On the conversion of solid cancer excess relative risk into lifetime attributable risk.
Risk coefficients representing the lifetime radiation-induced cancer mortality (or incidence) attributable to an exposure to ionizing radiation, have been published by major international scientific committees. The calculations involve observations in an exposed population and choices of a standard population (for risk transportation), of suitable numerical models, and of computational techniques. The present lack of a firm convention for these choices makes it difficult to inter-compare risk estimates presented by different scientific bodies. Some issues that relate to a necessary harmonization and standardization of risk estimates are explored here. Computational methods are discussed and, in line with the approach utilized by ICRP, conversion factors from excess relative risk (ERR) to lifetime attributable risk (LAR) are exemplified for exposures at all ages and for occupational exposures. A standard population is specified to illustrate the possibility of a simplified standard for risk transportation computations. It is suggested that a more realistic perception of lifetime risk could be gained by the use of coefficients scaled to the lifetime spontaneous cancer rates in the standard population. The resulting quantity lifetime fractional risk (LFR) is advantageous also because it depends much less on the choice of the reference population than the lifetime attributable risk (LAR).


Paper-based electrochemical biosensor for diagnosing COVID-19: Detection of SARS-CoV-2 antibodies and antigen.
Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is emerging as a global pandemic outbreak. To date, approximately one million deaths and over 32 million cases have been reported. This ongoing pandemic urgently requires an accurate testing device that can be used in the field in a fast manner. Serological assays to detect antibodies have been proven to be a great complement to the standard method of reverse transcription-polymerase chain reaction (RT-PCR), particularly after the second week of infection. We have developed a specific and sensitive immunosensor for immunoglobulin detection produced against SARS-CoV-2. Unlike other lateral flow-based assays (LFAs) involving the utilization of multiple antibodies, we have reported a label-free paper-based electrochemical platform targeting SARS-CoV-2 antibodies without the specific requirement of an antibody. The presence of SARS-CoV-2 antibodies will interrupt the redox conversion of the redox indicator, resulting in a decreased current response. This electrochemical sensor was proven effective in real clinical sera from patients with satisfactory results. In addition, the proposed format was also extended to antigen detection (the spike protein of SARS-CoV-2), which presents new possibilities for diagnosing COVID-19.


Expression of the cell surface markers mAb 2F7 and PSA-NCAM in the embryonic rat brain.
Cell surface markers of neuronal precursor cells are of interest since they allow the isolation of these cells from mixed populations of cells. The monoclonal antibody (mAb) 2F7, a cell surface marker, has been shown to label neuronal precursors and post-mitotic neurones in the embryonic rat spinal cord and cortex. Little is known about the expression of the epitope recognised by mAb 2F7 in other regions of the developing brain. The present study found expression of this epitope in the embryonic rat cortex, ventral mesencephalon (VM) and striatum at times at which neurogenesis is known to occur in these regions. The expression profile of mAb 2F7 was similar to that of the polysialylated form of the neural adhesion molecule (PSA-NCAM), a commonly used marker of neuronal precursor cells. The percentage of mAb 2F7-positive cells incorporating bromodeoxyuridine (BrdU) was found to be comparable to that of PSA-NCAM-positive cells in primary cell cultures of embryonic rat cortex, VM and striatum. These data demonstrate that mAb 2F7 can be used as a cell surface marker for neuronal precursor cells in several regions of the embryonic rat brain.


Assessing hydrodynamic effects of ecological restoration scenarios for a tidal-dominated wetland in Liaodong Bay (China).
Estuarine wetlands have experienced a variety of ecological and environmental problems caused by natural and anthropogenic factors. China has proposed a series of measures and made great efforts to control coastal degradation; however, decision makers still urgently need to know which measures to implement and how they will influence the estuarine environment and functions. This study used field observations, a hydrodynamic model, and statistical methods to investigate the effects of potential restoration scenarios on hydrodynamic conditions in the tidal-influenced estuarine wetland system, Liaodong Bay (China). Results reveal that the average total phosphorus, organic carbon, available phosphorus, pH, total nitrogen content, and moisture content in the soil and sediment environment were 0.04 ± 0.003%, 0.84 ± 0.25%, 16.3 ± 4.7 mg/kg, 8.3 ± 0.1, 0.07 ± 0.02%, and 44 ± 2%, respectively, exhibiting an overall trend of degradation. A series of restoration scenarios in regards to hydrodynamic regulation and tidal inputs were used to preserve the ecological value of the estuarine wetland. Model simulations indicate that the significant improvement of hydrodynamic fields (inundation depth and flow velocity) is more likely to occur when the tidal amplitudes reach around 2 m, while relatively weak responses can be observed when the tidal levels are lower than 1 m. Additionally, the construction of floodgates may play a key role in determining the tidal inputs and flowpaths across the wetland. The modifications in micro-topography of the wetland may play a complementary role in enhancing the connectivity condition via increased creek depth of 0.5 m and width up to around 20 m. This work represents a first attempt in exploring hydrodynamic effects of restoration scenarios for a tidal-dominated wetland. An improved understanding of the estuarine system also highlights that the design and implementation of wetland restoration projects should use more comprehensive measures to achieve long-term landscape management, connectivity planning, and ecological sustainability.


Efficient artificial intelligence forecasting models for COVID-19 outbreak in Russia and Brazil.
COVID-19 is a new member of the Coronaviridae family that has serious effects on respiratory, gastrointestinal, and neurological systems. COVID-19 spreads quickly worldwide and affects more than 41.5 million persons (till 23 October 2020). It has a high hazard to the safety and health of people all over the world. COVID-19 has been declared as a global pandemic by the World Health Organization (WHO). Therefore, strict special policies and plans should be made to face this pandemic. Forecasting COVID-19 cases in hotspot regions is a critical issue, as it helps the policymakers to develop their future plans. In this paper, we propose a new short term forecasting model using an enhanced version of the adaptive neuro-fuzzy inference system (ANFIS). An improved marine predators algorithm (MPA), called chaotic MPA (CMPA), is applied to enhance the ANFIS and to avoid its shortcomings. More so, we compared the proposed CMPA with three artificial intelligence-based models include the original ANFIS, and two modified versions of ANFIS model using both of the original marine predators algorithm (MPA) and particle swarm optimization (PSO). The forecasting accuracy of the models was compared using different statistical assessment criteria. CMPA significantly outperformed all other investigated models.


Alcoholism and dementia.
The controversy concerning the concept 'alcoholic dementia' is reviewed in brief. Evidence from neuroradiological and neuropathological studies contribute little to the solution of this controversy, if dementia is considered as a clinical syndrome. From clinical descriptions it can be concluded that a sub-population of alcoholics suffers from a syndrome typified by psychologic disturbances other than amnesia alone. These patients fulfill the criteria for the syndromal diagnosis of 'dementia'. The nosologic concept of 'alcoholic dementia' implies a direct neurotoxic effect of alcohol and it raises questions concerning pathogenetic mechanisms which can not be answered. The DSM-III-R category 'dementia associated with alcoholism' represents a solution for this controversy, because it gives a correct and complete (radically syndromal) clinical description without making assumptions on the relative contribution of multiple factors causing cognitive disturbances in alcoholics.


A rare submucosal tumour of stomach-glomus tumour: A case report.
Glomus tumour (GT) of the stomach is a rare submucosal mesenchymal tumour. Gastric glomus tumours are clinically recognized as benign. Nevertheless, some show biological behaviour similar to that of malignant lesions and presurgical confirmation is often impossible. A 32 year old female who presented with epigastric pain and was subsequently investigated for a antral tumour of the stomach and Wedge resection of tumour was done. Immunohistochemistry demonstrated strong positivity of smooth muscle actin and vimentin with low rate of mitosis studied by ki-67. We discuss the preoperative investigation, the diagnostic problems and the surgical treatment of the patient with gastric glomus tumour. Glomus tumours should be considered as differential diagnosis for submucosal tumours of stomach.


The effects of estrogen, insulin and dexamethasone on the synthesis and secretion of egg white proteins in primary cultured oviduct cells of laying Japanese quail (Coturnix coturnix japonica).
1. The effects of estrogen, insulin and dexamethasone on the synthesis of egg white proteins were investigated by employing primary cultured oviduct cells of laying Japanese quails. 2. It was demonstrated that oviduct cells require insulin and dexamethasone, besides estrogen, to synthesize and secrete egg white proteins maximally.


Noradrenaline and dopamine infusions modulate arachidonic acid cyclooxygenase and 5-lipoxygenase pathways ex vivo in man.
We have previously demonstrated that adrenaline infusion increases the thromboxane/leukotriene (TX/LT) ratio in whole blood in healthy volunteers. The aim of the present study was to see whether other catecholamines--noradrenaline and dopamine--are also capable of modulating arachidonic acid (AA) metabolism in man. Low doses of noradrenaline (0.025 microgram/kg/min) and dopamine (3.0 micrograms/kg/min), which did not change hemodynamics, were infused for 60 min into healthy male volunteers. Both dopamine and noradrenaline decreased TX synthesis stimulated by spontaneous clotting, but no remarkable effect was seen when calcium ionophore A23187 was used as a stimulus. Dopamine but not noradrenaline increased prostaglandin E2 (PGE2) synthesis in A23187-stimulated whole blood. They both marginally decreased LTB4 formation in A23187-stimulated whole blood. The findings indicate that not only adrenaline but also noradrenaline and dopamine modulate AA metabolism in man.


New hosts of Breinlia booliati with observations on its distribution in Southeast Asia.
Breinlia booliati Singh & Ho, 1973 first described from Peninsular Malaysia has been shown to infect a large range of murids ranging in distribution from southern Thailand, Peninsular Malaysia, Sarawak to Ciloto, Indonesia. Probably further work will reveal a greater host range as well as its geographical distribution. The vectors involved in its transmission need to be elucidated.


Characteristics of C6 glioma cells overexpressing a gap junction protein.
1. C6 glioma cells transfected with connexin43 cDNA display a dramatic increase in the level of connexin43 mRNA and protein. 2. This overexpression of connexin43 is evident at the cellular level, as revealed with in situ hybridization and immunocytochemistry. Transfection with connexin43 cDNA also induced actin stress fibers in these glioma cells. 3. Although we observed up to a 50-fold increase in the level of connexin43 mRNA following transfection, virtually all of this mRNA was present in the polysomal fraction. 4. Overexpression of connexin43 mRNA did not appear to compete with other cellular mRNAs for access to the translational machinery. 5. It is likely that the reduced proliferation rate of the transfected cells, reported earlier, is due to enhanced connexin43 expression and intercellular coupling.


