or liver biopsies should be obtained first.


Tissue plasminogen activator release in vivo in response to vasoactive agents.
Release of tissue plasminogen activator into the circulation of rats in response to intravascular injections of vasoactive agents is studied by using a sensitive and specific clot lysis assay. Intra-arterial bradykinin elicits a rapid and transient rise in circulating plasminogen activator, which is maximum within one minute and is cleared within four to eight minutes. The plasminogen activator is fibrin dependent and is neutralized by an antiserum to human tissue-type plasminogen activator. Bradykinin is 1,000-fold more potent than the other agonists tested, which include histamine, norepinephrine, epinephrine, eledoisin-related peptide, arginine-vasopressin, lysine-vasopressin, desmopressin acetate, carbachol, and acetylcholine. Potency of bradykinin is related to its amino acid sequence. Sequential infusions of bradykinin produce a tachyphylactoid response that could be overcome by increasing the dose of the sequential bradykinin challenge. It is concluded that the characteristics of the responses to bradykinin and other agents in vivo differ significantly from those observed in isolated tissue preparations.


Negative modulation of the gamma-aminobutyric acid response by extracellular zinc.
We have studied the effects of divalent cations on the gamma-aminobutyric acid (GABA) response of voltage-clamped spinal cord neurons, using the whole-cell recording configuration. Zn, Cd, Ni, and Mn (but not Ba, Ca, or Mg) inhibit GABA-induced whole-cell currents when applied extracellularly. Although Zn is an effective inhibitor when applied extracellularly, it is ineffective when applied intracellularly. Inhibition by these cations is mediated by a common saturable recognition site that is distinct from the recognition sites for GABA, benzodiazepines, barbiturates, picrotoxin, or steroids. The maximal inhibition, or efficacy of inhibition, of GABA-induced currents is greater for Zn than for Cd, Ni, or Mn. The order of potency is Cd greater than Zn much greater than Ni much greater than Mn. Inhibition by Zn is partially surmountable by GABA, consistent with a decrease in both the maximum response and the affinity for GABA. The dose-response curve for inhibition of the GABA response by Zn is shifted to the right at a high GABA concentration but is unaffected by the presence of chlordiazepoxide, pentobarbital, or 5 beta-pregnan-3 alpha-ol-20-one. The results are consistent with a model in which a Zn-sensitive modulatory site exerts negative allosteric control over GABA receptor function.


GLI1+ perivascular, renal, progenitor cells: The likely source of spontaneous neoplasia that created the AGMK1-9T7 cell line.
The AGMK1-9T7 cell line has been used to study neoplasia in tissue culture. By passage in cell culture, these cells evolved to become tumorigenic and metastatic in immunodeficient mice at passage 40. Of the 20 x 106 kidney cells originally plated, less than 2% formed the colonies that evolved to create this cell line. These cells could be the progeny of some type of kidney progenitor cells. To characterize these cells, we documented their renal lineage by their expression of PAX-2 and MIOX, detected by indirect immunofluorescence. These cells assessed by flow-cytometry expressed high levels of CD44, CD73, CD105, Sca-1, and GLI1 across all passages tested; these markers have been reported to be expressed by renal progenitor cells. The expression of GLI1 was confirmed by immunofluorescence and western blot analysis. Cells from passages 13 to 23 possessed the ability to differentiate into adipocytes, osteoblasts, and chondrocytes; after passage 23, their ability to form these cell types was lost. These data indicate that the cells that formed the AGMK1-9T7 cell line were GLI1+ perivascular, kidney, progenitor cells.


Endothelial adhesion molecules in glomerular lesions: association with their severity and diversity in lupus models.
To clarify whether vascular endothelial adhesion molecules in glomeruli might contribute to the severity and diversity of glomerular lesions in lupus nephritis, their expression in lupus models was analyzed. The expression levels of E- and P-selectin and vascular cell adhesion molecule-1 (VCAM-1) in glomeruli of different histopathologic grades of MRL/MpJ-lpr/lpr (MRL/lpr) lupus mice was studied using laser-capture microdissection of the glomeruli, followed by reverse transcription-polymerase chain reaction (RT-PCR) analysis. The glomerular lesions in SCID mice injected with the 2B11.3 and 7B6.8 clones, which are derived from an MRL/lpr mouse and induce endocapillary proliferative and wire loop type of glomerular lesions, respectively, were analyzed. To investigate the effect of a soluble form of E-selectin (sE-selectin) on the development of glomerular lesions, sE-selectin-producing L cells were prepared by transfection of the cDNA encoding sE-selectin and injected into SCID mice. The glomeruli in MRL/lpr mice showed increased expression of these adhesion molecules, corresponding to the severity of the glomerular lesions. The endocapillary proliferative type lesions in SCID mice induced by the 2B11.3 clone showed significantly increased expression of the adhesion molecules, especially E-selectin and P-selectin, but the wire loop type lesion induced by the 7B6.8 clone expressed only VCAM-1. Formation of the endocapillary proliferative type lesions induced by the 2B11.3 clone was markedly prevented in association with elevation of the serum level of sE-selectin produced by the tansfected L cells. The severity and diversity of the histopathology of lupus nephritis are partially associated with the expression of vascular endothelial adhesion molecules in glomeruli.


Light-stress avoidance mechanisms in a Sphagnum-dominated wet coastal Arctic tundra ecosystem in Alaska.
The Arctic experiences a high-radiation environment in the summer with 24-hour daylight for more than two months. Damage to plants and ecosystem metabolism can be muted by overcast conditions common in much of the Arctic. However, with climate change, extreme dry years and clearer skies could lead to the risk of increased photoxidation and photoinhibition in Arctic primary producers. Mosses, which often exceed the NPP of vascular plants in Arctic areas, are often understudied. As a result, the effect of specific environmental factors, including light, on these growth forms is poorly understood. Here, we investigated net ecosystem exchange (NEE) at the ecosystem scale, net Sphagnum CO2 exchange (NSE), and photoinhibition to better understand the impact of light on carbon exchange from a moss-dominated coastal tundra ecosystem during the summer season 2006. Sphagnum photosynthesis showed photoinhibition early in the season coupled with low ecosystem NEE. However, later in the season, Sphagnum maintained a significant CO2 uptake, probably for the development of subsurface moss layers protected from strong radiation. We suggest that the compact canopy structure of Sphagnum reduces light penetration to the subsurface layers of the moss mat and thereby protects the active photosynthetic tissues from damage. This stress avoidance mechanism allowed Sphagnum to constitute a significant percentage (up to 60%) of the ecosystem net daytime CO2 uptake at the end of the growing season despite the high levels of radiation experienced.


