The stressed female brain: neuronal activity in the prelimbic but not infralimbic region of the medial prefrontal cortex suppresses learning after acute stress.
Women are nearly twice as likely as men to suffer from anxiety and post-traumatic stress disorder (PTSD), indicating that many females are especially vulnerable to stressful life experience. A profound sex difference in the response to stress is also observed in laboratory animals. Acute exposure to an uncontrollable stressful event disrupts associative learning during classical eyeblink conditioning in female rats but enhances this same type of learning process in males. These sex differences in response to stress are dependent on neuronal activity in similar but also different brain regions. Neuronal activity in the basolateral nucleus of the amygdala (BLA) is necessary in both males and females. However, neuronal activity in the medial prefrontal cortex (mPFC) during the stressor is necessary to modify learning in females but not in males. The mPFC is often divided into its prelimbic (PL) and infralimbic (IL) subregions, which differ both in structure and function. Through its connections to the BLA, we hypothesized that neuronal activity within the PL, but not IL, during the stressor is necessary to suppress learning in females. To test this hypothesis, either the PL or IL of adult female rats was bilaterally inactivated with GABAA agonist muscimol during acute inescapable swim stress. About 24 h later, all subjects were trained with classical eyeblink conditioning. Though stressed, females without neuronal activity in the PL learned well. In contrast, females with IL inactivation during the stressor did not learn well, behaving similarly to stressed vehicle-treated females. These data suggest that exposure to a stressful event critically engages the PL, but not IL, to disrupt associative learning in females. Together with previous studies, these data indicate that the PL communicates with the BLA to suppress learning after a stressful experience in females. This circuit may be similarly engaged in women who become cognitively impaired after stressful life events.


Comparison of Riboflavin and Toluidine Blue O as Photosensitizers for Photoactivated Disinfection on Endodontic and Periodontal Pathogens In Vitro.
Photoactivated disinfection has a strong local antimicrobial effect. In the field of dentistry it is an emerging adjunct to mechanical debridement during endodontic and periodontal treatment. In the present study, we investigate the effect of photoactivated disinfection using riboflavin as a photosensitizer and blue LED light for activation, and compare it to photoactivated disinfection with the widely used combination of toluidine blue O and red light. Riboflavin is highly biocompatible and can be activated with LED lamps at hand in the dental office. To date, no reports are available on the antimicrobial effect of photoactivated disinfection using riboflavin/blue light on oral microorganisms. Planktonic cultures of eight organisms frequently isolated from periodontal and/or endodontic lesions (Aggregatibacter actinomycetemcomitans, Candida albicans, Enterococcus faecalis, Escherischia coli, Lactobacillus paracasei, Porphyromonas gingivalis, Prevotella intermedia and Propionibacterium acnes) were subjected to photoactivated disinfection with riboflavin/blue light and toluidine blue O/red light, and survival rates were determined by CFU counts. Within the limited irradiation time of one minute, photoactivated disinfection with riboflavin/blue light only resulted in minor reductions in CFU counts, whereas full kills were achieved for all organisms when using toluidine blue O/red light. The black pigmented anaerobes P. gingivalis and P. intermedia were eradicated completely by riboflavin/blue light, but also by blue light treatment alone, suggesting that endogenous chromophores acted as photosensitizers in these bacteria. On the basis of our results, riboflavin cannot be recommended as a photosensitizer used for photoactivated disinfection of periodontal or endodontic infections.


The effect of hydration status on appetite and energy intake.
This study investigated the effect of hypohydration produced by exercise and sub-optimal rehydration on appetite and energy intake. Ten males lost ~2% body mass through evening exercise in the heat (35°C). Over the next 13 h, participants were re-fed and either rehydrated (RE: water equal to 175% of body mass loss (BML)) or remained hypohydrated (HYPO: 200 ml water), until the following morning. Urine samples, blood samples and subjective feelings were collected pre-exercise, post-exercise and 13 h post-exercise, with an ad libitum breakfast provided 13 h post-exercise. Total BML at 13 h post-exercise was greater during HYPO (2.8 (0.5)%) than RE (0.5 (0.5)%). Energy intake at the ad libitum breakfast was similar between trials (RE: 4237 (1459) kJ; HYPO: 4612 (1487) kJ; P = 0.436), with no difference in energy consumed in foods (P = 0.600) or drinks (P = 0.147). Total water ingestion at the ad libitum breakfast meal was greater during HYPO (1641 (367) ml) than RE (797 (275) ml) (P < 0.001), with this being explained by increased water intake through fluids (P < 0.001). Thirteen hours post-exercise, participants reported greater thirst (P < 0.001) and lower fullness (P < 0.01) during HYPO. Alterations in hydration status produced by exercise are unlikely to influence post-exercise food intake and consequently other aspects of recovery or adaptation.


Transferrin Functionalized Liposomes Loading Dopamine HCl: Development and Permeability Studies across an In Vitro Model of Human Blood-Brain Barrier.
The transport of dopamine across the blood brain barrier represents a challenge for the management of Parkinson's disease. The employment of central nervous system targeted ligands functionalized nanocarriers could be a valid tactic to overcome this obstacle and avoid undesirable side effects. In this work, transferrin functionalized dopamine-loaded liposomes were made by a modified dehydration-rehydration technique from hydrogenated soy phosphatidylcoline, cholesterol and 1,2-stearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(poly(ethylene glycol)-2000)]. The physical features of the prepared liposomes were established with successive determination of their endothelial permeability across an in vitro model of the blood-brain barrier, constituted by human cerebral microvascular endothelial cells (hCMEC/D3). Functionalized dopamine-loaded liposomes with encapsulation efficiency more than 35% were made with sizes in a range around 180 nm, polydispersity indices of 0.2, and positive zeta potential values (+7.5 mV). Their stability and drug release kinetics were also evaluated. The apparent permeability (Pe) values of encapsulated dopamine in functionalized and unfunctionalized liposomes showed that transferrin functionalized nanocarriers could represent appealing non-toxic candidates for brain delivery, thus improving benefits and decreasing complications to patients subjected to L-dopa chronical treatment.


[Hyperparathyroidism and parathyroidectomy in dialyzed patients].
The authors present older and more recent views regarding the pathogenesis of hypocalcaemia and secondary hyperparathyroidism in patients with chronic renal failure with emphasis on the impact of inorganic phosphate retention and lack of 1,25-dihydroxyvitamin D3 in body fluids. As regards therapeutic procedures the initial problem is to control hyperphosphataemia and to suppress the increased parathormone secretion in particular in dialyzed patients. When treating hyperphosphataemia it is necessary with regard to the severity of the finding to use concurrently several procedures and avoid aluminium phosphate binders. Aimed reduction of high parathormone levels in the blood stream can be achieved by medicamentous--pharmacological means, using 1,25 (OH)2 D3 or surgery of the hypertrophic parathyroid glands. The term parathyroidectomy can comprise also percutaneous infiltration of the parathyroid glands with ethanol. From this aspect under certain circumstances a combination of different therapeutic procedures may prove useful. In the conclusion the authors mention basic data on para-thyroidectomies performed in their department: the favourable long-term results of operations amounted to 80.4%.


18.6-year Earth tide regulates geyser activity.
Over 40 years of records from Yellowstone National Park, Wyoming, show that the 18.6-year tidal component strongly regulates the frequencies of eruption of Grand and Steamboat geysers. The frequency of Grand Geyser increases with increasing tidal force and that of Steamboat Geyser decreases, which suggests that tidal dilatation is one factor affecting heat flow to a geyser.


Actinomadura bangladeshensis sp. nov. and Actinomadura chokoriensis sp. nov.
The taxonomic position of two soil isolates, 3-46-b(3)(T) and 3-45-a(11)(T), was clarified based on data from a polyphasic study. The organisms showed a combination of chemotaxonomic and morphological properties typical of the genus Actinomadura. They formed distinct phyletic lines in the Actinomadura 16S rRNA gene tree and were closely associated with the type strains of Actinomadura meyerae (sequence similarity of 98.3-98.5 %), Actinomadura napierensis (98.1-98.3 %) and Actinomadura latina (96.4-96.8 %). The level of 16S rRNA gene sequence similarity between the new isolates was 99.1 %. The level of DNA-DNA hybridization between strains 3-46-b(3)(T) and 3-45-a(11)(T) was 43.6 % and levels of relatedness between the two new isolates and the type strains of A. meyerae and A. napierensis were 21.0-27.3 %. On the basis of phenotypic and genotypic properties, the new isolates could be differentiated from each other and from their closest phylogenetic relatives. It is proposed that the organisms be classified as representing two novel species of the genus Actinomadura. The names proposed for these taxa are Actinomadura bangladeshensis sp. nov. [type strain 3-46-b(3)(T) =JCM 13933(T) =MTCC8057(T)] and Actinomadura chokoriensis sp. nov. [type strain 3-45-a(11)(T) =JCM 13932(T) =MTCC8056(T)].


Length of paternal lifespan is manifested in the DNA methylome of their nonagenarian progeny.
The heritability of lifespan is 20-30%, but only a few genes associated with longevity have been identified. To explain this discrepancy, the inheritance of epigenetic features, such as DNA methylation, have been proposed to contribute to the heritability of lifespan.We investigated whether parental lifespan is associated with DNA methylation profile in nonagenarians. A regression model, adjusted for differences in blood cell proportions, identified 659 CpG sites where the level of methylation was associated with paternal lifespan. However, no association was observed between maternal lifespan and DNA methylation. The 659 CpG sites associated with paternal lifespan were enriched outside of CpG islands and were located in genes associated with development and morphogenesis, as well as cell signaling. The largest difference in the level of methylation between the progeny of the shortest-lived and longest-lived fathers was identified for CpG sites mapping to CXXC5. In addition, the level of methylation in three Notch-genes (NOTCH1, NOTCH3 and NOTCH4) was also associated with paternal lifespan.There are implications for the inheritance of acquired traits via epigenetic mechanisms in mammals. Here we describe DNA methylation features that are associated with paternal lifespan, and we speculate that the identified CpG sites may represent intergenerational epigenetic inheritance.


