Illness severity indicators in newborns by COVID-19 status in the United States, March-December 2020.
To better understand COVID-19 in newborns, we compared in-hospital illness severity indicators by COVID-19 status during birth hospitalization. In a retrospective cohort of newborns born March-December 2020 in the Premier Healthcare Database Special COVID-19 Release, we classified COVID-19 status and severe illness indicators using ICD-CM-10 codes, laboratory data, and billing records. Illness severity indicators were compared by COVID-19 status, stratified by gestational age and race/ethnicity. Among 701,777 newborns, 209 had a COVID-19 diagnosis during the birth hospitalization. COVID-19 status differed significantly by race/ethnicity, gestational age, payor, and region. Late preterm/term newborns with COVID-19 had increased intensive care unit admission and sepsis risk; early preterm newborns with COVID-19 had increased risk for invasive ventilation. Risk for illness severity varied among racial/ethnic strata. From March to December 2020, COVID-19 diagnosis in newborns was rare. More clinical data are needed to describe the risk profiles of newborns with COVID-19.


Differences in Bone Mineral Density and Bone Turnover Markers Between Subjects With and Without Diffuse Idiopathic Skeletal Hyperostosis.
Japanese resident cohort study based on a municipal registry. This study of a community-dwelling elderly Japanese population employed random sampling from the basic resident registry of a rural town for subject selection to investigate the differences in bone mineral density (BMD) and bone turnover markers between subjects with and without diffuse idiopathic skeletal hyperostosis (DISH). DISH is a condition characterized by the calcification and ossification of soft tissues. Although some reports have addressed BMD in DISH, the precise status of BMD and bone metabolism in individuals with DISH remains unclear. Eight groups based on age (50s, 60s, 70s, and 80s) and sex after random sampling from the resident registry of Obuse town were established. A total of 411 participants (202 males and 209 females) were enrolled for the evaluation of BMD and bone turnover markers. All subjects underwent a single whole-spine lateral radiographic examination for the existence of DISH. The BMD and bone turnover markers of subjects with and without DISH were analyzed for associations with the disorder using multivariate analysis. DISH was detected in 66 (16.1%) participants in our population cohort. According to multivariate analysis, increased lumbar and hip BMD were significantly related to DISH (odds ratio: 7.47 and 22.8, respectively). This study clarified the differences in BMD and bone turnover markers between subjects with and without DISH on a general population basis. Multivariate analysis revealed increased lumbar and hip BMD to be significantly associated with DISH, with no remarkable findings for bone turnover markers. 4.


Intrathymic administration of B cells induces prolonged survival of fully allogeneic cardiac grafts without prolonged deletion of donor-specific thymocytes.
Intrathymic (IT) injection of alloantigen has been shown to induce unresponsiveness to allografts although the exact mechanisms of tolerance induction remains unclear. C57BL/10 (H2b) cardiac allografts were accepted in C3H/He (H2k) mice pretreated with IT inoculation of donor splenocytes (1 x 10(6)) in combination with a depleting anti-CD4 monoclonal antibody 27 days before cardiac transplantation. To investigate which cell types were responsible for tolerance induction by IT injection of alloantigen, resting B (rB) cells or dendritic cells were used as the thymic inoculum instead of whole splenocytes. IT injection of rB cells induced indefinite graft prolongation in all recipients while only 20% of mice that had received IT injection of dendritic cells accepted grafts for over 100 days. In contrast, IT injection of dendritic cells resulted in significant deletion of donor-specific thymocytes whereas rB cells were relatively ineffective. IT deletion is not essential for the induction of tolerance by IT injection of rB cells; nondeletional mechanisms can be involved.


Bilateral anterior uveitis as a presenting feature of Juvenile Xanthogranuloma in a neonate.
To report a case of diffuse xanthogranuloma presenting as bilateral anterior uveitis in a neonate. A neonate was brought by the parents with complaints of redness, watering, and photophobia in both eyes for 10 days. Examination under anesthesia revealed the presence of bilateral hyphema, fibrinous membrane, corneal haze, and raised intraocular pressure (IOP). Ultrasound Biomicroscopy revealed diffuse bilateral iris thickening. The child was managed medically with topical glaucoma medications, topical steroids, and cycloplegics. The child responded well with the resolution of hyphema, anterior chamber inflammation, and reduction of IOP. In neonates and infants presenting with bilateral uveitis, spontaneous hyphema, and secondary glaucoma, even in the absence of a well-defined iris lesion, diffuse juvenile xanthogranuloma should be considered as a differential diagnosis.


Central nervous system-directed therapy in the treatment of childhood acute lymphoblastic leukemia and studies of neurobehavioral outcome: Children's Cancer Group trials.
Long-term survival rates in childhood acute lymphoblastic leukemia (ALL) have improved due, in part, to the introduction and subsequent refinements in central nervous system (CNS)-directed therapy. Studies of cognitive, motor, and behavioral functioning, which characterize the patterns and severity of CNS sequelae, are being used increasingly as measurable treatment endpoints. This paper summarizes the advances in CNS-directed therapy derived from Children's Cancer Group randomized therapeutic trials. Results from neurobehavioral outcome studies built upon these trials are also presented. A section of this review is focused on CNS-directed treatments and the neurodevelopmental outcomes of infants diagnosed with ALL, an especially high-risk patient subset. Future studies of neurobehavioral outcome are briefly elaborated in the context of current chemotherapy approaches used in the treatment of childhood ALL.


Adaptive fuzzy integral sliding mode control of blood glucose level in patients with type 1 diabetes: In silico studies.
Currently, artificial pancreas is an alternative treatment instead of insulin therapy for patients with type 1 diabetes mellitus. Closed-loop control of blood glucose level (BGL) is one of the difficult tasks in biomedical engineering field due to nonlinear time-varying dynamics of insulin-glucose relation that is combined with time delays and model uncertainties. In this paper, we propose a novel adaptive fuzzy integral sliding mode control scheme for BGL regulation. System dynamics is identified online using fuzzy logic systems. The presented method is evaluated in silico studies by nine different virtual patients in three different groups for two continuous days. Simulation results demonstrate effective performance of the proposed control scheme of BGL regulation in presence of simultaneous meal and physical exercise disturbances. Comparison of the proposed control method with proportional-integral-derivative (PID) control and model predictive control (MPC) shows a superiority of the adaptive fuzzy integral sliding mode control with regard to two conventional methods of BGL regulation (PID and MPC) and sliding mode control.


Optical coherence tomography characteristics of responses to intravitreal bevacizumab in idiopathic choroidal neovascularization.
To investigate factors associated with responses to intravitreal bevacizumab (IVB) in naive idiopathic choroidal neovascularization (iCNV) by high domain optical coherence tomography (OCT). We retrospectively reviewed clinical data of 40 eyes of iCNV patients who received a single or multiple IVB on an as-needed basis (1.25 mg/0.05 mL). One month after the first injection, subretinal fluid (SRF) volume was evaluated and the eyes were divided into 3 groups based on responses to IVB. Good, moderate, and poor responses were defined as 61%-99%, 30%-60%, and <30% resolution of SRF on OCT after IVB in iCNV, respectively. OCT findings were analyzed to find factors associated with difference in response levels. Comparisons were made using Wilcoxon's matched-pairs signed-rank test, the Mann-Whitney U test for means with continuous data and Fisher's exact test for categorical data. The mean number of IVB was 1.28±1.50 and mean follow up time was 3.60±1.20mo. At postoperative 1mo, there were 8 (20%) eyes in good response, 20 (50%) in moderate response and 12 (30%) eyes in poor response group and at last visit there were 28 good responders (70%), 8 (20%) moderate responders and 4 (10%) poor responders. Statistically significant difference was detected between good responders and non good responders in choroidal neovessels thickness (P=0.029), SRF height (P=0.049) and SRF volume (P=0.031) at post treatment 1mo. OCT is a valuable diagnostic tool. Decrease in choroidal neovessels thickness, SRF height and volume predicts favorable response of iCNV to IVB therapy.


The role of pigs as transport hosts of the human helminths Oesophagostomum bifurcum and Necator americanus.
We conducted a study in an endemic area of both Oesophagostomum bifurcum and Necator americanus in northern Ghana to examine the possibility of pigs acting as transport hosts for these two human helminth species, due to the commonly observed coprophagic habits of pigs. Under controlled conditions four parasite-free pigs consumed fresh faeces from people heavily infected with both helminths, and faeces were subsequently collected from the rectum of the pigs from 5 to 50 h post-feeding. Four to five per cent of the O. bifurcum and N. americanus eggs fed to the pigs were viable and retrieved as third-stage larvae after coproculture of the pigs' faeces. We discuss the possible impact of the coprophagic habits of pigs as potential parasite transport hosts during different seasons in this area of West Africa.


Theophylline and prostaglandin E2 on duodenal bicarbonate secretion: role for 5'-cyclic adenosine monophosphate.
Cyclic adenosine monophosphate (cAMP) has been implicated as an intracellular "second" messenger in duodenal mucosal bicarbonate secretion in animals. The purpose of this study was to determine whether cAMP may mediate duodenal mucosal bicarbonate secretion in humans. In healthy volunteers, a 4-cm segment of proximal duodenum was isolated from gastric and pancreaticobiliary secretions. Either the phosphodiesterase inhibitor theophylline, prostaglandin (PG) E2, or a combination thereof was administered topically to the isolated duodenal mucosa. Theophylline (10(-2) mol/L) and PGE2 (10(-5)-10(-4) mol/L) each significantly increased bicarbonate secretion and transmucosal potential difference. Moreover, when theophylline and PGE2 were administered in combination, the duodenal bicarbonate output was additive compared to either agent alone. When theophylline was infused with increasing doses of PGE2, the dose-response curve was shifted to the left. Furthermore, increases in bicarbonate secretion and transmucosal potential difference were correlated significantly. These results suggest that cAMP may act as an intracellular mediator of human duodenal mucosal bicarbonate secretion.


Variations in diurnal and nocturnal waking state in air traffic controllers.
Physiological variables of 22 air traffic controllers (ATCs), mean age 32, were continuously telemetrically recorded from 08:00 to 17:30 and on the following day from 19:00 to either 00:00 or 0.3:00. EEG (alpha and theta indices, slow delta waves), EOG (palpebral blinks), EMG (from the neck muscles) and EKG (HR) were recorded. Comparison between day and night shows an increase at night of HR and slow waves, particularly after midnight. These results were compared with similar ones obtained from two other populations of the same age having very different professional activities (university personnel and factory workers). The EEG indices and HR are higher in ATCs. The work load imposed by the need in air traffic control to maintain a high level of vigilance, especially difficult after midnight, is in great part responsible for the high values of physiological parameters observed in this study.


