A quantitative microbial risk assessment for meatborne Toxoplasma gondii infection in The Netherlands.
Toxoplasma gondii is an important foodborne pathogen, and the cause of a high disease burden due to congenital toxoplasmosis in The Netherlands. The aim of this study was to quantify the relative contribution of sheep, beef and pork products to human T. gondii infections by Quantitative Microbial Risk Assessment (QMRA). Bradyzoite concentration and portion size data were used to estimate the bradyzoite number in infected unprocessed portions for human consumption. The reduction factors for salting, freezing and heating as estimated based on published experiments in mice, were subsequently used to estimate the bradyzoite number in processed portions. A dose-response relation for T. gondii infection in mice was used to estimate the human probability of infection due to consumption of these originally infected processed portions. By multiplying these probabilities with the prevalence of T. gondii per livestock species and the number of portions consumed per year, the number of infections per year was calculated for the susceptible Dutch population and the subpopulation of susceptible pregnant women. QMRA results predict high numbers of infections per year with beef as the most important source. Although many uncertainties were present in the data and the number of congenital infections predicted by the model was almost twenty times higher than the number estimated based on the incidence in newborns, the usefulness of the advice to thoroughly heat meat is confirmed by our results. Forty percent of all predicted infections is due to the consumption of unheated meat products, and sensitivity analysis indicates that heating temperature has the strongest influence on the predicted number of infections. The results also demonstrate that, even with a low prevalence of infection in cattle, consumption of beef remains an important source of infection. Developing this QMRA model has helped identify important gaps of knowledge and resulted in the following recommendations for future research: collect processing-effect data in line with consumer style processing and acquire product specific heating temperatures, investigate the presence and concentration of viable bradyzoites in cattle, determine the effect of mincing meat on bradyzoite concentrations using actual batch sizes, and obtain an estimate of the fraction of meat that has been frozen prior to purchase. With more accurate data this QMRA model will aid science-based decision-making on intervention strategies to reduce the disease burden from meatborne T. gondii infections in The Netherlands.


Massage, laser and shockwave therapy improve pain and scar pruritus after burns: a systematic review.
In adults with a burn injury, do non-invasive therapies improve pain and burn scar pruritus, elasticity and vascularisation? Are any effects maintained beyond the intervention period? Systematic review of randomised trials with meta-analyses. Adults with burn scars. The experimental intervention was a non-invasive (ie, non-surgical or non-pharmacological) therapy applied to the burn scar. Pain intensity, pruritus intensity, elasticity and vascularisation. Fifteen trials involving 780 participants were included. The results indicated a beneficial effect on pain intensity on a 0-to-10 scale after massage (MD -1.5, 95% CI -1.8 to -1.1), shockwave therapy (MD -0.8, 95% CI -1.2 to -0.4) and laser (MD -4.0, 95% CI -6.0 to -2.0). The results indicated a beneficial effect on pruritus intensity on a 0-to-10 scale after massage (MD -0.4, 95% CI -0.7 to -0.2), shockwave therapy (MD -1.3, 95% CI -2.3 to -0.3) and laser (MD -4.8, 95% CI -6.1 to -3.5). Massage, shockwave therapy and silicone produced negligible or unclear benefits on scar elasticity and vascularisation. The quality of evidence varied from low to moderate. Among all commonly used non-invasive therapies for the treatment of burn scars, low-to-moderate quality evidence indicated that massage, laser and shockwave therapy reduce pain and the intensity of scar pruritus. Low-to-moderate quality evidence suggested that massage, shockwave therapy and silicone have negligible or unclear effects for improving scar elasticity and vascularisation. PROSPERO (CRD42021258336).


Relationship between pre-existing viral reservoirs and the re-emergence of plasma viremia after discontinuation of highly active anti-retroviral therapy.
We examined the pathogenic significance of the latent viral reservoir in the resting CD4+ T cell compartment of HIV-1-infected individuals as well as its involvement in the rebound of plasma viremia after discontinuation of highly active anti-retroviral therapy (HAART). Using heteroduplex mobility and tracking assays, we show that the detectable pool of latently infected, resting CD4+ T cells does not account entirely for the early rebounding plasma HIV in infected individuals in whom HAART has been discontinued. In the majority of patients examined, the rebounding plasma virus was genetically distinct from both the cell-associated HIV RNA and the replication-competent virus within the detectable pool of latently infected, resting CD4 + T cells. These results indicate the existence of other persistent HIV reservoirs that could prompt rapid emergence of plasma viremia after cessation of HAART and underscore the necessity to develop therapies directed toward such populations of infected cells.


Sequential pictorial presentation of neural interaction in the retina. 2. The depolarizing and hyperpolarizing bipolar cells at rod terminals.
Each rod is connected to one depolarizing and one hyperpolarizing bipolar cell. The synaptic connections of cone processes to each bipolar cell and presynaptically to the two rod-bipolar cell synapses establishes conditions for lateral interaction at this level. Thus, the cones raise the threshold for bipolar cell depolarization which is the basis for spatial brightness contrast enhancement and consequently for high visual acuity (Sjöstrand, 2001a). The cones facilitate ganglion cell depolarization by the bipolar cells and cone input prevents horizontal cell blocking of depolarization of the depolarizing bipolar cell, extending rod vision to low illumination. The combination of reduced cone input and transient hyperpolarization of the hyperpolarizing bipolar cell at onset of a light stimulus facilitates ganglion cell depolarization extensively at onset of the stimulus while no corresponding enhancement applies to the ganglion cell response at cessation of the stimulus, possibly establishing conditions for discrimination between on- vs. off-signals in the visual centre. Reduced cone input and hyperpolarization of the hyperpolarizing bipolar cell at onset of a light stimulus accounts for Granit's (1941) 'preexcitatory inhibition'. Presynaptic inhibition maintains transmitter concentration low in the synaptic gap at rod-bipolar cell and bipolar cell-ganglion cell synapses, securing proportional and amplified postsynaptic responses at these synapses. Perfect timing of variations in facilitatory and inhibitory input to the ganglion cell confines the duration of ganglion cell depolarization at onset and at cessation of a light stimulus to that of a single synaptic transmission.


[The effectiveness of BACTEC MGIT 960 system hit analysis of surgery material of patients with tubercular spondylitis].
The article considers the comparison of effectiveness of cultivation of 290 surgery samples from focus of destruction in patients with tubercular spondylitis in liquid medium Middlebrook 7119 with fluorescent detection of growth and two dense egg medium -Levenschtein-Yensen and Finn-II. The sensitivity of methods of inoculation in liquid medium Middlebrook 7H9 and in dense egg mediums has no difference (38.2% and 43.1%, p = 0.271). The duration of growth consisted 2 +/- 2.3 days for liquid mediums and 40.6 +/- 3.2 days for dense mediums. The method of pre-inoculation processing of surgery material. In case of inoculation of 440 samples in liquid mediums contamination consisted 3.9%. In case of inoculation of bone fragments of focus of destruction in liquid medium Middlebrook 7119 the culture was isolated in 43.5% of samples of patients with tubercular spondylitis.


Development and validation of a nomogram for predicting all-cause mortality in patients with hemodialysis having pulmonary hypertension.
Patients with end-stage renal disease receiving hemodialysis (HD) have a high morbidity and mortality rate associated with pulmonary hypertension (PH). A nomogram was developed to predict all-cause mortality in HD patients with PH. In this study, we aimed to validate the usefulness of this nomogram. A total of 274 HD patients with PH were hospitalized at the Affiliated Hospital of Xuzhou Medical University between January 2014 and June 2019 and followed up for 3 years. Echocardiography detected PH when the peak tricuspid regurgitation velocity (TRV) was more than 2.8 m/s. To evaluate the all-cause mortality for long-term HD patients with PH, Cox regression analysis was performed to determine the factors of mortality that were included in the prediction model. Next, the area under the receiver-operating characteristic curve (AUC-ROC) was used to assess the predictive power of the model. Calibration plots and decision curve analysis (DCA) were used to assess the accuracy of the prediction results and the clinical utility of the model. The all-cause mortality rate was 29.1% throughout the follow-up period. The nomogram comprised six commonly available predictors: age, diabetes mellitus, cardiovascular disease, hemoglobin, left ventricular ejection fraction, and TRV. The 1-year, 2-year, and 3-year AUC-ROC values were 0.842, 0.800, and 0.781, respectively. The calibration curves revealed an excellent agreement with the nomogram, while the DCA demonstrated favorable clinical practicability. The first developed nomogram for predicting all-cause mortality in HD patients with PH could guide clinical decision-making and intervention planning.


Gut Microbiota Composition Changes in Constipated Women of Reproductive Age.
Chronic constipation is one of the most prevalent functional gastrointestinal disorders, yet its etiology is multifactorial, and the pathophysiological mechanism is still unclear. Previous studies have shown that the gut microbiota of constipated patients differs from healthy controls; however, many discrepancies exist in the findings, and no clear link has been confirmed between chronic constipation and changes in the gut microbiota. Growing evidence indicates that age, gender, and hormone levels can affect the composition of gut microbiota. The aim of this study is to examine the overall changes in gut microbiota within a specific sub-population of patients, namely, constipated women of reproductive age. We carried out a cross-sectional study comparing the fecal microbial composition of 30 healthy women and 29 constipated women using 16S rRNA gene sequencing. Only women of reproductive age were recruited to reduce the effects of age, gender, and hormone levels on the microbiome, and to prevent conflating the impact of these factors with the effects of constipation. There were obvious differences in the gut microbiota in constipated women of reproductive age compared with the healthy controls, manifesting mainly as a significant increase in the abundance of Bacteroides (p < 0.05) and a significant decrease in the abundance of Proteobacteria (p < 0.01). The overall composition of the gut microbiota in each group was different, which was reflected in the ratios of Firmicutes to Bacteroidetes (F/B), which was 1.52 in the constipated group vs. 2.21 in the healthy group. Additionally, there was a significant decrease in butyrate-producing bacteria, like Roseburia and Fusicatenibacter (p < 0.01). The overall composition of the gut microbiota changed in constipated women of reproductive age, characterized by a loss in Proteobacteria and an increase in Bacteroidetes. Furthermore, the abundance of some butyrate-producing bacteria also reduced. These changes may reflect the unique interactions between host and some bacteria, or some bacterial metabolic products, which may be important targets for future studies to explore the pathogenesis of constipation.


