Serum lipid profile and its association with hypertension in Bangladesh.
Hypertension and dyslipidemia are major risk factors for cardiovascular disease, accounting for the highest morbidity and mortality among the Bangladeshi population. The objective of this study was to determine the association between serum lipid profiles in hypertensive patients with normotensive control subjects in Bangladesh. A cross-sectional study was carried out among 234 participants including 159 hypertensive patients and 75 normotensive controls from January to December 2012 in the National Centre for Control of Rheumatic Fever and Heart Disease in Dhaka, Bangladesh. Data were collected on sociodemographic factors, anthropometric measurements, blood pressure, and lipid profile including total cholesterol (TC), triglyceride (TG), low density lipoprotein (LDL), and high density lipoprotein (HDL). The mean (± standard deviation) systolic blood pressure and diastolic blood pressure of the participants were 137.94±9.58 and 94.42±8.81, respectively, which were higher in the hypertensive patients (P<0.001). The serum levels of TC, TG, and LDL were higher while HDL levels were lower in hypertensive subjects compared to normotensives, which was statistically significant (P<0.001). Age, waist circumference, and body mass index showed significant association with hypertensive patients (P<0.001) but not with normotensives. The logistic regression analysis showed that hypertensive patients had 1.1 times higher TC and TG, 1.2 times higher LDL, and 1.1 times lower HDL than normotensives, which was statistically significant (P<0.05). Hypertensive patients in Bangladesh have a close association with dyslipidemia and need measurement of blood pressure and lipid profile at regular intervals to prevent cardiovascular disease, stroke, and other comorbidities.


Induction of MET by ionizing radiation and its role in radioresistance and invasive growth of cancer.
Ionizing radiation (IR) is effectively used in cancer therapy. However, in subsets of patients, a few radioresistant cancer cells survive and cause disease relapse with metastatic progression. The MET oncogene encodes the hepatocyte growth factor (HGF) receptor and is known to drive "invasive growth", a regenerative and prosurvival program unduly activated in metastasis. Human tumor cell lines (MDA-MB-231, MDA-MB-435S, U251) were subjected to therapeutic doses of IR. MET mRNA, and protein expression and signal transduction were compared in treated and untreated cells, and the involvement of the DNA-damage sensor ataxia telangiectasia mutated (ATM) and the transcription factor nuclear factor kappa B (NF-κB) in activating MET transcription were analyzed by immunoblotting, chromatin immunoprecipitation, and use of NF-κB silencing RNA (siRNA). Cell invasiveness was measured in wound healing and transwell assays, and cell survival was measured in viability and clonogenic assays. MET was inhibited by siRNA or small-molecule kinase inhibitors (PHA665752 or JNJ-38877605). Combinations of MET-targeted therapy and radiotherapy were assessed in MDA-MB-231 and U251 xenografts (n = 5-6 mice per group). All P values were from two-sided tests. After irradiation, MET expression in cell lines was increased up to fivefold via activation of ATM and NF-κB. MET overexpression increased ligand-independent MET phosphorylation and signal transduction, and rendered cells more sensitive to HGF. Irradiated cells became more invasive via a MET-dependent mechanism that was further enhanced in the presence of HGF. MET silencing by siRNA or inhibition of its kinase activity by treatment with PHA665752 or JNJ-38877605 counteracted radiation-induced invasiveness, promoted apoptosis, and prevented cells from resuming proliferation after irradiation in vitro. Treatment with MET inhibitors enhanced the efficacy of IR to stop the growth of or to induce the regression of xenografts (eg, at day 13, U251 xenografts, mean volume increase relative to mean tumor volume at day 0: vehicle = 438%, 5 Gy IR = 151%, 5 Gy IR + JNJ-38877605 = 76%; difference, IR vs JNJ-38877604 + IR = 75%, 95% CI = 59% to 91%, P = .01). IR induces overexpression and activity of the MET oncogene through the ATM-NF-κB signaling pathway; MET, in turn, promotes cell invasion and protects cells from apoptosis, thus supporting radioresistance. Drugs targeting MET increase tumor cell radiosensitivity and prevent radiation-induced invasiveness.


Human neural stem cells genetically modified for brain repair in neurological disorders.
Existence of multipotent neural stem cells (NSC) has been known in developing or adult mammalian CNS, including humans. NSC have the capacity to grow indefinitely and have multipotent potential to differentiate into three major cell types of CNS, neurons, astrocytes and oligodendrocytes. Stable clonal lines of human NSC have recently been generated from the human fetal telencephalon using a retroviral vector encoding v-myc. One of the NSC lines, HB1.F3, carries normal human karyotype of 46XX and has the ability to self-renew, differentiate into cells of neuronal and glial lineages, and integrate into the damaged CNS loci upon transplantation into the brain of animal models of Parkinson disease, HD, stroke and mucopolysaccharidosis. F3 human NSC were genetically engineered to produce L-dihydroxyphenylalanine (L-DOPA) by double transfection with cDNA for tyrosine hydroxylase and guanosine triphosphate cylohydrolase-1, and transplantation of these cells in the brain of Parkinson disease model rats led to L-DOPA production and functional recovery. Proactively transplanted F3 human NSC in rat striatum, supported the survival of host striatal neurons against neuronal injury caused by 3-nitropro-pionic acid in rat model of HD. Intravenously introduced through the tail vein, F3 human NSC were found to migrate into ischemic lesion sites, differentiate into neurons and glial cells, and improve functional deficits in rat stroke models. These results indicate that human NSC should be an ideal vehicle for cell replacement and gene transfer therapy for patients with neurological diseases. In addition to immortalized human NSC, immortalized human bone marrow mesenchymal stem cell lines have been generated from human embryonic bone marrow issues with retroviral vectors encording v-myc or teromerase gene. These immortalized cell lines of human bone marrow mesenchymal stem cells differentiated into neurons/glial cells, bone, cartilage and adipose tissue when they were grown in selective inducing media. There is further need for investigation into the neurogenic potential of the human bone marrow stem cell lines and their utility in animal models of neurological diseases.


A very short uranium-uranium bond: the predicted metastable U(2)2+.
Quantum chemical calculations, based on multiconfigurational wave functions and including relativistic effects, show that the U(2)2+ system has a large number of low-lying electronic states with S of 0 to 2 and Lambda ranging from zero to ten. These states share a very small bond length of about 2.30 A, compared to 2.43 A in neutral U2. The Coulomb explosion to 2 U+ lowers the energy by only 1.6 eV and is separated by a broad barrier.


Neurobiology of anxious depression: a review.
Anxious depression is a common, distinct clinical subtype of major depressive disorder (MDD). This review summarizes current neurobiological knowledge regarding anxious depression. Peer-reviewed articles, published January 1970 through September 2012, were identified via PUBMED, EMBASE, and Cochrane Library, using the following key words: anxious depression electroencephalography (EEG), anxious depression functional magnetic resonance imaging (fMRI), anxious depression genetics, anxious depression neurobiology, and anxious melancholia neurobiology. Despite a general dearth of neurobiological research, the results suggest that anxious depression-when defined either syndromally or dimensionally-has distinct neurobiological findings that separate it from nonanxious depression. Structural neuroimaging, EEG, genetics, and neuropsychiatric studies revealed differences in subjects with anxious depression compared to other groups. Endocrine differences between individuals with anxious depression and those with nonanxious depression have also been noted, as evidenced by abnormal responses elicited by exogenous stimulation of the system. Despite these findings, heterogeneity in the definition of anxious depression complicates the results. Because exploring the neurobiology of this depressive subtype is important for improving diagnosis, prognosis, and treatment, enrichment strategies to decrease heterogeneity within the field should be employed for future research.


Social Context Influences Resting Physiology in Dogs.
Domestication has affected the social life of dogs. They seem to be less dependent on their pack members than wolves, potentially causing dogs to be more alert towards their environment, especially when resting. Such a response has been found in dogs resting alone compared to wolves in the same situation. However, as this may be influenced by social context, we compared alertness (i.e., degree of activation along the sleep-wake continuum-measured via cardiac parameters) of pack-living and enclosure-kept dogs in two conditions: (1) alone, and (2) with pack members, and in two states of activation: (1) inactive wakefulness, and (2) resting. We found that when dogs were resting alone, alertness was higher than when resting in the pack; individual alertness was potentially influenced by social rank. However, alertness was similar in the two conditions during inactive wakefulness. Thus, depending on social context, familiar conspecifics may still provide support in dogs; i.e., domestication has probably only partly shifted the social orientation of dogs from conspecifics to humans. We suggest that cardiac responses of dogs may be more flexible than those of wolves because of their adaptation to the more variable presence of humans and conspecifics in their environment.


Neutrophil margination and extravasation in sinusoids and venules of liver during endotoxin-induced injury.
Neutrophils contribute to liver damage during endotoxin shock. The objective of this investigation was to document where neutrophils localize in the hepatic vasculature and whether they migrate out of sinusoids or postsinusoidal venules. A well-characterized model of galactosamine and endotoxin shock and immunostaining for neutrophil-associated migration inhibition factor-related protein complex 8/14 S100 calcium-binding proteins were used. Treatment of C3Heb/FeJ mice with 100 micrograms/kg Salmonella abortus equi endotoxin alone or in combination with 700 mg/kg galactosamine induced a time-dependent increase of neutrophil margination in sinusoids and postsinusoidal venules at 4 h. The number of venular neutrophils decreased in both groups at later time points without evidence for transmigration. Extravasation of neutrophils was only observed from sinusoids in galactosamine plus endotoxin-treated animals between 4 and 7 h, which correlated with parenchymal cell injury. After endotoxin alone, large numbers of neutrophils remained sequestered in sinusoids without injury. These data suggest that neutrophils cause hepatocellular injury during endotoxemia after extravasation and are less likely to cause damage when sequestered in the vasculature. In the liver, neutrophils migrate out of sinusoids and not out of postsinusoidal venules.


