Baseline sensitivity and resistance risk assessmemt of Rhizoctonia cerealis to thifluzamide, a succinate dehydrogenase inhibitor.
During 2010-2012, a total of 120 isolates of Rhizoctonia cerealis were collected from wheat with symptoms of sharp eyespot in four provinces (Henan, Shandong, Anhui and Jiangsu) in China. All the isolates were determined for baseline sensitivity to thifluzamide, a succinate dehydrogenase inhibitor (SDHI) with strong antifungal activity. The sampled pathogenic populations, never exposed to SDHIs, had similar sensitivity to trifluzamide (0.025-0.359 µg/ml) in the four regions and over the two years. The baseline sensitivity was distributed as a skewed unimodal curve with a mean EC50 value (effective concentrations for 50% inhibiting mycelial growth) of 0.064 ± 0.013 µg/ml. The resistance risk of R. cerealis to thifluzamide was further evaluated in vitro. Two thifluzamide-resistant mutants of R. cerealis were obtained by culturing on thifluzamide-amended plates. The resistance factors (RF = EC50 value of a mutant/EC50 value of the wild type progenitor of the mutant) were 120 and 40 for two R. cerealis mutants, respectively. All the mutants exhibited similar fitness after 10 successive transfers when compared to their wild-type parents in mycelial growth, sclerotia production, and virulence. However, the two thifluzamide-resistant mutants differed significantly in sensitivity to boscalid and flutolanil. Therefore, a low-to-moderate risk of resistance development was recommended for thifluzamide.


Fatigue in multiple sclerosis: relation to depression, physical impairment, personality and action control.
Although fatigue is one of the most common symptoms of multiple sclerosis, it is yet poorly understood and therefore difficult to manage. To clarify the nature of fatigue we investigated its relationship to depression, physical impairment, personality and action control and compared these variables between a sample of 41 MS patients and 41 healthy controls. Physical impairment was assessed by the EDSS and all other dimensions, using questionnaires. Stepwise linear regression analyses revealed that physical impairment was related to physical fatigue in MS patients. Depression was the main factor influencing fatigue among both, MS patients and controls. What clearly differentiated the two groups was the correlation between fatigue and action control. Decreased levels of action control imply attentional and motivational deficits and were only found in fatigued MS patients. Our study indicates that motivational disturbances might be specific for MS related fatigue.


Inhibition of lens epithelial cell migration by an acrylic intraocular lens in vitro.
We developed a new in vitro system to evaluate the effect of intraocular lenses (IOLs) on the migration of lens epithelial cells (LECs) and determined how acrylic and other IOLs influence LEC migration using this model. In an in vitro system, porcine LECs were cultured in a cell culture chamber insert, containing a collagen membrane, for 10 days with no IOL or with various types of IOLs. Migration of LECs beneath each IOL optic was observed with an inverted-phase microscope. The cell-free areas under the IOL optic, where the LECs had not migrated, were measured. Without IOL, LECs completely covered the collagen membrane within 5 days after plating (5.0 +/- 0.0 days). Complete coverage was slowed by a silicone IOL (6.7 +/- 1.2 days, p = 0.0305). LECs cultured with acrylic or with round- or sharp-edged polymethylmethacrylate (PMMA) IOLs did not completely cover the area. Ten days after initiating cultures, the cell-free areas under IOLs with sharp edges (acrylic, 41.1 +/- 8.0%; sharp-edged PMMA, 60.9 +/- 39.0%) were significantly larger than under IOLs with round edges (silicone, 0.0 +/- 0.0%; round-edged PMMA, 1.5 +/- 1.2%). A sharp edge may act as a barrier to LEC migration. Moreover, LEC migration under the acrylic IOL slowed after the LECs had crossed the barrier of the optic edge, perhaps due to acrylic adhesive properties. Only a few LECs reached the collagen membrane beneath the central 3 mm of the acrylic IOL. This new in vitro model was useful in evaluating the effect of various IOLs on LEC migration. Acrylic IOLs inhibited LEC migration by not only a sharp edge but also other factors, such as adhesive properties.


Gene-gene interactions and associations of six hypertension related single nucleotide polymorphisms with obesity risk in a Chinese children population.
Obesity is a major risk for hypertension. However, the associations between hypertension susceptibility loci and the risk of obesity as well as the effects of gene-gene interactions are unclear, especially in the Chinese children population. Six single nucleotide polymorphisms (SNPs) (ATP2B1 rs17249754, CSK rs1378942, MTHFR rs1801133, CYP17A1 rs1004467, STK39 rs3754777, FGF5 rs16998073) were genotyped for 3503 Chinese children, aged 6-18 years. Of them, 758 obese cases and 2745 controls were identified based on the International Obesity Task Force age- and sex-specific BMI references. Among the six SNPs, three were associated with obesity risk (CSK rs1378942: odds ratio (OR) = 1.20, 95% confidence interval (CI) 1.01-1.43, P = 0.042; MTHFR rs1801133: OR = 1.19, 95% CI 1.05-1.34, P = 0.006; FGF5 rs16998073: OR = 1.14, 95% CI 1.00-1.29, P = 0.047). The genetic risk score (GRS), based on these three SNPs (CSK rs1378942, MTHFR rs1801133, FGF5 rs16998073), showed a positive association with risk of obesity (OR = 1.18, 95% CI 1.09-1.28, P = 7.60 × 10-5). The same association signals were also detected in the subgroups of puberty and inactivity. In addition, interaction analyses among these loci implied a potential gene-gene interaction between MTHFR and FGF5. These findings show a significant association of hypertension susceptibility loci in Chinese children, suggesting a likely influence of genetic and environmental factors on the risk of obesity.


Pentacyclic triterpenes as α-glucosidase and α-amylase inhibitors: Structure-activity relationships and the synergism with acarbose.
In this paper, the inhibition of α-amylase and α-glucosidase by nine pentacyclic triterpenes was determined. For α-amylase inhibitory activity, the IC50 values of ursolic acid, corosolic acid, and oleanolic acid were 22.6±2.4μM, 31.2±3.4μM, and 94.1±6.7μM, respectively. For α-glucosidase inhibition, the IC50 values of ursolic acid, corosolic acid, betulinic acid, and oleanolic acid were 12.1±1.0μM, 17.2±0.9μM, 14.9±1.9μM, and 35.6±2.6μM, respectively. The combination of corosolic acid and oleanolic acid with acarbose showed synergistic inhibition against α-amylase. The combination of the tested triterpenes with acarbose mainly exhibited additive inhibition against α-glucosidase. Kinetic studies revealed that corosolic acid and oleanolic acid showed non-competitive inhibition and acarbose showed mixed-type inhibition against α-amylase. The results provide valuable implications for the triterpenes (ursolic acid, corosolic acid, and oleanolic acid) alone or in combination with acarbose as a therapeutic agent for the treatment of diabetes mellitus.


Interactions between anti-infective agents and immunosuppressants-Guidelines from the American Society of Transplantation Infectious Diseases Community of Practice.
These updated guidelines from the Infectious Diseases Community of Practice of the American Society of Transplantation provide an update on potential drug-drug interactions between anti-infectives and immunosuppressants, which are most notable with calcineurin and mTOR inhibitors. Drug-drug interactions may occur through pharmacokinetic mechanisms leading to altered drug concentrations of either the anti-infective or immunosuppressive drug, or by pharmacodynamic interactions increasing or decreasing the efficacy or toxicity of the medications. Many of the significant pharmacokinetic interactions occur through inhibition or induction of the cytochrome 3A4 system by anti-infective agents leading to increased or decreased immunosuppressive agent levels, respectively. The membrane transporter P-glycoprotein is also often involved in drug interactions. Since the last iteration of these guidelines, multiple new hepatitis C virus direct-acting antivirals have become available for use in SOT recipients. Of these agents, some are substrates of cytochrome and drug transporter systems, while others inhibit these systems and may affect immunosuppressive agents. Due to the high risk for drug-drug interactions in the solid organ transplant population, practitioners must be aware of potential interactions and be vigilant in monitoring and adjusting drug dosing when appropriate.


The interrelationship of Plasmodium falciparum and P. vivax in the Punjab.
Analysis of data obtained from Giemsa-stained blood films from patients with mixed Plasmodium vivax and P. falciparum parasitaemias seen in outpatient clinics held over 20 consecutive months in 4 villages in the Pakistani Punjab suggest that infections with P. falciparum and P. vivax were independent of each other. There was no evidence to support the hypothesis that P. falciparum suppressed P. vivax. A likely explanation for the seasonal variation in species parasitaemia rates in the Punjab is that P. vivax was predominant early in the transmission season due to late relapses, while P. falciparum was predominant later in the transmission season because of community-wide development of immunity to P. vivax.


