Long-lasting effects of briefly flashed words and pseudowords in ultrarapid serial visual presentation.
Our ability to identify even complex scenes in rapid serial visual presentation (RSVP) is astounding, but memory for such items seems lacking. Rather than pictures, we used streams of more than 200 verbal stimuli, rushing by on the screen at a rate of more than 12 items per second while participants had to detect infrequent names (Experiments 1 and 2) or words written in capitals (Experiment 3). By direct and indirect tests, we investigated what is remembered of these masses of task-irrelevant distractor words and pseudowords embedded in an RSVP stream. Lexical decision, the indirect test applied either immediately after each stimulus train or with a delay, revealed strong long-term priming effects. Relative to stimuli not shown before, lexical decisions were faster and more accurate to words but slower to pseudowords. The size of these effects mirrored how often words and pseudowords had occurred in a stream, suggesting that memory traces are strengthened with successive presentations and survive for several minutes at least. Moreover, in a direct test (old-new categorization), words as well as pseudowords benefited from prior occurrence in an RSVP stream if they had occurred more than once. These findings parallel recent physiological and behavioral evidence for memory consolidation of distractor pictures in RSVP and highlight that, despite huge numbers of interfering stimuli, distractor words and pseudowords exhibit long-lasting memory effects. Consolidation seems to progress at higher cognitive levels at the same time that subsequent stimuli are perceptually processed.


Mental Health Services Provision in Primary Care and Emergency Department Settings: Analysis of Blended Fee-for-Service and Blended Capitation Models in Ontario, Canada.
Treating mental illnesses in primary care is increasingly emphasized to improve access to mental health services. Although family physicians (FPs) or general practitioners are in an ideal position to provide the bulk of mental health care, it is unclear how best to remunerate FPs for the adequate provision of mental health services. We examined the quantity of mental health services provided in Ontario's blended fee-for-service and blended capitation models. We evaluated the impact of FPs switching from blended fee-for-service to blended capitation on the provision of mental health services in primary care and emergency department using longitudinal health administrative data from 2007 to 2016. We accounted for the differences between those who switched to blended capitation and non-switchers in the baseline using propensity score weighted fixed-effects regressions to compare remuneration models. We found that switching from blended fee-for-service to blended capitation was associated with a 14% decrease (95% CI 12-14%) in the number of mental health services and an 18% decrease (95% CI 15-20%) in the corresponding value of services. This result was driven by the decrease in services during regular-hours. During after-hours, the number of services increased by 20% (95% CI 10-32%) and the corresponding value increased by 35% (95% CI 17-54%). Switching was associated with a 4% (95% CI 1-8%) decrease in emergency department visits for mental health reasons. Blended capitation reduced provision of mental health services without increasing emergency department visits, suggesting potential efficiency gain in the blended capitation model in Ontario.


[Predicting the efficacy of rehabilitation in patients with prior myocardial infarction].
The results of a 2-year follow-up of 400 patients with prior myocardial infarction (MI) and bicycle ergometric findings of intracardiac hemodynamic parameters and oxygen supply during exercise tests, and the criteria for tetrachoric index significance within the confidence intervals were used to reveal the factors predicting the efficacy of rehabilitative treatment. To predict decreased working capacity in the long-term period is determined by the extent of lesion after myocardial reinfarction, while angina pectoris and arterial hypertension are of significance in patients without reinfarction. A role of dynamic indices was defined in predicting decreased working capacity. Further lowered working capacity may be judged from the changes occurring in threshold exercise capacity and left ventricular end-diastolic volume in the first 6 months of postinfarction.


[Diagnosis and treatment of early bleedings after open-heart surgery].
On the basis of practical experience of the clinic for Cardiovascular Surgery and up-to-date literature data the causes of early bleedings after open-heart surgery are summarized. The main clinical, roentgenological and laboratory features of the bleeding and the methods for the assessment of their origin are demonstrated. The authors consider pathophysiologic causes of hemocoagulation disturbances after surgery with artificial circulation. Characteristics of clinical and laboratory tests for coagulation and hemostasis disturbances and the algorhythms for their interpretation are described. Both nonspecific and pathogenetic methods for management of coagulopathy bleedings in early postoperative period have been described and discussed.


Retrospective analysis of axial skeleton osteosarcoma in 22 large-breed dogs.
Medical-records of 22 large-breed dogs (>15 kg) with osteosarcoma (OSA) of the axial skeleton were reviewed to determine prevalence of metastasis and survival associated with this neoplasm. All dogs were treated with more than 1 mode of therapy including palliative radiation (n = 12), definitive radiation (n = 8), surgery (n = 7), chemotherapy (n = 12), or some combination of these therapies. Metastasis was documented in 10 of 22 dogs (46%), and the median survival for all dogs was 137 days. Primary cause of death was local tumor recurrence (54%). Breed (retriever versus purebred versus mixed-breed survival was 100, 182, and 264 days, respectively) and radiation therapy protocol (survival in dogs treated with palliative radiation therapy versus those treated with definitive radiation therapy was 79 and 265 days, respectively) were significantly related to survival (P < .05). Prevalence of metastasis and median survival for large-breed dogs with axial skeleton OSA seems to be similar to that reported for large-breed dogs with appendicular skeleton OSA. Definitive radiation therapy may have a role in the treatment of axial skeleton osteosarcoma.


[Peptic ulcer: facts and questions -- 2010].
Etiology and clinical manifestation of the peptic ulcer keep changes nowadays. Helicobacter pylori-infection, nonsteroidal anti-inflammatory drugs and small dosage acetic acid treatment are the main etiological factors. Helicobacter pylori positive peptic ulcer can be treated with eradication of the bacterium. Prevention of the NSAID-ulcer and the prescription of the acid suppressive therapy depend on the gastrointestinal and cardiovascular risk factors of patient. Despite of the effective therapies, there are still questions to answer. The number of Helicobacter pylori and NSAID negative ulcers is likely to increase, their therapy must be clarified. There's a fall in the eradication rate of Helicobacter pylori infection, the optimal treatment is missing.


Marine compounds inhibit growth of multiple myeloma in vitro and in vivo.
The prognosis of patients with multiple myeloma (MM) is still dismal despite recent improvements achieved by introducing new therapeutic agents. However, there remains an urgent need for progress in myeloma drug development. We here show that novel marine-derived compounds can exert potent anti-myeloma activity. Nine marine-derived compounds were applied at low nM concentrations (0.1-100 nM) to MM cell lines (OPM-2, NCI-H929, U266, RPMI-8226), to primary human myeloma cells and to peripheral blood mononuclear cells. Apoptosis was determined by flow cytometry. In addition, eGFP-transgenic MM cell lines growing with mesenchymal cells from bone marrow were used to visualize tumors by fluorescence stereomicroscopy. Anti-myelomaactivities were studied in vitro in 3D spheroids and in vivo in myeloma xenografts on chicken embryos. Tumor size was analyzed by measuring GFP content with a GFP ELISA. Anti-angiogenic activities of compounds were tested in an in vivo gelatin sponge assay with conditioned media from primary bone marrow-derived endothelial cells. We identified a subset of marine compounds with strong anti-myeloma activity in vitro and in vivo. Moreover, some of the compounds inhibited myeloma-related angiogenesis in the in vivo gelatin sponge assay. They merit further drug development to improve treatment options for MM.


Life Cycle Assessment on Wave and Tidal Energy Systems: A Review of Current Methodological Practice.
Recent decades have witnessed wave and tidal energy technology receiving considerable attention because of their low carbon emissions during electricity production. However, indirect emissions from their entire life cycle should not be ignored. Therefore, life cycle assessment (LCA) has been widely applied as a useful approach to systematically evaluate the environmental performance of wave and tidal energy technologies. This study reviews recent LCA studies on wave and tidal energy systems for stakeholders to understand current status of methodological practice and associated inherent limitations and reveal future research needs for application of LCA on wave and tidal technologies. The conformance of the selected LCAs to ISO 14040 (2006) and 14044 (2006) are critically analyzed in strict accordance with the ISO stepwise methodologies, namely, goal and scope definition, life cycle inventory (LCI) analysis, as well as life cycle impact assessment (LCIA). Our systematically screening of these studies indicates that few of the selected studies are of strict conformance with ISO 14040 and 14044 standards, which makes the results unreliable and thus further reduces the confidence of interested stakeholders. Further, our review indicates that current LCA practice on wave and tidal energies is lacking consideration of temporal variations, which should be addressed in future research, as it causes inaccuracy and uncertainties.


[Influence of immobilized forms of sodium hypochlorite on the immediate and long-term results of treatment of the patients with diffuse peritonitis].
An analysis of complex examination and results of treatment was made in 290 patients with diffuse peritonitis. The patients were divided into two groups according to way of sanation of the abdominal cavity. The sanation with 0.03% aqueous solution of sodium hypochlorite was used for the first group of 155 patients. The immobilized forms of sodium hypochlorite in carboxymethyl cellulose gel were applied in the second group. The rate of postoperative complications was decreased on 15.4%, the lethality--on 8.2% in the case of application of the immobilized forms of sodium hypochlorite. The developed technology allowed increasing of physical component of life quality of the patients in 1.3 times, though it didn't influence on psychical component.


Analysis for calibration pre-post difference in BP estimation of Galaxy Watch.
The use of smartwatches has become increasingly common with the release of major products such as the Galaxy Watch by Samsung and the Apple Watch by Apple. The common aim of smartwatches is to target the healthcare market with a wearable, physically-attached device, with blood pressure at the core. As blood pressure is an important biomarker for cardiovascular-related diseases, it is a necessary index to inspect in hospitals when checking an individual's health state. Smartwatches are expected to provide a cuff-less, non-invasive method of estimating blood pressure. However, not many experiments have been conducted on blood pressure datasets obtained from smartwatches. Smartwatches are unique compared to other devices because they require "calibration" to sustain their accuracy.In this paper, we investigate the difference between before and after calibration to better understand the calibration pattern. Not only do we seek to understand the demographic differences in calibration, but we also analyze the possible variables that influence calibration differences. Our results show that hypertensive patients are more prone to high calibration differences, which implies that the calibration period should be adjusted by considering the average blood pressure of users.Clinical Relevance- This paper investigates the possibility for daily BP measurement to be used as clinical data while suggesting proper method to sustain its validity.


