Higher cardiovascular disease prevalence and mortality among younger blacks compared to whites.
Blacks have higher rates of cardiovascular disease than whites. The age at which these differential rates emerge has not been fully examined. We examined cardiovascular disease prevalence and mortality among black and white adults across the adult age spectrum and explored potential mediators of these differential disease prevalence rates. We conducted a cross-sectional analysis of National Health and Nutrition Examination Survey data from 1999-2006. We estimated age-adjusted and age-specific prevalence ratios (PR) for cardiovascular disease (heart failure, stroke, or myocardial infarction) for blacks versus whites in adults aged 35 years and older and examined potential explanatory factors. From the National Compressed Mortality File 5-year aggregate file of 1999-2003, we determined age-specific cardiovascular disease mortality rates. In young adulthood, cardiovascular disease prevalence was higher in blacks than whites (35-44 years PR 1.9; 95% confidence interval [CI], 1.1-3.4). The black-white PR decreased with each decade of advancing age (P for trend=.04), leading to a narrowing of the racial gap at older ages (65-74 years PR 1.2; 95% CI, 0.8-1.6; > or =75 years PR 1.0; 95% CI, 0.7-1.4). Clinical and socioeconomic factors mediated some, but not all, of the excess cardiovascular disease prevalence among young to middle-aged blacks. Over a quarter (28%) of all cardiovascular disease deaths among blacks occurred in those aged <65 years, compared with 13% among whites. Reducing black/white disparities in cardiovascular disease will require a focus on young and middle-aged blacks.


Rho kinase phosphorylation promotes ezrin-mediated metastasis in hepatocellular carcinoma.
During progression of hepatocellular carcinoma, multiple genetic and epigenetic alterations act to posttranslationally modulate the function of proteins that promote cancer invasion and metastasis. To define such abnormalities that contribute to liver cancer metastasis, we carried out a proteomic comparison of primary hepatocellular carcinoma and samples of intravascular thrombi from the same patient. Mass spectrometric analyses of the liver cancer samples revealed a series of acidic phospho-isotypes associated with the intravascular thrombi samples. In particular, we found that Thr567 hyperphosphorylation of the cytoskeletal protein ezrin was tightly correlated to an invasive phenotype of clinical hepatocellular carcinomas and to poor outcomes in tumor xenograft assays. Using phospho-mimicking mutants, we showed that ezrin phosphorylation at Thr567 promoted in vitro invasion by hepatocarcinoma cells. Phospho-mimicking mutant ezrinT567D, but not the nonphosphorylatable mutant ezrinT567A, stimulated formation of membrane ruffles, suggesting that Thr567 phosphorylation promotes cytoskeletal-membrane remodeling. Importantly, inhibition of Rho kinase, either by Y27632 or RNA interference, resulted in inhibition of Thr567 phosphorylation and a blockade to cell invasion, implicating Rho kinase-ezrin signaling in hepatocellular carcinoma cell invasion. Our findings suggest a strategy to reduce liver tumor metastasis by blocking Rho kinase-mediated phosphorylation of ezrin.


Putative functional domains of human cytomegalovirus pUL56 involved in dimerization and benzimidazole D-ribonucleoside activity.
Benzimidazole D-ribonucleosides inhibit DNA packaging during human cytomegalovirus (HCMV) replication. Although they have been shown to target pUL56 and pUL89 (the large and small subunits of the HCMV terminase, respectively) their mechanism of action is not yet fully understood. We aimed here to better understand HCMV DNA maturation and the mechanism of action of benzimidazole derivatives. The HCMV pUL56 protein was studied by sequence analysis of the HCMV UL56 gene and herpesvirus counterparts combined with primary structure analysis of the corresponding amino acid sequences. The UL56 sequence analysis of 45 HCMV strains and counterparts among herpesviruses allowed the identification of 12 conserved regions. Moreover, comparison with the product of gene 49 (gp49) of bacteriophage T4 suggested that the pUL56 zinc finger is localized close to the dimerization site of pUL56, providing a spatial organization of the catalytic site that allows recognition and cleavage of DNA. This study provides a basis to investigate the mechanism of concatemeric DNA cleavage and a biochemical basis for DNA packaging inhibition by benzimidazole derivatives.


Hypnosis in film and television.
When a hypnotist appears on screen, expect evil. If his induction features 'magnetic' hand passes, he's probably about to compel someone to commit a crime. Ifhe hypnotizes with an intense stare, his intent is likelier seduction-in fact many screen inductions are identical to the eye contact ethologists have labeled "the copulatory gaze." This paper explores to role of hypnosis in more than 230 films in which it has been depicted and categorizes the--mostly negative--stereotypes about it. A handful of exceptions in which hypnosis is positive and/or realistic are examined. The discussion compares this to the role of psychotherapy and dreams in cinema. It discusses why hypnosis is so maligned and whether there is anything practitioners can do to alter the stereotype.


Quantitative analysis of dietary protein intake and stroke risk.
To perform a meta-analysis of prospective studies to evaluate the relation between dietary protein intake and stroke risk. Relevant studies were identified by searching PubMed and Embase through November 2013, and by reviewing the reference lists of retrieved articles. We included prospective cohort studies that reported relative risks (RRs) with 95% confidence intervals (CIs) for the association between dietary protein intake and stroke risk. The meta-analysis included 7 prospective studies involving 254,489 participants. The pooled RR of stroke for the highest compared with the lowest dietary protein intake was 0.80 (95% CI 0.66-0.99). Dose-response analysis indicated that a 20-g/d increment in dietary protein intake was associated with a 26% reduction in stroke risk. Stratifying by protein type, the RR of stroke for animal protein was 0.71 (95% CI 0.50-0.99). Sensitivity analysis restricted to studies with control for common risk factors yielded similar results, and omission of any single study did not change the overall result. These findings suggest that moderate dietary protein intake may lower the risk of stroke.


Multiple genetic origins of histidine-rich protein 2 gene deletion in Plasmodium falciparum parasites from Peru.
The majority of malaria rapid diagnostic tests (RDTs) detect Plasmodium falciparum histidine-rich protein 2 (PfHRP2), encoded by the pfhrp2 gene. Recently, P. falciparum isolates from Peru were found to lack pfhrp2 leading to false-negative RDT results. We hypothesized that pfhrp2-deleted parasites in Peru derived from a single genetic event. We evaluated the parasite population structure and pfhrp2 haplotype of samples collected between 1998 and 2005 using seven neutral and seven chromosome 8 microsatellite markers, respectively. Five distinct pfhrp2 haplotypes, corresponding to five neutral microsatellite-based clonal lineages, were detected in 1998-2001; pfhrp2 deletions occurred within four haplotypes. In 2003-2005, outcrossing among the parasite lineages resulted in eight population clusters that inherited the five pfhrp2 haplotypes seen previously and a new haplotype; pfhrp2 deletions occurred within four of these haplotypes. These findings indicate that the genetic origin of pfhrp2 deletion in Peru was not a single event, but likely occurred multiple times.


Multi-detector CT features of acute intestinal ischemia and their prognostic correlations.
Acute intestinal ischemia is an abdominal emergency occurring in nearly 1% of patients presenting with acute abdomen. The causes can be occlusive or non occlusive. Early diagnosis is important to improve survival rates. In most cases of late or missed diagnosis, the mortality rate from intestinal infarction is very high, with a reported value ranging from 60% to 90%. Multi-detector computed tomography (MDCT) is a fundamental imaging technique that must be promptly performed in all patients with suspected bowel ischemia. Thanks to the new dedicated reconstruction program, its diagnostic potential is much improved compared to the past and currently it is superior to that of any other noninvasive technique. The increased spatial and temporal resolution, high-quality multi-planar reconstructions, maximum intensity projections, vessel probe, surface-shaded volume rending and tissue transition projections make MDCT the gold standard for the diagnosis of intestinal ischemia, with reported sensitivity, specificity, positive and negative predictive values of 64%-93%, 92%-100%, 90%-100% and 94%-98%, respectively. MDCT contributes to appropriate treatment planning and provides important prognostic information thanks to its ability to define the nature and extent of the disease. The purpose of this review is to examine the diagnostic and prognostic role of MDCT in bowel ischemia with special regard to the state of art new reconstruction software.


Increased oxidative damage in nuclear and mitochondrial DNA in Alzheimer's disease.
Increasing evidence suggests that oxidative stress is associated with normal aging and several neurodegenerative diseases, including Alzheimer's disease (AD). Here we quantified multiple oxidized bases in nuclear and mitochondrial DNA of frontal, parietal, and temporal lobes and cerebellum from short postmortem interval AD brain and age-matched control subjects using gas chromatography/mass spectrometry with selective ion monitoring (GC/MS-SIM) and stable labeled internal standards. Nuclear and mitochondrial DNA were extracted from eight AD and eight age-matched control subjects. We found that levels of multiple oxidized bases in AD brain specimens were significantly (p < 0.05) higher in frontal, parietal, and temporal lobes compared to control subjects and that mitochondrial DNA had approximately 10-fold higher levels of oxidized bases than nuclear DNA. These data are consistent with higher levels of oxidative stress in mitochondria. Eight-hydroxyguanine, a widely studied biomarker of DNA damage, was approximately 10-fold higher than other oxidized base adducts in both AD and control subjects. DNA from temporal lobe showed the most oxidative damage, whereas cerebellum was only slightly affected in AD brains. These results suggest that oxidative damage to mitochondrial DNA may contribute to the neurodegeneration of AD.


Heminasal proboscis with associated microphthalmos and encephalocele.
Heminasal proboscis is a rare congenital malformation that presents complex management issues when associated with other craniofacial abnormalities. A newborn male, known to have a facial mass on prenatal ultrasonography, was delivered by planned induction at 37 weeks' gestation. He was intubated immediately because of anticipated respiratory difficulty. He had a right-sided proboscis, pedicled on the right medial canthal region. Additional airway evaluation identified a piriform aperture and choanal stenosis. Magnetic resonance imaging confirmed a hypoplastic orbit with aplastic optic nerve and a naso-orbito-ethmoidal encephalocele. Right upper and lower eyelid colobomas were present. The airway was initially stabilized with a tracheostomy. Beginning at the age of 10 weeks, he underwent several staged procedures to excise the encephalocele and to reconstruct the nose, orbit, eyelid, and lacrimal drainage system. The encephalocele was exposed via a bicoronal approach and frontal craniotomy. The dural defect was repaired with a pericranial flap. Nasal reconstruction provided an adequate nasal passage and tip after three staged procedures. Creation of a conjunctival flap prepared the right eye for later insertion of a prosthetic shell. The patient remained successfully decannulated 3 years after his last reconstructive procedure. Identification of all associated anomalies is important before initiating surgical repair. The presence of coexisting craniofacial abnormalities requires a multispecialty approach and coordination of surgical procedures.