Hormone replacement therapy and risk of hip fracture: population based case-control study. The Swedish Hip Fracture Study Group.
To determine the relative risk of hip fracture associated with postmenopausal hormone replacement therapy including the effect of duration and recency of treatment, the addition of progestins, route of administration, and dose. Population based case-control study. Six counties in Sweden. 1327 women aged 50-81 years with hip fracture and 3262 randomly selected controls. Use of hormone replacement therapy. Compared with women who had never used hormone replacement therapy, current users had an odds ratio of 0.35 (95 % confidence interval 0.24 to 0.53) for hip fracture and former users had an odds ratio of 0.76 (0.57 to 1.01). For every year of therapy, the overall risk decreased by 6% (3% to 9%): 4% (1% to 8%) for regimens without progestin and 11% (6% to 16%) for those with progestin. Last use between one and five years previously, with a duration of use more than five years, was associated with an odds ratio of 0.27 (0.08 to 0.94). After five years without hormone replacement therapy the protective effect was substantially diminished (-7% to 48%). With current use, an initiation of therapy nine or more years after the menopause gave equally strong reduction in risk for hip fracture as an earlier start. Oestrogen treatment with skin patches gave similar risk estimates as oral regimens. Recent use of hormone replacement therapy is required for optimum fracture protection, but therapy can be started several years after the menopause. The protective effect increases with duration of use, and an oestrogen-sparing effect is achieved when progestins are included in the regimen.


[Ulcerative colitis initial presentation with multiple extra-intestinal manifestations].
Multiple extraintestinal diseases are present in 0.3- 4.5 % of inflammatory bowel disease patients. A 39-year-old woman was admitted with a 3 months history of cervicalgia with functional incapacity, asthenia, tibio-tarsal bilateral arthritis and bloody diarrhoea. She had ferropenic anemia, SR-120 mm, creatinine clearance-42 mL/min, proteinuria-1.2 g/24h. Colonoscopy with biopsy showed active ulcerative rectossigmoiditis. She had bilateral sacroileitis more pronounced at the right side which was suggestive of ankylosing spondylitis. HLA B27 was positive. Because of colestasis, colangio-MRI and CPRE were done and were suggestive of primary sclerosing colangitis. Renal disease was interpreted as an analgesic nephropathy versus glomerulonephritis associated with ulcerative colitis. Cardiac ecodoppler showed pericardial thickening with a thin pericardial effusion. Full improvement of gastrointestinal complaints was observed with 5-ASA topic enemas, sulfassalazine, corticosteroids and azathioprine and full remission of ankylosing spondylitis with adalimumab. This case illustrates extraintestinal wide involvement as the initial presentation of ulcerative colitis, remarking its systemic nature.


[Role of LH in folliculogenisis during the menstrual cycle].
LH participates, with FSH, in normal follicle growth. LH and the ovarian follicle LH and the egg Implication of LH in oocyte modification via paracrine mediation and via the action of somatic cells following stimulation of the receptors present on the granulosa cells. LH and ovulation Control of ovulation by the LH peak inducing, about 36 hours later, rupture of the follicle, secretion of progesterone, and formation of the corpus luteum. Activation of LH by a pro-inflammatory cascade during follicle rupture and, in response, an anti-inflammatory cascade leading to repair of the ovary surface.


Measuring economic impact of applying daily average consumption limits.
Health plans may achieve cost savings by limiting the daily average consumption (DACON) of certain medications and encouraging members and prescribers to select lower cost dosing options. Various strengths of a given medication may be similarly priced per unit; therefore, a single unit of a higher-strength medication may cost less than multiple lower-strength units that provide the same dose. For instance, a single 10 mg tablet may cost less than two 5 mg tablets. To measure the economic impact of implementing DACON limits for selected medications. RegenceRx prescription claims data for the top 200 brand and select generic medications from the first quarter of 2011 were searched for DACON limit opportunities. DACON limits were placed on medications that were available in multiple strengths that were similar in cost, and at least one strength was double another (e.g., 5 mg and 10 mg).Phase 1 of the program occurred in December 2011 and consisted of messaging to dispensing pharmacies (either electronic or direct contact). In Phase 2 (effective January 1, 2012), the claims system was coded to prevent payment for prescription claims in quantities exceeding DACON limits ( greater than 1.9 tablets/day). During this phase, dispensing pharmacists received electronic messaging at the point of service recommending a transition to the least costly dosing option. If the dispensing pharmacist determined transition was not clinically appropriate, the pharmacy was able to contact RegenceRx customer service for an override.Impact was determined by analyzing prescription claims for the selected medications for the 3 months following implementation of DACON limits (January-March 2012). Specific measurements analyzed included number of claims not paid because of exceeding DACON limits, health plan administrative burden, and cost avoidance. DACON limits were placed on 41 medications for commercial lines of business and 35 medications for Medicare Part D lines of business, based on the medication selection criteria (DACON limits were not placed on classes of clinical concern for Medicare Part D). A total of 5,100 claims across both commercial and Medicare Part D lines of business for January to March 2012 were impacted by implementation of DACON limits at the point of service. Duloxetine, niacin CR, and generic temazepam were responsible for more than 60% of the DACON limit claims volume. Implementing DACON limits resulted in a total cost avoidance of approximately $730,000 across both commercial and Medicare Part D lines of business for January to March 2012. Duloxetine, niacin CR, and aripiprazole were responsible for nearly 60% of the total aggregate cost avoidance. After adjustment for health plan administrative costs, the total cost avoidance was just under $720,000. Implementing DACON limits on selected medications provided a cost avoidance of approximately $720,000 over a 3-month period with limited interruption to patient access and relatively low administrative burden. This reduction could result in annualized savings of nearly $3 million.


[Malignant fibrous histiocytoma of the liver].
We report on a 43-year-old man with a primary sarcoma of the liver. The patient was admitted to the hospital for evaluation of dyspnea, abdominal pain in the right upper quadrant, diarrhea, and fever. Physical examination revealed hepatomegaly. Increased laboratory values were found for gamma-GT, LDH, CA 125, and NSE, but not for aspartate and alanine aminotransferase. Computed tomography presented a tumor in the right lobe of the liver. Venous cavography revealed a caval tumor thrombus reaching up to the right atrium. Major liver resection combined with replacement of the vena cava inferior was proposed, but before operation the patient complained about shortness of breath. Spontaneous fragmentation of the tumor thrombus with consecutive embolization of the lungs was suspected. Despite lysis therapy the patient died because of right ventricular failure. Autopsy revealed a tumor measuring 8 cm in diameter, which was located in the right lobe of the liver and invaded the inferior vena cava. Because of multiple tumor aggregates seen in the left and right main pulmonary arteries acute tumor embolization of the lungs was regarded as cause of death. Histologically the tumor was composed of bizarre giant cells surrounded by irregular spindle cells. The positive immunoreactivity pattern of the tumor cells for vimentin, lysozym, and CD68 justified the diagnosis of a malignant fibrous histocytoma (MFH) of the liver.


Action of 3-methylquercetin on poliovirus RNA replication.
3-Methylquercetin is a natural flavone that powerfully blocks poliovirus replication. This compound inhibits selectively poliovirus RNA synthesis both in infected cells and in cell-free systems. Poliovirus double-stranded RNA (replicative forms) is still made in the presence of this inhibitor, whereas the synthesis of single-stranded RNA and the formation of replicative intermediates are drastically blocked.


Redox status in the sentinel lymph node of women with breast cancer.
Lymphatic metastasis is regulated in multiple steps including the transit of tumor cells via the lymphatic vessels and the successful seeding in draining lymph nodes. Thus, several molecular signals and cellular changes must be involved in this complex process to facilitate tumor cell entry, colonization, and survival in the lymph node. To our knowledge, the present work explores, for the first time in the literature, the redox status (oxidative stress parameters and enzymatic and non-enzymatic antioxidant defense systems) in the sentinel lymph node (SLN) of women with breast cancer. SLNs from 75 women with breast cancer were identified using the one-step nucleic acid amplification (OSNA) method as negative (n = 43), with micrometastases (n = 13), or with macrometastases (n = 19). It will allow us to gain knowledge about the pro-oxidant/antioxidant mechanisms involved in the processes of distant metastases in breast cancer and also to assess whether these parameters may be alternative techniques for staging. We found different levels of lipid peroxidation in SLNs with micrometastases (increased) and macrometastases (decreased), a decrease in carbonyl group content in SLNs with macrometastases only, and an increase in total antioxidant capacity (TAC) in SNLs with micrometastases and macrometastases. A decrease in the levels of reduced glutathione (GSH) also appears in the SLNs with macrometastases only. Finally, we show increased levels of superoxide dismutase (SOD) and catalase (CAT) activity in SLNs with micrometastases and macrometastases, and decreased levels of glutathione peroxidase (GPx) activity in SNLs with macrometastases but not with micrometastases. Redox status of lymph node microenvironment participates in the progression of metastatic breast cancer.


Bergmann glia and the recognition molecule CHL1 organize GABAergic axons and direct innervation of Purkinje cell dendrites.
The geometric and subcellular organization of axon arbors distributes and regulates electrical signaling in neurons and networks, but the underlying mechanisms have remained elusive. In rodent cerebellar cortex, stellate interneurons elaborate characteristic axon arbors that selectively innervate Purkinje cell dendrites and likely regulate dendritic integration. We used GFP BAC transgenic reporter mice to examine the cellular processes and molecular mechanisms underlying the development of stellate cell axons and their innervation pattern. We show that stellate axons are organized and guided towards Purkinje cell dendrites by an intermediate scaffold of Bergmann glial (BG) fibers. The L1 family immunoglobulin protein Close Homologue of L1 (CHL1) is localized to apical BG fibers and stellate cells during the development of stellate axon arbors. In the absence of CHL1, stellate axons deviate from BG fibers and show aberrant branching and orientation. Furthermore, synapse formation between aberrant stellate axons and Purkinje dendrites is reduced and cannot be maintained, leading to progressive atrophy of axon terminals. These results establish BG fibers as a guiding scaffold and CHL1 a molecular signal in the organization of stellate axon arbors and in directing their dendritic innervation.


Silicon fractionations in coastal wetland sediments: Implications for biogeochemical silicon cycling.
Coastal wetland sediment is important reservoir for silicon (Si), and plays an essential role in controlling its biogeochemical cycling. However, little is known about Si fractionations and the associated factors driving their transformations in coastal wetland sediments. In this study, we applied an optimized sequential Si extraction method to separate six sub-fractions of non-crystalline Si (Sinoncry) in sediments from two coastal wetlands, including Si in dissolved silicate (Sidis), Si in the adsorbed silicate (Siad), Si bound to organic matter (Siorg), Si occluded in pedogenic oxides and hydroxides (Siocc), Si in biogenic amorphous silica (Siba), and Si in pedogenic amorphous silica (Sipa). The results showed that the highest proportion of Si in the Sinoncry fraction was Siba (up to 6.6 % of total Si (Sitot)), followed by the Sipa (up to 1.8 % of Sitot). The smallest proportion of Si was found in the Sidis and Siad fractions with the sum of both being <0.1 % of the Sitot. We found a lower Siocc content (188 ± 96.1 mg kg-1) when compared to terrestrial soils. The Sidis was at the center of the inter-transformation among Si fractions, regulating the biogeochemical Si cycling of coastal wetland sediments. Redundancy analysis (RDA) combined with Pearson's correlations further showed that the basic biogenic elements (total organic carbon and total nitrogen), pH, and sediment salinity collectively controlled the Si fractionations in coastal wetland sediments. Our research optimizes sediment Si fractionation procedure and provides insights into the role of sedimentary Si fractions in controlling Si dynamics and knowledge for unraveling the biogeochemical Si cycling in coastal ecosystems.


