Wake analysis of aerodynamic components for the glide envelope of a jackdaw (Corvus monedula).
Gliding flight is a relatively inexpensive mode of flight used by many larger bird species, where potential energy is used to cover the cost of aerodynamic drag. Birds have great flexibility in their flight configuration, allowing them to control their flight speed and glide angle. However, relatively little is known about how this flexibility affects aerodynamic drag. We measured the wake of a jackdaw (Corvus monedula) gliding in a wind tunnel, and computed the components of aerodynamic drag from the wake. We found that induced drag was mainly affected by wingspan, but also that the use of the tail has a negative influence on span efficiency. Contrary to previous work, we found no support for the separated primaries being used in controlling the induced drag. Profile drag was of similar magnitude to that reported in other studies, and our results suggest that profile drag is affected by variation in wing shape. For a folded tail, the body drag coefficient had a value of 0.2, rising to above 0.4 with the tail fully spread, which we conclude is due to tail profile drag.


Receptor-mediated biliary transport of immunoglobulin A and asialoglycoprotein: sorting and missorting of ligands revealed by two radiolabeling methods.
In the rat, all receptor-bindable immunoglobulin A (IgA), and 1-4% of injected asialoglycoprotein (ASG), are transported from blood to bile intact. The major fraction of the ASG is degraded in hepatic lysosomes. The study described here was designed to elucidate the sorting that occurs in hepatocytes subsequent to receptor binding of ligands not sharing the same fate. We show that conjugation of protein with the Bolton and Hunter reagent can be used as a probe for the lysosomal pathway, since 50% of the reagent is released into bile after lysosomal degradation of internalized protein. Radiolabeling by iodine monochloride was alternatively used to follow the direct pathways that deliver intact IgA and ASG to bile. After intravenous injection of labeled proteins, first intact ASG and IgA, and then radioactive catabolites from degraded protein, were released into bile. No proteolytic intermediates were detected, and the transport of IgA or ASG directly to bile was not affected by the lysosomal protease inhibitor leupeptin. These observations indicate that divergence of the direct biliary transport pathways from the degradation pathway occurs at a stage preceding delivery to lysosomes, possibly at the cell surface. Competition studies showed that all three pathways (including the biliary transport of intact ASG) are receptor mediated, but even at supersaturating doses the uptake and processing of IgA and ASG occur independently. We propose that IgA and ASG receptors are not frequently in juxtaposition on the plasma membrane, but that ASG, after binding to its receptor, is occasionally missorted into the biliary transport pool.


Traffic light labelling could prevent mortality from noncommunicable diseases in Canada: A scenario modelling study.
Traffic-light labelling (TLL) is a promising front-of-pack system to help consumers make informed dietary choices. It has been shown that adopting TLL in Canada, through an optimistic scenario of avoiding, if possible, foods with red traffic lights, could effectively reduce Canadians' intakes of energy, total fat, saturated fat, and sodium by 5%, 13%, 14% and 6%, respectively. However, the potential health impact of adopting TLL has not been determined in the North American context. This study modelled the potential impact of adopting TLL on mortality from noncommunicable diseases (NCDs) in Canada, due to the previously predicted improved nutrient intakes. Investigators used data from adults (n = 19,915) in the 2004 nationally representative Canadian Community Health Survey (CCHS)-Cycle 2.2. Nutrient amounts in foods consumed by CCHS respondents were profiled using the 2013 United Kingdom's TLL criteria. Whenever possible, foods assigned at least one red light (non-compliant foods) were replaced with similar, but compliant, foods identified from a Canadian brand-specific food database. Respondents' nutrient intakes were calculated under the original CCHS scenario and the counterfactual TLL scenario, and entered in the Preventable Risk Integrated ModEl (PRIME) to estimate the health impact of adopting TLL. The primary outcome was the number of deaths attributable to diet-related NCDs that could be averted or delayed based on the TLL scenario compared with the baseline scenario. PRIME estimated that 11,715 deaths (95% CI 10,500-12,865) per year due to diet-related NCDs, among which 72% are specifically related to cardiovascular diseases, could be prevented if Canadians avoided foods labelled with red traffic lights. The reduction in energy intakes would by itself save 10,490 deaths (9,312-11,592; 90%). This study, although depicting an idealistic scenario, suggests that TLL (if used to avoid red lights when possible) could be an effective population-wide intervention to improve NCD outcomes in Canada.


Revision total hip arthoplasty: factors associated with re-revision surgery.
The survivorship of implants after revision total hip arthroplasty and risk factors associated with re-revision are not well defined. We evaluated the re-revision rate with use of the institutional total joint replacement registry. The purpose of this study was to determine patient, implant, and surgeon factors associated with re-revision total hip arthroplasty. A retrospective cohort study was conducted. The total joint replacement registry was used to identify patients who had undergone revision total hip arthroplasty for aseptic reasons from April 1, 2001, to December 31, 2010. The end point of interest was re-revision total hip arthroplasty. Risk factors evaluated for re-revision total hip arthroplasty included: patient risk factors (age, sex, body mass index, race, and general health status), implant risk factors (fixation type, bearing surface, femoral head size, and component replacement), and surgeon risk factors (volume and experience). A multivariable Cox proportional hazards model was used. Six hundred and twenty-nine revision total hip arthroplasties with sixty-three (10%) re-revisions were evaluated. The mean cohort age (and standard deviation) was 57.0 ± 12.4 years, the mean body mass index (and standard deviation) was 29.5 ± 6.1 kg/m(2), and most of the patients were women (64.5%) and white (81.9%) and had an American Society of Anesthesiologists score of <3 (52.9%). The five-year implant survival after revision total hip arthroplasty was 86.8% (95% confidence interval, 83.57% to 90.25%). In adjusted models, age, total number of revision surgical procedures performed by the surgeon, fixation, and bearing surface were associated with the risk of re-revision. For every ten-year increase in patient age, the hazard ratio for re-revision decreases by a factor of 0.72 (95% confidence interval, 0.58 to 0.90). For every five revision surgical procedures performed by a surgeon, the risk of revision decreases by a factor of 0.93 (95% confidence interval, 0.86 to 0.99). At the time of revision, a new or retained cemented femoral implant or all-cemented hip implant increases the risk of revision by a factor of 3.19 (95% confidence interval, 1.22 to 8.38) relative to a retained or new uncemented hip implant. A ceramic on a highly cross-linked polyethylene bearing articulation decreases the hazard relative to metal on highly cross-linked polyethylene by a factor of 0.32 (95% confidence interval, 0.11 to 0.95). Metal on constrained bearing increases the hazard relative to metal on highly cross-linked polyethylene by a factor of 3.32 (95% confidence interval, 1.16 to 9.48). When evaluating patient, implant, and surgical factors at the time of revision total hip arthroplasty, age, surgeon experience, implant fixation, and bearing surfaces had significant impacts on the risk of re-revision.


Administration of rectal cytotec versus rectal buscopan before hysteroscopy.
Our objective was to compare the effect of rectal misoprostol (Cytotec) versus rectal hyoscine-n-butyl bromide (Buscopan) on patients undergoing hysteroscopy. We hypothesised that HBB may have a role in cervical priming. This trial was conducted at Bezmialem Vakif University Hospital. Women of reproductive age between 18-50 years who were scheduled for operative hysteroscopy indicated by type 1 submucous myoma or endometrial polyps were recruited for the study. Ninety patients were divided randomly into three groups. Group 1 received placebo treatment. Group 2 received rectal 200 mcg misoprostol and Group 3 received rectal 20 mg hyoscine-n-butyl bromide two hours before the procedure. Procedures were performed using a bipolar 26 F (9 mm) continuous-flow rigid resectoscope with a 30° lens. The outcome measures included cervical dilation width and time, ease of cervical dilation, procedure time and operative complications. Postoperative self-rated pain was assessed one hour after the procedure. Thirteen patients (43. 3%) in the placebo treatment group, 11 patients (36.7%) in the misoprostol group and four patients (13.3%) in the hyoscine-n-butyl bromide group needed analgesics postoperatively (p = .02). The mean duration of cervical dilation time was longest in Group 1 and shortest in Group 3, however this difference did not reach statistical significance (p=.11). There was no difference with regard to other studied parameters. HBB reduced the need for pain medication compared to placebo. Larger studies are needed to further investigate the role of HBB in facilitating pre-operative cervical priming.


Urotensin II, from fish to human.
The cyclic peptide urotensin II (UII) was originally isolated from the urophysis of teleost fish on the basis of its ability to contract intestinal smooth muscle. The UII peptide has subsequently been isolated from frog brain and, later on, the pre-proUII cDNA has been characterized in mammals, including humans. A UII paralog called urotensin II-related peptide (URP) has been identified in the rat brain. The UII and URP genes originate from the same ancestral gene as the somatostatin and cortistatin genes. In the central nervous system (CNS) of tetrapods, UII is expressed primarily in motoneurons of the brainstem and spinal cord. The biological actions of UII and URP are mediated through a G protein-coupled receptor, termed UT, that exhibits high sequence similarity with the somatostatin receptors. The UT gene is widely expressed in the CNS and in peripheral organs. Consistent with the broad distribution of UT, UII and URP exert a large array of behavioral effects and regulate endocrine, cardiovascular, renal, and immune functions.


Organic carbon effect on nitrifying bacteria in a mixed culture.
This study investigated the effect of organic carbon source on ammonia oxidizing community in single sludge laboratory scale sequencing batch reactors (SBR). Two sequencing batch reactors performing simultaneous carbon oxidation and nitrification were operated. Operationally and functionally, these two reactors were identical, except that one reactor was fed peptone and sodium acetate, and the other was fed glucose and sodium acetate as external organic carbon sources. The peptone-fed reactor had 98.1 + or - 1.84% COD removal and 97.3 + or - 6.69% NH(3)-N oxidation. The glucose-fed reactor had 99.1 + or - 1.29% COD removal and 99.4 + or - 0.76% NH(3)-N oxidation. The reactor fed with peptone, a complex organic carbon source comprised of enzymatic digests of animal proteins, had greater diversity in both the heterotrophic bacterial community and the ammonia oxidizing bacteria community than in the reactor fed with glucose, a simple sugar as evidenced by automated ribosomal intergenic spacer analysis (ARISA) and terminal restriction fragment length polymorphism (TRFLP) experiments respectively.


