Internal versus external motivation in referral of primary care patients with depression to an internet support group: randomized controlled trial.
Depressive disorders and symptoms affect more than one-third of primary care patients, many of whom do not receive or do not complete treatment. Internet-based social support from peers could sustain depression treatment engagement and adherence. We do not know whether primary care patients will accept referral to such websites nor do we know which methods of referral would be most effective. We conducted a randomized clinical trial to determine whether (1) a simple generic referral card (control), (2) a patient-oriented brochure that provided examples of online postings and experience (internal motivation), or (3) a physician letter of recommendation (external motivation) would generate the greatest participation in a primary care Internet depression treatment support portal focused around an Internet support group (ISG). We used 3 offline methods to identify potential participants who had not used an ISG in the past 6 months. Eligibility was determined in part by a brief structured psychiatric interview based on the Patient Health Questionnaire-9 (PHQ-9). After consent and enrollment, participants were randomly assigned to 1 of 3 groups (control, internal motivation, or external motivation). We constructed a portal to connect primary care patients to both fact-based information and an established ISG (Psycho-Babble). The ISG allowed participants to view messages and then decide if they actually wished to register there. Participation in the portal and the ISG was assessed via automated activity tracking. Fifty participants were assigned to the 3 groups: a motivation-neutral control group (n=18), an internal motivation group (n=19), and an external motivation group (n=13). Of these participants, 31 (62%) visited the portal; 27 (54%) visited the ISG itself. The internal motivation group showed significantly greater participation than the control group on several measures. The external motivation group spent significantly less time logged onto the portal than the control group. The internal motivation group showed significantly greater participation than the external motivation group on several measures. Referral of primary care patients with depressive disorders and symptoms to an ISG is feasible even if they have never previously used one. This may best be accomplished by enhancing their internal motivation.


[Orthostatic hypotension: an unusual manifestation of pheochromocytoma].
Pheochromocytoma, though an uncommon cause of hypertension, can be a lethal condition. Because of this it is mandatory to diagnose it or rule it out in presence of suggestive symptoms. Typical symptoms are palpitations, sweating, severe headaches and hypertension. However, there are other suggestive symptoms of this dangerous endocrine entity, one of which is the orthostatic hypotension. We report the case of a 65 years old female patient with long standing hypertension in whom the pheochromocytoma was suspected after episodes of orthostatic hypotension. Although this manifestation was described almost fifty years ago, its frequency and pathophysiology has not yet been well established and fully elucidated. Moreover, it has meaningful implications in relation to preoperatory management and the timing of surgery.


[Attention and physical presence: expressive dimensions and the dialogical practice of nursing care according to the perpective of the hospitalized client].
Qualitative study, discusses the attention and the physical presence as the fundamental care in the dialogical relation between the client living with AIDS and the hospital nursing, using concepts of expressive activities and human care, according to Watson and dialogue, according to Freire. Five persons participated with internment experience, under ambulatory follow up in a hospital of Rio de Janeiro city. It used the triangulation techniques: almanac, semi-structured interview and participant observation. It showed the importance of the valorization of that is necessary and of interest of the client from the attention and the physical presence as essential requirements in the human care, expressed in the dialogical experience and in the participation of the client in the whole care process.


Cost of breast cancer treatment in Medicaid: implications for state programs providing coverage for low-income women.
To date, no study has reported on the cost of treating breast cancer among Medicaid beneficiaries younger than 65 years of age. This information is essential for assessing the funding required for treatment programs established by the Breast and Cervical Cancer Prevention and Treatment Act of 2000. This study assesses the incremental cost of breast cancer treatment among Medicaid beneficiaries aged below 65 years. Administrative data from the North Carolina Medicaid program linked with cancer registry data were analyzed to derive monthly Medicaid costs for cancer patients and the incremental costs of breast cancer treatment at 6, 12, and 24 months from diagnosis. We compared 848 beneficiaries diagnosed with cancer during the years 2002 to 2004 with 1696 comparison cases matched on age. With the exception of in situ cancers, the cost of cancer care continued to increase beyond the initial 6-month period. The incremental costs at 6 months after diagnosis are $14,341, $24,002, and $34,469 for those with local, regional, and distant breast cancers, respectively; and these costs increased to $22,343, $41,005, and $117,033 at 24 months. The extended period of health care utilization, beyond the immediate 6-month period after diagnosis, indicates that Medicaid coverage may be required for many months after diagnosis to complete treatment. Continuous Medicaid coverage should be provided for an adequate time period to ensure that complete and comprehensive treatment is provided.


Clinical use of intracoronary imaging. Part 2: acute coronary syndromes, ambiguous coronary angiography findings, and guiding interventional decision-making: an expert consensus document of the European Association of Percutaneous Cardiovascular Interventions.
This consensus document is the second of two reports summarizing the views of an expert panel organized by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) on the clinical use of intracoronary imaging including intravascular ultrasound (IVUS), optical coherence tomography (OCT), and near infrared spectroscopy (NIRS)-IVUS. Beyond guidance of stent selection and optimization of deployment, invasive imaging facilitates angiographic interpretation and may guide treatment in acute coronary syndrome. Intravascular imaging can provide additional important diagnostic information when confronted with angiographically ambiguous lesions and allows assessment of plaque morphology enabling identification of vulnerability characteristics. This second document focuses on useful imaging features to identify culprit and vulnerable coronary plaque, which offers the interventional cardiologist guidance on when to adopt an intracoronary imaging-guided approach to the treatment of coronary artery disease and provides an appraisal of intravascular imaging-derived metrics to define the haemodynamic significance of coronary lesions.


Mapping global environmental suitability for Zika virus.
Zika virus was discovered in Uganda in 1947 and is transmitted by Aedes mosquitoes, which also act as vectors for dengue and chikungunya viruses throughout much of the tropical world. In 2007, an outbreak in the Federated States of Micronesia sparked public health concern. In 2013, the virus began to spread across other parts of Oceania and in 2015, a large outbreak in Latin America began in Brazil. Possible associations with microcephaly and Guillain-Barré syndrome observed in this outbreak have raised concerns about continued global spread of Zika virus, prompting its declaration as a Public Health Emergency of International Concern by the World Health Organization. We conducted species distribution modelling to map environmental suitability for Zika. We show a large portion of tropical and sub-tropical regions globally have suitable environmental conditions with over 2.17 billion people inhabiting these areas.


Displaying a high-resolution digital hologram on a low-resolution spatial light modulator with the same resolution obtained from the hologram.
In this paper, a fast method for displaying a digital, real and off-axis Fresnel hologram on a lower resolution device is reported. Preserving the original resolution of the hologram upon display is one of the important attributes of the proposed method. Our method can be divided into 3 stages. First, a digital hologram representing a given three dimensional (3D) object is down-sampled based on a fix, jitter down-sampling lattice. Second, the down-sampled hologram is interpolated, through pixel duplication, into a low resolution hologram that can be displayed with a low-resolution spatial light modulator (SLM). Third, the SLM is overlaid with a grating which is generated based on the same jitter down-sampling lattice that samples the hologram. The integration of the grating and the low-resolution hologram results in, to a good approximation, the resolution of the original hologram. As such, our proposed method enables digital holograms to be displayed with lower resolution SLMs, paving the way for the development of low-cost holographic video display.


Clinical Encounters with Immigrants: What Matters for U.S. Psychiatrists.
About 3.2 percent of the population across the globe are migrants. Today, unprecedented numbers of people are relocating in the U.S. and more than ever, psychiatrists find themselves caring for immigrant patients. International migration is a multilayered issue that often has implications for the mental health of migrants. Thus, there is an increasing interest in understanding how the different factors associated with migration processes affect the mental health outcomes of immigrants. We group these factors into three categories: immigrant process, clinical encounter, and mental health services. When possible, we incorporate a gendered and life span perspective and suggest avenues for including what we know into the care of children, adults, and elderly psychiatric patients with immigrant backgrounds. We pay special attention to the immigrant paradox literature, which explains why some immigrants are healthier when they start their journey, and why their mental health deteriorates as they live longer in the host societies. We aim at providing psychiatrists an understanding of what to ask, assess, and consider when caring for patients who are international migrants.


Reference values of cardio-ankle vascular index in a random sample of a white population.
Cardio-ankle vascular index (CAVI), a parameter of arterial stiffness, has been increasingly used for cardiovascular risk estimation. Currently used CAVI reference values are derived from the Japanese population. It is not clear whether the same reference values can be used in the white population. The aim of the present study was to describe cardiovascular risk factors influencing CAVI and to establish CAVI reference values. A total of 2160 individuals randomly selected from the Brno city population aged 25-65 years were examined. Of these, 1347 patients were free from cardiovascular disease, nondiabetic and untreated by antihypertensive or lipid-lowering drugs, forming the reference value population. CAVI was measured using the VaSera VS-1000 device (Fukuda Denshi, Tokyo, Japan). At each blood pressure (BP) level, there was a quadratic association between CAVI and age, except for a linear association in the optimal BP group. Although there was no association between BP and CAVI in younger patients, there was a linear association between CAVI and BP after 40 years of age. Reference values by age and sex were established. In each age group, except for the male 60-65-year group, reference values in our population were lower than in the Japanese one with the difference ranging from -0.29 to 0.21 for men, and from -0.38 to -0.03 for women. This is the first study providing CAVI reference values in a random sample of the white population. Our results suggest that the currently used values slightly overestimate CAVI in younger white, possibly underestimating cardiovascular risk.


Laboratory-scale experimental and modelling investigations of 222Rn profiles in chemically heterogeneous LNAPL contaminated vadose zones.
The potential of LNAPL delineation by 222Rn soil-gas monitoring in a chemically heterogeneous vadose zone was investigated in this study based on laboratory (batch and columns) experiments and numerical modelling. An enhanced version of the MIN3P reactive transport code was used to simulate Rn transport in both uncontaminated and NAPL-contaminated vadose zones and results were validated against analytical solutions and laboratory experiments. Results show that 222Rn activity profiles are mainly controlled by porous media 222Rn production, vadose zone fluid saturations and especially the type and distribution of NAPL in contaminated areas. The results also show that decreases in 222Rn activity and variations in activity gradients provide evidence for the presence and saturation of NAPL. This study demonstrates that LNAPL delineation via 222Rn gas surveys at contaminated sites works best, if gas measurements extend as deep as possible and include regions where 222Rn activity decreases due to elevated NAPL content. In addition, collection and analysis of depth-discrete gas samples allows the characterization of vertical NAPL distribution based on the 222Rn activity gradient. The determination of 222Rn production in the unsaturated zone, as well as water capillary pressure curves are of key importance in enabling the discrimination of an uncontaminated from a NAPL-contaminated area.