Sam68 Is Required for DNA Damage Responses via Regulating Poly(ADP-ribosyl)ation.
The rapid and robust synthesis of polymers of adenosine diphosphate (ADP)-ribose (PAR) chains, primarily catalyzed by poly(ADP-ribose) polymerase 1 (PARP1), is crucial for cellular responses to DNA damage. However, the precise mechanisms through which PARP1 is activated and PAR is robustly synthesized are not fully understood. Here, we identified Src-associated substrate during mitosis of 68 kDa (Sam68) as a novel signaling molecule in DNA damage responses (DDRs). In the absence of Sam68, DNA damage-triggered PAR production and PAR-dependent DNA repair signaling were dramatically diminished. With serial cellular and biochemical assays, we demonstrated that Sam68 is recruited to and significantly overlaps with PARP1 at DNA lesions and that the interaction between Sam68 and PARP1 is crucial for DNA damage-initiated and PARP1-conferred PAR production. Utilizing cell lines and knockout mice, we illustrated that Sam68-deleted cells and animals are hypersensitive to genotoxicity caused by DNA-damaging agents. Together, our findings suggest that Sam68 plays a crucial role in DDR via regulating DNA damage-initiated PAR production.


A survey of antiemetic dexamethasone administration-frequency of use and perceptions of benefits and risks.
Postoperative nausea and vomiting (PONV) is a significant concern for anaesthetists. There are many agents from different classes that are effective in both preventing and treating PONV. Dexamethasone is a very effective antiemetic, but there are concerns regarding its safety. We performed an anonymous survey of a random selection of the fellows of the Australian and New Zealand College of Anaesthetists to ascertain patterns of practice in relation to PONV prophylaxis and treatment and also to determine awareness of the risks and benefits of perioperative dexamethasone administration. The response rate was 33%. From the responses, 71.2% of all patients undergoing general anaesthesia in the respondents' institutions receive PONV prophylaxis in total and 46.6% receive dexamethasone. No respondent gives more than a single dose of dexamethasone and there was an almost equal split between those who administer 4 and 8 mg, with a smaller number dosing on a weight basis. 5HT-3 receptor antagonists and dexamethasone are the preferred first-line PONV prophylactic agents and 5HT-3 receptor antagonists and droperidol are the preferred first-line PONV therapeutic agents. Concerns relating to the safety of dexamethasone were expressed by 80% of respondents. From this survey, we concluded that the PONV practice of the respondents is largely compliant with recent consensus guidelines, although PONV prophylaxis appears to be given more routinely. It also appears that more education is required on issues regarding dexamethasone safety.


Meta-analysis and the science of research synthesis.
Meta-analysis is the quantitative, scientific synthesis of research results. Since the term and modern approaches to research synthesis were first introduced in the 1970s, meta-analysis has had a revolutionary effect in many scientific fields, helping to establish evidence-based practice and to resolve seemingly contradictory research outcomes. At the same time, its implementation has engendered criticism and controversy, in some cases general and others specific to particular disciplines. Here we take the opportunity provided by the recent fortieth anniversary of meta-analysis to reflect on the accomplishments, limitations, recent advances and directions for future developments in the field of research synthesis.


Low plantar skin perfusion pressure predicts long-term atherosclerotic vascular events and mortality in maintenance haemodialysis patients.
End-stage renal disease is associated with an increased risk of atherosclerotic vascular disease (AVD). We investigated whether low plantar skin perfusion pressure (SPP), a useful indicator of peripheral arterial disease (PAD), predicts systemic AVD events and mortality in outpatients undergoing maintenance haemodialysis (HD). A total of 206 HD patients were enrolled and followed for 5 years. They were divided into 3 groups according to measured SPP: group 1 (G1), SPP >70 mmHg (n = 123); G2, SPP 50-70 mmHg (n = 61); and G3, SPP <50 mmHg (n = 22). During the follow-up period (median, 4.2 years), 56 AVD events (27.2%) and 68 deaths (33.0%) occurred. In G1, G2, and G3, the event-free survival rates were 74%, 55% and 19%, respectively, for AVD events (p < 0.01) and 73%, 54% and 26%, respectively, for mortality (p < 0.01). A Cox multivariate analysis showed that lower SPP was an independent predictor for AVD events [hazard ratio (HR) 3.12, 95% confidence interval (CI) 1.45-6.77, p < 0.01 for G3 vs. G1] and mortality (HR 3.06, 95% CI 1.57-5.98, p < 0.01 for G3 vs. G1). Furthermore, the addition of the SPP value to a model with established risk factors improved the predictability of increasing the net reclassification improvement (NRI; 0.463, p < 0.01) and integrated discrimination improvement (IDI; 0.039, p < 0.01) for AVD events. Similar results were obtained for mortality. Low plantar SPP can stratify risk and improve the predictability of both systemic AVD events and mortality in the maintenance HD population.


Unilateral Adrenal Cryptococcosis on FDG PET/CT.
A 70-year-old man with T-cell deficiency experienced continuous right waist pain and a low degree of fever. Abdominal CT found a large right adrenal mass. FDG PET/CT imaging was acquired to identify the nature of this likely malignant mass and search for potential metastases. The images revealed increased FDG activity in the mass. The patient received right adrenalectomy. Postsurgical pathological and microbial examination demonstrated adrenal cryptococcosis.


[Echocardiographic potentials in the diagnosis of the right ventricular hypoplasia syndrome].
A total of 15 patients with the right-ventricular hypoplasia syndrome and 3 with cyanosis of noncardiac nature were examined, 20 healthy subjects were controls. The authors noted that the localization of the tricuspid valve from usual position is rather difficult and suggested that the right parasternal lines be used for this purpose. Echocardiographic signs of the right-ventricular hypoplasia syndrome are the combination of the diminished size of the right ventricular cavity with reduction of the opening amplitude and deceleration of the early diastolic closing of the anterior cusps of the tricuspid valve and with increased opening amplitude of the anterior mitral cusp.


Induction of steady-state blood alcohol levels: application to the study of within-session alcohol tolerance in rats.
The study of within-session alcohol tolerance in the rat has been hampered by methodological difficulties related to the measurement of dependent variables at predictable blood alcohol concentrations (BAC) during a single session of alcohol exposure. This study characterizes a method for maintaining steady-state blood alcohol levels over several hours in the rat, referred to as the "alcohol clamp." Wistar rats were implanted with an indwelling catheter in the carotid artery for blood sampling and another in the external jugular vein for alcohol infusion. To clamp BAC at a predetermined level, rats first were infused with a priming dose of alcohol to establish the desired or "target" BAC, followed by a continuous infusion of alcohol at a rate equal to that of alcohol metabolism in the rat. This maintained BAC at a constant level over time. BACs of 100, 200, or 300 mg% were maintained over several hours in separate groups of rats. The alcohol clamp was applied to the study of acute (within-session) alcohol tolerance in rats selectively bred for high and low alcohol drinking. Alcohol-induced hypothermia was used to index tolerance, and within-session alcohol tolerance was defined as a return of body temperature toward baseline during the course of the alcohol infusion while BAC was maintained at a constant level. The continuous alcohol infusion procedure maintained BAC in a steady state throughout the 3 hr alcohol infusion session at each of the three target BAC levels. Alcohol infusion induced a drop in body temperature, followed by a return of temperature toward baseline during the course of infusion, which indicated the development of within-session alcohol tolerance. The continuous alcohol infusion procedure (alcohol clamp) maintained BAC in a steady state, both within and between subjects, across a wide range of blood alcohol levels. The alcohol clamp appears to be a useful tool for subsequent studies of within-session alcohol tolerance in the rat.


Further psychometric testing of an instrument to measure emotional care in hospital.
This paper describes further testing of the instrument Patient Evaluation of Emotional Care during Hospitalisation. In 2005, a questionnaire was developed that could be completed by patients to evaluate the quality of emotional care received during their time in hospital. This questionnaire was tested at an acute care private hospital in Perth, Western Australia, with encouraging estimates of reliability and validity. The purpose of this study was to further test this questionnaire in a larger sample of inpatients at a public hospital in the same state. Psychometric evaluation. A hospital-wide survey of 13 wards of a public hospital was conducted. Two hundred and fifty-one patients completed the questionnaire. Psychometric testing of the Patient Evaluation of Emotional Care during Hospitalisation demonstrated acceptable internal consistency reliability. Confirmatory factor analysis substantiated the four sub-scales as follows: Level of Security, Level of Knowing, Level of Personal Value and Level of Connection. The Level of Connection sub-scale was assessed for the first time in this study. This sub-scale had the lowest mean score of all the sub-scales across the hospital as well as in each of the wards surveyed. Qualitative data substantiated, from the patients' perspective, a lack of connection with hospital staff. Further psychometric testing of the Patient Evaluation of Emotional Care during Hospitalisation instrument has confirmed its psychometric properties and usefulness as an instrument to measure emotional care during hospitalisation. The Patient Evaluation of Emotional Care during Hospitalisation is a reliable and valid tool with which the emotional care of patients in hospital can be measured and the effectiveness of interventions assessed.


A sulfur amino acid deficiency changes the amino acid composition of body protein in piglets.
Experiments carried out to determine the amino acid requirement in growing animals are often based on the premise that the amino acid composition of body protein is constant. However, there are indications that this assumption may not be correct. The objective of this study was to test the effect of feeding piglets a diet deficient or not in total sulfur amino acids (TSAA; Met + Cys) on nitrogen retention and amino acid composition of proteins in different body compartments. Six blocks of three pigs each were used in a combined comparative slaughter and nitrogen balance study. One piglet in each block was slaughtered at 42 days of age, whereas the other piglets received a diet deficient or not in TSAA for 19 days and were slaughtered thereafter. Two diets were formulated to provide either 0.20% Met and 0.45% TSAA (on a standardized ileal digestible basis) or 0.46% Met and 0.70% TSAA. Diets were offered approximately 25% below ad libitum intake. At slaughter, the whole animal was divided into carcass, blood, intestines, liver, and the combined head, tail, feet and other organs (HFTO), which were analyzed for nitrogen and amino acid contents. Samples of the longissimus muscle (LM) were analyzed for myosin heavy chain (MyHC) and actin contents. Nitrogen retention was 20% lower in piglets receiving the TSAA-deficient diet (P < 0.01). In these piglets, the nitrogen content in tissue gain was lower in the empty body, carcass, LM and blood (P < 0.05) or tended to be lower in HFTO (P < 0.10), but was not different in the intestines and liver. The Met content in retained protein was lower in the empty body, LM and blood (P < 0.05), and tended to be lower in the carcass (P < 0.10). The Cys content was lower in LM, but higher in blood of piglets receiving the TSAA-deficient diet (P < 0.05). Skeletal muscle appeared to be affected most by the TSAA deficiency. In LM, the Met content in retained protein was reduced by 12% and total Met retention by more than 60%. The MyHC and actin contents in LM were not affected by the TSAA content of the diet. These results show that a deficient TSAA supply affects the amino acid composition of different body proteins. This questions the use of a constant ideal amino acid profile to express dietary amino acid requirements, but also illustrates the plasticity of the animal to cope with nutritional challenges.