The Direct and Indirect Relationship Between Social Cognition and Psychosocial Dysfunction in Major Depressive Disorder.
Background: Recent evidence suggests that depressed patients experience social cognitive deficits (e.g., poor affect recognition). However, very little is known regarding the contribution of social cognitive deficits to psychosocial dysfunction (e.g., occupational functioning). In particular, the mechanistic roles of depression severity and cognitive deficits (e.g., memory) in this domain have not been explored. The current study evaluated the extent to which mood symptoms and cognitive deficits provide a mechanistic explanation for the relationship between social cognitive and psychosocial deficits in major depressive disorder (MDD). Methods: Data were obtained from 111 participants with MDD (75 Female, mean age = 35, 84% Caucasian, 12% Asian, 4% Other) in the Cognitive Function and Mood Study (CoFaM-S), a cross-sectional study of mood, social cognition, cognition, and psychosocial functioning in mood disorders. Social cognitive abilities were assessed using the Social Perception subtest of the Wechsler Adult Intelligence Scale, and psychosocial dysfunction was clinically evaluated with the Functioning Assessment Short Test (FAST). Results: Cognitive deficits and mood symptoms did not significantly mediate relationships between social cognitive ability and psychosocial dysfunction. The exception was executive function, which mediated an indirect relationship between meaning interpretation (i.e., theory of mind) and self-perceived cognitive dysfunction. Conclusion: The results suggest that the relationship between social cognitive deficits and psychosocial dysfunction is not mechanistically explained by mood symptoms or nonsocial cognition. Development of treatment strategies targeting social cognitive deficits in patients with MDD is warranted.


Informed consent and the use of gametes and embryos for research: a committee opinion.
The ethical conduct of human gamete and embryo research depends upon conscientious application of principles of informed consent developed in the context of clinical research. This document explores these principles, which entail, for example, that investigations occur under Institutional Review Board oversight. This document also discusses the complexities in obtaining informed consent from the persons whose gametes or embryos are being used in research but were originally intended for reproductive purposes. This statement replaces the document of the same name last published in 2004 (Fertil Steril 2004;82:S251-252).


Successful long-term treatment with cyclosporin A in protein losing gastroenteropathy.
Protein-losing gastroenteropathy (PLG) can occur as a manifestation of various diseases including autoimmune disorders, and optimal therapy of these underlying diseases may be the only effective remedy for PLG. In the present report, we describe a case of a 54-year-old woman with PLG associated with an autoimmune disease, presumably CREST syndrome. She failed to respond to steroid treatment. Subsequently, cyclosporine was initiated, which resulted in a rapid recovery. The patient was successfully treated with low-dose cyclosporine for five years. There has not been, to our knowledge, any report of PLG successfully treated with cyclosporine. Cyclosporine therapy may be effective not only in inducing but also in maintaining complete remission in patients with autoimmune-associated PLG, especially refractory or intolerable to steroids and/or immunosuppressive therapies.


Carotid body resection for sympathetic modulation in systolic heart failure: results from first-in-man study.
Augmented reflex responses from peripheral chemoreceptors, which are mainly localized in the carotid bodies (CBs), characterize patients with systolic heart failure and contribute to adrenergic hyperactivation. We investigated whether surgical resection of CBs in these patients can be performed safely to decrease sympathetic tone. We studied 10 male patients with systolic heart failure (age, 59 ± 3 years; LVEF, 27 ± 7%) who underwent unilateral right-sided CB resection (four patients) or bilateral CB resection (six patients). Primary endpoints of the study were changes in muscle sympathetic nerve activity (MSNA) and peripheral chemosensitivity measured as ventilatory response to hypoxia from baseline to 1 month post-CB resection. Safety analysis included analysis of arterial blood gas and oxygenation at night through 2 months post-procedure and adverse events assessed up to 12 months. At the 1-month visit, CB resection was associated with a significant decrease both in MSNA (86.6 ± 3.1 vs. 79.7 ± 4.2 bursts/100 beats, P = 0.03) and in peripheral chemosensitivity (1.35 ± 0.19 vs. 0.41 ± 0.17 L/min/SpO2 , P = 0.005). It also resulted in improved exercise tolerance. Amongst some patients with bilateral CB resection, there was a trend towards worsening of oxygen saturation at night, which in one case required therapy with non-invasive ventilation. We present first-in-man evidence that CB resection in patients with systolic heart failure is associated with a decrease in sympathetic activity. A bilateral procedure may carry a risk of worsening oxygenation at night. CB modulation constitutes an interesting research avenue, but careful consideration of the balance between safety and efficacy is necessary before further clinical trials.


Chloride-mediated inhibitory junction potentials in opossum esophageal circular smooth muscle.
Intracellular recordings were made from circular smooth muscle cells of the opossum esophagus. Inhibitory junction potentials (IJPs) 8.3 +/- 0.7 mV in amplitude were observed in response to a single pulse (1 ms, 15 mA) of transmural nerve stimulation. Potassium channel blockers apamin (1 microM), tetraethylammonium (10 mM), 4-aminopyridine (250 microM), and cesium chloride (10 mM) did not reduce IJP amplitude. Conditioning hyperpolarizations to the equilibrium potential for potassium were associated with a significant increase in IJP amplitude. A small increase in membrane resistance was observed during the IJP. Changes in external potassium concentration had no significant effect on IJP amplitude acutely. However, prolonged perfusion with potassium-free Krebs solution resulted in a marked decrease in IJP amplitude as did prolonged perfusion with ouabain (0.1 mM). Low-chloride solution (12.4 mM) resulted acutely in an increase in IJP amplitude. Prolonged low-chloride perfusion resulted in a significant decrease in IJP amplitude. The anion exchange chloride channel inhibitor 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (600 microM) significantly reduced IJP amplitude. These findings suggest that the IJP observed in opossum esophageal circular smooth muscle in response to a single pulse of stimulation is due to a decrease in membrane chloride conductance. The ability of prolonged application of Na-K pump inhibitors to abolish the IJP appears to be due to known secondary effects of these agents in depleting intracellular chloride.


Regulation of gene expression by human foamy virus and potentials of foamy viral vectors.
The hallmarks of the spumaretrovirus or human foamy virus (HFV) are summarized and discussed with special focus on the potentials to use HFV as a new retroviral vector system. The special features of HFV are the expression of pol by splicing and start of translation at a defined initiation codon. The first Met of Pol is conserved in the six known foamy virus genomic sequences. Another remarkable characteristic of HFV is the presence of a Gly-Arg-rich sequence instead of the Cys-Cys motif of the classical retroviral nuclecapsid proteins. The preferential budding of HFV into cytoplasmic vesicles and the potential to exploit it in the application of corresponding vector systems is discussed. In addition, recent reports of transducing marker genes into susceptible cells will be reviewed.


Laterality phenotypes in patients with schizophrenia, their siblings and controls: associations with clinical and cognitive variables.
Various behavioural indices of brain lateralisation significantly intercorrelate, but current research in this area still focuses on single behavioural asymmetries, such as handedness. To describe a novel approach, which simultaneously integrates various laterality indices and delineates complex phenotypes. Grade of membership analysis was used to describe latent, complex lateralisation phenotypes in patients with schizophrenia (n=157), their siblings (n=74) and controls (n=77). The indices used were asymmetries of eye, foot and hand; hand motor proficiency; and handedness of patient's first-degree relatives. Three distinct pure types of lateralisation ('right', 'left' and 'mixed') were evident in patients compared with two ('right' and 'left') in siblings and controls. The 'mixed' type in patients featured absence of eye and foot lateralisation and presence of familial sinistrality, despite a right-hand dominance for writing. Patients with schizophrenia expressing the 'left' phenotype had a more severe course of illness, significantly increased scores on two schizotypy factors and poorer neurocognitive performance. The pure types in the siblings were similar to those in healthy controls. The findings suggest that a leftward reversal, rather than a reduction in lateralisation, is associated with clinical severity and neurocognitive deficits in patients with schizophrenia.


Secretome of senescent hepatic stellate cells favors malignant transformation from nonalcoholic steatohepatitis-fibrotic progression to hepatocellular carcinoma.
Background: Hepatic fibrosis is a premalignant lesion, and how injured hepatocytes transform into malignancy in a fibrotic microenvironment is poorly understood. Senescence is one of major fates of activated hepatic stellate cells (HSCs). Paucity of literature is available regarding the influence of senescent HSCs on behavior of steatotic hepatocytes. Methods: Senescent HSCs were identified in a murine model of nonalcoholic steatohepatitis (NASH)-fibrosis-hepatocellular carcinoma (HCC) and human NASH-HCC specimens. Secretome of senescent HSCs was analyzed by label-free mass-spectrum (NanoRPLC-MS/MS) and verified quantitatively. Results: Senescent HSCs were increased along with the progression from nonalcoholic fatty liver (NAFL), NASH to NASH-fibrosis, and reached a peak at the stage of advanced fibrosis and then decreased when hepatocellular dysplasia or HCC was developed. Critical components affecting proliferation, epithelial-mesenchymal transition (EMT) or migration were identified from secretome of senescent HSCs, and may activate morphogenic hedgehog or oncogenic Wnt signaling pathways to accelerate malignant transformation of steatotic or dysplastic hepatocytes. Primary hepatocytes stimulated with conditioned medium from senescent HSCs, in co-culture or co-cultured in 3D spheroids with senescent HSCs exhibited an enhanced proliferating or EMT profile. Conclusion: Senescent HSCs secreted a characterized protein profile favoring malignant transformation of steatotic or dysplastic hepatocytes through activating morphogenic hedgehog or oncogenic Wnt signaling pathways in the progression from NASH to malignancy.


Non-steroidal anti-inflammatory drug (NSAID) use and breast cancer risk in the Western New York Exposures and Breast Cancer (WEB) Study.
Chronic inflammation is suspected to have a role in breast carcinogenesis. Results of studies of non-steroidal anti-inflammatory drugs (NSAIDs) and breast cancer have been inconsistent. Timing of exposure and analysis of individual NSAIDs should be considered. We conducted a population-based case-control study in western New York State between 1996 and 2001. Cases, 35-79 years, had incident, primary, histologically confirmed breast cancer (n = 1,170). Controls (n = 2,115) were randomly selected from NY Department of Motor Vehicles records (<65 years) or Medicare rolls (>or=65 years). Participants were queried on use of aspirin, ibuprofen, and acetaminophen in the year prior and on aspirin during adulthood. Unconditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (95% CI). Recent aspirin use was inversely associated with breast cancer risk (adjusted OR 0.80, 95% CI: 0.68-0.94); the strongest reduction in risk was observed among those who took >or=2 pills/day on days that aspirin was taken (OR 0.74, 95% CI: 0.61-0. 90). Adult lifetime use was also associated with breast cancer risk (>10 days/month, adjusted OR 0.68, 95% CI: 0.46-1.00). Use of ibuprofen or acetaminophen was not associated with breast cancer. This is the first study to investigate the association of adult lifetime aspirin intake with breast cancer risk. Our findings provide evidence that aspirin use throughout a woman's life may confer some benefit.


