Radiofrequency ablation of atrioventricular nodal reentry tachycardia: a 14 year experience with 901 patients at the Tel Aviv Sourasky Medical Center.
Atrioventricular nodal reentry tachycardia is the most frequent cause of regular, paroxysmal supraventricular tachycardia. Radiofrequency ablation of the slow pathway has been recommended as first-line therapy for curing AVNRT. To report a 14 year experience of RFA of the slow pathway in patients with AVNRT treated in our laboratory. A total of 901 consecutive patients (aged 9-92, mean 50.8 +/- 18.2 years) underwent RFA of the slow pathway. All patients had sustained AVNRT induced with or without intravenous administration of isoproterenol. A standard electrophysiologic method with three diagnostic and one ablation catheter was used in 317 patients (35.2%); in the remaining 584 patients (64.8%), only two electrode catheters (one diagnostic, one ablation) were used ("two-catheter approach"). Catheter ablation of the slow pathway abolished AVNRT induction in 877 patients (97.3%). In 14 patients (1.6%) the procedure was discontinued while in 10 (1.1%) the procedure failed. In 864 patients (95.9%) there were no complications. Transient or permanent AV block occurred during the procedure in 31 patients (3.4%), of whom 8 (0.9%) eventually required pacemaker insertion (n = 7) or upgrade of a previously implanted WI pacemaker (n = 1) during the month following the procedure. The number of catheters used did not significantly affect the rate of results or complications of the ablation procedure. The success and complication rates remained stable over the years, although a significant trend for increased age and associated heart disease was observed during the study period. The results of this single-center large study, which included patients with a wide age range, showed results similar to those of previous studies. The use of a "two-catheter approach" (one diagnostic and one ablation) was as effective and safe as a multi-catheter approach.


[Dynamic monitoring of ecological environment in loess hilly and gully region of Loess Plateau based on remote sensing: A case study on Fuxian County in Shaanxi Province. Northwest China].
Based on the principal component analysis (PCA), four ecological evaluation indicators including vegetation index, wet index, land surface temperature and soil index were combined to evaluate the ecological environment quality of Fuxian County in hilly and gully area of Loess Plateau from year 1995 to 2014. The results showed that the RSEI integrated RS and PCA method could reveal regional ecological changes objectively and quantitatively. The level of overall regional ecological status in Fuxian County was good with a high vegetation fraction and rich biodiversity. The synthetical ecological environment quality index increased from 3.17 to 3.53 indicating the ecological environment had been improved greatly in recent 20 years. The area with best ecological environment quality was located in Niuwu town. The magnitude of change increased progressively from northwest to southeast, and the biggest change occurred in Jiaodao and Nandaode towns. From 1995 to 2014, the areas with decreased and increased ecological environment quality were 16.7% and 42.7% of the study area, respectively, and the improved regions were mainly distributed in plateau and hilly area in the center, rocky low mountainous area in northeast and the Ziwuling Nature Reserve area in southwest of the county.


Dietary intake, physical activity and sedentary behaviour patterns in a sample with established psychosis and associations with mental health symptomatology.
People with psychosis experience cardiometabolic comorbidities, including metabolic syndrome, coronary heart disease and diabetes. These physical comorbidities have been linked to diet, inactivity and the effects of the illness itself, including disorganisation, impairments in global function and amotivation associated with negative symptoms of schizophrenia or co-morbid depression. We aimed to describe the dietary intake, physical activity (PA) and sedentary behaviour patterns of a sample of patients with established psychosis participating in the Improving Physical Health and Reducing Substance Use in Severe Mental Illness (IMPaCT) randomised controlled trial, and to explore the relationship between these lifestyle factors and mental health symptomatology. A majority of participants had poor dietary quality, low in fruit and vegetables and high in discretionary foods. Only 29.3% completed ⩾150 min of moderate and/or vigorous activity per week and 72.2% spent ⩾6 h per day sitting. Cross-sectional associations between negative symptoms, global function, and PA and sedentary behaviour were observed. Additionally, those with more negative symptoms receiving IMPaCT therapy had fewer positive changes in PA from baseline to 12-month follow-up than those with fewer negative symptoms at baseline. These results highlight the need for the development of multidisciplinary lifestyle and exercise interventions to target eating habits, PA and sedentary behaviour, and the need for further research on how to adapt lifestyle interventions to baseline mental status. Negative symptoms in particular may reduce patient's responses to lifestyle interventions.


Distinguishing heat from light in debate over controversial fossils.
Fossil organisms offer our only direct insight into how the distinctive body plans of extant organisms were assembled. However, realizing the potential evolutionary significance of fossils can be hampered by controversy over their interpretation. Here, as a guide to evaluating palaeontological debates, we outline the process and pitfalls of fossil interpretation. The physical remains of controversial fossils should be reconstructed before interpreting homologies, and choice of interpretative model should be explicit and justified. Extinct taxa lack characters diagnostic of extant clades because the characters had not yet evolved, because of secondary loss, or because they have rotted away. The latter, if not taken into account, will lead to the spurious assignment of fossils to basally branching clades. Conflicting interpretations of fossils can often be resolved by considering all the steps in the process of anatomical analysis and phylogenetic placement, although we must accept that some fossil organisms are simply too incompletely preserved for their evolutionary significance to be realized.


The genetic basis and expanding role of molecular analysis in the diagnosis, prognosis, and therapeutic design for myelodysplastic syndromes.
The myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders of ineffective hematopoiesis that characteristically demonstrate peripheral blood cytopenia, bone marrow hypercellularity, and morphologically defined dysplasia of one or more hematopoietic lineages. Classical metaphase cytogenetics and judicious use of fluorescence in situ hybridization play central roles in the contemporary diagnosis and classification of MDS. An abundance of recent molecular studies are beginning to delineate additional genetic and epigenetic aberrations associated with these disorders. These alterations affect diagnosis, prognosis, and therapy, and with this understanding classification systems are evolving from a primarily hematological and morphological basis toward a multifactorial appreciation that includes histomorphology, metaphase cytogenetics, and directed molecular studies. In the present health-care environment, it is critical to develop a cost-effective, efficient testing strategy that maximizes the diagnostic potential of even limited specimens. Here, we briefly review the classical genetic approach to MDS, outline exciting new advances in the molecular understanding of this heterogeneous group of hematological neoplasms, and discuss how these advances are driving the evolution of classification and prognostic systems. Rapidly growing understanding of the genetic basis of MDS holds much promise for testing, and here we provide a frame of reference for discussion of current testing protocols and for addressing testing modalities likely to enter clinical practice in the near future.


Temporal changes in the prevalence of childhood asthma and allergies in urban and rural areas of Cyprus: results from two cross sectional studies.
The prevalence of childhood asthma and allergies in Cyprus was significantly higher in urban compared to rural areas back in the year 2000, against a background of an overall low prevalence (e.g. current wheeze 6.9%) by comparison to northern European countries. In this study we aimed to assess temporal changes in the prevalence of asthma and allergies in Cyprus after an 8-year interval and to examine whether any differential changes have occurred in urban and rural parts of the island. During the academic years 1999-2000 and 2007-2008, the parents of 7-8 year old children residing in the same set of urban and rural areas completed the ISAAC core questionnaire. In addition to providing prevalence estimates of allergic diseases in 2000 and 2008, changes between the two periods were expressed as odds ratios estimated in multiple logistic regression models adjusting for survey participants' characteristics. The prevalence of current wheeze was higher in 2008 (8.7%, 95% confidence interval 7.5%-9.9%, n = 2216) than the previously recorded figure in 2000 (6.9%, 95% CI 6.2%-7.6%, OR = 1.25, 95% CI: 1.02-1.53, n = 4944). Significant increases were also seen in the prevalence of lifetime asthma (11.3% vs. 17.4%, OR = 1.59, CI: 1.36-1.86), eczema (6.8% vs. 13.5%, OR = 1.91, CI: 1.59-2.29) and allergic rhinoconjuctivitis (2.6% vs. 5.2%, OR = 1.82, CI: 1.39-2.41). The prevalence of current wheeze nearly doubled between 2000 and 2008 in rural areas (5.4% vs. 9.7%, OR 1.81, CI: 1.24-2.64) while no significant change was observed in urban areas (7.5% vs. 8.4%, OR 1.08, CI: 0.84-1.37); p value for effect modification = 0.04. Rises in asthma and rhinitis prevalence, but not eczema were also more pronounced in rural compared to urban areas. The prevalence of allergic diseases in Cyprus is still on the rise; recent increases appear more pronounced among children living in rural areas possibly indicating recent environmental and lifestyle changes in these communities.


Mutants of Arabidopsis lacking a chloroplastic isoamylase accumulate phytoglycogen and an abnormal form of amylopectin.
Mutant lines defective for each of the four starch debranching enzyme (DBE) genes (AtISA1, AtISA2, AtISA3, and AtPU1) detected in the nuclear genome of Arabidopsis (Arabidopsis thaliana) were produced and analyzed. Our results indicate that both AtISA1 and AtISA2 are required for the production of a functional isoamylase-type of DBE named Iso1, the major isoamylase activity found in leaves. The absence of Iso1 leads to an 80% decrease in the starch content in both lines and to the accumulation of water-soluble polysaccharides whose structure is similar to glycogen. In addition, the residual amylopectin structure in the corresponding mutant lines displays a strong modification when compared to the wild type, suggesting a direct, rather than an indirect, function of Iso1 during the synthesis of amylopectin. Mutant lines carrying a defect in AtISA3 display a strong starch-excess phenotype at the end of both the light and the dark phases accompanied by a small modification of the amylopectin structure. This result suggests that this isoamylase-type of DBE plays a major role during starch mobilization. The analysis of the Atpu1 single-mutant lines did not lead to a distinctive phenotype. However, Atisa2/Atpu1 double-mutant lines display a 92% decrease in starch content. This suggests that the function of pullulanase partly overlaps that of Iso1, although its implication remains negligible when Iso1 is present within the cell.


