Sex differences in central hemodynamics and their relationship to left ventricular diastolic function.
This study aimed to investigate sex differences in the association between arterial stiffness and left ventricular (LV) diastolic dysfunction. Heart failure with preserved ejection fraction is more common in women. Arterial stiffness has been suggested as a significant contributor to the development of heart failure. We hypothesized that the association between arterial stiffness and LV diastolic function would be stronger in women than in men. Two-dimensional, Doppler echocardiography and radial artery tonometry were performed simultaneously in 158 age-matched subjects (79 males, 79 females; mean age: 58 ± 10 years) without any structural heart disease or LV systolic dysfunction. The peripheral blood pressure and pulse pressure (PP) were similar between sexes. However, central PP and augmentation index were significantly higher and PP amplification was significantly lower in women (1.31 vs. 1.19, p < 0.001). The associations of PP amplification with early diastolic mitral annular (Em) velocity and transmitral to mitral annular early diastolic velocity ratio (E/Em) were significant in women (r = 0.38, p = 0.001; r = -0.36, p = 0.001), whereas no significant association was found in men (r = 0.09, p = 0.428, r = -0.14, p = 0.215). Multiple regression analysis revealed that PP amplification had an independent correlation with Em velocity only in women. Despite similar peripheral PP, the central hemodynamics reflecting arterial stiffness were different between men and women. LV diastolic function correlates significantly with the parameters representing arterial stiffness only in women. We suggest that the effects of earlier wave reflection on central pressure may contribute to greater susceptibility to heart failure with preserved LV ejection fraction in women.


Rippling is a predatory behavior in Myxococcus xanthus.
Cells of Myxococcus xanthus will, at times, organize their movement such that macroscopic traveling waves, termed ripples, are formed as groups of cells glide together on a solid surface. The reason for this behavior has long been a mystery, but we demonstrate here that rippling is a feeding behavior which occurs when M. xanthus cells make direct contact with either prey or large macromolecules. Rippling has been observed during two fundamentally distinct environmental conditions: (i) starvation-induced fruiting body development and (ii) predation of other organisms. Our results indicate that case (i) does not occur in all wild-type strains and is dependent on the intrinsic level of autolysis. Analysis of predatory rippling indicates that rippling behavior is inducible during predation on proteobacteria, gram-positive bacteria, yeast (such as Saccharomyces cerevisiae), and phage. Predatory efficiency decreases under genetic and physiological conditions in which rippling is inhibited. Rippling will also occur in the presence of purified macromolecules such as peptidoglycan, protein, and nucleic acid but does not occur in the presence of the respective monomeric components and also does not occur when the macromolecules are physically separated from M. xanthus cells. We conclude that rippling behavior is a mechanism utilized to efficiently consume nondiffusing growth substrates and that developmental rippling is a result of scavenging lysed cell debris.


G6PD Orchestrates Genome-Wide DNA Methylation and Gene Expression in the Vascular Wall.
Recent advances have revealed the importance of epigenetic modifications to gene regulation and transcriptional activity. DNA methylation, a determinant of genetic imprinting and the de novo silencing of genes genome-wide, is known to be controlled by DNA methyltransferases (DNMT) and demethylases (TET) under disease conditions. However, the mechanism(s)/factor(s) influencing the expression and activity of epigenetic writers and erasers, and thus DNA methylation, in healthy vascular tissue is incompletely understood. Based on our recent studies, we hypothesized that glucose-6-phosphate dehydrogenase (G6PD) is a modifier of DNMT and TET expression and activity and an enabler of gene expression. In the aorta of CRISPR-edited rats with the Mediterranean G6PD variant, we determined DNA methylation by whole-genome bisulfite sequencing, gene expression by RNA sequencing, and large artery stiffness by echocardiography. Here, we documented higher expression of Dnmt1, Dnmt3a, Tet2, and Tet3 in aortas from Mediterranean G6PDS188F variant (a loss-of-function single nucleotide polymorphism) rats than their wild-type littermates. Concomitantly, we identified 17,618 differentially methylated loci genome-wide (5787 hypermethylated loci, including down-regulated genes encoding inflammation- and vasoconstriction-causing proteins, and 11,827 hypomethylated loci, including up-regulated genes encoding smooth muscle cell differentiation- and fatty acid metabolism-promoting proteins) in aortas from G6PDS188F as compared to wild-type rats. Our results demonstrated that nitric oxide, which is generated in a G6PD-derived NADPH-dependent manner, increases TET and decreases DNMT activity. Further, we observed less large artery (aorta) stiffness in G6PDS188F as compared to wild-type rats. These results establish a noncanonical function of the wild-type G6PD and G6PDS188F variant in the regulation of DNA methylation and gene expression in healthy vascular tissue and reveal that the G6PDS188F variant contributes to reducing large artery stiffness.


Does covid-19 pandemic tell us something about time and space to meet our being, belonging and becoming needs?
People's perceptions of events like a pandemic are shaped by individual experiences within their socio-cultural context. Attributing negative or positive meanings to an experience may influence the sense of Being, Belonging and Becoming. To investigate the impact of the isolation/social distancing measures on people's sense of Being, Belonging, Becoming and overall sense of Occupational Wholeness compared to the time before the Covid-19 Pandemic as it is perceived by an Iranian population. The Model of Occupational Wholeness used to inform the theoretical basis of this study and development of the survey questions. An internet-based survey using a convenient and snowball sampling method was conducted. A self-administered questionnaire was published using a software named Porsline. A sample of 1624 members of the general population in Iran (67% response rate) completed the questionnaire within the first four weeks of the isolation/social distancing period starting on 18 March 2020. The Data was analysed by the SPSS 22. The participants showed a more positive perceived level of Being and Belonging as well as an overall sense of Occupational Wholeness, and no difference in the perceived sense of Becoming during the isolation/social distancing period compared to the time before the Covid 19 pandemic. The findings show that the isolation/social distancing measures were perceived by participants as an opportunity to meet some of their Being, and Belonging needs that contribute to an overall sense of OccupationalWholeness.This highlights the role that Occupational science and Occupational therapy may have in helping people in situations when they need to rethink and replan for what they Do and the way they attribute meaning to their experiences.


The use of Luria's method for the neurobehavioral assessment of encephalopathy in an adolescent: application in a rehabilitation setting.
Standardized neuropsychological test batteries demonstrate their greatest reliability and validity in patients with focal, well-defined neurologic disease. In these patients, the test profiles typically highlight focal areas of strengths and weaknesses in the brain. However, the clinical utility of standard test batteries and their reliance on scaled score differences is limited when evaluating patients with severe or diffuse neurobehavioral disorders. In the present case study, we applied the qualitative approach of Alexander Luria to the neuropsychological evaluation of a severely impaired adolescent, unable to complete psychometric tests. Luria's investigative method was able to assist in the localization of the brain dysfunction and the neurologic diagnosis of a young patient with an unusual neurologic presentation secondary to serious multisystem disease. The initial neuropsychological diagnostic impressions were later confirmed by diagnostic testing. The test results were also used to provide recommendations for ongoing neurorehabilitation of the patient.


Evidence against egocentric prediction during language comprehension.
Although previous research has demonstrated that language comprehension can be egocentric, there is little evidence for egocentricity during prediction. In particular, comprehenders do not appear to predict egocentrically when the context makes it clear what the speaker is likely to refer to. But do comprehenders predict egocentrically when the context does not make it clear? We tested this hypothesis using a visual-world eye-tracking paradigm, in which participants heard sentences containing the gender-neutral pronoun They (e.g. They would like to wear…) while viewing four objects (e.g. tie, dress, drill, hairdryer). Two of these objects were plausible targets of the verb (tie and dress), and one was stereotypically compatible with the participant's gender (tie if the participant was male; dress if the participant was female). Participants rapidly fixated targets more than distractors, but there was no evidence that participants ever predicted egocentrically, fixating objects stereotypically compatible with their own gender. These findings suggest that participants do not fall back on their own egocentric perspective when predicting, even when they know that context does not make it clear what the speaker is likely to refer to.


Minimizing the Contribution of Enterohepatic Recirculation to Clearance in Rat for the NCINI Class of Inhibitors of HIV.
A scaffold replacement approach was used to identifying the pyridine series of noncatalytic site integrase inhibitors. These molecules bind with higher affinity to a tetrameric form compared to a dimeric form of integrase. Optimization of the C6 and C4 positions revealed that viruses harboring T124 or A124 amino acid substitutions are highly susceptible to these inhibitors, but viruses having the N124 amino acid substitution are about 100-fold less susceptible. Compound 20 had EC50 values <10 nM against viruses having T124 or A124 substitutions in IN and >800 nM in viruses having N124 substitions. Compound 20 had an excellent in vitro ADME profile and demonstrated reduced contribution of biliary excretion to in vivo clearance compared to BI 224436, the lead compound from the quinoline series of NCINIs.


Inverted repeats of Tn5 are transposable elements.
Experiments presented here show that each of the 1.5-kilobase inverted repeats of the kanamycin-resistance transposon Tn5 is transposable; we designate them IS50-L (left) and IS50-R (right). By DNA sequence analyses, IS50 is 1533 base pairs (bp) long and generates 9-bp direct repeats of target sequences. The ends of IS50 comprise a hyphenated 8-of-9-bp inverted repeat and are not used with equal efficiency; the outside ends are more active than the inside ends, suggesting that a strong transposase recognition site at the outside ends, suggesting that a strong transposase recognition site at the outside end extends beyond the 8 bp common to both ends.


Microstructural characterization of Ti-6Al-4V alloy subjected to the duplex SMAT/plasma nitriding.
In this study, microstructural characterization of Ti-6Al-4V alloy, subjected to the duplex surface mechanical attrition treatment (SMAT)/nitriding treatment, leading to improve its mechanical properties, was carried out through novel and original samples preparation methods. Instead of acid etching which is limited for morphological characterization by scanning electron microscopy (SEM), an original ion polishing method was developed. Moreover, for structural characterization by transmission electron microscopy (TEM), an ion milling method based with the use of two ions guns was also carried out for cross-section preparation. To demonstrate the efficiency of the two developed methods, morphological investigations were done by traditional SEM and field emission gun SEM. This was followed by structural investigations through selected area electron diffraction (SAED) coupled with TEM and X-ray diffraction techniques. The results demonstrated that ionic polishing allowed to reveal a variation of the microstructure according to the surface treatment that could not be observed by acid etching preparation. TEM associated to SAED and X-ray diffraction provided information regarding the nanostructure compositional changes induced by the duplex SMAT/nitriding process.


