Effects of lockdown during corona pandemic on children with neurodevelopmental disorders-A questionnaire-based survey.
Lockdown due to Corona pandemic is an unprecedented event, which has had a profound impact on the lives of children across all ages. Its effects on children with Neurodevelopmental Disorders (NDD) has not been adequately studied. This study was performed in order to explore the effects of lockdown during the Corona pandemic on children with NDD and their parents. The survey was conducted in three Indian tertiary-care hospitals wherein parents of children with NDD were requested to respond to an online questionnaire. The questions attempted to elicit various aspects of the children`s therapies and behavioural profiles as well as their parents` experiences during the pandemic related lockdown. 135/188 (71.8%) parents of children with Autism Spectrum Disorder (ASD)(n=104), Attention Deficit Hyperactivity Disorder (ADHD) (n=26) and Learning Disability (LD)(n=5) responded. Pre-lockdown, 133 (99%) children were receiving regular institution-based therapy, which ceased intra-lockdown. Mean cumulative home-based therapy duration significantly increased during lockdown (p=0.03). Parents reported significantly increased temper tantrums in children (p=0.02). They perceived that during lockdown, their children were bored and their interactions and speech worsened. Majority of parents reported worsening of own qualities of life, but felt confident of taking care of their children during lockdown. To conclude, children with NDD and their parents were significantly affected by Corona pandemicrelated lockdown. Institutional therapy discontinuation, behavioural deterioration (especially among ASD and ADHD) and parental stress were prominent challenges whereas parental motivation and reliance on homebased therapy were the positive highlights. The survey points to the role of regular parent-administered homebased therapy in children with NDD, especially to tide over similar unexpected adverse scenarios.


A Preliminary Study: Central Vestibular Sensitivity Affects Motion Sickness Susceptibility through the Efficacy of the Velocity Storage Mechanism.
Background/Objective: Slow-Phase Eye Velocity Time constant (SPEV TC) and Perceived Rotational Duration (PRD) are measurable objective outcomes of rotational chair step-velocity test. These two variables are dependent on the efficacy of the central velocity storage. If sensory conflict from the step-velocity of the rotational chair elicits motion sickness, the SPEV TC and PRD in individuals with varying susceptibility to motion sickness should be affected. We determined if Central Vestibular Sensitivity (CVS) characteristics differ among individuals with a range of Motion Sickness Susceptibility (MSS). Methods: Participants were allocated to two groups based on MSS (low and high) as identified on the short version of the Motion Sick Susceptibility Questionnaire (MSSQ-S). We evaluated the specific relationship between MSS and the characteristics of CVS through the SPEV TC and PRD from the step-velocity test. Results: Results showed significant differences in the PRD between these two groups. 180°/s Per-rotatory PRD is most significantly different (p = 0.005) followed by 50°/s post-rotatory PRD (CCW, p = 0.007; CW, p = 0.021) and log of 180°/s post-rotatory PRD (p = 0.042). Multiple regression analysis indicated that CCW post-rotatory PRD at 50°/s was a strong predictor of MSS. Conclusions: High MSS individuals were observed with elevated PRD in general, indirectly suggesting greater velocity storage efficiency, hence, greater CVS; CVS is therefore positively correlated with MSS. PRD could be a reliable clinical indicator of motion sick susceptibility and may help with the selection of personnel working in motion sick environments and with the verification of motion sickness therapeutic interventions.


A genome-wide screen for regulators of TORC1 in response to amino acid starvation reveals a conserved Npr2/3 complex.
TORC1 is a central regulator of cell growth in response to amino acid availability, yet little is known about how it is regulated. Here, we performed a reverse genetic screen in yeast for genes necessary to inactivate TORC1. The screen consisted of monitoring the expression of a TORC1 sensitive GFP-based transcriptional reporter in all yeast deletion strains using flow cytometry. We find that in response to amino acid starvation, but not to carbon starvation or rapamycin treatment, cells lacking NPR2 and NPR3 fail to fully (1) activate transcription factors Gln3/Gat1, (2) dephosphorylate TORC1 effector Npr1, and (3) repress ribosomal protein gene expression. Both mutants show proliferation defects only in media containing a low quality nitrogen source, such as proline or ammonia, whereas no defects are evident when cells are grown in the presence of glutamine or peptone mixture. Proliferation defects in npr2Delta and npr3Delta cells can be completely rescued by artificially inhibiting TORC1 by rapamycin, demonstrating that overactive TORC1 in both strains prevents their ability to adapt to an environment containing a low quality nitrogen source. A biochemical purification of each demonstrates that Npr2 and Npr3 form a heterodimer, and this interaction is evolutionarily conserved since the human homologs of NPR2 and NPR3 (NPRL2 and NPRL3, respectively) also co-immunoprecipitate. We conclude that, in yeast, the Npr2/3 complex mediates an amino acid starvation signal to TORC1.


Multinutrient supplement containing ephedra and caffeine causes weight loss and improves metabolic risk factors in obese women: a randomized controlled trial.
To determine the safety and efficacy of a dietary supplement with a low dose of ephedra and caffeine in overweight/obese premenopausal female subjects. A 9-month, double-blind, randomized control study compared the efficacy and safety of a dietary supplement with ephedra and caffeine to a control supplement. Sixty-one healthy, premenopausal women with body mass index (BMI) from 27 to 39 kg/m2 were randomly assigned and received a dietary supplement (40 mg/day ephedra alkaloids, 100 mg/day caffeine, high potency mixture of vitamins, minerals, omega-3 fatty acids) or a control supplement for 9 months. changes in body weight, body composition, lipids, insulin, leptin, adiponectin, ghrelin, and self-reports of physical activity, diet and quality of life indices. blood pressure, heart rate, electrocardiograms, urinalysis, blood histology, serum chemistry measures and self-reported symptoms. Forty-one women completed the study. The treatment group lost significantly more body weight (-7.18 kg) and body fat (-5.33 kg) than the control group (-2.25 and -0.99 kg, respectively), and showed significant declines in heart rate, serum cholesterol, triglycerides, cholesterol to high-density lipoprotein ratio, glucose, fasting insulin, and leptin. Blood pressure, electrocardiograms, other clinical chemistry measures, blood histology, urinalysis, and self-reported physical activity were similar in the groups. Minor symptoms included dry mouth, insomnia, nervousness and palpitations. The treatment group reported more energy and decreased appetite compared to controls and scored higher on a quality of life domain assessing vitality. A dietary supplement containing a low potency ephedra/caffeine mixture appeared safe and effective in causing loss of weight and body fat, and improving several metabolic parameters, including insulin sensitivity and lipid profiles when tested under physician supervision. Such supplements could be a useful tool to assist with weight loss.


The effect of melatonin administration on ethanol-induced lipid peroxidation in rats.
This study was carried out in order to determine the role of melatonin in preventing lipid peroxidation due to acute ethanol intoxication. Male Wistar Albino rats, 2.5-3 months old, were divided into two groups. Melatonin (in 1% ethanol, 2 mg kg-1 body weight) was given intraperitoneally (i.p.) for 21 days to experimental rats whereas controls received 1% ethanol only. On day 21, 6 g kg-1 body weight ethanol was injected to half of the animals in each group and the remainder were kept as corresponding controls. Animals were killed 5 h after ethanol injection. Malondialdehyde (MDA), reduced glutathione (GSH) and the antioxidant enzyme activities (superoxide dismutase, glutathione peroxidase and catalase) were determined in liver tissue homogenates. MDA levels were increased whereas GSH levels tend to decrease following alcohol injection. Melatonin administration prior to ethanol did not alter MDA and GSH levels of tissue and among antioxidant defence enzymes studied, only CuZn-SOD was found to be increased in animals that received melatonin + ethanol. According to the findings of this study, melatonin did not appear to have any direct effect on alcohol-induced lipid peroxidation.


Optimization of batch fermentor sterilization.
This article presents a calculation procedure useful for the optimization and scale up of batch sterilization cycles in large-scale fermentors. This technique determines the sterilization temperature and hold-time necessary to minimize nutrient damage in a specific fermentor. The method can also be used for "scaledown" experiments to eliminate sterilization conditions as a scale up parameter. A method for the systematic evaluation of different sterilization conditions on product yield is also presented. This procedure is useful in determining if scale up of sterilization conditions is important for a given process. The validity of the techniques presented are supported by data showing significant yield improvements in a 1.2 x 10(5) L antibiotic fermentation.


Acute heat priming promotes short-term climate resilience of early life stages in a model sea anemone.
Across diverse taxa, sublethal exposure to abiotic stressors early in life can lead to benefits such as increased stress tolerance upon repeat exposure. This phenomenon, known as hormetic priming, is largely unexplored in early life stages of marine invertebrates, which are increasingly threatened by anthropogenic climate change. To investigate this phenomenon, larvae of the sea anemone and model marine invertebrate Nematostella vectensis were exposed to control (18 °C) or elevated (24 °C, 30 °C, 35 °C, or 39 °C) temperatures for 1 h at 3 days post-fertilization (DPF), followed by return to control temperatures (18 °C). The animals were then assessed for growth, development, metabolic rates, and heat tolerance at 4, 7, and 11 DPF. Priming at intermediately elevated temperatures (24 °C, 30 °C, or 35 °C) augmented growth and development compared to controls or priming at 39 °C. Indeed, priming at 39 °C hampered developmental progression, with around 40% of larvae still in the planula stage at 11 DPF, in contrast to 0% for all other groups. Total protein content, a proxy for biomass, and respiration rates were not significantly affected by priming, suggesting metabolic resilience. Heat tolerance was quantified with acute heat stress exposures, and was significantly higher for animals primed at intermediate temperatures (24 °C, 30 °C, or 35 °C) compared to controls or those primed at 39 °C at all time points. To investigate a possible molecular mechanism for the observed changes in heat tolerance, the expression of heat shock protein 70 (HSP70) was quantified at 11 DPF. Expression of HSP70 significantly increased with increasing priming temperature, with the presence of a doublet band for larvae primed at 39 °C, suggesting persistent negative effects of priming on protein homeostasis. Interestingly, primed larvae in a second cohort cultured to 6 weeks post-fertilization continued to display hormetic growth responses, whereas benefits for heat tolerance were lost; in contrast, negative effects of short-term exposure to extreme heat stress (39 °C) persisted. These results demonstrate that some dose-dependent effects of priming waned over time while others persisted, resulting in heterogeneity in organismal performance across ontogeny following priming. Overall, these findings suggest that heat priming may augment the climate resilience of marine invertebrate early life stages via the modulation of key developmental and physiological phenotypes, while also affirming the need to limit further anthropogenic ocean warming.