The onset repulsion effect.
There have been many previous reports of mislocalization associated with moving objects (e.g. flash-lag effect, Frohlich effect, representational momentum). Across four experiments, a new form of mislocalization--the onset repulsion effect (ORE)--is explored in which the error is always back along the observed path of motion. That is, when observers are asked to localize both the initial onset and the final offset positions of a moving object, by far the largest and most systematic error they make is in placing the onset point too early along the correct path of motion. Errors orthogonal to the path of motion and errors in localizing the offset point are minimal by comparison. Errors are also very small when motion is implied rather than continuous. The ORE can be observed with and without fixation, and as with other mislocalization effects, shows some dependence on direction and velocity. As the most obvious prediction in these studies, based on previous reports of mislocalization and the known properties of the visual system, would be for forward rather than backward errors, discussion will focus on the type of mechanism that may have given rise to the observed pattern of results.


Lower than expected morbidity and mortality for an Australian Aboriginal population: 10-year follow-up in a decentralised community.
To examine mortality from all causes and from cardiovascular disease (CVD), and CVD hospitalisation rate for a decentralised Aboriginal community in the Northern Territory. For a community-based cohort of 296 people aged 15 years or older screened in 1995, we reviewed hospital and primary health care records and death certificates for the period up to December 2004 (2800 person-years of follow-up). Mortality from all causes and CVD, and hospitalisation with CVD coded as a primary cause of admission; comparison with prior trends (1988 to 1995) in CVD risk factor prevalence for the community, and with NT-specific Indigenous mortality and hospitalisation rates. Mortality in the cohort was 964/100,000 person-years, significantly lower than that of the NT Indigenous population (standardised mortality ratio [SMR], 0.62; 95% CI, 0.42-0.89). CVD mortality was 358/100,000 person-years for people aged 25 years or older (SMR, 0.52; 95% CI, 0.23-1.02). Hospitalisation with CVD as a primary cause was 13/1000 person-years for the cohort, compared with 33/1000 person-years for the NT Indigenous population. Contributors to lower than expected morbidity and mortality are likely to include the nature of primary health care services, which provide regular outreach to outstation communities, as well as the decentralised mode of outstation living (with its attendant benefits for physical activity, diet and limited access to alcohol), and social factors, including connectedness to culture, family and land, and opportunities for self-determination.


The effect of music amplitude on the relaxation response.
The purposes of this study were (a) to ascertain how 3 different volume levels of music affect the relaxation response both psychologically (preference scores and self-report) and physiologically (heart rate), (b) to determine the amplitude preference for relaxation among young adults, and (c) to compare differences in preference response between music and nonmusic majors and between the genders. One hundred forty-four college-age music and nonmusic majors were participants in this study. Subjects listened to 27 minutes of music while relaxing. The amplitude of the music was changed every 3 minutes in a randomized order so that each subject received loud (80-90 dB) medium (70-80 dB) or soft (60-70 dB) music 3 times each during the experimental period for a total of 9 amplitude changes. A sample of subjects wore a small heart rate monitor on their wrist and chest during the procedure. Simultaneously with the selected listening, they were encouraged to turn a dial on a Continuous Response Digital Interface (CRDI) indicating their amplitude preference for relaxation. Self-report information was gathered at the beginning and end of the experiment. Results of the CRDI analyses indicate that overall, subjects showed overwhelming preference for the soft music in comparison to medium or loud. Males, however, preferred the loud music more than females, and music majors preferred softer music over non-majors who preferred louder music. There were no differences attributed to amplitude level in the analysis of heart rate data. Analysis of the self report data yielded a wide variety of responses concerning their individual preferences, not always consistent with the empirical measures. Overall, there was an increase in relaxation reported over the duration of the experiment. Response differentiation to loudness levels indicates a long line of useful research not only on relaxation and stress reduction in health related fields, but also on the effects of background amplitude of music while studying, driving, and engaging in other cognitive and motor tasks.


[Extracorporeal membrane oxygenation (ECMO). II. The development of an experimental model in newborn lambs].
Extracorporeal membrane oxygenation (ECMO) is a technique used for cardiorespiratory support in the treatment of newborns with severe respiratory insufficiency. ECMO has not been used yet in newborns in Spain. The aim of this work was to develop an experimental veno-arterial ECMO model in newborn lambs for training the NICU medical and nursing staff before the clinical application of this technique. Six newborn lambs were anesthetized, traqueotomized and connected to a neonatal ventilator. The right jugular vein and left carotid artery were cannulated and the catheters were located in the right atrium and aortic arch, respectively. A venous-arterial ECMO was performed during three hours, with an experimental ECMO circuit developed by us. Arterial pH and blood gases, systemic and airway pressures, heart rate, and rectal temperature were monitored. The experimental ECMO circuit developed by use had a very low cost, but was capable of maintaining adequate gas exchange, acid-base balance and a normal rectal temperature. The development of an experimental ECMO model in newborn lambs may allow the establishment of an initial training program and to maintain the expertise of the NICU staff of a perinatal center planning to start an ECMO program.


Shared resources between visual attention and visual working memory are allocated through rhythmic sampling.
Attention and visual working memory (VWM) are among the most theoretically detailed and empirically tested constructs in human cognition. Nevertheless, the nature of the interrelation between selective attention and VWM still presents a fundamental controversy: Do they rely on the same cognitive resources or not? The present study aims at disentangling this issue by capitalizing on recent evidence showing that attention is a rhythmic phenomenon, oscillating over short time windows. Using a dual-task approach, we combined a classic VWM task with a visual detection task in which we densely sampled detection performance during the time between the memory and the test array. Our results show that an increment in VWM load was related to reduced detection of near-threshold visual stimuli. Importantly, we observed an oscillatory pattern in detection at ~7.5 Hz in the low VWM load conditions, which decreased towards ~5 Hz in the high VWM load condition. These findings suggest that the frequency of this sampling rhythm changes according to the allocation of attentional resources to either the VWM or the detection task. This pattern of results is consistent with a central sampling attentional rhythm which allocates shared attentional resources both to the flow of external visual stimulation and to the internal maintenance of visual information.


Parkinsonism as a Third Wave of the COVID-19 Pandemic?
Since the initial reports of COVID-19 in December 2019, the world has been gripped by the disastrous acute respiratory disease caused by the SARS-CoV-2 virus. There are an ever-increasing number of reports of neurological symptoms in patients, from severe (encephalitis), to mild (hyposmia), suggesting the potential for neurotropism of SARS-CoV-2. This Perspective investigates the hypothesis that the reliance on self-reporting of hyposmia has resulted in an underestimation of neurological symptoms in COVID-19 patients. While the acute effect of the virus on the nervous system function is vastly overshadowed by the respiratory effects, we propose that it will be important to monitor convalescent individuals for potential long-term implications that may include neurodegenerative sequelae such as viral-associated parkinsonism. As it is possible to identify premorbid harbingers of Parkinson's disease, we propose long-term screening of SARS-CoV-2 cases post-recovery for these expressions of neurodegenerative disease. An accurate understanding of the incidence of neurological complications in COVID-19 requires long-term monitoring for sequelae after remission and a strategized health policy to ensure healthcare systems all over the world are prepared for a third wave of the virus in the form of parkinsonism.


Rational use of oral bisphosphonates for the treatment of osteoporosis.
Osteoporosis has become a major public health concern worldwide. Significant morbidity, mortality, and health expenditures are associated with osteoporotic fractures. Evidence from randomized controlled trials and meta- analyses supports the efficacy and safety of oral bisphosphonates as first-line pharmacologic agents for the prevention and treatment of osteoporosis. This article reviews the evidence demonstrating the beneficial effects of etidronate, alendronate, and risedronate on improving bone mass and preventing fractures in individuals with or at risk for osteoporosis. Issues surrounding dosing intervals and optimal duration of therapy are also discussed. We conclude that the nitrogen-containing bisphosphonates alendronate and risedronate are safe and efficacious agents in preventing and treating osteoporosis. They are superior to cyclical etidronate in improving appendicular bone mass, and in reducing future risk for nonvertebral fractures. Once-weekly dosing options with alendronate and risedronate are effective and reduce serious adverse drug effects, and therefore, are welcome additions to our therapeutic armamentarium.


Which variables help explain the poor health-related quality of life after subarachnoid hemorrhage? A meta-analysis.
Patients with subarachnoid hemorrhage (SAH) are younger than typical stroke patients. Poor psychosocial outcome after SAH therefore leads to a disproportionately high impact on patients, relatives, and society. Addressing this problem requires an understanding of what causes poor psychosocial outcome. Numerous studies have examined potential predictors but produced conflicting results. We aim to resolve this uncertainty about the potential value of individual predictors by conducting a meta-analysis. This approach allows us to quantitatively combine the findings from all relevant studies to identify promising predictors of psychosocial outcome and determine the strength with which those predictors are associated with measures of psychosocial health. Psychosocial health was measured by health-related quality of life (HRQOL). We included in our analysis those predictors that were most frequently examined in this context, namely patient age, sex, neurologic state at the time of hospital admission, bleed severity, physical disability, cognitive impairment, and time between ictus and psychosocial assessment. Only 1 of the traditional variables, physical disability, had any notable affect on HRQOL. Therefore, the cause of most HRQOL impairment after SAH remains unknown. The situation is even worse for mental HRQOL, an area that is often significantly affected in SAH patients. Here, 90% of the variance remains unexplained by traditional predictors. Studies need to turn to new factors to account for poor patient outcome.


Human papillomavirus detection in paraffin-embedded colorectal cancer tissues.
Human papillomavirus (HPV) has a well-recognized aetiological role in the development of cervical cancer and other anogenital tumours. Recently, an association between colorectal cancer and HPV infection has been suggested, although this is still controversial. This study aimed at detecting and characterizing HPV infection in 57 paired biopsies from colorectal cancers and adjacent intact tissues using a degenerate PCR approach. All amplified fragments were genotyped by means of sequencing. Overall, HPV prevalence was 12.3 %. In particular, 15.8 % of tumour tissues and 8.8 % of non-cancerous tissue samples were HPV DNA-positive. Of these samples, 85.7 % were genotyped successfully, with 41.7 % of sequences identifying four genotypes of the HR (high oncogenic risk) clade Group 1; the remaining 58.3 % of HPV-genotyped specimens had an unclassified β-HPV. Examining additional cases and analysing whole genomes will help to outline the significance of these findings.