Real-time telementoring with 3D drawing annotation in robotic surgery.
In telementoring, differences in teaching methods affect local surgeons' comprehension. Because the object to be operated on is a three-dimensional (3D) structure, voice or 2D annotation may not be sufficient to convey the instructor's intention. In this study, we examined the usefulness of telementoring using 3D drawing annotations in robotic surgery. Kyushu University and Beppu Hospital are located 140 km apart, and the study was conducted using a Saroa™ surgical robot by RIVERFIELD Inc. using a commercial guarantee network on optical fiber. Twenty medical students performed vertical mattress suturing using a swine intestinal tract under surgical guidance at the Center for Advanced Medical Innovation Kyushu University. Surgical guidance was provided by Beppu Hospital using voice, 2D, and 3D drawing annotations. All robot operations were performed using 3D images, and only the annotations were independently switched between voice and 2D and 3D images. The operation time, needle movement, and performance were also evaluated. The 3D annotation group tended to have a shorter working time than the control group (25.6 ± 63.2 vs. - 36.7 ± 65.4 min, P = 0.06). The 3D annotation group had fewer retries than the control group (1.3 ± 1.7 vs. - 1.1 ± 0.7, P = 0.006), and there was a tendency for fewer needle drops (0.4 ± 0.7 vs. - 0.5 ± 0.9, P = 0.06). The 3D annotation group scored significantly higher than the control group on the Global Evaluate Assessment of Robot Skills (16.8 ± 2.0 vs. 22.8 ± 2.4, P = 0.04). The 3D annotation group also scored higher than the voice (13.4 ± 1.2) and 2D annotation (16.2 ± 1.8) groups (3D vs. voice: P = 0.03, 3D vs. 2D: P = 0.03). Telementoring using 3D drawing annotation was shown to provide good comprehension and a smooth operation for local surgeons.


Pollen feeding in an orb-weaving spider.
Juvenile orb-weaving spiders appear in spring, when insect prey are scarce but when aerial plankton, such as pollen and fungus spores, is abundant. Microscopic organic matter may be the main food of orb-weaving spiderlings, with insects providing only a dietary supplement. Pollen, which is caught on the sticky spirals of Araneus diadematus orb webs, doubles the life expectancy of spiderlings and alters their web-spinning behavior, so that they spin more frequently than do fasting controls. Fungus spores do not have the same nutritional value as pollen and may be deleterious to the spiderlings.


Potent Half-Sandwich 16-/18-Electron Iridium(III) and Ruthenium(II) Anticancer Complexes with Readily Available Amine-Imine Ligands.
The synthesis and biological evaluation of stable 16-electron half-sandwich complexes have remained scarce. We herein present the different coordination modes (16-electron or 18-electron) between half-sandwich iridium(III) complexes and ruthenium(II) complexes derived from the same amine-imine ligands chelating hybrid sp3-N/sp2-N donors. The 16-electron iridium(III) and 18-electron ruthenium(II) complexes with different counteranions were obtained and identified by various techniques. The promising cytotoxicity of these complexes against A549 lung cancer cells, cisplatin-resistant A549/DPP cells, cervical carcinoma HeLa cells, and human hepatocellular liver carcinoma HepG2 cells was observed with IC50 values ranging from 5.4 to 16.3 μM. Moreover, these complexes showed a certain selectivity (selectivity index: 2.1-3.7) toward A549 cells and BEAS-2B normal cells. The variation of metal center, counteranion, 16/18-electron coordination mode, and ligand substituents showed little influence on the cytotoxicity and selectivity of these complexes. The mechanism of action study showed that these complexes could target mitochondria, induce the depolarization of the mitochondrial membrane, and promote the generation of intracellular reactive oxygen species (ROS). Further, the induction of cell apoptosis and the perturbation of the cell cycle in the G0/G1 phase were also observed for these complexes. Overall, it seems that the redox mechanism dominated the anticancer efficacy of these complexes.


Recombinant adiponectin ameliorates liver ischemia reperfusion injury via activating the AMPK/eNOS pathway.
It is of importance to minimize ischemia reperfusion (I/R) injury during liver operations. Reducing the inflammatory reaction is an effective way to achieve this goal. Notably, adiponectin (APN) was found to have anti-inflammatory activity in heart and renal I/R injury. Herein, we investigated the role of APN in liver I/R injury. WISTAR RATS WERE RANDOMIZED TO FOUR GROUPS: (1) sham group; (2) I/R control group; (3) I/R+APN group; and (4) I/R+APN+AMPK inhibitor group. Liver and blood samples were collected 6h and 24h after reperfusion. Liver function and histopathologic changes were assessed. Macrophage and neutrophil infiltration was detected by immunohistochemistry staining, while pro-inflammatory cytokines and chemokines released in the liver were measured using ELISA and RT-PCR, respectively. Apoptosis was analyzed by TUNEL staining and caspase-3 expression in the liver. Downstream molecules of APN were investigated by Western blotting. Circulatory APN was down-regulated during liver I/R. When exogenous APN treatment was administered during liver I/R, alanine transaminase (ALT) and aspartate aminotransferase (AST) were decreased, and less hepatocyte necrosis was observed. Less inflammatory cell infiltration and pro-inflammatory cytokines/chemokines release were also observed in the I/R+APN group when compared with the I/R control group. APN treatment also reduced hepatocyte apoptosis, evidenced by reduced TUNEL positive cells and less caspase-3 expression in the reperfused liver. Finally, the AMPK/eNOS pathway was found to be activated by APN, and administration of an AMPK inhibitor reversed the beneficial effects of APN. APN can protect the liver from I/R injury by reducing the inflammatory response and hepatocyte apoptosis, a process that likely involves the AMPK/eNOS pathway. The current study provides a potential pharmacologic target for liver I/R injury.


The contributions of study abroad to home countries: an agential perspective.
Contributions to home country after international higher education (IHE) have long been considered within the traditional frameworks of brain drain or brain circulation. However, recent scholarship has hinted at more nuances into this issue than what has been predominantly discussed. This study focuses on IHE graduate agency to investigate the contributions of studying abroad to a home country. It builds from international-comparative fieldwork that included interviews with 50 recent Turkish IHE graduates who studied in four purposefully selected countries-Azerbaijan, Bulgaria, Germany and the UK-and who either stayed or returned to their home country afterwards. The findings highlight the role of agency in IHE graduates' contributions to their home country. Returning to the home country does not equate to contributing to it, as some participants expressed that they contribute better from abroad while others refuse to contribute even after returning. The study also demonstrates that combining individual agency with push-pull factors emanating from the home country provides a more holistic explanation, as the home country dynamics have been found to be influential on agential stances regarding contributions.


Expression of sperm microRNAs related to bull fertility: A systematic review.
In this study we proposed to address the following question: "Are there differentially expressed sperm microRNAs related to fertility in bulls?". A systematic review of scientific literature until November 2022 was performed, in accordance with PRISMA guidelines. The main outcome was differentially expressed sperm microRNA from bulls with low versus high fertility profiles identified by using different methods such as field fertility evaluation and sperm laboratory analysis. Were identified 786 documents, of which 13 were selected for qualitative analysis. A total of 182 unique differentially expressed miRNAs were identified, among these, 49 miRNAs were found in common between at least two studies. It is believed that from these 49 miRNAs, it is possible that miRNAs such as miR-10a, -10b, -103, -15b, -122, -125b, -126-5p, -151-5p, -193a-5p, -196a, -27a-5p and -99b could be potential universal biomarkers to assess the reproductive potential of males.


Improving access to primary care and annual health checks for people who have a learning disability: a multistakeholder qualitative study.
To investigate key stakeholders' views on how to improve access to primary care in general practice settings for people with learning disabilities (or intellectual disabilities). Further to explore how inequalities and barriers in specific areas including annual health checks might be addressed. A qualitative study design was used with data collected during focus groups, interviews and open-response surveys; data analysis was thematic and informed by stakeholder consultation. Processes to facilitate quality included triangulation of stakeholder perspectives, triangulation of data collection methods and checking interpretation of findings with participants. UK regional services including learning disability organisations, primary care general practitioner (GP) clinical practice networks and supported housing organisations. Sixteen people participated in the study: four people with learning disabilities participated in a focus group; four relatives completed an interview or survey; eight GPs, practice nurses and supported housing managers participated in interviews. Five overarching themes describing approaches to improve primary care access for people with learning disabilities were identified including: prioritisation, proactivity, innovation and improvement, personalisation and prevention and follow-up. Definitions of themes were described and illustrated with quotes. Ten recommendations informed by the thematic analysis, stakeholder consultation, research and primary care guidance were codeveloped with people with learning disabilities. All stakeholders identified problems, with primary care interfaces being misaligned with the needs of people with learning disabilities. The recommendations informed by all stakeholders can be used to guide development of service provision to better meet the needs of people with learning disabilities in primary care. Future research should explore professionals' understanding of reasonable adjustments.


Have drivers at alcohol outlets changed their behavior after the new traffic law?
In an attempt to reduce high levels of traffic crashes, a new legislation was approved in Brazil in 2008. This study aimed to assess behavioral change among drivers who had drunk at alcohol outlets (AO) after implementation of the law. A three-stage probability sampling survey was conducted in Porto Alegre, state of Rio Grande do Sul, Brazil. Individuals seen leaving AOs after drinking were approached (n=3,018). Selected drivers (n=683) answered a structured interview, were breathalyzed, and had saliva specimens collected for drug screening. Overall, 60.3% (SE 4.5) of drivers reported they did not change their behavior. Among those who reported behavioral changes, most reported drinking less as their main strategy toward safer driving behavior. Variables independently associated with behavior change included having drunk at a high outlet density area (odds ratio [OR] 1.7 [1.1-2.8]) and having a favorable opinion about the law (OR 4.3 [2.1-8.9]). Our findings suggest that awareness of the law has not been enough to promote behavioral change. As most drivers had a favorable opinion of the law and this variable was found to be the strongest predictor of behavior change, efforts to better integrate education and enforcement seem to be pivotal and might be well received by the population.