Living donor liver transplantation for neonatal fulminant hepatitis due to herpes simplex virus infection.
Although rare, ALF caused by disseminated HSV infection is associated with high mortality in the neonatal population. This condition is often diagnosed relatively late due to the absence of specific signs. We present a case involving a neonate with ALF submitted to living donor liver transplantation without a prior diagnosis. The patient had no skin or mucosal lesions, and IgM serology was negative for HSV-1 and HSV-2. Immunohistochemical staining of the liver explant was positive for herpes virus infection, and the patient subsequently received antiviral drug treatment, with a good outcome. Due to organ shortages and the rarity of the aforementioned condition, LT has seldom been reported for the treatment of ALF caused by herpes virus infection; however, LT may be the only option for neonates with fulminant hepatitis. The use of living donors in an urgent scenario is well established in Eastern countries and safely applicable for pediatric patients with ALF.


A 2D ferromagnetic semiconductor in monolayer Cr-trihalide and its Janus structures.
Using first principles calculations, we explored the physical properties of two-dimensional (2D) Cr-trihalide X3-Cr2-X3 or CrX3 (X = Cl, Br, I) and its Janus monolayers X3-Cr2-Y3 (X and Y = Cl, Br, I) where X ≠ Y. We found that Janus monolayer X3-Cr2-Y3 materials are dynamically stable and that it is feasible to synthesize X3-M2-Y3 2D-crystals. Both pristine and Janus layers have intrinsic two-dimensional ferromagnetic semiconducting band structures; the largest band gap of 2.3 eV was found in Cl3-Cr2-Cl3, while the band gaps decreased in heavier halide systems. Using Monte Carlo simulations, we found that the Curie temperatures (Tc) showed the same feature of strong dependence on the X and Y halides. In non-polar systems with X = Y, we found no dipole moment, while the polar systems with X ≠ Y had induced dipole moments. Thus, the pristine layer has the same function on both sides, while the Janus layer displays dissimilar work functions in two different surface directions; this was related to the dipole moment and the value of electronegativity. We found that both pristine and Janus layer systems displayed rather weak frequency-dependent dielectric functions. Thus, the variation of the refractive index with frequency was small, and almost zero reflectivity was found in all systems.


SMAD4 alteration associates with invasive-front pathological markers and poor prognosis in colorectal cancer.
SMAD4 acts as a tumour suppressor, and the loss of SMAD4 is associated with poor prognosis in colorectal cancer (CRC) patients. Although next-generation sequencing (NGS) enabled us to detect numerous genetic alterations in a single assay, the clinical significance of SMAD4 alteration detected with NGS has not been fully investigated. The aim of this study was to evaluate the clinicopathological characteristics and clinical significance of SMAD4 alteration detected with NGS in CRC. We retrospectively investigated 201 patients with stage I-IV CRC, by using a 415-gene panel. To analyse the relationship between SMAD4 alteration and other clinicopathological characteristics, we evaluated clinicopathological variables, including invasive-front pathological markers: tumour budding, poorly differentiated cluster, and Crohn-like lymphoid reaction. Fifty-six patients (28%) had SMAD4 alteration: 24 and 32 patients had SMAD4 mutation and deletion, respectively. SMAD4 alteration was significantly associated with T category (P = 0.027), N category (P = 0.037), M category (P = 0.028), and invasive-front pathological markers, such as poorly differentiated cluster grade 3 (P = 0.020) and absence of Crohn-like lymphoid reaction (P = 0.004). Immunohistochemistry revealed that SMAD4 alteration was significantly associated with loss of SMAD4 (P = 0.023). In 90 patients with stage I-III disease, SMAD4 alteration was significantly associated with poor prognosis for relapse-free and overall survival (P = 0.047; P = 0.022, respectively). Conversely, in 111 patients with stage IV disease, SMAD4 alteration was not significantly associated with overall survival. SMAD4 alteration is associated with invasive-front pathological markers and poor prognosis in stage I-III CRC patients.


Socio-demographic pattern of drug and alcohol dependents.
The widespread abuse of drugs and Alcohol has become a human tragedy. Each year the abuse of Alcohol and Illicit drugs exact an enormous toll in deaths, decline in productivity, more crime and accidents and also increased expenditure in rehabilitation. The situation is likely to worsen and even may get out of hand if adequate measure are not taken to clearly identify the vulnerable group so as to provide them proper and maximal help. The present paper proposes to examine the sociodemographic correlates viz. Age, Sex group. Educational Status, Income Group, Marital Status and also possible causes of drug abuse of these patients. For this purpose patients of Dr. Vidya Sagar Hospital's drug-de-addition cum rehabilitation unit were statistically analysed. The findings have been discussed.


Involving Moral and Ethical Principles in Safety Management Systems.
Some organisations, and some individual humans, violate moral and ethical rules, whether or not they are written down in laws or codes of conduct. Corporate transgressions, as this behaviour is called, occur because of the actions of those in charge, usually bright and dedicated people. Immoral and unethical conduct can adversely affect the safety of workers, the general public and the environment. A scoping review method for a literature search is used to explore morality and ethics in relation to health and safety management. Our findings show that controlling the risks associated with misconduct and corporate transgression is not usually seen as a responsibility allocated to safety systems but is left to general management and corporate governance. The moral and ethical principles, however, can be applied in safety management systems to prevent misconduct and transgression-related safety risks. Our results show that ethical leadership, ethical behaviour, sustaining an ethical climate and implementation of an ethical decision-making process emerge as key preventive measures. The discussion presents a proposed way to include these measures in safety management systems. Conclusion and recommendations underline that unwanted behaviour and transgression risks can be brought under control, starting from a set of best practices. Not only the managers themselves but also board members, independent external supervisors and government regulators need to embrace these practices.


Serotype-specific effect of influenza on adult invasive pneumococcal pneumonia.
Influenza affects host susceptibility to pneumococcus. We sought to evaluate whether this relationship varies by pneumococcal serotype using a large epidemiological database covering 3 decades. Weekly rates of invasive pneumococcal pneumonia (IPP) were obtained from the Danish National Laboratory Surveillance System, and influenza-like illness (ILI) data were collected from Danish sentinel surveillance, Statens Serum Institut, 1977-2007. We fit Poisson regression models for each age and comorbidity group, with predictors for seasonality and secular changes, ILI activity, and serotype. Among individuals with low levels of comorbidities, influenza had the largest impact on IPP incidence among low-invasiveness serotypes (influenza attributable percent: 17.9%, 95% confidence interval [CI], 13.6-21.9) as compared with high-invasiveness serotypes (6.7%, 95% CI, 3.8%-11.7%). Among those with higher levels of comorbidities, the effect of influenza was smaller, but high-invasiveness serotypes increased more than low-invasiveness serotypes (8.9% [95% CI, 6.6-11.8] vs. 1.3% [95% CI, -1.6-5.4]. Influenza was associated with the greatest increases in the incidence of disease caused by serotypes with lower invasive potential and among individuals with low levels of comorbid conditions. The importance of influenza for adult IPP varies by serotype and host comorbidity.


[Laparoscopic splenectomy as an alternative to open surgery in the treatment of autoimmune thrombocytopenia].
Several studies have shown the potential advantages laparoscopic splenectomy (LS) over open surgery. The aim of this study has been to evaluate the advantages of LS over open surgery in the treatment of autoimmune thrombocytopenia. 54 consecutive patients splenectomized for the treatment of idiopathic thrombocytopenic purpura (ITP) or HIV-related thrombocytopenia were analyzed. Operative features (operative time, conversion to open surgery, accessory spleens), immediate (stay, analgesia and blood transfusion requirements) and late postoperative features (platelet count), as well as splenectomy-related complications in both surgical procedures were compared. Between February 1990 and February 1997, 54 splenctomies were performed for the treatment of autoimmune thrombocytopenia (ITP, n = 47, and HIV-related thrombocytopenia, n = 7). Eighteen were performed through an open approach, and 36 by laparoscopy. Both groups were comparable with regard to age, sex, platelet count, disease duration and body mass index. LS was completed in 34 cases (conversion to open surgery: 5.5%). The incidence of accessory spleens was 11% in the LS group and 5.5% in the open surgery group. Postoperative morbidity (16% vs 28%) and blood requirements (25% vs 33%) were lower after LS, but the differences did not reach statistical significance. Analgesia requirements (7 [SD 3] vs 11 [6]; p < 0.01) and postoperative stay (3.8 [2.6] vs 7.4 [3] days; p < 0.01) were significantly shorter after LS. Following splenectomy, the platelet counts became normal in 72% of patients submitted to LS and 78% of patients in the open surgery group. After 20 and 63 months mean follow-up, one patient in each group developed late complications. As compared to open surgery, LS offers a better immediate clinical outcome, with similar long-term results.


[Irritable bowel syndrome: frequency and phylogenetic relationship of Blastocystis sp. from Mexican patients].
Recent studies reported increased presence of Blastocystis in patients with Irritable Bowel Syndrome (IBS) and an etiologic role has been proposed. The pathogenic role of Blastocystis is controversial, because it is frequently found not only in individuals with enteric symptoms but also in healthy and asymptomatic subjects. Furthermore, there are few studies of blastocistosis in Mexico. To assess the frequency of Blastocystis sp. in IBS patients using molecular techniques and to describe its phylogenetic relationship with sequences of other countries. IBS patients according to Rome III criteria were enrolled. In all patients evaluations included: colonoscopies, coproparasitoscopic studies, coproculture, fecal virus screening. PCR and sequencing for Blastocystis sp. were also performed. We recruited 11 men and 51 women with a mean age of 45.6 (SD ± 15.7) years. Eighty-six percent of the IBS patients presented a normal colonoscopy, 8% showed polyps and 6% diverticular disease. Blastocystis sp. was identified in 25% patients (all of them with normal colonoscopy), while two patients had Endolimax nana and Entamoeba histolytica/E. dispar, respectively. Phylogenetic analysis showed that major sequences of Mexican carriers clustered together with sequences of parasites from Japan and Denmark; furthermore, two sequences from IBS patients were grouped in a single cluster. Blastocystis sp. was identified in 25% of the IBS patients. Our data support the hypothesis of clonal lineages in distinct geographical areas in the world.