Resurfacing shoulder hemi arthroplasty in ballistic injuries. A case report.
Ballistic traumatology of the shoulder joint is uncommon. Usually, it is associated to comminuted fractures of the upper humerus. Total shoulder arthroplasty has been proposed to restore a good function. The indication of resurfacing hemi arthroplasty still controversial and is not commonly reported after ballistic traumatology. We report the case of a 26-year-old soldier victim of a gunshot of the left shoulder entailing a comminuted complex fracture of the upper extremity of the humerus. After shoulder immobilization of 3 months joint mobility was very limited. Radiographs showed bone malunion with a total loss of the hemispherical form of the humeral head. Patient has undergone a resurfacing hemi arthroplasty. Surgery outcome was good. At five years of follow-up, there were no major functional complaints. Clinical and radiological result was satisfactory with a good shoulder mobility. Shoulder arthroplasty provided good functional outcome in case of post fracture sequelae. Difficulty was to choose between total arthroplasty and hemi arthroplasty. In young and active patients, authors disapproved total arthroplasty in post traumatic gleno-humeral arthrosis to prevent revision difficulties especially after glenoid erosion. Although follow-up still be limited, the indication of shoulder hemi arthroplasty was appropriate regarding functional outcome and patient satisfaction. Further clinical and radiological supervision still necessary to detect glenoid erosion.


Red blood cell "ghosts" as look-alikes for infectious organisms. A report of two cases.
Two cases are reported in which degenerated red blood cells were initially interpreted as representing infectious organisms. The morphology and staining characteristics of the altered red blood cells are discussed.


Prolonged Mechanical Ventilation: Symptomatology, Well-Being, and Attitudes to Life.
Although prolonged mechanical ventilation (PMV) is increasingly common, little is known concerning patient symptom burden or attitudes toward PMV. This study aims to describe the mood, well-being, distressing symptoms, and attitudes toward prolonged ventilation among PMV patients treated either at home or long-term acute care (LTAC). An observational study. 62 communicative participants treated with PMV, aged ≥18 years, insurees of a single HMO, treated at home hospital or LTAC specializing in ventilation in Jerusalem. Sociodemographic characteristics; chronic conditions; functional status; symptom burden measured by revised Edmonton Symptomatic Assessment System (r-ESAS); attitudes toward PVM. Participants were aged 61.7 ± 20.7 years, commonly suffered progressive neuromuscular disease (43.5%) or chronic lung disease (29%), were functionally dependent, treated at home (64.5%) or LTAC (35.5%), and had a mean PMV duration of 36.6 months (interquartile range 10.8-114.1). The 5-item, short Geriatric Depression Scale identified depression among 38% of participants, and was less at home vs LTAC (34% vs 44%, P < .001). Mean revised Edmonton Symptom Assessment System score was 24.5 ± 14.8 (maximum severity = 100), and participants reported severe or distressing symptoms for tiredness (27%/20%), pain (10%/25%), anxiety (16%/14%), depression (9%/21%), drowsiness (12%/17%), shortness of breath (9%/15%), poor appetite (7%/9%), and nausea (0%/10%). Impaired general well-being was reported as severe, moderate, mild, or none among 15%, 40%, 30%, and 15%, respectively. Only 1 patient had advance directives concerning ventilation prior to intubation, and when asked if they had to choose again today, 85% of patients would again opt for ventilation. Few PMV patients reported distressing symptoms, and 85% would choose ventilation if asked again. These findings might be useful in clinical practice to assist in decision making concerning prolonged ventilation.


Anomalous arrangement of the pancreatobiliary ductal system in patients with a choledochal cyst.
An anomalous arrangement of the pancreatobiliary ductal system is usually observed in patients with a congenital choledochal cyst and is represented by a long common channel distal to the pancreatobiliary junction. According to the angle of the pancreatobiliary junction, anomalous junctions can be classified into four groups: right angle, acute angle, complex union, and normal union (presented here in the order of their incidence). The right-angle type tends to have cystic dilatation of the choledochus, whereas the acute-angle type generally has cylindrical dilatation. However, the grade and length of the stenosis on the distal part of the choledochus tend to determine the type of choledochal cyst. Cystic dilatation is usually observed in patients with high-grade and long stenosis, whereas cylindrical dilatation is seen in those with low-grade and short stenosis. Patients with an acute angle junction seem to only suffer from abdominal pain, and those in the complex union group tend to have jaundice and an abdominal tumor. A high amylase level in the bile within the cyst is observed frequently. In patients with obstructive jaundice, however, the amylase level is usually not elevated, because pancreatic juice cannot enter the choledochus.


Inhibition of miR-448-3p Attenuates Cerebral Ischemic Injury by Upregulating Nuclear Factor Erythroid 2-Related Factor 2 (Nrf2).
Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key regulator responsible for oxidative stress in brain injury. This study aimed to investigate the potential mechanism of miR-448-3p and Nrf2 in cerebral ischemia/reperfusion (I/R) injury. In vitro and in vivo cerebral I/R injury models were constructed, and Nrf2 expression levels were detected by qRT-PCR and Western blot. The potential miRNAs for Nrf2 were predicted by bioinformatic analysis. The binding interaction between miR-448-3p and Nrf2 was determined by luciferase reporter assay. The effects of miR-448-3p on neurological deficit, infarct volume, and brain water content in mice were tested. The effects of miR-448-3p on oxidative stress indicators (SOD activity, MDA content, and ROS production) were detected by commercial assay kits. The levels of HO-1 and cleaved caspase-3 were evaluated by Western blot. Cell viability was evaluated by MTT assay, and cell apoptosis was evaluated by TUNEL staining and flow cytometry. Nrf2 was significantly downregulated and miR-448-3p was upregulated in cerebral I/R injury both in vivo and in vitro. MiR-448-3p downregulation efficiently attenuated brain injury and reduced oxidative stress and apoptosis. MiR-448-3p was identified to act as ceRNA of Nrf2 and negatively regulated Nrf2 expression, which was consistent with the animal studies. In addition, Nrf2 silencing obviously attenuated the neuroprotective effects of miR-448-3p inhibitor in vitro. MiR-448-3p participated in the regulation of cerebral I/R injury via inhibiting Nrf2.


Two new cytotoxic quinone type compounds from the halotolerant fungus Aspergillus variecolor.
Two new quinone type compounds, variecolorquinones A (1) and B (2) together with eleven known related compounds 3 approximately 13 have been isolated from the metabolites produced by the halotolerant fungal strain Aspergillus variecolor B-17. The structures of 1 and 2 were determined by spectroscopic methods. 1 exhibited selective cytotoxicity against A-549 cells with the IC50 values of 3.0 microM. 2 showed cytotoxicity against HL60 and P388 cells with the IC50 values of 1.3 and 3.7 microM, respectively.


Assessment of Anthropometric and Physical Health Indicators before and after Pituitary Surgery in Patients with Nonfunctioning Pituitary Adenomas, Acromegaly, and Cushing Disease.
Individuals with pituitary adenomas may have organic consequences of their disease or therapy, and psychological changes can compromise their quality of life (QoL). This study aimed to determine the anthropometric profile and health indicators of patients with pituitary adenoma before and after pituitary surgery. Forty-four patients were included in this study. Out of these, 22 patients had nonfunctioning adenomas (50%), 17 acromegaly (38.6%), and 5 patients with Cushing's disease (11.4%). Anthropometric measurements included body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR). Health indicators included body fat percentage (BF%), basal metabolic rate (BMR), maximal oxygen uptake (VO2 max), and hand grip strength. Physical activity level (the International Physical Activity Questionnaire [IPAQ]), subjective perception of health, body image (Body Shape Questionnaire), body satisfaction (Stunkard Figure Rating Scale) were used. The mean patient age was 47.2 ± 14.6 years; of which 25 were women (56.8%). Before surgery, 75.0% were overweight or obese, 84.1% had WC with risk of metabolic complications, and 90.0% had WHR with cardiovascular risk. There was a high BF% in 56.4% of cases, low BMR in 65.1%, lower VO2 max in 16.2%, and below-average grip strength in 88.6%. Hypopituitary patients had poorer cardiorespiratory fitness. The IPAQ showed reduction in physical activity, and 79.5% of patients were dissatisfied with their body image. Patients with nonfunctioning adenomas had better perception of their health while those with Cushing's disease had more distorted body image. Postoperatively, patients with acromegaly showed improvement in WHR and physical activity level, and patients with Cushing's disease showed improvement in anthropometric variables. These findings emphasize the need for continuous monitoring of this population for anthropometric indicators associated with metabolic and cardiovascular comorbidities as well as body satisfaction.


Molecular mechanisms underlying the renoprotective effects of 1,4,7-triazacyclononane: a βeta-lactamase inhibitor.
Broad-spectrum β-lactam antibiotics such as penicillin are routinely used against both Gram-negative and Gram-positive bacteria. However, bacteria that produce β-lactamase have developed resistance against these antibiotics by cleaving the β-lactam ring and rendering the antibiotic inactive. To combat this effect, 1,4,7- Triazacyclononane (TACN), a cyclic organic compound derived from cyclononanes has been shown to preserve the activity of β-lactam antibiotics by inhibiting β-lactamase. However, its cytotoxic effects require elucidation. Given that the cytotoxic target for many therapeutics is the kidney, this study investigated the effects of TACN on human embryonic kidney cells (Hek293) cells. Hek293 cells were treated with TACN (0-500 µM) for 24 h and the cytotoxicity was assessed (MTT and LDH assay). Apoptosis was luminometrically detected by measuring phosphatidylserine externalisation and caspase activity and fluorescently detecting necrosis. DNA fragmentation was visualised using fluorescent microscopy. Expression of the apoptosis-related protein were determined by western blot. The results generated indicate that TACN does not initiate necrosis as LDH was decreased. Likewise, decreased apoptosis was supported by the decreased phosphatidylserine, caspases, Bax, cleaved PARP, IAP and NF-kB. However, increased DNA fragmentation was associated with increased p53. Therefore, effects of TACN at the nucleus, produced a p53 response to initiate DNA repair and did not culminate in cell death. The findings show that TACN is not cytotoxic to Hek293 cells via the apoptotic route. Since TACN did not induce cell death, its potential as a metallo-β-lactamase inhibitor (MBLI) may be exploited to counteract the effect of MBL-producing bacteria. Restoring β-lactam activity will curb the global menace of antibiotic resistance.