The Croydon Assessment of Learning Study: prevalence and educational identification of mild mental retardation.
Mild mental retardation is an enduring and impairing condition. Its prevalence has varied widely across different studies from .5 to over 8%, with higher rates in completely ascertained samples. The current study estimates the prevalence of low IQ in the mental retardation range (intellectual disability) in a population sample and examines the factors that relate to educational identification. A total of 2,730 children in school years 8 and 9 attending local authority schools were assessed in school with the group-administered Cognitive Abilities Test (CAT). A sample of 304 pupils at high, moderate and low risk of mild mental retardation was selected for in-depth study. This included the individually measured full-scale IQ (WISC-III(UK)), the Wechsler Quicktest of attainments, the Strengths and Difficulties Questionnaire from parents and teachers and an abbreviated version of the Social Communication Questionnaire. Of those selected for the in-depth study, 204 (67%) participated, with a greater proportion from the low risk group. A range of prevalence estimates were calculated using different imputation methods and assumptions about individuals not screened. Rates of pupils with WISC IQ < 70 varied from 5.8% to 10.6%. There were no significant gender differences. In contrast to the high prevalence estimates using the WISC, the proportion of pupils scoring in the lowest stanine on the CAT was as expected. Only 15% of those with IQ < 70 had a statement of special educational needs or attended a school for moderate learning difficulties. Behaviour, particularly social communication problems, predicted educational identification. The current study produced a high estimate of the prevalence of mild intellectual disability based on the WISC but not on the CAT. The findings highlight that the majority of mild intellectual disability in the UK would not be detected using registers. Cases that are detected by registers are more behaviourally disturbed than others.


Is family history of breast cancer a marker of susceptibility to exposures in the incidence of de novo adult acute leukemia?
The risk factors for adult acute leukemia incidence have been difficult to establish. Family history of cancer might interact with environmental exposures to produce associations that are otherwise difficult to detect. In addition to family history of leukemia or other hematopoietic cancers, family history of breast cancer could be a marker of susceptibility, because leukemia and breast cancer are known to cluster in families that have specific germ-line mutations. In a population-based case control study of 779 incident adult acute leukemia patients and 625 controls, we estimated the relative risk for exposed individuals with a family history compared with unexposed individuals without a family history (RR(11)), along with a measure of interdependence, the interaction contrast ratio. Combined with a family history of breast cancer, ever-smoking [RR(11) = 2.4, 95% confidence interval (CI): 1.2-4.8], general solvent exposure (RR(11) = 1.9, 95% CI: 1.1-3.4), aromatic hydrocarbon exposure (RR(11) = 3.8, 95% CI: 1.1-14), and diagnostic ionizing radiation exposure (RR(11) = 2.1, 95% CI: 1.2-3.8) were all associated with increased incidence. Furthermore, there was no increased incidence associated with any of these exposures in the absence of a family history of breast cancer and no increased incidence for family history of breast cancer in the absence of exposures. The pattern of relative risks strongly suggested synergy across exposures. Family history of breast cancer might be a marker of susceptibility to a range of leukemia risk factors, whose effects are generally weak or nonexistent when considered alone.


Calcium-dependent Pyk2 activation: a role for calmodulin?
Pyk2 (proline-rich tyrosine kinase 2) and FAK (focal adhesion kinase) are highly related tyrosine kinases. One distinguishing feature is the differential regulation of the two enzymes in response to elevation of cytoplasmic calcium. In the latest issue of the Biochemical Journal, Sasaki and co-workers have provided insight into the calcium-dependent regulation of Pyk2. The findings suggest that calmodulin may bind the FERM (4.1/ezrin/radixin/moesin) domain to promote Pyk2 activation in response to calcium signals triggered by vasopressin. While the molecular details of the protein-protein interaction and mechanism of activation remain to be firmly established, this study is the first to provide mechanistic insight into the regulation of Pyk2 by calcium.


Hormone therapy and risk of lung cancer: a meta-analysis.
The association between hormone therapy (HT) use and lung cancer risk is inconsistent in epidemiological studies. This meta-analysis was conducted to examine the association between HT and lung cancer risk. We searched MEDLINE (PubMed), EMBASE, and the Cochrane Library in April 2008. All articles searched were independently reviewed and selected by two evaluators according to predetermined inclusion and exclusion criteria. We included a total of 11 studies (8 case-control studies and 3 prospective cohort studies), involving a total of 220,599 participants. When all studies were pooled, the odds ratio (OR) of HT use for lung cancer risk was 0.87 (95% confidence interval (CI) 0.74-1.02). In subgroup meta-analyses, there was no association among cohort studies (relative risk (RR) 1.01; 95% CI 0.74-1.38), while there was a significant association between HT use and lung cancer risk among case-control studies (OR 0.81; 95% CI 0.68-0.97) based on a random-effects model. No significant association between HT use and lung cancer risk was observed in most of the subgroup meta-analyses by methodological quality of study, type of HT use, duration of HT use, and histology of lung cancer, while significant protective effects were observed among former and never smokers except for current smokers. However, cumulative meta-analyses based on year of publication showed a distinct trend toward a protective effect of HT use on lung cancer risk in the recent studies. Overall, the findings of this meta-analysis do not support the hypothesis that there is a link between HT use and lung cancer risk. Our findings should be evaluated in further prospective cohort studies.


Malaria parasites regulate intra-erythrocytic development duration via serpentine receptor 10 to coordinate with host rhythms.
Malaria parasites complete their intra-erythrocytic developmental cycle (IDC) in multiples of 24 h suggesting a circadian basis, but the mechanism controlling this periodicity is unknown. Combining in vivo and in vitro approaches utilizing rodent and human malaria parasites, we reveal that: (i) 57% of Plasmodium chabaudi genes exhibit daily rhythms in transcription; (ii) 58% of these genes lose transcriptional rhythmicity when the IDC is out-of-synchrony with host rhythms; (iii) 6% of Plasmodium falciparum genes show 24 h rhythms in expression under free-running conditions; (iv) Serpentine receptor 10 (SR10) has a 24 h transcriptional rhythm and disrupting it in rodent malaria parasites shortens the IDC by 2-3 h; (v) Multiple processes including DNA replication, and the ubiquitin and proteasome pathways, are affected by loss of coordination with host rhythms and by disruption of SR10. Our results reveal malaria parasites are at least partly responsible for scheduling the IDC and coordinating their development with host daily rhythms.


Postdischarge Adverse Events Among Neonates Admitted to the Neonatal Intensive Care Unit.
We aimed to determine the rate of postdischarge adverse events (AEs), classify the types of postdischarge AEs, and identify risk factors for postdischarge AEs among neonates admitted to the neonatal intensive care unit (NICU). This was a prospective cohort study of neonates admitted to the NICU from February 2017 through June 2019. We enrolled 170 neonates from a level 4 NICU who were being discharged home and whose parents can speak English and could be contacted after discharge. The main outcome of the study was postdischarge AEs based on structured telephone interviews, health record review, and adjudication by 2 blinded, trained physicians using a previously established methodology. Fourteen percent of 170 neonates admitted to the NICU experienced postdischarge AEs, with 48% being either preventable or ameliorable. Adverse drug events and procedural complications comprised most of the AEs (48%), but most of the preventable and ameliorable AEs were due to management, therapeutic, or diagnostic errors. Seventy-nine percent of neonates who suffered an AE experienced either a readmission to the hospital or an emergency department visit. Neonates admitted to a level 4 NICU from another NICU (level 1, 2, or 3) (adjusted odds ratio, 3.62; 95% confidence interval, 1.27-12.60; P = 0.01) and those 28 to 36 weeks (adjusted odds ratio, 11.38; 95% confidence interval, 1.67-127.98; P = 0.01) had a significantly higher risk of AEs at discharge. Neonates discharged from a level 4 NICU were at high risk for experiencing postdischarge AEs. The identification of AE types and risk factors can be used to guide efforts to develop interventions to improve neonatal patient safety during the postdischarge period.


Effects of histone deacetylase inhibitors on regenerative cell responses in human dental pulp cells.
To investigate the growth, migratory and adhesive effects of trichostatin A (TSA) and valproic acid (VPA), two histone deacetylase inhibitors (HDACis), on human dental pulp stem cells (hDPSCs). To verify that TSA or VPA functions as an HDAC inhibitor, the expressions of histones H3 and H4 were examined using Western blotting analysis. hDPSC growth and metabolic activity was evaluated by MTT viability analysis at different time-points and by cell count experiments. The expression of cell cycle regulatory proteins and apoptosis-associated proteins was examined by Western blot analysis. Migration effects were investigated using wound healing and transwell migration assays. An adhesion assay was also performed in the presence and absence of HDACis. The levels of chemokines and adhesion molecules relevant to repair in hDPSCs were also assessed by qRT-PCR and Western blot analysis. The data were analysed, where appropriate, using Student's t-test or one-way anova followed by the Student-Newman-Keuls test using SPSS software. Trichostatin A and VPA enhanced acetylation of histones H3 and H4 (P < 0.05). Significant increases (P < 0.05) in MTT levels in hDPSCs were observed after treatment with TSA (2 and 20 nmol L-1 ) or VPA (1 and 10 mmol L-1 ). Cell numbers were not significantly affected at the concentration of TSA (0.2-10 nmol L-1 ) or VPA (0.01-100 mmol L-1 ) applied compared with the control at 3, 5 or 7 days (P > 0.05). At the same time, the expression of Cdx2 and cyclin A was upregulated by 2 nmol L-1 TSA and 1 mmol L-1 VPA (P < 0.05). Higher TSA or VPA concentrations induced apoptosis in hDPSCs in the cell count and apoptosis experiments (P < 0.05). Moreover, TSA and VPA significantly depressed the expression of Cdx2 and cyclin A (P < 0.05), whilst it significantly improved the level of p21 (P < 0.05). TSA and VPA promoted migration and adhesion of hDPSCs (P < 0.05). The levels of chemokines and adhesion molecules were significantly upregulated after exposure of hDPSCs to 20 nmol L-1 TSA or 1 mmol L-1 VPA (P < 0.05). Histone deacetylase inhibitors at specific concentrations promoted proliferation, migration and adhesion of hDPSCs, which may contribute to novel regenerative therapies for pulpal disease treatment.


