Management of health care services for flood victims: the case of the shelter at Nakhon Pathom Rajabhat University Central Thailand.
In Central Thailand basic health care services were affected by a natural disaster in the form of a flood situation. Flood Relief Operations Centers were established from the crisis. Nakhon Pathom Rajabhat University and including the faculty of nursing volunteered to care for those affected and assist in re-establishing a functioning health care system. The aim of this study was to make explicit knowledge of concept, lesson learned, and the process of management for re-establishing a health care service system at a flood victims at Relief Operations Center, Nakhon Pathom Rajabhat University. We used a qualitative design with mixed methods. This involved in-depth interviews, focus group, observational participation and non-observational participation. Key informants included university administrators, instructors, leaders of flood victims and the flood victims. Data was collected during October-December, 2010. Data were analysed using content analysis and compared matrix. We found that the concept and principle of health care services management were community based and involved home care and field hospital services. We had prepared a management system that placed emphasise on a community based approach and holistic caring such as 24h Nursing Clinic Home, visits with family, a referral system, field hospital. The core of management was to achieve integrated instruction started from nursing students were practiced skills as Health promotion and nursing techniques practicum. Rules were established regarding the health care service system. The outcomes of Health Care Service at the Flood Relief Operations Center were direct and sincere help without conditions, administrations concerned and volunteer nursing students instructors, University Officer have sympathetic and charitable with flood victims and environment.


Combined apexification and orthodontic intrusion of a traumatically extruded immature permanent incisor.
A patient with a traumatic extrusion of the maxillary right central incisor was referred to the Pedodontic Clinic of Gazi University Faculty of Dentistry after 15 days. Orthodontic repositioning of the tooth was planned in 6 months. At the beginning of orthodontic therapy it was observed that the tooth was necrotic and needed an apexification procedure. The apexification procedure and orthodontic intrusion were successfully performed at the same time. In addition, a "walking bleach" was performed after the orthodontic and endodontic procedures were completed. At the 3-year recall, the tooth appeared normal in all respects.


Initiation of translation and cellular localization of Theileria annulata casein kinase IIalpha: implication for its role in host cell transformation.
Theileria annulata and T. parva are protozoa that infect bovine leukocytes which leads to subsequent transformation and uncontrolled proliferation of these cells. It has been proposed that the CKIIalpha subunit of T. parva induces mitogenic pathways of host leukocytes by being exported into the host cell. The evidence for this is the existence of a predicted N-terminal secretion signal-like peptide. We tested this hypothesis by analyzing gene structure, translation, and protein localization of the T. annulata CKIIalpha (TaCKIIalpha). The determined TaCKIIalpha-ORF potentially codes for a 50 kDa protein with an N-terminal extension including a possible signal sequence not present in CKIIalpha proteins of non-Theileria species. However, antisera raised against TaCKIIalpha recognized a protein of a molecular weight of about 40 kDa and, therefore, inconsistent with this predicted molecular weight. We demonstrate by in vitro transcription/translation that this discrepancy is due to translation from a downstream initiation site omitting the putative N-terminal signal sequence and thus excluding the notion that the protein product is secreted via the classical secretory pathway. In corroboration immunofluorescence investigations suggest that the TaCKIIalpha subunit is confined to the parasite schizonts within the host cell. On the basis of the above findings it seems highly unlikely that export via the classical pathway of the parasite CKIIalpha is the way in which this protein possibly contributes to host cell transformation.


Hemodynamic effects of atrial synchronization in acute and long-term ventricular pacing.
The acute and long-term hemodynamic benefit from atrial synchronization in ventricular (VAT) pacing has been investigated at rest and during exercise in 10 patients undergoing pacemaker implantation for complete A-V block. The results were compared to conventional (VOO) ventricular stimulation at rates of 70 BPM and 96 BPM. Cardiac index (CI) in VAT-pacing increased at rest by 8% and during exercise by 15% more than with VOO pacing (p less than 0.01). No significant change between the two different rates of asynchronous pacing was observed. CI at rest and during exercise was unchanged after 10 weeks of VAT-pacing. CI is regulated by change of stroke volume in VOO-pacing and by heart rate only with VAT-pacing. In contrast to earlier results with asynchronous ventricular pacing, the hemodynamic benefit of pacing in an atrial synchronized mode is long-lasting. Physiologic mechanisms regulate hemodynamics during exercise and in heart failure.


Adenosine deaminase activity in the serum and malignant tumors of breast cancer: the assessment of isoenzyme ADA1 and ADA2 activities.
The potential relationship between adenosine deaminase activity and cancer progression was examined by investigating the activity of total ADA and its isoenzymes in serum and simultaneously in the cancerous tissue of each patient with breast cancer. Total ADA and its isoenzymes were measured using the Giusti method. ADA2 activity was measured in the presence of a specific ADA1 inhibitor, EHNA. Our results indicated that ADA2 and total ADA activities were higher in serum and malignant tissues than those of corresponding controls (P < 0.05). Tumor ADA2 and total ADA activities were significantly (P < 0.05) correlated with lymph node involvement, histological grade and tumor size, whereas their levels in serum were significantly (P < 0.05) correlated with menopausal status and patient age. Although serum and tumor total ADA activity and its ADA2 isoenzyme were both found to be increased, distinct correlation patterns were observed with some of the prognostic factors. It can be speculated that increased ADA and isoenzyme activities in serum originated from sources other than the breast tumors.


[Recent advances in breast cancer surgery: the sentinel-node biopsy technique].
Sentinel lymph node biopsy is progressively replaces axillary conventional dissection for the treatment of breast cancer. In patients with small breast tumours avoiding axillary clearance and its potential morbidity is an important advance in the quality of care. The technique, detailed in this paper, is robust, safe and widely used today. Nevertheless it is not always well understood, and is in constant evolution regarding both the technique and the interpretation of its results.


Abiotic factors and aging alter the physicochemical characteristics and toxicity of Phosphorus nanomaterials to zebrafish embryos.
Nanoscale phosphorus (P)-based formulations are being investigated as potentially new fertilizers to overcome the challenges of conventional bulk P fertilizers in agriculture, including low efficacy rates and high application levels. After agricultural applications, the NMs may be released into aquatic environments and transform over time (by aging) or in the presence of abiotic factors such as natural organic matter or sunlight exposure. It is, therefore, important to investigate the physicochemical changes of NMs in environmentally realistic conditions and assess their potential acute and sublethal toxic effects on aquatic organisms. To investigate this, two separate studies were conducted: 1. the effects of 3-months aged P-based NMs on zebrafish embryos, and 2. the influence of humic acid (HA), UV exposure, or a combination of both on P-based NM toxicity in zebrafish embryos. Four different types of nanohydroxyapatites (nHAPs) and a nanophosphorus (nP) were included in the study. These NMs differed in their physicochemical properties, most prominently their shape and size. Environmental transformations were observed for P-based NMs due to aging or interaction with abiotic factors. The aging of the NMs increased the hydrodynamic diameter (HDD) of rod- and needle-shaped NMs and decreased the size of the platelet and spherical NMs, whereas interactions with HA and UV decreased the NMs' HDD. It was observed that no LC50 (survival) and IC50 (hatch and heart rates) were obtained when the zebrafish embryos were exposed to the aged NMs or when NMs were added in the presence of HA and UV. Overall, these results suggest that P-based NMs cause no acute toxicity and minimal sub-lethal toxicity to zebrafish embryos in environmentally realistic experimental conditions.


Grb2-related adaptor protein GRAP is a novel regulator of liver fibrosis.
Excessive liver fibrosis is frequently observed in chronic liver diseases and associated with decline of liver functions. Hepatic stellate cells (HSCs) are considered the principal mediator of liver fibrosis by trans-differentiating into myofibroblasts. In the present study we investigated the role of Grb2-related adaptor protein (GRAP) in HSC activation and liver fibrosis. Liver fibrosis was induced by carbon tetrachloride (CCl4) injection. Gene expression was examined by quantitative PCR. Cell proliferation was evaluated by EdU incorporation. DNA-protein interaction was examined by chromatin immunoprecipitation (ChIP). GRAP expression was up-regulated during HSC-myofibroblast transition both in vivo and in vitro. Mechanistically, serum response factor (SRF) and myocardin-related transcription factor A (MRTF-A) formed a complex to bind to the GRAP promoter and activate GRAP transcription. Small interfering RNA (siRNA) mediated GRAP silencing blocked HSC-myofibroblast transition in vitro. Importantly, adeno-associated virus 6 (AAV6) mediated GRAP knockdown in myofibroblasts attenuated liver fibrosis in mice. Of note, inhibition of ERK signaling abrogated enhancement of HSC-myofibroblast transition by GRAP over-expression. Our data suggest that GRAP, possibly via ERK activation, regulates HSC-myofibroblast transition and contributes to liver fibrosis. Screening for small-molecule GRAP inhibitors may yield novel therapeutic solutions against liver fibrosis.


Pleural empyema associated with Gemella morbillorum: report of a case and review of the literature.
Gemella morbillorum, a microaerophilic Gram-positive coccus, is a natural inhabitant of the human oropharyngeal, gastrointestinal and urogenital flora. However, it is an infrequently isolated organism and a rare cause of pulmonary or pleural infections. We report on a 26-y-old male subject with a past medical history of epilepsy and intravenous drug abuse, who presented with imminent sepsis and respiratory failure. Computed tomography of the thorax revealed a pleuropulmonary consolidation of the left lower lobe, and ultrasound guided thoracentesis resulted in aspiration of pus. Microbiological analysis revealed Gemella morbillorum in the pleural fluid. Thoracic drainage and antibiotic therapy resulted in full recovery. We discuss previous cases of pleuropulmonary infections due to Gemella morbillorum and review the available literature of this rare occurrence.


Early exposure to parental depression and parenting: associations with young offspring's stress physiology and oppositional behavior.
Hypothalamic-pituitary-adrenal (HPA) axis reactivity to stress is posited to play a role in the intergenerational transmission of risk for psychopathology and other negative outcomes in the offspring of depressed parents. We tested the hypothesis that the joint, interactive effects of exposure to parental depression during early childhood and parental hostility impact the development of young children's stress physiology and early emerging behavior problems. A sample of 165 preschool-age children (81 boys, 84 girls), of whom 103 had a parent with a history of depression, was exposed to a stress-inducing laboratory task, and five salivary cortisol samples were obtained. Parents completed clinical interviews and an observational parent-child interaction task. We found that the offspring exposed to maternal depression during early childhood and whose parents displayed hostile parenting behaviors during an observational task evidenced high and increasing cortisol levels in response to a laboratory stressor. In addition, the total amount of exposure to maternal depression over the child's life exerted a dose-response effect on the positive relation between parental hostility and child observed oppositional behavior. This study underscores the importance of the early rearing environment on young children's stress physiology and early emerging behavior problems.