Immunoassay of serum polypeptide hormones by using 125I-labelled anti(-immunoglobulin G) antibodies.
1. A technique for indirectly labelling antibodies to polypeptide hormones, by combining them with radioactively labelled anti-(immunoglobulin G) is described. (a) 125I-labelled anti-(rabbit immunoglobulin G) and anti-(guinea-pig immunoglobulin G) antibodies with high specific radioactivity were prepared after purification of the antibodies on immunoadsorbents containing the respective antigens. (b) Rabbit immunoglobulin G antibodies to human growth hormone, porcine glucagon and guinea-pig immunoglobulin G antibodies to bovine insulin and bovine parathyroid hormone were combined with immunoadsorbents containing the respective polypeptide hormone antigen. (c) The immunoglobulin G antibodies to the polypeptide hormones were reacted with 125-I-labelled anti-(immunoglobulin G) antibodies directed against the appropriate species of immunoglobulin G,and the anti-hormone antibodies were combined with the hormone-containing immunoadsorbent. (d) 125I-labelled anti-(immunoglobulin G) antibodies and anti-hormone antibodies were simultaneously eluted from the hormone-containing immunoadsorbent by dilute HCl, pH 2.0. After elution the anti-(immunoglobulin G) antibodies and antihormone antibodies were allowed to recombine at pH 8.0 and 4 degrees C. 2. The resultant immunoglobulin G-anti-immunoglobulin G complex was used in immunoradiometric (labelled antibody) and two-site assays of the respective polypeptide hormone. 3. By using these immunoassays, concentrations down to 90pg of human growth hormone/ml, 100 pg of bovine insulin/ml, 80 pg of bovine parathyroid hormone/ml and 150 pg of glucagon/ml were readily detected. Assays of human plasma for growth hormone and insulin by these methods showed good agreement with results obtained by using a directly 125I-labelled anti-hormone antibody in an immunoradiometric assay of human growth hormone or by radioimmunoassay of human insulin. 4. The method described allows immunoradiometric or two-site assays to be performed starting with as little as 450 ng of polypeptide hormone-antibody protein. An additional advantage of the method is that a single iodination of the readily available antibodies to immunoglobulin G allows the establishemnt of several polypeptide hormone assays


Diversity in thermal affinity among key piscivores buffers impacts of ocean warming on predator-prey interactions.
Asymmetries in responses to climate change have the potential to alter important predator-prey interactions, in part by altering the location and size of spatial refugia for prey. We evaluated the effect of ocean warming on interactions between four important piscivores and four of their prey in the U.S. Northeast Shelf by examining species overlap under historical conditions (1968-2014) and with a doubling in CO2 . Because both predator and prey shift their distributions in response to changing ocean conditions, the net impact of warming or cooling on predator-prey interactions was not determined a priori from the range extent of either predator or prey alone. For Atlantic cod, an historically dominant piscivore in the region, we found that both historical and future warming led to a decline in the proportion of prey species' range it occupied and caused a potential reduction in its ability to exert top-down control on these prey. In contrast, the potential for overlap of spiny dogfish with prey species was enhanced by warming, expanding their importance as predators in this system. In sum, the decline in the ecological role for cod that began with overfishing in this ecosystem will likely be exacerbated by warming, but this loss may be counteracted by the rise in dominance of other piscivores with contrasting thermal preferences. Functional diversity in thermal affinity within the piscivore guild may therefore buffer against the impact of warming on marine ecosystems, suggesting a novel mechanism by which diversity confers resilience.


Stereotactic Body Radiotherapy for Elderly Patients With Medically Inoperable Pancreatic Cancer.
People over the age of 75 years account for approximately 40% of patients diagnosed with pancreatic cancer, many with comorbidities that may limit their treatment options. This study reports on the use of stereotactic body radiation therapy (SBRT) in this population. Twenty consecutively treated patients over the age of 75 with pathologically proven localized pancreatic cancer were included in this retrospective review. All had been evaluated by a multidisciplinary team as unable to tolerate surgery or combined chemoradiation therapy. Patient outcomes were analyzed to determine the safety and efficacy of SBRT in this elderly cohort. The median age was 83.2 years (minimum 77 y, maximum 90 y). Eighteen patients were treated at time of initial diagnosis, and 2 for recurrence after surgery. Eleven (55%) of the patients had an Adult Comorbidity Evaluation-27 comorbidity index score of 3 (severe) and 6 (30%) had a score of 2 (moderate). Fourteen patients were treated with 35 Gy in 5 fractions, 5 with 30 Gy in 5 fractions, and 1 patient with 36 Gy in 3 fractions. Seven (35%) patients had common terminology criteria for adverse events (CTCAE) V4.0 toxicity grade of 1-2, and 3 patients had a CTCAE V4.0 toxicity grade of 3-4, 2 with dehydration, and 1 had episodes of gastrointestinal bleeding. Three patients recurred locally, 10 had distant metastases, 4 of whom were found on the first posttreatment scan. Median overall survival was 6.4 months (95% confidence interval, 3.5-10.8 mo). Median recurrence-free survival was 6.8 months (95% confidence interval, 1.3-23.5 mo). Two patients survived >23 months. SBRT for pancreatic cancer appears to be a safe and effective method for treatment of elderly patients, even in the setting of severe comorbidities.


A tale of two unconventional adult diaphragmatic hernias.
Diaphragmatic hernias can be congenital or acquired and are a protrusion of intra-abdominal contents through an abnormal opening in the diaphragm. Acquired defects are rare and occur secondary to direct penetrating injury or blunt abdominal trauma. This case review demonstrates two unconventional cases of large diaphragmatic hernias with viscero-abdominal disproportion in adults. Case 1 is a 27-year-old man with no prior medical or surgical history. He presented following a 24-h history of increasing shortness of breath and left-sided pleuritic chest pain, and no history of trauma. Chest X-ray demonstrated loops of bowel within the left hemithorax with displacement of the mediastinum to the right. Computed tomography (CT) scan confirmed a large diaphragmatic defect causing herniation of most of his abdominal contents into the left hemithorax. He underwent emergency surgery, which confirmed the viscero-abdominal disproportion. He required an extended right hemicolectomy to reduce the volume of the abdominal comtents and laparostomy to reduce the risk of abdominal compartment syndrome and recurrence of the hernia. Case 2 is a 76-year-old man with significant medical comorbidities who presented with acute onset of abdominal pain. He had a history of traumatic right-sided chest injury as a child resulting in right-sided diaphragmatic paralysis. Chest X-ray demonstrated a large right-sided diaphragmatic hernia with abdominal viscera in the right thoracic cavity. CT scan of the chest, abdomen and pelvis demonstrated both small and large bowel loops within the right hemithorax, compression of the right lung and displacement of the mediastinum to the left. The CT scan also demonstarted viscero-abdominal disproportion. Operative management was considered initially but following improvement with basic medical management and no further deterioration, a non-operative approach was adopted. Both cases illustrate atypical presentations of adults with diaphragmatic hernias. In an ideal scenario, these are repaired surgically. When the presumed diagnosis shows characteristics of a viscero-abdominal disproportion and surgery is pursued, the surgeon must consider that primary abdominal closure may not be possible and multiple operations may be necessary to correct the defect and achieve closure. Sacrifice of abdominal viscera may also be necessary to reduce the volume of abdominal contents.


Rare X-linked variants carry predominantly male risk in autism, Tourette syndrome, and ADHD.
Autism spectrum disorder (ASD), Tourette syndrome (TS), and attention-deficit/hyperactivity disorder (ADHD) display strong male sex bias, due to a combination of genetic and biological factors, as well as selective ascertainment. While the hemizygous nature of chromosome X (Chr X) in males has long been postulated as a key point of "male vulnerability", rare genetic variation on this chromosome has not been systematically characterized in large-scale whole exome sequencing studies of "idiopathic" ASD, TS, and ADHD. Here, we take advantage of informative recombinations in simplex ASD families to pinpoint risk-enriched regions on Chr X, within which rare maternally-inherited damaging variants carry substantial risk in males with ASD. We then apply a modified transmission disequilibrium test to 13,052 ASD probands and identify a novel high confidence ASD risk gene at exome-wide significance (MAGEC3). Finally, we observe that rare damaging variants within these risk regions carry similar effect sizes in males with TS or ADHD, further clarifying genetic mechanisms underlying male vulnerability in multiple neurodevelopmental disorders that can be exploited for systematic gene discovery.


Efficacy of pyrvinium pamoate against Cryptosporidium parvum infection in vitro and in a neonatal mouse model.
No effective approved drug therapy exists for Cryptosporidium infection of immunocompromised patients. Here we investigated the nonabsorbed anthelmintic drug pyrvinium pamoate for inhibition of the growth of the intestinal protozoan parasite Cryptosporidium parvum. The concentration of pyrvinium that effected 50% growth inhibition in human enterocytic HCT-8 cells by a quantitative alkaline phosphatase immunoassay was 354 nM. For comparison, in the same assay, 50% growth inhibition was obtained with 711 microM paromomycin or 27 microM chloroquine. We used a neonatal mouse model to measure the anti-Cryptosporidium activity of pyrvinium pamoate in vivo. Beginning 3 days after infection, pyrvinium at 5 or 12.5 mg/kg of body weight/day was administered to the treatment group mice for 4 or 6 consecutive days. Nine days after infection, the mice were sacrificed, and drug efficacy was determined by comparing the numbers of oocysts in the fecal smears of treated versus untreated mice. The intensities of trophozoite infection in the ileocecal intestinal regions were also compared using hematoxylin-and-eosin-stained histological slides. We observed a >90% reduction in infection intensity in pyrvinium-treated mice relative to that in untreated controls, along with a substantial reduction in tissue pathology. Based on these results, pyrvinium pamoate is a potential drug candidate for the treatment of cryptosporidiosis in both immunocompetent and immunocompromised individuals.


Ambient air pollution particles and the acute exacerbation of chronic obstructive pulmonary disease.
Investigation has repeatedly demonstrated an association between exposure to ambient air pollution particles and numerous indices of human morbidity and mortality. Individuals with chronic obstructive pulmonary disease (COPD) are among those with an increased sensitivity to air pollution particles. Current and ex-smokers account for 80 to 85% of all those with COPD. The human breathing in an urban site with a significant level of particulate matter (PM) may be exposed to 720 microg daily. A single cigarette introduces 15,000 to 40,000 microg particle into the respiratory tract of the smoker. It is subsequently confounding why such a relatively small mass of airborne PM should have any biological effect in the patient with COPD, as these individuals are repeatedly exposed to particles (with a similar size and composition) at perhaps a thousandfold the mass of ambient PM. Regarding this increased sensitivity of COPD patients to air pollution particles, there are several possible explanations for this seeming contradiction, including correlations of PM levels with other components of air pollution, an accumulation of multiple independent risk factors in a patient, changes in individual activity patterns, disparities in dosimetry between healthy subjects and COPD patients, and some unique characteristic of an ambient air pollution PM. Regardless of the underlying mechanism for the increased sensitivity of COPD patients, exposures of these individuals to elevated levels of PM should be discouraged. To provide a greater awareness of PM levels, the U.S. Environmental Protection Agency now includes levels of air pollution particles in an air quality index.