Urinary function in patients with corticobasal degeneration; comparison with normal subjects.
Corticobasal degeneration (CBD) is a rare neurodegenerative disorder affecting cerebral cortex and basal ganglia, both of which are crucial for regulating the lower urinary tract function. However, urinary function of this disorder has not been fully delineated. We investigated urinary function in patients with CBD. A questionnaire for storage and voiding urinary symptoms was performed in all 10 patients with CBD (four men, six women; mean age, 67.3 years; mean duration of disease, 3.9 years) and 11 age-matched control subjects (four men and seven women; mean age, 73.0 years). Urodynamic studies were performed in six of the patients and all control subjects, including electromyography (EMG)-cystometry and analysis of motor unit potentials of the external sphincter. As compared to the control subjects (27%), patients with CBD had more common urinary symptoms (80%, P < 0.05). The urinary symptoms appeared 1-3 years after the onset of the disease, and were more common in patients with longer disease duration (>5 years) and in patients with forced grasp reflex. Nocturnal frequency was the most common and tended to be the initial urinary symptom (seven), followed by urinary incontinence (six), urinary urgency (six), diurnal frequency (five), and difficulty in voiding (five). None was in a state of urinary retention. While, one asymptomatic patient showed normal urodynamic finding, all five symptomatic patients showed various abnormalities, including decreased bladder capacity (four), detrusor overactivity (DO) (three), which was noted only in one of the control subjects, detrusor hypocontractility on voiding (three), and low compliance detrusor (one). None of the patients had post-void residuals, detrusor-sphincter dyssynergia, or neurogenic motor unit potentials of the external sphincter muscles. Although the number of our patients was small, the present study suggests that urinary dysfunction is a common feature in patients with CBD. Since decreased bladder capacity and DO were common in the symptomatic patients, lesions in the supranuclear parasympathetic system are mainly responsible for their dysfunction.


Hypercalciuria in idiopathic Fanconi syndrome.
A 9 year old girl with idiopathic Fanconi syndrome and hypercalciuria is described. In order to determine whether the increased calcium excretion was directly or indirectly due to the disturbed phosphate metabolism, the behavior of the calcium excretion during therapy, the serum levels of 1,25-dihydroxyvitamin D and parathyroid hormone, and the effect of parathyroid hormone on the renal tubules were investigated. Normal serum 1,25-dihydroxyvitamin D and parathyroid hormone levels, lack of a correlation between the serum phosphate concentration and the degree of hypercalciuria, as well as unsuccessful therapy of the hypercalciuria with oral phosphate indicate that the increased calcium excretion cannot be explained by impaired renal phosphate reabsorption. The hypercalciuria in the patient was therefore regarded as being due to a primary decrease of tubular calcium reabsorption.


Myocardial rupture after small acute myocardial infarction in the absence of coronary artery disease.
A 73-year-old woman with a past medical history of hypertension suffered a cardiac arrest. After successful resuscitation, she was hypotensive and tachycardic and the ECG showed ST elevation in the inferior and lateral precordial leads. Coronary angiography did not show evidence of obstructive coronary artery disease. A bedside echocardiogram demonstrated a large pericardial effusion with signs of cardiac tamponade. The echocardiogram and subsequent aortic root angiography did not reveal evidence of dissection. Pericardiocentesis removed 700 cc of bloody fluid with relief of tamponade. A few minutes later the patient again arrested. Fluid was again drained but she suffered recurrent hemodynamic collapse and could not be resuscitated. Autopsy revealed a small transmural myocardial infarction with external rupture and hemopericardium. There was only mild coronary artery disease without evidence of plaque rupture. This case illustrates that mild coronary artery disease and a small myocardial infarction can lead to catastrophic mechanical complications.


Role of isosorbide dinitrate in management of chronic congestive heart failure.
Congestive heart failure is accompanied by a number of compensatory mechanisms that may overshoot the mark. Among these are excessive arteriolar and venous constriction. Nitrates are effective in producing venodilation, redistributing blood from the chest to the periphery, and lowering right and left atrial pressures. Although oral isosorbide dinitrate is effective in producing acute beneficial hemodynamic effects, it usually does not increase exercise tolerance in the short term. Prolonged administration, however, does increase exercise tolerance and improve clinical class. Isosorbide dinitrate can be effectively combined with an arteriolar dilator such as hydralazine, which increases cardiac output. Such vasodilator therapy is symptomatically effective in patients with heart failure, although there is no evidence to date to suggest a prolongation of life.


The Pamela study: main findings and perspectives.
PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) is an epidemiological study, originally designed to determine the normality of home and ambulatory blood pressure values. The study was performed on 3,200 subjects, aged 25 to 74 years, randomly selected from the general population of Monza (Milan, Italy). In the study context we performed clinical, home and ambulatory blood pressure measurements, echocardiographic assessment of cardiac structure and function as well as laboratory examinations (glucose and lipids). Personal and family histories were collected. The same procedures were repeated 10 years later. During a 12-year follow-up, the incident cardiovascular events were validated. Cardiovascular and all-cause fatal events were collected for a 16-year follow-up. This article will review the main results of the PAMELA study, with particular emphasis on (1) the prognostic value of the different blood pressure measurements, (2) the relationships between metabolic variables and blood pressure and (3) the clinical relevance and prognostic importance of left ventricular mass values and alterations.


Evidence for host-cell selection of influenza virus antigenic variants.
Extensive antigenic variability and a capricious epidemiology are characteristics of influenza A and B viruses of man. The haemagglutinin (HA) undergoes frequent and progressive antigenic drift as a result of selection, under immunological pressure, of viruses possessing alterations in the amino acid sequences at specific sites in the molecule. Here we present evidence for an additional selection mechanism for antigenic variants of influenza virus that depends on differing host cell tropisms of virus subpopulations. These studies were initiated after earlier observations of the occurrence of a marked degree of antigenic variation during passage of laboratory strains of influenza virus in eggs and cell cultures (J.C.J., in preparation). We have now shown that cultivation of influenza B viruses in eggs selects subpopulations which are antigenically distinct from virus from the same source grown in mammalian cell cultures. As antigenic characterization of influenza virus strains for epidemiological purposes and for the preparation of influenza vaccines conventionally relies on the cultivation of virus in eggs, our findings may have important practical implications for vaccine design and efficacy.


Laryngeal carcinoma in patients 40 years of age and younger.
Between 1950 and 1985, 570 patients with squamous cell carcinoma of the larynx were diagnosed and treated in the Otolaryngology Department of the Beilinson Medical Center. Of these, 20 patients (2.8%) were aged 40 years or younger. Twelve patients (60%) had glottic carcinoma in Stage I (T1N0M0) when initially diagnosed, one patient had supraglottic carcinoma in Stage I (T1N0M0) and seven patients (35%) had laryngeal carcinoma in Stage II (T2N0M0) and III (T3N0M0). Patients with T1N0M0 received only radiotherapy. Three patients with T2N0M0 underwent total laryngectomy and also received postoperative radiotherapy. Four patients with the tumor in T3N0M0 received pre-operative and postoperative radiotherapy in addition to total laryngectomy. The 5-year survival rate for T1N0M0 and T2N0M0 was 100% and for T3N0M0 66%. Although a high percentage of the young patients presented for treatment with advanced disease, the survival rate compared the same or favorably with rates in older patients. This supports the concept of aggressive treatment when there is a recurrence or second primary, particularly because it is well tolerated in the young age group who do not exhibit many of the conventional risk factors and therefore, have a better prognosis.


Characterization of the low-copy HERV-Fc family: evidence for recent integrations in primates of elements with coding envelope genes.
In a previous search based on the envelope gene, we had identified two related proviral elements that could not be included in identified ERV families. An in silico database screening associated with an in vivo polymerase chain reaction search using primers in the reverse transcriptase domain, now allowed identification of a series of related elements, found at a limited number in simians. A phylogenetic analysis led to their inclusion in a new family of endogenous retroviruses with limited expansion, which we named ERV-Fc, and which is part of the enlarged ERV-F/H family. The human genome comprises only six HERV-Fc, among which two possess full-length coding envelope genes. A complete provirus was identified in the baboon, also disclosing a fully open envelope gene. Cloning of the sites orthologous to the envelope-coding human proviruses demonstrated presence of the integrated proviruses in chimpanzee and gorilla, but not in orangutan. For the baboon element, the orthologous locus was found empty even in the phylogenetically most closely related macaque, again suggesting, together with the complete identity of its LTRs, "recent" integration. The data presented are compatible with an evolutionary scheme in which the ERV-Fc proviruses would be the endogenous traces of an active retroviral element, possibly acting as an infectious retrovirus with low endogeneization potency, with evidence for integrations at two distinct periods of primate evolution.


[Weight, height, skull and chest circumferences, biparietal diameter in the newborn infant as a function of gestational age, weight, height and weight gain of the mother].
The weights, heights, skull and chest circumferences and biparietal diameters were measured in 7,905 newborns in 1972, in the 5 maternity hospitals of Lyon. These data were studied with respect to the gestational ages of the children and according to the usual weights, heights and weight gains of the mothers. The evolution of these parameters was compared to each other; tentative explanations are given.


The National Heart Lung and Blood Institute Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease Alliance.
To describe the National Heart Lung and Blood Institute (NHLBI) sponsored Disparities Elimination through Coordinated Interventions to Prevent and Control Heart and Lung Disease (DECIPHeR) Alliance to support late-stage implementation research aimed at reducing disparities in communities with high burdens of cardiovascular and/or pulmonary disease. NHBLI funded seven DECIPHeR studies and a Coordinating Center. Projects target high-risk diverse populations including racial and ethnic minorities, urban, rural, and low-income communities, disadvantaged children, and persons with serious mental illness. Two projects address multiple cardiovascular risk factors, three focus on hypertension, one on tobacco use, and one on pediatric asthma. The initial phase supports planning activities for sustainable uptake of evidence-based interventions in targeted communities. The second phase tests late-stage evidence-based implementation strategies. Not applicable. We provide an overview of the DECIPHeR Alliance and individual study designs, populations, and settings, implementation strategies, interventions, and outcomes. We describe the Alliance's organizational structure, designed to promote cross-center partnership and collaboration. The DECIPHeR Alliance represents an ambitious national effort to develop sustainable implementation of interventions to achieve cardiovascular and pulmonary health equity.