Economic assessment of different modalities of immunoglobulin replacement therapy.
The delivery (intravenous or subcutaneous), location (home or hospital), and other factors of immunoglobulin replacement therapy are examined for cost effectiveness. Cost-minimization studies from several countries are reviewed and analyzed. A Canadian cost-minimization study is performed. Although common themes emerge, there are cost differences between the various countries.


A new member of the ras superfamily, the rac1 homologue from Caenorhabditis elegans. Cloning and sequence analysis of cDNA, pattern of developmental expression, and biochemical characterization of the protein.
A new member of the ras superfamily, designated CErac1 has been identified. The CErac1 cDNA clone was isolated from a Caenorhabditis elegans mixed stage library and encodes a protein of 191 amino acids with 82 and 79% identity to human rac1 and rac2 proteins, respectively. The CErac1 cDNA maps to a position on C. elegans chromosome IV in close proximity to cha-1, a choline acetyltransferase gene. The CErac1 cDNA hybridizes to two mRNAs (1.7 and 0.9 kilobases). Their expression is developmentally regulated, that of the more abundant 1.7 kilobases being highest at the embryonic stage and decreasing dramatically during development with 10% of the embryonic level in adult nematodes. The glutathione-S-transferase/CErac1 fusion protein expressed in Escherichia coli binds GTP and exhibits intrinsic GTPase activity. The GTPase activity of the CErac1 protein is stimulated by human n-chimaerin, a GTPase-activating protein for p21 rac1. These data suggest a role of CErac1 in C. elegans early development. The conserved biochemical properties indicate that further characterization of CErac1 by genetic analysis will be helpful in elucidating not only its role in the signal transduction, but also the biological function of its mammalian homologues.


Towards a pathogenesis-oriented therapy of acute myeloid leukemia.
Genetic and molecular techniques have provided increasing insights into the biology of acute myeloid leukemia (AML). These investigations showed that AML is not a homogeneous disease but a heterogeneous group of biologically different subentities. These subentities are currently primarily defined by cytogenetics by which three main subgroups can be discriminated: AML with balanced translocations, AML with unbalanced aberrations and AML without cytogenetically detectable aberrations. Within the latter group molecular alterations are identified in more than half of cases such as NPM mutations, FLT3 mutations, MLL duplications and mutations of CEBP-alpha. The clinical meaning of these findings is illustrated by substantial differences in response to therapy and long-term outcome. As demonstrated by the recent multicenter trial of the German AML Cooperative Group (AMLCG) and other studies intensification of induction therapy may improve the results in distinct subtypes but fails to do so in others. Therefore, new strategies need to be explored which incorporate the knowledge about the biology of AML to develop biology adapted treatment strategies. This process has just begun and is predominantly determined by the availability of new agents and their evaluation in clinical phase I and II studies. A variety of targets are currently explored and some trials have yielded promising results already. The step towards a biology adapted treatment of AML is long and requires the combined efforts of researchers, clinicians and the pharmaceutical industry. The first steps towards this goal have been taken and give rise to the hope for more effective and more specific therapies of AML.


A comparison of realised niche relations of species in New Zealand and Britain.
Many plant species prominent in the native vegetation of the dry shingle banks at Dungeness (Britain) are also prominent as exotics in the dry Upper Clutha catchment (New Zealand). To examine the realised niche relations of these species, vegetation was sampled in the two areas. Inverse classification and ordination were used to determine the relative beta niches of the species in the two areas. There was little agreement; it seems that the exotic species in the Upper Clutha were pre-adapted to different niches from those in their native range.


Efficacy and safety of immune checkpoint inhibitors plus anlotinib in small cell lung cancer with brain metastases: a retrospective, multicentre study.
Previous studies showed that both immune checkpoint inhibitors (ICIs) and anlotinib have central nervous system (CNS) efficacy. This study aimed to evaluate the efficacy and safety of ICIs combined with anlotinib in small cell lung cancer (SCLC) patients with brain metastases (BMs). We retrospectively reviewed SCLC patients with CNS metastases confirmed by brain magnetic resonance imaging (MRI). Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) and Response assessment in neuro-oncology brain metastases (RANO-BM) were used to evaluate treatment response to ICIs plus anlotinib. Kaplan-Meier analysis and Cox regression analysis were performed to determine patient's prognosis. Sixty-six patients with baseline BMs were included. For patients with measurable intracranial lesions, the intracranial objective response rate (ORR) was 29.2% based on RECIST 1.1 criteria and was 27.1% based on RANO-BM criteria. The median intracranial progression-free survival (PFS) was 9.0 months (95% confidence interval [CI], 6.5-11.5 months). The median overall survival (OS) was 13.4 months (95% CI, 10.7-20.5 months). Multivariate Cox regression analysis showed that high disease burden (hazard ratio [HR] = 4.83, P < 0.001), multiple BMs (HR = 2.71, P = 0.036), and more than or equal to 3 prior lines of therapy (HR = 2.56, P = 0.023) were independent negative predictors of OS. The overall incidence of treatment-related adverse events (TRAEs) was 75.8%, and grade 3-4 TRAEs were reported in 19.7% of patients. Our results suggested that ICIs plus anlotinib had potent CNS efficacy with tolerable toxicity and could be a promising treatment option for SCLC patients with BMs.


(R1441C) LRRK2 induces the degeneration of SN dopaminergic neurons and alters the expression of genes regulating neuronal survival in a transgenic mouse model.
Mutation of leucine-rich repeat kinase 2 (LRRK2) is the most common genetic cause of both familial and sporadic Parkinson's disease (PD) cases. Several mutations in LRRK2 gene were reported in PD patients. R1441 is the second most frequent site of LRRK2 mutation. We generated (R1441C) LRRK2 transgenic mice that displayed motor deficits at the age of 16 months. Compared with wild-type mice, 16-month-old (R1441C) LRRK2 mice exhibited a significant reduction in the number of substantia nigra (SN) dopaminergic neurons. To elucidate molecular pathogenic pathways involved in (R1441C) LRRK2-induced death of SN dopaminergic neurons, we performed microarray analysis to visualize altered mRNA expressions in the SN of (R1441C) LRRK2 mouse. In the SN of (R1441C) LRRK2 transgenic mouse, the mRNA expression of three genes that promote cell death was upregulated, while the mRNA expression of seven genes that contribute to neurogenesis/neuroprotection was significantly downregulated. Our results suggest that altered expression of these genes involved in regulating neuronal survival may contribute to the pathogenesis of (R1441C) LRRK2-induced PD.


[Pyoderma gangrenosum: a rare pathology or an omitted diagnosis?].
Pyoderma gangrenosum is a rare pathology of uncertain etiology. It is an inflammatory dermatosis that causes cutaneous necrosis with a characteristically rapid evolution. No precise diagnosis criteria has been established and pyoderma gangrenosum remains an exclusion diagnosis. In 40 to 50% of the cases, the evolution of pyoderma gangrenosum can be worsened by a nonspecific external stimulus such as a trauma or a surgery. This phenomenon, called pathergy, conduces to avoid any surgical excision of the lesion. However, the diagnosis is often omitted and the rapid evolution of the cutaneous necrosis forces the surgeon to perform a surgical debridement of the wound. It causes a worsening of the lesion. It can have disastrous consequences. We present here three different case reports.


Factors influencing aggregation patterns in the sand crab Emerita analoga (Crustacea: Hippidae).
Aggregation patterns in Emerita analoga (in southern California) are delineated with respect to their spatial, daily, and seasonal components. Both abiotic and biotic factors are found to be associated with patterns of aggregation. Spatially, E. analoga aggregates from March through September to a significantly greater degree in the upper one-third area of the wash zone where exposure to wave shock and fish predation are probably decreased. Sand crabs are more aggregated on a daily basis during low tides than at high tides. This may be due to differential rates of migration caused by a decrease in the beach slope angle. Two seasonal peak periods of aggregation are present, one in the early spring, and one in the late summer. These periods occur during the times of highest reproductive female abundance. High seasonal intensities of aggregation probably function to facilitate mating through the maintenance of close proximity between males and females. Visual methods and/or quantitative sampling based on visual observations do not adequately reflect patterns of aggregation in E. analoga.


Partial deletions of the W chromosome due to reciprocal translocation in the silkworm Bombyx mori.
In the silkworm, Bombyx mori (female, ZW; male, ZZ), femaleness is determined by the presence of a single W chromosome, irrespective of the number of autosomes or Z chromosomes. The W chromosome is devoid of functional genes, except the putative female-determining gene (Fem). However, there are strains in which chromosomal fragments containing autosomal markers have been translocated on to W. In this study, we analysed the W chromosomal regions of the Zebra-W strain (T(W;3)Ze chromosome) and the Black-egg-W strain (T(W;10)+(w-2) chromosome) at the molecular level. Initially, we undertook a project to identify W-specific RAPD markers, in addition to the three already established W-specific RAPD markers (W-Kabuki, W-Samurai and W-Kamikaze). Following the screening of 3648 arbitrary 10-mer primers, we obtained nine W-specific RAPD marker sequences (W-Bonsai, W-Mikan, W-Musashi, W-Rikishi, W-Sakura, W-Sasuke, W-Yukemuri-L, W-Yukemuri-S and BMC1-Kabuki), almost all of which contained the border regions of retrotransposons, namely portions of nested retrotransposons. We confirmed the presence of eleven out of twelve W-specific RAPD markers in the normal W chromosomes of twenty-five silkworm strains maintained in Japan. These results indicate that the W chromosomes of the strains in Japan are almost identical in type. The Zebra-W strain (T(W;3)Ze chromosome) lacked the W-Samurai and W-Mikan RAPD markers and the Black-egg-W strain (T(W;10)+(w-2) chromosome) lacked the W-Mikan RAPD marker. These results strongly indicate that the regions containing the W-Samurai and W-Mikan RAPD markers or the W-Mikan RAPD marker were deleted in the T(W;3)Ze and T(W;10)+(w-2) chromosomes, respectively, due to reciprocal translocation between the W chromosome and the autosome. This deletion apparently does not affect the expression of Fem; therefore, this deleted region of the W chromosome does not contain the putative Fem gene.


Comparison of the effects of MK-801 and phencyclidine on catecholamine uptake and NMDA-induced norepinephrine release.
MK-801 was found to be more potent than phencyclidine (PCP) as an inhibitor of N-methyl-D-aspartate-induced [3H]norepinephrine (NE) release and [3H]TCP binding in the hippocampus. On the other hand, MK-801 was slightly less potent than PCP to enhance kainate-stimulated [3H]NE release and to inhibit hippocampal [3H]NE uptake. Further, MK-801 was strikingly less potent than PCP as an inhibitor of striatal synaptosomal [3H]dopamine uptake. These data are discussed with reference to the therapeutic potential of MK-801.


