A putative inhibitory mechanism in the tenase complex responsible for loss of coagulation function in acquired haemophilia A patients with anti-C2 autoantibodies.
Acquired haemophilia A (AHA) is caused by the development of factor (F)VIII autoantibodies, demonstrating type 1 or type 2 inhibitory behaviour, and results in more serious haemorrhagic symptoms than in congenital severe HA. The reason(s) for this remains unknown, however. The global coagulation assays, thrombin generation tests and clot waveform analysis, demonstrated that coagulation parameters in patients with AHA-type 2 inhibitor were more significantly depressed than those in patients with moderate HA with similar FVIII activities. Thrombin and intrinsic FXa generation tests were significantly depressed in AHA-type 1 and AHA-type 2 compared to severe HA, and more defective in AHA-type 1 than in AHA-type 2. To investigate these inhibitory mechanism(s), anti-FVIII autoantibodies were purified from AHA plasmas. AHA-type 1 autoantibodies, containing an anti-C2 ESH4-epitope, blocked FVIII(a)-phospholipid binding, whilst AHA-type 2, containing an anti-C2 ESH8-epitope, inhibited thrombin-catalysed FVIII activation. The coagulation function in a reconstituted AHA-model containing exogenous ESH4 or ESH8 was more abnormal than in severe HA. The addition of anti-FIX antibody to FVIII-deficient plasma resulted in lower coagulation function than its absence. These results support the concept that global coagulation might be more suppressed in AHA than in severe HA due to the inhibition of FIXa-dependent FX activation by steric hindrance in the presence of FVIII-anti-C2 autoantibodies. Additionally, AHA-type 1 inhibitors prevented FVIIIa-phospholipid binding, essential for the tenase complex, whilst AHA-type 2 antibodies decreased FXa generation by inhibiting thrombin-catalysed FVIII activation. These two distinct mechanisms might, in part, contribute to and exacerbate the serious haemorrhagic symptoms in AHA.


Blindness in a woman with human immunodeficiency virus infection and syphilis.
A concomitant infection with human immunodeficiency virus (HIV) may alter the natural history of other infections. Several reports indicate that syphilis may behave more aggressively when HIV infection is present. A woman presented with a rash involving her hands and feet and progressive loss of the vision in her right eye. Her serologic tests for syphilis and HIV infection were positive. A diagnosis of neurosyphilis was confirmed by an analysis of cerebrospinal fluid (CSF). She was treated with high-dose intravenous (IV) penicillin. Her skin lesions resolved, but her vision did not improve. The incidence of HIV infection among women is rising. A patient with HIV and syphilis may develop neurosyphilis in a much shorter time than a patient without HIV infection.


Inhibition of p38 MAPK reduces expression of vascular endothelial growth factor in allergic airway disease.
The p38 mitogen-activated protein kinase (MAPK) appears to play an important role in various pathophysiological responses and has been suggested to be involved in many processes considered critical to the inflammatory response and tissue remodeling. Bronchial asthma is a chronic inflammatory disorder of the airway accompanied by increased vascular permeability. Vascular endothelial growth factor (VEGF) is a potent stimulator of bronchial inflammation, airway remodeling, and physiologic dysregulation that augments antigen sensitization and T-helper type 2 cell (Th2)-mediated inflammation in allergic airway diseases. However, there are little data on the relationship between p38 MAPK signaling and VEGF expression in allergic airway disease. This study aimed to investigate the role of p38 MAPK on the pathogenesis of allergic airway disease, more specifically in VEGF expression. Using ovalbumin (OVA)-inhaled mice and a selective p38 MAPK inhibitor, SB 239063, the involvement of p38 MAPK in allergen-induced VEGF expression in the airway was evaluated. The increases of phosphorylation of p38 MAPK, VEGF protein expression, and vascular permeability in the lung after OVA inhalation were decreased substantially by the administration of SB 239063. In addition, SB 239063 significantly reduced the increase of Th2 cytokines and OVA-specific IgE. The inhibition of p38 MAPK or VEGF signaling prevented and also decreased the increases in the number of inflammatory cells and airway hyperresponsiveness in OVA-induced allergic airway disease. These results indicate that inhibition of p38 MAPK may attenuate allergen-induced airway inflammation and vascular leakage through modulation of VEGF expression in mice.


[Conventional angiography and digital subtraction angiography in arterial occlusive disease of the extracranial branches of cerebral arteries].
In this paper the advantages and disadvantages of different arteriographic methods, i.e. conventional angiography, intraarterial DSA and intravenous DSA, are discussed for the purpose of examining the extracranial supraaortic branches. The analysis of individual vascular regions in arteriography of the aortic arch is assessed. In addiction, the value of i.v. DSA is demonstrated, comparing own results with data in the literature. Indications of the three different angiographic techniques are outlined.


Diabetes and SGLT2-iss inhibitors in patients with heart failure with preserved or mid-range left ventricular ejection fractions.
Diabetic patients frequently develop heart failure with preserved (HFpEF) or mid-range (HFmEF) cardiac ejection fractions. This condition may be secondary to diabetic cardiomyopathy or one of several relevant comorbidities, mainly hypertension. Several mechanisms link diabetes to HFpEF or HFmEF. Among these, non-enzymatic glycation of interstitial proteins, lipotoxicity, and endothelial dysfunction may promote structural damage and ultimate lead to heart failure. Findings from several large-scale trials indicated that treatment with sodium/glucose cotransporter 2 inhibitors (SGLT2-iss) resulted in significant improvements in cardiovascular outcomes in diabetic patients with high cardiovascular risk. However, there is currently some evidence that suggests a clinical advantage of using SGLT2-iss specifically in cases of HFpEF or HFmEF. Preclinical and clinical studies revealed that SGLT2-iss treatment results in a reduction in left ventricular mass and improved diastolic function. While some of the beneficial effects of SGLT2-iss have already been characterized (e.g., increased natriuresis and diuresis as well as reduced blood pressure, plasma volume, and arterial stiffness, and nephron-protective activities), there is increasing evidence suggesting that SGLT2-iss may have direct actions on the heart. These findings include SGLT2-iss-mediated reductions in the expression of hypertrophic foetal genes and diastolic myofilaments stiffness, increases in global phosphorylation of myofilament regulatory proteins (in HFpEF), inhibition of cardiac late sodium channel current and Na+/H+ exchanger activity, metabolic shifts, and effects on calcium cycling. Preliminary data from previously published studies suggest that SGLT2-iss could be useful for the treatment of HFpEF and HFmEF. Several large ongoing trials, including DELIVER AND EMPEROR -preserved have been designed to evalute the efficacy of SGLT2-iss in improving clinical outcomes in patients diagnosed with HFpEF. The goal of this manuscript is to review the use of SGLT2-iss inhibitors for HFpEF or HFmEF associated with diabetes.


Amplification of HTLV-1-related sequences among patients with neurological disorders in highly endemic Nagasaki: lack of evidence for association of HTLV-1 with multiple sclerosis.
We studied DNA sequences homologous to HTLV-1 in peripheral blood mononuclear cells (PBMC) of 30 patients with neurological disorders in Kyushu, where HTLV-1 is highly endemic. The regions of HTLV-1 amplified by means of polymerase chain reaction (PCR) included U3, U5, gag, pol, env and pX. Our system specifically detected HTLV-1 sequences only from HTLV-1-positive cells and was sufficiently sensitive to detect one proviral copy per 10(3) PBMC. All PCR-positive cases were seropositive, including 4 cases of tropical spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM) (4/4), and one case each of myasthenia gravis (1/7) and multiple sclerosis (1/8). The PCR-positive rate of patients, excluding 4 TSP/HAM cases, was 8% (2/26), which is similar to the seroprevalence of the adult population in the area. The data suggest that multiple sclerosis is not associated with prototype HTLV-1.


The epidemiology of IgE-mediated food allergy and anaphylaxis.
The rise in food allergy prevalence in developed countries is evident from anecdotal reports but has been difficult to document and until recently good quality prevalence data were lacking. Although most emerging risk factors seem related to the "modern lifestyle" the reasons for the rise in food allergy prevalence remain poorly understood. The incidence of food allergy-related anaphylaxis is rising particularly in children younger than 5 years of age. Emerging studies are better designed to assess the true prevalence of IgE-mediated food allergy using formal population sampling frames, standardized and objective outcome data including use of the gold standard oral food challenge, and the capacity to adjust for potential selection bias.


Synthesis and structure-activity relationship studies on tryprostatin A, an inhibitor of breast cancer resistance protein.
Tryprostatin A is an inhibitor of breast cancer resistance protein, consequently a series of structure-activity studies on the cell cycle inhibitory effects of tryprostatin A analogues as potential antitumor antimitotic agents have been carried out. These analogues were assayed for their growth inhibition properties and their ability to perturb the cell cycle in tsFT210 cells. SAR studies resulted in the identification of the essential structural features required for cytotoxic activity. The absolute configuration L-Tyr-L-pro in the diketopiperazine ring along with the presence of the 6-methoxy substituent on the indole moiety of 1 was shown to be essential for dual inhibition of topoisomerase II and tubulin polymerization. Biological evaluation also indicated the presence of the 2-isoprenyl moiety on the indole scaffold of 1 was essential for potent inhibition of cell proliferation. Substitution of the indole N(a)-H in 1 with various alkyl or aryl groups, incorporation of various L-amino acids into the diketopiperazine ring in place of L-proline, and substitution of the 6-methoxy group in 1 with other functionality provided active analogues. The nature of the substituents present on the indole N(a)-H or the indole C-2 position influenced the mechanism of action of these analogues. Analogues 68 (IC(50)=10 microM) and 67 (IC(50)=19 microM) were 7-fold and 3.5-fold more potent, respectively, than 1 (IC(50)=68 microM) in the inhibition of the growth of tsFT210 cells. Diastereomer-2 of tryprostatin B 8 was a potent inhibitor of the growth of three human carcinoma cell lines: H520 (IC(50)=11.9 microM), MCF-7 (IC(50)=17.0 microM) and PC-3 (IC(50)=11.1 microM) and was equipotent with etoposide, a clinically used anticancer agent. Isothiocyanate analogue 71 and 6-azido analogue 72 were as potent as 1 in the tsFT210 cell proliferation and may be useful tools in labeling BCRP.