A role for L-type calcium channels in the maturation of parvalbumin-containing hippocampal interneurons.
While inhibitory interneurons are well recognized to play critical roles in the brain, relatively little is know about the molecular events that regulate their growth and differentiation. Calcium ions are thought to be important in neuronal development and L-type voltage gated Ca(+2) channels have been implicated in activity-dependent mechanisms of early-life. However, few studies have examined the role of these channels in the maturation of interneurons. The studies reported here were conducted in hippocampal slice cultures and indicate that the L-type Ca(+2) channel agonists and antagonists accelerate and suppress respectively the growth of parvalbumin-containing interneurons. The effects of channel blockade were reversible suggesting they are not the result of interneuronal cell death. Results from immunoblotting showed that these drugs have similar effects on the expression of the GABA synthetic enzymes, glutamic acid decarboxylase65, glutamic acid decarboxylase67 and the vesicular GABA transporter. This suggests that L-type Ca(+2) channels regulate not only parvalbumin expression but also interneuron development. These effects are likely mediated by actions on the interneurons themselves since the alpha subunits of L-type channels, voltage-gated calcium channel subunit 1.2 and voltage-gated calcium channel subunit 1.3 were found to be highly expressed in neonatal mouse hippocampus and co-localized with parvalbumin in interneurons. Results also showed that while these interneurons can contain either subunit, voltage-gated calcium channel subunit 1.3 was more widely expressed. Taken together results suggest that an important subset of developing interneurons expresses L-type Ca(+2) channels alpha subunits, voltage-gated calcium channel subunit 1.2 and especially voltage-gated calcium channel subunit 1.3 and that these channels likely regulate the development of these interneurons in an activity-dependent manner.


Diagnostic difficulties in aortic dissection. Retrospective study of 89 surgically treated patients.
During the years 1964-1985, a total of 89 patients were operated on for aortic dissection: 55 were treated for proximal dissection and 34 for distal dissection of the aorta. In the former group a diagnostic delay more than 24 hours after hospitalization occurred in 17 instances (31%), and in the latter group in 18 instances (53%). The most common incorrect diagnosis in both groups was myocardial infarction. In the proximal group of aortic dissection, other cardiac diseases suspected were pericarditis, endocarditis and congestive heart failure. In the distal group of aortic dissection, acute surgical abdomen was the most common cause of incorrect diagnosis after ischaemic heart disease. Four case reports with diagnostic delay are presented.


Development and validation of a particle-enhanced turbidimetric immunoassay for C-reactive protein.
The development of a particle-enhanced turbidimetric immunoassay for C-reactive protein is described. The method demonstrates excellent precision, with the calibration curve remaining stable for at least 16 weeks. The method compares well with established techniques and there is no interference from a variety of autoantibodies, endogenous serum constituents or commonly used drugs.


Nutrition support in major burn injury: case analysis of dietetic activity, resource use and cost implications.
Patients with major burn injury are among the most catabolic and nutritionally vulnerable of all hospital admissions. A considerable amount of dietetic intervention is often required. To date, UK practice has not been described in detail. This study aimed to identify nutritional interventions, resource use and associated costs for a typical patient admitted with major burns. A 28-year-old male with 43.5% total body surface area flame injury was selected for study. Dietetic, medical and pharmacy records were reviewed for data regarding nutritional status, interventions and product use. Costs of dietetic staffing, nutrition support products, related ancillary items and hospital food provision were calculated. The patient required 68 days of nutrition support, including 40 days of nasogastric tube feeding. Seventy per cent of bedside reviews resulted in dietetic intervention. Initiation of nutrition support, substrate use, and frequency of biochemical and weight monitoring were largely in compliance with practice guidelines. Overall cost of nutritional care for the inpatient episode was pound 1377. Work is now required to assess current nutrition practices across different UK centres and for a range of burn severities, to establish a baseline from which resource and financial requirements can ultimately be developed.


Valence processing in pons.
In this issue of Neuron, Xiao et al.1 reported that inhibitory and excitatory neurons in the pontine central gray encode and transmit opposite valences of sensory stimuli through parallel circuits to a distributed brain network.


Hypoglycemic and antioxidative effects of hydroxyethyl methylcellulose in mice fed with high fat diet.
The effect of hydroxyethyl methylcellulose (HEMC) with different viscosities on the glucose metabolism and antioxidative defense system in high fat-fed mice was investigated. The mice were randomly divided into five dietary groups: normal control diet (NC), high fat diet (HF), and high fat diet supplemented with high viscosity (HF-HV), moderate viscosity (HF-MV), and low viscosity (HF-LV) HEMC fibers. After 6 weeks, the HF group showed a marked increase in body weight gain, body fat, blood glucose concentration, insulin level, and erythrocyte lipid peroxidation rate relative to the NC group. However, supplementation of HEMC in the diet suppressed these high fat-induced hyperglycemia and oxidative stress through enhancement of the activities of hepatic glucokinase and antioxidant enzymes. The hypoglycemic and antioxidative effects increased with increased viscosity of the HEMC consumed. These results illustrate that HEMC with high viscosity may be useful in the management of high fat diet-induced hyperglycemia and oxidative stress.


Complete Genome Sequence and Manual Reannotation of Mycobacterium avium subsp. paratuberculosis Strain DSM 44135.
Here, we report the complete genome sequence of the Mycobacterium avium subsp. paratuberculosis reference strain DSM 44135, amended with a manual genome reannotation. The strain was originally described as M. paratuberculosis strain 6783. It was isolated from feces from a dairy cow in northern Germany.


Investigation of a MOSFET dosimetry system for midpoint dose verification in prostate 3D CRT/IMRT.
The suitability of MOSFETs (Metal Oxide Semiconductor Field Effect Transistors) for use in in-vivo dosimetry for IMRT prostate treatment and patient setup errors has been investigated in this work. MOSFETs were placed on entrance and exit surfaces of a number of different phantoms (with varying complexities from homogeneous to anthropomorphic). Dose measurements were then used to calculate a midpoint dose, which was compared with an IC placed at the isocentre. The agreements found between the calculated (MOSFETs) and the measured midpoint dose (IC) was: 0.7% for a prostate treatment verification and 3.5% for an IMRT treatment. MOSFETs placed on entry and exit surfaces can detect patient setup offsets of 2 cm, but do not have the sensitivity to confidently detect offsets of 1 cm or smaller.


M2-polarized tumor-associated macrophages promote epithelial-mesenchymal transition via activation of the AKT3/PRAS40 signaling pathway in intrahepatic cholangiocarcinoma.
Tumor-associated macrophages (TAMs) have been considered as a major component of the tumor microenvironment. However, the crosstalk between M2-polarized tumor-associated macrophages (M2-TAMs) and intrahepatic cholangiocarcinoma (ICC) remains undetermined. In the present study, we aimed to clarify the role of M2-TAMs in ICC and the underlying mechanism. The in vitro assay demonstrated M2-TAMs promoted epithelial-mesenchymal transition (EMT) of ICC cells, resulting in enhanced cell invasion and metastasis ability. Moreover, M2-TAMs modulated the microenvironment of ICC by increasing the secretion of cytokines (GM-CSF, tumor necrosis factor-α [TNF-α], ICAM-1, interleukin-6 [IL-6], etc) and chemokines (CCL1, CCL3, etc). In addition, p-AKT (Ser473) and p-PRAS40 (Thr246) were upregulated in ICC cells when cocultured with M2-TAMs or treated with M2-TAMs secreted core cytokines (GM-CSF, TNF-α, ICAM-1, and IL-6). Consistently, AKT3 silencing (but not AKT1 silencing and AKT2 silencing) markedly inhibited phosphorylation of AKT and PRAS40 of ICC cells and inhibited the EMT process when cocultured with M2-TAMs. Taken together, the current data indicated that M2-TAMs promoted ICC cells EMT, partially through increasing secretion of cytokines and chemokines, thus modulating the microenvironment and activating the AKT3/PRAS40 signaling pathway.


Stability, optoelectronic and thermal properties of two-dimensional Janusα-Te2S.
Motivated by recent progress in the two-dimensional (2D) materials of group VI elements and their experimental fabrication, we have investigated the stability, optoelectronic and thermal properties of Janusα-Te2S monolayer using first-principles calculations. The phonon dispersion and MD simulations confirm its dynamical and thermal stability. The moderate band gap (∼1.5 eV), ultrahigh carrier mobility (∼103cm2V-1s-1), small exciton binding energy (0.26 eV), broad optical absorption range and charge carrier separation ability due to potential difference (ΔV = 1.07 eV) on two surfaces of Janusα-Te2S monolayer makes it a promising candidate for solar energy conversion. We propose various type-II heterostructures consisting of Janusα-Te2S and other transition metal dichalcogenides for solar cell applications. The calculated power conversion efficiencies of the proposed heterostructures, i.e.α-Te2S/T-PdS2,α-Te2S/BP andα-Te2S/H-MoS2are ∼21%, ∼19% and 18%, respectively. Also, the ultralow value of lattice thermal conductivity (1.16 W m-1K-1) of Janusα-Te2S makes it a promising material for the fabrication of next-generation thermal energy conversion devices.


[Lung scintigraphy after diphragmatic hernia (author's transl)].
Recuperation of pulmonary function after surgical repair of Bochdaleck's hernia is considered. Gasometric and radiologic features as well as scintigraphy are related in order of prognosis. Of 16 cases, seven had sudden fatal outcome. Survivals achieved total pulmonary recuperation, but some in two to three years.


Therapy response assessment in metastatic melanoma patients treated with a BRAF inhibitor: adapted Choi criteria can reflect early therapy response better than does RECIST.
Targeted therapy can lead to considerable tumor reduction and may result initially in altered tissue at constant tumor size. In this setting, Response Evaluation Criteria in Solid Tumors (RECIST) can be inadequate for assessing early treatment response. Choi-criteria combine both size and density measurements. Our purpose was to evaluate computed tomography (CT) images of melanoma patients under BRAF-inhibitor therapy according to Choi-criteria which were adapted to our study (aChoi). Twelve patients (four male, eight female, mean age 49) with stage IV melanoma treated with a BRAF inhibitor were included. Response was assessed according to RECIST for 39 lesions in contrast-enhanced CT. Target volumes are semiautomatically segmented to calculate mean density for aChoi-criteria, thus using a two-dimensional nonstandardized region of interest could be prevented. Eight patients are RECIST responders. aChoi-criteria indicate therapy response earlier compared to RECIST in five of eight patients. In seven cases, tumor density in CT had decreased 8 weeks after therapy start, whereas in some cases tumor size diminished less or even increased. Response according to aChoi was diagnosed in seven patients who showed in RECIST-evaluation stable disease in five and partial response in two cases. Fifteen weeks after therapy start almost all patients within the aChoi responders were RECIST responders, too. Only one aChoi responder showed still stable disease in RECIST. Our initial data indicate that aChoi-criteria can reflect response to vemurafenib earlier compared to RECIST. This is of clinical significance as BRAF-inhibitors are cost-intensive targeted therapies and can cause severe side effects, so criteria for early therapy response have to be evaluated.


