Urine and serum analysis of consumed curcuminoids using an IkappaB-luciferase surrogate marker assay.
curcumin metabolites are detectable in body fluids such as serum and urine. We have developed a novel assay that can detect metabolites in such body fluids by measuring their effect on the nuclear factor kappa B/inhibitor of kappa B (NF-κB/IκB) pathway. fifteen healthy individuals were enrolled in the study and randomly assigned to two groups: control group (five) and curcumin group (ten). The test group ingested 8 g of the curcuminoids (C(3)-Complex) with 16 oz of bottled water. Blood and urine were collected at 0, 4, 8, and 24 h after ingestion. Degradation of the NF-κB/IκB complex was detected by the Genetic Expression and Measurement (GEM) assay using HCT116 cells stably transfected with PGL3-IκB firefly luciferase. using our novel GEM assay, the five controls who had not taken curcumin were identified. the GEM assay is a very sensitive and accurate non-invasive assay that could be utilized to detect metabolites in body fluids. It could also serve as a tool to determine participants' compliance during clinical research studies.


Pathophysiological Mechanisms Underlying Excess Risk for Diabetes and Cardiovascular Disease in South Asians: The Perfect Storm.
South Asians are at a significantly increased risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), are diagnosed at relatively younger ages, and exhibit more severe disease phenotypes as compared with other ethnic groups. The pathophysiological mechanisms underlying T2D and CVD risk in South Asians are multifactorial and intricately related. A narrative review of the pathophysiology of excess risk of T2D and CVD in South Asians. T2D and CVD have shared risk factors that encompass biological factors (early life influences, impaired glucose metabolism, and adverse body composition) as well as behavioral and environmental risk factors (diet, sedentary behavior, tobacco use, and social determinants of health). Genetics and epigenetics also play a role in explaining the increased risk of T2D and CVD among South Asians. Additionally, South Asians harbor several lipid abnormalities including high concentration of small-dense low-density lipoprotein (LDL) particles, elevated triglycerides, low high-density lipoprotein (HDL)- cholesterol levels, dysfunctional HDL particles, and elevated lipoprotein(a) that predispose them to CVD. In this comprehensive review, we have discussed risk factors that provide insights into the pathophysiology of excess risk of T2D and CVD in South Asians.


Acute gastric dilatation and necrosis: a case report.
Massive gastric dilatation with necrosis and rupture is a very rare event. Here we describe the case of a 13-year-old girl with acute gastric dilatation, infarction, necrosis and perforation. It began with acute abdominal pain, but an absence of vomiting after eating a heavy meal. Laparotomy showed massive gastric dilatation with infarction and perforation. Early diagnosis is essential to reduce morbidity and mortality, and therefore treatment must be started promptly.


Effective induction of pblac1 laccase by copper ion in Polyporus brumalis ibrc05015.
Polyporus brumalis ibrc05015 is a strain capable of high laccase (Lac) production. Among several inducers, 0.25 mM copper was most effective for Lac production. One of the Lacs induced by copper was PbLac1, and its transcription was induced within 60 min after copper addition. The promoter region of pblac1 contained six putative metal response elements and one Ace1 consensus cis-element. We cloned the P. brumalis PbAce1 transcription factor, a homologue of Saccharomyces cerevisiae transcription factor Ace1, which regulates metallothionein genes in response to excess copper. PbAce1 complemented the function of Ace1 in an S. cerevisiae Δace strain. The conserved N-terminal copper-fist DNA binding domain of PbAce1 was required for complementation. In the PbAce1 complemented Δace1 strain, the pblac1 promoter was constitutively expressed at a high level, independent of copper concentration. PbAce1 has two Cys-rich repeat motifs (PbC1 and PbC2), which are similar to the Cys-rich repeat domain in metallothionein proteins, and are uniquely conserved in the C-terminal domain of basidiomycetous Ace1 sequences. These C-terminal domains could be involved in copper sensing and concentration-dependent Lac production in basidiomycetous fungi.


Pretreatment body mass index affects achievement of target blood pressure with sodium-glucose cotransporter 2 inhibitors in patients with type 2 diabetes mellitus and chronic kidney disease.
Sodium-glucose cotransporter 2 inhibitor (SGLT2-I) shows excellent antihypertensive effects in addition to its hypoglycemic effects. However, whether body mass index (BMI) affects the antihypertensive effect of SGLT2-I remains unknown. We investigated the impact of baseline BMI on the achievement of target blood pressure (BP) with SGLT2-I treatment in Japanese patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). We retrospectively evaluated 447 Japanese patients with T2DM and CKD treated with SGLT2-I for at least 1 year. The primary outcome was achieving the target BP (<130/80 mmHg) after SGLT2-I treatment. Patients were divided into two groups according to a baseline BMI of 29.1 determined by receiver operating characteristic analysis and analyzed in a cohort model with propensity score matching. In each group, 130 patients were compared by propensity score matching. The target BP achievement rate was significantly higher in the BMI < 29.1 group than in the BMI ≥ 29.1 group (34% and 21%, respectively, p = 0.03). The odds ratio for achieving the target BP in the BMI ≥ 29.1 group was 0.50 (95% confidence interval, 0.28-0.90, p = 0.02). The BMI < 29.1 group had significantly lower systolic and diastolic BPs after SGLT2-I treatment than the BMI ≥ 29.1 group. Only the BMI < 29.1 group was showed a significant decrease in the logarithmic albumin-to-creatinine ratio from baseline after SGLT2-I treatment. In patients with T2DM and CKD, baseline BMI was associated with the antihypertensive effects of SGLT2-I. Patients in the lower baseline BMI group were more likely to achieve the target BP after SGLT2-I treatment. Pretreatment BMI affects the antihypertensice effect of SGLT2 inhibirors in patients with T2DM and CKD.


[P300 cognitive event-related potentials in the diagnosis and classification of possible Alzheimer-type neurocognitive disorders].
The value of the P300 cognitive event-related potential in the diagnosis of Alzheimer subtype neurocognitive disorders is still incipient. Recent studies suggest that combining it with neuropsychological tests by cognitive domains would allow an objective and early characterisation of the cognitive impairment in its initial stages. To characterise the electrophysiological patterns in the P300 potential that obtain a discriminatory value for the diagnosis and classification of the neurocognitive disorders with a possible Alzheimer-type aetiology. This study examines 39 patients classified, according to the DSM-5, with possible Alzheimer-type minor and major neurocognitive disorders, aged between 50 and 85 years, and 53 control subjects with normal cognitive functions. The P300 potential is registered in the auditory mode, oddball paradigm and centroparietal recording. P300 latency is significantly prolonged in subjects with neurocognitive disorder; there are significant differences in the mean values and confidence intervals between healthy controls and patients. No significant differences are obtained in P300 latency between groups with minor and major neurocognitive disorder. The mean amplitude value decreases in neurocognitive disorder, and the P300 amplitude logarithm of the control groups and those with minor and major neurocognitive disorder reaches significantly different mean values and confidence intervals. The parameters quantified in the P300 potential can be used as complementary biomarkers to classify the presence and level of cognitive dysfunction with a possible Alzheimer-type aetiology.


Long-term impact of post COVID-19 pandemic quarantine on eating habits changes among adult residents of Riyadh, Saudi Arabia.
COVID-19 outbreak and quarantine measures clearly had an impact on the population's eating habits-related behavior. This study aimed to explore the long-term impact of the COVID-19 pandemic and physical quarantine on eating habits after quarantine among Riyadh city residents, Saudi Arabia. A cross-sectional study was conducted through an online survey between December 2022 and April 2023 on a convenient sample of Saudi adults in Riyadh, Saudi Arabia. A valid questionnaire was used to measure study outcomes. A comparison between dietary habits before and after COVID-19 was performed to identify the changes in dietary habits. 1,451 Saudi adults residing in Riyadh completed the online survey. The majority (88.6%) of the respondents reported changes in dietary habits after COVID-19. About 50% had 1-3 dietary habits changes and slightly more than one-third had 4-7 dietary habits change. About 33.8% of the participants reported stable weight during the COVID-19 pandemic. However, 40.9% reported weight gain, and 20.7% reported weight loss. The participants reported several unhealthy dietary changes most commonly eating fast food (33%), eating junk food/fast food due to boredom/distress/disappointment (29.8%), and high sugar such as sweet porridge, pastry, sweets, and chocolate (28.5%). On the other side, the participants showed healthy dietary habits such as having a balanced healthy ingredients diet (34.4%), an increase in the consumption of fruits and vegetables, and a decrease in the intake of junk foods (28.9%). Males were more likely to exhibit unhealthy dietary habits than females (Odd Ratio:1.43, p = 0.038, CI: 1.02-2.02). Increasing age was associated with a reduction in the likelihood of exhibiting unhealthy dietary habits (OR: 0.98, p = 0.011, CI: 0.96-0.99). Moreover, participants who reported stable weight or weight loss during COVID-19 were 0.29 (p = 0.043, 0.09-0.96) and 0.34 (p = 0.020, 0.07-0.79), respectively, less likely to have unhealthy dietary habits. Although healthy dietary habits have been reported in this study, such as consumption of fruits and vegetables, COVID-19 confinement has also led to negative dietary behaviors reflected by high consumption of fast/junk food and sugar intake resulting in weight gain, a potential adverse impact on the population wellbeing.


Contribution of cattle products to dietary intake of trace and toxic elements in Galicia, Spain.
In Galicia, Spain, liver copper concentrations, muscle zinc concentrations and kidney cadmium concentrations (in adult cattle) can exceed acceptable maximum concentrations which have been adopted by some countries. The aim was to calculate the contribution of cattle products to the daily intake of trace and toxic metals by humans in Galicia and to evaluate whether there was any health risk to consumers. This was done by comparing calculated intakes with published acceptable daily intake rates for toxic elements and with the accepted safe ranges for population mean intakes of the essential metals. Typically, the contribution of cattle meat and offal to the daily cadmium, lead and arsenic intake of people in Galicia was minimal because offal is rarely eaten. However, liver from older cattle, especially animals from relatively contaminated areas, could pose a health risk if offal was consumed in substantial quantities. Muscle and liver from Galician cattle that exceeded acceptable maximum concentrations for copper and zinc did not pose a risk to human health.