The pattern of genetic transmission of the leukocyte defect in fatal granulomatous disease of childhood.
The leukocyte-phagocytic function test which was found to be abnormal in boys with fatal granulomatous disease of childhood has been found to be abnormal to an intermediate extent in their mothers. Nine of nine mothers were shown to be abnormal, whereas none of eight fathers and none of five healthy brothers exhibited a defect. 10 of 16 female siblings were abnormal to the same degree as their mothers, as were all three maternal grandmothers available for study. Assuming that this intermediate functional defect represents the heterozygous state, the nine family pedigrees are entirely compatible with the concept that the trait is transmitted on the X-chromosome.A tetrazolium dye-phagocytosis histochemical test was also abnormal in the carrier females and provided independent confirmation of the selection of the female siblings suspected of being carriers for the trait. In addition, this procedure gives indirect evidence that the gene in question is subject to the random inactivation that appears to affect many X-linked genes in mammalian females. The family members were also studied with two of the metabolic assays that have been shown to be abnormal in the cells of affected boys. One assay, the oxidation of the first carbon of glucose-1-(14)C by the isolated leukocytes, was significantly abnormal in the cells of carrier females. The other assay, the oxidation of formate-(14)C by leukocytes of heterozygotes was not significantly different from control values. The practical problem of diagnosing patients would appear to be best solved with a tetrazolium dye procedure, whereas the more subtle abnormality in carrier females is best detected with the leukocyte function test. Improved methods for the function test are being developed.


A systematic examination of the nature and content of vignettes in schizophrenia research.
Vignettes are often used in psychiatric research, yet there are few systematic studies on their content, creation, and use. This article describes a study of: (a) how researchers create vignettes in research on schizophrenia and (b) how these vignettes portray individuals with schizophrenia. We conducted a systematic search of the PubMed database for articles between 2008 and 2012 that used vignettes to measure attitudes about schizophrenia. We analyzed the identified vignettes using a tool developed in reference to DSM criteria. Within the vignettes, 98% of individuals portrayed demonstrated delusions, 91% demonstrated hallucinations and 29% demonstrated disorganized speech. The majority of vignettes portrayed individuals under 25 years and when both genders were not depicted, researchers chose to depict men much more frequently than women (41% vs. 8%). A majority of articles did not use original vignettes (55%), and many of the articles (53%) contained vignettes created by one team of researchers. Most vignettes did not include positive language or recovery-oriented information. This study highlights a need for critical thought on vignette development and utilization, especially as psychiatry is now moving towards a recovery-based understanding of mental illness.


Global evacuation of burn patients does not increase the incidence of venous thromboembolic complications.
Case-control studies have suggested that air travel may be a risk factor for the development of Venous Thromboembolism (VTE). Burned patients from the current war in Iraq and Afghanistan, are transported across three continents to our Burn Center with total ground and air transport time being approximately 24 hours spread over 3 days to 4 days. We hypothesized global evacuation results in increased VTE rates. Retrospective review of 1,107 consecutive patients admitted to our burn center from January 2003 to December 2005. In the time period evaluated, no detectible differences were found in incidence of VTE between air-evacuated soldiers and those admitted to our facility from South Texas (1.31% vs. 0.83%, p = ns). The air-evacuated soldiers were younger (26 +/- 7 vs. 41 +/- 19, p < 0.0001) but had a higher incidence of inhalation injury (14.4% vs. 8.0%, p < 0.0001) and higher Injury Severity Score (10.9 +/- 13.0 vs. 6.5 +/- 9.2, p < 0.0001). No difference in average percent total body surface area involvement was found (15.8 +/- 19.4 vs. 15.5 +/- 18.4, p = ns). Overall, 11 of 1,107 (0.99%) burned patients developed VTE. Prolonged global evacuation is not associated with increased risk of VTE.


Postmarketing surveillance of corneal edema, Fuchs dystrophy, and amantadine use in the Veterans Health Administration.
To determine the proportion of patients who were dispensed amantadine and diagnosed with corneal edema or Fuchs dystrophy within specified time frames. Postmarketing surveillance study. The national Veterans Health Administration pharmacy and clinical databases were used to identify a cohort of veterans without a prior history of corneal edema, Fuchs dystrophy, or a prescription for amantadine. During fiscal years 2005-2006, 2 databases were used to identify patients with new diagnoses of corneal disease and new prescriptions for amantadine. Patients from each were cross-referenced. The outcome measure was concurrent diagnosis of corneal edema or Fuchs dystrophy and new prescription for amantadine within specified intervals. Thirty-six (0.27%) patients among the 13,137 who were dispensed amantadine were diagnosed with corneal edema or Fuchs dystrophy within the 2-year study period. The relative risk of corneal edema for a person prescribed amantadine was 1.7 (95% confidence interval: 1.1-2.8). In 12 (0.09%) patients, the corneal diagnoses were recorded within a month of being prescribed amantadine. Retrospective examination of a large national medical database revealed that amantadine was temporally associated with a small proportion of patients diagnosed with corneal edema or Fuchs dystrophy. Although additional studies are needed to confirm the risk of corneal edema with amantadine, the development of corneal edema in persons prescribed amantadine warrants clinical attention. In such a situation, physicians may consider stopping amantadine to see if the edema subsides.


Is the integration of nutritional care in the different assistance levels possible? Refl ections from the perspective of chronicity and clinical complexity
Nowadays, chronicity is the leitmotiv in all healthcare systems. Consequently, multimorbidity and the management of complex care needs become a critical challenge in modern welfare societies. Professionals and other agents' difficulties to identify and satisfy healthcare related needs of these patients is especially signifi cant in a 5% of the population. This has an enormous impact not only from a clinical perspective, but also in terms of the resilience of public health care systems. In this context, nutritional status plays an outstanding role as a health indicator and also as a determinant vector of morbidity and mortality. However, improvement possibilities regarding the evolution of epidemiological knowledge and the implementation of person-centered attention models are still vast. The management of malnutrition related to complex chronic conditions is not limited to the profi le of the patient's conditions, since the explanatory role of social factors, which become key to clinical management, is crucial. As a result of the above, integrated and person-centered approaches, where nutritional factors often play an important role, are required to provide care to the most vulnerable patients within our settings. Therefore, collaborative work appears as one of the keys to success.


Synthesis and analgesic effects of new pyrrole derivatives of phencyclidine in mice.
Phencyclidine (1-(1-phenylcyclohexyl)piperidine, CAS 956-90-1, PCP, I) and many of its analogues have shown some pharmacological effects. In this study, new pyrrole derivatives of I (1-(1-phenylcyclohexyl)pyrrole, II and 1-[1-(4-methylphenyl)(cyclohexyl)]pyrrole, III) and their intermediates were synthesized and the acute and chronic pains were examined on mice using tail immersion (as a model of acute thermal pain) and formalin (as a model of acute and chronic chemical pain) tests and the results were compared with the PCP and control groups. The results indicated that III generated higher analgesic effects in the tail immersion test compared to the PCP and control (dimethyl sulfoxide, DMSO) groups, demonstrating a marked and significant increase in tail immersion latency, but this effect was not observed for II in the dose of 1 mg/kg. The formalin test showed that III was effective in acute chemical pain (phase I, 0-5 min after injection), but was not effective for II at the same dosage compared to the PCP and control groups. Also chronic pain will be significantly attenuated by III but II was not effective as compared to the other groups. It is concluded that substitution of the aromatic pyrrole ring instead of piperidine in the PCP molecule will not be effective alone in tail immersion and formalin tests but the addition of a methyl group (with high electron donating and dipole moments) on the phenyl group plus substitution of the aromatic pyrrole ring can be effective in acute and chronic pain compared to the PCP and control groups.


Photoinactivation of Propionibacterium acnes by near-ultraviolet light.
Photodestruction of Propionibacterium acnes was investigated by broad-band near-ultraviolet light. The inactivation of the bacteria was found to be oxygen dependent, and without O2 practically no photoinactivation occurred. D2O caused an increased inactivation (D10 = 5 kJ/m2 in D2O as compared to D10 = 11 kJ/m2 in normal water). Decreased temperature during illumination increased the ability to form colonies. The results are compared with corresponding results for other types of cells and the destruction mechanism is discussed.


Gastric carcinoid associated with achlorhydria, hypergastrinemia, and Addison's disease.
We have described a 40-year-old woman whose classic adrenal insufficiency, achlorhydria, and hypergastrinemia was complicated by the development of a gastric carcinoid. There is now evidence that patients with elevated serum gastrin levels are at increased risk for this rare tumor.


TQM implementation for the healthcare sector.
Purpose The purpose of this paper is to enlarge the debate on total quality management (TQM) implementation in the healthcare sector and to evaluate how and whether leadership can affect TQM implementation. Design/methodology/approach This paper is based on findings from a literature review of TQM and leadership. The authors analysed these findings to categorise causes of a lack of leadership in TQM programme implementations. Findings The authors propose three categories of causes of a lack of leadership in TQM programme implementation. The first cause is well-known: a lack of senior managers' involvement and commitment. The second category is the "combined leadership" that occurs in large healthcare organisations; and the third category is the influence of an external "political leadership" on public healthcare. Research limitations/implications This paper presents researchers with three categories of causes of failure of leadership in TQM implementation that can be investigated. It also encourages reflections from practitioners concerning TQM leadership in the healthcare sector. Practical implications The authors request that practitioners reflect on ways to create or sustain a "monolithic" leadership, especially in large organisations, to ensure a common vision, values and attitude for unitary TQM governance. Originality/value In an original way, this paper analyses and proposes three categories of causes linked to a lack of TQM leadership in the healthcare sector.


[Identification of pathogenic Escherichia coli strains in various clinical material and their antibiotic susceptibility].
In this study 200 E. coli strains were isolated and identified from 95 fecal, 96 urinary and 9 vaginal specimens. The pathogenic species isolated from feces were 61.05% of all identified E. coli strains. This percentage was 26.04% for urinary specimens. The distribution of E. coli serotypes was determined. Mostly E. coli O111 K58 B4 strain was isolated from the pathological materials such as 20% in feces, 12.5% in urine, 11.11% in vaginal secretions. The sex distribution of isolated E. coli strains from urine was 77.08% for female patients and 22.92% male patients. We can say that E. coli species which have been isolated and identified from pathological materials are susceptible to seftriaxon 73.5% and sefotaxime 72.5%, but they have been readily gaining resistance against gentamicin and nalidixic acid. Broad spectrum antibiotics and chemotherapeutic agents are widely used in the treatment of E. coli infections. However medical therapy doesn't always produce good result. Because E. coli strains have been gaining resistance to chemotherapeutic agents and antibiotics. So, it is suggested that the most effective antibiotic should be determined by antibiogram and used.