Polymerase chain reaction in the staging of solid tumors.
Polymerasechain reaction (PCR) is a molecular biology technique that holds great promise as a way to perform molecular staging of cancer by detecting very early metastatic disease. Significant data suggest that PCR analysis may play an important role in the management of colorectal cancer in the future. However, for PCR staging of breast cancer, progress awaits identification of gene markers that have sufficient sensitivity and specificity. Within the next few years, the results of the Sunbelt Melanoma Trial and other ongoing studies will determine whether PCR evaluation of sentinel lymph nodes and peripheral blood cells has prognostic relevance in melanoma. The future of cancer management will likely revolve around the molecular staging of tumors, and PCR is but one method that may better define subgroups of patients that are appropriate candidates forvarious anticancer therapies.


[The action of long-wave ultraviolet light on the body].
A review of data obtained lately on the effect of ultraviolet radiation (lambda greater than 280 nm) on organism is given. The role of oxidative processes and first of all of photo lipid peroxidation of biomembranes in developing of a number of effects due to UV radiation are considered.


Compliance assessment of ambulatory Alzheimer patients to aid therapeutic decisions by healthcare professionals.
Compliance represents a major determinant for the effectiveness of pharmacotherapy. Compliance reports summarising electronically compiled compliance data qualify healthcare needs and can be utilised as part of a compliance enhancing intervention. Nevertheless, evidence-based information on a sufficient level of compliance is scarce complicating the interpretation of compliance reports. The purpose of our pilot study was to determine the compliance of ambulatory Alzheimer patients to antidementia drugs under routine therapeutic use using electronic monitoring. In addition, the forgiveness of donepezil (i.e. its ability to sustain adequate pharmacological response despite suboptimal compliance) was characterised and evidence-based guidance for the interpretation of compliance reports was intended to be developed. We determined the compliance of four different antidementia drugs by electronic monitoring in 31 patients over six months. All patients were recruited from the gerontopsychiatric clinic of a university hospital as part of a pilot study. The so called medication event monitoring system (MEMS) was employed, consisting of a vial with a microprocessor in the lid which records the time (date, hour, minute) of every opening. Daily compliance served as primary outcome measure, defined as percentage of days with correctly administered doses of medication. In addition, pharmacokinetics and pharmacodynamics of donepezil were simulated to systematically assess therapeutic undersupply also incorporating study compliance patterns. Statistical analyses were performed with SPSS and Microsoft Excel. Median daily compliance was 94% (range 48%-99%). Ten patients (32%) were non-compliant at least for one month. One-sixth of patients taking donepezil displayed periods of therapeutic undersupply. For 10 mg and 5 mg donepezil once-daily dosing, the estimated forgiveness of donepezil was 80% and 90% daily compliance or two and one dosage omissions at steady state, respectively. Based on the simulation findings we developed rules for the evidence-based interpretation of donepezil compliance reports. Compliance in ambulatory Alzheimer patients was for the first time assessed under routine conditions using electronic monitoring: On average compliance was relatively high but variable between patients. The approach of pharmacokinetic/pharmacodynamic in silico simulations was suitable to characterise the forgiveness of donepezil suggesting evidence-based recommendations for the interpretation of compliance reports.


Diastereoselective Synthesis of Potent Antimalarial Cis-β-lactam Agents.
Fifteen novel β-lactams bearing N-ethyl tert-butyl carbamate group 5a-o and fifteen N-(2- aminoethyl) β-lactams 6a-o were synthesized by [2+2] ketene-imine cycloaddition reaction (Staudinger). The cycloaddition reaction was found to be totally diastereoselective leading exclusively to theformation of cis-β-lactam derivatives. These newly synthesized β-lactams were evaluated for their antimalarial activity against p. falciparum K14 resistant strain and showed good to excellent EC50 values. Of the thirty β-lactams tested, 5 h, 6a and 6c showed IC50 < 20 µM while 5b, 5c, 5e, 5f, 5g, 5i, 5j, 6d, 6g and 6h exhibited IC50 <50 . Compounds 5c, 5h, and 5q-t were examined for their anticancer properties against K562 Leukemia cell line and 5s showed the best activity. Compounds 3a-j, 5a-o, 6a-o, were tested against S. aureus , E. coli, C. albicans and showed no activity below 125 µg/mL.


Malignant peripheral nerve sheath tumor as a cause of chronic cardiac insufficiency in cattle.
Chronic cardiac insufficiency was associated with a malignant peripheral nerve sheath tumor in a cow. An eight-year-old cow developed a progressive condition (over a period of three months) characterized by an enhanced abdominal volume, reluctance to move, a positive jugular pulse, watery diarrhea and death. At necropsy, moderate subcutaneous edema and an enhanced hepatic lobular pattern were observed. A 23x20x11 cm firm, grayish-white mass adhered to and infiltrated the right atrium. Multiple firm, yellowish-white nodules of 0.5 to 12 cm in diameter were diffusely scattered in the epicardium and parietal pericardium. Histologically, the tumor was poorly circumscribed with foci of infiltration of the myocardium. The neoplastic cells had two major histologic patterns, Antoni types A and B. Within occasional foci, pleomorphic cells with an epithelioid appearance were present in addition to multinucleated cells with periodic acid Schiff (PAS)-positive cytoplasmic globules. Foci of cartilaginous and granular differentiations were interspersed among the neoplastic cells. Multiple vessels presented wall hyalinization and tumoral embolus. Large necrotic foci with mineralization and cholesterol clefts were also observed. Immunohistochemically, the tumor was positive for S100 protein, vimentin and neuron-specific enolase labeling.


The potent bactericidal activity of streptomycin in the guinea pig model of tuberculosis ceases due to the presence of persisters.
The biphasic kill curve of isoniazid against Mycobacterium tuberculosis in guinea pigs is due to the presence of persisters rather than selection of isoniazid-resistant mutants. To determine whether this phenomenon is common to other bactericidal drugs, we studied the activity of streptomycin and its ability to select for streptomycin-resistant mutants in the guinea pig model of tuberculosis. Pharmacokinetic studies were performed to establish the human-equivalent dose of streptomycin. Guinea pigs were aerosol-infected with M. tuberculosis and 2 weeks later streptomycin was given for 5 days/week via intramuscular injection. Bactericidal activity was assessed by homogenizing and plating lungs for cfu until 10 weeks of treatment. At each timepoint, cfu were isolated, suspended in normal saline and re-plated on plates containing 0.5, 1.0, 2.0 or 10.0 mg/L streptomycin. The human-equivalent dose of streptomycin was determined to be 70 mg/kg. Streptomycin showed potent activity during the first 14 days of treatment, rescuing all animals from acute tuberculosis-related death and reducing lung cfu by ∼4 log(10). However, streptomycin activity was dramatically reduced thereafter, as lung cfu declined by only ∼1 log(10) over the next 56 days of treatment. Although streptomycin-resistant mutants were detectable, their frequency of isolation was identical at treatment initiation and after 70 days of treatment. The reduced activity of streptomycin during the second phase of monotherapy is not associated with the selection of streptomycin-resistant mutants but, rather, with the presence of phenotypically tolerant 'persisters'.


Improved diet quality and increased nutrient intakes associated with grape product consumption by U.S. children and adults: National Health and Nutrition Examination Survey 2003 to 2008.
Fruit contributes to dietary nutrient density and consumption of fruit in several forms (whole, dried, or 100% juice) has been reported to be associated with a healthier dietary pattern. The goal of this study was to examine the associations of the consumption of grapes (including fresh grapes, raisins, and 100% grape juice) with diet quality and food group/nutrient intake. A secondary analysis of Natl. Health and Nutrition Examination Survey (NHANES) 2003 to 2008 data was conducted to compare grape consumers (GC) with nongrape consumers (NGC) among children aged 2 to 19 y (n = 9622) and adults 20+ y (n = 12251). GC were defined as those who mentioned the consumption of fresh grapes, raisins, or 100% grape juice during 1 or both 24-h recall interviews. Compared to NGC, GC had higher Healthy Eating Index 2005 (HEI-2005) scores and higher intakes of total and whole fruit along with lower intakes of solid fat, added sugars, and calories from solid fats, alcohol, and added sugars (SoFAAS). Among adults, GC also had higher intakes than NGC of total and dark green/orange vegetables. Among both age groups, GC had higher intake than NGC of several key nutrients including dietary fiber, vitamin A, vitamin C, calcium, magnesium, and potassium. Consumption of grape products is associated with a healthier dietary pattern and higher intake of key nutrients by both children and adults.