Benefits and drawbacks of guanidinoacetic acid as a possible treatment to replenish cerebral creatine in AGAT deficiency.
Arginine-glycine amidinotransferase (AGAT) deficiency is a rare inherited metabolic disorder that severely affects brain bioenergetics. Characterized by mental retardation, language impairment, and behavioral disorders, AGAT deficiency is a treatable condition, where long-term creatine supplementation usually restores brain creatine levels and improves its clinical features. In some cases of AGAT deficiency, creatine treatment might be somewhat limited due to possible shortcomings in performance and transport of creatine to the brain. Guanidinoacetic acid (GAA), a direct metabolic precursor of creatine, has recently been suggested as a possible alternative to creatine to tackle brain creatine levels in experimental medicine. AGAT patients might benefit from oral GAA due to upgraded bioavailability and convenient utilization of the compound, while possible drawbacks (e.g. brain methylation issues, neurotoxicity, and hyperhomocysteinemia) should be accounted as well.


Notable Papers and Trends from 2019 in Sensors, Signals, and Imaging Informatics.
To highlight noteworthy papers that are representative of 2019 developments in the fields of sensors, signals, and imaging informatics. A broad literature search was conducted in January 2020 using PubMed. Separate predefined queries were created for sensors/signals and imaging informatics using a combination of Medical Subject Heading (MeSH) terms and keywords. Section editors reviewed the titles and abstracts of both sets of results. Papers were assessed on a three-point Likert scale by two co-editors, rated from 3 (do not include) to 1 (should be included). Papers with an average score of 2 or less were then read by all three section editors, and the group nominated top papers based on consensus. These candidate best papers were then rated by at least six external reviewers. The query related to signals and sensors returned a set of 255 papers from 140 unique journals. The imaging informatics query returned a set of 3,262 papers from 870 unique journals. Based on titles and abstracts, the section co-editors jointly filtered the list down to 50 papers from which 15 candidate best papers were nominated after discussion. A composite rating after review determined four papers which were then approved by consensus of the International Medical Informatics Association (IMIA) Yearbook editorial board. These best papers represent different international groups and journals. The four best papers represent state-of-the-art approaches for processing, combining, and analyzing heterogeneous sensor and imaging data. These papers demonstrate the use of advanced machine learning techniques to improve comparisons between images acquired at different time points, fuse information from multiple sensors, and translate images from one modality to another.


Modeling laser induced molecule excitation using real-time time-dependent density functional theory: application to 5- and 6-benzyluracil.
The fully propagated real time-dependent density functional theory method has been applied to study the laser-molecule interaction in 5- and 6-benzyluracil (5BU and 6BU). The molecular geometry optimization and the time-dependent electronic dynamics propagation were carried out using the M11-L local meta-NGA (nonseparable gradient approximations) exchange-correlation functional together with the def2-TZVP basis set. Different laser field parameters like direction, strength, and wavelength have been varied in order to estimate the conditions for an efficient excitation of the molecules. The results show that the two molecules respond differently to the applied laser field and therefore specific laser field parameters have to be chosen for each of them in order to get efficient and selective excitation behavior. It was also found that from the molecular excitation point of view not only the magnitude of the transition dipoles between the involved orbitals but also their orientation with respect to the laser field is important. On the other hand, it was shown that the molecular excitation is a very complex overlapping of different one-electron orbital depopulation-population processes of the occupied and virtual orbitals.


A double-blind randomized within-subject study to evaluate clinical applicability of four digital workflows for the fabrication of posterior single implant crown.
To compare efficiency and clinical efficacy of posterior single implant crowns (PSIC) fabricated using four digital workflows. Twenty-two patients with one missing first molar were included. Each patient received four screw-retained implant crowns fabricated through four different workflows including a fully digital workflow with immediate digital impression (Group i-IOS), a fully digital workflow with digital impression after implant osseointegration (Group d-IOS), a model-based hybrid workflow using immediate analogue impression (Group i-AI), and a model-based hybrid workflow with conventional analogue impression after implant osseointegration (Group d-AI). The crown delivery sequence was randomized and blinded. The efficiency for each workflow and clinical outcome of each crown were recorded. The average clinical working time in fully digital workflows (i-IOS 46.90 min, d-IOS 45.66 min) was significantly lower than that in the hybrid workflows (i-AI 54.59 min, d-AI 55.96 min; p < .001). Significantly more laboratory time was spent in hybrid workflows (i-AI 839.60 min, d-AI 811.73 min) as compared to fully digital workflows (i-IOS 606.25 min, d-IOS 607.83 min, p < .01). No significant differences in the chairside time at delivery were found. More crowns in Group i-AI (15%) needed additional laboratory interventions than in the other groups (p = .029). Digital impression and model-free fully digital workflow improved prosthetic efficiency in the fabrication of PSIC. With the limitation that the results were only applicable to the implant system used and the digital technologies applied, findings suggested that workflows integrating immediate impression with implant surgery procedure was clinically applicable for restoration of PSIC.


Brain lipoprotein metabolism and its relation to neurodegenerative disease.
Lipoproteins are macromolecular complexes composed of lipids and proteins. The role of these complexes is to provide cells of the organism with lipids to be used as a source of energy, building blocks for biomembrane synthesis, and lipophilic molecules (e.g., steroid hormones and vitamin E) for other physiological purposes, such as cell signaling and antioxidative mechanisms. Lipoproteins also promote the cellular efflux of cholesterol for its disposal into bile. Thus, lipoproteins play an important role in the maintenance of lipid homeostasis throughout the organism. Accordingly, lipoprotein particles have been found circulating in blood, lymph, and interstitial fluid. Despite the existence of the blood-brain barrier, lipoprotein particles have been shown to be also present in the cerebrospinal fluid (CSF). Although a portion of their protein components may filter through the barrier from the vascular compartment, experimental evidence indicates that these particles originate from the nervous tissue. The other protein components include apolipoproteins E, J, and D, and these have been shown to be synthesized by cells within the central nervous system (CNS). Furthermore, it was shown that lipoprotein particles can be isolated from the conditioned medium of astrocytic cultures. The differences in size, structure, and composition of in vitro assembled particles compared with those isolated from the CSF suggest that the particles are modified following their secretion in vivo. This is supported by observations that lipoprotein-modifying enzymes and transfer proteins are also present within CNS tissue and CSF. The fate of CSF lipoproteins is unclear but is probably related to the turnover and clearance of lipids from the CNS or, alternatively, the particles may be recaptured and recycled back into the CNS tissue. The presence of several cell surface receptors for apoE-containing lipoproteins on ependymal cells, as well as on neurons and glial cells, supports this notion and suggests that the isolated brain possesses its own system to maintain local lipid homeostasis. This is further exemplified by the salvage and recycling of lipids shown to occur following a lesion in order to allow surviving neurons to sprout and reestablish lost synapses. Not much is currently known about lipoprotein metabolism in neurodegenerative diseases, but lipid alterations have been repeatedly reported in Alzheimer brains in which neuronal loss and deafferentation are major features. Although the mechanism underlying the link between the epsilon4 allele of the apolipoprotein E gene and Alzheimer's disease is presently unclear, it may well be postulated that it is related to disturbances in brain lipoprotein metabolism.


Is the low-fat message giving people a license to eat more?
In the past decade, technology for modifying the fat content of foods has progressed and led to the development of highly palatable low-fat foods. Many Americans believe that weight loss can be accomplished by eating an ad libitum low-fat diet, and the development of highly palatable foods that are low in fat provides welcome additions to the food supply. However, in order to maintain high palatability, some of these foods have added sugars and other energy-bearing substances resulting in some low-fat foods which remain high in energy content and are energy-dense. Using such products as substitutes for higher-fat versions of foods is likely to bring about only small reductions in energy intake. A better strategy to reduce energy intake is to consume a low-fat diet made up of low-energy density foods such as fruits, vegetables, and other foods high in fiber and complex carbohydrates. Such a diet may include fat-replaced foods which are also reduced in energy since, for weight loss, a sustained reduction in energy intake is necessary. This can be best accomplished by eating a balanced diet not only low in fat content but also lower in energy.


Activation of GLP-1 receptors attenuates oxycodone taking and seeking without compromising the antinociceptive effects of oxycodone in rats.
Despite the effectiveness of current medications to treat opioid use disorder, there is still a high rate of relapse following detoxification. Thus, there is critical need for innovative studies aimed at identifying novel neurobiological mechanisms that could be targeted to treat opioid use disorder. A growing body of preclinical evidence indicates that glucagon-like peptide-1 (GLP-1) receptor agonists reduce drug reinforcement. However, the efficacy of GLP-1 receptor agonists in attenuating opioid-mediated behaviors has not been thoroughly investigated. Using recently established models of opioid-taking and -seeking behaviors, we showed that systemic administration of the GLP-1 receptor agonist exendin-4 reduced oxycodone self-administration and the reinstatement of oxycodone-seeking behavior in rats. We also identified behaviorally selective doses of exendin-4 that reduced opioid-taking and -seeking behaviors and did not produce adverse feeding effects in oxycodone-experienced rats. To identify a central site of action, we showed that systemic exendin-4 penetrated the brain and bound putative GLP-1 receptors on dopamine D1 receptor- and dopamine D2 receptor-expressing medium spiny neurons in the nucleus accumbens shell. Consistent with our systemic studies, infusions of exendin-4 directly into the accumbens shell attenuated oxycodone self-administration and the reinstatement of oxycodone-seeking behavior without affecting ad libitum food intake. Finally, exendin-4 did not alter the analgesic effects of oxycodone, suggesting that activation of GLP-1 receptors attenuated opioid reinforcement without reducing the thermal antinociceptive effects of oxycodone. Taken together, these findings suggest that GLP-1 receptors could serve as potential molecular targets for pharmacotherapies aimed at reducing opioid use disorder.


Remodeling tumor microenvironment by liposomal codelivery of DMXAA and simvastatin inhibits malignant melanoma progression.
Anti-angiogenic therapies for melanoma have not yet been translated into meaningful clinical benefit for patients, due to the development of drug-induced resistance in cancer cells, mainly caused by hypoxia-inducible factor 1α (HIF-1α) overexpression and enhanced oxidative stress mediated by tumor-associated macrophages (TAMs). Our previous study demonstrated synergistic antitumor actions of simvastatin (SIM) and 5,6-dimethylxanthenone-4-acetic acid (DMXAA) on an in vitro melanoma model via suppression of the aggressive phenotype of melanoma cells and inhibition of TAMs-mediated angiogenesis. Therefore, we took the advantage of long circulating liposomes (LCL) superior tumor targeting capacity to efficiently deliver SIM and DMXAA to B16.F10 melanoma in vivo, with the final aim of improving the outcome of the anti-angiogenic therapy. Thus, we assessed the effects of this novel combined tumor-targeted treatment on s.c. B16.F10 murine melanoma growth and on the production of critical markers involved in tumor development and progression. Our results showed that the combined liposomal therapy almost totally inhibited (> 90%) the growth of melanoma tumors, due to the enhancement of anti-angiogenic effects of LCL-DMXAA by LCL-SIM and simultaneous induction of a pro-apoptotic state of tumor cells in the tumor microenvironment (TME). These effects were accompanied by the partial re-education of TAMs towards an M1 phenotype and augmented by combined therapy-induced suppression of major invasion and metastasis promoters (HIF-1α, pAP-1 c-Jun, and MMPs). Thus, this novel therapy holds the potential to remodel the TME, by suppressing its most important malignant biological capabilities.