[Trained stroke helpers : Voluntary care model in outpatient stroke aftercare].
The rehabilitation of people after suffering a stroke is a long-term process, in which patients, their families and friends are reliant on social support and assistance. Therefore, the individual promotion of available resources and autonomy of those affected represents an important task. The College for Health in Bochum and the German Stroke Help Foundation have developed the volunteer-supported model "Trained stroke helpers-a partnership-based model for local care (GeSa)" that educates stroke helpers as experts for individual local support of stroke patients and their relatives. The stroke helpers offer a patient-oriented care and individual assistance in the daily routine and therefore make a contribution to improvement of the health-related quality of life of those affected and their relatives. A training curriculum was developed and successfully tested and evaluated in a course with 21 stroke helpers. Up to summer 2020 a total of 480 stroke helpers have been trained at 16 locations in 37 courses. The experiences with the project have so far been consistently positive, which was confirmed by two scientific studies. The inclusion of cooperation partners for the coordination of the volunteers, which was already implemented in the model project, has been shown to be the most important success factor for the sustainability of the project. This article presents the results of the pilot study and the standardized process on implementation of a regional stroke helper project and describes the experiences with the previous course of the project.


The EQ-5D: a new tool for studying clinical outcomes in chronic rhinosinusitis.
To describe the role and applicability of the EuroQol 5-Dimension, 5-Level (EQ-5D-5L) questionnaire for the assessment of general health-related quality of life in patients with chronic rhinosinusitis. Prospective cohort study. The EQ-5D-5L was administered to 462 patients with refractory chronic rhinosinusitis before and 3 months after sinus surgery. Preoperative and postoperative scores across each of five health dimensions were analyzed and the results compared to those obtained from two widely used chronic rhinosinusitis outcomes instruments: the Chronic Sinusitis Survey (CSS) and SinoNasal Outcomes Test-22 (SNOT-22). Three hundred and fifty patients completed the five questions and visual analog scale (VAS) of the EQ-5D at baseline and at 3 months for a response rate of 75.8%. There were no incomplete questionnaires. The frequency of patients reporting problems in the EQ-5D domains of pain/discomfort, anxiety/depression, and usual activities decreased following sinus surgery (74.3% vs. 34.4%, 48.6% vs. 31.4%, and 30.6% vs. 19.4%, respectively; all P < 0.001). The domains of mobility and self-care did not demonstrate statistically significant change. EQ-5D VAS (standard deviation) improved from 73.4 (16.9) before surgery to 82.0 (14.4) after surgery (P < 0.001). Preoperative VAS correlated with SNOT-22 scores (Pearson coefficient of 0.50; P < 0.01). Postoperative change in VAS and SNOT-22 scores demonstrated moderate correlation (Pearson coefficient of 0.36, P < 0.01). The EQ-5D is a general health measure with sensitivity to clinical change in rhinosinusitis that support its use for monitoring patient outcomes. The limited response burden and ability to directly calculate health utility make it an attractive tool for rhinosinusitis outcomes research.


Insulin-like androgenic gland hormone 1 (IAG1) regulates sexual differentiation in a hermaphrodite shrimp through feedback to neuroendocrine factors.
Insulin-like androgenic gland hormone (IAG) is regarded as a key sexual differentiation regulator in gonochoristic crustaceans. However, until now the knowledge concerning its functions in hermaphroditic crustaceans is scanty. Herein, we investigated the function of IAG (Lvit-IAG1) in peppermint shrimp Lysmata vittata, a species that possesses protandric simultaneous hermaphroditism (PSH) reproductive system, which is rare among crustaceans. Lvit-IAG1 was exclusively expressed in the androgenic gland. The qRT-PCR demonstrated that its mRNA expression level was relatively high at the functional male phase but decreased sharply in the subsequent euhermaphrodite phase. Both the short-term and long-term silencing experiments showed that Lvit-IAG1 negatively regulated both the gonad-inhibiting hormone (Lvit-GIH) and crustacean female sex hormone (Lvit-CFSH) expressions in the eyestalk ganglion. Besides, Lvit-IAG1 gene knockdown induced a retarded development of the appendices masculinae (AM) and male gonopores while suppressing the germ cells at the primary spermatocyte stage. Also, Lvit-IAG1 gene silencing hindered ovarian development. This in turn led to small vitellogenic oocytes and decreased expression of vitellogenin and vitellogenin receptor genes in hepatopancreas and ovarian region, respectively. Generally, this study's findings imply that Lvit-IAG1 modulated the male sexual differentiation in PSH species L. vittata, and exhibited negative feedback on Lvit-GIH and Lvit-CFSH genes expression in the species' eyestalk ganglion.


Patient Satisfaction with Virtual Clinic Encounters: Analysis of Factors that Impact the Press Ganey Survey in the Hand Surgery Population.
Our purpose was to identify patient characteristics and visit components that affect patient satisfaction with virtual new patient visits in an outpatient hand surgery clinic as measured by the Press Ganey Outpatient Medical Practice Survey (PGOMPS) total score (primary outcome) and provider subscore (secondary outcome). Adult patients evaluated through virtual new patient visits at a tertiary academic medical center between January 2020 and October 2020 who completed the PGOMPS for virtual visits were included. Data regarding demographics and visit characteristics were collected via chart review. Factors associated with satisfaction were identified using a Tobit regression model on the continuous score outcomes (Total Score and Provider Subscore) to account for substantial ceiling effects. A total of 95 patients were included: 54% were men and the mean age was 54 ± 16 years. Mean area deprivation index was 32 ± 18, and the mean driving distance to the clinic was 97 ± 188 mi. Common diagnoses include compressive neuropathy (21%), hand arthritis (19%), hand mass (12%), and fracture/dislocation (11%). Treatment recommendations included small joint injection (20%), in-person evaluation (25%), surgery (36%), and splinting (20%). Multivariable Tobit regressions showed notable differences in satisfaction by the provider on the Total Score but not on the Provider Subscore. Other factors known to affect the PGOMPS scores for in-person visits were not notably associated with the Total or Provider Sub-Scores for virtual visits (area deprivation index, age, and offer of surgery or injection) other than the body mass index. Virtual clinic visit satisfaction was affected by the provider. Wait time strongly affects satisfaction with in-person visits but is not accounted for by the PGOMPS scoring system for virtual visits, which is a limitation of their survey. Further work is required to determine how to improve the patient experience with virtual visits. Prognostic IV.


Reverend Paley's naturalist revival.
This paper analyzes the remarkable popularity of William Paley's argument from design among contemporary naturalists in biology and the philosophy of science. In philosophy of science Elliott Sober has argued that creationism should be excluded from the schools not because it is not science but because it is 'less likely' than evolution according to fairly standard confirmation theory. Creationism is said to have been a plausible scientific option as presented by Paley but no longer to be acceptable according to the same standards that once approved it. In biology C. G. Williams and Richard Dawkins have seen in Paley a proto-adaptationist. This paper shows that the historical assumptions of Sober's arguments are wrong and that the philosophical arguments themselves take alternatives to science to be alternatives in science and conflate the null hypothesis, chance, with a competing explanatory hypothesis. It is also shown that the similarity of Paley's adaptationism to that of contemporary biology is not what it is made out to be.


An unusual transitory increase of lupus anticoagulant in dengue virus infection complicated with cerebral ischaemia.
Dengue is a common mosquito-transmitted viral disease prevalent at many undeveloped and developing countries. Although, neurological complication and hemostatic disturbance are common in dengue virus infection, cerebral ischaemia is barely mentioned. A 61-year-old woman experienced an acute onset of right hemiparesis in her early course of dengue virus type II infection. Extensive laboratory investigation revealed an increase of lupus anticoagulant activity and a prolonged activated partial thromboplastin time that were normalized in the convalescent stage. Her human leucocyte antigens were A2, A11, B8, Cw7, DR4 and DR9. This patient highlights the co-operation between transient activation of humoral immunity and preferential immunogenetic for coagulopathic thrombosis in specific viral disease.


Panel 2.12: the health sector contribution to disaster reduction.
This is a summary of the presentations and discussion of Panel 2.12, The Health Sector Contribution to Disaster Reduction, of the Conference, Health Aspects of the Tsunami Disaster in Asia, convened by the World Health Organization (WHO) in Phuket, Thailand, 04-06 May 2005. The topics discussed included issues related the health sector's contribution to disaster reduction as pertain to the damage created by the Tsunami. It is presented in the following major sections: (1) issues; (2) lessons learned; and (3) recommendations.


Heterogeneity in resistance to food-related stresses and biofilm formation ability among verocytotoxigenic Escherichia coli strains.
This study assessed the resistance of ten verocytotoxigenic Escherichia coli (VTEC) isolates of commonly encountered serogroups/-types and two non-pathogenic E. coli strains to various food-related stresses (acid, alkaline, heat and high hydrostatic pressure treatments) and their biofilm formation ability. In addition, the global changes in the cellular composition in response to the exposure to these adverse environments were monitored by Fourier Transform Infrared (FT-IR) spectroscopy for two of the strains. Large inter-strain variations in stress resistance were observed. The most tolerant strains belonged to serogroup O157 which included both the O157:H7 type strain EDL933 and a representative isolate of the sorbitol fermenting O157:H- VTEC clone (strain MF3582). Strain C-600, a non-pathogenic laboratory strain, was sensitive to multiple stresses. Although wide variation in biofilm-forming ability was observed among VTEC isolates, no consistent relationships between biofilm-forming ability and capacity to withstand stress exposures were found. Analysis of the allelic status of the rpoS gene, involved in the general stress response of stationary-phase cells, allowed detection of loss-of-function mutations for two strains, E218/02 and MF2411, both of them showing as common features a high sensitivity to alkaline and heat treatments and a poor ability to form mature biofilms. Evidences found in this study confirm rpoS as a highly mutable gene in nature, and suggest its relevance not only for the mount of an active stress response but also for the establishment of mature biofilm communities. Our findings contribute to increase the knowledge on the resistance of VTEC to environmental stresses commonly encountered in the food chain, which can lead to improved strategies for preventing VTEC infections.