A convolutional route to abbreviation disambiguation in clinical text.
Abbreviations sense disambiguation is a special case of word sense disambiguation. Machine learning methods based on neural networks showed promising results for word sense disambiguation (Festag and Spreckelsen, 2017) [1] and, here we assess their effectiveness for abbreviation sense disambiguation. Convolutional Neural Network (CNN) models were trained, one for each abbreviation, to disambiguate abbreviation senses. A reverse substitution (of long forms with short forms) method from a previous study was used on clinical narratives from Cleveland Clinic, USA, to auto-generate training data. Accuracy of the CNN and traditional Support Vector Machine (SVM) models were studied using: (a) 5-fold cross validation on the auto-generated training data; (b) a manually created, set-aside gold standard; and (c) 10-fold cross validation on a publicly available dataset from a previous study. CNN improved accuracy by 1-4 percentage points on all the three datasets compared to SVM, and the improvement was the most for the set-aside dataset. The improvement was statistically significant at p < 0.05 on the auto-generated dataset. We found that for some common abbreviations, sense distributions mismatch between the test and auto generated training data, and mitigating the mismatch significantly improved the model accuracy. The neural network models work well in disambiguating abbreviations in clinical narratives, and they are robust across datasets. This avoids feature-engineering for each dataset. Coupled with an enhanced auto-training data generation, neural networks can simplify development of a practical abbreviation disambiguation system.


Utility of apolipoprotein measurements in predicting incident type 2 diabetes: A Chinese cohort study.
There is conflicting data regarding the utility of measuring apolipoproteins in addition to traditional lipid measures in risk assessment of cardiometabolic diseases. The aim of this study was to determine whether apolipoprotein measurements can improve the ability to predict the future development of type 2 diabetes beyond what is possible based on traditional type 2 diabetes risk factors and clinical routine lipid measurements. A total of 4,223 Chinese adults without diabetes were followed for a mean duration of 5.42 years. The hazard ratios (HRs) with 95% confidence intervals (CIs) derived from the Cox proportional hazards model were used to analyze the longitudinal associations of apolipoprotein B (apo B), apolipoprotein A-I (apo A-I), and the apo B/apo A-I ratio with the risk of type 2 diabetes. Further, the analysis of the area under receiver operating characteristics curves (AUC) was performed to test the predictive value of apolipoprotein measurements. After adjusting for potential confounders, the HRs of diabetes consistently showed an increasing trend across both the apo B and the apo B/apo A-I ratio quartiles (p for trend = 0.004). In analyses of AUC, the predictive ability for type 2 diabetes risk for the apo B and the apo B/apo A-I ratio was superior to that of routine lipid and lipoprotein measurements. Apolipoprotein measurements significantly predict diabetes risk in an Asian population. Furthermore, the predictive ability of apo B alone to detect diabetes was comparable with that of the apo B/apo A-I ratio and better than the routine lipid measurements.


Distributed feedback diode laser spectrometer at 2.7 microm for sensitive, spatially resolved H2O vapor detection.
A new, compact, spatially scanning, open-path 2.7 microm tunable diode laser absorption spectrometer with short absorption path lengths below 10 cm was developed to analyze the spatiotemporal dynamics of one-dimensional (1D) spatial water vapor gradients. This spectrometer, which is based on a room-temperature distributed feedback diode laser, is capable of measuring absolute, calibration-free, line-of-sight averaged, but laterally resolved 1D H(2)O concentration profiles with a minimum fractional optical resolution of 2.1x10(-3) optical density (OD) (2.5x10(-4) OD after a background subtraction procedure), which permits a signal-to-noise-ratio of 407 (3400) at 10,000 parts in 10(6) (ppm)H(2)O, or normalized sensitivities of 2.6 ppm x m (0.32 ppm m) at 0.5 Hz duty cycle. The spectrometer's lateral spatial resolution (governed by the 500 microm sampling beam diameter) was validated by analyzing a well-defined laminar jet of nitrogen gas in humidified air. This scanning setup was then used to (a) quantitatively investigate for what we believe to be the first time the H(2)O boundary layer from 0.7 to 11 mm beneath the stomatous side of a single, undetached plant leaf, and (b) to study the temporal boundary layer dynamics and its dependence on stepwise light stimulation of the photosynthetic system. In addition the 2.7 microm diode laser was carefully characterized in terms of spectral purity, beam profile, as well as quasi-static and dynamic wavelength tuning coefficients.


Regional lidocaine infusion reduces postischemic spinal cord injury in rabbits.
Paraplegia secondary to spinal cord ischemia is a devastating complication in operations on the descending and thoracoabdominal aorta. We hypothesized that the tolerance of the spinal cord to an ischemic insult could be improved by means of regional administration of lidocaine. Thirty-one New Zealand white rabbits were anesthetized and spinal cord ischemia was induced by the placement of clamps both below the left renal vein and above the aortic bifurcation. The animals were divided into 5 groups. Aortic occlusion time was 20 minutes in Group 1 and 30 minutes in all other groups. Groups 1 and 2 functioned as controls. Lidocaine (Group 5) or normal saline solution (Group 3) was infused into the isolated aortic segment after cross-clamping. Group 4 animals received 20% mannitol regionally, before and after reperfusion. Postoperatively, rabbits were classified as either neurologically normal or injured (paralyzed or paretic). Among controls, 20 minutes of aortic occlusion did not produce any neurologic deficit (Group 1: 0/4 injured), while 30 minutes of occlusion resulted in more consistent injury (Group 2: 6/8 injured). Animals that received normal saline (Group 3) or mannitol (Group 4) regionally showed 80% neurologic injury (4/5). Animals treated with the regional lidocaine infusion (Group 5) showed much better neurologic outcomes (7/9 normal: 78%). This superiority of Group 5 over Groups 2, 3, and 4 was significant (P <0.02). We conclude that regional administration of lidocaine reduced neurologic injury secondary to spinal cord ischemia and reperfusion after aortic occlusion in the rabbit model.


Background ionizing radiation and the risk of childhood cancer: a census-based nationwide cohort study.
Exposure to medium or high doses of ionizing radiation is a known risk factor for cancer in children. The extent to which low-dose radiation from natural sources contributes to the risk of childhood cancer remains unclear. In a nationwide census-based cohort study, we investigated whether the incidence of childhood cancer was associated with background radiation from terrestrial gamma and cosmic rays. Children < 16 years of age in the Swiss National Censuses in 1990 and 2000 were included. The follow-up period lasted until 2008, and incident cancer cases were identified from the Swiss Childhood Cancer Registry. A radiation model was used to predict dose rates from terrestrial and cosmic radiation at locations of residence. Cox regression models were used to assess associations between cancer risk and dose rates and cumulative dose since birth. Among 2,093,660 children included at census, 1,782 incident cases of cancer were identified including 530 with leukemia, 328 with lymphoma, and 423 with a tumor of the central nervous system (CNS). Hazard ratios for each millisievert increase in cumulative dose of external radiation were 1.03 (95% CI: 1.01, 1.05) for any cancer, 1.04 (95% CI: 1.00, 1.08) for leukemia, 1.01 (95% CI: 0.96, 1.05) for lymphoma, and 1.04 (95% CI: 1.00, 1.08) for CNS tumors. Adjustment for a range of potential confounders had little effect on the results. Our study suggests that background radiation may contribute to the risk of cancer in children, including leukemia and CNS tumors.


Rapid conditional targeted ablation model for hemolytic anemia in the rat.
Effective methods for cell ablation are important tools for examining the anatomical, functional, and behavioral consequences of selective loss of specific cell types in animal models. We have developed an ablation system based on creating genetically modified animals that express human CD59 (hCD59), a membrane receptor, and administering intermedilysin (ILY), a toxin produced by Streptococcus intermedius, which binds specifically to hCD59 to induce cell lysis. As proof-of-concept in the rat, we generated an anemia model, SD-Tg(CD59-HBA1)Bryd, which expresses hCD59 on erythrocytes. Hemolysis is a common complication of inherited or acquired blood disorders, which can result in cardiovascular compromise and death. A rat model that can replicate hemolysis through specific ablation of erythrocytes would allow further study of disease and novel treatments. In vitro, complete lysis of erythrocytes expressing hCD59 was observed at and above 250 pM ILY, while no lysis was observed in wild-type erythrocytes at any ILY concentration (8-1,000 pM). In vivo, ILY intravenous injection (100 ng/g body wt) dramatically reduced the hematocrit within 10 min, with a mean hematocrit reduction of 43% compared with 1.4% in the saline control group. Rats injected with ILY at 500 ng/g intraperitoneally developed gross signs of anemia. Histopathology confirmed anemia and revealed hepatic necrosis, with microthrombi present. These studies validate the hCD59-ILY cell ablation technology in the rat and provide the scientific community with a new rapid conditional targeted ablation model for hemolytic anemia and hemolysis-associated sequelae.


Patient safety in inpatient mental health settings: a systematic review.
Patients in inpatient mental health settings face similar risks (eg, medication errors) to those in other areas of healthcare. In addition, some unsafe behaviours associated with serious mental health problems (eg, self-harm), and the measures taken to address these (eg, restraint), may result in further risks to patient safety. The objective of this review is to identify and synthesise the literature on patient safety within inpatient mental health settings using robust systematic methodology. Systematic review and meta-synthesis. Embase, Cumulative Index to Nursing and Allied Health Literature, Health Management Information Consortium, MEDLINE, PsycINFO and Web of Science were systematically searched from 1999 to 2019. Search terms were related to 'mental health', 'patient safety', 'inpatient setting' and 'research'. Study quality was assessed using the Hawker checklist. Data were extracted and grouped based on study focus and outcome. Safety incidents were meta-analysed where possible using a random-effects model. Of the 57 637 article titles and abstracts, 364 met inclusion criteria. Included publications came from 31 countries and included data from over 150 000 participants. Study quality varied and statistical heterogeneity was high. Ten research categories were identified: interpersonal violence, coercive interventions, safety culture, harm to self, safety of the physical environment, medication safety, unauthorised leave, clinical decision making, falls and infection prevention and control. Patient safety in inpatient mental health settings is under-researched in comparison to other non-mental health inpatient settings. Findings demonstrate that inpatient mental health settings pose unique challenges for patient safety, which require investment in research, policy development, and translation into clinical practice. CRD42016034057.