Alveolar macrophage activation in experimental legionellosis.
Legionella pneumophila is a facultative intracellular parasite of alveolar macrophages. In vitro studies have shown that lymphokine-activated mononuclear phagocytes inhibit intracellular replication of L. pneumophila. To determine if recovery from legionellosis is associated with activation of alveolar macrophages in vivo to resist L. pneumophila, we studied an animal model of Legionnaires' disease. Rats were exposed to aerosolized L. pneumophila and alveolar macrophages were harvested during the recovery phase of infection. We compared these alveolar exudate macrophages with normal resident alveolar macrophages for the capacity to support or inhibit the intracellular growth of L. pneumophila. We also measured Ia expression as a marker of immunologic activation, and studied binding of bacteria, superoxide release, and the expression of transferrin receptors as potential mechanisms of resistance to L. pneumophila. For perspective on the specificity of these responses, we also studied alveolar exudate cells elicited by inhalation of heat-killed L. pneumophila, live Listeria monocytogenes, and live Escherichia coli. We found that alveolar exudate macrophages elicited by live L. pneumophila, but not heat-killed L. pneumophila, resisted the intracellular growth of L. pneumophila. Exudate macrophages in resolving legionellosis exhibited increased Ia expression, diminished superoxide production, and downregulation of transferrin receptors. Binding of L. pneumophila to exudate macrophages was indistinguishable from that to resident macrophages in the presence of normal serum, and augmented in the presence of immune serum. Alveolar exudate macrophages elicited by E. coli also inhibited growth of L. pneumophila, and exhibited a modest increase in Ia expression without change in transferrin receptors. Exudate cells induced by L. monocytogenes exhibited up-regulation of Ia without diminution of superoxide release. Alveolar cells harvested after inhalation of heat-killed L. pneumophila did not differ from resident alveolar macrophages in the expression of surface markers. These findings suggest that alveolar macrophages are immunologically activated in vivo to serve as effector cells in resolving legionellosis, and that live bacteria are required to induce this expression of immunity. The mechanism of resistance to parasitism by L. pneumophila may entail restriction of the intracellular availability of iron, but does not involve diminished bacterial binding or an augmented respiratory burst.


Awareness of state legislation on naloxone accessibility associated with willingness to prescribe naloxone.
Increasing rates of opioid-related deaths, state naloxone legislation changes, and negativity prompted investigation of predictive factors associated with willingness to prescribe naloxone to populations at risk of overdose, including knowledge of risk factors, assessment of persons at risk, awareness of legislative changes, perceptions of professional responsibility, and confidence around naloxone prescribing and distribution. Cross-sectional, Web-based, anonymous, voluntary survey to prescribers of 2 regional health care systems serving urban and rural North Dakota, northern Minnesota, and northwestern Wisconsin. Human subject research was approved by university and health care systems' institutional review boards. Overall, 203 of 1586 prescribers responded; however, not all prescribers completed each survey item. A majority (89.4%, n = 127/142) of respondents had never prescribed naloxone for overdose prevention. Willingness to prescribe naloxone for 4 patient care scenarios involving substantial opioid overdose risk ranged from 43.4% to 70.5%. Knowledge mean score was 15.5 (SD = 2.9) out of 22 with median 15 (range: 5-22). Naloxone legislation awareness score was 8.8 (SD = 3.8) out of 15 with median 8 (range: 3-15). There was a statistically significant but modest correlation between willingness to prescribe naloxone and the other variables, including awareness of state naloxone-related legislation (r = 0.43, P < .0001), level of self-confidence about dosing, prescribing, and writing protocols for naloxone (r = 0.37, P < .0001), general knowledge (r = 0.24, P = .0032), and perception of professional responsibility (r = 0.19, P = .03). Multivariate regression analysis indicated willingness to prescribe naloxone was associated with statistically significant predictors, including awareness of the naloxone laws (P = .0016) and self-confidence about dosing, prescribing, and writing protocols (P = .0011). Prescribers who are more aware of state laws regarding naloxone and confident in their knowledge of dosing, administration, and writing protocols may be more willing to prescribe naloxone.


A pramoxine-based anti-itch lotion is more effective than a control lotion for the treatment of uremic pruritus in adult hemodialysis patients.
The objective of this study was to evaluate the efficacy of a commercially available anti-itch lotion containing 1% pramoxine hydrochloride versus control lotion in the treatment of uremic pruritus in adult hemodialysis patients. This was a randomized, double-blind, controlled comparative trial set in a community hemodialysis center. The study population comprised 28 individuals (mean age 53.5) with moderate to severe uremic pruritus who had been receiving hemodialysis for at least 3 months. All participants were recruited from one community hemodialysis center. Topical anti-itch lotion containing 1% pramoxine was applied twice daily to all affected areas of pruritus for 4 weeks. The main outcome measure was a reduction in itch intensity. Secondary outcomes included increases in the investigator's global assessment and improvement in skin hydration. There was a 61% decrease in itch intensity in the treatment group, whereas a 12% reduction in itch intensity was observed in the control group. The rate of decline in itching was also greater in the treatment arm versus the control arm. No significant differences were displayed in other studied disease-related variables. Our study shows that individuals using pramoxine 1% lotion experienced a reduction in pruritus to a greater degree than those using the control lotion. This safe, convenient and effective topical lotion may potentially benefit the large number of patients affected by pruritus associated with end-stage renal disease.


Comparative cost-effectiveness of SARS-CoV-2 testing strategies in the USA: a modelling study.
To mitigate the COVID-19 pandemic, countries worldwide have enacted unprecedented movement restrictions, physical distancing measures, and face mask requirements. Until safe and efficacious vaccines or antiviral drugs become widely available, viral testing remains the primary mitigation measure for rapid identification and isolation of infected individuals. We aimed to assess the economic trade-offs of expanding and accelerating testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) across the USA in different transmission scenarios. We used a multiscale model that incorporates SARS-CoV-2 transmission at the population level and daily viral load dynamics at the individual level to assess eight surveillance testing strategies that varied by testing frequency (from daily to monthly testing) and isolation period (1 or 2 weeks), compared with the status-quo strategy of symptom-based testing and isolation. For each testing strategy, we first estimated the costs (incorporating costs of diagnostic testing and admissions to hospital, and salary lost while in isolation) and years of life lost (YLLs) prevented under rapid and low transmission scenarios. We then assessed the testing strategies across a range of scenarios, each defined by effective reproduction number (Re), willingness to pay per YLL averted, and cost of a test, to estimate the probability that a particular strategy had the greatest net benefit. Additionally, for a range of transmission scenarios (Re from 1·1 to 3), we estimated a threshold test price at which the status-quo strategy outperforms all testing strategies considered. Our modelling showed that daily testing combined with a 2-week isolation period was the most costly strategy considered, reflecting increased costs with greater test frequency and length of isolation period. Assuming a societal willingness to pay of US$100 000 per YLL averted and a price of $5 per test, the strategy most likely to be cost-effective under a rapid transmission scenario (Re of 2·2) is weekly testing followed by a 2-week isolation period subsequent to a positive test result. Under low transmission scenarios (Re of 1·2), monthly testing of the population followed by 1-week isolation rather than 2-week isolation is likely to be most cost-effective. Expanded surveillance testing is more likely to be cost-effective than the status-quo testing strategy if the price per test is less than $75 across all transmission rates considered. Extensive expansion of SARS-CoV-2 testing programmes with more frequent and rapid tests across communities coupled with isolation of individuals with confirmed infection is essential for mitigating the COVID-19 pandemic. Furthermore, resources recouped from shortened isolation duration could be cost-effectively allocated to more frequent testing. US National Institutes of Health, US Centers for Disease Control and Prevention, and Love, Tito's.


Association of PPP1R13L and CD3EAP polymorphisms with risk and survival of non-small cell lung cancer in Chinese non-smoking females.
PPP1R13L and CD3EAP were confirmed to play important roles in transcription and apoptosis. SNPs in PPP1R13L and CD3EAP may be associated with lung cancer risk and survival. This study investigated the association of PPP1R13L rs1005165 and CD3EAP rs967591 with non-small cell lung cancer (NSCLC) risk and survival in Chinese non-smoking females. 442 NSCLC cases and 480 cancer-free controls were conducted in the case-control study, and 283 cases were in cohort study. Genotype was determined by Taqman real-time PCR. The statistical analyses were performed by SPSS 22.0 software. We found that rs1005165 and rs967591 were significantly associated with NSCLC risk in Chinese non-smoking females. For rs1005165, compared with homozygous wild CC genotype, carriers of CT or TT genotype had lower risk of NSCLC (adjusted ORs were 0.675 and 0.713, 95% CI were 0.461-0.988 and 0.525-0.968, respectively), adjusted OR for dominant model was 0.702, 95% CI was 0.526-0.937. For rs967591, AA genotype (adjusted OR = 0.721, 95% CI = 0.532-0.978) and at least one A allele (GA+AA) (adjusted OR = 0.716, 95% CI = 0.536-0.956) were significantly correlated with lower risk of NSCLC, compared with GG genotype. But we didn't find correlation between the two SNPs and survival time in Chinese non-smoking NSCLC females. In general, we found PPP1R13L rs1005165 and CD3EAP rs967591 might be associated with lower NSCLC risk in Chinese non-smoking females, but no significant relationship was found with NSCLC survival.


Arterial graft infections. Delayed v immediate vascular reconstruction.
We evaluated the treatment and clinical outcome of 20 patients with major abdominal vascular graft infections and found that immediate reconstruction of arterial inflow to the lower extremities after complete removal of contaminated graft material may not always be necessary or advisable. Patients were treated by the following categories: group 1, graft removal with immediate vascular reconstruction (seven patients, two aortoiliac and five aortofemoral grafts); group 2, graft removal with delayed vascular reconstruction (13 patients, three aortoiliac, five aortofemoral, and five extra-abdominal grafts). The mortality (57%) and the incidence of major amputation (14%) were highest when immediate vascular reconstruction was attempted. Patient survival, the incidence of recurrent graft infection, and the need for major amputation were favorably altered with delayed reconstruction even when prosthetic material was used.