Dependence of the tray transmission factor on collimator setting and source-surface distance.
When blocks are placed on a tray in megavoltage x-ray beams, generally a single correction factor for the attenuation by the tray is applied for each photon beam quality. In this approach, the tray transmission factor is assumed to be independent of field size and source-surface distance (SSD). Analysis of a set of measurements performed in beams of 13 different linear accelerators demonstrates that there is, however, a slight variation of the tray transmission factor with field size and SSD. The tray factor changes about 1.5% for collimator settings varying between 4x4 cm and 40 x 40 cm for a 1 cm thick PMMA tray and approximately 3% for a 2 cm thick PMMA tray. The variation with field size is smaller if the source-surface distance is increased. The dependence on the collimator setting is not different, within the experimental uncertainty of about 0.5% (1 s.d.), for the nominal accelerating potentials and accelerator types applied in this study. It is shown that the variation of the tray transmission factor with field size and source-surface distance can easily be taken into account in the dose calculation by considering the volume of the irradiated tray material and the position of the tray in the beam. A relation is presented which can be used to calculate the numerical value of the tray transmission factor directly. These calculated values can be checked with only a few measurements using a cylindrical beam coaxial miniphantom.


Circadian variation in salivary testosterone across age classes in Ache Amerindian males of Paraguay.
Testosterone levels exhibit a circadian rhythm in healthy men, with morning levels tending to be higher compared to evening titers. However, circadian rhythms wane with age. Although this has been described in males living within industrialized settings, age-related changes have not received similar attention in populations outside these contexts. Because many nonindustrialized populations, such as Ache Amerindians of Paraguay, exhibit testosterone levels that are lower than what is commonly reported in the clinical literature and lack age-associated variation in testosterone, it was hypothesized that Ache men would not show age-related variation in testosterone circadian rhythms. Diurnal rhythmicity in testosterone within and between Ache men in association with age (n = 52; age range, 18-64) was therefore examined. A significant negative association was evident between the ratio of morning and evening salivary testosterone and age (r = -0.28, P = 0.04). Men in their third decade of life exhibited significant diurnal variation (P = 0.0003), whereas older and younger age classes did not. Men between the ages of 30 and 39 also exhibited a higher AM:PM testosterone ratio compared to 40-49 and 50< year old men (P = 0.002, 0.006). Overall, declines in testosterone with aging may not be universal among human males, however, within-individual analyses of diurnal variation capture age-related contrasts in daily testosterone fluctuations. Circadian rhythmicity differs with age among the Ache and may be a common aspect of reproductive senescence among men regardless of ecological context.


Rostral Anterior Cingulate Cortex Oscillatory Power Indexes Treatment-Resistance to Multiple Therapies in Major Depressive Disorder.
High rostral anterior cingulate cortex (rACC) activity is proposed as a nonspecific prognostic marker for treatment response in major depressive disorder, independent of treatment modality. However, other studies report a negative association between baseline high rACC activation and treatment response. Interestingly, these contradictory findings were also found when focusing on oscillatory markers, specifically rACC-theta power. An explanation could be that rACC-theta activity dynamically changes according to number of previous treatment attempts and thus is mediated by level of treatment-resistance. Primarily, we analyzed differences in rACC- and frontal-theta activity in large national cross-sectional samples representing various levels of treatment-resistance and resistance to multimodal treatments in depressed patients (psychotherapy [n = 175], antidepressant medication [AD; n = 106], repetitive transcranial magnetic stimulation [rTMS; n = 196], and electroconvulsive therapy [ECT; n = 41]), and the respective difference between remitters and non-remitters. For exploratory purposes, we also investigated other frequency bands (delta, alpha, beta, gamma). rACC-theta activity was higher (p < 0.001) in the more resistant rTMS and ECT patients relative to the less resistant psychotherapy and AD patients (psychotherapy-rTMS: d = 0.315; AD-rTMS: d = 0.320; psychotherapy-ECT: d = 1.031; AD-ECT: d = 1.034), with no difference between psychotherapy and AD patients. This association was even more pronounced after controlling for frontal-theta. Post hoc analyses also yielded effects for delta, beta, and gamma bands. Our findings suggest that by factoring in degree of treatment-resistance during interpretation of the rACC-theta biomarker, its usefulness in treatment selection and prognosis could potentially be improved substantially in future real-world practice. Future research should however also investigate specificity of the theta band.


Increased Mortality Associated with Higher Pre-Dialysis Serum Sodium Variability: Results of the International MONitoring Dialysis Outcome Initiative.
Low serum sodium (SNa) is associated with an increased mortality in chronic hemodialysis (HD) patients. Dialysis patients are thought to have an individual pre-dialysis SNa set-point, yet there is evidence for variability of pre-dialysis SNa in individual patient. In this study, we explored the association of several SNa variability metrics with all-cause mortality in a large patient population from the international MONitoring Dialysis Outcomes (MONDO) Initiative. All adult incident patients from the MONDO database with more than 5 SNa measurements during the first year on HD were included. All patients were required to survive the first year on HD (defined as the baseline). During the subsequent 2 years of follow-up, all-cause mortality was recorded. The following variability indicators were calculated during baseline: mean SNa and its SD; average real variability (ARV, average the absolute distance of the 2 consecutive SNa measurements), and average directional range (DR, the difference between minimum and maximum values). We used Cox Proportional hazard model with bivariate spline terms to analyze the joint association of SNa and SD, ARV and DR, respectively, with all-cause mortality. While conducting the multivariate Cox regression analyses, patients were stratified into 3 groups of DR (Negative DR: -20≤ DR ≤ -6, Null DR: -6< DR < 6 and Positive DR: 6≤ DR ≤20) with the Null DR as the reference group. We included 20,216 patients in the study. A SNa ≤135 mEq/L was observed to be the strongest predictor of evaluated mortality risk. Higher SNa variability (quantified as SD, ARV, and DR) was also associated with an increased mortality irrespective of SNa levels. When compared with higher SD or ARV, greater DR showed a stronger association with an elevated risk of death. Controlling the Cox Proportional hazard models for additional parameters showed consistent results. Higher SNa variability associated with increased all-cause mortality at all levels of SNa. DR of SNa showed the strongest association with mortality and may constitute a Simple and novel prognostic indicator, easily applicable at the bedside.


The value of innovation in decision-making in health care in Central Eastern Europe - The Sixth International Conference, 2 June 2017, Belgrade, Serbia.
The Pharmacoeconomics Section of the Pharmaceutical Association of Serbia organised a one day international conference on the value of innovation in decision-making in health care in Central and Eastern Europe. The focus of the conference was on reimbursement decisions for medicines using health technology assessment and the use of managed entry agreements (MEAs). The objectives of this conference were firstly to discuss the challenges and opportunities with the use of MEAs in Central and Eastern European countries; secondly the role of patient registries especially with outcome based schemes, and finally new approaches to improve accessibility to new medicines including better managing their entry.