Preparing nurses to prescribe medicines for patients with diabetes: a national questionnaire survey.
This paper is a report of a study to examine Nurse Independent/Nurse Supplementary Prescribing for people with diabetes and the extent to which these nurses feel prepared for this role. An area of care in which nurses, caring for people with diabetes, are involved is the management of medications. There is little or no evidence examining the prescription of medicines by nurses for people with this condition. The United Kingdom Nursing and Midwifery Council database was used to select a random sample of 1992 Registered Nurse Independent/Nurse Supplementary Prescribers. Of these, 1400 questionnaires were returned. Medicines for people with diabetes were prescribed by 439 respondents. This paper reports on the findings of these 439 nurses. The data were collected in 2006. Four hundred and nine (95.1%) participants had used independent prescribing and 214 (49.8%) used supplementary prescribing. The majority of respondents were highly experienced and worked in primary care. Some nurses (7.6%) reported that the prescribing programme did not meet their need. The needs of nurses who had undertaken specialist training in diabetes were met to a statistically and significantly greater extent than those without this training. Nurse prescribing was viewed positively by nurses prescribing for people with diabetes. Prescribing has extended the role that nurses in the United Kingdom are able to play in the management of diabetes. Specialist training is a prerequisite for nurses adopting this role. There is a need to explore the prescribing programme and the extent to which it meets the needs of nurses prescribing for people with diabetes.


Functions of interneurons in mouse cerebellum.
The output signal of Purkinje cells is conveyed by the modulated discharge of simple spikes (SSs) often ascribed to mossy fiber-granule cell-parallel fiber inputs to Purkinje cell dendrites. Although generally accepted, this view lacks experimental support. We can address this view by controlling afferent signals that reach the cerebellum over climbing and mossy fiber pathways. Vestibular primary afferents constitute the largest mossy fiber projection to the uvula-nodulus. The discharge of vestibular primary afferent mossy fibers increases during ipsilateral roll tilt. The discharge of SSs decreases during ipsilateral roll tilt. Climbing fiber discharge [complex spikes (CSs)] increases during ipsilateral roll tilt. These observations suggest that the modulation of SSs during vestibular stimulation cannot be attributed directly to vestibular mossy fiber afferents. Rather we suggest that interneurons driven by vestibular climbing fibers may determine SS modulation. We recorded from cerebellar interneurons (granule, unipolar brush, Golgi, stellate, basket, and Lugaro cells) and Purkinje cells in the uvula-nodulus of anesthetized mice during vestibular stimulation. We identified all neuronal types by juxtacellular labeling with neurobiotin. Granule, unipolar brush, stellate, and basket cells discharge in phase with ipsilateral roll tilt and in phase with CSs. Golgi cells discharge out of phase with ipsilateral roll tilt and out of phase with CSs. The phases of stellate and basket cell discharge suggests that their activity could account for the antiphasic behavior of CSs and SSs. Because Golgi cells discharge in phase with SSs, Golgi cell activity cannot account for SS modulation. The sagittal array of Golgi cell axon terminals suggests that they contribute to the organization of discrete parasagittal vestibular zones.


Adaptation of the Recreovía During COVID-19 Lockdowns: Making Physical Activity Accessible to Older Adults in Bogotá, Colombia.
The community restrictions during the coronavirus disease 2019 pandemic adversely impacted older adults' physical activity levels. This convergent mixed-method study assessed the adaptation of the Recreovía, a community-based physical activity program in Bogotá, and characterized physical activity levels among older adult participants. Our results showed how the Recreovía adapted during the pandemic to continue promoting physical activity, through indoor and outdoor strategies, including virtual physical activity sessions and safety protocols. During this time, 72%-79% of the older adults attending the adapted program were physically active. A greater proportion of park users (84.2%) and more people involved in vigorous physical activity were observed during Recreovía days. Older adults had positive experiences and perceptions of the Recreovía program related to their health and social well-being. Even though the older adults prefer being outdoors, the adapted program allowed participants to continue with their physical activity routines as much as possible during the pandemic.


Body mass index in Belgian schoolchildren and its relationship with sensitization and allergic symptoms.
Results of studies of the influence of body mass index (BMI) on the allergic status are controversial. As a part of the Aalst Allergy Study, we assessed the prevalence of the different BMI categories (underweight, normal weight, overweight, and obesity) and a possible association between BMI and atopy in 1576 unselected Belgian schoolchildren, aged from 3.4 to 14.8 yr. BMI was used to determine weight status. Skin prick testing with the most common aeroallergens was performed. A parental questionnaire documented data on respiratory and allergic disorders, demographic characteristics and other potential risk factors for sensitization. Among the total children, 4.1% of the children were underweight, 14.5% were overweight, and 7.4% were obese. More girls than boys were overweight (p = 0.015). In the group of children older than 12 yr, we found more overweight (p = 0.03) and obese (p = 0.004) girls, and more obese boys (p = 0.004) than in the younger age groups. In contrast with reports in the literature, an increased prevalence of allergic sensitization in underweight girls only [adjusted odd ratio (OR(adj)) = 2.9, 95% confidence interval (CI): 1.3-6.4] was documented. A strong association between obesity and exercise-induced respiratory symptoms was found in both boys (OR(adj) = 14.5, 95% CI: 2.9-73.3) and girls (OR(adj) = 4.9, 95% CI: 1.3-17.4). No correlations with allergic respiratory symptoms, eczema, or rhinoconjunctivitis could be documented.


Volume repletion after exercise-induced volume depletion in humans: replacement of water and sodium losses.
Sodium and water loss during, and replacement after, exercise-induced volume depletion was investigated in six volunteers volume depleted by 1.89 +/- 0.17% (SD) of body mass by intermittent exercise in a warm, humid environment. Subjects exercised in a large, open plastic bag, allowing collection of all sweat secreted during exercise. For over 60 min beginning 40 min after the end of exercise, subjects ingested drinks containing 0, 25, 50, or 100 mmol/l sodium (trials 0, 25, 50, and 100) in a volume (ml) equivalent to 150% of the mass lost (g) by volume depletion. Body mass loss and sweat electrolyte (Na+, K+, and Cl-) loss were the same on each trial. The measured sweat sodium concentration was 49.2 +/- 18.5 mmol/l, and the total loss (63.9 +/- 38.7 mmol) was greater than that ingested on trials 0 and 25. Urine production over the 6-h recovery period was inversely related to the amount of sodium ingested. Subjects were in whole body negative sodium balance on trials 0 (-104 +/- 48 mmol) and 25 (-65 +/- 30 mmol) and essentially in balance on trial 50 (-13 +/- 29 mmol) but were in positive sodium balance on trial 100 (75 +/- 40 mmol). Only on trial 100 were subjects in positive fluid balance at the end of the study. There was a large urinary loss of potassium over the recovery period on trial 100, despite a negligible intake during volume repletion. These results confirm the importance of replacement of sodium as well as water for volume repletion after sweat loss. The sodium intake on trial 100 was appropriate for acute fluid balance restoration, but its consequences for potassium levels must be considered to be undesirable in terms of whole body electrolyte homeostasis for anything other than the short term.


TSPO ligands prevent the proliferation of vascular smooth muscle cells and attenuate neointima formation through AMPK activation.
Abnormal growth of the intimal layer of blood vessels (neointima formation) contributes to the progression of atherosclerosis and in-stent restenosis. Recent evidence shows that the 18-kDa translocator protein (TSPO), a mitochondrial membrane protein, is involved in diverse cardiovascular diseases. In this study we investigated the role of endogenous TSPO in neointima formation after angioplasty in vitro and in vivo. We established a vascular injury model in vitro by using platelet-derived growth factor-BB (PDGF-BB) to stimulate rat thoracic aortic smooth muscle cells (A10 cells). We found that treatment with PDGF-BB (1-20 ng/mL) dose-dependently increased TSPO expression in A10 cells, which was blocked in the presence of PKC inhibitor or MAPK inhibitor. Overexpression of TSPO significantly promoted the proliferation and migration in A10 cells, whereas downregulation of TSPO expression by siRNA or treatment with TSPO ligands PK11195 or Ro5-4864 (104 nM) produced the opposite effects. Furthermore, we found that PK11195 (10-104 nM) dose-dependently activated AMPK in A10 cells. PK11195-induced inhibition on the proliferation and migration of PDGF-BB-treated A10 cells were abolished by compound C (an AMPK-specific inhibitor, 103 nM). In rats with balloon-injured carotid arteries, TSPO expression was markedly upregulated in the carotid arteries. Administration of PK11195 (3 mg/kg every 3 days, ip), starting from the initial balloon injury and lasting for 2 weeks, greatly attenuated carotid neointima formation by suppressing balloon injury-induced phenotype switching of VSMCs (increased α-SMA expression). These results suggest that TSPO is a vascular injury-response molecule that promotes VSMC proliferation and migration and is responsible for the neointima formation after vascular injury, which provides a novel therapeutic target for various cardiovascular diseases including atherosclerosis and restenosis.


Parameters of the Endocannabinoid System as Novel Biomarkers in Sepsis and Septic Shock.
Sepsis represents a dysregulated immune response to infection, with a continuum of severity progressing to septic shock. This dysregulated response generally follows a pattern by which an initial hyperinflammatory phase is followed by a state of sepsis-associated immunosuppression. Major challenges in improving sepsis care include developing strategies to ensure early and accurate identification and diagnosis of the disease process, improving our ability to predict outcomes and stratify patients, and the need for novel sepsis-specific treatments such as immunomodulation. Biomarkers offer promise with all three of these challenges and are likely also to be the solution to determining a patient's immune status; something that is critical in guiding effective and safe immunomodulatory therapy. Currently available biomarkers used in sepsis lack sensitivity and specificity, among other significant shortcomings. The endocannabinoid system (ECS) is an emerging topic of research with evidence suggesting a ubiquitous presence on both central and peripheral tissues, including an intrinsic link with immune function. This review will first discuss the state of sepsis biomarkers and lack of available treatments, followed by an introduction to the ECS and a discussion of its potential to provide novel biomarkers and treatments.