Critical role of WNK1 in MYC-dependent early mouse thymocyte development.
WNK1, a kinase that controls kidney salt homeostasis, also regulates adhesion and migration in CD4+ T cells. Wnk1 is highly expressed in thymocytes, and since migration is important for thymocyte maturation, we investigated a role for WNK1 in mouse thymocyte development. We find that WNK1 is required for the transition of double negative (DN) thymocytes through the β-selection checkpoint and subsequent proliferation and differentiation into double positive (DP) thymocytes. Furthermore, we show that WNK1 negatively regulates LFA1-mediated adhesion and positively regulates CXCL12-induced migration in DN thymocytes. Despite this, migration defects of WNK1-deficient thymocytes do not account for the developmental arrest. Instead, we show that in DN thymocytes WNK1 transduces pre-TCR signals via OXSR1 and STK39 kinases, and the SLC12A2 ion co-transporter that are required for post-transcriptional upregulation of MYC and subsequent proliferation and differentiation into DP thymocytes. Thus, a pathway regulating ion homeostasis is a critical regulator of thymocyte development.


A tale of two continents: a multilevel comparison of the determinants of child nutritional status from selected African and Indian regions.
This paper compares individual and household predictors of underweight among young children in sub-Saharan Africa and India, while also assessing the impact of clustering of weight for age z-scores at the household, community and regional levels. Multilevel statistical models are employed to compare the strength of the correlates of underweight (using weight-for-age z-scores) in six sub-Saharan African countries and four Indian states. The multilevel approach controls for correlation among children resulting from clustering within families, communities, or regions and in addition enables tests for differences in the regional, community and household effects for children from families of different socio-economic characteristics. Findings demonstrate the importance of individual and household level predictors such as age, the size of child at birth, prolonged breast-feeding, recent diarrhoea episodes, and maternal education as predictors of low weight-for-age z-scores across regions. Strong family effects are observed as well as significant community and regional random effects on variation in weight for age z-scores. In some regions, socio-economic characteristics of the household result in significant differences in the household or community level variance in weight for age z-scores, suggesting that the impact of the geographical context varies by socio-economic status of the household.


Effect of preventive supplementation with ready-to-use therapeutic food on the nutritional status, mortality, and morbidity of children aged 6 to 60 months in Niger: a cluster randomized trial.
Ready-to-use therapeutic foods (RUTFs) are an important component of effective outpatient treatment of severe wasting. However, their effectiveness in the population-based prevention of moderate and severe wasting has not been evaluated. To evaluate the effect of a 3-month distribution of RUTF on the nutritional status, mortality, and morbidity of children aged 6 to 60 months in Niger. A cluster randomized trial of 12 villages in Maradi, Niger. Six villages were randomized to intervention and 6 to no intervention. All children in the study villages aged 6 to 60 months were eligible for recruitment. Children with weight-for-height 80% or more of the National Center for Health Statistics reference median in the 6 intervention villages received a monthly distribution of 1 packet per day of RUTF (92 g [500 kcal/d]) from August to October 2006. Children in the 6 nonintervention villages received no preventive supplementation. Active surveillance for conditions requiring medical or nutritional treatment was conducted monthly in all 12 study villages from August 2006 to March 2007. Changes in weight-for-height z score (WHZ) according to the World Health Organization Child Growth Standards and incidence of wasting (WHZ <-2) over 8 months of follow-up. The number of children with height and weight measurements in August, October, December, and February was 3166, 3110, 2936, and 3026, respectively. The WHZ difference between the intervention and nonintervention groups was -0.10 z (95% confidence interval [CI], -0.23 to 0.03) at baseline and 0.12 z (95% CI, 0.02 to 0.21) after 8 months of follow-up. The adjusted effect of the intervention on WHZ from baseline to the end of follow-up was thus 0.22 z (95% CI, 0.13 to 0.30). The absolute rate of wasting and severe wasting, respectively, was 0.17 events per child-year (140 events/841 child-years) and 0.03 events per child-year (29 events/943 child-years) in the intervention villages, compared with 0.26 events per child-year (233 events/895 child-years) and 0.07 events per child-year (71 events/1029 child-years) in the nonintervention villages. The intervention thus resulted in a 36% (95% CI, 17% to 50%; P < .001) reduction in the incidence of wasting and a 58% (95% CI, 43% to 68%; P < .001) reduction in the incidence of severe wasting. There was no reduction in mortality, with a mortality rate of 0.007 deaths per child-year (7 deaths/986 child-years) in the intervention villages and 0.016 deaths per child-year (18 deaths/1099 child-years) in the nonintervention villages (adjusted hazard ratio, 0.51; 95% CI, 0.25 to 1.05). Short-term supplementation of nonmalnourished children with RUTF reduced the decline in WHZ and the incidence of wasting and severe wasting over 8 months. clinicaltrials.gov Identifier: NCT00682708.


Visual number beats abstract numerical magnitude: format-dependent representation of Arabic digits and dot patterns in human parietal cortex.
In numerical cognition, there is a well-known but contested hypothesis that proposes an abstract representation of numerical magnitude in human intraparietal sulcus (IPS). On the other hand, researchers of object cognition have suggested another hypothesis for brain activity in IPS during the processing of number, namely that this activity simply correlates with the number of visual objects or units that are perceived. We contrasted these two accounts by analyzing multivoxel activity patterns elicited by dot patterns and Arabic digits of different magnitudes while participants were explicitly processing the represented numerical magnitude. The activity pattern elicited by the digit "8" was more similar to the activity pattern elicited by one dot (with which the digit shares the number of visual units but not the magnitude) compared to the activity pattern elicited by eight dots, with which the digit shares the represented abstract numerical magnitude. A multivoxel pattern classifier trained to differentiate one dot from eight dots classified all Arabic digits in the one-dot pattern category, irrespective of the numerical magnitude symbolized by the digit. These results were consistently obtained for different digits in IPS, its subregions, and many other brain regions. As predicted from object cognition theories, the number of presented visual units forms the link between the parietal activation elicited by symbolic and nonsymbolic numbers. The current study is difficult to reconcile with the hypothesis that parietal activation elicited by numbers would reflect a format-independent representation of number.


Time-resolved 3-dimensional velocity mapping in the thoracic aorta: visualization of 3-directional blood flow patterns in healthy volunteers and patients.
An analysis of thoracic aortic blood flow in normal subjects and patients with aortic pathologic findings is presented. Various visualization tools were used to analyze blood flow patterns within a single 3-component velocity volumetric acquisition of the entire thoracic aorta Time-resolved, 3-dimensional phase-contrast magnetic resonance imaging (3D CINE PC MRI) was employed to obtain complete spatial and temporal coverage of the entire thoracic aorta combined with spatially registered 3-directional pulsatile blood flow velocities. Three-dimensional visualization tools, including time-resolved velocity vector fields reformatted to arbitrary 2-dimensional cut planes, 3D streamlines, and time-resolved 3D particle traces, were applied in a study with 10 normal volunteers. Results from 4 patient examinations with similar scan prescriptions to those of the volunteer scans are presented to illustrate flow features associated with common pathologic findings in the thoracic aorta. Previously reported blood flow patterns in the thoracic aorta, including right-handed helical outflow, late systolic retrograde flow, and accelerated passage through the aortic valve plane, were visualized in all volunteers. The effects of thoracic aortic disease on spatial and temporal blood flow patterns are illustrated in clinical cases, including ascending aortic aneurysms, aortic regurgitation, and aortic dissection. Time-resolved 3D velocity mapping was successfully applied in a study of 10 healthy volunteers and 4 patients with documented aortic pathologic findings and has proven to be a reliable tool for analysis and visualization of normal characteristic as well as pathologic flow features within the entire thoracic aorta.


Wheat Transcription Factor TaAREB3 Participates in Drought and Freezing Tolerances in Arabidopsis.
AREB (ABA response element binding) proteins in plants play direct regulatory roles in response to multiple stresses, but their functions in wheat (Triticum aestivum L.) are not clear. In the present study, TaAREB3, a new member of the AREB transcription factor family, was isolated from wheat. Sequence analysis showed that the TaAREB3 protein is composed of three parts, a conserved N-terminal, a variable M region, and a conserved C-terminal with a bZIP domain. It belongs to the group A subfamily of bZIP transcription factors. TaAREB3 was constitutively expressed in stems, leaves, florets, anthers, pistils, seeds, and most highly, in roots. TaAREB3 gene expression was induced with abscisic acid (ABA) and low temperature stress, and its protein was localized in the nucleus when transiently expressed in tobacco epidermal cells and stably expressed in transgenic Arabidopsis. TaAREB3 protein has transcriptional activation activity, and can bind to the ABRE cis-element in vitro. Overexpression of TaAREB3 in Arabidopsis not only enhanced ABA sensitivity, but also strengthened drought and freezing tolerances. TaAREB3 also activated RD29A, RD29B, COR15A, and COR47 by binding to their promoter regions in transgenic Arabidopsis. These results demonstrated that TaAREB3 plays an important role in drought and freezing tolerances in Arabidopsis.


"I Have a Cough": An Interactive Virtual Respiratory Case-Based Module.
The COVID-19 pandemic has radically disrupted traditional models of medical education, forcing rapid evolution in the delivery of clinical training. As a result, clinical educators must quickly transition away from in-person sessions and develop effective virtual learning opportunities instead. This virtual resource was designed to replace a clinical simulation session for the physical examination course for medical students in the preclinical years. We designed an online interactive module in three sections for preclinical (first- or second-year) medical students who had not yet learned the respiratory physical exam. The first section incorporated demonstration and practice of the components of the respiratory physical exam that could be effectively taught via videoconferencing software. Following this, students conducted a telemedicine encounter with a standardized patient and received patient-centered feedback evaluating their communication skills. The final segment involved a case discussion and clinical reasoning component. These sessions were implemented for 122 first-year medical students. The module was well received by the students. A majority felt that it helped improve their telemedicine communication skills (93%), interpretation of physical exam findings (84%), development of differential diagnosis (95%), and correlation of clinical and basic science content (93%). Our pilot educational session demonstrates that this virtual instruction method is an effective tool for teaching basic clinical skills during medical school. Virtual learning resources allow remote instruction to take place and can be a supplement when face-to-face clinical teaching is not possible.