Can concurrent chemoradiotherapy replace surgery and postoperative radiation for locally advanced stage III/IV tonsillar squamous cell carcinoma?
To compare surgery and postoperative radiotherapy (PORT) with the non-surgical combination of chemotherapy and radiation therapy (CCRT) for locally advanced squamous cell carcinoma (SCC) of the tonsil by measuring treatment outcomes and treatment-related complications. The records of 114 patients with non-metastatic stage III/IV tonsillar SCC treated between July, 1998 and December, 2010 were reviewed retrospectively. Among the 114 patients, 65 received PORT and 49 received CCRT. In the PORT group, treatment included wide surgical resection of the tumor with neck dissection and administration of PORT to the primary tumor bed with a median dose of 60 Gy. In the CCRT group, a median dose of 70 Gy was delivered to the gross tumor, and 46 patients received concurrent chemotherapy with i.v. cisplatin. The median follow-up time was 58 months in the PORT group and 44 months in the CCRT group. There was no significant difference between PORT and CCRT in terms of 5-year locoregional recurrence-free survival (88.4% vs. 91.4%, p=0.68), distant metastasis-free survival (88.9% vs. 92.3%, p=0.60), disease-free survival (79.5% vs. 84.2%, p=0.63) or overall survival (78.9% vs. 88.9%, p=0.45). More CCRT patients than PORT patients experienced grade 3 (or higher) hematological toxicities and grade 2 pharyngitis during treatment. Chronic toxicity, manifested as swallowing difficulty, dry mouth and trismus, was similar between the two treatment groups. CCRT provides similar levels of local and distant control in patients with locally advanced tonsillar SCC as PORT, yet fails to show any superiority in preserving functions such as swallowing, saliva production, and mastication.


Six minute walking distance in healthy elderly subjects.
The six minute walking distance (6MWD) test is a commonly used test to estimate functional exercise capacity in patients with chronic diseases including chronic obstructive lung disease. Surprisingly, no attempt has been made to establish normal values for the 6MWD. The aim of this study, therefore, was to evaluate the 6MWD in healthy elderly volunteers and to evaluate its determining factors. Fifty-one healthy subjects aged 50-85 yrs volunteered to participate in the trial. All subjects were free of diseases that could interfere with performance in a walking test. Tests were performed in a quiet 50-m long hospital corridor. Patients were encouraged every 30 s to continue walking as quickly as possible. Walking distance averaged 631+/-93 m and was 84 m greater in the male compared to female subjects (p<0.001). The 6MWD showed significant correlations with age (r=-0.51, p<0.01) and height (r=0.54, p<0.01). Stepwise multiple regression analysis showed that age, height, sex and weight were independent contributors to the 6MWD in healthy subjects, thus explaining 66% of the variability. It is concluded that the six minute walking distance can be predicted adequately using a clinically useful model in healthy elderly subjects. Its variability is explained largely by age, sex, height and weight. Results of the six minute walking distance may be interpreted more adequately if expressed as a percentage of the predicted value.


γ-Tocotrienol-Loaded Liposomes for Radioprotection from Hematopoietic Side Effects Caused by Radiotherapeutic Drugs.
With the successful development and increased use of targeted radionuclide therapy for treating cancer comes the increased risk of radiation injury to bone marrow-both direct suppression and stochastic effects, leading to neoplasia. Herein, we report a novel radioprotector drug, a liposomal formulation of γ-tocotrienol (GT3), or GT3-Nano for short, to mitigate bone marrow radiation damage during targeted radionuclide therapy. Methods: GT3 was loaded into liposomes using passive loading. 64Cu-GT3-Nano and 3H-GT3-Nano were synthesized to study the in vivo biodistribution profile of the liposome and GT3 individually. The radioprotection efficacy of GT3-Nano was assessed after acute 137Cs whole-body irradiation at a sublethal (4 Gy), a lethal (9 Gy), or a single high-dose administration of 153Sm-ethylenediamine-N,N,N',N'-tetrakis(methylene phosphonic acid) (EDTMP). Flow cytometry and fluorescence microscopy were used to analyze hematopoietic cell population dynamics and the cellular site of GT3-Nano localization in the spleen and bone marrow, respectively. Results: Bone marrow uptake and retention (percentage injected dose per gram of tissue) at 24 h was 6.98 ± 2.34 for 64Cu-GT3-Nano and 7.44 ± 2.52 for 3H-GT3-Nano. GT3-Nano administered 24 h before or after 4 Gy of total-body irradiation (TBI) promoted rapid and complete hematopoietic recovery, whereas recovery of controls stalled at 60%. GT3-Nano demonstrated dose-dependent radioprotection, achieving 90% survival at 50 mg/kg against lethal 9-Gy TBI. Flow cytometry of the bone marrow indicated that progenitor bone marrow cells MPP2 and CMP were upregulated in GT3-Nano-treated mice. Immunohistochemistry showed that GT3-Nano accumulates in CD105-positive sinusoid epithelial cells. Conclusion: GT3-Nano is highly effective in mitigating the marrow-suppressive effects of sublethal and lethal TBI in mice. GT3-Nano can facilitate rapid recovery of hematopoietic components in mice treated with the endoradiotherapeutic agent 153Sm-EDTMP.


Progress Toward Polio Eradication - Worldwide, January 2018-March 2020.
Since the Global Polio Eradication Initiative (GPEI) was established in 1988, two of the three wild poliovirus (WPV) serotypes (types 2 and 3) have been eradicated.* Transmission of WPV type 1 (WPV1) remains uninterrupted only in Afghanistan and Pakistan. This report summarizes progress toward global polio eradication during January 1, 2018-March 31, 2020 and updates previous reports (1,2). In 2019, Afghanistan and Pakistan reported the highest number of WPV1 cases (176) since 2014. During January 1-March 31, 2020 (as of June 19), 54 WPV1 cases were reported, an approximate fourfold increase from 12 cases during the corresponding period in 2019. Paralytic poliomyelitis can also be caused by circulating vaccine-derived poliovirus (cVDPV), which emerges when attenuated oral poliovirus vaccine (OPV) virus reverts to neurovirulence following prolonged circulation in underimmunized populations (3). Since the global withdrawal of type 2-containing OPV (OPV2) in April 2016, cVDPV type 2 (cVDPV2) outbreaks have increased in number and geographic extent (4). During January 2018-March 2020, 21 countries reported 547 cVDPV2 cases. Complicating increased poliovirus transmission during 2020, the coronavirus disease 2019 (COVID-19) pandemic and mitigation efforts have resulted in suspension of immunization activities and disruptions to poliovirus surveillance. When the COVID-19 emergency subsides, enhanced support will be needed to resume polio eradication field activities.


Outcome analysis in clinical trial design for acute stroke: physicians' attitudes and choices.
Thrombolysis remains the only proven therapy to benefit acute ischemic stroke (AIS) patients. Recent studies have introduced more sensitive outcome measures such as the shift analysis to detect a treatment effect in AIS trials and are also including imaging as a surrogate of injury. We conducted a cross-sectional, internet-based survey of academic neurologists regarding their attitudes, choices and understanding of various outcome measures in clinical trial design for AIS. The survey population consisted of neurologists who specialize in the care of stroke patients and are on faculty at university-affiliated hospitals in the USA. 152 of 300 neurologists completed the survey. There were 79% men and 21% women. Among commonly used outcome scales in acute stroke, the most frequent ones selected for use as trial primary endpoints were the global statistic (59%), modified Rankin scale (mRS) (52%), and NIHSS (30%). When given choices about which outcome on the mRS would justify a therapeutic intervention, 54% chose a shift analysis of change in the distribution of outcomes and 39% chose a dichotomized outcome (mRS <or=2). A majority of respondents favored health transition states of 4-3, 3-2 and 2-1 on the mRS as clinically worthwhile. Only 2% of the respondents thought that a single transition point on the mRS was clinically meaningful. However, 20% of the respondents did not understand the shift analysis. In addition, nearly two thirds of the respondents believed that the presence of a mismatch on brain imaging is relevant to the success of neuroprotective agents. The majority of respondents accepted an analysis of the entire distribution of the mRS scores as an appropriate endpoint analytic technique in AIS trials and did not require the traditional dichotomized outcome to demonstrate a treatment effect; however, a better understanding of the shift strategy is needed. Our data also support the importance of incorporating mismatch imaging into future neuroprotection trials.