Identification of phosphate oxygens that are important for self-cleavage activity of the HDV ribozyme by phosphorothioate substitution interference analysis.
A phosphorothioate substitution interference assay was used to investigate the role of the pro-Rp oxygens of phosphate groups in the self-cleavage reaction of the genomic human hepatitis delta virus (HDV) ribozyme. Incorporation of several different phosphorothioates (NTP alpha S) into the HDV ribozyme inhibited the self-cleavage activity. Incorporation of uridine 5' phosphorothioate or adenosine 5' phosphorothioate maintained 72% of the original self-cleavage activity whereas incorporation of guanosine 5' phosphorothioate or cytosine 5' phosphorothioate into the precursor reduced self-cleavage activity to about 20% in each case. Using partially substituted phosphorothioate-modified transcripts, we identified the pro-Rp oxygens that are important for the ribozyme activity, and they are located at positions 0, 1, 4, 5, 21, 24, 25, 27, 28, 30-34, 40, 43 and 75. In particular, the pro-Rp oxygens at positions 0, 1 and 21 are appear to be critical for the self-cleavage activity of the HDV ribozyme.


Mechanisms and clinical significance of cell volume regulation.
A wide variety of factors challenge constancy of cell volume. Alterations of cell volume activate diverse cell volume regulatory mechanisms including ion transport, osmolyte accumulation, metabolism and expression of appropriate genes. A wealth of cellular signalling pathways link cell volume to the respective regulatory mechanisms. Cell volume emerges as a pathophysiologically important parameter in several diseases including diabetes mellitus, uraemia, hepatic insufficiency and hypercatabolic states. The role of altered cell volume in disease is a challenge which requires more experimental research and clinical investigation.


Longer ovarian stimulation reduces embryo number and clinical pregnancy rate in long GnRH agonist cycles.
The aim of this study was to analyze whether the length of controlled ovarian stimulation affects in vitro fertilization (IVF) cycle outcomes. This retrospective cohort study was performed at a private, university-affiliated fertility centre. We reviewed 1522 IVF cycles, comprising 979 long gonadotropin-releasing hormone (GnRH) agonist and 543 GnRH antagonist protocols. All subjects underwent controlled ovarian stimulation followed by fresh embryo transfer. Logistic regression analysis was used to examine the relationship between trigger day and the following cycle outcomes: normal fertilization rate (FR), proportion of mature oocytes, proportion of cycles with embryos for cryopreservation, and clinical pregnancy rate (CPR). In long agonist cycles, having more days of stimulation was associated with a lower clinical pregnancy rate (OR=0.87, 95% CI=0.80-0.96, P=0.01). Longer stimulation also resulted in fewer cycles with supernumerary embryos for cryopreservation (OR=0.84, 95% CI=0.77-0.92, P=0.0005), despite a having greater number of mature oocytes retreived (OR=1.05, 95% CI=1.01-1.10, P=0.04). For each additional day of stimulation in a long agonist protocol, the odds of achieving a clinical pregnancy were reduced by 13% and of achieving cryopreservation by 16%. In the antagonist protocol group, the length of ovarian stimulation did not have an effect on the clinical pregnancy and cryopreservation rates. Longer duration of ovarian stimulation appears to reduce clinical pregnancy and embryo cryopreservation rates in subjects undergoing long GnRH agonist cycles. The number of days of stimulation does not appear to affect those using the GnRH antagonist protocol.


A mechanism of action for morphine-induced immunosuppression: corticosterone mediates morphine-induced suppression of natural killer cell activity.
Morphine is a drug of abuse with an ability to down-regulate immune responsiveness that could have potentially serious consequences in both heroin addicts and in the clinical environment. The exact mechanism of action by which morphine induces immunosuppression has yet to be clearly determined. A direct mechanism of action is suggested to operate through lymphocyte opiate receptors, but the nature of such receptors is still in question. The alternative, an indirect mechanism of action is proposed to be mediated by two possible pathways, hypothalamic-pituitary-adrenal axis activation with increased production of adrenal corticosteroids, or activation of the sympathetic nervous system and concomitant catecholamine release. Natural killer (NK) cell activity was used to determine potential indirect mechanisms of action for morphine. NK activity in the B6C3F1 mouse was suppressed between 12 and 48 hr after implantation of 75 mg timed-release morphine pellets. Morphine suppressed NK activity in a dose-responsive manner. The opiate antagonists naloxone and naltrexone completely blocked morphine-induced suppression of NK activity, whereas naloxone methiodide, a congener that crosses the blood-brain barrier much more slowly than naloxone, produced very little blockade. Implantation of the 75-mg morphine pellets produced a significant elevation in serum corticosterone levels. In vitro exposure to corticosterone is known to suppress NK activity directly, whereas in vitro morphine was unable to alter directly NK activity. The glucocorticoid receptor antagonist Roussel-Uclaf 38486 blocked morphine-induced suppression of NK activity in a dose-responsive fashion. Naltrexone (10-mg pellet) antagonized the morphine-induced elevation in serum corticosterone.(ABSTRACT TRUNCATED AT 250 WORDS)


Addressing anaemia in pregnancy in rural plains Nepal: A qualitative, formative study.
Maternal anaemia prevalence in low-income countries is unacceptably high. Our research explored the individual-, family- and community-level factors affecting antenatal care uptake, iron folic acid (IFA) intake and consumption of micronutrient-rich diets among pregnant women in the plains of Nepal. We discuss how these findings informed the development of a home visit and community mobilisation intervention to reduce anaemia in pregnancy. We used a qualitative methodology informed by the socio-ecological framework, conducting semi-structured interviews with recently pregnant women and key informants, and focus group discussions with mothers-in-law and fathers. We found that harmful gender norms restricted women's access to nutrient-rich food, restricted their mobility and access to antenatal care. These norms also restricted fathers' role to that of the provider, as opposed to the caregiver. Pregnant women, mothers-in-law and fathers lacked awareness about iron-rich foods and how to manage the side effects of IFA. Fathers lacked trust in government health facilities affecting access to care and trust in the efficacy of IFA. Our research informed interventions by (1) informing the development of intervention tools and training; (2) informing the intervention focus to engaging mothers-in-law and men to enable behaviour change; and (3) demonstrating the need to work in synergy across individual, family and community levels to address power and positionality, gender norms, trust in health services and harmful norms. Participatory groups and home visits will enable the development and implementation of feasible and acceptable strategies to address family and contextual issues generating knowledge and an enabling environment for behaviour change.


[Ruifuping pectin protects against intestinal mucosal injury in the rat exertional heat stroke model].
To evaluate the intestinal function in rats with exertional heat stroke (EHS) and explore the protective role of Ruifuping pectin (RFP) against heat related intestinal mucosal injury. One hundred and twenty healthy special pathogen free (SPF) male Sprague-Dawley (SD) rats were randomly divided into normothermic control group, EHS model group, hyperthermic plus drinking water group (H2O+EHS group) and hyperthermic plus pectin group (RFP+EHS group) with 30 rats in each group. The rats in the H2O+EHS group and RFP+EHS group were given water 20 mL/kg or RFP 20 mL/kg orally for 5 days during adaptive training period. After 1 week, the temperature control range was adjusted to (37±1) centigrade using the temperature control treadmill, and the rat model of EHS was reproduced by one-time high temperature exhaustive exercise. No rehydration intervention was given during the training adaptation period in the EHS model group. The rats in the normothermic control group were maintained to room temperature (25±2) centigrade and humidity (55±5)% without other treatment. Behavior tests including withdraw response, righting, and muscle strength were performed immediately after onset of EHS. Blood of inferior vena cava was collected, and the serum inflammatory cytokines [tumor necrosis factor-α (TNF-α) and interleukins (IL-6, IL-1β, IL-10)] and activity of diamine oxidase (DAO) were detected by enzyme linked immunosorbent assay (ELISA). The intestinal mucosa was collected, after hematoxylin-eosin (HE) staining, and Chiu score was performed to assess EHS induced pathological changes under light microscope. The rats in the EHS model group had behavioral, inflammatory and pathological changes, such as delayed withdraw response and righting, decreased forelimb pulling, increased inflammatory index, and obvious intestinal mucosal injury, which indicated that the reproduction of the EHS model was successful. There was no significant difference in above parameters between the H2O+EHS group and the EHS model group except that the inflammatory index in the RFP+EHS group was improved. Compared with the EHS model group, the withdraw reflex to pain and righting after RFP pretreatment in the RFP+EHS group were significantly improved (righting score: 1.4±0.2 vs. 0.3±0.2, withdraw reflex to pain score: 1.0±0.1 vs. 0.2±0.1, both P < 0.05), the muscle strength was significantly increased (N: 13.0±0.5 vs. 8.2±0.6, P < 0.01). The levels of pro-inflammatory factors in the RFP+EHS group were significantly lower than those in the EHS model group [TNF-α (ng/L): 67.5±9.2 vs. 194.3±13.7, IL-6 (ng/L): 360.0±54.1 vs. 981.2±84.4, IL-1β (ng/L): 33.7±9.0 vs. 88.7±6.1, all P < 0.01], while the level of anti-inflammatory factor IL-10 was higher than that in the EHS model group (ng/L: 208.7±10.5 vs. 103.7±7.0, P < 0.01). The degree of intestinal mucosal injury in the RFP+EHS group was less severe than that in the EHS model group, and the Chiu score and DAO were significantly lower than those in the EHS model group [Chiu score: 1.5±0.2 vs. 3.8±0.0, DAO (U/L): 83.7±6.7 vs. 128.7±10.5, both P < 0.05]. High temperature training can damage the intestinal barrier function, and induce endotoxemia and systemic inflammatory response syndrome (SIRS) in rats. Oral prophylactic RFP can protect the intestinal barrier function, alleviate SIRS, and promote the recovery of basic nerve reflex and muscle strength after the occurrence of EHS in rats.


Histiocytic necrotising lymphadenitis (Kikuchi-Fujimoto disease) in Saudi Arabia: clinicopathology and immunohistochemistry.
Kikuchi-Fujimoto disease (KFD) is a rare entity of uncertain cause that commonly presents as a benign self-limiting disease of unknown origin. The objective of this study was to document the clinical features, mode of presentation, histopathological and immunohisto-chemical (IHC) features of KFD at our institutions since little is known about this disease in our region. We reviewed the histopathological reports of all lymph nodes resected at or referred to King Abdulaziz University Hospital between 1990 and 2003 and King Faisal Specialist Hospital & Research Center, Jeddah, Kingdom of Saudi Arabia between 2000 and 2003. All cases diagnosed as KFD were identified and the histological slides and clinical data were reviewed. IHC was performed for the proliferative marker Ki-67 and the apoptosis-related markers Bcl-2 and p53. In 2500 lymph node biopsies, 15 cases were diagnosed as KFD. The female to male ratio was 2.7:1. One patient presented with axillary lymphadenopathy and the others presented with cervical lymphadenopathy. Ages averaged 29 years and ranged from 13 to 46 years. There was no recurrence of the lymphadenopathy over 1 to 10 years of follow up. Bcl-2 and p53 were negative and Ki-67 was positive in 11 of 15 cases. The results support earlier findings that KFD is a self-limiting disorder that requires no specific management. We suggest a clinical follow-up for several years. The female predominance was striking. Apoptosis-regulating proteins are not helpful in the diagnosis. KFD usually expressed the proliferation-associated nuclear antigen Ki-67. Increased awareness of KFD will minimize the risk of confusing this entity with malignant lymphoma or other serious conditions.