Model-based cost-effectiveness analyses comparing combinations of urate lowering therapy and anti-inflammatory treatment in gout patients.
To assess the cost-effectiveness of various combinations of urate lowering therapy (ULT) and anti-inflammatory treatment in the management of newly diagnosed gout patients, from the Dutch societal perspective. A probabilistic patient-level simulation estimating costs and quality-adjusted life years (QALYs) comparing gout and hyperuricemia treatment strategies was performed. ULT options febuxostat, allopurinol and no ULT were considered. Flare treatments naproxen, colchicine, prednisone, and anakinra were considered. A Markov Model was constructed to simulate gout disease. Health states were no flare, and severe pain, mild pain, moderate pain, or no pain in the presence of a flare. Model input was derived from patient level clinical trial data, meta-analyses or from previously published health-economic evaluations. The results of probabilistic sensitivity analyses were presented using incremental cost-effectiveness ratios (ICERs), and summarized using cost-effectiveness acceptability curves (CEACs). Scenario analyses were performed. The ICER for allopurinol versus no ULT was €1,381, when combined with naproxen. Febuxostat yielded the highest utility, but also the highest costs (€4,385 vs. €4,063 for allopurinol), resulting in an ICER of €25,173 when compared to allopurinol. No ULT was not cost-effective, yielding the lowest utility. For the gout flare medications, comparable effects on utility were achieved. Combined with febuxostat, naproxen was the cheapest option (€4,404), and anakinra the most expensive (€4,651). The ICER of anakinra compared to naproxen was €818,504. Colchicine and prednisone were dominated by naproxen. Allopurinol and febuxostat were both cost-effective compared to No ULT. Febuxostat was cost-effective in comparison with allopurinol at higher willingness-to-pay thresholds. For treating gout flares, colchicine, naproxen and prednisone offered comparable health economic implications, although naproxen was the favoured option.


Evaluation of the effects of platelet-rich fibrin and diode laser on gingival blood perfusion and early bone healing of the extraction socket: a randomized controlled clinical trial.
Evaluation and comparison of the effect of platelet-rich fibrin (PRF), diode laser, and combination of PRF and diode laser on gingival blood perfusion and early bone formation of the extraction socket. Forty maxillary premolar sockets were randomized to four groups: control group, PRF group, diode laser group, and PRF + diode laser group. Gingival blood perfusion was measured at preoperative and postoperative 1, 3, 7, and 30 days. Fractal dimension analysis was performed immediately after the procedure and in the postoperative first month. Gingival perfusions significantly increased during 1 week compared to baseline for all groups with a mean of -4.43 ± 3.20, -5.99 ± 3.68, -5.45 ± 3.01, and -4.78 ± 2.82 respectively, and were at baseline 1 month later. There were no statistically significant differences between the groups at any time point. Although the increase of fractal dimension was higher in the PRF or diode laser group than in the control group with a mean of 0.085 ± 0.05, 0.100 ± 0.04, and 0.072 ± 0.04 respectively, no statistically significant differences were detected. Fractal dimension was significantly greater in PRF + diode laser group than in the control group with a mean of 0.138 ± 0.05 (p = 0.04). PRF, diode laser, and PRF + diode laser did not significantly affect the gingival perfusion, and the combined application of PRF and diode laser had positive effects on early bone regeneration in the extraction socket. PRF, diode laser, and PRF + diode laser provide better tissue healing of the extraction socket.


Recombination in feline immunodeficiency virus from feral and companion domestic cats.
Recombination is a relatively common phenomenon in retroviruses. We investigated recombination in Feline Immunodeficiency Virus from naturally-infected New Zealand domestic cats (Felis catus) by sequencing regions of the gag, pol and env genes. The occurrence of intragenic recombination was highest in env, with evidence of recombination in 6.4% (n = 156) of all cats. A further recombinant was identified in each of the gag (n = 48) and pol (n = 91) genes. Comparisons of phylogenetic trees across genes identified cases of incongruence, indicating intergenic recombination. Three (7.7%, n = 39) of these incongruencies were found to be significantly different using the Shimodaira-Hasegawa test.Surprisingly, our phylogenies from the gag and pol genes showed that no New Zealand sequences group with reference subtype C sequences within intrasubtype pairwise distances. Indeed, we find one and two distinct unknown subtype groups in gag and pol, respectively. These observations cause us to speculate that these New Zealand FIV strains have undergone several recombination events between subtype A parent strains and undefined unknown subtype strains, similar to the evolutionary history hypothesised for HIV-1 "subtype E".Endpoint dilution sequencing was used to confirm the consensus sequences of the putative recombinants and unknown subtype groups, providing evidence for the authenticity of these sequences. Endpoint dilution sequencing also resulted in the identification of a dual infection event in the env gene. In addition, an intrahost recombination event between variants of the same subtype in the pol gene was established. This is the first known example of naturally-occurring recombination in a cat with infection of the parent strains. Evidence of intragenic recombination in the gag, pol and env regions, and complex intergenic recombination, of FIV from naturally-infected domestic cats in New Zealand was found. Strains of unknown subtype were identified in all three gene regions. These results have implications for the use of the current FIV vaccine in New Zealand.


Missed opportunities for NCD multimorbidity prevention in adolescents and youth living with HIV in urban South Africa.
Epidemiological transition in high HIV-burden settings is resulting in a rise in HIV/NCD multimorbidity. The majority of NCD risk behaviours start during adolescence, making this an important target group for NCD prevention and multimorbidity prevention in adolescents with a chronic condition such as HIV. However, there is data paucity on NCD risk and prevention in adolescents with HIV in high HIV-burden settings. The aim of this study was to investigate the extent to which NCD comorbidity (prevention, diagnosis, and management) is incorporated within existing adolescent HIV primary healthcare services in Cape Town, South Africa. We reviewed medical records of 491 adolescents and youth living with HIV (AYLHIV) aged 10-24 years across nine primary care facilities in Cape Town from November 2018-March 2019. Folders were systematically sampled from a master list of all AYLHIV per facility and information on HIV management and care, NCDs, NCD risk and NCD-related health promotion extracted. The median age was 20 years (IQR: 14-23); median age at ART initiation 18 years (IQR: 6-21) and median duration on ART 3 years (IQR: 1.1-8.9). Fifty five percent of participants had a documented comorbidity, of which 11% had an NCD diagnosis with chronic respiratory diseases (60%) and mental disorders (37%) most common. Of those with documented anthropometrics (62%), 48% were overweight or obese. Fifty nine percent of participants had a documented blood pressure, of which 27% were abnormal. Twenty-six percent had a documented health promoting intervention, 42% of which were NCD-related; ranging from alcohol or substance abuse (13%); smoking (9%); healthy weight or diet (9%) and mental health counselling (10%). Our study demonstrates limited NCD screening and health promotion in AYLHIV accessing healthcare services. Where documented, our data demonstrates existing NCD comorbidity and NCD risk factors highlighting a missed opportunity for multimorbidity prevention through NCD screening and health promotion. Addressing this missed opportunity requires an integrated health system and intersectoral action on upstream NCD determinants to turn the tide on the rising NCD and multimorbidity epidemic.


[X-ray effect on patients with upper urinary tract calculi during extracorporeal shock wave lithotripsy].
This study reports the results of radiation exposure to 90 patients with upper urinary tract calculi during Extracorporeal Shock Wave Lithotripsy (ESWL). A domestically made JT-ESWL-I lithotripter was used. Radiation exposure to the patients averaged 67.02 mSv at 65-70 kV, 2 mA. The data indicated that the amount of radiation exposure is related to the number, size, location and the radiodensity of the stone, and also the number of shock wave and the time of fluoroscopy exposure given to the patients. The results of the chromosome aberration and the micronucleus of lymphocytes assay in the human blood are reported and the prevention of radiation exposure is discussed.


Understanding Multicellularity: The Functional Organization of the Intercellular Space.
The aim of this paper is to provide a theoretical framework to understand how multicellular systems realize functionally integrated physiological entities by organizing their intercellular space. From a perspective centered on physiology and integration, biological systems are often characterized as organized in such a way that they realize metabolic self-production and self-maintenance. The existence and activity of their components rely on the network they realize and on the continuous management of the exchange of matter and energy with their environment. One of the virtues of the organismic approach focused on organization is that it can provide an understanding of how biological systems are functionally integrated into coherent wholes. Organismic frameworks have been primarily developed by focusing on unicellular life. Multicellularity, however, presents additional challenges to our understanding of biological systems, related to how cells are capable to live together in higher-order entities, in such a way that some of their features and behaviors are constrained and controlled by the system they realize. Whereas most accounts of multicellularity focus on cell differentiation and increase in size as the main elements to understand biological systems at this level of organization, we argue that these factors are insufficient to provide an understanding of how cells are physically and functionally integrated in a coherent system. In this paper, we provide a new theoretical framework to understand multicellularity, capable to overcome these issues. Our thesis is that one of the fundamental theoretical principles to understand multicellularity, which is missing or underdeveloped in current accounts, is the functional organization of the intercellular space. In our view, the capability to be organized in space plays a central role in this context, as it enables (and allows to exploit all the implications of) cell differentiation and increase in size, and even specialized functions such as immunity. We argue that the extracellular matrix plays a crucial active role in this respect, as an evolutionary ancient and specific (non-cellular) control subsystem that contributes as a key actor to the functional specification of the multicellular space and to modulate cell fate and behavior. We also analyze how multicellular systems exert control upon internal movement and communication. Finally, we show how the organization of space is involved in some of the failures of multicellular organization, such as aging and cancer.


The placenta in hematogenous infections.
Although congenital infections have been known since ancient times, at present they constitute an evolution due to the broadening of diagnostic methods. Also, the histopathological examination of selected placentas has increased in perinatal pathology. All placentas should be examined grossly by the obstetrician or the neonatologist who must select the specimens to be sent for pathologic examination. The indications for selection at delivery to detect hematogenous infection are listed in Table 1. The placentas that do not meet guidelines for pathologic examination must be kept stored at 40 degrees C for at least 72 h. This routine ensures that the placentas of asymptomatic newborns who might present early manifestations suggestive of infection would be submittedfor pathologic examination.


Impact of interpregnancy intervals on perinatal and neonatal outcomes in a multiethnic Pakistani population.
Short birth intervals (SBIs) and long birth intervals (LBIs) have been shown to have serious implications for health of both mothers and their children. This study was aimed to investigate the determinants and reproductive outcome of SBI and LBI in a multiethnic Pakistani population. In a cross-sectional prospective study design, 2798 women admitted in a tertiary-care hospital in Islamabad for delivery were recruited and data on second or higher birth order deliveries were collected. Birth intervals were defined as short (<24 months) and long (>36 months). The reproductive outcome was defined in terms of perinatal and neonatal mortalities, and neonatal complications. Univariate and multivariate logistic regression analyses were performed. Pregnancies with SBI and LBI were observed in 20% and 24% of 2798 women, respectively. Women with SBI had increased odds of perinatal death [adjusted odd ratio (AOR): 1.50] and neonatal death (AOR: 1.47) as compared to women with optimal birth intervals, while women with LBI had slightly lower odds of perinatal deaths (AOR: 0.96), but increased odds of neonatal deaths (AOR: 1.12). Further, the pregnancies with both SBI and LBI were associated with increased odds of short body length, low birth weight, small head circumference and low APGAR score. Nearly half of all pregnancies do not have optimal birth spacing albeit there is wide heterogeneity in the distribution of BI in various Pakistani ethnicities. Pregnancies with SBI and LBI had high risk of adverse reproductive outcome. Intervention programs for maternal and child health need to emphasize optimal birth spacing.