Review of adsorption-membrane hybrid systems for water and wastewater treatment.
Adsorption is an effective method for the removal of inorganic and organic contaminants and has been commonly used as a pretreatment method to improve contaminant removal and control flux during membrane filtration. Over the last two decades, many researchers have reported the use of hybrid systems comprising various adsorbents and different types of membranes, such as nanofiltration (NF), ultrafiltration (UF), and microfiltration (MF) membranes, to remove contaminants from water. However, a comprehensive evaluation of the removal mechanisms and effects of the operating conditions on the transport of contaminants through hybrid systems comprising various adsorbents and NF, UF, or MF membranes has not been performed to date. Therefore, a systematic review of contaminant removal using adsorption-membrane hybrid systems is critical, because the transport of inorganic and organic contaminants via the hybrid systems is considerably affected by the contaminant properties, water quality parameters, and adsorbent/membrane physicochemical properties. Herein, we provide a comprehensive summary of the most recent studies on adsorption-NF/UF/MF membrane systems using various adsorbents and membranes for contaminant removal from water and wastewater and highlight the future research directions to address the current knowledge gap.


Is Neighborhood Green Space Protective against Associations between Child Asthma, Neighborhood Traffic Volume and Perceived Lack of Area Safety? Multilevel Analysis of 4447 Australian Children.
Heavy traffic is a source of air pollution and a safety concern with important public health implications. We investigated whether green space lowers child asthma risk by buffering the effects of heavy traffic and a lack of neighborhood safety. Multilevel models were used to analyze affirmative asthma cases in nationally representative cross-sectional data from 4447 children aged 6-7 years old in Australia. Case-finding was based upon a triangulation of affirmative responses to three questions on doctor-diagnosed asthma, asthma-related medications and illness with wheezing lasting for at least 1 week within the 12 months prior. Among children considered to be exposed to high traffic volumes and areas with 0 to 20% green space quantity, the odds ratio of affirmative asthma was 1.87 (95% CI 1.37 to 2.55). However, the association between heavy traffic and asthma was significantly lower for participants living in areas with over 40% green space coverage (odds ratio for interaction 0.32, 95% CI 0.12 to 0.84). No association between affirmative asthma and green space coverage was observed for participants not exposed to heavy traffic, nor for the area safety variable. Protecting existing and investing in new green space may help to promote child respiratory health through the buffering of traffic-related air pollution.


An analytical review of vasculobiliary injury in laparoscopic and open cholecystectomy.
Biliary injuries are frequently accompanied by vascular injuries, which may worsen the bile duct injury and cause liver ischemia. We performed an analytical review with the aim of defining vasculobiliary injury and setting out the important issues in this area. A literature search of relevant terms was performed using OvidSP. Bibliographies of papers were also searched to obtain older literature. Vasculobiliary injury was defined as: an injury to both a bile duct and a hepatic artery and/or portal vein; the bile duct injury may be caused by operative trauma, be ischaemic in origin or both, and may or may not be accompanied by various degrees of hepatic ischaemia. Right hepatic artery (RHA) vasculobiliary injury (VBI) is the most common variant. Injury to the RHA likely extends the biliary injury to a higher level than the gross observed mechanical injury. VBI results in slow hepatic infarction in about 10% of patients. Repair of the artery is rarely possible and the overall benefit unclear. Injuries involving the portal vein or common or proper hepatic arteries are much less common, but have more serious effects including rapid infarction of the liver. Routine arteriography is recommended in patients with a biliary injury if early repair is contemplated. Consideration should be given to delaying repair of a biliary injury in patients with occlusion of the RHA. Patients with injuries to the portal vein or proper or common hepatic should be emergently referred to tertiary care centers.


Exploring the limits of crop productivity: beyond the limits of tipburn in lettuce.
The productivity of lettuce in a combination of high light, high temperature, and elevated CO2 has not been commonly studied because rapid growth usually causes a calcium deficiency in meristems called tipburn, which greatly reduces quality and marketability. We eliminated tipburn by blowing air directly onto the meristem, which allowed us to increase the photosynthetic photon flux (PPF) to 1000 micromoles m-2 s-1 (57.6 mol m-2 d-1); two to three times higher than normally used for lettuce. Eliminating tipburn doubled edible yield at the highest PPF level. In addition to high PPF, CO2 was elevated to 1200 micromoles m-2 mol-1, which increased the temperature optimum from 25 to 30 degrees C. The higher temperature increased leaf expansion rate, which improved radiation capture and more than doubled yield. Photosynthetic efficiency, measured as canopy quantum yield in a whole-plant gas exchange system, steadily increased up to the highest temperature of 32 degrees C in high CO2. The highest productivity was 19 g m-2 d-1 of dry biomass (380 g d-1 fresh mass) averaged over the 23 days the plants received light. Without the limitation of tipburn, the combination of high PPF, high temperature, and elevated CO2 resulted in a 4-fold increase in growth rate over productivity in conventional environments.


A potyvirus P1 protein interacts with the Rieske Fe/S protein of its host.
ABSTRACT Yeast two-hybrid (Y2H) screens were used to test for interactions between the P1 protein of Soybean mosaic virus Pinellia isolate (SMV-P) and a cDNA expression library of its host, the aroid Pinellia ternata. Of the 13 independent interacting clones identified, ten were identical and had an open reading frame predicted to encode a 23.7-kDa protein closely related to the cytochrome b6/f complex Rieske Fe/S genes of plants. The interaction between SMV-P-P1 and the mature Rieske Fe/S protein (without transit peptide) of the host was confirmed by in vitro co-immunoprecipitation of the two proteins. Y2H assays using different parts of the two proteins showed that only the N-terminal part (amino acids 1-82) of SMV-P P1 was responsible for the interaction with the Rieske Fe/S protein and that amino acids 1-33 interacted only with the transit peptide, while amino acids 34-82 could interact with the entire Rieske Fe/S protein. SMV-P P1 also interacted moderately with the Rieske Fe/S protein of its other hosts, soybean and Zantedeschia aethiopica, but weakly with that of the non-host Arabidopsis thaliana. The P1-Rieske Fe/S protein interactions are likely to be involved in symptom development, and the very variable N-terminus of P1 may play an important role in host adaptation.


Lymphocyte subpopulation and dendritic cell phenotyping during antineoplastic therapy in human solid tumors.
Patients with cancer show variable levels of immunosuppression at the time of the presentation, and cytotoxic antineoplastic therapy is the primary contributor to the clinical immunodeficiency often observed during the course of the disease. In both hematological and solid tumors, this phenomenon is primarily related to the T-cell depletion associated with inhibition of dendritic cell ability to induce both primary and secondary T- and B-cell responses. Complete restoration of immunocompetence following antineoplastic therapy implicates the progressive recovery of various cell subpopulations, and it is a complex process that also depends on the type, the dose, the scheduling, and the associations of the employed drugs. In the era of target therapies, several antiangiogenic drugs are increasingly used in combination with standard chemotherapy in the treatment of advanced solid tumors. Their clinical efficacy has been recently related not only to the specific antiangiogenic properties but also to an indirect hypothetical effect on the host immune system. In the present work, we have reviewed the most recent information regarding (1) the capacity of standard antineoplastic therapy to induce and maintain an immunodeficiency in patients with solid tumors and (2) the influence of the antiangiogenic treatment in association with standard chemotherapy on lymphocyte and dendritic cell subsets and the possible resulting additional antitumor mechanism.


Intravenous nutrition. A clinical evaluation of a 50 per cent dextrose in water solution, containing 1 mg. of hydrocortisone per 100 ml.
A 50 per cent dextrose in water solution, containing 1 mg. of hydrocortisone per 100 ml., was used successfully in 70 patients for intravenous nutritional maintenance and repletion. There were no adverse systemic effects during or following 216 infusions. The only undesirable local reaction was the rare occurrence of pain in the arm when the concentrated solutions were given too rapidly. Glycosuria was minimal if the infusion rate did not exceed 0.85 gm. of glucose per kilogram of body weight per hour, particularly if 50 units of insulin were added to each 550 ml. bottle of 50 per cent dextrose. In patients without significantly elevated serum potassium content, 30 mEq. of potassium chloride, acetate or phosphate was added to each bottle to prevent hypokalemia.Preliminary observations suggest that this new solution may be given safely intravenously, without need for cutdowns or plastic catheters, if the needle is carefully inserted and well immobilized in the arm vein and the duration of the infusion is not too prolonged. Further studies on the effect of such high caloric supplementation plus protein hydrolysates in parenteral nutritional repletion and maintenance are indicated.


RELEVANCE OF WHOLE BODY VIBRATION EXERCISE IN SPORT: A SHORT REVIEW WITH SOCCER, DIVER AND COMBAT SPORT.
Whole body vibration exercise (WBVE) has been used as a safe and accessible exercise and important reviews have been published about the use of this exercise to manage diseases and to improve physical conditions of athletes The aim of this paper is to highlight the relevance of WBVE to soccer players, divers and combat athletes. This study was made through a systematic review of publications involving WBVE and the selected sports in two databases (Pubmed and PEDRo). It were identified 10 studies involving WBVE and sports (6 of soccer, 2 of diving and 2 of sport combat) with 156 subjects (80 soccer players, 32 divers and 44 combat athletes), with age from 17 to 44 years old. The use of WBVE has proven to be a safe and useful strategy to improve the physical conditions of players of different sports. These findings may have clinical relevance and should be considered as a strategy to be used to try improve the physical conditions of players.


[Antimicrobial activity of hyaluronic acid].
In this work the biological activity of hyaluronic acid (HA), isolated from fowl crests, is evaluated. The data on the physico-chemical analysis of HA are presented. The preparation obtained is characterized by a high content of the main substance and high relative viscosity. Sterilization conditions for HA, depending on the degree of microbial contamination of the preparation, were carried out. As revealed in this study, irradiation with a dose of 1.0 Mrad is sufficient for obtaining a sterile preparation. HA has been found to possess inhibiting activity with respect to Pseudomonas.


