Cellular automata simulation of osteoblast growth on microfibrous-carbon-based scaffolds.
The objective of this study was to investigate the use of three fibrous carbon materials (T300, P25, and P120) for bone repair and develop and validate theoretical and computational methods in which bone tissue regeneration and repair could be accurately predicted. T300 was prepared from polyacrylonitrile precursor while P25 and P120 fibers were prepared from pitch, both common fiber precursors. Results showed that osteoblast growth on carbon scaffolds was enhanced with increased crystallinity, surface roughness, and material orientation. For unidirectional scaffolds at 120 h, there was 33% difference in cell growth between T300 and P25 fibers and 64% difference between P25 and P120 fibers. Moreover, for multidirectional fibers at 120 h, there was 35% difference in cell growth between T300 and P25 fibers and 43% difference between P25 and P120 fibers. Results showed that material alignment was integral to promoting cell growth with multidirectional scaffolds having the capacity for greater growth over unidirectional scaffolds. At 120 h there was 24% increase in cell growth between unidirectional alignment and multidirectional alignment on high-crystalline carbon fibers. Ultimately, data indicated that carbon scaffolds exhibited excellent bioactivity and may be tuned to stimulate unique reactions. Additionally, numerical and computational simulations provided evidence that corroborated experimental data with simulations. Results illustrated the capability of cellular automata models for assessing osteoblast cell response to biomaterials.


A note on a nonparametric regression test through penalized splines.
We examine a test of a nonparametric regression function based on penalized spline smoothing. We show that, similarly to a penalized spline estimator, the asymptotic power of the penalized spline test falls into a small- K or a large-K scenarios characterized by the number of knots K and the smoothing parameter. However, the optimal rate of K and the smoothing parameter maximizing power for testing is different from the optimal rate minimizing the mean squared error for estimation. Our investigation reveals that compared to estimation, some under-smoothing may be desirable for the testing problems. Furthermore, we compare the proposed test with the likelihood ratio test (LRT). We show that when the true function is more complicated, containing multiple modes, the test proposed here may have greater power than LRT. Finally, we investigate the properties of the test through simulations and apply it to two data examples.


Protein kinases in chronic lymphocytic leukemia.
Experiments were performed to characterize the protein kinase activity in blood lymphocytes from patients with chronic lymphocytic leukemia (CLL). Using histone as a substrate, the average specific activity was 397 pmole/min/mg protein. The Km for ATP was 8 muM and for histone 0.3 mg/ml. The addition of optimal concentrations of cyclic adenosine monophosphate (cAMP) (1 muM) or cyclic guanosine monophosphate (cGMP) (10muM) resulted in a 2.2-fold stimulation in activity but had no effect on the Km for ATP or histone. Most of the properties of the CCL protein kinase were similar to those of the normal lymphocyte enzyme. These include the pH response, substrate affinity, as well as rates of phosphorylation and dephosphorylation. The phosphorylation pattern of endogenous proteins was determined using intact lymphocytes incubated with 32P and cell-free homogenates with AT32P. These results indicate that: (1) the cyclicnucleotide-protein kinase interactions are unimpaired in CLL lymphocytes; and (2) a sharply defined cyclic nucleotide concentration response occurs for CLL (as well as normal) lymphocytes, which may explain the reports of variable inhibitory (and stimulatory) effects on mitogenesis by these agents.


[Acute limbic encephalitis and NMDA type-glutamate receptor].
We compared clinical characteristics and autoantibodies against GluRepsilon2 between 95 patients with nonparaneoplastic non-herpetic acute limbic encephalitis (NPNHALE) and 19 patients with non-herpetic acute encephalitis accompanying ovarian teratoma (NHAE-OT). Onset age (mean +/- SD) was 27.7 +/- 18.6 years old in NPNHALE, 27.5 +/- 6.5 in NHALE-OT. Preceding factors were found in 63.8% of patients with NPNHALE and 89.5% of patients with NHALE-OT (Fisher's exact test, p = 0.025), and major preceding factors were upper respiratory infections or fever in both groups. Symptoms at the onset were disorder of behavior and talk > seizures > impairment of consciousness in NPNHALE, and disorder of behavior and talk > seizures > disorientation in NHALE-OT. Symptoms at the acute stage were similar between NPNHALE and NHAE-OT, but duration of hospital stay was longer in NHAE-OT (209.0 days) than NPNHALE (87.5 days) (Mann Whitney test, p<0.0001). At the onset, cell counts in CSF were 51.6 +/- 66.4/mm3 and protein levels were 35.4 +/- 14.7 mg/dl, and IgG levels were 6.6 +/- 4.2 mg/dl in NHAE-OT, and these data were not significantly different between NPNHALE and NHAE-OT. In acute stage, autoantibodies against whole molecule of GluRepsilon2 in CSF were detected in 51.8% (29/56) of adult NPNHALE, and 40% (6/15) of NHAE-OT patients by immunoblot. These autoantibodies in both groups included epitopes to n-terminal of GluRepsilon2. Antibodies against NMDAR complex (Dalmau's method) in CSF were detected in 90.9% (10/11) of NHAE-OT patients.


Exploring the Impact of a Low-Protein High-Carbohydrate Diet in Mature Broodstock of a Glucose-Intolerant Teleost, the Rainbow Trout.
Sustainable aquaculture production requires a greater reduction in the use of marine-derived ingredients, and one of the most promising solutions today is the augmentation in the proportion of digestible carbohydrates in aquafeed. This challenge is particularly difficult for high trophic level teleost fish as they are considered to be glucose-intolerant (growth delay and persistent postprandial hyperglycemia observed in juveniles fed a diet containing more than 20% of carbohydrates). It was previously suggested that broodstock could potentially use carbohydrates more efficiently than juveniles, probably due to important metabolic changes that occur during gametogenesis. To investigate this hypothesis, 2-year old male and female rainbow trout (Oncorhynchus mykiss) were either fed a diet containing no carbohydrates (NC) or a 35%-carbohydrate diet (HC) for an entire reproductive cycle. Zootechnical parameters as well as the activities of enzymes involved in carbohydrate metabolism were measured in livers and gonads. Fish were then reproduced to investigate the effects of such a diet on reproductive performance. Broodstock consumed the HC diet, and in contrast to what is commonly observed in juveniles, they were able to grow normally and they did not display postprandial hyperglycemia. The modulation of their hepatic metabolism, with an augmentation of the glycogenesis, the pentose phosphate pathway and a possible better regulation of gluconeogenesis, may explain their improved ability to use dietary carbohydrates. Although the HC diet did induce precocious maturation, the reproductive performance of fish was not affected, confirming that broodstock are able to reproduce when fed a low-protein high-carbohydrate diet. In conclusion, this exploratory work has shown that broodstock are able to use a diet containing digestible carbohydrates as high as 35% and can then grow and reproduce normally over an entire reproductive cycle for females and at least at the beginning of the cycle for males. These results are highly promising and suggest that dietary carbohydrates can at least partially replace proteins in broodstock aquafeed.


The use of virtual world-based cardiac rehabilitation to encourage healthy lifestyle choices among cardiac patients: intervention development and pilot study protocol.
Despite proven benefits through the secondary prevention of cardiovascular disease (CVD) and reduction of mortality, cardiac rehabilitation (CR) remains underutilized in cardiac patients. Underserved populations most affected by CVD including rural residents, low socioeconomic status patients, and racial/ethnic minorities have the lowest participation rates due to access barriers. Internet-and mobile-based lifestyle interventions have emerged as potential modalities to complement and increase accessibility to CR. An outpatient CR program using virtual world technology may provide an effective alternative to conventional CR by overcoming patient access limitations such as geographics, work schedule constraints, and transportation. The objective of this paper is to describe the research protocol of a two-phased, pilot study that will assess the feasibility (Phase 1) and comparative effectiveness (Phase 2) of a virtual world-based (Second Life) CR program as an extension of a conventional CR program in achieving healthy behavioral change among post-acute coronary syndrome (ACS) and post-percutaneous coronary intervention (PCI) patients. We hypothesize that virtual world CR users will improve behaviors (physical activity, diet, and smoking) to a greater degree than conventional CR participants. In Phase 1, we will recruit at least 10 patients enrolled in outpatient CR who were recently hospitalized for an ACS (unstable angina, ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction) or who recently underwent elective PCI at Mayo Clinic Hospital, Rochester Campus in Rochester, MN with at least one modifiable, lifestyle risk factor target (sedentary lifestyle, unhealthy diet, and current smoking). Recruited patients will participate in a 12-week, virtual world health education program which will provide feedback on the feasibility, usability, and design of the intervention. During Phase 2, we will conduct a 2-arm, parallel group, single-center, randomized controlled trial (RCT). Patients will be randomized at a 1:1 ratio to adjunct virtual world-based CR with conventional CR or conventional CR only. The primary outcome is a composite including at least one of the following (1) at least 150 minutes of physical activity per week, (2) daily consumption of five or more fruits and vegetables, and (3) smoking cessation. Patients will be assessed at 3, 6, and 12 months. The Phase 1 feasibility study is currently open for recruitment which will be followed by the Phase 2 RCT. The anticipated completion date for the study is May 2016. While research on the use of virtual world technology in health programs is in its infancy, it offers unique advantages over current Web-based health interventions including social interactivity and active learning. It also increases accessibility to vulnerable populations who have higher burdens of CVD. This study will yield results on the effectiveness of a virtual world-based CR program as an innovative platform to influence healthy lifestyle behavior and self-efficacy.


[Diabetes yesterday, today and tomorrow. Work of the International Federation of Diabetes].
Diabetes mellitus is a frequent disorder affecting individuals of all ages. In children, adolescents and young adults, but also sometimes in older people, Type 1 diabetes is the consequence of insulin deficiency, resulting from an autoimmune process destroying the insulin producing cells in the pancreatic islets of Langerhans. In the adults and older persons (but sometimes also in young individuals), Type 2 diabetes (non-insulin dependent diabetes) occurs in genetically predisposed individuals and is favoured by weight excess and sedentarity. This form of diabetes is undiagnosed in about 50% of those affected. This concise review surveys the history of diabetes, the current situation and the expected changes in terms of epidemiology, prevention and treatment. The role of the International Diabetes Federation (IDF) whose headquarters are located in Brussels, is briefly described, particularly in the scope of its fight against a disease currently affecting 180 millions people worldwide, a figure likely to reach 325 millions at the 2025 horizon.