Tanshinone IIA exerts autophagic cell death through down-regulation of β-catenin in renal cell carcinoma cells.
Renal cell carcinoma (RCC), also called kidney cancer, is one of the most common malignancies worldwide, including the United States and China. Because of the characteristics of RCC that are both insidious and largely insensitive to chemo-radiation, the incidence and mortality of RCC are increasing every year. However, there are few studies describing anti-cancer effects of the natural compounds on RCC as compared to other cancers. Here, we analyzed the anti-neoplastic impact of Tanshinone IIA (TSN) on RCC cells. We noted that TSN increased the expression of LC3 proteins while having little effect on PARP and Alix protein expression. We found that TSN up-regulated the expression of autophagy-related proteins such as Atg7 and Beclin-1. Moreover, TSN promoted the formation of autophagic vacuoles such as autophagosomes and autolysosomes. However, treatment with 3-Methyladenine (3-MA) or Chloroquine (CQ), slightly decreased the ability of TSN to induce autophagy, but still autophagy occurred. In addition, TSN inhibited translocation of β-catenin into the nucleus, and β-catenin deletion and TSN treatment in RCC increased the expression of LC3 protein. Overall, our findings indicate that TSN can exert significant anti-tumor effects through down-regulation of β-catenin to induce autophagic cell death.


Mendelian randomisation reveals Sodium-glucose Cotransporter-1 inhibition's potential in reducing Non-Alcoholic Fatty Liver Disease risk.
Non-alcoholic fatty liver disease (NAFLD) has no approved pharmacological treatments. Sodium-glucose cotransporter (SGLT)-1 is a glucose transporter that mediates small intestinal glucose absorption. We evaluated the impact of genetically proxied SGLT-1 inhibition (SGLT-1i) on serum liver transaminases and NAFLD risk. We used a missense variant, rs17683430, in the SLC5A1 gene (encoding SGLT1) associated with HbA1c in a genome-wide association study (n = 344 182) to proxy SGLT-1i. Outcome genetic data comprised 1483 NAFLD cases and 17 781 controls. Genetically proxied SGLT-1i was associated with reduced NAFLD risk (OR 0.36; 95%CI 0.15, 0.87; P = .023) per 1 mmol/mol HbA1c reduction, and with reductions in liver enzymes (alanine transaminase, aspartate transaminase, gamma-glutamyl transferase). Genetically proxied HbA1c, not specifically via SGLT-1i, was not associated with NAFLD risk. Colocalisation did not demonstrate genetic confounding. Overall, genetically proxied SGLT-1i is associated with improved liver health, this may be underpinned by SGLT-1-specific mechanisms. Clinical trials should evaluate the impact of SGLT-1/2 inhibitors on the prevention and treatment of NAFLD.


Ewing's sarcoma of bone: clinicopathologic aspects of 303 cases from the Intergroup Ewing's Sarcoma Study.
Clinicopathologic features of 303 cases of Ewing's sarcoma of bone collected by the Intergroup Ewing's Sarcoma Study group are described. Ewing's sarcoma was found to arise predominantly in the inferior segment of the skeleton in young white patients from 10 to 15 years of age. Of the several recognized histologic patterns, the filagree pattern--an organoid pattern consisting of bicellular strands of tissue separated by filmy vascular stroma--was associated with the lowest survival rates. Light microscopic evidence of cytoplasmic glycogen in tumor cells was found to be useful in but not requisite for diagnoses. The most important predictor of clinical behavior, regardless of treatment modality, was the site of primary involvement. Survival among patients with primary tumors in pelvic bones was lowest, whereas survival among patients with lesions in distal bones of the extremities was highest.


Copper-Catalyzed Aqueous N-O Bond Cleavage of 2-Oxa-3-Azabicyclo Compounds to Cyclic cis-1,4-Amino Alcohols.
The N-O bond cleavage of 2-oxa-3-azabicyclo substrates, which are readily prepared by the hetero Diels-Alder reaction between nitroso dienophiles and cyclic 1,3-dienes, was effectively catalyzed by heterogeneous copper-on-carbon (Cu/C) under aqueous conditions to give the corresponding cyclic cis-1,4-amino alcohol derivatives. The present method was applied to the direct incorporation of the hydroxy and amino groups derived from a nitroso substrate into cyclic 1,3-dienes with cis-selectivity by the combination of the in situ formation of 2-oxa-3-azabicyclo compounds and following Cu/C-catalyzed N-O bond cleavage. The obtained cis-4-aminocyclohexenols, derived from cyclohexadiene as a cyclic 1,3-diene, could be selectively oxidized by using the ruthenium-on-carbon (Ru/C) catalyst under oxygen atmosphere to the corresponding 4-aminocyclohexenones at 50-65 °C or para-iminoquinones at 100-110 °C as useful reactive synthetic precursors.


Synthesis, characterization, and in vitro antitumor properties of gold(III) compounds with the traditional Chinese medicine (TCM) active ingredient liriodenine.
Liriodenine, an oxoaporphine alkaloid with anticancer activity isolated from Zanthoxylum nitidum (rutaceous anticancer traditional Chinese medicine), was selected as a bioactive ligand to react with HAuCl(4) and NaAuCl(4) to afford [LH][AuCl(4)] (1) and [AuCl(3)L] (2), respectively (where L is liriodenine). The structures of 1 and 2 were characterized by IR spectroscopy, electrospray ionization mass spectrometry, (1)H-NMR spectroscopy, and elemental analysis. The single-crystal X-ray diffraction analysis of 1 revealed that it is an ionic compound consisting of protonated liriodenine cation [LH](+) and [AuCl(4)](-) anion. The spectroscopic analysis showed that 2 is a coordination compound, in which one liriodenine coordinates to gold via its 7-N donor. In aqueous solution, 1 is relatively stable, but 2 undergoes rapid hydrolysis. The in vitro cytotoxicity towards five human tumor cell lines shows that 1 and 2 manifest roughly similar biological behavior and appreciable antiproliferative properties, with IC(50) values falling in the 2-16 μM range. The flow-cytometric analysis of 1 and 2 suggests that both compounds induced an S-phase arrest. Compounds 1 and 2 significantly poison topoisomerase I in vitro at low concentration (25 μM or less). DNA binding studies indicate that both 1 and 2 interact with DNA mainly via intercalation between the neighboring base pairs of the DNA double helix. Electrostatic interactions of 1 and 2 with the polyanionic DNA phosphate backbone may reinforce the intercalation because both 1 and 2 are composed of planar cationic species.


Intraspecific differentiation of Colletotrichum gloeosporioides sensu lato based on in silico multilocus PCR-RFLP fingerprinting.
Colletotrichum gloeosporioides sensu lato is one of the most common and widely distributed plant pathogens in the world. Understanding fungal biodiversity is hinged on accurate identification and delimitation at the inter- and intraspecific levels. Sequences of the ITS1-5.8S-ITS2 region (ITS), β-tubulin (TUB), actin (ACT), and glyceraldehyde-3-phosphate dehydrogenase (GPDH) genes of 30 C. gloeosporioides sensu lato isolates, collected from anthracnose infected papaya fruits grown in the main production areas in Trinidad, were analyzed by in silico PCR-RFLP analysis with the aim of identifying which gene region(s) had the highest level of intraspecific polymorphism. Restriction site polymorphisms generated from 13 restriction enzymes enabled the identification of specific enzymes that were successful at intraspecific discrimination of the C. gloeosporioides isolates. Genetic distance values were reflective of the level of polymorphisms obtained for the four different gene regions. In both cases (calculated genetic distance and percentage of polymorphic loci from RFLP profiles), ACT and ITS gene regions had the highest level of restriction site polymorphisms and genetic diversity, GPDH and TUB had the lowest. Cluster analysis based on PCR-RFLP genetic distance data revealed sub-specific placement of the isolates which appeared to be gene-dependent. The implications of these findings are discussed relative to biodiversity monitoring and the need for multilocus, polyphasic investigations which must take into account the possibility of exaggerated estimates of genetic diversity.


Adequate protection of the public against food-transmitted diseases of microbial aetiology. Achievements and challenges, half a century after the introduction of the Prescott-Meyer-Wilson strategy of active intervention.
No dramatic change in the approach to supplying microbiologically safe foods and meals to the consumer occurred immediately upon the introduction, in the 1930's, by S.C. Prescott and K.F. Meyer in the U.S. and Sir Graham Wilson in the U.K. of the principle of taking preventive remedial measures rather than merely examining final product samples. Thus morbidity and the economic impact of food-borne disease of microbial aetiology continued to rise and new food-transmitted pathogens continued to be identified. The 1930 strategy was not implemented until 1970 when food processing specialists in the U.S. launched a similar approach under the new acronym 'HACCP' (hazard analysis: critical control points). This relies on (i) identification, by meticulous ecological studies, of hazardous practices and locations, termed 'critical points' by the new generation; (ii) elimination of such hazards by developing processing techniques designed to control contamination and colonization of foods--also given an innovative term, viz. GMP; (iii) validation of the elaborated procedures by a new stem to the Science of Public Health: risk assessment, perhaps better termed Safety Science; (iv) upon introduction of the validated GMP's monitoring limited numbers of samples--which have become fully representative because of process management--for ecologically valid marker organisms, indicating incidental going-out-of-control of manufacture or distribution. This implementation of the Prescott-Meyer-Wilson maxim has been given the name longitudinally integrated safety assurance, charmingly acronymized to LISA. Introduction of LISA eliminates all previously existing or perceived difficulties about microbiological target values ('standards') for foods. These can henceforth be empirically assessed from surveys on samples obtained from factories or catering establishments previously inspected for adherence to LISA, deficiencies having, where necessary, been rectified prior to the examination of samples. Unfortunately, a more general adoption of the LISA maxim in food technology occurred at almost the same time as people became concerned about the perceived negative health impact of processing food for safety. This culminated in widespread rejection of foods decontaminated by low dose gamma irradiation. While behaviourial scientists seriously attempt to identify the mechanisms of this anxiety and devise means of reassurance, food scientists should continue to elaborate innovative LISA procedures. In this context three promising areas of research and development are briefly discussed.