Complexation of Chol-DsiRNA in place of Chol-siRNA greatly increases the duration of mRNA suppression by polyplexes of PLL(30)-PEG(5K) in primary murine syngeneic breast tumors after i.v. administration.
RNA interference has tremendous potential for cancer therapy but is limited by the insufficient potency of RNAi molecules after i.v. administration. We previously found that complexation with PLL(30)-PEG(5K) greatly increases the potency of 3'-cholesterol-modified siRNA [Chol-siRNA] in primary murine syngeneic 4T1 breast tumors after i.v. administration but mRNA suppression decreases 24 h after the final dose. We hypothesized that complexation of cholesterol-modified Dicer-substrate siRNA (Chol-DsiRNA) in place of Chol-siRNA can increase the potency and duration of suppression by polyplexes of PLL(30)-PEG(5K) in solid tumors. We found that replacing Chol-siRNA with Chol-DsiRNA increased polyplex loading and nuclease protection, suppressed stably expressed luciferase to the same extent in primary murine 4T1-Luc breast tumors under the current dosage regimen, but maintained suppression ~72 h after the final dose. The kinetics of suppression in 4T1-Luc over 72 h, however, were similar between DsiLuc and siLuc after electroporation and between polyplexes of Chol-DsiLuc and Chol-siLuc after transfection, suggesting that Chol-DsiRNA polyplexes increase the duration of mRNA suppression through differences in polyplex activities in vivo. Thus, replacing Chol-siRNA with Chol-DsiRNA may significantly increase the duration of mRNA suppression by polyplexes of PLL(30)-PEG(5K) and possibly other PEGylated polycationic polymers in primary tumors and metastases after i.v. administration.


Long term effects of an integrated care intervention on hospital utilization in patients with severe COPD: a single centre controlled study.
Chronic obstructive pulmonary disease (COPD) is one of the main causes of morbidity and mortality globally. In Trondheim in 2008 an integrated care model (COPD-Home) consisting of an education program, self-management plan, home visits and a call centre for patient support and communication was developed. The objective was to determine the efficacy of an intervention according to the COPD-Home model in reducing hospital utilization among patients with COPD stage III and IV (GOLD 2007) discharged after hospitalization for acute exacerbations of COPD (AECOPD). A single centre, prospective, open, controlled clinical study comparing COPD-Home integrated care (IC) with usual care (UC). Ninety-one versus 81 patients mean age 73.4 ± 9.3 years (57% women) were included in the IC group (ICG) and the UC group (UCG) respectively, and after 2 years 51 and 49 patients were available for control in the respective groups. During the year prior to study start there were 71 hospital admissions (HA) in the ICG and 84 in the UCG. There was a 12.6% reduction in HA in the ICG during the first year of follow-up and a 46.5% reduction during the second year (p = 0.01) compared to an 8.3% increase during the first year and no change during the second year in the ICG. During the year prior to study start, the number of hospital days (HD) was 468 in the ICG and 479 in the UCG. In the IC group, the number of HD was reduced by 48.3% during the first year (p = 0.01), and remained low during the second year of follow-up (p=0.02). In the UC group, the number of HD remained unchanged during the follow-up period. There was a trend towards a shorter survival time among patients in the ICG compared to the UCG, hazard ratio 1.33 [95% CI 0.77 to 2.33]. Intervention according to the COPD-Home model reduced hospital utilization in patients with COPD III and IV with a persisting effect throughout the 2 years of follow-up. However, there was a trend towards a shorter survival time in the intervention group.


Sleep assessments in healthy school-aged children using actigraphy: concordance with polysomnography.
Actigraphic (ACT) recordings are used widely in schoolchildren as a less intrusive and more extended approach to evaluation of sleep problems. However, critical assessment of the validity and reliability of ACT against overnight polysomnography (NPSG) are unavailable. Thus, we explored the degree of concordance between NPSG and ACT in school-aged children to delineate potential ACT boundaries when interpreting pediatric sleep. Non-dominant wrist ACT was recorded simultaneously with NPSG in 149 healthy school-aged children (aged 4.1-8.8 years, 41.7% boys, 80.4% Caucasian) recruited from the community. Analyses were limited to the Actiware (MiniMitter-64) calculated parameters originating from 1-min epoch sampling and medium sensitivity threshold value of 40; i.e. sleep period time (SPT), total sleep time (TST) and wake after sleep onset (WASO). SPT was not significantly different between ACT and NPSG. However, ACT underestimated TST significantly by 32.2±33.4 min and overestimated WASO by 26.3±34.4 min. The decreased precision of ACT was also evident from moderate to small concordance correlation coefficients (0.47 for TST and 0.09 for WASO). ACT in school-aged children provides reliable assessment of sleep quantity, but is relatively inaccurate during determination of sleep quality. Thus, caution is advocated in drawing definitive conclusions from ACT during evaluation of the sleep-disturbed child.


Continuous airway pressure with oxygen minimizes the metabolic lesion of 'pump lung'.
Water distribution and energy status of the lung were measured in ten rabbits at two hours of hypothermic cardiopulmonary bypass (CPB) with left heart venting and incision of the parietal pleurae. During CPB, half the animals had their airways open to room air at ambient atmospheric pressure (ZEEP), and the remainder had their lungs inflated (CPAP) at a pressure of 5 cms H2O with the oxygen-enriched (70-75 per cent) gas mixture exiting from the disc oxygenator. In both the ZEEP and CPAP groups, there was more than doubling of the pulmonary extravascular sodium-free water (intracellular) space and reciprocal reduction of the pulmonary extravascular sodium (extracellular) space, compared with 12 control animals not undergoing CPB. In the ZEEP group, there was an 18-fold increase in the pulmonary lactate/pyruvate (L/P) ratio compared with controls, and the pulmonary energy charge (E.C.) was significantly less than in controls (0.74 +/- 0.02 vs. 0.89 +/- 0.01). In the CPAP group the pulmonary L/P ratio was 2 1/2 times control values and the pulmonary E.C. was virtually identical with that of the control group. These data suggest that CPB results in a shift of fluid from the pulmonary interstitium into the pulmonary intracellular compartment with no net increase in total pulmonary extravascular water. The data also suggest that pulmonary deflation during CPB results in a significant pulmonary energy deficit which can be prevented by keeping the lung inflated with an oxygen-enriched gas mixture during CPB.


Colloids on the frontier of ferrofluids. Rheological properties.
This paper is devoted to the steady-state rheological properties of two new kinds of ferrofluids. One of these was constituted by CoNi nanospheres of 24 nm in diameter, whereas the other by CoNi nanofibers of 56 nm in length and 6.6 nm in width. These ferrofluids were subjected to shear rate ramps under the presence of magnetic fields of different intensity, and the corresponding shear stress values were measured. From the obtained rheograms (shear stress vs shear rate curves) the values of both the static and the dynamic yield stresses were obtained as a function of the magnetic field. The magnetoviscous effect was also obtained as a function of both the shear rate and the magnetic field. The experimental results demonstrate that upon magnetic field application these new ferrofluids develop yield stresses and magnetoviscous effects much greater than those of conventional ferrofluids, based on nanospheres of approximately 10 nm in diameter. Besides some expected differences, such as the stronger magnetorheological effect in the case of ferrofluids based on nanofibers, some intriguing differences are found between the rheological behaviors of nanofiber ferrofluids and nanosphere ferrofluid. First, upon field application the rheograms of nanofiber ferrofluids present N-shaped dependence of the shear stress on the shear rate. The decreasing part of the rheograms takes place at low shear rate. These regions of negative differential viscosity, and therefore, unstable flow is not observed in the case of nanosphere ferrofluids. The second intriguing difference concerns the curvature of the yield stress vs magnetic field curves. This curvature is negative in the case of nanosphere ferrofluid, giving rise to saturation of the yield stress at medium field, as expected. However, in the case of nanofiber ferrofluid this curvature is positive, which means a faster increase of the yield stress with the magnetic field the higher the magnitude of the latter. These interesting differences may be due to the existence of strong interparticle solid friction in the case of nanofiber ferrofluids. Finally, theoretical models for the static yield stress of the ferrofluids were developed. These models consider that upon field application the ferrofluid nanoparticles are condensed in drops of dense phase. These drops tend to be aligned along the field direction, opposing the flow of the ferrofluids and being responsible for the static quasielastic deformation and the yield-stress phenomena. By considering the existence of interparticle dry friction only in the case of nanofiber ferrofluids, the developed models predicted quite well not only the magnitude of the static yield stress but also the differences in curvature of the yield stress vs magnetic field curves.


Contamination: The Case of Civets, Companionship, COVID, and SARS.
This research explores the intersection between zoonosis and the trade in wild animals by applying the Asian palm civet (Paradoxurus hermaphroditus) as a lens through which to analyse the ways humans and animals shape, and are shaped by, multi-species entanglements. Civets occupy a unique space within contemporary human-animal relations, as they have become an increasingly popular companion species despite being vectors of severe acute respiratory syndrome (SARS) coronavirus. The 2002 SARS outbreak not only killed 774 humans, but its confirmed species origin instigated the retribution-like public slaughter of an estimated 10,000 civets. Guided by the theory of "contamination", this paper compares human-civet relations during SARS and COVID-19 outbreaks through content analysis of global news media and the social media activity of "Civet Lover" clubs, dedicated social spaces for civet pet keeping enthusiasts. Results show that amidst the COVID-19 pandemic, the civet pet trade is thriving with considerable implications for humans and animals. This paper argues for the exotic pet trade to receive greater monitoring and regulation, for compromised animal welfare and health could present the opportunity for further disease emergence.