Almost all irritable bowel syndromes are post-infectious and respond to probiotics: controversial issues.
Acute infectious gastroenteritis is the strongest known risk factor for the development of irritable bowel syndrome (IBS), one of the most common functional gastrointestinal disorders. However, knowledge about the incidence and prevalence of post-infectious IBS (PI-IBS) in the general population is still limited. Some of the published epidemiological studies on PI-IBS lack an appropriate control population, and were limited by a short follow-up symptom assessment post-infection. A number of risk factors have been associated with the development of PI-IBS, including the virulence of the pathogen, younger age, female sex, the long duration of the initial illness and the presence of psychological disturbances. However, much work has to be done to establish whether multifactorial mechanisms actually concur to the pathophysiology of PI-IBS. The discovery that an infective episode may trigger the development of IBS has not substantially changed the clinical management of this subset of patients compared to the classical (non-infective) form of IBS. Probiotics have been claimed to be of some benefit in IBS, but the majority of studies have been performed in non-specific IBS rather than in PI-IBS and a number of issues still remain to be elucidated.


Tissue Response and Biodistribution of Injectable Cellulose Nanocrystal Composite Hydrogels.
Interest in cellulose nanocrystal (CNC)-based hydrogels for drug delivery, tissue engineering, and other biomedical applications has rapidly expanded despite the minimal in vivo research reported to date. Herein, we assess both in vitro protein adsorption and cell adhesion as well as in vivo subcutaneous tissue responses and CNC biodistribution of injectable CNC-poly(oligoethylene glycol methacrylate) (POEGMA) hydrogels. Hydrogels with different PEG side chain lengths, CNC loadings, and with or without in situ magnetic alignment of the CNCs are compared. CNC loading has a minimal impact on protein adsorption but significantly increases cell adhesion. In vivo, both CNC-only and CNC-POEGMA injections largely stay at their subcutaneous injection site over one month, with minimal bioaccumulation of CNCs in any typical clearance organ. CNC-POEGMA hydrogels exhibit mild acute and chronic inflammatory responses, although significant fibroblast penetration was observed with the magnetically aligned hydrogels. Collectively, these results suggest that CNC-POEGMA hydrogels offer promise in practical biomedical applications.


Chronological alterations of neurofilament 150 immunoreactivity in the gerbil hippocampus and dentate gyrus after transient forebrain ischemia.
In this study, we observed the chronological alterations of neurofilament 150 (NF-150) immunoreactivity in the gerbil hippocampus and dentate gyrus after 5 min transient forebrain ischemia. NF-150 immunoreactivity in the sham-operated group was mainly detected in mossy fibers and in the hilar region of the dentate gyrus. NF-150 immunoreactivity and protein contents of NF-150 and RT 97 (polyphosphorylation epitopes of neurofilament) were significantly decreased at 15 min after ischemic insult. Between 30 min and 12 h after ischemic insult, NF-150 immunoreactivity and protein content were significantly increased as compared with the sham-operated group. Thereafter, NF-150 immunoreactivity and protein content started to decrease. At 12 h after ischemic insult, unlike dentate gyrus, NF-150 immunoreactivity increased in pyramidal cells of the CA1 region. Thereafter, NF-150 immunoreactivity in the CA1 region started to decrease, and 4 days after ischemic insult, NF-150 immunoreactivity nearly was similar to that of the sham-operated group. These biphasic patterns of NF-150 immunoreactivity in the hippocampus and dentate gyrus are reverse correlated with that of the intracellular calcium influx. For calcium detection in the CA1 region, we also conducted alizarin red staining. Alizarin red positive neurons were detected in some neurons at 15-30 min after ischemic insult. At 12 h after ischemia, alizarin red positive neurons were decreased. Thereafter, alizarin red positive neurons started to decrease, but alizarin positive neurons were significantly increased in dying neurons 4 days after ischemia. These results suggest that ischemia-related changes of NF-150 expression may be caused by the calcium following transient forebrain ischemia.


Grappling with complexity: Medical students' reflective writings about challenging patient encounters as a window into professional identity formation.
Clerkship-specific interactive reflective writing (IRW)-enhanced reflection may enhance professional identity formation (PIF), a fundamental goal of medical education. PIF process as revealed in students? reflective writing (RW) has been understudied. The authors developed an IRW curriculum within a Family Medicine Clerkship (FMC) and analyzed students? reflections about challenging/difficult patient encounters using immersion-crystallization qualitative analysis. The qualitative analysis identified 26 unique emergent themes and five distinct thematic categories (1. Role of emotions, 2. Role of cognition, 3. Behaviorally responding to situational context, 4. Patient factors, and 5. External factors) as well as an emergent PIF model from a directed content analysis. The model describes students? backgrounds, emotions and previous experiences in medicine merging with external factors and processed during student?patient interactions. The RWs also revealed that processing often involves polarities (e.g. empathy/lack of empathy or encouragement/disillusionment) as well as dissonance between idealized visions and lived reality. IRW facilitates and ideally supports grappling with the lived reality of medicine; uncovering a "positive hidden curriculum" within medical education. The authors propose engaging learners in guided critical reflection about complex experiences for meaning-making within a safe learning climate as a valuable way to cultivate reflective, resilient professionals with "prepared" minds and hearts for inevitable challenges of healthcare practice.


Timing of antiepileptic drug withdrawal in adult epilepsy patients after neocortical surgical resection: a critically appraised topic.
The ideal efficacy outcome after surgery for medically refractory epilepsy is seizure freedom without need for antiepileptic drug (AED) therapy but the appropriate timing of AED withdrawal and other prognostic factors remain unclear. To critically evaluate current evidence regarding factors that influence the risk of seizure relapse after tapering AEDs in adult postepilepsy surgery patients. The objective was addressed through the development of a structured, critically appraised topic. This included a clinical scenario, structured question, literature search strategy, critical appraisal, results, evidence summary, commentary, and bottom-line conclusions. Participants included consultant and resident neurologists, a medical librarian, clinical epidemiologists, and a content expert in the field of epilepsy. A structured literature search led to selection and appraisal of a retrospective cohort study. Of 147 patients who underwent AED tapering after epilepsy surgery, 61 (41.5%) ended up seizure-free off AEDs, 47 (32%) were seizure-free with AED continuation, and 39 (26.5%) continued to have seizures while on AEDs. Risk factors associated with seizure recurrence included: less time to AED reduction [<9 mo vs. ≥9 mo; P<0.001; hazard ratio (HR)=2.83; 95% confidence interval (CI)=1.62-4.94), seizure recurrence before AED reduction (P=0.002; HR=2.43; 95% CI=1.37-4.31], normal preoperative magnetic resonance imaging (P=0.01; HR=1.96; 95% CI=1.15-3.34), and longer epilepsy duration (>11 y vs. ≤11 y; P=0.02; HR=1.75; 95% CI=1.09-2.81). Cortical location of the epileptic focus was not associated with taper success. In adults who have undergone neocortical resection surgery for medically refractory epilepsy, longer time from surgery to beginning AED taper (eg, greater than 9 months) is associated with a greater proportion of patients maintaining seizure freedom. Other risk factors associated with lower rate of seizure freedom after AED taper include longer duration of epilepsy, normal preoperative magnetic resonance imaging, and occurrence of postoperative seizures before initiation of AED withdrawal, but not cortical location of the epilepsy focus.


Ursolic acid alleviates airway-vessel remodeling and muscle consumption in cigarette smoke-induced emphysema rats.
This study assessed the effects of ursolic acid (UA) on airway-vessel remodeling and muscle atrophy in cigarette smoke (CS)-induced emphysema rats and investigated potential underlying mechanisms. Emphysema was induced in a rat model with 3 months of CS exposure. Histology and immunohistochemistry (IHC) stains were used to assess airway-vessel remodeling and muscle atrophy-associated changes. Levels of cleaved-caspase3, 8-OHdG, and S100A4 were measured in airways and associated vessels to evaluate cell apoptosis, oxidant stress, epithelial-to-mesenchymal transition (EMT), and endothelial-to-mesenchymal transition (EndMT)-associated factors. Western blot and/or IHC analyses were performed to measure transforming growth factor-beta 1(TGF-β1)/Smad2.3, alpha-smooth muscle actin (α-SMA), and insulin-like growth factor 1 (IGF1) expression. We also gave cultured HBE and HUVEC cells Cigarette Smoke Extract (CSE) administration and UA intervention. Using Western blot method to measure TGF-β1/Smad2.3, α-SMA, S100A4, and IGF1 molecules expression. UA decreased oxidant stress and cell apoptosis in airway and accompanying vascular walls of cigarette smoke-induced emphysema model rats. UA alleviated EMT, EndMT, changes associated with airway-vessel remodeling and muscle atrophy. The UA effects were associated with IGF1 and TGF-β1/Smad2.3 pathways. UA reduced EMT, EndMT, airway-vessel remodeling, and musculi soleus atrophy in CS-induced emphysema model rats at least partly through IGF1 and TGF-β1/Smad2.3 signaling pathways.


Decrypting Integrins by Mixed-Solvent Molecular Dynamics Simulations.
Integrins are a family of α/β heterodimeric cell surface adhesion receptors which are capable of transmitting signals bidirectionally across membranes. They are known for their therapeutic potential in a wide range of diseases. However, the development of integrin-targeting medications has been impacted by unexpected downstream effects including unwanted agonist-like effects. Allosteric modulation of integrins is a promising approach to potentially overcome these limitations. Applying mixed-solvent molecular dynamics (MD) simulations to integrins, the current study uncovers hitherto unknown allosteric sites within the integrin α I domains of LFA-1 (αLβ2; CD11a/CD18), VLA-1 (α1β1; CD49a/CD29), and Mac-1 (αMβ2, CD11b/CD18). We show that these pockets are putatively accessible to small-molecule modulators. The findings reported here may provide opportunities for the design of novel allosteric integrin inhibitors lacking the unwanted agonism observed with earlier as well as current integrin-targeting drugs.