1,3,3,5-Tetra-methyl-1H-1,5-benzodiazepine-2,4(3H,5H)-dione.
The seven-membered ring in the title compound, C(13)H(16)N(2)O(2), adopts a boat-shaped conformation (with the C atoms of the fused-ring as the stern and the C atom bearing two methyl groups) as the prow.


Sexual Dimorphism in the Th17 Signature of Ankylosing Spondylitis.
To identify an immunologic basis for the male sex bias in ankylosing spondylitis (AS). Cohorts of male and female patients with AS and age- and sex-matched healthy control subjects were selected, and the levels of serum cytokines (interferon-γ [IFNγ], tumor necrosis factor α, interleukin-17A [IL-17A], and IL-6) were examined by enzyme-linked immunosorbent assay, the frequencies of Th1 and Th17 cells were assessed by flow cytometry, and whole blood gene expression was analyzed using both microarray and NanoString approaches. The frequency of IL-17A and Th17 cells, both of which are key factors in the inflammatory Th17 axis, was elevated in male patients with AS but not in female patients with AS. In contrast, AS-associated alterations in the Th1 axis, such as the frequency of IFNγ and Th1 cells in serum, were independent of a patient's sex. Results of microarray analysis supported an altered Th17 axis in male patients, with a specific increase in IL17RA. In addition, male and female patients with AS displayed shared gene expression patterns, while male patients with AS had additional alterations in gene expression that were not seen in female patients with AS. The differential sex-related immune profiles were independent of HLA-B27 status, clinical disease activity (as measured by the Bath Ankylosing Spondylitis Disease Activity Index), or treatment (with nonsteroidal antiinflammatory drugs or biologic agents), implicating intrinsic sexual dimorphism in AS. The results of this study demonstrate distinct sexual dimorphism in the activation status of the immune system in patients with AS, particularly in the Th17 axis. This dimorphism could underlie sex-related differences in the clinical features of AS and could provide a rationale for sex-specific treatment of AS.


Electroencephalogram spectral edge frequency, lower esophageal contractility, and autonomic responsiveness during general anesthesia.
Both the electroencephalogram (EEG) spectral edge frequency (SEF) and lower esophageal contractility (LEC) indices have been reported to be useful indicators of anesthetic depth. We designed a prospective study to evaluate the relationship between changes in these two variables and objective measurements of physiologic responsiveness to surgical stress (i.e., changes in hemodynamic variables and plasma levels of norepinephrine, epinephrine, total catecholamines, and vasopressin). Eighty-nine consenting adult males undergoing radical prostatectomy procedures under a standardized general anesthetic technique were studied according to a randomized, single-blinded protocol. General anesthesia was induced with 30 micrograms/kg intravenous (i.v.) alfentanil, 2.5 mg/kg i.v. thiopental, and 0.1 mg/kg i.v. vecuronium, and subsequently maintained with 0.5 microgram/kg/min alfentanil, nitrous oxide (N2O) 67% in oxygen, and 0.8 microgram/kg/min vecuronium. Following retropubic dissection, 81 patients (92%) manifested acute hypertensive responses, with mean arterial pressure increasing from 90 +/- 14 to 122 +/- 14 mm Hg (mean +/- SD). This acute hypertensive response was treated with one of three different treatment modalities (20 to 60 micrograms/kg i.v. alfentanil, 0.5 to 2.0% inspired isoflurane, or 0.05 to 0.15 mg/kg i.v. trimethaphan) to return the mean arterial pressure to within 10% of the preincisional (baseline) value within 5 to 10 minutes. Although the mean arterial pressure, heart rate, and plasma levels of catecholamines and vasopressin significantly increased following the surgical stimulus, and decreased after adjunctive therapy, the EEG-SEF and LEC index (LECI) values did not significantly change during these study intervals. Furthermore, using a logistic regression analysis, we observed that preincision EEG-SEF and LECI values could not predict whether patients would manifest a hypertensive response. Therefore, the EEG-SEF and LECI were unreliable indicators of anesthetic depth.


Gastroduodenal safety of cyclooxygenase-2 inhibitors.
Cyclooxygenase-1 (COX-1) derived eicosanoids promote gastroprotective mucosal defenses and induce platelet aggregation. By sparing COX-1, COX-2 specific inhibitors provide effective anti-inflammatory and analgesic activity while substantially reducing the risk of peptic ulcer disease and GI bleeding compared to dual COX inhibitors (traditional NSAIDs). Clinical studies of the COX-2-selective inhibitors have demonstrated efficacy equivalent to nonselective NSAIDs with significantly lower rates of GI toxicity. The incidence of endoscopic ulcers in some studies with coxibs has approximated placebo. However, as the detection of endoscopic lesions is not always correlated with symptomatic ulcers and ulcer complications, outcome studies of GI safety were performed. The results of large outcome studies have evaluated rofecoxib and celecoxib in over 39,000 patients with osteoarthritis or rheumatoid arthritis. Results of these studies showed that patients taking a supratherapeutic dose of rofecoxib or celecoxib had significantly lower rates of GI-related adverse events than those taking a nonselective NSAID. The GI safety of coxibs for patients using low dose aspirin concomitantly with a coxib appears to be reduced, particularly with regard to ulcer complications. Such data provide support for the COX-2 hypothesis and demonstrate that coxibs provide effective treatment of pain and inflammation with a reduced risk of gastropathy.


Extinction measurements for optical band gap determination of soot in a series of nitrogen-diluted ethylene/air non-premixed flames.
Visible light extinction was measured in a series of nitrogen-diluted, ethylene/air, non-premixed flames and this data was used to determine the optical band gap, OBG, as a function of flame position. Collimated light from a supercontinuum source is telescopically expanded and refocused to match the f- number of a dispersing monochromator. The dispersed light is split into a power metering channel and a channel that is periscoped and focused into the flame. The transmitted light is then recollimated and focussed onto a silicon photodiode detector. After tomographic reconstruction of the radial extinction field, the OBG was derived from the near-edge absorption feature using Tauc/Davis-Mott analysis. A slight evolution in OBG was observed throughout all flame systems with a consistent range of OBG observed between approximately 1.85 eV and 2.35 eV. Averaging over all positions the mean OBG was approximately 2.09 eV for all flame systems. Comparing these results to previously published computational results relating calculated HOMO-LUMO gaps for a variety of D2h PAH molecules to the number of aromatic rings in the structure, showed that the observed optical band gap is consistent with a PAH of about 14 rings or a conjugation length of 0.97 nm. This work provides experimental support to the model of soot formation where the transition from chemical to physical growth starts at a modest molecular size; about the size of circumpyrene.


Variations in serum sCD23 in conditions with either enhanced humoral or cell-mediated immunity.
Soluble CD23 (sCD23) is increased by interleukin-4 (IL-4) and decreased by interferon-gamma (IFN-gamma). On the basis of cytokine profiles T-helper (Th) cells may be functionally divided into IL-2- and IFN-gamma-secreting Th1 cells, which are involved in cell-mediated immunity (CMI), and IL-4- and IL-5-producing Th2 cells, which are involved in humoral immunity. Compared with sex-matched controls (median 8.5) we found significantly elevated levels of serum sCD23 in patients with rheumatoid arthritis (median 22.7, P < 0.0002), with the highest levels detected in patients fulfilling an increasing number of the American Association revised criteria for rheumatoid arthritis. Soluble CD23 levels were also significantly raised in autoimmune thyroiditis (median 11.7, P < 0.02) and myasthenia gravis (median 10.4, P < 0.05). In contrast patients with either coeliac (median 6.5) or Crohn's disease (median 5.8) had reduced levels of sCD23 compared to appropriate controls (median 11.8), in both cases significant at P < 0.01. Variations in sCD23 may, therefore, reflect enhanced Th1 activity in the two later conditions in contrast to heightened Th2 activity within the three classical autoimmune conditions.


Facial reanimation by means of the hypoglossal nerve: anatomic comparison of different techniques.
The goal of this study was to determine the various anatomical and surgical relationships between the facial and hypoglossal nerves to define the required length of each for a nerve transfer, either by means of a classical hypoglossal-facial nerve anastomosis or combined with any of its variants developed to reduce tongue morbidities. Five adult cadaver heads were bilaterally dissected in the parotid and submaxillary regions. Two clinical cases are described for illustration. The prebifurcation extracranial facial nerve is found 4.82 +/- 0.88 mm from the external auditory meatus, 5.31 +/- 1.50 mm from the mastoid tip, 15.65 +/- 0.85 mm from the lateral end of C1, 17.19 +/- 1.64 mm from the border of the mandible condyle, and 4.86 +/- 1.29 mm from the digastric muscle. The average lengths of the mastoid segment of the facial nerve and the prebifurcation extracranial facial nerve are 16.35 +/- 1.21 mm and 18.93 +/- 1.41 mm, respectively. The average distance from the bifurcation of the facial nerve to the hypoglossal nerve turn is 31.56 +/- 2.53 mm. For a direct hypoglossal-facial nerve anastomosis, a length of approximately 19 mm of the hypoglossal nerve is required. For the interposition nerve graft technique, a 35 mm-long graft is required. For the technique using a longitudinally dissected hypoglossal nerve, an average length of 31.56 mm is required. Exposure of the facial nerve within the mastoid process drilling technique requires 16.35 mm of drilling. This study attempts to establish the exact graft, dissection within the hypoglossal nerve, and mastoid drilling requirements for hypoglossal to facial nerve transfer.


Aptamer-Based Biosensor for Detection of Mycotoxins.
Mycotoxins are a large type of secondary metabolites produced by fungi that pose a great hazard to and cause toxic reactions in humans and animals. A majority of countries and regulators, such as the European Union, have established a series of requirements for their use, and they have also set maximum tolerance levels. The development of high sensitivity and a specific analytical platform for mycotoxins is much in demand to address new challenges for food safety worldwide. Due to the superiority of simple, rapid, and low-cost characteristics, aptamer-based biosensors have successfully been developed for the detection of various mycotoxins with high sensitivity and selectivity compared with traditional instrumental methods and immunological approaches. In this article, we discuss and analyze the development of aptasensors for mycotoxins determination in food and agricultural products over the last 11 years and cover the literatures from the first report in 2008 until the present time. In addition, challenges and future trends for the selection of aptamers toward various mycotoxins and aptasensors for multi-mycotoxins analyses are summarized. Given the promising development and potential application of aptasensors, future research studies made will witness the great practicality of using aptamer-based biosensors within the field of food safety.