From image processing to computer vision: plant imaging grows up.
Image analysis is a field of research which, combined with novel methods of capturing images, can help to bridge the genotype-phenotype gap, where our understanding of the genotype has until now been leaps and bounds ahead of our ability to work with the phenotype. Methods of automating image capture in plant science research have increased in usage recently, as has the need to provide objective and highly accurate measures on large image datasets, thereby bringing the phenotype back to the centre of interest. In this special issue of Functional Plant Biology, we present some recent advances in the field of image analysis, and look at examples of different kinds of image processing and computer vision, which is occurring with increasing frequency in the plant sciences.


Organic-inorganic hybrid microdisk laser with dye and silica mixed doping prepared by ink-jet printing method.
We developed an ink-jet printing method for fabricating inorganic microdisks at room temperature, which is much lower than the melting point of solid-state inorganic oxide, and have fabricated an organic-inorganic hybrid microdisk laser. Silica was used as the inorganic disk material, and microdisk-shaped aggregates were formed by the ink-jet printing method using a solution in which nanosilica particles were dispersed in propylene glycol monomethylether (PGME) solvent. Then, a microdisk capable of laser oscillation was also prepared by preliminarily adding the laser dye rhodamine 6G to the ink to form a mixed organic material. The structural evaluation of the printed microdisk was first conducted using an optical microscope, a scanning electron microscope (SEM), and an atomic force microscope (AFM). The results of laser oscillation evaluation by optical excitation showed that the printed microdisk sufficiently functions as an optical resonator with a low optical loss. In these evaluations, excellent values such as a surface roughness of 5.83 nm from root mean square (R. M. S.) which is one forth smaller than the particle diameter, and a laser oscillation threshold of 4.76 µJ/mm2 at a wavelength of 601.4 nm were obtained. To the best of our knowledge, this is the first time that an inorganic microdisk has been fabricated at room temperature to realize an organic-inorganic hybrid microdisk laser.


Changes of microbial characteristics of retained sludge during low-temperature operation of an EGSB reactor for low-strength wastewater treatment.
In this study, a lab scale EGSB reactor was operated for 400 days to investigate the influence of temperature-decrease on the microbial characteristic of retained sludge. The EGSB reactor was started-up at 15 degrees C seeding with 20 degrees C-grown granular sludge. The influent COD of synthetic wastewater was set at 0.6-0.8 gCOD/L. The process-temperature was stepwise reduced from 15 degrees C to 5 degrees C during 400 days operation. Decrease of temperature of the reactor from 15 degrees C to 10 degrees C caused the decline of COD removal efficiency. However, continuous operation of the EGSB reactor led the efficient treatment of wastewater (70% of COD removal, 50% of methane recovery) at 10 degrees C. We confirmed that the both acetate-fed and hydrogen-fed methanogenic activities of retained sludge clearly increased under 15 to 20 degrees C. Changes of microbial profiles of methanogenic bacteria were analyzed by 16S rDNA-targeted DGGE analysis and cloning. It shows that genus Methanospirillum as hydrogen-utilizing methanogen proliferated due to low temperature operation of the reactor. On the other hand, genus Methanosaeta presented in abundance as acetoclastic-methanogen throughout the experiment.


A review of the factors affecting sunlight inactivation of micro-organisms in waste stabilisation ponds: preliminary results for enterococci.
Waste stabilisation ponds (WSP) are efficient, cost-effective methods of treating wastewater in rural and remote communities in Australia. It is recognised that sunlight plays a significant role in their disinfection, however, due to the poor penetration of light in turbid waters it has been hypothesised that other mechanisms may also contribute to disinfection in WSPs. To date, studies have reported various and conflicting results with regards to the relative contributions of UVA, UVB, PAR and environmental factors including pH, DO and photo-sensitisers on micro-organism disinfection. Initially we investigated the role of these environmental factors on the solar disinfection of enterococci in buffered distilled water to control for potential confounding factors within the wastewater. Die-off rate constants were measured, in sterile buffered distilled water at varying pH and dissolved oxygen concentrations, for enterococci irradiated with UVA and UVB. Enterococci were found to be predominantly inactivated by UVB (p<0.001), however, UVA was also observed to increase inactivation rates relative to the dark control (p<0.001). DO and pH were found to have no effect on inactivation rate when enterococci were irradiated with UVB (p>0.05), however, when irradiated with UVA, both DO and pH were observed to further increase inactivation rates (p<0.01).


Acetyl-homocysteine-thiolactone-induced increase of superoxide dismutase counteracts the effect of subdiabetogenic doses of streptozocin.
Acetyl-homocysteine-thiolactone (CYT) is an organic thio compound that exerts free radical scavenger activity and increases superoxide dismutase (SOD) activity. Administration of 32 mg CYT/kg body wt/day/30 days in rats increased SOD activity in erythrocytes by 126%, and in pancreatic islets by 202%. Treatment affected only the Cu-Zn fraction of the enzyme. Transmission electron microscope observations showed that the damage to the pancreatic beta cells induced by single or multiple subdiabetogenic doses of streptozocin (STZ) (45 mg/kg body wt) was attenuated in animals treated with CYT. This protective effect was not observed with 65 mg of STZ. The experimental results seem to support the hypothesis that pancreatic beta cells are particularly vulnerable to the effect of oxygen radicals and that the cytotoxic effect of STZ is related to free radical-induced peroxidation.


Association of Single and Dual Sensory Impairment with Falls among Medicare Beneficiaries.
Objective: The purpose of this study was to determine if dual sensory impairment (DSI) is associated with falls and fear of falling among older adults. Methods: Using data from the 2019 Medicare Current Beneficiary Survey (MCBS), we studied the cross-sectional association of self-reported hearing/vision impairment with self-reported history/number of falls over the past year, fear of falling (scale 1-6), and a fall requiring medical help using weighted multivariable regressions adjusted for demographic and clinical covariates. Results: Among 11,089 Medicare beneficiaries (mean age = 74, 55% female, 9% Black), DSI is associated with increased prevalence (prevalence ratio = 1.45 [1.28-1.65]) and incidence (incidence ratio = 2.21 [1.79-2.75]) rate of falls, and greater odds of a higher fear of falling score (odds ratio = 1.38 [1.08-1.77]). Discussion: DSI is associated with falls among older adults. Consideration of DSI as a marker to initiate fall prevention programs and inclusion of sensory interventions in these programs may be valuable.


Combining deep learning and coherent anti-Stokes Raman scattering imaging for automated differential diagnosis of lung cancer.
Lung cancer is the most prevalent type of cancer and the leading cause of cancer-related deaths worldwide. Coherent anti-Stokes Raman scattering (CARS) is capable of providing cellular-level images and resolving pathologically related features on human lung tissues. However, conventional means of analyzing CARS images requires extensive image processing, feature engineering, and human intervention. This study demonstrates the feasibility of applying a deep learning algorithm to automatically differentiate normal and cancerous lung tissue images acquired by CARS. We leverage the features learned by pretrained deep neural networks and retrain the model using CARS images as the input. We achieve 89.2% accuracy in classifying normal, small-cell carcinoma, adenocarcinoma, and squamous cell carcinoma lung images. This computational method is a step toward on-the-spot diagnosis of lung cancer and can be further strengthened by the efforts aimed at miniaturizing the CARS technique for fiber-based microendoscopic imaging.


Energy Migration Processes in Re(I) MLCT Complexes Featuring a Chromophoric Ancillary Ligand.
We present the synthesis, structural characterization, electronic structure calculations, and ultrafast and supra-nanosecond photophysical properties of a series of five Re(I) bichromophores exhibiting metal to ligand charge transfer (MLCT) excited states based on the general formula fac-[Re(N∧N)(CO)3(PNI-py)]PF6, where PNI-py is 4-piperidinyl-1,8-naphthalimidepyridine and N∧N is a diimine ligand (Re1-5), along with their corresponding model chromophores where 4-ethylpyridine was substituted for PNI-py (Mod1-5). The diimine ligands used include 1,10-phenanthroline (phen, 1), 2,9-dimethyl-4,7-diphenyl-1,10-phenanthroline (bcp, 2), 4,4'-di-tert-butyl-2,2'-bipyridine (dtbb, 3), 4,4'-diethyl ester-2,2'-bipyridine (deeb, 4), and 2,2'-biquinoline (biq, 5). In these metal-organic bichromophores, structural modification of the diimine ligand resulted in substantial changes to the observed energy transfer efficiencies between the two chromophores as a result of the variation in 3MLCT excited-state energies. The photophysical properties and energetic pathways of the model chromophores were investigated in parallel to accurately track the changes that arose from introduction of the organic chromophore pendant on the ancillary ligand. All relevant photophysical and energy transfer processes were probed and characterized using time-resolved photoluminescence spectroscopy, ultrafast and nanosecond transient absorption spectroscopy, and time-dependent density functional theory calculations. Of the five bichromophores in this study, four (Re1-4) exhibited a thermal equilibrium between the 3PNI-py and the 3MLCT excited state, drastically extending the lifetimes of the parent model chromophores.


L-arginine attenuates trauma-hemorrhage-induced liver injury.
Liver injury is common after trauma-hemorrhage for which the underlying mechanism is not clear. Although administration of the essential amino acid L-arginine has been reported to restore the depressed cardiovascular functions and cell-mediated immune responses after trauma-hemorrhage, it remains unknown whether L-arginine protects against liver injury under those conditions. A prospective, controlled animal study. A university research laboratory. Male Sprague-Dawley rats. Rats underwent sham operation or laparotomy and were bled to and maintained at a mean arterial blood pressure of 40 mm Hg until 40% of the maximum shed blood volume was returned in the form of lactated Ringer's solution. Hemorrhaged rats were then resuscitated with lactated Ringer's solution, four times the maximum shed blood volume over 1 hr. During resuscitation, animals received either 300 mg/kg of L-arginine or saline (vehicle) intravenously. At 3 and 5 hrs after resuscitation, rats were killed, blood was obtained, and the liver was fixed for histology (hematoxylin & eosin staining). Plasma glutathione S-transferase (a marker of liver damage), L-arginine, citrulline, and ornithine concentrations were assessed. The increased concentrations of plasma glutathione S-transferase observed in vehicle-treated hemorrhage animals were normalized with L-arginine treatment at 5 hrs after resuscitation. Moreover, the histology indicated that L-arginine prevented liver edema and neutrophil infiltration after trauma-hemorrhage. Plasma L-arginine and citrulline were increased in L-arginine-treated rats. Because citrulline is a by-product of nitric oxide generation by nitric oxide synthase from L-arginine, this amino acid may be a useful adjunct for preventing hepatic injury after trauma-hemorrhage via endothelial derived nitric oxide production.