Spinopelvic Parameters in Asymptomatic Subjects Without Spine Disease and Deformity: A Systematic Review With Meta-Analysis.
A systematic review with meta-analysis. To combine published data, focusing on the development of optimal spinopelvic parameters in adult asymptomatic subjects without spine deformity while taking into consideration the impact of potential confounders. A well-grounded approach to define the optimal spinopelvic parameters is necessary for planning surgical correction of spine deformity. Selection criteria: (1) randomized and nonrandomized prospective, cross-sectional, and retrospective studies; (2) participants: asymptomatic subjects without spine deformity aged above 18 years; (3) studied parameters: lumbar lordosis (LL), pelvic incidence, sacral slope, and pelvic tilt; (4) potential confounders: method of measurement, sex, age, ethnicity, weight, height, and body mass index. Search method: Ovid MEDLINE (1946-current) and EMBASE (1980-current), all years through October 2015 were included. Data were collected: number of enrolled subjects, means of the studied characteristics, SD, SE of the means, 95% confidence intervals. A meta-analysis was performed to evaluate the pooled means and range of optimal values (pooled mean±pooled SD) taking into consideration the impact of confounders. The GRADE approach was applied to evaluate the level of evidence. Seventeen of 1018 studies were included (2926 subjects from 9 countries). The pooled means and the optimal ranges were: LL (L1-S1), 54.6 (42-67) degrees; LL (L1-L5), 37.0 (22-53) degrees; pelvic incidence, 50.6 (39-62) degrees; sacral slope, 37.7 (28-48) degrees; pelvic tilt, 12.6 (3-22) degrees. The pooled results were statistically significant (P<0.001), but heterogeneous. Impact of the following confounders was revealed: method of measurement, ethnicity, age, and body mass index. A methodology was created to define an individualized optimal value and range of each studied parameter taking into consideration the influence of confounders. The pooled results and developed methodology can be used as diagnostic criteria for evaluation of the spinopelvic parameters, planning of surgical interventions and evaluation of the treatment effect.


The presence of leuko-araiosis in patients with Alzheimer's disease predicts poor tolerance to tacrine, but does not discriminate responders from non-responders.
approximately one-third of patients with Alzheimer's disease (AD) respond favourably to the anticholinesterase tacrine, but the drug's usefulness is marred by a high incidence of side-effects. to discover if AD patients with white matter low attenuation (WMLA) represents a subgroup that responds differently to tacrine from those with no WMLA. the results come from a combination of double-blind and open studies. Seventy-two AD patients prescribed tacrine in our centre were divided into two groups according to the presence or absence of WMLA on brain CT scans. We compared the rate of response to and withdrawal from tacrine between the groups. Response was defined as an improvement in the Mini-Mental State Examination score of three or more points at 3 months. 18 of the 72 patients were found to have WMLA. There was no significant difference in the proportion of patients responding to tacrine in each group (28.5% in those with WMLA and 31% in those without), but the rate of withdrawal from tacrine did differ: 11 patients with WMLA (61%) had to be withdrawn prematurely, compared with 14 patients (26%) in the group without evidence of WMLA (P = 0.015). AD patients with WMLA can still respond to tacrine, although the rate of withdrawal from treatment is much higher in such patients.


Explosive and maximal strength before and 6 months after total hip arthroplasty.
Patients with unilateral hip osteoarthritis experience impairments in lower limb muscle function due to pain and disuse of the affected limb. The influence of hip osteoarthritis and subsequent total hip arthroplasty (THA) has mostly been evaluated by maximal strength tests, yet the functionally important explosive strength capabilities of hip and knee muscles are largely unknown. We aimed to evaluate hip and knee explosive and maximal strength in hip osteoarthritis patients before and after THA. Twenty-one patients with unilateral hip osteoarthritis were evaluated before and 6 months after THA. They performed rapid maximal contractions of hip (flexor, extensor, abductor, adductor) and knee (flexor, extensor) muscles, from which explosive and maximal strength asymmetries were evaluated (involved versus uninvolved limb). Before THA, the involved limb showed significantly lower hip flexor, extensor, adductor, and knee extensor explosive and maximal strength compared to the uninvolved limb. Six months after THA surgery, hip flexor, extensor and adductor maximal and explosive strength asymmetries persisted, except for knee extensors. Explosive, but not maximal strength of hip abductors and knee extensors was lower in the involved limb before surgery and the reduced explosive strength capabilities may compromise daily living activities in hip osteoarthritis patients. After hip replacement, explosive strength asymmetries of knee extensors resolved, yet lingering asymmetries in hip flexor muscles should receive focused attention during postoperative rehabilitation. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:425-431, 2018.


Immediate versus delayed loading of strategic mini dental implants for the stabilization of partial removable dental prostheses: a patient cluster randomized, parallel-group 3-year trial.
Acceptable short-term survival rates (>90 %) of mini-implants (diameter < 3.0 mm) are only documented for mandibular overdentures. Sound data for mini-implants as strategic abutments for a better retention of partial removable dental prosthesis (PRDP) are not available. The purpose of this study is to test the hypothesis that immediately loaded mini-implants show more bone loss and less success than strategic mini-implants with delayed loading. In this four-center (one university hospital, three dental practices in Germany), parallel-group, controlled clinical trial, which is cluster randomized on patient level, a total of 80 partially edentulous patients with unfavourable number and distribution of remaining abutment teeth in at least one jaw will receive supplementary min-implants to stabilize their PRDP. The mini-implant are either immediately loaded after implant placement (test group) or delayed after four months (control group). Follow-up of the patients will be performed for 36 months. The primary outcome is the radiographic bone level changes at implants. The secondary outcome is the implant success as a composite variable. Tertiary outcomes include clinical, subjective (quality of life, satisfaction, chewing ability) and dental or technical complications. Strategic implants under an existing PRDP are only documented for standard-diameter implants. Mini-implants could be a minimal invasive and low cost solution for this treatment modality. The trial is registered at Deutsches Register Klinischer Studien (German register of clinical trials) under DRKS-ID: DRKS00007589 ( www.germanctr.de ) on January 13(th), 2015.


Parallel evoluton in lichen-forming fungi.
The asexual lichen-forming fungus Parmelia hypotropa has two common chemical races that differ sharply in biogeography and niche characteristics and appear to have been derived by morphologic parallelism from chemically identical races of the closely related Parmelia perforata, which is sexual. Among the lichen fungi many chemically variable asexual morphs, which conventional taxonomies treat as species, are probably polyphyletic like Parmelia hypotropa.


Presence of HIV-1 reverse transcriptase inhibitory antibodies in the sera of some HTLV-1 carriers and absence of neutralizing antibodies against HIV-1 in the sera of HTLV-1 carriers.
We have detected inhibitory antibody against HIV-1 reverse transcriptase (RT) in the sera of HTLV-1 carriers, although the lack of immunological cross reaction between HIV-RT and other mammalian retroviruses, including HTLV-1, has been reported elsewhere (1). Sera from 72 HTLV-1 carriers in the southern part of Kyushu in Japan and 61 controls from the same district were studied and controlled for age and sex. One of the 72 HTLV-1 carriers was HTLV-1 antibody-positive, while the others were HIV-1 antibody-negative by ELISA and Western blot method. Sera from two HTLV-1 carriers and one hemophiliac with combined HIV-1 and HTLV-1 infections were found to inhibit HIV-1 RT activity. The inhibition ratios were 72, 65 and 72%, respectively. Protein A effluents of inhibitory sera retained no inhibitory capacity. These results might suggest that HTLV-1 and HIV-1 reverse transcriptase may share common or similar epitopes and that antibodies raised to the HTLV-1 RT react with that of HIV-1 RT in an inhibitory mode. However, the RT inhibitory antibody-positive sera had no neutralizing capacity against HIV-1 infection, supporting the idea that HIV-1 RT inhibitory antibody may not contribute to neutralization against HIV-1. The results also suggest that previous exposure to HTLV-1 does not contribute to neutralizing antibodies against HIV-1 in HIV-1 infected individuals.


Population effectiveness of pharmaceutical aids for smoking cessation: what is associated with increased success?
Although nicotine replacement therapy (NRT) has shown efficacy in randomized controlled trials, population effectiveness has appeared to diminish after it became available over the counter. The present study examined the population effectiveness of bupropion. It also examined whether population effectiveness of pharmaceutical-aid use in general (NRT, bupropion, or both) might be influenced by environmental factors: Having a smoke-free home (possible indication of motivation to quit) or no other smoker in the household. Data from the large population-based cross-sectional 1999 and 2002 California Tobacco Surveys were combined to improve statistical power for subgroup analyses of duration of abstinence following the most recent quit attempt in the past year. Moderate-to-heavy daily smokers (at least 15 cigarettes/day) a year prior to the survey (N = 2,640) were the main focus. A Cox proportional-hazards analysis suggested that bupropion was effective, perhaps even in the longer term. Further analyses identified significant interactions on abstinence duration between having a smoke-free home and any pharmaceutical-aid use (NRT, bupropion, or both), and between having a smoke-free home and no other smoker in the household. Although pharmaceutical aids may have had a slight short-term benefit if the home was not smoke free, they appeared particularly effective if the home was smoke free, both in the short and longer term. The California population experience supports the policy that programs subsidizing pharmaceutical aids to help smokers quit (particularly bupropion, if appropriate) should target highly motivated smokers who have already taken a behavioral action, such as implementing a smoke-free home.


Variable positions of NORs in Mus musculus.
Silver-NOR staining has been applied to mouse (Mus musculus) chromosomes of different feral populations from Italy, Yougoslavia, and Germany and to chromosomes of M. spretus, a closely related species, from Portugal. In addition to the known pattern of proximal sites on smaller autosomes, terminal sites with silver-NORs on chromosomes 4 and 13 were detected. In M. spretus only terminal NORs were present on chromosomes 4, 13, and 19. Thus, the location of silver-NORs within the genus Mus and M. musculus subspecies shows wide variation.


Biological Activities of p-Hydroxycinnamic Acids in Maintaining Gut Barrier Integrity and Function.
It is well established that p-Hydroxycinnamic acids (HCAs), including ferulic, caffeic, sinapic, and p-coumaric acids, possess a characteristic phenylpropanoid C6-C3 backbone and account for about one-third of the phenolic compounds in our diet. HCAs are typically associated with various plant cell wall components, including mono-, di-, and polysaccharides, sterols, polyamines, glycoproteins, and lignins. Interestingly, enzymes produced by intestinal microbes liberate HCAs from these associations. HCAs are completely absorbed in their free form upon ingestion and undergo specific reactions upon absorption in the small intestine or liver. The gut epithelium, composed of intestinal epithelial cells (IECs), acts as a physical barrier against harmful bacteria and a site for regulated interactions between bacteria and the gut lumen. Thus, maintaining the integrity of the epithelial barrier is essential for establishing a physiochemical environment conducive to homeostasis. This review summarizes the protective effects of HCAs on the intestinal barrier, achieved through four mechanisms: preserving tight junction proteins (TJPs), modulating pro-inflammatory cytokines, exerting antioxidant activity, and regulating the intestinal microbiota.