Autonomic nervous activity before and after eradication of Helicobacter pylori in patients with chronic duodenal ulcer.
Helicobacter pylori infection is involved in the formation of chronic peptic ulcer. However, a previously reported hypothesis concerning the involvement of central autonomic nervous disorder in this condition cannot be ruled out. To use spectrum analysis of heart rate viability to examine autonomic nervous activity before and after H. pylori eradication. Twenty patients with chronic duodenal ulcer (duodenal ulcer group) and 20 age-matched normal adults (N group). In both groups, 24-h Holter electrocardiograms (ECGs) were recorded and spectrum analysis of heartrate variability was performed. In the duodenal ulcer group, Holter ECG was recorded before and after H. pylori eradication. In the N group, analysis of heart rate variability showed that high frequency (HF) power, an index of parasympathetic activity, was high at night, while the low frequency (LF)/HF ratio, an index of sympathetic function, was high during the daytime. In the duodenal ulcer group, HF power was higher at night than during the daytime, showing a similar pattern to the N group, but the power value was higher than in the N group (P < 0.05). In the duodenal ulcer group, LF/HF at night was significantly higher than that of the N group. In addition, in the duodenal ulcer group, autonomic activity after H. pylori eradication did not differ significantly from that before H. pylori eradication. In patients with chronic peptic ulcer, both sympatheticotonia and parasympatheticotonia may occur at night, and this abnormality in autonomic nervous activity may cause increased gastric acid secretion and gastric mucosal vasoconstriction. Abnormalities in autonomic activity persist even after H. pylori eradication, suggesting that they may be an independent risk factor in the formation of chronic peptic ulcer in addition to H. pylori infection.


[Analysis of inheritance of morphological and biochemical characters introgressed into common wheat from Aegilops speltoides Tausch].
Genetic control of some morphological traits and the gliadin composition were examined in plants of two lines of common wheat carrying genes introgressed from the wild diploid cereal Aegilops speltoides. Leaf hairiness was shown to be controlled by a single introgressed dominant gene that was not allelic to the known common wheat gene Hl1. Waxlessness of the whole plant is controlled by the introgressed from Ae. speltoides inhibitor gene allelic to gene W1 located on chromosome 2B. This gene was epistatic to the introgressed gene controlling spike waxlessness. The introgressed gene of spike color was shown to be allelic to Rg1 located on chromosome 1B of common wheat. However, the former gene proved to be linked to an allele of the Gli-B1 locus other than in wheat.


Quorum quenching bacteria isolated from industrial wastewater sludge to control membrane biofouling.
N-acylhomoserine lactone (AHL)-based bacterial communication through quorum sensing (QS) is one of the main causes of biofouling. Although quorum quenching (QQ) has proven to be an effective strategy against biofouling in membrane bioreactors (MBRs) for municipal wastewater treatment, its applicability for industrial wastewater treatment has rarely been studied. This is the first study to isolate QQ strains from the activated sludge used to treat industrial wastewater containing toxic tetramethylammonium hydroxide (TMAH) and 1-methyl-2-pyrrolidinone. The two QQ strains from genus Bacillus (SDC-U1 and SDC-A8) survived and effectively degraded QS signals in the presence of TMAH. They also showed resistance to toxic byproducts of TMAH degradation such as ammonium and formaldehyde. They effectively reduced the biofilm formation of Pseudomonas aeruginosa PAO1 and mixed community of activated sludge. The strains isolated in this study thus have the potential to be employed to reduce membrane biofouling in MBRs during the treatment of TMAH-containing wastewater.


Use of high throughput qPCR screening to rapidly clone low frequency tumour specific T-cells from peripheral blood for adoptive immunotherapy.
The adoptive transfer of autologous tumor reactive lymphocytes can mediate significant tumor regression in some patients with refractory metastatic cancer. However, a significant obstacle for this promising therapy has been the availability of highly efficient methods to rapidly isolate and expand a variety of potentially rare tumor reactive lymphocytes from the natural repertoire of cancer patients. We developed a novel in vitro T cell cloning methodology using high throughput quantitative RT-PCR (qPCR assay) as a rapid functional screen to detect and facilitate the limiting dilution cloning of a variety of low frequency T cells from bulk PBMC. In preclinical studies, this strategy was applied to the isolation and expansion of gp100 specific CD8+ T cell clones from the peripheral blood of melanoma patients. In optimization studies, the qPCR assay could detect the reactivity of 1 antigen specific T cell in 100,000 background cells. When applied to short term sensitized PBMC microcultures, this assay could detect T cell reactivity against a variety of known melanoma tumor epitopes. This screening was combined with early limiting dilution cloning to rapidly isolate gp100154-162 reactive CD8+ T cell clones. These clones were highly avid against peptide pulsed targets and melanoma tumor lines. They had an effector memory phenotype and showed significant proliferative capacity to reach cell numbers appropriate for adoptive transfer trials (approximately 1010 cells). This report describes a novel high efficiency strategy to clone tumor reactive T cells from peripheral blood for use in adoptive immunotherapy.


Intravascular ultrasonic imaging: histologic and echographic correlation.
The feasibility of assessing arterial wall characteristics with an intravascular 40 MHz ultrasonic imaging device was determined in vitro. Ten autopsy specimens of human arteries, with and without atherosclerosis, were studied. A close relationship was observed between the histologic section and the corresponding ultrasonic cross-section with regard to the location, maximum plaque thickness and extent of the atherosclerotic lesion along the circumference of the vessel wall. Based on echogenicity of the atherosclerotic lesion, ultrasound could distinguish four basic types of atherosclerotic plaque components: 1. hypoechoic: a reflection of lipid deposits; 2. soft echoes: reflective of fibromuscular tissue; 3. bright echoes: representative of fibrous tissue; 4. bright echoes with shadowing behind the lesion: representative of calcium deposits. It is anticipated that development of such a catheter-tip imaging system combined with recanalisation methods will be of immense benefit for the precise localisation and identification of vessel wall pathology, precise positioning of a recanalisation instrument (laser device, atherectomy catheter) and subsequent use of this recanalisation procedure and for assessing the effect of recanalisation.


No difference in patient compliance between full-strength versus low-dose aspirin for VTE prophylaxis following total hip and total knee replacement.
The utilization of aspirin for VTE prophylaxis following TJA has increased due to updated clinical practice guidelines. Aspirin is the only approved VTE prophylaxis medication that does not require a prescription, but adherence and tolerance remain unknown. We hypothesized decreased patient compliance utilizing full-strength 325 mg aspirin twice daily following TJA when compared to low-dose 81 mg twice daily. We also investigated the reasons why patients may elect to stop the medication earlier than 28 days. A consecutive series of patients undergoing primary total hip or knee arthroplasty utilizing 325 or 81 mg of EC aspirin twice daily for 4 weeks were surveyed to determine compliance with use and any adverse events related to the medication. Fisher's exact test was used to determine statistical significance. 404 patients were enrolled with 199 patients prescribed the 325 mg regimen. Fifty-two patients who were prescribed 325 mg missed a dose versus 51 patients who were prescribed 81 mg (p = 0.082). No significant difference in the frequency of missed doses (missing < 5 doses, 5-10 doses, > 10 doses) between the treatment regimens (p = 0.78, 0.39 and 0.83, respectively). Most commonly cited reason for stopping aspirin in both treatment groups was gastrointestinal issues (10.5% and 7%, respectively). By surveying patients on their use of aspirin we find no difference in adherence between full-strength and low-dose treatment regimens. Additionally, we have a better understanding of the reasons for noncompliance as GI upset was a relatively common complaint with both doses.


Impact of duodenal feeding on the oxygen balance of the splanchnic region during different phases of severe burn injury.
Enteral nutrition is recommended in burned patients. Depending on the amount administered, enteral feeding causes an increase of intestinal oxygen-demand. Since intestinal perfusion is decreased after major burns the aim of this study was to evaluate, whether duodenal feeding might be a cofactor for the development of a splanchnic O(2)-imbalance. In 15 severely burned patients during duodenal feeding starting within 6 h after injury the assessment of the CO(2)-gap between arterial and gastric CO(2), as a parameter for the measurement of intestinal O(2)-balance was performed. Beginning prior to enteral nutrition CO(2)-gap measurements were carried out to show when the CO(2)-gap increased above 30 mmHg during the whole critical illness phase of the patients. When the CO(2)-gap increased above 30 mmHg enteral nutrition was reduced by 50% and the CO(2)-gap was measured 1 h later. In none of the patients the CO(2)-gap increased during increase of enteral nutrition. In seven patients, the CO(2)-gap increased between the 6th and 13th day above 30 mmHg and fell significantly 1 h after reduction of enteral nutrition. Contrary to the early postburn phase, enteral feeding might have adverse effects on the oxygen balance of the intestine in the later stages of the critical illness phase.


Molecular genetics of Red biosynthesis in Streptomyces.
We have studied the molecular biology of undecylprodigiosin (Red) biosynthesis by Streptomyces coelicolor as a model system for understanding the genetic regulation of antibiotic biosynthesis. A collection of new red mutants was obtained using a directed screen. Regions of DNA involved in the transcriptional regulation of red gene expression were also isolated.


The vomiting infant: recent advances and unsettled issues in imaging.
The evaluation of infantile vomiting is bound up with many unresolved questions and continually evolving imaging technologies. This article addresses three specific areas of interest: the use of newer low-osmolality, water-soluble contrast media in the infant's gastrointestinal tract; the ever-controversial subject of gastroesophageal reflux; and the burgeoning role of gastrointestinal ultrasonography.


TrkB blockade in the hippocampus after training or retrieval impairs memory: protection from consolidation impairment by histone deacetylase inhibition.
Relatively little is known about the requirement of signaling initiated by brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin receptor kinase B (TrkB), in the early phases of memory consolidation, as well as about its possible functional interactions with epigenetic mechanisms. Here we show that blocking TrkB in the dorsal hippocampus after learning or retrieval impairs retention of memory for inhibitory avoidance (IA). More importantly, the impairing effect of TrkB antagonism on consolidation was completely prevented by the histone deacetylase (HDAC) inhibitor sodium butyrate (NaB). Male Wistar rats were given an intrahippocampal infusion of saline (SAL) or NaB before training, followed by an infusion of either vehicle (VEH) or the selective TrkB antagonist ANA-12 immediately after training. In a second experiment, the infusions were administered before and after retrieval. ANA-12 after either training or retrieval produced a significant impairment in a subsequent memory retention test. Pretraining administration of NaB prevented the effect of ANA-12, although NaB given before retrieval did not alter the impairment resulting from TrkB blockade. The results indicate that inhibition of BDNF/TrkB in the hippocampus can hinder consolidation and reconsolidation of IA memory. However, TrkB activity is not required for consolidation in the presence of NaB, suggesting that a dysfunction in BDNF/TrkB signaling can be fully compensated by HDAC inhibition to allow hippocampal memory formation.