Temporally defined neocortical translation and polysome assembly are determined by the RNA-binding protein Hu antigen R.
Precise spatiotemporal control of mRNA translation machinery is essential to the development of highly complex systems like the neocortex. However, spatiotemporal regulation of translation machinery in the developing neocortex remains poorly understood. Here, we show that an RNA-binding protein, Hu antigen R (HuR), regulates both neocorticogenesis and specificity of neocortical translation machinery in a developmental stage-dependent manner in mice. Neocortical absence of HuR alters the phosphorylation states of initiation and elongation factors in the core translation machinery. In addition, HuR regulates the temporally specific positioning of functionally related mRNAs into the active translation sites, the polysomes. HuR also determines the specificity of neocortical polysomes by defining their combinatorial composition of ribosomal proteins and initiation and elongation factors. For some HuR-dependent proteins, the association with polysomes likewise depends on the eukaryotic initiation factor 2 alpha kinase 4, which associates with HuR in prenatal developing neocortices. Finally, we found that deletion of HuR before embryonic day 10 disrupts both neocortical lamination and formation of the main neocortical commissure, the corpus callosum. Our study identifies a crucial role for HuR in neocortical development as a translational gatekeeper for functionally related mRNA subgroups and polysomal protein specificity.


How Much Is Enough? The Relationship Between Prosocial Effort and Moral Character Judgments.
The amount of effort required to bring about a prosocial outcome can vary from low-handing a stranger the wallet she just dropped-to high-spending days tracking down the owner of a lost wallet. The goal of the current research is to characterize the relationship between prosocial effort and moral character judgments. Does more prosocial effort always lead to rosier moral character judgments? Across four studies (N = 1,658), we find that moral character judgments increase with prosocial effort to a point and then plateau. We find evidence that this pattern is produced, in part, by descriptive and prescriptive norms: exceeding descriptive norms increases moral character judgments, but exceeding prescriptive norms has the opposite effect, which leads to a tapering off of moral character judgments at higher levels of effort.


Prioritizing COVID-19 vaccination efforts and dose allocation within Madagascar.
While mass COVID-19 vaccination programs are underway in high-income countries, limited availability of doses has resulted in few vaccines administered in low and middle income countries (LMICs). The COVID-19 Vaccines Global Access (COVAX) is a WHO-led initiative to promote vaccine access equity to LMICs and is providing many of the doses available in these settings. However, initial doses are limited and countries, such as Madagascar, need to develop prioritization schemes to maximize the benefits of vaccination with very limited supplies. There is some consensus that dose deployment should initially target health care workers, and those who are more vulnerable including older individuals. However, questions of geographic deployment remain, in particular associated with limits around vaccine access and delivery capacity in underserved communities, for example in rural areas that may also include substantial proportions of the population. To address these questions, we developed a mathematical model of SARS-CoV-2 transmission dynamics and simulated various vaccination allocation strategies for Madagascar. Simulated strategies were based on a number of possible geographical prioritization schemes, testing sensitivity to initial susceptibility in the population, and evaluating the potential of tests for previous infection. Using cumulative deaths due to COVID-19 as the main outcome of interest, our results indicate that distributing the number of vaccine doses according to the number of elderly living in the region or according to the population size results in a greater reduction of mortality compared to distributing doses based on the reported number of cases and deaths. The benefits of vaccination strategies are diminished if the burden (and thus accumulated immunity) has been greatest in the most populous regions, but the overall strategy ranking remains comparable. If rapid tests for prior immunity may be swiftly and effectively delivered, there is potential for considerable gain in mortality averted, but considering delivery limitations modulates this. At a subnational scale, our results support the strategy adopted by the COVAX initiative at a global scale.


European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ) - 2019 Update.
This overview presents the updated European Association of Urology (EAU) guidelines for non-muscle-invasive bladder cancer (NMIBC), TaT1, and carcinoma in situ (CIS). To provide practical recommendations on the clinical management of NMIBC with a focus on clinical presentation and recommendations. A broad and comprehensive scoping exercise covering all areas of the NMIBC guidelines has been performed annually since the last published version in 2017. Databases covered by the search included Medline, EMBASE, and the Cochrane Libraries. Previous guidelines were updated, and the level of evidence and grade of recommendation were assigned. Tumours staged as Ta, T1, and/or CIS are grouped under the heading of NMIBC. Diagnosis depends on cystoscopy and histological evaluation of the tissue obtained by transurethral resection (TURB) in papillary tumours or by multiple bladder biopsies in CIS. In papillary lesions, a complete TURB is essential for the patient's prognosis and correct diagnosis. Where the initial resection is incomplete, where there is no muscle in the specimen, or where a T1 tumour is detected, a second TURB should be performed within 2-6 wk. The risks of both recurrence and progression may be estimated for individual patients using the European Organisation for Research and Treatment of Cancer (EORTC) scoring system. Stratification of patients into low-, intermediate-, and high-risk groups is pivotal to the recommendation of adjuvant treatment. In patients with tumours presumed to be at a low risk and in those presumed to be at an intermediate risk with a low previous recurrence rate and an expected EORTC recurrence score of <5, one immediate chemotherapy instillation is recommended. Patients with intermediate-risk tumours should receive 1 yr of full-dose bacillus Calmette-Guérin (BCG) intravesical immunotherapy or instillations of chemotherapy for a maximum of 1 yr. In patients with high-risk tumours, full-dose intravesical BCG for 1-3 yr is indicated. In patients at the highest risk of tumour progression, immediate radical cystectomy should be considered. Cystectomy is recommended in BCG-unresponsive tumours. The extended version of the guidelines is available at the EAU website: https://uroweb.org/guideline/non-muscle-invasive-bladder-cancer/. These abridged EAU guidelines present updated information on the diagnosis and treatment of NMIBC for incorporation into clinical practice. The European Association of Urology Non-muscle-invasive Bladder Cancer (NMIBC) Panel has released an updated version of their guidelines, which contains information on classification, risk factors, diagnosis, prognostic factors, and treatment of NMIBC. The recommendations are based on the current literature (until the end of 2018), with emphasis on high-level data from randomised clinical trials and meta-analyses. Stratification of patients into low-, intermediate-, and high-risk groups is essential for deciding appropriate use of adjuvant intravesical chemotherapy or bacillus Calmette-Guérin (BCG) instillations. Surgical removal of the bladder should be considered in case of BCG-unresponsive tumours or in NMIBCs with the highest risk of progression.


2DB: a Proteomics database for storage, analysis, presentation, and retrieval of information from mass spectrometric experiments.
The amount of information stemming from proteomics experiments involving (multi dimensional) separation techniques, mass spectrometric analysis, and computational analysis is ever-increasing. Data from such an experimental workflow needs to be captured, related and analyzed. Biological experiments within this scope produce heterogenic data ranging from pictures of one or two-dimensional protein maps and spectra recorded by tandem mass spectrometry to text-based identifications made by algorithms which analyze these spectra. Additionally, peptide and corresponding protein information needs to be displayed. In order to handle the large amount of data from computational processing of mass spectrometric experiments, automatic import scripts are available and the necessity for manual input to the database has been minimized. Information is in a generic format which abstracts from specific software tools typically used in such an experimental workflow. The software is therefore capable of storing and cross analysing results from many algorithms. A novel feature and a focus of this database is to facilitate protein identification by using peptides identified from mass spectrometry and link this information directly to respective protein maps. Additionally, our application employs spectral counting for quantitative presentation of the data. All information can be linked to hot spots on images to place the results into an experimental context. A summary of identified proteins, containing all relevant information per hot spot, is automatically generated, usually upon either a change in the underlying protein models or due to newly imported identifications. The supporting information for this report can be accessed in multiple ways using the user interface provided by the application. We present a proteomics database which aims to greatly reduce evaluation time of results from mass spectrometric experiments and enhance result quality by allowing consistent data handling. Import functionality, automatic protein detection, and summary creation act together to facilitate data analysis. In addition, supporting information for these findings is readily accessible via the graphical user interface provided. The database schema and the implementation, which can easily be installed on virtually any server, can be downloaded in the form of a compressed file from our project webpage.


Developing a predictive model for fine particulate matter concentrations in low socio-economic households in Durban, South Africa.
In low-resource settings, there is a need to develop models that can address contributions of household and outdoor sources to population exposures. The aim of the study was to model indoor PM2.5 using household characteristics, activities, and outdoor sources. Households belonging to participants in the Mother and Child in the Environment (MACE) birth cohort, in Durban, South Africa, were randomly selected. A structured walk-through identified variables likely to generate PM2.5 . MiniVol samplers were used to monitor PM2.5 for a period of 24 hours, followed by a post-activity questionnaire. Factor analysis was used as a variable reduction tool. Levels of PM2.5 in the south were higher than in the north of the city (P < .05); crowding and dwelling type, household emissions (incense, candles, cooking), and household smoking practices were factors associated with an increase in PM2.5 levels (P < .05), while room magnitude and natural ventilation factors were associated with a decrease in the PM2.5 levels (P < .05). A reasonably robust PM2.5 predictive model was obtained with model R2 of 50%. Recognizing the challenges in characterizing exposure in environmental epidemiological studies, particularly in resource-constrained settings, modeling provides an opportunity to reasonably estimate indoor pollutant levels in unmeasured homes.


Recognition and ordering at surfaces: the importance of handedness and footedness.
The expression of chirality at surfaces, arising from the adsorption of chiral molecules, is usually discussed in terms of the molecular handedness. However, the adsorption process often leads to a new manifestation of chirality in the form of the adsorption footprint. Therefore, in order to fully define the chirality of the interface we propose that both the handedness and the footedness of the system must be considered. To illustrate this point, we describe the ordering behavior of the molecules tartaric acid, succinic acid, proline, and 3-pyrroline-2-carboxylic (PCA) on a Cu(110) surface using deconvolution maps separating the arrangement of enantiomers, conformers, adsorption footprints and rotamers within an organized assembly. Tartaric and succinic acid mimic the behavior of a conventional 3D conglomerate and racemic compound in terms of both the handedness and footedness, respectively. However, racemic PCA and proline, while expressing a random solid solution of enantiomers and conformers, both display unexpected degrees of order when adsorbate footprint and orientation are considered.