Cu(II)-nitroxyl radicals as catalytic galactose oxidase mimics.
Results from Hammett correlation studies and primary kinetic isotope effects for the CuCl-TEMPO catalysed aerobic benzyl alcohol oxidations are inconsistent with an oxoammonium based mechanism. We postulate a copper-mediated dehydrogenation mechanism, in which TEMPO regenerates the active Cu(II)-species. This mechanism is analogous to that observed for Galactose Oxidase and mimics thereof.


[Diagnosis of erectile dysfunction].
Erectile dysfunction is a disorder with multifactorial causes. The pathophysiological origin can be severe general disease. Consequently each patient has to undergo a general diagnostic procedure so that severe disease is not missed. The diagnostic work-up of erectile dysfunction follows a three-step scheme of increasing invasiveness. The non-invasive step is the most important. These investigations comprise taking an extensive general history including a detailed sexual history, psychological diagnosis, physical examination, and laboratory tests. The semi-invasive procedures include the intracavernous injection test, colour-coded duplex sonography and optional neurophysiological examinations. The invasive investigations include dynamic infusion pharmacological cavernosography and cavernosometry, and penile angiography. The extensiveness of the diagnostic procedures should be adapted to the complexity of the history and the therapeutic expectations. However, if there is any suspicion of a severe disease remaining undiagnosed, the diagnostic procedures should be adequately comprehensive.


Paraovarian cyst with torsion in children.
Paraovarian cyst is very uncommon in children, and its preoperative diagnosis is difficult. This report describes 2 cases of surgically proven paraovarian cyst with torsion. It is important to be aware of torsion as a complication of paraovarian cyst.


Acetylation-induced TDP-43 pathology is suppressed by an HSF1-dependent chaperone program.
TDP-43 pathology marks a spectrum of multisystem proteinopathies including amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and sporadic inclusion body myositis. Surprisingly, it has been challenging to recapitulate this pathology, highlighting an incomplete understanding of TDP-43 regulatory mechanisms. Here we provide evidence supporting TDP-43 acetylation as a trigger for disease pathology. Using cultured cells and mouse skeletal muscle, we show that TDP-43 acetylation-mimics promote TDP-43 phosphorylation and ubiquitination, perturb mitochondria, and initiate degenerative inflammatory responses that resemble sporadic inclusion body myositis pathology. Analysis of functionally linked amyotrophic lateral sclerosis proteins revealed recruitment of p62, ubiquilin-2, and optineurin to TDP-43 aggregates. We demonstrate that TDP-43 acetylation-mimic pathology is potently suppressed by an HSF1-dependent mechanism that disaggregates TDP-43. Our study illustrates bidirectional TDP-43 processing in which TDP-43 aggregation is targeted by a coordinated chaperone response. Thus, activation or restoration of refolding mechanisms may alleviate TDP-43 aggregation in tissues that are uniquely susceptible to TDP-43 proteinopathies.TDP-43 aggregation is linked to various diseases including amyotrophic lateral sclerosis. Here the authors show that acetylation of the protein triggers TDP-43 pathology in cultured cells and mouse skeletal muscle, which can be cleared through an HSF1-dependent chaperone mechanism that disaggregates the protein.


Practices in management of cancer treatment-related cardiovascular toxicity: A cardio-oncology survey.
Cardiovascular toxicity has become a challenging issue during cancer therapy. Nonetheless, there is a lack of consensual guidelines for their management. We aimed to determine the current practices of oncologists regarding cardiovascular toxicity related to anthracyclines, trastuzumab and angiogenic inhibitors and to gather their opinions on the development of cardio-oncology programs. A cross-sectional declarative study was submitted to French oncologists in the form of an individual, structured questionnaire. A total of 303 oncologists responded to the survey. Ninety-nine percent of oncologists prescribed cardiotoxic therapies, including anthracyclines (83%), trastuzumab (51%) and other angiogenic inhibitors (64%). The method adopted for managing cardiovascular toxicity was based on guidelines from expert oncology societies for only 35% of oncologists. None was aware of recommendations from expert cardiology societies. Prescription of pre-, peri- and post-therapy cardiovascular assessment was inconsistent and significantly less frequent for all classes of angiogenic inhibitors than for anthracyclines and trastuzumab (P<0.0001). Relative to pre-therapy assessment, post-therapy assessment was prescribed significantly less often for all cancer therapies (P<0.0001). Attitudes regarding the onset of left ventricular dysfunction were much more inconsistent when angiogenic inhibitors were involved. Additionally, the management of hypertension and QT prolongation was also inconsistent. Finally, 88% of oncologists supported projects of cardio-oncology programs development. Practices of oncologists are disparate in the field of cardiovascular toxicity. This finding underlines the complexity of managing many different situations and the need for distribution of formal guidelines from oncology and cardiology expert societies. The development of personalized cardio-oncology programs seems essential.


Missouri casino self-excluders: distributions across time and space.
According to public health research, exposure to casinos is a risk factor for disordered gambling. Consequently, casino self-exclusion programs, which provide gamblers with the opportunity to voluntarily seek limits on their access to gambling venues, can serve as a barometer of the concentration of disordered gambling in an area. This study reports on the distribution, both temporally and geographically, of 6,599 people who applied to exclude themselves from Missouri casinos between November, 1996 and February, 2004. Analyses used Microsoft MapPoint to plot the location of casinos and self-excluders (SEs) across Missouri and its constituent counties. These regional exposure analyses showed that the Western region around Kansas City is an epicenter of disordered gambling as, to a lesser extent, is the Eastern region around St. Louis. The annual number of SE enrollments increased during the first few years of the Missouri self-exclusion program and then leveled off during the later years. These findings have important implications for public health and the development of public health interventions for disordered gamblers.


Soft-leadership competencies for today's healthcare finance executives.
With the healthcare industry changing rapidly, organizations seek finance leaders who have skills that go beyond traditional expertise in revenue and expenses. These additional competencies fall under the heading of soft-leadership skills and include the ability to be strategy-oriented, agile, passionate, inspirational, influential, communicative, dependable, driven, integrative, and engaged. Networking, participation in a mentoring program, and continuing education provide avenues for finance leaders to develop these sorts of skills.


Is OVX1 a suitable marker for endometrial cancer?
The single most common cause leading to the diagnosis of endometrial cancer is postmenopausal bleeding. Although most patients with early-stage disease (FIGO stage I and II) can be cured, prognosis worsens considerably with increasing stage. While serum CA 125 levels are elevated only in a significant proportion of patients with advanced disease, recently a new serum marker (OVX1) for the detection of early-stage endometrial cancer was reported. Serum OVX1 levels were measured using an OVX1 radioimmunoassay (RIA) or enzyme immunoassay (EIA) in 192 patients with endometrial cancer. CA 125 levels were measured in 112 patients using the CIS ELSA CA 125 kit. Apparently healthy females had mean serum OVX1 levels measured with the OVX1-EIA of 1.34 +/- 0.74 U/ml, while patients with endometriosis had mean OVX1 serum levels of 3.15 +/- 2.45 U/ml. The mean OVX1 serum level for endometrial cancer patients was 2.00 +/- 1.32 U/ml. These values were 2.76 +/- 1.62, 6.10 +/- 4.66, and 5.37 +/- 3.49, respectively, using the OVX1-RIA assay. Applying a cutoff value of 2.8 U/ml, serum OVX1-EIA levels in endometrial cancer patients were increased in 25 of 127 patients (19.7%) with stage I disease, 5 of 17 patients with stage II (29.4%), 5 of 22 patients (22.7%) with stage III, and 4 of 11 patients (36.4%) with stage IV disease. Using the OVX1-RIA and a cutoff of 7.2 U/ml, serum levels were increased in 22 of 127 (17.3%) stage I, 6 of 17 (35.3%) stage II, 5 of 22 (22.7%) stage III, and 6 of 11 (54.5%) stage IV patients. Serum CA 125 levels, determined in a total of 112 patients, were elevated above 35 U/ml in 12 of 79 patients (15.2%) with stage I, 4 of 12 patients (33.3%) with stage II, 8 of 13 patients (61.5%) with stage III, and all of 8 patients (100%) with stage IV disease. While a good correlation between serum CA 125 levels and the clinical stage of the disease was found, no correlation could be detected for OVX1 and stage.


A crab-hole mosquito, Ochlerotatus baisasi, feeding on mudskipper (Gobiidae: Oxudercinae) in the Ryukyu Islands, Japan.
Ochlerotatus baisasi was observed and photographed feeding on a mudskipper (Periophthalmus argentilineatus). Origin of blood meals in the stomachs of female mosquitoes collected at burrows of land crabs and mud lobsters in the mangrove forests of Oura, Okinawa, and Komi, Iriomote (the Ryukyu Islands), was determined by enzyme-linked immunosorbent assay to be from a fish source.


Contrast-enhanced MR angiography and perfusion imaging of the hand.
The goal of this investigation was to develop a technique for producing high-resolution gadolinium-enhanced MR images of the hand that show three-dimensional angiographic anatomy and permit measurement of distal soft-tissue perfusion. High-resolution MR angiograms of the hand, as well as qualitative perfusion information, can be produced using a rapid sequential gadolinium-enhanced three-dimensional gradient-echo technique.


Effect of nanoshell geometries, sizes, and quantum emitter parameters on the sensitivity of plasmon-exciton hybrid nanoshells for sensing application.
A proposed nanosensor based on hybrid nanoshells consisting of a core of metal nanoparticles and a coating of molecules is simulated by plasmon-exciton coupling in semi classical approach. We study the interaction of electromagnetic radiation with multilevel atoms in a way that takes into account both the spatial and the temporal dependence of the local fields. Our approach has a wide range of applications, from the description of pulse propagation in two-level media to the elaborate simulation of optoelectronic devices, including sensors. We have numerically solved the corresponding system of coupled Maxwell-Liouville equations using finite difference time domain (FDTD) method for different geometries. Plasmon-exciton hybrid nanoshells with different geometries are designed and simulated, which shows more sensitive to environment refractive index (RI) than nanosensor based on localized surface plasmon. The effects of nanoshell geometries, sizes, and quantum emitter parameters on the sensitivity of nanosensors to changes in the RI of the environment were investigated. It was found that the cone-like nanoshell with a silver core and quantum emitter shell had the highest sensitivity. The tapered shape of the cone like nanoshell leads to a higher density of plasmonic excitations at the tapered end of the nanoshell. Under specific conditions, two sharp, deep LSPR peaks were evident in the scattering data. These distinguishing features are valuable as signatures in nanosensors requiring fast, noninvasive response.