Generalizability of deep learning models for predicting outdoor irregular walking surfaces.
Observations from laboratory-based gait analysis are difficult to extrapolate to real-world environments where gait behavior is modulated in response to complex environmental conditions and surface profiles. Inertial measurement units (IMUs) permit real-world gait analysis; however, automatic detection of surfaces encountered remains largely unexplored. The aims of this study are to quantify for machine learning models the effect of (1) random and subject-wise data splitting and (2) sensor location and count on surface classification performance. Thirty participants walked on nine surface conditions (flat-even, slope-up, slope-down, stairs-up, stairs-down, cobblestone, grass, banked-left, banked-right) wearing IMUs (wrist, trunk, bilateral thighs, bilateral shanks). Data were separated into gait cycles, normalized to 101 samples, and spilt into train and test sets (85 and 15%, respectively). For random splitting, trials were randomly assigned to the train or test set. In subject-wise splitting, all trials from 4 random participants were selected for testing. Linear discriminant analysis extracted features from the IMUs. Features were delivered to a neural network. F1-score evaluated model performance. Models achieved F1 scores of 0.96 and 0.78 using random and subject-wise splitting, respectively. Random splitting performance was mainly invariant to sensor location/count; however, subject-wise splitting showed best performance using lower-limb sensors. In general, stairs and sloped surfaces were easily predicted (F1 > 0.85) while banked surfaces were challenging, especially for subject-wise models (F1 ≈ 0.6). Neural networks can detect surfaces based on subtle changes in walking behavior captured by IMUs. Data splitting approaches and sensor location/count (subject-wise) have a non-negligible effect on model performance.


The relationship between maternal prenatal and postnatal vegetable intake and repeated measures of infant vegetable intake frequency in a national U.S. sample.
Experimental research suggests that passive flavor transfer from maternal diet to the infant via amniotic fluid and breastmilk may improve infant vegetable intake. This secondary analysis examined associations between maternal (prenatal and postnatal) and infant vegetable intake in 696 mothers with eligible dietary data from the U.S. longitudinal Infant Feeding Practices Study II. Adjusted mixed models examined associations between 4 levels of maternal vegetable intake (mean splits of high/low on prenatal and postnatal food frequency questionnaires) and repeated measures of infant vegetable intake frequency (times/day, from monthly surveys). Mothers were on average 29.5 years old, mostly non-Hispanic White (86.2%) and educated (84.0% ≥some college). In base models, mothers with consistently high vegetable intake (vs. consistently low) reported more frequent infant vegetable intake. In multivariable models, infant vegetable intake was significantly more frequent amongst mothers with consistently high prenatal/high postnatal intake (0.9 times/day) versus consistently low intake (0.8 times/day). In this sample, maternal vegetable consumption was associated with frequency of infant vegetable consumption; consistently high vegetable intake across prenatal and postnatal periods was most strongly associated with infant intake. While infant vegetable intake is multifactorial, maternal prenatal and postnatal vegetable intake appeared to have a small but significant influence.


Difference in acute and chronic stage ischemic stroke metabolic markers with controls.
Acute Ischemic Stroke (AIS), a major cause of disability, was previously associated with multiple metabolomic changes, but many findings were contradictory. Case-control and longitudinal study designs could have played a role in that. To clarify metabolomic changes, we performed a simultaneous comparison of ischemic stroke metabolome in acute, chronic stages of stroke and controls. Through the nuclear magnetic resonance (NMR) platform, we evaluated 271 serum metabolites from a cohort of 297 AIS patients in acute and chronic stages and 159 controls. We used Sparse Partial Least Squares-Discriminant analysis (sPLS-DA) to evaluate group disparity; multivariate regression to compare metabolome in acute, chronic stages of stroke and controls; and mixed regression to compare metabolome acute and chronic stages of stroke. We applied false discovery rate (FDR) to our calculations. The sPLS-DA revealed separation of the metabolome in acute, chronic stages of stroke and controls. Regression analysis identified 38 altered metabolites. Ketones, branched-chain amino acids (BCAAs), energy, and inflammatory compounds were mostly elevated, while alanine and glutamine were decreased in the acute stage. These metabolites declined/increased in the chronic stage, often to the same levels as in controls. Levels of fatty acids, phosphatidylcholines, phosphoglycerides, and sphingomyelins did not change between acute and chronic stages, but were different comparing to controls. Our pilot study identified metabolites associated with acute stage of ischemic stroke and those that are altered in stroke patients comparing to controls regardless of stroke acuity. Future investigation in a larger independent cohort is needed to validate these findings.


Psychological and behavioral mechanisms influencing the use of complementary and alternative medicine (CAM) in cancer patients.
This study explored the psychological and behavioral mechanisms of complementary and alternative medicine (CAM) use in Japanese cancer patients using two applied behavioral models, the transtheoretical model (TTM), and theory of planned behavior (TPB). Questionnaires were distributed to 1100 patients at three cancer treatment facilities in Japan and data on 521 cancer patients were used in the final analysis. The questionnaire included items based on TTM and TPB variables, as well as three psychological batteries. According to the TTM, 88 patients (17%) were in precontemplation, 226 (43%) in contemplation, 33 (6%) in preparation, 71 (14%) in action, and 103 (20%) in maintenance. The model derived from structural equation modeling revealed that the stage of CAM use was significantly affected by the pros, cons, expectation from family, norms of medical staff, use of chemotherapy, period from diagnosis, and place of treatment. The primary factor for the stage of CAM use was the expectation from family. The findings revealed the existence of a number of psychologically induced potential CAM users, and psychological variables including positive attitude for CAM use and perceived family expectation greatly influence CAM use in cancer patients.


Quantitative assessment of hemodynamic changes during spinal dural arteriovenous fistula surgery.
We aimed to evaluate the efficacy of FLOW 800 (Carl Zeiss Meditec, Jena, Thuringia, Germany) with indocyanine green (ICG) videoangiography for the quantitative assessment of flow dynamics in spinal dural arteriovenous fistula (dAVF) surgeries. We prospectively enrolled nine patients with spinal dAVF diagnosed within the past year and performed FLOW 800 analyses using ICG videoangiography before and after surgical obliteration of the fistula. A color-coded map was semi-automatically generated by FLOW 800 and used for high-resolution visualization of the vasculature and instant interpretation of the dynamic flow changes. The FLOW 800-specific hemodynamic parameters were employed for real-time measurements of parenchymal perfusion alterations. Overall, 18 intraoperative FLOW 800 analyses using ICG videoangiography were performed in nine patients. The color-coded map aided the detection and complete obliteration of the fistulas in all patients and the results were verified by postoperative spinal digital subtraction angiography. The transit time parameter was significantly shorter in the preobliteration phase than in the postobliteration phase (p < 0.01), the rise time parameter exhibited the same pattern (p = 0.08) and maximum intensity and blood flow index were not significantly different between these phases. FLOW 800 with ICG videoangiography provided an intuitive and objective understanding of blood flow dynamics intraoperatively and enabled easy and confident identification and treatment of this pathology. The FLOW 800-specific hemodynamic analyses provided additional perfusion information that enabled real-time measurements of parenchymal perfusion alterations. FLOW 800 with ICG videoangiography is useful for intraoperative quantitative assessment of flow dynamics, facilitating safety and confidence in the treatment of spinal dAVF.


The relationship between socioeconomic status/income and prevalence of diabetes and associated conditions: A cross-sectional population-based study in Saskatchewan, Canada.
The role that socioeconomic status/income play in accounting for the increased prevalence of type 2 diabetes has not been sufficiently studied in Canada. The primary purpose of the present study was to determine the unadjusted and adjusted effect of income on type 2 diabetes. The secondary purpose was to determine the adjusted effect of income on diabetes associated conditions such as high blood pressure and being overweight or obese, and its main behavioral factor of physical inactivity. This is a cross-sectional, population-based study. Data was analyzed from four cycles of the Canadian Community Health Survey (CCHS). It was conducted by Statistics Canada and covered the time period of 2000-2008 in the province of Saskatchewan, Canada. In this study, four separate and distinct multivariate models were built to determine the independent effect of income on type 2 diabetes and the associated conditions of high blood pressure, being overweight or obese, and physical inactivity. The total sample size was comprised of 27,090 residents from Saskatchewan. After statistically controlling for age, only six covariates were independently associated with type 2 diabetes prevalence including: having high blood pressure (OR = 3.26), visible minority cultural status (OR = 2.17), being overweight or obese (OR = 1.97), being of male gender (OR = 1.76), having a household income of $29,999 per year (OR = 1.63) and being physically inactive (OR = 1.15). In this study, household income was strongly and independently associated with type 2 diabetes prevalence, its associated conditions of high blood pressure and being overweight or obese, and its main behavioral factor of physical inactivity. We suggest that income is an important but frequently overlooked factor for type 2 diabetes and worthy of further investigation, appropriate public debate and timely policy intervention.


[Sport activities from the lifespan perspective].
Considering lifespan developmental psychology, engagement in sport can be seen as a dynamic process of phases of participation and inactivity that varies from individual to individual. Depending on the individual biography, specific categories and patterns of sport participation evolve over a lifetime. Changes of sport participation rates over the last 30 years are discussed on the basis of general social changes. Six patterns of reasons will be discussed. The focus is set on a heuristic model as a base to explain the individual changes of behavior in sports over the lifespan. This model depicts engagement in sports as a process of dynamic changes (aspect of process and time) influenced by specific determinants in the different phases of changes (aspect of determinants). Finally, three of these determinants--(health) motives, barriers and preferences for sport and exercises--are specified because they seem to be important for adherence to adults' sports activities.


Identification of a new site in the S1 ligand binding region of the NMDA receptor NR2A subunit involved in receptor activation by glutamate.
Activation of N-methyl-d-aspartate (NMDA) receptors requires the binding of both glutamate and glycine to independent sites on the receptor. These ligands bind to NR2 and NR1 subunits respectively. Ligand binding residues are located in two non-contiguous domains, S1 and S2, which have been implicated in glutamate binding in other ionotropic glutamate receptor subunits. To further define the amino acids through which glutamate activates the receptor, we generated single-site mutations to the NR2A subunit, and expressed them with wild type NR1 in HEK 293 cells. Using calcium imaging and whole cell patch clamp we determined glutamate and glycine potencies. Of the eight residues mutated we identified five (E413, K484, A508, G685 and G688), whose mutation leads to a large reduction (from 4- to 1000-fold) in glutamate potency, consistent with a role for these residues in receptor activation by glutamate. The potency of glycine was largely unchanged by these mutations. Thus our results extend the knowledge base of residues involved in NMDA receptor function and identifies a new site in S1, in the region of A508, that has a role in receptor activation by glutamate.