From Waste Collection Vehicles to Landfills: Indication of Per- and Polyfluoroalkyl Substance (PFAS) Transformation.
Municipal solid waste contain diverse and significant amounts of per- and polyfluoroalkyl substances (PFAS), and these compounds may transform throughout the "landfilling" process from transport through landfill degradation. Fresh vehicle leachates, from commercial and residential waste collection vehicles at a transfer station, were measured for 51 PFAS. Results were compared to PFAS levels obtained from aged landfill leachate at the disposal facility. The landfill leachate was dominated by perfluoroalkyl acids (PFAAs, including perfluoroalkyl carboxylic acids (PFCAs) and perfluoroalkyl sulfonic acids (PFSAs); 86% of the total PFAS, by median mass concentration), while the majority of PFAS present in commercial and residential waste vehicle leachate were PFAA-precursors (70% and 56% of the total PFAS, by median mass concentration, respectively), suggesting precursor transformation to PFAAs during the course of landfill disposal. In addition, several PFAS, which are not routinely monitored-perfluoropropane sulfonic acid (PFPrS), 8-chloro-perfluoro-1-octane sulfonic acid (8Cl-PFOS), chlorinated polyfluoroether sulfonic acids (6:2, 8:2 Cl-PFESAs), sodium dodecafluoro-3H-4,8-dioxanonanoate (NaDONA), and perfluoro-4-ethylcyclohexanesulfonate (PFECHS)-were detected. Potential degradation pathways were proposed based on published studies: transformation of polyfluoroalkyl phosphate diester (diPAPs) and fluorotelomer sulfonic acids (FTS) to form PFCAs via formation of intermediate products such as fluorotelomer carboxylic acids (FTCAs).


History of Parkinson's Disease-Associated Gene, Parkin: Research over a Quarter Century in Quest of Finding the Physiological Substrate.
Parkin, the gene responsible for hereditary Parkinson's disease (PD) called "Autosomal Recessive Juvenile Parkinsonism (AR-JP)" was discovered a quarter of a century ago. Owing to its huge gene structure and unique protein functions, parkin has become a subject of interest to those involved in PD research and researchers and clinicians in various fields and is being vigorously studied worldwide in relation to its nature and disease. The gene structure was registered under the gene name "parkin" in the GenBank in 1997. In 1998, deletion and point mutations in the parkin gene were reported, thereby demonstrating parkin is the causative gene for hereditary PD. Although 25 years have passed since the gene's discovery and many researchers have worked tirelessly to elucidate the function of the Parkin protein and the mechanism of its role against neuronal cell death and pathogenesis remain unknown, which raises a major question concerning the current leading hypothesis. In this review, we present the results of related research on the parkin gene in chronological order and discuss unresolved problems concerning its function and pathology as well as new trends in the research conducted to solve them. The relationship between parkin and tumorigenesis has also been addressed from the perspective of Parkin's redox molecule.


In vivo measurement of breast cancer growth rate.
S-phase cells of 66 primary breast cancers were labeled in vivo by preoperative infusion of the thymidine analogue bromodeoxyuridine. A monoclonal antibody specific for DNA-incorporated bromodeoxyuridine was used to identify positive cells and compute a labeling index on histologic sections. The labeling index (the percentage of cells in S-phase) ranged from 0.1% to 23.9%; it correlated positively with poorly differentiated cancer, higher mitotic counts on routine histologic examination, and tumor size; and it correlated inversely with estrogen and progesterone receptors. The labeling index did not correlate with nodal involvement or ploidy. Of the 15 patients with a labeling index greater than 12%, three died and one had systemic disease after a median follow-up of 19 months. No other patients had recurrences. There were no clinical complications of bromodeoxyuridine infusion.


The effect of transcendental meditation on right hemispheric functioning.
This study reports two experiments investigating the effects of transcendental meditation on right hemispheric functioning. The task used in both experiments was the Seashore Tonal Memory Test. In the first experiment a non-meditator group and an experienced meditator group were run. The design involved three periods: a pretest, a meditation or rest period, and then a posttest. The results showed the experienced meditators were significantly better in both pretest and posttest performance. There were no pretest-posttest differences. The second experiment was done to replicate the first experiment and to control for possible selection bias. The design was the same as the first experiment, except that an additional group of inexperienced meditators was included. The results again showed significantly superior performance for the experienced meditators compared to the non-meditators. In addition, the experienced meditators were superior to the inexperienced meditators. There were no significant differences between the non-meditators and the inexperienced meditators. These results support the hypothesis that meditation facilitates right hemispheric functioning. Alternative explanations, such as selection bias, are also discussed.


Long term nucleotide and nucleoside analogs treatment in chronic hepatitis B HBeAg negative genotype D patients and risk for hepatocellular carcinoma.
BACKGROUND AND RATIONALE OF THE STUDY: Effect of Long-term nucleoside/nucleotide (NUC) on hepatocellular carcinoma (HCC) incidence in a population of HBeAg-negative genotype D patients has not been adequately studied in real-life cohorts. Our aim was to evaluate the impact of liver fibrosis and other variables on HCC incidence in this population of patients. Of 745 patients with chronic hepatitis B (CHB), 306 HBeAg-negative genotype D were selected and included in this study. All patients received treatment with NUC for at least 18 months. Patients with CHB or compensated cirrhosis were included. Patients with HCC diagnosed before or during the first 18 months of NUC therapy were excluded. HCC was diagnosed in 2 CHB patients (1.0%) and 23 cirrhosis patients (20%) (OR = 24.41, 95% CI 5.40 < OR < 153.2; p < 0.0001). Multivariate analysis revealed that HCC risk was independently associated with age ≥ 60 years (OR = 6.45, 95% CI 1.22 to 34.0; p = 0.02) and liver cirrhosis (OR = 12.1, 95% CI 1.39 to 106.2; p = 0.02), but not with virological response (VR), and previous resistance to NUC, or rescue therapy. Multivariate analysis in cirrhosis patients revealed that only age ≥ 60 years was an independent risk factor associated with HCC (p = 0.003). Liver cirrhosis and age ≥ 60 years are the stronger risk factors for HCC in genotype D HBeA-gnegative patients. Previous resistance to NUC in patients that achieved a VR after rescue therapy was not a predictive factor regarding HCC. VR does not appear to significantly reduce the overall incidence of HCC when a patient has already progressed to liver cirrhosis.


Mechanisms of pattern formation in plant embryogenesis.
Many of the patterning mechanisms in plants were discovered while studying postembryonic processes and resemble mechanisms operating during animal development. The emergent role of the plant hormone auxin, however, seems to represent a plant-specific solution to multicellular patterning. This review summarizes our knowledge on how diverse mechanisms that were first dissected at the postembryonic level are now beginning to provide an understanding of plant embryogenesis.


Health care system redesign: a strategic management framework.
The current health care environment can best be characterized as uncertain, unfamiliar, ambiguous, unexpected, untraveled, and amorphous. All administrators and managers are facing a tremendous challenge in managing available human, technological, materiel, and fiscal resources to accomplish their organization's mission. They must be able to assess organizational environments, identify strategies to align the organization and the environment, implement these strategies, and continuously evaluate the outcomes of those strategies. Therefore, health care administrators and managers must adopt a management perspective that is responsive, dynamic, comprehensive, systematic, and both process and outcome oriented. Such a perspective is strategic management.


A novel biomarker of MMP-cleaved cartilage intermediate layer protein-1 is elevated in patients with rheumatoid arthritis, ankylosing spondylitis and osteoarthritis.
Rheumatic joints have an altered cartilage turnover. Cartilage intermediate layer protein 1 (CILP-1) is secreted from articular chondrocytes and deposited into the cartilage extracellular matrix. We developed an immunoassay targeting a Matrix Metalloproteinase (MMP)-generated neo-epitope of CILP-1, named CILP-M. Human articular cartilage was cleaved with proteolytic enzymes and CILP-M levels were measured. We also quantified CILP-M in two studies from patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS) and osteoarthritis (OA) and explored the monitoring and prognostic potential of CILP-M in TNF-α inhibitory treatment and modified Stoke AS Spine Score (mSASSS) progression. CILP-M was generated by MMP-1, -8 and -12. In the discovery study, CILP-M was significantly higher in patients with RA, AS and OA than healthy donors (p < 0.01, p < 0.001, p < 0.05) with an area under the curve (AUC) between the diseased groups and healthy donors > 0.95 (p < 0.001). In the validation study, patients with RA and AS had significantly higher CILP-M levels than healthy controls (p < 0.001) and AUC > 0.90 (p < 0.001). Patients with AS treated with TNF- α inhibitory treatment in the validation study had significantly lower CILP-M levels after treatment (p = 0.004). CILP-M may provide useful insights into cartilage degradation processes in rheumatic diseases.


Insula as the Interface Between Body Awareness and Movement: A Neurofeedback-Guided Kinesthetic Motor Imagery Study in Parkinson's Disease.
Intentional movement is an internally driven process that requires the integration of motivational and sensory cues with motor preparedness. In addition to the motor cortical-basal ganglia circuits, the limbic circuits are also involved in the integration of these cues. Individuals with Parkinson's disease (PD) have a particular difficulty with internally generating intentional movements and maintaining the speed, size, and vigor of movements. This difficulty improves when they are provided with external cues suggesting that there is a problem with the internal motivation of movement in PD. The prevailing view attributes this difficulty in PD to the dysfunction of motor cortical-basal ganglia circuits. First, we argue that the standard cortical-basal ganglia circuit model of motor dysfunction in PD needs to be expanded to include the insula which is a major hub within the limbic circuits. We propose a neural circuit model highlighting the interaction between the insula and dorsomedial frontal cortex which is involved in generating intentional movements. The insula processes a wide range of sensory signals arising from the body and integrates them with the emotional and motivational context. In doing so, it provides the impetus to the dorsomedial frontal cortex to initiate and sustain movement. Second, we present the results of our proof-of-concept experiment demonstrating that the functional connectivity of the insula-dorsomedial frontal cortex circuit can be enhanced with neurofeedback-guided kinesthetic motor imagery using functional magnetic resonance imaging in subjects with PD. Specifically, we found that the intensity and quality of body sensations evoked during motor imagery and the emotional and motivational context of motor imagery determined the direction (i.e., negative or positive) of the insula-dorsomedial frontal cortex functional connectivity. After 10-12 neurofeedback sessions and "off-line" practice of the successful motor imagery strategies all subjects showed a significant increase in the insula-dorsomedial frontal cortex functional connectivity. Finally, we discuss the implications of these results regarding motor function in patients with PD and propose suggestions for future studies.