[Natriuretic peptide system].
Natriuretic peptide system consists of three endogenous ligands, ANP (atrial natriuretic peptide), BNP (brain natriuretic peptide) and CNP (C-type natriuretic peptide), and three receptor subtypes, natriuretic peptide receptor (NPR)-A or guanylate cyclase (GC)-A and NPR-B or GC-B and C receptor (NPR-C). ANP and BNP are mainly secreted from the atrium and ventricle of the heart respectively to act as cardiac hormones whereas CNP is secreted from the endothelium to act as an endothelium-derived relaxing peptide. ANP and BNP regulate body fluid and blood pressure to reduce cardiac pre- and after-load. Recent molecular biology and developmental biotechnology demonstrated the physiological role of ANP and BNP for the determination of basal blood pressure. CNP can modulate the phenotype of vascular smooth muscle cells to regulate vascular remodeling. Therefore, natriuretic peptide system is implicated in the pathophysiology of hypertension, congestive heart failure atherosclerosis and renal diseases. Clinical application of natriuretic peptide system is actively going on progress. Determination of plasma ANP and BNP levels are useful for the evaluation of congestive heart failure, cardiac hypertrophy and acute myocardial infarction. Infusion of ANP improves acute heart failure. Application of NEP (neutral endopeptidase) inhibitor for the treatment of congestive heart failure and hypertension is under clinical trial.


Formation of the D-loop structure complexes between DNA and oligonucleotides and affinity modification of DNA by chemically reactive derivatives of oligonucleotides lead to the recombination.
Affinity modification of DNA by chemically reactive derivatives of complementary oligonucleotides (ODNs) and antisense ODNs has shown an application for the inhibition of gene expression and the growth of viruses and parasites in high organisms. Unfortunately, the rapid advancement of antisense therapeutic approaches is not parallel to the investigation of possible consequences of antisense and gene-directed ODNs on genetic material of the cells being treated. Here we tried for the first time to estimate a possible genetic impact of antisense ODNs and their chemically reactive derivatives on the cells using bacteria and the plasmid DNA. Recombination of direct repeats, induced by the formation of reversible complexes of plasmid DNA with complementary ODNs and after covalent binding of the alkylating derivative of the ODNs with DNA, has been investigated. For this purpose, a polylinker sequence flanked by 165 bp direct repeats was inserted within the tet gene of pBR 327. This plasmid was used to construct DNA containing AT- and GC-rich sequences placed in the central region of the polylinker. Transformation of E. coli cells with the plasmids (and with mixtures of the plasmids with d(pN)17 complementary to the AT- and GC-rich sequences) did not produce deletions. After modification of plasmids with alkylating derivatives of d(pN)17, the deletion of the polylinker DNA region (recombination) revealed the restoration of the tet gene function. The same effect was found at the cell transformations with the D-loop complex of the plasmids with ODNs, but the frequency of the transformants was about 1.5-2 times lower. The data obtained demonstrate that the complexes of DNA with complementary ODNs and the modification of the plasmids by reactive ODN derivatives result in induction of the recombination process and in loss of genetic material.


Bacteria under SOS evolve anticancer phenotypes.
The anticancer drugs, such as DNA replication inhibitors, stimulate bacterial adhesion and induce the bacterial SOS response. As a variety of bacterial mutants can be generated during SOS, novel phenotypes are likely to be selected under the drug pressure. Bacteria growing with cancer cells in the presence of the replication inhibitors undergo the SOS response and evolve advantageous phenotypes for the bacteria to invade the cancer cells in order to evade the drug attack. This hypothesis predicts that bacteria produce the proteins that mediate bacterial capture and invasion of cancer cells--the advantageous phenotypes. Generation of the phenotypes may be facilitated during the SOS response induced by anticancer drugs. 1) Examine attachment and invasion of bacterium Pseudomonas aeruginosa and the SOS mutant control to cancer cells in the presence of the anticancer drugs that inhibit DNA replication enzymes and trigger the SOS response. 2) Reveal the bacterial proteins that exhibit changes in expression. 3) Identify the genes encoding cancer adhesion and invasion. 4) Construct the mutants for the genes, clone and express these genes. 5) Examine the bacterial capture and invasion of cancer cells in contrast to non-cancer control. 1) The bacterial proteins will be differentially induced during bacteria-cancer interaction under the SOS response to the anticancer drugs. 2) Knocking out the bacterial cancer-adhesion-invasion genes will disrupt the adhesion-invasion phenotypes of the bacteria. 3) Expressing these genes will direct the bacterial capture and invasion of cancer cells. Bacteria can evolve anticancer phenotypes targeting metastatic cells. If this hypothesis is true, the outcomes will contribute to development of a novel bacterial anti-metastasis regimen.


Structure, subunit organization and behavior of the asymmetric Type IIT restriction endonuclease BbvCI.
BbvCI, a Type IIT restriction endonuclease, recognizes and cleaves the seven base pair sequence 5'-CCTCAGC-3', generating 3-base, 5'-overhangs. BbvCI is composed of two protein subunits, each containing one catalytic site. Either site can be inactivated by mutation resulting in enzyme variants that nick DNA in a strand-specific manner. Here we demonstrate that the holoenzyme is labile, with the R1 subunit dissociating at low pH. Crystallization of the R2 subunit under such conditions revealed an elongated dimer with the two catalytic sites located on opposite sides. Subsequent crystallization at physiological pH revealed a tetramer comprising two copies of each subunit, with a pair of deep clefts each containing two catalytic sites appropriately positioned and oriented for DNA cleavage. This domain organization was further validated with single-chain protein constructs in which the two enzyme subunits were tethered via peptide linkers of variable length. We were unable to crystallize a DNA-bound complex; however, structural similarity to previously crystallized restriction endonucleases facilitated creation of an energy-minimized model bound to DNA, and identification of candidate residues responsible for target recognition. Mutation of residues predicted to recognize the central C:G base pair resulted in an altered enzyme that recognizes and cleaves CCTNAGC (N = any base).


Deciphering the hunting strategy of a bacterial wolfpack.
Myxococcus xanthus is a common soil bacterium with an intricate multicellular lifestyle that continues to challenge the way in which we conceptualize the capabilities of prokaryotic organisms. Myxococcus xanthus is the preferred laboratory representative from the Myxobacteria, a family of organisms distinguished by their ability to form highly structured biofilms that include tentacle-like packs of surface-gliding cell groups, synchronized rippling waves of oscillating cells and massive spore-filled aggregates that protrude upwards from the substratum to form fruiting bodies. But most of the Myxobacteria are also predators that thrive on the degradation of macromolecules released through the lysis of other microbial cells. The aim of this review is to examine our understanding of the predatory life cycle of M. xanthus. We will examine the multicellular structures formed during contact with prey, and the molecular mechanisms utilized by M. xanthus to detect and destroy prey cells. We will also examine our understanding of microbial predator-prey relationships and the prospects for how bacterial predation mechanisms can be exploited to generate new antimicrobial technologies.


Review of Ethnobotanical and Ethnopharmacological Evidence of Some Ethiopian Medicinal Plants Traditionally Used for Peptic Ulcer Disease Treatment.
A peptic ulcer is described as the rupture of the mucosal integrity of the stomach, the duodenum, and, in certain cases, the lower esophagus as a result of contact with chloridopeptic secretions. The two most common kinds of peptic ulcer disorders are referred to as "gastric ulcer" and "duodenal ulcer." The name is derived from the location of the ulceration. Despite the promise of a wide range of antiulcer treatments, these therapies are associated with several adverse reactions, including hypersensitivity, arrhythmia, impotence, gynecomastia, galactorrhea, hematological abnormalities, and kidney disease, which are intolerable for many patients. Nowadays, there is a lot of emphasis on finding new and innovative agents. As a result, herbal medicines are commonly utilized in circumstances when drugs are used for long periods and are also cost-efficient, effective, and readily available. In this review paper, a total of 82 medicinal plants have been identified and reported for their use in the treatment of peptic ulcer disease. The majority of these medicinal plants are widely used throughout Ethiopia. However, only the safety and efficacy of Plantago lanceolata, Osyris quadripartita, Rumex nepalensis, Cordia africana, Croton macrostachyus, and Urtica simensis have been scientifically studied in animal models. Despite this, many medicinal plants' pharmacological effects and chemistry have not been well studied scientifically. As a result, further bioactive compound characterization, efficacy, mechanism of action evaluation, and toxicity evaluation of medicinal plants should be carried out. A study that can improve the documentation of indigenous knowledge and contribute to drug development and future self-reliance is also recommended.


Gap-edge Asymptotics of defect modes in 2D Photonic Crystals.
We consider defect modes created in complete gaps of 2D photonic crystals by perturbing the dielectric constant in some region. We study their evolution from a band edge with increasing perturbation using an asymptotic method that approximates the Green function by its dominant component which is associated with the bulk mode at the band edge. From this, we derive a simple exponential law which links the frequency difference between the defect mode and the band edge to the relative change in the electric energy. We present numerical results which demonstrate the accuracy of the exponential law, for TE and TM polarizations, hexagonal and square arrays, and in each of the first and second band gaps.


Association of plasma pentraxin 3 with arterial stiffness in overweight and obese individuals.
Obesity and increased arterial stiffness are independent risk factors for cardiovascular disease. The degree of arterial stiffness in obese individuals is greater than that in normal-weight subjects. Pentraxin 3 (PTX3) is mainly produced by vascular tissues and exerts a cardioprotective effect. However, the relationship between PTX3 and arterial stiffness in obese individuals has not yet been clarified. In this study, we examined the relationships between obesity, arterial stiffness, and PTX3 levels in 282 subjects. All participants were classified as normal weight, overweight, or obese on the basis of their body mass index. We measured the brachial-ankle pulse wave velocity (baPWV; an index of arterial stiffness) and plasma PTX3 concentrations in all subjects. Additionally, the carotid-femoral PWV (cfPWV) was measured in 173 subjects. We found that baPWV and cfPWV in overweight and obese subjects were significantly higher than those in normal-weight subjects. Plasma PTX3 concentrations in normal-weight subjects were significantly higher than those in overweight and obese subjects. Moreover, PTX3 had a significant negative correlation with baPWV. However, stepwise multivariable linear regression analysis did not indicate any associations between these parameters. Arterial stiffness is increased in overweight and obese individuals. The increase in arterial stiffness may, at least in part, be associated with an obesity-related reduction in plasma PTX3 concentrations.