Controlling the degradation of cellulose scaffolds with Malaprade oxidation for tissue engineering.
This study was conducted to develop biodegradable cellulose scaffolds by oxidising porous cellulose sponges for tissue engineering applications. Cellulose powder was dissolved in ionic liquid using a salt leaching method, and porous cellulose scaffolds of various pore sizes were prepared. The scaffolds were oxidised with periodate to introduce aldehyde at a rate controlled by the periodate concentration. Oxidised scaffolds exhibited weight loss in cell culture medium, but not in phosphate buffer. Therefore, we confirmed that Schiff base formation between the aldehyde and amino groups through a Maillard reaction triggered cellulose molecular degradation. The degradation rate was controlled by the oxidation degree, whereas the aldehyde content controlled protein adsorption and cell proliferation. Additionally, in vivo implantation tests revealed that optimising the oxidation ratio not only improved biodegradability but also reduced inflammation. In conclusion, our results suggest that simple oxidised cellulose is useful as a low-toxicity biodegradable scaffold.


Elastin mRNA levels during foetal development of sheep nuchal ligament and lung. Hybridization to complementary and cloned DNA.
Elastin mRNA levels were quantified in sheep nuchal ligament and lung during the latter half of foetal development with elastin-specific cDNA (complementary DNA) probes using both hybridization in solution (saturation analysis) and hybridization on a fixed support (Northern analysis). For the solution-hybridization studies, cDNA prepared from nuchal-ligament mRNA was enriched to 65% for elastin sequences by hybridizing it to its template at a R0t (mol X s X litre-1) value that included only the abundant class of mRNA sequences. Hybridization of this probe to RNA extracted from nuchal ligament between 70 and 138 days after conception demonstrated elastin sequences increased about 10-fold (from 0.047 to 0.438% of total RNA). In contrast, lung elastin mRNA levels increased only 3-fold (from 0.009 to 0.022% of total RNA) during the same period. Over this development period these values correspond to increases in the average number of elastin mRNA molecules from 950 to 20 000 molecules/ligament cell and from 130 to 330 molecules/lung cell. For Northern analysis, elastin mRNA was purified from near-term-sheep nuchal ligament on sucrose density gradients. Analysis of the translation products of this elastin mRNA showed that relative elastin precursor synthesis was at least 80% of total [3H]valine incorporation. The Mr of this elastin mRNA, determined by methylmercury-agarose-gel electrophoresis, was approx. 1.25 X 10(6). Northern hybridization of nuchal ligament and lung RNA to a [32P]cDNA probe, transcribed from this sucrose-gradient-purified elastin mRNA, confirmed the developmental changes in elastin mRNA levels detected by solution-hybridization techniques. The specificity of this method was confirmed by using a cloned elastin gene fragment. These studies demonstrate that elastin mRNA levels in organs such as nuchal ligament and lung increase with foetal development, but that there are significant differences in the average cellular elastin mRNA content of these two organs.


[Association of aortic coarctation with patent ductus arteriosus (analysis of clinical and surgical data].
A retrospective analysis of clinical and operative data was made covering 56 cases with combined coarctation of the aorta and patent ductus arteriosus. Prior to surgery both anomalies were recognized in 27 patients. Clinical data failed to furnish an reliable criteria as to the difference in anatomic variants of combined aortic coarctation and patent ductus arteriosus. The clinical picture and diagnosis of this congenital pathology are largely contingent upon the conspicuousness of each abnormality and consequently, on a definite orientation of the clinical diagnosis. There is a direct relation between the frequency of detection of the patent ductus arteriosus and its size.


Mechanism of sodium transport inhibition by epidermal growth factor in cortical collecting ducts.
Epidermal growth factor (EGF) inhibits Na transport in the cortical collecting ducts (CCD). To gain insight into the signal transduction of this effect, several potential mechanisms were examined in rabbit CCD perfused in vitro. Pretreatment with pertussis toxin, indomethacin, or the protein kinase C inhibitor H7 did not prevent the acute 34-50% decrease in lumen-to-bath 22Na flux (JNa) on exposure to peritubular EGF, indicating that the inhibition is not mediated by a Gi protein, prostaglandin E2 (PGE2), or protein kinase C. Inhibition of the basolateral Na-H exchanger was also without an effect. Lowering the bath Ca concentration from 1.2 to 0.11 mM did not prevent the inhibition of JNa by EGF (JNa decreased significantly by 38.7 +/- 6.9% and 29.1 +/- 5.3%, respectively); in contrast, reduction of the bath free Ca to 0.005 mM totally abolished the effect of EGF. The response to EGF was also assessed in the setting of chronic stimulation of Na transport; inhibition of JNa by EGF was still observed in CCD from remnant kidneys and in CCD from mineralocorticoid-treated rabbits. The results demonstrate that the inhibition of CCD Na transport by EGF is dependent on peritubular Ca. This suggests that the signal transduction involves Ca influx across the basolateral membrane and that increased cytosolic free Ca may be a common pathway for the counterregulatory control of Na reabsorption by several agonists.


Different irradiances of UV and PAR in the same ratios alter the flavonoid profiles of Arabidopsis thaliana wild types and UV-signalling pathway mutants.
The UVR8 photoreceptor in Arabidopsis thaliana is specific for ultraviolet-B (UV-B; 280-315 nm) radiation and its activation leads to a number of UV-B acclimation responses, including the accumulation of flavonoids. UVR8 participates in a signaling cascade involving COP1 and HY5 so that the absence of any of these components results in a reduction in the ability of a plant to accumulate flavonoids in response to UV; Cop1 mutants show high dropouts and hy5-ks50 hyh double mutants show very low levels of flavonoids. The predominant phenolics in Arabidopsis thaliana are sinapic acid derivatives as well as non-aclyated quercetin and kaempferol di- and triglycosides containing glucose and rhamnose as glycosylated sugar moieties. How this flavonoid profile in Arabidopsis thaliana is affected by UV radiation, how rapidly these changes occur in changing UV conditions, and which components of the UV-B signalling pathway are involved in rapid UV acclimatization reactions is poorly understood. In the present study, we examined these questions by characterizing the flavonoid profiles of Arabidopsis thaliana signalling mutants and wild types grown under different UV levels of constant UV-B+PAR ratios and then transferring a subset of plants to alternate UV conditions. Results indicate that flavonoid accumulation in Arabidopsis thaliana is triggered by UV and this response is amplified by higher levels of UV but not by all compounds to the same extent. The catechol structure in quercetin seems to be less important than the glycosylation pattern, e.g. having 2 rhamnose moieties in determining responsivity. At low UV+PAR intensities the introduction of UV leads to an initial tendency of increase of flavonoids in the wild types that was detected after 3 days. It took 7 days for these changes to be detected in plants grown under high UV+PAR intensities suggesting a priming of PAR. Thus, the flavonoid profile in Arabidopsis thaliana is altered over time following exposure to UV and PAR, but the functional significance of these changes is currently unclear.


The syndrome of right bundle branch block ST segment elevation in V1 to V3 and sudden death--the Brugada syndrome.
In 1992 a new syndrome was described consisting of syncopal episodes and/or sudden death in patients with a structurally normal heart and an electrocardiogram (ECG) characteristic of right bundle branch block with ST segment elevation in leads V1 to V3. The disease is genetically determined, with an autosomal dominant pattern of transmission. Three different mutations that affect the structure and function of the cardiac sodium channel gene SCN5A have been identified. Two mutations result in total loss of function of the sodium channel. The other mutation results in acceleration of the recovery of the sodium channel from inactivation. The incidence of the disease is difficult to estimate, but it causes 4 to 10 sudden deaths per 10000 inhabitants per year in areas like Thailand and Laos. In these countries, the disease represents the most frequent cause of death in young adults. Up to 50% of the yearly sudden deaths in patients with a structurally normal heart are caused by this syndrome. The diagnosis is easily made by means of the ECG. The presence of concealed and intermittent forms, however, make the diagnosis difficult in some patients. The ECG can be modulated by changes in autonomic balance and the administration of antiarrhythmic drugs. Beta-adrenergic stimulation normalizes the ECG, while intravenous ajmaline, flecainide or procainamide accentuate ST segment elevation and are capable of unmasking concealed and intermittent forms of the disease. Recent data suggest that loss of the action potential dome in the right ventricular epicardium but not the endocardium underlies ST segment elevation seen in the Brugada syndrome. Also, electrical heterogeneity within the right ventricular epicardium leads to the development of closely coupled extrasystoles via a phase 2 reentrant mechanism, which then precipitates ventricular tachycardia-ventricular fibrillation. Right ventricular epicardium is preferentially affected because of the predominance of transient outward current in this tissue. Antiarrhythmic drugs like amiodarone and beta-blockers do not prevent sudden death in symptomatic or asymptomatic individuals. Gene therapy may offer a cure in future years. Implantation of an automatic cardioverter-defibrillator is the only currently proven effective therapy.


IL28B alleles associated with poor hepatitis C virus (HCV) clearance protect against inflammation and fibrosis in patients infected with non-1 HCV genotypes.
Genetic polymorphisms near IL28B are associated with spontaneous and treatment-induced clearance of hepatitis C virus (HCV), two processes that require the appropriate activation of the host immune responses. Intrahepatic inflammation is believed to mirror such activation, but its relationship with IL28B polymorphisms has yet to be fully appreciated. We analyzed the association of IL28B polymorphisms with histological and follow-up features in 2335 chronically HCV-infected Caucasian patients. Assessable phenotypes before any antiviral treatment included necroinflammatory activity (n = 1,098), fibrosis (n = 1,527), fibrosis progression rate (n = 1,312), and hepatocellular carcinoma development (n = 1,915). Associations of alleles with the phenotypes were evaluated by univariate analysis and multivariate logistic regression, accounting for all relevant covariates. The rare G allele at IL28B marker rs8099917-previously shown to be at risk of treatment failure-was associated with lower activity (P = 0.04), lower fibrosis (P = 0.02) with a trend toward lower fibrosis progression rate (P = 0.06). When stratified according to HCV genotype, most significant associations were observed in patients infected with non-1 genotypes (P = 0.003 for activity, P = 0.001 for fibrosis, and P = 0.02 for fibrosis progression rate), where the odds ratio of having necroinflammation or rapid fibrosis progression for patients with IL28B genotypes TG or GG versus TT were 0.48 (95% confidence intervals 0.30-0.78) and 0.56 (0.35-0.92), respectively. IL28B polymorphisms were not predictive of the development of hepatocellular carcinoma. In chronic hepatitis C, IL28B variants associated with poor response to interferon therapy may predict slower fibrosis progression, especially in patients infected with non-1 HCV genotypes.