Detection of Salmonella enterotoxin using rabbit ileal loops.
The presence of an enterotoxin produced by Salmonella in broth culture has been demonstrated by using the rabbit ileal loop model. Response by the animal to enterotoxin in sterile culture supernatant fluids is enhanced when the intestinal lumen is washed with a mucolytic agent prior to the administration of toxin. Fluid secretion is untreated intestinal loops was also observed if enterotoxin was administered with a live, invasive Salmonella strain which did not evoke a secretory response. A limited survey of Salmonella isolated for clinical and food sources indicated the common occurrence of enterotoxin production, and stock cultures maintained the ability to produce the toxin. The host-adapted species which were tested varied in their ability to produce enterotoxin.


Picolinic acid, a catabolite of tryptophan, as the second signal in the activation of IFN-gamma-primed macrophages.
We have studied the effects of picolinic acid, a product of tryptophan degradation, on the activation of mouse peritoneal macrophages (M phi). Picolinic acid acts synergistically with IFN-gamma in activating M phi from C57BL/6 mice. Moreover, M phi from C3H/HeJ mice and C3H/HeN that do not become cytotoxic in response to IFN-gamma alone could be fully activated by exposure to picolinate plus IFN-gamma. These results indicate that picolinic acid is a potent costimulator of M phi activation that functions as a second signal. Inasmuch as we have previously demonstrated that the activation of cytotoxic M phi correlates with specific changes in ribosomal RNA (rRNA), we investigated whether picolinic acid could modify M phi RNA metabolism. Picolinic acid inhibited the synthesis of total M phi RNA, the accumulation of newly synthesized 28S rRNA, and augmented the steady state levels of rRNA precursors (pre-rRNA). These changes in RNA metabolism were similar to those previously described in murine M phi activated in vitro or in vivo to express tumoricidal activity. These results demonstrate that picolinic acid is a potent, biologic M phi second signal, suggest that the changes in rRNA are causally connected with the expression of tumoricidal activity, and suggest the existance of an autocrine effect mediated by picolinic acid.


A purified mutant HemA protein from Salmonella enterica serovar Typhimurium lacks bound heme and is defective for heme-mediated regulation in vivo.
Archaea, plants, and most bacteria synthesize heme using the C5 pathway, in which the first committed step is catalyzed by the enzyme glutamyl-tRNA reductase (GluTR or HemA). In some cases, an overproduced and purified HemA enzyme contains noncovalently bound heme. The enteric bacteria Salmonella enterica and Escherichia coli also synthesize heme by the C5 pathway, and the HemA protein in these bacteria is regulated by proteolysis. The enzyme is unstable during normal growth due to the action of Lon and ClpAP, but becomes stable when heme is limiting for growth. We describe a method for the overproduction of S. enterica HemA that yields a purified enzyme containing bound heme, identified as a b-type heme by spectroscopy. A mutant of HemA (C170A) does not contain heme when similarly purified. The mutant was used to test whether heme is directly involved in HemA regulation. When expressed from the S. enterica chromosome in a wild-type background, the C170A mutant allele of hemA is shown to confer an unregulated phenotype, with high levels of HemA regardless of the heme status. These results strongly suggest that the presence of bound heme targets the HemA enzyme for degradation and is required for normal regulation.


[Structural organization of human yolk sac epithelium during first three months of intrauterine development].
Epithelium of the endodermal origin in the human yolk sac was studied at prenatal weeks 5-12. In the beginning of the period studied the epithelium was characterized by high volume density, distribution in the different zones of the organ and polymorphism. The highest secretory activity of epitheliocytes was observed at weeks 7-8 of intrauterine development. After this period, epithelium total volume density decreased, while the fraction of inner epithelial lining layer increased. The epithelium-lined cavities in the yolk sac wall shrinked and disappeared, and the volumes of the cells and nuclei decreased. These morphological changes of the epithelium are indicative of the loss of the organ basic functions already by the end of embryonic period of human development.


[Presence of Salmonella Wien in Gela in 1976].
The spreading of Salmonella Wien at Gela is proved by its isolation from the faeces of twelve patients hospitalized in the isolation department of Vittorio Emanuele II Hospital at Gela (Italy) from May to October in 1976. The isolated Salmonella shows the same serological characteristics and the same features of resistance to the antibiotics of the stocks responsable for the epidemics in Algeria and in France.


A validation study on the Recovery-Promoting Relationship Scale (RPRS) in a Chinese population.
This study examined the psychometric properties of a Chinese language version of the Recovery-Promoting Relationship Scale (RPRS) scale in a sample of persons with severe mental illness in Taiwan. Five hundred ninety-two participants from 32 community psychiatric rehabilitation centers in Taiwan agreed to participate in this study. Principal component factor analysis with oblique rotation was performed. Internal consistency and external construct validity were also examined. The results revealed a 2-factor solution that differed from the structure of the original RPRS. The first factor (F1) comprised 7 items in the Core Relationship Index and 7 items in the Recovery-Promotion Strategies Index of the original RPRS. The second factor (F2) comprised 8 items in the Recovery-Promotion Strategies Index and 1 item (I5) in the Core Relationship Index of the original RPRS. The reliability of F1 and F2 was 0.961 and 0.941, respectively. The entire scale and subscales all had a significant and moderate correlation with recovery and service use. This study provides initial psychometric support for a Chinese language version of the RPRS. Additionally, the use of core interpersonal skills was correlated with recovery-promoting strategies. The findings support the use of the RPRS as a guide to promote recovery-oriented services in Taiwan. (PsycINFO Database Record (c) 2019 APA, all rights reserved).


Preventive Anti-CD2 Treatment does not Impair Parasite Control in a Murine Toxoplasmosis Model.
Targeting human CD2 with the monoclonal antibody (mAb) CB.219 reduces intestinal inflammation in a colitis model where T cells carry human CD2. Here, we asked whether this mAb has adverse effects on infection control. Mice expressing human CD2 on T cells (huCD2tg) were orally infected with Toxoplasma (T.) gondii and treated with the human CD2-specific mAb CB.219 in a preventive setting. The intestinal T. gondii loads in CB.219 treated mice did not differ from the control group. Histologically, huCD2tg mice showed moderate ileal inflammation that did not change with CB.219 treatment. In the ileum, CB.219 treatment reduced the protein levels of interferon-γ, transforming growth factor β and interleukin-6, whereas interleukin-18 mRNA was slightly increased. The infiltration of neutrophils, macrophages, and T cells into the ileum was unaffected by CB.219 treatment. However, CB.219 treatment decreased the numbers of forkhead box P3(+) regulatory T cells (Treg) in ileum and liver of huCD2tg mice. This was confirmed in vitro using human peripheral blood mononuclear cells. Taken together, targeting CD2(+) T cells by the human CD2 mAb CB.219 does not prevent beneficial immune reactions necessary for pathogen control. Further experiments will address gut specificity, underlying mechanisms, and general applicability of CB.219 treatment.


[Trends in pediatric infective endocarditis in a tertiary pediatric center in Israel].
The characteristics of pediatric infective endocarditis (IE) are continuously changing. To describe trends in pediatric IE over a period of 25 years. Children (< 18 years old] treated at Schneider Children's Medical Center during 1992-2004 who met Duke criteria for definite or possible IE were included in the study. Demographic, clinical and laboratory data were collected and compared to data gathered during 1980-1991. Compared to 1980-1991, during 1992-2004 we noted a decrease in the mean age from 6.5 to 4 years and in the incidence of congenital heart defects from 96% to 61% (p = 0.001). Incidence of significant underlying diseases and non-cardiac predisposing factors rose from 4% to 43%. Significantly Less children presented with fever, splenomegaly and murmur during 1992-2004; a 4-fold increase in surgical intervention [p = 0.024) and a 3-fold increase in mortality p = 0.257 were observed. Viridans streptococci (37.5%), Staphylococcus aureus (20.8%) and gram-negative bacilli 2.5%] caused most of IE during 1980-1992, whereas viridians streptococci (19.1%), Candida spp (17%), S. aureus (17%) and coagulase-negative staphylococci (12.8%) were the common causes during 1992-2004. Considerable changes in pediatric IE were observed. Pediatric IE became an infection of young children, especially those with significant noncardiac underlying diseases. It is less commonly caused by viridans streptococci and is increasingly caused by Candida spp and coagulase-negative staphylococci. These trends may affect the management of pediatric IE.


Information yield from routine pre-operative chest radiography and electrocardiography.
Studies in First-World settings suggest that routine pre-operative investigations are of minimal usefulness. A retrospective study of 797 case records determined the yield of significant information from routine chest radiography and ECG in a provincial general hospital serving a broad socio-economic sector. The results were in agreement with those of other studies, viz. that routine investigation may be worthwhile only in older patients. Routine chest radiographs showed an overall positive yield of 6%; 17% in those over 60 years but only 2% in those under 60 years. Routine ECGs showed a positive yield of 7% overall; 7.4% in those older than 40 years and 4.5% in those under 40 years. Investigations indicated by history or physical examination had a significantly greater yield: 34% for chest radiography and 31% for ECGs. Positive results of indicated investigations were more evenly spread across the age groups. The pre-eminence of clinical skills in determining which patients require special investigations is reaffirmed.