Cold exposure induces tissue-specific modulation of the insulin-signalling pathway in Rattus norvegicus.
Cold exposure provides a reproducible model of improved glucose turnover accompanied by reduced steady state and glucose-induced insulin levels. In the present report we performed immunoprecipitation and immunoblot studies to evaluate the initial and intermediate steps of the insulin-signalling pathway in white and brown adipose tissues, liver and skeletal muscle of rats exposed to cold. Basal and glucose-induced insulin secretion were significantly impaired, while glucose clearance rates during a glucose tolerance test and the constant for glucose decay during a 15 min insulin tolerance test were increased, indicating a significantly improved glucose turnover and insulin sensitivity in rats exposed to cold. Evaluation of protein levels and insulin-induced tyrosine (insulin receptor, insulin receptor substrates (IRS)-1 and -2, ERK (extracellular signal-related kinase)) or serine (Akt; protein kinase B) phosphorylation of proteins of the insulin signalling cascade revealed a tissue-specific pattern of regulation of the molecular events triggered by insulin such that in white adipose tissue and skeletal muscle an impaired molecular response to insulin was detected, while in brown adipose tissue an enhanced response to insulin was evident. In muscle and white and brown adipose tissues, increased 2-deoxy-D-glucose (2-DG) uptake was detected. Thus, during cold exposure there is a tissue-specific regulation of the insulin-signalling pathway, which seems to favour heat-producing brown adipose tissue. Nevertheless, muscle and white adipose tissue are able to take up large amounts of glucose, even in the face of an apparent molecular resistance to insulin.


Development of methicillin-resistant Staphylococcus aureus keratitis in a dry eye patient with a therapeutic contact lens.
The aim was to report a case of methicillin-resistant Staphylococcus aureus (MRSA) keratitis possibly associated with the use of a silicone hydrogel soft contact lens in a patient with dry eye. This is a case report. A 61-year-old woman who wore a silicone hydrogel lens as therapy for filamentary keratitis with severe dry eye presented with pain and redness in her left eye. She developed severe keratitis with ulceration and hypopyon. The MRSA grew in the culture, and intensive systemic and topical antibiotics resolved the corneal keratitis. The MRSA may cause infectious keratitis associated with silicone hydrogel contact lens therapy.


Enough Sight to Fight? The history of military visual system requirements.
Medicine has a six-fold role to play in war, 1) selection of suitable military personnel, 2) to protect against disease, 3) to give medical attention and treatment to those who are ill and injured, 4) to assist in the rehabilitation of the disabled, 5) research to improve etiology and treatments of disease, and 6) the unit surgeon serves as a special staff officer to the military commander at all levels of a battalion and above, along with the attorney and chaplain, and supplies medical input into all plans whether it be training or combat operations. This article focuses on the realization by soldiers, since antiquity, the importance of the visual system in battle, how this was measured, and how modern military visual requirements have evolved along with the science of ophthalmology. Necessity and natural selection were the driving forces for recruitment and assignment in ancient and medieval armies. Since the advent of mechanized warfare, more soldiers can perform more tasks, more uniformly, radically changing the way soldiers are selected. Modern military duty eligibility requirements and assignments are now the result of special tests and documentation procedures resulting from a mixture of medical knowledge, science, and potential legal consequences. Nowhere is this more evident in the stringent visual system requirements for military service.


Effect of season and climate on choice of therapy for breast cancer in older women.
We and others have previously found a relative underutilization of breast-conserving surgery with adjuvant radiation therapy in older women diagnosed with early stage breast cancer. Because adjuvant radiotherapy involves daily trips to a facility for 6 weeks, we reasoned that season and climate might influence choice of therapy. Specifically we hypothesized that in northern states, a lower proportion of women would receive breast-conserving surgery plus radiation in the winter months than in summer, whereas in sunbelt states there would be no relationship between season and therapy. Analysis of national Medicare billing tapes for 1990 and SEER tumor registry data for 1983-1990. 43,083 women aged 65 to 79, diagnosed with local or regional breast cancer in 50 states or Washington, DC, who underwent mastectomy or breast-conserving surgery in 1990, and 32,502 women aged 65 to 79 who underwent mastectomy or breast-conserving surgery from 1983 to 1989 at any of the nine SEER sites. Using a variety of analytical approaches, we could find no consistent effect of cold winter climate on choice of breast cancer therapy. Bad weather does not appear to discourage the choice of breast-conserving treatment. It is not known if bad weather influences actual receipt of radiotherapy.


Pharmacological and Non-Pharmacological Treatments for Depression in Parkinson's Disease: An Updated Review.
Depression represents one of the most common non-motor disorders in Parkinson's disease (PD) and it has been related to worse life quality, higher levels of disability, and cognitive impairment, thereby majorly affecting not only the patients but also their caregivers. Available pharmacological therapeutic options for depression in PD mainly include selective serotonin reuptake inhibitors, serotonin and norepinephrine reuptake inhibitors, and tricyclic antidepressants; meanwhile, agents acting on dopaminergic pathways used for motor symptoms, such as levodopa, dopaminergic agonists, and monoamine oxidase B (MAO-B) inhibitors, may also provide beneficial antidepressant effects. Recently, there is a growing interest in non-pharmacological interventions, including cognitive behavioral therapy; physical exercise, including dance and mind-body exercises, such as yoga, tai chi, and qigong; acupuncture; therapeutic massage; music therapy; active therapy; repetitive transcranial magnetic stimulation (rTMS); and electroconvulsive therapy (ECT) for refractory cases. However, the optimal treatment approach for PD depression is uncertain, its management may be challenging, and definite guidelines are also lacking. It is still unclear which of these interventions is the most appropriate and for which PD stage under which circumstances. Herein, we aim to provide an updated comprehensive review of both pharmacological and non-pharmacological treatments for depression in PD, focusing on recent clinical trials, systematic reviews, and meta-analyses. Finally, we discuss the pharmacological agents that are currently under investigation at a clinical level, as well as future approaches based on the pathophysiological mechanisms underlying the onset of depression in PD.


Analytical and clinical evaluation of four commercial SARS-CoV-2 serological immunoassays in hospitalized patients and ambulatory individuals.
This study aimed to compare four anti-SARS-CoV-2 immunoassays in populations presenting different clinical severity levels. Three populations were included: "severe-to-critical" ICU-hospitalized patients (n = 18), "mild-to-moderate" hospitalized patients (n = 16) and non-hospitalized symptomatic patients (n = 24). Four commercial immunoassays were analyzed and validated: anti-IgG ARCHITECT® (Abbott), anti-Total antibodies (Ab) VITROS® (Ortho Clinical Diagnostics), anti-IgG NovaLisa® (NovaTec Immundiagnostica) and Healgen® IgM and IgG (Zhejiang Orient Gene Biotech). Sensitivities were evaluated according to days post-symptoms onset (pso). Specificities were evaluated on SARS-CoV-2-negative control sera collected before January 2020. A majority of severe-to-critically ill patients showed detectable Ab already at day 14 and sensitivities reached 100 % after 22 days pso. For patients with "mild-to-moderate" illness, sensitivities increased by at least 5-fold from day 0 to day 14 pso. Non-hospitalized symptomatic individuals already seroconverted at day 14 days pso with 100 % sensitivities for Total Ab VITROS®. Specificities were evaluated at 97 % for ARCHITECT® and NovaLisa®, 98 % for VITROS® and at 94 % for Healgen® combined IgM and IgG. Five "severe-to-critically" ill patients presented high positive Ab levels for at least 16 weeks pso. The Ab levels and the evaluated sensitivities, representing the true positive rate, increased overtime and were related to the COVID-19 severity. Automated Total Ab immunoassay showed better sensitivities and specificity for immunological surveillance and vaccine evaluation.


CURRENT OPTIONS IN PHARMACOLOGICAL INTERVENTIONS FOR MICROVASCULAR ANASTOMOSIS PATENCY: REVIEW.
The key point for microvascular reconstruction is to preserve patency of flap vessels. Despite great improvement in reconstruction success rates in the last 30 years, ischemic complications are still an undesirable event. The authors assessed recent as well as older literature and compared progression in perioperative pharmacology interventions in antithrombotic prevention.


Diagnostic ability of different tools for detection of glaucoma with confocal scanning laser tomography (Heidelberg Retina Tomograph II).
We evaluated the diagnostic ability of various diagnostic tools to detect glaucomatous damage in 101 normal eyes and 102 glaucomatous eyes. Mikelberg's linear discriminant function (LDF) obtained the best sensitivity followed by our own four formulas. With respect to specificity, Burk's LDF showed better results than Mikelberg's LDF and our formulae. Several Heidelberg retina tomograph analysis tools are useful to discriminate healthy from patients with glaucoma. Alternative tools based on normative databases derived from different autochthon populations add evidence needed to support their global use.


Root zone temperature affects the phytoextraction of Ba, Cl, Sn, Pt, and Rb using potato plants (Solanum tuberosum L. var. Spunta) in the field.
Three consecutive years of field experiments were conducted to investigate how different root-zone temperatures, manipulated by using different mulches, affect the phytoextraction of Ba, Cl, Sn, Pt and Rb in different organs of potato plants (roots, tubers, stems and leaves). Four different plastic covers were used (T1: transparent polyethylene; T2: white polyethylene; T3: white and black coextruded polyethylene, and T4: black polyethylene), using uncovered plants as control (T0). The different treatments had a significant effect on mean root zone temperatures (T0 = 16 degrees C, T1 = 20 degrees C, T2 = 23 degrees C, T3 = 27 degrees C and T4 = 30 degrees C) and induced a significantly different response in Ba, Cl, Sn, Pt and Rb concentration and accumulation. The T3 treatment gave rise to the greatest phytoextraction of Ba, Pt, Cl and Sn in the roots, leaflets and tubers. In terms of the relative distribution of the phytoaccumulated elements (as percentage of the total within the plant), Pt and Ba accumulated mainly in the roots whereas Rb, Sn and Cl accumulated primarily in tubers, establishing a close relationship between the biomass development of each organ and phytoaccumulation capacity of metals in response to temperature in the root zone.


Malperfusion syndrome in acute type A aortic dissection: Thinking beyond the proximal repair.
Malperfusion syndrome (MPS) is associated with the highest mortality and major morbidity risk in patients with acute Type A aortic dissection (TAAD). The timing of the open proximal aortic repair in the presence of MPS remains debatable given variability in clinical presentation and different local treatment algorithms. This paper provides an up to date and comprehensive overview of published outcomes and available techniques for addressing malperfusion in the setting of acute TAAD. We have reviewed published data from the major aortic dissection registries including the International Registry of Acute Aortic Dissection, the German Registry for Acute Aortic Dissection In Type A, and the Nordic Consortium for Acute Type A Aortic Dissection, as well as the most up to date literature involving malperfusion in the setting of acute TAAD. This data highlights unique strategies that have been adopted at aortic centers internationally to address malperfusion in this setting pre-, intra-, and postoperatively, which are summarized here and may be of great clinical benefit to other centers treating this disease with more traditional methods. The review of the available data has definitively shown an increased mortality up to 43% and morbidity in patients presenting with MPS in the setting of acute TAAD. More specifically, preoperative MPS has been shown to be an independent predictor of mortality with mesenteric malperfusion associated with the worst mortality outcomes from 70% to 100%. Addressing MPS pre or intraoperatively is associated with significantly reduced mortality outcomes down to 4%-13%. Adapting a dynamic and easily accessible diagnostic method for the comprehensive assessment of different forms of malperfusion (dynamic/static) and incorporating it within the surgical plan is the first step toward early diagnosis and prevention of malperfusion related complications.