What Can We Learn About the Others Present During Incidents of Child Abuse?: Key Lessons and Future Directions Based on a Scoping Review.
Child abuse (CA) is a global problem that has received attention from policymakers, researchers, and practitioners. The majority of studies have focused on the phenomenon's epidemiology and consequences, alongside groundbreaking writing on victims and perpetrators. The concept of others who are present during the abuse is understudied and underdeveloped, despite its vital importance in better understanding children's experiences as well as their disclosure. The current study was designed to spotlight the phenomenon of others' presence, beyond the victims and perpetrators, during child abuse incidents. The current literature review was guided by a scoping review strategy. The results revealed scant empirical data, with only 15 studies meeting the inclusion criteria of the study. The articles that met the inclusion criteria addressed other people's presence during CA incidents, were published in peer-reviewed journals, and were written in the English language. These articles' analyses addressed the relations of the survivors with these others, pointing mainly to two identities: accidental bystanders who are not familiar with the child and family members of the child. The results provided a glance into the process that accidental bystanders go through during the abuse and the meaning of their presence for those who are family members. The perceptions and experiences of the children themselves with respect to the presence of the others during the abuse are noticeably lacking. The key conclusion from the current scoping review pinpoints the urgent need to advance the empirical knowledge on the presence of others during incidents of child abuse, especially others who are familiar to the children and are a significant part of their lives. The conceptualization of this phenomenon has the potential to better adapt prevention and intervention efforts in the field of child abuse.


An Arg-Gly-Asp-directed receptor on the surface of human melanoma cells exists in an divalent cation-dependent functional complex with the disialoganglioside GD2.
The disialogangliosides GD2 and GD3 play a major role in the ability of human melanoma cells to attach to Arg-Gly-Asp-containing substrates such as fibronectin and vitronectin, since pretreatment of these cells with monoclonal antibodies to the oligosaccharide of GD2 and GD3 can inhibit their attachment and spreading on such adhesive proteins. This report demonstrates that human melanoma cells (M21) synthesize and express a glycoprotein receptor that shares antigenic epitopes with the vitronectin receptor on human fibroblasts and is capable of specifically recognizing the Gly-Arg-Gly-Asp-Ser-Pro sequence. In the presence of calcium, GD2, the major ganglioside of M21 cells, colocalized with this receptor on the surface of human melanoma cells and their focal adhesion plaques as demonstrated by double-label transmission immunoelectron microscopy and indirect immunofluorescence. Biochemical evidence is presented indicating that the vitronectin receptor on M21 human melanoma cells contains associated calcium and GD2. This ganglioside copurified with the glycoprotein receptor for vitronectin on affinity columns containing either an Arg-Gly-Asp-containing peptide, concanavalin A, or lentil lectin. This major Arg-Gly-Asp-directed receptor on M21 cells could be metabolically labeled with 45Ca2+. Chelation of this ion with EDTA caused the dissociation of GD2 from the receptor and rendered the remaining glycoprotein incapable of binding to an Arg-Gly-Asp-containing peptide. Reconstitution experiments demonstrated a requirement for calcium, and not magnesium, for receptor binding to Arg-Gly-Asp and indicated that addition of ganglioside can enhance this interaction.


In vitro selection of bacteriophage phi29 prohead RNA aptamers for prohead binding.
Prohead RNA (pRNA) of the Bacillus subtilis bacteriophage phi29 is needed for in vitro packaging of DNA-gene product 3 (DNA-gp3). Residues 22-84 of the 174-base pRNA bind the portal vertex of the prohead, the site of DNA packaging. To define the nucleotides of pRNA needed for prohead binding and DNA-gp3 packaging and to seek biologically active variants of pRNA, segments of pRNA were randomized to obtain vast repertoires of RNA molecules. RNA aptamers, ligands best suited for prohead binding, were obtained by multiple rounds of in vitro selection. Evolution of pRNA aptamers was followed by a competition binding assay and nucleotide sequencing, and mutants were tested for DNA-gp3 packaging. Aptamers selected following randomization of the E stem and loop and a part of the C-E loop that were active in DNA-gp3 packaging were invariably wild-type. DNA-gp3 packaging activity also required nucleotides G82 and G83 that form base pairs intermolecularly with C47 and C48 to produce a novel hexameric oligomer of pRNA. The only mutant aptamers that retained full DNA-gp3 packaging activity showed changes of the U residues at positions 81, 84, and 85 of the D loop. Thus, the in vitro selections essentially recapitulated the natural evolution of pRNA.


Estimation of kinetic and thermodynamic ligand-binding parameters using computational strategies.
Kinetic and thermodynamic ligand-protein binding parameters are gaining growing importance as key information to consider in drug discovery. The determination of the molecular structures, using particularly x-ray and NMR techniques, is crucial for understanding how a ligand recognizes its target in the final binding complex. However, for a better understanding of the recognition processes, experimental studies of ligand-protein interactions are needed. Even though several techniques can be used to investigate both thermodynamic and kinetic profiles for a ligand-protein complex, these procedures are very often laborious, time consuming and expensive. In the last 10 years, computational approaches have enormous potential in providing insights into each of the above effects and in parsing their contributions to the changes in both kinetic and thermodynamic binding parameters. The main purpose of this review is to summarize the state of the art of computational strategies for estimating the kinetic and thermodynamic parameters of a ligand-protein binding.


Development and demolition: a career in mental health nursing and 10 lessons learned.
Presented as part of the Ellen Skellern lifetime achievement award in 2016 this paper reflects on a career in mental health nursing and academia spanning 53 years. The presentation offers a series of key lessons learned in that time. They include observations on health care organisations, educational experiences, the nursing profession and the illusion of permanence in health care service organisations and the buildings that house them. The paper offers an account of how a profession must constantly develop to be relevant and how the demolition of both buildings and organisations have been a fact of life in the five decades reported.


Patient recovery after infrainguinal bypass grafting for limb salvage.
The outcome of infrainguinal bypass surgery for limb salvage has traditionally been assessed by graft patency rates, limb salvage rates, and patient survival rates. Recently, functional outcome of limb salvage surgery has been assessed by patient ambulatory status and independent living status. These assessments fail to consider the adverse long-term patient effects of delayed wound healing, episodes of recurrent ischemia, and need for repeat operations. An ideal result of infrainguinal bypass surgery for limb salvage includes an uncomplicated operation, elimination of ischemia, prompt wound healing, and rapid return to premorbid functional status without recurrence or repeat surgery. The present study was performed to determine how often this ideal result is actually achieved. The records of 112 consecutive patients who underwent initial infrainguinal bypass surgery for limb salvage 5 to 7 years before the study were reviewed for operative complications, graft patency, limb salvage, survival, patient functional status, time to achieve wound healing, need for repeat operations, and recurrence of ischemia. The mean patient age was 66 years. The mean postoperative follow-up was 42 months (range, 0 to 100.1 months). After operation 99 patients (88%) lived independently at home and 103 (92%) were ambulatory. There were seven perioperative deaths (6.3%), and wound complications occurred in 27 patients (24%). By life table, the assisted primary graft patency and limb salvage rates of the index extremity 5 years after operation were 77% and 87%, respectively, and the patient survival rate was 49%. At last follow-up or death, 73% of the patients (72 of 99) who lived independently at home before the operation were still living independently at home, and 70% (72 of 103) of those who were ambulatory before the operation remained ambulatory. Wound (operative and ischemic) healing required a mean of 4.2 months (range, 0.4 to 48 months), and 25 patients (22%) had not achieved complete wound healing at the time of last follow-up or death. Repeat operations to maintain graft patency, treat wound complications, or treat recurrent or contralateral ischemia were required in 61 patients (54%; mean, 1.6 reoperations/patient), and 26 patients (23.2%) ultimately required major limb amputation of the index or contralateral extremity. Only 16 of 112 patients (14.3%) achieved the ideal surgical result of an uncomplicated operation with long-term symptom relief, maintenance of functional status, and no recurrence or repeat operations. Most patients who undergo infrainguinal bypass surgery for limb salvage require ongoing treatment and have persistent or recurrent symptoms until their death. A significant minority have major tissue loss despite successful initial surgery. Clinically important palliation is frequently achieved by bypass surgery, but ideal results are distinctly infrequent.


Lack of Response to HBHA in HIV-Infected Patients with Latent Tuberculosis Infection.
Heparin-binding haemagglutinin (HBHA) has been proposed as an immunological biomarker for discriminating active tuberculosis (TB) from latent TB infection (LTBI) and to identify those at higher risk of progressing to active disease. Few data are available in immune-compromised patients, which are those with increased risk of TB reactivation. The aim of this stusy was to evaluate the immune response to HBHA in HIV-infected subjects with LTBI (HIV-LTBI) or active TB (HIV-TB) in comparison with the immune response to additional Mycobacterium tuberculosis (Mtb) or HIV and CMV antigens. The responses are evaluated in relation to TB status and in the LTBI subjects with the progression to active TB within 2 years. Forty-one HIV-infected antiretroviral-naïve subjects were prospectively enrolled: 18 were HIV-TB and 23 HIV-LTBI. Whole blood was in vitro stimulated overnight with several antigens and mitogen. Interferon-γ response in the harvested plasma was evaluated by ELISA. Despite that CD4 cell count was significantly different between HIV-LTBI and HIV-TB, no differences were observed in response to Mtb- or HIV-specific antigens. Differently, low responses to HBHA were observed in both HIV-LTBI and HIV-TB subjects. Importantly, none of the six HIV-LTBI responding to HBHA developed TB, while two of 17 non-HBHA responders developed active disease. HIV-TB-coinfected subjects, regardless of their TB status, showed low responses to HBHA despite maintaining detectable responses to other antigens; moreover, among the HIV-LTBI, the lack of HBHA responses indicated an increased risk to develop active TB. These results, although preliminary, suggest that a positive response to HBHA in HIV-LTBI correlates with Mtb containment.