Cellular stress due to impairment of collagen prolyl hydroxylation complex is rescued by the chaperone 4-phenylbutyrate.
Osteogenesis imperfecta (OI) types VII, VIII and IX, caused by recessive mutations in cartilage-associated protein (CRTAP), prolyl-3-hydroxylase 1 (P3H1) and cyclophilin B (PPIB), respectively, are characterized by the synthesis of overmodified collagen. The genes encode for the components of the endoplasmic reticulum (ER) complex responsible for the 3-hydroxylation of specific proline residues in type I collagen. Our study dissects the effects of mutations in the proteins of the complex on cellular homeostasis, using primary fibroblasts from seven recessive OI patients. In all cell lines, the intracellular retention of overmodified type I collagen molecules causes ER enlargement associated with the presence of protein aggregates, activation of the PERK branch of the unfolded protein response and apoptotic death. The administration of 4-phenylbutyrate (4-PBA) alleviates cellular stress by restoring ER cisternae size, and normalizing the phosphorylated PERK (p-PERK):PERK ratio and the expression of apoptotic marker. The drug also has a stimulatory effect on autophagy. We proved that the rescue of cellular homeostasis following 4-PBA treatment is associated with its chaperone activity, since it increases protein secretion, restoring ER proteostasis and reducing PERK activation and cell survival also in the presence of pharmacological inhibition of autophagy. Our results provide a novel insight into the mechanism of 4-PBA action and demonstrate that intracellular stress in recessive OI can be alleviated by 4-PBA therapy, similarly to what we recently reported for dominant OI, thus allowing a common target for OI forms characterized by overmodified collagen.This article has an associated First Person interview with the first author of the paper.


First case report of Schistosoma japonicum in Nepal.
Schistosomiasis, globally, is significant public as well as veterinary health problem as it is associated with a wide range of clinical conditions in humans and animals. Schistosomiasis is mostly caused by the following species of genus Schistosoma: Schistosoma japonicum, Schistosoma haematobium, Schistosoma mekongi, Schistosoma intercalatum Schistosoma guineensis, Schistosoma malayensis and Schistosoma mansoni. S. japonicum might be considered as the most pathogenic among these species as the clinical disease caused by this parasite ranges from mild diarrhea, nausea, Katayama fever, portal hypertension, splenomegaly and ascites to liver cirrhosis and fibrosis. S. japonicum has been commonly encountered in China, the Philippines and Indonesia. According to WHO, at least 220.8 million people required preventive treatment for schistosomiasis in 2017 but only 102.3 million people were reported to have been treated. To our knowledge, there are no cases reported from Nepal. Hence, this is the first reported case of S. japonicum in Nepal. A case of acute schistosomiasis due to S. japonicum was identified in CIWEC Hospital and Travel Medicine Center, Kathmandu, Nepal. The patient arrived with gastrointestinal symptoms without any pre-existing chronic illness with no evidence of travel outside of Spain since last August, but had travelled to many other countries 2 years ago. Timely diagnosis by stool routine and microscopic examination and formal-ether concentration technique led to successful treatment of the disease. As the parasite has not been reported to date in Nepal, many people are unaware of its mode of infection and pathogenesis. Many laboratory workers are heedless with the egg of the parasite due to which this parasite might be misdiagnosed or undiagnosed. This case report might help laboratory workers to be sentient about the parasite and further diagnosis in future.


Properties of tofus and soy milks prepared from soybeans having different subunits of glycinin.
The contribution of soybean protein to the physical properties of tofu, a product manufactured by curdling soy milk with coagulants such as calcium or magnesium chloride, was studied by comparing the properties of soy milk prepared from soybeans with different subunits (I, IIa, and IIb) of glycinin with amino acid residues deleted. The breaking stress value of the tofu curds prepared from soybeans having group I was higher than those without group I. The soy milks having group I contained more protein particles and showed more sensitivity to calcium and magnesium ions than those without group I. The amounts of glycinin and protein particles were higher in the soy milks having group I than those in the soy milks without group I. To elucidate the influence of each group on the breaking stress, the glycinin content was adjusted to an identical level in soy milks having each group. Among the tofu curds from three groups, their order of hardness according to their breaking stress was IIa, IIb, and I. The order of particle content among these soy milks was also IIa, IIb, and I. Therefore, the results suggested that the breaking stress value of the tofu curd is dependent upon the number of protein particles in the soy milk and that the number of the particles is determined by the proportion and structure of glycinin in the soybean.


Reaction of alpha-(N-carbamoyl)alkylcuprates with propargyl substrates: synthetic route to alpha-amino allenes and delta3-pyrrolines.
[reaction: see text] Carbamate deprotonation followed by treatment with CuCN.2LiCl affords alpha-(N-carbamoyl)alkylcuprates which react with propargyl halides, mesylates, tosylates, phosphates, acetates, and epoxides to give alpha-(N-carbamoyl) allenes via an anti-S(N)2' substitution process. Propargyl halides, sulfonates, and phosphates give good yields of carbamoyl allenes, while the acetates afford low yields. Propargyl substrates undergo regiospecific S(N)2' substitution in the absence of severe steric hindrance. The alpha-(N-carbamoyl) allenes can be cyclized to 2-oxazolidinones or deprotected to afford the free amines which can be cyclized to Delta(3)-pyrrolines with either AgNO(3) or Ru(3)(CO)(12).


Targeting EZH2 by microRNA-449a inhibits osteosarcoma cell proliferation, invasion and migration via regulation of PI3K/AKT signaling pathway and epithelial-mesenchymal transition.
Osteosarcoma (OS) is one common bone malignant tumor prevailing in young adults and children. It is increasingly recognized microRNA 449a (miR 449a) as an anti-tumor factor in various tumours. However, little is known about the biological significance of miR 449a in OS. The intent of our study was to seek the prognostic values of miR-449a in OS. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to examine the level of miR-449a expression in 48 pairs of OS tissues and para-cancerous specimens, and the relationship between miR-449a level and clinical features of OS patient prognosis was analyzed. Moreover, we measured the miR-449a expression levels in OS cells. Transwell assay was further performed to investigate whether miR-449a influenced MG63 cell migration and invasion, which was important for malignant metastases. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis demonstrated a notable decrease of miR-449a expressions in OS. The declined miR-449a expression was relevant with the poor prognosis and malignant clinicopathologic characteristics of OS patients. Thereafter, the functional assay was performed to determine the role of miR-449a in OS progression. Results of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assays and transwell assays indicated that miR-449a overexpression significantly repressed OS cell proliferation, invasion, and migration. Furthermore, luciferase reporter assay showed that enhancer of zeste homolog 2 (EZH2) was a downstream target of miR-449a in OS cells. Additionally, Western blot analysis demonstrated that miR-449a exerted anti-OS functions via the regulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) signaling pathway and epithelial-mesenchymal transition. We also indicated that miR-449a restoration could inhibit in vivo tumor growth. These results manifested that miR-449a may thus be used as a therapeutic target in OS treatments.


Effect of resistance training on non-alcoholic fatty-liver disease a randomized-clinical trial.
To evaluate the effect of resistance training (RT) on non alcoholic liver disease (NAFLD) patients. A randomized clinical trial enrolling NAFLD patients without secondary liver disease (e.g., without hepatitis B virus, hepatitis C virus or excessive alcohol consumption). Patients were randomly allocated either to RT, three times weekly, for 3 mo or a control arm consisting of home stretching. The RT included leg press, chest press, seated rowing, latissimus pull down etc. with 8-12 repetitions, 3 sets for each exercise, for a total duration of 40 min. Hepatic ultrasound, fasting blood tests, anthropometrics and body composition by dual energy X-ray absorptiometry were assessed. At baseline and follow-up, patients filled out a detailed semi-quantitative food frequency questionnaire reporting their habitual nutritional intake. Steatosis was quantified by the hepatorenal-ultrasound index (HRI) representing the ratio between the brightness level of the liver and the right kidney. The HRI has been previously demonstrated to be highly reproducible and was validated against liver biopsy and proton magnetic resonance spectroscopy. Eighty two patients with primary NAFLD were randomized to receive 3 mo of either RT or stretching. After dropout or exclusion from analysis because of protocol violation (weight change > 3 kg), thirty three patients in the RT arm and 31 in the stretching arm completed the study per protocol. All baseline characteristics were similar for the two treatment groups with respect to demographics, anthropometrics and body composition, blood tests and liver steatosis on imaging. HRI score was reduced significantly in the RT arm as compared to the stretching arm (-0.25 ± 0.37 vs -0.05 ± 0.28, P = 0.017). The RT arm had a significantly higher reduction in total, trunk and android fat with increase in lean body mass. There was no correlation between the reduction in HRI in the RT arm and weight change during the study, but it was positively correlated with the change in trunk fat (r = 0.37, P = 0.048). The RT arm had a significant reduction in serum ferritin and total cholesterol. There was no significant difference between arms in dietary changes and these did not correlate with HRI change. Three months RT improves hepatic fat content accompanied by favorable changes in body composition and ferritin. RT may serve as a complement to treatment of NAFLD.


Infant mortality rate as an indicator of population health.
The infant mortality rate (IMR) has been criticised as a measure of population health because it is narrowly based and likely to focus the attention of health policy on a small part of the population to the exclusion of the rest. More comprehensive measures such as disability adjusted life expectancy (DALE) have come into favour as alternatives. These more comprehensive measures of population health, however, are more complex, and for resource poor countries, this added burden could mean diverting funds from much needed programmes. Unfortunately, the conjecture, that DALE is a better measure of population health than IMR, has not been empirically tested. IMR and DALE data for 1997 were obtained from the World Bank and the World Health Organisation, respectively, for 180 countries. There is a strong (generally) linear association between DALE and IMR (r=0.91). Countries with low DALE tend to have a high IMR. The countries with the lowest IMRs had DALEs above that predicted by the regression line. There is little evidence that the use of IMR as a measure of population health has a negative impact on older groups in the population. IMR remains an important indicator of health for whole populations, reflecting the intuition that structural factors affecting the health of entire populations have an impact on the mortality rate of infants. For countries with limited resources that require an easily calculated, pithy measure of population health, IMR may remain a suitable choice.