Unusual manifestation of heat stroke: Isolated trochlear nerve palsy.
Heat stroke is a life-threatening disease characterized by hyperthermia and neurological dysfunction. The central nervous system is highly sensitive to hyperthermia, which causes neurological complications due to the involvement of the cerebellum, basal ganglia, anterior horn cells, and peripheral nerves. Several studies reported about clinical symptoms and brain image findings of heat stroke. Isolated cranial nerve dysfunction caused by lacunar infarction is an extremely rare condition in patient with heat stroke. We experienced a rare case of trochlear nerve palsy due to midbrain infarction caused by heat stroke.


Putative apolipoprotein receptor gene (LRP, A2MR) is not rearranged in either myxoid liposarcoma or lipomas with translocations in 12q13-14.
The APR, also known as LRP, gene is highly homologous to the low-density lipoprotein (LDL)-receptor and encodes a cell surface molecule with biochemical properties consistent with function as a lipoprotein receptor. This gene has been mapped to human chromosomal bands 12q13-q14, a region commonly altered in tumors of adipose cells. The proximity of APR to these breakpoints, coupled with its presumed role in lipid metabolism and possible affect on cell proliferation, suggest it as a candidate gene for adipose tissue tumor formation. Pulsed-field gel analysis was used to develop a physical map covering 750 kilobases (kb) surrounding this gene. Examination of myxoid liposarcomas and lipomas bearing the characteristic translocations (12;16)(q13;p11) or (12;variable)(q14;variable), respectively, excluded the breakpoints from within a 750-kb region surrounding the APR gene. These results suggest that APR is not involved directly in the genetic changes that underlie development or progression of these tumors.


Developmental toxicity of orally administered sildenafil citrate (Viagra) in SWR/J mice.
Normal adult inbred SWR/J mice were used to investigate the teratogenic and other possible toxic effects of various dose levels of sildenafil citrate (Viagra) on fetuses. Multiple dose levels of 6.5, 13.0, 19.5, 26.0, 32.5 or 40.0 mg of sildenafil citrate/kg body weight (which correspond to the multiples of 1, 2, 3, 4, 5 or 6 of human 50 mg Viagra, respectively) were orally administered into pregnant mice on days 7-9, 10-12 or 13-15 of gestation. On day 17 of pregnancy, all fetuses were removed and examined for toxic phenomena (embryo-fetal toxicity) and for external, internal and skeletal malformations. A total of 285 pregnant mice were used in the present study. None of the dams treated with sildenafil citrate at any of the oral dose levels used in the present study died during the experimental period and all dams treated with the drug failed to reveal overt signs of maternal toxicity. Moreover, the results of the present study clearly demonstrate that none of the multiple oral dose levels of the drug at any time interval used has induced any external, internal or skeletal malformations in the fetuses obtained from treated females. However, the dose level of 40 mg/kg body weight of sildenafil citrate has a growth suppressing effect on alive fetuses when it was administered at all the time intervals used in the present study. Furthermore, the dose levels 26.0, 32.5 and 40 mg/kg of the drug have embryo-fetal toxicity when the drug is applied on days 13-15 of gestation. The possible mechanisms involved in the embryo-fetal toxicity and fetal growth suppressing effects of sildenafil citrate were discussed. The results of this study have important implications for the widespread use of this drug.


Chondrogenesis by bone marrow-derived mesenchymal stem cells grown in chondrocyte-conditioned medium for auricular reconstruction.
Bone marrow-derived mesenchymal stem cells (BMSCs) can be obtained by minimally invasive means and would be a favourable source for cell-based cartilage regeneration. However, controlling the differentiation of the BMSCs towards the desired chondrogenic pathway has been a challenge hampering their application. The major aim of the present study was to determine if conditioned medium collected from cultured auricular chondrocytes could promote chondrogenic differentiation of BMSCs. Auricular chondrocytes were isolated and grown in BMSC standard culture medium (SM) that was collected and used as chondrocyte-conditioned medium (CCM). The BMSCs were expanded in either CCM or SM for three passages. Cells were seeded onto fibrous collagen scaffolds and precultured for 2 weeks with or without transforming growth factor-beta 3 (TGF-β3). After preculture, constructs were implanted subcutaneously in nude mice for 6 and 12 weeks and evaluated with real-time polymerase chain reaction, histology, immunohistochemistry and biochemistry. Real-time polymerase chain reaction results showed upregulation of COL2A1 in the constructs cultured in CCM compared with those in SM. After 12 weeks in vivo, abundant neocartilage formation was observed in the implants that had been cultured in CCM, with or without TGF-β3. In contrast, very little cartilage matrix formation was observed within the SM groups, regardless of the presence of TGF-β3. Osteogenesis was only observed in the SM group with TGF-β3. In conclusion, CCM even had a stronger influence on chondrogenesis than the supplementation of the standard culture medium with TGF-β3, without signs of endochondral ossification. Efficient chondrogenic differentiation of BMSCs could provide a promising alternative cell population for auricular regeneration. Copyright © 2016 John Wiley & Sons, Ltd.


Advances in machine learning technology for sustainable biofuel production systems in lignocellulosic biorefineries.
In view of the global climate change concerns, the society is approaching towards the development of 'green' and renewable energies for sustainable future. The non-renewable fossil fuels may be largely replaced by renewable energy sources, which could facilitate sustainable growth, energy development and lessen the reliance on conventional energy sources. The traditional methods employed in biorefineries to estimate the data values for the biofuel production systems are often complicated, time-consuming and labour-intensive. Modern machine learning (ML) technologies hold enormous potential in managing high-dimensional complex scientific tasks and improving decision-making in energy distribution networks and systems. The data-driven probabilistic ML algorithms could be applied to smart biofuel systems and networks that may reduce the cost of experimental research while providing accurate estimates of product yields. The current review demonstrates a thorough understanding of the application of different ML models to regulate and monitor the production of biofuels from waste biomass through prediction, optimization and real-time monitoring. The in-depth analysis of the most recent advancements in ML-assisted biofuel production methods, including thermochemical and biochemical processes is provided. Moreover, the ML models in addressing the issues of biofuel supply chains, case studies, scientific challenges and future direction in ML applications are also summarized.


Umbrella Systematic Review and Meta-analysis: Physical Activity as an Effective Therapeutic Strategy for Improving Psychosocial Outcomes in Children and Adolescents.
Physical activity (PA) interventions are part of many interdisciplinary programs for the management of children and adolescents with or without physical or psychological conditions or disabilities. Aiming to summarize the available evidence, we conducted an umbrella review of meta-analyses of PA interventions that included psychosocial outcomes in populations of children and adolescents. Literature searches were conducted in PubMed, Cochrane Central, Web of Science, Medline, SPORTDiscus, and PsychInfo from January 1, 2010, to May 6, 2022. Meta-analyses of randomized and quasi-randomized studies investigating the efficacy of PA interventions for psychosocial outcomes in children and adolescents were included. Summary effects were recalculated using common metric and random-effects models. We assessed between-study heterogeneity, predictive intervals, publication bias, small study effects, and whether the results of the observed positive studies were greater than expected due to chance. On the basis of these calculations, strength of associations was assessed using quantitative umbrella review criteria, and credibility of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Quality was assessed using the AMSTAR 2 tool. This study is registered with the Open Science Framework, https://osf.io/ap8qu. A total of 112 studies from 18 meta-analyses generating 12 new meta-analyses comprising 21,232 children and adolescents in population groups including attention-deficit/hyperactivity disorder, cancer, cerebral palsy, chronic respiratory diseases, depression, neuromotor impairment, and obesity and in general populations were included. PA interventions were efficacious in reducing psychological symptoms in all meta-analyses across the different population groups using random-effects models. However, umbrella review criteria suggested a weak strength of association for this outcome, and GRADE credibility of evidence ranged from moderate to very low. For psychological well-being, 3 out of 5 meta-analyses identified significant effects, but the strength of these associations was weak, and GRADE credibility of evidence ranged from moderate to very low. Similarly, for social outcomes, meta-analyses reported a significant summary effect, but the strength of association was weak, and GRADE credibility of evidence ranged from moderate to very low. For self-esteem, one meta-analysis in children with obesity failed to show any effect. Even though existing meta-analyses suggested a beneficial effect of PA interventions on psychosocial outcomes across different population groups, the strength of associations was weak, and the credibility of evidence was variable depending on the target population, outcome, and condition or disability. Randomized studies of PA interventions in children and adolescents with and without different physical and psychological conditions or disabilities should always include psychosocial outcomes as an important dimension of social and mental health. Prenatal Maternal Infection and Adverse Neurodevelopment: A Structural Equation Modelling Approach to Downstream Environmental Hits; https://osf.io/; cp85a.


Decomposition and insect succession on human cadavers in a humid, continental (Dfb) climate (Quebec, Canada).
Forensic entomology has been developing globally for decades. Despite this discipline being used in criminal investigations around the world, only a few controlled studies have been performed on human cadavers in human decomposition facilities, with the majority of these being conducted in warm and often dry climates. Therefore, the purpose of our research was to catalogue the first published data on insects associated with decomposed human bodies in a humid, continental (Dfb) climate. Specifically, our objective was to document the diversity and succession of the entomofauna associated with human cadavers throughout the decomposition process, in the Quebec province of Canada, during the summer season. Two human cadavers were studied in 2020 at the site for Research in Experimental and Social Thanatology, REST, located in Bécancour (Quebec, Canada). Insects (and other arthropods) were regularly sampled by visual observations, collection from the cadavers, and by using an entomological net and pitfall traps. Our results highlight that the decomposition process is a heterogeneous and complex process in Quebec, with cadavers showing signs of precocious desiccation/mummification. In addition, our observations confirm that the presence of superficial skin lesions accelerates the colonization of blow flies (Diptera: Calliphoridae) and, consequently, the process of decomposition. Finally, we were able to discriminate between "early colonizers" (e.g., Calliphoridae Lucilia sp. or Calliphora livida), "late colonizers" (e.g., larvae of Piophilidae or Heleomyzidae), and "non-specific colonizers." We also officially report the first observation of Cochliomyia macellaria (Diptera: Calliphoridae) in Quebec. These findings will provide new information to help medico-legal death investigations by determining the minimum time elapsed since death and the circumstances surrounding death.