Mechanism of hydrogen peroxide dismutation by a dimanganese catalase mimic: dominant role of an intramolecular base on substrate binding affinity and rate acceleration.
Several modifications of the manganese coordination environment and oxidation states of a family of synthetic dimanganese complexes have been introduced in search of the structural features that promote high rates of hydrogen peroxide dismutation (catalase activity). The X-ray structure of reduced catalase (T thermophilus) reveals a dimanganese(II,II) site linked by three bridges: mu 13-glutamate-, mu-OH-, and mu-OH2. The roles of a bridging hydroxide vs mu-aqua and the carboxylate have been examined in the reduced Mn2(II,II) complexes, [(L1,2)Mn2(mu-O2CCH3)(mu-X)]2+ for X- = OH- (7A) or X = H2O (1-4), and their oxidized Mn2(III,III) analogues, [(L1,2)Mn2(mu-O)(O2CCH3)(OH)]+ (6) (L1 is N,N,N',N'-tetrakis(2-methylenebenzamidazolyl)-1,3-diaminopropan- 2-ol, and L2 is the tetrakis-N-ethylated analogue of L1, which has all amine protons replaced by ethyl groups). The steady-state catalase rate is first-order in concentration of both substrate and reduced catalyst and saturates at high peroxide concentrations in all cases, confirming peroxide/catalyst complex formation. No catalyst decomposition is seen after > 2000 turnovers. Catalysis proceeds via a ping-pong mechanism between the Mn2(II,II/III,III) redox states, involving complexes 6 and 7A/7A'. The Mn2(III,IV) oxidation state was not active in catalase activity. Replacement of the mu-aqua bridge by mu-hydroxide eliminates a kinetic lag phase in production of the O2 product, increases the affinity for substrate peroxide in the rate-limiting step as seen by a 5-fold. decrease in the Michaelis constant (KM), and accelerates the maximum rate (kcat) by 65-fold The kinetic and spectroscopic data are consistent with substrate deprotonation by the hydroxide bridge, yielding a hydroperoxyl bridge coordinated between the Mn ions (mu, eta 2 geometry, "end-on") as the basis for catalysis: mu-OH- + H2O2-->mu-O2H- + H2O. Binding of a second hydroxide ion to 7A causes a further increase in kcat by 4-fold with no further change in substrate affinity (KM). By contrast, free (noncoordinating) bases in solution have no effect on catalysis, thus establishing intramolecular sites for both functional hydroxide anions. Solution structural studies indicate that the presence of 2-5 equiv of hydroxide in solution leads to formation of a bishydroxide species, [(L1,2)Mn2(mu 13-O2CCH3)(OH)2], which in the presence of air or oxygen auto-oxidizes to yield complex 6, a Mn2(III,III)(mu-O) species. Complex 6 oxidizes H2O2 to O2 without a kinetic lag phase and is implicated as the active form of the oxidized catalyst. A maximum increase by 240-fold in catalytic efficiency (kcat/KM = 700 s-1 M-1) is observed with the bishydroxide species versus the aquo complex 1, or only 800-fold less efficient than the enzyme. Deprotonation of the amine groups of the chelate ligand L was shown not to be involved in the hydroxide effects because identical results were obtained using the catalyst with tetrakis(N-ethylated)-L. Uncoupling of the Mn(II) spins by protonation of the alkoxyl bridge (LH) was observed to lower the catalase activity. Comparisons to other dimanganese complexes reveals that the Mn2(II,II)/Mn2(III,III) redox potential is not the determining factor in the catalase rate of these complexes. Rather, rate acceleration correlates with the availability of an intramolecular hydroxide for substrate deprotonation and with binding of the substrate at the bridging site between Mn ions in the reductive O-O bond cleavage step that forms water and complex 6.


Theoretical and DFT Study of Atypical Pentanuclear [(iPr3P)Ni]5Hn (n = 4, 6, 8) Clusters: What are the Rules?
The structure, bonding, and properties of a series of atypical pentanuclear nickel hydride clusters supported by electron-rich iPr3P of the type [(iPr3P)Ni]5Hn (n = 4, 6, 8; H4, H6, H8) and their anionic models where iPr3P are substituted by H- (H4', H6', H8') were investigated by density functional theory (DFT) calculations. All clusters were calculated to adopt a similar square pyramidal core geometry. Calculations indicate singlet ground states with small singlet-triplet gaps for H4 and H6, similar to previously reported experimental values. Molecular orbital theory description clusters were investigated using the simplified model complexes [HNi]5Hn5- (n = 4, 6, 8; H4', H6', H8'). The results show that there are three skeletal electron pairs (SEPs) in H4'. The addition of two molecules of H2 to form H6' and H8' results in the partial or full occupation of two degenerate MOs (e* set) that give two SEPs and one SEP, respectively. Indeed, the occupation of these low-lying weakly antibonding orbitals governs the multielectron chemistry available for these clusters and plays a role in their unique reactivity.


Rosacea and Associated Comorbidities: A Google Search Trends Analysis.
BACKGROUND: There is recent evidence linking rosacea to systemic disease. OBJECTIVE: We sought to identify correlations in Google searches (Google LLC, Mountain View, California) for rosacea and comorbid conditions to assess whether the public is seeking information regarding these trends. METHODS: Google search data from January 1, 2004, to February 28, 2018, for rosacea and search terms representing common comorbid conditions were investigated. This analysis included searches occurring in the United States (US), Canada, the United Kingdom (UK), and Australia. Search volume index (SVI) data were plotted over time and Pearson correlation coefficients were calculated from search data to assess for correlations between search terms. RESULTS: The level of interest in rosacea was highest in the spring and lowest in the winter in the US, Canada, and UK. Seasonal search trends in Australia were the inverse of those in northern hemisphere nations. Significant correlations were found between depression and rosacea SVI in the US (R=0.481; p<0.001), dementia and rosacea SVI in the UK (R=0.774; p=0.011), and hypothyroidism and rosacea SVI (R=0.752; p<0.001) in the UK. Additionally, search trends for irritable bowel syndrome (R=0.399; p<0.001) and ulcerative colitis (R=0.514; p=0.032) correlated significantly with rosacea in Canada and the UK, respectively. In Australia, search trends for osteoporosis significantly correlated with rosacea (R=0.394; p<0.001). CONCLUSIONS: Our findings indicate growing interest among the general public regarding rosacea and comorbid diseases, which behooves clinicians to adopt a more comprehensive approach in managing rosacea patients.


Phellinus caribaeo-quercicolus sp. nov., parasitic on Quercus cubana: taxonomy and preliminary phylogenetic relationships.
Phellinus caribaeo-quercicolus sp. nov. is described from several collections made in western Cuba, so far exclusively on Quercus cubana. The species is characterized by a perennial, resupinate basidiomes, cushion-shaped to nodulose and multi-layered when old, apically hooked to hamate hymenial setae, and ellipsoid to broadly ellipsoid, thin- to thick-walled, hyaline to faintly yellowish basidiospores, 4.5-5.5 x 3.5-4.5 microm. The species is compared to other Phellinus species with hooked setae, especially Phellinus undulatus, also recorded in Cuba. The preliminary phylogenetic relationships of Ph. caribaeo-quercicolus within the poroid Hymenochaetales complex of genera is presented and discussed here.


New Evidence on Self-Affirmation Effects and Theorized Sources of Heterogeneity from Large-Scale Replications.
Brief, targeted self-affirmation writing exercises have recently been offered as a way to reduce racial achievement gaps, but evidence about their effects in educational settings is mixed, leaving ambiguity about the likely benefits of these strategies if implemented broadly. A key limitation in interpreting these mixed results is that they come from studies conducted by different research teams with different procedures in different settings; it is therefore impossible to isolate whether different effects are the result of theorized heterogeneity, unidentified moderators, or idiosyncratic features of the different studies. We addressed this limitation by conducting a well-powered replication of self-affirmation in a setting where a previous large-scale field experiment demonstrated significant positive impacts, using the same procedures. We found no evidence of effects in this replication study and estimates were precise enough to reject benefits larger than an effect size of 0.10. These null effects were significantly different from persistent benefits in the prior study in the same setting, and extensive testing revealed that currently theorized moderators of self-affirmation effects could not explain the difference. These results highlight the potential fragility of self-affirmation in educational settings when implemented widely and the need for new theory, measures, and evidence about the necessary conditions for self-affirmation success.


Oxidative Stress Markers and the Retinopathy of Prematurity.
Retinopathy of prematurity (ROP) is a leading cause of potentially preventable blindness in low birth weight preterm infants. Several perinatal and postnatal factors contribute to the incomplete maturation of retinal vascularization, leading to oxidative stress damage. Literature data suggest that the lack of equilibrium between pro-oxidants and anti-oxidants plays a key role. In the last decade, there has been an increasing interest in identifying the antecedents of ROP and the relevant pathogenic mechanisms involved. In this context, a panel of biomarkers was investigated in order to achieve early detection of oxidative stress occurrence and to prevent retinal damage. Several nutritional elements have been found to play a relevant role in ROP prevention. At this stage, no conclusive data have been shown to support the usefulness of one biomarker over another. Recently, the Food and Drugs Administration, the European Medicine Agency, and the National Institute of Health proposed a series of criteria in order to promote the inclusion of new biomarkers in perinatal clinical guidelines and daily practice. The aim of the present review is to offer an update on a panel of biomarkers, currently investigated as potential predictors of ROP, highlighting their strengths and weaknesses.


How can a computer be useful to you? A feasibility study to elicit perceptions of computers in rural India.
The growing influx of information and communication technologies (ICTs) into rural India provides new opportunities for the prevention and treatment of diseases across millions of residents. However, little is known about how rural Indians with little or no exposure to computers perceive computers and their uses, and how best to elicit those perceptions. Such perceptions could lead to new insights for using ICTs to affect health behavior change in developing countries. We therefore developed a semi-structured interview approach to probe how residents of a north Indian village perceived computers and their uses. The results suggest that besides helping to overturn several assumptions of the researchers through unexpected insights, the approach could be easily implemented in rural settings, which could lead to deeper insights for developing future culturally and medically-relevant ICTs for rural residents.


The effects of mood upon imaginal thought.t.
The effects of mood upon imaginal thought were explored with a highly trained undergraduate female hypnotic subject. She was hypnotically programmed to experience free-floating anxiety or pleasure in varying degrees just before the exposure of combinations of three Blacky Pictures, and to produce dreamlike imagery in response to the Blacky stimuli while under sway of the mood. Data from 98 dream trials, separated by amnesia, indicated that the affective states clearly influenced imaginal processes. Blind ratings by a psychoanalyst showed anxiety moods to be more closely associated with primary-process features characteristic of nocturnal dreams, whereas pleasure had a relatively higher incidence of daydreamlike ratings. Empirical analysis of themes yielded significant relationships of anxiety to physical injury to the self and verbal aggression toward others; pleasure was associated with circular movements and overt sex themes.


Remitting seronegative symmetrical synovitis with pitting edema (RS3PE syndrome).
A 63-year-old man presented with acute symmetrical polysynovitis associated with pitting edema of both the hands and feet. He was seronegative for rheumatoid factor and no radiologically evident erosion was noted in the joints of his hands and feet. Evaluation excluded congestive heart failure, nephrotic syndrome, and hypothyroidism as the cause of edema. Treatment with nonsteroidal anti-inflammatory drugs and low-dose steroids induced complete remission. The clinical manifestations of this patients were consistent with those of a distinctive, although rare, form of arthritis called remitting seronegative symmetrical synovitis with pitting edema (RS3PE) syndrome. This syndrome has a good prognosis in elderly patients.


[Wild silk: a strong inhalation allergen (author's transl)].
In the course of 18 months, allergic bronchial asthma due to wild silk was diagnosed in 26 patients (19 women, 7 men) of the relatively high mean age at onset of 34 years. In 25 patients the allergy started 1-36 months after acquiring a so-called wild-silk rug, which contains wild-silk waste; one patient fell ill after occupational contact with the waste of wild silk. In all patients the scratch test with wild-silk waste was strongly positive. Elimination of the rug or the occupational exposure made all the symptoms disappear. Wild-silk waste, product of wild-growing oak silkworms, is thus a relatively strong inhalation allergen. Exposure to wild-silk rugs should routinely be considered in the diagnostic work-up of allergies.