Endemic Goiter and Iodine Prophylaxis in Calabria, a Region of Southern Italy: Past and Present.
Iodine, a micronutrient that plays a pivotal role in thyroid hormone synthesis, is essential for proper health at all life stages. Indeed, an insufficient iodine intake may determine a thyroid dysfunction also with goiter, or it may be associated to clinical features such as stunted growth and mental retardation, referred as iodine deficiency disorders (IDDs). Iodine deficiency still remains an important public health problem in many countries, including Italy. The effective strategy for the prevention and control of IDDs is universal salt iodization, which was implemented in Italy in 2005 as a nationwide program adopted after the approval of an Italian law. Despite an improvement in the iodine intake, many regions in Italy are still characterized by mild iodine deficiency. In this review, we provide an overview of the historical evolution of the iodine status in the Calabria region, located in the South of Italy, during the past three decades. In particular, we have retraced an itinerary from the first epidemiological surveys at the end of the 1980s to the establishment of the Regional Observatory of Endemic Goiter and Iodine Prophylaxis, which represents an efficient model for the surveillance of IDDs and monitoring the efficacy of iodine prophylaxis.


Antagonism of convulsions but failure to enhance GABA(A) receptor function by felbamate in mice tolerant to diazepam.
The transfer of tolerance between drugs may indicate a common mode of action. The development of cross-tolerance to the anticonvulsant effect of felbamate after long-term treatment of mice with diazepam, a positive modulator of gamma-aminobutyric acid (GABA)-mediated transmission, was therefore studied in order to clarify the mechanism of this action of felbamate. A challenge injection of felbamate, administered 36 h after the last dose of chronic diazepam treatment, antagonized convulsions elicited by administration of isoniazid. In contrast, felbamate had no effect on the isoniazid-induced increase in t-[35S]butylbicyclophosphorothionate binding to cerebral cortical membranes of diazepam-tolerant mice. These results suggest that the action of felbamate on GABAergic transmission is not required for the anticonvulsant effect of this drug. This conclusion is consistent with studies that have indicated that the antiepileptic activity of felbamate depends on its modulatory activity at excitatory amino acid receptors.


The role of inbreeding depression and mating system in the evolution of heterostyly.
We investigated the role of morph-based differences in the expression of inbreeding depression in loss of the mid-styled morph from populations of tristylous Oxalis alpina. The extent of self-compatibility (SC) of reproductive morphs, the degree of self-fertilization, and the magnitude of inbreeding depression were investigated in three populations of O. alpina differing in their tristylous incompatibility relationships. All three populations exhibited significant inbreeding depression. In two populations with highly modified tristylous incompatibility, manifested as increased reciprocal compatibility between short- and long-styled morphs, substantial SC and self-fertilization of mid-styled morphs were detected, and expected to result in expression of inbreeding depression in the progeny of mid-styled morphs in the natural populations. In contrast, significant self-fertility of the mid-styled morph was absent from the population with typical tristylous incompatibility, and no self-fertilization could be detected. Although self-fertilization and expression of inbreeding depression should result in selection against the mid-styled morph in the later stages of the transition from tristyly to distyly, in O. alpina selection against the mid-styled morph in the early phases of the evolution of distyly is likely due to genic selection against mid-alleles associated with modified tristylous incompatibility, rather than expression of inbreeding depression.


LncRNA SNHG4 Attenuates Inflammatory Responses by Sponging miR-449c-5p and Up-Regulating STAT6 in Microglial During Cerebral Ischemia-Reperfusion Injury.
Inflammatory response mediated by microglia plays a key role in cerebral ischemia-reperfusion injury. This study intends to probe the role of lncRNA SNHG4 in regulating the inflammatory response of the microglia during cerebral ischemia reperfusion. Blood samples and cerebrospinal fluid samples were collected from acute cerebral infarction (ACI) patients and healthy controls. The middle cerebral artery occlusion (MCAO) models were constructed with rats. LPS induction and oxygen-glucose deprivation methods were respectively applied to simulate the activation of microglia in vitro. qRT-PCR was employed to determine the expressions of SNHG4, miR-449c-5p and related inflammatory factors in vivo and in vitro. The inflammatory responses of the microglia subject to the varied expressions of SNHG4 and miR-449c-5p were detected. Luciferase assays were conducted to verify the crosstalk involving SNHG4, miR-449c-5p and STAT6. Compared with the control group, the expression of SNHG4 derived from the samples of ACI patients and the microglia of MCAO group were remarkably down-regulated, but the expression of miR-449c-5p was dramatically up-regulated. Overexpression of SNHG4 and knock-down of miR-449c-5p could inhibit the expression of pro-inflammatory cytokine in the microglia and promote the expression of anti-inflammatory factors. Meanwhile, the phospho-STAT6 was up-regulated, whereas the knock-down of SNHG4 and over-expression of miR-449c-5p in microglia had the opposite effects. Luciferase assay confirmed that SNHG4 could target miR-449c-5p, while miR-449c-5p could target STAT6. SNHG4 can regulate STAT6 and repress inflammation by adsorbing miR-449c-5p in microglia during cerebral ischemia-reperfusion injury.


Links between mental health care professionals and general practices in England and Wales: the impact of GP fundholding.
Fundholding general practitioners are able to determine the type of contracts they place with providers of mental health care, and are able to employ some categories of mental health care professionals directly. The impact of this on the care of the mental health of patients in non-fundholding practices is not yet fully known. A survey was undertaken of 100 fundholding general practices and 100 similarly sized non-fundholding practices in order to investigate the changes in mental health provision made by general practitioners. A sample of 100 fundholding general practices in England and Wales was randomly chosen from the list supplied by the Association of Fundholders and matched to a similarly randomly chosen sample of non-fundholding practices. Postal questionnaires were sent to the senior partner and to the practice manager in each practice. The number of mental health care professionals who are either employed by or attached to general practices, or who visit the general practice on a regular basis appears to have increased substantially since 1991. This increase was particularly marked in fundholding practices. The results suggest that general practitioners with specific links to particular mental health care providers were more satisfied with the service provided by the mental health care team, and more likely to increase referrals to that service in the last 2 years, than general practitioners without such links. There was little evidence to suggest that increasing the number of mental health care professionals in primary care had brought about a major reduction in referrals to psychiatrists. General practitioners, particularly fundholders, are increasing their links with mental health professionals, and community psychiatric nurses, psychiatrists, psychologists and counsellors are spending more time either based in general practice or visiting regularly. While the shift of resources to primary care, particularly to fundholders, may increase the treatment options available to patients with less severe illnesses, this may have the effect of reducing the services available for the long-term and severely mentally ill.


How many are underinsured? Trends among U.S. adults, 2003 and 2007.
With health insurance moving toward greater patient cost sharing, this study finds a sharp increase in the number of underinsured people. Based on indicators of cost exposure relative to income, as of 2007 an estimated twenty-five million insured people ages 19-64 were underinsured-a 60 percent increase since 2003. The rate of increase was steepest among those with incomes above 200 percent of poverty, where underinsurance rates nearly tripled. In total, 42 percent of U.S. adults were underinsured or uninsured. The underinsured report high levels of access problems and financial stress. The findings underscore the need for policy attention to benefit design, to assure care and affordability.


Exposure levels and determinants of placental polybrominated diphenyl ethers in Chinese pregnant women.
Polybrominated diphenyl ethers (PBDEs) are a group of widely used chemicals and humans are exposed to them in their daily life. PBDEs exposure during pregnancy may have adverse effects on pregnant women and their fetuses. Nevertheless, limited information is available on the levels and determinants of PBDEs exposure in Chinese pregnant women. The internal exposure levels of eight PBDEs (BDE-28, 47, 99, 100, 153, 154, 183, and 209) in placental samples of 1280 pregnant women from Zunyi birth cohort were analyzed using gas chromatography tandem mass spectrometry. All PBDEs concentrations were lipid adjusted (ng/g lw). Determinants of exposure were assessed by multivariable logistic regression model. Eight PBDE homologues were quantifiable in more than 70% of the samples. The highest median concentrations were found for BDE-209 (2.78 ng/g lw), followed by BDE-153 (1.00 ng/g lw) and BDE-183 (0.93 ng/g lw). The level of ΣPBDEs ranged from 0.90 to 308.78 ng/g lw, with a median concentration of 10.02 ng/g lw. Multivariate logistic regression analysis showed that maternal age older than 30 years old (OR: 1.59; 95% CI: 1.14, 2.23), pre-pregnancy obesity (1.51; 1.08, 2.10), home renovation within 2 years (1.43; 1.08, 1.91), spending more time outdoors during pregnancy (0.70; 0.55, 0.89), high consumption of fish/seafood (1.46; 1.13, 1.90) and eggs (1.44; 1.04, 2.00), male infant sex (1.69; 1.18, 2.42) were associated with PBDEs exposure. The study population is generally exposed to PBDEs, of which BDE-209 is the dominant congener, indicating extensive application of products containing deca-BDE mixtures. Maternal age, pre-pregnancy BMI, home decoration, average outdoor time during pregnancy, fish, seafood, eggs consumption, and fetal sex were exposure-determinning factors. This study contributes to the knowledge on region-specific PBDEs contamination in pregnant women and related risk factors.


Safety profile of dalfampridine extended release in multiple sclerosis: 5-year postmarketing experience in the United States.
Dalfampridine extended release tablets (dalfampridine-ER; prolonged-, modified, or sustained-release fampridine outside the US), 10 mg twice daily, was approved by the US Food and Drug Administration (FDA) in January 2010 to improve walking in people with multiple sclerosis, as determined by an increase in walking speed. To provide a descriptive analysis of reported adverse events (AEs) for commercially available dalfampridine-ER from March 2010 through March 31, 2015. Five-year postmarketing data for dalfampridine-ER were available from the exposure of approximately 107,000 patients in the US (103,700 patient-years). Commonly reported AEs (≥2% of all reported AEs) and serious AEs were determined. The incidence of reported seizures was determined and the events were further investigated. Among the 107,000 patients exposed to dalfampridine-ER (70% female; mean age 52.1), the most common AEs were dizziness (3.7%), insomnia (3.2%), balance disorder (3%), fall (2.4%), headache (2.4%), nausea (2.1%), and urinary tract infection (2%). Other common AEs were drug ineffectiveness (5.8%), gait disturbance (4.6%), and inappropriate dosing (3.1%). Serious AEs included rare anaphylactic reactions (five cases) and drug hypersensitivity reactions (eight cases). A total of 657 seizure cases were reported (6.3/1,000 patient-years); of these, 324 were medically confirmed (3.1/1,000 patient-years). Incidence of reported seizures was stable over time. Duration of treatment prior to a seizure ranged from a single dose to >4 years; 12% of the seizures occurred within a week of starting treatment. The 5-year US postmarketing safety data of dalfampridine-ER is consistent with the safety profile observed in clinical trials. Incidence of reported seizures remained stable over time. Since commercial availability in March 2010, a warning regarding the risk of anaphylaxis and severe allergic reactions was added to the US prescribing information.