Association of serum lipids and glucose with the risk of colorectal adenomatous polyp in men: a case-control study in Korea.
Previous studies on life style for colorectal cancer risk suggest that serum lipids and glucose might be related to adenomatous polyps as well as to colorectal carcinogenesis. This case-control study was conducted to investigate the associations between serum lipids, blood glucose, and other factors and the risk of colorectal adenomatous polyp. Male cases with colorectal adenomatous polyp, histologically confirmed by colonoscopy (n=134), and the same number of male controls matched by age for men were selected in hospitals in Seoul, Korea between January 1997 and October 1998. Serum lipids and glucose levels were tested after the subjects had fasted for at least 12 hr. Conditional logistic regression showed that there was a significant trend of increasing adenomatous polyp risk with the rise in serum cholesterol level (Ptrend=0.07). Increasing trend for the risk with triglyceride was also seen (Ptrend=0.01). HDL-cholesterol and LDL-cholesterol had increasing trends for the risk, which were not significant. In particular, it was noted that higher fasting blood glucose level reduced the adenomatous polyp risk for men (Ptrend=0.001). This study concluded that both serum cholesterol and triglyceride were positively related to the increased risk for colorectal adenomatous polyp in Korea. Findings on an inverse relationship between serum glucose and the risk should be pursued in further studies.


Mathematical prediction of the time evolution of the COVID-19 pandemic in Italy by a Gauss error function and Monte Carlo simulations.
In this paper are presented mathematical predictions on the evolution in time of the number of positive cases in Italy of the COVID-19 pandemic based on official data and on the use of a function of the type of a Gauss error function, with four parameters, as a cumulative distribution function. We have analyzed the available data for China and Italy. The evolution in time of the number of cumulative diagnosed positive cases of COVID-19 in China very well approximates a distribution of the type of the error function, that is, the integral of a normal, Gaussian distribution. We have then used such a function to study the potential evolution in time of the number of positive cases in Italy by performing a number of fits of the official data so far available. We then found a statistical prediction for the day in which the peak of the number of daily positive cases in Italy occurs, corresponding to the flex of the fit, that is, to the change in sign of its second derivative (i.e., the change from acceleration to deceleration), as well as of the day in which a substantial attenuation of such number of daily cases is reached. We have also analyzed the predictions of the cumulative number of fatalities in both China and Italy, obtaining consistent results. We have then performed 150 Monte Carlo simulations to have a more robust prediction of the day of the above-mentioned peak and of the day of the substantial decrease in the number of daily positive cases and fatalities. Although official data have been used, those predictions are obtained with a heuristic approach since they are based on a statistical approach and do not take into account either a number of relevant issues (such as number of daily nasopharyngeal swabs, medical, social distancing, virological and epidemiological) or models of contamination diffusion.


Reversal of topical antiglaucoma medication effects on the conjunctiva.
To determine whether the adverse effects of antiglaucoma medications could be reversed before filtration surgery, potentially reducing the risk of subsequent failure. One month before surgery, 30 patients who were receiving multiple antiglaucoma medications underwent an inferior bulbar conjunctival biopsy, ceased using sympathomimetic drops, and began treatment with topical corticosteroid, (1% fluorometholone four times daily). At the time of surgery two conjunctival biopsy specimens were obtained, one from the operation site (superior bulbar region), and one from the inferior bulbar region. The biopsy specimens were quantitatively analyzed by light microscopy. In addition, the outcome of first trabeculectomy for 16 of these patients was compared with that of 16 matched patients who had not undergone an altered preoperative regimen of topical therapy. During a 1-month period a notable decrease occurred in the number of fibroblasts and inflammatory cells throughout the conjunctiva. Inferior bulbar conjunctiva was found to be representative of superior bulbar conjunctiva with respect to these changes. Furthermore, evidence comparing the matched patients suggested that the altered preoperative regimen may have improved the success rate of trabeculectomy. The preoperative regimen used reversed the adverse conjunctival effect of topical medication. The regimen may be of clinical benefit in improving the success rate of trabeculectomy.


Interventions to support children's engagement in health-related decisions: a systematic review.
Children often need support in health decision-making. The objective of this study was to review characteristics and effectiveness of interventions that support health decision-making of children. A systematic review. Electronic databases (PubMed, the Cochrane Library, Web of Science, Scopus, ProQuest Dissertations and Theses, CINAHL, PsycINFO, MEDLINE, and EMBASE) were searched from inception until March 2012. Two independent reviewers screened eligibility: a) intervention studies; b) involved supporting children (≤18 years) considering health-related decision(s); and c) measured decision quality or decision-making process outcomes. Data extraction and quality appraisal were conducted by one author and verified by another using a standardized data extraction form. Quality appraisal was based on the Cochrane Risk of Bias tool. Of 4313 citations, 5 studies were eligible. Interventions focused on supporting decisions about risk behaviors (n = 3), psycho-educational services (n = 1), and end of life (n = 1). Two of 5 studies had statistically significant findings: i) compared to attention placebo, decision coaching alone increased values congruence between child and parent, and child satisfaction with decision-making process (lower risk of bias); ii) compared to no intervention, a workshop with weekly assignments increased overall decision-making quality (higher risk of bias). Few studies have focused on interventions to support children's participation in decisions about their health. More research is needed to determine effective methods for supporting children's health decision-making.


Premenstrual Syndrome: Symptomatic and Diagnosed Prevalence, Dualistic Treatment Approach - A Cross-Sectional Study in Ukraine.
Diagnosing and treatment of premenstrual syndrome (PMS) still pose a challenge in the routine medical practice which usually focuses on single pharmacological therapy. Recent research suggests that the combination of treatments including complementary alternative medicine (CAM) therapies may be more beneficial. The objective of this study was to assess the percentage of diagnosed and nondiagnosed PMS/premenstrual dysphoric disorder (PMDD) based on the presence of adequate symptoms and to compare population using hormonal or pharmaceutical agents versus CAM therapies. This is a cross-sectional study targeting sample population of 160 females of potentially reproductive age done in Ukraine between May 2014 and April 2015. According to declared symptoms, 29% females versus 26% previously diagnosed by a medical professional qualify for "moderate/severe PMS," P > 0.05. In 30% persons using pharmacological agents, major side effects, namely, nausea, insomnia, headache was caused by painkillers, contraceptives, and antidepressants. Only 37.5% of study population has been using CAM therapy methods to deal with the symptoms of PMS. Of these, 22% have achieved moderate degree in relief of the symptoms long term. We have concluded that when dealing with the burden of PMS/PMDD, the affected treatment-seeking women should have choice and access to the variety of therapies within integrative medicine (both conventional and nonconventional).


A suicide awareness and intervention program for health professional students.
Many emergency service professionals and health professionals play important roles in the assessment and management of suicide risk but often receive inadequate mental health training in this area. A 'Suicide Awareness and Intervention Program' (SAIP) was developed for first year medical, paramedical and pharmacy students at the University of Tasmania, Australia. The program aimed to increase students' knowledge and awareness about suicide-related issues, develop interpersonal skills around suicide screening and increase awareness of available support services. A 5-hour experiential SAIP was embedded within the curriculum. A pre and post evaluation of knowledge, skills and attitudes was conducted, with an open-ended follow-up survey regarding use of what was learned in the program. Pre and post SAIP surveys showed significant improvement inknowledge and practical skills. Feedback from students and the counselling service indicated enduring impact of the program. Participation in the SAIP increased knowledge, skills and attitudes related to the assessment and management of individuals at risk for suicide, and the application of this ability to students' personal and professional lives.


cAMP response element-mediated gene transcription is upregulated by chronic antidepressant treatment.
Regulation of gene transcription via the cAMP-mediated second messenger pathway has been implicated in the actions of antidepressant drugs, but studies to date have not demonstrated such an effect in vivo. To directly study the regulation of cAMP response element (CRE)-mediated gene transcription by antidepressants, transgenic mice with a CRE-LacZ reporter gene construct were administered one of three different classes of antidepressants: a norepinephrine selective reuptake inhibitor (desipramine), a serotonin selective reuptake inhibitor (fluoxetine), or a monoamine oxidase inhibitor (tranylcypromine). Chronic, but not acute, administration of these antidepressants significantly increased CRE-mediated gene transcription, as well as the phosphorylation of CRE binding protein (CREB), in several limbic brain regions thought to mediate the action of antidepressants, including the cerebral cortex, hippocampus, amygdala, and hypothalamus. These results demonstrate that chronic antidepressant treatment induces CRE-mediated gene expression in a neuroanatomically differentiated pattern and further elucidate the molecular mechanisms underlying the actions of these widely used therapeutic agents.


Watershed sediment cannot offset sea level rise in most US tidal wetlands.
Watershed sediment can increase elevation of tidal wetlands struggling against rising seas, but where and how much watershed sediment helps is unknown. By combining contiguous US datasets on sediment loads and tidal wetland areas for 4972 rivers and their estuaries, we calculated that river sediment accretion will be insufficient to match sea level rise in 72% of cases because most watersheds are too small (median 21 square kilometers) to generate adequate sediment. Nearly half the tidal wetlands would require 10 times more river sediment to match sea level, a magnitude not generally achievable by dam removal in some regions. The realization that watershed sediment has little effect on most tidal wetland elevations shifts research priorities toward biological processes and coastal sediment dynamics that most influence elevation change.


Protocols.io: Virtual Communities for Protocol Development and Discussion.
The detailed know-how to implement research protocols frequently remains restricted to the research group that developed the method or technology. This knowledge often exists at a level that is too detailed for inclusion in the methods section of scientific articles. Consequently, methods are not easily reproduced, leading to a loss of time and effort by other researchers. The challenge is to develop a method-centered collaborative platform to connect with fellow researchers and discover state-of-the-art knowledge. Protocols.io is an open-access platform for detailing, sharing, and discussing molecular and computational protocols that can be useful before, during, and after publication of research results.