Defining the "community" in community consultation for emergency research: findings from the community VOICES study.
This article explores the application of the concept "community consultation" in the context of emergency medical research. Emergency medicine researchers are permitted, by the World Medical Association regulations and in the United States by U.S. Federal Regulations, to conduct emergency medical research on individuals with a life-threatening condition without obtaining their consent or that of their surrogates if certain conditions are met. Among these conditions is the requirement that researchers observe a number of special protections for the participants, including "community consultation and notification" prior to the initiation of such studies. The term "community" is not defined clearly and the process for conducting community consultations is not specified in these regulations. This study explores the feasibility of conducting community consultation in the context of emergency medical research by examining: research participant's definitions of community in New York, the factors that help shape their definitions of community and the people they would authorize to render participation decisions on their behalves. Findings from this study suggest that participants' definitions of community vary as a function of the purpose of the definition and the demographics of the respondents. Most significantly, this study reveals that although respondents can identify potential spokespersons for their communities, these community spokespersons were rarely identified as those who should have decision-making authority in medical emergencies. Finally, this article explores the implications of these findings for the definition of community as it applies to community consultation for emergency medical research.


HPV vaccine acceptability in high-risk Greek men.
HPV is associated with malignancy in men, yet there is a lack of data on HPV knowledge, vaccine acceptability, and factors affecting vaccine acceptability in Greek men. This study aims to identify determinants of knowledge and willingness to vaccinate against HPV among high-risk Greek men. Men (n = 298) between the ages of 18 and 55 were enrolled from the STI and HIV clinics at "Andreas Syggros" Hospital in Athens, Greece from July-October 2015. Participants completed a survey on demographics, economic factors, sexual history, HPV knowledge, and vaccine acceptability. The majority of participants were younger than 40 (76.6%) and unmarried (84.6%). Our sample was 31.2% MSM (men who have sex with men), and 20.1% were HIV-positive. Most participants (>90%) were aware that HPV is highly prevalent in both men and women; however, fewer identified that HPV causes cancers in both sexes (68%) and that vaccination protects men and women (67%). Amongst participants, 76.7% were willing to vaccinate themselves against HPV, 71.4% an adolescent son, and 69.3% an adolescent daughter. HIV-positive men were more likely to be willing to vaccinate themselves (OR 2.83, p = .015), a son (OR 3.3, p = .015) or a daughter (3.01, p = .020). Higher income levels were associated with increased willingness to vaccinate oneself (OR 1.32, p = .027), a son (1.33, p = .032) or daughter (1.34, p = .027). Although there is a HPV knowledge gap, HPV vaccine acceptability is high despite lack of vaccine promotion to Greek men. Future studies should include lower-risk men to adequately inform public health efforts.


Cannabinoid receptor-mediated disruption of sensory gating and neural oscillations: A translational study in rats and humans.
Cannabis use has been associated with altered sensory gating and neural oscillations. However, it is unclear which constituent in cannabis is responsible for these effects, or whether these are cannabinoid receptor 1 (CB1R) mediated. Therefore, the present study in humans and rats examined whether cannabinoid administration would disrupt sensory gating and evoked oscillations utilizing electroencephalography (EEG) and local field potentials (LFPs), respectively. Human subjects (n = 15) completed four test days during which they received intravenous delta-9-tetrahydrocannabinol (Δ9-THC), cannabidiol (CBD), Δ9-THC + CBD, or placebo. Subjects engaged in a dual-click paradigm, and outcome measures included P50 gating ratio (S2/S1) and evoked power to S1 and S2. In order to examine CB1R specificity, rats (n = 6) were administered the CB1R agonist CP-55940, CP-55940+AM-251 (a CB1R antagonist), or vehicle using the same paradigm. LFPs were recorded from CA3 and entorhinal cortex. Both Δ9-THC (p < 0.007) and Δ9-THC + CBD (p < 0.004) disrupted P50 gating ratio compared to placebo, while CBD alone had no effect. Δ9-THC (p < 0.048) and Δ9-THC + CBD (p < 0.035) decreased S1 evoked theta power, and in the Δ9-THC condition, S1 theta negatively correlated with gating ratios (r = -0.629, p < 0.012 (p < 0.048 adjusted)). In rats, CP-55940 disrupted gating in both brain regions (p < 0.0001), and this was reversed by AM-251. Further, CP-55940 decreased evoked theta (p < 0.0077) and gamma (p < 0.011) power to S1, which was partially blocked by AM-251. These convergent human/animal data suggest that CB1R agonists disrupt sensory gating by altering neural oscillations in the theta-band. Moreover, this suggests that the endocannabinoid system mediates theta oscillations relevant to perception and cognition.


The personalization of engagement: the symbolic construction of social media and grassroots mobilization in Canadian newspapers.
This article explores the symbolic construction of civic engagement mediated by social media in Canadian newspapers. The integration of social media in politics has created a discursive opening for reimagining engagement, partly as a result of enthusiastic accounts of the impact of digital technologies upon democracy. By means of a qualitative content analysis of Canadian newspaper articles between 2005 and 2014, we identify several discursive articulations of engagement: First, the articles offer the picture of a wide range of objects of engagement, suggesting a civic body actively involved in governance processes. Second, engagement appears to take place only reactively, after decisions are made. Finally, social media become the new social glue, bringing isolated individuals together and thus enabling them to pressure decision-making institutions. We argue that, collectively, these stories construct engagement as a deeply personal gesture that is nevertheless turned into a communal experience by the affordances of technology. The conclusion unpacks what we deem as the ambiguity at the heart of this discourse, considering its implications for democratic politics and suggesting avenues for the further monitoring of the technologically enabled personalization of engagement.


Histologic evaluation of ulcerative colitis: a systematic review of disease activity indices.
Ulcerative colitis (UC) is an idiopathic inflammatory disorder. Currently, the main goals of treatment are to induce and maintain clinical and/or endoscopic remission. However, evidence indicates that persistent disease activity on colonic biopsies in the setting of clinical or endoscopic remission is an independent predictor of poor outcomes. A number of previous studies have proposed histologic indices for use in specific trials of UC. The aim of this study was to systematically review the existing histological indices for UC and assess their potential use in both patient management and clinical trials. We performed a systematic review of histological indices evaluating disease activity in UC. MEDLINE (Ovid), EMBASE (Ovid), PubMed, the Cochrane Library (CENTRAL), and Digestive Diseases Week (DDW) abstracts of randomized and/or controlled trials clinical trials were searched from inception to February 2013 for applicable studies. Data from these studies were reviewed and analyzed. After systematically applying inclusion criteria, we identified 108 scientific articles including 88 clinical studies and 21 related clinical reviews. Eighteen indices of histological activity in UC were identified and reviewed. Although multiple histological scoring indices for assessment of UC disease activity currently exist, none of these instruments were developed using a formal validation process and their operating properties remain poorly understood. Future studies are needed to address this deficiency.


Synergism between acid and gastric contractile activity in the genesis of ulceration and hemorrhage in the phenylbutazone-treated rat.
The nonsteroid anti-inflammatory drugs including phenylbutazone produce significant gastric ulceration and hemorrhage even when administered by an extragastric route. To investigate the mechanism involved, cervical sectioned rats received an intraileal injection of phenylbutazone as the sodium salt in methylcellulose. Gastric contractile activity as recorded with a miniature gastric balloon, and the stomach was perfused with either acid at pH 1 or buffer at pH 7. Rats receiving phenylbutazone developed a pattern of abnormally strong contractile activity that began 60 to 90 minutes after drug administration. The contracting stomachs of rats perfused with acid developed significantly more ulceration and bled more severely than buffer-perfused rats. Vagotomy or atropine prevented the gastric contractile response to phenylbutazone, and such rats failed to develop significant ulceration in spite of the fact that their stomachs were perfused with acid. Cervical sectioned rats treated with methylcellulose alone failed to develop the abnormal contractile pattern and showed no significant gastric injury or hemorrhage. It is concluded that the focal hemorrhagic lesions induced by the extragastric administration of phenylbutazone in the rat are the result of mucosal compression at specific sites secondary to the passage of extremely strong peristaltic waves. They are vagally mediated and although the presence of acid does not appear essential for their initiation, it plays a synergistic role in their development and hemorrhage.U


[Screening on tuberculosis: an occasion for public debate?].
This article focuses on the public debate in the mid-twentieth century concerning government-directed screening on tuberculosis as reflected in newspapers and medical literature. According to communication theory, media show a variety of functions within the process of democratic political decision-making. This study points out that all national Dutch newspapers, in contradiction to the theory underlined the ideology of screening without any critical contribution. The debate within the medical profession shows a defence of positions in a 'pillarized' society rather than a more ethical discussion.


Predicting and Reducing Driving Mishaps Among Drivers With Type 1 Diabetes.
Two aims of this study were to develop and validate A) a metric to identify drivers with type 1 diabetes at high risk of future driving mishaps and B) an online intervention to reduce mishaps among high-risk drivers. To achieve aim A, in study 1, 371 drivers with type 1 diabetes from three U.S. regions completed a series of established questionnaires about diabetes and driving. They recorded their driving mishaps over the next 12 months. Questionnaire items that uniquely discriminated drivers who did and did not have subsequent driving mishaps were assembled into the Risk Assessment of Diabetic Drivers (RADD) scale. In study 2, 1,737 drivers with type 1 diabetes from all 50 states completed the RADD online. Among these, 118 low-risk (LR) and 372 high-risk (HR) drivers qualified for and consented to participate in a 2-month treatment period followed by 12 monthly recordings of driving mishaps. To address aim B, HR participants were randomized to receive either routine care (RC) or the online intervention "DiabetesDriving.com" (DD.com). Half of the DD.com participants received a motivational interview (MI) at the beginning and end of the treatment period to boost participation and efficacy. All of the LR participants were assigned to RC. In both studies, the primary outcome variable was driving mishaps. Related to aim A, in study 1, the RADD demonstrated 61% sensitivity and 75% specificity. Participants in the upper third of the RADD distribution (HR), compared with those in the lower third (LR), reported 3.03 vs. 0.87 mishaps/driver/year, respectively (P < 0.001). In study 2, HR and LR participants receiving RC reported 4.3 and 1.6 mishaps/driver/year, respectively (P < 0.001). Related to aim B, in study 2, MIs did not enhance participation or efficacy, so the DD.com and DD.com + MI groups were combined. DD.com participants reported fewer hypoglycemia-related driving mishaps than HR participants receiving RC (P = 0.01), but more than LR participants receiving RC, reducing the difference between the HR and LR participants receiving RC by 63%. HR drivers differed from LR drivers at baseline across a variety of hypoglycemia and driving parameters. The RADD identified higher-risk drivers, and identification seemed relatively stable across time, samples, and procedures. This 11-item questionnaire could inform patients at higher risk, and their clinicians, that they should take preventive steps to reduce driving mishaps, which was accomplished in aim B using DD.com.