Ethylene perception by the ERS1 protein in Arabidopsis.
Ethylene perception in Arabidopsis is controlled by a family of five genes, including ETR1, ERS1 (ethylene response sensor 1), ERS2, ETR2, and EIN4. ERS1, the most highly conserved gene with ETR1, encodes a protein with 67% identity to ETR1. To clarify the role of ERS1 in ethylene sensing, we biochemically characterized the ERS1 protein by heterologous expression in yeast. ERS1, like ETR1, forms a membrane-associated, disulfide-linked dimer. In addition, yeast expressing the ERS1 protein contains ethylene-binding sites, indicating ERS1 is also an ethylene-binding protein. This finding supports previous genetic evidence that isoforms of ETR1 also function in plants as ethylene receptors. Further, we used the ethylene antagonist 1-methylcyclopropene (1-MCP) to characterize the ethylene-binding sites of ERS1 and ETR1. We found 1-MCP to be both a potent inhibitor of the ethylene-induced seedling triple response, as well as ethylene binding by yeast expressing ETR1 and ERS1. Yeast expressing ETR1 and ERS1 showed nearly identical sensitivity to 1-MCP, suggesting that the ethylene-binding sites of ETR1 and ERS1 have similar affinities for ethylene.


Predicting length of stay for patients with psychoses.
The Computerized Psychiatric Severity Index (CPSI) and 22 patient variables were used to predict length of hospitalization for 304 psychiatric patients in DRG 430 who were diagnosed with schizophrenia or affective disorder and had no secondary diagnoses. Length of stay, which correlated .96 with total charges, was used as the dependent variable (measure of resource use). The patient variables and CPSI score explained 32.5 percent of the variation in length of stay for all of DRG 430 (27.5 percent for affective disorder patients and 70.3 percent for schizophrenia patients). Addition of the treatment variable "receipt of ECT" (electroconvulsive therapy) permitted the regression models to explain 40.9 percent of the variation in length of stay (36.24 percent for affective disorder and 71.22 percent for schizophrenia). In each regression model, maximum CPSI score was significant, indicating that much heterogeneity in DRG 430 can be explained by CPSI. Using one payment for such a diverse group places health care institutions at great risk of financial loss. Our study indicates that a continuing need exists for research in the area of case-mix measures for psychiatric inpatients.


Public reporting of quality data for stroke: is it measuring quality?
Public reporting of quality data is becoming more common and increasingly used to improve choices of patients, providers, and payers. We reviewed the scope and content of stroke data being reported to the public and how well it captures the quality of stroke care. We performed a cross-sectional survey of all report cards within the Agency for Healthcare Research and Quality Report Card Compendium. Stroke quality data were categorized into one of 5 groups: structure, process, outcomes, utilization, and finances. We also determined the congruence of mortality ratings of New York hospitals provided by 2 different report cards. Of 221 available report cards, 19 (9%) reported quality information regarding stroke and 17 specifically addressed the quality of hospital-based stroke care. The most frequent data reported were utilization measures (n=15 report cards) and outcome measures (n=14 report cards). Data regarding finances (n=4), structure of care (n=2), and process of care (n=1) were reported infrequently. Ratings were incongruent in 61 of the 157 hospitals (39%) with the same hospital being rated below average on one report care and average on another in 44 hospitals. Publicly reported quality data pertaining to patients with stroke are incomplete, confusing, and inaccurate. Without further improvements and a better understanding of the needs and limitations of the many stakeholders, targeted transparency policies for stroke care may lead to worse quality and large economic losses.


RLetters: A Web-Based Application for Text Analysis of Journal Articles.
While textual analysis of the journal literature is a burgeoning field, there is still a profound lack of user-friendly software for accomplishing this task. RLetters is a free, open-source web application which provides researchers with an environment in which they can select sets of journal articles and analyze them with cutting-edge textual analysis tools. RLetters allows users without prior expertise in textual analysis to analyze word frequency, collocations, cooccurrences, term networks, and more. It is implemented in Ruby and scripts are provided to automate deployment.


Successive Standardization of Rectangular Arrays.
In this note we illustrate and develop further with mathematics and examples, the work on successive standardization (or normalization) that is studied earlier by the same authors in [1] and [2]. Thus, we deal with successive iterations applied to rectangular arrays of numbers, where to avoid technical difficulties an array has at least three rows and at least three columns. Without loss, an iteration begins with operations on columns: first subtract the mean of each column; then divide by its standard deviation. The iteration continues with the same two operations done successively for rows. These four operations applied in sequence completes one iteration. One then iterates again, and again, and again, … In [1] it was argued that if arrays are made up of real numbers, then the set for which convergence of these successive iterations fails has Lebesgue measure 0. The limiting array has row and column means 0, row and column standard deviations 1. A basic result on convergence given in [1] is true, though the argument in [1] is faulty. The result is stated in the form of a theorem here, and the argument for the theorem is correct. Moreover, many graphics given in [1] suggest that except for a set of entries of any array with Lebesgue measure 0, convergence is very rapid, eventually exponentially fast in the number of iterations. Because we learned this set of rules from Bradley Efron, we call it "Efron's algorithm". More importantly, the rapidity of convergence is illustrated by numerical examples.


The interferon-inducible isoform of NCOA7 inhibits endosome-mediated viral entry.
Interferons (IFNs) mediate cellular defence against viral pathogens by upregulation of IFN-stimulated genes whose products interact with viral components or alter cellular physiology to suppress viral replication1-3. Among the IFN-stimulated genes that can inhibit influenza A virus (IAV)4 are the myxovirus resistance 1 GTPase5 and IFN-induced transmembrane protein 3 (refs 6,7). Here, we use ectopic expression and gene knockout to demonstrate that the IFN-inducible 219-amino acid short isoform of human nuclear receptor coactivator 7 (NCOA7) is an inhibitor of IAV as well as other viruses that enter the cell by endocytosis, including hepatitis C virus. NCOA7 interacts with the vacuolar H+-ATPase (V-ATPase) and its expression promotes cytoplasmic vesicle acidification, lysosomal protease activity and the degradation of endocytosed antigen. Step-wise dissection of the IAV entry pathway demonstrates that NCOA7 inhibits fusion of the viral and endosomal membranes and subsequent nuclear translocation of viral ribonucleoproteins. Therefore, NCOA7 provides a mechanism for immune regulation of endolysosomal physiology that not only suppresses viral entry into the cytosol from this compartment but may also regulate other V-ATPase-associated cellular processes, such as physiological adjustments to nutritional status, or the maturation and function of antigen-presenting cells.


Best interests, dementia and the Mental Capacity Act (2005).
The Mental Capacity Act (2005) is an impressive piece of legislation that deserves serious ethical attention, but much of the commentary on the Act has focussed on its legal and practical implications rather than the underlying ethical concepts. This paper examines the approach that the Act takes to best interests. The Act does not provide an account of the underlying concept of best interests. Instead it lists factors that must be considered in determining best interests, and the Code of Practice to the Act states that this list is incomplete. This paper argues that this general approach is correct, contrary to some accounts of best interests. The checklist includes items that are unhelpful. Furthermore, neither the Act nor its Code of Practice provides sufficient guidance to carers faced with difficult decisions concerning best interests. This paper suggests ways in which the checklist can be developed and discusses cases that could be used in an updated Code of Practice.


Pictorial review: endovascular repair of abdominal aortic aneurysms.
Endovascular repair of abdominal aortic aneurysms is an exciting new procedure. Depending on aneurysm morphology, tube grafts, bifurcated grafts or aorto-uni-iliac systems may be used. Early results are encouraging but many problems will require solving before the technique comes into general use.


The computational basis of an identified neuronal circuit for elementary motion detection in dipterous insects.
Based on comparative anatomical studies and electrophysiological experiments, we have identified a conserved subset of neurons in the lamina, medulla, and lobula of dipterous insects that are involved in retinotopic visual motion direction selectivity. Working from the photoreceptors inward, this neuronal subset includes lamina amacrine (alpha) cells, lamina monopolar (L2) cells, the basket T-cell (T1 or beta), the transmedullary cell Tm1, and the T5 bushy T-cell. Two GABA-immunoreactive neurons, the transmedullary cell Tm9 and a local interneuron at the level of T5 dendrites, are also implicated in the motion computation. We suggest that these neurons comprise the small-field elementary motion detector circuits the outputs of which are integrated by wide-field lobula plate tangential cells. We show that a computational model based on the available data about these neurons is consistent with existing models of biological elementary motion detection, and present a comparable version of the Hassenstein-Reichardt (HR) correlation model. Further, by using the model to synthesize a generic tangential cell, we show that it can account for the responses of lobula plate tangential cells to a wide range of transient stimuli, including responses which cannot be predicted using the HR model. This computational model of elementary motion detection is the first which derives specifically from the functional organization of a subset of retinotopic neurons supplying the lobula plate. A key prediction of this model is that elementary motion detector circuits respond quite differently to small-field transient stimulation than do spatially integrated motion processing neurons as observed in the lobula plate. In addition, this model suggests that the retinotopic motion information provided to wide-field motion-sensitive cells in the lobula is derived from a less refined stage of processing than motion inputs to the lobula plate.


Evolving Immunologic Perspectives in Chronic Inflammatory Demyelinating Polyneuropathy.
Chronic inflammatory demyelinating polyneuropathy (CIDP) is the commonest chronic idiopathic dysimmune neuropathy. Pathophysiologic processes involve both cellular and humoral immunity. There are various known forms of CIDP, likely caused by varying mechanisms. CIDP in its different forms is a treatable disorder in the majority of patients. The diagnosis of CIDP is clinical, supported routinely by electrophysiology. Cerebrospinal fluid analysis may be helpful. Routine immunology currently rarely adds to the diagnostic process but may contribute to the identification of an associated monoclonal gammopathy with or without hematologic malignancy and the consideration of alternative diagnoses, such as POEMS syndrome, anti-myelin associated glycoprotein (MAG) neuropathy or chronic ataxic neuropathy, with ophthalmoplegia, M-protein, cold aglutinins and disialosyl antibodies (CANOMAD). The search for antibodies specific to CIDP has been unsuccessful for many years. Recently, antibodies to paranodal proteins have been identified in a minority of patients with severe CIDP phenotypes, often unresponsive to first-line therapies. In conjunction with reports of high rates of antibody responses to neural structures in CIDP, this entertains the hope that more discoveries are to come. Although still arguably for only a small minority of patients, in view of current knowledge, such progress will enable earlier accurate diagnosis with direct management implications but only if the important, unfortunately and infrequently discussed issues of immunologic technique, test reliability and reproducibility are adequately tackled.