Misdiagnosed microcystic adnexal carcinoma on the lateral forehead and challenges in reconstruction of a large and bone-deep defect.
Microcystic adnexal carcinoma (MAC) is a rare cutaneous malignancy characterized by aggressive local infiltration, including a high propensity for perineural invasion. Histologically it can be easily confused with benign adnexal tumors, which often leads to inappropriate initial treatment. As a consequence delayed surgical excision often requires removal of large cutaneous masses which can be followed by challenges in reconstruction. We report the case of a challenging reconstruction of a large forehead defect by a modified AT flap with central Burow's triangle grafting and previous wound conditioning using hyaluronic acid after complete micrographic removal of MAC. A 80-year-old healthy female presented with an almost six year history of an asymptomatic slowly progressing skin mass previously biopsied and diagnosed as benign syringoma five years in advance. Deep biopsies confirmed MAC. She underwent staged surgical excision with Tübingen torte technique with removal of the frontal periostium. A skin substitute of esterified hyaluronic acid was applied for three weeks to the bone-deep 6 × 7 cm defect leading to good granulation tissue above the bone. Final reconstruction was achieved by an AT flap combined with full thickness skin transplantation of the central dog ear. The cosmetic outcome was satisfactory, no recurrence was observed within 18 months follow-up. We confirm the histological difficulties in the diagnosis of this tumor entity and the large extension of MAC due to delay in diagnosis and treatment. Deep tumor removal including the periostium might be necessary to achieve tumor free margins. Fast granulation tissue above the frontal bone might be achieved by applying hyaluronic acid products. The combination an AT flap with transplantation of the adjacent Burow's triangles gives optimal skin texture and color matching and seems to be a good option to close even large defects of the front especially for supra brow defects.


Anti-tumor Effect of Quercetin Loaded Chitosan Nanoparticles on Induced Colon Cancer in Wistar Rats.
Purpose: This study was aimed to evaluate the site-specific drug delivery of 5-FU with chitosan (CS) as a carrier and quercetin (Qu) against induced colon cancer in Wistar rats. Methods: Cross-linked CS-Qu nanoparticles (NPs) were prepared by ionotropic gelation method. Physicochemical characterization of NPs was performed by Fourier-transform infrared (FTIR) spectroscopy, dynamic light scattering (DLS), in vitro drug release, and drug loading efficiency (LE). 1, 2-Dimethylhydrazine (DMH) and dextran sulfate sodium (DSS) were applied to induce adenocarcinoma tumors on inbred male Wistar rats' colon. The treatment group of rats was administered through enema with NPs dispersion. Hematoxylin and eosin staining were performed to the histopathological examination of tumors. Results: Zeta potential and particle size for NPs were +53.5 ± 5 mV and 179 ± 28 nm, respectively. About 96% Qu LE was obtained with a maximum release of 5.63 ±1.59% and 4.62 ± 1.33% after 24 hours in PB solution with pH values of 6 and 7.4, respectively. The numbers of 8 to 21 tumors were observed in all rats administered with DMH and DSS. Significantly decreasing of microvascular density and mitosis count was detected in the treatment group in comparison with cancerous group (P = 0.032 for the former compared to P = 0.016 for the later), respectively. Furthermore, the treatment group showed a high apoptosis rate (P = 0.038). Conclusion: The developed Qu-loaded CS NPs were good candidates for site-specific and sustained drug release in enema treatment. Decreasing of microvascular density and mitosis count, along with increasing the apoptosis percent in the treatment group proved that the NPs could have promising results in site-specific and sustained drug delivery against colorectal cancer.


The evolution of early hominin food production and sharing.
How did humans evolve from individualistic to collective foraging with sex differences in production and widespread sharing of plant and animal foods? While current evolutionary scenarios focus on meat, cooking, or grandparental subsidies, considerations of the economics of foraging for extracted plant foods (e.g., roots, tubers), inferred to be important for early hominins (∼6 to 2.5 mya), suggest that early hominins shared such foods with offspring and others. Here, we present a conceptual and mathematical model of early hominin food production and sharing, prior to the emergence of frequent hunting, cooking, and increased lifespan. We hypothesize that extracted plant foods were vulnerable to theft, and that male mate guarding protected females from food theft. We identify conditions favoring extractive foraging and food sharing across mating systems (i.e., monogamy, polygyny, promiscuity), and we assess which system maximizes female fitness with changes in the profitability of extractive foraging. Females extract foods and share them with males only when: i) extracting rather than collecting plant foods pays off energetically; and ii) males guard females. Males extract foods when they are sufficiently high in value, but share with females only under promiscuous mating and/or no mate guarding. These results suggest that if early hominins had mating systems with pair-bonds (monogamous or polygynous), then food sharing by adult females with unrelated adult males occurred before hunting, cooking, and extensive grandparenting. Such cooperation may have enabled early hominins to expand into more open, seasonal habitats, and provided a foundation for the subsequent evolution of human life histories.


Effects of nutrients on exopolysaccharide production and surface properties of Aeromonas salmonicida.
Extracellular polysaccharide (EPS) and capsular polysaccharide (CPS) production by Aeromonas salmonicida A450 and the influence of the capsule on cell surface properties were studied. A. salmonicida did not produce CPS or EPS when glucose, phosphate, magnesium chloride, or trace mineral components were absent from the medium. The addition of yeast extract improved capsule production. Neither EPS nor CPS formation depended on the C/N ratio, although it appeared to be influenced by the level of carbon and nitrogen in the culture. Both EPS and CPS production started at the end of the logarithmic growth phase. The amounts of EPS and CPS produced were not influenced by temperature changes between 15 and 20 degrees C and was maximal from pH 7 to 7.5. Cell surface properties were strongly influenced by capsule production; high CPS production was associated with enhanced cell hydrophilicity and autoagglutination. The effect of CPS on cell surface properties was independent of the presence of the surface protein array (A-layer).


Live imaging of root-bacteria interactions in a microfluidics setup.
Plant roots play a dominant role in shaping the rhizosphere, the environment in which interaction with diverse microorganisms occurs. Tracking the dynamics of root-microbe interactions at high spatial resolution is currently limited because of methodological intricacy. Here, we describe a microfluidics-based approach enabling direct imaging of root-bacteria interactions in real time. The microfluidic device, which we termed tracking root interactions system (TRIS), consists of nine independent chambers that can be monitored in parallel. The principal assay reported here monitors behavior of fluorescently labeled Bacillus subtilis as it colonizes the root of Arabidopsis thaliana within the TRIS device. Our results show a distinct chemotactic behavior of B. subtilis toward a particular root segment, which we identify as the root elongation zone, followed by rapid colonization of that same segment over the first 6 h of root-bacteria interaction. Using dual inoculation experiments, we further show active exclusion of Escherichia coli cells from the root surface after B. subtilis colonization, suggesting a possible protection mechanism against root pathogens. Furthermore, we assembled a double-channel TRIS device that allows simultaneous tracking of two root systems in one chamber and performed real-time monitoring of bacterial preference between WT and mutant root genotypes. Thus, the TRIS microfluidics device provides unique insights into the microscale microbial ecology of the complex root microenvironment and is, therefore, likely to enhance the current rate of discoveries in this momentous field of research.


[Sensitivity of the early mouse embryos to antifolic preparation chloridine].
A study was made of antifolic preparation chloridine (2,4-diamino-5-p-chlorphenyl-6-ethylpyrimidine) on the cleavage of CBA mouse embryos. Chloridine failed to influence the development of early mouse embryos in the maternal organism and considerably inhibited the cleavage of embryos explanted into the chloridine-containing medium. Chloridine sensitivity in the mouse and rat embryos was compared and a conclusion was drawn on the absence of interspecies differences in their reaction to teratogen at the level of the embryonic cells.


Myosin gene expression in the respiratory muscles.
Myosin is one of the basic structural components of skeletal muscles. Its interaction with actin results in muscle contraction. The myosin molecule is composed of two heavy (MyHC) and two light chains (MyLC) that, together with the adenosine triphosphatase (ATPase) activity, determine the functional characteristics of the fibre. Both MyHC and MyLC present different isoforms. The main MyHC isoforms in adult mammals are the slow MyHC (MyHC-I) and fast MyHCs (MyHC-IIa, MyHC-IIb and MyHC-IIx). Muscle fibres can express only one isoform or coexpress different forms. The muscle phenotype is the product of genome plus environmental stimuli. The family of genes that codifies the MyHC isoforms is located in two different clusters, each isoform being encoded by a separate gene. The gene corresponding to slow MyHC is located in chromosome 14, both in humans and in mice. The other genes are positioned in chromosome 17 in humans, and in chromosome 11 in mice. The transcriptional and translational mechanisms that control the expression of MyHC isoforms are not well known, although it is believed that the main regulation is dependent on mechanical signals. These signals are probably mediated by a biochemical messenger. As a general rule, fast MyHC genes seem to be expressed "by default", whereas the slow MyHC gene would be expressed as a response to changes in load. So far, few studies have analysed the in vivo regulation of MyHC gene expression in respiratory muscles. It has recently been reported that breathing against moderate levels of inspiratory resistance quickly induces an increase in the genetic expression of slow MyHC in the diaphragm. This suggests the possibility of eliciting a phenotypic adaptation of respiratory muscles using specific training protocols.


Do arsenic levels in rice pose a health risk to the UK population?
Consumption of rice and rice products can be a significant exposure pathway to inorganic arsenic (iAs), which is a group 1 carcinogen to humans. The UK follows the current European Commission regulations so that iAs concentrations must be < 0.20 mg kg-1 in white (polished) rice and <0.25 mg kg-1 in brown (unpolished) rice. However, iAs concentration in rice used for infant food production or direct consumption has been set at a maximum of 0.1 mg kg-1. In this context, this study aimed to evaluate iAs concentrations in different types of rice sold in the UK and to quantify the health risks to the UK population. Here, we evaluated 55 different types of rice purchased from a range of retail outlets. First, we analysed all rice types for total As (tAs) concentration from which 42 rice samples with tAs > 0.1 mg kg-1 were selected for As speciation using HPLC-ICP-MS. Based on the average concentration of iAs of our samples, we calculated values for the Lifetime Cancer Risk (LCR), Target Hazard Quotient (THQ) and Margin of Exposure (MoE). We found a statistically significant difference between organically and non-organically grown rice. We also found that brown rice contained a significantly higher concentration of iAs compared to white or wild rice. Notably, 28 rice samples exceeded the iAs maximum limit stipulated by the EU (0.1 mg kg-1) with an average iAs concentration of 0.13 mg kg-1; therefore consumption of these rice types could be riskier for infants than adults. Based on the MoE, it was found that infants up to 1 year must be restricted to a maximum of 20 g per day for the 28 rice types to avoid carcinogenic risks. We believe that consumers could be better informed whether the marketed product is fit for infants and young children, via appropriate product labelling containing information about iAs concentration.