[Host specificity of homoxenous trypanosomatids].
Some problems in a correct using of the term "host specificity" for parasitic protozoans and specifically for the trypanosomatids are discussed. Results of investigation the host specificity of the trypanosomatids obtained by traditional methods are summarized. Host specificity data of some insect-associated trypanosomatids based on the identification of parasites by means of molecular methods is discussed. The subjectivity is an imminent distinctive feature of host specificity investigation in parasitic protozoans--trypanosomatids, especially in parasites of insects and plants. There is a vicious circle, when the conclusions about specificity are related with the necessity of taxonomic identification of the parasites during the process of biodiversity and ecological studies. The taxonomic position of parasite is often determined based on a data of observed hosts specificity. This is quite common in cases, when reliable morphological characters are absent, and it indeed takes place in the homoxenous trypanosomatids. The using of molecular markers only allows to reliably identify and compare the parasites, without involving the properly taxonomic data, and finally to make more objective conclusions about their host specificity. A crucial question in this kind of investigation is an obtaining of adequate and wide set of laboratory cultures (isolates) correctly reflecting the diversity of the hosts. It is always necessary to take in attention a possibility of occasional infections, which could misrepresent obtained results. About 50 cultures isolated from different hosts (mostly Hemiptera: Heteroptera) and places (mostly North Russia) have been examined by means of RAPD, UP-PCR, MLEE and cross DNA hybridization. Some of them were placed in rRNA-based molecular phylogeny. As it was found out, none natural groups of homoxenous trypanosomatids (groups of similar genomes) demonstrated a clear preferential distribution on certain insect taxon of any taxonomic rank,--species, genera, family and even order. It is postulated that the host specificity of insect-associated trypanosomatids is extremely wide.


Bacterial gene abundances as indicators of greenhouse gas emission in soils.
Nitrogen fixing and denitrifying bacteria, respectively, control bulk inputs and outputs of nitrogen in soils, thereby mediating nitrogen-based greenhouse gas emissions in an ecosystem. Molecular techniques were used to evaluate the relative abundances of nitrogen fixing, denitrifying and two numerically dominant ribotypes (based on the > or =97% sequence similarity at the 16S rRNA gene) of bacteria in plots representing 10 agricultural and other land-use practices at the Kellogg biological station long-term ecological research site. Quantification of nitrogen-related functional genes (nitrite reductase, nirS; nitrous oxide reductase, nosZ; and nitrogenase, nifH) as well as two dominant 16S ribotypes (belonging to the phyla Acidobacteria, Thermomicrobia) allowed us to evaluate the hypothesis that microbial community differences are linked to greenhouse gas emissions under different land management practices. Our results suggest that the successional stages of the ecosystem are strongly linked to bacterial functional group abundance, and that the legacy of agricultural practices can be sustained over decades. We also link greenhouse gas emissions with specific compositional responses in the soil bacterial community and assess the use of denitrifying gene abundances as proxies for determining nitrous oxide emissions from soils.


Extraction of the volatile oil from Carum carvi of Tunisia and Lithuania by supercritical carbon dioxide: chemical composition and antiulcerogenic activity.
This study investigates whether the essential oil prepared from Carum carvi seeds exhibits antiulcerogenic activity. Its volatile oil was obtained by supercritical fluid extraction (SFE) and by hydrodistillation. The essential oils were analysed by GC-MS to monitor their composition. The chemical analysis revealed that the essential oils extracted under SFE conditions had high carvone and limonene contents. The antiulcerogenic activity was evaluated by the HCl/ethanol method, which causes injury to the gastric mucosa. Three treated groups received the essential oil (100-300 mg/kg). The reference group received omeprazole (30 mg/kg) and the control group received NaCl. After 30 min, all groups were treated with HCl/EtOH for gastric ulcer induction. The results show C. carvi essential oil enhanced a significant inhibition of 47%, 81% and 88%, respectively, for three doses of essential oil used, which was similar to that induced by omeprazole (95%) (p < 0.005).


SOCIOECONOMIC VARIATIONS IN INDUCED ABORTION IN TURKEY.
This study aimed to identify the levels of, and socioeconomic variations in, income-related inequality in induced abortion among Turkish women. The study included 15,480 ever-married women of reproductive age (15-49) from the 2003 and 2008 waves of the Turkish Demographic and Health Survey. The measured inequalities in abortion levels and their changes over time were decomposed into the percentage contributions of selected socioeconomic factors using ordinary least square analysis and concentration indices were calculated. The inequalities and their first difference (difference in inequalities between 2003 and 2008) were decomposed using the approaches of Wagstaff et al. (2003). Higher socioeconomic characteristics (such as higher levels of wealth and education and better neighbourhood) were found to be associated with higher rates of abortion. Inequality analyses indicated that although deprived women become more familiar with abortion over time, abortion was still more concentrated among affluent women in the 2008 survey. The decomposition analyses suggested that wealth, age, education and level of regional development were the most important contributors to income-related inequality in abortion. Therefore policies that (i) increase the level of wealth and education of deprived women, (ii) develop deprived regions of Turkey, (iii) improve knowledge about family planning and, especially (iv) enhance the accessibility of family planning services for deprived and/or rural women, may be beneficial for reducing socioeconomic variations in abortion in the country.


Virulence genes in the pathogenic yeast Candida albicans.
In recent years, the incidence of fungal infections has been rising all over the world. Although the amount of research in the field of pathogenic fungi has also increased, there is still a need for the identification of reliable determinants of virulence. In this review, we focus on identified Candida albicans genes whose deletant strains have been tested in experimental virulence assays. We discuss the putative relationship of these genes to virulence and also outline the use of new different systems to examine the precise effect in virulence of different genes.


The Role of Autologous Dermal Micrografts in Regenerative Surgery: A Clinical Experimental Study.
The aim of the study was the objective assessment of the effectiveness of a microfragmented dermal extract obtained with Rigenera™ technology in promoting the wound healing process in an in vivo homogeneous experimental human acute surgical wound model. The study included 20 patients with 24 acute postsurgical soft tissue loss and a planned sequential two-stage repair with a dermal substitute and an autologous split-thickness skin graft. Each acute postsurgical soft tissue loss was randomized to be treated either with an Integra® dermal substitute enriched with the autologous dermal micrografts obtained with Rigenera™ technology (group A-Rigenera™ protocol) or with an Integra® dermal substitute only (group B-control). The reepithelialization rate in the wounds was assessed in both groups at 4 weeks through digital photography with the software "ImageJ." The dermal cell suspension enrichment with the Rigenera™ technology was considered effective if the reepithelialized area was higher than 25% of the total wound surface as this threshold was considered far beyond the expected spontaneous reepithelialization rate. In the Rigenera™ protocol group, the statistical analysis failed to demonstrate any significant difference vs. the controls. The old age of the patients likely influenced the outcome as the stem cell regenerative potential is reduced in the elderly. A further explanation for the unsatisfying results of our trial might be the inadequate amount of dermal stem cells used to enrich the dermal substitutes. In our study, we used a 1 : 200 donor/recipient site ratio to minimize donor site morbidity. The gross dimensional disparity between the donor and recipient sites and the low concentration of dermal mesenchymal stromal stem cells might explain the poor epithelial proliferative boost observed in our study. A potential option in the future might be preconditioning of the dermal stem cell harvest with senolytic active principles that would fully enhance their regenerative potential. This trial is registered with trial protocol number NCT03912675.