Single-Cell RNA Sequencing Revealed a 3-Gene Panel Predicted the Diagnosis and Prognosis of Thyroid Papillary Carcinoma and Associated With Tumor Immune Microenvironment.
The objective of this research was to screen prognostic related genes of thyroid papillary carcinoma (PTC) by single-cell RNA sequencing (scRNA-seq), to construct the diagnostic and prognostic models based on The Cancer Genome Atlas Thyroid Cancer (TCGA-THCA) data, and to evaluate the association between tumor immune microenvironment and the prognostic model. The differentially expressed genes (DEGs) and tumor evolution were analyzed by scRNA-seq based on public databases. The potential regulatory networks of DEGs related to prognosis were analyzed by multi-omics data in the THCA. Logistic regression and Cox proportional hazards regression were utilized to construct the diagnosis and prognostic model of PTC. The performance of the diagnostic model was verified by bulk RNA sequencing (RNA-seq) of our cohort. The tumor immune microenvironment associated with the prognostic model was evaluated using multi-omics data. In addition, qRT-PCR was performed on tumor tissues and adjacent normal tissues of 20 patients to verify the expression levels of DEGs. The DEGs screened by scRNA-seq can distinguish between tumor and healthy samples. DEGs play different roles in the evolution from normal epithelial cells to malignant cells. Three DEGs ((FN1, CLU, and ANXA1)) related to prognosis were filtered, which may be regulated by DNA methylation, RNA methylation (m6A) and upstream transcription factors. The area under curve (AUC) of the diagnostic model based on 3-gene in the validation of our RNA-seq was 1. In the prognostic model based on 3-gene, the overall survival (OS) of high-risk patients was shorter. Combined with the clinical information of patients, a nomogram was constructed by using tumor size (pT) and risk score to quantify the prognostic risk. The age and tumor size of high-risk patients in the prognostic model were greater. In addition, the increase of tumor mutation burden (TMB) and diversity of T cell receptor (TCR), and the decrease of CD8+ T cells in high-risk group suggest the existence of immunosuppressive microenvironment. We applied the scRNA-seq pipeline to focus on epithelial cells in PTC, simulated the process of tumor evolution, and revealed a prognostic prediction model based on 3 genes, which is related to tumor immune microenvironment.


Responses to life events as predictors of suicidal behavior.
This study, built on Jacobs' conceptual work, considered the interaction of a complex of predictor variables (hopelessness; locus of control; preference for inclusion, control, and affection; and stress from life events) in relation to the degree of suicide intent. Although the multiple regression equation computed for the combination of variables was significantly related to the criterion variable, suicide intent, hopelessness and preference for affection were the only major variables that contributed a significant amount of variance. Hopelessness, however, was the only variable that significantly related to suicide intent when considered outside the context of the multiple regression equation. In addition, the correlations between locus of control and hopelessness, as well as preference for affection and hopelessness, were significant and appeared to account for different variance than accounted for by the correlation of hopelessness and suicide intent.


Nose to Brain Delivery of Nanoformulations for Neurotherapeutics in Parkinson`s disease: Defining the Preclinical, Clinical and toxicity issues.
Parkinson`s disease (PD) is depicted as the most prevailed neurodegenerative disease being secondary to the alzheimer`s disease. PD is featured by severe dropping of dopamine related neurons present in substantia nigra as well as cytoplasmic inclusions. A number of therapeutic agents are available to treat initial as well as later complications of PD. However, transport of neurotherapeutics into the brain has been a consistent challenge for researchers, because of the existence of blood-brain barrier (BBB). In some last decades, nasal delivery pathway has gained extensive deliberations. Intranasal administration as a way to target neurotherapeutics to the central nervous system bypassing blood brain barrier, exhibit several advantages for treating neurodegenerative disorders. This route for transport of neurotherapeutics offers the merits of convenience of administration, avoidance of pre-systemic hepatic metabolism, and non- invasiveness. The present review explores the novel nano sized formulations of various actives researched for intranasal drug transport to be used in PD therapy. Feasibility of various nano-carriers systems such as nano-emulsions, lipid nanoparticles and polymeric micelles has been elaborated. The write up traces the pre-clinical and pharmacokinetic aspects of the nano-formulations. The neuroprotection and neurotoxicity aspects have also been furnished. Nano-formulations are the rising formulations in PD treatment as they offer targeted drug delivery, enhanced therapeutic efficacy and decreased systemic side effects of neurotherapeutics. These formulations provide effective intranasal transport by encapsulating drug, protecting it from biological/chemical degradation and extracellular transport through P-glycoprotein (P-gp) efflux thus, and enhancing CNS availability for drugs.


Epiphora due to compression of the lacrimal sac by a supernumerary blind sac.
A 23-year-old male had suffered from epiphora in the left eye since childhood. There was no history of infection or trauma. A supernumerary punctum was seen in the left lacrimal caruncle on examination. Subsequent dacryocystography and computer tomography showed a blind-ended sac that was connected to the supernumerary punctum, but not to the normally developed nasolacrimal system. When distended with secretion, this blind-ended lacrimal sac caused compression and obstruction of the normal lacrimal drainage pathway, which led to epiphora. The epiphora disappeared after surgical removal of the supernumerary system.


Response of shear stress to ac electric fields under steady shear flow in a droplet-dispersed phase.
We have measured the response of shear stress to ac electric fields under steady shear flow in the droplet-dispersed phase of an immiscible polymer blend. A characteristic mode was found under steady shear flow, the relaxation frequency of which increased with increasing the shear rate. In the frequency dispersion, a scaling relation derived from dimensional analysis was confirmed to hold. The origin of the mode was investigated on the basis of the Maffettone-Minale (MM) model, in which the droplet shape is described by a second-rank tensor. The frequency dispersion of the response was also calculated using a modified MM model.


From Molecular Docking to 3D-Quantitative Structure-Activity Relationships (3D-QSAR): Insights into the Binding Mode of 5-Lipoxygenase Inhibitors.
Pharmacological intervention with 5-Lipoxygenase (5-LO) is a promising strategy for treatment of inflammatory and allergic ailments, including asthma. With the aim of developing predictive models of 5-LO affinity and gaining insights into the molecular basis of ligand-target interaction, we herein describe QSAR studies of 59 diverse nonredox-competitive 5-LO inhibitors based on the use of molecular shape descriptors and docking experiments. These studies have successfully yielded a predictive model able to explain much of the variance in the activity of the training set compounds while predicting satisfactorily the 5-LO inhibitory activity of an external test set of compounds. The inspection of the selected variables in the QSAR equation unveils the importance of specific interactions which are observed from docking experiments. Collectively, these results may be used to design novel potent and selective nonredox 5-LO inhibitors.


High-Grade Transformation (Dedifferentiation) of Acinic Cell Carcinoma of the Parotid Gland: Report of an Unusual Variant.
Acinic cell carcinoma with high-grade transformation of the salivary gland is an unusual variant with less than fifty cases being reported in the literature. It is characterized by a low- and high-grade component juxtaposed with one another and tends to take on a more aggressive clinical course than its low-grade counterpart, suggesting a poor clinical outcome. We, hereby, report a case of acinic cell carcinoma in a 48-year-old woman with a 6-month history of a right parotid facial swelling rapidly increasing in size. The tumor was initially resected; however, residual focal tissue subsequently revealed areas typical of low-grade acinic cell carcinoma as well as high-grade transformation/dedifferentiation via histopathology.


Registration-assisted segmentation of real-time 3-D echocardiographic data using deformable models.
Real-time three-dimensional (3-D) echocardiography is a new imaging modality that presents the unique opportunity to visualize the complex 3-D shape and motion of the left ventricle (LV) in vivo and to measure the associated global and local function parameters. To take advantage of this opportunity in routine clinical practice, automatic segmentation of the LV in the 3-D echocardiographic data, usually hundreds of megabytes large, is essential. We report a new segmentation algorithm for this task. Our algorithm has two distinct stages, initialization of a deformable model and its refinement, which are connected by a dual "voxel + wiremesh" template. In the first stage, mutual-information-based registration of the voxel template with the image to be segmented helps initialize the wiremesh template. In the second stage, the wiremesh is refined iteratively under the influence of external and internal forces. The internal forces have been customized to preserve the nonsymmetric shape of the wiremesh template in the absence of external forces, defined using the gradient vector flow approach. The algorithm was validated against expert-defined segmentation and demonstrated acceptable accuracy. Our segmentation algorithm is fully automatic and has the potential to be used clinically together with real-time 3-D echocardiography for improved cardiovascular disease diagnosis.


Sensitively detecting endogenous homocysteine in human serum and cardiomyocytes with a specific fluorescent probe.
The elevated level of homocysteine (Hcy) in circulating blood is generally regarded as a risk factor for a variety of diseases including acute myocardial infarction (AMI), but there is no clear answer to whether circulating Hcy can be used for AMI diagnosis. To address it, here we have designed a tetraazacycle-based fluorescent probe for sensitive detection of endogenous Hcy in AMI patients' serum and cardiomyocytes, showing a perfect selectivity over other biothiols (e.g. Cys and GSH). It mainly relies on the formation of a stable six-membered ring structure when this probe responds to Hcy, which is accompanied by a weakening of photoinduced electron transfer (PET) that induces a sharp increase in the fluorescence emission. In this way, Hcy can be probed in biofluids with high sensitivity. We then employed this fluorescent sensor to statistically analyze the levels of Hcy in human circulating blood, indicating a big difference between AMI patients and the healthy participants. To tell whether such a difference is applicable to AMI diagnosis, we further compare the expression levels of Hcy in cardiomyocytes and other tissue cells. It reveals a lower level of endogenous Hcy in cardiomyocytes, implying no direct relationship between the elevated Hcy and cardiomyocyte damage. This observation suggests that Hcy in circulating blood cannot be utilized as a potential biomarker for AMI diagnosis, although it is proven as a risk factor for this disease.


Spatiotemporal visual processing in schizophrenia.
Studies examining visual processing in schizophrenia have provided inconsistent results. In this study, the authors measured static and dynamic visual contrast sensitivity (CS) in patients with schizophrenia (n=20) and control subjects (n=15). Extrapyramidal symptoms were evaluated with the Simpson-Angus scale. In the static condition, the patients with schizophrenia showed reduced CS in the spatial frequency range of 2.9-14.4 cycles per degree of visual angle (c/d). In the dynamic condition, CS loss was present over the whole range tested (0.5-14.4 c/d). Higher Simpson-Angus scores and higher doses of antipsychotic medication were associated with more severe CS deficits. These results suggest that the hypodopaminergic state induced by antipsychotic medication may produce parkinsonian visual impairments in schizophrenia patients.