The diagnosis of acute abdominal pain with computer assistance: worldwide perspective.
This presentation describes the use of computer aided decision support in acute abdominal pain. The development of such support and the feasability of providing it are described with reference to worldwide studies involving nearly 100,000 patients in the UK, the European Community and worldwide. This presentation will give an overview of the experienced gained in these and other studies. As a result of this experience, it will be suggested: a) The diagnosis of acute abdominal pain by inexperienced emergency surgeons remains a difficult problem. 2) Doctors who have been assisted by a computer have, in many instances, improved their diagnostic and decision-making performance. 3) This improvement has not been due to superior "artificial intelligence" of the computer--but due to the computer acting as an educational focus and a stimulus to good clinical practice. 4) On an international level, these studies have been immensely valuable. They have helped bring together different national groups and helped to develop common medical terminology--as well as foster collaborative "spin-off" in terms of research around the world.


On the perils of poor editing: regulation of peptide loading by HLA-DQ and H2-A molecules associated with celiac disease and type 1 diabetes.
This review discusses mechanisms that link allelic variants of major histocompatibility complex (MHC) class II molecules (MHCII) to immune pathology. We focus on HLA (human leukocyte antigen)-DQ (DQ) alleles associated with celiac disease (CD) and type 1 diabetes (T1D) and the role of the murine DQ-like allele, H2-Ag7 (I-Ag7 or Ag7), in murine T1D. MHCII molecules bind peptides, and alleles vary in their peptide-binding specificity. Disease-associated alleles permit binding of disease-inducing peptides, such as gluten-derived, Glu-/Pro-rich gliadin peptides in CD and peptides from islet autoantigens, including insulin, in T1D. In addition, the CD-associated DQ2.5 and DQ8 alleles are unusual in their interactions with factors that regulate their peptide loading, invariant chain (Ii) and HLA-DM (DM). The same alleles, as well as other T1D DQ risk alleles (and Ag7), share nonpolar residues in place of Asp at β57 and prefer peptides that place acidic side chains in a pocket in the MHCII groove (P9). Antigen-presenting cells from T1D-susceptible mice and humans retain CLIP because of poor DM editing, although underlying mechanisms differ between species. We propose that these effects on peptide presentation make key contributions to CD and T1D pathogenesis.


Chinese herbal medicine and cognitive and emotional functions during 60-day head-down bed rest.
This study aimed to test the efficacy of an oral-intake Chinese herbal medicine in enhancing the cognitive and emotional functions of individuals in a simulated microgravity condition. The herbal medicine consisted of ingredients that may enhance cognitive and emotional functions in an extreme environment. There were 14 healthy male subjects who were randomly assigned to a Chinese medicine (CMG) or a control (CG) group and underwent a 60-d 6 degree head-down bed-rest protocol. Testing was conducted before (Day -3), throughout (Days 3, 7, 20, 40, 57), and after (Days +3, +10) the bedrest protocol. The Arrow Test, Balloon Analog Risk Task (BART), Dual Task, and Affect Grid were administered on all testing days. The CMG demonstrated consistently higher scores on the BART (Days 20 to 40; Mean: CMG, 43.0 to 46.2 and CG, 30.2 to 25.5) and lower levels of arousal on the Affect Grid (Days 7 to 40; Mean: CMG, 6.9 to 6.7 and CG, 8.1 to 8.0) than did the CG. The CMG showed significantly higher performance on the Arrow Test (incompatible condition) at the beginning of the bed-rest period (Day 3 to 7; Mean: 799.5 ms and 763.1 ms, respectively) which was not observed in the CG. Results suggest that the Chinese herbal medicine may calm subjects' emotions by lowering the arousal level. At the same time, it may have produced positive effects in enhancing advantageous risk-taking and to a lesser extent self-regulatory behaviors (in the early phase).


Hyperprolactinemia increases and hypoprolactinemia decreases tyrosine hydroxylase messenger ribonucleic acid levels in the arcuate nuclei, but not the substantia nigra or zona incerta.
The effects of experimentally produced hypoprolactinemia and hyperprolactinemia on tyrosine hydroxylase (TH) mRNA signal levels were examined in dopaminergic neurons ovariectomized rats. TH mRNA signal levels and relative TH quantity in the arcuate nuclei, zona incerta, and substantia nigra were evaluated by in situ hybridization and immunocytochemistry, respectively. The catalytic activity of TH in the stalk-median eminence (SME) was determined from the in vitro rate of 3,4-dihydroxyphenylalanine (DOPA) accumulation after inhibiting DOPA decarboxylase with brocresine. Chronic administration of bromocriptine (BROMO), a dopamine (DA) agonist, for 3 days reduced circulating rat PRL (rPRL) levels compared to those in the vehicle-treated controls. BROMO treatment decreased TH mRNA signal levels in the arcuate nuclei, the intensity of TH immunostaining in the arcuate-median eminence area, and the rate of DOPA accumulation in the SME. Concomitant administration of ovine PRL (oPRL) reversed the effects of BROMO on TH, resulting in markedly increased TH mRNA signal levels, intensity of TH immunostaining, and rate of DOPA accumulation. Treatment with oPRL by itself for 3 days increased TH mRNA signal levels in the arcuate nuclei and TH activity in the SME, compared to vehicle. Chronic treatment with haloperidol, a DA antagonist, increased circulating levels of endogenous rPRL and increased TH activity in the SME to values similar to those after oPRL treatment. However, in contrast to oPRL, mRNA levels in the arcuate nuclei of haloperidol-treated rats were similar to levels in vehicle-treated animals. To evaluate whether the effect of PRL on TH was species specific, oPRL or rPRL was continuously infused into the jugular vein using an osmotic minipump. TH mRNA levels in the arcuate nuclei were elevated above control levels by either oPRL or rPRL administration. TH mRNA levels in the DA perikarya located in the zona incerta and substantia nigra were not altered by treatment with a DA agonist, a DA antagonist, or PRL. These results indicate that hypoprolactinemia or hyperprolactinemia can selectively reduce or augment, respectively, TH mRNA levels in the tuberoinfundibular dopaminergic neurons. The alterations in TH mRNA content probably contribute to the decrease or increase in TH activity associated with hypoprolactinemia or hyperprolactinemia, respectively.


Prognostic value of stromal tumour infiltrating lymphocytes and programmed cell death-ligand 1 expression in breast cancer.
The present work aims to evaluate the presence of stromal tumour-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PDL1) expression in breast carcinomas and their correlation with available clinicopathological features. Two independent series of invasive breast cancer (IBC), one including ductal carcinoma in situ (DCIS) pair-matched cases, were selected, and quantification of TILs was accomplished in each case. Immunohistochemistry was also performed to evaluate the expression of PDL1. In both cohorts evaluated, increased stromal TILs and PDL1 expression were present in about 10% of IBCs, being significantly associated with each other and both with grade 3 and triple-negative subtype. We observed a similar distribution of stromal TILs and PDL1 expression between DCIS and IBC. Finally, we observed that increased stromal TILs and PDL1 expression were significantly associated with cancer stem cell (CSC) markers, basal cell markers and vimentin expression. Interestingly, in IBC cases with vimentin expression, increased stromal TILs, as well as decreased PDL1 expression, disclosed a better clinical outcome, independently of the main classical BC prognostic factors. We have confirmed the association of stromal TILs and PDL1 expression with aggressive forms of BC and that both are already found in in situ stages. We also showed that stromal TILs and PDL1 expression are associated with clinical outcome in cases enriched for a mesenchymal immunophenotype. We describe for the first time a close relationship between CSC markers and PDL1 expression.


Engineering the carrier dynamics of g-C3N4 by rolling up planar sheets into nanotubes via ultrasonic cavitation.
Rolling up 2D atomic layered materials into 1D nanotubes gives rise to fascinating properties due to their lower dimension, higher anisotropy, and strain effects. In this work, the curving of 2D graphitic C3N4 (g-C3N4) sheets into 1D nanotubes is demonstrated for the first time through simple and clean ultrasonic treatments. The steady-state optical transitions are slightly enhanced while the localized trapping of excited carriers is considerably suppressed after rolling up the planar sheets into nanotubes. The mechanical method to modulate the dimension scarcely changes the chemical structures, enabling the pure investigation on shape-induced physical effects. As a proof of principle, this work confirms the dynamics of excited carriers, and the photoelectronic properties of 2D semiconductors can be significantly engineered by a simple morphological evolution.


Genome-wide analysis of aromatase inhibitor-resistant, tamoxifen-resistant, and long-term estrogen-deprived cells reveals a role for estrogen receptor.
Acquired resistance to either tamoxifen or aromatase inhibitors (AI) develops after prolonged treatment in a majority of hormone-responsive breast cancers. In an attempt to further elucidate mechanisms of acquired resistance to AIs, MCF-7aro cells resistant to letrozole (T+LET R), anastrozole (T+ANA R), and exemestane (T+EXE R), as well as long-term estrogen deprived (LTEDaro) and tamoxifen-resistant (T+TAM R) lines were generated. This is the first complete panel of endocrine therapy-resistant cell lines, which were generated as multiple independent biological replicates for unbiased genome-wide analysis using affymetrix microarrays. Although similarities are apparent, microarray results clearly show gene signatures unique to AI-resistance were inherently different from LTEDaro and T+TAM R gene expression profiles. Based on hierarchical clustering, unique estrogen-responsive gene signatures vary depending on cell line, with some genes up-regulated in all lines versus other genes up-regulated only in the AI-resistant lines. Characterization of these resistant lines showed that LTEDaro, T+LET R, and T+ANA R cells contained a constitutively active estrogen receptor (ER)alpha that does not require estrogen for activation. This ligand-independent activation of ER was not observed in the parental cells, as well as T+EXE R and T+TAM R cells. Further characterization of these resistant lines was performed using cell cycle analysis, immunofluorescence experiments to visualize ER subcellular localization, as well as cross-resistance studies to determine second-line inhibitor response. Using this well-defined model system, our studies provide important information regarding differences in resistance mechanisms to AIs, TAM, and LTEDaro, which are critical in overcoming resistance when treating hormone-responsive breast cancers.


The role of activation energy and reduced viscosity on the enhancement of water flow through carbon nanotubes.
Molecular dynamics simulations are carried out to study the pressure driven fluid flow of water through single walled carbon nanotubes. A method for the calculation of viscosity of the confined fluid based on the Eyring theory of reaction rates is proposed. The method involves the calculation of the activation energy directly from the molecular dynamics trajectory information. Computations are performed using this method to study the effect of surface curvature on the confined fluid viscosity. The results indicate that the viscosity varies nonlinearly with the carbon nanotube diameter. It is concluded that the reason behind the observed enhancement in the rate of fluid flow through carbon nanotubes could be the nonlinear variation of viscosity.