Divergent ecological histories of two sister Antarctic krill species led to contrasted patterns of genetic diversity in their heat-shock protein (hsp70) arsenal.
The Arctic and the Antarctic Peninsula are currently experiencing some of the most rapid rates of ocean warming on the planet. This raises the question of how the initial adaptation to extreme cold temperatures was put in place and whether or not directional selection has led to the loss of genetic variation at key adaptive systems, and thus polar species' (re)adaptability to higher temperatures. In the Southern Ocean, krill represents the most abundant fauna and is a critical member at the base of the Antarctic food web. To better understand the role of selection in shaping current patterns of polymorphisms, we examined genetic diversity of the cox-1 and hsp70 genes by comparing two closely related species of Euphausiid that differ in ecology. Results on mtcox-1 agreed with previous studies, indicating high and similar effective population sizes. However, a coalescent-based approach on hsp70 genes highlighted the role of positive selection and past demographic changes in their recent evolution. Firstly, some form of balancing selection was acting on the inducible isoform C, which reflected the maintenance of an ancestral adaptive polymorphism in both species. Secondly, E. crystallorophias seems to have lost most of its hsp70 diversity because of a population crash and/or directional selection to cold. Nonsynonymous diversities were always greater in E. superba, suggesting that it might have evolved under more heterogeneous conditions. This can be linked to species' ecology with E. superba living in more variable pelagic conditions, while E. crystallorophias is strictly associated with continental shelves and sea ice.


Smoking behavior: a cross-sectional study to assess the dimensionality of the brief Wisconsin inventory of smoking dependence motives and identify different typologies among young daily smokers.
The present study aims to investigate the dimensionality of the brief version of the Wisconsin Inventory of Smoking Dependence Motives (B-WISDM) and identify different smoking motivational profiles among young daily smokers (N = 375). We tested 3 measurement models of the B-WISDM using confirmatory factor analysis, whereas cluster analysis was used to identify the smokers' motivational profiles. Furthermore, we compared clusters toward dependence level and the number of cigarettes smoked per day using analysis of variance tests. The results confirmed that the B-WISDM measures 11 first-order intercorrelated factors. The second-order model, originally proposed for the longer version of the questionnaire, showed adequate fit indices but fitted the data significantly worse than the first-order model. Five motivational clusters were identified and differed in terms of tobacco addiction and the number of cigarettes smoked per day. Although each cluster had specific features, 2 main smoker groups were distinguished: Group A (composed of 3 clusters), which was mainly characterized by high levels of secondary dependence motives, and Group B (composed of 2 clusters), in which the primary and secondary dependence motives reached similar levels. In general, the clusters of Group B were more addicted to cigarettes than Group A clusters. Using the B-WISDM to identify different smoking motivational profiles has important practical implications because they might help characterize addiction, which represents the first step to help an individual quit smoking.


Prediction of cardiovascular events from systolic or diastolic blood pressure.
Over time, a focus on blood pressure has transferred from diastolic pressure to systolic pressure. Formal analyses of differences in predictive value are scarce. Our goal of the study was whether office SBP adds prognostic information to office DBP and whether both 24-h ambulatory SBP and 24-h ambulatory DBP is specifically important. The authors examined 2097 participants from a population cohort recruited in Copenhagen, Denmark. Cause-specific Cox regression was performed to predict 10-year person-specific absolute risks of fatal and non-fatal cardiovascular (CV) events. Also, the time-dependent area under the receiver operator curve (AUC) was utilized to evaluate discriminative ability. The calibration plots of the models (Hosmer-May test) were calculated as well as the Brier score which combines (discrimination and calibration). Adding both 24-h ambulatory SBP and 24-h ambulatory diastolic blood pressure did not significantly increase AUC for CV mortality and CV events. Moreover, adding both office SBP and office DBP did not significantly improve AUC for both CV mortality and CV events. The difference in AUC (95% confidence interval; p-value) was .26% (-.2% to .73%; .27) for 10-year CV mortality and .69% (-.09% to 1.46%; .082) for 10-year risk of CV events. The difference in AUC was .12% (-.2% to .44%; .46) for 10-year CV mortality and .04% (-.35 to .42%; .85) for 10-year risk of CV events. Moreover, for both CV mortality and CV events, office SBP did not improve prognostic information to office DBP. In addition, the Brier scores of office BP in both CV mortality and CV events were .078 and .077, respectively. Furthermore, the Brier scores were .077 and .078 in CV mortality and CV events of 24-h ambulatory. For the average population as those participating in a population survey, the 10-year discriminative ability for long-term predictions of CV death and CV events is not improved by adding systolic to diastolic blood pressure. This finding is found for ambulatory as well as office blood pressure.


Myofascial pain associated to trigger points: a literature review. Part 2: differential diagnosis and treatment.
During the last decades the advance in knowledge of myofascial pain has been constant in the medical and dental community. However, although several aspects have been clarified in relation to its epidemiology, clinical characteristics and etiopathogenesis, many uncertainties remain. Many clinical conditions are included in the differential diagnosis of myofascial pain associated to trigger points. A good anamnesis and clinical exploration is thus required in order to ensure correct diagnosis and treatment. Among the numerous treatments used in application to trigger points, the spray-and-stretch technique and direct injection targeted to such trigger points have been found to be the most effective options. In chronic cases, psychosocial intervention is required, due to the high incidence of mood disorders and/or anxiety observed in these patients, who in turn present a poorer prognosis. This underscores the importance of early diagnosis and treatment.


Doxorubicin and lapatinib combination nanomedicine for treating resistant breast cancer.
Our objective was to design a polymeric micelle-based doxorubicin and lapatinib combination therapy for treating multidrug resistant (MDR) breast cancers. Poly(ethylene glycol)-block-poly(2-methyl-2-benzoxycarbonylpropylene carbonate) (PEG-PBC) polymers were synthesized for preparing doxorubicin and lapatinib loaded micelles using a film dispersion method. Micelles were characterized by determining critical micelle concentration (CMC), particle size distribution, and drug loading. The anticancer effects were determined in vitro with MTT assays as well as with lactate dehydrogenase (LDH) release studies. In addition, the cellular uptake of drug-loaded micelles was determined with fluorescence microscopy and flow cytometry. Finally, in vivo anticancer activity and tolerance of developed formulations were evaluated in resistant breast tumor bearing mice. PEG5K-PBC7K polymer synthesized in this study had a low CMC value (1.5 mg/L) indicating an excellent dynamic stability. PEG-PBC micelles could efficiently load both doxorubicin and lapatinib drugs with a loading density of 21% and 8.4%, respectively. The mean particle size of these micelles was 100 nm and was not affected by drug loading. The use of lapatinib as an adjuvant sensitized drug resistant MCF-7/ADR cells to doxorubicin treatment. Cellular uptake studies showed enhanced doxorubicin accumulation in MCF-7/ADR cells in the presence of lapatinib. The doxorubicin and lapatinib combination therapy showed a significant decrease in tumor growth compared to doxorubicin monotherapy. In conclusion, we have developed PEG-PBC micelle formulations for the delivery of doxorubicin and lapatinib. The combination therapy of doxorubicin plus lapatinib has a great potential for treating MDR breast cancer.


Metabolomic-based study of the leafy gall, the ecological niche of the phytopathogen Rhodococcus fascians, as a potential source of bioactive compounds.
Leafy gall is a plant hyperplasia induced upon Rhodococcus fascians infection. Previously, by genomic and transcriptomic analysis, it has been reported that, at the early stage of symptom development, both primary and secondary metabolisms are modified. The present study is based on the hypothesis that fully developed leafy gall, could represent a potential source of new bioactive compounds. Therefore, non-targeted metabolomic analysis of aqueous and chloroform extracts of leafy gall and non-infected tobacco was carried out by 1H-NMR coupled to principal component analysis (PCA) and orthogonal projections to latent structures-discriminant analysis (OPLS-DA). Polar metabolite profiling reflects modifications mainly in the primary metabolites and in some polyphenolics. In contrast, main modifications occurring in non-polar metabolites concern secondary metabolites, and gas chromatography and mass spectrometry (GC-MS) evidenced alterations in diterpenoids family. Analysis of crude extracts of leafy galls and non-infected tobacco leaves exhibited a distinct antiproliferative activity against all four tested human cancer cell lines. A bio-guided fractionation of chloroformic crude extract yield to semi-purified fractions, which inhibited proliferation of glioblastoma U373 cells with IC50 between 14.0 and 2.4 µg/mL. Discussion is focused on the consequence of these metabolic changes, with respect to plant defense mechanisms following infection. Considering the promising role of diterpenoid family as bioactive compounds, leafy gall may rather be a propitious source for drug discovery.


Comparison of the effects of drugs on hyperexcitability induced in hippocampal slices by withdrawal from chronic ethanol consumption.
1 The effects of drugs, previously demonstrated to have a range of effects on the behavioural signs of ethanol withdrawal hyperexcitability, were examined in area CA1 in isolated hippocampal slices prepared after withdrawal from chronic ethanol in vivo. 2 The decreases seen after the ethanol treatment in the thresholds for production of single and multiple population spikes were prevented when the dihydropyridine calcium channel antagonist, isradipine, was included in the perfusion medium at 4 microM. 3 Another dihydropyridine, felodipine, which had no activity against withdrawal signs in vivo, did not affect the changes in field potentials, at concentrations up to 10 microM. 4 Diltiazem, which increased withdrawal hyperexcitability in vivo, had no effect on the withdrawal changes in field potentials at 30 microM; higher concentrations affected the control slices. 5 The novel anticonvulsant, gabapentin, at 1 microM but not at 100 nM, significantly decreased the signs of withdrawal hyperexcitability in the hippocampal slices. When the CCKB antagonist, CI988, was added to the bathing medium, at 1 microM, there were small, but significant decreases in the withdrawal hyperexcitability. 6 The results showed that the actions of these drugs on the changes in the field potentials in isolated hippocampal slices were very similar to their previously demonstrated effects on the convulsive signs of ethanol withdrawal in vivo, but differences were seen in the corresponding comparison with anxiolytic actions in vivo.