Carbon cycle feedbacks and future climate change.
Climate and carbon cycle are tightly coupled on many timescales, from interannual to multi-millennial timescales. Observations always evidence a positive feedback, warming leading to release of carbon to the atmosphere; however, the processes at play differ depending on the timescales. State-of-the-art Earth System Models now represent these climate-carbon cycle feedbacks, always simulating a positive feedback over the twentieth and twenty-first centuries, although with substantial uncertainty. Recent studies now help to reduce this uncertainty. First, on short timescales, El Niño years record larger than average atmospheric CO2 growth rate, with tropical land ecosystems being the main drivers. These climate-carbon cycle anomalies can be used as emerging constraint on the tropical land carbon response to future climate change. Second, centennial variability found in last millennium records can be used to constrain the overall global carbon cycle response to climatic excursions. These independent methods point to climate-carbon cycle feedback at the low-end of the Earth System Models range, indicating that these models overestimate the carbon cycle sensitivity to climate change. These new findings also help to attribute the historical land and ocean carbon sinks to increase in atmospheric CO2 and climate change.


Short-term response of the slow growing seagrass Posidonia oceanica to simulated anchor impact.
Experimental evaluations about the impact of anchors of small vessels have previously shown that each anchoring can on average damage up to six shoots of Posidonia oceanica, removing small amount of biomass and, at the same time, interrupting continuity among shoots. The aim of the paper was to investigate the response of P. oceanica to different damage intensity at two levels of substrata compactness. Three treatments were considered: control (no damage); low damage (simulated anchor damage by three strokes of a hoe); and high damage (six strokes). Disturbance was higher where the substratum was highly penetrable and after one year significant variation was observed among treatments for both the number of leaves per shoot and shoot density. Conversely, the number of leaves per shoot by the end of the study was similar among all treatment combinations, suggesting that this was the only phenological feature that recovered, and probably the only result that through clonal integration could be achieved. These data strongly highlighted the role that anchoring might have on the slow growing seagrass P. oceanica meadow.


Arrhythmias in patients with X-linked myotubular myopathy.
Myotubular myopathy is a congenital muscle disease caused by a mutation in the myotubularin (MTM1) gene. The X-linked myotubular myopathy (XLMTM) affects males with early-onset symptoms such as muscle weakness, hypotonia, and respiratory distress. To our knowledge, cardiac involvement has not been previously described in this condition, in contrast to other types of congenital myopathies such as nemaline myopathy or core myopathy. We report two clinical cases of XLMTM that started with severe sinus bradycardia or auriculoventricular block from the first days of life, with pathologic 24-hours Holter monitoring in both cases. A primary cardiac affection was excluded by electrophysiological studies and normal heart rate was recovered with proper respiratory support. These cases with sever bradyarrhythmia in a well know pathology such the XLMTM represents a nuance on the usual differential diagnostics of congenital myopathies.


Treatment optimization for HIV/HCV co-infected patients.
Human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections affect millions of persons around the globe and cause profound morbidity and mortality. A major intersection exists between these two epidemics, with HCV infection being more common in persons with HIV than in the general population, largely due to shared routes of transmission. HCV co-infection increases risk for liver- and non-liver-related morbidity and mortality, making HCV treatment a priority in HIV co-infected persons, but the treatment of HCV in co-infected patients has been daunting for multiple reasons. Until recently, HCV treatment has frequently been deferred due to the low rates of cure, significant adverse effects, burdensome duration of therapy and drug-drug interactions with HIV antiretroviral medications. Untreated HCV has resulted in significant health consequences for the millions of those infected and has led to multiple downstream impacts on our healthcare systems around the world. The development of a remarkable number of new HCV direct-acting agents (DAAs) that are significantly more efficacious and tolerable than the previous interferon-based regimens has transformed this important field of medicine, with the potential to dramatically reduce the burden of infection and improve health outcomes in this population. This review will summarize the epidemiology and clinical impact of HIV/HCV co-infection and current approaches to the treatment of HCV in HIV/HCV co-infected patients.


Evidence that alpha 2-adrenergic pathways play a major role in growth hormone (GH) neuroregulation: alpha 2-adrenergic agonism counteracts the inhibitory effect of muscarinic cholinergic receptor blockade on the GH response to GH-releasing hormone, while alpha 2-adrenergic blockade diminishes the potentiating effect of increased cholinergic tone on such stimulation in normal men.
The aim of this study was to investigate the interrelationships between alpha 2-adrenergic and cholinergic pathways in the control of hypothalamic somatostatin (SRIF) secretion in humans. In eight normal volunteers subjects we compared the pattern of GHRH-induced GH release to that elicited by similar challenge given 60 min after a pretreatment with drugs affecting alpha 2-adrenergic and muscarinic cholinergic neurotransmission. In a control study, synthetic GHRH [GRF-(1-29); 1 microgram/kg, iv] was administered 60 min after giving placebo. In other experiments, the administration of atropine (1 mg, im), or clonidine (0.300 mg, orally), or atropine plus clonidine, or pyridostigmine (120 mg, orally), or yohimbine (30 mg, orally), or pyridostigmine plus yohimbine, at 0 min was followed by GHRH administration 60 min later. The administration of both clonidine and pyridostigmine significantly (P less than 0.01) enhanced the GH responses to GHRH compared to those elicited by this challenge when given after placebo. Conversely, atropine pretreatment significantly (P less than 0.01) blocked the GH response to GHRH challenge, whereas yohimbine did not significantly affect it. When atropine and clonidine were given together, the inhibitory effect of the former was overcame and mean GHRH-elicited GH peak response was significantly (P less than 0.05) higher than that in the control study. In contrast, pretreatment with yohimbine significantly (P less than 0.05) blunted the pyridostigmine-induced enhancement of GHRH-elicited GH release. These data confirm our previous postulate suggesting that the stimulatory effect of clonidine on GH release is mainly exerted by inhibiting the hypothalamic SRIF release. Moreover, the effect of cholinergic neurons on SRIF release seems to be, at least in part, dependent on alpha 2-adrenergic pathways. Based on these data, it can be proposed that the alpha 2-adrenergic system plays a major role in the control of hypothalamic SRIF release, and hence in GH neuroregulation, whereas the muscarinic cholinergic system would participate in such regulation by modulating the functional activity of the former.


Electrostatic interactions control the adsorption of extracellular vesicles onto supported lipid bilayers.
Communication between cells located in different parts of an organism is often mediated by membrane-enveloped nanoparticles, such as extracellular vesicles (EVs). EV binding and cell uptake mechanisms depend on the heterogeneous composition of the EV membrane. From a colloidal perspective, the EV membrane interacts with other biological interfaces via both specific and non-specific interactions, where the latter include long-ranged electrostatic and van der Waals forces, and short-ranged repulsive "steric-hydration" forces. While electrostatic forces are generally exploited in most EV immobilization protocols, the roles played by various colloidal forces in controlling EV adsorption on surfaces have not yet been thoroughly addressed. In the present work, we study the adsorption of EVs onto supported lipid bilayers (SLBs) carrying different surface charge densities using a combination of quartz crystal microbalance with dissipation monitoring (QCM-D) and confocal laser scanning microscopy (CLSM). We demonstrate that EV adsorption onto lipid membranes can be controlled by varying the strength of electrostatic forces and we theoretically describe the observed phenomena within the framework of nonlinear Poisson-Boltzmann theory. Our modelling results confirm the experimental observations and highlight the crucial role played by attractive electrostatics in EV adsorption onto lipid membranes. They furthermore show that simplified theories developed for model lipid systems can be successfully applied to the study of their biological analogues and provide new fundamental insights into EV-membrane interactions with potential use in developing novel EV separation and immobilization strategies.


Preliminary Analysis of an Advanced Health Care Practitioner-Led Home-Visit Primary Care Program for High-Risk Patients Reduced Health Care Costs and Utilization.
Background: MemorialCare Medical Group (MCMG) designed and implemented an advanced health care practitioner (AHP)-led home-visit primary care program to address the needs of a frail older adult population, who struggled with arriving for in-office care. We sought to perform a preliminary analysis to determine the program's efficacy. Methods: We conducted a retrospective review of patients enrolled in the program through tabulation of total costs of care, inpatient visits (IPVs), emergency department visits (EDVs), and 30-day readmissions (30DRs) 1-year pre-enrollment and postenrollment. Results: For the prior year and postyear windows, per-member per-month total cost of care decreased 21.4% ($5,883.44-$4,622.31), reflecting a gross savings of $2,693,480.32. Mean IPVs (2.42-1.56), EDVs (1.53-0.93), and 30DRs (0.27-0.13) were reduced. Conclusions: Initial analysis of an AHP-led in-home primary care program for frail seniors shows promise for improved outcomes with a clear decrease in the total cost of care.


Three-dimensional patterning in biomedicine: Importance and applications in neuropharmacology.
Nature manufactures biological systems in three dimensions with precisely controlled spatiotemporal profiles on hierarchical length and time scales. In this article, we review 3D patterning of biological systems on synthetic platforms for neuropharmacological applications. We briefly describe 3D versus 2D chemical and topographical patterning methods and their limitations. Subsequently, an overview of introducing a third dimension in neuropharmacological research with delineation of chemical and topographical roles is presented. Finally, toward the end of this article, an explanation of how 3D patterning has played a pivotal role in relevant fields of neuropharmacology to understand neurophysiology during development, normal health, and disease conditions is described. The future prospects of organs-on-a--like devices to mimic patterned blood-brain barrier in the context of neurotherapeutic discovery and development for the prioritization of lead candidates, membrane potential, and toxicity testing are also described. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1369-1382, 2018.


Hyperhomocysteinemia in end stage renal disease: is treatment necessary?
Hyperhomocysteinemia occurs in 85% of patients with end stage renal disease (ESRD) and may contribute to their increased risk of cardiovascular disease (CVD). This population experiences excess morbidity and mortality due to CVD, presenting a unique challenge in terms of preventative medicine. The treatment of hyperhomocysteinemia in the renal population has been a topic recently considered in published studies. It is thought, but not yet supported by evidence, that lowering homocysteine (Hcy) levels in ESRD patients will decrease the incidence of CVD. Nephrology nurses need to be aware of the pathophysiology, treatment, and current research regarding hyperhomocysteinemia in patients with ESRD and integrate this knowledge into clinical practice.