Digital economy: an effective path for promoting residents' health in China.
The primary prerequisite for socioeconomic growth is good health, hence promoting residents' health is a vital objective of public policies. It is yet up for debate whether or not the digital economy (DE), which will be crucial to future economic growth, will eventually result in improvements in residents' health. Utilizing the China Family Panel Studies (CFPS) data in 2020, we explore how the DE affects residents' health. The findings reveal that residents' health is greatly enhanced by the DE. The eastern region sees a more dramatic improvement in residents' health as a result of the DE. Additionally, the DE can improve residents' health through the promotion of regional green development. The study's findings add to our knowledge of how the DE impacts residents' health while also offering recommendations for achieving universal health.


PROM1 and PROM2 expression differentially modulates clinical prognosis of cancer: a multiomics analysis.
Prominin 1 (PROM1) is considered a biomarker for cancer stem cells, although its biological role is unclear. Prominin 2 (PROM2) has also been associated with certain cancers. However, the prognostic value of PROM1 and PROM2 in cancer is controversial. Here, we performed a systematic data analysis to examine whether prominins can function as prognostic markers in human cancers. The expression of prominins was assessed and their prognostic value in human cancers was determined using univariate and multivariate survival analyses, via various online platforms. We selected a group of prominent functional protein partners of prominins by protein-protein interaction analysis. Subsequently, we investigated the relationship between mutations and copy number alterations in prominin genes and various types of cancers. Furthermore, we identified genes that correlated with PROM1 and PROM2 in certain cancers, based on their levels of expression. Gene ontology and pathway analyses were performed to assess the effect of these correlated genes on various cancers. We observed that PROM1 was frequently overexpressed in esophageal, liver, and ovarian cancers and its expression was negatively associated with prognosis, whereas PROM2 overexpression was associated with poor overall survival in lung and ovarian cancers. Based on the varying characteristics of prominins, we conclude that PROM1 and PROM2 expression differentially modulates the clinical outcomes of cancers.


Functional segmentation of the mammalian nephron.
Although each of the major experimental techniques applied to the study of renal physiology has provided its fair share of new information, the technique of in vitro microperfusion of nephron segments is notable for two major contributions. First, it has supplied a more direct and controlled means of studying epithelial transport processes, some of which already have helped us to understand certain aspects of kidney function and others of which have yet to find their application in unraveling the mysteries of the kidney. Second, in the process of delineating these transport characteristics, it has served to emphasize the epithelial specialization present in the kidney, providing functional counterparts to the already recognized anatomic heterogeneity present in the kidney. In this second role microperfusion has spawned the application of biochemical analysis of the hormonal responses of various nephron segments and contributed to the impetus for work in culturing the various cell types present in each nephron segment. This review outlines the functional characteristics of the 11 major segments of the nephron, incorporating what has been learned from some of the biochemical work on hormone response and correlating the latter with transport events.


Risk of developing asthma in young children with atopic eczema: a systematic review.
It is commonly believed that the majority of infants and young children with early atopic eczema will develop asthma in later childhood. This belief is mainly based on cross-sectional population studies. Recent evidence suggests a more complex relationship between early eczema and asthma. This systematic review was conducted to assess the risk of developing asthma in children with atopic eczema during the first 4 years of life. A sensitive search was performed to identify all prospective cohort studies on the topic. By pooling the eligible reports, we calculated the risk of developing asthma at 6 years of age or older in children with atopic eczema in the first 4 years of life. Thirteen prospective cohort studies were included, with 4 representing birth cohort studies and 9 representing eczema cohort studies. The pooled odds ratio for the risk of asthma after eczema, compared with children without eczema, in birth cohort studies was 2.14 (95% CI, 1.67-2.75). The prevalence of asthma at the age of 6 years in eczema cohort studies was 35.8% (95% CI, 32.2% to 39.9%) for inpatients and 29.5% (95% CI, 28.2% to 32.7%) for a combined group of inpatients and outpatients. Although there is an increased risk of developing asthma after eczema in early childhood, only 1 in every 3 children with eczema develops asthma during later childhood. This is lower than previously assumed. Our results may have important consequences for counseling patients with atopic eczema and their parents.


Solving fluid-flow control problems with porous plastics.
To tackle fluid-flow control problems, traditional porous materials, such as ceramics, glass, metal, fabric, paper, and fibres, are now being replaced by an increasing range of porous plastics. In this article, the author discusses some of those that are available, and outlines the advantages of using these materials to replace traditional ones.


Ultrastructural observations at pineal gland capillaries in four rodent species.
The fine structure of the capillaries of the pineal glands of the rat, mouse, chinchilla, and ground squirrel were investigated. The pineal endothelial cells in the rat, mouse and ground squirrel were often composed of attenuated cytoplasmic portions which contained numerous fenestrations, in contrast to pineal capillaries in the chinchilla which were lined by thick non-fenestrated endothelial cells. Marked morphological differences were also apparent in terms of the types of vesicles within the cytoplasm and abutting on the cell surface of pineal endothelial cells from the various species investigated. The interendothelial junctions exhibited remarkable species differences with the chinchilla pineal possessing typical tight endothelial junctions while those in the rat, mouse and ground squirrel lacked such endothelial cell associations. Generally, capillary lining cells in the chinchilla pineal resembled similar cells within the brain, while endothelial cells in pineal glands of rat, mouse and ground squirrel were more typical of those found in other endocrine organs. Species differences in the structure of the pineal capillaries may represent physiological differences as well.


Incarceration among street-involved youth in a Canadian study: implications for health and policy interventions.
Risk factors for incarceration have been well described among adult drug using populations; however, less is known about incarceration among at-risk youth. This study examines the prevalence and correlates of incarceration among street-involved youth in a Canadian setting. From September 2005 to May 2012, data were collected from the At-Risk Youth Study, a prospective cohort of street-involved youth aged 14-26 who use illicit drugs. Generalized estimating equation (GEE) logistic regression was used to identify factors associated with recent incarceration defined as incarceration in the previous six months. Among 1019 participants, 362 (36%) reported having been recently incarcerated during the study period. In multivariate GEE analysis, homelessness (adjusted odds ratio [AOR]=1.60), daily crystal methamphetamine use (AOR=1.56), public injecting (AOR=1.33), drug dealing (AOR=1.48) and being a victim of violence (AOR=1.68) were independently associated with incarceration (all p<0.05). Conversely, female gender (AOR=0.48), lesbian, gay, bisexual, transgender or two-spirited (LGBTT) identification (AOR=0.47) and increasing age of first hard drug use (AOR=0.96) were negatively associated with incarceration (all p<0.05). Incarceration was common among our study sample. Youth who were homeless, used crystal methamphetamine, and engaged in risky behaviors including public injection and drug dealing were significantly more likely to have been recently incarcerated. Structural interventions including expanding addiction treatment and supportive housing for at-risk youth may help reduce criminal justice involvement among this population and associated health, social and fiscal costs.


Office-based evaluation of renal function in elderly patients receiving nonsteroidal anti-inflammatory drugs.
Elderly patients with multiple diseases who are receiving diuretics are at risk for renal dysfunction from nonsteroidal anti-inflammatory drugs (NSAIDs). Fifty-two elderly patients (mean age = 72 years, range = 63-87 years) with degenerative joint disease and multiple concomitant illnesses were randomly selected to receive ibuprofen suspension (400 mg) or aspirin (650 mg) 4 times a day. Serum creatinine (Cr), blood urea nitrogen (BUN), weight, and blood pressure were measured at baseline and at weekly intervals for 6 weeks. There were no significant changes from baseline in any tests reflective of renal function, no significant differences between ibuprofen and aspirin, and no influence of concomitant diuretic therapy. Ibuprofen and aspirin administered in the doses examined for 6 weeks appear to have little effect on renal function as measured by serum Cr and BUN in a sample of elderly patients for whom these drugs are commonly employed. Concomitant diuretic therapy does not appear to increase the risk. While these drugs are contraindicated in patients with severe hemodynamic insult, they should not be withheld from elderly patients who require this therapy for analgesic/anti-inflammatory effects because of concern for renal impairment. Further prospective research should be undertaken to clarify levels of patient risk and to define appropriate monitoring in such patients.


National Hospital Ambulatory Medical Care Survey: 2000 outpatient department summary.
This report describes ambulatory care visits to hospital outpatient departments (OPDs) in the United States. Statistics are presented on selected hospital, clinic, patient, and visit characteristics. Highlights of trends in OPD utilization from 1997 through 2000 are also presented. The data presented in this report were collected from the 2000 National Hospital Ambulatory Medical Care Survey (NHAMCS). NHAMCS is part of the ambulatory care component of the National Health Care Survey that measures health care utilization across various types of providers. NHAMCS is a national probability sample survey of visits to emergency and outpatient departments of non-Federal, short-stay, and general hospitals in the United States. Sample data are weighted to produce annual national estimates. Trends are based on NHAMCS data from 1997 through 2000. During 2000, an estimated 83.3 million visits were made to hospital OPDs in the United States, about 30.4 visits per 100 persons. Females had higher OPD visit rates than males (35.3 versus 25.2 visits per 100 persons). The OPD utilization rate for black persons was higher than for white persons (48.3 versus 28.0 visits per 100 persons). Of all visits made to hospital OPDs in 2000, private insurance (38.5 percent), Medicaid (22.1 percent), and Medicare (16.9 percent) were listed as the leading primary expected source of payment. Approximately 21 percent of OPD visits reported that patients belonged to an HMO. There were an estimated 9.5 million injury-related OPD visits in 2000. Since 1997, the percent of OPD visits that were for injuries increased by 24% (from 9.2 percent to 1.4 percent). Most of these visits were for unintentional injuries (57.6 percent), including those caused by falls (12.9 percent). Medications were prescribed at 64.0 percent of visits. On average, 1.6 medications were ordered at each OPD visit. In 2000, patients saw one or more physicians (i.e., staff physician, resident/intern, or other physician) at approximately 79 percent of visits. Most patients were given an appointment to return to the clinic (57.2 percent).