Identification and reactivity of the catalytic site of pig liver thioltransferase.
The active site cysteine of pig liver thioltransferase was identified as Cys22. The kinetics of the reaction between Cys22 of the reduced enzyme and iodoacetic acid as a function of pH revealed that the active site sulfhydryl group had a pKa of 2.5. Incubation of reduced enzyme with [1-14C]cysteine prevented the inactivation of the enzyme by iodoacetic acid at pH 6.5, and no stable protein-cysteine disulfide was found when the enzyme was separated from excess [1-14C]cysteine, suggesting an intramolecular disulfide formation. The results suggested a reaction mechanism for thioltransferase. The thiolated Cys22 first initiates a nucleophilic attack on a disulfide substrate, resulting in the formation of an unstable mixed disulfide between Cys22 and the substrate. Subsequently, the sulfhydryl group at Cys25 is deprotonated as a result of micro-environmental changes within the active site domain, releasing the mixed disulfide and forming an intramolecular disulfide bond. Reduced glutathione, the second substrate, reduces the intramolecular disulfide forming a transient mixed disulfide which is then further reduced by glutathione to regenerate the reduced enzyme and form oxidized glutathione. The rate-limiting step for a typical reaction between a disulfide and reduced glutathione is proposed to be the reduction of the intramolecular disulfide form of the enzyme by reduced glutathione.


Effects of global warming on fish reproductive endocrine axis, with special emphasis in pejerrey Odontesthes bonariensis.
The ongoing of global warming trend has led to an increase in temperature of several water bodies. Reproduction in fish, compared with other physiological processes, only occurs in a bounded temperature range; therefore, small changes in water temperature could significantly affect this process. This review provides evidence that fish reproduction may be directly affected by further global warming and that abnormal high water temperature impairs the expression of important genes throughout the brain-pituitary-gonad axis. In all fishes studied, gonads seem to be the organ more readily damaged by heat treatments through the inhibition of the gene expression and subsequent synthesis of different gonadal steroidogenic enzymes. In view of the feedback role of sex steroids upon the synthesis and release of GnRH and GtHs in fish, it is possible that the inhibition observed at brain and pituitary levels in treated fish is consequence of the sharp decrease in plasma steroids levels. Results of in vitro studies on the inhibition of pejerrey gonad aromatase expression by high temperature corroborate that ovary functions are directly disrupted by high temperature independently of the brain-pituitary axis. For the reproductive responses obtained in laboratory fish studies, it is plausible to predict changes in the timing and magnitude of reproductive activity or even the total failure of spawning season may occur in warm years, reducing annual reproductive output and affecting future populations.


The effect of chloramphenicol and cycloheximide on platelet aggregation and protein synthesis.
This study investigated the role of platelet protein synthesis in platelet aggregation. Cycloheximide (Cx) and chloramphenicol (Cm) were used as inhibitors of cytoplasmic (80S ribosome directed) and mitochondrial protein synthesis respectively. The effect of these agents on human platelet aggregation and L-[U-14C]leucine incorporation into platelet protein was investigated. Cm exhibited dose-dependent inhibition of collagen, thrombin and secondary ADP aggregatory responses, but had no effect on arachidonate or primary ADP responses over a similar concentration range (3.1 X 10(-3), 3.1 X 10(-4) and 3.1 X 10(-5) M). Cm also inhibited platelet secretion associated with collagen and secondary ADP responses. Furthermore, Cm exhibited a similar dose-dependent inhibition of L-[U-14C]leucine incorporation into platelet protein reaching 80% inhibition of incorporation at 3 X 10(-3) M. At similar concentrations (3.5 X 10(-3), 3.5 X 10(-4) and 3.5 X 10(-5) M) Cx failed to show inhibition of human platelet aggregation by all agonists used with the exception of collagen where some inhibition was seen at high Cx concentration (3.5 X 10(-3) M). Cx was also found to be ineffective at inhibiting L-[U-14C]leucine incorporation into platelet protein at all concentrations tested. These results suggest that the majority of platelet protein synthesis is mitochondrial and that this protein synthesis may have a role in human platelet aggregation.


A combined action of amylose and amylopectin fine molecular structures in determining the starch pasting and retrogradation property.
Starch fine molecular structures are of essentially important in determining its pasting and retrogradation properties. In this study, 10 different starches from various botanical sources were selected to investigate the combined action of amylose and amylopectin molecules in determining the starch physicochemical properties. Correlation between starch structural parameters with the pasting and retrogradation properties showed that amylose and amylopectin CLDs do not affect these properties in isolation. Such as, the amount of amylose long chains and amylopectin short chains are both positively correlated with the melting temperatures and enthalpy of retrograded starches. Furthermore, relatively longer amylose short to medium chains can result in higher trough and breakdown viscosity, while higher amount of amylopectin medium to long chains result in higher peak viscosity. The results help a better understanding of the importance of amylose and amylopectin fine molecular structures in determining starch functional properties.


Matteuinterins A-C, three new glycosides from the rhizomes of Matteuccia intermedia.
Phytochemical investigation on the rhizomes of Matteuccia intermedia C.Chr. led to the isolation of three new compounds, named matteuinterins A-C (1-3), together with seven known compounds (4-10). Their structures were elucidated by extensive NMR analyses and chemical derivatization. Compounds 5-10 were evaluated for their anti-inflammatory activities on PGE2 release in LPS-stimulated RAW 264.7 murine macrophages. Compounds 5 and 10 exhibited inhibitory effect on PGE2 production in LPS-activated murine macrophages with IC50 values of 17.8 ± 1.5 and 30.3 ± 2.1 μM, respectively.[Formula: see text].


PRES and RCVS: Two Distinct Entities or a Spectrum of the Same Disease?
To report a case of a patient with overlapping posterior reversible encephalopathy syndrome (PRES) and reversible cerebral vasoconstriction syndrome (RCVS), and review the existing literature emphasizing the pathophysiological overlap of these two entities. We conducted a literature search in electronic database PubMed identifying studies reporting the overlap of PRES and RCVS. PRES and RCVS are two increasingly recognized entities that share similar clinical and imaging features. PRES is characterized by vasogenic edema predominantly in the parieto-occipital regions, associated with acute onset of neurological symptoms including encephalopathy, seizures, headaches, and visual disturbances. RCVS is characterized by reversible segmental and multifocal vasoconstriction of the cerebral arteries and classically presents with thunderclap headache, with or without associated focal neurological deficits and seizures. PRES is frequently associated with uncontrolled hypertension but can also be seen in the setting of renal failure, exposure to cytotoxic agents, or pre-eclampsia. RCVS is often triggered by exposure to vasoactive agents, postpartum state, or immunosuppression. We report a case of a patient presenting with vision changes and hemiparesis, and found to have extensive cytotoxic and vasogenic edema involving the cortex and subcortical white matter on brain imaging. These changes were primarily noted in the parieto-occipital and brainstem regions, along with features of reversible vasculopathy on vascular imaging suggestive of coexisting PRES and RCVS. PRES and RCVS share precipitating factors, clinical and radiological features, and frequently co-exist, suggesting a common pathophysiological mechanism related to reversible dysregulation of cerebral vasculature, endothelial dysfunction, and breakdown of the blood-brain barrier.


Assessing the relationship between groundwater nitrate and animal feeding operations in Iowa (USA).
Nitrate-nitrogen is a common contaminant of drinking water in many agricultural areas of the United States of America (USA). Ingested nitrate from contaminated drinking water has been linked to an increased risk of several cancers, specific birth defects, and other diseases. In this research, we assessed the relationship between animal feeding operations (AFOs) and groundwater nitrate in private wells in Iowa. We characterized AFOs by swine and total animal units and type (open, confined, or mixed), and we evaluated the number and spatial intensities of AFOs in proximity to private wells. The types of AFO indicate the extent to which a facility is enclosed by a roof. Using linear regression models, we found significant positive associations between the total number of AFOs within 2km of a well (p trend <0.001), number of open AFOs within 5km of a well (p trend <0.001), and number of mixed AFOs within 30km of a well (p trend <0.001) and the log nitrate concentration. Additionally, we found significant increases in log nitrate in the top quartiles for AFO spatial intensity, open AFO spatial intensity, and mixed AFO spatial intensity compared to the bottom quartile (0.171log(mg/L), 0.319log(mg/L), and 0.541log(mg/L), respectively; all p<0.001). We also explored the spatial distribution of nitrate-nitrogen in drinking wells and found significant spatial clustering of high-nitrate wells (>5mg/L) compared with low-nitrate (≤5mg/L) wells (p=0.001). A generalized additive model for high-nitrate status identified statistically significant areas of risk for high levels of nitrate. Adjustment for some AFO predictor variables explained a portion of the elevated nitrate risk. These results support a relationship between animal feeding operations and groundwater nitrate concentrations and differences in nitrate loss from confined AFOs vs. open or mixed types.


[International ophthalmology and travel medicine].
Medical eye care in developing countries is very different from the situation in industrialized nations. In order to prevent rising numbers of blind people worldwide due to increased life expectancy and population growth, the global initiative Vision 2020 "The Right to Sight" was established in 1999. Coordinated initiatives are important as most causes of blindness are either preventable or curable (e.g. cataract surgery); however, due to a lack of resources eye care in developing countries cannot implement all necessary preventive and therapeutic measures at present. The epidemiology of causes of blindness and the situation of ophthalmic care are discussed. Because of increased mobility of people and goods (e.g. air travel and trucking), imported eye diseases are of increasing importance. The difference between travel medicine, which deals with the medical situation of travelers and international ophthalmology (i.e. diseases in tropical countries) is discussed and illustrated on the basis of several important disease patterns.