Emotion Dysregulation Moderates the Association Between Stress and Problematic Cannabis Use.
Background: Research suggests emotion dysregulation is a transdiagnostic risk factor for substance use and addiction and that stress may lead to problematic cannabis use. Thus, the current study examines how emotion dysregulation moderates the associations between stress (stressful life events and perceived stress) and problematic cannabis use. Methods: Eight hundred and fifty-two adults reporting any lifetime cannabis use completed an anonymous online survey. Participants completed a brief demographic questionnaire and were asked to report their past 30-day use of cannabis, alcohol, nicotine, and illicit substances. Problematic cannabis use (via the Marijuana Problem Scale), emotion dysregulation (via the Difficulties in Emotion Regulation Scale), perceived stress (via the Perceived Stress Scale), and stressful life events (via the Holmes-Rahe Life Stress Inventory) were assessed. Hierarchical multiple linear regressions were conducted. Results: Findings indicate that when examining the moderating role of emotion dysregulation, more stressful life events and less perceived stress were associated with more severe problematic cannabis use, and these associations were stronger at higher levels of emotion dysregulation. Conclusions: These results demonstrate a strong step toward understanding how emotion dysregulation moderates the relationship between stress and problematic cannabis use; however, longitudinal studies are needed to determine directionality of effects. Overall, these results suggest the importance of examining emotion dysregulation as a moderator of both stressful life events and stress perception as they relate to problematic cannabis use.


Short-term beta-hydroxy-beta-methylbutyrate supplementation does not reduce symptoms of eccentric muscle damage.
We examined the effects of short-term beta-hydroxy-beta-methylbutyrate (HMB) supplementation on symptoms of muscle damage following an acute bout of eccentric exercise. Non-resistance trained subjects were randomly assigned to a HMB supplement group (HMB, 40mg/kg bodyweight/day, n = 8) or placebo group (CON, n = 9). Supplementation commenced 6 days prior to a bout of 24 maximal isokinetic eccentric contractions of the elbow flexors and continued throughout post-testing. Muscle soreness, upper arm girth, and torque measures were assessed pre-exercise, 15 min post-exercise, and 1, 2, 3, 4, 7, and 10 days post-exercise. No pre-test differences between HMB and CON groups were identified, and both performed a similar amount of eccentric work during the main eccentric exercise bout (p > .05). HMB supplementation had no effect on swelling, muscle soreness, or torque following the damaging eccentric exercise bout (p > .05). Compared to a placebo condition, short-term supplementation with 40mg/kg bodyweight/day of HMB had no beneficial effect on a range of symptoms associated with eccentric muscle damage. If HMB can produce an ergogenic response, a longer preexercise supplementation period may be necessary.


Microbial invasion of the amniotic cavity in pregnancies with small-for-gestational-age fetuses.
Microbial invasion of the amniotic cavity (MIAC) has been detected in women with preterm labor, preterm prelabor rupture of membranes (PROM), and in patients at term with PROM or in spontaneous labor. Intrauterine infection is recognized as a potential cause of fetal growth restriction; yet, the frequency of MIAC in pregnancies with small-for-gestational-age (SGA) fetuses is unknown. The aim of this study was to determine the frequency, diversity and relative abundance of microbes in amniotic fluid (AF) of women with an SGA neonate using a combination of culture and molecular methods. AF from 52 subjects with an SGA neonate was analyzed with both cultivation and molecular methods in a retrospective cohort study. Broad-range and group-specific PCR assays targeted small subunit rDNA, or other gene sequences, from bacteria, fungi and archaea. Results of microbiologic studies were correlated with indices of the host inflammatory response. 1) All AF samples (n=52) were negative for microorganisms based on cultivation techniques, whereas 6% (3/52) were positive based on PCR; and 2) intra-amniotic inflammation was detected in one of the three patients with a positive PCR result, as compared with three patients (6.1%) of the 49 with both a negative culture and a negative PCR (P=0.2). MIAC is detected by PCR in some patients with an SGA fetus who were not in labor at the time of AF collection.


Autophagy regulates endoplasmic reticulum homeostasis and calcium mobilization in T lymphocytes.
Macroautophagy (hereafter referred to as autophagy) is an evolutionarily conserved intracellular bulk degradation pathway that plays critical roles in eliminating intracellular pathogens, presenting endogenous Ags, and regulating T lymphocyte survival and proliferation. In this study, we have investigated the role of autophagy in regulating the endoplasmic reticulum (ER) compartment in T lymphocytes. We found that ER content is expanded in mature autophagy-related protein (Atg) 7-deficient T lymphocytes. Atg7-deficient T cells stimulated through the TCR display impaired influx, but not efflux, of calcium, and ER calcium stores are increased in Atg7-deficient T cells. Treatment with the ER sarco/ER Ca(2+)-ATPase pump inhibitor thapsigargin rescues the calcium influx defect in Atg7-deficient T lymphocytes, suggesting that this impairment is caused by an intrinsic defect in ER. Furthermore, we found that the stimulation-induced redistribution of stromal interaction molecule-1, a critical event for the store-operated Ca(2+) release-activated Ca(2+) channel opening, is impaired in Atg7-deficient T cells. Together, these findings indicate that the expanded ER compartment in Atg7-deficient T cells contains increased calcium stores, and the inability of these stores to be depleted causes defective calcium influx in these cells. Our results demonstrate that autophagy plays an important role in maintaining ER and calcium homeostasis in T lymphocytes.


Maintaining Plasma Fibrinogen Levels and Fibrinogen Replacement Therapies for Treatment of Intracranial Hemorrhage.
Intracranial hemorrhage is characterized by the blood vessel rupture and subsequent hematoma expansion. It is the least treatable stroke subtype, resulting in higher morbidity and mortality per incidence than ischemic stroke. Recent studies have observed lower than normal levels of plasma fibrinogen in patients of intracerebral hemorrhage. Furthermore, in other cases of severe hemorrhage, plasma fibrinogen levels have been identified as an indicator of prognosis. Current clinical management of cerebral hemorrhage includes adjunctive therapies and possible surgical evacuation. However, a possible therapeutic target for intracranial hemorrhage is fibrinogen. During intracranial hemorrhage with hematoma expansion, fibrinogen levels are rapidly depleted and thus are in need of replacement. Maintaining high levels of fibrinogen can promote rapid clotting and reduction of hematoma expansion. Within this review, we examine the role of fibrinogen in intracranial hemorrhage and evaluate the use of fibrinogen replacement therapies for maintaining normal levels of this key hemostatic protein. The pros and cons are discussed and an opinion of the most appropriate fibrinogen replacement therapy for intracranial hemorrhage is made. It is concluded that fibrinogen concentrate seems to be the most suitable therapy for elevating plasma fibrinogen for the treatment of intracranial hemorrhage with hematoma expansion.


Sagittal plane movement at the tibiofemoral joint influences patellofemoral joint structure in healthy adult women.
The influence exerted on cartilage and bone volumes by locomotor patterns is poorly understood, particularly at the patellofemoral joint. The aim of this study was to investigate the relationship between sagittal plane movement at the tibiofemoral joint and patella cartilage and bone volumes during the locomotion of healthy adult females. Three-dimensional Vicon gait analyses and magnetic resonance imaging were performed on 20 healthy adult women. The relationships between the degree of tibiofemoral flexion and extension at varying stages of the gait cycle and the concomitant medial, lateral and total patella cartilage and total bone volumes were examined. For every degree the knee flexed during mid-stance, there was a 62.8 microL (95% confidence interval 3.7-122.0) increase in the medial patella facet cartilage volume after adjustment for age and the body mass index (BMI) (P = 0.04). A similar relationship that approached significance was observed for the lateral patella facet cartilage volume after adjustment for age and the BMI (P = 0.08). No association was observed between the sagittal plane tibiofemoral movements and the patella bone volume. The association between patella cartilage volume and tibiofemoral knee movement suggests that for every degree increase in knee flexion during mid-stance, there is an associated increase in patella cartilage volume. This may be the result of the geometry of the femoral condyle influencing patella tracking and or the retropatellar load exerted on the patella during walking. These results may have important implications for people who hyperextend their knee during gait and the pathogenesis of patellofemoral osteoarthritis.


Alzheimer's disease and Down's syndrome: an in vivo MRI study.
Individuals with Down's syndrome (DS) are at high risk of developing Alzheimer's disease (AD). However, few studies have investigated brain anatomy in DS individuals with AD. We compared whole brain anatomy, as measured by volumetric magnetic resonance imaging (MRI), in DS individuals with and without AD. We also investigated whether volumetric differences could reliably classify DS individuals according to AD status. We used volumetric MRI and manual tracing to examine regional brain anatomy in 19 DS adults with AD and 39 DS adults without AD. DS individuals with AD had significantly smaller corrected volumes bilaterally of the hippocampus and caudate, and right amygdala and putamen, and a significantly larger corrected volume of left peripheral cerebrospinal fluid (CSF), compared to DS individuals without AD. The volume of the hippocampus and caudate nucleus correctly categorized 92% and 92% respectively of DS individuals without AD, and 75% and 80% respectively of DS individuals with AD. DS individuals with AD have significant medial temporal and striatal volume reductions, and these may provide markers of clinical AD.