Does the resting state connectivity have hemispheric asymmetry? A near-infrared spectroscopy study.
Near-infrared spectroscopy (NIRS) is a novel technology for low-cost noninvasive brain imaging suitable for use in virtually all subject and patient populations. Numerous studies of brain functional connectivity using fMRI, and recently NIRS, suggest new tools for the assessment of cognitive functions during task performance and the resting state (RS). We analyzed functional connectivity and its possible hemispheric asymmetry measuring coherence of optical signals at low frequencies (0.01-0.1 Hz) in the prefrontal cortex in 13 right-handed (RH) and 2 left-handed (LH) healthy subjects at rest (4-8 min) using a continuous-wave NIRS instrument CW5 (TechEn, Milford, MA). Two optical probes were placed bilaterally over the inferior frontal gyrus (IFG) and the middle frontal gyrus (MFG) using anatomical landmarks of the 10-20 system. As a result, 28 optical channels (14 for each hemisphere) were recorded for changes in oxygenated (HbO) and de-oxygenated (HbR) hemoglobin. Global physiological signals (respiratory and cardiac) were removed using Principal and Independent Component Analyses. Inter-channel coherences for HbO and HbR signals were calculated using Morlet wavelets along with correlation coefficients. Connectivity matrices showed specific patterns of connectivity which was higher within each anatomical region (IFG and MFG) and between hemispheres (e.g., left IFG<->right IFG) than between IFG and MFG in the same hemisphere. Laterality indexes were calculated as t-values for the 'left>right' comparisons of intrinsic connectivity within each regional group of channels in each subject. Regardless of handedness, the group average laterality indexes were negative thus revealing significantly higher connectivity in the right hemisphere in the majority of RH subjects and in both LH subjects. The analysis of Granger causality between hemispheres has also shown a greater flow of information from the right to the left hemisphere which may point to an important role of the right hemisphere in the resting state. These data encourage further exploration of the NIRS connectivity and its application for the analysis of hemispheric relationships within the functional architecture of the brain.


Acclimation of killifish to thermal extremes of hot spring: Transcription of gonadal and liver heat shock genes.
In this study, we explored the hypothesis that killifish acclimate to thermal extremes through regulation of genes involved in stress and metabolism. We examined the liver and gonadal transcription of heat shock proteins (hsp70, hsp90a, hsp90b), glucokinase (gck), and high mobility group b1 (hmgb1) protein in wild killifish species from hot springs and rivers using quantitative real-time PCR. Moreover, we exposed a river killifish species to a long-term thermal regime of hot spring (37-40°C) and examined the liver transcription of the heat shock genes. Our results showed that hot spring killifish showed a significant, strong upregulation of liver hsp90a. Moreover, the testicular transcript levels of hsp90a, hsp90b, and hsp70 were higher in hot spring killifish than the river ones. The results of the common garden experiments showed that the transcripts of hsp70, hsp90b, and hmgb1 were mildly induced (> twofold) at the time when temperature reached to 37-40°C, while the transcripts of hsp90a were strongly induced (17-fold increase). The level of hsp90a was dramatically more upregulated when fish were maintained in thermal extreme (42-fold change higher than in ambient temperature). Moreover, a significant downregulation of gck transcripts was observed at the time when temperature was raised to 37-40°C (80-fold decrease) and during exposure to long-term thermal extreme (56-fold decrease). It can be concluded that the regulation of heat shock genes particularly hsp90a might be a key factor of the acclimation of fish to high temperature environments like hot springs.


Subcontracture depolarizations increase sarcoplasmic ionized calcium in frog skeletal muscle.
The hypothesis that the sarcoplasmic concentration of ionized calcium (Cai) of frog skeletal muscle may control its rate of metabolism was examined by monitoring the changes in Cai due to perturbations that are known, from the work of previous investigators, to alter the rate of metabolism. Cai was measured with aequorin, which was microinjected into isolated fibers in sufficient quantity to detect basal Cai. When these fibers were exposed to 5-18 mM KCl, 75 mM RbCl2, or 100 mM CsCl2, there was an increase in the aequorin signal. The potassium-evoked increase in the aequorin signal was diminished by an increase in the extracellular concentration of Ca or by Ca-free media containing 3.6 mM Mg, Mn, Sr, or Zn but was enhanced by subcontracture concentrations of caffeine or media containing nitrate instead of chloride. These results are consistent with the hypothesis that Cai may control the rate of metabolism in frog skeletal muscle fibers.


Motor activity of the rat duodenum in vivo: evidence for the existence of an atropine-resistant peristalsis.
The motor activity of the proximal duodenum has been investigated by means of a balloon method in urethane-anaesthetized rats. A series of atropine- (1 mg/kg i.v.) or hexamethonium- (20 mg/kg i.v.) sensitive rhythmic contractions can be demonstrated in the rat duodenum which represents a peristaltic reflex mediated by intramural cholinergic neurons. The atropine-sensitive peristaltic reflex is transiently suppressed by intravenous DMPP (0.1 mg/kg) GABA (3 mg/kg) or noradrenaline (10 micrograms/kg). In rats pretreated with guanethidine (20 mg/kg s.c.) plus naloxone (2 mg/kg i.v.) and theophylline (2 mg/kg i.v.) a second type of peristaltic reflex which is atropine-resistant but hexamethonium-sensitive can be demonstrated. These findings indicate that in the rat small intestine a peristaltic activity can be sustained by both atropine-sensitive and atropine-resistant mechanism, which may explain failure of atropine to affect intestinal motility in conscious rats.


Fruit composition diversity in land races and modern pepino (Solanum muricatum) varieties and wild related species.
Pepino (Solanum muricatum) fruits from 15 accessions of cultivated pepino as well as six accessions from wild relatives were evaluated for contents in dry matter, protein, β-carotene, chlorophylls and seven minerals. Several-fold differences among accessions were found for most traits. Average values obtained were similar to those of melon and cucumber, but the phenolic contents were much higher. Wild species had significantly higher average contents for all traits vs. the cultivated pepino accessions. And, the comparisons among the cultivated pepino varieties showed that the modern varieties were more uniform in composition, and they possessed significantly lower concentrations of protein, P, K, and Zn than local land races. Most of the significant correlations among composition traits were positive. Our studies show that regular consumption of pepino fruits could make a significant contribution to the recommended daily intake of P, K, Fe and Cu as well as to the average daily intake of phenolics. Furthermore, the higher values for most nutrients measured in the wild species and in the local land races indicate that new pepino varieties with improved fruit contents in nutrient and bioactive compounds can be developed.


C24 and C25 substituted marcfortine A derivatives.
The dioxepinoindole ring found in marcfortine A (1) is unique among natural products. In order to determine the importance of the substitution pattern of the C24-C25 olefin, we synthesized a variety of analogs at these positions. With the exception of compound 5, none of these compounds exhibited any anthelmintic activity.


Hemodynamic dose-response effects of flecainide in acute myocardial infarction with and without left ventricular decompensation.
We evaluated the hemodynamic effects of the class I antiarrhythmic flecainide in 20 patients within 18 hours of an acute myocardial infarction. Equal numbers of patients with normal (group 1) or decompensated (group 2) ventricular function were studied. Both groups received flecainide, 1 mg/kg, as an intravenous bolus over 10 minutes, followed by infusion (1.6 mg/kg/hr) over the next 120 minutes. Plasma concentrations increased linearly with the cumulative flecainide dosage in both groups. There was no difference between the groups in the plasma levels reached, which were within the recognized antiarrhythmic range for flecainide (200 to 1000 ng/ml) throughout the infusion. The hemodynamic effects of flecainide for each group were decreases in systolic blood pressure (maximum 3% fall in group 1 and 8% fall in group 2), cardiac index (9% fall in group 1 and 18% fall in group 2), stroke volume index (13% fall in group 1 and 23% fall in group 2), stroke work index (14% fall in group 1 and 27% fall in group 2), with an increased heart rate (8% rise in group 1 and 5% rise in group 2), pulmonary artery occluded pressure (27% rise in group 1 and 21% rise in group 2), and systemic vascular resistance (11% rise in group 1 and 18% rise in group 2). Diastolic and mean arterial blood pressures did not change. Our data demonstrate that flecainide induced significant cardiodepression in both groups of patients. These effects were not significantly greater in patients with adequately controlled heart failure. These data suggest that the mild negative inotropic properties of flecainide in patients with recent myocardial infarction are comparable to those described for other class I antiarrhythmics.