Intensity and frequency of moral distress in mental health nurses in Brazil.
To assess the intensity and frequency of moral distress in mental health nurses in Brazil. Cross-sectional study with 173 nurses from the Psychosocial Care Network in Brazil. The Brazilian Scale of Moral Distress in Nurses, adapted for the context of mental health, was used. For data processing, descriptive and inferential statistical analysis was used. Mostly moderate levels of intensity and frequency of moral distress (medians between 2.25 - 3.73 and 2.00 - 3.22, respectively) were observed, with emphasis on the factors working conditions and social conflicts. The level of moral distress evidenced in mental health nurses in Brazil reflects the dimension and amplitude of the phenomenon in different points of the Psychosocial Care Network. The relevance of discussions on coping strategies for moral distress is highlighted, articulating elements such as sensitivity, resilience, and moral courage, so that ethical deliberation is applied in care and management settings.


The fatiguing effects of camera use in virtual meetings: A within-person field experiment.
The COVID-19 pandemic propelled many employees into remote work arrangements, and face-to-face meetings were quickly replaced with virtual meetings. This rapid uptick in the use of virtual meetings led to much popular press discussion of virtual meeting fatigue (i.e., "Zoom fatigue"), described as a feeling of being drained and lacking energy following a day of virtual meetings. In this study, we aimed to better understand how one salient feature of virtual meetings-the camera-impacts fatigue, which may affect outcomes during meetings (e.g., participant voice and engagement). We did so through the use of a 4-week within-person experience sampling field experiment where camera use was manipulated. Drawing from theory related to self-presentation, we propose and test a model where study condition (camera on versus off) was linked to daily feelings of fatigue; daily fatigue, in turn, was presumed to relate negatively to voice and engagement during virtual meetings. We further predict that gender and organizational tenure will moderate this relationship such that using a camera during virtual meetings will be more fatiguing for women and newer members of the organization. Results of 1,408 daily observations from 103 employees supported our proposed model, with supplemental analyses suggesting that fatigue affects same-day and next-day meeting performance. Given the anticipated prevalence of remote work even after the pandemic subsides, our study offers key insights for ongoing organizational best practices surrounding virtual meetings. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


[Detection of cell culture tumorigenic activity by heterotransplantation into hamster cheek pouch tissue using immunodepressants].
Different strains of diploid cells were studied experimentally in Syrian hamsters by heterotransplantation into cheek pouch tissue for detection of their tumorigenic activity. Cortisone and antilymphocyte serum were used as immunodepressors. The results showed that the use of antilymphocyte serum increased considerably the sensitivity of the method of determination of cell culture tumorigenic activity.


Treatment refusal: analysis of 15 cases.
In this paper, we investigate the reasons for treatment refusal at Linkou and Kaohsiung Chang Gung Memorial Hospitals, and offer ways to improve the doctor-patient relationship. Cases were collected during a 2-year period according to the criterion of notification of "refused treatment" on consultation sheets, with a total of 1631 consultation sheets. All cases were discussed once a week in detail by psychiatrists and the consulting medical staff, and were followed up from 1 to 4 weeks. All cases were treated by the processes of informed consent and crisis intervention. The final results for the reasons of treatment refusal and psychiatric diagnoses were made by psychiatrists and the consulting medical staff. The number of cases compatible with the criterion was 15 (10 men and 5 women). The reasons for treatment refusal included poor communication, inadequate information, lack of competency, denial and shock reaction, reappearance of the suffered experience, and autonomy of patients. The distribution of psychiatric diagnoses included 8 with major depressive disorders, 2 with delirium, 1 with schizophrenic disorder, 1 with adjustment disorder, 1 with acute stress disorder (post-traffic accident), 1 with alcohol dependence, and 1 was deferred. After adequate processes of informed consent and crisis intervention, 12 persons accepted medical treatment. We should give patients adequate informed consent and crisis intervention to establish a good doctor-patient relationship and to respect the patients' autonomy for their choice of treatment.


Maternal prenatal stress and later child behavioral problems in an urban South African setting.
Findings from a number of cohort studies suggest that children who are exposed to maternal stress during pregnancy have an increased risk of behavioral problems. All of the research assessing this association to date has been conducted in developed countries; yet the majority of the child population, and the majority of the burden of psychopathology, exist in developing nations, where different patterns and levels of stressors may exist. The present study set out to examine whether maternal prenatal stress is associated with an increased risk of subsequent child behavioral problems in a developing country. Participants (n = 953) were from Birth to Twenty, a longitudinal birth cohort study based in Soweto-Johannesburg, South Africa, a socioeconomically disadvantaged urban area. Pregnant women completed questionnaires assessing stressors, and children's behavioral functioning was subsequently assessed when they were aged 2 and 4 years. Children whose mothers had high levels of prenatal stressors did not have an increased risk of behavioral problems at age 2 years, but they did at 4 years (adjusted odds ratio 2.52 [CI = 1.04, 6.09]). Partner conflict and family adversity were the stressors most strongly associated with adverse child outcome. These findings highlight the importance of the psychological health of pregnant women in developing countries, both for the mother and her offspring, and the need for greater research in resource-poor settings.


The tactile experience paired with vagus nerve stimulation determines the degree of sensory recovery after chronic nerve damage.
Loss of sensory function is a common consequence of neurological injury. Recent clinical and preclinical evidence indicates vagus nerve stimulation (VNS) paired with tactile rehabilitation, consisting of delivery of a variety of mechanical stimuli to the hyposensitive skin surface, yields substantial and long-lasting recovery of somatosensory function after median and ulnar nerve transection and repair. Here, we tested the hypothesis that a specific component of the tactile rehabilitation paired with VNS is necessary for recovery of somatosensory function. In a second experiment in a separate cohort, we investigated whether VNS paired with tactile rehabilitation could improve skilled forelimb motor function. Elements of the study design, including planned sample size, assessments, and statistical comparisons, were preregistered prior to beginning data collection (https://osf.io/3tm8u/). Animals received a peripheral nerve injury (PNI) causing chronic sensory loss. Eight weeks after injury, animals were given a VNS implant followed by six weeks of tactile rehabilitation sessions consisting of repeated application of one of two distinct mechanical stimuli, a filament or a paintbrush, to the previously denervated forepaw. VNS paired with either filament indentation or brushing of the paw significantly improved recovery of forelimb withdrawal thresholds after PNI compared to tactile rehabilitation without VNS. The effect size was twice as large when VNS was paired with brushing compared to VNS paired with point indentation. An independent replication in a second cohort confirmed that VNS paired with brush restored forelimb withdrawal thresholds to normal. These rats displayed significant improvements in performance on a skilled forelimb task compared to rats that did not receive VNS. These findings support the utility of pairing VNS with tactile rehabilitation to improve recovery of somatosensory and motor function after neurological injury. Additionally, this study demonstrates that the sensory characteristics of the rehabilitation paired with VNS determine the degree of recovery.


Single-stage photofermentative biohydrogen production from sugar beet molasses by different purple non-sulfur bacteria.
Biohydrogen production via fermentative routes offers considerable advantages in waste recycling and sustainable energy production. This can be realized by single-stage dark or photofermentative processes, or by a two-stage integrated process; the latter offering the higher production yields due to complete conversion of sugar substrates into H2 and CO2. However, problems arising from the integration of these two processes limit its scale-up and implementation. Hence, high efficiency one-step fermentative biohydrogen production processes from sugar-rich wastes are preferable. In this study, different strains of purple non-sulfur bacteria were investigated for their biohydrogen production capacity on pure sucrose and sugar beet molasses, and the feasibility of single-stage photofermentative biohydrogen production was evaluated. A single-stage photofermentation process was carried out using four different strains of purple non-sulfur bacteria (Rhodobacter capsulatus DSM 1710, R. capsulatus YO3, Rhodobacter sphaeroides O.U.001, and Rhodopseudomonas palustris DSM 127) on different initial sucrose concentrations. The highest hydrogen yield obtained was 10.5 mol H2/mol of sucrose and the maximum hydrogen productivity was 0.78 mmol/L h by Rp. palustris on 5 mM sucrose. A hydrogen yield of 19 mol H2/mol sucrose, which represents 79% of theoretical yield, and a maximum hydrogen productivity of 0.55 mmol/L h were obtained by Rp. palustris from sugar beet molasses. The yield was comparable to those values obtained in two-stage processes. The present study demonstrates that single-stage photofermentation using purple non-sulfur bacteria on sucrose-based wastes is promising.


The effect of warming on adrenergic neurotransmission in canine cutaneous vein.
The effect of warming on adrenergic neurotransmission was examined in canine cutaneous veins. Isometric tension was recorded from rings of saphenous veins of the dog in organ chambers filled with physiological salt solution. During contractions caused by potassium or prostaglandin F2 alpha, warming from 37 to 41 degrees C caused an augmentation. During contractions caused by stimulation of the adrenergic nerves, and by exogenous norepinephrine, warming caused a relaxation. The relaxation with warming was not altered by the beta-adrenergic antagonist, propranolol, or by inhibitors of extraneuronal and neuronal uptake of norepinephrine. During contractions evoked by the alpha 2-adrenergic agonists, alpha-methyl norepinephrine and B-HT 920, warming caused a relaxation, whereas during contractions due to the alpha 1-adrenergic agonists, cirazoline , methoxamine, ST 587, and phenylephrine, it caused an augmentation. The relaxation caused by warming during norepinephrine-induced contractions was prevented by the preferential alpha 2-antagonists yohimbine and rauwolscine, but not by the preferential alpha 1-antagonist, prazosin. In strips of saphenous vein incubated with [3H] norepinephrine , warming did not affect the release of labeled transmitter evoked by nerve stimulation. These experiments indicate that warming directly enhances contractility of vascular smooth muscle, while depressing the responsiveness of cutaneous vessels to sympathetic nerve activation by a selective inhibitory effect on postjunctional alpha 2-adrenoceptors. Relaxation with warming is greater during nerve stimulation than during administration of exogenous norepinephrine, which may be due to a predominance of postjunctional alpha 2-adrenoceptors in the neuromuscular junction.