Effects of the stimuli-dependent enrichment of 8-oxoguanine DNA glycosylase1 on chromatinized DNA.
8-Oxoguanine DNA glycosylase 1 (OGG1) initiates the base excision repair pathway by removing one of the most abundant DNA lesions, 8-oxo-7,8-dihydroguanine (8-oxoG). Recent data showed that 8-oxoG not only is a pro-mutagenic genomic base lesion, but also functions as an epigenetic mark and that consequently OGG1 acquire distinct roles in modulation of gene expression. In support, lack of functional OGG1 in Ogg1-/- mice led to an altered expression of genes including those responsible for the aberrant innate and adaptive immune responses and susceptibility to metabolic disorders. Therefore, the present study examined stimulus-driven OGG1-DNA interactions at whole genome level using chromatin immunoprecipitation (ChIP)-coupled sequencing, and the roles of OGG1 enriched on the genome were validated by molecular and system-level approaches. Results showed that signaling levels of cellular ROS generated by TNFα, induced enrichment of OGG1 at specific sites of chromatinized DNA, primarily in the regulatory regions of genes. OGG1-ChIP-ed genes are associated with important cellular and biological processes and OGG1 enrichment was limited to a time scale required for immediate cellular responses. Prevention of OGG1-DNA interactions by siRNA depletion led to modulation of NF-κB's DNA occupancy and differential expression of genes. Taken together these data show TNFα-ROS-driven enrichment of OGG1 at gene regulatory regions in the chromatinized DNA, which is a prerequisite to modulation of gene expression for prompt cellular responses to oxidant stress.


HIV-1 and AIDS: what are protective immune responses?
HIV-1 is the leading cause of death in sub-Saharan Africa, responsible for one in five deaths in the region. Although potent antiretroviral therapy has had a huge impact on HIV-associated morbidity and mortality in economically advantaged countries, it is beyond the reach of most infected people in the world. The development of an effective HIV vaccine would be a huge step towards stopping the pandemic, but an important precondition for such a vaccine is that it must induce a host immune response that can protect the host from HIV acquisition or disease progression. This article reviews the evidence that protective host immune responses do exist, either in highly exposed, persistently seronegative (HEPS) subjects or in HIV-1-infected long-term non-progressors (LTNPs), as well as efforts to reproduce putative protective immunity in animal vaccine models. HIV-1-specific cellular responses are a key to viral control in infected subjects, but generally fail in the long term. This suggests that the goal of a preventive HIV-1 vaccine should be sterile immunity, rather than improved virus control after infection. Achieving this goal will at least require the induction of HIV-1-specific cellular immune responses at the site of initial viral contact (generally the genital tract), perhaps in combination with HIV-1-specific neutralising antibody.


Human Salmonella Typhi exposure generates differential multifunctional cross-reactive T-cell memory responses against Salmonella Paratyphi and invasive nontyphoidal Salmonella.
There are no vaccines for most of the major invasive Salmonella strains causing severe infection in humans. We evaluated the specificity of adaptive T memory cell responses generated after Salmonella Typhi exposure in humans against other major invasive Salmonella strains sharing capacity for dissemination. T memory cells from eleven volunteers who underwent controlled oral challenge with wt S. Typhi were characterised by flow cytometry for cross-reactive cellular cytokine/chemokine effector responses or evidence of degranulation upon stimulation with autologous B-lymphoblastoid cells infected with either S. Typhi, Salmonella Paratyphi A (PA), S. Paratyphi B (PB) or an invasive nontyphoidal Salmonella strain of the S. Typhimurium serovar (iNTSTy). Blood T-cell effector memory (TEM) responses after exposure to S. Typhi in humans evolve late, peaking weeks after infection in most volunteers. Induced multifunctional CD4+ Th1 and CD8+ TEM cells elicited after S. Typhi challenge were cross-reactive with PA, PB and iNTSTy. The magnitude of multifunctional CD4+ TEM cell responses to S. Typhi correlated with induction of cross-reactive multifunctional CD8+ TEM cells against PA, PB and iNTSTy. Highly multifunctional subsets and T central memory and T effector memory cells that re-express CD45 (TEMRA) demonstrated less heterologous T-cell cross-reactivity, and multifunctional Th17 elicited after S. Typhi challenge was not cross-reactive against other invasive Salmonella. Gaps in cross-reactive immune effector functions in human T-cell memory compartments were highly dependent on invasive Salmonella strain, underscoring the importance of strain-dependent vaccination in the design of T-cell-based vaccines for invasive Salmonella.


Intrathyroidal cytokine production in thyroid disease.
The intrathyroidal production of Interferon gamma, tumour necrosis factor alpha and beta, Interleukin-1 alpha and beta, Interleukin-6, platelet-derived growth factor A and of transforming growth factor-beta was analysed in patients with autoimmune and non-autoimmune thyroid disease. Cytokines were assessed indirectly by slot blot mRNA analysis in fresh tissue samples (unpurified cells, infiltrating mononuclear cells and thyroid follicular cells), in thyroid follicular cells in primary culture, as well as in thyroid-derived T-cell clones. The production of Interleukin-1 alpha and beta, Interleukin-6 and transforming growth factor beta was additionally measured by bioassay. Cytokine production by thyroid-infiltrating mononuclear cells generally did not differ between autoimmune and non-autoimmune samples, the whole panel of all cytokines being found in freshly purified cells as well as in thyroid-derived T-cell clones from patient with Graves' disease, as well as with multinodular non-toxic goitre. Thyroid follicular cells produced Interleukin-1 alpha, Interleukin-6 and transforming growth factor beta. Interleukin-1 and Interleukin-6 production did not differ between thyroid follicular cells from autoimmune and non-autoimmune thyroids. Transforming growth factor beta was, however, lower in non-toxic goitre than in Graves' disease and in normal thyroid tissue, but could be increased by exposure of the cells to micromolar concentrations of iodide. This seemed of special interest, as transforming growth factor beta proved to inhibit thyroid follicular cell growth in response to known growth stimuli, such as insulin-like growth factor I or epidermal growth factor.(ABSTRACT TRUNCATED AT 250 WORDS)


Manufacture, characterization, and pharmacodynamic evaluation of engineered ipratropium bromide particles.
The intent of this research was to generate and characterize respirable particles of ipratropium bromide (IPB), a short-acting anticholinergic bronchodilator, to achieve demonstrable sustained-release properties. The value of a long-acting anticholinergic agent is evident in the use of tiotropium for the treatment of chronic obstructive pulmonary disease. Hollow, spherical particles of ipratropium bromide suitable for inhalation were generated using a spray-drying process and characterized by laser diffraction particle size analysis, scanning electron microscopy, dynamic vapor sorption, X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, and dissolution testing. Experimental design techniques were used to identify critical process parameters and optimize the spray drying process. Pharmacodynamic studies were conducted to determine duration of effect. Crystalline, stable, respirable particles with a range of dissolution profiles were manufactured by application of polylactic acid (PLA) coatings of 1, 5, 10, 15, 30, and 50% w/w. A novel, robust, modified Type IV dissolution method discriminated between formulations and guided their development. Preliminary studies in guinea pigs indicated an increased duration of bronchodilatory effect for 30% PLA-coated particles (56.3 min) particles compared with IPB powders alone (11.0 min). Sustained-release respirable particles of ipratropium bromide were developed using a PLA spray coating approach and a trend for increased duration of effect was demonstrated in guinea pigs.


A scoping review of unintended harm associated with public health interventions: towards a typology and an understanding of underlying factors.
Unintended harm theory as related to public health interventions (PHI) is under developed, with harm evaluation and reporting often absent or incomplete. This review presents a typology for, and underlying factors linked to, PHI-associated unintended harm. This scoping review was conducted electronically and includes articles from 1992 to June of 2013. Out of 2,490 originally identified titles, 26 full-text articles were included that discussed unintended harm associated with PHI. An iterative data analysis process was utilized to identify both a typology and underlying factors associated with unintended harm. A typology of PHI-associated unintended harm was identified: (1) physical; (2) psychosocial; (3) economic; (4) cultural and (5) environmental. Five underlying factors associated with PHI unintended harm emerged: (1) limited and/or poor quality evidence; (2) prevention of one extreme leads to another (boomerang effects); (3) lack of community engagement; (4) ignoring root causes; and (5) higher-income country PHI implementation in a lower- or middle-income country. PHI planning and evaluation frameworks may benefit from the consideration and potential incorporation of the unintended harm typology and underlying factors.


Association between atrial fibrillation and Helicobacter pylori.
The connection between atrial fibrillation (AF) and H. pylori (HP) infection is still matter of debate. We performed a systematic review and metanalysis of studies reporting the association between AF and HF. A systematic review of all available reports in literature of the incidence of HP infection in AF and comparing this incidence with subjects without AF were analysed. Risk ratio and 95% confidence interval (CI) and risk difference with standard error (SE) were the main statistics indexes. Six retrospective studies including a total of 2921 were included at the end of the selection process. Nine hundred-fifty-six patients (32.7%) were in AF, whereas 1965 (67.3%) were in normal sinus rhythm (NSR). Overall, 335 of 956 patients with AF were HP positive (35%), whereas 621 were HP negative (65%). In addition, 643 of 1965 NSR patients (32.7%) were HP positive while 1,322 were negative (67.3%; Chi-square 2.15, p = 0.21). The Cumulative Risk Ratio for AF patients for developing an HP infection was 1.19 (95% CI 1.08-1.41). In addition, a small difference risk towards AF was found (0.11 [SE = 0.04]). Moreover, neither RR nor risk difference were influenced by the geographic area at meta-regression analysis. Finally, there was a weak correlation between AF and HP (coefficient = 0.04 [95% CI -0.01-0.08]). We failed to find any significant correlation between H. pylori infection and AF and, based on our data, it seems unlikely than HP can be considered a risk factor for AF. Further larger research is warranted.


Body weight after stroke: lessons from the obesity paradox.
Outcome after acute stroke is determined to a large extent by poststroke complications. Nutritional status and metabolic balance may substantially contribute to outcome after stroke. Key mechanisms of stroke pathophysiology can induce systemic catabolic imbalance with impaired metabolic efficiency and degradation of body tissues. Tissue wasting, sarcopenia, and cachexia may impair and delay poststroke rehabilitation and worsen the prognosis. Although current guidelines for secondary prevention after stroke recommend weight reduction, increasing evidence suggests that patients who are overweight and mildly obese may actually have a better outcome. An "obesity paradox" has been identified to describe the contrasting impact of being overweight in patients with chronic illness compared with healthy populations. We present an overview on the metabolic regulation in patients with stroke and evaluate current data on the impact of body weight and weight change after stroke. The emerging picture suggests that being overweight and obese may impact patients with stroke differently than it does healthy subjects. We propose that current knowledge on obesity and its management in primary prevention cannot be transferred to patients with established stroke. Systematic studies on changes in body composition after stroke and on treatment options are warranted to establish the pathophysiology and evidence-driven management of nutritional status in these patients.