Combinations of anti-LFA-1, everolimus, anti-CD40 ligand, and allogeneic bone marrow induce central transplantation tolerance through hemopoietic chimerism, including protection from chronic heart allograft rejection.
Central transplantation tolerance through hemopoietic chimerism initially requires inhibition of allogeneic stem cell or bone marrow (BM) rejection, as previously achieved in murine models by combinations of T cell costimulation blockade. We have evaluated LFA-1 blockade as part of regimens to support mixed hemopoietic chimerism development upon fully allogeneic BALB/c BM transfer to nonirradiated busulfan-treated B6 recipient mice. Combining anti-LFA-1 with anti-CD40 ligand (CD40L) induced high incidences and levels of stable multilineage hemopoietic chimerism comparable to chimerism achieved with anti-CD40L and everolimus (40-O-(2-hydroxyethyl)-rapamycin) under conditions where neither Ab alone was effective. The combination of anti-LFA-1 with everolimus also resulted in high levels of chimerism, albeit with a lower incidence of stability. Inhibition of acute allograft rejection critically depended on chimerism stability, even if maintained at very low levels around 1%, as was the case for some recipients without busulfan conditioning. Chimerism stability correlated with a significant donor BM-dependent loss of host-derived Vbeta11(+) T cells 3 mo after BM transplantation (Tx). Combinations of anti-CD40L with anti-LFA-1 or everolimus also prevented acute rejection of skin allografts transplanted before established chimerism, albeit not independently of allospecific BMTx. All skin and heart allografts transplanted to stable chimeras 3 and 5 mo after BMTx, respectively, were protected from acute rejection. Moreover, this included prevention of heart allograft vascular intimal thickening ("chronic rejection").


[Selenium deficiency in celiac disease: risk of autoimmune thyroid diseases].
The essential trace mineral selenium is of fundamental importance to human health. It is incorporated in the proteome in the forms of the genetically encoded amino acids selenocysteine and selenomethionine, which are the characteristic components of selenoproteins (SeP) such as glutathione peroxidases (GPx), thioredoxin reductases and iodothyronine deiodinase families. Thyroid is especially sensitive to selenium deficiency, because SeP can modify thyreocytes function by acting as antioxidants and modifying redox status and thyroid hormone metabolism. SeP are also involved in apoptosis, cell growth and modification of the action of cell signalling systems and transcription factors. Some intestinal GPx modulate apoptosis by removing the cells affected by oxidative damage preserving tissue integrity. The malfunctioning of the GPx antioxidant system in intestinal mucosa can trigger a continuous cycle of reactive oxygen species and inflammation. Selenium deficiency is a risk factor, due to the malabsorption, in celiac disease (CD) because the inflammatory damage affects the small intestine; this deficiency can modulate SeP genes expression, with consequent reiteration of inflammation and increase of mucosal damage. In active CD, overexpression of interleukin-15 (IL-15) may increase activation of effector mechanisms of epithelial damage by stimulating T helper 1 cytokine proliferation and production and intraepithelial lymphocytes cytotoxicity by protecting these lymphocytes from apoptosis. Blocking IL-15 has the potential to provide new therapeutic tools to prevent both tissue damage and complication of CD such as autoimmune thyroid diseases (AITD) where IL-15 expression is also increases. In view of the role played by SeP in apoptosis inhibition, the presence of environmental factors such as selenium deficiency can be considered an important direct factor of thyroidal damage in development of AITD.


An axosomatic and axodendritic multipolar neuron in the lizard cerebral cortex.
The morphology and synaptic organisation of a type of multipolar neuron of the lizard cerebral cortex were studied by Golgi impregnation, intracellular injection of horseradish peroxidase, electron microscopy, and immunocytochemistry. It is a GABA-immunoreactive interneuron and most likely parvalbumin-immunoreactive. Its conspicuous axonal arbor is characterised by an initial segment arising from the soma or from a juxtasomatic dendritic segment. The initial axon segment ramifies and gives rise to thick myelinated segments that terminate in short unmyelinated branches studded with thick boutons 'en passant' that (1) make axosomatic synapses on bipyramidal neuronal somata and (2) synapse on initial apical dendritic segments of bipyramidal neurons forming climbing-like cartridges. The dendrites extend throughout the thickness of the cortex, receiving synaptic input from a variety of sources of which the most prominent is that of zinc-positive boutons coming from granule cells of the medial cortex. According to its synaptology, this interneuron may play a role in regulating the activity of bipyramidal neurons by both feed-forward and feed-back inhibition mechanisms. From a comparative standpoint, it may be related to the sparsely spiny or nonspiny multipolar neurons of the stratum oriens of the mammalian hippocampus.


Shame, guilt, and communication in lung cancer patients and their partners.
Lung cancer patients report the highest distress levels of all cancer groups. In addition to poor prognosis, the self-blame and stigma associated with smoking might partially account for that distress and prevent patients from requesting help and communicating with their partners. The present study used innovative methods to investigate potential links of shame and guilt in lung cancer recovery with distress and marital adjustment. A specific emphasis was an examination of the impact of shame on partner communication. Lung cancer patients (n = 8) and their partners (n = 8) completed questionnaires and interviews that were videotaped. We report descriptive statistics and Spearman correlations between shame and guilt, relationship talk, marital satisfaction, distress, and smoking status. We coded the interviews for nonverbal expressions of shame. Greater self-reported shame was associated with decreased relationship-talk frequency and marital satisfaction, and with increased depression and smoking behaviour. Nonverbal shame behaviour also correlated with higher depression and increased smoking behaviour. Guilt results were more mixed. More recent smoking behaviour also correlated with higher depression. At a time when lung cancer patients often do not request help for distress, possibly because of shame, our preliminary study suggests that shame can also disrupt important partner relationships and might prevent patients from disclosing to physicians their need for psychosocial intervention and might increase their social isolation. Even if patients cannot verbally disclose their distress, nonverbal cues could potentially give clinicians an opportunity to intervene.


Short pregnancy interval, low birthweight, and the sudden infant death syndrome.
Pregnancy intervals were calculated for 54,369 later-born singletons delivered during 1969 in the State of North Carolina. Subsequent infant deaths among this cohort were categorized into probable sudden infant death syndrome (SIDSp), other postneonatal home deaths, all postneonatal hospital deaths, all neonatal deaths, and all deaths due to congenital malformations. Each death was matched with a control drawn from the population of infants surviving the first year of life. The matching variables were maternal age, race, mother's education and number of previous live births. All categories of death showed higher proportions of short intervals among cases than controls. Comparing the interval distributions by means of the X2 test for linearity produced significant results for only SIDSp and neonatal deaths. It was concluded, however, that short-pregnancy interval probably has a similar effect on the risk of death from all five cause of death groups. The introduction of birthweight as a fifth matching variable left no significant differences in the distributions of pregnancy intervals between cases and controls. This was interpreted as evidence that short pregnancy interval exerts its influence on risk of death in infancy through its effect on birthweight. The estimated reduction in prematurity and infant mortality that might result from the elimination of short pregnancy intervals was 5% and 6%, respectively.


Bone mineral loss and cognitive impairment: The PRESENT project.
Low bone mineral density (BMD) is correlated with Alzheimer's disease and its severity, but the association remains unclear in adults (≥50 years) without a history of stroke or dementia.We assessed BMD and cognitive function using the Mini-Mental Status Examination (MMSE) in 650 stroke- and dementia-free subjects (≥50 years) who were recruited for an early health check-up program between January 2009 and December 2010.The mean age was 62.9 ± 8.0 years and mean MMSE score was 27.6 ± 3.6. A total of 361 subjects had reduced BMD: 197 (30.3%) had osteopenia and 154 (23.6%) had osteoporosis, based on criteria of world health organization. A total of 5.4% of the male subjects had osteoporosis, versus 19.8% of the female subjects. After adjusting for age, sex, education, and other possible confounding factors such as hypertension, diabetes mellitus, and smoking, the estimated odds ratio for cognitive impairment was 1.72 for the osteopenia group (95% confidence interval [CI] 1.09-2.14, P = .019) and 2.81 for the osteoporosis group (95% CI 1.78-4.45, P < .001).Low BMD is correlated with cognitive impairment in community-dwelling adults aged 50 years and above without any medical history of stroke or dementia, especially in women. A community-based, early life, preventive osteoporosis education campaign might decrease the incidence of dementia.


Clonidine, acebutolol and their interaction in essential hypertension: effects on blood pressure and the control of water and electrolyte balance.
The effects of 0.5 mg of slow-release (sr) clonidine, 800 mg of acebutolol, and of both drugs combined on blood pressure and the water-salt balance were compared in 10 patients with essential hypertension. An initial placebo period was followed by three 72-h periods during which 5 patients were given sr-clonidine, acebutolol plus sr-clonidine, and acebutolol, respectively in that order whereas the other 5 received the same drugs in the opposite order. Placebo and active medications were given once a day, and the recorded variables were measured 24 h after the last intake. Sr-clonidine, acebutolol and their combined administration reduced mean blood pressure by 23, 16 and 39 mmHg, respectively, indicating first, that single daily doses of sr-clonidine and/or acebutolol constitute satisfactory antihypertensive treatments and second, that the interaction of these drugs is additive. All three treatments reduced plasma renin activity significantly and similarly. A reduction in plasma and urinary aldosterone was observed with sr-clonidine, and a decrease in plasma noradrenaline with the combined treatment. Both water diuresis and natriuresis rose significantly during combined therapy. The additive antihypertensive effects of sr-clonidine and acebutolol might be due to the parallel inhibition observed in the renin and sympathetic systems, and to the increase in natriuresis.


Application of flow cytometry in diagnosis of hydatidiform moles.
We analyzed the nuclear DNA content of 219 hydropic placentas and 68 control (nonhydropic) placentas by flow cytometry (FCM) using formalin-fixed paraffin-embedded tissues. Of 129 cases originally diagnosed as complete hydatidiform mole (CM), 91 were diploid, 25 tetraploid, one triploid, and 12 aneuploid. Of five invasive CM, two were diploid, and three (including one metastasizing mole) were tetraploid. Of 49 partial hydatidiform moles (PM), 36 were triploid and 13 were diploid. Of 41 hydropic abortuses (HA), 34 were diploid, one tetraploid, four triploid, and two aneuploid. Three control placentas were triploid, and the remaining 65 placentas were diploid. Based on FCM and review of the histology, 10 PM were reclassified as HA, and one PM was revised as CM. Four HA were reclassified as PM. One CM was revised as PM. These results show that the difficulty of histologic diagnosis of gestational trophoblastic diseases may lie in PM. Clinical follow-up information was available in 51 CM and 20 PM, and persistent trophoblastic disease followed 18% of CM and 0% of PM. Among diploid complete moles, DNA ploidy did not associate with persistent disease. A significant increase S-phase fraction (SPF) was detected in diploid CM when compared with HA and control placentas. However, among diploid CM, there was no significant difference of SPF between those with and without persistent disease. These findings suggest that DNA measurements by FCM may be an important aid in the diagnosis of hydropic placentas, but not a useful tool for predicting persistent disease.