Diet or medically treated gestational diabetes: is there any difference for obstetrical and neonatal complications? A French cohort study.
The aim of the present study was to determine specific obstetrical and neonatal complications associated with diet-treated gestational diabetes (DTGD) and medically treated gestational diabetes (MTGD). This is a prospective cohort study of women followed in the Robert Debré Hospital (France, Paris) and who have given birth between 1 January, 2004, and 19 November, 2010. Clinical, biological, maternal and neonatal data were reported in the maternity database. Associations between obstetrical and neonatal complications and gestational diabetes were evaluated by estimating odd ratios (ORs) and their 95% CIs, using a logistic regression model. 16,244 pregnancies were included in the study. 1515 (9.3%) women had gestational diabetes: 1108 (7.3%) had DTGD, 243 (1.7%) had MTGD. After full adjustment, MTGD was associated with an increased risk of nonscheduled cesarean (ORnonscheduled=2.3; 95% CI: 1.6-3.3; P<0.001) while DTGD was not (ORnonscheduled=1.0; 95% CI: 0.8-1.3; P<0.96). Clinical macrosomia was positively associated with DTGD (OR=2; 95% CI: 1.7-2.4; P<0.0001) or MTGD (OR=2.9; 95% CI: 2.1-3.9; P<0.0001). This study confirms that macrosomia is the main complication of DTGD. By contrast, DTGD was not associated with neonatal hypoglycemia and cesarean, while these complications were associated with MTGD.


What Emotion Facial Expressions Tell Us About the Health of Others.
To avoid contagion, we need information about the health status of those whom we engage with. This is especially important when we have cause for concern that the other is indeed sick, such as is the case during the world-wide outbreak of the coronavirus in 2020. In three studies, one conducted several years before the pandemic, and two during the pandemic, we showed that facial expressions of emotions are used as signals of health status. Specifically, happy expressers are perceived as healthier than expressers showing negative emotions or neutrality (Studies 1-3), whereas anger was interpreted as a signal of ill health (Study 3). Importantly, however, facial expressions affected health perception only when there was a prior reason to suspect ill health. This was the case for older expressers before and after the pandemic for whom age-related stereotypes set expectations of ill health and for all ages during a wide-spread pandemic, which extends this suspicion to everyone. In Study 3, we showed that the effect of emotion expressions was also generalized to the physical distance that the observer wishes to keep from the expresser. Overall, this research is the first to show a role of emotion expressions in informing health perception.


Language dominance in neurologically normal and epilepsy subjects: a functional MRI study.
Language dominance and factors that influence language lateralization were investigated in right-handed, neurologically normal subjects (n = 100) and right-handed epilepsy patients (n = 50) using functional MRI. Increases in blood oxygenation-dependent signal during a semantic language activation task relative to a non-linguistic, auditory discrimination task provided an index of language system lateralization. As expected, the majority of both groups showed left hemisphere dominance, although a continuum of activation asymmetry was evident, with nearly all subjects showing some degree of right hemisphere activation. Using a categorical dominance classification, 94% of the normal subjects were considered left hemisphere dominant and 6% had bilateral, roughly symmetric language representation. None of the normal subjects had rightward dominance. There was greater variability of language dominance in the epilepsy group, with 78% showing left hemisphere dominance, 16% showing a symmetric pattern and 6% showing right hemisphere dominance. Atypical language dominance in the epilepsy group was associated with an earlier age of brain injury and with weaker right hand dominance. Language lateralization in the normal group was weakly related to age, but was not significantly related to sex, education, task performance or familial left-handedness.


Granulocyte/macrophage-, megakaryocyte-, eosinophil- and erythroid-colony-stimulating factors produced by mouse spleen cells.
The formation of mature haemopoietic cells is controlled by hormones that specifically stimulate the progenitor cells of the granulocyte/macrophage, eosinophil, megakaryocyte and erythroid pathways. PWMSC medium (pokeweed-mitogen-stimulated spleen-cell-conditioned medium) is known to contain the biological activities that control the clonal proliferation of these four progenitor cells in vitro in semi-solid agar cultures. In this study the molecular properties of these biological activities were characterized, and all four colony-stimulating factors appear to be associated with glycoproteins. These factors were precipitated between 50 and 80%-satd. (NH(4))(2)SO(4) and could be concentrated by ultrafiltration over a 10000-mol.wt.-cut-off hollow-fibre membrane. Megakaryocyte- and erythroid-colony-stimulating factors were lost when the conditioned medium was dialysed at low ionic strength (<0.03m). Neither asialo- nor sialo-erythropoietin was detectable in concentrated PWMSC medium or in the fractions purified from it by gel filtration on Sephadex G-150. The factors bound to concanavalin A-Sepharose were eluted with alpha-methyl-d-glucopyranoside (0.10m). Analysis by gel filtration on Sephadex G-150 indicated that the apparent molecular-weight distributions of all colony-stimulating factors were identical (37000). Treatment with neuraminidase did not alter the biological activities of any of these factors, but when the molecular weights were analysed, after neuraminidase treatment, on Sepharose CL-6B in the presence of guanidine hydrochloride (6m) all were eluted with a mol.wt. of 24000. Although the apparent molecular weights of the different factors were identical, charge differences were detectable by isoelectric focusing on thin-layer granulated gels. There appeared to be considerable charge heterogeneity associated with each factor, as all were focused over 2-4 pH units. The maximum activity of the granulocyte/macrophage-colony-stimulating factor on isoelectric focusing was at pH4.8, whereas the maximum activity for the eosinophil-colony-stimulating factor was at pH5.8. The erythroid- and megakaryocyte-colony-stimulating activities were detected in the pH ranges 4.8-5.8 and 4.6-7.1 respectively. Chromatographic differences between the granulocyte/macrophage- and eosinophil-colony-stimulating factors were also detected by hydrophobic chromatography at low ionic strength (0.15m-NaCl) on Cibacron Blue-Sepharose and at high ionic strength [2m-(NH(4))(2)SO(4)] on phenyl-Sepharose. Eosinophil-colony-stimulating factor bound more strongly than the other factors to both matrices. The megakaryocyte- and erythroid-colony-stimulating activities were always associated with those for granulocytes/macrophages and eosinophils. Preparations highly enriched for eosinophil-colony-stimulating factor were also obtained by DEAE-cellulose chromatography. An overall purification of 100-fold for all of the factors was achieved with the present techniques, and, although differences were observed, only granulocyte/macrophage-stimulating factors and a small proportion of the eosinophil-stimulating factors could be completely separated from the others. Our results are consistent with the existence of separable factors for granulocyte/macrophage and eosinophil stimulation, but the megakaryocyte- and erythroid-stimulating activities were always associated with the granulocyte/macrophage- and eosinophil-stimulating activities. Thus there may be one molecule that is able to stimulate all four colony types or four very similar molecules that are difficult to separate.


Synthesis of an MOF-based Hg2+-fluorescent probe via stepwise post-synthetic modification in a single-crystal-to-single-crystal fashion and its application in bioimaging.
Although post-synthetic modification (PSM) has been successfully applied to NMOF decoration, only a handful of PSM-based single-crystal-to-single-crystal (SCSC) examples have been reported, particularly those involving multistep MOF-based SCSC transformations. In this contribution, three new MOFs, namely, UiO-68-NCS, UiO-68-R6G and UiO-68-R6G', were prepared via the single-crystal-to-single-crystal post-synthetic modification approach. For bioimaging, nanosized UiO-68-NCS, UiO-68-R6G, and UiO-68-R6G' were also prepared. Herein, nanosized UiO-68-R6G with a rhodamine-based fluorescence switch was found to be a highly sensitive and selective fluorescent probe for the detection of Hg2+ both in vitro and in vivo.


[Effects of PAC (personal attitude construct) analysis in counseling].
The aim of the present study is to prove that the use of PAC Analysis will enhance and facilitate counseling effects. Eleven functions were hypothetically presented: (1a) Intake Facilitation Function, (1b) Self-Disclosure Facilitation Function, (1c) Trust Formation Function, (1d) Dialogue Development Function, (2a) Mutual Understanding Function, (2b) Clarification Function, (2c) Self-Understanding Facilitation Function, (2d) Counselor's Awareness Function, (3a) Descriptive Documentation Function, (3b) Practical Explanation Function, and (3c) Evaluation-Assessment Function. By examining two case studies of international students' counseling process, these functions were analyzed. Results showed that all the functions were confirmed. Introducing PAC Analysis into counseling is proved to be effective in the direct intermental function field in counseling process (1a to 1d), the intramental function field between a client and a counselor (2a to 2d), and the indirect intermental function field including description, explanation, and assessment (3a to 3c). It is discussed that PAC Analysis is expected to take an important role in counseling in general.


[Tissue respiration in chronic bronchitis].
Altogether 445 patients with chronic bronchitis were under observation. Changes in tissue respiration were monitored by shifts in the concentration of pyruvic and lactic acids, LDH and cytochrome c oxidase activity and changes in the concentration of indices of the thiol spectrum. The results obtained showed that chronic bronchitis during exacerbation was characterized by disorders of tissue respiration which did not return to normal even in the course of therapy; aerobic as well as anaerobic oxidation was disturbed. In 91 patients 10-year shifts in indices were detected, however they were less than during exacerbation. Disorders of tissue respiration can be caused by two factors: inflammatory intoxication of organs and tissues and chronic oxygen insufficiency in tissues. Drugs promoting normal tissue respiration are recommended for pathogenetic treatment of chronic bronchitis.


Effects of Temephos (Abate®), Spinosad (Natular®), and Diflubenzuron on the Survival of Cyclopoid Copepods.
Dracunculus medinensis, also known as the African Guinea worm, is the causative agent of dracunculiasis and the focus of the global Guinea Worm Eradication Program (GWEP). Transmission of D. medinensis to humans occurs primarily by drinking water containing cyclopoid copepods infected with third-stage D. medinensis larvae. A common intervention to interrupt transmission and decrease the number of copepods in infected water bodies is the application of the organophosphate larvicide Abate® (temephos). However, the use of alternative compounds to help decrease copepod populations would be beneficial to the GWEP. We compared the immobilization of copepods by three compounds: Abate, Natular® (spinosad), and diflubenzuron. Our results confirm that neither diflubenzuron nor Natular immobilized copepods as quickly or as effectively as Abate. However, doubling or tripling the suggested concentration of Natular resulted in immobilization rates similar to Abate over 72 hours of continuous exposure. Further research on the possible effects of higher concentrations of Natular on the environment and nontarget organisms is necessary to determine whether this compound can be used safely to control the copepod population.