Investigation of AGE, their receptor and NF-kappaB activation and apoptosis in patients with ATTR and Gelsolin amyloidosis.
Transthyretin (TTR) and gelsolin amyloidoses represent two types of hereditary amyloidosis in which point mutations in the respective protein lead to conformational changes of the protein with subsequent amyloid fibril formation. Tissues from Finnish gelsolin amyloid patients, Danish, Japanese and Swedish ATTR patients were immunostained for AGE, RAGE, NF-kappaB, PARP, and caspases 3 and 8. Amyloid was heavily deposited in myocard, kidney and gastrointestinal tract of all patients. Immunoreactive areas to AGE and RAGE were detected in the heart, kidney, rectum, gut and appendix. AGE and RAGE were well co-localised with amyloid deposits. In five out of 14 patients neither NF-kappaB activation nor induction of apoptosis marked by positive immunostaining for NF-kappaB, PARP, or caspases 3 and 8 was found, and markers of apoptosis were detected in some samples without accompanying NF-kappaB activation. Our results suggest that both AGE and RAGE may have a common role in evolution of TTR and gelsolin-related amyloidoses. Apart from AGE-RAGE interactions both amyloid proteins may directly bind to RAGE and result in cellular perturbations; but in view of this study cytotoxic effects other than those triggered by activation of NF-kappaB or apoptosis should be considered.


Postprandial glycaemic response of foxtail millet dosa in comparison to a rice dosa in patients with type 2 diabetes.
Millets are rich source of dietary fibre and non-starchy polysaccharides with low glycaemic index (GI), hence can be used as a therapeutic diet. This study was conducted to estimate the effects of a millet-based dosa (foxtail dosa) compared to a rice dosa for breakfast on postprandial glucose levels in patients with type 2 diabetes mellitus (T2DM). The GI of rice dosa and foxtail millet dosa was estimated. A total of 105 T2DM participants were randomly selected for the study. The participants were on oral hypoglycaemic agents (OHA) and not on insulin. In this study, each individual served as their own control and experimental group. The postprandial increase in blood glucose was compared after a breakfast of rice dosa and millet dosa. Single and paired t test was used to note the change in blood glucose levels and the level of the significance. The GI of foxtail millet dosa was 59.25 and rice dosa was 77.96. There was a significant reduction (P<0.001) in the postprandial glucose level of patients who consumed a millet-based dosa when compared to those who consumed a rice-based dosa. No significant reduction was observed in the fasting glucose levels. The results suggested that replacing a rice-based breakfast item with a millet-based breakfast item lowers the postprandial blood glucose levels in T2DM patients. Thus, millets may have a protective role in the management of hyperglycaemia. Further studies need to be done in a systematic manner to confirm these findings.


Regulation of endothelial cell motility by complexes of tetraspan molecules CD81/TAPA-1 and CD151/PETA-3 with alpha3 beta1 integrin localized at endothelial lateral junctions.
Cell-to-cell junction structures play a key role in cell growth rate control and cell polarization. In endothelial cells (EC), these structures are also involved in regulation of vascular permeability and leukocyte extravasation. To identify novel components in EC intercellular junctions, mAbs against these cells were produced and selected using a morphological screening by immunofluorescence microscopy. Two novel mAbs, LIA1/1 and VJ1/16, specifically recognized a 25-kD protein that was selectively localized at cell-cell junctions of EC, both in the primary formation of cell monolayers and when EC reorganized in the process of wound healing. This antigen corresponded to the recently cloned platelet-endothelial tetraspan antigen CD151/PETA-3 (platelet-endothelial tetraspan antigen-3), and was consistently detected at EC cell-cell contact sites. In addition to CD151/PETA-3, two other members of the tetraspan superfamily, CD9 and CD81/ TAPA-1 (target of antiproliferative antibody-1), localized at endothelial cell-to-cell junctions. Biochemical analysis demonstrated molecular associations among tetraspan molecules themselves and those of CD151/ PETA-3 and CD9 with alpha3 beta1 integrin. Interestingly, mAbs directed to both CD151/PETA-3 and CD81/ TAPA-1 as well as mAb specific for alpha3 integrin, were able to inhibit the migration of ECs in the process of wound healing. The engagement of CD151/PETA-3 and CD81/TAPA-1 inhibited the movement of individual ECs, as determined by quantitative time-lapse video microscopy studies. Furthermore, mAbs against the CD151/PETA-3 molecule diminished the rate of EC invasion into collagen gels. In addition, these mAbs were able to increase the adhesion of EC to extracellular matrix proteins. Together these results indicate that CD81/TAPA-1 and CD151/PETA-3 tetraspan molecules are components of the endothelial lateral junctions implicated in the regulation of cell motility, either directly or by modulation of the function of the associated integrin heterodimers.


Positive Disintegration as a Process of Symmetry Breaking.
This article presents an analysis of the positive disintegration as a process of symmetry breaking. Symmetry breaking plays a major role in self-organized patterns formation and correlates directly to increasing complexity and function specialization. According to Dabrowski, a creator of the Theory of Positive Disintegration, the change from lower to higher levels of human development requires a major restructuring of an individual's psychological makeup. Each level of human development is a relatively stable and coherent configuration of emotional-cognitive patterns called developmental dynamisms. Their main function is to restructure a mental structure by breaking the symmetry of a low level and bringing differentiation and then integration to higher levels. The positive disintegration is then the process of transitions from a lower level of high symmetry and low complexity to higher levels of low symmetry and high complexity of mental structure.


Biomarkers probed in saliva by surface plasmon resonance imaging coupled to matrix-assisted laser desorption/ionization mass spectrometry in array format.
Detection of protein biomarkers is of major interest in proteomics. This work reports the analysis of protein biomarkers directly from a biological fluid, human saliva, by surface plasmon resonance imaging coupled to mass spectrometry (SPRi-MS), using a functionalized biochip in an array format enabling multiplex SPR-MS analysis. The SPR biochip presented a gold surface functionalized by a self-assembled monolayer of short poly(ethylene oxide) chains carrying an N-hydroxysuccinimide end-group for the immobilization of antibodies. The experiments were accomplished without any sample pre-purification or spiking with the targeted biomarkers. SPRi monitoring of the interactions, immune capture from the biochip surface, and finally on-chip matrix-assisted laser desorption/ionization-MS structural identification of two protein biomarkers, salivary α-amylase and lysozyme, were successively achieved directly from saliva at the femtomole level. For lysozyme, the on-chip MS identification was completed by a proteomic analysis based on an on-chip proteolysis procedure and a peptide mass fingerprint.


A unified density matrix functional construction of quantum baths in density matrix embedding theory beyond the mean-field approximation.
The equivalence in one-electron quantum baths between the practical implementation of density matrix embedding theory (DMET) and the more recent Householder-transformed density matrix functional embedding theory has been shown previously in the standard but special case where the reference full-size (one-electron reduced) density matrix, from which the bath is constructed, is idempotent [S. Yalouz et al., J. Chem. Phys. 157, 214112 (2022)]. We prove mathematically that the equivalence remains valid when the density matrix is not idempotent anymore, thus allowing for the construction of correlated (one-electron) quantum baths. A density-matrix functional exactification of DMET is derived within the present unified quantum embedding formalism. Numerical examples reveal that the embedding cluster can be quite sensitive to the level of density-matrix functional approximation used for computing the reference density matrix.


Characteristics of residents living in residential care communities, by community bed size: United States, 2012.
In 2012, there was a higher percentage of older, female residents in communities with more than 25 beds compared with communities with 4–25 beds. Residents in communities with 4–25 beds were more racially diverse than residents in larger communities. The percentage of Medicaid beneficiaries was higher in communities with 4–25 beds than it was in communities with 26–50 and more than 50 beds. A higher percentage of residents living in communities with 4–25 beds had a diagnosis of Alzheimer's disease or other dementias compared with residents in larger communities. Need for assistance with each of the activities of daily living (ADLs) examined (except walking or locomotion) was substantially higher among residents in communities with 4–25 beds, compared with residents in larger communities. Emergency department visits and discharges from an overnight hospital stay in a 90-day period did not vary across residents by community bed size. This report presents national estimates of residents living in residential care, using data from the first wave of NSLTCP. This brief profile of residential care residents provides useful information to policymakers, providers, researchers, and consumer advocates as they plan to meet the needs of an aging population. The findings also highlight the diversity of residents across the different sizes of residential care communities. Corresponding state estimates and their standard errors for the national figures in this data brief can be found on the NSLTCP website, available from: http://www.cdc.gov/nchs/nsltcp/nsltcp_products.htm. These national and state estimates establish a baseline for monitoring trends among residents living in residential care.


NOX4-derived ROS Regulates Aerobic Glycolysis of Breast Cancer through YAP Pathway.
Background: NOX4 is highly expressed in breast cancer and is closely associated with cell invasion and metastasis. The involvement of NOX4 in glycolysis in breast cancer remains unclear. The aim of this study was to investigate the role and mechanism of NOX4 in glycolysis in breast cancer. Methods: NOX4 expression in breast cancer cells was detected by qRT-PCR and western blotting. siRNAs and plasmids were used to silence or enhance the expression of NOX4. The mRNA and protein expression of HK2, GLUT1, PKM2, LDHA, and YAP was detected by qRT-PCR and western blotting, and the 18F-FDG uptake rate was detected by γ-radiometer. Detection of reactive oxygen species (ROS) in cells was performed using a commercial ROS kit. After transfection, CCK8, EDU and Transwell experiments were conducted to detect cell proliferation and migration ability. MicroPET imaging was used to detect the effects of NOX4 on tumor metabolism. Immunohistochemistry was used to detect the expression of NOX4, glycolytic enzymes HK2, GLUT1, PKM2, LDHA, the proliferation index KI67, and the activation of YAP pathway molecule. Results: In this study, the expression of NOX4 in MDA-MB-231 and MDA-MB-453 was higher than in MCF10A. qRT-PCR and western blotting experiments showed that NOX4 downregulation decreased the expression of glycolytic enzymes HK2, GLUT1, PKM2, LDHA, and 18F-FDG uptake. Conversely, the overexpression of NOX4 enhanced the expression of HK2, GLUT1, PKM2, LDHA, and 18F-FDG uptake. Proliferation and migration experiments showed that after down-regulation of NOX4, cell proliferation and migration ability decreased, while NOX4 overexpression promoted cell proliferation and migration ability. Additionally, ROS content and YAP expression decreased after NOX4 down-regulation, while ROS content and YAP expression increased following NOX4 overexpression, which was reversed by N-acetyl cysteine (NAC), a ROS inhibitor. Furthermore, exposure to NAC and Peptide17, a YAP inhibitor, blocked the increase in glycolytic enzyme expression, and the enhancement of proliferation and migration caused by NOX4 overexpression. In addition, in animal experiments, the results of the MicroPET imaging showed that the glucose metabolism rate of the NOX4 inhibitor group was significantly lower than that of the control group. ROS levels in the NOX4 inhibitor group was lower than that in the control group. Immunohistochemistry showed that the expression of HK2, GLUT1, PKM2, LDHA, KI67, and YAP in the NOX4 knock-down group were decreased. Conclusions: NOX4 affects breast cancer glycolysis through ROS-induced activation of the YAP pathway, further promoting the proliferation and migration of breast cancer cells.