Synthetic Antioxidants as Contaminants of Emerging Concern in Indoor Environments: Knowns and Unknowns.
Synthetic antioxidants, including synthetic phenolic antioxidants (SPAs), amine antioxidants (AAs), and organophosphite antioxidants (OPAs), are essential additives for preventing oxidative aging in various industrial and consumer products. Increasing attention has been paid to the environmental contamination caused by these chemicals, but our understanding of synthetic antioxidants is generally limited compared to other emerging contaminants such as plasticizers and flame retardants. Many people spend a significant portion (normally greater than 80%) of their time indoors, meaning that they experience widespread and persistent exposure to indoor contaminants. Thus, this Perspective focuses on the problem of synthetic antioxidants as indoor environmental contaminants. The wide application of antioxidants in commercial products and their demonstrated toxicity make them an important family of indoor contaminants of emerging concern. However, significant knowledge gaps still need to be bridged: novel synthetic antioxidants and their related transformation products need to be identified in indoor environments, different dust sampling strategies should be employed to evaluate human exposure to these contaminants, geographic scope and sampling scope of research on indoor contamination should be broadened, and the partition coefficients of synthetic antioxidants among different media need to be investigated.


Comparison of outcomes in infected cardiovascular implantable electronic devices between complete, partial, and failed lead removal: an ESC-EHRA-EORP ELECTRa (European Lead Extraction ConTrolled) registry.
The present study sought to determine predictors for success and outcomes of patients who underwent cardiac implantable electronic devices (CIED) extraction indicated for systemic or local CIED related infection in particular where complete lead removal could not be achieved. ESC-EORP ELECTRa (European Lead Extraction ConTRolled Registry) is a European prospective lead extraction registry. Out of the total cohort, 1865/3510 (52.5%) patients underwent removal due to CIED related infection. Predictors and outcomes of failure were analysed. Complete removal was achieved in 1743 (93.5%) patients, partial (<4 cm of lead left) in 88 (4.7%), and failed (>4 cm of lead left) in 32 (1.8%) patients. Removal success was unrelated to type of CIED infection (pocket or systemic). Predictors for failure were older leads and older patients [odds ratio (OR) 1.14 (1.08-1.19), P < 0.0001 and OR 2.68 (1.22-5.91), P = 0.0146, respectively]. In analysis by lead, predictors for failure were: pacemaker vs. defibrillator removal and failure to engage the locking stylet all the way to the tip [OR 0.20 (0.04-0.95), P = 0.03 and OR 0.32 (0.13-0.74), P = 0.008, respectively]. Significantly higher complication rates were noted in the failure group (40.6% vs. 15.9 for partial and 8.7% for success groups, P < 0.0001). Failure to remove a lead was a strong predictor for in hospital mortality [hazard ratio of 2.05 (1.01-4.16), P = 0.046]. A total of 6.5% of infected CIED patients failed attempted extraction. Only were >4 cm of lead remained resulted in higher procedural complications and mortality rates.


IFI27 may predict and evaluate the severity of respiratory syncytial virus infection in preterm infants.
Preterm infants are a special population that vulnerable to respiratory syncytial virus (RSV) infection and the lower respiratory tract infections (LRTIs) caused by RSV could be severe and even life-threating. The purpose of the present study was to identify candidate genes of preterm infants who are susceptible to RSV infection and provide a new insight into the pathogenesis of RSV infection. Three datasets (GSE77087, GSE69606 and GSE41374) containing 183 blood samples of RSV infected patients and 33 blood samples of healthy controls from Gene Expression Omnibus (GEO) database were downloaded and the differentially expressed genes (DEGs) were screened out. The function and pathway enrichments were analyzed through Database for Annotation, Visualization and Integrated Discovery (DAVID) website. The protein-protein interaction (PPI) network for DEGs was constructed through Search Tool for the Retrieval of Interacting Genes (STRING). The module analysis was performed by Cytoscape software and hub genes were identified. Clinical verification was employed to verify the expression level of top five hub genes among 72 infants including 50 RSV infected patients and 22 non-RSV-infected patients hospitalized in our center. Further, the RSV infected infants with high-expression IFI27 and those with low-expression IFI27 were compared (defined as higher or lower than the median mRNA level). Finally, the gene set enrichment analysis (GSEA) focusing on IFI27 was carried out. Totally, 4028 DEGs were screened out and among which, 131 most significant DEGs were selected. Subsequently, 13 hub genes were identified, and function and pathway enrichments of hub genes mainly were: response to virus, defense response to virus, regulation of viral genome replication and regulation of viral life cycle. Furthermore, IFI27 was confirmed to be the most significantly expressed in clinical verification. Gene sets associated with calcium signaling pathway, arachidonic acid metabolism, extracellular matrix receptor interaction and so on were significantly enriched when IFI27 was highly expressed. Moreover, high-expression IFI27 was associated with more severe cases (p = 0.041), more requirements of mechanical ventilation (p = 0.034), more frequent hospitalization (p < 0.001) and longer cumulative hospital stay (p = 0.012). IFI27 might serve to predict RSV infection and evaluate the severity of RSV infection in preterm infants.


Surgical journal club as a community of practice: a case study.
Journal club has become a signature pedagogy in postgraduate medical education. In this article, social learning theory, through the lens of "communities of practice" (CoP), is applied to elucidate the process of learning in journal club. The study is a case study of a surgical journal club. Video recordings of 2 journal club sessions were followed by semistructured audio-recorded interviews with a sample of journal club participants. Thematic content analysis was performed, mapping data to themes arising based on the key tenets of CoP. Features of the 4 tenets of CoP learning (community, meaning, identity, and practice) were identified in both the video recordings of journal club and the participant interviews. A shared enterprise and common sense of purpose (community) was seen throughout the video recordings, but feelings of belonging to the community were much stronger for senior members (consultants/attending staff and senior trainees) compared with junior members (junior trainees and students). Experiences and perspectives were more commonly exchanged between senior trainees and consultants, with junior trainees not partaking in discussions, an example of newcomers beginning at the periphery. The main impediment to learning was found with low senior member attendance at journal club, thus limiting access to narratives of senior experience of practice and feedback. In attempting to improve journal club design for learning, ensuring the participation of senior community members and thus access to narratives of experience along with active engagement of junior members to allow them develop their own meaning should be incorporated into the journal club design.


Translationally controlled tumor protein interacts with nucleophosmin during mitosis in ES cells.
Somatic cell nuclear transfers and the generation of induced pluripotent stem cells provide potential routes towards non-immunogenic cell replacement therapies. Translationally controlled tumor protein (Tpt1) was recently suggested to regulate cellular pluripotency. Here we explore functions of Tpt1 in mouse embryonic stem (ES) cells. We find that Tpt1 is present in the nucleus and cytoplasm of ES cells, and that specifically nuclear Tpt1 decreases upon cell differentiation. We also find that endogenous Tpt1 forms a complex with endogenous nucleophosmin/nucleoplasmin family member 1 (Npm1) in a cell cycle dependent manner. The Tpt1-Npm1 complex peaks sharply during mitosis and is independent of phosphorylation by Polo-like kinase. Differentiation by retinoic acid decreases Tpt1-Npm1 complex levels. Moreover, Tpt1 knock-down or over-expression reduces proliferation whereas Npm1 over-expression increases proliferation in ES cells. Cells depleted for both Tpt1 and Npm1 exhibit significantly reduced proliferation compared to cells depleted for Tpt1 alone, whereas cells over-expressing both Tpt1 and Npm1 show normal proliferation. Our findings reveal a role for the Tpt1-Npm1 complex in cell proliferation and identify the Tpt1-Npm1 complex as a potential biomarker for mitotic ES cells.


Role of bradykinin B2 receptors in the developmental changes of renal hemodynamics in the neonatal rat.
The present study was performed to evaluate the role of bradykinin, acting via B2 receptors, in the developmental rise in renal blood flow (RBF) and glomerular filtration rate (GFR) in the rat. Newborn rats were chronically treated from birth with the kinin B2 receptor antagonist HOE-140 (600 micrograms/kg sc, every 12 h, n = 9) or 0.9% saline (n = 7). Weanling rats (mean age 23 days) were anesthetized with pentobarbital sodium (50 mg/kg ip) for measurements of mean arterial pressure (MAP), GFR, and renal plasma flow estimated from p-aminohippurate (PAH) clearance (ERPF). Outer cortical RBF (OCBF) was measured by laser-Doppler flowmetry. Baseline MAP was similar in HOE-140- and saline-treated rats (96 +/- 4 vs. 97 +/- 4 mmHg). Also, baseline GFR (0.65 +/- 0.05 vs. 0.52 +/- 0.08 ml.min-1.g-1) and ERPF (1.6 +/- 0.2 vs. 1.3 +/- 0.1 ml.min-1.g-1) were not different in HOE-140- and saline-treated rats, respectively. Intravenous infusion of 200 ng bradykinin did not change MAP or OCBF in HOE-140 rats but decreased MAP (-29 +/- 3%, P < 0.05) and OCBF (-20 +/- 2%, P < 0.05) in controls. Intravenous infusion of 25 ng angiotensin II increased MAP equally in both groups (-32 +/- 4%) and caused a similar reduction in OCBF (-37 +/- 14 vs. -46 +/- 5%). The angiotensin type 1 (AT1) receptor antagonist losartan (10 mg/kg iv) decreased MAP equally in both groups (-22 +/- 2%). However, AT1 blockade increased ERPF to 3.1 +/- 0.8 ml.min-1.g-1 (P < 0.05 vs. baseline) in saline but not in HOE-140 rats (1.9 +/- 0.4 ml.min-1.g-1). Kidney renin mRNA and angiotensin II contents were not different in HOE-140 vs. saline groups. The present findings indicate that bradykinin is not a primary mediator of the maturational rise in RBF or GFR in the rat. However, the data suggest that under control conditions, angiotensin II, acting via AT1 receptors, counteracts the renal vasodilatory effects of endogenous bradykinin in the developing kidney.