Genetic diversity and population structure of African village dogs based on microsatellite and immunity-related molecular markers.
The village and street dogs represent a unique model of canine populations. In the absence of selective breeding and veterinary care, they are subject mostly to natural selection. Their analyses contribute to understanding general mechanisms governing the genetic diversity, evolution and adaptation. In this study, we analyzed the genetic diversity and population structure of African village dogs living in villages in three different geographical areas in Northern Kenya. Data obtained for neutral microsatellite molecular markers were compared with those computed for potentially non-neutral markers of candidate immunity-related genes. The neutral genetic diversity was similar to other comparable village dog populations studied so far. The overall genetic diversity in microsatellites was higher than the diversity of European pure breeds, but it was similar to the range of diversity observed in a group composed of many European breeds, indicating that the African population has maintained a large proportion of the genetic diversity of the canine species as a whole. Microsatellite marker diversity indicated that the entire population is subdivided into three genetically distinct, although closely related subpopulations. This genetical partitioning corresponded to their geographical separation and the observed gene flow well correlated with the communication patterns among the three localities. In contrast to neutral microsatellites, the genetic diversity in immunity-related candidate SNP markers was similar across all three subpopulations and to the European group. It seems that the genetic structure of this particular population of Kenyan village dogs is mostly determined by geographical and anthropogenic factors influencing the gene flow between various subpopulations rather than by biological factors, such as genetic contribution of original migrating populations and/or the pathogen-mediated selection. On the other hand, the study of oldest surviving dogs suggested a biological mechanism, i.e. a possible advantage of the overal heterozygosity marked by the the microsatellite loci analyzed.


BRCA2 variants and cardiovascular disease in a multi-ethnic study.
Germline mutations of BRCA1/2 are associated with hereditary breast and ovarian cancer. Recent data suggests excess mortality in mutation carriers beyond that conferred by neoplasia, and recent in vivo and in vitro studies suggest a modulatory role for BRCA proteins in endothelial and cardiomyocyte function. We therefore tested the association of BRCA2 variants with clinical cardiovascular disease (CVD). Using data from 1,170 individuals included in two multi-ethnic population-based studies (SHARE and SHARE-AP), the association between BRCA2 variants and CVD was evaluated. 15 SNPs in BRCA2 with minor allele frequencies (MAF) > 0.01 had been previously genotyped using the cardiovascular gene-centric 50 k SNP array. 115 individuals (9.8%) reported a CVD event, defined as myocardial infarction (MI), angina, silent MI, stroke, and angioplasty or coronary artery bypass surgery. Analyses were adjusted for age and sex. The SNPs rs11571836 and rs1799943 were subsequently genotyped using the MassARRAY platform in 1,045 cases of incident MI and 1,135 controls from the South Asian subset of an international case-control study of acute MI (INTERHEART), and rs11571836 was imputed in 4,686 cases and 4500 controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS). Two BRCA2 SNPs, rs11571836 and rs1799943, both located in untranslated regions, were associated with lower risk of CVD (OR 0.47 p = 0.01 and OR 0.56 p = 0.03 respectively) in the SHARE studies. Analysis by specific ethnicities demonstrated an association with CVD for both SNPs in Aboriginal People, and for rs11571836 only in South Asians. No association was observed in the European and Chinese subgroups. A non-significant trend towards an association between rs11571836 and lower risk of MI was observed in South Asians from INTERHEART [OR = 0.87 (95% CI: 0.75-1.01) p = 0.068], but was not evident in PROMIS [OR = 0.96 (95% CI: 0.90-1.03) p = 0.230]. Meta-analysis of both case-control studies resulted in a combined OR of 0.94 (95% CI: 0.89-1.004, p = 0.06). Although there was an association between two SNPs in BRCA2 and CVD in a multi-ethnic population, these results were not replicated in two South Asian case-control studies of incident MI. Future studies exploring the association between BRCA variants and cardiovascular disorders are needed to clarify the role, if any, for BRCA variants in CVD pathogenesis.


Looking up to the sky! An exploration of new graduate nurses' perceptions of remote area nursing.
Remote area nursing is characterised by two known realities: health inequalities and nursing challenges. The health inequalities are complex consequences of social determinants and health care access. Remote area nurses must negotiate these realities that powerfully interact. Yet we, as new graduate nurses, contemplate a remote area nursing career pathway with additional points of view, including a strong attraction to the long-lasting image of the 'Flying Nurse' within aero medical remote health services. This image holds for us the possibilities of excitement, drama, vital service, and intensive care. This paper explores the realities of this career attraction, and consequently explores the aspirations of contemplative new graduate nurses, as they assimilate their knowledge of remote area nursing with their plans for their future transitions into nursing practice.


Concentrations and correlations of disinfection by-products in municipal drinking water from an exposure assessment perspective.
Although disinfection by-products (DBPs) occur in complex mixtures, studies evaluating health risks have been focused in few chemicals. In the framework of an epidemiological study on cancer in 11 Spanish provinces, we describe the concentration of four trihalomethanes (THMs), nine haloacetic acids (HAA), 3-chloro-4-(dichloromethyl)-5-hydroxy-2(5H)-furanone (MX), four haloacetonitries, two haloketones, chloropicrin and chloral hydrate and estimate correlations. A total of 233 tap water samples were collected in 2010. Principal component analyses were conducted to reduce dimensionality of DBPs. Overall median (range) level of THMs and HAAs was 26.4 (0.8-98.1) and 26.4 (0.9-86.9) μg/l, respectively (N=217). MX analysed in a subset (N=36) showed a median (range) concentration of 16.7 (0.8-54.1)ng/l. Haloacetonitries, haloketones, chloropicrin and chloral hydrate were analysed in a subset (N=16), showing levels from unquantifiable (<1 μg/l) to 5.5 μg/l (dibromoacetonitrile). Spearman rank correlation coefficients between DBPs varied between species and across areas, being highest between dibromochloromethane and dibromochloroacetic acid (r(s)=0.87). Principal component analyses of 13 DBPs (4 THMs, 9 HAAs) led 3 components explaining more than 80% of variance. In conclusion, THMs and HAAs have limited value as predictors of other DBPs on a generalised basis. Principal component analysis provides a complementary tool to address the complex nature of the mixture.


The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Initiative: methods of the EGAPP Working Group.
The Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Initiative, established by the National Office of Public Health Genomics at the Centers for Disease Control and Prevention, supports the development and implementation of a rigorous, evidence-based process for evaluating genetic tests and other genomic applications for clinical and public health practice in the United States. An independent, non-federal EGAPP Working Group (EWG), a multidisciplinary expert panel selects topics, oversees the systematic review of evidence, and makes recommendations based on that evidence. This article describes the EGAPP processes and details the specific methods and approaches used by the EWG.


[Cadmium and lead concentrations in the amniotic fluid of pregnant smokers and non-smokers].
Many studies showed the unhealthy effect of smoking on the fetus. Several mechanisms for the unfavorable effect are discussed. In the last few years interest has been shown in the occurrence of heavy metals such as cadmium and lead in smoke. In animal experiments high doses of cadmium showed mutations, teratogenicity and low doses showed retardation of fetal growth. Amniotic fluid examinations of smoking and non-smoking pregnant women showed that there is no barrier to cadmium from the placenta. A direct correlation between cigarette smoking and cadmium concentration in the amniotic fluid was found. Cadmium was discussed as a reason for hypertension. But this was not verified in our study. There were no correlations between the cadmium and lead content of amniotic fluid and the gestational age, and disturbances of the pregnancy nor a correlation to the incidence of abortions. The lead concentration in the amniotic fluid of smokers and non-smokers showed no significant difference. This is attributed to the ubiquitous exposition to lead with increasing pollution of the environment. The relatively small additional amounts of lead in cigarettes do not increase the amount of lead in the amniotic fluid.


Esophageal and pulmonary metastases from ovarian carcinoma: a case report of long-term survival following metastatic resections.
A case of ovarian carcinoma which has been followed up for more than 28 years after the initial ovarian resection is reported. A 50-year-old woman came forward with a metastatic esophageal tumor 16 years after a salpingo-oophorectomy for ovarian carcinoma. After irradiation with a dose of 3090 cGy, an esophagectomy and a partial resection of the directly invaded pericardium was successfully performed. Ten years later, progressive dyspnea due to a total collapse of the right lung developed. The right main stem bronchus was almost occluded by an endobronchial tumor, contiguous with the recurrent mass at the previous resectional margin. A right pneumonectomy and a combined resection of the pericardium and left atrium were performed. The patient has been followed up for further two years, and no signs of recurrence are evident. In spite of distant thoracic involvement and its local regrowth, the patient has survived for 28 years following her initial resection with surgical interventions.


Effect of left ventricular assistance on sympathetic tone.
To determine the effect of left ventricular assist device (LVAD) pumping on sympathetic tone, renal sympathetic nerve activity (RSNA) was detected in acute animal experiments. Our TH-7B pneumatically driven, sac-type ventricular assist device was used in 7 adult mongrel dogs. RSNA was detected by the use of bipolar electrodes attached to the left renal sympathetic nerve. RSNA was amplified and integrated by use of an R-C integrator circuit. The area of the integrated nerve discharge per unit time was calculated in the computer system and expressed as RSNA per unit time. During LVAD pumping, RSNA decreased with increase in blood pressure, with an increase in pulmonary artery flow, and with a decrease in left atrial pressure. These data suggest that LVAD has an effect on the sympathetic nervous system which is mediated by the aortic and cardiopulmonary baroreflex system.


HIV-1-specific CTL responses primed in vitro by blood-derived dendritic cells and Th1-biasing cytokines.
Vaccine strategies designed to elicit strong cell-mediated immune responses to HIV Ags are likely to lead to protective immunity against HIV infection. Dendritic cells (DC) are the most potent APCs capable of priming both MHC class I- and II-restricted, Ag-specific T cell responses. Utilizing a system in which cultured DC from HIV-seronegative donors were used as APC to present HIV-1 Ags to autologous T cells in vitro, the strength and specificity of primary HIV-specific CTL responses generated to exogenous HIV-1 Nef protein as well as intracellularly expressed nef transgene product were investigated. DC expressing the nef gene were able to stimulate Nef-specific CTL, with T cells from several donors recognizing more than one epitope restricted by a single HLA molecule. Primary Nef-specific CTL responses were also generated in vitro using DC pulsed with Nef protein. T cells primed with Nef-expressing DC (via protein or transgene) were able to lyse MHC class I-matched target cells pulsed with defined Nef epitope peptides as well as newly identified peptide epitopes. The addition of Th1-biasing cytokines IL-12 or IFN-alpha, during priming with Nef-expressing DC, enhanced the Nef-specific CTL responses generated using either Ag-loading approach. These results suggest that this in vitro vaccine model may be useful in identifying immunogenic epitopes as vaccine targets and in evaluating the effects of cytokines and other adjuvants on Ag-specific T cell induction. Successful approaches may provide information important to the development of prophylactic HIV vaccines and are envisioned to be readily translated into clinical DC-based therapeutic vaccines for HIV-1.