Pharmacological properties of glycine transport in the frog retina.
The high-affinity glycine transport in neurons and glial cells is the primary means for inactivating synaptic glycine. Two different glycine transporter genes, Glyt-1 and Glyt-2, have been cloned. Glyt-1 has been reported to occur in the retina, but there is no evidence for expression of the Glyt-2 transporter. We have pharmacologically characterized glycine transport in the frog retina. 3H-Glycine uptake in the retina was insensitive to modulation by phorbol esters or changes in cAMP levels, and was partially inhibited by sarcosine. Differential sensitivity of glycine transport to sarcosine was exhibited by synaptosomal fractions from the inner and outer plexiform layers of the frog retina. The Na+ Hill coefficient of glycine uptake was 2.0, as has been reported for Glyt-2. In addition, amoxapine, a specific inhibitor of the Glyt-2a isoform, reduced by 60% glycine uptake by P2 synaptosomal fraction. Our results indicate the presence of different glycine transporter isoforms in the frog retina, acting mainly through the classical inhibitory glycine system.


Postinfarction angina: an expanding subset of patients undergoing coronary artery bypass.
An analysis of patients undergoing coronary artery bypass for unstable postinfarction angina (less than or equal to 30 days of infarct) during two time periods was undertaken: Group I, January, 1982, through December, 1982; Group II, September, 1983, through August, 1984. Clinical, angiographic, and operative data were coded, and statistical analysis was used to compare the two patient groups, evaluate operative results, and identify risk factors. The incidence of unstable postinfarction angina as an indication for bypass grafting increased significantly (p less than 0.01) from the first to the second time frame, 8.7% (24/276) to 18% (51/283). A greater proportion of Group II patients were operated upon within 7 days of infarct (37% versus 21%, p less than 0.01). All other variables examined were similar in the two patient groups. Analysis of the combined Group I and II patients (N = 75) indicates the following: The ratio of transmural to nontransmural infarction was 39%/61%, and 39% of patients had a previous infarction. Three-vessel disease was present in 76%, two-vessel in 21%, one-vessel in 3%, and left main disease in 20%. Left ventricular ejection fraction was greater than or equal to 40% in 27% of patients, less than 40% in 32%, and not obtained in 41%. Mean left ventricular end-diastolic pressure was 19.5 mm Hg. Intra-aortic balloon pumping was necessary preoperatively in 39%. The mean interval from infarction to revascularization was 12 days, and the mean number of grafts was 3.1 (range one to six). The overall in-hospital mortality was 8% (6/75). Statistical analysis demonstrated that decreased ejection fraction was associated with an increased risk of mortality. No other variables were correlated with mortality. Mean follow-up for the combined Group I and II patients is 13 months (range 4 to 32). Ninety percent of survivors remain in Canadian Heart Association Functional Class I and 6% in Class II. No late deaths have occurred. Patients with unstable postinfarction angina constitute an ever-increasing subset of the coronary bypass population of the 1980s. Operation can be performed with a satisfactory mortality and excellent long-term outlook compared to less acceptable published results with medical management alone. Preoperative left ventricular function constitutes the major indicator of operative risk.


Medium-term safety and efficacy profile of paraesophageal hernia repair with Phasix-ST® mesh: a single-institution experience.
Hernia recurrence after laparoscopic repair is a perplexing problem. In an effort to reduce anatomical and clinical recurrences, different type of meshes have been used to bolster the esophageal hiatus. The aim of this study was to assess safety, medium-term efficacy, and quality of life improvement after laparoscopic repair of hiatal hernia reinforced with a biosynthetic absorbable mesh (Phasix-ST®). Observational single-center retrospective single-arm cohort study (November 2015-February 2021). We included all adult patients (> 18 years old) who underwent laparoscopic paraesophageal hernia repair with Phasix-ST® mesh and Toupet fundoplication. Sixty-eight patients were included. The median postoperative stay was 3.2 days (range 2-9) and the postoperative complication rate was 11.7%. The median follow-up time was 27 months (range 1-53). No mesh-related complications were detected. Hernia recurrence was diagnosed in six patients (8.8%). The recurrence-free probability at 34 months was 0.89 (95% CI 0.807-0.988) while at 60 months was 0.86 (95% CI 0.76-0.97). Hernia recurrences were mostly observed between 21 and 36 months after the operation. None of the patients required surgical revision and all were managed with PPI. Postoperative dysphagia requiring endoscopic balloon dilatation occurred in 2.9% of patients. Compared to baseline, both the GERD-HRQL (15.2 ± 6.2 vs. 3.2 ± 3.1; p = 0.026) and all SF-36 items were significantly improved (p < 0.001). Laparoscopic crura augmentation with Phasix-ST® mesh combined with a Toupet fundoplication is safe and seems effective in the medium-term follow-up. Phasix-ST® crural reinforcement resulted in low hernia recurrence rate with a sustained symptoms and quality of life improvement.


Subtotal cholecystectomy: An operative option for Salmonellae typhi gangrenous cholecystitis.
Typhoid gangrenous cholecystitis is uncommon and can be managed by subtotal cholecystectomy with nonclosure of the cystic duct if that is required for patient safety.


Isolation, structure elucidation, and absolute configuration of 26-deoxyactein from Cimicifuga racemosa and clarification of nomenclature associated with 27-deoxyactein.
A new triterpene glycoside, 26-deoxyactein (1), along with two known compounds, 23-epi-26-deoxyactein (2), previously designated as "27-deoxyactein", and actein (3), were isolated from the roots/rhizomes of Cimicifuga racemosa. The structures and absolute stereochemistry of 1 and 2 were established by spectroscopic methods (FABMS, (1)H and (13)C NMR) and single-crystal X-ray data analysis.


Effect of different ultrasound contrast materials and temperatures on patient comfort during intrauterine and tubal assessment for infertility.
Hysterosalpingo-contrast sonography (HyCoSy) is safe and easy to perform outpatient method in the evaluation of female infertility. During this procedure a certain level of discomfort and pain are experienced by patients. On the basis of reducing avoidable pain inductors the aim of this study was to compare pain sensation due to different warmth of applied contrasts (sterile saline and Echovist(®)). Prospective and randomized study was performed on patients requiring tubal and uterine assessment during standard infertility work up. One group of patients was examined using both contrasts at room temperature and the other group using preheated contrasts at body temperature. Pain experience of the procedure was rated by patients for each contrast by numerical scale (0-10) immediately after the procedure. There was significant statistical difference between pain scores during application of two contrasts in each group; Echovist induces significantly less pain in comparison to sterile saline at the same temperature (P=0.002, 0.001). Between two groups there is also statistically significant difference in pain during introduction of the same contrast at different temperature (P<0.001). The most tolerable for the patient is body temperature of the applied contrasts although their structure and concentrations can be another factor associated with tolerability of the procedure.


Effects of leaf removal on the accumulation of anthocyanins and the expression of anthocyanin biosynthetic genes in Cabernet Sauvignon (Vitis vinifera L.) grapes.
Anthocyanins, a major flavonoid class, determine the color and quality of wine. Recent research revealed that basal leaf removal can increase the content of these compounds. This study determined the effects of basal leaf removal on the anthocyanin profiles of Cabernet Sauvignon grapes. The effects of basal leaf removal on anthocyanin composition in Cabernet Sauvignon grapes were investigated over two growing seasons. Leaf removal at 5% veraison (VB6) and at 100% veraison (VC6) was compared with a control. Reducing sugar and total anthocyanin contents in the leaf removal group were significantly higher than in the control group at harvest for both vintages. Leaf removal increased the content of individual anthocyanins and significantly improved the malvidin-3-O-glucoside (Mv-3-glc), peonidin-3-O-glucoside (Pn-3-glc), and malvidin-3-O-(6-acetyl)-glucoside (Mv-3-acglc) content of the VB6 group. At harvest, VB6 treatment increased the transcript abundance of structural and regulator genes in the anthocyanin pathway, especially VvF3'5'H, VvLDOX, and VvDFR. Our results suggest that leaf removal at 5% veraison may be useful for improving the anthocyanin content in grapes. © 2020 Society of Chemical Industry.


Generalized Worry in Patients With Chronic Fatigue Syndrome Following Cognitive Behavioral Therapy: A Prospective Cohort Study in Secondary Care.
Research has shown that generalized anxiety disorder is commonly associated with Chronic Fatigue Syndrome (CFS). This prospective cohort study aimed to investigate the prevalence of generalized worry in CFS patients and its relationship with fatigue, anxiety and social functioning, before and after Cognitive Behavioral Therapy (CBT). Our cohort consisted of 470 patients diagnosed with CFS who received CBT at a secondary care, specialist clinic. Patients completed self-report measures investigating levels of generalized worry, fatigue, work and social adjustment, anxiety and depression at baseline (pretreatment), discharge from treatment, 3-month and 6-month follow up (posttreatment). Analysis indicated a high prevalence of generalized worry (72.4%) at assessment. A significant reduction in worry following CBT (M = -3.42, p < .001, 95% CIs: 2.26, 4.57) was observed at discharge, which remained stable at follow-up. Severe baseline worriers had greater overall fatigue score (M = 3.74, p = .026, 95% CIs: .33, 7.15) and worse overall work and social adjustment than mild worriers across time-points (M = 5.42, p = .035 95% CIs: .27, 10.58). Avoidance behavior mediated the association between generalized worry and work and social adjustment (95% bootstrap CIs: 013, .080). The majority of patients with CFS had comorbid generalized worry and severe worriers reported greater fatigue, anxiety, and worse work and social adjustment. This suggests that CFS patients may benefit from targeting generalized worry during CBT.