Human Induced Pluripotent Stem Cell-Derived Engineered Heart Tissue as a Sensitive Test System for QT Prolongation and Arrhythmic Triggers.
Cardiac repolarization abnormalities in drug-induced and genetic long-QT syndrome may lead to afterdepolarizations and life-threatening ventricular arrhythmias. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) should help to overcome the limitations of animal models based on species differences in repolarization reserve. Here, we compared head-to-head the contribution of IKs (long QT1) and IKr (long QT2) on action potentials (APs) in human left ventricular (LV) tissue and hiPSC-CM-derived engineered heart tissue (EHT). APs were measured with sharp microelectrodes in EHT from 3 different control hiPSC-CM lines and in tissue preparations from failing LV. EHT from hiPSC-CMs showed spontaneous diastolic depolarization and AP generation that were sensitive to low concentrations of ivabradine. IKr block by E-4031 prolonged AP duration at 90% repolarization with similar half-effective concentration in EHT and LV but larger effect size in EHT (+281 versus +110 ms in LV). Although IKr block alone evoked early afterdepolarizations and triggered activity in 50% of EHTs, slow pacing, reduced extracellular K+, and blocking of IKr, IKs, and IK1 were necessary to induce early afterdepolarizations in LV. In accordance with their clinical safety, moxifloxacin and verapamil did not induce early afterdepolarizations in EHT. In both EHT and LV, IKs block by HMR-1556 prolonged AP duration at 90% repolarization slightly in the combined presence of E-4031 and isoprenaline. EHT from hiPSC-CMs shows a lower repolarization reserve than human LV working myocardium and could thereby serve as a sensitive and specific human-based model for repolarization studies and arrhythmia, similar to Purkinje fibers. In both human LV and EHT, IKs only contributed to repolarization under adrenergic stimulation.


Health impact of hospital restrictions on seriously ill hospitalized patients: lessons from the Toronto SARS outbreak.
Restrictions on non-urgent hospital care imposed to control the 2003 Toronto severe acute respiratory syndrome outbreak led to substantial disruptions in hospital clinical practice, admission, and transfer patterns. We assessed whether there were unintended health consequences to seriously ill hospitalized patients. STUDY DESIGN, SETTING, AND POPULATION: Population-based longitudinal cohort study of patients residing in Toronto or an urban control region with an incident admission for 1 of 7 serious conditions in the 3 years before, or the 4 months during or after restrictions. Short-term mortality, overall readmissions, cardiac readmissions for acute myocardial infarction patients, serious complications for very low birth weight babies, and quality of care measures, comparing adjusted rates across time periods within regions. Mortality, readmission, and complication rates did not change for any condition during or after severe acute respiratory syndrome restrictions. Although rates of invasive cardiac procedures for acute myocardial infarction patients decreased 11-37% in Toronto, rates of nonfatal cardiac outcomes did not change. Restrictions on non-urgent hospital utilization and hospital transfers may be a safe public health strategy to employ to control nosocomial outbreaks or provide hospital surge capacity for up to several months, in large, well-developed healthcare systems with good availability of community-based care.


A non-long terminal repeat retrotransposon family is restricted to the germ line micronucleus of the ciliated protozoan Tetrahymena thermophila.
The ciliated protozoan Tetrahymena thermophila undergoes extensive programmed DNA rearrangements during the development of a somatic macronucleus from the germ line micronucleus in its sexual cycle. To investigate the relationship between programmed DNA rearrangements and transposable elements, we identified several members of a family of non-long terminal repeat (LTR) retrotransposons (retroposons) in T. thermophila, the first characterized in the ciliated protozoa. This multiple-copy retrotransposon family is restricted to the micronucleus of T. thermophila. The REP (Tetrahymena non-LTR retroposon) elements encode an ORF2 typical of non-LTR elements that contains apurinic/apyrimidinic endonuclease (APE) and reverse transcriptase (RT) domains. Phylogenetic analysis of the RT and APE domains indicates that the element forms a deep-branching clade within the non-LTR retrotransposon family. Northern analysis with a probe to the conserved RT domain indicates that transcripts from the element are small and heterogeneous in length during early macronuclear development. The presence of a repeated transposable element in the genome is consistent with the model that programmed DNA deletion in T. thermophila evolved as a method of eliminating deleterious transposons from the somatic macronucleus.


Infection at the subcellular level. II. Distribution and fate of intravenously injected brucellae within phagocytic cells of guinea pigs.
Cells of Brucella melitensis strain 16 M were labeled with (32)P. When injected into normal guinea pigs, labeled, viable bacteria were taken up and inactivated in liver and spleen during the 60 min after infection. Both uptake and inactivation increased if brucellae were coated with antibrucella antibody. Neither viability nor radioactivity were lost when labeled brucellae were incubated for 60 min in vitro with normal guinea pig blood, liver homogenates, or in defined medium. Incubation for 12 h with antibrucella rabbit immunoglobulin G similarly was innocuous. Livers were removed from infected animals at various times up to 60 min after injection and were separated into subcellular fractions. The numbers of total (determined by radioactivity measurements) and viable brucellae as well as the acid phosphatase activity in the various fractions were determined. Total bacteria and acid phosphatase activity were progressively transferred from the mitochondrial plus light mitochondrial (M + L) fraction to the nuclear (N) fraction. Viability of brucellae declined more rapidly in the N fraction than in other fractions. Examination of M + L fractions by isopycnic centrifugation showed a decrease in viability of both free brucellae and those in particles. The results indicated the formation of bacteria-containing heterolysosomes which progressively increased in size and in which brucellae were inactivated. The antibrucella activity of phagocytes of guinea pig liver in vivo appeared to be greater than that of peritoneal macrophages from immune rabbits or of bovine leukocytes studied in vitro.


Shock wave lithotripsy of stones implanted in the proximal ureter of the pig.
Ureteral stones can be difficult to treat with shock wave (SW) lithotripsy. A strategy for lithotripsy of proximal ureteral stones is to push them back into the renal pelvis prior to administering SWs. However, push-back is invasive and not always possible. Since there are few clues to suggest how best to treat ureteral stones with SWs in situ, we developed an animal model for research on lithotripsy for ureteral stones. Gypsum model stones were implanted bilaterally in the proximal ureter and renal calix of the pig via percutaneous access. Lithotripsy was performed using a HM3 lithotripter (Dornier Medical Systems, Marietta, Georgia) and stones at each location were treated with the same dose (400 SWs, 20 kV and 30 SWs per minute). Fragments were collected and the percent increase in projected surface area of the particles was determined. The breakage (mean percent area increase) of stones implanted in the proximal ureter was significantly less than that of stones located in the renal calix treated with the same dose of shock waves (134% vs 327%, p <0.001). Also, stones that were fully confined by the ureter did not break as well as stones located at the ureteropelvic junction. This indicates that the physical environment surrounding a stone can have a significant effect on the efficiency of SW action. The observation that stones implanted in the ureter showed decreased breakage compared with stones in the kidney is consistent with clinical experience. This finding is a valuable and even essential prerequisite for any experimental animal model system intended for the study of SW action in the breakage of ureteral stones.


Light-induced plasticity in leaf hydraulics, venation, anatomy, and gas exchange in ecologically diverse Hawaiian lobeliads.
Leaf hydraulic conductance (Kleaf ) quantifies the capacity of a leaf to transport liquid water and is a major constraint on light-saturated stomatal conductance (gs ) and photosynthetic rate (Amax ). Few studies have tested the plasticity of Kleaf and anatomy across growth light environments. These provided conflicting results. The Hawaiian lobeliads are an excellent system to examine plasticity, given the striking diversity in the light regimes they occupy, and their correspondingly wide range of Amax , allowing maximal carbon gain for success in given environments. We measured Kleaf , Amax , gs and leaf anatomical and structural traits, focusing on six species of lobeliads grown in a common garden under two irradiances (300/800 μmol photons m(-2) s(-1) ). We tested hypotheses for light-induced plasticity in each trait based on expectations from optimality. Kleaf , Amax , and gs differed strongly among species. Sun/shade plasticity was observed in Kleaf , Amax, and numerous traits relating to lamina and xylem anatomy, venation, and composition, but gs was not plastic with growth irradiance. Species native to higher irradiance showed greater hydraulic plasticity. Our results demonstrate that a wide set of leaf hydraulic, stomatal, photosynthetic, anatomical, and structural traits tend to shift together during plasticity and adaptation to diverse light regimes, optimizing performance from low to high irradiance.


Nonlinear Anomalous Hall Effect for Néel Vector Detection.
Antiferromagnetic (AFM) spintronics exploits the Néel vector as a state variable for novel spintronic devices. Recent studies have shown that the fieldlike and antidamping spin-orbit torques (SOTs) can be used to switch the Néel vector in antiferromagnets with proper symmetries. However, the precise detection of the Néel vector remains a challenging problem. In this Letter, we predict that the nonlinear anomalous Hall effect (AHE) can be used to detect the Néel vector in most compensated antiferromagnets supporting the antidamping SOT. We show that the magnetic crystal group symmetry of these antiferromagnets combined with spin-orbit coupling produce a sizable Berry curvature dipole and hence the nonlinear AHE. As a specific example, we consider the half-Heusler alloy CuMnSb, in which the Néel vector can be switched by the antidamping SOT. Based on density-functional theory calculations, we show that the nonlinear AHE in CuMnSb results in a measurable Hall voltage under conventional experimental conditions. The strong dependence of the Berry curvature dipole on the Néel vector orientation provides a new detection scheme of the Néel vector based on the nonlinear AHE. Our predictions enrich the material platform for studying nontrivial phenomena associated with the Berry curvature and broaden the range of materials useful for AFM spintronics.


Identification and its vicissitudes as observed in adolescence.
The author emphasizes two main types of identification processes: primary or narcissistic identification prevailing in self-selfobject relationships, and implying the use of idealizing libido, before the differentiation self-selfobject is achieved; secondary identification occurring at a later developmental phase, when there is a clearcut differentiation between self and object. Differing from Kohut's point of view on identity, she feels that what is described by self psychology as the feeling of 'cohesion, continuity in time and the affective colouring of the self' corresponds to the sense of identity. Adolescence is viewed, not only as a chronological phase, but primarily as a state of mind, with specific characteristics, resulting from the transformations of the self, culminating in the establishment of the sense of identity. When there is a traumatic disillusionment in the idealized self-object during early development, this leads to a fixed adolescent state of mind, independent of chronological age, which can be more clearly observed in the analysis of adult patients with self pathology. A clinical case of an adult patient illustrates the author's point and shows that the processes of idealization, de-idealization and transmuting internalizations, occurring both in adolescence and during the analytic treatment, are typical of this mental state.