Improved Molecular Diagnosis of COVID-19 by the Novel, Highly Sensitive and Specific COVID-19-RdRp/Hel Real-Time Reverse Transcription-PCR Assay Validated In Vitro and with Clinical Specimens.
On 31 December 2019, the World Health Organization was informed of a cluster of cases of pneumonia of unknown etiology in Wuhan, China. Subsequent investigations identified a novel coronavirus, now named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), from the affected patients. Highly sensitive and specific laboratory diagnostics are important for controlling the rapidly evolving SARS-CoV-2-associated coronavirus disease 2019 (COVID-19) epidemic. In this study, we developed and compared the performance of three novel real-time reverse transcription-PCR (RT-PCR) assays targeting the RNA-dependent RNA polymerase (RdRp)/helicase (Hel), spike (S), and nucleocapsid (N) genes of SARS-CoV-2 with that of the reported RdRp-P2 assay, which is used in >30 European laboratories. Among the three novel assays, the COVID-19-RdRp/Hel assay had the lowest limit of detection in vitro (1.8 50% tissue culture infective doses [TCID50]/ml with genomic RNA and 11.2 RNA copies/reaction with in vitro RNA transcripts). Among 273 specimens from 15 patients with laboratory-confirmed COVID-19 in Hong Kong, 77 (28.2%) were positive by both the COVID-19-RdRp/Hel and RdRp-P2 assays. The COVID-19-RdRp/Hel assay was positive for an additional 42 RdRp-P2-negative specimens (119/273 [43.6%] versus 77/273 [28.2%]; P < 0.001), including 29/120 (24.2%) respiratory tract specimens and 13/153 (8.5%) non-respiratory tract specimens. The mean viral load of these specimens was 3.21 × 104 RNA copies/ml (range, 2.21 × 102 to 4.71 × 105 RNA copies/ml). The COVID-19-RdRp/Hel assay did not cross-react with other human-pathogenic coronaviruses and respiratory pathogens in cell culture and clinical specimens, whereas the RdRp-P2 assay cross-reacted with SARS-CoV in cell culture. The highly sensitive and specific COVID-19-RdRp/Hel assay may help to improve the laboratory diagnosis of COVID-19.


Biocompatibility of calcined mesoporous silica particles with ventricular myocyte structure and function.
In vivo and in vitro systems were employed to investigate the biocompatibility of two forms of calcined mesoporous silica microparticles, MCM41-cal and SBA15-cal, with ventricular myocytes. These particles have potential clinical use in delivering bioactive compounds to the heart. Ventricular myocytes were isolated from 6 to 8 week male Wistar rats. The distribution of the particles in ventricular myocytes was investigated by transmission electron microscopy and scanning electron microscopy. The distribution of particles was also examined in cardiac muscle 10 min after intravenous injection of 2.0 mg/mL MCM41-cal. Myocyte shortening and the Ca(2+) transient were determined following exposure to 200 μg/mL MCM41-cal or SBA15-cal for 10 min. Within 10 min of incubation at 25 °C, both MCM41-cal and SBA15-cal were found attached to the plasma membrane, and some particles were observed inside ventricular myocytes. MCM41-cal was more abundant inside the myocytes than SBA15-cal. The particles had a notable affinity to mitochondrial membranes, where they eventually settled. Within 10 min of intravenous injection (2.0 mg/mL), MCM41-cal traversed the perivascular space, and some particles entered ventricular myocytes and localized around the mitochondrial membranes. The amplitude of shortening was slightly reduced in myocytes superperfused with MCM41-cal or SBA15-cal. The amplitude of the Ca(2+) transient was significantly reduced in myocytes superperfused with MCM41-cal but was only slightly reduced with SBA15-cal. Overall, the results show reasonable bioavailability and biocompatibility of MCM41-cal and SBA15-cal with ventricular myocytes.


Adapting the stretched sample method from tissue profiling to imaging.
The characterization and localization of peptides and proteins in tissues provides information that aids in understanding their function and in characterizing disease states. Over the past decades, the use of MS for the profiling and imaging of biological compounds from tissues has evolved into a powerful modality to accomplish these studies. One recently described sampling approach, the stretched sample method (Monroe, E. B. et al.., Anal. Chem. 2006, 78, 6826-6832), places a tissue section onto an array of glass beads embedded on a Parafilm M membrane. When the membrane is stretched, it separates the tissue section into thousands of cell-sized pieces for tissue profiling by MALDI-MS. The physical separation between beads eliminates analyte redistribution during matrix application and allows long analyte extraction periods without loss of spatial resolution. Here, we enhance this sampling approach by introducing algorithms that enable the reconstruction of ion images from these stretched samples. As the first step, a sample-tailored data acquisition method is devised to obtain mass spectra exclusively from the beads, thereby reducing the time, instrument resources, and data handling required for such MS imaging (MSI) experiments. Next, an image reconstruction algorithm matches data acquired from the stretched sample to the initial bead locations. The efficacy of this method is demonstrated using peptide-coated beads with known peptide distributions and appears well-suited to the MSI of heterogeneous tissue samples.


P53 and C-FOS overexpression in patients with thyroid cancer: an immunohistochemical study.
A sequence of genetic events characterized by deletion and expression of several oncogenes may lead progressively to tumorgenesis. The expression of certain oncogenes is believed to be related with thyroid carcinogenesis and tumor progression. We investigated immunohistochemically p53 tumor suppressor gene and c-fos oncogene expression in forty patients with thyroid cancer. Thyroid biopsies from twenty patients with benign thyroid diseases were also examined. The forty patients with thyroid cancer varied histologically; 24 with papillary carcinoma (60%), 12 with follicular carcinoma (30%), 3 with anaplastic carcinoma (7.5%) and one with medullary carcinoma (2.5%). The patients with benign thyroid diseases consisted of 10 with adenomatous goiter (50%), 7 with goiter (35%) and three with Hashimoto thyroiditis (15%). Individual p53 and c-fos expression was more prevalent in thyroid carcinomas compared to benign tumors (p=0.001 and p=0.04, respectively). A marked increase of p53 and c-fos coexpression was found (p=0.02) in patients with thyroid cancer and metastasis to the regional lymph nodes. Furthermore c-fos was overexpressed in only female thyroid cancer patients. In conclusion, p53 and c-fos are significantly overexpressed in thyroid cancer patients, indicating their role in the genetic mechanisms leading to thyroid tumorigenesis. This hypothesis is further supported by the observation that p53/c-fos coexpression was related with more advanced disease status.


Introduction to the special issue: The WHO World Mental Health International College Student (WMH-ICS) initiative.
Most mental disorders have their first onset in early adulthood. Epidemiological research, as well as research on preventive and early interventions, is therefore very important. This thematic issue focuses on one of the first systematic attempts to develop such services for college students. The WHO World Mental Health International College Student (WMH-ICS) initiative is based on the largest and continuously growing epidemiological dataset ever collected in college students. Based on these results, the initiative has now started to implement internet-based interventions for common mental disorders and emotional problems. In this special issue, a general paper about the initiative is presented, as well as a paper on the implementation of the WMH-ICS initiative in low and middle income countries. It also includes several papers with core epidemiological results of the initiative, a meta-analysis of internet-based interventions for mental health problems in college students and the first results of trials conducted as part of the initiative. Taken together, the papers in this special issue show that WMH-ICS is on its way to becoming a major initiative in addressing the problem of unmet need for treatment of mental health problems among college students.


Concurrent hyperglycemia does not influence the long-term prognosis of unresectable hepatocellular carcinomas.
The association has been established between the disorder of carbohydrate metabolism and liver cancer. However, little is known regarding the impact of concurrent hyperglycemia on prognosis of hepatocellular carcinoma (HCC). The present study aimed at solving this problem. A total of 225 patients included in this study, were admitted from January 1998 to December 2001 for an unresectable HCC proven by histological and imaging examinations. Most of the patients received interventional treatment, radiation and biotherapy. Response was evaluated by computerized tomography (CT) scan conducted 4-6 weeks following completion of the treatment, and then every 3 months. Survival was calculated from the beginning of treatment using the Kaplan-Meier method. Pretreatment, treatment and follow-up variables with possible prognostic significance were analyzed. A stepwise multivariate analysis was performed using the Cox regression model, and a prognostic index was obtained. No differences were observed in survival parameters between the patients with and without hyperglycemia, median survival times of the patients were being 26+/-3.46 months and 29.5+/-2.04 months, respectively, and the 3-year survival rate was 8.36 % and 9.62 %, respectively. The univariate analysis indicated that there were several survival-associated variables including serum AFP level, clinical stage, Child-Pugh grade, method of treatment, size and number of tumor nodule (s). However, only the clinical stage, Child-Pugh grade and the treatment procedure were proved to be independent prognostic factors in the multivariate analysis. This study indicates that hyperglycemia does not influence the long-term prognosis of HCC, and concurrent hyperglycemia should not be considered as an unfavorable prognostic factor during the treatment of patients with HCC.


Minimally Invasive Transverse Aortic Constriction in Mice.
Minimally invasive transverse aortic constriction (MTAC) is a more desirable method for the constriction of the transverse aorta in mice than standard open-chest transverse aortic constriction (TAC). Although transverse aortic constriction is a highly functional method for the induction of high pressure in the left ventricle, it is a more difficult and lengthy procedure due to its use of artificial ventilation with tracheal intubation. TAC is oftentimes also less survivable, as the newer method, MTAC, neither requires the cutting of the ribs and intercostal muscles nor tracheal intubation with a ventilation setup. In MTAC, as opposed to a thoracotomy to access to the chest cavity, the aortic arch is reached through a midline incision in the anterior neck. The thyroid is pulled back to reveal the sternal notch. The sternum is subsequently cut down to the second rib level, and the aortic arch is reached simply by separating the connective tissues and thymus. From there, a suture can be wrapped around the arch and tied with a spacer, and then the sternal cut and skin can be closed. MTAC is a much faster and less invasive way to induce left ventricular hypertension and enables the possibility for high-throughput studies. The success of the constriction can be verified using high-frequency trans-thoracic echocardiography, particularly color Doppler and pulsed-wave Doppler, to determine the flow velocities of the aortic arch and left and right carotid arteries, the dimension of the blood vessels, and the left ventricular function and morphology. A successful constriction will also trigger significant histopathological changes, such as cardiac muscle cell hypertrophy with interstitial and perivascular fibrosis. Here, the procedure of MTAC is described, demonstrating how the resulting flow changes in the carotid arteries can be examined with echocardiography, gross morphology, and histopathological changes in the heart.