Brain thiobarbituric acid-reactive substances in rats after short periods of ozone exposure.
It has been proposed that molecules derived from reactions that occur between the ozone and the lung tissue mediate nonpulmonary effects caused by ozone exposure. Free radicals are among those proposed molecules that flow throughout the bloodstream to other organs producing lipid peroxidation. In order to elucidate on aspect of ozone toxicity mechanisms, we measured the thiobarbituric acid-reactive products (TBARS), as an index of lipid peroxidation, in a variety of brain regions in rats exposed to 1 ppm of ozone for 1, 3, 6, and 9h. Another group exposed to 9h of O(3) plus 3h of clean-air exposure was also included. The results showed an important increase in TBARS content in all the studied structures. Such effect seems to be transient. These findings indicates that acute ozone exposure can produce cerebral peroxidation as it has been found in rats exposed chronically, suggesting an involvement of free radicals in brain effects of ozone exposure.


Stress on external hexagon and Morse taper implants submitted to immediate loading.
This study aimed to evaluate the stress distribution around external hexagon (EH) and Morse taper (MT) implants with different prosthetic systems of immediate loading (distal bar (DB), casting technique (CT), and laser welding (LW)) by using photoelastic method. Three infrastructures were manufactured on a model simulating an edentulous lower jaw. All models were composed by five implants (4.1 mm × 13.0 mm) simulating a conventional lower protocol. The samples were divided into six groups. G1: EH implants with DB and acrylic resin; G2: EH implants with titanium infrastructure CT; G3: EH implants with titanium infrastructure attached using LW; G4: MT implants with DB and acrylic resin; G5: MT implants with titanium infrastructure CT; G6: MT implants with titanium infrastructure attached using LW. After the infrastructures construction, the photoelastic models were manufactured and a loading of 4.9 N was applied in the cantilever. Five pre-determined points were analyzed by Fringes software. Data showed significant differences between the connection types (p < 0.0001), and there was no significant difference among the techniques used for infrastructure. The reduction of the stress levels was more influenced by MT connection (except for CT). Different bar types submitted to immediate loading not influenced stress concentration.


[The alternative androgen synthesis pathway in humans].
During the last year, alternative androgen synthesis pathways have been discovered in humans. This review article highlights these new concepts of androgen synthesis.We performed a selective literature research using PubMed.After the discovery of a new androgen synthesis pathway in marsupials, this new path-way of androgen synthesis could be established in humans during the last year from two independent studies. One of them could demonstrate that two pathways of androgen synthesis are needed for male sexual differentiation in humans; the other study established that the new pathway is an important source of androgen synthesis in congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Additionally, it has been shown that an alternative androgen synthesis pathway that bypasses testosterone drives castration resistant prostate cancer.New and alternative androgen path-ways occur in humans. Importantly, these path-ways remain cryptic for the clinician, because the androgen synthesis circumvents classical intermediates like dehydroepiandrosterone, androstenedione and testosterone.


Serial determination of serum neuron-specific enolase in patients with neuroblastoma and other pediatric tumors.
The importance of determination of serum neuron-specific enolase (NSE) in patients with neuroblastoma has been emphasized by several authors. However, the specificity and sensitivity of NSE have not yet been well studied in tumors of infancy and childhood, nor is the role of serial determination of NSE in monitoring these patients fully understood. Concentrations of serum NSE were determined by a newly developed radioimmunoassay technique in 241 samples from 111 patients. NSE was also assayed in sera of nude mice bearing human pediatric tumors (16 samples), as well as in 30 tumor specimens. Eighty-two serum samples from 19 patients with neuroblastoma all showed NSE values (mean 120.2 ng/mL, range 16.2 to 722.0 ng/mL) elevated beyond the upper border of the normal range (14.6 ng/mL), even though four of the 19 patients had normal urinary excretion of 3-methoxy-4-hydroxymandelic acid (VMA) and 3-methoxy-4-hydroxy-phenylacetic acid (HVA). Twelve of these patients were monitored with serial NSE determinations, and their serum NSE were found to correlate well with the tumor burden, but were transiently modified by chemotherapeutically induced cell death. All 68 samples from nine patients, free of neuroblastoma at assessment, showed NSE values within the normal range. Thirteen of 25 patients with tumors other than neuroblastoma, however, showed serum NSE values mildly elevated beyond the upper border of the normal range (mean of the 25 patients 36.7 ng/mL, range 5.0 to 234.0 ng/mL). Results from our nude mouse study and from NSE analysis of the tumor extracts paralleled the clinical results.(ABSTRACT TRUNCATED AT 250 WORDS)


The theory of sliding filament models for muscle contraction. I. The two-state model.
The mechanical and thermal properties of Huxley's 1957 sliding filament model for striated muscle contraction are reconsidered, with emphasis on general relationships between two-state models and muscle behaviour. New empirical forms for the rate functions f(x) and g(x) are proposed, which give an improved fit to experiments. A specific procedure, based on the shortening heat, for determining model parameters is described and applied to various choices of rate functions. The change in slope of the tension-velocity curve observed by Katz is shown to require at least one discontinuity in the binding rate f(x), and a general formula is given. The two-state model also gives a symmetric cusp in the ATP-rate vs velocity curve at v = 0. The theory is extended to time-varying situations and applied to transient responses following isometric activation by tetanus (including latency relaxation), and unloaded and after-loaded contractions. The early burst of heat production can also be fitted by assigning appropriate values to the heats of binding and dissociation.


A novel functional polymorphism in the uridine diphosphate-glucuronosyltransferase 2B7 promoter with significant impact on promoter activity.
To clarify the molecular determinants of the metabolic variability of morphine, we searched for genetic polymorphisms in the gene for uridine diphosphate-glucuronosyltransferase 2B7 (UGT2B7) and evaluated their functional impact in vitro and in patients with cancer receiving long-term morphine therapy. Genetic analysis revealed the existence of 8 single-nucleotide polymorphisms (SNPs), 6 of which are tightly linked and are at positions -1248, -1241, -1054, -842, -268, and -102 relative to the hepatic start site. In contrast, an SNP at position -66 occurs independently, whereas a novel variation at position -79 appears to be in linkage disequilibrium with the codon 268 SNP (UGT2B7*2). At least 4 haplotypes were observed in white subjects included in the initial SNP screening. On functional in vitro characterization, promoter-reporter gene constructs with the -79 variation displayed 2.5- to 7-fold less activity compared with the wild-type construct in Caco-2 colon cells and HepG2 hepatoma cells, respectively (P =.015 and P <.001, respectively). To investigate a possible effect of the -79 variation in vivo, serum morphine and morphine glucuronide concentrations were measured by liquid chromatography-mass spectrometry in patients with cancer who received long-term oral morphine therapy, and subjects were then genotyped for the -79 polymorphism. Among 175 patients with normal hepatic and renal function, 6 were heterozygous for the -79 variation, and the morphine-6-glucuronide (M6G)/morphine and morphine-3-glucuronide (M3G)/morphine ratios versus those in the 169 noncarriers were 5.9 +/- 3.5 versus 7.1 +/- 7.0 for M6G/morphine (P =.96) and 31.2 +/- 17.1 versus 42.9 +/- 31.2 for M3G/morphine (P =.53), respectively. Further studies in larger samples are needed to make conclusions about the possible clinical relevance of the -79 polymorphism in the UGT2B7 gene.


CNS-directed gene therapy for lysosomal storage diseases.
Lysosomal storage diseases (LSDs) are a group of inherited metabolic disorders usually caused by deficient activity of a single lysosomal enzyme. As most lysosomal enzymes are ubiquitously expressed, a deficiency in a single enzyme can affect multiple organ systems, including the central nervous system (CNS). At least 75% of all LSDs have a significant CNS component. Approaches such as bone marrow transplantation (BMT) or enzyme replacement therapy (ERT) can effectively treat the systemic disease associated with LSDs in some patients. However, CNS disease remains a major challenge. Gene therapy represents a promising approach for the treatment of CNS disease as it has the potential to provide a permanent source of the deficient enzyme. Direct intracranial injection of viral gene transfer vectors has resulted in reduced lysosomal storage and functional improvement in certain small (rodent) and large (canine and feline) animal models of LSDs. The addition of protein transduction domains (PTDs) to the recombinant enzymes increased the distribution of enzyme and the extent of correction. Therapeutic levels of lysosomal enzymes can also be delivered to distant sites in the brain by anterograde and retrograde axonal transport. Finally, combining disparate approaches such as BMT and CNS-directed gene therapy can increase treatment efficacy in LSDs with severe CNS disease that are refractory to more conventional approaches. The development of gene transfer vectors that mediate persistent expression in vivo, the addition of PTDs, a better understanding of lysosomal enzyme trafficking and combining different therapies provide hope that the CNS component of LSDs can be effectively treated.