SARS transmission among hospital workers in Hong Kong.
Despite infection control measures, breakthrough transmission of severe acute respiratory syndrome (SARS) occurred for many hospital workers in Hong Kong. We conducted a case-control study of 72 hospital workers with SARS and 144 matched controls. Inconsistent use of goggles, gowns, gloves, and caps was associated with a higher risk for SARS infection (unadjusted odds ratio 2.42 to 20.54, p < 0.05). The likelihood of SARS infection was strongly associated with the amount of personal protection equipment perceived to be inadequate, having <2 hours of infection control training, and not understanding infection control procedures. No significant differences existed between the case and control groups in the proportion of workers who performed high-risk procedures, reported minor protection equipment problems, or had social contact with SARS-infected persons. Perceived inadequacy of personal protection equipment supply, infection control training <2 hours, and inconsistent use of personal protection equipment when in contact with SARS patients were significant independent risk factors for SARS infection.


Food Additives, Gut Microbiota, and Irritable Bowel Syndrome: A Hidden Track.
The interactions between diet, gut microbiota, and irritable bowel syndrome (IBS) have many complex mechanisms that are not fully understood. Food additives are one component of the modern human diet that deserves attention from science and government policies. This review aims at identifying the current knowledge about the impact of food additives on gut microbiota and their potential role in the development of IBS. To date, few data on the effect of food additives on gut microbiota in IBS patients are available. However, exposure to food additives could induce the dysbiosis and dysregulation of gut homeostasis with an alteration of the gut barrier and activation of the immune response. These microbial changes could exacerbate the gut symptoms associated with IBS, such as visceral pain, low-grade inflammation, and changes in bowel habits. Some additives (polyols) are excluded in the low fermentable oligo-, di- and monosaccharide, and polyol (FODMAP), diets for IBS patients. Even if most studies have been performed in animals, and human studies are required, many artificial sweeteners, emulsifiers, and food colorants could represent a potential hidden driver of IBS, through gut microbiota alterations. Consequently, food additives should be preventively avoided in the diet as well as dietary supplements for patients with IBS.


A randomized, multicentre, open-label phase II proof-of-concept trial investigating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19: the Donated Antibodies Working against nCoV (DAWn-Plasma) trial.
The COVID-19 pandemic has imposed an enormous burden on health care systems around the world. In the past, the administration of convalescent plasma of patients having recovered from SARS and severe influenza to patients actively having the disease showed promising effects on mortality and appeared safe. Whether or not this also holds true for the novel SARS-CoV-2 virus is currently unknown. DAWn-Plasma is a multicentre nation-wide, randomized, open-label, phase II proof-of-concept clinical trial, evaluating the clinical efficacy and safety of the addition of convalescent plasma to the standard of care in patients hospitalized with COVID-19 in Belgium. Patients hospitalized with a confirmed diagnosis of COVID-19 are eligible when they are symptomatic (i.e. clinical or radiological signs) and have been diagnosed with COVID-19 in the 72 h before study inclusion through a PCR (nasal/nasopharyngeal swab or bronchoalveolar lavage) or a chest-CT scan showing features compatible with COVID-19 in the absence of an alternative diagnosis. Patients are randomized in a 2:1 ratio to either standard of care and convalescent plasma (active treatment group) or standard of care only. The active treatment group receives 2 units of 200 to 250 mL of convalescent plasma within 12 h after randomization, with a second administration of 2 units 24 to 36 h after ending the first administration. The trial aims to include 483 patients and will recruit from 25 centres across Belgium. The primary endpoint is the proportion of patients that require mechanical ventilation or have died at day 15. The main secondary endpoints are clinical status on day 15 and day 30 after randomization, as defined by the WHO Progression 10-point ordinal scale, and safety of the administration of convalescent plasma. This trial will either provide support or discourage the use of convalescent plasma as an early intervention for the treatment of hospitalized patients with COVID-19 infection. ClinicalTrials.gov NCT04429854 . Registered on 12 June 2020 - Retrospectively registered.


Collective dynamics of flowing colloids during pore clogging.
Based on direct numerical simulations of the coupled motion of particles and fluid, this study analyzes the collective hydrodynamic and colloidal effects of flowing microparticles during the formation of different 3D clogging patterns at a pore entrance. Simulations of flowing suspensions through a pore with various simulation conditions show that particle concentration and surface interactions play a major role in the occurrence of the bridging phenomenon (simultaneous adhesion of many particles). In the absence of DLVO repulsive forces, plugging is characterized by the temporal reduction of the bulk permeability when increasing the volume fraction of the flowing suspension up to 20%. Under these conditions, different structures of particle aggregates (from cluster to cake plug) are formed at the pore entrance yielding different evolution rates of hydrodynamic resistance to the flow. Taking into account DLVO repulsive forces in simulations for a particle concentration equal to 10%, we observe the transition from dendritic structures (for low repulsion) to dense aggregates (for high repulsion). At high DLVO repulsive forces, the scenario of pore clogging is controlled by the collective behavior of many interacting particles. It leads to the formation of a jamming phase (Wigner glass phase) with transient clusters of interacting particles at the pore entrance. The network of jammed particles collapses when the force chains among the particles are overcome by the flow stress. The build-up and the collapse of the jammed phase at the pore entrance induce temporal permeability fluctuations. According to the relative magnitude of particle-particle and particle-wall interactions, when the jammed phase is disorganized by the flow, the residual force in the network can accelerate particles and lead to particle adhesion at the wall inducing a pore blockage and a rapid reduction of the bulk permeability.


Profound tumor-specific Th2 bias in patients with malignant glioma.
Vaccination against tumor-associated antigens is one promising approach to immunotherapy against malignant gliomas. While previous vaccine efforts have focused exclusively on HLA class I-restricted peptides, class II-restricted peptides are necessary to induce CD4+ helper T cells and sustain effective anti-tumor immunity. In this report we investigated the ability of five candidate peptide epitopes derived from glioma-associated antigens MAGE and IL-13 receptor α2 to detect and characterize CD4+ helper T cell responses in the peripheral blood of patients with malignant gliomas. Primary T cell responses were determined by stimulating freshly isolated PBMCs from patients with primary glioblastoma (GBM) (n = 8), recurrent GBM (n = 5), meningioma (n = 7), and healthy controls (n = 6) with each candidate peptide, as well as anti-CD3 monoclonal antibody (mAb) and an immunodominant peptide epitope derived from myelin basic protein (MBP) serving as positive and negative controls, respectively. ELISA was used to measure IFN-γ and IL-5 levels, and the ratio of IFN-γ/IL-5 was used to determine whether the response had a predominant Th1 or Th2 bias. We demonstrate that novel HLA Class-II restricted MAGE-A3 and IL-13Rα2 peptides can detect T cell responses in patients with GBMs as well as in healthy subjects. Stimulation with a variety of peptide antigens over-expressed by gliomas is associated with a profound reduction in the IFN-γ/IL-5 ratio in GBM patients relative to healthy subjects. This bias is more pronounced in patients with recurrent GBMs. Therapeutic vaccine strategies to shift tumor antigen-specific T cell response to a more immunostimulatory Th1 bias may be needed for immunotherapeutic trials to be more successful clinically.


Active ageing: independence through technology assisted health optimisation.
The potential doubling in the percentage of the elderly within the populations of Europe and beyond over the next decades has focused informatics research on the development Assistive Technologies and Smart Homes. However its concentration on creating a supportive home environment also has the potential for makings its users over dependent on its facilities and as a result trapped within it. This paper outlines an approach that extends the smart homes concept out into the wider community to create a smart environment that not only maintains contact with all their home-based services, but also expands these to include other facilities needed to assist them whilst on the move. This involves the convergence of physiological monitoring, communications and computing with leading-edge textile technologies, which uses a multi-layered, multi-functional clothing system as a mobile and extended variant of a smart home IP hub. In addition to variable functionality capabilities of the clothing layers in terms of thermal, shock-absorbent and other characteristics, wireless IP connectivity is provided between layers with external links typically being WiFi enabled. Health optimisation is provided by on-going lifestyle guidance/action feedback based on auto-diagnostic analysis.


Effect of atomic charge, solvation, entropy, and ligand protonation state on MM-PB(GB)SA binding energies of HIV protease.
The molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) and MM-generalized-Born surface area (MM-GBSA) approaches are commonly used in molecular modeling and drug design. Four critical aspects of these approaches have been investigated for their effect on calculated binding energies: (1) the atomic partial charge method used to parameterize the ligand force field, (2) the method used to calculate the solvation free energy, (3) inclusion of entropy estimates, and (4) the protonation state of the ligand. HIV protease has been used as a test case with six structurally different inhibitors covering a broad range of binding strength to assess the effect of these four parameters. Atomic charge methods are demonstrated to effect both the molecular dynamics (MD) simulation and MM-PB(GB)SA binding energy calculation, with a greater effect on the MD simulation. Coefficients of determination and Spearman rank coefficients were used to quantify the performance of the MM-PB(GB)SA methods relative to the experimental data. In general, better performance was achieved using (i) atomic charge models that produced smaller mean absolute atomic charges (Gasteiger, HF/STO-3G and B3LYP/cc-pVTZ), (ii) the MM-GBSA approach over MM-PBSA, while (iii) inclusion of entropy had a slightly positive effect on correlations with experiment. Accurate representation of the ligand protonation state was found to be important. It is demonstrated that these approaches can distinguish ligands according to binding strength, underlining the usefulness of these approaches in computer-aided drug design.


A sulfur dioxide climate feedback on early Mars.
Ancient Mars had liquid water on its surface and a CO2-rich atmosphere. Despite the implication that massive carbonate deposits should have formed, these have not been detected. On the basis of fundamental chemical and physical principles, we propose that climatic conditions enabling the existence of liquid water were maintained by appreciable atmospheric concentrations of volcanically degassed SO2 and H2S. The geochemistry resulting from equilibration of this atmosphere with the hydrological cycle is shown to inhibit the formation of carbonates. We propose an early martian climate feedback involving SO2, much like that maintained by CO2 on Earth.