Mapping of highly ordered membrane domains in the plasma membrane of the ciliate Cyclidium glaucoma.
The entire cortex of Cyclidium glaucoma has been analysed in a correlated freeze-fracturing and ultrathin-sectioning study. Three types of highly ordered domains of intramembranous particles were found in the plasma membrane; owing to the many landmarks in the cortex of C. glaucoma it was possible to map their location in relation to the precisely known position of every single cilium. Eight particle plates made of parallel tripartite particle ridges have been found in precisely determined locations at the anterior pole of the cell and in the buccal cavity. It is suggested that these membrane specializations represent mechanosensitive sites. An array of three parallel rows of particles, termed a 'simple pellicular rug', forms a second type of membrane domain, which is closely associated with somatic dikinetids found exclusively in the anterior half of the cell. A third extremely complex array, termed a 'complex pellicular rug', is associated with the monokinetids in the posterior half of the cell. There is no gradient in the distribution of these domains but a sharp boundary at the level of the future fission zone. The function of the pellicular rugs is unknown, but their specific distribution will be helpful in further studies on their assembly prior to or during cell division. The intracellular diversification of the cell surface is further augmented by the disclosure of three different aspects of the proximal part of the ciliary membrane. Beyond the double-stranded ciliary necklace, which is a common feature of all cilia, only the motile somatic cilia of C. glaucoma have typical ciliary plaques made of three rows of particles, while all oral cilia have modified plaques, which consist of four rows of particles. the single stiff caudal cilium has no plaques at all. The functional significance of the topographic differences in the plaque areas is discussed. Obviously, the plasma membrane and at least parts of the ciliary membrane form a non-fluid mosaic membrane.


A Distinct Neural Code Supports Prospection of Future Probabilities During Instrumental Information-Seeking.
To make adaptive decisions, we must actively demand information, but relatively little is known about the mechanisms of active information gathering. An open question is how the brain estimates expected information gains (EIG) when comparing the current decision uncertainty with the uncertainty that is expected after gathering information. We examined this question using fMRI in a task in which people placed bids to obtain information in conditions that varied independently by prior decision uncertainty, information diagnosticity, and the penalty for an erroneous choice. Consistent with value of information theory, bids were sensitive to EIG and its components of prior certainty and expected posterior certainty. Expected posterior certainty was decoded above chance from multivoxel activation patterns in the posterior parietal and extrastriate cortices. This representation was independent of instrumental rewards and overlapped with distinct representations of EIG and prior certainty. Thus, posterior parietal and extrastriate cortices are candidates for mediating the prospection of posterior probabilities as a key step to estimate EIG during active information gathering.


Sympatric speciation: when is it possible in bacteria?
According to theory, sympatric speciation in sexual eukaryotes is favored when relatively few loci in the genome are sufficient for reproductive isolation and adaptation to different niches. Here we show a similar result for clonally reproducing bacteria, but which comes about for different reasons. In simulated microbial populations, there is an evolutionary tradeoff between early and late stages of niche adaptation, which is resolved when relatively few loci are required for adaptation. At early stages, recombination accelerates adaptation to new niches (ecological speciation) by combining multiple adaptive alleles into a single genome. Later on, without assortative mating or other barriers to gene flow, recombination generates unfit intermediate genotypes and homogenizes incipient species. The solution to this tradeoff may be simply to reduce the number of loci required for speciation, or to reduce recombination between species over time. Both solutions appear to be relevant in natural microbial populations, allowing them to diverge into ecological species under similar constraints as sexual eukaryotes, despite differences in their life histories.


Intracranial Lesions with Low Signal Intensity on T2-weighted MR Images - Review of Pathologies.
In this article we presented intracranial pathological substances and lesions with low signal intensity on T2-weighted images. Eight groups of substances were discussed i.e. 1. Gadolinium-based contrast materials, 2. hemoglobin degradation products 3. melanin, 4. mucous- or protein-containing lesions, 5. highly cellular lesions, 6. lesions containing mineral substances such as: calcium, copper and iron, 7. turbulent and rapid blood or CSF flow 8. air-containing spaces. Appropriate interpretation of signal intensity as well as analysis of lesion location and clinical symptoms enable a correct choice of a further diagnostic algorithm or, in many cases, final diagnosis based exclusively on an MRI examination.


Suggestion in the treatment of depression.
Meta-analyses consistently reveal that most of the response to antidepressant treatment can be obtained by placebo, and the difference between response to the drug and the response to any treatment is not clinically significant for most individuals diagnosed with major depressive disorder. Furthermore, the best predictor of antidepressant efficacy is the response to placebo during the so-called placebo run-in period. It can also be shown that a significant portion of the placebo effect is expectancy. These data thus indicate that suggestion is a central factor in treating depression. Therefore, the use of hypnosis, which is based on suggestion, as a treatment adjunct can be expected to enhance treatment outcome.


Correlations between clinical probability and Doppler ultrasound results in the assessment of deep venous thrombosis.
Although the assessment of deep venous thrombosis (DVT) is based on clinical examination, the complementary tests and especially Doppler ultrasound plays the most important role in DVT diagnosis. We aimed to establish the correlations between the clinical probability of DVT based on Wells score and the results of Doppler ultrasound exam. We included 382 patients with clinical supposition of DVT divided into 3 groups based upon the probability of DVT (Wells score): low, moderate and high, respectively. All the patients were examined by Doppler ultrasonography. We noticed that DVT was confirmed by Doppler ultrasonography in more than half of the cases; the highest percent of confirmed cases were in the patients with a high probability of DVT (70.58%) whereas the lowest percent was associated with the low clinical probability (14.63%). These findings show the importance of the correct management of cases, starting with clinical data and including a complete anamnesis to identify the risk factors for DVT. There is a significant correlation between the Wells score reflected in the probability of DVT and the Doppler ultrasonography findings.


Rapidly fabricating a large area nanotip microstructure for high-sensitivity SERS applications.
Here, we propose a novel nanotip microstructure which can be easily fabricated through a simply Reactive Ion Etching (RIE) process combined with anodic aluminum oxide (AAO) membranes. When combined with Ag coating and annealing on the surface of micro-sized nanotip arrays, the as-formed Ag-nanoparticles (Ag-NPs)/Si-nanotip hybrid structure exhibited a significantly high enhancement factor and highly sensitive surface enhanced Raman scattering (SERS) for rhodamine 6G molecules. The nanotip microstructure showed a sharp curvature with an apex diameter which significantly affected the SERS results. The Ag-NPs/Si-nanotip hybrid structure verified a very prominent "hot spot" effect that exists around the nanotip structures, which contributed mainly to an enhanced SERS signal with an enhancement factor (EF) of 1.6 × 106. Moreover, the Ag-NPs/Si-nanotip hybrid structure demonstrated superior sensitivity, with obvious featured Raman peaks even when the concentration was as low as 10-10 M. Our work demonstrated a feasible way to prepare a novel nanotip microstructure with a highly localized surface plasmon resonance response which could be feasibly applied for highly sensitive and reproducible SERS applications.


[Effect of age on electrocardiogram entropy value of parameters by sleep respiratory disturbance].
Spectral entropy of electrocardiogram (ECG), which was calculated using the MemCalc method with a portable bio-signal measurement instrument (PBSM), might be a possible parameter for evaluating the quality of sleep. This study assessed the effects of ECG spectral entropy on obstructive sleep apnea/hypopnea syndrome (OSAHS) depending on age. ECG was recorded using a PBSM, and the maximum entropy of ECG every 9 RR intervals was calculated. These entropies were compared with the age and sleeping indices obtained with a conventional polysomnography (PSG) system. Seventy-six patients suspected of OSAHS were recorded from 20:00 to 06:00 using a conventional PSG system (Alice III) and a PBSM (MemCalc-Makin2) simultaneously. ECG entropy showed correlations to high frequency (HF, 0.15-0.40 Hz) heart rate variability in the cardiac parasympathetic activity index, as did the ECG entropy value, and a negative correlation was found with the age (r = 0.538, p < 0.0001), and positive correlation with the HF value (r = 0.810, p < 0.0001). The ECG entropy value in subjects aged > or = 40 with no different sleep respiratory disturbance index by PSG data (AHI, Arousal Index, DSI, and sleep efficiency, etc.) to 60 years old was compared with those aged > or = 60. The ECG entropy value and HF value decreased at > or = 60 years old with statistically significant. The value of ECG entropy corresponds to cardiac parasympathetic function, and it decreases according to age (increase by the absolute value).


A versatile robotic platform for the design of natural, three-dimensional reaching and grasping tasks in monkeys.
Translational studies on motor control and neurological disorders require detailed monitoring of sensorimotor components of natural limb movements in relevant animal models. However, available experimental tools do not provide a sufficiently rich repertoire of behavioral signals. Here, we developed a robotic platform that enables the monitoring of kinematics, interaction forces, and neurophysiological signals during user-defined upper limb tasks for monkeys. We configured the platform to position instrumented objects in a three-dimensional workspace and provide an interactive dynamic force-field. We show the relevance of our platform for fundamental and translational studies with three example applications. First, we study the kinematics of natural grasp in response to variable interaction forces. We then show simultaneous and independent encoding of kinematic and forces in single unit intra-cortical recordings from sensorimotor cortical areas. Lastly, we demonstrate the relevance of our platform to develop clinically relevant brain computer interfaces in a kinematically unconstrained motor task. Our versatile control structure does not depend on the specific robotic arm used and allows for the design and implementation of a variety of tasks that can support both fundamental and translational studies of motor control.