Immunosenescence and COVID-19.
Ageing is associated with modified function of both innate and adaptive immunity. It is believed that changes occurring in ageing immune system are responsible for increased severity and deadliness of COVID-19 in the elderly. Although supported by statistics and epidemiology, these finding do not compute at the mechanistic level as depending solely on chronological and biological ageing. The phenomena describing changes in the aging immune system are immunosenescence and inflammageing, which develop in time depending on challenges to the individual immune system (immunobiography). Thus, "richer" immunobiography (in addition to other factors, including genetic, epigenetics or metabolic) may adversely affect the reactivity to the SARS-CoV-2 not only at later decades of life, but also earlier, in young and middle-aged individuals. On the other hand, infection with SARS-CoV-2 is affecting the function of both innate and adaptive branches of the immune system, adding to the individual immunobiography. Summarizing, immunosenescence and inflammaging may aggravate, but also may be aggravated by SARS-CoV-2 infection.


Long-term outcome of laparoscopic surgery for colorectal cancer: a cochrane systematic review of randomised controlled trials.
The aim of this systematic review is to evaluate long-term outcome of laparoscopically assisted versus open surgery for non-metastasised colorectal cancer. Cochrane library, EMBASE, Pub med and CancerLit were searched for published and unpublished randomised controlled trials. RevMan 4.2 was used for statistical analysis. Twelve trials (3346 patients) reported long-term outcome and were included in the current analyses. No significant differences were found between laparoscopic and open surgery in the occurrence of incisional hernias or the number of reoperations for adhesions (p=0.32 and 0.30, respectively). Port-site metastases and wound recurrences were rare and no differences in occurrence after laparoscopic and open surgery were observed (p=0.16). Cancer-related mortality at maximum follow-up was similar after laparoscopic and open surgery (p=0.15 and 0.16 for colon and rectal cancer, respectively). No significant difference in tumour recurrence after laparoscopic and open surgery for colon cancer was observed (3 RCTs, hazard ratio for tumour recurrence in the laparoscopic group 0.86; 95% CI 0.70-1.08). In colon cancer patients, no significant differences in overall mortality were found (2 RCTs, hazard ratio for overall mortality after laparoscopic surgery 0.86; 95% CI 0.86-1.07). Laparoscopic resection of carcinoma of the colon is associated with a long-term outcome that is similar to that after open colectomy. Laparoscopic surgery for cancer of the upper rectum is feasible, but more randomised trials need to be conducted to assess long-term outcome.


The different perspectives of patients, informal caregivers and professionals on patient involvement in primary care teams. A qualitative study.
Patient involvement in the decision-making process, especially for chronically ill elderly patients, has become an important element of patient-centred primary care in many countries, including the Netherlands. This study openly explores different perspectives of patients, informal caregivers and primary care professionals on patient involvement in primary care team interactions. Sixty-four qualitative semi-structured interviews with chronically ill elderly patients, informal caregivers and primary care professionals from various disciplines. Underpinned by a phenomenology approach, this study used conventional content analysis for data analysis. Participants have different views of the roles of patients and informal caregivers in the primary care team and thus different expectations of the extent and level of patient involvement. Three challenges impact patient involvement in the team: (a) patients feel misunderstood and less involved that they would like when professionals take control, (b) patients have to balance the conflicting opinions of different professionals and (c) informal caregivers act undesirably as team leaders due to their own view of the level of patient involvement. Patient involvement is formed in complex interactions between patients, informal caregivers and multiple professionals whose perspectives and expectations can be misaligned. Recognizing the value of patients and informal caregivers on the team could help professionals to understand them better and thus limit the likelihood of challenges arising in team interactions.


A neuroactive steroid, allotetrahydrocorticosterone inhibits sensory nerves activation in guinea-pig airways.
We examined the effects of a neuroactive steroid, allotetrahydrocorticosterone on the activation of capsaicin-sensitive afferent sensory nerves (C-fibers). Allotetrahydrocorticosterone (0.0001-1.0 microg/ml) dose-dependently inhibited electrical field stimulation-induced guinea-pig bronchial smooth muscle contraction, but not the substance P-induced contraction at 1.0 microg/ml. Allotetrahydrocorticosterone (0.01-1.0 microg/ml) also reduced the capsaicin-induced release of substance P-like immunoreactivity from guinea-pig airway tissues in a dose-dependent manner. The inhibitory effect of allotetrahydrocorticosterone on electrical field stimulation-induced bronchial contraction were reduced by the pretreatment of voltage-dependent K+ channel blockers, tetraethylammonium (1 mM). This evidence suggests that allotetrahydrocorticosterone negatively modulate the activation of C-fibers and substance P release from their endings in airway tissues via the opening of voltage-dependent K+ channels.


What role does digital finance play in low-carbon development? Evidence from five major urban agglomerations in China.
In the epoch of the digital economy, digital finance (DF) has become an indispensable engine driving the high-quality development of the Chinese economy. The issues of how DF can be used to alleviate environmental pressure and how a long-term governance mechanism for carbon emissions reduction be formed have become particularly important. Based on the panel data of five national urban agglomerations in China from 2011 to 2020, this study utilizes the panel double fixed-effects model and chain mediation model to verify the impact mechanism of DF on carbon emissions efficiency (CEE). Some valuable findings are drawn below. First, the overall CEE of the urban agglomerations has potential for improvement, and the CEE and DF development level of each urban agglomeration have regional heterogeneity. Second, a U-shaped correlation is observed between DF and CEE. Technological innovation and industrial structure upgrading have a chain mediating effect in DF affecting CEE. In addition, the breadth and depth of DF have a notable negative impact on CEE, and the digitalization degree of DF shows a significant positive correlation with CEE. Third, the influencing factors of CEE have regional heterogeneity. Finally, this study provides relevant suggestions based on the empirical conclusions and analysis.


Single-Molecule Live-Cell Visualization of Pre-mRNA Splicing.
Microscopy protocols that allow live-cell imaging of molecules and subcellular components tagged with fluorescent conjugates are indispensable in modern biological research. A breakthrough was recently introduced by the development of genetically encoded fluorescent tags that combined with fluorescence-based microscopic approaches of increasingly higher spatial and temporal resolution made it possible to detect single protein and nucleic acid molecules inside living cells. Here, we describe an approach to visualize single nascent pre-mRNA molecules and to measure in real time the dynamics of intron synthesis and excision.


Relationship between pharyngeal or esophageal reconstruction and esophageal pressure after swallowing.
High-resolution manometry, which measures esophageal luminal pressure changes after swallowing, could shed more light on food-transport dynamics after pharyngeal/esophageal reconstruction. This prospective cohort study assessed the influence of two head-and-neck and esophageal tumor-resection and reconstruction approaches on esophageal pressure. The cohort consisted of 17 patients who underwent esophageal/pharyngeal resection/reconstruction for cancer and then participated in postoperative high-resolution manometry. Five healthy controls also underwent manometry for comparison. Partial pharyngectomy with patch grafts associated with smooth and continuous esophageal/pharyngeal movement. By contrast, surgery that removed the thoracic esophagus led to complete loss of peristalsis and poor food transport. High-resolution manometry effectively characterized the changes in food-transport dynamics caused by pharyngeal/esophageal resection/reconstruction. These findings suggest that continuous and smooth movement of the pharynx and esophagus is important for swallowing and high resolution manometry could be useful in patients after pharyngeal/esophageal resection/reconstruction.


Accuracy of stroke volume measurement with phase-contrast cardiovascular magnetic resonance in patients with aortic stenosis.
Phase contrast (PC) cardiovascular magnetic resonance (CMR) in the ascending aorta (AAo) is widely used to calculate left ventricular (LV) stroke volume (SV). The accuracy of PC CMR may be altered by turbulent flow. Measurement of SV at another site is suggested in the presence of aortic stenosis, but very few data validates the accuracy or inaccuracy of PC in that setting. Our objective is to compare flow measurements obtained in the AAo and LV outflow tract (LVOT) in patients with aortic stenosis. Retrospective analysis of patients with aortic stenosis who had CMR and echocardiography. Patients with mitral regurgitation were excluded. PC in the AAo and LVOT were acquired to derive SV. LV SV from end-systolic and end-diastolic tracings was used as the reference measure. A difference ≥ 10% between the volumetric method and PC derived SVs was considered discordant. Metrics of turbulence and jet eccentricity were assessed to explore the predictors of discordant measurements. We included 88 patients, 41% with bicuspid aortic valve. LVOT SV was concordant with the volumetric method in 79 (90%) patients vs 52 (59%) patients for AAo SV (p = 0.015). In multivariate analysis, aortic stenosis flow jet angle was a strong predictor of discordant measurement in the AAo (p = 0.003). Mathematical correction for the jet angle improved the concordance from 59 to 91%. Concordance was comparable in patients with bicuspid and trileaflet valves (57% and 62% concordance respectively; p = 0.11). Accuracy of SV measured in the LVOT was not influenced by jet eccentricity. For aortic regurgitation quantification, PC in the AAo had better correlation to volumetric assessments than LVOT PC. LVOT PC SV in patients with aortic stenosis and eccentric jet might be more accurate compared to the AAo SV. Mathematical correction for the jet angle in the AAo might be another alternative to improve accuracy.