Eye-hand synergy and intermittent behaviors during target-directed tracking with visual and non-visual information.
Visual feedback and non-visual information play different roles in tracking of an external target. This study explored the respective roles of the visual and non-visual information in eleven healthy volunteers who coupled the manual cursor to a rhythmically moving target of 0.5 Hz under three sensorimotor conditions: eye-alone tracking (EA), eye-hand tracking with visual feedback of manual outputs (EH tracking), and the same tracking without such feedback (EHM tracking). Tracking error, kinematic variables, and movement intermittency (saccade and speed pulse) were contrasted among tracking conditions. The results showed that EHM tracking exhibited larger pursuit gain, less tracking error, and less movement intermittency for the ocular plant than EA tracking. With the vision of manual cursor, EH tracking achieved superior tracking congruency of the ocular and manual effectors with smaller movement intermittency than EHM tracking, except that the rate precision of manual action was similar for both types of tracking. The present study demonstrated that visibility of manual consequences altered mutual relationships between movement intermittency and tracking error. The speed pulse metrics of manual output were linked to ocular tracking error, and saccade events were time-locked to the positional error of manual tracking during EH tracking. In conclusion, peripheral non-visual information is critical to smooth pursuit characteristics and rate control of rhythmic manual tracking. Visual information adds to eye-hand synchrony, underlying improved amplitude control and elaborate error interpretation during oculo-manual tracking.


Strategic planning for residency training programs.
Residency training is practice-based learning that is reflective of the practice environment. As practice changes, changes in residency training are needed. Strategic planning is a process that considers internal and external factors that will impact the future. The planning process includes gathering input, focusing on important issues, developing a consensus, and writing clearly defined goals. The strategic planning process was applied to residency training at Hamot Medical Center. A retreat was held, consensus was developed, and a plan was written. The planning process prepared us to make changes in the types of residency programs we offered. This article describes strategic planning for our residency and progress on our goals.


Kininogenase activity of tonin.
Tonin, known for its specific and direct generation of angiotensin II, was highly purified from rat submaxillary gland and investigated for kininogenase activity. For the substrate, heat-treated plasma from ox blood, and highly purified low-molecular-weight (LMW) and high-molecular-weight (HMW) kininogens, were used. The reaction product formed at pH 8.0 well satisfied the characteristics of kinin, i.e., depressor and oxytocic activities and reactivity with antibradykinin antiserum. Kinin formed by tonin from purified LMW kininogen was identified with bradykinin in high performance liquid chromatography and radioimmunoassay. The results revealed tonin's new capability of forming kinin in addition to the hitherto known pressor angiotensin II, indicating tonin, too, is a member of the "kinin- tensin enzyme system."


Effects of long-term stimulation of textured insoles on postural control in health elderly.
The aim of this study was to confirm the effects of long term (chronic) stimulating surface (textured insole) on body balance of elderly people. Twenty-four healthy elderly individuals were randomly distributed in two groups: control and experimental (67.75±6.04 years, 74.55±12.14 kg, 163.7±8.55 cm, 27.75±3.04 kg/m2). Over one month, control group (CG) used smooth insoles and the experimental group (ExG) used textured insoles every day. Velocity net (Vnet), anteroposterior (VA/P), mediolateral (VM/L) and sway path of CoP were assessed in different eye conditions before and after the experimental procedure. A mixed between-within subject ANOVA was conducted to assess the impact of soft and textured insoles and two visual conditions (vision vs. no vision) across two time periods (α≤0.05). The results showed any statistical difference between groups in each parameter assessed in this study. CoP, Vnet and VM/L in the experimental group showed a statistically significant effect of textured insoles only without vision (CoP: P=0.002; η2=0.35), Vnet P=0.02; η2=0.24, VM/L P=0.04; η2=0.177) whereas VA/P showed no statistically significant effect in the same group and condition. There was no significant effect in Vnet, VA/P, VM/L and COP in control group that used smooth insole for both eye conditions. The results confirm that postural stability improved in healthy elderly individuals, increasing somatosensory information's from feet plantar mechanoreceptors. Long term stimulation with textured insoles decreased CoP, Vnet and VM/L with eyes closed.


Selective unresponsiveness to HBsAg vaccine in newborns related with an in utero passage of hepatitis B virus DNA.
Thirty four out of 158 (22%) newborns to mothers chronically infected by the hepatitis B virus (HBV) did not produce antibodies (Ab) to HBsAg 1 month after the last injection of the HBV vaccine supplemented with HBV specific immunoglobulins. At birth, HBV genome was detected by polymerase chain reaction (PCR) in the peripheral blood mononuclear cells (PBMC) of a large majority (28 out of 34) of these non-responder newborns but never in the other newborns who responded to the HBsAg vaccine. HBV genome was detected in serum, only in some cases (nine out of 34) and never in the absence of HBV DNA in PBMC. For nine out of 14 followed newborns, the absence of response was transitory since anti-HBs Abs appeared after 15 months, without booster, while the HBV genome had disappeared. Unresponsiveness was specific to the HBV envelope protein since all late responders and 15-months-non-responders to the HBsAg vaccine produced normal levels of Abs to the three poliovirus serotypes, to tetanus toxoid and to the pneumococcus polysaccharides. An in utero induced immune tolerance to low doses of HBsAg appears as the most plausible hypothesis to explain this unresponsiveness to HBV vaccine.


Nucleotide polymorphism and phenotypic associations within and around the phytochrome B2 Locus in European aspen (Populus tremula, Salicaceae).
We investigated the utility of association mapping to dissect the genetic basis of naturally occurring variation in bud phenology in European aspen (Populus tremula). With this aim, we surveyed nucleotide polymorphism in 13 fragments spanning an 80-kb region surrounding the phytochrome B2 (phyB2) locus. Although polymorphism varies substantially across the phyB2 region, we detected no signs for deviations from neutral expectations. We also identified a total of 41 single nucleotide polymorphisms (SNPs) that were subsequently scored in a mapping population consisting of 120 trees. We identified two nonsynonymous SNPs in the phytochrome B2 gene that were independently associated with variation in the timing of bud set and that explained between 1.5 and 5% of the observed phenotypic variation in bud set. Earlier studies have shown that the frequencies of both these SNPs vary clinally with latitude. Linkage disequilibrium across the region was low, suggesting that the SNPs we identified are strong candidates for being causally linked to variation in bud set in our mapping populations. One of the SNPs (T608N) is located in the "hinge region," close to the chromophore binding site of the phyB2 protein. The other SNP (L1078P) is located in a region supposed to mediate downstream signaling from the phyB2 locus. The lack of population structure, combined with low levels of linkage disequilibrium, suggests that association mapping is a fruitful method for dissecting naturally occurring variation in Populus tremula.