Pho85 and PI(4,5)P2 regulate different lipid metabolic pathways in response to cold.
Lipid homeostasis allows cells to adjust membrane biophysical properties in response to changes in environmental conditions. In the yeast Saccharomyces cerevisiae, a downward shift in temperature from an optimal reduces membrane fluidity, which triggers a lipid remodeling of the plasma membrane. How changes in membrane fluidity are perceived, and how the abundance and composition of different lipid classes is properly balanced, remain largely unknown. Here, we show that the levels of phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], the most abundant plasma membrane phosphoinositide, drop rapidly in response to a downward shift in temperature. This change triggers a signaling cascade transmitted to cytosolic diphosphoinositol phosphate derivatives, among them 5-PP-IP4 and 1-IP7, that exert regulatory functions on genes involved in the inositol and phospholipids (PLs) metabolism, and inhibit the activity of the protein kinase Pho85. Consistent with this, cold exposure triggers a specific program of neutral lipids and PLs changes. Furthermore, we identified Pho85 as playing a key role in controlling the synthesis of long-chain bases (LCBs) via the Ypk1-Orm2 regulatory circuit. We conclude that Pho85 orchestrates a coordinated response of lipid metabolic pathways that ensure yeast thermal adaptation.


Retrospective diagnosis of childhood ADHD using the Wender Utah Rating Scale.
An external validation of the Wender Utah Rating Scale (WURS) against a clinical assessment is lacking, especially for French-speaking populations. Participants completed three subsets of the WURS-61 and were assessed for ADHD using the DIVA 2.0 semi-structured interview. Exploratory factor analyses were performed. Logistic regression models and Receiver-Operating Curves were used to determine the cut-off scores that predicted childhood ADHD with best accuracy. One hundred three adults were included. Three factors were extracted for the WURS-25 and WURS-K, and four for the WURS-29. Cut-off scores are 44, 24 and 42, respectively. When considering DSM-5 rather than DSM-IV criteria, these values changed to 44, 36 and 44, respectively. More than 83% of the participants had been correctly classified. All three subsets of the WURS-61 retrospectively predict the presence of ADHD in childhood. This result might prove to be useful in screening and research procedures.


Letting wet spots be wet: restoring natural bioreactors in the dissected glacial landscape.
In this paper, we argue that there is tremendous potential for nitrate-N reductions to occur throughout the Corn Belt region of the USA if we simply let naturally occurring wet spots on the landscape be wet. Geologic and hydrologic data gathered in the Walnut Creek watershed located in south-central Iowa provides compelling evidence that substantial nutrient-processing capacity exists in this dissected glacial landscape. Self-similarity of stratigraphy, sedimentology and hydrology observed at all spatial scales in the watershed suggests that Holocene alluvial fill deposits provide a natural bioreactor for denitrification of upland groundwater nitrate-N; the occurrence of such deposits can be mapped to identify potential nitrogen sinks across the landscape. This approach to identifying potential nitrogen sinks is geology focused and extends potential locations for nutrient processing upstream into the headwater catchments of individual fields.


Behavioral responses to host foodplants of two populations of the insect parasitoid Cotesia congregata (Say).
To test the hypothesis that natural enemy populations differ in their behavioral responses to plants or to plant allelochemicals, we compared two populations of the gregarious larval endoparasitoid, Cotesia congregata (Say) (Hymenoptera: Braconidae) that differed in their historical and present exposure to tobacco. The major hosts for both populations were Manduca sexta L. and M. quinquemaculata (Haworth) (Lepidoptera: Sphingidae), but these hosts were typically encountered on tobacco by parasitoids in one population (Upper Marlboro) and on tomato by parasitoids in another population (Wye). Early in the season, Wye parasitoids preferred to oviposit in M. sexta on tomato rather than on tobacco and Upper Marlboro parasitoids showed no preference; neither population showed any preference later in the season. Neither of the strains originating from the two populations showed a landing preference for tobacco or tomato in flight chamber trials, but Upper Marlboro parasitoids searched longer on tobacco than on tomato, and Wye parasitoids searched longer on tomato. When nicotine solutions were applied to tobacco leaf, searching responses of Upper Marlboro parasitoids were enhanced by 0.001-1.0% nicotine, and searching responses of Wye parasitoids were decreased by 0.01-1.0% nicotine. We speculate that population differences in searching responses to tobacco and nicotine may explain the differential parasitism responses found early in the season.


Word-list learning in normally developing children: effects of semantic organization and retention interval.
Immediate and 15-min delayed recall of semantically related or unrelated word lists was investigated in 144 normally developing children ranging from 5 to 10 years of age. Immediate recall for the related and unrelated lists increased in a parallel fashion as a function of age. The ability to cluster semantically related items during immediate recall also improved with age. However, in no age class recall scores and clustering indexes were significantly associated. Forgetting rate passing from the last immediate to the delayed recall trial increased for the unrelated list but decreased for the related list of words as a function of age. Results of regression analyses revealed that a developmental increase in forgetting on the unrelated list was actually due to the higher number of words recalled in the last immediate trial by older children. As for the related list, instead, the larger reliance on the clustering strategy of recall by older children was responsible for the progressive reduction of forgetting.


Valuing humans over animals - Gender differences in meat-eating behavior and the role of the Dark Triad.
Empirical findings demonstrate gender differences in attitudes toward meat consumption and actual meat-eating behavior. Furthermore, several studies have found that men score higher on all three Dark Triad personality dimensions (Machiavellianism, narcissism, and psychopathy). In this study, we investigated whether these personality differences mediate the association between gender and meat-eating justification, which in turn was expected to predict meat consumption. Two-hundred-fifty-seven participants took part in the study. We replicated the finding that men score higher on direct justification strategies with respect to meat consumption and report less often that they are vegetarians or vegans. Moreover, and most importantly, gender differences in Machiavellianism (but not in the other Dark Triad traits) significantly mediated these gender differences in meat-eating justification strategies, which in turn predicted meat consumption. These findings support the idea that Machiavellianism is partly able to explain gender differences in meat-eating justification, which is associated with higher meat consumption.


Organization of ribosomal RNA genes in Alternaria alternata Japanese pear pathotype, a host-selective AK-toxin-producing fungus.
DNA encoding ribosomal RNA (rRNA) of Alternaria alternata Japanese pear pathotype has been cloned in lambda replacement vector, lambda Fix. Restriction endonuclease mapping and Southern hybridization with the 18S and 28S rRNAs of Saccharomyces cerevisiae revealed the A. alternata rDNA to be tandemly repeating 8.15-kilobase pair unit. The restriction fragments of the unit were then subcloned in the plasmid vector Bluescribe M13- and partially sequenced. The determined sequences were compared with previously reported sequences of S. cerevisiae rRNAs and their genes. The locations of DNA sequences encoding the 5.8S, 18S, and 28S rRNAs were determined by homology search using reported sequences. The complete DNA sequence for 5.8S rRNA of the fungus was found to be highly conserved at more than 90% homology in the fungi analyzed. However, sequence diversities were observed in limited regions involved in a helix structure, the helix (e), found at position 116-137.


Mechanisms of long range silencing by imprinted macro non-coding RNAs.
Non-coding (nc) RNA silencing of imprinted genes in extra-embryonic tissues provides a good model for understanding an underexamined aspect of gene regulation by macro or long ncRNAs, that is their action as long-range cis-silencers. Numerous long intergenic ncRNAs (lincRNAs) have been recently discovered that are thought to regulate gene expression, some of which have been associated with disease. The few shown to regulate protein-coding genes are suggested to act by targeting repressive or active chromatin marks. Correlative evidence also indicates that imprinted macro ncRNAs cause long-range cis-silencing in placenta by targeting repressive histone modifications to imprinted promoters. It is timely, however, to consider alternative explanations consistent with the published data, whereby transcription alone could cause gene silencing at a distance.


Experimental allergic encephalomyelitis. Water, sodium and potassium concentration in spinal cord and hemispheres and their changes after dexamethasone treatment.
Water content, Na+, K+ and Cl- concentration were measured in rats with experimentally produced allergic encephalomyelitis. Increase of water content by 10%, accumulation of Na+ by 13%, of Cl- by 20% and decrease of K+ by 10% was observed in the spinal cord, but no substantial changes were found in the brain tissue. The hydration of spinal cord is accompanied by perivascular infiltrates. Dexamethasone, administered from day 5, after injecting sensitising encephalitogenic basic protein, effects normal levels of water content and Na+, K+ and Cl- concentration.


Opioid agonist treatment uptake within provincial correctional facilities in British Columbia, Canada.
Multiple interventions and policy changes related to opioid agonist treatment (OAT) have been introduced in British Columbia, Canada to increase engagement and retention in OAT. We aimed to estimate the impact of policy changes and the announcement of the opioid overdose-related public health emergency on the use of OAT for incarcerated individuals with opioid use disorder. Interrupted time-series analysis. Events of interest included the expansion of buprenorphine/naloxone into provincial health-care insurance coverage in October 2015 and the public health emergency declared in April 2016. Our study included 9220 incarcerated individuals from 12 provincial corrections facilities in British Columbia, Canada for a total of 75 649 calendar months of incarceration. Monthly measures of OAT use during incarceration from 1 January 2013 to 30 September 2017. We estimated changes in OAT use, controlling for individual and facility-level factors, using a general estimating equation, specified with a logit link and an autoregressive correlation matrix. After the provincial health insurance coverage expansion, a sharp increase in OAT use during incarceration was observed [adjusted odds ratio (aOR) = 1.16, 95% confidence interval (CI) = 1.13, 1.19]. The public health emergency coincided with an immediate but temporary increase in OAT receipt (aOR = 1.34, 95% CI = 1.22, 1.47). During the entire study period, we estimated a 10-fold increase in the adjusted odds of OAT use during incarceration (aOR = 10.10, 95% CI = 8.98, 11.37). Following an expansion of health-care insurance coverage to include buprenorphine/naloxone, receipt of opioid agonist treatment (OAT) within correctional facilities in British Columbia, Canada increased, largely driven by an increase in buprenorphine/naloxone prescriptions among individuals without recent OAT experience.


Fluphenazine and social therapy in the aftercare of schizophrenic patients. Relapse analyses of a two-year controlled study of fluphenazine decanoate and fluphenazine hydrochloride.
The ability of long-acting fluphenazine decanoate and oral fluphenazine hydrochloride to forestall relapse among newly discharge schizophrenic patients is examined in the context of high and low degrees of social therapy (ST). A total of 105 patients were randomly assigned to the various treatments and maintained under controlled conditions for two years or until relapse. Relapse rates for all treatments remained traditionally high. Relpase rates for long-acting fluphenazine decanoate and oral fluphenazine hydrochloride are nearly identical in the first year, indicating that drug noncompliance does not adequately explain early schizophrenic relapse. However, patients who received long-acting fluphenazine decanoate and ST have a reduced risk of relapse over time. Relapsers who received long-acting fluphenazine decanoate appeared more affectively disturbed than other relapsers, yet both groups were diagnostically and symptomatically equivalent prior to treatment. Personal discomfort and intrafamilial stress are important predictors.