A patient-derived olfactory stem cell disease model for ataxia-telangiectasia.
The autosomal recessive disorder ataxia-telangiectasia (A-T) is characterized by genome instability, cancer predisposition and neurodegeneration. Although the role of ataxia-telangiectasia mutated (ATM) protein, the protein defective in this syndrome, is well described in the response to DNA damage, its role in protecting the nervous system is less clear. We describe the establishment and characterization of patient-specific stem cells that have the potential to address this shortcoming. Olfactory neurosphere (ONS)-derived cells were generated from A-T patients, which expressed stem cell markers and exhibited A-T molecular and cellular characteristics that included hypersensitivity to radiation, defective radiation-induced signaling and cell cycle checkpoint defects. Introduction of full-length ATM cDNA into these cells corrected defects in the A-T cellular phenotype. Gene expression profiling and pathway analysis revealed defects in multiple cell signaling pathways associated with ATM function, with cell cycle, cell death and DNA damage response pathways being the most significantly dysregulated. A-T ONS cells were also capable of differentiating into neural progenitors, but they were defective in neurite formation, number of neurites and length of these neurites. Thus, ONS cells are a patient-derived neural stem cell model that recapitulate the phenotype of A-T, do not require genetic reprogramming, have the capacity to differentiate into neurons and have potential to delineate the neurological defect in these patients.


[Partial replacement of the pelvis with the hip joint and proximal femur. A possibility in tumor treatment].
In cases of extensive destructive osteolytic processes in the pelvis and hip region, alloplastic replacement of a part of the pelvis with a total hip replacement and, if necessary, partial replacement of the femur, can represent a therapeutic alternative to hemipelvectomy for preserving the limb in the presence of malignancies; it offers the same degree of radicality in removing the affected bone and soft tissue while preserving the bone. This applies with regard both to primary malignant growths as well as extensive isolated metastases and aseptic osteolysis following multiple total replacement procedures. The partial pelvic prostheses, produced individually on the basis of roentgenograms, are adapted to a great degree intraoperatively and fixed with screws, locknuts, and Palacos, and if possible lined with autogenous bone. Where the defects are extensive the pubic bone of the unaffected side is incorporated in the stabilization. Experience gathered so far and follow-up examinations show that all patients regain full mobility and weight-bearing ability, with almost complete lack of complaints and adequate to good motility. This is demonstrated by examples.


Cerebral metabolism, cognition, and functional abilities in Alzheimer disease.
Patients with Alzheimer disease (AD) exhibit profound difficulties in completing instrumental activities of daily living (IADLs), such as managing finances, organizing medications, and food preparation. It is unclear which brain areas underlie IADL deficits in AD. To address this question, we used voxel-based analysis to correlate the performance of IADLs with resting cerebral metabolism as measured during [(18)F] fluorodeoxyglucose-positron emission tomography (FDG-PET) imaging in 44 patients with AD. Poorer ability to complete IADLs was associated with hypometabolism in right-sided cortical regions, including the parietal lobe, posterior temporal cortex, dorsolateral prefrontal cortex, and frontal pole. Follow-up path analyses examining anatomically defined regions of interest (ROI) demonstrated that the association between metabolism and IADLs was mediated by global cognition in frontal ROIs, and partially mediated by global cognition in the parietal ROI. Findings suggest that hypometabolism of right sided brain regions involved in executive functioning, visuospatial processing, attention, and working memory underlie functional impairments in patients with AD.


Strong coupling of a spin ensemble to a superconducting resonator.
We report the realization of a quantum circuit in which an ensemble of electronic spins is coupled to a frequency tunable superconducting resonator. The spins are nitrogen-vacancy centers in a diamond crystal. The achievement of strong coupling is manifested by the appearance of a vacuum Rabi splitting in the transmission spectrum of the resonator when its frequency is tuned through the nitrogen-vacancy center electron spin resonance.


[Mutagenic activity of native and inactivated herpes simplex virus].
The mutagenic activity of native and inactivated herpes simplex virus (HSV-1) has been studied. The native HSV-1 strain has been shown to induce the gene mutations of 6-mercaptopurine resistance in Chinese hamster cells. The 1.5- to 2-fold decrease of mutagenic activity is due to HSV inactivation by thiophosphamide and formalin treatment. These data indicate the possibility of the given agents application for decreasing of the genetic danger of antiviral vaccine.


Microbiota as Predictor of Mortality in Allogeneic Hematopoietic-Cell Transplantation.
Relationships between microbiota composition and clinical outcomes after allogeneic hematopoietic-cell transplantation have been described in single-center studies. Geographic variations in the composition of human microbial communities and differences in clinical practices across institutions raise the question of whether these associations are generalizable. The microbiota composition of fecal samples obtained from patients who were undergoing allogeneic hematopoietic-cell transplantation at four centers was profiled by means of 16S ribosomal RNA gene sequencing. In an observational study, we examined associations between microbiota diversity and mortality using Cox proportional-hazards analysis. For stratification of the cohorts into higher- and lower-diversity groups, the median diversity value that was observed at the study center in New York was used. In the analysis of independent cohorts, the New York center was cohort 1, and three centers in Germany, Japan, and North Carolina composed cohort 2. Cohort 1 and subgroups within it were analyzed for additional outcomes, including transplantation-related death. We profiled 8767 fecal samples obtained from 1362 patients undergoing allogeneic hematopoietic-cell transplantation at the four centers. We observed patterns of microbiota disruption characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota was associated with a lower risk of death in independent cohorts (cohort 1: 104 deaths among 354 patients in the higher-diversity group vs. 136 deaths among 350 patients in the lower-diversity group; adjusted hazard ratio, 0.71; 95% confidence interval [CI], 0.55 to 0.92; cohort 2: 18 deaths among 87 patients in the higher-diversity group vs. 35 deaths among 92 patients in the lower-diversity group; adjusted hazard ratio, 0.49; 95% CI, 0.27 to 0.90). Subgroup analyses identified an association between lower intestinal diversity and higher risks of transplantation-related death and death attributable to graft-versus-host disease. Baseline samples obtained before transplantation already showed evidence of microbiome disruption, and lower diversity before transplantation was associated with poor survival. Patterns of microbiota disruption during allogeneic hematopoietic-cell transplantation were similar across transplantation centers and geographic locations; patterns were characterized by loss of diversity and domination by single taxa. Higher diversity of intestinal microbiota at the time of neutrophil engraftment was associated with lower mortality. (Funded by the National Cancer Institute and others.).


Improving pregnancy outcome in obese women.
The global pandemic of maternal obesity presents a major challenge for healthcare providers, and has significant short- and long-term implications for both maternal and fetal health. Currently, the evidence-base underpinning many of the interventions either currently in use or recommended to improve pregnancy outcome in obese women is limited. The nature and timing of these interventions vary widely, ranging from simple advice to more intensive dietary and exercise programmes, cognitive behavioural therapy and drug trials. In addition, a growing number of very severely obese women now enter pregnancy having had surgical interventions. Although surgical interventions such as gastric bypass or banding may be associated with improved pregnancy outcomes, these women have particular nutritional requirements, which need to be addressed to optimise pregnancy outcome. Until the outcomes of ongoing current trials are reported and provide a firm evidence base on which to base future intervention strategies and guide evidence based care for obese pregnant women, pregnancy outcome is best optimised by high-risk antenatal care delivered by healthcare providers who are experienced in supporting these high-risk women.


Clinicians' Concerns About Mobile Ecological Momentary Assessment Tools Designed for Emerging Psychiatric Problems: Prospective Acceptability Assessment of the MEmind App.
Many mental disorders are preceded by a prodromal phase consisting of various attenuated and unspecific symptoms and functional impairment. Electronic health records are generally used to capture these symptoms during medical consultation. Internet and mobile technologies provide the opportunity to monitor symptoms emerging in patients' environments using ecological momentary assessment techniques to support preventive therapeutic decision making. The objective of this study was to assess the acceptability of a Web-based app designed to collect medical data during appointments and provide ecological momentary assessment features. We recruited clinicians at 4 community psychiatry departments in France to participate. They used the app to assess patients and to collect data after viewing a video of a young patient's emerging psychiatric consultation. We then asked them to answer a short anonymous self-administered questionnaire that evaluated their experience, the acceptability of the app, and their habit of using new technologies. Of 24 practitioners invited, 21 (88%) agreed to participate. Most of them were between 25 and 45 years old, and greater age was not associated with poorer acceptability. Most of the practitioners regularly used new technologies, and 95% (20/21) connected daily to the internet, with 70% (15/21) connecting 3 times a day or more. However, only 57% (12/21) reported feeling comfortable with computers. Of the clinicians, 86% (18/21) would recommend the tool to their colleagues and 67% (14/21) stated that they would be interested in daily use of the app. Most of the clinicians (16/21, 76%) found the interface easy to use and useful. However, several clinicians noted the lack of readability (8/21, 38%) and the need to improve ergonometric features (4/21, 19%), in particular to facilitate browsing through various subsections. Some participants (5/21, 24%) were concerned about the storage of medical data and most of them (11/21, 52%) seemed to be uncomfortable with this. We describe the first step of the development of a Web app combining an electronic health record and ecological momentary assessment features. This online tool offers the possibility to assess patients and to integrate medical data easily into face-to-face conditions. The acceptability of this app supports the feasibility of its broader implementation. This app could help to standardize assessment and to build up a strong database. Used in conjunction with robust data mining analytic techniques, such a database would allow exploration of risk factors, patterns of symptom evolution, and identification of distinct risk subgroups.