Dendritic Glycerol-Cholesterol Amphiphiles as Drug Delivery Systems: A Comparison between Monomeric and Polymeric Structures.
The application of micelles as drug delivery systems has gained a great deal of attention as a means to overcome the current several drawbacks present in conventional cancer treatments. In this work, we highlight the comparison of polymeric and monomeric amphiphilic systems with a similar hydrophilic-lipophilic balance (HLB) in terms of their biocompatibility, aggregation behavior in aqueous solution, and potential in solubilizing hydrophobic compounds. The polymeric system consists of non-ionic polymeric amphiphiles synthesized via sequential RAFT polymerization of polyglycerol first-generation [G1] dendron methacrylate and cholesterol methacrylate to obtain poly(G1-polyglycerol dendron methacrylate)-block-poly(cholesterol methacrylate) (pG1MA-b-pCMA). The monomeric system is a polyglycerol second-generation [G2] dendron end-capped to a cholesterol unit. Both amphiphiles form spherical micellar aggregations in aqueous solution, with differences in size and the morphology in which hydrophobic molecules can be encapsulated. The polymeric and monomeric micelles showed a low critical micelle concentration (CMC) of 0.2 and 17 μg/mL, respectively. The results of our cytotoxicity assays showed that the polymeric system has significantly higher cell viability compared to that of the monomeric amphiphiles. The polymeric micelles were implemented as drug delivery systems by encapsulation of the hydrophobic small molecule doxorubicin, achieving a loading capacity of 4%. In summary, the results of this study reveal that using cholesterol as a building block for polymer synthesis is a promising method of preparation for efficient drug delivery systems while improving the cell viability of monomeric cholesterol.


Development and validation of climate and ecosystem-based early malaria epidemic prediction models in East Africa.
Malaria epidemics remain a serious threat to human populations living in the highlands of East Africa where transmission is unstable and climate sensitive. An existing early malaria epidemic prediction model required further development, validations and automation before its wide use and application in the region. The model has a lead-time of two to four months between the detection of the epidemic signal and the evolution of the epidemic. The validated models would be of great use in the early detection and prevention of malaria epidemics. Confirmed inpatient malaria data were collected from eight sites in Kenya, Tanzania and Uganda for the period 1995-2009. Temperature and rainfall data for the period 1960-2009 were collected from meteorological stations closest to the source of the malaria data. Process-based models were constructed for computing the risk of an epidemic in two general highland ecosystems using temperature and rainfall data. The sensitivity, specificity and positive predictive power were used to validate the models. Depending on the availability and quality of the malaria and meteorological data, the models indicated good functionality at all sites. Only two sites in Kenya had data that met the criteria for the full validation of the models. The additive model was found most suited for the poorly drained U-shaped valley ecosystems while the multiplicative model was most suited for the well-drained V-shaped valley ecosystem. The +18°C model was adaptable to any of the ecosystems and was designed for conditions where climatology data were not available. The additive model scored 100% for sensitivity, specificity and positive predictive power. The multiplicative model had a sensitivity of 75% specificity of 99% and a positive predictive power of 86%. The additive and multiplicative models were validated and were shown to be robust and with high climate-based, early epidemic predictive power. They are designed for use in the common, well- and poorly drained valley ecosystems in the highlands of East Africa.


Refined structure of Pyrococcus furiosus ornithine carbamoyltransferase at 1.87 A.
Using synchrotron radiation, X-ray data have been collected from Pyrococcus furiosus ornithine carbamoyltransferase (Pfu OTCase) to a maximal resolution of 1.87 A, allowing the refinement of a previous structure at 2.7 A [Villeret et al. (1998), Proc. Natl Acad. Sci. USA, 95, 2801-2806]. Thanks to the high resolution of this refined structure, two sulfate ions and 191 water molecules could be localized directly from the electron-density maps. The identification of these molecules allowed a more rigorous description of the active site and the identification of residues involved in binding carbamoyl phosphate. The improved quality of the model resulted in a better definition of several loops and the various interfaces. The dodecameric protein is composed of four catalytic trimers disposed in a tetrahedral manner. The extreme thermal stability of Pfu OTCase is mainly the result of the strengthening of the intersubunit interactions in a trimer and oligomerization of the trimers into a dodecamer. Interfaces between monomers in a catalytic trimer are characterized by an increase in ion-pair networks compared with mesophilic OTCases. However, the interfaces between catalytic trimers in the dodecameric oligomer are mainly hydrophobic and also involve aromatic-aromatic and cation-pi interactions.


[Postoperative pulmonary torsion after upper lobectomy by thoracotomy].
The aim of this case report is to describe a lobar torsion after elective pulmonary resection. This is a rare but potentially fatal condition in which the lung rotates on its own axis. Although this condition may occur spontaneously, it most often follows lobectomy. Early diagnosis and prompt surgical intervention are essential to prevent complications. Treatment is surgical, and involves repositioning the lung in a physiological position. However, the presence of ischaemic lesions may lead to the resection of the lung portion concerned.


CpG immunostimulatory sequences enhance contact hypersensitivity responses in mice.
Bacterial DNA and synthetic cytidine-phosphate-guanosine-oligodeoxynucleotides (CpG ODN) potently activate dendritic cells (DC) and therefore have been proposed as adjuvants for vaccination strategies. Although CpG ODN are considered as safe adjuvants this study shows that CpG ODN are responsible for enhanced antigen-specific skin inflammatory reactions. We used the murine model of contact hypersensitivity (CHS) to 2,4-dinitrofluorobenzene (DNFB) in which hapten-specific CD8+T cytotoxic 1 cells are effector cells. Subcutaneous injection of CpG ODN, 1 d before sensitization enhanced the CHS response to DNFB and resulted in increased recruitment of CD8+ T cells at the challenge sites, whereas control ODN injection did not have any effect. This effect was local and not systemic as it was only observed when DNFB was applied at the same site as the CpG motifs. CpG ODN-induced enhancement of CHS was due to increased antigen-presenting cell functions of DC since: (i) CpG ODN-injected skin revealed upregulated expression of major histocompatibility complex class II, CD80, and CD86 molecules and (ii) CpG ODN treatment of DNFB-derivatized DC enhanced the intensity of CHS responses after in vivo transfer. Taken together, the results show that CpG ODN may be responsible for immune side-effects such as worsening of T cell-mediated skin diseases.


Association of Severe COVID-19 and Persistent COVID-19 Symptoms With Economic Hardship Among US Families.
Little is known about the association of severe COVID-19 and post-COVID-19 conditions with household finances. To examine associations between COVID-19 outcomes, pandemic-related economic hardship, and prepandemic socioeconomic status among families in the US. This cohort study used data from the Panel Study of Income Dynamics (PSID), a nationally representative, longitudinal study. Data included 6932 families active in the PSID in both 2019 and 2021. Ordinal exposure categories were defined based on whether the reference person or spouse or partner reported a positive COVID-19 diagnosis and (1) persistent COVID-19 symptoms, (2) previous severe COVID-19, or (3) previous moderate, mild, or asymptomatic COVID-19. Families with no history of COVID-19 served as the reference group. Outcomes included whether a resident family member was laid off or furloughed, lost earnings, or had any financial difficulties due to the COVID-19 pandemic. In this cohort study of 6932 families (772 Hispanic families [weighted, 13.5%; 95% CI, 12.4%-14.6%], 2725 non-Hispanic Black families [weighted, 13.1%; 95% CI, 12.3%-14.1%], and 3242 non-Hispanic White families [weighted, 66.8%; 95% CI, 65.2%-68.3%]), close to 1 in 4 (2222 [weighted, 27.0%; 95% CI, 25.6%-28.6%]) reported income below 200% of the US Census Bureau poverty threshold. In survey-weighted regression models adjusted for prepandemic sociodemographic characteristics and experiences of economic hardship, the odds of reporting pandemic-related economic hardship were 2.0 to 3.7 times higher among families headed by an adult with persistent COVID-19 symptoms (laid off or furloughed: adjusted odds ratio [AOR], 1.98 [95% CI, 1.37-2.85]; lost earnings: AOR, 2.86 [95% CI, 2.06-3.97]; financial difficulties: AOR, 3.72 [95% CI, 2.62-5.27]) and 1.7 to 2.0 times higher among families headed by an adult with previous severe COVID-19 (laid off or furloughed: AOR, 1.69 [95% CI, 1.13-2.53]; lost earnings: AOR, 1.99 [95% CI, 1.37-2.90]; financial difficulties: AOR, 1.87 [95% CI, 1.25-2.80]) compared with families with no history of COVID-19. Families headed by an adult with persistent COVID-19 symptoms had increased odds of reporting financial difficulties due to the pandemic regardless of prepandemic socioeconomic status (families with lower income: AOR, 3.71 [95% CI, 1.94-7.10]; families with higher income: AOR, 3.74 [95% CI, 2.48-5.63]). Previous severe COVID-19 was significantly associated with financial difficulties among families with lower income (AOR, 2.59 [95% CI, 1.26-5.31]) but was not significantly associated with financial difficulties among those with high income (OR, 1.56 [95% CI, 0.95-2.56]). This cohort study suggests that persistent COVID-19 symptoms and, to a lesser extent, previous severe COVID-19 were associated with increased odds of pandemic-related economic hardship in a cohort of US families. The economic consequences of COVID-19 varied according to socioeconomic status; families with lower income before the pandemic were more vulnerable to employment disruptions and earnings losses associated with an adult family member's COVID-19 illness.


Mice with alopecia, osteoporosis, and systemic amyloidosis due to mutation in Zdhhc13, a gene coding for palmitoyl acyltransferase.
Protein palmitoylation has emerged as an important mechanism for regulating protein trafficking, stability, and protein-protein interactions; however, its relevance to disease processes is not clear. Using a genome-wide, phenotype driven N-ethyl-N-nitrosourea-mediated mutagenesis screen, we identified mice with failure to thrive, shortened life span, skin and hair abnormalities including alopecia, severe osteoporosis, and systemic amyloidosis (both AA and AL amyloids depositions). Whole-genome homozygosity mapping with 295 SNP markers and fine mapping with an additional 50 SNPs localized the disease gene to chromosome 7 between 53.9 and 56.3 Mb. A nonsense mutation (c.1273A>T) was located in exon 12 of the Zdhhc13 gene (Zinc finger, DHHC domain containing 13), a gene coding for palmitoyl transferase. The mutation predicted a truncated protein (R425X), and real-time PCR showed markedly reduced Zdhhc13 mRNA. A second gene trap allele of Zdhhc13 has the same phenotypes, suggesting that this is a loss of function allele. This is the first report that palmitoyl transferase deficiency causes a severe phenotype, and it establishes a direct link between protein palmitoylation and regulation of diverse physiologic functions where its absence can result in profound disease pathology. This mouse model can be used to investigate mechanisms where improper palmitoylation leads to disease processes and to understand molecular mechanisms underlying human alopecia, osteoporosis, and amyloidosis and many other neurodegenerative diseases caused by protein misfolding and amyloidosis.