Effect of Helicobacter pylori infection on outcomes in resected gastric and gastroesophageal junction cancer.
Helicobacter pylori (H pylori) infection is a known risk factor for gastric cancer (GC) and has been linked with gastroesophageal junction (GEJ) cancer. Studies examining the relationship between H. pylori infection, GC characteristics and prognosis are limited and have yielded conflicting results. We report on the clinicopathologic characteristics and oncologic outcomes of gastric and GEJ cancer patients with and without a history of H. pylori treated at our institution. We retrospectively reviewed the medical records of patients over the age of 18 years who underwent curative resection for GEJ and GC at Mount Sinai Hospital between 2007 and 2012 who had histopathologic documentation of the presence or absence of H pylori infection. Demographic, clinical, pathologic, treatment characteristics and outcomes including recurrence-free survival (RFS) and overall survival (OS) were compared. Ninety-five patients were identified. The majority of patients were male (61%), white (36%) or Asian (34%), with median age at diagnosis 64. Tumors were stage I (51%), stage II (23%), stage III (25%), and stage IV (1%). H pylori infection status was documented at the time of cancer diagnosis in 89 (94%) patients, and following cancer diagnosis and treatment in 6 (6%) patients. Younger age at diagnosis, Asian race and Lauren histologic classification were associated with H Pylori infection. H pylori positive patients exhibited higher 5-year OS and 5-year RFS compared to H pylori negative patients, though the difference was not statistically significant in either univariate or multivariate analyses. In this retrospective series of predominantly early stage GC and GEJ cancers, H. pylori positive patients were significantly younger at cancer diagnosis and were more frequently Asian compared to H. pylori negative patients. Other demographic and histologic classifications except for Lauren histologic classification were similar between the two groups. H pylori positive patients appeared to have improved outcomes compared to H. pylori negative patients.


The Interaction between Arbuscular Mycorrhizal Fungi and Endophytic Bacteria Enhances Plant Growth of Acacia gerrardii under Salt Stress.
Microbes living symbiotically in plant tissues mutually cooperate with each other by providing nutrients for proliferation of the partner organism and have a beneficial effect on plant growth. However, few studies thus far have examined the interactive effect of endophytic bacteria and arbuscular mycorrhizal fungi (AMF) in hostile conditions and their potential to improve plant stress tolerance. In this study, we investigated how the synergistic interactions of endophytic bacteria and AMF affect plant growth, nodulation, nutrient acquisition and stress tolerance of Acacia gerrardii under salt stress. Plant growth varied between the treatments with both single inoculants and was higher in plants inoculated with the endophytic B. subtilis strain than with AMF. Co-inoculated A. gerrardii had a significantly greater shoot and root dry weight, nodule number, and leghemoglobin content than those inoculated with AMF or B. subtilis alone under salt stress. The endophytic B. subtilis could alleviate the adverse effect of salt on AMF colonization. The differences in nitrate and nitrite reductase and nitrogenase activities between uninoculated plants and those inoculated with AMF and B. subtilis together under stress were significant. Both inoculation treatments, either B. subtilis alone or combined with AMF, enhanced the N, P, K, Mg, and Ca contents and phosphatase activities in salt-stressed A. gerrardii tissues and reduced Na and Cl concentration, thereby protecting salt-stressed plants from ionic and osmotic stress-induced changes. In conclusion, our results indicate that endophytic bacteria and AMF contribute to a tripartite mutualistic symbiosis in A. gerrardii and are coordinately involved in the plant adaptation to salt stress tolerance.


Methods for concentration of urinary immunoreactive insulin.
Insulin is readily concentrated from 10 to 50 ml of urine with better than 75% recovery using octadecylsilyl (ODS) silica columns (C18Sep-Pak cartridge) and can then be measured by radioimmunoassay. Fractionation on Sephadex G50 gel filtration reveals that the apparent immunoreactivity corresponds for the most part to 6000 dalton insulin. Renal clearance of insulin in 5 normal subjects does not appear to differ in the fasted or fed state and ranged from 0.34 to 0.58 ml/min with an average of 0.44 +/- 0.10 (S.D.) ml/min. Increased urinary insulin output was observed following feeding and fell during prolonged fasting. Insulin output in urine from 7 non-diabetic subjects ranged from 11 to 39 mU/24 hr, averaging 25 +/- 10 mU/24 hr. In normal subjects without renal disease a single determination of renal insulin clearance and a timed urinary insulin output appear to be sufficient for determination of mean plasma insulin during that time period. Concentration of urine using this methodology could provide the material for HPLC screening for abnormal insulins and for their subsequent purification to determine the site of change in amino acid sequence.


Vectors for Glioblastoma Gene Therapy: Viral & Non-Viral Delivery Strategies.
Glioblastoma multiforme is the most common and aggressive primary brain tumor. Even with aggressive treatment including surgical resection, radiation, and chemotherapy, patient outcomes remain poor, with five-year survival rates at only 10%. Barriers to treatment include inefficient drug delivery across the blood brain barrier and development of drug resistance. Because gliomas occur due to sequential acquisition of genetic alterations, gene therapy represents a promising alternative to overcome limitations of conventional therapy. Gene or nucleic acid carriers must be used to deliver these therapies successfully into tumor tissue and have been extensively studied. Viral vectors have been evaluated in clinical trials for glioblastoma gene therapy but have not achieved FDA approval due to issues with viral delivery, inefficient tumor penetration, and limited efficacy. Non-viral vectors have been explored for delivery of glioma gene therapy and have shown promise as gene vectors for glioma treatment in preclinical studies and a few non-polymeric vectors have entered clinical trials. In this review, delivery systems including viral, non-polymeric, and polymeric vectors that have been used in glioblastoma multiforme (GBM) gene therapy are discussed. Additionally, advances in glioblastoma gene therapy using viral and non-polymeric vectors in clinical trials and emerging polymeric vectors for glioma gene therapy are discussed.


Retrospective analysis of 18 cases of antithyroid drug (ATD)-induced agranulocytosis.
In this study, we retrospectively analyzed 18 patients in whom antithyroid drug (ATD)-induced agranulocytosis developed during treatment of Graves' disease. All patients were more than 20 years of age, and we saw no correlation between age and the development of agranulocytosis. In 17 of 18 patients, ATD-induced agranulocytosis developed within 2 to 12 weeks of starting ATD treatment. Development of agranulocytosis was related to the dose of ATD. In some patients, agranulocytosis developed abruptly, and even weekly routine WBC and granulocyte counts failed to predict all case occurrences. Fever and sore throat were the earliest symptoms of agranulocytosis; patients who developed either of these symptoms were closely monitored immediately with WBC and granulocyte count examinations. In this series of patients, treatment with granulocyte-macrophage colony stimulating factor (GM-CSF) increased the granulocyte counts, whereas the effectiveness of glucocorticoid treatment was not confirmed.


1D Narrow-Bandgap Tin Oxide Materials: Systematic High-Resolution TEM and Raman Analysis.
We demonstrate for the first time the structure identification and narrow-bandgap property of 1D hybridized SnO/SnO2 nanoparticles derived from the calcination of a single-source precursor, i.e., tin(II) oxalate. Systematic Raman analysis together with high-resolution TEM (HR-TEM) measurements of the tin oxide samples were carried out by changing the calcination temperatures. These data revealed the simultaneous formation of 1D SnO/SnO2 in the rod particles that grew in air. It was also found that Sn(II) can be introduced by changing the concentration of Sn(II) salt in the precursor synthesis and the maximum temperature in calcination. Particles measuring 20~30 nm were sintered to produce tin oxide nanorods including tin monoxide, SnO. Photoabsorption properties associated with the formation of the SnO/SnO2 nanocomposites were also investigated. Tauc plots indicate that the obtained tin oxide samples had a lower bandgap of 2.9~3.0 eV originating from SnO in addition to a higher bandgap of around 3.5~3.7 eV commonly observed for SnO2. Such 1D SnOx/SnO2 hybrids via tin oxalate synthesis with this optical property would benefit new materials design for photoenergy conversion systems, such as photocatalysts.


The role of pharmacogenomics in precision psychiatry.
The field of psychiatry is facing an important paradigm shift in the provision of clinical care and mental health service organization toward personalization and integration of multimodal data science. This approach, termed precision psychiatry, aims at identifying subgroups of patients more prone to the development of a certain phenotype, such as symptoms or severe mental disorders (risk detection), and/or to guide treatment selection. Pharmacogenomics and computational psychiatry are two fundamental tools of precision psychiatry, which have seen increasing levels of integration in clinical settings. Here we present a brief overview of these two applications of precision psychiatry in clinical settings.


Exclusive J/ψ photoproduction off protons in ultraperipheral p-Pb collisions at √(s(NN))=5.02 TeV.
We present the first measurement at the LHC of exclusive J/ψ photoproduction off protons, in ultraperipheral proton-lead collisions at sqrt[s_{NN}]=5.02 TeV. Events are selected with a dimuon pair produced either in the rapidity interval, in the laboratory frame, 2.5<y<4 (p-Pb) or -3.6<y<-2.6 (Pb-p), and no other particles observed in the ALICE acceptance. The measured cross sections σ(γ+p→J/ψ+p) are 33.2±2.2(stat)±3.2(syst)±0.7(theor) nb in p-Pb and 284±36(stat)_{-32}^{+27}(syst)±26(theor) nb in Pb-p collisions. We measure this process up to about 700 GeV in the γp center of mass, which is a factor of two larger than the highest energy studied at HERA. The data are consistent with a power law dependence of the J/ψ photoproduction cross section in γp energies from about 20 to 700 GeV, or equivalently, from Bjorken x scaling variable between ∼2×10^{-2} and ∼2×10^{-5}, thus indicating no significant change in the gluon density behavior of the proton between HERA and LHC energies.