Di- and trihydroxy analogs of chlorpromazine influence the central activity of adenylate cyclase and cyclic AMP phosphodiesterase.
We previously demonstrated that chlorpromazine (CPZ), 7,8 diOH-CPZ and 3,7,8 triOH-CPZ were potent inhibitors of central adenylate cyclase systems. The present studies were thus designed to observe whether further substitutions of dihydroxy groups on the CPZ molecule would influence adenylate cyclase in broken cell preparations of the rat frontal cortex. The inhibition of adenylate cyclase by 7,8 diOH-CPZ was further found to be noncompetitive with respect to ATP concentration. Raising the Ca++ concentration obliterated adenylate cyclase activation by either dopamine or 5'-guanylylimidodiphosphate (Gpp(NH)p) alone or in combination, while inhibition by 7,8 diOH-CPZ was overcome. The enzyme inhibition by 7,8 diOH-CPZ was not influenced, however, by increasing Mg++ concentration. Incubation of rat cortical homogenates with CPZ, 3,7,8 triOH-CPZ or 6,9 diOH-CPZ inhibited stimulation of adenylate cyclase activity while either 3,7- or 3,8 diOH-CPZ resulted in an enhancement of enzyme activity. In further study, using the high speed cortical supernatant, the high Km form of cyclic AMP phosphodiesterase and its activation by the Ca++-dependent, heat stable regulator protein were inhibited by CPZ, 6,9 dioxo-, 7,8 dioxo-, 3,7diOH-, 3,8 diOH-, 6,9 diOH-, 7,9 diOH- and 7,8 diOH-CPZs, but not by 3,7,8 triOH-CZP. The high affinity-low Km form of the enzyme was inhibited to a considerably lesser extent by these analogs. The studies reveal rather diverse and complicated actions of CPZ and its putative metabolites on central enzyme systems.


Causal criteria: time has come for a revision.
Epidemiologists study associations but they are usually interested in causation that could lead to disease prevention. Experience show, however, that many of the associations we identify are not the causes we take an interest in (correlation is not causation). In order to proper translate association into causes, a set of causal criteria was developed 50-60 years ago and they became important tools guiding this translational process (sometimes correlation is causation). Best known of these are the Bradford Hill 'criteria'. In these last 50 years, epidemiologic theory and infrastructure have advanced rapidly without changes in these causal criteria. We think time has come to revisit the 'old' criteria to see which ones we should keep and which ones should be taken out or be replaced by new measures of association. Robustness of these criteria in attempts to make the association go away should have high priority. A group of renowned internationally recognized researchers should have this task. Since classifying associations as causes is often done in order to reduce or eliminate the exposures of concern results from conditional outcome research should also be used. We therefore suggest to add a 'consequence' criterion. We argue that a consequence criterion that provides a framework for assessing or prescribing action worthy or right in social contexts is needed. A consequence criterion will also influence how strict our causal criteria need to be before leading to action and will help in separating the 'causal discussion' and the discussion on what to do about it. A consequence criterion will be a tool in handling dilemmas over values (as social solidarity, fairness, autonomy). It will have implications for the interpretation and use of the procedural criteria of causality. Establishing interconnected procedural and consequence criteria should be a task for institutions representing and being recognized by experts, civil society and the state.


[A case report of spontaneous pneumothorax in Marfan's syndrome and an immunohistochemical study of type I collagen in lung tissue].
A 19-year-old male was admitted to Teikyo University Hospital because of dyspnea. The chest film revealed pneumothorax of the right side. The patient was tall and thin, with long tapered extremities. The lens showed ectopia lentis. Echography of the heart showed dilatation of the aorta. A diagnosis of Marfan's syndrome was established on the basis of characteristic skeletal, ocular and cardiovascular findings. At thoracotomy, several bullae were removed by wedge resection. Collagen type distribution in the lung was investigated by an indirect immunohistochemical study using type-special antibody of type I collagen. There were no significant differences in collagen type I in the lung between Marfan's syndrome and control. This suggests that type I collagen in Marfan's syndrome cannot be distinguished from normal collagen I by indirect immunochemical study.


Estrogen receptor alpha (Esr1) regulates aromatase (Cyp19a1) expression in the mouse brain.
Local estrogen production in the brain regulates critical functions including neuronal development, gonadotropin secretion and sexual behavior. In the mouse brain, a 36 kb distal promoter (l.f) regulates the Cyp19a1 gene that encodes aromatase, the key enzyme for estrogen biosynthesis. In vitro, promoter l.f interacts with estrogen receptor alpha (Esr1) to mediate Cyp19a1 mRNA expression and enzyme activity in mouse hypothalamic neuronal cell lines. The in vivo mechanisms that control mammalian brain aromatase expression during fetal and adult development, however, are not thoroughly understood. Our aim was to elucidate the basis of the in vivo connection between Esr1 and Cyp19a1. Pregnant mice were sacrificed at gestational days 9, 11, 13, 15, 16, 19, 21 and the brain tissues of the fetuses were harvested along with five newborns at the age of postnatal day 2. Esr1KO (female) were also sacrificed and their hypothalamus were excised out. Then both fetuses and adults RNA were isolated, reverse transcribed and amplified employing primers specific for Esr1 and Cyp19a1 with Real time PCR. In the fetal mouse brain, Cyp19a1 mRNA levels are inversely correlated with estrogen receptor alpha (Esr1) mRNA levels in a temporal manner. Moreover, Cyp19a1 mRNA levels increased in the hypothalamus of estrogen receptor-alpha knockout female mice (Esr1KO). Taken together, our findings might indicate that Esr1 has crucial roles in the in vivo regulation of aromatase expression in the brain during fetal and adult life.


PRE-surgical Metformin In Uterine Malignancy (PREMIUM): a Multi-Center, Randomized Double-Blind, Placebo-Controlled Phase III Trial.
Endometrioid endometrial cancer is strongly associated with obesity and insulin resistance. Metformin, an insulin sensitizer, reduces endometrial tumor growth in vitro. Presurgical window studies allow rapid in vivo assessment of antitumor activity. Previous window studies found metformin reduced endometrial cancer proliferation but these lacked methodological rigor. PREMIUM measured the anti-proliferative effect of metformin in vivo using a robust window study design.Patients and Methods: A multicenter, double-blind, placebo-controlled trial randomized women with atypical hyperplasia or endometrioid endometrial cancer to receive metformin (850 mg daily for 3 days, and twice daily thereafter) or placebo for 1 to 5 weeks until surgery. The primary outcome was posttreatment IHC expression of Ki-67. Secondary outcomes investigated the effect of metformin on markers of the PI3K-Akt-mTOR and insulin signaling pathways and obesity. Eighty-eight women received metformin (n = 45) or placebo (n = 43) and completed treatment. There was no overall difference in posttreatment Ki-67 between the metformin and placebo arms, in an ANCOVA analysis adjusting for baseline Ki-67 expression (mean difference -0.57%; 95% CI, -7.57%-6.42%; P = 0.87). Metformin did not affect expression of markers of the PI3K-Akt-mTOR or insulin signaling pathways, and did not result in weight loss. Short-term treatment with standard diabetic doses of metformin does not reduce tumor proliferation in women with endometrioid endometrial cancer awaiting hysterectomy. This study does not support a biological effect of metformin in endometrial cancer and casts doubt on its potential application in the primary and adjuvant treatment settings.


Consistent use of lipid lowering therapy in HIV infection is associated with low mortality.
In people living with HIV (PLWH), statins may be disproportionately effective but remain underutilized. A large prospective trial in patients with low to moderate cardiovascular (ASCVD) risk will reveal whether they should be considered in all PLWH. But its effect size may not apply to real-world PLWH with higher ASCVD and mortality risk. Also, the clinical role of non-statin lipid-lowering therapy (LLT) and LLT adherence in this population is unknown. Comparative multi-level marginal structural model for all-cause mortality examining four time-updated exposure levels to LLT, antihypertensives, and aspirin in a virtual cohort of older PLWH. Incident coronary, cerebrovascular, and overall ASCVD events, serious infections, and new cancer diagnoses served as explanatory outcomes. In 23,276 HIV-infected US-veterans who were followed for a median of 5.2 years after virologic suppression overall mortality was 33/1000 patient years: > 3 times higher than in the US population. Use of antihypertensives or aspirin was associated with increased mortality. Past LLT use (> 1 year ago) had no effect on mortality. LLT exposure in the past year was associated with a reduced hazard ratio (HR) of death: 0.59, 95% confidence interval (CI) 0.51-0.69, p < 0.0001 for statin containing LLT and 0.71 (CI: 0.54-0.93), p = 0.03 for statin-free LLT. For consistent LLT use (> 11/12 past months) the HR of death was 0.48 (CI: 0.35-0.66) for statin-only LLT, 0.34 (CI: 0.23-0.52) for combination LLT, and 0.27 (CI: 0.15-0.48) for statin-free LLT (p < 0.0001 for all). The ASCVD risk in these patients was reduced in similar fashion. Use of statin containing LLT was also associated with reduced infection and cancer risk. Multiple contrasting subgroup analyses yielded comparable results. Confounding is unlikely to be a major contributor to our findings. In PLWH, ongoing LLT use may lead to substantially lower mortality, but consistent long-term adherence may be required to reduce ASCVD risk. Consistent non-statin LLT may be highly effective and should be studied prospectively.


[Long-term results of atriopulmonary fontan connection for complex cardiac anomalies].
To evaluate the long-term results of atriopulmonary Fontan connection, we reviewed the outcome of 20 consecutive patients (single ventricle 8, double outlet right ventricle 8, tricuspid atresia 3, mitral atresia 1; mean age, 13 +/- 11) who underwent this operation between 1981 and 1997 at our institution. Glenn shunt preceded Fontan operation in 1 patient. Four patients had a concomitant bidirectional Glenn anastomosis at the time of the Fontan operation. Follow-up was 100% complete, and total cumulative follow-up of all patients was 241 patient-years (maximum, 20 years). Three hospital deaths and 5 late deaths were observed, resulting in 58 +/- 11% of cumulative survival at 20 years after the operation. Sudden death probably due to arrhythmias was the major cause of the late death, and occurred in 3 patients. Reoperation was required in 5 patients (2%/patient-year) at 1 to 17 years postoperatively. Re-closure of an atrioventricular valve was performed for failure of the valve closure in 3 patients at 1 to 6 years postoperatively. Reconstruction of the stenotic atriopulmonary connection (APC) was concomitantly required in 2 of the 3 patients. Pacemaker implantation was required for bradycardia with atrial fibrillation in 1 patient at 17 years. One patient with atrial flutter developed intraright atrial thrombosis at 12 years after the initial Fontan operation, and this patient underwent conversion to extracardiac conduit cavopulmonary connection with right atrial maze procedure. Atrial tachyarrhythmias are most common complications, and occurred in 12 patients (5.0%/patient-year), resulting in 40 +/- 13% of the cumulative free rate at 15 years after the operation. Thus, failure of the atrioventricular valve closure and stenosis of APC were important early to intermediate complications after the atriopulmonary Fontan connection. On the other hand, atrial tachyarrhythmias were inevitable, and were most common late complications leading to intra-right atrial thrombosis, which was successfully resolved by conversion of the conventional atriopulmonary Fontan anastomosis to extracardiac conduit cavopulmonary connection.