Advanced maternal age and risk of adverse perinatal outcome among women with congenital heart disease: A nationwide register-based cohort study.
Women with maternal congenital heart disease have a higher risk of preterm birth (PTB) and giving birth to a small for gestational age (SGA) infant. Advanced maternal age (≥35 years) likewise increases the risk of PTB and SGA, probably explained by poorer cardiovascular status. It is likely that advanced maternal age is particularly detrimental in women with congenital heart disease. We aimed to determine whether the pattern of higher risk of PTB and SGA with higher maternal age varied among women with and without congenital heart disease. We hypothesised that the effect of age is higher among women with congenital heart disease. We did a cohort study using Danish nationwide registers. Births from 1997 to 2014 were included. Cox regressions were used to estimate hazard ratios (HRs) for PTB and SGA. Universal and congenital heart disease-specific references were used for comparison. We included 932 772 births among 548 314 women. HRs of PTB and SGA were 1.55 (95% confidence interval [CI] 1.37, 1.77) and 1.43 (95% CI 1.29, 1.58) in women with congenital heart disease as compared to women without. For both PTB and SGA, HRs were higher for women ≥35 years as compared to women aged 25-29 years. HRs of PTB and SGA were higher among women with congenital heart disease within all strata of maternal age as compared to women without (eg 3.71, 95% CI 1.80, 7.63 vs 1.63, 95% CI 1.56, 1.70) for SGA for women aged 40-44 years). The pattern of higher risk of PTB and SGA with higher maternal age was, however, similar among women with and without congenital heart disease. Women with congenital heart disease had a higher risk of PTB and giving birth to an SGA infant at all maternal ages. These two risk factors did not, however, seem to potentiate each other.


Long-term results of 185 consecutive osseointegrated hearing device implantations: a comparison among children, adults, and elderly.
To determine the occurrence and type of perioperative and postoperative complications in patients implanted with an osseointegrated hearing device (OHD) (also known as BAHA/BAHS) and compare results in children, adults, and elderly and for different surgical techniques. Retrospective case file review. Tertiary referral center. Patients implanted with an OHD between 2004 and 2012, with more than 6 months of follow-up. OHD implantation. Implant loss, adverse skin reactions (Holgers' score, ≥2), skin overgrowth, and discomfort resulting in abutment and/or implant removal. One hundred eighty-five implantations in 176 patients were reviewed. Overall, 3.8% of the implants were lost spontaneously after a mean of 2.5 years. Implant loss in children was 18% versus 2.5% in adults and 3.8% in elderly. Adverse skin reactions occurred in 14% of observations overall; in 10% in children compared with 16% in adults and 9% in elderly. Partial or total skin overgrowth was seen in 4% and 6% of the observations in children and adults, respectively, whereas none of the elderly experienced this problem. The abutment was removed because of discomfort and/or no benefit in 10% overall, in 13% of adults, and in 6% of the elderly; none of the children opted for removal. Linear incision technique showed fewest complications. OHD implantation is a procedure with few major complications. Adverse skin reaction is the most common complication. Children lose the implant more frequently than adults. Elderly patients have less adverse skin reactions/skin overgrowth. Discomfort leading to abutment removal is a concern especially among adults.


ASK1 (MAP3K5) is transcriptionally upregulated by E2F1 in adipose tissue in obesity, molecularly defining a human dys-metabolic obese phenotype.
Obesity variably disrupts human health, but molecular-based patients' health-risk stratification is limited. Adipose tissue (AT) stresses may link obesity with metabolic dysfunction, but how they signal in humans remains poorly-characterized. We hypothesized that a transcriptional AT stress-signaling cascade involving E2F1 and ASK1 (MAP3K5) molecularly defines high-risk obese subtype. ASK1 expression in human AT biopsies was determined by real-time PCR analysis, and chromatin immunoprecipitation (ChIP) adopted to AT explants was used to evaluate the binding of E2F1 to the ASK1 promoter. Dual luciferase assay was used to measure ASK1 promoter activity in HEK293 cells. Effects of E2F1 knockout/knockdown in adipocytes was assessed utilizing mouse-embryonal-fibroblasts (MEF)-derived adipocyte-like cells from WT and E2F1-/- mice and by siRNA, respectively. ASK1 depletion in adipocytes was studied in MEF-derived adipocyte-like cells from WT and adipose tissue-specific ASK1 knockout mice (ASK1-ATKO). Human visceral-AT ASK1 mRNA (N = 436) was associated with parameters of obesity-related cardio-metabolic morbidity. Adjustment for E2F1 expression attenuated the association of ASK1 with fasting glucose, insulin resistance, circulating IL-6, and lipids (triglycerides, HDL-cholesterol), even after adjusting for BMI. Chromatin-immunoprecipitation in human-AT explants revealed BMI-associated increased occupancy of the ASK1 promoter by E2F1 (r2 = 0.847, p < 0.01). In adipocytes, siRNA-mediated E2F1-knockdown, and MEF-derived adipocytes of E2F1-knockout mice, demonstrated decreased ASK1 expression and signaling to JNK. Mutation/truncation of an E2F1 binding site in hASK1 promoter decreased E2F1-induced ASK1 promoter activity, whereas E2F1-mediated sensitization of ASK1 promoter to further activation by TNFα was inhibited by JNK-inhibitor. Finally, MEF-derived adipocytes from adipocyte-specific ASK1-knockout mice exhibited lower leptin and higher adiponectin expression and secretion, and resistance to the effects of TNFα. AT E2F1 -ASK1 molecularly defines a metabolically-detrimental obese sub-phenotype. Functionally, it may negatively affect AT endocrine function, linking AT stress to whole-body metabolic dysfunction.


Obsessive-compulsive syndromes and disorders: significance of comorbidity with bipolar and anxiety syndromes.
To determine the prevalence and clinical characteristics of comorbid obsessive compulsive disorders and syndromes (OCD/OCS), compared with pure OCD/OCS among adults in the community. Data were drawn from the Zurich Study, a longitudinal cohort study of 591 adults in the canton of Zurich. Comorbid OCD/OCS was compared with pure OCD/OCS groups in terms of distress, impairment, family history, suicide behavior and treatment using multivariable logistic regression analyses. OCD was significantly comorbid with bipolar I/II and minor bipolar disorders, anxiety states (GAD, repeated panic attacks) and social phobia, whereas there was no clear association between OCD and major depressive disorder or phobias other than social phobia. Results suggest that comorbid OCD/OCS is common among adults in the community, with the majority of those with OCD/OCS having at least one comorbid mood or anxiety disorder with a prevalence of 7.4% compared to 4.8% of remaining OCD/OCS. Comorbidity of OCD/OCS and anxiety states was more common among women (85.6 %) and comorbidity with bipolar spectrum was more common among men (69.6%). Comorbid OCD/OCS was associated with significantly higher levels of treatment seeking, impairment,distress and suicidality compared with pure OCD/OCS. Comorbidity with bipolar disorders significantly increased the risk for alcohol abuse/dependence. Comorbidity of OCD/OCS with bipolar disorder and bipolar spectrum disorders is common and very probably explains the association between OCD and depression found in other studies. The early recognition of bipolar/cyclothymic OCD/OCS may help to prevent the abuse of/dependence on alcohol.


Cognitive Intervention Through Photo-Integrated Conversation Moderated by Robots (PICMOR) Program: A Randomized Controlled Trial.
Social interaction might prevent or delay dementia, but little is known about the specific effects of various social activity interventions on cognition. This study conducted a single-site randomized controlled trial (RCT) of Photo-Integrated Conversation Moderated by Robots (PICMOR), a group conversation intervention program for resilience against cognitive decline and dementia. In the RCT, PICMOR was compared to an unstructured group conversation condition. Sixty-five community-living older adults participated in this study. The intervention was provided once a week for 12 weeks. Primary outcome measures were the cognitive functions; process outcome measures included the linguistic characteristics of speech to estimate interaction quality. Baseline and post-intervention data were collected. PICMOR contains two key features: 1) photos taken by the participants are displayed and discussed sequentially; and 2) a robotic moderator manages turn-taking to make sure that participants are allocated the same amount of time. Among the primary outcome measures, one of the subcategories of cognitive functions, verbal fluency significantly improved in the intervention group. Among the process outcome measures, a part of the subcategories of linguistic characteristics of speech, the amount of speech and richness of words, proportion of providing topics, questions, and answers in total utterances were larger for the intervention group. This study demonstrated for the first time the positive effects of a robotic social activity intervention on cognitive function in healthy older adults via RCT. The group conversation generated by PICMOR may improve participants' verbal fluency since participants have more opportunity to provide their own topics, asking and answering questions which results in exploring larger vocabularies. PICMOR is available and accessible to community-living older adults. Clinical Trial Registration: UMIN Clinical Trials Registry, identifier UMIN000036667.


Comparison of outcomes after UKA in patients with and without chondrocalcinosis: a matched cohort study.
Chondrocalcinosis can be associated with an inflammatory arthritis and aggressive joint destruction. There is uncertainty as to whether chondrocalcinosis represents a contraindication to unicompartmental knee arthroplasty (UKA). This study reports the outcome of a consecutive series of patients with chondrocalcinosis and medial compartment osteoarthritis treated with UKA matched to controls. Between 1998 and 2008, 88 patients with radiological chondrocalcinosis (R-CCK) and 67 patients with histological chondrocalcinosis (H-CCK) were treated for end-stage medial compartment arthritis with Oxford UKA. One-to-two matching was performed to controls, treated with UKA, but without evidence of chondrocalcinosis. Functional outcome and implant survival were assessed in each group. The mean follow-up was 10 years. The mean Oxford Knee Score (OKS) at final follow-up was 43, 41 and 41 in H-CCK, R-CCK and control groups (change from baseline OKS was 21, 18 and 15, respectively). The change was significantly higher in H-CCK than in control but was not significantly different in R-CCK. Ten-year survival was 96 % in R-CCK, 86 % in H-CCK and 98 % in controls. Although the survival in H-CCK was significantly worse than in control, only one failure was due to disease progression. The presence of R-CCK does not influence functional outcome or survival following UKA. Pre-operative radiological evidence of CCK should not be considered to be a contraindication to UKA. H-CCK is associated with significantly improved clinical outcomes but also a higher revision rate compared with controls. Case control study, Level III.