Psychiatric morbidity among informal caregivers of children suffering from intellectual developmental disorders.
To assess the presence of psychiatric morbidity and associated socio-demographic factors among informal caregivers of children suffering from intellectual developmental disorders. The analytical cross-sectional study was conducted at the Neurology Department of a tertiary care hospital in Rawalpindi, Pakistan, from January 1, 2018, to December 31, 2019, and comprised informal caregiver of children diagnosed with intellectual developmental disorders presenting at the paediatric or neurology outpatient clinics of the hospital. Intellectual developmental disorder was diagnosed by consultant neurologists or psychiatrists or paediatricians on the basis of International Classification of Diseases-11 criteria. Psychiatric morbidity in the informal caregiver was assessed using the 12-item general health questionnaire. Data was analysed using SPSS 23, and binary logistic regression was applied to assess association. Of the 500 informal caregivers, 323(64.6%) showed psychiatric morbidity. Increasing age and comorbid epilepsy among the patients were significantly related to the presence of psychiatric morbidity among the informal caregivers (p<0.05). Majority of informal caregivers of children with learning difficulties were found to have psychiatric morbidity.


Human pulmonary dirofilariasis in India: a case report.
Dirofilaria immitis is a common parasite of the canine cardiovascular system. In dogs, it often produces pulmonary lesions and rarely dilatation of portal vessels. Most of the human cases reported showed pulmonary lesions. We describe here a child manifesting as portal cavernoma with pulmonary dirofilariasis detected at autopsy. This is the first case of pulmonary dirofilariasis reported from India.


Banned from working in social care: a secondary analysis of staff characteristics and reasons for their referrals to the POVA list in England and Wales.
Since July 2004, employers of social care staff working with vulnerable adults in England and Wales have been legally required to refer workers or volunteers dismissed for misconduct because they have harmed vulnerable adults or placed them at risk of harm to the Protection of Vulnerable Adults (POVA) list. The POVA list is unique to England and Wales, and is a powerful tool of quality assurance for the care sector and for the safeguarding of vulnerable adults. This article reports on part of a multi-method study including quantitative and qualitative elements to produce a rounded picture of the factors involved in decisions to place staff members on the POVA list. Based on secondary data analysis of all records of POVA referrals from August 2004 to November 2006 (5294 records) as well as a detailed sample of 298 referrals, this article focuses on the prevalence of different types of alleged harm and their association with various staff, employer and service-users' characteristics. The most common form of alleged abuse was physical abuse (33%), while the least was sexual abuse (6%). Some of the other key findings are the over-representation of men referred (31% compared to an average of 15% in the workforce) and significantly different types of abuse in care home and domiciliary settings, where financial abuse was less likely in care homes [odds ratio (OR) 0.17; P < 0.001], while physical abuse more likely in the same setting (OR 3.60; P < 0.001).


A Pilot Randomized Controlled Trial of Acceptance and Commitment Therapy Guided Self-Help for Overweight and Obese Adults High in Weight Self-Stigma.
Weight self-stigma, in which individuals internalize stigmatizing messages about weight, is a prevalent problem that contributes to poor quality of life and health. This pilot randomized controlled trial evaluated acceptance and commitment therapy (ACT) guided self-help using The Diet Trap for 55 overweight/obese adults high in weight self-stigma. Participants were randomized to the ACT self-help book plus phone coaching (GSH-P; n = 17), self-help book plus email prompts only (GSH-E; n = 20), or a waitlist condition (n = 18), with online self-report assessments at baseline and posttreatment (8 weeks later). Participants reported high satisfaction ratings and engagement with the ACT self-help book, with no differences between GSH-P and GSH-E. Both GSH-P and GSH-E improved weight self-stigma relative to waitlist with large effect sizes. There were mixed findings for health outcomes. The GSH-P condition improved more on healthy eating behaviors and general physical activity, but neither ACT condition improved more than waitlist on self-reported body mass index, emotional eating, and a second measure of physical activity. Results suggest an ACT self-help book with email prompts can reduce weight self-stigma and potentially improve some health behavior outcomes. Phone coaching may provide additional benefits for generalizing ACT to diet and physical activity.


Feasibility and safety of same-day discharge after complex percutaneous coronary intervention using forearm approach.
We sought to assess the feasibility and safety of same-day discharge (SDD) after complex percutaneous coronary intervention (PCI) using a forearm approach. SDD has been shown to be safe after elective, low-risk PCI. However, the feasibility and safety of SDD in more complex patients and lesions has received limited study. We retrospectively reviewed 1190 elective PCIs that were performed between January 2013 and December 2015 at the Red Cross General Hospital. Of the 1190 PCIs, 166 (13.9%) were complex (bifurcations, vein and arterial grafts, unprotected left main, last remaining vessel, chronic total occlusions, or with utilization of rotational atherectomy or hemodynamic support). As compared with non-complex cases, complex cases were associated with older age, male gender, higher prevalence of diabetes mellitus and prior coronary artery bypass graft surgery, lower prevalence of smoking, higher utilization of femoral access and 7F guiding catheters, higher contrast utilization and fluoroscopy dose, longer fluoroscopy time, more stents per lesion, more frequent single vessel treatment and non-complete revascularization, and treatment with ticagrelor and bivalirudin. Among the patients who underwent complex PCI (n=166), twenty eight (16.9%) were discharged the same day. SDD after complex PCI was associated with younger age and more frequent use of forearm access. The 30-day incidence of major adverse cardiac events after complex PCI was 0% vs 3.6% (p=0.59) in patients with SDD vs. overnight hospitalization. SDD is feasible and safe in selected patients undergoing elective complex PCI using the forearm approach.


Arterial thrombo-embolic events in cardiac amyloidosis: a look beyond atrial fibrillation.
Intracardiac thrombosis is reported to occur frequently in cardiac amyloidosis (CA). However, data regarding arterial thrombo-embolic events (AEs) in CA are limited. We aimed at assessing prevalence, clinical characteristics and predictors of AEs in a large multicentric CA cohort. Four-hundred-six consecutive CA patients (134 AL, 73 ATTRm and 199 ATTRwt) from 5 Italian referral centres were retrospectively evaluated and followed-up for a median time of 19 months. Thirty-one patients (7.6%) suffered from an AE, of whom 10 (32.2%) were in sinus rhythm and had no history of AF. There were no significant differences in terms of age, gender and type of CA between patients with or without AEs. Fourteen (7.6%) of 185 patients on anticoagulation had an AE despite therapy. Anticoagulation therapy did not appear to fully protect from the risk of events (HR 1.23, 95%CI 0.52-2.92, p = .64). The only predictor of AEs, in particular among CA patients in sinus rhythm, was a CHA2DS2-VASC score ≥ 3 (HR 2.84, 95%CI 1.02-7.92, p = .05 in overall population; HR 10.13, 95%CI 1.12-91.19, p = .04 in patients in sinus rhythm). In our large, multicentric, real-world cohort, prevalence and incidence rate of AEs was high. A consistent proportion of events occurred despite anticoagulation therapy or in patients in sinus rhythm. A higher CHA2DS2-VASc score might identify patients at risk of AEs also among those in sinus rhythm.


Risk of Pancreatic Cancer and Use of Dipeptidyl Peptidase 4 Inhibitors in Patients with Type 2 Diabetes: A Propensity Score-Matching Analysis.
The effects of dipeptidyl peptidase 4 (DPP-4) inhibitors over the course of long-term treatment remain unclear, and concerns have been raised regarding the role of DPP-4 inhibitors in carcinogenesis in the pancreas. Earlier studies of pancreatic adverse events have reported conflicting results. This study analyzed Korean National Health Insurance Service data from January 2009 to December 2012. Patients who had type 2 diabetes mellitus and took two or more oral glucose-lowering drugs (GLDs) were included. Patients prescribed DPP-4 inhibitors (n=51,482) or other GLDs (n=51,482) were matched at a 1:1 ratio using propensity score matching. The risk of pancreatic cancer was calculated using Kaplan-Meier curves and Cox proportional-hazards regression analysis. During a median follow-up period of 7.95 years, 1,051 new cases of pancreatic cancer were identified. The adjusted hazard ratio (HR) for DPP-4 inhibitor use was 0.99 (95% confidence interval [CI], 0.88 to 1.12) compared with the other GLD group. In an analysis limited to cases diagnosed with pancreatic cancer during hospitalization, the adjusted HR for the use of DPP-4 inhibitors was 1.00 (95% CI, 0.86 to 1.17) compared with patients who took other GLDs. Using the other GLD group as the reference group, no trend was observed for elevated pancreatic cancer risk with increased DPP-4 inhibitor exposure. In this population-based cohort study, DPP-4 inhibitor use over the course of relatively long-term follow-up showed no significant association with an elevated risk of pancreatic cancer.


Outcome following colon surgery in the octagenarian.
The results of colon surgery in all individuals aged 80 years or greater at one teaching institution during the 1987-1993 time period were reviewed. Sixty patients, ranging in age from 80 to 92 years, underwent 41 elective operations and 21 emergency procedures. Emergency procedures resulted in death or a major complication in over one-half of patients, and only six were ultimately able to return home. Conversely, elective procedures were relatively well tolerated, and 31 of 37 survivors returned immediately to independent living (P = 0.006). Mortality was 33.3 per cent in emergency cases versus 9.8 per cent in elective operations (P < 0.03). The occurrence of a postoperative complication increased the length of stay by an average of 12 days. These data suggest that elective colon surgery in the elderly produces results little different from the population at large. Conversely, emergency operations are associated with a high morbidity and mortality rate. Age alone should not be a determining factor in who undergoes an elective colon operation. Greater efforts should be made to screen elderly individuals to limit emergency surgery.