[Biochemical characterization and study of the sensitivity to Plasmodium falciparum infection. Apropos of a case of double CN Baltimore hemoglobinopathy discovered in Senegal].
The discovery of a double CNBalt hemoglobinopathy allowed the authors, after a family background investigation, to study the possible biological effects linked to that dual heterozygoty and to look for a protection against Plasmodium falciparum infections. It hasn't been possible to make evident any protection.


A novel porous carbon material derived from the byproducts of bean curd stick manufacture for high-performance supercapacitor use.
The exploitation of efficient renewable energy resources and the promotion of added value of agricultural products are always hot topics. In this study, we present a novel porous carbon material for high performance supercapacitor applications made from the byproduct of bean curd stick manufacture. The as-prepared carbon material possesses a hollow interconnected structure with a large specific surface area (2609 m2 g-1), while containing 5.01% oxygen and 1.75% nitrogen heteroatoms. Therefore, besides electrical double-layer capacitance, it can also produce additional pseudocapacitance to enhance the overall capacitance. Benefiting from these advantages of structure and composition, the bean curd stick based porous carbon material demonstrates a high specific capacitance of 405 F g-1 at 0.5 A g-1. Moreover, the presented porous carbon material based symmetric supercapacitor also offers a high energy density (11.35 W h kg-1 at a power density of 125 W kg-1). All the above findings indicate that the byproduct of bean curd stick manufacture is an excellent optional material for preparing high-performance supercapacitor material. Simultaneously, this work also provides an effective strategy for adding value to agricultural products.


A simple clinical coding strategy to improve recording of child maltreatment concerns: an audit study.
Recording concerns about child maltreatment, including minor concerns, is recommended by the General Medical Council (GMC) and National Institute for Health and Clinical Excellence (NICE) but there is evidence of substantial under-recording. To determine whether a simple coding strategy improved recording of maltreatment-related concerns in electronic primary care records. Clinical audit of rates of maltreatment-related coding before January 2010-December 2011 and after January-December 2012 implementation of a simple coding strategy in 11 English family practices. The strategy included encouraging general practitioners to use, always and as a minimum, the Read code 'Child is cause for concern'. A total of 25,106 children aged 0-18 years were registered with these practices. We also undertook a qualitative service evaluation to investigate barriers to recording. Outcomes were recording of 1) any maltreatment-related codes, 2) child protection proceedings and 3) child was a cause for concern. We found increased recording of any maltreatment-related code (rate ratio 1.4; 95% CI 1.1-1.6), child protection procedures (RR 1.4; 95% CI 1.1-1.6) and cause for concern (RR 2.5; 95% CI 1.8-3.4) after implementation of the coding strategy. Clinicians cited the simplicity of the coding strategy as the most important factor assisting implementation. This simple coding strategy improved clinician's recording of maltreatment-related concerns in a small sample of practices with some 'buy-in'. Further research should investigate how recording can best support the doctor-patient relationship. HOW THIS FITS IN: Recording concerns about child maltreatment, including minor concerns, is recommended by the General Medical Council (GMC) and National Institute for Health and Clinical Excellence (NICE), but there is evidence of substantial under-recording. We describe a simple clinical coding strategy that helped general practitioners to improve recording of maltreatment-related concerns. These improvements could improve case finding of children at risk and information sharing.


Local treatment in the setting of de novo metastatic rectal cancer: reappraisal of prognostic factors.
This retrospective study was conducted to: (1) provide more modern data on real-life local management of metastatic rectal cancer; (2) compare therapeutic strategies; and (3) identify prognostic factors of local failure, overall survival and progression-free survival. Data about efficacy and acute toxicity were collected. Patients were diagnosed with metastatic rectal cancer between 2004 and 2015, and were treated at least with radiotherapy. Local failure, overall survival and progression-free survival were correlated with patient, tumour and treatment characteristics using univariate and multivariate analyses. Data of 148 consecutive patients with metastatic rectal cancer were analysed. Median follow-up was 19 months. Median overall survival was 16 months. All patients received local radiotherapy, with a median equivalent 2 Gy per fraction dose of 47.7 Gy. Rectal surgery was performed in 97 patients (65.6%). The majority of patients (86/97, 88.7%) received pre-operative chemoradiation. In multivariate analysis, rectal surgery was found to be the only independent predictor of increased overall survival (24.6 vs 7.1 months, p <0.001). Of the patients undergoing surgical treatment, 22.8% presented with significant complications that required a delay of systemic treatment. Grade 3-4 acute radiation therapy-related toxicities were observed in 6.1% of patients, mainly gastrointestinal toxicities (5.4%). Rectal surgery was a key predictive factor of increased progression-free survival and overall survival in patients receiving at least local radiotherapy. In our series of real-life patients, local surgery and radiation seemed as well tolerated as reported in selected phase III non-metastatic rectal cancer patients. These data suggested that local management could be beneficial for metastatic rectal cancer patients.


Cell Communication-mediated Nonself-Recognition and -Intolerance in Representative Species of the Animal Kingdom.
Why has histo-incompatibility arisen in evolution and can cause self-intolerance? Compatible/incompatible reactions following natural contacts between genetically-different (allogeneic) colonies of marine organisms have inspired the conception that self-nonself discrimination has developed to reduce invasion threats by migratory foreign germ/somatic stem cells, in extreme cases resulting in conquest of the whole body by a foreign genome. Two prominent model species for allogeneic discrimination are the marine invertebrates Hydractinia (Cnidaria) and Botryllus (Ascidiacea). In Hydractinia, self-nonself recognition is based on polymorphic surface markers encoded by two genes (alr1, alr2), with self recognition enabled by homophilic binding of identical ALR molecules. Variable expression patterns of alr alleles presumably account for the first paradigm of autoaggression in an invertebrate. In Botryllus, self-nonself recognition is controlled by a single polymorphic gene locus (BHF) with hundreds of codominantly expressed alleles. Fusion occurs when both partners share at least one BHF allele while rejection develops when no allele is shared. Molecules involved in allorecognition frequently contain immunoglobulin or Ig-like motifs, case-by-case supplemented by additional molecules enabling homophilic interaction, while the mechanisms applied to destroy allogeneic grafts or neighbors include taxon-specific tools besides common facilities of natural immunity. The review encompasses comparison with allorecognition in mammals based on MHC-polymorphism in transplantation and following feto-maternal cell trafficking.


Oxidant stress responses in premature infants during exposure to hyperoxia.
To assess oxidant stress responses in newborn infants treated with elevated concentrations of oxygen, we measured plasma concentrations of glutathione (GSH) and glutathione disulfide (GSSG) in newborn infants ranging from 23 to 42 wk gestational age. All infants recruited into the study were mechanically ventilated and had catheters placed in their umbilical arteries as part of their normal clinical management. Blood samples were obtained on d 1, 3, and 5 and weekly thereafter or until the catheters were removed. We observed plasma concentrations of GSSG in these infants that were frequently an order of magnitude higher than the 0.1 to 0.3 microM we find in adults. Interestingly, plasma GSSG concentrations were inversely correlated to the inspired oxygen tensions. This effect appeared to arise from the patient selection criteria whereby, of the infants studied, those breathing the lowest partial pressures of oxygen were the smallest and gestationally youngest. A second observation was that plasma concentrations of GSH in the premature infants were substantially, indeed often dramatically, lower than we have observed in adult humans (6 to 10 microM). Finally, we found that in patients with both umbilical arterial and umbilical venous catheters arterial GSSG concentrations were consistently higher than venous concentrations; conversely, arterial GSH concentrations were lower than venous concentrations. The elevated GSSG concentrations we observed in these infants indicate marked oxidant stress responses in prematurely born infants, even in those infants exposed only to room air. The positive arteriovenous gradients of GSSG concentrations across the lungs of these infants suggest that at least some of the increased plasma GSSG originates in the lung.(ABSTRACT TRUNCATED AT 250 WORDS)


Estrogen modulation of ovariectomy-induced hyperalgesia in adult mice.
Some chronic pain conditions are more prevalent in women. However, the evidence from both human and animal studies as to whether estrogen is pro- or anti-nociceptive is inconsistent. We have used a model of functional abdominal pain in mice to examine the role of estrogen in the modulation of a hyperalgesic state induced by ovariectomy. C57/BL6 female mice were either ovariectomized (OVX), received the same surgery without removing the ovaries or were tested without any surgical procedure. Mechanical hyperalgesia was assessed by von Frey filaments and thermal pain was measured using a hot-plate at 50 degrees C. OVX mice, but not sham-operated, developed mechanical hyperalgesia localized to the abdominal region, the hindlimbs and the proximal tail, 4-5 weeks after OVX as well as a reduction in response latency to the hot plate. OVX animals were implanted with 17beta-estradiol pellets or with similar pellets with no hormone five weeks after OVX, when the hyperalgesic state was fully developed, and the estrogen reversed both mechanical and thermal hyperalgesia. Vaginal smears were taken to record the phase of the cycle at the time of the test from all animals and no significant differences were detected in mechanical hyperalgesia or in thermal pain threshold between normal animals in different phases of their estrous cycle. These results show that OVX induces a hyperalgesic state of slow onset and long duration that can be reversed by estrogen. We have also observed no estrous cycle modulation of pain sensitivity in normal animals.