Case report: relief of acute obstruction of the Detour subcutaneous pyelovesical bypass.
A 36-year-old patient was admitted to the emergency department with complaints of severe flank pain, nausea, vomiting, anuria, and general illness. Five months earlier, we had placed a subcutaneous pyelovesical prosthesis (Detour; Porges) of the ureter for treatment of a chronically dilated upper urinary tract in a solitary right kidney previously treated by double-J stenting. Ultrasonography of the right kidney revealed severe hydronephrosis. A percutaneous nephrostomy catheter was placed, and antegrade pyelography showed complete obstruction of the prosthesis. Urinalysis and culture demonstrated a Candida infection. A systemic antimycotic was administered, and fluid management was started. On the third day, diuresis appeared, and antegrade nephrostomography confirmed patency of the bypass.


Survey of organotin compounds in blended wines.
An extraction method for butyltin, cyclohexyltin, octyltin and phenyltin compounds in wines was developed using 0.05% tropolone in 75% diethyl ether/pentane. Recoveries averaged 96.8% (range 78-121%). Methyl derivatives made by Grignard reaction were quantitated by gas chromatography (GC)-atomic absorption spectrometry (AAS). Twenty-nine of the 90 samples (32.2%) tested contained at least one of the analytes. Mono- and diocyltin were found in one sample only, at levels of 2.41 and 0.12 ng/ml respectively. Dibutyltin levels ranged from < 0.08 to 1.44 ng/ml. Monobutyl and tributyltin were found less frequently and at lower levels than dibutyltin. GC/mass spectrometric analysis confirmed the presence of butyl- and octyltins. No other organotin compounds were detected by either GC-AAS or GC-MS.


Unique Challenges of Type 1 Diabetes in the Preschool Population.
Extremely young children aged ≤6 years old represent a unique population among patients with type 1 diabetes in terms of glycemic variation, diabetes management and complications. We describe distinct features of diabetes care and outcomes in preschool age children. We searched PubMed, Google Scholar, and authors' bibliographies in order to extract articles specific to type 1 diabetes in preschool age children. The preschool age group is beset by many challenges to diabetes care, including more frequent hypo- and hyperglycemia, hypoglycemia unawareness, decreased residual beta cell function, and greater long-term neurocognitive effects from severe hypoglycemia and chronic hyperglycemia. Randomized controlled trials show that equally good metabolic control can be obtained with multiple daily injections or an insulin pump. Several non-randomized trials, including an 8 year longitudinal study, show lower hemoglobin A1C and decreased hypoglycemia on insulin pumps. Sensor augmented pump therapy resulted in superior A1C as long as sensors were used regularly. In contrast to adults, continuous glucose monitoring has little to no impact on A1C, although parents appreciate the improved monitoring for hypoglycemia. Children with onset of diabetes prior to age 5 are at risk for younger onset of microalbuminuria, however do not develop earlier onset retinopathy than children diagnosed after 5 years. Both severe hypoglycemia and chronic hyperglycemia have negative impact on neurocognition. Special knowledge about this young population is helpful for practitioners and parents.


Picornavirus Identified in Alzheimer's Disease Brains: A Pathogenic Path?
We investigated formalin-fixed postmortem brain tissue from the hippocampus region of 18 AD cases and 11 age-matched controls using a polyclonal antibody against Ljungan virus (LV) capsid protein 1. Evidence of a LV antigen was found in all AD cases but in none of the control specimens (p < 0.0001). The antibodies reacted with neurons and astrocytes and also showed distinct positive reaction in the amyloid/neuritic plaques. The possible role of an incompletely characterized picornavirus as the etiologic agent in AD open up the possibility of treatment with antiviral therapy directed against picornaviruses. The positive result of such treatment in a small number of patients is presented separately back to back to this report.


Preclinical cardiovascular changes in children with obesity: A real-time 3-dimensional speckle tracking imaging study.
The aims of this study were (1) to quantify changes in 3-dimensional (3D) strain in obese children using real-time 3D echocardiography (RT3DE) and 3D speckle tracking echocardiography (3DSTE), and (2) to investigate the utility of left ventricular (LV) strain variables in measuring early cardiovascular changes in children with obesity. A total of 181 obese children (study group) aged 4-18 years old were prospectively enrolled and compared with 229 healthy subjects (control group). We acquired demographic, clinical, biochemical, and 2D echocardiography/Doppler data. Also, RT3DE and 3DSTE were performed to measure LV volume, left ventricular ejection fraction (LVEF), LV mass (LVM), LV peak systolic global longitudinal strain (GLS), radial strain (GRS), circumferential strain (GCS), and global strain (GS). There were significant differences in anthropometric measurements, blood pressures, Cholesterol, C-reactive protein (CRP), Intima-media thickness (IMT), left atrium end-systolic dimension (LASD), interventricular septal end-diastolic dimension (IVSD), LV posterior wall end-diastolic dimension (LVPWD), LV end-diastolic dimension (LVEDD), LV end-systolic dimension (LVESD), LV end-diastolic volumes (LVEDV), and LV end-systolic volumes (LVESV), E and A velocities, E/A,e', e'/a', E/e', LVM, LV mass index (LVMI), GLS, GRS, GCS, and GS between the study and control groups. The receiver operating characteristic curves (ROC) for the statistically significant echocardiographic variables showed that the range of areas of ROC curves varied from 0.76 (GLS), 0.74 (GRS), 0.72 (LASD), to 0.58 (LVESD), respectively. In conclusion, LV 3D strain variables by RT3DE and 3DSTE decrease in obese children. LV 3D strain is more sensitive than other echocardiographic and vascular ultrasound variables in detecting cardiovascular changes in children with obesity.


Comparison of Outcomes: Nurse-Driven vs. Physician-Driven Weight-Based Intravenous Heparin Protocol.
The transition from a physician-driven heparin protocol to a nurse- driven heparin protocol at one institution resulted in shorter times to therapeutic activated partial thromboplastin time (aPTT), increased time within goal aPTT range, and an increased percent- age of patients who ultimately achieved a therapeutic aPTT.


Beyond scoops to best practices.
Authors submitting a manuscript to eLife are encouraged to upload it to a recognized preprint server at the same time in order to make their results available as quickly and as widely as possible.


Naked (C5Me5)2M cations (M = Sc, Ti, and V) and their fluoroarene complexes.
The ionic metallocene complexes [Cp*(2)M][BPh(4)] (Cp* = C(5)Me(5)) of the trivalent 3d metals Sc, Ti, and V were synthesized and structurally characterized. For M = Sc, the anion interacts weakly with the metal center through one of the phenyl groups, but for M = Ti and V, the cations are naked. They each contain one strongly distorted Cp* ligand, with one (V) or two (Ti) agostic C-H...M interactions involving the Cp*Me groups. For Sc and Ti, these Lewis acidic species react with fluorobenzene and 1,2-difluorobenzene to yield [Cp*(2)M(kappaF-FC(6)H(5))(n)][BPh(4)] (M = Sc, n = 2; M = Ti, n = 1) and [Cp*(2)M(kappa(2)F-1,2-F(2)C(6)H(4))][BPh(4)], the first examples of kappaF-fluorobenzene and kappa(2)F-1,2-difluorobenzene adducts of transition metals. With the perfluorinated anion [B(C(6)F(5))(4)](-), both Sc and Ti form [Cp*(2)M(kappa(2)F-C(6)F(5))B(C(6)F(5))(3)] contact ion pairs. The nature of the metal-fluoroarene interaction was studied by density functional theory (DFT) calculations and by comparison with the corresponding tetrahydrofuran (THF) adducts and was found to be predominantly electrostatic for all metals studied.


Overcoming Tumor Hypoxia through Multiple Pathways Using an All-in-One Polymeric Therapeutic Agent to Enhance Synergistic Cancer Photo/Chemotherapy Effects.
Hypoxia is a significant characteristic of tumors, which causes aggressive tumor growth and strong therapy resistance. Inspired by the improved therapeutic efficacy of synergistic treatment, herein, an all-in-one polymeric therapeutic agent was developed, which could overcome tumor hypoxia through multiple pathways. Multiple therapeutic agents were incorporated into the polymer, including the singlet oxygen (1O2) carrier unit to store cytotoxic reactive oxygen species, the photosensitized and photothermal unit to trigger the capture and release of 1O2, and the hypoxia-responsive prodrug unit to maintain a long-term tumor inhibition. In addition, the hydrophilic polyethylene glycol unit was also introduced to improve water-solubility and biocompatibility. Importantly, this study achieved the capture and controllable release of 1O2 just by regulating the power of an 808 nm laser for the first time, which is more convenient and flexible than previous works. As expected, the as-prepared copolymer displayed reduced oxygen dependence, accompanied with promising synergistic anti-tumor and anti-recurrence efficacies under hypoxic in vitro and in vivo environments. Consequently, this synergistic anti-hypoxia strategy may open up new avenues in the design of all-in-one therapeutic platforms for promoting the development of accurate, efficient, and long-acting treatment in clinical studies.


Pelvic actinomycosis following insertion of an intrauterine contraceptive device.
A case of actinomycosis following insertion of an intrauterine contraceptive device is reported. The patient was treated successfully by antibiotic therapy and conservative surgery.


[Analysis of clinical phenotype and ACAT1 gene mutation in a family affected with beta-ketothiolase deficiency].
To investigate the clinical phenotype and ACAT1 gene mutation in a family affected with beta-ketothiolase deficiency (BKTD). Clinical features and laboratory test data were collected. The probands were monozygotic twin brothers. Genomic DNA was isolated from peripheral blood leukocytes obtained from the probands and their family members. Molecular genetic testing of the ACAT1 gene was carried out. The probands have presented with fever, vomiting and severe ketoacidosis. By arterial blood gas testing, pH was determined to be 7.164, bicarbonate was 4.0 mmol/L, and urine ketone was ++++. Urinary organic acid gas chromatography-mass spectrometry analysis showed excessive excretion of 3-hydroxybutyric acid, 2-methyl-3-hydroxybutyric acid and tiglylglycine. Increased 3-hydroxybutyrylcarnitine (C4-OH), tiglylcarnitine(C5:1) and 3-hydroxyisovalerylcarnitine (C5-OH) levels. The clinical phenotype of proband's parents were both normal, but an elder sister turned out to be an affected patient. Genetic analysis has identified two heterozygous mutations [c.622C>T(p.R208X) and c.653C>T (p.S218F)] in the proband, which were respectively detected in the mother and father. The c.653C>T (p.S218F) mutation was not found among the 100 healthy controls and has not been included in the Human Gene Mutation Database(HGMD). The primary clinical manifestations of BKTD is ketoacidosis. Urine organic acid and blood acylcarnitine analyses play an important role in the diagnosis of the disease. The compound heterozygous of ACAT1 gene mutations probably underlie the BKTD in our patient.