Maternal-perinatal calcium relationships.
Serum concentrations of total and ionic calcium, magnesium, phosphorus, and albumin were measureed in maternal and cord blood of 115 near-term deliveries. The same measurements (except for ionic calcium) were made in blood obtained from corresponding newborns at 24 hours of age. Cord levels of all components exceeded maternal values, and maternal and cord levels correlated significantly with each other. In the case of calcium, the cord-maternal difference involved both ionic and protein-bound forms. Significant umbilical arterio-venous differences were found only in the case of total calcium, and this difference reflected variation in the protein-bound form only. During the first 24 hours postpartum, total calcium concentration fell (by an average of 0.75 mEq/liter), phosphorus levels rose (by an average of 0.63 mg/dl), and magnesium and albumin did not change significantly. Cord levels of all agents correlated significantly with corresponding neonatal values. In view of the significant positive relationships demonstrated between maternal and cord levels and between cord and neonatal levels, these results substantiate the importance of the maternal serum ionic calcium concentration in normal perinatal calcium homeostasis.


Soluble interleukin 2 receptors are released from activated human lymphoid cells in vitro.
With the use of an enzyme-linked immunoabsorbent assay to measure soluble human interleukin 2 receptors (IL 2R), certain human T cell leukemia virus I (HTLV I)-positive T cell lines were found to spontaneously release large quantities of IL 2R into culture supernatants. This was not found with HTLV I-negative and IL 2 independent T cell lines, and only one of seven B cell-derived lines examined produced small amounts of IL 2R. In addition to this constitutive production of soluble IL 2R by certain cell lines, normal human peripheral blood mononuclear cells (PBMC) could be induced to release soluble IL 2R by plant lectins, the murine monoclonal antibody OKT3, tetanus toxoid, and allogeneic cells. Such activated cells also expressed cellular IL 2R measurable in detergent solubilized cell extracts. The generation of cellular and supernatant IL 2R was: dependent on cellular activation, rapid, radioresistant (3000 rad), and inhibited by cycloheximide treatment. NaDodSO4-polyacrylamide gel electrophoresis analysis of soluble IL 2R released from either the HTLV I-positive T cell line HUT 102B2 or normal phytohemagglutinin-activated PBMC demonstrated molecules of apparent Mr = 35,000 to 40,000, and 45,000 to 50,000, respectively, somewhat smaller than the mature surface receptor on these cells. The release of soluble IL 2R appears to be a characteristic marker of T lymphocyte activation and might serve an immunoregulatory function during both normal and abnormal cell growth and differentiation.


[The voice of municipal administrators on access to health in management practices].
Universal access to health services is a challenge for municipal administration in a society that treats health as a commodity and gives preference to the individual consumer to the detriment of the citizen. This study sought to identify the social representations in the narrative of local health managers in a micro-region of southeast Brazil about access to health services. It consists of qualitative research with interviews conducted with 16 managers. The Collective Subject Discourse technique was employed with the use of Qualiquantisoft software in the data analysis. Four core ideas were identified: coordination between federal states; reorganization of admission procedures; user service and the precariousness of guaranteed access. It was revealed that the quality, resolvability, approach to the user's needs and the care network organization are poorly addressed, which reflects an understanding that does not consider 'access quality and resolution.' It is understood that the managers' impotence to make changes and the lack of society and worker engagement in management bolster the supremacy of market interests and contribute to 'limited access' and the continuity of the hegemonic model of care.


Improving the accessibility of health care for internal migrants in China: Achieving the aim of equalization.
Although equitable access to healthcare is considered key to the health of internal migrants, more concerted efforts are needed to improve the accessibility of healthcare in low- and middle-income countries. The software CiteSpace was used to analyze scientific literature on healthcare utilization among internal migrants in China since 2000. We focused on factors influencing access to healthcare, including geographical, economic, sociocultural, and institutional aspects. The government is urged to play a role in ensuring equal access to healthcare through policies, resource distribution, and information technology. Improving the accessibility of healthcare for internal migrants and achieving egalitarian goals is of great significance to promoting public health and fostering social equity and inclusivity.


Pseudohermaphroditism due to XY gonadal absence syndrome.
A 21-year-old phenotypic female with a 46,XY chromosome complement and gonadal absence was studied. Basal levels of plasma immunoreactive luteinizing hormone (LH), follicle stimulating hormone (FSH), testosterone, and oestradiol were measured. Pituitary sensitivity and reserve was evaluated by the exogenous administration of synthetic luteinizing hormone-releasing hormone. The episodic release of gonadotrophins was assessed by measuring plasma LH and FSH in plasma samples obtained at 20-minute intervals for a 4-hour period. Endocrine gonadal function was evaluated by a stimulation test with human chorionic gonadotrophin for 3 days. The results showed: a) persistently raised plasma levels of both LH and FSH; b) a pulsatile pattern of release of both gonadotrophins and a normal pituitary response to the synthetic hypothalamic decapeptide; and c) extremely low levels of circulating testosterone and oestradiol with a lack of response to the HCG stimulus. A careful exploratory laparotomy revealed absence of uterus, Fallopian tubes, the Mullerian portion of the vagina, and gonads. No Wolffian derivatives were found. A dissociation of testosterone and the so-called Jost substance effects during early sexual development may explain the findings in this unusual abnormality. The term 'XY gonadal absence syndrome' including five types of variants to designate this condition is proposed.


The impact of direct oral anti-coagulants on hip fracture management : a systematic review and meta-analysis.
Hip fractures are a common presentation in the elderly, a group who commonly have co-morbidities requiring the use of anticoagulants. Recently, direct oral anti-coagulants (DOAC) have become a popular method of anticoagulating patients. The primary aim of this review is to determine if the use of DOAC in elderly patients with hip fractures results in delays to theatre and/or an increased mortality risk. Major databases including Pubmed, MEDLINE and Embase were searched for relevant studies and the included studies reference lists were screened for further studies. A total of 6 studies were included in meta-analysis which was undertaken using RevMan software with 95% confidence interval (CI). Compared to control groups, patients who were anticoagulated with DOAC and required operative management of a hip fracture experienced a statistically significant delay to treatment. However independent analysis showed these patients did not experience an increased mortality risk when compared to the control group. While data is limited, treating clinicians should be comforted by these findings as operative manage- ment can be safely delayed to reduce the risk of intraoperative bleeding.


Risk and resistance perspectives in translation-oriented etiology research.
Risk for a disorder and the mechanisms that determine its elevation, risk factors, are the focus of medical research. Targeting risk factors should serve the goal of prevention and treatment intervention. Risk, however, is but one of the aspects of liability to a disorder, a latent trait that encompasses effects of all factors leading to or from the diagnostic threshold. The coequal but opposite aspect of liability is resistance to a disorder. The factors that increase resistance and thus enable prevention or recovery may differ from those that elevate risk. Accordingly, there are nontrivial differences between research perspectives that focus on risk and on resistance. This article shows how this distinction translates into goals and methods of research and practice, from the choice of potential mechanisms tested to the results sought in intervention. The resistance concept also differs from those of "resilience" and "protective factors," subsuming but not limited to them. The implications of the concept are discussed using substance use disorder as an example and substantiate the need for biomedical research and its translation to shift to the resistance perspective.


Magnetically-actuated blood filter unit attachable to pre-made biochips.
We present a novel blood filter unit that is designed to separate blood plasma from whole blood by simple magnetic actuation. A non-diluted blood sample is dropped into the filter unit and magnetic attraction is applied to squeeze out only blood plasma while blood particles are filtered by membranes stacked in the filter unit. The new filter device yields good filtering performance with nearly perfect filtering efficiency (∼99.999%), high plasma recovery (∼30%), low blood consumption (<50 μl), and fast operation (∼1 min). Because it is simple to operate and is attachable to any kind of pre-made biochip, it has commercial potential in various lab-on-a-chip applications for blood tests.


The gut microbiome and degradation enzyme activity of wild freshwater fishes influenced by their trophic levels.
Vertebrate gut microbiome often underpins the metabolic capability and provides many beneficial effects on their hosts. However, little was known about how host trophic level influences fish gut microbiota and metabolic activity. In this study, more than 985,000 quality-filtered sequences from 24 16S rRNA libraries were obtained and the results revealed distinct compositions and diversities of gut microbiota in four trophic categories. PCoA test showed that gut bacterial communities of carnivorous and herbivorous fishes formed distinctly different clusters in PCoA space. Although fish in different trophic levels shared a large size of OTUs comprising a core microbiota community, at the genus level a strong distinction existed. Cellulose-degrading bacteria Clostridium, Citrobacter and Leptotrichia were dominant in the herbivorous, while Cetobacterium and protease-producing bacteria Halomonas were dominant in the carnivorous. PICRUSt predictions of metagenome function revealed that fishes in different trophic levels affected the metabolic capacity of their gut microbiota. Moreover, cellulase and amylase activities in herbivorous fishes were significantly higher than in the carnivorous, while trypsin activity in the carnivorous was much higher than in the herbivorous. These results indicated that host trophic level influenced the structure and composition of gut microbiota, metabolic capacity and gut content enzyme activity.