Targeting the c-Met pathway potentiates glioblastoma responses to gamma-radiation.
Resistance to current cytotoxic therapies limits the treatment of most solid malignancies. This results, in part, from the overactivation of receptor tyrosine kinases and their downstream pathways in tumor cells and their associated vasculature. In this report, we ask if targeting the multifunctional mitogenic, cytoprotective, and angiogenic scatter factor/hepatocyte growth factor (SF/HGF)/c-Met pathway potentiates antitumor responses to gamma-radiation. Endogenous expression of SF/HGF and c-Met was targeted in U87 MG human malignant glioma cells and xenografts using chimeric U1/ribozymes. The effects of U1/ribozymes +/- gamma-radiation on glioma cell proliferation, apoptosis, xenograft growth, and animal survival were examined. U1/ribozymes knocked down SF/HGF and c-Met mRNA and protein levels, sensitized cells to gamma-radiation (P < 0.005), and enhanced radiation-induced caspase-dependent cytotoxicity in vitro (P < 0.005). Intravenous U1/ribozyme therapy as liposome/DNA complexes or radiation alone modestly and transiently inhibited the growth of s.c. U87 xenografts. Combining the therapies caused tumor regression and a 40% tumor cure rate. In animals bearing intracranial xenografts, long-term survival was 0% in response to radiation, 20% in response to intratumoral adenoviral-based U1/ribozyme delivery, and 80% (P < 0.0005) in response to combining U1/ribozymes with radiation. This apparent synergistic antitumor response was associated with a approximately 70% decrease in cell proliferation (P < 0.001) and a approximately 14- to 40-fold increase in apoptosis (P < 0.0001) within xenografts. Targeting the SF/HGF/c-Met pathway markedly potentiates the anti-glioma response to gamma-radiation. Clinical trials using novel SF/HGF/c-Met pathway inhibitors in glioma and other malignancies associated with c-Met activation should ultimate include concurrent radiation and potentially other cytotoxic therapeutics.


Serotonin-immunoreactivity in peripheral tissues of the opisthobranch molluscs Pleurobranchaea californica and Tritonia diomedea.
The distribution of serotonin (5-HT)-immunoreactive elements in peripheral organs of the sea-slugs Pleurobranchaea californica and Tritonia diomedea was studied in cryostat sections. For Pleurobranchaea, 5-HT-immunoreactive (5-HT-IR) neuron cell bodies were found only in the central nervous system (CNS); 5-HT-IR cell bodies were not observed in foot, tentacles, rhinophores, oral veil, mouth, buccal mass, esophagus, gills, salivary glands, skin, reproductive system, and acidic glands, nor in peripheral tentacle and rhinophore ganglia. However, 5-HT-IR neuronal processes were widely distributed in these structures and the patterns of 5-HT-IR elements were characteristic for each particular peripheral tissue. 5-HT-IR elements were most dense in the sole of the foot and the reproductive system, followed by rhinophores, tentacles, oral veil, mouth, buccal mass, and esophagus. The sensory epithelium of rhinophores, tentacles, and mouth showed a highly structured glomerular organization of 5-HT-IR fibers, suggesting a role for 5-HT in sensory signaling. A much lower density of 5-HT-IR innervation was observed in gills, skin, salivary, and acidic glands. 5-HT-IR was observed in neuropil of tentacle and rhinophore ganglia with many transverse 5-HT-IR axons running to peripheral sensory areas. The distribution of 5-HT-IR elements in Tritonia was similar to that of Pleurobranchaea. A significant suggestion of the data is that central serotonergic neurons may modulate afferent pathways from sensory epithelia at the periphery.


[Effect of nicotinic acid on phosphodiesterase and adenyl cyclase activities in chicken liver].
Stimulation of fatty acid biosynthesis by feeding high-carbohydrate diet to chickens after fasting induces a 38% and 23% rise in the 3':5'-cyclo-nucleotide phosphodiesterase and adenylate cyclase activities in the liver tissue, respectively. Administration of nicotinic acid (150 mg per 1 kg of weight) to chickens with stimulated biosynthesis of fatty acids leads to a sharp (70% at an average) decrease of 3':5'-cyclo-nucleotide phosphodiesterase activity, the adenylate cyclase activity under these conditions remains practically unchanged. The participation of the adenylate cyclase system in regulating the fatty acid biosynthesis under mentioned conditions, the role of phosphodiesterase are discussed.


Medium chain acyl-CoA dehydrogenase deficiency.
From 65 reported cases of medium chain acyl-CoA dehydrogenase deficiency, we found an average presenting age of 13.5 months and a mean age at death of 18.5 months. One quarter of patients died of a Reye-like syndrome and/or sudden infant death. In half the cases there had been at least one sibling death. Asymptomatic cases were not uncommon (12% of cases). The crises were generally induced by a prolonged fast and after a viral prodromal phase in three quarters of cases. The crises consisted of somnolence progressing to lethargy which could lead to coma. Vomiting was frequent (60% of cases). Seizures, which were found in 29% of cases, represented a bad prognosis. The physical examinations revealed frequently a variable and regressive anicteric hepatomegaly. Blood and urine analysis revealed in most instances hypoglycaemia (96% of cases) with hypoketonuria and sometimes metabolic acidosis. Hepatic and muscular cytolytic enzymes were frequently raised, as were plasma ammonia, urea, and uric acid. Plasma total or free carnitine concentrations, especially non-fasting, were diminished in most cases. Plasma saturated medium chain fatty acids and particularly unsaturated cis-4-decenoate were on the other hand raised during the crises or during fasting. Urinary organic acid analysis revealed a characteristic profile of medium chain aciduria: C6-C10 dicarboxylic acids, hydroxy acids, glycine conjugates, and carnitine conjugates. Oral loading tests with carnitine or phenylpropionate allow a precise diagnosis. The diagnosis is confirmed by specific assays in various tissues. Avoidance of prolonged fasting seems to be the mainstay of treatment.


Understanding roles and improving reporting and response relationships across professional boundaries.
Child abuse is underreported. The author, a child protective service professional with extensive field and management experience, provides his perspective on some of the barriers that inhibit an effective response to reporting and collaboration between the professionals evaluating and investigating possible child abuse. Then presented are his ideas for improving the collaboration, including recommendations for changes in training, child protective service procedures, child protective service staffing, confidentiality requirements, and the adoption of a Child Advocacy Center (CAC) model.


In1-ghrelin splicing variant is overexpressed in pituitary adenomas and increases their aggressive features.
Pituitary adenomas comprise a heterogeneous subset of pathologies causing serious comorbidities, which would benefit from identification of novel, common molecular/cellular biomarkers and therapeutic targets. The ghrelin system has been linked to development of certain endocrine-related cancers. Systematic analysis of the presence and functional implications of some components of the ghrelin system, including native ghrelin, receptors and the recently discovered splicing variant In1-ghrelin, in human normal pituitaries (n = 11) and pituitary adenomas (n = 169) revealed that expression pattern of ghrelin system suffers a clear alteration in pituitary adenomasas compared with normal pituitary, where In1-ghrelin is markedly overexpressed. Interestingly, in cultured pituitary adenoma cells In1-ghrelin treatment (acylated peptides at 100 nM; 24-72 h) increased GH and ACTH secretion, Ca(2+) and ERK1/2 signaling and cell viability, whereas In1-ghrelin silencing (using a specific siRNA; 100 nM) reduced cell viability. These results indicate that an alteration of the ghrelin system, specially its In1-ghrelin variant, could contribute to pathogenesis of different pituitary adenomas types, and suggest that this variant and its related ghrelin system could provide new tools to identify novel, more general diagnostic, prognostic and potential therapeutic targets in pituitary tumors.


Rational Design of Nanomaterials for Various Radiation-Induced Diseases Prevention and Treatment.
Radiation treatments often unfavorably damage neighboring healthy organs and cause a series of radiation sequelae, such as radiation-induced hematopoietic system diseases, radiation-induced gastrointestinal diseases, radiation-induced lung diseases, and radiation-induced skin diseases. Recently, emerging nanomaterials have exhibited good superiority for these radiation-induced disease treatments. Given this background, the rational design principle of nanomaterials, which helps to optimize the therapeutic efficiency, has been an increasing need. Consequently, it is of great significance to perform a systematic summarization of the advances in this field, which can trigger the development of new high-performance nanoradioprotectors with drug efficiency maximization. Herein, this review highlights the advances and perspectives in the rational design of nanomaterials for preventing and treating various common radiation-induced diseases. Furthermore, the sources, clinical symptoms, and pathogenesis/injury mechanisms of these radiation-induced diseases will also be introduced. Furthermore, current challenges and directions for future efforts in this field are also discussed.


Abscisic acid regulates TSRF1-mediated resistance to Ralstonia solanacearum by modifying the expression of GCC box-containing genes in tobacco.
Although recent studies have established a significant regulatory role for abscisic acid (ABA) and ethylene response factor (ERF) proteins in plant pathogen resistance, it is not clear whether and how ABA performs this role. Previously, it was reported that an ERF protein, TSRF1, activates the expression of GCC box-containing genes and significantly enhances the resistance to Ralstonia solanacearum in both tobacco and tomato plants. Here, it is reported that TSRF1-regulated pathogen resistance is modified by ABA application. TSRF1 activates the expression of ABA biosynthesis-related genes, resulting in the increase of ABA biosynthesis, which further stimulates ethylene production. More interestingly, ABA application decreases, while the inhibitor of ABA biosynthesis fluridone increases, the TSRF1-enhanced resistance to R. solanacearum. This observation is further supported by the finding that ABA and fluridone reversibly modify the ability of TSRF1 to bind the ethylene-responsive GCC box, consequently altering the expression of element-controlled genes. These results therefore establish that TSRF1-regulated resistance to R. solanacearum can be modified in tobacco by ABA.


The role of alpha 1 protease inhibitor (alpha 1 antitrypsin) in the regulation of immunologic and inflammatory reactions.
Twenty-six different alleles have been identified for alpha 1 protease inhibitor (alpha 1 antitrypsin), each designated by a letter of the alphabet. In any individual two alleles codominantly determine the characteristics of alpha 1 protease inhibitor (Pi), including mobility on electrophoresis, serum concentration and acute phase response. Recent evidence has linked some mildly deficient phenotypes of Pi with a variety of chronic immunologic and inflammatory disorders, such as rheumatoid arthritis, juvenile chronic arthritis, systemic lupus erythematosus, ankylosing spondylitis, uveitis, asthma and fibrosing alveolitis, in addition to the well recognised association of severe deficiency with emphysema and chronic liver disease. This disease susceptibility in phenotypes associated with reduced serum levels may be due to alteration in lymphocyte responses, complement activation and leukocyte migration. Pi can also influence the autolytic effects of leukocytic enzymes on tissues and may inhibit some aspects of coagulation and fibrinolysis. Therefore patients with deficient Pi phenotypes are likely to have exaggerated immunologic and inflammatory responses.