Harnessing Advances in T Regulatory Cell Biology for Cellular Therapy in Transplantation.
Cellular therapy with CD4FOXP3 T regulatory (Treg) cells is a promising strategy to induce tolerance after solid-organ transplantation or prevent graft-versus-host disease after transfer of hematopoietic stem cells. Treg cells currently used in clinical trials are either polyclonal, donor- or antigen-specific. Aside from variations in isolation and expansion protocols, however, most therapeutic Treg cell-based products are much alike. Ongoing basic science work has provided considerable new insight into multiple facets of Treg cell biology, including their stability, homing, and functional specialization; integrating these basic science discoveries with clinical efforts will support the development of next-generation therapeutic Treg cells with enhanced efficacy. In this review, we summarize recent advances in knowledge of how Treg cells home to lymphoid and peripheral tissues, and control antibody production and tissue repair. We also discuss newly appreciated pathways that modulate context-specific Treg cell function and stability. Strategies to improve and tailor Treg cells for cell therapy to induce transplantation tolerance are highlighted.


KiMoSys 2.0: an upgraded database for submitting, storing and accessing experimental data for kinetic modeling.
The KiMoSys (https://kimosys.org), launched in 2014, is a public repository of published experimental data, which contains concentration data of metabolites, protein abundances and flux data. It offers a web-based interface and upload facility to share data, making it accessible in structured formats, while also integrating associated kinetic models related to the data. In addition, it also supplies tools to simplify the construction process of ODE (Ordinary Differential Equations)-based models of metabolic networks. In this release, we present an update of KiMoSys with new data and several new features, including (i) an improved web interface, (ii) a new multi-filter mechanism, (iii) introduction of data visualization tools, (iv) the addition of downloadable data in machine-readable formats, (v) an improved data submission tool, (vi) the integration of a kinetic model simulation environment and (vii) the introduction of a unique persistent identifier system. We believe that this new version will improve its role as a valuable resource for the systems biology community. Database URL: www.kimosys.org.


Population-based occupational cancer incidence surveillance. Utilization of the telephone interview.
Because population-based surveillance of cancer incidence across a wide variety of industries and occupations is quite rare and because the vast literature in occupational cancer epidemiology concentrates to a great extent on cancer risks among white males, new methods are needed to generate hypotheses about occupational cancer risks. The results of a series of studies conducted during the past six years suggested that the telephone interview could be utilized as an effective method for occupational cancer surveillance. A 10-minute telephone interview that was developed to collect occupational histories, smoking histories, and other related data and some methodologic issues that were tested during a pilot study are described. The authors found the telephone interview to be an effective instrument for obtaining these data. This study suggests that it is important to obtain as high a proportion as possible of the responses from the study patients rather than proxy respondents; that when one cannot interview the patient, proxy respondents can provide much of the data requested; and that supplementing population-based cancer surveillance system data with these interview data is useful in routine monitoring.


Sex differences in acute luteinizing hormone responses to gonadectomy remain after progesterone antagonist and dopamine agonist treatment.
In male rats, LH pulse frequency and amplitude increase dramatically by 24 h after gonadectomy; in females they increase only slightly by this time. Mean FSH levels increase significantly in both sexes by 24 h after gonadectomy. The objectives of the present studies were to compare pulsatile LH, FSH, and prolactin (PRL) secretion in intact versus gonadectomized and in male versus female rats, and to determine whether the acute postovariectomy lag in LH rise is due to a lingering effect of the higher PRL and/or progesterone (P) levels seen in intact females. LH pulse amplitude, frequency, and mean levels increased significantly by 24 h after gonadectomy in both sexes, but the increases were greater in the males. FSH mean levels, but not pulse amplitude or frequency, increased similarly in both sexes by 24 h after gonadectomy. PRL did not change with gonadectomy. Treatment with CB-154 (a dopamine agonist), with or without RU486 (a P antagonist), 1 h before gonadectomy significantly suppressed pulsatile PRL secretion 1 day later in both sexes. There was no effect of either treatment on LH secretion. We have demonstrated that there is a sex difference in LH, but not FSH or PRL, pulsatility at 24 h after gonadectomy, and that female rats' higher PRL and P levels do not account for their slow rate of LH rise after ovariectomy.


Foster care youth and the development of autonomy.
Homelessness, unemployment, and food insecurity are the unfortunate reality for many young adults who age out of the foster care system. These rates remain high even for youth who participate in independent living programmes prior to exiting foster care. These high rates of poor outcomes suggest that many foster care youth are inadequately prepared to transition to adulthood. In order to improve services for youth preparing to age out of foster care, it is important to identify factors that contribute to these adverse outcomes and that could become targets of further interventions. One such factor, an underdeveloped sense of autonomy, may predispose youth to poor outcomes such as limited educational attainment, unstable housing, and unemployment. At least in Western cultures that value individualism, interventions that foster the development of autonomy during adolescence could potentially improve outcomes for youth in foster care. This article aims to review factors that promote the development of autonomy and discusses the unique barriers to autonomy development faced by youth in foster care. I conclude with several intervention strategies that could facilitate the development of autonomy in foster care youth and recommendations for future research.


The Clinical Trials Mosaic: Toward a Range of Clinical Trials Designs to Optimize Evidence-Based Treatment.
Dichotomizing clinical trials designs into nomothetic (e.g., randomized clinical trials or RCTs) versus idiographic (e.g., N-of-1 or case studies) precludes use of an array of hybrid designs and potential research questions between these extremes. This paper describes unique clinical evidence that can be garnered using idiographic clinical trials (ICTs) to complement RCT data. Proposed and illustrated herein is that innovative combinations of design features from RCTs and ICTs could provide clinicians with far more comprehensive information for testing treatments, conducting pragmatic trials, and making evidence-based clinical decisions. Mixed model trajectory analysis and unified structural equations modeling were coupled with multiple baseline designs in (a) a true N-of-1 pilot study to improve severe autism-related communication deficits and (b) a small sample preliminary study of two complimentary interventions to relieve wheelchair discomfort. Evidence supported certain mechanisms of treatment outcomes and ruled out others. Effect sizes included mean phase differences (i.e., effectiveness), trajectory slopes, and differences in path coefficients between study phases. ICTs can be analyzed with equivalent rigor as, and generate effect sizes comparable to, RCTs for the purpose of developing hybrid designs to augment RCTs for pilot testing innovative treatment, efficacy research on rare diseases or other small populations, quantifying within-person processes, and conducting clinical trials in many situations when RCTs are not feasible.