Elastic band exercise induces greater neuromuscular fatigue than phasic isometric contractions.
This study investigated the neuromuscular fatigue following an elastic band exercise (EB) of the plantar flexors, compared to an intermittent phasic isometric exercise (ISO). Eleven young healthy males (age: 24.2 ± 3.7) took part in the study, consisting of one experimental session involving two 5-min fatiguing protocols separated by 20 min rest and performed randomly. Both exercises were performed at maximal motor output of the plantar flexor muscles, EMG being used as a feedback signal. Neuromuscular fatigue was assessed through changes in maximal voluntary contraction (MVC) and in evoked responses of soleus and gastrocnemii muscles to posterior tibial nerve stimulation (H-reflex, M-wave, V-wave). Both conditions induced significant decrease in MVC force, but to a greater extent after EB (-20.0 ± 5.1%, P < 0.001) than after ISO (-12.3 ± 4.6%, P = 0.037). While no effect was observed in M-wave amplitude after both exercises, EB resulted in greater decrease of normalized H-reflexes compared to isometric condition. Normalized V-wave significantly decreased only after EB. As a conclusion, the greater fatigability found after EB as compared to ISO was underlain by muscular as well as nervous factors. This higher impact was attributed to the dynamic nature of elastic band exercise as compared to isometric contractions.


Evolution of a small phage protein overcomes antiphage defense in Enterococcus faecalis.
The prevalence of multidrug resistant (MDR) bacterial infections continues to rise as the development of new antibiotics needed to combat these infections remains stagnant. MDR enterococci, which are a common cause of hospital-acquired infections, are emerging as one of the major contributors to this crisis. A potential therapeutic approach for combating MDR enterococci is bacteriophage (phage) therapy, which entails the use of lytic viruses to infect and kill pathogenic bacteria. While phages that lyse some strains of MDR enterococci have been identified, other strains display high levels of phage resistance and the mechanisms underlying this resistance are unknown. Here, we use a CRISPR interference (CRISPRi) screen to identify a genetic locus found on a mobilizable plasmid from vancomycin-resistant Enterococcus faecalis involved in phage resistance. This locus encodes a putative serine recombinase followed by a Type IV restriction enzyme (TIV-RE) and we show that this enzyme is sufficient to restrict the replication of the lytic phage in E. faecalis. We further find that phages can evolve to overcome restriction by acquiring a missense mutation in a novel TIV-RE inhibitor protein encoded by many enterococcal phages. We show that this inhibitor, which we have named anti-restriction-factor A (arfA), directly binds to and inactivates diverse TIV-REs. Overall, our findings significantly advance our understanding of phage defense in drug-resistant E. faecalis and provide mechanistic insight into how phages can evolve to overcome antiphage defense systems.


Frequency resolved transverse mode instability in rod fiber amplifiers.
Frequency dynamics of transverse mode instabilities (TMIs) are investigated by testing three 285/100 rod fibers in a single-pass amplifier setup reaching up to ~200W of extracted output power without beam instabilities. The pump power is increased well above the TMI threshold to uncover output dynamics, and allowing a simple method for determining TMI threshold based on standard deviation. The TMI frequency component is seen to appear on top of system noise that may trigger the onset. A decay of TMI threshold with test number is identified, but the threshold is fully recovered between testing to the level of the pristine fiber by thermal annealing the fiber output end to 300°C for 2 h.


The Tolerance Model of Non-Inflammatory Immune Competence in Acute Pediatric Malnutrition: Origins, Evidence, Test of Fitness and Growth Potential.
The tolerance model rests on the thesis of a physiologically regulated, albeit unsustainable, systemic attempt to adapt to the catabolic challenge posed by acute prepubescent malnutrition even in its severe forms. The model centers on the immunological component of the attempt, positing reorientation toward a non-inflammatory form of competence in place of the classic paradigm of immunological attrition and exhaustion. The foundation of the model was laid in 1990, and sixteen years later it was articulated formally on the basis of a body of evidence centered on T cell cytokines and interventions with cytokine and hormonal mediators. The benefit originally suggested was a reduced risk of autoimmune pathologies consequent to the catabolic release of self-antigens, hence the designation highlighting immune tolerance. Herein, the emergence of the tolerance model is traced from its roots in the recognition that acute malnutrition elicits an endocrine-based systemic adaptive attempt. Thereafter, the growth of the evidence base supporting the model is outlined, and its potential to shed new light on existing information is tested by application to the findings of a published clinical study of acutely malnourished children. Finally, some knowledge gaps pertinent to the model are identified and its potential for growth consonant with evolving perceptions of immunobiology is illustrated.


Estuarine versus coastal marinas: Influence of the habitat on the settlement of non-indigenous peracarids on the polychaete Sabella spallanzanii (Gmelin, 1791).
Recreational marinas are key points for the introduction and secondary spread of non-indigenous species (NIS). However, little is known about the influence of the habitat surrounding the marina on NIS communities. To explore this issue, we compared peracarid assemblages associated to the widespread ecosystem engineer Sabella spallanzanii in lower estuarine marinas (with oceanic salinity) and coastal marinas of the south of the Iberian Peninsula. Sabella spallanzanii hosted a total of 23 species, 7 of them NIS. While NIS richness was similar between marinas located in estuaries and coastal habitats, NIS abundance was significantly higher in estuarine marinas. The NIS community structure was influenced by both the marina itself and the surrounding habitat. These results suggest that lower estuarine conditions promote NIS abundance in marinas, increasing potential invasion risks. This supports prioritization of estuarine marinas in NIS monitoring programs and the suitability of S. spallanzanii as a bioinvasion monitoring tool.


Underreporting in traffic accident data, bias in parameters and the structure of injury severity models.
Injury severities in traffic accidents are usually recorded on ordinal scales, and statistical models have been applied to investigate the effects of driver factors, vehicle characteristics, road geometrics and environmental conditions on injury severity. The unknown parameters in the models are in general estimated assuming random sampling from the population. Traffic accident data however suffer from underreporting effects, especially for lower injury severities. As a result, traffic accident data can be regarded as outcome-based samples with unknown population shares of the injury severities. An outcome-based sample is overrepresented by accidents of higher severities. As a result, outcome-based samples result in biased parameters which skew our inferences on the effect of key safety variables such as safety belt usage. The pseudo-likelihood function for the case with unknown population shares, which is the same as the conditional maximum likelihood for the case with known population shares, is applied in this study to examine the effects of severity underreporting on the parameter estimates. Sequential binary probit models and ordered-response probit models of injury severity are developed and compared in this study. Sequential binary probit models assume that the factors determining the severity change according to the level of the severity itself, while ordered-response probit models assume that the same factors correlate across all levels of severity. Estimation results suggest that the sequential binary probit models outperform the ordered-response probit models, and that the coefficient estimates for lap and shoulder belt use are biased if underreporting is not considered. Mean parameter bias due to underreporting can be significant. The findings show that underreporting on the outcome dimension may induce bias in inferences on a variety of factors. In particular, if underreporting is not accounted for, the marginal impacts of a variety of factors appear to be overestimated. Fixed objects and environmental conditions are overestimated in their impact on injury severity, as is the effect of separate lap and shoulder belt use. Combined lap and shoulder belt usage appears to be unaffected. The parameter bias is most pronounced when underreporting of possible injury accidents in addition to property damage only accidents is taken into account.


Effect of permeation enhancers on the penetration mechanism of transfersomal gel of ketoconazole.
The aim of the present research work was to investigate the potential of transfersome formulations for transdermal delivery of Ketoconazole (KTZ). KTZ is a broad-spectrum antifungal agent that is active against a wide variety of fungi and yeasts. It is readily but incompletely absorbed after oral dosing and is highly variable. The transfersomes were formulated by lipid film hydration technique using Rotary vacuum Evaporator. The prepared transfersomes were converted into suitable gel formulation and is evaluated for their gel characteristics like pH, viscosity, spreadability, extrudability, homogeneity, drug content, etc. Suitable essential oils acting as natural permeation enhancers were added to the transfersomal formulation of KTZ for their release studies. Studies proved that addition of suitable permeation enhancers to the transfersomal formulation improved the release and permeation of KTZ, which showed that the permeation enhancers modify the barrier to penetration present in skin without itself undergoing any change. From the various essential oils which are used as permeation enhancers, the formulation containing Eucalyptus oil showed better in vitro release and permeation as compared with other formulations containing different permeation enhancers.


[Results of 1000 electrocardiographic exercise tests. Their correlation with previous ischemic cardiopathy and arteriosclerotic risk factors].
Exercise electrocardiograms were done on one thousand patients referred to the laboratory of exercise tests for: suggestive symptoms of acute heart failure, old miocardial infarction abnormal resting ECG, or evaluation of coronary reserve. The average value of cardiac rate reached for the group, was close to 80%. The maximum exercise loads managed by the men were superior to those of the women, and in general those managed in the negative test were superior in relation to the positive tests. Of the one thousand cases, 20.2% had positive exercise ECG's. There was no difference inthe percentages of positivity between the two sexes, 20.75% and 19.11% for men and women respecitvely. The percentages of positivity are greater in those subjects sent to the laboratory for suspicion of angina pectoris, old MI, or abnormal resting ECG, than in those referred for detection of ischemic heart disease. The groups of patients with diabetes mellitus, arterial hypertension, old MI, and abnormal resting ECG had the highest incidence of positive tests: 41%, 37.5%, 30.6%, and 28.2% respectively. The most frequent localization of the ST segment alterations was the anterior portion, with percentages of 85.1% similar to those mentioned in the literature. The frequency of arrithmias, of 12.4% in this group, is a little less than that described in similar groups, but it corroborates the predominance of non-lethal ventricular arrithmias. The mortality in the tests performed was null.


Long-term effects of bupivacaine on cartilage in a rabbit shoulder model.
Previous investigations have reported on the chondrotoxicity of bupivacaine in short-term in vivo and in vitro models. This study was designed to provide additional information on the long-term effects of bupivacaine infusion on articular cartilage in an established rabbit shoulder model. Infusion of bupivacaine into the rabbit shoulder will have long-term deleterious effects on articular cartilage. Controlled laboratory study. Thirty-six rabbits were randomized into 3 groups and were infused over 48 hours with saline (S), bupivacaine alone (B), or bupivacaine with epinephrine (B+E) into the glenohumeral joint. Animals were sacrificed after 3 months, and tissue samples were analyzed with live/dead cell assay, proteoglycan (PG) synthesis and content assays, and conventional histological evaluation. No macroscopic or radiographic changes were detected in the infused shoulders. Sulfate uptake of infused shoulders relative to controls was elevated to 112% +/-39% (S), 166% +/-67% (B), and 210% +/-127% (B+E). Statistical analysis of PG content demonstrated significantly increased levels in bupivacaine groups compared with saline. There were no significant differences among groups in cell count, percentage of living cells, or histological grade. No permanent impairment of cartilage function was detected 3 months after intra-articular infusion of bupivacaine. Cartilage metabolism was increased, indicating a possible reparative response. This suggests that, at least in the model used, articular cartilage has the ability to recover from the chondrotoxic effects of bupivacaine infusion. Before extrapolating these results to human cartilage, other factors including underlying cartilage injury or disease, decreased chondrocyte density, and increased bupivacaine dosing need to be taken into account. Clinical Relevance Bupivacaine toxicity has recently been implicated in the development of chondrolysis after arthroscopic shoulder procedures, but these findings suggest that additional noxious stimuli might be required before permanent damage ensues.