Development and efficacy assessment of hand sanitizers and polylactic acid films incorporating caffeic acid and vanillin for enhanced antiviral properties against HCoV-229E.
Although three years after the outbreak of SARS-CoV-2, the virus is still having a significant impact on human health and the global economy. Infection through respiratory droplets is the main transmission route, but the transmission of the virus by surface contact cannot be ignored. Hand sanitizers and antiviral films can be applied to control SARS-CoV-2, but sanitizers and films show drawbacks such as resistance of the virus against ethanol and environmental problems including the overuse of plastics. Therefore, this study suggested applying natural substrates to hand sanitizers and antiviral films made of biodegradable plastic (PLA). This approach is expected to provide advantages for the easy control of SARS-CoV-2 through the application of natural substances. Antiviral disinfectants and films were manufactured by adding caffeic acid and vanillin to ethanol, isopropyl alcohol, benzalkonium chloride, and PLA. Antiviral efficacies were evaluated with slightly modified international standard testing methods EN 14,476 and ISO 21,702. In suspension, all the hand sanitizers evaluated in this study showed a reduction of more than 4 log within 2 min against HCoV-229E. After natural substances were added to the hand sanitizers, the time needed to reach the detection limit of the viral titer was shortened both in suspension and porcine skin. However, no difference in the time needed to reach the detection limit of the viral titer was observed in benzalkonium chloride. In the case of antiviral films, those made using both PLA and natural substances showed a 1 log reduction of HCoV-229E compared to the neat PLA film for all treatment groups. Furthermore, the influence of the organic load was evaluated according to the number of contacts of the antiviral products with porcine skin. Ten rubs on the skin resulted in slightly higher antiviral activity than 50 rubs. This study revealed that caffeic acid and vanillin can be effectively used to control HCoV-229E for hand sanitizers and antiviral films. In addition, it is recommended to remove organic matter from the skin for maintaining the antiviral activity of hand sanitizer and antiviral film as the antiviral activity decreased as the organic load increased in this study.


Ultrastructural organization of actin filaments in neurosecretory axons of the rat.
The ultrastructural organization of actin filaments was studied in the neurohypophysial system of the rat after heavy meromyosin (HMM) labeling. This structural pattern is characterized by (1) a straight arrangement of the filaments parallel to the axonal axis in the proximal nondilated parts of axons, (2) a central location within axonal dilatations, and (3) a higher concentration within axonal endings where the filaments form a complex three-dimensional network. The relationships of the filaments to other axonal structures and organelles was further studied by use of electron microscopic stereoscopy. The actin filaments frequently appear anchored to the axolemma with either polar arrangements of the arrowhead decoration (i) at structurally undifferentiated sites, and (ii) more particularly within perivascular endings, at sites with electron-dense thickenings. In all axonal divisions actin filaments are also found to bind to filamentous material surrounding the microtubules and to various organelles. Within the terminal portions of the axons actin filaments exhibit close relationships to neurosecretory granules and to the numerous smooth microvesicles found in this region. Such preferential relationships are particularly observed both in axon ;terminals and in pituicytes, with coated vesicles frequently binding actin filaments. In water-deprived rats, the concentration of actin filaments is conspicuously increased along the axons and more clearly in the axonal swellings and endings, where they form a more complex and interconnected network. These data are discussed in the light of a possible involvement of contractile proteins in the mechanisms of axonal transport and terminal release of neurosecretory products.


Administration of angiotensin II in the paraventricular nucleus protects gastric mucosa from ischemia-reperfusion injury.
Our previous study demonstrated that electrical stimulation of the hypothalamic paraventricular nucleus (PVN) protects against gastric ischemia-reperfusion (GI-R) injury, but it is still unknown whether angiotensin II (Ang II) in the PVN plays a role in the development of GI-R. The purpose of this study was to investigate the effect of Ang II in the PVN on GI-R injury. GI-R injury was induced in rats by clamping the celiac artery for 30 min, and then reperfusing for 30 min, 1 h, 3 h, 6 h or 24 h, respectively. A cannula was inserted into the unilateral PVN for microinjection of Ang II. The extent of gastric mucosal damage was determined by gross and histological methods. We found that microinjection of pharmacological doses of Ang II (3, 30, and 300 ng) into the PVN dose-dependently inhibited GI-R injury, and that Ang II (30 ng) markedly attenuated GI-R injury at 1 h and 3 h after reperfusion. The effect of Ang II was prevented by pretreatment with the Ang II AT1 receptor antagonist losartan (5 microg) into the lateral cerebral ventricle. Furthermore, the protective effect of Ang II on GI-R injury was abolished by propranolol (1 mg/kg, i.v.) or disconnection of the nerves innervating the adrenal glands, was augmented by sympathectomy or phentolamine (1 mg/kg, i.v.), and was not affected by subdiaphragmatic vagotomy or atropine (1 mg/kg, i.v.). These results indicate that the PVN is a responsive site for central Ang II-induced protection against GI-R injury. The central effects of Ang II are mediated by AT1 receptors in the PVN, and the peripheral effects by a sympathetic-adrenal gland/beta-adrenoceptor pathway.


Genome-wide association study and meta-analysis in Northern European populations replicate multiple colorectal cancer risk loci.
Genome-wide association studies have been successful in elucidating the genetic basis of colorectal cancer (CRC), but there remains unexplained variability in genetic risk. To identify new risk variants and to confirm reported associations, we conducted a genome-wide association study in 1,701 CRC cases and 14,082 cancer-free controls from the Finnish population. A total of 9,068,015 genetic variants were imputed and tested, and 30 promising variants were studied in additional 11,647 cases and 12,356 controls of European ancestry. The previously reported association between the single-nucleotide polymorphism (SNP) rs992157 (2q35) and CRC was independently replicated (p = 2.08 × 10-4 ; OR, 1.14; 95% CI, 1.06-1.23), and it was genome-wide significant in combined analysis (p = 1.50 × 10-9 ; OR, 1.12; 95% CI, 1.08-1.16). Variants at 2q35, 6p21.2, 8q23.3, 8q24.21, 10q22.3, 10q24.2, 11q13.4, 11q23.1, 14q22.2, 15q13.3, 18q21.1, 20p12.3 and 20q13.33 were associated with CRC in the Finnish population (false discovery rate < 0.1), but new risk loci were not found. These results replicate the effects of multiple loci on the risk of CRC and identify shared risk alleles between the Finnish population isolate and outbred populations.


Differential pulse voltammetric determination of 7-hydroxycoumarin in human urine.
The electrochemical behaviour of 7-OH-coumarin at the bare glassy carbon electrode has been studied using differential pulse voltammetry, and based on anodic detection of this metabolite at 0.66 V (vs SCE) using DC amperometry, a method has been developed for the determination of 7-OH-coumarin levels in urine samples, and a pharmacokinetic profile established.


Ultrasound-Guided Cradle-Like Infiltrative Anesthesia for Percutaneous Transluminal Angioplasty of Stenotic Autogenous Arteriovenous Hemodialysis Access.
Percutaneous transluminal angioplasty (PTA) is an effective treatment for autogenous arteriovenous hemodialysis access (AAVA) stenosis; however, it causes pain in most cases. Therefore, safe and effective anesthesia for PTA is required. We introduced a method of ultrasound-guided cradle-like infiltration anesthesia (UCIA) to administer analgesia during PTA. Using ultrasound guidance, 1% lidocaine was injected into the bilateral and inferior perivascular spaces of the stenosis to form a cradle-like region. In this study, 100 consecutive patients were divided into two groups, and the analgesic effect of UCIA was evaluated using a numerical rating scale with non-ultrasound-guided infiltration anesthesia as a control. Meanwhile, we compared the effect of PTA between the two groups with the postoperative internal diameter of the stenosis. The numerical rating scale score was 4.6 ± 1.9 and 2.0 ± 1.6 (P < 0.001) in UCIA group and non-ultrasound-guided infiltration anesthesia group, respectively. The postoperative internal diameter of stenosis was 3.9 ± 0.6 mm and 4.1 ± 0.7 mm (P = 0.113); the postoperative AAVA flow volume was 627 ± 176 mL/min and 644 ± 145 mL/min (P = 0.600). This study preliminarily showed that UCIA is effective and safe for the analgesia of AAVA PTA.


Finding Shangri-La: Limiting the Impact of Senescence on Aging.
Senescence plays an important role in the age-associated decline of tissue functions. Recent studies now show that targeting senescent cells can enhance the functions of stem/progenitor cells in aged mice and extend lifespan.


An interactive individualized intervention to promote behavioral change to increase personal well-being in US surgeons.
Evaluate the utility of a computer-based, interactive, and individualized intervention for promoting well-being in US surgeons. Distress and burnout are common among US surgeons. Surgeons experiencing distress are unlikely to seek help on their own initiative. A belief that distress and burnout are a normal part of being a physician and lack of awareness of distress level relative to colleagues may contribute to this problem. Surgeons who were members of the American College of Surgeons were invited to participate in an intervention study. Participating surgeons completed a 3-step, interactive, electronic intervention. First, surgeons subjectively assessed their well-being relative to colleagues. Second, surgeons completed the 7-item Mayo Clinic Physician Well-Being Index and received objective, individualized feedback about their well-being relative to national physician norms. Third, surgeons evaluated the usefulness of the feedback and whether they intended to make specific changes as a result. A total of 1150 US surgeons volunteered to participate in the study. Surgeons' subjective assessment of their well-being relative to colleagues was poor. A majority of surgeons (89.2%) believed that their well-being was at or above average, including 70.5% with scores in the bottom 30% relative to national norms. After receiving objective, individualized feedback based on the Mayo Clinic Physician Well-Being Index score, 46.6% of surgeons indicated that they intended to make specific changes as a result. Surgeons with lower well-being scores were more likely to make changes in each dimension assessed (all Ps<0.001). US surgeons do not reliably calibrate their level of distress. After self-assessment and individualized feedback using the Mayo Clinic Physician Well-Being Index, half of participating surgeons reported that they were contemplating behavioral changes to improve personal well-being.