Molecular characterization of berberine bridge enzyme genes from opium poppy.
In Papaver somniferum (opium poppy) and related species, (S)-reticuline serves as a branch-point intermediate in the biosynthesis of numerous isoquinoline alkaloids. The berberine bridge enzyme (BBE) ([S]-reticuline:oxygen oxidoreductase [methylene bridge forming], EC 188.8.131.52) catalyzes the stereospecific conversion of the N-methyl moiety of (S)-reticuline into the berberine bridge carbon of (S)-scoulerine and represents the first committed step in the pathway leading to the antimicrobial alkaloid sanguinarine. Three unique genomic clones (bbe1, bbe2, and bbe3) similar to a BBE cDNA from Eschscholtzia californica (California poppy) were isolated from opium poppy. Two clones (bbe2 and bbe3) contained frame-shift mutations of which bbe2 was identified as a putative, nonexpressed pseudogene by RNA blot hybridization using a gene-specific probe and by the lack of transient expression of a chimeric gene fusion between the bbe2 5' flanking region and a beta-glucuronidase reporter gene. Similarly, bbe1 was shown to be expressed in opium poppy plants and cultured cells. Genomic DNA blot-hybridization data were consistent with a limited number of bbe homologs. RNA blot hybridization showed that bbe genes are expressed in roots and stems of mature plants and in seedlings within 3 d after germination. Rapid and transient BBE mRNA accumulation also occurred after treatment with a fungal elicitor or with methyl jasmonate. However, sanguinarine was found only in roots, seedlings, and fungal elicitor-treated cell cultures.


Natural immunity to Sindbis virus is influenced by host tissue sialic acid content.
Recent studies have shown that the sialic acid content of Sindbis virus influences both its ability to active the alternative pathway in vitro and its susceptibility to complement dependent clearance from the bloodstream in vivo. Other studies have shown that the sialic acid content of Sindbis virus is determined by the host in which it is propagated. Because individuals vary in their cell surface sialic acid content, it is possible they also vary in their ability to defend themselves against Sindbis virus infection by virtue of their ability to modify the virus sialic acid content and thereby the capacity of the virus to activate the alternative pathway. To test this hypothesis, outbred Swiss mice were injected subcutaneously with Sindbis virus. There was a significant positive correlation between the level of viremia 18 hr after infection and the sialic acid content of the host's erythrocytes. In addition, animals with erythrocyte sialic acid levels equal to or greater than the mean had a higher level of viremia than animals with erythrocyte sialic acid levels less than the mean. Finally, animals that had muscle sialic acid levels equal to or greater than the mean had a higher incidence of viremia than animals with muscle sialic acid levels less than the mean. These studies suggest that the amount of tissue sialic acid in an individual host influences its ability to resist Sindbis virus infection.


Sonographic evaluation of intravascular volume status in the surgical intensive care unit: a prospective comparison of subclavian vein and inferior vena cava collapsibility index.
Traditional methods for intravascular volume status assessment are invasive and are associated significant complications. While focused bedside sonography of the inferior vena cava (IVC) has been shown to be useful in estimating intravascular volume status, it may be technically difficult and limited by patient factors such as obesity, bowel gas, or postoperative surgical dressings. The goal of this investigation is to determine the feasibility of subclavian vein (SCV) collapsibility as an adjunct to IVC collapsibility in intravascular volume status assessment. A prospective study was conducted on a convenience sample of surgical intensive care unit patients to evaluate interchangeability of IVC collapsibility index (IVC-CI) and SCV-CI. After demographic and acuity of illness information was collected, all patients underwent serial, paired assessments of IVC-CI and SCV-CI using portable ultrasound device (M-Turbo; Sonosite, Bothell, WA). Vein collapsibility was calculated using the formula [collapsibility (%) = (max diameter - min diameter)/max diameter × 100%]. Paired measurements from each method were compared using correlation coefficient and Bland-Altman measurement bias analysis. Thirty-four patients (mean age 56 y, 38% female) underwent a total of 94 paired SCV-CI and IVC-CI sonographic measurements. Mean acute physiology and chronic health evaluation II score was 12. Paired SCV- and IVC-CI showed acceptable correlation (R(2) = 0.61, P < 0.01) with acceptable overall measurement bias [Bland-Altman mean collapsibility difference (IVC-CI minus SCV-CI) of -3.2%]. In addition, time needed to acquire and measure venous diameters was shorter for the SCV-CI (70 s) when compared to IVC-CI (99 s, P < 0.02). SCV collapsibility assessment appears to be a reasonable adjunct to IVC-CI in the surgical intensive care unit patient population. The correlation between the two techniques is acceptable and the overall measurement bias is low. In addition, SCV-CI measurements took less time to acquire than IVC-CI measurements, although the clinical relevance of the measured time difference is unclear.


Vitex negundo Linn.: phytochemical composition, nutritional analysis, and antioxidant and antimicrobial activity.
Vitex negundo (VN) is a widely used plant in folk medicine, namely for the treatment of jaundice, wounds, body ache, toothache, asthma, eye pain, and migraine. These effects have been increasingly attributed to its chemical composition. Here, we assessed the VN chemical and nutritional composition and biological activity, with particular emphasis on antioxidant and antimicrobial effects. VN methanol and hexane extracts revealed the presence of important phytochemical, such as terpenoids, polyphenol, steroids, saponins, phenolic compound and flavonoids. Total phenolic content of VN methanol extract from bark was 1082.473 mg/g GAE and that of leaves was 1382.984 mg/g GAE. The total flavonoids content in VN methanol extract from VN bark was 127.744 mg/g QE and that of leaves was 123.776 mg/g QE. VN methanol extract from bark exhibited high antioxidant effects (IC50=38.47 ppm). The content (%) of ash, moisture, crude fiber, crude protein and fat in VN leaves was, respectively, 7.86%, 18.35%, 6.52%, 9.687% and 6.19%. VN leaves methanol extract revealed antimicrobial activity against Bacillus subtilis and Staphylococcus aureus, with inhibition halos being, respectively, 13 mm and 14 mm, and the MBC values were found to be 1.562 mg/mL and 6.25 mg/mL, respectively. Similarly, VN bark methanol extract led to inhibition halos of 18 mm and 15 mm for B. subtilis and S. aureus, respectively, and the MBC values were found to be 2.372 mg/mL and 0.245 mg/mL. GC-MS analysis of the VN bark methanol extract revealed that monoolein was the major compounds, with an area of 0.57%. Thus, our results encourage the potential use of VN as a medicinal product, with high protein contents, and prominent antioxidant and anti-bacterial effects.


Physical Activity, Parental History of Premature Coronary Heart Disease, and Incident Atherosclerotic Cardiovascular Disease in the Atherosclerosis Risk in Communities (ARIC) Study.
The effects of some atherosclerotic cardiovascular disease (ASCVD) risk factors vary according to whether an individual has a family history (FHx) of premature coronary heart disease (CHD). Physical activity (PA) is associated with reduced risk of ASCVD, but whether this association varies by FHx status is not well established. We evaluated 9996 participants free of ASCVD at baseline. FHx of premature CHD was defined as CHD occurring in a father before age 55 or mother before age 60. PA, assessed by a Baecke questionnaire, was converted into minutes/week of moderate or vigorous exercise and categorized per American Heart Association guidelines as recommended, intermediate, or poor. Incident ASCVD was defined as incident myocardial infarction, fatal CHD, or stroke. Multivariable-adjusted Cox hazard models were used. The mean age was 54±6 years, 56% were women, and 21% of black race. Participants with and without a FHx of premature CHD reported similar levels of PA at baseline (423 versus 409 metabolic equivalents of task×min/week, respectively, P=0.852), and ≈40% of both groups met American Heart Association recommended PA levels. Over a mean follow-up of 20.9 years, there were 1723 incident ASCVD events. Compared to those with poor PA adherence to American Heart Association guidelines, participants who reported PA at recommended levels had significantly lower risk of incident ASCVD after adjustment for demographics and lifestyle factors (hazard ratio 0.84, 95% CI 0.74-0.94), but this association was not modified by FHx status (P-interaction=0.680). PA was associated with a reduced risk of ASCVD among individuals with and without a FHx of premature CHD.