Test-retest intra-rater reliability of grip force in patients with stroke.
Coefficients of repeatability and reproducibility can be guides in differentiating between real changes and measurement error. The aim was to evaluate test-retest intra-rater reliability of a clinical procedure measuring grip force with Grippit in stroke patients, to assess relationship between grip force of the hands and between sustained and peak grip force. Eighteen patients were tested using the Grippit at two occasions one hour apart. Each occasion comprised three consecutive trials per hand. The paretic hand needs to score a 50 N change within and between occasions to exceed the measurement error in 95% of the observations, irrespective of calculation method. Expressed by CV(within) the measurement error was 10%. There was no learning or fatigue effect during measuring. There was a wide variation between subjects but the mean ratio between sides was 0.66. The mean ratio between sustained and peak grip force was 0.80-0.84. The measurement errors were acceptable and the instrument can be recommended for the use in stroke patients at a department of rehabilitation medicine.


Expression of an X-linked gene family (XLR) in late-stage B cells and its alteration by the xid mutation.
One of the most extensively studied X-linked immunodeficiency disorder is the xid mutation of the mouse strain CBA/N. This mutation may involve a maturational defect as xid animals are unable to raise antibodies to soluble polysaccharide antigens, a function normally attributed to late-stage B cells. Moreover, studies using monoclonal antibodies have defined a B-cell surface antigen (BLA-2 or 14G8) that is expressed on most or all immature B lymphocytes, but not on a subpopulation of mature splenic B lymphocytes; this late-stage, 14G8 antigen-negative splenic B-cell subpopulation is apparently absent from mice bearing the xid defect. In the accompanying paper we describe the isolation of a cDNA clone recognizing a family of genes on the X chromosome, at least some of whose members are closely linked to the xid trait. We report here that this gene family, XLR, is transcribed in certain B- and T-cell lineage tumours, but not in macrophage tumours, or liver or kidney cells. We show that it is transcribed principally in late-stage, 14G8-negative B-cell tumours and plasmacytomas, but not in immature B-cell or pre-B-cell tumours. We are able to detect transcription in all of 12 plasmacytomas (secretory B-cell tumours) derived from mice with normal X chromosomes, but not in three plasmacytomas carrying the xid mutation. These data, combined with the restriction fragment length polymorphism analysis linking the XLR gene family to the xid mutation, suggests that the xid defect occurs within a member of this gene family.


Effect of dilute acid pretreatment on the conversion of barley straw with grains to fermentable sugars.
This study investigated the effects of pretreatment conditions, dilute sulfuric acid concentration and treatment time, on the carbohydrate solubility of a mixture of barley straw and grain. The conditions were expressed as combined severity (CS) to evaluate sugar recovery from pretreated samples. Enzymatic hydrolysates from the lignocellulose pretreatment residues were also included to the results. CS was positively correlating with glucose recovery in all conditions, but in higher acid concentrations CS did not predict xylose recovery. It appeared that the residual xylan better indicate the xylose release. An optimal fermentable sugar yield from the mixture of barley straw and grain was obtained by maintaining the CS at around 1.38, corresponding to an overall glucose yield of 96% and a xylose yield of 57%.


Astrocytes Render Memory Flexible by Releasing D-Serine and Regulating NMDA Receptor Tone in the Hippocampus.
NMDA receptor (NMDAR) hypofunction has been implicated in several psychiatric disorders with impairment of cognitive flexibility. However, the molecular mechanism of how NMDAR hypofunction with decreased NMDAR tone causes the impairment of cognitive flexibility has been minimally understood. Furthermore, it has been unclear whether hippocampal astrocytes regulate NMDAR tone and cognitive flexibility. We employed cell type-specific genetic manipulations, ex vivo electrophysiological recordings, sniffer patch recordings, cutting-edge biosensor for norepinephrine, and behavioral assays to investigate whether astrocytes can regulate NMDAR tone by releasing D-serine and glutamate. Subsequently, we further investigated the role of NMDAR tone in heterosynaptic long-term depression, metaplasticity, and cognitive flexibility. We found that hippocampal astrocytes regulate NMDAR tone via BEST1-mediated corelease of D-serine and glutamate. Best1 knockout mice exhibited reduced NMDAR tone and impairments of homosynaptic and α1 adrenergic receptor-dependent heterosynaptic long-term depression, which leads to defects in metaplasticity and cognitive flexibility. These impairments in Best1 knockout mice can be rescued by hippocampal astrocyte-specific BEST1 expression or enhanced NMDAR tone through D-serine supplement. D-serine injection in Best1 knockout mice during initial learning rescues subsequent reversal learning. These findings indicate that NMDAR tone during initial learning is important for subsequent learning, and hippocampal NMDAR tone regulated by astrocytic BEST1 is critical for heterosynaptic long-term depression, metaplasticity, and cognitive flexibility.


Concentrations of interleukin (IL)-1alpha, IL-1 soluble receptor type II (IL-1 sRII) and IL-1 receptor antagonist (IL-1 Ra) in the peritoneal fluid and serum of infertile women with endometriosis.
Endometriosis is an immune system-related gynaecological disease, characterised by an increase in number and activation of peritoneal macrophages. One of macrophage-derived factors is interleukin (IL)-1. The effects of IL-1 are inhibited by IL-1 receptor type II (IL-1 RII), soluble forms of IL-1 RII (IL-1 sRII) and IL-1 receptor antagonist (IL-1 Ra). The aim of our work was to study the IL-1alpha, IL-1 sRII and IL-1 Ra levels in the peritoneal fluid (PF) and serum of women with endometriosis in relation to stage of disease. Concentrations of IL-1alpha, IL-1 sRII and IL-1 Ra were measured by ELISA assay in the PF and serum of 58 women; 43 with and 15 without endometriosis (control group). Elevated PF and serum IL-1alpha and IL-1 Ra levels in the women with endometriosis in comparison with the control group were observed. IL-1 sRII levels in PF and serum were higher in the controls than in the women with endometriosis. Concentrations of IL-1alpha and IL-1 sRII were higher in advanced endometriosis, but higher IL-1 Ra was observed in the early stage of the disease. Impairment of regulation IL-1 activity in the peritoneal fluid and serum of women with endometriosis may play an important role in the pathogenesis and development of the disease.


Volcanic controls on seawater sulfate over the past 120 million years.
Changes in the geological sulfur cycle are inferred from the sulfur isotopic composition of marine barite. The structure of the 34S/32S record from the Mesozoic to present, which includes ∼50- and 100-Ma stepwise increases, has been interpreted as the result of microbial isotope effects or abrupt changes to tectonics and associated pyrite burial. Untangling the physical processes that govern the marine sulfur cycle and associated isotopic change is critical to understanding how climate, atmospheric oxygenation, and marine ecology have coevolved over geologic time. Here we demonstrate that the sulfur outgassing associated with emplacement of large igneous provinces can produce the apparent stepwise jumps in the isotopic record when coupled to long-term changes in burial efficiency. The record of large igneous provinces map onto the required outgassing events in our model, with the two largest steps in the sulfur isotope record coinciding with the emplacement of large igneous provinces into volatile-rich sedimentary basins. This solution provides a quantitative picture of the last 120 My of change in the ocean's largest oxidant reservoir.


Discrimination by dipyridamole of two types of responses to adenosine and ATP of the carbachol-induced contraction of guinea-pig trachea.
Two types of effect of purines on the carbachol-induced contraction of the guinea-pig trachea in the presence or absence of glucose were evaluated using dipyridamole, and adenosine uptake inhibitor. ATP exerted a greater relaxant effect on the carbachol (10(-6) M)-induced contraction than did adenosine in concentrations ranging from 10(-4) to 10(-3) M. These effects of purines were enhanced by pretreatment with dipyridamole (10(-5) M) but were virtually unaffected by the purine receptor antagonists theophylline (10(-5) M) and quinidine (10(-5) M). The contraction evoked by carbachol was gradually reduced and was almost abolished 4-5 h after exposure to the glucose-free solution. This reduction was almost eliminated by readmitting glucose, and was restored to a certain degree by introducing ATP or adenosine. ATP was less effective than adenosine. This effect of purines but not that of glucose, was markedly diminished by pretreatment with dipyridamole (3 X 10(-6) M to 10(-5) M). The restoration of the carbachol-induced contraction following introduction of purines or glucose was completely antagonized by atropine (10(-6) M). These results suggest that the extracellular effects of adenosine and ATP on the carbachol-induced contraction in normal solution are potentiated by dipyridamole, whereas the possible intracellular effects of these purines in the glucose-free solution are inhibited by this adenosine uptake inhibitor.


De novo sequencing of proteolytic peptides by a combination of C-terminal derivatization and nano-electrospray/collision-induced dissociation mass spectrometry.
A series of synthetic peptides (3-15 residues), C-terminally derivatized with 4-aminonaphthalenesulfonic acid (ansa), have been analyzed on a hybrid magnetic sector-orthogonal acceleration time-of-flight tandem mass spectrometer, fitted with a nano-electrospray (nano-ES) interface. Deprotonated molecules generated by negative-ion ES were subjected to collision-induced dissociation (CID) using either methane or xenon as the collision gas, at a collision energy of 400 eV (laboratory frame of reference). As a consequence of charge localization on the sulfonate group, only C-terminal fragment ions were formed, presumably by charge-remote fragmentation mechanisms. Interpretable CID spectra were obtained from fmol amounts of the small peptides (up to 6 residues), whereas low pmol amounts were required for the larger peptides. CID spectra were also recorded of derivatized, previously noncharacterised peptides obtained by proteolysis of cytosolic hamster liver aldehyde dehydrogenase. Interpretation of these CID spectra was based on rules established for the fragmentation of the synthetic peptides. This study shows that derivatization with ansa may be useful in the de novo sequencing of peptides.