Association of the MedWise Risk Score with health care outcomes.
Older patients are especially vulnerable to drug-related problems due to multiple prescription drugs, which increases their risk of drug-drug interactions and adverse drug events (ADEs). This study aimed to examine outcomes associated with the MedWise Risk Score (MRS) in a Medicare Part D population, including total medical expenditures, ADEs, falls, mortality, emergency department (ED) visits, hospital admissions, and length of stay (LOS). Retrospective observational study. The association between MRS and patient health outcomes was derived using drug claims data from 213,561 beneficiaries and medication risk stratification using outcomes data in 2018 with 1 year of follow-up. Analyses were conducted with the Max MRS and the Mean MRS calculated over the year. Analyses utilizing the Max MRS performed better, and results using the Max MRS are presented. Statistical analyses were performed using linear regression, logistic regression, negative binomial regression, and zero-inflated Poisson (ZIP) models. Of 203,630 patients studied (mean ± SD age, 76.0 ± 8.0 years), 4.9%, 9.8%, 24.5%, and 15.5% experienced at least 1 ADE, fall, ED visit, and hospital admission, respectively, in 2018. The MRS was associated with an 8.5% change in total medical expenditure per 1-unit increase. The adjusted odds ratio (OR) of ADE was 1.058 (95% CI, 1.055-1.06)/unit MRS. ADEs, falls, and death were more likely in elevated MRS categories (eg, OR of 4.45 for ADEs [95% CI, 4.10-4.83], 5.51 for falls [95% CI, 5.17-5.87], and 4.42 for death [95% CI, 3.82-5.12], respectively forSevere MRS group). Our model predicts 7000 ED visits for every 100,000 patients per unit increase of the MRS. The ZIP models estimated ORs of 1.03 and 1.01 for hospital admissions and increase in hospital LOS, respectively, per MRS unit. This study shows that MRS was associated with health outcomes and therefore could be used to identify patients at increased risk of negative outcomes based primarily on their medication regimens.


Minimizing external indirect health costs due to aerosol population exposure: a case study from Northern Italy.
Environmental Agencies require Decision Support Systems, in order to plan Air Quality Policies considering the cost of emission reduction measures and the human health effects (with related social costs). The use of Decision Support Systems is also useful to spread information to general public, explaining the effectiveness of proposed air quality plans. In this paper, a multi-objective approach to control PM10 concentration at a regional level is presented. The problem considers both the internal costs (due to the implementation of emission reduction measures) and the external costs (due to population exposure to high PM10 concentrations). To model PM10 concentrations, a single surrogate model is used for the entire domain, allowing the implementation of a very efficient optimization procedure. The surrogate model is derived through a set of 10 simulations, performed using a Chemistry Transport Model fed with different emission reduction scenarios. The methodology is applied to Northern Italy, a region affected by very high PM10 concentrations that exceed the limit values specified by the EU legislation.


Beaked whale (Mesoplodon densirostris) passive acoustic detection in increasing ambient noise.
Passive acoustic detection is being increasingly used to monitor visually cryptic cetaceans such as Blainville's beaked whales (Mesoplodon densirostris) that may be especially sensitive to underwater sound. The efficacy of passive acoustic detection is traditionally characterized by the probability of detecting the animal's sound emissions as a function of signal-to-noise ratio. The probability of detection can be predicted using accepted, but not necessarily accurate, models of the underwater acoustic environment. Recent field studies combining far-field hydrophone arrays with on-animal acoustic recording tags have yielded the location and time of each sound emission from tagged animals, enabling in-situ measurements of the probability of detection. However, tagging studies can only take place in calm seas and so do not reflect the full range of ambient noise conditions under which passive acoustic detection may be used. Increased surface-generated noise from wind and wave interaction degrades the signal-to-noise ratio of animal sound receptions at a given distance leading to a reduction in probability of detection. This paper presents a case study simulating the effect of increasing ambient noise on detection of M. densirostris foraging clicks recorded from a tagged whale swimming in the vicinity of a deep-water, bottom-mounted hydrophone array.


Comparison of laparoscopic versus abdominal radical hysterectomy for FIGO stage IB and IIA cervical cancer with tumor diameter of 3 cm or greater.
There have been many comparative reports on laparoscopic radical hysterectomy (LRH) versus abdominal radical hysterectomy (ARH) for early-stage cervical cancer. However, most of these studies included patients with International Federation of Gynecology and Obstetrics (FIGO) stage IA2 and small (tumor diameter ≤2 or 3 cm) IB1 disease. The purpose of this study was to compare the feasibility, morbidity, and recurrence rate of LRH and ARH for FIGO stage IB and IIA cervical cancer with tumor diameter of 3 cm or greater. We conducted a retrospective analysis of 88 patients with FIGO stage IB and IIA cervical cancer with tumor diameter of 3 cm or greater. All patients had no evidence of parametrial invasion and lymph node metastasis in preoperative gynecologic examination, pelvic magnetic resonance imaging, and positron emission tomography-computed tomography, and they all underwent LRH or ARH between February 2006 and March 2013. Among 88 patients, 40 patients received LRH whereas 48 underwent ARH. The mean estimated blood loss was 588.0 mL for the ARH group compared with 449.1 mL for the LRH group (P < 0.001). The mean operating time was similar in both groups (246.0 minutes in the ARH vs 254.5 minutes in the LRH group, P = 0.589). Return of bowel motility was observed earlier after LRH (1.8 vs 2.2 days, P = 0.042). The mean hospital stay was significantly shorter for the LRH group (14.8 vs 18.0 days, P = 0.044). There were no differences in histopathologic characteristics between the 2 groups. The mean tumor diameter was 44.4 mm in the LRH and 45.3 mm in the ARH group. Disease-free survival rates were 97.9% in the ARH and 97.5% in the LRH group (P = 0.818). Laparoscopic radical hysterectomy might be a feasible therapeutic procedure for the management of FIGO stage IB and IIA cervical cancer with tumor diameter of 3 cm or greater. Further randomized studies that could support this approach are necessary to evaluate long-term clinical outcome.


Evaluation of hand bone loss by digital X-ray radiogrammetry as a complement to clinical and radiographic assessment in early rheumatoid arthritis: results from the SWEFOT trial.
To investigate hand bone loss (HBL) measured by digital X-ray radiogrammetry (DXR) in patients with early rheumatoid arthritis (RA) receiving different treatment regimens, and to evaluate if DXR change rates during the first 12 months correlate with radiological damage after 24 months. From the total SWEFOT trial population, 159 patients had hand radiographs correctly timed and taken with same modality to be analyzed with DXR. All patients started treatment with methotrexate. After 3-4 months, patients with DAS28 > 3.2 were randomized to add sulfasalazine and hydroxychloroquine (triple therapy) or infliximab (MTX + INF). Those with DAS28 ≤3.2 were followed in regular care. Radiographic progression over 24 months was scored according to the Sharp van der Heijde score (SHS) and defined as >5 increase in T-SHS over 24 months. Hand bone mineral density (BMD) was measured by DXR at inclusion and 12 months and a change ≥2.5 mg/cm2/month was used as a cut-off for HBL. In the MTX responders, triple therapy, and MTX + INF groups, the proportions with HBL were 4.1%, 22.2% and 16.4%, respectively (p = 0.01), and the mean (SD) radiological progression in these groups was 3.91 (6.72), 7.40 (14.63) and 2.72 (4.55) respectively (p = 0.06). Patients with HBL had significantly greater risk for radiographic progression, compared with patients without HBL (odds ratio 3.09, 95% CI =1.20-7.79, p = 0.02). Non-responders to MTX had a significantly greater risk of HBL than MTX-responders, despite the add-on therapies. Patients with HBL during the 12 months had greater risk of radiographic progression after 24 months. Evaluation of HBL may help to identify patients who are at risk of radiographic progression.


Crossing the bridge to VATS lobectomy.
Introduction The impact of the introduction of video assisted thoracoscopic surgery (VATS) on the management of lung cancer 20 years ago has been well documented. However, the uptake of VATS lobectomy in surgical practice worldwide has been slower than expected. We believe that this is partly due to a lack of consensus on how this procedure should be integrated into training programmes. We present our initial experience with a newly developed training model, which could help bridge the divide between open and VATS lobectomy. Methods Two surgical registrars were initiated into this model, supervised by a single consultant. All cases were performed using a standardised three-port anterior approach with systematic lymph node dissection. Both registrars were scrubbed for each case, alternating as first surgeon and assistant, with the supervising consultant operating the camera. Results Over a 6-month period, 22 lung resections for non-small cell lung carcinoma were performed as VATS lobectomies. Thirteen of them were upper lobectomies. There were no emergency conversions to open surgery. The mean operative time for the registrars was 155 minutes compared with 140 minutes for consultant-led operations (p=0.22). There was no perioperative mortality. The most common postoperative complications were atrial fibrillation (4 cases) and prolonged air leak (3 cases). Conclusions VATS lobectomy involves a team approach. Especially in upper lobectomies, the assistant surgeon plays a significant role in the operation, often helping with the dissection as well as stapling of the bronchial and vascular structures. With a team consisting of two trainees and a supervising surgeon, the teaching process becomes more intuitive and is accelerated. This should reduce the learning curve considerably and improve safety during training.


Activity of the antiarrhythmic drug amiodarone against Leishmania (L.) infantum: an in vitro and in vivo approach.
Considering the high toxicity and limited therapies available for treating visceral leishmaniasis (VL), the drug repositioning approach represents a faster way to deliver new therapies to the market. In this study, we described for the first time the activity of a potent antiarrhythmic, amiodarone (AMD), against L. (L.) infantum and its in vitro and in vivo activity. The evaluation against promastigotes has shown that amiodarone presents leishmanicidal effect against the extracellular form, with an IC50 value of 10 μM. The activity was even greater against amastigotes in comparison with promastigotes with an IC50 value of 0.5 μM. The selectivity index in relation to the intracellular form demonstrated that the antiparasitic activity was approximately 56 times higher than its toxicity to mammalian cells. Investigation of the in vivo AMD activity in the L. infantum-infected hamster model showed that 51 days after the initial infection, amiodarone was unable to reduce the parasite burden in the spleen and liver when treated for 10 consecutive days, intraperitoneally, at 50 mg/kg/day, as determined by qPCR. Although not statistically significant, AMD was able to reduce the parasite burden by 20% in the liver when treated for 10 consecutive days, orally, at 100 mg/kg/day; no reduction in the spleen was found by qPCR. Our findings may help further drug design studies seeking new AMD derivatives that may provide new candidates with an in vitro selectivity close to or even greater than that observed in the prototype delivering effectiveness in the experimental model of VL.