Desensitization: achieving immune detente.
Antibodies to donor HLA (human leukocyte antigen) and/or ABO antigens were a contraindication to transplantation of most organs for decades. Desensitization protocols have shown the ability to produce reduction of such antibodies sufficient to achieve a successful transplantation. The two major protocols in use are high-dose IVIg or plasmapheresis with low-dose IVIg. The protocols differ in the basic treatment and, to some degree, in their application, but both use standard immunosuppressive agents as well as more recently developed adjunctive agents such as cell-depleting antibodies. Graft and patient survival with both types of protocol are comparable to that of non-sensitized patients, although desensitized patients do have a higher incidence of antibody-mediated rejection (AMR). Antibodies to donor antigens may persist after transplantation, and while the initial antibody titer represents the level of difficulty for successful desensitization, the strength of antibodies that persist after transplantation reflects the risk of AMR. Current protocols do not eliminate B cell clones specific for donor HLA; therefore, desensitized patients remain at an increased risk of antibody rebound if patients experience pro-inflammatory events. Therefore, ongoing antibody monitoring is crucial for early detection of antibody-mediated graft injury. Importantly, the results of numerous programs show that ABOi- and HLA-positive crossmatch renal transplantation, with proper desensitization, can be performed successfully. Further, in addition to increasing the rate of transplantation among sensitized patients, desensitization is providing insight into immunoregulatory processes and may provide information useful in diseases involving immune dysfunction.


Inactivation of heparan sulfate 2-O-sulfotransferase accentuates neutrophil infiltration during acute inflammation in mice.
Neutrophil recruitment and extravasation at sites of inflammation provide a mechanism for host defense. We showed previously that heparan sulfate, a type of sulfated glycosaminoglycan, facilitates neutrophil recruitment based on the reduction of neutrophil infiltration in mice in which the overall sulfation of the chains was reduced by selective inactivation of N-acetylglucosamine N-deacetylase-N-sulfotransferase (Ndst1) in endothelial cells. Here we show that inactivation of uronyl 2-O-sulfotransferase in endothelial cells (Hs2st), an enzyme that acts downstream from Ndst1, results in enhanced neutrophil recruitment in several models of acute inflammation. Enhanced neutrophil infiltration resulted in part from reduced rolling velocity under flow both in vivo and in vitro, which correlated with stronger binding of neutrophil L-selectin to mutant endothelial cells. Hs2st-deficient endothelial cells also displayed a striking increase in binding of IL-8 and macrophage inflammatory protein-2. The enhanced binding of these mediators of neutrophil recruitment resulted from a change in heparan sulfate structure caused by increased N-sulfation and 6-O-sulfation of glucosamine units in response to the decrease in 2-O-sulfation of uronic acid residues. This gain-of-function phenotype provides formidable evidence demonstrating the importance of endothelial heparan sulfate in inflammation and suggests a novel enzyme target for enhancing the innate immune response.


Removal of an N-terminal peptide from mitochondrial aspartate aminotransferase abolishes its interactions with mitochondria in vitro.
Treatment of mitochondrial aspartate aminotransferase from rat liver with trypsin leads to specific cleavage of the bonds between residues 26 and 27, and residues 31 and 32. The proteolysed enzyme has only a small residual catalytic activity, but retains a conformation similar to that of the native form as judged by accessibility and reactivity of cysteine residues. Proteolysis abolishes the ability of the enzyme either to bind to mitochondria or to be imported into the organelles. This suggests that the N-terminal segment of the native enzyme is essential for both of these functions, at least in the model system used to study the import process.


Regression methods for pricing complex American-style options.
We introduce and analyze a simulation-based approximate dynamic programming method for pricing complex American-style options, with a possibly high-dimensional underlying state space. We work within a finitely parameterized family of approximate value functions, and introduce a variant of value iteration, adapted to this parametric setting. We also introduce a related method which uses a single (parameterized) value function, which is a function of the time-state pair, as opposed to using a separate (independently parameterized) value function for each time. Our methods involve the evaluation of value functions at a finite set, consisting of "representative" elements of the state space. We show that with an arbitrary choice of this set, the approximation error can grow exponentially with the time horizon (time to expiration). On the other hand, if representative states are chosen by simulating the state process using the underlying risk-neutral probability distribution, then the approximation error remains bounded.


Development of a disease-specific quality-of-life questionnaire for anterior and central skull base pathology--the skull base inventory.
Anterior and central skull base lesions and their surgical treatment (endoscopic or open approaches) can affect quality of life. A disease-specific instrument is needed to compare quality of life for different surgical approaches. Items were generated using a composite strategy consisting of chart review, systematic review of skull base instruments, expert interviews, and qualitative analysis of patient focus groups. A cross-sectional survey study was performed to reduce items based on an item impact score. Charts of 138 patients who underwent skull base surgery were reviewed to identify physical items and domains. Five experts were interviewed for item and domain identification. Thirty-four patients were recruited into eight focus groups based on their surgical approach (open or endoscopic) and tumor location (anterior or central). Items were generated using a composite approach and then reduced into a final questionnaire using item impact scores. Chart review identified 47 physical items. Systematic review revealed nine relevant instruments with 217 relevant items. Experts identified 11 domains with 69 additional items. Qualitative analysis of focus groups generated 49 items. A total of 382 items were identified and reduced to 77 items after eliminating overlapping and irrelevant items. Further item reduction using item impact scores yielded 41 items. The Skull Base Inventory is a disease-specific quality-of-life instrument. Psychometric properties have yet to be tested. It may serve to compare quality of life for endoscopic or open procedures.


Association of CSF Biomarkers With Hippocampal-Dependent Memory in Preclinical Alzheimer Disease.
To determine whether memory tasks with demonstrated sensitivity to hippocampal function can detect variance related to preclinical Alzheimer disease (AD) biomarkers, we examined associations between performance in 3 memory tasks and CSF β-amyloid (Aβ)42/Aβ40 and phosopho-tau181 (p-tau181) in cognitively unimpaired older adults (CU). CU enrolled in the Stanford Aging and Memory Study (n = 153; age 68.78 ± 5.81 years; 94 female) completed a lumbar puncture and memory assessments. CSF Aβ42, Aβ40, and p-tau181 were measured with the automated Lumipulse G system in a single-batch analysis. Episodic memory was assayed using a standardized delayed recall composite, paired associate (word-picture) cued recall, and a mnemonic discrimination task that involves discrimination between studied "target" objects, novel "foil" objects, and perceptually similar "lure" objects. Analyses examined cross-sectional relationships among memory performance, age, and CSF measures, controlling for sex and education. Age and lower Aβ42/Aβ40 were independently associated with elevated p-tau181. Age, Aβ42/Aβ40, and p-tau181 were each associated with (1) poorer associative memory and (2) diminished improvement in mnemonic discrimination performance across levels of decreased task difficulty (i.e., target-lure similarity). P-tau mediated the effect of Aβ42/Aβ40 on memory. Relationships between CSF proteins and delayed recall were similar but nonsignificant. CSF Aβ42 was not significantly associated with p-tau181 or memory. Tests designed to tax hippocampal function are sensitive to subtle individual differences in memory among CU and correlate with early AD-associated biomarker changes in CSF. These tests may offer utility for identifying CU with preclinical AD pathology.


Hepatitis E: does it cause chronic hepatitis?
Hepatitis E virus (HEV) is considered an agent responsible for acute hepatitis that does not progress to chronic hepatitis. We identified 14 cases of acute HEV infection in three patients receiving liver transplants, nine receiving kidney transplants, and two receiving kidney and pancreas transplants. All patients were positive for serum HEV RNA. Chronic hepatitis developed in eight patients, as confirmed by persistently elevated aminotransferase levels, serum HEV RNA, and histologic features of chronic hepatitis. The time from transplantation to diagnosis was significantly shorter and the total counts of lymphocytes and of CD2, CD3, and CD4 T cells were significantly lower in patients in whom chronic disease developed.


Clinical value of ultrasound in adult Wilms' tumor patient with uremia: A case report and literature review.
Wilms' tumor (WT) is the most common pediatric kidney malignancy and is rarely found in adults. Nonspecific clinical symptoms and imaging features often lead to delayed diagnosis or misdiagnosis of adult WT, resulting in poor clinical outcomes. Ultrasound (US), as an efficient and noninvasive examination method, has been widely used in clinical diagnosis and treatment. Therefore, various US evidence is meaningful to improve understanding of adult WT characteristics in ultrasound. A 45-year-old female patient with uremia (regular hemodialysis for 13 years) with painless gross hematuria was diagnosed with a right kidney tumor penetrating to the lung. Preoperatively, B-mode ultrasonography showed an ill-defined hyperechoic mass in the right kidney, which revealed an unclear border, uneven internal echoes, and calcification. Besides, the internal blood flow signal of the tumor was detected. Contrast-enhanced ultrasound (CEUS) showed an uneven hyper-enhancement in the tumor ("fast in and slow out"). Contrast-enhanced computed tomography of the kidney indicated a similar result as the CEUS. Moreover, the chest CT identified multiple pulmonary metastatic nodules. An ultrasound-guided percutaneous core needle biopsy of the tumor proceeded to make a definite diagnosis of adult WT (epithelial type). The patient was treated with tislelizumab. No progress was found to date. We report the first case in which CEUS was performed in an adult WT patient with uremia and multiple pulmonary metastases. The features obtained by the US can help in the diagnosis of adult WT and direct further diagnostic procedures.


The effect of biofeedback on function in patients with heart failure.
Decreased HRV has been consistently associated with increased cardiac mortality and morbidity in HF patients. The aim of this study is to determine if a 6-week course of heart rate variability (HRV) biofeedback and breathing retraining could increase exercise tolerance, HRV, and quality of life in patients with New York Heart Association Class I-III heart failure (HF). Participants (N = 29) were randomly assigned to either the treatment group consisting of six sessions of breathing retraining, HRV biofeedback and daily practice, or the comparison group consisting of six sessions of quasi-false alpha-theta biofeedback and daily practice. Exercise tolerance, measured by the 6-min walk test (6MWT), HRV, measured by the standard deviation of normal of normal beats (SDNN), and quality of life, measured by the Minnesota Living with Congestive Heart Failure Questionnaire, were measured baseline (week 0), post (week 6), and follow-up (week 18). Cardiorespiratory biofeedback significantly increased exercise tolerance (p = .05) for the treatment group in the high (>or=31%) left ventricular ejection fraction (LVEF) category between baseline and follow-up. Neither a significant difference in SDNN (p = .09) nor quality of life (p = .08), was found between baseline and follow-up. A combination of HRV biofeedback and breathing retraining may improve exercise tolerance in patients with HF with an LVEF of 31% or higher. Because exercise tolerance is considered a strong prognostic indicator, cardiorespiratory biofeedback has the potential to improve cardiac mortality and morbidity in HF patients.