Ginseng protects against respiratory syncytial virus by modulating multiple immune cells and inhibiting viral replication.
Ginseng has been used in humans for thousands of years but its effects on viral infection have not been well understood. We investigated the effects of red ginseng extract (RGE) on respiratory syncytial virus (RSV) infection using in vitro cell culture and in vivo mouse models. RGE partially protected human epithelial (HEp2) cells from RSV-induced cell death and viral replication. In addition, RGE significantly inhibited the production of RSV-induced pro-inflammatory cytokine (TNF-α) in murine dendritic and macrophage-like cells. More importantly, RGE intranasal pre-treatment prevented loss of mouse body weight after RSV infection. RGE treatment improved lung viral clearance and enhanced the production of interferon (IFN-γ) in bronchoalveolar lavage cells upon RSV infection of mice. Analysis of cellular phenotypes in bronchoalveolar lavage fluids showed that RGE treatment increased the populations of CD8+ T cells and CD11c+ dendritic cells upon RSV infection of mice. Taken together, these results provide evidence that ginseng has protective effects against RSV infection through multiple mechanisms, which include improving cell survival, partial inhibition of viral replication and modulation of cytokine production and types of immune cells migrating into the lung.


[Influence of EDTA injection in the blood of the rat on the process of self-warming after deep hypothermia].
With the help of thermometry and general calorimetry, changes in the heat exchange were determined in rats upon their getting out of artificial deep hypothermia (the temperature in the rectum was 19-20 degrees C) at the temperature in the calorimeter chamber of 20 degrees C. In initial study of self-warming (the temperature in the rectum was 21-22 degrees C), the rats were injected with 1 ml 0.5% ethylenediaminetetraacetic acid disodium salt (EDTA) with purpose of speeding up the recovery to normal state. The experiments showed that EDTA increased the total heat production and kept in on high level during 3 hous. During that time, the rectal temperature of the rats was 37.6 +/- 0.6 degrees C in the end of the experiments, but in the control that value was only 35.1 +/- 0.5 degrees C.


Early recurrence in paroxysmal versus sustained atrial fibrillation in patients with acute ischaemic stroke.
The relationship between different patterns of atrial fibrillation and early recurrence after an acute ischaemic stroke is unclear. In a prospective cohort study, we evaluated the rates of early ischaemic recurrence after an acute ischaemic stroke in patients with paroxysmal atrial fibrillation or sustained atrial fibrillation which included persistent and permanent atrial fibrillation. In patients with acute ischaemic stroke, atrial fibrillation was categorised as paroxysmal atrial fibrillation or sustained atrial fibrillation. Ischaemic recurrences were the composite of ischaemic stroke, transient ischaemic attack and symptomatic systemic embolism occurring within 90 days from acute index stroke. A total of 2150 patients (1155 females, 53.7%) were enrolled: 930 (43.3%) had paroxysmal atrial fibrillation and 1220 (56.7%) sustained atrial fibrillation. During the 90-day follow-up, 111 ischaemic recurrences were observed in 107 patients: 31 in patients with paroxysmal atrial fibrillation (3.3%) and 76 with sustained atrial fibrillation (6.2%) (hazard ratio (HR) 1.86 (95% CI 1.24-2.81)). Patients with sustained atrial fibrillation were on average older, more likely to have diabetes mellitus, hypertension, history of stroke/ transient ischaemic attack, congestive heart failure, atrial enlargement, high baseline NIHSS-score and implanted pacemaker. After adjustment by Cox proportional hazard model, sustained atrial fibrillation was not associated with early ischaemic recurrences (adjusted HR 1.23 (95% CI 0.74-2.04)). After acute ischaemic stroke, patients with sustained atrial fibrillation had a higher rate of early ischaemic recurrence than patients with paroxysmal atrial fibrillation. After adjustment for relevant risk factors, sustained atrial fibrillation was not associated with a significantly higher risk of recurrence, thus suggesting that the risk profile associated with atrial fibrillation, rather than its pattern, is determinant for recurrence.


The hip and knee replacement operation: an extensive life event.
A total hip replacement and a total knee replacement have shown to effectively reduce pain and disability in patients with osteoarthritis of the hip and knee joint despite associated risks. Even though the intervention primarily concerns older people with additional health problems, the patients stand on their feet the day after the operation and are discharged a few days later. Previous research indicates that reflections about life are related to the operation. The aim of this study was to illuminate the meaning of reflections related to hip and knee replacement surgery. A phenomenological hermeneutical approach with a longitudinal design was chosen in order to study the participants' experiences of the hip and knee replacement intervention across the entire perioperative period. Four themes emerged from the structural analysis; choosing the challenge, past memories connect to the current situation, moving from happiness to ordinary everyday life and moving from despair towards reluctant acceptance of unexpected bad conditions for everyday life. There was inner negotiations about having surgery or not, and existential anxiety that reminded people that life cannot be taken for granted. Our findings indicate the operation was seen as an extensive life event including reflections about life and death and about hope and fear. Previous bad experiences of care seemed to influence the way patients dealt with fear and hope. Fear had to be overcome by inner negotiations about undergoing surgery or not. Relief was expressed about surviving the actual operation, but soon after fears arose about how to manage on the actual road to recovery. Hope for a good life grew either stronger or weaker, depending on the progress following the operation. The outcome eventually generated a transition from happiness to ordinary everyday life, or a transition from despair towards reluctant acceptance of unfulfilled expectations.


PKB/AKT and ERK regulation of caspase-mediated apoptosis by methylseleninic acid in LNCaP prostate cancer cells.
Methylselenol has been implicated as an active metabolite for the anticancer effect of selenium in part through the induction of cancer cell apoptosis. Since inactivation of the AKT/protein kinase B negative regulator gene PTEN (phosphatase and tensin homologue deleted on chromosome 10) is common in prostate cancer (PCa), we compared PTEN wild-type DU145 PCa cells (low basal AKT activity) with PTEN-mutant LNCaP PCa cells (high basal AKT activity) for their apoptosis responses to the methylselenol precursor methylseleninic acid (MSeA) and sodium selenite, an inorganic salt. Our results show that LNCaP cells withstood approximately 4 times higher doses of MSeA than DU145 cells, although they were slightly more sensitive than the latter to selenite-induced apoptosis. Treatment by MSeA modestly attenuated AKT phosphorylation and increased phospho-ERK1/2 in LNCaP cells. Selenite treatment increased the phosphorylation of p53 Ser15 and both kinases, but the selenite-induced apoptosis was not influenced by chemical inhibitors of either kinase. In contrast, PI3K/AKT inhibitors greatly sensitized LNCaP cells to apoptosis induced by MSeA, accompanied by increased mitochondrial release of cytochrome c and multiple caspase activation without changing p53 Ser15 phosphorylation. The apoptosis was further accentuated by extracellular signal regulated kinases 1 and 2 (ERK1/2) inhibition without further increase in cytochrome c release. The general caspase inhibitor z-VAD-fmk completely blocked MSeA-induced apoptosis when both kinases were inhibited, whereas a caspase-8 inhibitor exerted a greater protection than did a caspase-9 inhibitor. Transfection of DU145 cells with a constitutively active AKT increased their resistance to MSeA-induced apoptosis. In summary, AKT played an important role in regulating apoptosis sensitivity of LNCaP and DU145 cells to MSeA. An MSeA-induced activation of ERK1/2 in LNCaP cells also contributed to resistance to apoptosis. However, these kinases did not significantly regulate caspase-mediated apoptosis induced by selenite in LNCaP cells. These findings support the differential involvement of these protein kinase pathways in regulating apoptosis induction by different forms of selenium.


Mental state attributions and diffusion tensor imaging after traumatic brain injury in children.
We studied social cognition in 49 children 3 months after moderate to severe traumatic brain injury (TBI) and in 39 children with orthopedic injury (OI). Children underwent diffusion tensor imaging (DTI) and a mental attribution task showing two triangles. Mental state attributions increased when one triangle reacted to intentions of the other, but less so in the TBI than the OI group. DTI identified injury to white matter microstructure in the TBI group, but the relation of DTI to mental attributions did not differ between groups. Moderate to severe TBI produces white matter disconnections that may affect social cognitive networks.


Monoclonal immunoglobulin-secreting lymphoma in a patient with severe combined immunodeficiency disease.
A 3.5 year old boy with X-linked severe combined immunodeficiency disease (SCID), who had been in laminar flow isolation throughout his life, developed a B cell tumour producing up to 3008 mg/dl of an IgM kappa paraprotein 1 month after infusion of both liver and thymus cells from a fetal donor and 6 months after the last of six fetal liver cell infusions given over a 3 year period. Pretransplant studies revealed a high percentage of circulating B lymphocytes. HLA typing suggests that the tumour was of host origin.


Portable electrical impedance tomography (EIT) system stages non-alcoholic fatty liver disease for potential screening and monitoring at home.
This study demonstrates the feasibility of predicting NAFLD using multi-spectral electrical impedance tomography (EIT), group source separation, constant reference EIT and anthropometric measures. Vibration-controlled Transient Elastography (VCTE) Controlled Attenuated Parameter (CAP; n = 121) and magnetic resonance imaging-proton density fat fraction (MRI-PDFF; n = 34) achieved a sensitivity of 70.9% and specificity of 73.8% with our CAP predicting model and sensitivity of 77.8% and specificity of 80.0% with our MRI-PDFF predicting model. In summary, a portable EIT can be a cost-effective and self-administrable alternative for widespread home-based and community-based diagnostic screening and treatment monitoring of NAFLD.Clinical Relevance- Portable multi-spectral EIT system has the sensitivity and specificity to potentially unlock biomedical imaging in telemedicine for home-based and community-based screening, staging and monitoring for NAFLD.