Children with problematic sexualized behaviors in the child welfare system.
This study assessed the utility of the Child Sexual Behavior Inventory (CSBI) in a child welfare sample. In this study, 97 children from ages 10 to 12 from either foster boarding homes or a residential treatment center participated. Researchers interviewed foster parents or primary therapists about children's sexual behavior, traumatic events, clinical symptoms, and their attitudes toward the child. Findings revealed that problematic sexualized behaviors were more prevalent in the residential treatment center (RTC) sample than they were in a normative sample. The pattern of associations between sexual behavior problems, traumatic events, and clinical syndromes in both the RTC and the foster boarding home (FBH) samples was similar to what has been found in samples in which biological custodial parents were the respondents. Analyses comparing youth who met the criterion for having problematic sexualized behaviors and youth who did not meet the criterion revealed that the two groups differed on clinical symptoms, prior traumatic events, and negative reports by caregivers. Results confirm the utility of the CSBI measure for this population and highlight several important clinical and programmatic concerns for addressing problematic sexual behavior in children in the child welfare system.


Characterization of long-term survival of syngeneic hepatocytes in rat peritoneum.
Hepatocyte transplantation is a potential therapy for both acute and chronic hepatic insufficiency and also for treatment of inborn errors of metabolism affecting the liver. The peritoneum is one site for implantation and has several advantages: cells implanted there can be easily identified and observed, and it has a relatively large capacity. Long-term survival using "pure" hepatocytes in the peritoneum have been disappointing. We hypothesized that cotransplantation of hepatocytes with nonparenchymal cells would help maintain differentiated hepatocyte function. Rat liver cells transplanted intraperitoneally into August rats were sacrificed at 7 days, 1, 3, 6, 9, and 12 months and analyzed for presence, basal proliferation, and functionality of hepatocytes. To demonstrate that ectopic hepatocytes remained susceptible to exogenous growth factors affecting cell proliferation, rats 9 and 12 months after transplantation were stimulated with tri-iodothyronine and KGF. Hepatocytes were identified 7 days to >12 months, by H&E and immunohistochemically, as ectopic islands in the omental fat. Functionality was confirmed by glycogen deposition. Basal proliferation in 7-day rats was 28.0 +/- 10/1000 hepatocytes in ectopic islands (cf. 5.70 +/- 2.7/1000 in recipient liver). Proliferation in ectopic islands was greater than host liver. Growth factor-stimulated proliferation in ectopic islands induced a 70-fold increase in DNA synthesis. In conclusion, hepatocytes transplanted with nonparenchymal cells survive, proliferate, and function in the peritoneum of normal rats, and respond to exogenous growth stimuli. Their survival and proliferation in the presence of a normal functioning liver has implications for the potential use of the peritoneal site clinically for supplementation of liver function in metabolic disorders.


Complex wave patterns in an effective reaction-diffusion model for chemical reactions in microemulsions.
An effective medium theory is employed to derive a simple qualitative model of a pattern forming chemical reaction in a microemulsion. This spatially heterogeneous system is composed of water nanodroplets randomly distributed in oil. While some steps of the reaction are performed only inside the droplets, the transport through the extended medium occurs by diffusion of intermediate chemical reactants as well as by collisions of the droplets. We start to model the system with heterogeneous reaction-diffusion equations and then derive an equivalent effective spatially homogeneous reaction-diffusion model by using earlier results on homogenization in heterogeneous reaction-diffusion systems [S.Alonso, M.Bär, and R.Kapral, J. Chem. Phys. 134, 214102 (2009)]. We study the linear stability of the spatially homogeneous state in the resulting effective model and obtain a phase diagram of pattern formation, that is qualitatively similar to earlier experimental results for the Belousov-Zhabotinsky reaction in an aerosol OT (AOT)-water-in-oil microemulsion [V.K.Vanag and I.R.Epstein, Phys. Rev. Lett. 87, 228301 (2001)]. Moreover, we reproduce many patterns that have been observed in experiments with the Belousov-Zhabotinsky reaction in an AOT oil-in-water microemulsion by direct numerical simulations.


African KhoeSan ancestry linked to high-risk prostate cancer.
Genetic diversity is greatest within Africa, in particular the KhoeSan click-speaking peoples of southern Africa. South African populations represent admixture fractions including differing degrees of African, African-KhoeSan and non-African genetic ancestries. Within the United States, African ancestry has been linked to prostate cancer presentation and mortality. Together with environmental contributions, genetics is a significant risk factor for high-risk prostate cancer, defined by a pathological Gleason score ≥ 8. Using genotype array data merged with ancestry informative reference data, we investigate the contribution of African ancestral fractions to high-risk prostate cancer. Our study includes 152 South African men of African (Black) or African-admixed (Coloured) ancestries, in which 40% showed high-risk prostate cancer. Genetic fractions were determined for averaging an equal African to non-African genetic ancestral contribution in the Coloured; we found African ancestry to be linked to high-risk prostate cancer (P-value = 0.0477). Adjusting for age, the associated African ancestral fraction was driven by a significant KhoeSan over Bantu contribution, defined by Gleason score ≥ 8 (P-value = 0.02329) or prostate specific antigen levels ≥20 ng/ml (P-value = 0.03713). Additionally, we observed the mean overall KhoeSan contribution to be increased in Black patients with high-risk (11.8%) over low-risk (10.9%) disease. Linking for the first time KhoeSan ancestry to a common modern disease, namely high-risk prostate cancer, we tested in this small study the validity of using KhoeSan ancestry as a surrogate for identifying potential high-risk prostate cancer risk loci. As such, we identified four loci within chromosomal regions 2p11.2, 3p14, 8q23 and 22q13.2 (P-value = all age-adjusted < 0.01), two of which have previously been associated with high-risk prostate cancer. Our study suggests that ancient KhoeSan ancestry may be linked to common modern diseases, specifically those of late onset and therefore unlikely to have undergone exclusive selective pressure. As such we show within a uniquely admixed South African population a link between KhoeSan ancestry and high-risk prostate cancer, which may explain the 2-fold increase in presentation in Black South Africans compared with African Americans.


[Effects of nitrogen fertilization on leaf senescence, photosynthetic characteristics, yield, and quality of different flue-cured tobacco varieties].
Taking three flue-cured tobacco (Nicotiana tabacum L.) varieties Y5, Y7, and NC89 as test objects, this paper studied the effects of nitrogen fertilization on their leaf senescence, photosynthetic characteristics, yield, and quality. Increasing nitrogen supply increased the leaf superoxide dismutase (SOD) activity, chlorophyll content, and photosynthetic performance, and decreased the leaf malondialdehyde (MDA) content significantly. Accordingly, the leaf senescence was delayed. Compared with Y5 and NC89, variety Y7 had higher leaf MDA content and lower leaf SOD activity, chlorophyll content, and photosynthetic performance, and thus, its leaves senesced faster. High quality tobacco leaves with higher average price, gross value, superior leaves percentage, and reasonable chemical constituents were harvested under the application of 45 kg N x hm(-2), compared with applying 60 and 75 kg N x hm(-2). It was suggested that different flue-cured tobacco varieties had obvious differences in their leaf senescence physiological characteristics, and nitrogen fertilization played important roles in regulating their leaf senescence, yield, and quality. Appropriate nitrogen fertilization could improve the quality of tobacco leaves, and achieve higher economic benefits.


[Prevalence and predictive value of GAD65 autoantibodies and their correlation with HLA DR-DQ genotypes in children with type-1 diabetes].
Development of type 1 diabetes is caused by immune mediated destruction of pancreatic beta-cells and is associated with development of islet cell specific antibodies that are molecular markers of the diabetogenic process. Studies on islet cell antibodies will lead to a better understanding of the pathomechanism and improved prediction of the disease. AIMS AND PATIENTS: In present study prevalence of glutamate-decarboxylase (GAD65) antibodies was analysed in a registry based collection of childhood type 1 diabetes cases (n = 122), first degree relatives (n = 164) and ethnically and geographically matched healthy children (n = 2664) in Hungary. Association of GADA with various HLA DQA1-DQB1 genotypes was also studied. GADA was determined using a routine radioligand assay and HLA DQA1-DQB1 genotypes were identified with allele-specific polymerase chain reaction method. GADA was more prevalent in children with type 1 diabetes as compared to first degree relatives or the healthy population (71.3%, 95% CI:63.3-79.3 versus 9.1%, 95% CI: 4.7-13.5 and 1.3%, 95% CI: 0.9-1.7; p < 10(-4) and p < 10(-4), respectively). Girls with diabetes were more often positive for GADA than boys (84.1%, 57.6%, p = 0.003) which tendency was seen also among healthy children (1.8%, 0.8%, p = 0.03). Among parents of diabetic children fathers had higher prevalence of GADA than mothers (16.1%, 3.9%, p = 0.03). Diagnostic sensitivity, specificity and positive predictive value of GADA were as follows: 71.3%, 98.7% and 3.7%, respectively. GADA titer was higher in diabetes patients than in first degree relatives or healthy children (62.4 rU +/- 45.8 rU, 23.6 +/- 14.1 rU; p < 10(-4), 17.2 +/- 9.6; p < 10(-4)). GADA was more prevalent among patients with HLA DR3-DQ2 haplotype while it was less prevalent in cases with HLA DR4-DQ8 haplotype as compared to cases not carrying these haplotypes (p < 10(-4) and p = 0.01, respectively). GAD65 antibodies are specific disease markers for type 1 diabetes. The increased prevalence of GADA among first degree relatives of type 1 diabetes patients indicates an increased risk for development of diabetes in this population. GADA is associated with HLA DR3-DQ2 haplotype and female sex. Positive predictive value of GADA is considerably lower in the general population than in first degree relatives, consequently, for more accurate diabetes prediction the use of additional immune and genetic markers is necessary.