3-Methyl-anilinium hydrogen phthalate.
The asymmetric unit of the title salt, C(7)H(10)N(+)·C(8)H(5)O(4) (-), consists of two 3-methyl-phenyl-ammonium cations and two hydrogen phthalate anions. There are strong intra-molecular O-H⋯O hydrogen bonds in the virtually planar (r.m.s. deviations = 0.054 Å) phthalate anions. In the crystal, the cations and anions are connected via an extensive sytem of N-H⋯O hydrogen bonds into a corrugated layer extended parallel to (001).


Effects of serum, albumin and immunoglobulins on urease-induced crystallization in urine.
The effects of serum, albumin and gammaglobulins on urease-induced crystallization have been studied in synthetic and in human urine. Serum and the studied proteins increased urease enzymatic activity in synthetic urine. In human urine only serum had this effect. In synthetic urine, the proteins and serum markedly decreased the precipitation attached to glass surfaces, while the intraluminal precipitation was increased. In human urine, similar but weaker effects on the precipitation were found for serum and albumin. These findings suggest that the proteins studied, in the concentrations in which they are present in human urine, have profound effects on urease-induced crystallization and may be physiological crystallization inhibitors.


Inhibition of Maillard reaction during alkaline thermal hydrolysis of sludge.
The Maillard reaction (MR) occurs during the alkaline thermal hydrolysis (ATH) of sludge, which affects the quantity and quality of recovered protein. In this paper, four different sulfites were added to investigate their inhibitory effects on melanoidin production. The results showed that sulfites inhibited melanoidin production during ATH of sludge and the inhibitory rate increased with their concentration. At a concentration of 5.71 g/L, the inhibitory rates of NaHSO3 on melanoidin were 63.27%. Furthermore, the 3D-EEM (Three-Dimension Excitation-Emission-Matrix) fluorescence spectroscopy and protein testing data showed that the inhibition of melanoidin production was accompanied by an increased protein concentration, and protein increased with increasing sulfites concentration. A 2.5-fold increase in protein concentration with Na2S2O4 significantly enhanced the quantity of protein recovered. Therefore, the addition of sulfite during ATH of sludge reduces the amount of non-biodegradable melanoidin, which in turn benefits protein recovery.


The effect of financial incentives on gatekeeping doctors: evidence from a natural experiment.
In many health care systems generalist physicians act as gatekeepers to secondary care. Under the English fundholding scheme from 1991/1992 to 1998/1999 general practices could elect to be given a budget to meet the costs of certain types of elective surgery (chargeable electives) for their patients and could retain any surplus. They did not pay for non-chargeable electives or for emergency admissions. Non-fundholding practices did not bear the cost of any type of hospital admissions. Fundholding is to be reintroduced from April 2005. We estimate the effect of fundholding using a differences in differences methodology on a large 4-year panel of English general practices before and after the abolition of fundholding. The abolition of fundholding increased ex-fundholders' admission rates for chargeable elective admissions by between 3.5 and 5.1%. The effect on the early wave fundholders was greater (around 8%) than on later wave fundholders. We also use differences in differences for two types of admissions (non-chargeable electives, emergencies) not covered by fundholding as additional controls for unobserved temporal factors. These differences in differences in differences estimates suggest that the abolition of fundholding increased ex-fundholders' chargeable elective admissions by 4.9% (using the non-chargeables DID) and by 3.5% (using the emergencies DID).


Genetic mapping of two pairs of linked ribosomal protein genes in Saccharomyces cerevisiae.
We have used the 2 mu mapping method described by Falco and Botstein (1983) and tetrad analysis to map four ribosomal protein genes (two linked pairs) in S. cerevisiae. One pair (rp28-rp55 copy 1) is on chromosome XV, 14 cM proximal to ARG8. The other pair (rp55-rp28 copy 2) is 19 cM from the centromere on the left arm of chromosome XIV. To map copy 1 we used the E. coli beta-galactosidase gene rather than a yeast gene to mark the ribosomal protein chromosomal locus. This provided a more sensitive color screening assay for chromosome loss in the 2 mu method. It also removed the restriction that the mapping tester strains must be mutant for the plasmid marker.


Relationship between neonatal birth weight and maternal plasma amino acid profiles in lean and obese nondiabetic women and in type I diabetic pregnant women.
Profiles of hemoglobin A1c (HbA1c) and concentrations of plasma glucose and 18 plasma amino acids were obtained in ten nonobese, insulin-dependent type I diabetic women, in 9 age- and weight-matched normal women and in ten obese nondiabetic women throughout pregnancy and postpartum. In late gestation, the period of maximum fetal growth, average HbA1c, plasma glucose, and total amino acid concentrations in diabetic mothers were significantly elevated above lean control values. No differences existed between the obese and lean control groups. Lean diabetic mothers also had significantly heavier babies (mean +/- SEM) relative to the 50th percentile for gestational age and sex (119 +/- 9%) than did the lean control group (94 +/- 3%, P less than .05). Relative birth weights among control lean and obese mothers did not differ significantly (94 +/- 3% v 104 +/- 5%). Late pregnancy profiles of HbA1c and average plasma glucose did not correlate with relative weight of neonates whereas average total plasma amino acids and six individual amino acids did correlate with this parameter. These data suggest that maternal plasma amino acid concentrations may influence fetal weight generally and may have an important role in the development of fetal macrosomia in diabetic pregnancies.


Use of sildenafil for safe improvement of erectile function and quality of life in men with New York Heart Association classes II and III congestive heart failure: a prospective, placebo-controlled, double-blind crossover trial.
Erectile dysfunction (ED) is common in patients with congestive heart failure (CHF) and is often associated with symptoms of depression. Although sildenafil citrate, a phosphodiesterase 5 inhibitor, is effective in treating ED, its use is considered a relative contraindication in CHF. We hypothesized that sildenafil is a safe and effective treatment for ED in patients with New York Heart Association classes II and III CHF and that treatment of ED will improve symptoms of depression and enhance perceived of quality of life. We studied 35 patients in a prospective, placebo-controlled, crossover trial for 12 weeks. Inclusion required a history of chronic ED and absence of ischemia (negative results from exercise stress test or nuclear perfusion scan) or nitrate use. The tolerability of sildenafil citrate was established by monitoring the ambulatory blood pressure for 4 hours after a single 50-mg dose. Improvement in ED, the primary end point, was assessed using the International Index of Erectile Function survey. The effect of improved erectile function on quality of life and mood was assessed using the Minnesota Living With Heart Failure Questionnaire, the Beck Depression Index, and the Center for Epidemiological Studies-Depression Scale. Sildenafil caused a mean +/- SEM asymptomatic decrease in blood pressure of 6 +/- 3 mm Hg, and no patient experienced symptomatic hypotension or other significant adverse effects. Sildenafil improved the International Index for Erectile Function (P<.001) and both sets of depression scores. The Living With Heart Failure Questionnaire index also improved with sildenafil (P =.02). Sildenafil is a safe and effective treatment for ED in men with New York Heart Association classes II and III CHF and provides relief of depressive symptoms, explaining an improvement in the perception of quality of life.


A pilot study to investigate the efficacy and tolerability of lesion network guided transcranial electrical stimulation in outpatients with psychosis spectrum illness.
Transcranial electrical stimulation (tES) may improve psychosis symptoms, but few investigations have targeted brain regions causally linked to psychosis symptoms. We implemented a novel montage targeting the extrastriate visual cortex (eVC) previously identified by lesion network mapping in the manifestation of visual hallucinations. To determine if lesion network guided High Definition-tES (HD-tES) to the eVC is safe and efficacious in reducing symptoms related to psychosis. We conducted a single-blind crossover pilot study (NCT04870710) in patients with psychosis spectrum disorders. Participants first received HD-tDCS (direct current), followed by 4 weeks of wash out, then 2 Hz HD-tACS (alternating current). Participants received 5 days of daily (2×20 min) stimulation bilaterally to the eVC. Primary outcomes included the Positive and Negative Syndrome Scale (PANSS), biological motion task, and Event Related Potentials (ERP) from a steady state visual evoked potential (SSVEP) paradigm. Secondary outcomes included the Montgomery-Asperg Depression Rating Scale, Global Assessment of Functioning (GAF), velocity discrimination and visual working memory task, and emotional ERP. HD-tDCS improved PANSS general psychopathology in the short-term (d=0.47; pfdr=0.03), with long-term improvements in general psychopathology (d=0.62; pfdr=0.05) and GAF (d=-0.56; pfdr=0.04) with HD-tACS. HD-tDCS reduced SSVEP P1 (d=0.25; pfdr=0.005), which correlated with general psychopathology (β = 0.274, t = 3.59, p = 0.04). No significant differences in safety or tolerability measures were identified. Lesion network guided HD-tES to the eVC is a safe, efficacious, and promising approach for reducing general psychopathology via changes in neuroplasticity. These results highlight the need for larger clinical trials implementing novel targeting methodologies for the treatments of psychosis.


Important role for methionine sulfoxide reductase in the oxidative stress response of Xanthomonas campestris pv. phaseoli.
A methionine sulfoxide reductase gene (msrA) from Xanthomonas campestris pv. phaseoli has unique expression patterns and physiological function. msrA expression is growth dependent and is highly induced by exposure to oxidants and N-ethylmaleimide in an OxyR- and OhrR-independent manner. An msrA mutant showed increased sensitivity to oxidants but only during stationary phase.


Validation of a quantitative lateral flow immunoassay (LFIA)-based point-of-care (POC) rapid test for SARS-CoV-2 neutralizing antibodies.
With the widespread use of coronavirus disease 2019 (COVID-19) vaccines, a rapid and reliable method to detect SARS-CoV-2 neutralizing antibodies (NAbs) is extremely important for monitoring vaccine effectiveness and immunity in the population. The purpose of this study was to evaluate the performance of the RapiRead™ reader and the TestNOW™ COVID-19 NAb rapid point-of-care (POC) test for quantitative measurement of antibodies against the spike protein receptor-binding domain of severe respiratory syndrome coronavirus 2 (SARS-CoV-2) in different biological matrices compared to chemiluminescence immunoassay (CLIA) methods. Ninety-four samples were collected and analyzed using a RapiRead™ reader and TestNOW™ COVID-19 NAb kits for detecting neutralizing antibodies, and then using two CLIAs. The data were compared statistically using the Kruskal-Wallis test for more than two groups or the Mann-Whitney test for two groups. Specificity and sensitivity were evaluated using a receiver operating characteristic (ROC) curve. Good correlation was observed between the rapid lateral flow immunoassay (LFIA) test system and both CLIA methods. RapiRead™ reader/TestNOW™ COVID-19 NAb vs. Maglumi: correlation coefficient (r) = 0.728 for all patients; r = 0.841 for vaccinated patients. RapiRead™ reader/TestNOW™ COVID-19 NAb vs. Mindray: r = 0.6394 in all patients; r = 0.8724 in vaccinated patients. The time stability of the POC serological test was also assessed considering two times of reading, 12 and 14 minutes. The data revealed no significant differences. The use of a RapiRead™ reader and TestNOW™ COVID-19 NAb assay is a quantitative, rapid, and valid method for detecting SARS-CoV-2 neutralizing antibodies and could be a useful tool for screening studies of SARS-CoV-2 infection and assessing the efficacy of vaccines in a non-laboratory context.