Minimally invasive bronchoscopic resection of benign tumors of the bronchi.
Primary benign tumors of the trachea and main bronchi are uncommon. Interventional bronchoscopy allows the diagnosis and the treatment of some of these lesions. We reviewed four cases endoscopically treated at our institution. Two patients had hamartoma, and two patients had endobronchial lipoma. In all of the cases, the interventional technique for the resection was the use of a polypectomy snare and electrocautery. The only complication reported was one episode of bronchospasm. Minimally invasive bronchoscopic resection is a safe, effective method for treating selected benign tumors of the main airway and has a low complication rate.


Proteolysis efficiency and structural traits of corn gluten meal: Impact of different frequency modes of a low-power density ultrasound.
The influence of varying frequency modes of a low-power density ultrasound (LPDU) on the enzymolysis efficacy and structural property of corn gluten meal (CGM) was investigated. Sonication pretreatment (of CGM) with sequential and simultaneous duple-frequency modes enhanced notably the relative enzymolysis efficiency, compared to other LPDU frequency modes. With a sequential duple-frequency of 20/40 kHz showing the most significant effect, the maximum value of enzymolysis efficiency and protein dissolution rate were 15.99% and 61.69%, respectively. Changes in the surface hydrophobicity, secondary structure and microstructure revealed alterations of conformation of CGM by ultrasound-induced effect. Furthermore, the molecular weight distribution CGM hydrolysates primarily distributed in 200-500 Da following ultrasonication. Sonication efficaciously enhanced the susceptibility of CGM to alcalase proteolysis. Thus, the use of various LPDU frequency modes in pretreating target proteins (CGM) may be considered as a practical approach to improve protein-enzyme reactions (proteolysis).


[THE TREATMENT TACTICS AND PERIOPERATIVE INTENSIVE THERAPY IN STENOSING ESOPHAGEAL DISEASES].
The treatment tactics and intensive therapy in stenosing esophageal diseases for 222 patients in 2003 - 2015 yrs were analyzed. Expediency of application of the proposed treatment tactics was noted.


The correlation between antiphospholipid syndrome and cryoglobulinemia: case series of 4 patients and review of the literature.
Cryoglobulinemia is an immune-complex-mediated small vessel vasculitis that classically involves the skin, kidneys and peripheral nerves. Antiphospholipid syndrome (APS) is an autoimmune hypercoagulable disorder which causes blood vessel thrombosis. It can present as a multi-organ microthrombotic disorder which is called catastrophic APS. In this case series we aim to describe the diagnostic and management challenges that arise when these two severe disorders simultaneously present in the same patient. We describe four patients who were admitted to our hospital due to multi-organ life threatening damage mediated by cryoglobulinemic vasculitis with concurrent APS. Clinical manifestations included leg ulcers, livedo reticularis, renal failure, and peripheral neuropathy. Suggested etiologies for the combined syndromes were hepatitis C, systemic lupus erythematosus and myeloproliferative disease rectal maltoma. All of our patients were treated with anticoagulation, high-dose corticosteroids, rituximab, intravenous gammaglobulins and plasma exchange. The rare association of severe or catastrophic APS with cryoglobulinemia in patients should be considered by physicians who treat patients with multi-organ ischemia or necrosis.


Synchronization of cultured retinoblastoma cells for high-resolution chromosomes showing up to 1000 bands.
A method that allows high-resolution cytogenetic analysis of retinoblastoma cells in primary culture and subpassages is described. This method is based on the addition of high concentrations of bromodeoxyuridine or thymidine to obtain chromosomes subsequently banded to show 600-1000 bands. The results are compared with the standard harvest after 24 hours or long-term culture, and with low-temperature synchronization after long-term culture. After blocking with bromodeoxyuridine or thymidine, the chromosomes are significantly longer than after cold synchronization or after the unsynchronized techniques. When they are GTG, RHG, or GBG banded, more than 40% of the mitoses are in the earlier phases with chromosomes showing more than 600 bands per haploid set. This method significantly improves the general quality of retinoblastoma tumor cell chromosomes and increases diagnostic and prognostic accuracy.


Granulomatosis with poliangiitis mimicking testicular torsion.
Granulomatosis with polyangiitis (GPA) is an autoimmune vasculitis which rarely affects the lower genitourinary tract. We share the case of a 53-year-old man who presented with a retroperitoneal mass and thereafter developed a left multiseptated hydrocele that conditioned a testicular infarction. The pathology report of the orchidectomy was consistent with GPA.


The impact of Anopheles gambiae egg storage for mass rearing and production success.
Mass rearing requires a large colony from which male individuals can be harvested for sterilization and release. Attention is needed when monitoring life parameters of the reared population, knowing that any variations within the target population would lead to mismatching between two populations. The aim of this study was to assess the impact of Anopheles gambiae sensu stricto (s.s.) egg storage on hatchability and life history traits. For each parameter, comparison was made between freshly laid and stored eggs in three densities (40, 80, 120 eggs). Anopheles gambiae s.s. freshly laid eggs were collected from the Tropical Pesticide Research Institute (TPRI) insectary. Eggs to be stored were kept at - 20 °C for 10 min and then transferred to refrigerators at 4 °C for intervals of 5, 10, 15, 20, and 25 days. After respective storage days, the eggs were transferred from refrigerators to ambient temperature of (25 ± 2) °C for 24 h and then placed in incubators for 24 h. Thereafter eggs were hatched. The egg hatchability, emerged larvae development, larvae survival and emerged adult sex ratios were monitored. This study found that hatching rates decreased with increase in storage time. The difference was significant in eggs stored for 10 and 15 days (P < 0.05). There were no significant differences in hatching rates between An. gambiae eggs stored for 5 days and freshly hatched eggs (P > 0.05). Anopheles larvae development (L1 to pupae) was not significantly affected by storage time across all hatching densities. The study also found that larvae survival decreased with increase in egg storage time. However, there was no significant difference between larvae from freshly hatched eggs and those from eggs at 5 and 10 storage days (P > 0.05) but not for eggs stored for 15 days. Furthermore, there was a decrease in emerged adult males and increase in females relative to increased time of egg storage. The difference was significant (P < 0.05) at 15 storage days but not for eggs stored for 5 and 10 days (in triplicate densities). From this study it was concluded that storing An. gambiae eggs at 4 °C and 48 ± 2% relative humidity (RH) for 5 days is the optimal condition and time that did not affect egg hatching rates, larval development and survivorship and emerged adult mosquito sex ratio.


Evaluation of preoperative anxiety and fear of anesthesia using APAIS score.
Preoperative anxiety is one of the most important problems for the patients, because it causes emotional and psychiatric problems as well as physical problems. It is crucial to detect the patient's existing anxiety to assist patients. Our primary aim in this study is to investigate how the patient's age, gender, the operation, surgical briefing, type of anesthesia recommended for the operation ahead, and patient's prior anesthesia experience affect the patient's anxieties. Our secondary aim is to reveal the causes of the patient's anxieties regarding anesthesia. Our study was conducted as a prospective cohort study between May 2016-2017. Interviews with the patients were performed in the anesthesia clinic for preoperative examination. For the study, The Amsterdam Preoperative Anxiety and Information Scale (APAIS) has been used. The answers were evaluated in two scales: the anxiety score and the desire for information score. Answers to the statements were evaluated with Likert Scale. In addition, our patients were asked whether they had received prior anesthesia, if so, the type of anesthesia, whether they received surgical briefing and anesthetic method we recommended. We also asked our patients about the cause of their anxiety regarding the anesthesia. A total of 637 patients were recruited to the study, after excluding the patients who do not meet the criteria for inclusion, and 499 patients were included. Between the age and desire for information sub-scores, a negative significant correlation was detected (r: - 0.241; p = 0.001). We found that the scores of graduates of university and higher were statistically significant than the primary school graduates (p = 0.003) and secondary school graduates (p = 0.034). Anxiety sub-scores of the patients who underwent general anesthesia were found to be significantly higher than the patients who underwent regional anesthesia (p = 0.029). Anxiety sub-scores of females were found to be significantly higher than the males (p = 0.001). We think that being aware of the patients' anxiety and finding appropriate approaches for their anxieties can be valuable. APAIS is an effective method to measure patient anxiety and it might be beneficial to use during preoperative visits. Patient satisfaction and superior outcomes can be achieved in this way. Trial registration ISRCTN43960422. Registered 19/02/2018-Retrospectively registered. http://www.isrctn.com/ISRCTN43960422.


Robot-assisted gastrectomy and oesophagectomy for cancer.
Robot-assisted surgery is a technically feasible alternative to open and laparoscopic surgery, which is being more frequently used in general surgery. We undertook this review to investigate whether robotic assistance provides a significant benefit for oesophagogastric cancer surgery. Electronic databases were searched for original English-language publications for robotic-assisted gastrectomy and oesophagectomy between January 1990 and October 2013. Sixty-one publications were included. Thirty-five included gastrectomy, 31 included oesophagectomy and five included both operations. Several publications suggest that robot-assisted subtotal gastrectomy can be as safe and effective as an open or laparoscopic procedure, with equal outcomes with regard to the number of lymph nodes resected, overall morbidity and perioperative mortality, and length of hospital stay. Robotic assistance is associated with longer operation times but also with less blood loss in some reports. A significant benefit for robotic assistance has not been shown for the more extensive operations of oesophagectomy or total gastrectomy with D2-lymphadenectomy. There are very few oncologic data regarding local recurrence or long-term survival for any of the robotic operations. No significant differences in morbidity, mortality or number of lymph node harvested have been shown between robot-assisted and laparoscopic gastrectomy or oesophagectomy. Robotic surgery, with its relatively short learning curve, may facilitate reproducible minimally invasive surgery in this field but operation times are reportedly longer and cost differences remain unclear. Randomized trials with oncologic outcomes and cost comparisons are needed.


Gap-filling of ocean color over the tropical Indian Ocean using Monte-Carlo method.
Continuous remote-sensed daily fields of ocean color now span over two decades; however, it still remains a challenge to examine the ocean ecosystem processes, e.g., phenology, at temporal frequencies of less than a month. This is due to the presence of significantly large gaps in satellite data caused by clouds, sun-glint, and hardware failure; thus, making gap-filling a prerequisite. Commonly used techniques of gap-filling are limited to single value imputation, thus ignoring the error estimates. Though convenient for datasets with fewer missing pixels, these techniques introduce potential biases in datasets having a higher percentage of gaps, such as in the tropical Indian Ocean during the summer monsoon, the satellite coverage is reduced up to 40% due to the seasonally varying cloud cover. In this study, we fill the missing values in the tropical Indian Ocean with a set of plausible values (here, 10,000) using the classical Monte-Carlo method and prepare 10,000 gap-filled datasets of ocean color. Using the Monte-Carlo method for gap-filling provides the advantage to estimate the phenological indicators with an uncertainty range, to indicate the likelihood of estimates. Quantification of uncertainty arising due to missing values is critical to address the importance of underlying datasets and hence, motivating future observations.