Characterization of airag collected in Ulaanbaatar, Mongolia with emphasis on isolated lactic acid bacteria.
Airag, alcoholic sour-tasting beverage, has been traditionally prepared by Mongolian nomads who naturally ferment fresh mares' milk. Biochemical and microbiological compositions of airag samples collected in Ulaanbaatar, Mongolia and physiological characteristics of isolated lactic acid bacteria were investigated. Protein composition and biochemical composition were determined using sodium dodecyl sulfate-gel electrophoresis and high performance liquid chromatography, respectively. Lactic acid bacteria were identified based on nucleotide sequence of 16S rRNA gene. Carbohydrate fermentation, acid survival, bile resistance and acid production in skim milk culture were determined. Equine whey proteins were present in airag samples more than caseins. The airag samples contained 0.10-3.36 % lactose, 1.44-2.33 % ethyl alcohol, 1.08-1.62 % lactic acid and 0.12-0.22 % acetic acid. Lactobacillus (L.) helveticus were major lactic acid bacteria consisting of 9 isolates among total 18 isolates of lactic acid bacteria. L. helveticus survived strongly in PBS, pH 3.0 but did not grow in MRS broth containing 0.1 % oxgall. A couple of L. helveticus isolates lowered pH of skim milk culture to less than 4.0 and produced acid up to more than 1.0 %. Highly variable biochemical compositions of the airag samples indicated inconsistent quality due to natural fermentation. Airag with low lactose content should be favorable for nutrition, considering that mares' milk with high lactose content has strong laxative effect. The isolates of L. helveticus which produced acid actively in skim milk culture might have a major role in production of airag.


Bowel wall MRI T1 relaxation estimates for assessment of intestinal inflammation in pediatric Crohn's disease.
To compare bowel wall T1 relaxation estimates in young patients with newly diagnosed ileal CD to healthy control participants, characterize their change over time in response to biologic medical therapy, and evaluate their associations with clinical markers of intestinal inflammation. Patients with newly diagnosed ileal CD and healthy control participants were prospectively recruited between December 2018 and October 2021. Patients underwent research MRI examinations of the bowel at baseline and at 6-weeks and 6-months into biologic medical treatment; control participants underwent single MRI examinations. MRI examinations included native T1 relaxometry of the terminal ileum using a modified Look-Locker inversion recovery (MOLLI) sequence. T1 estimates were measured on scanner-generated parametric maps. Clinical markers of intestinal inflammation were recorded at each visit. Group differences were assessed using the Mann-Whitney U test; the Friedman test was used to assess longitudinal changes in T1 estimates. Spearman correlation was used to evaluate associations between T1 estimates and inflammatory markers. Nineteen participants with CD (12 males; median age 14 years) and 15 control participants (7 males; median age 17 years) were included in the study. Bowel wall T1 estimates in CD patients (median 1302 ms) were significantly longer compared to control participants (median 1159 ms) (p < 0.001). In CD patients, T1 estimates changed over time after treatment (p = 0.001), with largest reductions between baseline and 6-weeks (p < 0.001). T1 estimates correlated with inflammatory markers, including erythrocyte sedimentation rate (ρ = 0.35; p = 0.01), c-reactive protein level (ρ = 0.34; p = 0.02), and weighted Pediatric Crohn's Disease Activity Index (ρ = 0.39; p = 0.005). T1 estimates did not correlate with serum albumin (ρ = - 0.28; p = 0.051) and fecal calprotectin (ρ = 0.07; p = 0.63). Bowel wall T1 estimates are abnormally increased in newly diagnosed ileal CD patients and decrease in response to medical therapy.


Aging and Immunometabolic Adaptations to Thermogenesis.
Brown and subcutaneous adipose tissues play a key role in non-shivering thermogenesis both in mice and human, and their activation by adrenergic stimuli promotes energy expenditure, reduces adiposity, and protects against age-related metabolic diseases such as type 2 diabetes (T2D). Low-grade inflammation and insulin resistance characterize T2D. Even though the decline of thermogenic adipose tissues is well-established during ageing, the mechanisms by which this event affects immune system and contributes to the development of T2D is still poorly defined. It is emerging that activation of thermogenic adipose tissues promotes type 2 immunity skewing, limiting type 1 inflammation. Of note, metabolic substrates sustaining type 1 inflammation (e.g. glucose and succinate) are also used by activated adipocytes to promote thermogenesis. Keeping in mind this aspect, a nutrient competition between adipocytes and adipose tissue immune cell infiltrates could be envisaged. Herein, we reviewed the metabolic rewiring of adipocytes during thermogenesis in order to give important insight into the anti-inflammatory role of thermogenic adipose tissues and delineate how their decline during ageing may favor the setting of low-grade inflammatory states that predispose to type 2 diabetes in elderly. A brief description about the contribution of adipokines secreted by thermogenic adipocytes in modulation of immune cell activation is also provided. Finally, we have outlined experimental flow chart procedures and provided technical advices to investigate the physiological processes leading to thermogenic adipose tissue impairment that are behind the immunometabolic decline during aging.


The age dependence of intracellular proteolysis: changes of the substrate proteins.
Liver cytosol proteins of young (4--6 months) and old (18--27 months) rats were degraded in vitro by papain, pronase, trypsin, pepsin, cathepsin D from rat liver and a soluble lysosomal enzyme mixture from rat liver. We could demonstrate the capability of the latter enzyme mixture to degrade proteolytically the cytosol proteins of young animals about 20% faster than those of the older animal group. Digesting radioactive labelled "young" cytosol in the presence of unlabelled "old" cytosol the possibility could be excluded, that this effect was due to an inhibitor of macromolecular size present in the "old" cytosol.


Adverse health effects and histological changes in white sturgeon (Acipenser transmontanus) exposed to dietary selenomethionine.
It has been shown that selenium (Se) released to the aquatic environment can have devastating effects on local wildlife. White sturgeon (Acipenser transmontanus) have a life history particularly susceptible to contaminants, and their protection is of interest as they are culturally and economically important, and many populations are classified as endangered. During the present 72-d dietary study, multiple signs of decreased health and Se lethality were observed. Juvenile white sturgeon were given diets containing 1.4 μg, 5.6 μg, 22.4 μg, or 104.4 μg selenomethionine/g food (dry mass). Selenium accumulated in muscle and liver tissue in a dose-dependent manner. Edema causing exophthalmos developed within 15 d and 23 d, and lethal effects occurred in 54% and 22% of fish in the high- and medium-dose groups, respectively. Growth and hepatosomatic index were significantly lower in the high-dose group, which also had a high incidence of food avoidance. Histology of the liver revealed a dose-dependent increase in melanomacrophage aggregates and decrease of energy stores, which indicated toxicity. These results indicate that white sturgeon are susceptible to the effects of Se accumulation over relatively short time periods. This stresses the need for continued sturgeon research and studies looking into the environmental fate and regulation of released Se. Environ Toxicol Chem 2016;35:1741-1750. © 2015 SETAC.


Malaria vaccine R&D in the Decade of Vaccines: breakthroughs, challenges and opportunities.
While recent progress has been made in reducing malaria mortality with other interventions, vaccines are still urgently needed to further reduce the incidence of clinical disease, including during pregnancy, and to provide "herd protection" by blocking parasite transmission. The most clinically advanced candidate, RTS,S, is presently undergoing Phase 3 evaluation in young African children across 13 clinical sites in eight African countries. In the 12-month period following vaccination, RTS,S conferred approximately 50% protection from clinical Plasmodium falciparum disease in children aged 5-17 months, and approximately 30% protection in children aged 6-12 weeks when administered in conjunction with Expanded Program for Immunization (EPI) vaccines. The development of more highly efficacious vaccines to prevent clinical disease caused by both P. falciparum and Plasmodium vivax, as well as vaccines to support elimination efforts by inducing immunity that blocks malaria parasite transmission, are priorities. Some key barriers to malaria vaccine development include: a paucity of well-characterized target immunogens and an absence of clear correlates of protection to enable vaccine development targeting all stages of the P. falciparum and P. vivax lifecycles; a limited number of safe and effective delivery systems, including adjuvants, that induce potent, long-lived protective immunity, be it by antibody, CD4+, and/or CD8+ T cell responses; and, for vaccines designed to provide "herd protection" by targeting sexual stage and/or mosquito antigens, the lack of a clear clinical and regulatory pathway to licensure using non-traditional endpoints. Recommendations to overcome these, and other key challenges, are suggested in this document.


Comparison of cervical vertebral anomalies and sella turcica bridging in different growth stages with various vertical skeletal growth patterns.
To compare cervical vertebral anomalies and sella turcica bridging (STB) in different growth stages in orthodontic patients with different vertical skeletal growth patterns. Lateral cephalometric radiographs (LCR) of 270 patients in the preadolescent, adolescent, or postadolescent periods and having low angle [LA], normal angle [NA], or high-angle [HA] vertical skeletal growth patterns were evaluated retrospectively. STB was visualized using LCRs while evaluating the deficiency of ponticulus posticus (PP) and atlas posterior arch (PAA) associated with the atlas bone. The Pearson chi-square and Fisher's exact tests were used for categorical data and one-way ANOVA for numerical data. The prevalence of fully calcified PP and STB increased from the preadolescent (PP, 10.0%; STB, 11.1%) to the postadolescent period (PP, 24.4; STB, 21.1%); they did not differ from vertical skeletal growth patterns (p > 0.05). The prevalence of PAA deficiency is significantly higher in individuals with LA (46.7%) than with other angles (NA, 27.8%; HA, 26.7%). The vertical skeletal growth pattern was significantly related to STB in the preadolescent period and PAA in the postadolescent period. Different anomalies during different growth periods correlate with the vertical skeletal growth pattern. It will be useful to evaluate a different anomaly according to the relevant growth period.