Navigating T-Cell Immunometabolism in Transplantation.
Recently, a new discipline termed "immunometabolism" has transformed the field of immunology. It encompasses the study of the intrinsic metabolic pathways of different immune subsets and their impact on cellular fate and function. For instance, broadly speaking, proinflammatory cells depend on glycolysis and glutamine oxidation, whereas cells involved in anti-inflammatory response, such as Foxp3+ regulatory T (Treg) cells, use predominantly fatty acid oxidation. However, although a useful paradigm, this actually is a reductionist view, and the engagement of these metabolic pathways is not mutually exclusive between these subsets. Over the past several years, new insights and new methods to better dissect, define, and harness the metabolic properties of immune cells for immunotherapeutic purposes have come to the forefront. In this review, we will discuss the metabolic heterogeneity of different T-cell subsets as well as basic principles of integrative technologies, such as metabolomics, which can be used to better understand the metabolic signatures of immune responses. Given the interest of exploiting this information in the context of transplantation, we will highlight the scope of immunometabolism in unraveling novel mechanisms of immune regulation that can be manipulated to promote Treg cell stability and function while inhibiting T effectors to establish long-term transplantation tolerance.


Occupational Competence and Activities of Daily Living Performance in Bronchial Asthma : Compétence professionnelle et performance des activités de la vie quotidienne pour la bronchite asthmatique.
Background. Activity restriction is one of the most common symptoms reported by people living with bronchial asthma. Purpose. The study aimed to determine occupational competence and values in people living with bronchial asthma and compare with the occupational competence and activities of daily living (ADL) of healthy controls. Methods. Twenty individuals with asthma and 20 healthy controls were enrolled. Occupational competence and values were assessed using the Occupational Self-Assessment (OSA) questionnaire. Restriction of ADL was determined using the London Chest ADL Scale. Findings. Occupational competence was lower, and all London Chest ADL scores were significantly higher in asthma individuals compared to controls (p < .05). The most affected parameters reported by asthma individuals on the OSA were the ability to concentrate, perform physical tasks, work toward goals, and use abilities effectively. Implications. Evaluating occupational competence in people living with bronchial asthma is important to identify their occupational problem areas and provide appropriate interventions.


Distal renal tubular acidosis in primary hyperparathyroidism.
Primary hyperparathyroidism manifests biochemically as a disturbance in serum calcium homeostasis. The kidney appears to be the central organ that sets the serum calcium level. Hyperchloraemia, defective urinary acidification and renal tubular acidosis have been reported to be associated with primary hyperparathyroidism. Distal renal tubular acidosis due to primary hyperparathyroidism is rarely reported. Renal tubular dysfunction due to significant hypercalciuria appears to be one of the proposed mechanisms. This case report will highlight a case of primary hyperparathyroidism in a 26-year old Filipino man due to a solitary functioning parathyroid adenoma presenting with recurrent nephrolithiasis leading to distal renal tubular acidosis manifesting with hypokalaemia and hypomagnesaemia. The patient underwent a minimally invasive selective parathyroidectomy that resulted in full reversal of hypercalcaemia and hyperparathyroidism together with the features of distal renal tubular acidosis. He is currently on frequent follow-up for monitoring of electrolyte abnormalities and gradual resolution of nephrocalcinosis.


[Outpatient operations and inpatient care changes according to section sign 115 b SGB V].
The German self-governing bodies have concluded an agreement about ambulant operations and procedures which replaces the inpatient health care situation. It came into force on January 1, 2004. The published catalogue contains specific treatment procedures which define more clearly some problems that occur between the provision of outpatient and inpatient services in the German health care system. Clinical physicians and practising specialists now have equal rights to provide and to charge for the ambulant services that are included in this agreement. These conditions will play a role in the daily routine of hospitals and will influence treatment patterns. A comprehensive knowledge of the basic principles is essential. In the present article, the compulsory agreement and some resulting consequences are elucidated with special relevance to gastroenterology.


Perceptual grouping impairs temporal resolution.
Performance on multisensory temporal order judgment (TOJ) tasks is enhanced when the sensory stimuli are presented at different locations rather than the same location. In our first experiment, we replicated this result for spatially separated stimuli within the visual modality. In Experiment 2, we investigated the effect of perceptual grouping on this spatial effect. Observers performed a visual TOJ task in which two stimuli were presented in a configuration that encouraged perceptual grouping or not (i.e., one- and two-object conditions respectively). Despite a constant spatial disparity between targets across the two conditions, a smaller just noticeable difference (i.e., better temporal resolution) was found when the two targets formed two objects than when they formed one. This effect of perceptual grouping persisted in Experiment 3 when we controlled for apparent motion by systematically varying the spatial distance between the targets. Thus, in contrast to the putative same-object advantage observed in spatial discrimination tasks, these findings indicate that perceptual grouping impairs visual temporal resolution.


Cost-effectiveness of tooth replacement strategies for partially dentate elderly: a randomized controlled clinical trial.
To conduct a cost-effectiveness analysis comparing two different tooth replacement strategies for partially dentate older patients, namely partial removable dental prostheses (RDP) and functionally orientated treatment based on the shortened dental arch concept (SDA). Ninety-two partially dentate older patients completed a randomized controlled clinical trial. Patients were randomly allocated to two treatment groups: the RDP group and the SDA group. Treatment effect was measured using impact on oral health-related quality of life (OHrQOL), and the costs involved in providing and maintaining care were recorded for all patients. Patients were followed for 12 months after treatment intervention. All treatment was provided by a single operator. The total cost of achieving the minimally important clinical difference (MID) in OHrQOL for an average patient in the RDP group was €464.64. For the SDA group, the cost of achieving the MID for an average patient was €252.00. The cost-effectiveness ratio was therefore 1:1.84 in favour of SDA treatment. With an increasingly ageing population, many patients will continue to benefit from removable prostheses to replace their missing natural teeth. From a purely economic standpoint, the results from this analysis suggest that the treatment of partially dentate older adults should be focused on functionally orientated treatment because it is simply more cost-effective.


RELATIONSHIP OF DONOR AGE TO IN VITRO PRODUCTION OF FOOT-AND-MOUTH DISEASE VIRUS BY MOUSE KIDNEY CELLS.
Multiplication of foot-and-mouth disease virus (FMDV) was compared in kidney cells from 7- to 35-day-old mice representing various degrees of age resistance to this virus. Three types of cell preparations were used: primary monolayer cultures, suspensions of dispersed cells, and suspensions of minced tissue. Virus multiplication in the two types of cell suspensions was related to the age of the donors both in regard to time when multiplication first became evident and to the amount of virus produced. While adsorption rates were similar in the cells from all age groups, virus multiplication began earlier in cells from younger mice and more virus was produced by these cells than by cells from older animals. There was no significant difference in the virus growth rates in the primary monolayer cultures of cells. The results indicate that kidney cells from mice 7 to 35 days old vary in their ability to produce virus in relation to the degree of susceptibility of the cell donors. After propagation of the cells in primary monolayer cultures, however, this difference no longer exists probably because of cell selection under the cultural conditions.


ROBO4 deletion ameliorates PAF-mediated skin inflammation via regulating the mRNA translation efficiency of LPCAT1/LPCAT2 and the expression of PAF receptor.
The diminished level of platelet-activating factor acetylhydrolase (PAFAH) in milk causes an enhanced level of platelet activating factor (PAF) in the skin, leading to a severe hair loss phenotype during neonatal pup's lactation. The deletion of very-low-density-lipoprotein receptor (VLDLR) prevents the expression and secretion of PAFAH. Here we revealed that deletion of Roundabout 4 (ROBO4) in mice ameliorated hair loss phenotype via reducing PAF concentration in skin. As a consequence, the neonatal pups with ROBO4 deletion lactated by mother with VLDLR deletion showed normal hair phenotype during lactation. In details,ROBO4 deletion reduced the protein but not mRNA expression of two PAF synthetic enzymes LPCAT1/LPCAT2 in macrophage as well as the expression of PAF receptor in both macrophage and ocular tissue, but increased PAFAH protein in serum. On the other hand, RNA expression profile analysis in macrophages revealed that the genes involving in oxidative phosphorylation and ribosome obviously decreased their expression in response to ROBO4 deletion. Moreover, through High Performance Liquid Chromatography (HPLC) analysis, we found that ATP concentration also reduced in ROBO4 deletion macrophages. Because ribosome and energy are very important factors for the mRNA translation, we then tested whether ROBO4 deletion affects LPCAT1/LPCAT2 mRNA translation using polyribosome assay. As expected, the mRNA level of LPCAT1/LPCAT2 significantly decreased in polyribosome in ROBO4 deletion macrophage comparing to that of wild type. Additionally, mice with ROBO4 deletion suppressed LPS-induced IL-6 expression as well as the phosphorylation of p44/42 and p65, but enhanced the AKT phosphorylation. Collectively, ROBO4 deletion alleviates PAF- and LPS-mediated inflammation. And above results also indicate PAF signal might be a crosstalk point of ROBO4- and VLDLR-activated pathways.


Intrinsic aerobic capacity governs the associations between gut microbiota composition and fat metabolism age-dependently in rat siblings.
Host genetic factors affecting the gut microbiome play an important role in obesity, yet limited attention has been paid on the host genetic factors linked to physical fitness in modifying the microbiome. This study determined whether sibling-matched pairs of rats selectively bred for high (HCR) and low (LCR) aerobic capacity differ in their microbiome age-dependently and which taxa associate with differential in metabolism. Several taxa in young adult rats (hereafter young) linked to inherited aerobic capacity, while in older adult (hereafter old) rats most of the differences between the lines associated with body weight. Despite the absence of weight differential between LCR and HCR when young, the LCR microbiome contained more Actinobacteria, Veillonellaceae, Coriobacteriaceae, Phascolarctobacterium, and Ruminococcus; taxa previously linked to obesity. This raises the question whether the microbiome contributes to the later development of obesity in LCR. Age-related differences were detected in almost all taxa in both rat lines. The young HCR measured higher for serum glycerol and free fatty-acids and lower for cholesterol, HDL, LDL, and triglycerides than LCR. The old HCR differed from the old LCR by lower LDL. Several metabolites, including LDL, are associated age and genetic background-dependently with the microbiome, which might explain the metabolic differences between the lines. While old lines did not differ in visceral adipose tissue gene expression, the young HCR expressed more inflammatory genes than LCR, and several taxa including Proteobacteria associated with these genes. In conclusion, intrinsic aerobic capacity governs the microbiome, which may influence body weight, metabolism, and gene expression.