A longitudinal analysis of self-prescribed complementary and alternative medicine use by a nationally representative sample of 19,783 Australian women, 2006-2010.
Complementary and alternative medicine (CAM) use is increasingly popular amongst general populations around the world with women constituting substantial CAM users. However, self-prescribed CAM use does raise potential safety concerns and so it is important to identify those risk factors associated with self-prescribed CAM use. Data was obtained from the Australian Longitudinal Study on Women's Health (ALSWH). Longitudinal data analyses were conducted on questionnaire data from the 1973-78 cohort (n=9,145) and the 1946-51 cohort (n=10,638), collected over the period 2006-2010. In the 1973-78 cohort, use of self-prescribed CAM was 73.2% in 2006 and 75.3% in 2009. For the 1946-51 cohort, use of self-prescribed CAM was 73.9% in 2007 and 74.7% in 2010. There were similar levels of use of individual self-prescribed CAM, with the exception that the use of herbal medicine was much higher among the 1946-51 cohort (20% vs. 27%). There was a substantial increase over three years in the use of vitamins/minerals in both cohorts (21% and 19%, respectively). In contrast, there was a considerable decline over three years in use of aromatherapy oils in both cohorts (34% and 28%, respectively). Self-prescribed CAM use is popular amongst women in Australia and it is important that conventional practitioners providing women's health care be cognizant of such use amongst their patients. In order to ensure effective practice, there is a need for further research to explore women's decision-making and experiences around self-prescribed CAM use.


Effect of initial cell seeding density on 3D-engineered silk fibroin scaffolds for articular cartilage tissue engineering.
The repair of articular cartilage defects poses a continuing challenge. Cartilage tissue engineering through the culture of chondrocytes seeded in 3D porous scaffolds has the potential for generating constructs that repair successfully. It also provides a platform to study scaffold-cell and cell-cell interactions. The scaffold affects the growth and morphology of cells growing on it, and concomitantly, cells affect the properties of the resultant tissue construct. Silk fibroin protein from Antheraea mylitta, a non-mulberry Indian tropical tasar silkworm, is a potential biomaterial for diverse applications due to its widespread versatility as a mechanically robust, biocompatible, tissue engineering material. Analysis of silk fibroin scaffolds seeded with varying initial densities (25, 50 and 100 million cells/ml) and cultured for 2 weeks showed that thickness and wet weight increased by 60-70% for the highest cell density, and DNA, GAG and collagen content of the cartilaginous constructs increased with increasing cell density. Mechanical characterization of the constructs elucidated that the highest density constructs had compressive stiffness and modulus 4-5 times that of cell-free scaffolds. The present results indicate the importance of cell seeding density in the rapid formation of a functional cartilaginous tissue.


Osteoblast attachment to hydroxyapatite micro-tube scaffolds.
Tissue engineering offers a novel route for repairing damaged or diseased tissue by incorporating the patient's own healthy cells or donated cells into temporary scaffolds that act as a matrix for cell cultivation. Tissue scaffolds that are biocompatible and are porous with interconnected porous channels for cell ingrowth with a suitable degradation rate would be advantageous. In this study hydroxyapatite micro-tubes produced using the biomimetic coating technique will be pressed into a tissue scaffold. A compaction and sintering study will be done to observe appropriate pressure and heat treatment to produce a mechanically stable scaffold material. The ideal pressure was found to be 2.5 MPa where the tube-like structure was maintained, high porosity was achieved and suitable strength was possible. Sintering between 1,000 and 1,100 °C was found to produce good results. The average porosity for the chosen pressure of 2.5 MPa was 68%. The scaffold was observed with SEM, micro tomography (micro-CT), chemical analysis and degradation testing. Porous channels were established using micro-CT where the porous channels were roughly 100 µm. Chemical analysis showed constant release of calcium and phosphorous, and far below toxic levels of heavy metals from the die. Degradation testing showed high degradation compared to tested commercially available materials. Cell culturing was done on the scaffold to characterise the biological performance of the scaffolds. Cell culturing was done in a 7 and 24 day cell culture to examine cell morphology and cell ingrowth. The results showed cell ingrowth into a micro-tube and cell orientation in a longitudinal direction. SEM, confocal microscopy and histology were employed as characterisation tools for observing cell ingrowth.


Tau isoform composition influences rate and extent of filament formation.
The risk of developing tauopathic neurodegenerative disease depends in part on the levels and composition of six naturally occurring Tau isoforms in human brain. These proteins, which form filamentous aggregates in disease, vary only by the presence or absence of three inserts encoded by alternatively spliced exons 2, 3, and 10 of the Tau gene (MAPT). To determine the contribution of alternatively spliced segments to Tau aggregation propensity, the aggregation kinetics of six unmodified, recombinant human Tau isoforms were examined in vitro using electron microscopy assay methods. Aggregation propensity was then compared at the level of elementary rate constants for nucleation and extension phases. We found that all three alternatively spliced segments modulated Tau aggregation but through differing kinetic mechanisms that could synergize or compete depending on sequence context. Overall, segments encoded by exons 2 and 10 promoted aggregation, whereas the segment encoded by exon 3 depressed it with its efficacy dependent on the presence or absence of a fourth microtubule binding repeat. In general, aggregation propensity correlated with genetic risk reported for multiple tauopathies, implicating aggregation as one candidate mechanism rationalizing the correlation between Tau expression patterns and disease.


Role of Negatively Charged Lipids Achieving Rapid Accumulation of Water-Soluble Molecules and Macromolecules into Cell-Sized Liposomes against a Concentration Gradient.
Liposomes, molecular self-assemblies resembling biological membranes, are a promising scaffold to investigate the physicochemical logic behind the complexity of living cells. Despite elaborate synthetic studies constructing cell-like chemical systems using liposomes, less attention has been paid to the proactive role of the membrane emerging as dynamics of the molecular self-assembly. This study investigated the liposomes containing anionic phospholipids by exposing them to steady flow conditions using a newly constructed automatic microfluidic observation platform. We demonstrated that the liposomes accumulated even macromolecules under the microfluidic condition without pore formation. By investigating the effect of composition of liposomes and visualizing negatively charged phospholipids upon the flow, we presumed that the external flow caused a compositional asymmetry of anionic phospholipids between the inner/outer leaflets, and the asymmetry enabled a rapid accumulation of those molecules against the concentration gradient. The current study opens new research interests regarding the nature of biological membranes under steady flow conditions.


Effects of PC6 acupressure on acute and delayed nausea and vomiting induced by chemotherapy in patients with malignant neoplasm: a meta-analysis.
Evaluating the intervention effect of PC6 acupressure on chemotherapy-induced acute, delayed nausea, and vomiting in malignant tumor patients. Eleven databases had been retrieved from January 2010 through January 2022. The published meta-analysis literature was hand-searched, and the language was limited to English and Chinese. The protocol of this meta-analysis was registered with PROSPERO (registration number: CRD42022323693). Two reviewers independently selected relevant eligible articles, extracted data, and evaluated the risk of bias. Meta-analysis was statistically analyzed using software RevMan 5.3. Ten randomized controlled trials with 975 patients were included. Only two studies were assessed as high quality; eight studies were evaluated as moderate. Meta-analysis showed that compared with the control group, PC6 acupressure reduced the occurrence number of acute (SMD = -0.39,95CI (-0.73, -0.05) P = 0.02), delayed (SMD = -0.51, 95% CI (-0.96, -0.05) P = 0.03) nausea and acute (SMD = -0.42,95% CI (-0.79, -0.06) P = 0.02), delayed (SMD = -0.37, 95% CI (-0.77, 0.03) P = 0.07) vomiting; it reduced the severity of acute (SMD = -0.34, 95% CI (-0.57, -0.11) P = 0.004), delayed (SMD = -0.79, 95% CI (-1.33, -0.25) P = 0.004) nausea and acute (SMD = -0.51, 95% CI (-0.79, -0.23) P = 0.0004), delayed (SMD = -0.50, 95% CI (-0.84, -0.17) P = 0.003) vomiting, while it did not reduced the experience time on acute and delayed CINV. The meta-analysis shows the effectiveness of PC6 acupressure in preventing and treating nausea and vomiting. Large, high-quality, well-designed randomized controlled trials are needed in the future to determine the efficacy of PC6 acupressure on chemotherapy-induced nausea and vomiting.


Early response competition over the motor cortex underlies proactive control of error correction.
Response inhibition is a fundamental brain function that must be flexible enough to incorporate proactive goal-directed demands, along with reactive, automatic and well consolidated behaviors. However, whether proactive inhibitory processes can be explained by response competition, rather than by active top-down inhibitory control, remains still unclear. Using a modified version of the Eriksen flanker task, we examined the behavioral and electrophysiological correlates elicited by manipulating the degree of inhibitory control in a task that involved the fast amendment of errors. We observed that restraining or encouraging the correction of errors did not affect the behavioral and neural correlates associated to reactive inhibition. We rather found that an early, sustained and bilateral activation, of both the correct and the incorrect response, was required for an effective proactive inhibitory control. Selective unilateral patterns of response preparation were instead associated with defective response suppression. Our results provide behavioral and electrophysiological evidence of a simultaneous dual pre-activation of two motor commands, likely underlying a global operating mechanism suggesting competition or lateral inhibition to govern the amendment of errors. These findings are consistent with the response inhibitory processes already observed in speed-accuracy tradeoff studies, and hint at a decisive role of early response competition to determine the success of multiple-choice action selection.


STAT3 is a key transcriptional regulator of cancer stem cell marker CD133 in HCC.
Cancer stem cell (CSC) marker CD133 was found to be upregulated in many cancers including hepatocellular carcinoma (HCC). However, the molecular mechanism of CD133 regulation in the liver tumor microenvironment has remained elusive. In this study Won and colleagues report that interleukin-6 (IL-6) mediated signal transducer and activator of transcription factor 3 (STAT3) signaling and hypoxia enhance the expression of CD133 and promote the progression of HCC.