Developmental aspects of maleic acid-induced inhibition of sugar and amino acid transport in the rat renal tubule.
The transport of alpha-aminoisobutyric acid and alpha-methyl-d-glucoside by isolated tubules from Sprague-Dawley rats at different stages of development follows a separate age-dependent pattern for each substrate. The effects of 6 M maleic acid on transport processes differ for amino acids and sugars and become manifest at distinct points during development. Maximum inhibition by maleic acid occurs at a time subsequent to maturity of these transport systems. In an effort to explain these transport phenomena, the uptake and metabolism of 14C-labeled maleic acid by the newborn or adult renal tubule was studied, showing significant binding by the tubule membrane, penetration of the cell by diffusion, and no conversion to 14CO2. Maleic acid has no demonstrable effect on the membrane-associated enzymes which are thought to play a role in the transport of small molecules.


Splenectomy for idiopathic thrombocytopenic purpura: comparison of laparoscopic and conventional surgery.
This study aimed to compare the safety, efficacy, and clinical benefits of laparoscopic splenectomy (LS) to open splenectomy (OS) in patients with idiopathic thrombocytopenic purpura (ITP). The results from 14 consecutive patients who underwent LS for ITP were reviewed and compared with the results from patients who underwent OS for the same disease. Demographics, concomitant disease on admission, and platelet counts were evaluated, as were details of the surgical procedure, postoperative physiologic status, and hospital stay. Mean operative time was 88.3 min for OS and 146.4 min in LS group (p < 0.05). The conversion rate to open splenectomy was 7.1. Therapeutic response to splenectomy was 92.8% in the LS group and 86.6% in the OS group. Bowel canalization, return to liquid diet, and length of hospital stay were all significantly delayed in the OS group as compared with those who underwent LS (p = 0.01, p = 0.02, p = 0.005, respectively). In the OS group the morbidity rate was 13.3%, whereas in the LS group it was 7.1%. Laparoscopic splenectomy represents a valid alternative to conventional splenectomy in the treatment of ITP.


Radiotherapy with and without temozolomide in elderly patients with glioblastoma.
The optimal treatment for elderly patients (age ≥ 70 years) with glioblastoma (GBM) remains controversial. We conducted a retrospective analysis in 43 consecutive elderly patients with glioblastoma who either underwent radiotherapy (RT) or radiotherapy plus concomitant temozolomide (TMZ). A total of 43 patients (≥ 70 years of age, median age 75.8 years) with newly diagnosed glioblastoma and a Karnofsky performance status (KPS) ≥ 70 were treated with RT alone (median 60 Gy in 2 Gy single fractions) or RT plus TMZ at a dose of 75 mg/m(2) per day. The two groups were well-balanced; univariate (log-rank test) and multivariate Cox proportional hazards analysis were used to identify relevant prognostic factors. The median overall survival (mOS) of the entire patient cohort was 264 days (8.8 months) and the median progression-free survival (PFS) was 192 days (6.4 months). The factors age, sex, previous surgery, KPS, and concomitant use of TMZ had no significant influence on OS/PFS; multivariate analysis was performed to obtain adjusted hazard ratios. TMZ use resulted in a trend toward poorer overall survival when applied concomitantly (314 days compared to 192 days within the TMZ group, p = 0.106). The subgroup analysis revealed that TMZ use resulted in significantly worse survival rates in patients with KPS70 (p = 0.027), but for patients with KPS80 this difference was not detectable. TMZ should only be used carefully in elderly patients with unfavorable KPS. In this patient cohort, radiotherapy alone is a reasonable option. Standard RT plus concomitant TMZ may be an advantageous treatment option for elderly patients with newly diagnosed glioblastoma who present with good prognostic factors.


Comparative Effectiveness of Dexamethasone in Treatment of Hospitalized COVID-19 Patients during the First Year of the Pandemic: The N3C Data Repository.
Dexamethasone, a widely available glucocorticoid, was approved for use in hospitalized COVID-19 patients early in the pandemic based on the RECOVERY trial; however, evidence is still needed to support its real-world effectiveness in patients with a wide range of comorbidities and in diverse care settings. To conduct a comparative effectiveness analysis of dexamethasone use with and without remdesivir in hospitalized COVID-19 patients using electronic health record data. We conducted a retrospective real-world effectiveness analysis using the harmonized, highly granular electronic health record data of the National COVID Cohort Collaborative (N3C) Data Enclave. Analysis was restricted to COVID-19 patients in an inpatient setting, prior to vaccine availability. Primary outcome was in-hospital death; secondary outcome was combined in-hospital death and severe outcome as defined by use of ECMO or mechanical ventilation during stay. Missing data were imputed with single imputation. Matching of dexamethasone-treated patients to non-dexamethasone-treated controls was accomplished using propensity score (PS) matching, stratified by remdesivir treatment and based on demographics, baseline laboratory values, and comorbidities. Treatment benefit was quantified using logistic regression. Further sensitivity analyses were performed using clinical adjusters in matched groups and in strata defined by quartiles of PS. Regression analysis revealed a statistically significant association between dexamethasone use and reduced risk of in-hospital mortality for those not receiving remdesivir (OR=0.77, 95% CI:0.62 to 0.95, p=0.017), and a borderline statistically significant risk for those receiving remdesivir (OR=0.74, 95% CI: 0.53 to 1.02, p=0.054). Treatment also showed secondary outcome benefit. In sensitivity analyses, treatment effect size generally remained similar with some heterogeneity of benefit across strata of PS. We add evidence that dexamethasone provides benefit with respect to mortality and severe outcomes in a diverse, national hospitalized sample, prior to vaccine availability.


Micronutrients and macronutrients in the liver in experimental alimentary obesity.
Strong and very strong positive correlations differing from those in the control were found between chemical elements in the liver of rats with experimental alimentary obesity under conditions of physiological hunger and soon after fatty food intake. These findings attest to sustained metabolism disturbances in obesity and formation of a pathological system. Considering the appearance of strong and very strong correlations of Br and Rb in alimentary obesity, more attention should be paid to the investigation of the role of these poorly studied elements in lipid metabolism.


A radioimmunoassay for circulating human proinsulin.
A radioimmunoassay for human proinsulin (hPl) has been developed using biosynthetic hPl prepared by recombinant DNA technology as immunogen, standard, and tracer. The antiserum was raised in a guinea pig and then adsorbed against insulin and C-peptide conjugated to Sepharose to improve its specificity. After adsorption of the antiserum, the cross-reactivities to insulin and C-peptide were each less than 0.2%. Competition studies using in vitro enzymatically split forms of proinsulin demonstrated that the major antigenic determinant recognized was the junctional region between the B-chain of insulin and the C-peptide. The range of the assay extended from 10 to 150 fmol/tube, with a 50% displacement of 45-55 fmol/tube. This sensitivity proved suitable for measurements of serum hPl concentrations during infusion of biosynthetic hPl into normal subjects and type I diabetic subjects. Eighty-five of 89 serum samples from the normal subjects and each of 20 samples from diabetic subjects diluted in parallel with the hPl standard. Since the direct assay sensitivity was not sufficient for measurement of endogenous hPl levels, a simple procedure for quantitative extraction of proinsulin-like material (PLM) from up to 40 ml of plasma on insulin antibody-Sepharose columns was developed. Logit-log slopes were calculated for dilutions of extracts of samples collected in the fasting state and 60 min after 75 g or oral glucose from eight healthy subjects. The slopes of 15 of the 16 samples did not differ significantly from the slope of the hPl standard.(ABSTRACT TRUNCATED AT 250 WORDS)


Posttranslational modifications of endothelin receptor type B.
Endothelin receptor type B (ETb) is one of the two ET receptor subtypes, both of which belong to the G protein-coupled receptor (GPCR) superfamily. The primary amino acid sequence of ETb, published in 1990, predicted potential posttranslational modifications of the receptor protein, and in the last couple of years, we and others presented direct experimental evidence for palmitoylation and phosphorylation of ETb. Functional evaluation of both substitution and deletion mutants indicated a negative role on the part of these modifications in the ligand binding capacities and cellular sequestrations of the receptors. At least one of them, palmitoylation, however, appears to be critically involved in the coupling with G proteins.


Three-dimensional, biomimetic electrospun scaffolds reinforced with carbon nanotubes for temporomandibular joint disc regeneration.
Temporomandibular disorder (TMD) remained a huge clinical challenge, with high prevalence but limited, unstable, and only palliative therapeutic methods available. As one of the most vulnerable sites implicated in TMD, the temporomandibular joint disc (TMJD) displayed a complicated microstructure, region-specific fibrocartilaginous distribution, and poor regenerative property, which all further hindered its functional regeneration. To address the problem, with versatile and relatively simple electrospinning (ELS) technique, our study successfully fabricated a biomimetic, three-dimensional poly (ϵ-caprolactone) (PCL)/polylactide (PLA)/carbon nanotubes (CNTs) disc scaffold, whose biconcave gross anatomy and regionally anisotropic microstructure recapitulating those of the native disc. As in vitro results validated the superior mechanical, bioactive, and regenerative properties of the biomimetic scaffolds with optimal CNTs reinforcement, we further performed in vivo experiments. After verifying its biocompatibility and ectopic fibrochondrogenicity in nude mice subcutaneous implantation models, the scaffolds guided disc regeneration and subchondral bone protection were also confirmed orthotopically in rabbits TMJD defected areas, implying the pivotal role of morphological cues in contact-guided tissue regeneration. In conclusion, our work represents a significant advancement in complex, inhomogeneous tissue engineering, providing promising clinical solutions to intractable TMD ailments. STATEMENT OF SIGNIFICANCE: Complex tissue regeneration remains a huge scientific and clinical challenge. Although frequently implicated in temporomandibular joint disorder (TMD), functional regeneration of injured temporomandibular joint disc (TMJD) is extremely hard to achieve, mainly because of the complex anatomy and microstructure with regionally variant, anisotropic fiber alignments in the native disc. In this study, we developed the biomimetic electrospun scaffold with optimal CNTs reinforcement and regionally anisotropic fiber orientations. The excellent mechanical and bioactive properties were confirmed both in vitro and in vivo, effectively promoting defected discs regeneration in rabbits. Besides demonstrating the crucial role of morphological biomimicry in tissue engineering, our work also presents a feasible clinical solution for complex tissue regeneration.