Superiority of intracoronary papaverine to radiographic contrast for measuring coronary flow reserve in patients with ischemic heart disease.
Measurement of coronary flow reserve has been suggested as an adjunct to anatomic assessment of coronary stenoses in patients with ischemic heart disease. We compared papaverine hydrochloride and radiographic contrast to determine which agent was superior for the determination of coronary flow reserve. Coronary flow reserve was determined during cardiac catheterization by means of digital coronary angiography and parametric imaging. Two groups of patients were studied. Among patients in group 1, coronary flow reserve was determined by means of both papaverine and contrast. In group 1 patients with normal coronary arteries, papaverine-induced flow reserve was greater than contrast-induced reserve in all but one vascular region (n = 9, 4.98 +/- 1.15 vs 3.56 +/- 0.89; p = 0.29). Group 1 patients with coronary disease also demonstrated significantly greater flow reserve with papaverine (n = 25, 2.57 +/- 0.20 vs 1.83 +/- 0.11, p less than 0.01). Group 2 included patients with single-vessel coronary artery stenoses. These patients were studied by means of either papaverine or contrast to determine coronary flow reserve for both the stenotic "ischemic" region and an adjacent nonstenotic, "nonischemic" region. Those patients in group 2 who were studied by means of contrast had a modest difference between flow reserve values in the nonischemic and those in the ischemic regions (n = 15, 1.78 +/- 0.10 vs 1.26 +/- 0.09; p less than .0001) with considerable overlap. Patients studied by means of papaverine had a much greater separation in flow reserve between nonischemic and ischemic regions (n = 22, 2.78 +/- 0.19 vs 1.46 +/- 0.14; p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)


[Incidence of vestibular schwannoma in Denmark].
During the last 30 years the number of diagnosed vestibular schwannomas (VS) has increased from 15 in 1976 to 116 in 2006. The aim of this study is to describe and analyse this increase. In Denmark, the handling of VS patients has been centralised since 1976. Since 1976, 2046 new cases of unilateral VS have been diagnosed. In 1976, 15 VS were diagnosed. Since then, the number of diagnosed tumours has increased almost linearly to 116 in 2006. The size of the diagnosed tumours has decreased from 35 mm in 1979 to 10 mm in 2006. In the beginning of the period, giant tumours dominated in contrast to the end of the period where the small tumours dominated. The mean age at the time of diagnosis has been slowly increasing from 50 years in the beginning to almost 60 years at the end of the period. With easier access to MRI, vestibular schwannomas are found earlier when they are still small. The increase in the number of diagnosed tumours is mainly explained by the diagnosis of intrameatal and small tumours in the older age group which was not previously offered MRI examination.


Differences in mortality between late-preterm and term singleton infants in the United States, 1995-2002.
To assess differences in mortality between late-preterm (34-36 weeks) and term (37-41 weeks) infants. We used US period-linked birth/infant death files for 1995 to 2002 to compare overall and cause-specific early-neonatal, late-neonatal, postneonatal, and infant mortality rates between singleton late-preterm infants and term infants. Significant declines in mortality rates were observed for late-preterm and term infants at all age-at-death categories, except the late-neonatal period. Despite the decline in rates since 1995, infant mortality rates in 2002 were 3 times higher in late-preterm infants than term infants (7.9 versus 2.4 deaths per 1000 live births); early, late, and postneonatal rates were 6, 3, and 2 times higher, respectively. During infancy, late-preterm infants were approximately 4 times more likely than term infants to die of congenital malformations (leading cause), newborn bacterial sepsis, and complications of placenta, cord, and membranes. Early-neonatal cause-specific mortality rates were most disparate, especially deaths caused by atelectasis, maternal complications of pregnancy, and congenital malformations. Late-preterm infants have higher mortality rates than term infants throughout infancy. Our findings may be used to guide obstetrical and pediatric decision-making.


Potential optimized route for mesenchymal stem cell transplantation in a rat model of cerebral palsy.
Cerebral palsy (CP) is a movement and posture disorder that affects over 50 million people worldwide. Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation has emerged as an attractive therapeutic strategy for CP. The administration route appears to be crucial for hUC-MSC to provide adequate neuroprotection. Wistar rats were given hypoxia-ischemia to make the CP model on postnatal day 5. On postnatal day 21, DiR-labeled hUC-MSC were transplanted into the CP rats by intravenous, intrathecal, and lateral ventricle for cell tracking. Uninfused CP rats served as the negative control. The motor behavioral and pathological alteration was analyzed 11, 25, and 39 days after transplantation to assess motor function, immune inflammation, neurotrophy, and endogenous repair. In vivo imaging tracking techniques revealed that intravenous infusion resulted in fewer transplanted cells in the target brain than intrathecal and lateral ventricle infusion (p<0.05). Three different routes of hUC-MSC infusion improved the motor function of CP rats (p<0.05). At 11 days post-infusion, intrathecal infusion outperformed intravenous with a significant neurotrophic and oligodendrocyte maturation effect (p<0.05). Intrathecal infusion equaled lateral ventricle infusion after 25 days. At 39 days post-infusion, lateral ventricle infusion exceeded intravenous and intrathecal infusion with a significant immunosuppressive effect (p<0.05). Considering the improved effect and less trauma shown early in the intrathecal infusion, repeated intrathecal administration may ultimately lead to the greatest benefit.


The functional role of an interleukin 6-inducible CDK9.STAT3 complex in human gamma-fibrinogen gene expression.
The signal transducer and activator of transcription 3 (STAT3) is an IL-6-inducible transcription factor that mediates the hepatic acute phase response (APR). Using gamma-fibrinogen (FBG) as a model of the APR, we investigated the requirement of an IL-6-inducible complex of STAT3 with cyclin-dependent kinase 9 (CDK9) on gamma-FBG expression in HepG2 hepatocarcinoma cells. IL-6 induces rapid nuclear translocation of Tyr-phosphorylated STAT3 that forms a nuclear complex with CDK9 in nondenaturing co-immunoprecipitation and confocal colocalization assays. To further understand this interaction, we found that CDK9-STAT3 binding is mediated via both STAT NH2-terminal modulatory and COOH-terminal transactivation domains. Both IL-6-inducible gamma-FBG reporter gene and endogenous mRNA expression are significantly decreased after CDK9 inhibition using the potent CDK inhibitor, flavopiridol (FP), or specific CDK9 siRNA. Moreover, chromatin immunoprecipitation (ChIP) experiments revealed an IL-6-inducible STAT3 and CDK9 binding to the proximal gamma-FBG promoter as well as increased loading of RNA Pol II and phospho-Ser2 CTD Pol II on the TATA box and coding regions. Finally, FP specifically and efficiently inhibits association of phospho-Ser2 CTD RNA Pol II on the gamma-FBG promoter, indicating that CDK9 kinase activity mediates IL-6-inducible CTD phosphorylation. Our data indicate that IL-6 induces a STAT3.CDK9 complex mediated by bivalent STAT3 domains and CDK9 kinase activity is necessary for licensing Pol II to enter a transcriptional elongation mode. Therefore, disruption of IL-6 signaling by CDK9 inhibitors could be a potential therapeutic strategy for inflammatory disease.


Cord and maternal sera from small neonates share dysfunctional lipoproteins with proatherogenic properties: Evidence for Barker's hypothesis.
Fetal growth restriction (GR) is associated with perinatal mortality and subsequent metabolic disorders in adulthood. Until now, there is little information regarding changes in the properties of lipoproteins from growth-restricted fetuses and their maternal sera. To identify unique lipoprotein biomarkers for fetal GR in maternal and cord sera from small neonates, we analyzed lipoprotein compositions and functions. Lipoprotein compositions and functions were compared between cord blood and maternal blood among small for gestational age neonates (SGA; n = 15, 2589 ± 50 g) and appropriate for gestational age neonates (AGA; n = 15) in Korea. Cord blood from the SGA group showed 2-fold higher triglyceride (TG) and TG/high-density lipoprotein cholesterol levels than the AGA group as well as significantly lower (up to 20%) paraoxonase activity and apolipoprotein (apo) A-I content. The SGA group showed the highest cholesteryl ester transfer protein activities in both cord and maternal sera. SGA neonates showed elevated apo-B content in very low-density lipoprotein, 52% reduction of apo A-I content in high-density lipoprotein, and 30% increased glycation (P < .001) compared with AGA neonates. Especially, low-density lipoprotein from the SGA group showed 1.9-fold higher sensitivity to oxidation as well as 3-fold greater uptake into macrophages, suggesting stronger proatherosclerotic properties. Lipoproteins from maternal serum of SGA neonates showed greater oxidation along with TG enrichment and loss of antioxidant ability. On microinjection of cord serum (50 nL) into zebrafish embryos, the SGA group showed the most severe embryonic damage. Lipoproteins from cord and maternal sera of SGA neonates resulted in severe impairment of functional and structural correlations accompanied by greater pro-oxidant and proatherosclerotic properties.


New THAP1 mutation and role of putative modifier in TOR1A.
The prevalence of DYT1 (mutation in TOR1A) and DYT6 (mutation in THAP1) may vary in different populations, which can have important implications in clinical investigation. Our goal was to characterize patients with inherited and isolated dystonia and determine the frequency of mutations responsible for DYT1 and DYT6 in Brazilian patients. Two movement disorder specialists examined 78 patients with idiopathic isolated dystonia using a standardized questionnaire, before sequencing TOR1A and THAP1 genes. Clinically, our cohort was similar to those described in the international literature. Molecular studies of 68 subjects revealed only one potentially deleterious variant in THAP1 (1/68 patients, 1.47%). This was a novel 10-bp deletion at the end of exon 1, g.5308_5317del (ng_011837.1), which is predicted to create an alternative splicing and the insertion of a premature stop codon. Although we did not observe any potentially deleterious mutations in TOR1A, we found the missense variant rs1801968 (TOR1A p.D216H), previously reported as either a modifier of dystonia phenotype or a predisposing factor for dystonia. However, we did not identify any phenotypic impact related to the missense variant rs1801968 (P = 0.3387). Although clinically similar to most cohorts with dystonia worldwide, the classical mutation (c.907_909delGAG) in TOR1A (causing DYT1) is absent in our patients. However, we found a potentially deleterious THAP1 mutation not previously reported. In addition, we found no association of rs1801968 with dystonia.


Screening for colorectal, breast, and cervical cancer in the elderly: a review of the evidence.
There is general consensus that screening can reduce mortality from colorectal, breast, and cervical cancer among persons in their 50s and 60s. However, few screening trials have included persons over age 70 years. Therefore, indirect evidence must be used to determine when results in younger persons should be extrapolated to older persons. In this review, we focus on cancer screening tests that are well accepted in younger persons (mammography, Papanicolaou smears, and colorectal cancer screening) and discuss the strength of inference concerning benefits and harms of screening older persons. Some aspects of aging favor screening (eg, increased absolute risk of dying of cancer) whereas other aspects do not (eg, decreased life expectancy). Age also affects the behavior of some cancers (eg, increases the proportion of slow-growing breast cancers) and affects the accuracy of some screening tests (eg, increases the accuracy of mammography; decreases the accuracy of sigmoidoscopy). These effects make the application of evidence in younger populations to older populations complex. However, given the heterogeneity of the elderly population, there is no evidence of one age at which potential benefits of screening suddenly cease or potential harms suddenly become substantial for everyone. Therefore, characteristics of individual patients that go beyond age should be the driving factors in screening decisions. For example, persons who have a life expectancy less than 5 years or persons who would decline treatment should generally not be screened. Decisions to either continue or discontinue screening in the elderly should be based on health status, the benefits and harms of the test, and preferences of the patient, rather than solely on the age of the patient.