Diffuse histiocytic lymphoma after histologic conversion: a poor prognostic variant.
Diffuse histiocytic lymphoma (DHL) developed in 14 patients with a different non-Hodgkin's lymphoma and one with chronic lymphocytic leukemia. The median time from the diagnosis of the first malignancy to the appearance of DHL was 47 months (range, 8--112). The most common presentation of histologic conversion was new or recurrent lymphadenopathy. Hypercalcemia was associated with the onset of the DHL in four of 15 patients. Eight patients with DHL after histologic conversion were treated with doxorubicin, vincristine, and prednisone with or without cyclophosphamide, but none achieved complete remission. Two other patients did achieve a complete response with therapy (one with radiotherapy and one with cyclophosphamide, vincristine, procarbazine, and prednisone), but they had brief remissions, and no patient in this study achieved long-term, disease-free survival. This was reflected in the short (12-month) median survival after histologic transformation to DHL. It appears that patients with DHL after histologic conversion have a worse prognosis than those with de novo DHL.


Morinda lucida Aqueous Stem Bark Extract Ameliorates Hepato-Renal Dysfunctions in Experimental Diabetes Model.
Diabetes Mellitus (DM) is a leading pan-systemic endocrine disorder with attendant high morbidity and mortality owing to its deleterious effects on vital body organs caused by untreated chronic hyperglycemia, attendant oxidative stress and glycation processes. The present study is designed to investigate possible protective role and mechanism(s) of action 125-500 mg/kg/day of Morinda lucida aqueous stem bark extract (MLASE) on renal and hepatic functions in alloxan-induced hyperglycemic rats for 8 days. Forty-two alloxan-induced hyperglycemiic male Wistar rats were randomly allotted to Groups II-VI and orally treated with 10 ml/kg/day distilled water, 5 mg/kg/day glibenclamide, 125 mg/kg MLASE, 250 mg/kg MLASE, and 500 mg/kg/day MLASE, respectively. Group I normal rats served as untreated control and were orally treated with 10 ml/kg of distilled water, all under same sham-handling. Blood samples were taken for measurement of fasting blood glucose, renal and hepatic function profile. Liver and kidney tissue samples were taken for determination of the activities of oxidative stress markers such as malondialdehyde (MDA), reduced glutathione (GSH), and glutathione peroxidase (GPx), catalase (CAT) and superoxidase dismutase (SOD). Results showed that intraperitoneal injection with 120 mg/kg of alloxan in cold 0.9% normal saline reliably and significantly induced a steadily sustained hyperglycemia which were ameliorated by short-term oral treatment with 125-500 mg/kg/day of MLASE, dose dependently, similar to that ameliorated by the standard antihyperglycemic drug, glibenclamide. Similarly, MLASE significantly mitigated against derangements in the measured renal and hepatic function parameters as well as oxidative stress induced by alloxan-induced hyperglycemia. In conclusion, results of this study showed the protective role of 125-500 mg/kg/day of MLASE in chronic hyperglycemia-associated renal and hepatic dysfunctions which was mediated via antioxidant and free radical scavenging activities of MLASE.


N-(3-Acyloxy-2-benzylpropyl)-N'-(4-hydroxy-3-methoxybenzyl) thiourea derivatives as potent vanilloid receptor agonists and analgesics.
A series of N-(3-acyloxy-2-benzylpropyl)-N'-(4-hydroxy-3-methoxybenzyl) thiourea derivatives were investigated as vanilloid receptor ligands in an effort to discover a novel class of analgesics. The proposed pharmacophore model of resiniferatoxin. which includes the C20 homovanillic moiety, the C3-carbonyl and the orthoester phenyl ring as key pharmacophoric groups, was utilized as a guide for drug design. The compounds were synthesized after several steps from diethylmalonate and evaluated in vitro in a receptor binding assay and in a capsaicin-activated channel assay. Additional evaluation of analgesic activity, anti-inflammatory activity and pungency was conducted in animal models by the writhing test, the ear edema assay, and the eye-wiping test, respectively. Among the new compounds, 23 and 28 were found to be the most potent receptor agonists of the series with Ki values of 19 nM and 11 nM, respectively. Their strong in vitro potencies were also reflected by an excellent analgesic profile in animal tests with ED50 values of 0.5 microg kg for 23 and 1.0 microg/kg for 28. Relative to capsaicin these compounds appear to be ca. 600 and 300 times more potent. Both 23 and 28 were found to be less pungent than capsaicin based on the eye-wiping test. However, the compounds did not show significant anti-inflammatory activity. A molecular modeling study comparing the energy-minimized structures of resiniferatoxin and 35 demonstrated a good correlation in the spatial disposition of the corresponding key pharmacophores. The thioureas described in this investigation, which were designed as simplified resiniferatoxin surrogates, represent a novel class of potent vanilloid receptor agonists endowed with potent analgesic activity and reduced pungency.


Successful allogeneic bone marrow transplantation using immunosuppressive conditioning regimen for a patient with red blood cell transfusiondependent pyruvate kinase deficiency anemia.
Pyruvate kinase deficiency (PKD) is the rare glycolytic enzyme defect causing hemolytic anemia. Treatments are mainly red cell transfusion and/or splenectomy, leading to iron overload. Allogeneic bone marrow transplantation (BMT) is alternatively curative treatment for severe PKD. The intensity of conditioning is often controversial because of higher risk of graft failure and organ damage. Here, we present a transfusion-dependent PKD patient undergoing BMT from an HLA-identical sibling using intensively immunosuppressive conditioning regimen. This report suggests that BMT using immunosuppressive conditioning regimen may be a feasible and effective treatment for patients with severe PKD with iron overload. We suggest the timing of the transplantation at an earlier age in severe PKD predicted from gene mutation is preferred before cumulative damage of transfusion.


Enterobacterial repetitive intergenic consensus sequences as molecular targets for typing of Mycobacterium tuberculosis strains.
The presence of enterobacterial repetitive intergenic consensus (ERIC) sequences was demonstrated for the first time in the genome of Mycobacterium tuberculosis; these sequences have been found in transcribed regions of the chromosomes of gram-negative bacteria. In this study genetic diversity among clinical isolates of M. tuberculosis was determined by PCR with ERIC primers (ERIC-PCR). The study isolates comprised 71 clinical isolates collected from Sardinia, Italy. ERIC-PCR was able to identify 59 distinct profiles. The results obtained were compared with IS6110 and PCR-GTG fingerprinting. We found that the level of differentiation obtained by ERIC-PCR is greater than that obtained by IS6110 fingerprinting and comparable to that obtained by PCR-GTG. This method of fingerprinting is rapid and sensitive and can be applied to the study of the epidemiology of M. tuberculosis infections, especially when IS6110 fingerprinting is not of any help.


Beyond the era of NPH insulin--long-acting insulin analogs: chemistry, comparative pharmacology, and clinical application.
The new rDNA and DNA-derived "basal" insulin analogs, glargine and detemir, represent significant advancement in the treatment of diabetes compared with conventional NPH insulin. This review describes blood glucose homeostasis by insulin in people without diabetes and outlines the physiological application of exogenous insulin in patients with type 1 and type 2 diabetes. The requirements for optimal basal insulin treatment are discussed and the methods used in the evaluation of basal insulins are presented. An essential criterion in the development of an "ideal" basal insulin preparation is that the molecular modifications made to the human insulin molecule do not compromise safety. It is also necessary to obtain a clear understanding of the pharmacokinetic and pharmacodynamic characteristics of the two currently available basal insulin analogs. When comparing glargine and detemir, the different molar concentration ratios of the two insulin formulations should be considered along with the nonspecificity of assay systems used to determine insulin concentrations. However, euglycemic clamp studies in crossover study design provide a good basis for comparing the pharmacodynamic responses. When the latter is analyzed by results of intervention clinical trials, it is concluded that both glargine and detemir are superior to NPH in type 1 and type 2 diabetes. However, there is sufficient evidence to demonstrate that these two long-acting insulin analogs are different in both their pharmacokinetic and pharmacodynamic profiles. These differences should be taken into consideration when the individual analogs are introduced to provide basal insulin supplementation to optimize blood glucose control in patients with type 1 and type 2 diabetes as well. PubMed-Medline was searched for articles relating to pharmacokinetics and pharmacodynamics of glargine and detemir. Articles retrieved were reviewed and selected for inclusion if (1) the euglycemic clamp method was used with a duration >or=24 h, (2) a single subcutaneous dose of glargine/detemir was used, and (3) area under the curve for insulin concentrations or glucose infusion rates were calculated.


Ischaemic heart disease in Africa.
Ischaemic heart disease (IHD), previously considered rare in sub-Saharan Africa, now ranks 8th among the leading causes of death in men and women in the region. Furthermore, the prevalence of IHD and related morbidity may be increasing as a result of adverse behavioural and lifestyle changes associated with urbanisation and the epidemiological transition. The major risk factors for IHD in sub-Saharan Africa include hypertension, smoking, diabetes, abdominal obesity and dyslipidaemia. In the INTERHEART Africa study, these risk factors contributed a population-attributable risk of nearly 90% for acute myocardial infarction. Many cost-effective interventions exist at the individual and population levels, and they are likely to have a significant health impact in Africa. An aggressive approach that combines environmental, policy and legislative interventions for health promotion and primary prevention, coupled with improved access to evaluation, treatment and control of hypertension and other major risk factors, provides the best strategy for averting an epidemic of IHD in sub-Saharan Africa.


Neuroanatomical phenotype of Klinefelter syndrome in childhood: a voxel-based morphometry study.
Klinefelter syndrome (KS) is a genetic disorder characterized by a supernumerary X chromosome. As such, KS offers a naturally occurring human model for the study of both X-chromosome gene expression and androgen on brain development. Previous neuroimaging studies have revealed neuroanatomical variations associated with KS, but have differed widely with respect to subject inclusion criteria, including mosaicism, pubertal status, and history of testosterone replacement therapy (TRT), all factors likely to influence neurodevelopment. We conducted a voxel-based morphometry study of regional gray and white matter (GM and WM, respectively) volumes in 31 KS males (mean age, 9.69 ± 1.70 years) and 36 typically developing (TD) male controls (10.99 ± 1.72 years). None of the participants with KS had received TRT, and all were prepubertal and had nonmosaic 47,XXY karyotypes. After controlling for age, males with KS showed trends (0.05 < p < 0.10) for significantly reduced total gray matter volume (TGMV) and total white matter volume (TWMV), relative to TD males. After controlling for TGMV and age, the KS group had significantly increased sensorimotor and parietal-occipital GM and significantly reduced amygdalar, hippocampal, insular, temporal, and inferior frontal GM relative to TD controls. After controlling for TWMV and age, the KS group had significantly increased left parietal WM as well as significantly reduced frontal and temporal WM. These findings are indicative of a characteristic prepubertal neuroanatomical phenotype that may be associated with cognitive-behavioral features of KS. This work offers new insight into the relationships among X-chromosome gene expression, neuroanatomy, and cognitive-behavioral functions impaired in KS, including language and attention.