Group transdiagnostic cognitive-behavior therapy for anxiety disorders: a pragmatic randomized clinical trial.
Transdiagnostic group cognitive-behavioral therapy (tCBT) is a delivery model that could help overcome barriers to large-scale implementation of evidence-based psychotherapy for anxiety disorders. The aim of this study was to assess the effectiveness of combining group tCBT with treatment-as-usual (TAU), compared to TAU, for the treatment of anxiety disorders in community-based mental health care. In a multicenter single-blind, two-arm pragmatic superiority randomized trial, we recruited participants aged 18-65 who met DSM-5 criteria for principal diagnoses of generalized anxiety disorder, social anxiety disorder, panic disorder, or agoraphobia. Group tCBT consisted of 12 weekly 2 h sessions. There were no restrictions for TAU. The primary outcome measures were the Beck Anxiety Inventory (BAI) and clinician severity rating from the Anxiety and Related Disorders Interview Schedule for DSM-5 (ADIS-5) for the principal anxiety disorder at post-treatment, with intention-to-treat analysis. A total of 231 participants were randomized to either tCBT + TAU (117) or TAU (114), with outcome data available for, respectively, 95 and 106. Results of the mixed-effects regression models showed superior improvement at post-treatment for participants in tCBT + TAU, compared to TAU, for BAI [p < 0.001; unadjusted post-treatment mean (s.d.): 13.20 (9.13) v. 20.85 (10.96), Cohen's d = 0.76] and ADIS-5 [p < 0.001; 3.27 (2.19) v. 4.93 (2.00), Cohen's d = 0.79]. Our findings suggest that the addition of group tCBT into usual care can reduce symptom severity in patients with anxiety disorders, and support tCBT dissemination in routine community-based care.


Associations of different phenotypes of wheezing illness in early childhood with environmental variables implicated in the aetiology of asthma.
Asthma is a complex heterogeneous disease that has increased in prevalence in many industrialised countries. However, the causes of asthma inception remain elusive. Consideration of sub-phenotypes of wheezing may reveal important clues to aetiological risk factors. Longitudinal phenotypes capturing population heterogeneity in wheezing reports from birth to 7 years were derived using latent class analysis in the Avon Longitudinal Study of Parents and Children (ALSPAC). Probability of class membership was used to examine the association between five wheezing phenotypes (transient early, prolonged early, intermediate-onset, late-onset, persistent) and early life risk factors for asthma. Phenotypes had similar patterns and strengths of associations with early environmental factors. Comparing transient early with prolonged early wheezing showed a similar pattern of association with most exposure variables considered in terms of the direction of the effect estimates but with prolonged early wheezing tending to have stronger associations than transient early wheezing except for parity and day care attendance. Associations with early life risk factors suggested that prolonged early wheeze might be a severe form of transient early wheezing. Although differences were found in the associations of early life risk factors with individual phenotypes, these did not point to novel aetiological pathways. Persistent wheezing phenotype has features suggesting overlap of early and late-onset phenotypes.


Telomeric Transcription and Telomere Rearrangements in Quiescent Cells.
Despite the condensed nature of terminal sequences, the telomeres are transcribed into a group of noncoding RNAs, including the TElomeric Repeat-containing RNA (TERRA). Since the discovery of TERRA, its evolutionary conserved function has been confirmed, and its involvement in telomere length regulation, heterochromatin establishment, and telomere recombination has been demonstrated. We previously reported that TERRA is upregulated in quiescent fission yeast cells, although the global transcription is highly reduced. Elevated telomeric transcription was also detected when telomeres detach from the nuclear periphery. These intriguing observations unveil unexpected facets of telomeric transcription in arrested cells. In this review, we present the different aspects of TERRA transcription during quiescence and discuss their implications for telomere maintenance and cell fate.


Host tree age as a selective pressure leading to local adaptation of a population of a polyphagous Lepidoptera in virgin boreal forest.
We tested the hypothesis that host tree age may act as a selective factor and lead to local adaptation of the hemlock looper (Lambdina fiscellaria), a geometrid Lepidoptera that has a wide geographical distribution and has evolved in different eco-zones characterized by different levels of floristic composition, age structure and fragmentation level. Considering that hemlock looper outbreaks mainly occurred in old forests, we compared the biological performances of two populations. The first population was collected in the northern virgin boreal forest, which is dominated by mature and overmature coniferous stands that have not suffered from human disturbance. The other population was collected in the southern mixed-wood forest, which is more diversified and has been modified by forest harvesting. Larvae were reared under controlled conditions on foliage from three age classes of balsam fir trees: juvenile, mature and overmature. Although we measured significant variations of biological performances between the two populations, no significant effect of the age of the balsam fir trees could be detected for males from both populations or for females from the southern population. However, northern females were strongly affected by the age of balsam fir trees on which they fed, as their pupal weight was 12% higher and their fecundity increased by 27% on overmature trees compared with juvenile ones. These results indicate that under the same selective pressure, females adapt their strategy to maximize their fitness, and thus they appear as the driving force of evolution through the local adaptation concept. Furthermore, the two populations evolved in distinct habitats and their adaptation reflects selective pressures occurring inside their original environment. This is the first report on local adaptation of an herbivore that is mediated by host tree age. Changes in forest age structure may have a considerable impact on insect local adaptation and presumably on their population dynamics.


Role of the Escherichia coli FadR regulator in stasis survival and growth phase-dependent expression of the uspA, fad, and fab genes.
The increased expression of the uspA gene of Escherichia coli is an essential part of the cell's response to growth arrest. We demonstrate that stationary-phase activation of the uspA promoter is in part dependent on growth phase-dependent inactivation or repression of the FadR regulator. Transcription of uspA is derepressed during exponential growth in fadR null mutants or by including the fatty acid oleate in the growth medium of FadR+ cells. The results of DNA footprinting analysis show that FadR binds downstream of the uspA promoter in the noncoding region. Thus, uspA is a member of the fadR regulon. All the fad-lacZ fusions examined (fadBA, fadL, and fadD) are increasingly expressed in stationary phase with kinetics similar to that of the increased expression of uspA. In contrast, beta-galactosidase levels decrease during stationary phase in a fabA-lacZ lysogen, consistent with the role of FadR as an activator of fabA. The growth phase-dependent increased and decreased transcription of fad genes and fabA, respectively, is dependent on the status of the fadR gene. Cells carrying a mutation in the FadR gene (fadRS219N) that makes it nonderepressible exhibit a weak stationary-phase induction of uspA and fad genes. In addition, cells carrying fadRS219N survive long-term stasis poorly, indicating that FadR-dependent alterations in fatty acid metabolism are an integral and important part of the adaptation to stationary phase.


A Negative Feedback Loop Regulates Integrin Inactivation and Promotes Neutrophil Recruitment to Inflammatory Sites.
Neutrophils are abundant circulating leukocytes that are rapidly recruited to sites of inflammation in an integrin-dependent fashion. Contrasting with the well-characterized regulation of integrin activation, mechanisms regulating integrin inactivation remain largely obscure. Using mouse neutrophils, we demonstrate in this study that the GTPase activating protein ARAP3 is a critical regulator of integrin inactivation; experiments with Chinese hamster ovary cells indicate that this is not restricted to neutrophils. Specifically, ARAP3 acts in a negative feedback loop downstream of PI3K to regulate integrin inactivation. Integrin ligand binding drives the activation of PI3K and of its effectors, including ARAP3, by outside-in signaling. ARAP3, in turn, promotes localized integrin inactivation by negative inside-out signaling. This negative feedback loop reduces integrin-mediated PI3K activity, with ARAP3 effectively switching off its own activator, while promoting turnover of substrate adhesions. In vitro, ARAP3-deficient neutrophils display defective PIP3 polarization, adhesion turnover, and transendothelial migration. In vivo, ARAP3-deficient neutrophils are characterized by a neutrophil-autonomous recruitment defect to sites of inflammation.


The Effects of Bikram Yoga on Health: Critical Review and Clinical Trial Recommendations.
Bikram yoga is a style of hatha yoga involving a standarized series of asanas performed to an instructional dialogue in a heated environment (40.6°C, 40% humidity). Several studies evaluating the effect of Bikram yoga on health-related outcomes have been published over the past decade. However, to date, there are no comprehensive reviews of this research and there remains a lack of large-scale, robustly-designed randomised controlled trials (RCT) of Bikram yoga training. The purpose of this review is to contextualise and summarise trials that have evaluated the effects of Bikram yoga on health and to provide recommendations for future research. According to published literature, Bikram yoga has been shown to improve lower body strength, lower and upper body range of motion, and balance in healthy adults. Non-RCTs report that Bikram yoga may, in some populations, improve glucose tolerance, bone mineral density, blood lipid profile, arterial stiffness, mindfulness, and perceived stress. There is vast potential for further, improved research into the effects of Bikram yoga, particularly in unhealthy populations, to better understand intervention-related adaptations and their influence on the progression of chronic disease. Future research should adhere to CONSORT guidelines for better design and reporting to improve research quality in this field.


Albendazole Sulfoxide Plasma Levels and Efficacy of Antiparasitic Treatment in Patients With Parenchymal Neurocysticercosis.
The efficacy of albendazole therapy in patients with parenchymal neurocysticercosis (NCC) is suboptimal. Plasma levels of albendazole sulfoxide (ASOX), the active metabolite of albendazole, are highly variable among patients. We hypothesized that high ASOX plasma levels during albendazole therapy may be associated with an increased antiparasitic efficacy. ASOX plasma levels were measured at treatment day 7 in 118 patients with parenchymal NCC enrolled in a treatment trial. The relationships between increasing ASOX plasma levels with the proportion of cysts resolved and the proportion of patients with complete cyst resolution (evaluated by 6-month brain magnetic resonance) were assessed. There was a trend toward a higher proportion of cysts resolved and a higher proportion of patients cured with increasing quartiles of ASOX plasma levels. In patients with 3 or more brain cysts, the regression analysis adjusted by the concomitant administration of praziquantel (PZQ) showed a 2-fold increase in the proportion of cysts resolved (risk ratio [RR], 1.98; 95% confidence interval [CI], 1.01-3.89; P = .048) and 2.5-fold increase in the proportion of patients cured (RR, 2.45; 95% CI, .94-6.36; P = .067) when ASOX levels in the highest vs the lowest quartile were compared. No association was found in patients with 1-2 brain cysts. We suggest an association between high ASOX plasma levels and increased antiparasitic efficacy in patients with parenchymal NCC. Nonetheless, this association is also influenced by other factors including parasite burden and concomitant administration of PZQ. These findings may serve to individualize and/or adjust therapy schemes to avoid treatment failure.