Boundary Disputes: In Inflamed Skin, Mast Cells Expand and Disorganize Stable Clonal Territories.
Skin mast cells (MCs) are distinct from other MCs, and for years, we have tried to understand their origin and peculiarities. A recent study demonstrated that during development, MCs enter the skin from the yolk sac and embryonic liver and are later mixed with cells originating from the bone marrow. A report from Weitzmann et al. (2020) shows that MCs or their precursors occupy distinct areas in the fetal period and that they and their progeny maintain these geographic distributions throughout life. These stable clonal territories are altered only by the arrival of bone marrow‒derived MCs during inflammation.


Sequence analysis of the internal transcribed spacer 2 (ITS2) from Philornis seguyi (García, 1952) and Philornis torquans (Nielsen, 1913) (Diptera: Muscidae).
Philornis Meinert, 1890 (Diptera: Muscidae) is a genus of Neotropical dipterans that parasitise birds. The currently used external morphological characters to distinguish between species within this genus present some limitations. We used the second internal transcribed spacer region (ITS2) of the rRNA gene as a molecular marker to differentiate adult specimens of Philornis identified morphologically as Philornis torquans and Philornis seguyi from different localities. Specimens identified as P. seguyi from Magdalena (Buenos Aires Province) showed an ITS2 sequence different from that for P. torquans, whereas all other specimens of P. seguyi had sequences identical to those for P. torquans. These findings do not necessarily confirm that specimens from Magdalena indeed belong to P. seguyi, nor that P. seguyi is a valid species. Instead, they alert us about the potential for species misidentification when using morphological characters alone. The use of molecular approaches to aid the identification of Philornis spp. will shed light on the systematics of this group. P. torquans is reported for the first time in Mendoza Province and Uruguay.


Three way translocation in a new variant of t(8;21) acute myeloid leukemia involving Xp22.
The t(8;21)(q22;q22) is one of the most frequent chromosomal abnormality associated with acute myeloid leukemia (AML) M2 sub type. The additional chromosomal abnormalities including structural and numerical are frequently reported with the translocation, t (8;21)(q22;q22). We report a case of AML-M2 with t(X;8;21)(p22;q22;q22) associated with loss of Y chromosome. Using a dual color fluorescence in situ hybridization (FISH) analysis with ETO and AML1 probes, we demonstrated an ETO/AML1 fusion signal on the derivative chromosome 8 and one ETO signal on derivative Chromosome Xp22. The patient did not respond to therapy and follow-up of cytogenetics revealed same chromosome abnormality. Hence, this three way translocation involving X chromosome might be associated with poor prognosis.


[Design, evaluation and application of a model for evaluating the cognitive abilities related to scientific aptitude in medical students].
A model for evaluating the cognitive ability related to scientific aptitude consisting of 10 different problems is presented. The design conditions, validity and the application of the model to selected second year Medical students as well as randomly chosen first, third and sixth year students are described. The authors record and analyze global results as well as the results of individual or group of problems, concluding on the validity and fiability of the model as well as on the detection of failures in student's performances inspite of the effort made. Future action is proposed.


Frequency of bilateral cervical metastases in oropharyngeal squamous cell carcinoma: a retrospective analysis of 352 cases after bilateral neck dissection.
The decision whether to perform an elective neck dissection in patients with head and neck squamous cell carcinoma (HNSCC) and clinically negative lymph nodes (cN0) is made based on the probability of micrometastases in the neck for the given subsite and size of the primary. To date there is limited information about contralateral and bilateral cervical lymph node metastases of oropharyngeal carcinoma. A retrospective chart review was performed of 352 patients with oropharyngeal SCC who received a bilateral neck dissection. The frequency of histologically unveiled bilateral neck metastases was determined. Carcinomas of the tonsillar fossa starting with a T2 classification and carcinomas of the soft palate, base of tongue, and pharyngeal wall at any stage showed a high frequency of bilateral metastases. Bilateral neck dissection should be recommended for all but T1 and selected cases of T2 carcinomas of the tonsillar fossa.


Late results after carotid endarterectomy for amaurosis fugax.
Amaurosis fugax is considered an ocular transient ischemic attack with an ominous prognosis. One hundred twenty-eight patients with amaurosis fugax as the presenting symptom underwent carotid endarterectomy at the University of California, San Diego (UCSD) and Scripps Clinic between 1970 and 1985 with one death (0.8%) and one postoperative permanent stroke (0.8%). Subsequently, these patients were followed up for 6 to 160 months (mean 45.3 months). Only two subsequent late strokes were documented (at 2 and 5 years after operation). These results were significantly better (p less than 0.01) by life-table analysis than the late stroke rate after carotid endarterectomy performed to treat anterior motor transient ischemic attacks at both UCSD and Scripps Clinic, as well as the reported late follow-up for all transient ischemic attacks after carotid endarterectomy in the literature (1.8% per year, 17 publications, 1980 operations). Thus amaurosis fugax appears to be a particularly favorable indication for carotid endarterectomy. Left untreated, this event carries a high risk of stroke; after carotid endarterectomy, which has a low operative risk, there is a very low postoperative stroke rate (two strokes in 448 patient-years of follow-up).


[Personal experience with the difference limen in interrupted tones in differentiating between sensorineural and supracochlear hearing disorders].
The authors assessed the differences of the limen of interrupted sounds (sounds which last 500 ms, between which there are intervals of 200 ms) in healthy subjects and in patients with sensory neural and supracochlear hearing disorders. Essentially the results are consistent with those of Schorn and Fastl (2) and they suggest that patients with supracochlear hearing disorders are able to differentiate only much greater differences in intensity (more than 4 dB) between sounds, as compared with patients with sensory neural hearing disorders.


Risk factors for nosocomial pneumonia in the elderly.
Pneumonia is now the second most frequent hospital-acquired infection in acute-care facilities, and recent studies indicate that the incidence rate for nosocomial pneumonia in long-term-care facilities is of similar magnitude. The mortality rate is high, especially in the elderly. With prevention of this complication as an overall priority, this study was designed to determine the risk factors associated with nosocomial pneumonia in the elderly in both acute-care and long-term-care settings. An epidemiologic case-control study was undertaken to compare patients or residents who developed radiographically confirmed pneumonia with control subjects who did not have and did not develop respiratory infection. Thirty-three cases were identified in the acute-care setting during the 18-week period, and 27 cases were identified in the long-term-care setting. Two matched controls were chosen for each case. Data collection involved review of the medical record and verification by medical personnel while the cases or controls were still institutionalized. Risk factor variables were analyzed using an odds ratio and 95% confidence interval calculation for matched triplets, and chi-square analysis. Selected risk factors were entered into a backward stepwise logistic regression to determine the best combination of risk factors for each setting. In the acute-care setting, current neurologic disease, current renal disease, deteriorating health, altered level of consciousness, disorientation, dependent bathing, dependent bowel function, dependent feeding, aspiration, difficulty with oropharyngeal secretions, and presence of a nasogastric tube were significant risk factors. In the long-term-care setting, deteriorating health, malnourishment, recent weight change, altered level of consciousness, disorientation, aspiration, difficulty with oropharyngeal secretions, suctioning, presence of a nasogastric or gastric tube, upper respiratory infection, inhalation therapy, increased confusion, and increased agitation were determined to be significant. Current pulmonary disease, previous infection, and antibiotic therapy were found not to be associated with the onset of nosocomial pneumonia. Through logistic regression, the best models for prediction of nosocomial pneumonia in the elderly were identified. In the acute-care setting, difficulty with oropharyngeal secretions and presence of a nasogastric tube were the best predictors. In the long-term-care setting, difficulty with oropharyngeal secretions, deteriorating health, and occurrence of an unusual event were the best combination of predictors. These data confirm prior findi


Impact of phenolic composition and antioxidant parameters on the ageing potential of Syrah red wines measured by accelerated ageing tests.
Fourteen Syrah red wines with different initial composition and antioxidant properties (polyphenols, antioxidant capacity, voltammetric behaviour, colour parameters and SO2) were selected. Three different accelerated ageing tests (AATs) were then performed on these wines: thermal test at 60 °C (60 °C-ATT), enzymatic test with laccase (Laccase-ATT) and chemical test with H2O2 (H2O2-ATT). The results showed high correlations between the initial phenolic composition and antioxidant properties of the samples. Partial least squares (PLS) regressions were used in order to establish some models that can predict the AATs test results based on their different initial composition and antioxidant properties. The PLS regression models had overall very good accuracy and involved different explaining variables for each test. The models taking into account all the measured parameters and the phenolic composition alone showed good predictive capacities with correlation coefficients (r2) > 0.89.


Preparation and evaluation of molecularly imprinted polymer liquid chromatography column for the separation of Cathine enantiomers.
In this study molecular imprinting technology was employed to prepare a specific affinity sorbent for the resolution of Cathine, a chiral drug product. The molecularly imprinted polymer (MIP) was prepared by non-covalent molecular imprinting with either (+) or (-)-Cathine (threo-2-amino-1-hydroxy-1-phenyl propane; norpseudoephedrine) as the template. Methacrylic acid and ethylene glycol di-methacrylate were copolymerized in the presence of the template molecule. The bulk polymerization was carried out in chloroform with 2,2'-azobisisobutyronitrile as the initiator, at 5 °C and under UV radiation. The resulting MIP was ground into powders, which were slurry packed into analytical columns. After removal of template molecules, the MIP-packed columns were found to be effective for the resolution of (±)-Cathine racemates. The separation factor for the enantiomers ranged between 1.5 and 2.4 when the column was packed with MIP prepared with (+)-Cathine as the template. A separation factor ranging from 1.6 to 2.9 could be achieved from the column packed with MIP, prepared with (-)-Cathine as the template. Although the separation factor was higher with that previously obtained from reversed-phase column chromatography following derivatization with a chiral agent, elution peaks were broader due to the heterogeneity of binding sites on MIP particles and the possible non-specific interaction.