Experience sampling methods for the personalised prediction of mental health problems in Spanish university students: protocol for a survey-based observational study within the PROMES-U project.
There is a high prevalence of mental health problems among university students. Better prediction and treatment access for this population is needed. In recent years, short-term dynamic factors, which can be assessed using experience sampling methods (ESM), have presented promising results for predicting mental health problems. Undergraduate students from five public universities in Spain are recruited to participate in two web-based surveys (at baseline and at 12-month follow-up). A subgroup of baseline participants is recruited through quota sampling to participate in a 15-day ESM study. The baseline survey collects information regarding distal risk factors, while the ESM study collects short-term dynamic factors such as affect, company or environment. Risk factors will be identified at an individual and population level using logistic regressions and population attributable risk proportions, respectively. Machine learning techniques will be used to develop predictive models for mental health problems. Dynamic structural equation modelling and multilevel mixed-effects models will be considered to develop a series of explanatory models for the occurrence of mental health problems. The project complies with national and international regulations, including the Declaration of Helsinki and the Code of Ethics, and has been approved by the IRB Parc de Salut Mar (2020/9198/I) and corresponding IRBs of all participating universities. All respondents are given information regarding access mental health services within their university and region. Individuals with positive responses on suicide items receive a specific alert with indications for consulting with a health professional. Participants are asked to provide informed consent separately for the web-based surveys and for the ESM study. Dissemination of results will include peer-reviewed scientific articles and participation in scientific congresses, reports with recommendations for universities' mental health policy makers, as well as a well-balanced communication strategy to the general public. osf.io/p7csq.


Protosappanin A protects against atherosclerosis via anti- hyperlipidemia, anti-inflammation and NF-κB signaling pathway in hyperlipidemic rabbits.
Protosappanin A (PrA) is an effective and major ingredient of Caesalpinia sappan L. The current study was aimed to explore the effect of PrA on atherosclerosis (AS). Firstly, the experimental model of AS was established in rabbits by two-month feeding of high fat diet. Then, the rabbits were randomly divided into five groups and treated with continuous high lipid diet (model control), high lipid diet containing rosuvastatin (positive control), 5 mg/kg PrA (low dose) or 25 mg/kg PrA (high dose). Our results showed that PrA markedly alleviated AS as indicated by hematoxylin/eosin (HE) staining. PrA also reduced hyperlipidemia (as demonstrated by the serum levels of total blood cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) and high-density lipoprotein (HDL)) in a time and dose-dependent manner, and decreased inflammation (as indicated by the serum levels of matrix metalloproteinase-9 [MMP-9], interleukin-6 [IL-6] and tumor necrosis factor-α [TNF-α]). Moreover, PrA significantly inactivated nuclear factor kappa B (NF-κB) signaling as indicated by nuclear NF-κB p65 protein expression, as well as the mRNA expression and serum levels of downstream genes, interferon-γ (IFN-γ) and interferon-gamma-inducible protein 10 (IP10). This study proved that PrA might protect against atherosclerosis via anti-hyperlipidemia, anti-inflammation and NF-κB signaling pathways in hyperlipidemic rabbits.


Aetiological Evaluation of Oligodontia in a Three-Generation Family.
The aim of this study was to assess the genetic evaluation of a three-generation consanguineous family with isolated oligodontia. A 16-year-old male patient who had been referred for orthodontic treatment due to the presence of oligodontia, and his family members who presented several missing teeth had been enrolled in the study. Clinical and radiological assessments and genetic analysis including whole-exome sequencing were performed. Genetic evaluations revealed both homozygous and heterozygous mutations (c.T682A:p.F228I) in the WNT10A gene of six affected members of the family. Higher frequency of agenesis of mandibular second molar was found in homozygous relative to heterozygous WNT10A mutations. The present findings have provided evidence for a known variant in the WNT10A gene in a three-generation consanguineous family with isolated oligodontia, while the results confirmed that cases with homozygous mutation revealed clinical heterogeneity.


Increased Background Activity in DMSA Scintigraphy of a Nonazotemic Patient With β-Thalassemia Major.
Renal DMSA uptake provides an index for evaluation of the functional tubular mass, which depends on the renal blood flow, proximal tubular cell membrane function, and urinary acid-base balance. We present a case of a nonazotemic 48-year-old adult with β-thalassemia major under regular blood transfusions and iron chelation therapy that underwent DMSA scan showing minor cortical abnormalities and high background activity, featuring prominent cardiac blood pool and liver uptake. This case highlights the pitfall of high background activity during DMSA study in patients with β-thalassemia major due to tubular disorders.


Coevolution-based prediction of protein-protein interactions in polyketide biosynthetic assembly lines.
Polyketide synthases (PKSs) are enzymes that generate diverse molecules of great pharmaceutical importance, including a range of clinically used antimicrobials and antitumor agents. Many polyketides are synthesized by cis-AT modular PKSs, which are organized in assembly lines, in which multiple enzymes line up in a specific order. This order is defined by specific protein-protein interactions (PPIs). The unique modular structure and catalyzing mechanism of these assembly lines makes their products predictable and also spurred combinatorial biosynthesis studies to produce novel polyketides using synthetic biology. However, predicting the interactions of PKSs, and thereby inferring the order of their assembly line, is still challenging, especially for cases in which this order is not reflected by the ordering of the PKS-encoding genes in the genome. Here, we introduce PKSpop, which uses a coevolution-based PPI algorithm to infer protein order in PKS assembly lines. Our method accurately predicts protein orders (93% accuracy). Additionally, we identify new residue pairs that are key in determining interaction specificity, and show that coevolution of N- and C-terminal docking domains of PKSs is significantly more predictive for PPIs than coevolution between ketosynthase and acyl carrier protein domains. The code is available on http://www.bif.wur.nl/ (under 'Software'). Supplementary data are available at Bioinformatics online.


Few layer graphene matrix for matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.
We present the employment of few layer graphene (FLG) as a matrix for the analysis of low molecular weight polymeric compounds using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The practicality of FLG as a matrix for MALDI experiments is demonstrated by analyzing low molecular weight polymers, polar polyethylene glycol (PEG) of 1000 Da and nonpolar polymethylmethacrylate (PMMA) of 650 Da. The high quality MS spectra without low-mass interference signals without any further sampling procedure were acquired.


Wnt antagonist DKK-1 levels in systemic sclerosis are lower in skin but not in blood and are regulated by microRNA33a-3p.
Systemic sclerosis is an autoimmune skin disease which is associated with inflammation and resulting skin fibrosis. Myofibroblasts are the key cell type associated with the fibrosis but how they are differentiated is not clear. DKK-1 is a Wnt antagonist that blocks Wnt-mediated fibrosis and is reduced in fibrotic conditions. Thus, DKK-1 is a clear negative regulator of fibrosis in systemic sclerosis and its regulation is unknown. The aim of this work is to determine the levels of DKK-1 in serum and tissues of SSc and its regulation. Skin biopsies were taken from early diffuse systemic sclerosis patients and healthy controls and DKK-1 measured by ELISA; serum was also isolated and DKK-1 quantified. DKK-1 was also measured by qRT-PCR. MicroRNA33a-3p was measured by TaqMan PCR. miR mimics and controls were transfected into dermal fibroblasts. Bleomycin mouse model was employed and compared to vehicle control treated mice, and gene expression was employed for DKK-1 and various extracellular matrix genes. DKK-1 is reduced in SSc skin and fibroblasts but is not reduced in the circulation in patients. MicroRNA33a-3p regulates DKK-1 levels epigenetically and is significantly reduced in SSc cells and whole tissue. DKK-1 is also reduced in the bleomycin mouse model and pro-fibrotic genes elevated. DKK-1 is reduced in SSc cells and is regulated by miR33a-3p, and restoring DKK-1 levels through epigenetic means could be a therapeutic target in systemic sclerosis.


Racemization of aspartic acid in human proteins.
Aspartic acid racemization (AAR) represents one of the major types of non-enzymatic covalent modification that leads to an age-dependent accumulation of abnormal protein in numerous human tissues. In vivo racemization is an autonomic process during the "natural" ageing of proteins, and correlates with the age of long-lived proteins. Consequently AAR can be used as molecular indicator of protein ageing as well as for the identification of permanent proteins that age with the human organism. Although long-living, structural proteins are mainly affected, AAR may be significant on a time scale also relevant to enzymes and signaling proteins. It may result in a loss of protein function due to proteolysis or due to changes in the molecular structure. In vivo racemization may also increase in pathological conditions. AAR has already been discussed as a relevant pathophysiological factor in the pathogenesis of diseases of old age such as atherosclerosis, lung emphysema, presbyopia, cataract, degenerative diseases of cartilage and cerebral age-related dysfunctions. Although the details of the biological consequences of AAR have to be further elucidated, it is evident that AAR plays a role in the molecular biology of ageing.


High Performance Quasi-2D Perovskite Sky-Blue Light-Emitting Diodes Using a Dual-Ligand Strategy.
For quasi-2D perovskite light-emitting diodes, the introduction of insulating bulky cation reduces the charge transport property, leading to lowered brightness and increased turn-on voltage. Herein, a dual-ligand strategy is adopted to prepare perovskite films by using an appropriate ratio of i-butylammonium (iBA) and phenylethylammonium (PEA) as capping ligands. The introduction of iBA enhances the binding energy of the ligands on the surface of the quasi-2D perovskite, and effectively controls the proportion of 2D perovskite to allow more efficient energy transfer, resulting in the great enhancement of the electric and luminescent properties of the perovskite. The photoluminescence (PL) mapping of the perovskite films exhibits that enhanced photoluminescence performance with better uniformity and stronger intensity can be achieved with this dual-ligand strategy. By adjusting the proportion of the two ligands, sky-blue perovskite light-emitting diodes (PeLEDs) with electroluminescence (EL) peak located 485 nm are achieved with a maximum luminance up to 1130 cd m-2 and a maximum external quantum efficiency (EQE) up to 7.84%. In addition, the color stability and device stability are significantly enhanced by using a dual-ligand strategy. This simple and feasible method paves the way for improving the performance of quasi-2D PeLEDs.