Correlations Between Nutrition Habits, Anxiety and Metabolic Parameters in Greek Healthy Adults.
Anxiety combined with nervousness and apprehension consist a focal response to different life conditions. Lifestyle habits, anxiety and biochemical markers are in a constant interaction. To investigate the prevalence of anxiety in healthy adults and its possible association with biochemical factors-lipid profile, liver markers, thyroid hormones-and lifestyle habits. Quantitative descriptive correlation study. A total of 100 healthy adults participated in the research. A specially designed questionnaire and Hamilton's scale were used. Anthropometric and biochemical analyses were performed. Overall, 61% of the participants presented moderate to very serious anxiety. The average score on the Hamilton scale was 13.82 (±9.000), with men exhibiting less stress than women. For p ≤ 0.05: Stress was positively correlated with impaired thyroid and hepatic function. Hepatic function was affected by both sugar products and water melon, which were positively correlated with total bilirubin and AST/SGOT respectively. Tomato, peppers and legumes were negatively correlated with AST/SGOT. Deep fried food was positively correlated with GGT and triglycerides. Legumes and fish were negatively correlated with CPK. Regarding the lipid metabolism, it was found that food cooked with oil was positively associated with uric acid, but non-cooked olive oil was negatively correlated with the risk for CAD. Thyroid function was negatively correlated with non-homemade food and pasta consumption and positively correlated with consumption of whole grains and green tea. Participants with subclinical hypothyroidism seemed to consume less vitamin B12, folic acid and vegetables. No direct correlation between lifestyle habits and anxiety was found. Nevertheless, eating habits influenced biochemical markers-especially the thyroid hormones-which may be indirectly responsible for anxiety and related moods.


Bonded peptide stationary phases for the separation of amino acids and peptides using liquid chromatography.
Bonded optically active tripeptides have been applied as stationary phases for liquid chromatography. Significant retention variations are shown for some UV absorbing amino acids when compared to a silica gel column using the same mobile phase. The separation of certain isomeric dipeptides has been accomplished using the bonded optically active tripeptide stationary phases. It is shown that these separations are superior to those possible on silica gel, although the efficiencies of the column are low. Phenylthiohydatoin (PTH)-amino acids have also been analyzed using the bonded tripeptide L-Val-L-Ala-L-Ser on silica gel CT and 1% citric acid-water as the mobile phase. No two PTH-amino acids showed the same capacity ratio out of 25 tested and the separation of 15 in one isocratic run is presented. The implications and future for the use of bonded opitcally active peptides as stationary phases for liquid chromatography are discussed.


The amino-acid residues on the C-terminal side of the cleavage site of angiotensinogen influence the species specificity of reaction with renin.
The N-terminal sequences of human and canine angiotensinogen and two hybrid sequences were synthesized and used to determine whether the species specificity of renin is influenced by amino-acid residues adjacent to the cleavage site. kcat/Km for the generation of angiotensin I from the N-terminal tridecapeptide of human angiotensinogen by canine renin is 0.37% of that observed when the N-terminal tetradecapeptide from canine angiotensinogen is used as a substrate. Replacement of the valine residue at P'1 in the human tridecapeptide with the leucine residue from the canine sequence triples kcat and improves Km 4-fold. Replacement of isoleucine residue at P'2 with the valine residue from the canine sequence enhances Km 8-fold. Substitution of the histidine residue at P'3 with the tyrosine serine sequence of canine angiotensinogen increases kcat an order of magnitude. Results obtained with the synthetic substrate are similar to those observed with the protein substrates. Canine renin does not cleave human angiotensinogen. Also, kcat/Km of canine renin for its homologous substrate is about 6-times greater than the kcat/Km value for human renin acting on human angiotensinogen.


Development and disintegration of tapetum-specific lipid-accumulating organelles, elaioplasts and tapetosomes, in Arabidopsis thaliana and Brassica napus.
The pollen coat covering the surface of pollen grains has many important roles for pollination. In Brassicaceae plants, the pollen coat components are synthesized and temporarily accumulated in two tapetum-specific organelles, the elaioplast and the tapetosome. Although many biochemical and electron microscopic analyses have been attempted, the structure and biogenesis of these organelles have not been fully elucidated. To resolve this problem, we performed live imaging of these organelles using two markers, FIB1a-GFP and GRP17-GFP. FIB1a is an Arabidopsis fibrillin, a structural protein of elaioplast plastoglobules. In transgenic Arabidopsis, fluorescence of FIB1a-GFP appeared in young elaioplasts, in which small plastoglobules were developing. However, the fluorescence disappeared in later stages, while enlargement of plastoglobules continued. GRP17 is an Arabidopsis oleopollenin, an oleosin-like protein in tapetosomes. Fluorescence microscopy of GRP17-GFP expressed in Arabidopsis and Brassica napus revealed that tapetosomes do not contain oleopollenin-coated vesicles but have an outer envelope, indicating that the tapetosome structure is distinct from seed oil bodies. Visualization of GRP17-GFP also demonstrated that the tapetal cells become protoplasts and migrate into locules before pollen coat formation, and provided live imaging of the foot formation between pollen grains and stigmatic papilla cells.


Biomass in turtle populations: A neglected subject.
Biomass values for individual turtle species are as high as 586 kg/ha. Typical values are at least an order of magnitude greater than those typical of endotherms, but comparable to ectotherms with aquatic niches. Herbivorous turtle species tend to have higher biomasses than omnivorous or carnivorous species, but the differences are not statistically significant. Semiaquatic species typically have the lowest biomasses. Islands, ponds, and springs harbor species with the highest biomasses. Annual production estimates for two turtle species (three populations) are 1.4 to 14.9 and 6 kg/ha/yr, and are similar to estimates available for most other vertebrate groups except fishes (maximum, 528 kg/ha/yr).


High Incidence of Hepatic Encephalopathy After Viatorr Controlled Expansion Transjugular Intrahepatic Portosystemic Shunt Creation.
The Viatorr Controlled Expansion (VCX) stent-graft was designed to mitigate hepatic encephalopathy (HE) after transjugular intrahepatic portosystemic shunt (TIPS) creation. To determine the incidence and degree of HE after VCX TIPS. Thirty-three patients (M:F 17:16, mean age 58 years, mean MELD score 12) who underwent VCX TIPS between 2018 and 2019 were retrospectively studied. 11/33 (33%) patients had medically controlled pre-TIPS HE. TIPS indications included variceal hemorrhage (n = 12, 30%) and ascites (n = 21, 70%). Measured outcomes were post-TIPS HE (overall, recurrent, de novo) graded using the West Haven system, time-to-HE occurrence, HE-related hospitalization rate, and TIPS reduction rate. VCX TIPS were 8 mm in 28/33 (85%) and 10 mm in 5/33 (15%). Mean final portosystemic pressure gradient was 6 mmHg. Cumulative HE incidence post-TIPS was 61% (20/33). 1-, 3-, 6-, and 12-month HE rates were 24%, 30%, 53%, and 61% over 247-day median follow-up. Median time-to-HE was 180 days. HE grades spanned grade 1 (n = 6), grade 2 (n = 8), and grade 3 (n = 6); 9 and 11 cases were recurrent and de novo HE, respectively. Medication non-compliance/infection was implicated in HE in 9/20 (45%) cases. Medical therapy addressed HE in 18/20 (90%) cases; however, HE still resulted in 39 hospitalizations among 13 patients, and median time to first hospitalization was 75 days. Shunt reduction was necessary in 2 (10%) cases of medically refractory HE. The incidence of HE after VCX TIPS is high. Though HE symptoms may be medically controlled, hospitalization rates are high, and shunt reduction may be necessary.


Delay effects on the stability of large ecosystems.
The common intuition among the ecologists of the midtwentieth century was that large ecosystems should be more stable than those with a smaller number of species. This view was challenged by Robert May, who found a stability bound for randomly assembled ecosystems; they become unstable for a sufficiently large number of species. In the present work, we show that May's bound greatly changes when the past population densities of a species affect its own current density. This is a common feature in real systems, where the effects of species' interactions may appear after a time lag rather than instantaneously. The local stability of these models with self-interaction is described by bounds, which we characterize in the parameter space. We find a critical delay curve that separates the region of stability from that of instability, and correspondingly, we identify a critical frequency curve that provides the characteristic frequencies of a system at the instability threshold. Finally, we calculate analytically the distributions of eigenvalues that generalize Wigner's as well as Girko's laws. Interestingly, we find that, for sufficiently large delays, the eigenvalues of a randomly coupled system are complex even when the interactions are symmetric.


[Prevention and multimodal therapy of hyperthyroidism].
Subclinical and overt hyperthyroidism have been associated with various negative clinical outcomes as for example an increased risk of atrial fibrillation or increased cardiovascular mortality, especially in old age. In order to avoid hyperthyroidism it is strongly recommended not to start any iodine containing drug therapy or to avoid application of contrast agents unless the patient presents with an unremarkable clinical course. TSH suppressive therapy for the treatment of endemic goiter or differentiated low risk thyroid carcinoma is unnecessary, since it favours the development of subclinical hyperthyroidism. Overt hyperthyroidism is treated with antithyroid drugs and/or radioiodine therapy or surgery according to the underlying disease (toxic nodular goiter, Graves' disease).


Telemedicine efficiently improves access to hepatitis C management to achieve HCV elimination in the penitentiary setting.
Linkage to care for hepatitis C includes a new tool: teleconsultation. Micro-elimination in prison is a recommendation and is feasible. An economic evaluation of telemedicine for hepatitis C virus (HCV) treatment in prisons has not yet been performed. This study aimed to provide a cost-minimization analysis comparing two strategies of HCV treatment in a prison: telemedicine clinical practice (TCP) and the usual clinical practice (UCP). An observational cost-minimization study was carried out on a cohort of inmates who received anti-HCV treatment in El Dueso prison (May 2016-November 2017). A decision tree was constructed, incorporating different clinical profiles according to the severity of the disease, the results of diagnostic tests, and treatment outcomes as well as the costs of each profile. Satisfaction with telemedicine was evaluated through an 11-question questionnaire with a 5-point Likert scale. Seventy-five inmates were treated and underwent TCP with a follow-up of one year. The average cost per patient with the TCP strategy was €1,172 (€1,151 direct costs). Had UCP been carried out, the cost would have been €1,687 (€1,630 direct). Telemedicine consultation practice produced savings of €516 (30.6%) per patient, with total savings of €38,677. The transfer costs from prison to hospital represented the most important saving item, accounting for 99.3% of the TCP-related savings. The questionnaire revealed high levels of satisfaction with TCP, with a median score of 5 in each question. Sustained virological response rates were 94.7% after the first treatment and 100% after retreatment of the four relapses. Telemedicine consultation practice is a more efficient strategy than UCP, mainly due to the reduction of transfer costs while preserving effectiveness and user satisfaction.