Serum alpha-fetoprotein in the early stage of human hepatocellular carcinoma.
The serum alpha-fetoprotein levels of 17 patients with cancers less than or equal to 3 cm in size were studied using radioimmunoassay to determine alpha-fetoprotein response in the early stage of human hepatocellular carcinoma. The levels were normal in 6 patients (35%), and elevated to 645 +/- 1140 micrograms/L (mean +/- SD) in the remaining patients. The levels were not correlated with tumor size. In 10 surgically resected patients, 5 had elevated levels of alpha-fetoprotein that returned to normal after surgery. The levels and tumor sizes were serially observed for 3-26 mo in the remaining 7 patients not surgically treated. In 1 patient alpha-fetoprotein levels were persistently normal and in the other 6 patients, the levels tended to increase with a median doubling time of 60-75 days (range 30-223 days). Despite continued tumor growth, a spontaneous fall in serum alpha-fetoprotein levels was encountered in 4 patients; in 2 patients the levels even fell within the normal range. After this fall, the levels increased drastically in 4 patients. We concluded that in the early stage of hepatocellular carcinoma, serum alpha-fetoprotein level is frequently normal, and thus determination of serum alpha-fetoprotein levels only is not a reliable indicator in the early detection of human hepatocellular carcinoma. A spontaneous fall in the level of alpha-fetoprotein is not an uncommon finding in the early stages of this cancer and cannot be used to rule out the diagnosis of hepatocellular carcinoma.


[Traumatic injuries of the epiphyseal plate in the lower extremity of the tibia].
In a series of 110 fractures of the ankle in children the authors have observed 27 cases of "at risque" lesions: Mac Farland types of fractures and crush injuries. Epiphysiodesis occurs in all cases of crush injuries and in 25% of fracture-separation of the tibial malleolus. In order to prevent this complication the only procedure is to obtain an anatomical reduction. Desepiphysiodesis is uncommunly possible (2 cases) and rarely effective. In case of varus deformity an osteotomy must be performed and repeated if the child is still young.


Gestational transient hyperthyroxinaemia (GTH): screening for thyroid function in 23,163 pregnant women using dried blood spots.
Transient elevation of serum free T4 (gestational transient hyperthyroxinaemia; GTH) occurs occasionally during normal pregnancy, especially in early gestation. However, the frequency of GTH and its clinical features remain unclear to date. The aim of this study was to determine the occurrence rate of GTH and the relation between serum levels of hCG, free T4 (fT4), and TSH in a large number of pregnant women. The four criteria of GTH were as follows: (1) no past history of thyroid disease, (2) negative tests for MCHA and TGHA, (3) no multiple pregnancies or trophoblastic disease and (4) transient hyperthyroxinaemia at less than 16 weeks of gestation. Thyroid function and hCG levels in 23,163 pregnant women were evaluated by mass sreening. If individual fT4 levels were more than the upper limit, blood re-sampling and the clinical and laboratory analysis of thyroid function were performed to exclude women with thyroid disease. The concentrations of hCG, fT4, and TSH in women with GTH and normal pregnant controls (n = 218) were compared. Regression analysis was performed for the comparison between hCG, fT4, and TSH levels in women with GTH. Blood samples were obtained using dried blood spots. Blood levels of fT4 was measured by radioimmunoassay, TSH and hCG were measured by fluoroimmunoassay. Anti-microsome antibody (MCHA) and anti-thyroglobulin antibody (TGHA) were measured by indirect agglutination reaction. GTH was observed in 66 of 23,163 women. The overall occurrence rate of GTH was 0.285%. In 22 of the 66 GTH women, serum TSH was undetectable. Using regression analyses, the concentration of fT4 was correlated with hCG levels in women with GTH (P < 0.05, r = 0.269), whereas the concentration of TSH was not correlated with hCG or fT4 level. The concentrations (M +/- SD) of fT4, TSH, and hCG in women with GTH were 42.5 +/- 12.3 pmol/l, 0.20 +/- 0.31 mU/l and 190.2 +/- 98.8 x 10(3) IU/l, whereas those of controls were 14.6 +/- 3.8 pmol/l, 1.43 +/- 1.25 mU/l and 60.1 +/- 45.1 x 10(3) IU/l. The concentrations of fT4 and hCG were significantly (P < 0.0001) higher than those of normal controls, and TSH was significantly (P < 0.0001) lower than those of normal controls. The occurrence rate of gestational transient hyperthyroxinaemia was 0.285%, and could possibly be attributed to increased levels of circulating hCG. Based on the data obtained from a large number of pregnant women, we propose gestational transient hyperthyroxinaemia as a definite clinical entity.


Tracking chiral polychlorinated biphenyl sources near a hazardous waste incinerator: fresh emissions or weathered revolatilization?
The Swan Hills Treatment Centre (SHTC), located in central Alberta, is the primary facility in Canada for incinerating polychlorinated biphenyls (PCBs). Past studies have shown significant contamination by PCBs and other pollutants of the immediate surrounding region. However, it is unclear whether the major source of contamination to the region's atmosphere is historical release incidents or long-term emissions. To answer this question, concentrations of PCBs and enantiomer fractions of several PCB congeners were determined in soil and air, via polyurethane foam passive samplers, over several seasons between 2005 and 2008. Concentrations in both media were highest for samples collected closest to the SHTC, demonstrating a concentration profile typical of a point source. Enantiomer analysis revealed racemic profiles in air for all congeners, while soil was significantly nonracemic for PCB 95, indicating significant microbial degradation of this congener. However, the primary source of this congener, and likely others, in the surrounding atmosphere is recent and continual releases from the SHTC, rather than the release of weathered PCBs previously deposited to local soils. In addition, enantiomer compositions for PCBs 95 and 149 yielded minimum biotransformation half-lives of 25 and 97 years, respectively, suggesting an expected gradual decline in the region's PCB load once fresh inputs cease.


Evaluation of pemetrexed (Alimta, LY231514) as second line chemotherapy in persistent or recurrent carcinoma of the cervix: a phase II study of the Gynecologic Oncology Group.
To estimate the anti-tumor activity of pemetrexed in patients with advanced or recurrent carcinoma of the cervix that failed on higher priority treatment protocols and to determine the nature and degree of toxicity. A multicenter Phase II trial was conducted by the Gynecologic Oncology Group (GOG). Patients must have had advanced or recurrent measurable carcinoma of the cervix, and failed one prior chemotherapy regimen. Pemetrexed at a dose of 900 mg/m(2) was to be administered as an IV infusion over 10 min every 21 days. From July 6, 2004 to April 3, 2006, twenty-nine patients were entered by ten member institutions of the GOG. Two patients did not receive treatment and thus were inevaluable. A total of 128 cycles were administered with 37% of patients receiving six or more cycles. The treatment was well tolerated overall. More serious toxicities (grade 3 and 4) included anemia in 41%, leukopenia in 30%, neutropenia in 26%, and infection in 26%. No treatment related deaths were reported. Four patients (15%) had partial responses with a median response duration of 4.4 months. The response rate for non-radiated or radiated disease sites was 25% and 7% respectively. Sixteen patients (59%) had stable disease and seven (26%) patients had increasing disease. Median progression free survival (PFS) was 3.1 months and overall survival (OS) was 7.4 months. Pemetrexed at this dose and schedule showed moderate activity against advanced or recurrent cervical cancer that has failed prior chemotherapy. Data from other tumor sites has suggested synergy between pemetrexed and cisplatin and should be considered for further study.


Clinical trials for glaucoma neuroprotection are not impossible.
To discuss issues that affect development of new glaucoma treatments known as neuroprotection. There are barriers to neuroprotection trials for glaucoma. With design features discussed in the review, neuroprotection trials can be effectively carried out.


Biologic effects of parathyroid hormone metabolites: implications for renal bone disease.
PTH fragments consisting of the C-terminal portion of the molecule may have biologic effects and may modify the actions of PTH. Evidence for the presence of a C-terminal PTH receptor further supports a biologic role for such fragments. Because C-PTH fragments accumulate in patients with renal insufficiency, it is possible that they may contribute to renal bone disease. The precise role of circulating C-PTH fragments in the pathogenesis, diagnosis, and management of renal osteodystrophy, however, remains to be determined. Future studies of the biologic effects and regulation of these fragments may lead to better understanding of skeletal biology and may also improve our approach to the diagnosis and treatment of renal bone disease.


Consequences of the depletion of cellular deoxynucleoside triphosphate pools on the excision-repair process in cultured human fibroblasts.
DNA excision repair requires the insertion of bases into gaps in the DNA which arise during the removal of damaged sites from the chromatin. The number of bases required is dependent on the amount of damage and the patch size of repair in response to the particular type of damage. In cells in which the ability to synthesize deoxynucleoside triphosphates (dNTPs) has been compromised, repair cannot proceed to completion following doses of DNA-damaging agents which induce repair that requires greater than the steady-state level of dNTPs. Repair is thus not equally sensitive to depletion of dNTPs when measured in rapidly cycling cells with relatively high dNTP pools or in non-cycling cells with significantly smaller pools. Critical depletion of dNTPs results in the production of long-lived DNA strand breaks at repairing sites and reduction in the number of sites initiating repair. On the other hand, elevation of dNTP pools to 10-50-fold normal levels did not inhibit repair. This indicates that dNTP pool depletion but not general pool-imbalance affects DNA excision repair.


Interdigitating dendritic cell sarcoma presenting simultaneously with acute myelomonocytic leukemia: report of a rare case and literature review.
Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare tumor derived from interdigitating dendritic cells. We report the first case of a 64-year-old Chinese woman who was diagnosed with simultaneous IDCS and acute myelomonocytic leukemia (AML-M4). The patient had undergone chemotherapy for breast cancer 6 years previously. Based on the laboratory results, both the IDCS and the AML-M4 in this patient were determined to be of myelogenous origination. Furthermore, a review of 62 IDCS cases (Medline database, key word: IDCS) reported to date revealed that as many as 17 % of the patients had malignant disease and received radiotherapy and/or chemotherapy prior to developing IDCS, and that this group of patients showed worse prognosis compared with counterparts. The patient in the present report showed poor response to four cycles of sequential chemotherapy, and died 6 months after the initial diagnosis.