Effects of ranibizumab in patients with subfoveal choroidal neovascularization attributable to age-related macular degeneration.
To demonstrate not only prevention of vision loss but also improvement in best-corrected visual acuity (BCVA) after treatment with ranibizumab on a variable-dosing regimen over 24 months in patients with age-related macular degeneration (AMD). Interventional case series. Institutional. One hundred and thirty-eight eyes of 138 patients treated intravitreally with 0.5 mg ranibizumab (Lucentis; Novartis, Basel, Switzerland). Age above 50 years, BCVA 0.2 to 1.2 logarithm of the minimal angle of resolution (logMAR), primary or recurrent subfoveal choroidal neovascularization (CNV) secondary to AMD. After single initial treatment, monthly follow-up examination. Retreatment in case of one of the following: sign of subretinal fluid or intraretinal edema, increase in central retinal thickness (CRT) on optical coherence tomography (OCT), active CNV on fluorescein angiography, increase of metamorphopsia, and loss of BCVA > 5 letters on Early Treatment Diabetic Retinopathy Study (ETDRS) chart. Compared with baseline: proportion of eyes gaining > or = 15 letters, proportion of eyes losing or gaining < 15 letters, change in CRT. After 24 months, 30% of eyes gained > or = 15 letters. After 24 months, 55% of eyes lost or gained < 15 letters. Mean CRT of 386 +/- 145 microm at baseline was significantly reduced to 211 +/- 39 microm after 24 months (P = .036). Mean injection number per patient was 5.6 +/- 2.9 and 4.3 +/- 3.8 from baseline to month 12 and month 12 to 24, respectively. Intravitreal ranibizumab on a variable-dosing regimen was effective in significantly increasing mean BVCA and reducing CRT. This beneficial outcome was achieved with a low-rate of mild ocular adverse effects among our patients.


A comparative study on the structure and function of a cytolytic alpha-helical peptide and its antimicrobial beta-sheet diastereomer.
Antimicrobial peptides which adopt mainly or only beta-sheet structures have two or more disulfide bonds stabilizing their structure. The disruption of the disulfide bonds results in most cases in a large decrease in their antimicrobial activity. In the present study we examined the effect of d-amino acids incorporation on the structure and function of a cytolytic alpha-helical peptide which acts on erythrocytes and bacteria. The influence of a single or double d-amino acid replacement in alpha-helical peptides on their structure was reported previously in 50% 2,2,2, trifluoroethanol/water [Krause et al. (1995) Anal. Chem. 67, 252-258]. Here we used Attenuated Total Reflectance Fourier-Transform Infrared (ATR-FTIR) spectroscopy and found that the predominant structure of the wild-type peptide is alpha-helix in phospholipid membranes, whereas the structure of the diastereomer is beta-sheet. However, the linear, beta-sheet diastereomer preserved its cytolytic activity on bacteria but not on erythrocytes. Previous studies have shown that the ability of antimicrobial peptides to lyse bacteria but not normal mammalian cells correlated with their ability to disintegrate preferentially negatively charged, but not zwitterionic phospholipid membranes. In contrast, the diastereomer described here disrupts zwitterionic and negatively charged vesicles with similar potencies to those of the hemolytic wild-type peptide. Interestingly, whereas addition of a positive charge to the N-terminus of the wild-type peptide (which caused a minor effect on its structure) increased activity only towards some of the bacteria tested, similar modification in the diastereomer increased activity towards all of them. Furthermore, the modified wild-type peptide preserved its potency to destabilize zwitterionic and negatively charged vesicles, whereas the modified diastereomer had a reduced potency on zwitterionic vesicles but increased potency on negatively charged vesicles. Overall our results suggest that this new class of antimicrobial diastereomeric peptides bind to the membrane in 'carpet-like' manner followed by membrane disruption and breakdown, rather than forming a transmembrane pore which interfere with the bacteria potential. These studies also open a way to design new broad-spectrum antibacterial peptides.


Association between COVID-19 Risk-Mitigation Behaviors and Specific Mental Disorders in Youth.
Background : Although studies of adults show that pre-existing mental disorders increase risk for COVID-19 infection and severity, there is limited information about this association among youth. Mental disorders in general as well as specific types of disorders may influence their ability to comply with risk-mitigation strategies to reduce COVID-19 infection and transmission. Methods : Youth compliance (rated as "Never," "Sometimes," "Often," or "Very often/Always") with risk mitigation was reported by parents on the CoRonavIruS Health Impact Survey (CRISIS) in January 2021. Responses were summarized using factor analysis of risk mitigation, and their associations with lifetime mental disorders (assessed via structured diagnostic interviews) were identified with linear regression analyses (adjusted for covariates). All analyses used R Project for Statistical Computing for Mac (v.4.0.5). Results : A two-factor model was the best-fitting solution. Factor 1 (avoidance behaviors) included avoiding groups, indoor settings, and other peoples' homes; avoidance was more likely among youth with any anxiety disorder (p=.01). Factor 2 (hygiene behaviors) included using hand sanitizer, washing hands, and maintaining social distance; practicing hygiene was less likely among youth with ADHD (combined type) (p=.02). Mask wearing, which did not load on either factor, was not associated with any mental health disorder. Conclusion and Relevance : Findings suggest that education and monitoring of risk-mitigation strategies in certain subgroups of youth may reduce risk of exposure to COVID-19 and other contagious diseases. Additionally, they highlight the need for greater attention to vaccine prioritization for individuals with ADHD.


Understanding Medical Students' Concerns about Explicit Informed Consent for Pelvic Exams Under Anesthesia.
Medical student involvement in procedures, including pelvic exams under anesthesia (EUAs), is a fundamental part of medical education. While guidelines exist regarding informed consent for medical student participation, there is ongoing debate and uncertainty regarding the requirement and modality of obtaining explicit consent for pelvic EUAs. This study aims to explore the perceptions and experiences of medical students who do not favor an explicit informed consent process for pelvic EUAs. An anonymous online questionnaire was distributed to third- and fourth-year medical students at the University of Pittsburgh School of Medicine who had completed their obstetrics and gynecology core clerkship. The questionnaire included both quantitative and qualitative sections. Qualitative analysis was conducted using a mixed inductive and deductive coding approach, with key patterns, categories, and themes identified through content analysis. Among the 201 students included in the analysis, 50 students did not endorse an explicit informed consent process for pelvic EUAs. Themes that emerged from their open-ended responses included: (1) the belief that medical student involvement is implicitly included in patient agreements at teaching hospitals; (2) the perception that pelvic EUAs are an essential first step in gynecologic surgery; (3) the view that pelvic EUAs are comparable to other medical procedures; (4) concern that explicit consent would limit educational opportunities; and (5) the belief that pelvic EUAs are not harmful or traumatic to patients. The findings highlight the justifications provided by medical students who do not support explicit informed consent for pelvic EUAs. While some arguments align with previous ethical analyses, this study provides empirical and qualitative insights into students' perspectives. The belief that patients implicitly consent to medical student involvement at teaching hospitals warrants further examination, as patient awareness and understanding may vary. The differentiation between pelvic exams and other EUAs, as well as the perception of minimal harm, should be critically evaluated in the context of trauma-informed care and patient autonomy. Furthermore, the interconnectedness of educational and surgical aspects of pelvic EUAs should be clarified in patient-physician communication. Understanding the perspectives of medical students who do not favor explicit consent for pelvic EUAs is crucial for developing and implementing consent processes. The findings emphasize the need for enhanced patient-physician communication, standardized frameworks for learner involvement, and curricular adaptations to address patient perceptions and trauma-informed care. Future research should explore these themes in larger and more diverse cohorts to inform best practices in obtaining informed consent for medical student participation in pelvic EUAs.


Cometabolism of methyl tert-butyl ether by a new microbial consortium ERS.
The release of methyl tert-butyl-ether (MTBE) into the environment has increased the worldwide concern about the pollution of MTBE. In this paper, a microbial consortium was isolated from the soil sample near an oil station, which can degrade MTBE directly with a low biomass yield and MTBE degrading efficiency. Further research has indicated that this consortium can degrade MTBE efficiently when grown on n-octane as the cometabolic substrate. The results of 16S rDNA based on phylogenetic analysis of the selected operating taxonomic units (OTUs) involved in the consortium revealed that one OTU was related to Pseudomonas putida GPo1, which could cometabolically degrade MTBE on the growth of n-octane. This may help explain why n-octane could be the optimal cometabolic substrate of the consortium for MTBE degradation. Furthermore, the degradation of MTBE was observed along with the consumption of n-octane. Different K s values for MTBE were observed for cells grown with or without n-octane, suggesting that different enzymes are responsible for the oxidation of MTBE in cells grown on n-octane or MTBE. The results are discussed in terms of their impacts on our understanding of MTBE biodegradation and cometabolism.


The effects of financial pressures on adherence and glucose control among racial/ethnically diverse patients with diabetes.
The Affordable Care Act is designed to decrease the numbers of uninsured patients in U.S. However, even with insurance, patients who have financial hardships may have difficulty obtaining their medications because of cost issues. Among patients with type 2 diabetes, to examine the association between patients' self-reported financial pressures on cost-related medication non-adherence and glucose control. Additionally, to examine whether having insurance decrease the financial pressures of diabetes care. Racially/ethnically diverse patients (N = 1,361; 249 non-Hispanic whites, 194 Vietnamese, and 533 Mexican American) with type 2 diabetes were recruited from seven outpatient clinics for a cross-sectional, observational study. Although both Vietnamese and Mexican-American patients reported having low annual incomes, more Mexican Americans reported the presence of financial barriers to getting medical care and perceived financial burden due to their diabetes, compared to whites and Vietnamese (p < 0.001). Over half (53.2%) of Mexican Americans reported cost-related non-adherence compared to 27.2% of white and 27.6% of Vietnamese patients (p < 0.001). Perceived financial burden was found to be associated with poor glucose control (HbA1c ≥8%), after adjusting for sociodemographic and health characteristics (aOR = 1.70, 95%CI 1.09-2.63), but not when adjusting for non-adherence. Similarly, a significant association between presence of financial barriers and HbA1c (aOR = 1.69, 95%CI 1.23-2.32) was attenuated with the inclusion of insurance status in the model. Being uninsured (aOR = 1.90, 95%CI 1.13-3.21) and non-adherent (aOR = 1.49, 95%CI 1.06-2.08) were each independently associated with HbA1c. While having health insurance coverage eliminated some of the financial barriers associated with having diabetes, low-income patients still faced significant financial burdens. Thus, providing health insurance to more individuals is only the first step towards eliminating health disparities. It is important to address medication cost in order to improve medication adherence and glucose control.