Surgical training fit for the future: the need for a change.
Postgraduate training in surgical specialties is one of the longest training programmes in the medical field. Most of the surgical training programmes require 5-6 years of postgraduate training to become qualified. This is usually followed by 1-2 years of fellowship training in a subspecialised interest. This has been the case for the last 20-30 years with no significant change. The surgical practice is transforming quickly due to the advances in medical technology. This transformation is not matched in the postgraduate training, there is minimal exposure to the new technological advances in early years of postgraduate training. The current postgraduate training in surgical specialties is not fit for the future. Early exposure to robotic and artificial intelligence technologies is required. To achieve this, a significant transformation of surgical training is necessary, which requires a new vision and involves significant investment. We discuss the need for this transformation in the postgraduate surgical specialties training and analyse the threats and opportunities in relation to this transformation.


Description of Pelomonas aquatica sp. nov. and Pelomonas puraquae sp. nov., isolated from industrial and haemodialysis water.
Three Gram-negative, rod-shaped, non-spore-forming bacteria (strains CCUG 52769T, CCUG 52770 and CCUG 52771) isolated from haemodialysis water were characterized taxonomically, together with five strains isolated from industrial waters (CCUG 52428, CCUG 52507, CCUG 52575T, CCUG 52590 and CCUG 52631). Phylogenetic analysis based on 16S rRNA gene sequences indicated that these isolates belonged to the class Betaproteobacteria and were related to the genus Pelomonas, with 16S rRNA gene sequence similarities higher than 99% with the only species of the genus, Pelomonas saccharophila and to Pseudomonas sp. DSM 2583. The type strains of Mitsuaria chitosanitabida and Roseateles depolymerans were their closest neighbours (97.9 and 97.3% 16S rRNA gene sequence similarity, respectively). Phylogenetic analysis was also performed for the internally transcribed spacer region and for three genes [hoxG (hydrogenase), cbbL/cbbM (Rubisco) and nifH (nitrogenase)] relevant for the metabolism of the genus Pelomonas. DNA-DNA hybridization, major fatty acid composition and phenotypical analyses were carried out, which included the type strain of Pelomonas saccharophila obtained from different culture collections (ATCC 15946T, CCUG 32988T, DSM 654T, IAM 14368T and LMG 2256T), as well as M. chitosanitabida IAM 14711T and R. depolymerans CCUG 52219T. Results of DNA-DNA hybridization, physiological and biochemical tests supported the conclusion that strains CCUG 52769, CCUG 52770 and CCUG 52771 represent a homogeneous phylogenetic and genomic group, including strain DSM 2583, clearly differentiated from the industrial water isolates and from the Pelomonas saccharophila type strain. On the basis of phenotypic and genotypic characteristics, these strains belong to two novel species within the genus Pelomonas, for which the names Pelomonas puraquae sp. nov. and Pelomonas aquatica sp. nov. are proposed. The type strains of Pelomonas puraquae sp. nov. and Pelomonas aquatica sp. nov. are CCUG 52769T (=CECT 7234T) and CCUG 52575T (=CECT 7233T), respectively.


Gender differences in functional status in middle and older age: are there any age variations?
The present study examines gender differences in changes in functional status after age 50 and how such differences vary across different age groups. Data came from the Health and Retirement Study, involving up to six repeated observations of a national sample of Americans older than 50 years of age between 1995 and 2006. We employed hierarchical linear models with time-varying covariates in depicting temporal variations in functional status between men and women. As a quadratic function, the worsening of functional status was more accelerated in terms of the intercept and rate of change among women and those in older age groups. In addition, gender differences in the level of functional impairment were more substantial in older persons than in younger individuals, although differences in the rate of change between men and women remained constant across age groups. A life course perspective can lead to new insights regarding gender variations in health within the context of intrapersonal and interpersonal differences. Smaller gender differences in the level of functional impairment in the younger groups may reflect improvement of women's socioeconomic status, greater rate of increase in chronic diseases among men, and less debilitating effects of diseases.


2019nCoVAS: Developing the Web Service for Epidemic Transmission Prediction, Genome Analysis, and Psychological Stress Assessment for 2019-nCoV.
Since the COVID-19 epidemic is still expanding around the world and poses a serious threat to human life and health, it is necessary for us to carry out epidemic transmission prediction, whole genome sequence analysis, and public psychological stress assessment for 2019-nCoV. However, transmission prediction models are insufficiently accurate and genome sequence characteristics are not clear, and it is difficult to dynamically assess the public psychological stress state under the 2019-nCoV epidemic. Therefore, this study develops a 2019nCoVAS web service (http://www.combio-lezhang.online/2019ncov/home.html) that not only offers online epidemic transmission prediction and lineage-associated underrepresented permutation (LAUP) analysis services to investigate the spreading trends and genome sequence characteristics, but also provides psychological stress assessments based on such an emotional dictionary that we built for 2019-nCoV. Finally, we discuss the shortcomings and further study of the 2019nCoVAS web service.


PEPFAR Transitions to Country Ownership: Review of Past Donor Transitions and Application of Lessons Learned to the Eastern Caribbean.
The US President's Emergency Plan for AIDS Relief (PEPFAR) has shifted from an emergency response to a sustainable, country-owned response. The process of transition to country ownership is already underway in the Eastern Caribbean; the Office of the US Global AIDS Coordinator (OGAC) has advised the region that PEPFAR funding is being redirected away from the Eastern Caribbean toward Caribbean countries with high disease burden to strengthen services for key populations. This article seeks to highlight and apply lessons learned from other donor transitions to support a successful transition of HIV programs in the Eastern Caribbean. Based on a rapid review of both peer-reviewed and gray literature on donor transitions to country ownership in family planning, HIV, and other areas, we identified 48 resources that addressed key steps in the transition process and determinants of readiness for transition. Analysis of the existing literature revealed 6 steps that could help ensure successful transition, including developing a clear roadmap articulated through high-level diplomacy; investing in extensive stakeholder engagement; and supporting monitoring and evaluation during and after the transition to adjust course as needed. Nine specific areas to assess a country's readiness for transition include: leadership and management capacity, political and economic factors, the policy environment, identification of alternative funding sources, integration of HIV programs into the wider health system, the institutionalization of processes, the strength of procurement and supply chain management, identification of staffing and training needs, and engagement of civil society and the private sector. In the Caribbean, key areas requiring strengthening to ensure countries in the region can maintain the gains made under PEPFAR include further engaging civil society and the private sector, building the capacity of NGOs to take on essential program functions, and maintaining donor support for targeted capacity building and long-term monitoring and evaluation efforts.