[Does OCT morphology provide indications for prognosis of visual acuity after venous occlusion? : SD-OCT analysis in retinal vein occlusion before and after resolution of initial macular edema].
Even though macular edema (ME) in patients with retinal vein occlusion (RVO) is resolved after intravitreal treatment with anti-vascular endothelial growth factor (VEGF), impairment of visual acuity (VA) often persists. A qualitative and quantitative evaluation of spectral domain optical coherence tomography (SD-OCT) images was carried out in patients with RVO and resolved ME to investigate a correlation between retinal morphology and functional results. Foveal SD-OCT scans of 13 patients with RVO and resolved ME after treatment were retrospectively evaluated. The thickness of inner retinal layers up to the external limiting membrane (ELM) and up to the photoreceptors in the retinal pigment epithelium (RPE) was measured by automatic segmentation software. Foveal continuity of the four outer hyperreflective bands, the ellipsoid zone of the inner segments (ISe), the ELM, the interdigitation zone (IZ), the RPE and the location of the initial ME were evaluated. Patients with good (≤ 0.3 logMAR, n = 10) and poor VA (≥ 1.0 logMAR, n = 3) were compared. Inner retinal layers up to ELM were thinner in the the poor VA group. In the good VA group the initial ME was significantly more often above the ISe and after resolution of ME the ISe tended to be intact more frequently. In patients with poor VA despite resolved ME the inner retinal layers up to the ELM were significantly thinner, which could be a sign of atrophy. Qualitative differences were seen at the photoreceptor level, which could be explained by ischemia or an involvement of the outer retina during initial ME that leads to permanent destruction of the ISe.


The receptor-like properties of nitric oxide-activated soluble guanylyl cyclase in intact cells.
Soluble guanylyl cyclase (sGC) is the main receptor for nitric oxide (NO), and so mediates a wide range of effects (e.g. vasodilatation, platelet disaggregation and neural signalling) through the accumulation of cGMP and the engagement of various downstream targets, such as protein kinases and ion channels. Until recently, our understanding of sGC functioning has been derived exclusively from studies of the enzyme in tissue homogenates or in its purified form. Here, NO binds to the haem prosthetic group of sGC, triggering a conformational change and a large increase in catalytic activity. The potency (EC50) of NO appears to be about 100-200 nM. The rate of activation of sGC by NO is rapid (milliseconds) and, in the presence of excess substrate, cGMP is formed at a constant rate; on removal of NO, sGC deactivates slowly (seconds-minutes). Recent investigation of the way that sGC behaves in its natural environment, within cells, has revealed several key differences. For example, the enzyme exhibits a rapidly desensitizing profile of activity; the potency of NO is 45 nM for the minimally-desensitized enzyme but becomes higher with time, deactivation of sGC on removal of NO is 25-fold faster than the fastest estimate for purified sGC. Overall, within cells, sGC behaves in a way that is analogous to the way that classical neurotransmitter receptors operate. The properties of cellular sGC have important implications for the understanding of NO-cGMP signalling. For example, the dynamics of the enzyme means that fluctuations in the rate of NO formation, even on subsecond time scale, will result in closely synchronized sGC activity in neighbouring cells; desensitization of sGC provides an economical way of generating a cellular cGMP signal and, in concert with phosphodiesterases, provides the basis for cGMP signal diversity, allowing different targets (outputs) to be selected from a common input (NO). Thus, despite exhibiting only limited molecular heterogeneity, cellular sGC functions in a way that introduces speed, complexity, and versatility into NO-cGMP signalling pathways.


Spirometric reference equations for Cameroonians aged 4 to 89 years derived using lambda, mu, sigma (LMS) method.
Spirometric reference values are well known in several ethnic groups but the normative spirometric values of blacks living in Africa have been less studied. The purpose of this study is to establish normative spirometric equations from a representative population of Cameroonian children and adults and compare these equations with those developed by the Global Lung Initiative (GLI) and in Nigerians. Spirometric data from healthy Cameroonians aged 4-89 years randomly collected between 2014 and 2018 were used to derive reference equations using generalized additive model for location (mu), shape (lambda) and scale (sigma). A total of 625 children and adolescents (290 males and 335 females) and 1152 adults (552 males and 600 females) were included in the study. The prediction equation for spirometric index was written as: M = Exp[a0 + a1*ln (Height) + a2*ln (Age) + Mspline, Mspline was age related spline contribution]. Applying the GLI standards for African Americans resulted in overall values greater than those found in our study for forced expiratory volume in 1s (FEV1) and forced vital capacity (FVC). These values were very close in children and adolescents while the values obtained with the GLI equations for African Americans were significantly higher in adults. FEV1/FVC ratio in our study was similar for adult males but lower in adult females (88% vs 85%, difference = + 3.5%) when applying Nigerian standards. FEV1 and FVC of the Cameroonian infant and adolescent population are very close to those of black Americans. However, FEV1 and FVC of Cameroonian adults are significantly lower than those of black American adults. These equations should allow a more suitable interpretation of spirometry in the Cameroonian population.


Longitudinal investigation of the presence of different trajectories and associated health and socio-economic determinants, for participants who report suicidal ideation within a community-based public health survey.
Given the paucity of evidence-based research investigating different suicidal ideation profiles and trajectories, this project sought to investigate health and socio-economic factors associated with the presence of suicidal ideation and changes in ideation over time. Longitudinal cohort design, using logistic regression analysis. A public health survey was administered at two timepoints in a community setting across the North West of England. In the 2015/2016 survey, participants were recruited from high (n=20) and low (n=8) deprivation neighbourhoods. In the 2018 survey, only the 20 high-deprivation neighbourhoods were included. 4287 people were recruited in 2015/2016 and 3361 were recruited in 2018. The 2018 sample was subdivided into those who responded only in 2018 (n=2494: replication sample) and those who responded at both timepoints (n=867: longitudinal sample). Suicide ideation was the dependent variable which was assessed using item 9 of the Patient Health Questionnaire instrument. The prevalence of suicidal ideation was 11% (n=454/4319) at 2015/2016 and 16% (n=546/3361) at 2018.Replication study results highlighted: persistent debilitation from physical ill health and/or medication side effects; demographic factors (ie, middle-aged, single or never married); and personal coping strategies (ie, smoking) as risk factors for suicidal ideation. A static/improved financial position and high levels of empathy were protective factors.Longitudinal study results confirmed three suicidal ideation trajectories: 'onset', 'remission' and 'persistence'. Similar findings to the replication study were evidenced for the onset and persistence trajectories. Persistent suicidal ideation was synonymous with higher levels of practical support which may correspond to the higher levels of debilitation and functional disability reported within this group. Remission was characterised by fewer debilitating factors and higher levels of self-agency. A greater appreciation of the heterogeneity of suicidal trajectories should lead to the implementation of broad clinical assessments and targeted interventions.


Isolation of melanoma tumor-initiating cells from surgical tissues.
A new model of cancer progression has been put forward that predicts existence of tumor stem cells (TSCs) in the heterogeneous bulk tumor mass that self-renew, are resistant to chemo- and radiotherapies, and sustain tumor growth during the course of its progression or relapse (Ailles and Weissman, Curr Opin Biotechnol 18:460-466, 2007; Chan et al., Proc Natl Acad Sci U S A 106:14016-14021, 2009; D'Angelo and Wicha, Prog Mol Biol Transl Sci 95:113-158, 2010; O'Brien, Semin Radiat Oncol 19:71-77, 2009; Park et al., Mol Ther 17:219-230, 2009). Using most advanced methods of cell purification and transplantation, our laboratory and another independent study identified melanoma stem cells as CD271(NFGR/p75)+ cells from surgical human specimens (Boiko et al., Nature 466:133-137, 2010; Civenni et al., Cancer Res 71:3098-3109, 2011). Here we describe in great detail an approach for isolating tumor-initiating cells from freshly resected melanomas (Boiko et al., Nature 466:133-137, 2010).


[Analysis of the pediatric trauma score in patients wounded with shrapnel; the effect of explosives with high kinetic energy: results of the first intervention center].
We aimed to assess the pediatric trauma score analysis in pediatric trauma cases due to shrapnel effect of explosives material with high kinetic energy. The data of 17 pediatric injuries were reviewed retrospectively between February 2002 and August 2005. The information about age, gender, trauma-hospital interval, trauma mechanism, the injured organs, pediatric Glasgow coma score (PGCS), pediatric trauma score (PTS), hemodynamic parameters, blood transfusion, interventions and length of hospital stay (LHS) were investigated. While all patients suffered from trauma to the extremities, only four patients had traumatic lower-limb amputation. Transportation time was <=1 hour in 35% of cases, and >1 hour in 65% of cases. While PTS was found as <=8 in 35.3% of cases (n=6), the score was found to be higher than 8 in 64.7% of them (n=11). Median heart rate in patients with PTS <=8 was 94 beats/min. This value was 70 beats/min in those with PTS >8 (p=0.007). Morbidity rates of PTS <=8 cases and PTS >8 cases were 29.4% and 5.9%, respectively (p=0.026). While LHS was 22.8 days in PTS <=8 cases, LHS was found to be only 4 days in PTS >8 cases. This difference was found to be statistically significant (p=0.001). PTS is very efficient and a time-saving procedure to assess the severity of trauma caused by the shrapnel effect. The median heart rate, morbidity, and LHS increased significantly in patients with PTS <=8.


Adaptive modifications of post-saccadic smooth pursuit eye movements and their interaction with saccades and the vestibulo-ocular reflex in the primate.
Adaptation of the horizontal smooth pursuit eye movement was examined using step-ramp moving target paradigms in chronically prepared Macaca fuscata. Monkeys were trained to pursue a small target which moved in the horizontal plane in a 3 degrees step-10 degrees/s ramp or a 0 degrees step-10 degrees/s ramp mode for 300-400 ms. When the target moved from central fixation point in a step-ramp mode, the monkeys usually responded with an initial pursuit eye movement (latency, 100-120 ms) which reached to a nearly constant velocity of 4 degrees/s in 50 100 ms, followed by a 1-3.5 degrees catch-up saccade (latency, 170-230 ms). The catch-up saccade was followed by a 7-8 degrees/s post-saccadic pursuit. The post-saccadic pursuit velocity was measured 40-90 ms after the end of the catch-up saccade. When the target velocity was doubled (20 degrees/s) for 100-200 ms immediately after the onset of the catch-up saccade, the post-saccadic pursuit velocity increased by 40%. When the target velocity was decreased by half (5 degrees/s) immediately after the onset of the catch-up saccade for 150 ms, the post-saccadic pursuit velocity decreased by 30%. These increases or decreases of post-saccadic pursuit were observable within just 50-150 trials. The adaptation of post-saccadic pursuit occurred independent of the position of the target. The amplitude and latency of the catch-up saccade also increased correspondingly when the post-saccadic pursuit velocity was adaptively increased. Adaptation of smooth pursuit did not affect the dynamics of reflex eye movements, including the horizontal vestibulo-ocular reflex (HVOR) gain and phase measured by 0.33 Hz-10 degrees (peak-to-peak) turntable oscillations in darkness. Conversely, adaptation of the HVOR gain induced by a 2 h sustained oscillation of the turntable and screen in reversed direction at 0.33 Hz-10 degrees affected little the velocity of post-saccadic pursuit or the amplitude of the catch-up saccade. These results suggest that different neural mechanisms are respectively involved for the adaptation of horizontal smooth pursuit and HVOR in the primate.