Assessing the use of speech and language measures in relation to parental perceptions of development after early cochlear implantation.
Clinicians and investigators use multiple outcome measures after early cochlear implantation (CI) to assess auditory skills, speech, and language effects. Are certain outcome measures better associated with optimal childhood development from the perspective of parents? We studied the association between several commonly used outcome instruments and a measure of parental perceptions of development to gain insight into how our clinical tests reflect parental perceptions of a child's developmental status. Cross-sectional analysis. Six academic centers. One hundred eighty-eight deaf children (<6 yr) 1 year after CI activation enrolled in the longitudinal Childhood Development after CI study. Measures of auditory skills, speech, and language. Parental perceptions of development quantified with a visual analogue scale (visual analogue scale-development). Nonparametric and parametric regression methods were used to model the relationship between outcome measures and visual analogue scale-development scores. All outcome measures were positively associated with parental perceptions of development, but more robust associations were observed with language measures and a parent-report scale of auditory skills than with a selected measure of closed-set speech. For speech and language data, differences were observed in the trajectories of associations among younger (2-3 yr) versus older (4-5 yr) children. Our results demonstrate the importance of measuring multiple outcome measures after early pediatric CI. The degree to which an outcome measure reflects childhood development as perceived by parents may be affected by the child's age. Measures that are based on parental report and broader outcome measures focused on verbal language offer the potential for a fuller understanding of the true effectiveness of early implantation.


Ventricular tachycardia in pregnant patients.
Ventricular tachycardia although not common, can occasionally complicate pregnancy. Its presence may indicate an underlying cardiac structural abnormality, or undiagnosed congenital arrhythmic disease. However, some pregnant patients with ventricular tachycardia have structurally normal hearts. Two cases of ventricular tachycardia in pregnant patients with structurally normal hearts are presented and an approach to diagnosis and management of such patients are discussed.


The Arabidopsis thaliana Transcription Factor AtMYB102 Functions in Defense Against the Insect Herbivore Pieris rapae.
In Arabidopsis thaliana the R2R3-MYB transcription factor family consists of over 100 members and is implicated in many biological processes, such as plant development, metabolism, senescence, and defense. The R2R3-MYB transcription factor gene AtMYB102 has been shown to respond to salt stress, ABA, JA, and wounding, suggesting that AtMYB102 plays a role in the response of plants to dehydration after wounding. Here, we studied the role of AtMYB102 in the response of A. thaliana to feeding by larvae of the white cabbage butterfly Pieris rapae. A. thaliana reporter lines expressing GUS under control of the AtMYB102 promoter revealed that AtMYB102 is expressed locally at the feeding sites of herbivore-damaged leaves, but not systemically in uninfested plant parts. Knockout AtMYB102 transposon-insertion mutant plants (myb102) allowed a faster development of P. rapae caterpillars than wild-type Col-0 plants. Moreover, the number of caterpillars that had developed into pupae within 14 days was significantly higher on myb102, indicating that in wild-type plants AtMYB102 contributes to basal resistance against P. rapae feeding. Microarray analysis of wild-type Col-0 and AtMYB102 overexpressing 35S::MYB102 plants revealed a large number of differentially expressed genes. Besides several defense-related genes, a relatively large number of genes is associated with cell wall modifications.


Kinetic properties and metabolic contributions of yeast mitochondrial and cytosolic NADP+-specific isocitrate dehydrogenases.
To compare kinetic properties of homologous isozymes of NADP+-specific isocitrate dehydrogenase, histidine-tagged forms of yeast mitochondrial (IDP1) and cytosolic (IDP2) enzymes were expressed and purified. The isozymes were found to share similar apparent affinities for cofactors. However, with respect to isocitrate, IDP1 had an apparent Km value approximately 7-fold lower than that of IDP2, whereas, with respect to alpha-ketoglutarate, IDP2 had an apparent Km value approximately 10-fold lower than that of IDP1. Similar Km values for substrates and cofactors in decarboxylation and carboxylation reactions were obtained for IDP2, suggesting a capacity for bidirectional catalysis in vivo. Concentrations of isocitrate and alpha-ketoglutarate measured in extracts from the parental strain were found to be similar with growth on different carbon sources. For mutant strains lacking IDP1, IDP2, and/or the mitochondrial NAD+-specific isocitrate dehydrogenase (IDH), metabolite measurements indicated that major cellular flux is through the IDH-catalyzed reaction in glucose-grown cells and through the IDP2-catalyzed reaction in cells grown with a nonfermentable carbon source (glycerol and lactate). A substantial cellular pool of alpha-ketoglutarate is attributed to IDH function during glucose growth, and to both IDP1 and IDH function during growth on glycerol/lactate. Complementation experiments using a strain lacking IDH demonstrated that overexpression of IDP1 partially compensated for the glutamate auxotrophy associated with loss of IDH. Collectively, these results suggest an ancillary role for IDP1 in cellular glutamate synthesis and a role for IDP2 in equilibrating and maintaining cellular levels of isocitrate and alpha-ketoglutarate.


Region-wise distribution of high-risk human papillomavirus types in squamous cell carcinomas of the cervix in India.
Assessment of the prevalence and type distribution of human papillomavirus (HPV) in squamous cell carcinomas (SCC) of the cervix across India was undertaken to estimate the impact of available prophylactic HPV-L1 vaccines in the country and to find out additional types that might be needed to be incorporated in second-generation vaccines. High-risk (HR) HPVs were genotyped from 667 histopathologically confirmed cases of SCC from 6 different centers representing 4 regions across India: Advanced Centre for Treatment, Research and Education in Cancer, Mumbai; All India Institute of Medical Sciences, New Delhi; Cancer Foundation of India, Kolkata; Christian Medical College, Vellore; Kidwai Memorial Institute of Oncology, Bangalore; and Regional Cancer Center, Thiruvananthapuram. Human papillomaviruses in tumor biopsies were analyzed by Xcytonscreen HPV based on PGMY09/11 multiplex polymerase chain reaction and reverse dot blot assay. Overall viral prevalence across India was not different; 92.1% of 667 cases harbored HPV; 8% were negative. Infection with single HR type was seen in 86.8%: predominant types being HPV-16 followed by HPV-18, -45, -73, -31, -56, -52, -58, -59, -33, -68, -51, -35, -26, and -39. Human papillomavirus types 16/18-positive fraction formed 79.6%; other types comprised 12.4%. Prophylactic HPV-16/18-L1 vaccines would provide greater than 75% protection against SCC in India. Ranking and frequencies of non-16/18 types were different from earlier reports. Hence, considering the possibility of promotion of persistence of nonvaccine types in the vaccinees due to original antigenic sin and the lack of organized screening programs in India, a broad-based vaccine approach would be appropriate.


Elevated Levels of Atypical Handedness in Autism: Meta-Analyses.
An elevated prevalence of atypical handedness (left-, mixed-, or non-right-handedness) has been repeatedly reported in individuals with Autism Spectrum Disorder (ASD) compared to typically developing individuals. However, the exact magnitude of this difference as well as the presence of possible moderating factors remains unknown. Here, we present three sets of meta-analyses of studies that assessed the handedness prevalence among individuals with ASD, totaling 1199 individuals (n = 723 individuals with ASD and n = 476 typically developing individuals). Meta-analysis set 1 found that individuals with ASD are 3.48, 2.49, and 2.34 times more likely to be non-right-handed, left-handed, and mixed-handed compared to typically developing individuals, respectively. Meta-analysis set 2 found a 45.4%, 18.3%, and 36.1% prevalence of non-right-handedness, left-handedness, and mixed-handedness, respectively, amongst individuals with ASD. The classification of handedness, the instrument used to measure handedness, and the main purpose of the study were found to moderate the findings of meta-analysis set 2. Meta-analysis set 3 revealed a trend towards weaker handedness for individuals with ASD. The elevated levels of atypical handedness in individuals with ASD could be attributed to atypicalities in cerebral structure and lateralization for language in individuals with ASD.


Hypoalbuminaemic hyponatraemia: a new syndrome?
Six patients with severe hyponatraemia had neurological features of hyponatraemia and pronounced hypoalbuminaemia. All had biochemical features typical of the syndrome of inappropriate secretion of antidiuretic hormone with low serum osmolality and an inappropriately high urinary osmolality. All were given infusions of whole plasma or albumin solution, or both, to restore their plasma albumin concentrations to normal, which led to a dramatic increase in plasma sodium concentrations and serum osmolality, with a concomitant fall in urinary osmolality in all patients. Neurological features were reversed in four patients. It is suggested that severe hypoalbuminaemia is an important cause of appreciable hyponatraemia; infusions of plasma and albumin in such patients may reverse the biochemical and clinical features and should form the basis of management.


Cardiac output measurement by indicator dilution.
The measurement of cardiac output by the indicator dilution method is reviewed. Theoretical and practical problems relating to the direct and indirect Fick methods and the continuous and bolus injection methods are considered in detail. Choice of indicator is also discussed. Problems remain with all of these methods, but reasonable accuracy and consistency may be achieved if attention is paid to detail.


Cell-cycle-dependent effects of sodium-n-butyrate in Physarum polycephalum.
Sodium-n-butyrate affects the length of the mitotic cycle of Physarum polycephalum. Application during S- or early G2-period results in a delay of the subsequent mitosis, whereas application later in the cycle has no delaying effect. Interestingly, the second mitotic cycle after application is considerably shortened when butyrate has been administered during S- or early G2-period of the preceding cycle. In comparison, other homologous short-chain fatty acids were tested; the retarding effect on mitosis increases with the number of carbon atoms, although only butyrate can shorten the second mitotic cycle. It is shown that butyrate causes an immediate depression of synthesis of DNA, RNA and protein. After a certain time-interval the plasmodium overcomes the butyrate block. DNA synthesis is fully recovered and the inhibition of RNA and protein synthesis is even overcompensated until the next mitosis, as reflected by elevated levels of RNA and protein.


Structure of the active domain of the herpes simplex virus protein ICP47 in water/sodium dodecyl sulfate solution determined by nuclear magnetic resonance spectroscopy.
ICP47 encoded by herpes simplex virus (HSV) is a key factor in the evasion of cellular immune response against HSV-infected cells. By specific inhibition of the transporter associated with antigen processing (TAP), ICP47 prevents peptide transport into the endoplasmic reticulum and subsequent loading of major histocompatibility complex (MHC) class I molecules. Amino acid residues 3-34 have been identified as the active domain. This domain appeared to be unstructured in aqueous solution, whereas after binding to membranes an alpha-helical conformation was observed. Here, we have analyzed the structure of ICP47(2-34) in a lipidlike environment by nuclear magnetic resonance (NMR) spectroscopy. In micellar solution of deuterated sodium dodecyl sulfate, the viral TAP inhibitor adopts an ordered structure. There are two helical regions extending from residues 4 to 15 and from residues 22 to 32. Arg-16 is found on the C-terminus of the first helix, and Gly-33 serves as a terminator of the second helix. A loop between residues 17 and 21 is also evident in the structure. The relative orientation of the helices toward each other, however, could not be determined due to the paucity of NOEs from residues 18-21.