Post-mortem serum concentrations of GFAP correlate with agony time but do not indicate a primary cerebral cause of death.
The astroglial protein GFAP is a blood biomarker indicative of intracerebral hemorrhage in patients with acute stroke. Due to its brain specificity and the necessity of brain damage for its detectability in blood, we hypothesized that GFAP could be an interesting marker in cases with primary cerebral cause of death, e.g., traumatic brain injury. All corpses scheduled for an autopsy in the Frankfurt Department of Forensic medicine within a 15-month period were included in the study. Cases with a known history of brain disease in the 3 months before death were excluded. During autopsy, blood was collected and GFAP serum levels were determined using a commercially available ELISA. The autopsy protocols were reviewed for the presence of a primary cerebral or a primary non-cerebral cause of death. Agony time was also determined. A total of 129 autopsy cases were included. GFAP concentrations did not differ between cerebral (median 0.96 μg/l, IQR 5.03) and non-cerebral causes of death (1.21 μg/l, 3.58). GFAP levels were found to be unaffected by hemolysis or post-mortem interval. GFAP levels were found to be increased in cases with prolonged agony times (median 1.76 μg/l [IQR 4.70]) compared to short (0.58 μg/l [0.58]; p<0.001) and ultra-short agony times (0.21 μg/l [0.12]; p = 0.002). Post-mortem GFAP serum concentrations correlate with agony time and might therefore be useful for the evaluation of the severity of brain damage in prolonged death. Elevated GFAP serum levels do not indicate a primary cerebral cause of death.


Toxicity of pokeberries (fruit of Phytolacca americana large) for turkey poults.
Fresh pokeberries were picked from the cluster and liquified in a blender for 3 to 5 minutes. The liquified berries were mixed into a standard turkey starter at the rate of 0, 2-1/2, 5 and 10%. Addition was at the expense of the total diet. Two separate experiments were conducted with day old Broad White turkeys. Weight gain, mortality and gross lesions were observed to 3 weeks of age. Growth rate was reduced with each increase in level of pokeberries. In Experiment 1, 3-week gains were 376, 354, 314 and 205 g. for 0, 2-1/2, 5 and 10% pokeberries. Weight gains in Experiment 2 were 339, 317, 254 and 172. Mortality was 33 and 43% in the two experiments when 10% pokeberries were fed. Lower levels produced erratic mortality results. Poults fed 5 and 10% pokeberries exhibited ataxia and occasional inability to walk. The hock joints frequently became enlarged and crooked. Ascites was observed in some birds at all dietary levels of added pokeberries. The gall bladder of dead birds was frequently much enlarged and filled with brownish fluid rather than normal bile.


A rapid cytofluorometric method for quantitative DNA determination on fixed smears.
A study has been made of the possibility of using propidium iodide (PI) for the cytofluorometric determination of DNA in fixed smears. A preliminary spectrofluorometric study made it possible to define the optimal conditions for the excitation wavelength and the intensity of the emitted fluorescence. The stoichiometry and specificity of the DNA-PI bond were studied in different materials and for different fixation procedures. In order to check whether RNA might interfere, it was extracted enzymatically from test preparations selectively. The data from such treated sections were not significantly different from those obtained by means of the fluorescent Feulgen reaction (Pararosaniline-SO2) on the same material. On the other hand, some of the advantages of the PI method are important: (a) the time required for making ready and staining the preparations is very short, and in any case is considerably shorter than the Feulgen method; (b) the high quantum yield of the DNA-PI complex induces very high fluorescence intensities, which can, therefore, be easily measured, even with low sensitivity instruments; (c) the spectral conditions are particularly favourable for excluding the inner filter effect from the measurement; (d) the photo-decomposition is considerably lower compared to that found in preparations stained by the conventional Feulgen method. The wide possibility of excitation (from the u.v. to the green), together with the limited extent of the emission band (which is mainly in the red) are also conditions that are particularly favourable for obtaining multi-parametric determinations simultaneously from the same cell.


Mannose 2, 3, 4, 5, 6-O-pentasulfate (MPS): a partial activator of human heparin cofactor II with anticoagulation potential.
Thromboembolic diseases are a major cause of mortality in human and the currently available anticoagulants are associated with various drawbacks, therefore the search for anticoagulants that have better safety profile is highly desirable. Compounds that are part of the dietary routine can be modified to possibly increase their anticoagulant potential. We show mannose 2,3,4,5,6-O-pentasulfate (MPS) as a synthetically modified form of mannose that has appreciable anticoagulation properties. An in silico study identified that mannose in sulfated form can bind effectively to the heparin-binding site of antithrombin (ATIII) and heparin cofactor II (HCII). Mannose was sulfated using a simple sulfation strategy-involving triethylamine-sulfur trioxide adduct. HCII and ATIII were purified from human plasma and the binding analysis using fluorometer and isothermal calorimetry showed that MPS binds at a unique site. A thrombin inhibition analysis using the chromogenic substrate showed that MPS partially enhances the activity of HCII. Further an assessment of in vitro blood coagulation assays using human plasma showed that the activated partial thromboplastin time (APTT) and prothrombin time (PT) were prolonged in the presence of MPS. A molecular dynamics simulation analysis of the HCII-MPS complex showed fluctuations in a N-terminal loop and the cofactor binding site of HCII. The results indicate that MPS is a promising lead due to its effect on the in vitro coagulation rate.Communicated by Ramaswamy H. Sarma.


Living donor liver transplantation in a pediatric patient with congenital absence of the portal vein.
Congenital absence of the portal vein (CAPV) is a rare venous malformation in which mesenteric venous blood drains directly into the systemic circulation. We report a case of pediatric living donor liver transplantation (LDLT) for CAPV combined with focal nodular hyperplasia (FNH) and hepatocellular adenoma. A 9-year-old girl who had been diagnosed with multiple FNH had CAPV. Her blood ammonia level was raised to 137 μg/dL. However, she did not complain of any symptoms. To treat CAPV and FNH, we decided to perform LDLT. The graft was a left liver graft from 39-year-old mother of the patient. Recipient hepatectomy was performed according to standard procedures of pediatric LDLT. Portal vein reconstruction was performed using interposition of an iliac vein homograft conduit to the superior mesenteric vein-splenic vein confluence. The CAPV-associated congenital splenorenal shunt was securely ligated. The pathology report of the explant liver showed a 2 cm-sized hepatocellular adenoma and multiple FNH lesions measuring up to 7.1 cm. The patient recovered uneventfully from the LDLT operation. The reconstructed portal vein was maintained well without any hemodynamic abnormalities. In conclusion, as CAPV patients can have various vascular anomalies, combined vascular anomalies should be thoroughly assessed before and during liver transplantation operation. The most effective reconstruction techniques should be used to achieve satisfactory results following liver transplantation.


A method for the assessment of area-elastic surfaces.
A method is presented for the evaluation of area-elastic surfaces using two subject tests. Deformations and jump heights are determined for 12 sprung floor samples to accuracies of 0.12 mm and 0.4 cm respectively, using filming techniques. It is found that the deformation of a floor sample is dependent on both the subject group and the dimensions of the floor sample. The method showed significant differences in deformation values of the 12 floor samples but only small differences in jump heights.


Aliphatic long-chain C20 polyesters from olefin metathesis.
Self-metathesis of undecenoic acid with [(PCy3)2Cl2Ru=CHPh] (2), followed by exhaustive hydrogenation yielded pure 1,20-eicosanedioic acid (5) (>99%) free of side-products from isomerization. Polycondensation with eicosane-1,20-diol (6), formed by reduction of the diol, yielded polyester 20,20 (Tm = 108 °C). By comparison, the known ADMET polymerization of undec-10-enyl undec-10-enoate (7), and subsequent exhaustive polymer-analogous hydrogenation yielded a polyester (poly-8) with irregular structure of the ester groups in the polymer chain (-O(C=O)- vs. -C(=O)O-) (Tm = 103 °C). Hydrogenation of secondary dispersions of poly-7 yielded aqueous dispersions of the long-chain aliphatic polyester poly-8.


OMIP-065: Dog Immunophenotyping and T-Cell Activity Evaluation with a 14-Color Panel.
Companion dogs are increasingly recognized as large-animal models of diseases such as cancer, infectious-, inflammatory-, or autoimmune diseases. At the same time, compared to human clinics, veterinarians have only a fraction of the treatment options available. To study the immunological aspects of canine diseases and ultimately develop or adapt human treatments for the dog, the methodology also needs to be in place. Such tools include robust and reliable flow cytometric panels. The purpose of the panel described here is to assess the immune cell composition and their functionality in the peripheral blood mononuclear cells (PBMCs) of dogs. Moreover, its "plug and play" composition allows for an in-depth analysis of T-cell responses in ex vivo assays (Table 1). Initially, this panel has been designed for the analysis of cryopreserved PBMCs to allow batched analysis and to reduce interexperimental variation. Withers and colleagues published a comparable and-to our knowledge-currently the most extensive canine panel to date (1). While their study focused on the aging and activation status of T cells in dogs, our panel is designed to look at a broader range of cells with a higher number of markers. This allows a more in-depth analysis of functional extracellular and intracellular markers. In addition, all antibodies in our proposed panel are directly labeled. In combination with suitable lymphocyte isolation protocols, this panel could potentially also be adapted to analyze tissue biopsies from various different organs. © 2020 International Society for Advancement of Cytometry.


Tuning Electron Delocalization and Transfer Rates in Mixed-Valent Ru3O Complexes through "Push-Pull" Effects.
Electron transfer rates in a series of oxo-centered triruthenium clusters featuring an extended aromatic ancillary ligand of the type [Ru3(OAc)6(μ3-O)(CO)(L)(pep)], where L = 4-cyanopyridine (cpy), pyridine (py), or 4-(dimethylamino)pyridine (dmap) and pep = 4-(phenylethynyl)pyridine were investigated. The electron self-exchange rate constants for the 0/- couple were determined by (1)H NMR line broadening experiments and found to range from 4.3 to 9.2 (× 10(7) M(-1) s(-1)) in deuterated acetonitrile (ACN-d3). Relative rates of self-exchange can be rationalized on the basis of increased contact area between self-exchanging pairs, and a push-pull modulation of electron density between the pep vs ancillary pyridine ligands. Faster self-exchange was observed with increasing electron-donating character of the ancillary pyridine ligand substituent (dmap > py > cpy), and this was attributed to increased orbital overlap between self-exchanging pairs. These results are supported by trends observed in (1)H NMR contact shifts of the pep ligand that were found to depend on the electron-donating or -withdrawing nature of the ancillary pyridine ligand.