Characterization of opiate-mediated responses of the feline ileum and ileocecal sphincter.
Although opioid peptides have been demonstrated immunohistochemically in the feline intestine, the action of these peptides is unknown. The aims of this study were: (a) to determine the distal ileal and ileocecal sphincter (ICS) responses to morphine sulfate (MS), methionine enkephalin (ME) and leucine enkephalin (LE); (b) to determine the mechanism by which exogenous opiates mediate these responses; (c) to determine the type of receptor involved in mediating these responses and (d) to ascertain whether endogenous opiate-mediated responses may be vagally induced. The ICS responded to all three opiate agonists with tonic and phasic contractions, the latter being associated with increased spike activity. The ED(max) for ICS pressure response was 1 mug/kg for ME, 5 mug/kg for LE, and 150 mug/kg for MS. The distal ileum responded with increased spike activity and phasic contractions. The ED(max) for the ileal motility index response was 1.0 x 10(-1) mug/kg for ME, 1 mug/kg for LE, and 150 mug/kg for MS. Thus, both sites demonstrated similar dose-response relationships, both responding to at least 100 times lower doses of enkephalins than MS. The ICS contraction preceded ileal contractions. The ileal and ICS response was not antagonized by atropine, hexamethonium, phentolamine, propranolol, cinanserin, or tetrodotoxin. Naloxone, 600 mug/kg, antagonized the response to the enkephalins while 10 mug/kg antagonized the response to MS. Higher doses of the specific-receptor agonist SKF 10047 and kappa-receptor agonist ketocyclazocine were required before a contractile response was elicited. Electrical stimulation of the cervical vagus induced ICS contraction and a fall in blood pressure. The ICS contractile response but not the blood pressure response was inhibited by naloxone 1 mg/kg. These data indicate: (a) tonic and phasic ICS contraction followed by ileal contraction may be mediated through delta-type opiate receptors located in the muscle membrane and (b) opiate-mediated ICS contraction may be induced during vagal stimulation.


Recommendations on Weight Loss and Healthy Lifestyle in Prostate Cancer Clinical Guidelines: A Systematic Review.
Obesity is associated with negative prostate cancer outcomes (e.g., specific mortality, all-cause mortality, biochemical recurrence, etc.), according to the current scientific literature. Nevertheless, recommendations on weight loss and healthy lifestyles are poorly covered by clinicians. We aimed at identifying these recommendations from clinical practice guidelines (CPGs) for prostate cancer. We systematically searched MEDLINE, EMBASE, Web of Science, Scopus, guideline databases and online sources for CPGs updated from January 2015 to August 2021. The searches were independently conducted by two researchers, without language restrictions. A total of 97 prostate cancer guidelines, including 84 (86.6%) CPGs and 13 (13.4%) consensus statements, were included. Recommendations on reaching and maintaining a healthy weight or healthy lifestyles were provided by 7 (7.2%) and 13 (13.4%) documents, respectively. No differences regarding recommendations were found by type of document, year of publication or country. Our results suggest that professional societies and governments should update prostate cancer guidelines to include these recommendations for improving prostate cancer prognosis.


The nucleotide sequences of wild-type coxsackievirus A9 strains imply that an RGD motif in VP1 is functionally significant.
We have shown previously that, compared to other enteroviruses, the coxsackievirus A9 (CAV-9) prototype strain, Griggs, contains a C-terminal extension to the capsid protein VP1 and that within this extension there is an RGD (arginine-glycine-aspartic acid) motif. To determine whether these features are found in other CAV-9 strains and therefore analyse whether they are likely to be functionally important, we have determined the nucleotide sequence of the appropriate region from five strains, isolated over a 25 year period. The results indicate that there is considerable diversity between the strains and there is little correlation between nucleotide sequence identity and date of isolation. All isolates exhibit the VP1 extension and although its amino acid sequence is otherwise variable, the RGD motif is common to all. This conservation of sequence, within a region which can otherwise vary, implies that the RGD sequence must be functionally significant. The VP1 extension shows similarity to sequences found in foot-and-mouth-disease virus strains and to part of the precursor of the cellular protein, human transforming growth factor beta, and the possible significance of these observations is discussed.


Clinical Nurse Well-being Improved Through Transcendental Meditation: A Multimethod Randomized Controlled Trial.
To evaluate the impact of Transcendental Meditation® (TM®) practice on the multidimensional well-being of nurse clinicians affected by the COVID-19 pandemic. The health of clinical nurses has substantial impact on both the availability of a nursing workforce and the quality and safety of patient care. TM improved health and coping strategies across many populations. Clinical nurses were recruited from 3 Magnet®-designated hospitals during the COVID-19 pandemic. Well-being outcomes included flourishing, burnout, anxiety, and posttraumatic stress disorder. Participants were randomized following completion of baseline surveys into immediate (intervention) or delayed (control) TM instruction. Surveys were repeated at 1 and 3 months following baseline survey or TM instruction. Repeated-measures analysis of variance compared differences in groups over time. Across the 3 sites, there were 104 clinical nurse participants. Repeated-measures analysis of variance showed significant medium to large effects in improvement over time in well-being measures for the intervention group. TM improved multidimensional well-being of clinical nurses by reducing posttraumatic stress disorder, anxiety, and burnout and improving flourishing. TM is easy to practice anywhere. The benefits are immediate and cumulative. Organizations and individual nurses can use TM to support clinical nurses in the difficult and meaningful work of patient care, especially in challenging times. Future studies may consider the feasibility of integrating TM into clinical shifts and evaluating its impact on patient and organizational outcomes.


Cellular localization of five structural proteins of Sendai virus studied with peroxidase-labelled Fab fragments of monoclonal antibodies.
By the use of horseradish peroxidase-labelled Fab fragments of monoclonal antibodies, five major structural components of Sendai virus, namely the nucleocapsid (NP), polymerase (P), matrix (M), fusion (F), and haemagglutinin-neuraminidase (HN) proteins were localized in infected Vero cells. The P and NP proteins were found in association with large clusters of ribosome-like particles and nucleocapsids in the cell cytoplasm. They were not concentrated at the cytoplasmic membrane, except in nucleocapsids within budding viral particles. F and HN proteins, on the other hand, were found in connection with ribosomes and endoplasmic reticulum in the cell cytoplasm, but not in nucleocapsids. Both proteins were evenly distributed on the outer cytoplasmic membrane and appeared on the surface clearly before budding of viral particles. The M protein was seen in connection with both nucleocapsids and ribosomes. It was not found at the cell surface except in budding viral particles.


Impact of systematic dynamic maneuvers during computed tomography scan on the T classification of head and neck cancers.
To evaluate the impact of systematic dynamic maneuvers during CT scan on the T-staging of head and neck cancer (HNC). CT scans from the initial workup of 443 consecutive patients treated for HNC in our institution were retrospectively analyzed. CT scans were performed in both expert centers (comprehensive cancer center and university hospital) and non-expert centers. We noted whether dynamic maneuvers (DM) were performed, in 3 categories, namely: DM not done (DMND), done and inadequate (DMDI), done and adequate (DMDA). In the group with DMDA, T-stage was evaluated without and with DM. Interobserver agreement for T staging was assessed after independent double reading of CT scans with and without DM by two radiologists in a random sample. Among the 443 CT scans, DMND was observed in 36.3%, DMDI in 9.3% and DMDA in 54.4%. DMDA were significantly more frequent in expert than in non-expert centers (93.4 vs 6.6%, p < 0.001). In CT scans with DMDA, analysis of the 141 scans rated as T1, T2, T3, or T4 without DM showed agreement of 88.7% with scans with DM, corresponding to a reclassification rate of 11.3% (kappa = 0.85, 95%CI [0.78;0.92]). Among lesions initially classed as Tx without DM (N = 100), the reclassification rate was 76% including DM. The performance of systematic DM integrated into CT protocols is useful to reclassify the T stage in HNC and is essential in case of lesions initially classified as Tx without DM. DM should be performed routinely in expert and nonexpert centers.


Improving therapeutic engagement with adolescent sexual offenders.
This article reports a test of multisystemic predictors of therapeutic engagement (TE) with adolescent sexual offenders (ASOs), and an evaluation of clinical efforts to improve TE with this client group. First, clinicians rated their TE with 105 Australian court-referred male ASOs (M = 15.53 years; SD = 1.30 years), who participated in treatment between 2001 and 2005. For this cohort, correlation analysis showed impulsivity/antisociality, negative peer relationships, and indigenous race to be associated with poorer TE. Multiple regression analysis identified impulsivity/antisociality and indigenous race as significant unique predictors. Clinical efforts subsequently focused on improving TE, particularly with higher-antisocial youth and with indigenous youth and their families. Clinicians then rated TE with a second, independent cohort of 54 court-referred male ASOs (M = 15.44 years; SD = 1.22 years), who participated in the modified treatment between 2006 and 2009. A two-way ANCOVA, controlling for impulsivity/antisociality, indicated significant improvements in TE for both indigenous and non-indigenous ASOs. Despite these general improvements, indigenous ASOs remained comparatively less engaged than their non-indigenous counterparts.


An adjustment to the time-rescaling method for application to short-trial spike train data.
It is important to validate models of neural data using appropriate goodness-of-fit measures. Models summarizing some response features--for example, spike count distributions or peristimulus time histograms--can be assessed using standard statistical tools. Measuring the fit of a full point-process model of spike trains is more difficult. Recently, Barbieri, Quirk, Frank, Wilson, and Brown (2001) and Brown, Barbieri, Ventura, Kass, and Frank (2002) presented a method for rescaling time so that if an underlying description correctly describes the conditional intensity function of a point process, the rescaling will convert the process into a homogeneous Poisson process. The corresponding interevent intervals are exponential with mean 1 and can be transformed to be uniform; tests of the uniformity of the transformed intervals are thus tests of how well the model fits the data. When the lengths of interevent intervals are comparable to the length of the observation window, as can happen in common neurophysiology paradigms using short trials, the fact that long intervals cannot be observed (are censored) can cause the tests based on time rescaling to reject a correct model inappropriately. This article presents a simple adjustment to the time-rescaling method to account for interval censoring, avoiding inappropriate rejection of acceptable models for short-trial data. We illustrate the adjustment's effect using both simulated data and short-trial data from monkey primary visual cortex.