Effectiveness of Percutaneous Nephrolithotomy, Retrograde Intrarenal Surgery, and Extracorporeal Shock Wave Lithotripsy for Treatment of Renal Stones: A Systematic Review and Meta-Analysis.
Background and objectives: To perform a updated systematic review and meta-analysis comparing effectiveness of percutaneous nephrolithotomy (PCNL), retrograde intrarenal surgery (RIRS), and extracorporeal shock wave lithotripsy (ESWL) for treatment of renal stones (RS). Materials and Methods: A total of 37 studies were included in this systematic review and meta-analysis about effectiveness to treat RS. Endpoints were stone-free rates (SFR), incidence of auxiliary procedure, retreatment, and complications. We also conducted a sub-analysis of ≥2 cm stones. Results: First, PCNL had the highest SFR than others regardless of stone sizes and RIRS showed a higher SFR than ESWL in <2 cm stones. Second, auxiliary procedures were higher in ESWL than others, and it did not differ between PCNL and RIRS. Finally, in <2 cm stones, the retreatment rate of ESWL was higher than others. RIRS required significantly more retreatment procedures than PCNL in ≥2 cm stones. Complication was higher in PCNL than others, but there was no statistically significant difference in complications between RIRS and PCNL in ≥2 cm stones. For ≥2 cm stones, PCNL had the highest SFR, and auxiliary procedures and retreatment rates were significantly lower than others. Conclusions: We suggest that PCNL is a safe and effective treatment, especially for large RS.


Comparison of German Translations of the System Usability Scale - Which to Take?
The System Usability Scale (SUS) is a reliable tool for usability measurement and evaluation. Since its original language is English, a translation is required before a target group can answer it in their native language. The challenge of translating questionnaires lies in the preservation of its original properties. Different versions of a German SUS have been proposed and are currently in use. Objective of this work is to find and compare available German translations. Four versions were found and compared in terms of the translation process and the exact wording of the translation. Only the version of Gao et al. has been systematically validated, but has an unnatural wording. Although not validated yet, the proposed version of Rummel et al. is a good compromise between wording and methodically clean development. The version of Lohmann and Schäffer is the close runner up, as it may improve the wording at the expense of methodological accuracy. Since the version of Rauer gives no information about its translation process, it is considered least preferred of the four compared translations.


Isolation and characterization of a precursor form of lysosomal alpha-glucosidase from human urine.
A two-step procedure is described for the isolation of lysosomal alpha-glucosidase from human urine. In the second step, affinity chromatography on Sephadex G-100, two fractions with acid alpha-glucosidase activity were obtained. Fraction I contained alpha-glucosidase of Mr 109000, whereas fraction II contained components of Mr 76000 and 70000. alpha-Glucosidase in fraction I had an Mr similar to that of the precursor of alpha-glucosidase detected in the medium of fibroblasts after labelling with [14C]leucine. The components in fraction II had Mr identical to those of the mature forms of alpha-glucosidase found in placenta or cultured human skin fibroblasts. alpha-Glucosidase in fraction I contained mannose 6-phosphate (3.5 mol/mol polypeptide). No mannose 6-phosphate was present in the components in fraction II. Fraction I, but not fraction II, was avidly endocytosed by alpha-glucosidase-deficient cultured human skin fibroblasts. Endocytosis of fraction I was inhibited by mannose 6-phosphate. The pH optimum and Km values for p-nitrophenyl alpha-glucoside, maltose and glycogen of fractions I and II alpha-glucosidase were almost identical. However, the activity with glycogen relative to that of either p-nitrophenyl alpha-glucoside or maltose was lower in fraction I than in fraction II. It is concluded that fraction I consists of the precursor form of alpha-glucosidase and fraction II of the mature forms of the enzyme. The importance of urine as a source of precursors of lysosomal enzymes is discussed.


The Relationship Between Level of Catastrophizing and Mental Health Comorbidity in Individuals With Whiplash Injuries.
Pain catastrophizing has been shown to be correlated with measures of mental health problems such as depression and post-traumatic stress disorder (PTSD). However, the clinical implications of findings reported to date remain unclear. To date, no study has been conducted to determine meaningful cut-scores on measures of catastrophizing indicative of the heightened risk of mental health comorbidity. One objective of the present study was to identify the cut-score on the Pain Catastrophizing Scale (PCS) indicative of the heightened risk of the comorbidity of depression and PTSD. A second objective was to determine whether mental health comorbidity mediated the relationship between catastrophizing and occupational disability. The sample consisted of 143 individuals with whiplash injuries. Pain severity, pain catastrophizing, depression, and post-traumatic stress symptoms were assessed after admission to a rehabilitation program. Mental health comorbidity was operationally defined as obtaining a score above the clinical threshold on measures of depressive and/or post-traumatic stress symptom severity. A receiver operating characteristic curve analysis revealed that a PCS score of 22 best distinguished between participants with and without mental health comorbidity. Results also revealed that mental health comorbidity mediated the relationship between catastrophizing and occupational disability. The findings suggest that a score of ≥22 on the PCS should alert clinicians to the possibility that patients might also be experiencing clinically significant symptoms of depression or PTSD. Greater attention to the detection and treatment of mental health conditions associated with whiplash injury might contribute to more positive recovery outcomes.


Can dietary integrators provide a clinical benefit in the treatment of functional dyspepsia? results from a prospective study with TUBES Gastro.
Given the limited efficacy of conventional medical therapy for functional dyspepsia, patients frequently seek alternative medical approaches. The use of suc h alternative therapies has dramatically increased during the last decades. The scope of this prospective study was to provide evidence of the clinical benefit of the treatment of functional dyspepsia with a dietary integrator composed by sodium alginate, sodium bicarbonate, bromelin and essential oils. This study enrolled a total of 100 patients affected by functional dyspepsia diagnosed primarily on the basis of typical symptoms and the exclusion of non-functional gastrointestinal diseases (negative upper gastrointestinaltract endoscopy and negative for H. pylori infections, including acid-related diseases), non-gastrointestinal diseases, and psychiatric illness. All patients enrolled were categorized in two symptom-predominant subgroups: dysmotility-like dyspepsia (N.=60) and reflux-like dyspepsia (N.=40). Patients were treated with TUBES Gastro (0.80 g oral tablets bid after main meals) for 4 weeks, on top of their current treatment with proton pump inhibitors or not. Efficacy was measured by a Numerical Rating Scale (NRS) at baseline and after 14 and 28 days of treatment with TUBES Gastro while safety and tolerability were evaluated based on the adverse event reporting from the patients. Sixty patients were diagnosed with dysmotility-like dyspepsia and were enrolled into the study; the majority was females (68%) with a mean age of 48.5 years (19-81). The mean baseline NRS score was 5.7 (4-8). A high statistically significant reduction of the NRS score was observed at 14 and 28 days: -1.5 (-26.3%) and -3.4 (-59.6%), respectively (P<0.0001). Forty patients were diagnosed with reflux-like dyspepsia and were enrolled into the study; the majority was males (70%) with a mean age of 49.1 years (24-80). The mean baseline NRS score was 6.8 (5-9). A high statistically significant reduction of the NRS score was observed at 14 and 28 days: -2.8 (-41.2%) and -4.8 (70.6%), respectively (P<0.0001). No side effects were collected during the study duration. The data obtained from this four-week study indicate that TUBES Gastro treatment was effective and well tolerated in reducing the symptomatology of patients affected by functional dysmotility-like and reflux-like dyspepsia.


Clinical evaluation of naltrexone treatment of opiate-dependent individuals. Report of the National Research Council Committee on Clinical Evaluation of Narcotic Antagonists.
A multiclinic controlled trial of naltrexone in opiate-dependent persons led to these conclusions: (1) a narcotic antagonist is an acceptable treatment for a small number of patients undergoing treatment for opiate dependence; (2) the group most likely to be candidates for such treatment are those who are relatively opiate-free ("post-addicts") and well motivated to seek treatment; (3) although differences between patients treated with placebo and naltrexone were slight, both retention in treatment and opiate-free urine tests favored the naltrexone group; (4) adverse effects of relatively short-term treatment were slight, largely being symptoms and signs of precipitated abstinence in patients with residual dependence.


A case against the specificity of "cardiac" troponin-T.
A case of a spurious rise in cardiac troponin-T in an 85 year old Caucasian man with myelodysplastic syndrome and multiple malignancies but with intact cardiac and renal function is reported. The patient presented to the accident and emergency department with fever and chest pain. Inconsistent laboratory findings in biochemical markers diagnostic of myocardial infarction were observed. Discrepant findings included a rise in the concentration of the cardiac specific marker troponin-T in the absence of an increase in creatine kinase (CK) isoenzyme MB activity. Somewhat surprisingly, there was a significant and consistent increase in CK isoenzyme BB activity. Awareness of the increase in troponin-T concentrations in patients with multiple clinical non-cardiac problems may prevent an erroneous diagnosis of myocardial infarction and avert institution of unduly aggressive treatment.


Fetal MRI, lower acceptance by women in research vs. clinical setting.
To determine acceptance of pregnant women to undergo fetal magnetic resonance imaging (MRI) examination in research and clinical setting. A prospective study included a research group [part of a study comparing brain ultrasound (US) to MRI in fetuses at risk for acquired brain damage] and a clinical group [fetuses with suspected (brain) anomalies after structural US examination] from 2011 to 2014. All women were advised to use sedatives. MRI declinations, use of sedation, MRI duration and imaging quality were compared between both groups. Study participation was accepted in 57/104 (55%) research cases. Fetal MRI was performed in 34/104 (33%) research and 43/44 (98%) clinical cases. Reasons to decline study participation were MRI related in 41%, and participation was too burdensome in 46%. Acceptance was highest for indication infection and lowest in alloimmune thrombocytopenia and monochorionic twin pregnancy. Sedatives were used in 14/34 research and 43/43 clinical cases. Scan duration and quality were comparable (21 and 20 min in research and clinical cases, respectively, moderate/good quality in both groups). Pregnant women consider MRI more burdensome than professionals realize. Two-third of women at risk for fetal brain damage decline MRI examination. Future studies should evaluate which information about fetal MRI is supportive.