On optimal current patterns for electrical impedance tomography.
We develop a statistical criterion for optimal patterns in planar circular electrical impedance tomography. These patterns minimize the total variance of the estimation for the resistance or conductance matrix. It is shown that trigonometric patterns (Isaacson, 1986), originally derived from the concept of distinguishability, are a special case of our optimal statistical patterns. New optimal random patterns are introduced. Recovering the electrical properties of the measured body is greatly simplified when optimal patterns are used. The Neumann-to-Dirichlet map and the optimal patterns are derived for a homogeneous medium with an arbitrary distribution of the electrodes on the periphery. As a special case, optimal patterns are developed for a practical EIT system with a finite number of electrodes. For a general nonhomogeneous medium, with no a priori restriction, the optimal patterns for the resistance and conductance matrix are the same. However, for a homogeneous medium, the best current pattern is the worst voltage pattern and vice versa. We study the effect of the number and the width of the electrodes on the estimate of resistivity and conductivity in a homogeneous medium. We confirm experimentally that the optimal patterns produce minimum conductivity variance in a homogeneous medium. Our statistical model is able to discriminate between a homogenous agar phantom and one with a 2 mm air hole with error probability (p-value) 1/1000.


[Pulmonary nocardiosis].
Pulmonary nocardiosis is an opportunistic infection that manifests itself mostly in the context of decreased defences, due either to pre-existing pathology or to immunosuppressive therapy, and is often complicated by central nervous system involvement. The clinical and radiological picture is highly variable, requiring a broad spectrum of differential diagnosis, and leaving a decisive and difficult role to the laboratory. We present two cases that exemplify the clinical variability of this infection, the difficulty of the microbiological diagnosis in a routine laboratory, the problems of the antimicrobials' selection, and the importance of a long therapy course.


Minimally invasive "pocket incision" aortic valve surgery.
A minimally invasive approach to aortic valve surgery through a transverse incision ("pocket incision") at the right second intercostal space was examined. Sixteen patients with a mean age of 30 years underwent this approach. The third costal cartilage was either excised (n = 5) or dislocated (n = 11). The right internal mammary artery was preserved. Cardiopulmonary bypass (CPB) was established with aortic-right atrial cannulation in all except the first case. Aortic valve replacements (AVR) were performed in 15 patients and one had aortic valve repair with concomitant ventricular septal defect closure. There was no mortality and no major complications. The aortic cross-clamp, CPB and operative times were 72 +/- 19 mins, 105 +/- 26 mins and 3 hrs 00 min +/- 29 mins respectively. The mean time to extubation was 5.7 +/- 4.0 hrs, ICU stay of 27 +/- 9 hrs and postoperative hospital stay of 5.1 +/- 1.2 days. Minimally invasive "pocket incision" aortic valve surgery is technically feasible and safe. It has the advantages of central cannulation for CPB, preservation of the internal mammary artery and avoiding sternotomy. This approach is cosmetically acceptable and allows rapid patient recovery.


Evaluation of blood pressure control using a new arterial stiffness parameter, cardio-ankle vascular index (CAVI).
Arterial stiffness has been known to be a surrogate marker of arteriosclerosis, and also of vascular function. Pulse wave velocity (PWV) had been the most popular index and was known to be a predictor of cardiovascular events. But, it depends on blood pressure at measuring time. To overcome this problem, cardio-ankle vascular index (CAVI) is developed. CAVI is derived from stiffness parameter β by Hayashi, and the equation of Bramwell-Hill, and is independent from blood pressure at a measuring time. Then, CAVI might reflect the proper change of arterial wall by antihypertensive agents. CAVI shows high value with aging and in many arteriosclerotic diseases and is also high in persons with main coronary risk factors. Furthermore, CAVI is decreased by an administration of α1 blocker, doxazosin for 2-4 hours, Those results suggested that CAVI reflected the arterial stiffness composed of organic components and of smooth muscle cell contracture. Angiotensin II receptor blocker, olmesartan decreased CAVI much more than that of calcium channel antagonist, amlodipine, even though the rates of decreased blood pressure were almost same. CAVI might differentiate the blood pressure-lowering agents from the point of the effects on proper arterial stiffness. This paper reviewed the principle and rationale of CAVI, and the possibilities of clinical applications, especially in the studies of hypertension.


Short-term storage evaluation of quality and antioxidant capacity in chestnut-wheat bread.
Bread traditionally made from wheat is now often supplemented with alternative functional ingredients as chestnut flours; no data have been previously published about the staling of chestnut-containing bread. Thus short-term storage (3 days) for chestnut flour-supplemented soft wheat bread is evaluated by means of selected physicochemical properties (i.e. water dynamics, texture, colour, crumb grain characteristic, total antioxidant capacity). Bread prepared with a 20:80 ratio of chestnut:soft wheat flours maintained its moisture content in both crust and crumb. Crumb hardness, after baking, was found to be significantly higher than that of the soft wheat bread; it did not change during storage, whereas it significantly increased in the control bread until the end of the shelf life. The supplemented bread presented a heterogeneous crumb structure, with a significant decrease in the largest pores during shelf life, relative to the shrinkage of crumb grain. The control exhibited a significant redistribution of crumb holes, with a decrease in the smallest grain classes and an increase in the intermediate ones, most likely caused by cell wall thickening. The colour of the crumb remained unaltered in both breads. The crust of the control presented a significant decrease of a* (redness) and that of the supplemented bread exhibited a decrease of b* (yellowness). The antioxidant capacity was detected after day 1 of storage in the chestnut flour bread only. Chestnut flour supplementation could represent a feasible way of producing bread with improved characteristics, not only just after baking but also during shelf life.


Trends in Rates of Infections Requiring Hospitalization Among Adults With Versus Without Diabetes in the U.S., 2000-2015.
Vascular complications of diabetes have declined substantially over the past 20 years. However, the impact of modern medical treatments on infectious diseases in people with diabetes remains unknown. We estimated rates of infections requiring hospitalizations in adults (≥18 years) with versus without diabetes, using the 2000-2015 National Inpatient Sample and the National Health Interview Surveys. Annual age-standardized and age-specific hospitalization rates in groups with and without diabetes were stratified by infection type. Trends were assessed using Joinpoint regression with the annual percentage change (Δ%/year) reported. In 2015, hospitalization rates remained almost four times as high in adults with versus without diabetes (rate ratio 3.8 [95% CI 3.8-3.8]) and as much as 15.7 times as high, depending on infection type. Overall, between 2000 and 2015, rates of hospitalizations increased from 63.1 to 68.7 per 1,000 persons in adults with diabetes and from 15.5 to 16.3 in adults without diabetes. However, from 2008, rates declined 7.9% in adults without diabetes (from 17.7 to 16.3 per 1,000 persons; Δ%/year -1.5, P < 0.01), while no significant decline was noted in adults with diabetes. The lack of decline in adults with diabetes in the later period was driven by significant increases in rates of foot infections and cellulitis as well as by lack of decline for pneumonia and postoperative wound infections in young adults with diabetes. Findings from this study highlight the need for greater infectious risk mitigation in adults with diabetes, especially young adults with diabetes.


Evaluation of three chitin metal silicate co-precipitates as a potential multifunctional single excipient in tablet formulations.
The performance of the novel chitin metal silicate (CMS) co-precipitates as a single multifunctional excipient in tablet formulation using direct compression and wet granulation methods is evaluated. The neutral, acidic, and basic drugs Spironolactone (SPL), ibuprofen (IBU) and metronidazole (MET), respectively, were used as model drugs. Commercial Aldactone, Fleximex and Dumazole tablets containing SPL, IBU and MET, respectively, and tablets made using Avicel 200, were used in the study for comparison purposes. Tablets of acceptable crushing strength (>40 N) were obtained using CMS. The friability values for all tablets were well below the maximum 1% USP tolerance limit. CMS produced superdisintegrating tablets (disintegration time < 1 min) with the three model drugs. Regarding the dissolution rate, the sequence was as follow: CMS > Fleximex > Avicel 200, CMS > Avicel 200 > Dumazole and Aldactone > Avicel 200 > CMS for IBU, MET and SPL, respectively. Compressional properties of formulations were analyzed using density measurements and the compression Kawakita equation as assessment parameters. On the basis of DSC results, CMS co precipitates were found to be compatible with the tested drugs. Conclusively, the CMS co-precipitates have the potential to be used as filler, binder, and superdisintegrant, all-in-one, in the design of tablets by the direct compression as well as wet granulation methods.


[Complex evaluation of hand function after replantation of its segments for predicting the results of rehabilitation].
In 104 patients after replantation of upper extremity segments the hand function was estimated with due regard for the volume of active movements of the segment, value of deficiency of finger flexion, possibility of different kinds of grip, hand force, restoration of blood supply and innervation. A prognostic assessment of the above factors is given. Possibilities to restore working capacity is considered with special reference to the degree of disturbance of the hand function.


Animal husbandry: the period 1973-1995.
In the last decade the intensification of the pig and poultry industries has continued with increases in production unit size and in efficiency. This has come about as a response to rising costs, competition and reasonable end-product prices. The dairy industry has also expanded output through increasing milk yield per cow, encouraged by favourable market support. However, efficiency of feed conversion to milk production is still not directly selected for in dairy cattle. Developments in beef cattle have been away from intensive systems of production in an effort to reduce capital expenditure and increases in sheep productivity have been largely through increased stocking rates, greater fertilizer use and better grazing systems. In the next decade there are many feasible technological advances awaiting application. The use of computer simulation is likely to assist in predicting quantitative and qualitative body compositional responses to nutrition and in increasing the efficiency of grass utilization, while microprocessor technology will be developed into artificial aids to the stockman. Studies of reproductive physiology will continue to help increase output, especially with pigs and sheep. The building of sophisticated housing is likely to be justified for pigs, poultry, dairy cattle and calves, but not for suckler beef and sheep. There is likely to be greater use of centralized breeding schemes for dairy cattle, beef cattle and sheep. The future application of technology will be limited by a number of socio-economic factors. For example, the use of milk quotas to control surplus production will act as a powerful economic constraint to increased milk production and the growing public concern over animal welfare, pollution and health aspects of animal produce will exert increasing pressure on certain systems of production.


Screening to detect asymptomatic shedding of herpes simplex virus (HSV) in women with recurrent genital HSV infection.
To investigate the asymptomatic shedding of herpes simplex virus (HSV) from women with recurrent genital herpes infection, and to assess whether inapparent shedding could occur, eight such women were examined thrice weekly for one month. At each visit colposcopy was performed and multiple sites sampled for HSV. During the study four women had no recurrence of HSV infection, but four had at least one positive viral culture. One of these patients was asymptomatically shedding HSV on nine of her 11 clinic visits. Two episodes of urethral shedding were detected. In this group of patients the presence of inguinal lymphadenopathy was appreciably associated with the isolation of HSV from the urogenital tract.