The roles of integrin β4 in vascular endothelial cells.
Integrin heterodimers play diverse and important roles in physiological and pathological processes, such as cell adhesion, migration, proliferation, differentiation, angiogenesis, and tumor progression, via the outside-in and/or inside-out signaling pathways. Aberrant functions of integrins have been implicated in the causation and intervention of multiple diseases. Integrin β(4), a laminin-5 (LN5) receptor, mainly locates in the adhesion structure of hemidesmosome (HD). Most of the previous researches concentrated on the role of integrin β(4) in cancer and cancer therapy, and a few focused on the physiological roles of normal mammalian cells. Recently, accumulating data reveal that integrin β(4) participates in cell death, macroautophagy (hereafter autophagy), senescence, and differentiation regulations in various cell types including human umbilical vein endothelial cells (HUVECs), mesenchymal stem cells, and mouse neural cells, implying the key roles of integrin β(4) in the physiological alteration of mammalian cells. Thus, the elucidation of integrin β(4)-mediated signaling may undoubtedly contribute to novel therapeutic strategies for various human diseases, such as vascular and neural disorders. We have reviewed the roles of integrin β(4) in neural cells. In the present review we will discuss the recent research progress in the inherent functions and pharmacological modulation of integrin β(4) in vascular endothelial cells.


[Differential diagnosis of the low-echo thyroid gland].
Hypothyrosis as a result of inflammatory disease of the thyroid gland, often is a diagnostic problem because of the insidious onset and its lack of specific symptoms. In the rather large amount of literature about sonography of the thyroid no papers with a systematic approach to this entity are found. In a prospective study we evaluated 36 proven cases and found a characteristic sonographic pattern of the thyroid with regard to its size, contour and structure.


Reversal of established liver fibrosis by IC-2-engineered mesenchymal stem cell sheets.
Chronic hepatitis viral infection, alcoholic intoxication, and obesity cause liver fibrosis, which progresses to decompensated liver cirrhosis, a disease for which medical demands cannot be met. Since there are currently no approved anti-fibrotic therapies for established liver fibrosis, the development of novel modalities is required to improve patient prognosis. In this study, we clarified the anti-fibrotic effects of cell sheets produced from human bone marrow-derived mesenchymal stem cells (MSCs) incubated on a temperature-sensitive culture dish with the chemical compound IC-2. Orthotopic transplantation of IC-2-engineered MSC sheets (IC-2 sheets) remarkably reduced liver fibrosis induced by chronic CCl4 administration. Further, the marked production of fibrolytic enzymes such as matrix metalloproteinase (MMP)-1 and MMP-14, as well as thioredoxin, which suppresses hepatic stellate cell activation, was observed in IC-2 sheets. Moreover, the anti-fibrotic effect of IC-2 sheets was much better than that of MSC sheets. Finally, knockdown experiments revealed that MMP-14 was primarily responsible for the reduction of liver fibrosis. Here, we show that IC-2 sheets could be a promising therapeutic option for established liver fibrosis.


Contrasting healthcare costs of COPD and asthma in elderly.
Caring for ageing populations creates new challenges for society. Obstructive pulmonary diseases, asthma and especially COPD, are responsible for considerable morbidity, mortality, and financial costs in the elderly. We present the change in the burden of asthma and COPD in those aged ≥60 years in Finland from 1996 to 2018. We collected national register data from 1996 to 2018 from Statistics Finland, Care Register for Health Care, and the Social Insurance Institution. We estimated the prevalence of asthma and severe COPD, use of healthcare, social services, reimbursed inhalation medications, and societal costs. In subjects aged ≥60 years, the prevalence was 8% for asthma with reimbursed medication and 0·7% for severe COPD in 2018. In 1996-2018, total costs increased from 33 M€ to 58 M€ (+57%) for asthma and decreased from 38 M€ to 30 M€ (-27%) for COPD. Costs per patient decreased for asthma from 720 € to 460 € (-57%) and remained stable for COPD (2700 € in 2018). Potential years of life lost (PYLL) increased in COPD from 5000 to 6400 (+28%) and the number of emergency department visits increased from 3700 to 6000 (+62%). In a population aged ≥60 years, the total burden caused by asthma decreased but remained stable and high in COPD. PYLL and visits in emergency care increased in COPD.


Replitrons: A major group of eukaryotic transposons encoding HUH endonuclease.
HUH endonucleases of the Rep (replication protein) class mediate the replication of highly diverse plasmids and viral genomes across all domains of life. HUH transposases have independently evolved from Reps, giving rise to three major transposable element groups: the prokaryotic insertion sequences IS200/IS605 and IS91/ISCR, and the eukaryotic Helitrons. Here, I present Replitrons, a second group of eukaryotic transposons encoding Rep HUH endonuclease. Replitron transposases feature a Rep domain with one catalytic Tyr (Y1) and an adjacent domain that may function in oligomerization, contrasting with Helitron transposases that feature Rep with two Tyr (Y2) and a fused helicase domain (i.e., RepHel). Protein clustering found no link between Replitron transposases and described HUH transposases, and instead recovered a weak association with Reps of circular Rep-encoding single-stranded (CRESS) DNA viruses and their related plasmids (pCRESS). The predicted tertiary structure of the transposase of Replitron-1, the founding member of the group that is active in the green alga Chlamydomonas reinhardtii, closely resembles that of CRESS-DNA viruses and other HUH endonucleases. Replitrons are present in at least three eukaryotic supergroups and reach high copy numbers in nonseed plant genomes. Replitron DNA sequences feature short direct repeats at, or potentially near, their termini. Finally, I characterize copy-and-paste de novo insertions of Replitron-1 using long-read sequencing of C. reinhardtii experimental lines. These results support an ancient and evolutionarily independent origin of Replitrons, in line with other major groups of eukaryotic transposons. This work expands the known diversity of both transposons and HUH endonucleases in eukaryotes.


Mechanisms of disease: Oncogene addiction--a rationale for molecular targeting in cancer therapy.
There has been considerable progress in the systemic treatment of cancer because of the rapid development and clinical application of molecular targeted agents. Although patients with a particular type and stage of cancer are often treated as a single group, more-specific therapy is being considered, as subsets of these patients who are more likely to benefit from treatment with particular agents are being identified. We previously introduced the concept of 'oncogene addiction' to explain how some cancers that contain multiple genetic, epigenetic, and chromosomal abnormalities are dependent on or 'addicted' to one or a few genes for both maintenance of the malignant phenotype and cell survival. Thus, reversal of only one or a few of these abnormalities can inhibit cancer cell growth and in some cases translate to improved survival rates. This review summarizes current experimental and clinical evidence for the concept of oncogene addiction and describes molecular mechanisms that may explain this phenomenon. In addition, we discuss how high-throughput screening methods, including gene-expression profiling and proteomics, and emerging methods for analyzing complex cellular networks can be used to identify the state of oncogene addiction, i.e. the 'Achilles' heel,' in specific cancers. Finally, we discuss the use of molecular targeted agents in combination with other anticancer agents as a strategy to optimize therapy and prevent disease recurrence.


Establishment of the Ivermectin Research for Malaria Elimination Network: updating the research agenda.
The potential use of ivermectin as an additional vector control tool is receiving increased attention from the malaria elimination community, driven by the increased importance of outdoor/residual malaria transmission and the threat of insecticide resistance where vector tools have been scaled-up. This report summarizes the emerging evidence presented at a side meeting on "Ivermectin for malaria elimination: current status and future directions" at the annual meeting of the American Society of Tropical Medicine and Hygiene in New Orleans on November 4, 2014. One outcome was the creation of the "Ivermectin Research for Malaria Elimination Network" whose main goal is to establish a common research agenda to generate the evidence base on whether ivermectin-based strategies should be added to the emerging arsenal to interrupt malaria transmission.


Loop-mediated isothermal amplification for rapid detection of the causal agents of cassava brown streak disease.
The causal agents of cassava brown streak disease have recently been identified as Cassava brown streak virus (CBSV) and Ugandan cassava brown streak virus (UCBSV). Primers have been developed for rapid detection of these viruses by reverse transcription loop-mediated isothermal amplification (RT-LAMP). Performance of the RT-LAMP assays compared favourably with published RT-PCR and real-time RT-PCR methods. Furthermore, amplification by RT-LAMP is completed in 40 min and does not require thermal cycling equipment. Modification of the RT-LAMP reactions to use labelled primers allowed rapid detection of amplification products using lateral flow devices containing antibodies specific to the incorporated labels, avoiding the need for fluorescence detection or gel electrophoresis.


[Results of primary IOL implantation after extraction of congenital cataract in two-year babies].
The results of aspiration of congenital cataract and those of IOL implantation were analyzed for 15 children (17 eyes) aged 2 years or less. The specificity of the postoperative clinical course after implantation of different IOL types and of changes of refraction as well as peculiarities of the growth of the aphakic eye in unilateral cataract versus its match were analyzed. Exudative reaction, stages I-II, is the main problem encountered in the early postoperative period irrespective of a type of the implanted IOL. Implantation of rigid IOLs is associated with a higher risk of development of secondary cataract in the late postoperative period. The postoperative changes of refraction do not depend on an IOL type. The artiphakic eye becomes myopic as the anatomic-optic parameters of the growing eye change. There are no reliable differences between the growth indices in the anterior-posterior axis of the artiphakic and growing eyes.


Neurotensin Promotes the Development of Colitis and Intestinal Angiogenesis via Hif-1α-miR-210 Signaling.
Neurotensin (NT) via its receptor 1 (NTR1) modulates the development of colitis, decreases HIF-1α/PHD2 interaction, stabilizes and increases HIF-1α transcriptional activity, and promotes intestinal angiogenesis. HIF-1α induces miR-210 expression, whereas miR-210 is strongly upregulated in response to NT in NCM460 human colonic epithelial cells overexpressing NTR1 (NCM460-NTR1). In this study, we examined whether NT activates a NTR1-HIF-1α-miR-210 cascade using in vitro (NCM460-NTR1 cells) and in vivo (transgenic mice overexpressing [HIF-1α-OE] or lacking HIF-1α [HIF-1α-knockout (KO)] in intestinal epithelial cells and mice lacking NTR1 [NTR1-KO]) models. Pretreatment of NCM460-NTR1 cells with the HIF-1α inhibitor PX-478 or silencing of HIF-1α (small interfering HIF-1α) attenuated miR-210 expression in response to NT. Intracolonic 2,4,6-trinitrobenzenesulfonic acid (TNBS) administration (2-d model) increased colonic miR-210 expression that was significantly reduced in NTR1-KO, HIF-1α-KO mice, and wild-type mice pretreated intracolonically with locked nucleic acid anti-miR-210. In contrast, HIF-1α-OE mice showed increased miR-210 expression at baseline that was further increased following TNBS administration. HIF-1α-OE mice had also exacerbated TNBS-induced neovascularization compared with TNBS-exposed wild-type mice. TNBS-induced neovascularization was attenuated in HIF-1α-KO mice, or mice pretreated intracolonically with anti-miR-210. Intracolonic anti-miR-210 also reduced colitis in response to TNBS (2 d). Importantly, miR-210 expression was increased in tissue samples from ulcerative colitis patients. We conclude that NT exerts its proinflammatory and proangiogenic effects during acute colitis via a NTR1-prolyl hydroxylase 2/HIF-1α-miR-210 signaling pathway. Our results also demonstrate that miR-210 plays a proinflammatory role in the development of colitis.