Impact of lockdown due to the COVID-19 pandemic on mental health among the Libyan population.
The coronavirus disease 2019 (COVID-19) pandemic may have a potentially serious effect on mental health and increase the risk of anxiety, depression, and post-traumatic stress disorders in people. In this study, we aimed to determine the prevalence of psychological illness and the impact of the COVID-19 pandemic on the Libyan population's mental health. A cross-sectional survey, conducted in both online and paper modes and consisting of five sections, was completed in more than 30 cities and towns across Libya. The first section consisted of questions on basic demographic characteristics. The second section contained a survey related to the lockdown status, activities, related stress levels, and quarantine. The third section comprised the self-administered 9-item Patient Health Questionnaire (PHQ-9). The fourth section contained the 7-item Generalized Anxiety Disorder Scale (GAD-7), and the fifth section contained the Impact of Event Scale-Revised (IES-R). Of the 31,557 respondents, 4,280 (13.6%) reported severe depressive symptoms, with a mean [standard deviation (SD)] PHQ-9 score of 8.32 (5.44); 1,767 (5.6%) reported severe anxiety symptoms, with a mean (SD) GAD-7 score of 6 (4.6); and 6,245 (19.8%) of the respondents reported post-traumatic stress disorder (PTSD), with a mean (SD) score of 15.3 (18.85). In multivariate analysis, young age, being female, unmarried, educated, or victims of domestic violence or abuse, work suspension during the pandemic, and having increased workload, financial issues, suicidal thoughts, or a family member with or hospitalized due to COVID-19 were significantly associated with a high likelihood of depressive and anxiety symptoms, as well as PTSD. Internal displacement due to civil war was also associated with PTSD. To our knowledge, this is the first study to analyze the psychological impacts of the COVID-19 pandemic and civil war in Libya. Further study on the development of strategies and interventions aimed at reducing the mental disease burden on the Libyan population is warranted.


Reducing Streptococcal Testing in Patients <3 Years Old in an Emergency Department.
Although pharyngitis is common, group A Streptococcus is an uncommon etiology, and sequelae are rare in patients <3 years old. Inappropriate testing leads to increased cost of health care and unnecessary exposure to antibiotics. Rapid streptococcal tests (RSTs) for group A Streptococcus pharyngitis are not routinely indicated in this age group. At our urban, tertiary pediatric emergency department (ED), on average, 20 RSTs were performed each month for patients <3 years of age. Our objective was to reduce RSTs in the ED in patients aged <3 years by 50% in 18 months. We initiated this project in October 2016 at an urban, tertiary pediatric ED. We surveyed pertinent multidisciplinary stakeholders to identify factors leading to RSTs in children <3 years of age. We conducted multiple interventions and collected weekly data on the number of RSTs in children aged <3 years (outcome measure) and the number of family complaints and return visits for complications of pharyngitis (balancing measure). We used statistical process control for analysis. The mean number of RSTs ordered per month in patients aged <3 years declined by 52% in 10 months. The majority of tests during the study phase were ordered by nurse practitioners (62%) for patients aged 25 to 36 months (66%). There has been 1 family grievance and no patient complications attributable to the project. Our interventions led to a successful and sustained reduction of RSTs in patients aged <3 years. A local clinical practice guideline was developed, and the project was expanded to other acute care settings.


Cyclase-associated protein is a pro-formin anti-capping processive depolymerase of actin barbed and pointed ends.
Cellular actin networks display distinct assembly and disassembly dynamics resulting from multicomponent reactions occurring primarily at the two ends and the sides of actin filaments [1-3]. While barbed ends are considered the hotspot of actin assembly [4], disassembly is thought to primarily occur via reactions on filament sides and pointed ends [3, 5-11]. Cyclase-associated protein (CAP) has emerged as the main protagonist of actin disassembly and remodeling - it collaborates with cofilin to increase pointed-end depolymerization by 300-fold [6, 7], promotes filament "coalescence" in presence of Abp1 [12], and accelerates nucleotide exchange to regenerate monomers for new rounds of assembly [13-15]. CAP has also been reported to enhance cofilin-mediated severing [16, 17], but these claims have since been challenged [7]. Using microfluidics-assisted three-color single-molecule imaging, we now reveal that CAP also has important functions at filament barbed ends. We reveal that CAP is a processive barbed-end depolymerase capable of tracking both ends of the filament. Each CAP binding event leads to removal of about 5,175 and 620 subunits from the barbed and pointed ends respectively. We find that the WH2 domain is essential, and the CARP domain is dispensable for barbed-end depolymerization. We show that CAP co-localizes with barbed-end bound formin and capping protein, in the process increasing residence time of formin by 10-fold and promoting dissociation of CP by 4-fold. Our barbed-end observations combined with previously reported activities of CAP at pointed ends and sides, firmly establish CAP as a key player in actin dynamics.


Can we use interleukin-6 (IL-6) blockade for coronavirus disease 2019 (COVID-19)-induced cytokine release syndrome (CRS)?
The emergent outbreak of coronavirus disease 2019 (COVID-19) has caused a global pandemic. Acute respiratory distress syndrome (ARDS) and multiorgan dysfunction are among the leading causes of death in critically ill patients with COVID-19. The elevated inflammatory cytokines suggest that a cytokine storm, also known as cytokine release syndrome (CRS), may play a major role in the pathology of COVID-19. However, the efficacy of corticosteroids, commonly utilized antiinflammatory agents, to treat COVID-19-induced CRS is controversial. There is an urgent need for novel therapies to treat COVID-19-induced CRS. Here, we discuss the pathogenesis of severe acute respiratory syndrome (SARS)-induced CRS, compare the CRS in COVID-19 with that in SARS and Middle East respiratory syndrome (MERS), and summarize the existing therapies for CRS. We propose to utilize interleukin-6 (IL-6) blockade to manage COVID-19-induced CRS and discuss several factors that should be taken into consideration for its clinical application.


Mapping of local electrical properties in epitaxial graphene using electrostatic force microscopy.
Local electrical characterization of epitaxial graphene grown on 4H-SiC(0001) using electrostatic force microscopy (EFM) in ambient conditions and at elevated temperatures is presented. EFM provides a straightforward identification of graphene with different numbers of layers on the substrate where topographical determination is hindered by adsorbates. Novel EFM spectroscopy has been developed measuring the EFM phase as a function of the electrical DC bias, establishing a rigorous way to distinguish graphene domains and facilitating optimization of EFM imaging.


HIV-infected persons with type 2 diabetes show evidence of endothelial dysfunction and increased inflammation.
Increased incidence of cardiovascular diseases (CVD) in both HIV infection and type 2 diabetes (T2D) compared to the general population has been described. Little is known about the combined effect of HIV infection and T2D on inflammation and endothelial function, both of which may contribute to elevated risk of CVD. Cross-sectional study including 50 HIV-infected persons on combination anti-retroviral therapy (cART), with HIV RNA <200 copies/mL (n = 25 with T2D (HIV + T2D+), n = 25 without T2D (HIV + T2D-)) and 50 uninfected persons (n = 22 with T2D (HIV-T2D+) and n = 28 without T2D (HIV-T2D-)). Groups were matched on age and sex. High sensitive C-reactive protein (hsCRP) was used to determine inflammation (cut-off 3 mg/L). The marker of endothelial dysfunction asymmetric dimethylarginine (ADMA) was measured using high performance liquid chromatography. Trimethylamine-N-oxide (TMAO), a microbiota-dependent, pro-atherogenic marker was measured using stable isotope dilution LC/MS/MS. The percentage of HIV + T2D+, HIV + T2D-, HIV-T2D+, and HIV-T2D- with hsCRP above cut-off was 50%, 19%, 47%, and 11%, respectively. HIV + T2D+ had elevated ADMA (0.67 μM (0.63-0.72) compared to HIV + T2D- (0.60 μM (0.57-0.64) p = 0.017), HIV-T2D+ (0.57 μM (0.51-63) p = 0.008), and HIV-T2D- (0.55 μM (0.52-0.58) p < 0.001). No differences in TMAO between groups were found. However, a positive correlation between ADMA and TMAO was found in the total population (rs = 0.32, p = 0.001), which was mainly driven by a close correlation in HIV + T2D+ (rs = 0.63, p = 0.001). Elevated inflammation and evidence of endothelial dysfunction was found in HIV-infected persons with T2D. The effect on inflammation was mainly driven by T2D, while both HIV infection and T2D may contribute to endothelial dysfunction. Whether gut microbiota is a contributing factor to this remains to be determined.


Eye-Blink Parameters Detect On-Road Track-Driving Impairment Following Severe Sleep Deprivation.
Drowsiness leads to 20% of fatal road crashes, while inability to assess drowsiness has hampered drowsiness interventions. This study examined the accuracy of eye-blink parameters for detecting drowsiness related driving impairment in real time. Twelve participants undertook two sessions of 2-hour track-driving in an instrumented vehicle following a normal night's sleep or 32 to 34 hours of extended wake in a randomized crossover design. Eye-blink parameters and lane excursion events were monitored continuously. Sleep deprivation increased the rates of out-of-lane driving events and early drive terminations. Episodes of prolonged eyelid closures, blink duration, the ratio of amplitude to velocity of eyelid closure, and John's Drowsiness Score (JDS, a composite score) were also increased following sleep deprivation. A time-on-task (drive duration) effect was evident for out-of-lane events rate and most eye-blink parameters after sleep deprivation. The JDS demonstrated the strongest association with the odds of out-of-lane events in the same minute, whereas measures of blink duration and prolonged eye closure were stronger indicators of risk for out-of-lane events over longer periods of 5 minutes and 15 minutes, respectively. Eye-blink parameters also achieved moderate accuracies (specificities from 70.12% to 84.15% at a sensitivity of 50%) for detecting out-of-lane events in the same minute, with stronger associations over longer timeframes of 5 minutes to 15 minutes. Eyelid closure parameters are useful tools for monitoring and predicting drowsiness-related driving impairment (out-of-lane events) that could be utilized for monitoring drowsiness and assessing the efficacy of drowsiness interventions. This study is registered with the Australian New Zealand Clinical Trial Registry (ANCTR), http://www.anzctr.org.au/TrialSearch.aspx ACTRN12612000102875. Shekari Soleimanloo S, Wilkinson VE, Cori JM,Westlake J, Stevens B, Downey LA, Shiferaw BA, Rajaratnam SMW, Howard ME. Eye-blink parameters detect on-road track-driving impairment following severe sleep deprivation. J Clin Sleep Med. 2019;15(9):1271-1284.


A systematic evaluation of single cell RNA-seq analysis pipelines.
The recent rapid spread of single cell RNA sequencing (scRNA-seq) methods has created a large variety of experimental and computational pipelines for which best practices have not yet been established. Here, we use simulations based on five scRNA-seq library protocols in combination with nine realistic differential expression (DE) setups to systematically evaluate three mapping, four imputation, seven normalisation and four differential expression testing approaches resulting in ~3000 pipelines, allowing us to also assess interactions among pipeline steps. We find that choices of normalisation and library preparation protocols have the biggest impact on scRNA-seq analyses. Specifically, we find that library preparation determines the ability to detect symmetric expression differences, while normalisation dominates pipeline performance in asymmetric DE-setups. Finally, we illustrate the importance of informed choices by showing that a good scRNA-seq pipeline can have the same impact on detecting a biological signal as quadrupling the sample size.