Evidence of a growth hormone-releasing hormone-like molecule in salmon brain, Oncorhynchus keta and O. kisutch.
An antiserum with conformational specificity to human growth hormone-releasing hormone (hGH-RH 1-44 NH2) was produced and used to develop a radioimmunoassay to detect immunoreactive (ir) GH-RH in brain extracts of salmon, guinea pig, and mouse. Evidence of an immunoreactive GH-RH from salmon brain extracts with a retention time on reverse-phase high-performance liquid chromatography (HPLC) distinct from hGH-RH 1-44 is presented. Salmon irGH-RH from crude extracts elutes 1-2 min earlier than hGH-RH 1-44 (NH2) in a gradient HPLC system, whereas affinity-purified salmon irGH-RH elutes 12-13 min earlier in a near-isocratic system, suggesting that the salmon molecule is more hydrophilic.


Increased extent of object-selective cortex in schizophrenia.
Schizophrenia patients exhibit deficits in various stages of visual information processing. Despite recent informative efforts to examine visual processing in schizophrenia with functional magnetic resonance imaging (fMRI), much remains unknown about the basic function, structure, and organization of key early visual processing areas in schizophrenia. This study examined magnitude and topography of regional brain activity in three early visual processing areas: early retinotopically organized areas (V1-V4), motion-sensitive areas (human area MT, hMT+), and object-recognition areas (lateral occipital complex, LO). Using visual stimuli that are known to preferentially activate each respective region, we compared responses in these areas in 22 schizophrenia patients and 19 normal controls. Activity in all three regions was of similar amplitude in schizophrenia patients and normal controls. Activity in retinotopically organized areas and hMT+ showed good spatial overlap between groups. However, activation of LO was more widely distributed in patients compared with normal controls. The findings of abnormal spatial organization of LO in schizophrenia patients may converge with behavioral evidence of deficits in schizophrenia patients for object-recognition tasks that are believed to be mediated by LO activity.


Comparison of GnRH agonists and antagonists in normoresponder IVF/ICSI in Turkish female patients.
To evaluate the results of gonadotropin-releasing hormone agonist (GnRHa) and gonadotropin-releasing hormone antagonist (GnRHant) use in two demographically matched groups of normoresponder in-vitro fertilisation or intracytoplasmic sperm injection (IVF/ICSI) patients in a prospective study. We randomised 93 patients undergoing IVF/ICSI between May 2005 and August 2006. Patients with IVF indications were included except for those with polycystic ovary syndrome or azoospermia, women older than 38 years and those with follicle-stimulating hormone (FSH) > or =10 IU/ml. Patients were stimulated with standard 225 IU recombinant FSH. In Group I (n=45) a daily dose of GnRHant cetrorelix acetate 0.25 mg was administered when follicles reached a diameter of > or =14 mm. Group II (n=48) patients were desensitised with the GnRHa, leuprolide acetate, in a long protocol. Human chorionic gonadotropin (hCG) was administered when at least three follicles of 18 mm in diameter were observed. Oocyte retrieval was scheduled 36 hours following hCG administration and embryos were transferred on day 3 after oocyte retrieval. The two groups were homogenous for age, infertility duration, basal FSH and serum oestradiol (E2) (P=0.537, P=0.911, P=0.103 and P=0.733, respectively). In Group II (the GnRHa group) more antral follicles (P<0.001), a longer induction duration (P=0.017) and higher peak E2 levels (P<0.001) were observed. No differences were observed in the number of oocytes retrieved (P=0.749), embryos achieved and transferred (P=0.677), or fertilisation rates (P=0.839) between the two groups. There was no statistically significant difference between groups in clinical pregnancy rates, cycle cancellation and ovarian hyperstimulation (P=0.437, P=0.109 and P=0.415, respectively). GnRHant and GnRHa provide comparable results in normoresponder patients, while GnRHant allows a greater flexibility in their treatment.


[Mechanisms of compensating the evacuatory function of the stomach after exclusion of the pyloric sphincter].
The rate of solid food evacuation from the stomach was investigated in chronic experiments on dogs with the stomach and the duodenum (its first part) fistulae. It was found that in exclusion of the pyloric sphincter (operations of pyloroplastics or gastroduodenostomy) the stomach evacuation was mainly compensated. However, judging by the free passage of rubber balls (3 mm in diameter) into the duodenum no structures replacing the pyloric sphincter formed in the stomach. The compensation of the stomach evacuatory function under these conditions was provided by a significant increase of the enterogastric reflex.


Mast cell-derived serine proteinase regulates T helper 2 polarization.
Although mast cells play a critical role in allergic reactions, the cells are also involved in the protective immunity in the body. This study aims to investigate the role of mast cells in immune regulation during aberrant T helper (Th)2 responses. In this study, an adoptive antigen-specific Th2 response model was established with mast cell-deficient mice to test the role of mast cell in the immune regulation. Cell culture was employed to test the role of mast cells in the modulation of the expression of B cell lymphoma 6 protein (Bcl-6) in Th2 cells. The results showed that after adoptive transfer with immune cells, the mast cell-deficient mice showed stronger Th2 pattern responses in the intestine than that in the mast cell-sufficient mice. Mast cell-derived mouse mast cell protease-6 increased the expression of Bcl-6 in Th2 cells. Bcl-6 inhibited the expression of GATA-3 in Th2 cells, subsequently, forkhead box P3 was increased and the Th2 cytokines were reduced in the cells; the cells thus showed the immune regulatory properties similar to regulatory T cells. We conclude that bedsides initiating immune inflammation, mast cells also contribute to the immune regulation on Th2 polarization.


Flexible protein-ligand docking using the Fleksy protocol.
Considering protein plasticity is important in accurately predicting the three-dimensional geometry of protein-ligand complexes. Here, we present the first public release of our flexible docking tool Fleksy, which is able to consider both ligand and protein flexibility in the docking process. We describe the workflow and different features of the software and present its performance on two cross-docking benchmark datasets.


A silk-based self-adaptive flexible opto-electro neural probe.
The combination of optogenetics and electrophysiological recording enables high-precision bidirectional interactions between neural interfaces and neural circuits, which provides a promising approach for the study of progressive neurophysiological phenomena. Opto-electrophysiological neural probes with sufficient flexibility and biocompatibility are desirable to match the low mechanical stiffness of brain tissue for chronic reliable performance. However, lack of rigidity poses challenges for the accurate implantation of flexible neural probes with less invasiveness. Herein, we report a hybrid probe (Silk-Optrode) consisting of a silk protein optical fiber and multiple flexible microelectrode arrays. The Silk-Optrode can be accurately inserted into the brain and perform synchronized optogenetic stimulation and multichannel recording in freely behaving animals. Silk plays an important role due to its high transparency, excellent biocompatibility, and mechanical controllability. Through the hydration of the silk optical fiber, the Silk-Optrode probe enables itself to actively adapt to the environment after implantation and reduce its own mechanical stiffness to implant into the brain with high fidelity while maintaining mechanical compliance with the surrounding tissue. The probes with 128 recording channels can detect high-yield well-isolated single units while performing intracranial light stimulation with low optical losses, surpassing previous work of a similar type. Two months of post-surgery results suggested that as-reported Silk-Optrode probes exhibit better implant-neural interfaces with less immunoreactive glial responses and tissue lesions. A silk optical fiber-based Silk-Optrode probe consisting of a natural silk optical fiber and a flexible micro/nano electrode array is reported. The multifunctional soft probe can modify its own Young's modulus through hydration to achieve accurate implantation into the brain. The low optical loss and single-unit recording abilities allow simultaneous optogenetic stimulation and multichannel readout, which expands the applications in the operation and parsing of neural circuits in behavioral animals.


The Reliability of Estimating Ki Values for Direct, Reversible Inhibition of Cytochrome P450 Enzymes from Corresponding IC50 Values: A Retrospective Analysis of 343 Experiments.
In the present study, we conducted a retrospective analysis of 343 in vitro experiments to ascertain whether observed (experimentally determined) values of Ki for reversible cytochrome P450 (P450) inhibition could be reliably predicted by dividing the corresponding IC₅₀ values by two, based on the relationship (for competitive inhibition) in which Ki = IC₅₀/2 when [S] (substrate concentration) = Km (Michaelis-Menten constant). Values of Ki and IC₅₀ were determined under the following conditions: 1) the concentration of P450 marker substrate, [S], was equal to Km (for IC₅₀ determinations) and spanned Km (for Ki determinations); 2) the substrate incubation time was short (5 minutes) to minimize metabolism-dependent inhibition and inhibitor depletion; and 3) the concentration of human liver microsomes was low (0.1 mg/ml or less) to maximize the unbound fraction of inhibitor. Under these conditions, predicted Ki values, based on IC₅₀/2, correlated strongly with experimentally observed Ki determinations [r = 0.940; average fold error (AFE) = 1.10]. Of the 343 predicted Ki values, 316 (92%) were within a factor of 2 of the experimentally determined Ki values, and only one value fell outside a 3-fold range. In the case of noncompetitive inhibitors, Ki values predicted from IC₅₀/2 values were overestimated by a factor of nearly 2 (AFE = 1.85; n = 13), which is to be expected because, for noncompetitive inhibition, Ki = IC₅₀ (not IC₅₀/2). The results suggest that, under appropriate experimental conditions with the substrate concentration equal to Km, values of Ki for direct, reversible inhibition can be reliably estimated from values of IC₅₀/2.


Lung function tests in clinical decision-making.
In this article, we review the utility of the most common lung function tests (spirometry, reversibility test, peak expiratory flow, lung volumes, maximal respiratory pressure, carbon monoxide transference, arterial blood gas, 6-minute walk test and desaturation with exercise and ergospirometry) related to the most frequent pathologies (dyspnea of undetermined origin, chronic cough, asthma, COPD, neuromuscular diseases, interstitial diseases, pulmonary vascular diseases, pre-operative evaluation and disability evaluation). Our analysis has been developed from the perspective of decision-making, clinical interpretation or aspects that the physician should take into account with their use. Consequently, the paper does not deal with aspects of quality, technique or equipment, with the exception of when regarding costs as we believe that this is an important element in the decision-making process. The document is extensively supported by references from the literature.