Prenatal ultrasound diagnosis of Seckel syndrome with bi-allelic variant in TRAIP via exome sequencing.
We present two consecutive pregnancies with shared ultrasound findings-sloping forehead, micrognathia, ambiguous genitalia, brachycephaly, short extremities, single umbilical artery, choroid plexus cysts, and clenched hands. Subsequent whole exome sequencing identified TRAIP gene variants implicating diagnosis of Seckel syndrome 9 (SCKL9). Prenatal testing in subsequent pregnancy identified one variant. Our case highlights the utility of whole exome sequencing when prenatal ultrasound findings lend suspicion. Molecular confirmation allows for testing strategies in, or prior to, subsequent pregnancies. The finding of a rare, novel missense variant in TRAIP gene further implicates this mutation as having deleterious clinical manifestations.


Evaluation of a point-of-care assay for cardiac markers for patients suspected of acute myocardial infarction.
Creatine kinase MB (CK-MB), and cardiac troponin I (cTnI) are important biomarkers for the diagnosis and rule-out of acute myocardial infarction (AMI) of patients who presented to the emergency department (ED) with chest pain. With new rapid ED assessment protocols, there is increasing pressure to produce results with a short turnaround time (TAT), and point-of-care (POC) testing is one alternative for providing fast results. In a multicenter study, we evaluated the analytical precision, sensitivity and specificity of the RAMP (Response Biomedical) CK-MB and cTnI POC assays and compared results against the Triage (Biosite) POC and the Dimension RxL (Dade Behring) central-laboratory assays on 365 subjects, including 185 patients suspected of AMI, and determined the normal range on 180 healthy individuals. At one site, the clinical sensitivity and specificity were estimated in 121 patients and healthy subjects with AMI using the European Society of Cardiology (ESC)/American College of Cardiology (ACC) definition of AMI. Results from healthy individuals and those with ST elevation and non-ST elevation AMI were included in a receiver operating characteristic (ROC) curve analysis. Intra- and total imprecision ranged from 7.2% to 11.4% for cTnI at 0.22, 1 and 5 ng/ml and 4.8% to 8.6% for CK-MB at 7, 14 and 25 ng/ml. The upper limit of linearity was 32 ng/ml with an average recovery of 105% for cTnI and 80 ng/ml with a 106% recovery for CK-MB. The lower limit of detection was 0.03 ng/ml (10% coefficient of variance [CV] = 0.21 ng/ml) for cTnI and 0.32 ng/ml for CK-MB. The upper reference limit (normal range) was < 0.03 ng/ml for cTnI and 0-3.7 ng/ml for CK-MB. Analytical correlation against Dimension RxL were RAMP=(0.456 x RxL) + 0.11 (r = 0.988, n = 364) for cTnI and RAMP=(0.966 x RxL) + 0.60 (r = 0.986, n = 363) for CK-MB and against Triage, RAMP=(0.626 x Triage) + 0.164 (r = 0.969, n = 364) for cTnI and RAMP=(0.845 x RxL) - 0.495 (r = 0.952, n = 363) for CK-MB. On 39 AMI and 67 non-AMI patients, the clinical sensitivity, specificity and diagnostic efficiency of the cTnI and CK-MB RAMP assays were not significantly different from predicate assays. The RAMP cardiac marker assays are alternatives to other FDA-cleared central laboratory and POC testing devices.


Physiology-Guided Management of Serial Coronary Artery Disease: A Review.
Ischemia-guided revascularization is the cornerstone of contemporary management of coronary artery disease and has evolved from noninvasive functional evaluation to real-time assessment with invasive physiological indices during diagnostic catheterization. However, serial/diffuse disease is common, and revascularization decisions often need to be made about individual lesions within the same vessel. It is unclear whether current physiological techniques, such as fractional flow reserve, can be reliably used to discern the individual contribution of lesions within a serially diseased vessel with erroneous measurements, potentially leading to suboptimal revascularization decisions. This review addresses the application of physiological techniques to serial coronary disease, highlighting challenges and potential solutions. Physiological indices, such as fractional flow reserve, are well validated and correlated with clinical outcomes; however, the challenging physiology of serial stenoses makes it difficult to apply conventional techniques to identify the physiological significance of individual lesions. The 2 methods are most accurate in assessing serial disease are the manual pullback, with treatment of the greatest pressure gradient, or adopting the use of a large disease-free side branch to isolate the significance of the proximal lesion in the context of serial disease involving the left main coronary artery. In addition, resting indices, such as instantaneous wave-free ratio, have theoretical benefits that may make them more reliable in serial disease, with further data awaited. Serial coronary artery disease is common, and physiological assessment is prone to errors. The future, whether it be in improving the interpretation of fractional flow reserve, using resting indices such as instantaneous wave-free ratio, or examining novel flow-based resistance indices, will hopefully improve our management of this common yet unresolved clinical conundrum. In the meantime, revascularisation decisions in this challenging scenario should focus on clinical presentation and physiologic evaluation using a pressure-wire pullback maneuver and left main disease-free side branch where appropriate.


Longevity extension of worker honey bees (Apis mellifera) by royal jelly: optimal dose and active ingredient.
In the Western honey bee, Apis mellifera, queens and workers have different longevity although they share the same genome. Queens consume royal jelly (RJ) as the main food throughout their life, including as adults, but workers only eat worker jelly when they are larvae less than 3 days old. In order to explore the effect of RJ and the components affecting longevity of worker honey bees, we first determined the optimal dose for prolonging longevity of workers as 4% RJ in 50% sucrose solution, and developed a method of obtaining long lived workers. We then compared the effects of longevity extension by RJ 4% with bee-collected pollen from rapeseed (Brassica napus). Lastly, we determined that a water soluble RJ protein obtained by precipitation with 60% ammonium sulfate (RJP60) contained the main component for longevity extension after comparing the effects of RJ crude protein extract (RJCP), RJP30 (obtained by precipitation with 30% ammonium sulfate), and RJ ethanol extract (RJEE). Understanding what regulates worker longevity has potential to help increase colony productivity and improve crop pollination efficiency.


A comparative study between traditional and sports school uniforms on cardiorespiratory and muscular fitness and waist-height-to-ratio in adolescents.
Improving health of children and adolescents is crucial for their overall development. Therefore, it is essential to explore factors that may influence their health at both the public health and school system levels. This study compares physical fitness components and waist-height-to-ratio (WHtR) in adolescents according to school uniforms, namely the traditional uniform (i.e., shirt and school necktie in boys and skirt and blouse in girls) and the sports uniform (i.e., polo shirts or t-shirts and sport or short trousers). Additionally, it seeks to investigate potential differences in these measures based on sex and school type (i.e., public, subsidized, and private). This cross-sectional study used data from the Chilean national learning outcome assessment system (SIMCE)-2014 and involved 8,030 adolescents. Cardiorespiratory fitness (CRF) and muscular fitness (MF) were measured. WHtR was assessed as a health cardiovascular indicator. Mixed models and ANCOVA were performed to compare uniform types, adjusting for multiple covariates. value of p and effect size (ES) was used to establish significant results. Overall, sports uniforms (SU) were linked to higher CRF (p < 0.001) than the traditional uniform (TU). Boys from private schools wearing SU presented higher CRF (p = 0.016; ES = 0.37), and a positive trend was observed for MF (p = 0.645; ES = 0.21). In subsidized, a trend was found in CRF (p = 0.005; ES = 0.16). Girls wearing SU from private schools showed a positive trend in CRF (p = 0.167; ES = 0.28). Trends in WHtR were found in both sexes from private (p = 0.555; ES = 0.24; p = 0.444; ES = 0.25, respectively). Wearing SU seems a promissory alternative to promote healthy physical fitness and body composition at the educational level. However, the relationship between higher physical activity and CRF, MF, and lower WHtR due to SU must be verified. Finally, when deciding to implement this measure, special attention must be paid to boys from public schools and girls from all types of schools.


Protection by cyclosporin A of mitochondrial and cellular functions during a cold preservation-warm reperfusion of rat liver.
Liver transplantation is an effective therapeutic option for end-stage liver disease, but initial poor graft function still occurs, often related to cold preservation-warm reperfusion (CPWR) conditions. Damages to mitochondria could be implicated in hepatocyte cell death since opening of the permeability transition pore (PTP) can lead to necrosis and apoptosis. The purpose of this study was to test the hypothesis that inhibition of mitochondrial permeability transition by cyclosporin A could improve rat liver mitochondrial and hepatocellular parameters after 24-h cold preservation followed by a warm reperfusion in Krebs-Henseleit Buffer. Mitochondrial functions were assessed by measuring respiratory parameters, swelling, cytochrome c release and caspases activation. Hepatocyte injury was assessed by evaluation of ATP energetic charge, lactate dehydrogenase (LDH) leakage, apoptosis and necrosis. Results show that CPWR induces liver mitochondrial and cellular damages. CPWR induced damages on the mitochondrial respiratory chain, leading to mitochondrial swelling. The consequences are the loss of ATP energetic charge, the initiation of apoptosis through cytochrome c release and the activation of caspases. Cyclosporin A partially protects respiratory chain integrity and totally prevents mitochondrial swelling, allowing better recovery of energetic charge. It also partially limits the activation of the apoptotic machinery and subsequent cell death by apoptosis in both the organ and isolated hepatocytes. Inhibition of permeability transition thus provides only partial protection against CPWR. However, this target can be considered as a promising adjunct therapeutic approach to improve the primary function of the grafted liver after transplantation.


Impacts of improved agricultural technology adoption on welfare in Africa: A meta-analysis.
A large body of researches have widely examined the impact of adopting improved agricultural practices and technologies on general welfare of smallholder farmers. The results of deep literature review show that varies agricultural technologies have significant impacts on different welfare measures identified in the primary studies. However, the estimated effects of technology adoption differ among studies. The current study presents a meta-analysis of empirical estimates using a sample of 52 studies that investigated the impact of improved agricultural technologies in Africa on three key sets of outcome variables: output or expenditure, food security, and poverty. The study also conducted tests for publication bias to see if researchers tend to report results in similar or different ways for the same outcome variable. The findings the study shed light on the ways of identifying potential factors explaining the differences in the effects of estimated technology adoption. Results of the meta-regression analysis revealed that differences in the reported impact of technologies is explained by factors like data type, model specification, sample size, region of the study, and journal type. It was also observed that no publication bias in the studies reviewed for the effect size measures of output (expenditure) and poverty models, but in the food security model there is some evidence of publication bias. One of the core implications of the current study is that, based on the sensitivity of effect sizes to study attributes (i.e. data type, econometric methods, sample size, region of the study, and journal type), interested researchers and academicians need to pay attention to these attributes to provide more reliable estimates for policy interventions. We believe this study provides information useful to interested decision-makers in designing policy intervention measures that could encourage the adoption of improved agricultural practices and technologies in the African context. Finally, the study also highlighted future research directions.