Healthcare workers' experiences of patient safety in the intensive care unit during the COVID-19 pandemic: A multicentre qualitative study.
To describe healthcare workers' experiences of preconditions and patient safety risks in intensive care units during the COVID-19 pandemic. Healthcare workers' ability to adapt to changing conditions is crucial to promote patient safety. During the COVID-19 pandemic, healthcare workers' capacity to maintain safe care was challenged and a more in-depth understanding on frontline experiences of patient safety is needed. A qualitative descriptive design. Individual interviews were conducted with 29 healthcare workers (nurses, physicians, nurse assistants and physiotherapists) from three Swedish hospitals directly involved in intensive care of COVID-19 patients. Data were analysed with inductive content analysis. Reporting followed the COREQ checklist. Three categories were identified. Hazardous changes in working conditions describes patient safety challenges associated with the extreme workload with high stress level. Imperative adaptations induced by changed preconditions for patient safety which include descriptions of safety risks following adaptations related to temporary intensive care facilities, handling shortage of medical equipment and deviations from routines. Safety risks triggered by reorganisation of care describe how the diluted skill-mix and team disruptions exposed patients to safety risks, and that safety performance mostly relied on individual healthcare worker's responsibility. The study suggests that healthcare workers experienced an increase in patient safety risks during the COVID-19 pandemic mainly because the extremely high workload, imperative adaptations, and reorganisation of care regarding skill-mix and teamwork. Patient safety performance relied on the individuals' adaptability and responsibility rather than on system-based safety. This study provides insights on how healthcare workers' experiences can be used as a source of information for recognition of patient safety risks. To improve detection of safety risks during future crises, guidelines on how to approach safety from a system perspective must include healthcare workers' perceptions on safety risks. None in the conceptualisation or design of the study.


Genotoxic methylating agents modulate extracellular signal regulated kinase activity through MEK-dependent, glutathione-, and DNA methylation-independent mechanisms in lung epithelial cells.
Mitogen-activated protein kinases (MAPKs) play a central role in transmitting stress-induced signals stimulated by genotoxic agents. The present study is the first to investigate the mechanisms by which genotoxic alkylating agents modulate MAPKs by directly measuring the effects of methylating agents on MAPK activity, DNA methylation, and intracellular glutathione levels. The effects of acetoxymethylmethylnitrosamine (AMMN), N-nitroso-N-methylurethane (NMUR), and N-methyl-N-nitrosourea (MNU) on these parameters were compared in a fetal rat lung cell line model (MP48). These compounds were chosen because they methylate DNA via a methanediazonium intermediate and, therefore, should induce similar cellular methylation patterns, although they produce different side products upon decomposition. All three compounds stimulated the activation of the stress-activated MAPKs, c-Jun N-terminal kinase, and p38. In contrast to what has been reported for other methylating agents, these compounds also stimulated the activation of extracellular signal regulated kinase (ERK), a MAPK typically activated by mitogenic agents. O6-methylguanine (O6-mG) is widely considered to be the critical toxic lesion induced by methylating agents, including AMMN, NMUR, and MNU, which form DNA adducts through SN1 reactions. O6-mG does not appear to be a key regulator of MAPK activity by these compounds, however. There is no direct relationship between the levels of O6-mG and the levels of MAPK activation, and formation of O6-mG does not appear to be sufficient to stimulate MAPK activation. The present studies also indicate that depletion of glutathione is not required or sufficient to stimulate MAPK activation by the methylating agents investigated here. The use of a pharmacological inhibitor indicates that these methylating agents activate ERK through a signaling pathway that requires the ERK kinase MEK. Altogether, these data indicate that genotoxic methylating agents activate MAPKs through mechanisms that are likely to involve the alkylation of cellular targets other than DNA.


Cell surface receptors for ecotropic murine retroviruses: mobile membrane proteins that mediate binding and slow endocytosis of the viral envelope glycoprotein.
The gp70 envelope glycoproteins of ecotropic murine leukemia viruses bind to receptors that occur only on mouse and rat cells and on interspecies hybrid cells that contain mouse chromosome 5. A substantial fraction of the gp70 that was bound specifically by these criteria remained undegraded and accessible to extracellular labeling reagents for many hours. Accordingly, cells with ecotropic receptors could be labeled specifically. As seen by immunofluorescence microscopy, the gp70-receptor complexes were uniformly dispersed on mouse fibroblast plasma membranes. These complexes were mobile, and they aggregated into patches when crosslinked by antibodies at 37 degrees, but not when membrane lipid fluidity was frozen at 0 degrees. Ecotropic receptors still bound gp70 specifically after cells were fixed with 3.7% formaldehyde, but these receptors could not be patched, indicating that they were nondiffusible. Viable cells slowly endocytosed gp70-receptor complexes at 37 degrees (approximate half-life 5-7 hr) and the gp70 was then proteolytically degraded in lysosomes. In the presence of 20 microM chloroquine, a lysosomal inhibitor, undegraded gp70 was seen to slowly accumulate in these intracellular organelles. These results suggest that ecotropic receptors mediate a slow internalization of attached ligand. Long-lived binding of gp70 onto surfaces of uninfected cells may explain important features of viral-induced leukemia, the host immune response, and immunosuppression.


The Role of Powerlessness Among Health Care Workers in Tuberculosis Infection Control.
Due to their occupational exposure in health care settings, health care workers (HCW) have increased risk of Mycobacterium tuberculosis infection. They face challenges to remain up-to-date with evidence-based clinical practices and translate educational information into actions in infection control practices. Our purpose was to examine this "knowledge-action" gap about how HCWs understand their occupational M. tuberculosis risk and use recommended infection control measures in clinical practices in the Dominican Republic (DR). We conducted 10 focus groups with 40 physicians and nurses at two tertiary-level DR institutions. Using grounded theory methods, we developed a theoretical model to describe the decision-making process related to adherence to M. tuberculosis infection control measures in clinical practice. Findings highlight intrinsic and extrinsic factors that influenced the observed knowledge-action gap related to M. tuberculosis infection control practices in two DR health institutions.


Occurrence of microcystins in water, bloom, sediment and fish from a public water supply.
Microcystin (MC) accumulation was determined in the liver and muscle of two omnivorous fish species which are consumed and are economically important, and in a planktivorous-carnivorous fish from Lake Eğirdir, Turkey. Free extractable MCs in fish tissue samples were detected by enzyme-linked immunosorbent assay (ELISA) with confirmation by high performance liquid chromatography with photodiode array detection (HPLC-PDA). MC-LA and -YR, were detected in both liver and muscle, followed by MCs -LY, -LF, -RR and -LR respectively. The MC concentrations varied between 0.043 and 1.72μg/g dry weight in liver and muscle tissues. MCs were also determined in samples of water, sediment and a bloom sample of Microcystis aeruginosa from the lake by HPLC-PDA. MC-LY and -YR were most commonly identified in water samples, with total MC concentrations ranging from 2.9±0.05 to 13.5±2.3μg/L. Sediment analyses, showed that MC-YR was present in samples between 7.0 and 17.6μg/g dw, especially in October, November and December when no MC-YR was recorded in water, followed by MC-LW. The findings indicate that water and sediment contained MCs, and more importantly that fish were contaminated with MCs that may pose an MC-associated human health risk.


Barriers and Facilitators for Health Behavior Change among Adults from Multi-Problem Households: A Qualitative Study.
Multi-problem households are households with problems on more than one of the following core problem areas: socio-economic problems, psycho-social problems, and problems related to child care. The aim of this study was to examine barriers and facilitators for health behavior change among adults from multi-problem households, as well as to identify ideas for a health promotion program. A qualitative study involving 25 semi-structured interviews was conducted among Dutch adults who received intensive family home care for multi-problem households. Results were discussed with eight social workers in a focus group interview. Data were analyzed using the Framework Method. The results revealed that the main reason for not engaging in sports were the costs. Physical activity was facilitated by physically active (transport to) work and by dog ownership. Respondents who received a food bank package reported this as a barrier for healthy eating. Those with medical conditions such as diabetes indicated that this motivated them to eat healthily. Smokers and former smokers reported that stress was a major barrier for quitting smoking but that medical conditions could motivate them to quit smoking. A reported reason for not using alcohol was having difficult past experiences such as violence and abuse by alcoholics. Mentioned intervention ideas were: something social, an outdoor sports event, cooking classes, a walking group, and children's activities in nature. Free or cheap activities that include social interaction and reduce stress are in line with the identified barriers and facilitators. Besides these activities, it may be important to influence the target group's environment by educating social workers and ensuring healthier food bank packages.


Exiting Medicine Faculty Want the Organizational Culture and Climate to Change.
National data indicate about 50% of junior faculty leave a School of Medicine (SOM) within eight years of hire. The long-term goal of the study was to determine innovative strategies for promoting SOM faculty retention. The study objective was to determine factors influencing SOM faculty to exit, and what would encourage them to stay or return. All faculty exiting the University of New Mexico (UNM) SOM were surveyed and their responses analyzed to the following items: (a) If something could have been done differently that might have resulted in staying at UNM, what would it have been? (b) What would need to change at UNM SOM for you to return? and (c) general comments offered. Qualitative analysis of open-ended responses used an iterative process and systematic thematic approach and NVivo software. 173 faculty respondents surveyed between July 2017 and June 2019 included 86 women, 33 non-Caucasians, and 14 Hispanics. A total of 110 faculty reported an MD degree and 117 were assistant professors. Seventy-eight faculty were on clinician educator track. The 367 responses to the three questions were categorized into 10 themes. The most common themes included (a) people (leadership and others) and workplace culture (25.1% of responses); (b) extent of career support and resources (15.3%); (c) organizational systems and administration (13.6%); and (d) faculty feelings of autonomy and value (10.9%). Exiting faculty frequently discussed the need for a change of leadership and changes in organizational climate and culture, which may have influenced their willingness to stay or to return to UNM SOM. To retain faculty, SOM leaders need to strengthen and/or modify organizational climate and culture components. Innovative strategies for this purpose may include organizational interventions followed by evidence-based leadership training programs, and the use of exit surveys for monitoring interventions.