Obstructive sleep apnea and fatigue in head and neck cancer patients.
There is a systematic relationship between fatigue, sleep, and decreased quality of life in cancer patients, with notably poor sleep quality among many head and neck cancer patients during and after treatment. An often overlooked cause of sleep disturbance in this patient population is obstructive sleep apnea (OSA). This review explores the current literature on the prevalence and clinical correlates of OSA, management outcomes, and data on cytokine-mediated fatigue in OSA. OSA appears to be prevalent in head and neck cancer patients, both at baseline and after treatment, especially with multimodality therapy including radiation therapy. Predictors of developing OSA include larger tumor size and hypopharynx or larynx primary site. There is evidence that the level of fatigue seen in these patients is not necessarily correlated with the severity of their OSA. Current research highlights the role of proinflammatory cytokines, which can also be synergistically activated by radiation therapy, as mediators of fatigue. Primary management of OSA consists of continuous positive airway pressure. Although continuous positive airway pressure has been shown to improve clinical symptoms, compliance with its use remains a problem and will be an area of future research.


Rolandic arteriovenous malformations: improvement in limb function by IBC embolization.
Three patients with arteriovenous malformations in the rolandic region and significant limb deficit showed virtually complete functional recovery after awake operative embolization of most of the malformations using isobutyl-2 cyanoacrylate. Two of these patients, with functionally useless hands, had sustained the deficits months earlier as the result of a specific brain-damaging event: one as a result of surgery and the other as a result of a hemorrhage. Both of these showed significant return of function during the awake operative embolization procedure. The other patient had had progressive leg weakness over a 2 year period. The theory of steal phenomenon as an explanation for progressive neurologic deficits in association with large arteriovenous malformations must be extended to explain apparently stable deficits after some brain trauma (surgery or hemorrhage). These results suggest that some patients with arteriovenous malformations and without clinical deficits who are near a critical level of "near ischemia" may be thrown out of balance by an acute interceding event.


22q11.2 duplications in a UK cohort with bladder exstrophy-epispadias complex.
The bladder exstrophy-epispadias complex (BEEC) comprises of a spectrum of anterior midline defects, all affecting the lower urinary tract, the external genitalia, and the bony pelvis. In extreme cases, the gastrointestinal tract is also affected. The pathogenesis of BEEC is unclear but chromosomal aberrations have been reported. In particular, duplications of 22q11.2 have been identified in eight unrelated individuals with BEEC. The current study aimed to identify chromosomal copy number variants in BEEC. Analyses was performed using the Affymetrix Genome-wide SNP6.0 assay in 92 unrelated patients cared for by two UK pediatric urology centers. Three individuals had a 22q11.2 duplication, a significantly higher number than that found in a control group of 12,500 individuals with developmental delay who had undergone microarray testing (p < .0001). Sequencing of CRKL, implicated in renal tract malformations in DiGeorge syndrome critical region at 22q11, in 89 individuals with BEEC lacking 22q11 duplications revealed no pathogenic variants. To date, 22q11.2 duplication is the genetic variant most commonly associated with BEEC. This is consistent with the hypothesis that altered expression of a single, yet to be defined, gene therein is critical to the pathogenesis of this potentially devastating congenital disorder.


Continuing our work: transplant surgery and surgical oncology in a tertiary referral COVID-19 center.
COVID-19 is rapidly spreading worldwide. Healthcare systems are struggling to properly allocate resources while ensuring cure for diseases outside of the infection. The aim of this study was to demonstrate how surgical activity was affected by the virus outbreak and show the changes in practice in a tertiary referral COVID-19 center. The official bulletins of the Italian National Institute for the Infectious Diseases "L. Spallanzani" were reviewed to retrieve the number of daily COVID-19 patients. Records of consecutive oncological and transplant procedures performed during the outbreak were reviewed. Patients with a high probability of postoperative intensive care unit (ICU) admission were considered as high risk and defined by an ASA score ≥ III and/or a Charlson Comorbidity Index (CCI) ≥ 6 and/or a Revised Cardiac Risk Index for Preoperative Risk (RCRI) ≥ 3. 72 patients were operated, including 12 (16.6%) liver and kidney transplantations. Patients had few comorbidities (26.3%), low ASA score (1.9 ± 0.5), CCI (3.7 ± 1.3), and RCRI (1.2 ± 0.6) and had overall a low risk of postoperative ICU admission. Few patients had liver cirrhosis (12.5%) or received preoperative systemic therapy (16.6%). 36 (50%) high-risk surgical procedures were performed, including major hepatectomies, pancreaticoduodenectomies, total gastrectomies, multivisceral resections, and transplantations. Despite this, only 15 patients (20.8%) were admitted to the ICU. Only oncologic cases and transplantations were performed during the COVID-19 outbreak. Careful selection of patients allowed to perform major cancer surgeries and transplantations without further stressing hospital resources, meanwhile minimizing collateral damage to patients.


Impact of a national helminth control programme on infection and morbidity in Ugandan schoolchildren.
We aimed to assess the health impact of a national control programme targeting schistosomiasis and intestinal nematodes in Uganda, which has provided population-based anthelmintic chemotherapy since 2003. We conducted longitudinal surveys on infection status, haemoglobin concentration and clinical morbidity in 1871 randomly selected schoolchildren from 37 schools in eight districts across Uganda at three time points - before chemotherapy and after one year and two years of annual mass chemotherapy. Mass treatment with praziquantel and albendazole led to a significant decrease in the intensity of Schistosoma mansoni - 70% (95% confidence interval (CI): 66-73%) after one year and 82% (95% CI: 80-85%) after two years of treatment. Intensity of hookworm infection also decreased (75% and 93%; unadjusted). There was a significant increase in haemoglobin concentration after one (0.135 g/dL (95% CI: 0.126-0.144)) and two years (0.303 g/dL (95% CI: 0.293-0.312)) of treatment, and a significant decrease in signs of early clinical morbidity. The impact of intervention on S. mansoni prevalence and intensity was similar to that predicted by mathematical models of the impact of chemotherapy on human schistosomiasis. Improvements in haemoglobin concentration were greatest among children who were anaemic or harbouring heavy S. mansoni infection at baseline. Anthelmintic treatment delivered as part of a national helminth control programme can decrease infection and morbidity among schoolchildren and improve haemoglobin concentration.


Combined Gene Expression and Chromatin Immunoprecipitation From a Single Mouse Hippocampus.
All neuronal cells hold the same genetic information but vary by their structural and functional plasticity depending on the brain area and environmental influences. Such variability involves specific gene regulation, which is driven by transcription factors (TFs). In the field of neuroscience, epigenetics is the main mechanism that has been investigated to understand the dynamic modulation of gene expression by behavioral responses, stress responses, memory processes, etc. Nowadays, gene expression analyzed by real-time quantitative PCR and TF binding estimated by chromatin immunoprecipitation (ChIP) enables one to dissect this regulation. Because of the wide range of transgenic models, as well as cost-effective aspects, mouse models are widely used neuroscience. Thus, we have set up a protocol that allows extraction of both RNA for gene expression analysis and chromatin for ChIP experiment from a single mouse hippocampus. Using such protocols, information regarding gene expression and regulatory molecular mechanisms from the same animal can be integrated and correlated with neurobiological and behavioral outcomes. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Hippocampus isolation from mouse brain Basic Protocol 2: RNA extraction and gene expression analysis from a mouse half hippocampus Basic Protocol 3: ChIP from one hemisphere side mouse hippocampus.


Predicting Indoor Concentrations of Black Carbon in Residential Environments.
Black carbon (BC) is a descriptive term that refers to light-absorbing particulate matter (PM) produced by incomplete combustion and is often used as a surrogate for traffic-related air pollution. Exposure to BC has been linked to adverse health effects. Penetration of ambient BC is typically the primary source of indoor BC in the developed world. Other sources of indoor BC include biomass and kerosene stoves, lit candles, and charring food during cooking. Home characteristics can influence the levels of indoor BC. As people spend most of their time indoors, human exposure to BC can be associated to a large extent with indoor environments. At the same time, due to the cost of environmental monitoring, it is often not feasible to directly measure BC inside multiple individual homes in large-scale population-based studies. Thus, a predictive model for indoor BC is needed to support risk assessment in public health. In this study, home characteristics and occupant activities that potentially modify indoor levels of BC were documented in 23 homes, and indoor and outdoor BC concentrations were measured twice. The homes were located in the Cincinnati-Kentucky-Indiana tristate region and measurements occurred from September 2015 through August 2017. A linear mixed-effect model was developed to predict BC concentration in residential environments. The measured outdoor BC concentrations and the documented home characteristics were utilized as predictors of indoor BC concentrations. After the model was developed, a leave-one-out cross-validation algorithm was deployed to assess the predictive accuracy of the output. The following home characteristics and occupant activities significantly modified the concentration of indoor BC: outdoor BC, lit candles and electrostatic or high efficiency particulate air (HEPA) filters in heating, ventilation and air conditioning (HVAC) systems. Predicted indoor BC concentrations explained 78% of the variability in the measured indoor BC concentrations. The data show that outdoor BC combined with home characteristics can be used to predict indoor BC levels with reasonable accuracy.


[Distribution of physicians in Costa Rica].
This article provides detailed information on the location of medical practitioners of Costa Rica by rural and urban area and by province, further broken down by medical specialty and place of practice. The data were obtained from a survey made from 1967 through 1975. The authors emphasize the apparent close correlation between the development of health institutions, the characteristics of the health care given the population, and the level of economic development of a country.