Radical cystectomy and orthotopic ileal bladder substitution with serous lined extramural ureteral reimplantation--report of 8 cases.
We review the functional and oncoloic outcomes of radical cystectomy and orthotog pic ileal bladder substitution with serous lined extramural ureteral reimplantation. From 1985 to 2009 a total of 125 male patients (mean age 62.5 years, range 37 to 74) underwent orhotopic ileal bladder substitute at the urological Clinic in Belgrade. Of these, 8 patients underwent modified technique with serous lined extramural ureteral reimplantation. The median follow-up (available for 88 patients) period was 30 (2-72) months. Perioperative lethality was nil. Modified operative technique was associated with low postoperative complication rates and without ureteric implantation site stenosis, reflux or deteriorization of renal function. All patients had satisfied day and night continence rates. The serous-lined extramural ureteral reimplantation is an attractive technique regarding its safety, versality and functional outcome. It is especially favorable for reimplantation to ureters of various calibers as well as dilated ureters.


Pediatric patch testing in a multi-ethnic Asian population: A retrospective review.
Pediatric allergic contact dermatitis (ACD) is increasingly prevalent. Patch testing is the gold-standard diagnostic investigation. The aims of our study were to describe the clinical profile of pediatric patients with ACD in a multi-ethnic Asian population and identify the common contact allergens. This was a retrospective study involving children and adolescents aged 16 years or younger with clinically suspected ACD who underwent patch testing between January 2007 and March 2020 at two institutions in Singapore. Information pertaining to their demographics, atopy history, clinical presentation, and patch test results was analyzed. A total of 252 patients were included. The mean age was 10.9 years (1.0-16.7 years). The majority were Chinese (79.8%) and girls (57.5%). Many (66.3%) had atopic dermatitis (AD), which was mild. The most common presentation was an acral eczematous rash. The sensitization rate was 50.0%. The most frequent reactions were to nickel sulfate (49.2%) and fragrance mix (19.1%). The overall rate of relevant positive patch tests was 72.5%. Patients with AD were less likely to have a reaction to fragrance mix (p = .019) and more likely to have a reaction to disperse blue (p = .041). Compared to younger children, adolescents were less likely to have a positive patch test (p = .008). Indians were also less likely to have a positive reaction (p = .004). Metals and fragrances were the most common allergens causing childhood ACD in Singapore. Patients with AD were less likely to be sensitized to fragrances and more likely to be sensitized to disperse blue dye.


The use of the FST statistic of Wright for estimating the effects of genetic drift, selection and migration populations, with special reference to Ireland.
The Fst of Wright has been used to examine the available blood group, serum protein and enzyme data for the world, NW Europe and the counties of Ireland. These include the ABO, secretor, Lewis, MNSs, Rh, Kell, Duffy, Lutheran, Kidd, P, Diego, haptoglobin, Gc, Lp, Ag, adenosine deaminase, adenylate kinase, acid phosphatase, 6-phosphogluconate, phosphoglucomutase and transferrin systems. The highest value was found for the Fy gene. Much lower values than those calculated for world data were found for NW Europe and Ireland with the exception of the Lpa antigen which had high values in Ireland. sigma2p was used to estimate rates of genetic drift in an Irish population and it was estimated that a migration rate of 4% would counter genetic drift in Ireland.


Cutting edge: Compartmentalization of Th1-like noninvariant CD1d-reactive T cells in hepatitis C virus-infected liver.
Murine intrahepatic lymphocytes (IHL) are dominated by invariant TCR alpha-chain expressing CD1d-reactive NKT cells, which can cause model hepatitis. Invariant NKT (CD56(+/-)CD161(+)) and recently identified noninvariant CD1d-reactive T cells rapidly produce large amounts of IL-4 and/or IFN-gamma and can regulate Th1/Th2 responses. Human liver contains large numbers of CD56(+) NKT cells but few invariant NKT. Compared with matched peripheral blood T cell lines, primary IHL lines from patients with chronic hepatitis C had high levels of CD161 and CD1d reactivity, but the invariant TCR was rare. CD1d-reactive IHL were strikingly Th1 biased. IHL also demonstrated CD1d-specific cytotoxic activity. Hepatocytes and other liver cells express CD1d. These results identify a novel population of human T cells that could contribute to destructive as well as protective immune responses in the liver. CD1d-reactive T cells may have distinct roles in different tissues.


Predicting evolutionary responses to interspecific interference in the wild.
Many interspecifically territorial species interfere with each other reproductively, and in some cases, aggression towards heterospecifics may be an adaptive response to interspecific mate competition. This hypothesis was recently formalised in an agonistic character displacement (ACD) model which predicts that species should evolve to defend territories against heterospecific rivals above a threshold level of reproductive interference. To test this prediction, we parameterised the model with field estimates of reproductive interference for 32 sympatric damselfly populations and ran evolutionary simulations. Asymmetries in reproductive interference made the outcome inherently unpredictable in some cases, but 80% of the model's stable outcomes matched levels of heterospecific aggression in the field, significantly exceeding chance expectations. In addition to bolstering the evidence for ACD, this paper introduces a new, predictive approach to testing character displacement theory that, if applied to other systems, could help in resolving long-standing questions about the importance of character displacement processes in nature.


Analgesic response to single and multiple doses of controlled-release morphine tablets and morphine oral solution in cancer patients.
Immediate-release oral morphine, given every four hours in individually titrated doses, is effective in the control of severe cancer pain. To evaluate the analgesic efficacy of a controlled-release morphine sulfate preparation, MS Contin tablets (MSC, Purdue Frederick, Toronto, Ontario, Canada), after a single dose and under steady-state conditions, the authors compared MSC administered every 12 hours with morphine oral solution (MOS) administered every 4 hours in 17 adult cancer patients with chronic severe pain. In the single-dose evaluation, in which the patients were randomly assigned to receive MSC or MOS, there were no significant differences in analgesic efficacy or requirement for supplemental morphine between the two treatments. With both preparations, pain severity ratings increased toward the end of the 12-hour, single-dose observation period and were higher than the pain scores reported after dose titration. In the steady-state evaluation, which was a randomized crossover comparison, both preparations provided effective pain control with minimal side effects. There was no significant difference between MSC and MOS in overall pain scores or in pain scores analyzed by time of day and day of therapy. In conclusion, that an individualized twice-daily regimen of MSC is as effective as 4-hourly MOS for the control of chronic severe cancer pain. The twice-daily regimen has several advantages: it allows an uninterrupted night's sleep, it is substantially more convenient, and it can be expected to reduce both medication errors and noncompliance.


What Is a Medication-Related Problem? A Qualitative Study of Older Adults and Primary Care Clinicians.
Older adults often take multiple medications, leading to a myriad of medication-related problems. Addressing these problems requires thoughtful approaches that align with patients' perspectives and experiences. To (1) identify and categorize medication-related problems from the patient perspective and (2) understand patient and clinician attitudes toward these problems and experiences with addressing these problems. Qualitative, semi-structured interviews with patients and focus groups with physicians and pharmacists. Twenty older adults recruited from an academic medical center and from a community senior center; 14 primary care physicians and 6 pharmacists affiliated with an academic medical center. Hybrid deductive-inductive thematic analysis. Older adults identified a variety of medication-related problems that could be classified into four broad categories: (1) obtaining medications (e.g., problems with cost and insurance coverage); (2) taking medications (e.g., organization and remembering to take pills); (3) medication effects, including side effects and concerns over lack of effectiveness; and (4) communication and care coordination, including information related to medications. Many of the problems described by older adults were framed within the person's socioemotional context, including the impact of medications on interpersonal relationships, emotional wellbeing, and activities that add meaning and quality to life. In contrast, clinicians almost exclusively focused on discrete medication issues without reference to this larger context and expressed relatively little interest in learning more about their patients' perspectives. Older adults experience medication-related problems as inseparable from their broader life context. Incorporating the social and emotional context of medications and related communication into a problem-focused framework can guide clinicians in specific actions and interventions to address medication-related problems from the patient perspective.


Conservative surgical approaches for small volume FIGO stage IB1 cervical cancer. Updated survival and obstetric outcomes of an expanded cohort.
Standard surgical treatment of FIGO stage 1B1 cervical cancer is open radical surgery. However, there is increasing evidence that for small tumours a more conservative approach can minimise fertility consequences without impacting on long term oncologic outcomes. The objective of our study is to present survival and obstetric outcomes following extended follow-up for patients who underwent conservative management of small-volume stage 1B1 disease. All patients with FIGO stage 1B1 cancer and estimated tumour volume of <500 mm3 in a loop biopsy specimen treated in Northern Gynaecological Oncology Centre between December 2000 and December 2021, were included in the study. Clinico-pathological and demographic data were collated alongside detailed follow-up and obstetric outcomes in conjunction with primary care and death register. 117 patients underwent conservative surgery for small volume stage 1B1 disease. 58 (49.5%) underwent fertility sparing conservative management with LLETZ while 59 (50.5%) underwent simple hysterectomy. Overall, 95% (111/117) of the patients underwent bilateral pelvic lymphadenectomy and 1 positive node was identified. There was no death related to cervical cancer and 1 recurrence identified during a median follow up of 8.5 years (1-20). 17 pregnancies have been recorded in patients underwent LLETZ and 17 live babies were born. No second trimester miscarriages were noted and there was one preterm delivery (36 weeks). Non-radical surgery with negative pelvic lymphadenectomy for smallvolume stage 1B1 cervical cancer ensures excellent survival without compromising obstetric outcomes. Should these results be verified by the ongoing prospective studies, radical surgery for these patients may be avoided.


Analysis of a waterborne disease model with socioeconomic classes.
Waterborne diseases such as cholera continue to pose serious public health problems in the world today. Transmission parameters can vary greatly with socioeconomic class (SEC) and the availability of clean water. We formulate a multi-patch waterborne disease model such that each patch represents a particular SEC with its own water source, allowing individuals to move between SECs. For a 2-SEC model, we investigate the conditions under which each SEC is responsible for driving a cholera outbreak. We determine the effect of SECs on disease transmission dynamics by comparing the basic reproduction number of the 2-SEC model to that of a homogeneous model that does not take SECs into account. We conclude by extending several results of the 2-SEC model to an n-SEC model.


[Some new fleas of Chile (Siphonaptera) parasites of Ctenomys (Rod., Octodontidae)].
The authors examined 355 fleas of 9 species from Chili. These were collected from 7 species or subspecies of Ctenomys (Rod., Octodontidae). Tiamastus callens and Polygenis platensis cisandinus are new for this country; Tetrapsyllus maulinus sp. n., Plocopsylla fuegina sp. n. and Plocopsylla reigi sp. n. are described in this work.