Influence of juice pressing conditions on polyphenols, antioxidants, and varietal aroma of Sauvignon blanc microferments.
The impact of juice press fractions upon the content of varietal thiols in Sauvignon blanc has been examined for wines fermented at the laboratory scale (750 mL). Wines made from pressed juices (taken at 0.25 and 1.0 bar) contained less than half the concentration of 3-mercaptohexan-1-ol (3MH) and 3-mercaptohexyl acetate (3MHA), important contributors to the tropical and passion fruit character of Sauvignon blanc wines, compared to wines made from free run juices. The pressed juices and wines exhibited lower acidity values, more rapid decline in glutathione content, and more advanced polyphenol oxidation. Supplementation of the juices with glutathione (at 67 mg/L) prior to fermentation led to lower varietal thiol concentrations in the finished wines, typically by several percent, whereas treatment with polyvinylpolypyrrolidone (PVPP) made no impact on wine parameters. Pasteurization of pressed juices increased 3MHA content in the finished wines, but also led to a decline in 3MH concentrations.


Higher incidence of diabetes in liver transplant recipients with hepatitis C.
We assessed the clinical and biochemical parameters associated with the development of posttransplantation diabetes (PTDM) in 52 liver transplant recipients followed up for 1 year. Diabetes was present before transplantation in 9.6% (5 of 52) of patients, and PTDM occurred in 23% (11 of 47) of the remaining liver transplant recipients. Of the 13 patients who had hepatitis C as the cause of their liver failure (HC-LD), 8 (62%) developed PTDM; of the 34 patients with other causes of liver failure, 3 (9%) developed PTDM (p < 0.001). Posttransplantation diabetes was also associated with the development of early posttransplantation hyperglycemia, a higher number of liver rejection episodes, and lower serum albumin levels at 6 months. The association of PTDM with HC-LD remained significant in a logistic regression model after adjustment for potential confounding variables. We conclude that PTDM is common in liver transplant recipients. Associated clinical parameters predictive of PTDM include a diagnosis of HC-LD before transplantation, the development of early hyperglycemia after transplantation, multiple episodes of posttransplantation liver rejection and low serum albumin levels at 6 months. The fact that HC-LD remained an independent risk factor for the development of PTDM may suggest a direct or immune-mediated pancreatic effect of the virus.


An observational study of patient experiences with a direct-to-patient telehealth abortion model in Australia.
While abortion care is widely legal in Australia, access to care is often poor. Many Australians must travel long distances or interstate to access abortion care, while others face stigma when seeking care. Telehealth-at-home medical abortion is a potential solution to these challenges. In this study, we compared the experience of accessing an abortion via telehealth-at-home to accessing care in-clinic. Over a 20-month period, we surveyed patients who received medical abortion services at Marie Stopes Australia via the telehealth-at-home service or in-clinic. We conducted bivariate analyses to assess differences in reported acceptability and accessibility by delivery model. In total, 389 patients were included in the study: 216 who received medical abortion services in-clinic and 173 through the telehealth-at-home service. Telehealth-at-home and in-clinic patients reported similarly high levels of acceptability: satisfaction with the service (82% vs 82%), provider interaction (93% vs 84%), and recommending the service to a friend (73% vs 72%). Only 1% of telehealth-at-home patients reported that they would have preferred to be in the same room as the provider. While median time between discovering the pregnancy to first contact with a clinic was similar between groups, median time from first contact to taking the first abortion medication was 7 days longer for telehealth-at-home patients versus in-clinic patients (14 days (IQR 9-21) vs 7 days (IQR 4-14); p<0.01). The telehealth-at-home medical abortion service has the potential to address some of the challenges with provision of abortion care in Australia.


Naproxen aggravates doxorubicin-induced cardiomyopathy in rats.
The repercussion of the heated dispute on cyclooxygenase-2 (COX-2) selective nonsteroidal anti-inflammatory drugs (NSAIDs) led to the national and international withdrawal of several of the recently introduced coxibs. Further debate and research have highlighted risks of the classical NSAIDs too. There is much controversy about the cardiovascular safety of a nonselective NSAID naproxen (NAP) and its possible cardioprotective effect. The study was undertaken to determine the cardiovascular effects of NAP on doxorubicin-induced cardiomyopathy in rats. Male albino rats received a single i.p. injection of normal saline (normal control group) and doxorubicin (DOX) 15 mg/kg (toxic control group). Naproxen was administered alone (50 mg/kg/day, p.o.) and in combination with DOX and DOX + trimetazidine (TMZ) (10 mg/kg/day, p.o.) for 5 days after 24 h of DOX treatment. DOX-induced cardiomyopathy was assessed in terms of increased activities of serum lactate dehydrogenase (LDH), tissue thiobarbituric acid reactive substances (TBARS) and decreased activities of myocardial glutathione, superoxide dismutase and catalase, followed by transmission electron microscopy of the cardiac tissue. Doxorubicin significantly increased oxidative stress as evidenced by increased levels of LDH and TBARS and decreased antioxidant enzymes levels. Both biochemical and electron microscopic studies revealed that NAP itself was cardiotoxic and aggravated DOX-induced cardiomyopathy and abolished the protective effect of TMZ in rats. This study indicates that NAP has the potential to worsen the situation in patients with cardiovascular disease. Therefore, it should be used cautiously in patients with compromised cardiac function.


Gold nanorods together with HSP inhibitor-VER-155008 micelles for colon cancer mild-temperature photothermal therapy.
Enhancing the heat-sensitivity of tumor cells provides an alternative solution to maintaining the therapeutic outcome of photothermal therapy (PTT). In this study, we constructed a therapeutic system, which was composed of methoxy-polyethylene-glycol-coated-gold-nanorods (MPEG-AuNR) and VER-155008-micelles, to evaluate the effect of VER-155008 on the sensitivity of tumor cells to heat, and further investigate the therapeutic outcome of MPEG-AuNR mediated PTT combined with VER-155008- micelles. VER-155008- micelles down-regulate the expression of heat shock proteins and attenuate the heat-resistance of tumor cell. The survival of HCT116 cells treated with VER-155008- micelles under 45 °C is equal to that treated with high temperature hyperthermia (55 °C) in vitro. Furthermore, we proved either the MPEG-AuNR or VER-155008- micelles can be accumulate in the tumor site by photoacoustic imaging and fluorescent imaging. In vivo anti-cancer evaluation showed that tumor size remarkably decreased (smaller than 100 mm3 or vanished) when treated with combing 45 °C mild PTT system, which contrasted to the tumor size when treated with individual 45 °C mild PTT (around 500 nm3) or normal saline as control (larger than 2000 nm3). These results proved that the VER-155008- micelles can attenuate the heat-resistance of tumor cells and enhance the therapeutic outcome of mild-temperature photothermal therapy.


Effects of structural properties of electrospun TiO2 nanofiber meshes on their osteogenic potential.
Ideal outcomes in the field of tissue engineering and regenerative medicine involve biomaterials that can enhance cell differentiation and production of local factors for natural tissue regeneration without the use of systemic drugs. Biomaterials typically used in tissue engineering applications include polymeric scaffolds that mimic the three-dimensional structural environment of the native tissue, but these are often functionalized with proteins or small peptides to improve their biological performance. For bone applications, titanium implants, or more appropriately the TiO2 passive oxide layer formed on their surface, have been shown to enhance osteoblast differentiation in vitro and to promote osseointegration in vivo. In this study we evaluated the effect on osteoblast differentiation of pure TiO2 nanofiber meshes with different surface microroughness and nanofiber diameters, prepared by the electrospinning method. MG63 cells were seeded on TiO2 meshes, and cell number, differentiation markers and local factor production were analyzed. The results showed that cells grew throughout the entire surfaces and with similar morphology in all groups. Cell number was sensitive to surface microroughness, whereas cell differentiation and local factor production was regulated by both surface roughness and nanofiber diameter. These results indicate that scaffold structural cues alone can be used to drive cell differentiation and create an osteogenic environment without the use of exogenous factors.


Brain morphological changes and early marijuana use: a magnetic resonance and positron emission tomography study.
The focus of this report is on the possible role that the age of first use of marijuana may play on brain morphology and function. Magnetic resonance imaging (MRI) and positron emission tomography (PET) were utilized to study 57 subjects. Brain volume measures (whole brain, gray matter, white matter and lateral ventricle volumes), global cerebral blood flow (CBF) and body size were evaluated. There are three primary findings related to age of first use of marijuana. Subjects who started using marijuana before age 17, compared to those who started later, had smaller whole brain and percent cortical gray matter and larger percent white matter volumes. Functionally, males who started using marijuana before 17 had significantly higher CBF than other males. Both males and females who started younger were physically smaller in height and weight, with the effects being greater in males. These findings suggest that the age at which exposure to marijuana begins is important. Early adolescence may be a critical period for effects that are not present when exposure begins later. These results are discussed in light of reported effects of marijuana on gonadal and pituitary hormones.


Assessment of Knowledge and Level of Radiation Safety Awareness among Radiographers Working in Nuclear Medicine.
Radiopharmaceuticals are used for the diagnosis, treatment, staging, and follow- up of various diseases. However, there is concern that the ionizing radiation (gamma rays, α and ß particles) may result in the exposure of radiographers with limited knowledge of the principles of radiation protection and safety, raising the risk of cancer induction. The aim of the study is to investigate the knowledge and level of radiation safety awareness among radiographers at a tertiary hospital. It is an analytical cross-sectional study. A validated two-part questionnaire was administered to consenting radiographers at a Nuclear Medicine Department. Part 1 gathered demographic information (age, gender, work experience, attendance to/or passing ionizing radiation protection courses), and part 2 covered questions related to knowledge and level of awareness of radiation protection principles. Five radiographers voluntary participated (2/5 males and 3/5 females). Three age groups were distinguishable, 21-30, 41-50 and 51-60 years. In the age group of 21-30 years, there was one male with just over 4 years of experience while in the age group 41-50, there were three females with less than three years of experience, and in the age group 51-60, there was one male radiographer with over 20 years of experience. All the radiographers showed a high level of awareness and knowledge of radiation safety principles. Education coupled with training in radiation protection is an essential tool for instilling radiation awareness among the radiographers. However, education alone is not enough; further skills in the preparation and administration of radiopharmaceuticals will reduce the exposure.