Cellular response to ectopically implanted silk sutures and osteopetrotic bone.
Faulty osteoclasts, characteristic of the incisors-absent (ia) rat mutation of osteopetrosis, cause a resorptive defect which results in the persistence of immature, highly mineralized bone matrix. We implanted osteopetrotic bone subcutaneously into normal and ia rats to determine if ia bone could induce functionally active and morphologically identifiable osteoclasts at the implant surface. Assays of 45Ca released from the preparations showed that normal and ia recipients were capable of equivalent cell-mediated release of Ca over a 2-week implant period, indicating that the ia resorptive defect was not reproduced at the subcutaneous site. Freeze-thawed osteopetrotic bone released twice as much 45Ca as normal bone. This difference was eliminated by collagenase treatment. Cellular profiles were similar in both normal and ia animals regardless of the implant preparation. At 3 days after implantation, both bone and suture were surrounded by mononuclear cells. By 14 days, multinucleated cells appeared at the implant surfaces. Morphological comparison of implant-induced multinucleated cells and tibial osteoclasts indicated that bone-elicited multinucleated cells lacked the ruffled borders characteristic of normal osteoclasts or the extensive clear zones typical of ia osteoclasts, but more closely resembled suture-induced macrophage-polykaryons. We conclude that ectopically implanted ia bone as compared to normal bone elicits a different functional response from structurally similar cell populations. Bone-elicited multinucleated cells could not be classified as active osteoclasts despite evidence of release of 45Ca. Release of labeled Ca was probably due to the action of mononuclear phagocytes and macrophage-polykaryons rather than to osteoclastic resorption.


Inhaled prostacyclin following surgical repair of congenital heart disease--a pilot study.
The development of additional therapies for the treatment of pulmonary hypertension would be a significant advancement in the treatment of congenital heart disease. Recently, studies have found inhaled prostacyclin (PGI2) is an effective pulmonary vasodilator, comparable with nitric oxide. In this prospective interventional pilot study, we examined the physiologic effects of inhaled PGI2 in children with congenital heart disease and pulmonary hypertension. Six children (median age 6 months, range 5 to 21 months) with congenital heart disease and preoperative pulmonary hypertension (mean pulmonary artery pressure [MPAP] greater than 50% systemic) received a 15-minute course of inhaled PGI2 intraoperatively postrepair. The inhaled PGI2 was delivered by aerosolizing the IV formulation (Flolan, Glaxo-Wellcome) to achieve a dose of 50 ng/kg/min. Physiologic parameters measured during the medication period were compared with measurements taken during two 15-minute baseline periods before and after the medication period. Inhaled PGI2 significantly reduced the mean pulmonary artery pressure from 25 +/- 3 to 21 +/- 3 (p < 0.01) and improved the PaO2/FiO2 ratio from 275 +/- 181 to 433 +/- 285 (p = 0.01). There were no significant changes in systemic blood pressure, heart rate, or cardiac index. Children with congenital heart disease and pulmonary hypertension may benefit from inhaled PGI2. Inhaled PGI2 reduced pulmonary blood pressures and improved oxygenation in this small study. PGI2 acts through cyclic adenosine monophosphate mediated pulmonary vasodilation, a mechanism different from nitric oxide. In children with inadequate response to nitric oxide, inhaled PGI2 may be a useful alternative pulmonary vasodilator.


Deregulation of Cdk2 causes Bim-mediated apoptosis in p53-deficient tumors following actin damage.
We previously reported that actin damage by treatment with an actin-depolymerizing agent including pectenotoxin-2 induces Bim-mediated apoptosis in p53-deficient human tumors. In this study, we investigated a molecular mechanism underlying Bim-mediated apoptosis of p53-deficient tumor cells following actin damage. We found that actin inhibitors increased the protein levels of p53 and p21 and thereby inactivated both Cdk2 and Cdc2 kinases. However, p53- or p21-knockout cells fail to induce p21 and hence kept both Cdk2 and Cdc2 kinases active even after treatment with actin inhibitor. The p53- or p21-knockout cells became multinucleate and polyploidy in association with induction of apoptosis. Expression of Bcl-x(L) resulted in accumulation of polyploid cells in association with inhibition of apoptosis. However, expression of a dominant negative mutant (Cdk2dn) and treatment with chemical inhibitors for Cdk2 suppressed not only accumulation of multinucleated cells, but also induction of Bim expression and apoptosis. Therefore, these results suggest that Bim-mediated apoptosis following actin damage due to deregulation of Cdk2 and the cell cycle by the absence of functional p53.


Ketopantoic acid and ketopantoyl lactone reductases. Stereospecificity of transfer of hydrogen from reduced nicotinamide adenine dinucleotide phosphate.
The stereospecificity of hydrogen transfer from NADPH to the appropriate carbonyl substrate catalyzed by ketopantoic acid and ketopantoyl acid and ketopantoyl lactone reductases of yeast (Saccharomyces cerevisiae) and Escherichia coli has been determined. Yeast and E. coli ketopantoic acid reductases are B-specific enzymes which transfer hydrogen from [4B-3H]-NADPH to ketopantoic acid to form [3H]pantoic acid. In contrast to the usual observations on the stereospecificity of functionally similar dehydrogenases from different species, yeast and E. coli ketopantoyl lactone reductases exhibit opposite stereospecificities. Both of two forms of yeast ketopantoyl lactone reductases are A-specific enzymes which form [3H]pantoyl lactone from ketopantoyl lactone and [4A-3H]NADPH, whereas, two forms of E. coli ketopantoyl lactone reductases are B-specific enzymes.


Serum levels of cartilage oligomeric matrix protein. A predicting factor and a valuable parameter for disease management in rheumatoid arthritis.
To examine whether cartilage oligomeric matrix protein (COMP) correlates with inflammation and/or joint destruction of patients with rheumatoid arthritis (RA) and to test COMP as predicting factor for the outcome of patients with established RA. Serum levels of COMP were measured in sera of 62 patients, suffering from RA according to the ACR criteria and treated in intervals in our department, over a period of 5 years. A commercially available sandwich--type ELISA-kit developed by AnaMar Medical AB, Sweden, was used. The results of serum COMP were compared with the Disease Activity Score (DAS), the Larsen Score, and clinical and laboratory parameters. We found a positive correlation between serum levels of COMP at baseline and deterioration of Larsen score even after 5 years (p < 0.007; r = 0.34). To confirm serum COMP as an independent predicting factor for patients with RA we looked at a subgroup of patients (n = 17) with elevated serum levels of COMP (mean 11,7 U/l) and low clinical prognostic factors. In this subgroup we also found a significant correlation with delta Larsen score (p < 0.01; r = 0.59) after 5 years. Serum levels of COMP is known to reflect increased cartilage turnover. The results indicate that serum COMP may be used as a prognostic marker of cartilage degradation in a patient group with established RA.


Clear cell papillary renal cell carcinoma: an update after 15 years.
Fifteen years since the first recognition of clear cell papillary renal cell carcinoma, this distinct renal tumour type is now well accepted as a distinct entity in major classification schemes. It occurs both with and without end-stage renal disease and may be multifocal or bilateral in both scenarios. Recognisable morphological features include clear cells lining branching glands and variable papillary formations with nuclear alignment. Most tumours are small (pT1a) and nucleolar grade 1-2. Immunohistochemistry consistently shows positivity for carbonic anhydrase IX and cytokeratin 7, and often high molecular weight cytokeratin or GATA3, the latter suggesting distal nephron phenotype. Labeling for AMACR and CD10 is consistently negative or minimal. Despite a resemblance to clear cell renal cell carcinoma, molecular alterations of VHL and chromosome 3p are typically lacking, with debatable rare exceptions. Potential mimics include clear cell renal cell carcinoma (with branching architecture or nuclear alignment), papillary renal cell carcinoma with clear cytoplasm, or rarely MITF family translocation renal cell carcinoma. Clinical behaviour is highly favourable with rare, debatable reports of aggressive behaviour. Combined with striking similarity to several extrarenal benign neoplasms, it would be reasonable to reclassify this entity as a benign or low malignant potential neoplasm. Using the nomenclature of the extrarenal counterparts, clear cell papillary (cyst)adenoma is proposed.


Factors Affecting the Resilience of New Nurses in Their Working Environment.
Resilience and working environment are variables that affect turnover. However, how these two variables impact each other is unclear. This study is a descriptive correlation study to identify the factors of the nursing working environment affecting the resilience of new nurses in general tertiary hospitals. This study was conducted by convenience sampling of 233 new nurses with less than 1 year of working experience. Data were collected through questionnaires from 20 to 27 October 2019, and analyzed using correlation analysis and stepwise multiple regression analysis. The results show that the work environment impacts the resilience of new nurses by 30.2%. Specifically, the following qualities of a work environment were found to affect new nurses' resilience, including "nursing foundation for quality of care", "nurse participation in hospital affairs", "nurse manager ability, leadership, and support of nurses", "collegial nurse-physician relations", and "staffing and resource adequacy". These findings imply that a satisfactory working environment improves new nurses' resilience and reduces their intent to leave their workplace. Further studies are needed to elucidate this relationship, especially considering the ever-changing work environments.


Sirtuin-2 activity is required for glioma stem cell proliferation arrest but not necrosis induced by resveratrol.
Glioblastomas, the most common form of primary brain tumors, are the fourth cause of death by cancer in adults. Increasing evidences suggest that glioblastoma resistance to existing radio- and chemotherapies rely on glioblastoma stem cells (GSCs). GSCs are endowed with a unique combination of stem-like properties alike to normal neural stem cells (NSCs), and of tumor initiating properties. The natural polyphenol resveratrol is known to exert opposite actions on neural cells according to their normal or cancerous status. Here, we used resveratrol to explore the molecular mechanisms differing between GSCs and NSCs. We observed a dual action of resveratrol on GSCs: resveratrol blocked GSC proliferation up to 150 μM and induced their necrosis at higher doses. On the opposite, resveratrol had no effect on NSC behavior. To determine the mechanisms underlying resveratrol effects, we focused our attention on the family of NAD-dependent deacetylases sirtuins (SIRT). A member of this family, SIRT1, has been repetitively shown to constitute a preferential resveratrol target, at least in normal cells. Western blot analysis showed that SIRT1 and SIRT3 were expressed by both GSCs and NSCs whereas SIRT2 expression was restricted to GSCs. Pharmacological blockade of SIRT2 activity or down-regulation of SIRT2 expression with siRNAs counteracted the inhibitory effect of resveratrol on cell proliferation. On the contrary, inhibition of SIRT2 activity or expression did not counteract GSC necrosis observed in presence of high doses of resveratrol. Our results highlight SIRT2 as a novel target for altering GSC properties.