Inheritance, Fitness Cost, and Management of Lambda-Cyhalothrin Resistance in a Laboratory-Selected Strain of Ceratitis capitata (Wiedemann).
The management of the medfly, Ceratitis capitata, in Spanish citrus crops relies mainly on the use of insecticides and the release of sterile males. However, the development of resistance to different insecticides in field populations, including lambda-cyhalothrin, implies a threat for the sustainable control of this pest. The inheritance, fitness cost, and management of lambda-cyhalothrin resistance were examined in the laboratory-selected W-1Kλ strain. We have demonstrated that lambda-cyhalothrin resistance in W-1Kλ is autosomic, completely dominant, and polygenic. In addition, individuals from W-1Kλ showed a lower embryo to pupal viability, a slower developmental time from egg to pupae, and an increase in adults' weight and longevity. We did not find significant trade-offs in the activity of digestive hydrolytic enzymes, with the exception of higher α-amylase activity in W-1Kλ females. A comparative study with different insecticide treatment strategies showed that lambda-cyhalothrin resistance increased when several consecutive treatments with this insecticide were applied. However, the alternation of this insecticide with spinosad was enough to delay the development of resistance. Our results indicate that the rotation of lambda-cyhalothrin with spinosad-a practice already used in some fields-may contribute to prevent the development of resistance.


Cell components required for deletion of an autoreactive T cell repertoire.
T cells become tolerant to self antigens during their development in the thymus. Clonal deletion of thymocytes bearing T cell receptor (TcR) which recognize self antigens is a major mechanism for generating tolerance. In the present study we have used allogeneic bone marrow (BM) chimeras, prepared with various combinations of mouse strains and focusing especially on expressions of I-E molecules and Mls-1a antigens on the cell surface, to investigate both immunohistochemically and by flow cytometry the cell components that contribute to the clonal deletion of T cells positive for V beta 6 TcR. The V beta 6 TcR expression is strongly associated with T cell recognition of both I-E and Mls-1a antigens. We found that I-E+ cells derived from donor BM (and thus not of recipient lineage) represented a primary requirement for deletion of Mls-1a-reactive thymocytes which bear V beta 6 TcR. Immunohistochemical analysis revealed that the donor-derived I-E+ cells were distributed mainly to the thymic medulla and that the V beta 6+ cells were eliminated from the thymic medulla between 2 and 3 weeks following BM transplantation. In contrast, Mls-1a+ cells of either donor or recipient origin might be responsible for the deletion, even though cortical epithelial cells appeared not to express Mls-1a antigens.


In vitro suppression of the epidermal Langerhans' cells in necro split skin.
The effect of ultraviolet light B irradiation and glucocorticosteroid incubation on the epidermal Langerhans' cell density and tissue viability was investigated, in vitro, on human thin necro split skin.


Ada Lovelace: A Simple Solution to a Lengthy Controversy.
Ada Lovelace's mathematical abilities have been widely questioned due to a misdating of her correspondence with Augustus de Morgan. Despite its correction in the academic record, this error persists in popular depictions of her work, undermining Lovelace herself and women in general. More scholarly examinations of historical women in STEM would enrich our understanding of their contributions and bolster their positions as role models.


Clinical characteristics of somatization in dental practice.
This study was a first attempt to derive an estimate of the likely incidence of somatization-specific behaviour in a dental setting and its relationship with both somatic symptoms and symptoms of depression. Somatization-specific behaviour was operationalized as reporting of inexplicable dental symptoms (eg pain), remarkable frequent attendance at a dental surgery, inexplicably high treatment use or unreasonable requests with regard to treatment. Of the 309 patients surveyed, 8.7%o fulfilled one or more of the criteria for somatization-specific behaviour. This was particularly manifested by a high attendance rate (6.8%). Women exhibited somatization-specific behaviour significantly more often (73%) than men (27%9). Support was found for the hypothesis that individuals exhibiting characteristics of somatization-specific behaviour would present themselves to dentists more often with dental complaints and would suffer more from symptoms of depression than patients that did not display these characteristics. The results suggest that somatization is a factor in dental practice.


Importance of metabolism in pharmacological studies: possible in vitro predictability.
Metabolic transformation of drug leads to the formation of a large number of secondary compounds. These metabolites may (a) participate to the elimination of the patent drug, (b) have similar or different therapeutic effects compared to the parent drug (c) exert toxic effects. Cytochromes P450 are the main enzymes involved in the biotransformation of exogenous drugs, leading to oxidized, reduced or peroxidized metabolites. Different isozymes of P450 are present in already all the organs and differ by their affinity for substrate families. P450 3A is the most abundant P450 protein in the adult human liver and is able to transform hundreds of substrates into either drugs or endogenous compounds such as testosterone. Its catalytic activities are regulated either by induction or by inhibition. Attempts to predict metabolic transformation of a given drug are based on the amount of P450 expressed in heterologous systems, induction, and inhibition experiments and by comparison to classical P450 substrates. Erythromycin metabolism and its P450 effects are used to illustrate the complexity and the consequences of metabolic transformation of a given drug.


Mechanical characterization of TiO2 nanowires flexible scaffold by nano-indentation/scratch.
Mechanical properties of nanowires (NWs) flexible scaffold biomaterials with open pores and channels are important factors to cell reorganize in growth for tissue regeneration engineering. However, accurate test the mechanical properties of the NWs scaffold is still a challenge because of their flexible property and porous structure. Herein, we measured the mechanical characterizes of TiO2 nanowires (TiO2NWs) flexible scaffold by multi-loads, multi-displacements mixed verification method in nano-indentation/scratch. The results showed that the hardness and Young's modulus of the TiO2NWs flexible scaffold had a certain change rules with a change of the indentation load from 5 μN to 400 μN. Meanwhile, the tangential force of the TiO2NWs flexible scaffold had significantly tensile fracture characteristic under nano-scratch. The multi-loads, multi-displacements mixed verification method by nano-indentation/scratch could be widely applied to measure the mechanical properties of all 3D NWs flexible scaffold nanostructure conveniently and accurately, which is helpful to cover the shortage of bending method for only measure the mechanical properties of 1D nanostructures.


Lentiviral transduction of neuronal cells.
Here we describe a general method for the construction of a lentivirus vector using a specific example of the construction of a lentivirus containing the luciferase reporter gene under the control of two hypothetical promoters and derived HIV-1 based lentivirus expression vector pLVX-Puro. This method can be used to compare the strength and regulation of different promoters. In this example, the target cells for transduction are human primary fetal astrocytes but the method is applicable to any primary cell culture from the CNS or other tissue and can be used to examine the strength of a particular promoter in different cell types. HIV based lentivirus particles are prepared by transfection of 4 plasmids into 293T cells using the Fugene 6 transfection reagent.


Pulsatile GnRH-stimulated LH release from the human fetal pituitary in vitro: sex-associated differences.
An in-vitro perfusion system was utilized to examine LH release from human fetal (19-24 weeks gestation) anterior pituitaries during repetitive GnRH stimulations. Pituitaries (five male, four female) were dissected into halves, and one hemipituitary of each pair was stimulated with 10-min pulses of 1 nM GnRH administered at 60-min intervals over 24h, whereas the matching hemipituitary received pulses of medium alone. Basal (no GnRH stimulation) LH release from female hemipituitaries was significantly (P less than 0.01) greater than from male hemipituitaries, and the amplitude of LH release associated with GnRH pulses was sixfold greater (P less than 0.001) with female hemipituitaries. Furthermore, the magnitude of LH release associated with individual GnRH pulses was significantly (P less than 0.001) enhanced during the course of female hemipituitary perfusions, but not during perifusion of male hemipituitaries. These studies demonstrate that LH secretion by the female, but not male, mid-gestational human fetal pituitary is increased in response to a physiological pattern and interval of repeated pulsatile GnRH stimulation in vitro.


Relation of myocardial perfusion at rest and during pharmacologic stress to the PET patterns of tissue viability in patients with severe left ventricular dysfunction.
Stress perfusion imaging can assess effectively the amount of jeopardized myocardium, but its use for identifying underperfused but viable myocardium has yielded variable results. We evaluated the relation between measurements of myocardial perfusion at rest and during pharmacologic stress and the patterns of tissue viability as determined by positron emission tomographic (PET) imaging. We studied 33 patients with coronary artery disease and left ventricular (LV) dysfunction (LV ejection fraction, 30%+/-8%). PET imaging was used to evaluate regional myocardial perfusion at rest and during pharmacologic stress with [13N]-ammonia as a flow tracer, and to delineate patterns of tissue viability (i.e., perfusion-metabolism mismatch or match) using [18F]-deoxyglucose (FDG). We analyzed 429 myocardial regions, of which 229 were dysfunctional at rest. Of these, 30 had normal perfusion and 199 were hypoperfused. A severe resting defect (deficit >40% below normal) predicted lack of significant tissue viability; 31 of 35 regions (89%) had a PET match pattern denoting transmural fibrosis. Although regions with mild or moderate resting defects (deficit <40% below normal) showed evidence of metabolic activity, perfusion measurements alone failed to identify regions with PET mismatch (reflecting hibernating myocardium). Reversible stress defects were observed with slightly higher frequency in regions with a PET mismatch (10 of 37) than in those with a PET match (36 of 162) pattern of viability. A reversible stress defect was a specific (78%) marker, but was a relatively insensitive marker (27%) of viable myocardium as defined by the PET mismatch pattern. In patients with LV dysfunction, the severity of regional contractile abnormalities correlates with the severity of flow deficit at rest. Severe reductions in resting blood flow in these dysfunctional regions identify predominantly nonviable myocardium that is unlikely to have improved function after revascularization. Although dysfunctional myocardium with mild to moderate flow reductions contains variable amounts of viable tissue (as assessed by FDG uptake), flow measurements alone do not distinguish between regions with PET mismatch (potentially reversible dysfunction) and PET match (irreversible dysfunction). The presence of an irreversible defect on stress imaging is a relatively specific (78%) marker of PET match, whereas a reversible stress defect is a rather insensitive (27%) marker of viability, as defined by the PET mismatch pattern.