Visceral Fat Area, Not Subcutaneous Fat Area, is Associated with Cardiac Hemodynamics in Type 2 Diabetes.
This study was conducted in patients with type 2 diabetes mellitus (T2DM) to assess the association between visceral fat area (VFA) and cardiac hemodynamics. A total of 568 patients with type 2 diabetes (mean age 54±12 years; 40.8% of women) were enrolled. Visceral fat area (VFA, m2) and subcutaneous fat area (SFA, m2) were evaluated by a bioelectrical impedance analyzer. Cardiac hemodynamics were measured by echocardiography, and other clinical and laboratory variables were also assessed and recorded. Patients were divided into those with VFA ≤ 100 (n=369) and those with VFA > 100 (n=199). VFA, SFA, LVMI (left ventricular mass index), left atrial diameter, left ventricular diastolic diameter (LvDd), interventricular septal thickness (IVST), left ventricular systolic diameter (LvSd), and posterior wall thickness (PWT) levels in high-V groups were significantly higher than those in low-V groups. Correlation analysis showed that VFA was positively correlated with LVMI (r=0.120, p=0.004), LVM (r=0.249, p<0.0001), left atrial diameter (r=0.375, p<0.0001), aortic root diameter (r=0.243, p<0.0001), left ventricular systolic diameter (LvSd) (r=0.211, p<0.0001) and negatively correlated with LVEF (r=-0.107, p=0.011). In multivariate linear regression analysis, VFA was the strongest independent determinant of LVMI (β=0.04, p=0.016), LVEF (β=-0.01, p=0.023), and left atrial diameter (β=0.035, p<0.0001), Internal diameter of the aortic root (β=0.014, p<0.0001) and LvSd (β=0.017, p<0.0001). In addition, the VFA also better predicted cardiovascular disease risk with AUC of 0.609 (95% CI:0.563-0.656), compared with SFA, waist-hip ratio (WHR), in a statistically significant manner. We found a significant correlation between VFA (but not SFA) and cardiac hemodynamic parameters. The VFA has advantages as a predictor of visceral obesity and is significantly associated with the development of cardiovascular risk factors (CVD) in T2DM patients.


Derivation and characterization of hepatocytes from embryonic stem cells in vitro.
From a therapeutic perspective on liver, the use of embryonic stem (ES) technology in the generation of a large number of high-functional hepatocytes developed from ES cells for cell transplantation is anticipated. We have explored a three-dimensional culture system in which hepatocytes differentiated from mouse ES cells by transfection with the hepatocyte nuclear factor-3beta possess high metabolic functions that can be maintained long term.


Cisplatin sensitivity of testis tumour cells is due to deficiency in interstrand-crosslink repair and low ERCC1-XPF expression.
Cisplatin based chemotherapy cures over 80% of metastatic testicular germ cell tumours (TGCT). In contrast, almost all other solid cancers in adults are incurable once they have spread beyond the primary site. Cell lines derived from TGCTs are hypersensitive to cisplatin reflecting the clinical response. Earlier findings suggested that a reduced repair capacity might contribute to the cisplatin hypersensitivity of testis tumour cells (TTC), but the critical DNA damage has not been defined. This study was aimed at investigating the formation and repair of intrastrand and interstrand crosslinks (ICLs) induced by cisplatin in TTC and their contribution to TTC hypersensitivity. We observed that repair of intrastrand crosslinks is similar in cisplatin sensitive TTC and resistant bladder cancer cells, whereas repair of ICLs was significantly reduced in TTC. γH2AX formation, which serves as a marker of DNA breaks formed in response to ICLs, persisted in cisplatin-treated TTC and correlated with sustained phosphorylation of Chk2 and enhanced PARP-1 cleavage. Expression of the nucleotide excision repair factor ERCC1-XPF, which is implicated in the processing of ICLs, is reduced in TTC. To analyse the causal role of ERCC1-XPF for ICL repair and cisplatin sensitivity, we over-expressed ERCC1-XPF in TTC by transient transfection. Over-expression increased ICL repair and rendered TTC more resistant to cisplatin, which suggests that ERCC1-XPF is rate-limiting for repair of ICLs resulting in the observed cisplatin hypersensitivity of TTC. Our data indicate for the first time that the exceptional sensitivity of TTC and, therefore, very likely the curability of TGCT rests on their limited ICL repair due to low level of expression of ERCC1-XPF.


A sensitive HPLC method for the quantification of free and total p-cresol in patients with chronic renal failure.
Para-cresol (4-methylphenol) is a volatile phenolic compound which is retained in chronic renal failure. Several recent studies suggest that p-cresol interferes with various biochemical and physiological functions at concentrations currently observed in uremia. Only a few methods are available for the determination of p-cresol concentration in serum. In addition, these methods have only been used for the determination of total p-cresol. In particular, the evolution of free (non-protein bound) p-cresol is of concern, because conceivably this is the biologically active fraction. The concentration of free p-cresol, is, however, markedly lower than that of total p-cresol, in view of its important protein binding. We report a method enabling the measurement of total and free p-cresol concentration in serum of healthy controls and uremic patients. Deproteinization, extraction and HPLC procedure are efficient, without interference of other protein bound ligands and/or precursors of p-cresol or phenol. By means of spiking experiments, the measurement of the UV absorbance over the 200-400 nm wavelength range, and capillary gas chromatography-mass spectrometry, the considered compound is identified as p-cresol. With a fluorescence detection at 284/310 nm as extinction/emission wavelengths the detection limit of p-cresol is 1.3 micromol/l (0.14 microg/ml). Recovery of added p-cresol to normal serum is 95.4+/-4.1%. For free p-cresol and total p-cresol determinations, intra-assay and day-to-day variation co-efficients are 3.2%, 4.2%, 6.9% and 7.3%, respectively. Compared to healthy controls, the serum p-cresol levels are 7-10 times higher in continuous ambulatory peritoneal dialysis patients (CAPD), uremic outpatients, and hemodialysis patients: 8.6+/-3.0 vs. 62.0+/-19.5, 87.8+/-31.7 and 88.7+/-49.3 micromol/l (0.93+/-0.32 vs. 6.70+/-2.11, 9.49+/-3.43, and 9.60+/-5.30 microg/ml) (p<0.05), respectively. The difference is even more important if free p-cresol is considered. This corresponds to a decreased protein binding in uremic patients. We conclude that the present method allows an accurate measurement of both total and free p-cresol, and that the measured concentrations in uremia are in the range which may cause biochemical alterations.


Associations between Missed Colonoscopy Appointments and Multiple Prior Adherence Behaviors in an Integrated Healthcare System: An Observational Study.
Missed colonoscopy appointments delay screening and treatment for gastrointestinal disorders. Prior nonadherence with other care components may be associated with missed colonoscopy appointments. To assess variability in prior adherence behaviors and their association with missed colonoscopy appointments. Retrospective cohort study. Patients scheduled for colonoscopy in an integrated healthcare system between January 2016 and December 2018. Prior adherence behaviors included: any missed outpatient appointment in the previous year; any missed gastroenterology clinic or colonoscopy appointment in the previous 2 years; and not obtaining a bowel preparation kit pre-colonoscopy. Other sociodemographic, clinical, and system characteristics were included in a multivariable model to identify independent associations between prior adherence behaviors and missed colonoscopy appointments. The median age of the 57,590 participants was 61 years; 52.8% were female and 73.4% were white. Of 77,684 colonoscopy appointments, 3,237 (4.2%) were missed. Individuals who missed colonoscopy appointments were more likely to have missed a previous primary care appointment (62.5% vs. 38.4%), a prior gastroenterology appointment (18.4% vs. 4.7%) or not to have picked up a bowel preparation kit (42.4% vs. 17.2%), all p < 0.001. Correlations between the three adherence measures were weak (phi < 0.26). The rate of missed colonoscopy appointments increased from 1.8/100 among individuals who were adherent with all three prior care components to 24.6/100 among those who were nonadherent with all three care components. All adherence variables remained independently associated with nonadherence with colonoscopy in a multivariable model that included other covariates; adjusted odds ratios (with 95% confidence intervals) were 1.6 (1.5-1.8) for outpatient appointments, 1.9 (1.7-2.1) for gastroenterology appointments, and 3.1 (2.9-3.4) for adherence with bowel preparation kits, respectively. Three prior adherence behaviors were independently associated with missed colonoscopy appointments. Studies to predict adherence should use multiple, complementary measures of prior adherence when available.


Detailed PCB congener patterns in incinerator flue gas and commercial PCB formulations (Kanechlor).
In this study, we determined the detailed PCB congener patterns in flue gases from eight incinerators and four commercial PCB formulations (Kanechlors). About 160 PCB peaks were identified in samples using a DB-5 column and HRGC/HRMS. The concentration of incinerator stack emission gas ranged from 0.02 to 44 ngWHO-TEQ/Nm3. The ratios of dioxin-like PCBs in the total PCB concentration were from 3.4% to 25.7% and from 0.63% to 9.1% in stack emission gases and Kanechlor samples, respectively. The PCB congener profiles of Kanechlor samples were similar to those of previous studies. To determine characteristic congeners in flue gas and Kanechlor samples, principal component analysis (PCA) of the data was conducted using STATISTICA for Windows 5.0J (StatSoft, Inc.). As a result, we obtained four principal components (PCs) and accounted for 74% of the total variance. PC 1 was interpreted combustion, PC 2 and PC 3 were interpreted the difference in the number of substituted chlorines and, PC 4 could not be determined. Moreover, we obtained three groups according to the PCB congeners pattern among samples by PCA. These specific congeners that represent characteristics of each class were identified. These data will be useful for the source analysis of PCBs in the environment.


Novel hydrazone derivatives of N-amino-11-azaartemisinin with high order of antimalarial activity against multidrug-resistant Plasmodium yoelii nigeriensis in Swiss mice via intramuscular route.
Novel hydrazone derivatives 10a-m were prepared from N-Amino-11-azaartemisinin (9) and screened for their antimalarial activity by oral and intramuscular (i.m.) routes against multidrug-resistant Plasmodium yoelii in Swiss mice model. Several of the hydrazone derivatives showed higher order of antimalarial activity. Compounds 10b, 10g, 10m provided 100% protection to the infected mice at the dose of 24 mg/kg × 4 days via oral route. Fluorenone based hydrazone 10m the most active compound of the series, provided 100% protection at the dose of 6 mg/kg × 4 days via intramuscular route and also provided 100% protection at the dose of 12 mg/kg × 4 days via oral route. While artemisinin gave 100% protection at 48 mg/kg × 4 days and only 60% protection at 24 mg/kg × 4 days via intramuscular (i.m.) route. Compound 10m found to be four-fold more active than artemisinin via intramuscular route.