Severe dyslipidemia in pregnancy: The role of therapeutic apheresis.
During pregnancy physiological changes occur in the lipid metabolism due to changing hormonal conditions: the LDL cholesterol (LDL-C), triglycerides (TG) and lipoprotein(a) [Lp(a)] increase throughout pregnancy. Common lipoprotein disorders are associated in pregnancy with two major clinical disorders: severe hypertriglyceridemia (SHTG) is a potent risk factor for development of acute pancreatitis and elevated cholesterol due to greater concentrations of LDL and remnant lipoproteins and reduced levels of HDL promote atherosclerosis. The combination of homozygous Familial Hypercholesterolemia (HoFH) and pregnancy can be a fatal condition. Therapeutic plasma exchange (TPE) may be used for an urgent need of a fast and effective lowering of TG levels in order to prevent a severe pancreatitis episode or hypertriglyceridemia-induced complications during pregnancy. LDL apheresis can decrease LDL-C and prevent complications and can be considered in the treatment of pregnancies complicated by high LDL-C. These conditions are configured in patients with HeFH who were taking statins before pregnancy (selected cases), patients already receiving apheresis before pregnancy suffering from HoFH, patients suffering from hypertriglyceridemia due to familial hyperlipoproteinemia types I and V, and cases of hypertriglyceridemia secondary to diabetes.


Organization and expression of a two-gene cluster in the arginine biosynthesis of Saccharomyces cerevisiae.
In Saccharomyces cerevisiae, argB and argC define two adjacent and complementing loci, with mutants defective in two consecutive steps of arginine biosynthesis: N-acetylglutamate kinase (AG-kinase) and N-acetylglutamyl-phosphate reductase (AGPreductase). These enzymic activities are readily separated by ammonium sulfate fractionation or Sephadex G-200 chromatography. This suggests that each activity is carried in vivo by a different protein. The synthesis of the two enzymes is coordinately regulated, with an 85-fold difference in specific activities between fully repressed and fully derepressed cells. Missence mutations of the argB locus are defective in AGkinase only. Nonsense mutations in the argB locus are defective in both activities. Missense and nonsense mutations in the argC locus are defective in AGPreductase, with a few alleles also showing a reduced level of AGkinase. These data are best explained by assuming that argB and argC are two genes transcribed as a single messenger from argB to argC. This messenger produces in vivo two distinct proteins corresponding to the argB and argC gene products, either because translation can be initiated at the beginning of both genes, or because a large polypeptide is specifically cut in vivo to yield the gene products of argB and argC.


On the capacity of ozonation to remove antimicrobial compounds, resistant bacteria and toxicity from urban wastewater effluents.
The degradation of erythromycin (ERY) and ethylparaben (EtP) in urban wastewater effluents at low concentration level during ozonation was investigated under different experimental conditions. Both substrates were rapidly eliminated within 2min at low ozone dose of 0.3mgL-1 and the experimental data were well fitted in the pseudo-first-order kinetic model. The ratio of HO- and O3-exposure (Rct) at the inherent pH was found to be 1.9×10-8. The degradation of ERY and EtP was pronounced at pH 8 compared to acidic pH conditions, while the degradation rate of both substrates was found to be matrix-depended. It was also shown that both O3- and HO-mediated pathways are involved in the degradation of EtP, whereas the saturated-rich structure of ERY renders it O3-recalcitrant. Under the optimum O3 dose, the BrO3- concentration was found to be lower than 10μgL-1. Five and fifteen transformation products were elucidated during ERY and EtP oxidation, respectively. The root and shoot inhibition can be attributed to the oxidation products formed upon dissolved effluent organic matter transformation. Escherichia coli harbouring resistance to ERY survived ozonation better than EtP-resistant E. coli. However, neither ERY- nor EtP-resistant E. coli were detected after 15min of ozonation.


Coupled ripple oscillations between the medial temporal lobe and neocortex retrieve human memory.
Episodic memory retrieval relies on the recovery of neural representations of waking experience. This process is thought to involve a communication dynamic between the medial temporal lobe memory system and the neocortex. How this occurs is largely unknown, however, especially as it pertains to awake human memory retrieval. Using intracranial electroencephalographic recordings, we found that ripple oscillations were dynamically coupled between the human medial temporal lobe (MTL) and temporal association cortex. Coupled ripples were more pronounced during successful verbal memory retrieval and recover the cortical neural representations of remembered items. Together, these data provide direct evidence that coupled ripples between the MTL and association cortex may underlie successful memory retrieval in the human brain.


Slow-Channel Congenital Myasthenic Syndrome due to a Novel Mutation in the Acetylcholine Receptor Alpha Subunit in a South Asian: A Case Report.
Congenital myasthenic syndromes (CMS) result from genetic mutations that cause aberrations in structure and/or function of proteins involved in neuromuscular transmission. The slow-channel CMS (SCCMS) is an autosomal dominant postsynaptic defect caused by mutations in genes encoding alpha, beta, delta, or epsilon subunits of the acetylcholine receptor resulting in a functional defect which is an increase of the opening time of the receptor. We report a case of SCCMS due to a heterozygous mutation in the M2 domain of the AChR alpha subunit - CHRNA1:ENST00000348749.6:exon7:c.806T>G:p.Val269Gly and corresponding kinetic defect. A substitution of valine with phenylalanine in the same position has been previously described. This is the first reported case of a new CHRNA1 variant in a patient with SCCMS from South Asia. We also highlight the phenotype that would favour a genetic basis over an autoimmune one, in an adult presenting with fatigable weakness.


Developmental Exposure to Pesticides Alters Motor Activity and Coordination in Rats: Sex Differences and Underlying Mechanisms.
It has been proposed that developmental exposure to pesticides contributes to increasing prevalence of neurodevelopmental disorders in children, such as attention deficit with hyperactivity (ADHD) and to alterations in coordination skills. However, the mechanisms involved in these alterations remain unclear. We analyzed the effects on spontaneous motor activity and motor coordination of developmental exposure to a representative pesticide of each one of the four main chemical families: organophosphates (chlorpyrifos), carbamates (carbaryl), organochlorines (endosulfan), and pyrethroids (cypermethrin). Pesticides were administered once a day orally, in a sweet jelly, from gestational day 7 to post natal day 21. Spontaneous motor activity was assessed by an actimeter and motor coordination using the rotarod, when rats were adults. The effects were analyzed separately in males and females. Extracellular GABA in cerebellum and NMDA receptor subunits in hippocampus were assessed as possible underlying mechanisms of motor alterations. Motor coordination was impaired by developmental exposure to endosulfan, cypermethrin, and chlorpyrifos in females but not in males. The effect of endosulfan and cypermethrin would be due to increased extracellular GABA in cerebellum, which remains unaltered in male rats. Chlorpyrifos increased motor activity in males and females. Cypermethrin decreased motor activity mainly in males. In male rats, but not in females, expression of the NR2B subunit of NMDA receptor in hippocampus correlated with motor activity. These results show sex-specific effects of different pesticides on motor activity and coordination, associated with neurotransmission alterations. These data contribute to better understand the relationship between developmental exposure to the main pesticide families and motor disorders in children.


Gum tragacanth-polyvinyl alcohol cryogel and xerogel blends for oral delivery of silymarin: Structural characterization and mucoadhesive property.
In this study silymarin (SM) loaded cryo- and xerogels of gum tragacanth-polyvinyl alcohol (GT-PVA) were prepared and their physico-mechanical, microstructural and release properties were investigated. The results showed that unlike cryogels, which were highly porous, xerogels exhibited a densely packed agglomerated microstructure with a continuous network of cracks. The bulk density, mechanical strength and SM retention of xerogels were also much higher than those of cryogels. Furthermore, it was revealed that increasing the ratio of GT adversely influenced both physico-mechanical and structural features of the dried gels, but improved the release profile of SM. Incorporation of SM into the gels led to a distinct enhancement in their porosity, microstructure and physical properties. Rheological measurements indicated that rising the ratio of GT and inclusion of SM increased the viscosity of mucin-polymers blend and improved mucoadhesive property of the gels.


Youth cancer education through a combined American Cancer Society-Boy Scouts of America pilot program.
A pilot cancer education program for Boy Scouts in grades six through nine was developed. Motivation to complete requirements was provided by awarding a "Cancer Awareness Patch." Content of the program included health issues related to smoking and tobacco use, diet, and sun exposure, plus education about the practice of testicular self-examination, and sunscreen usage. Retention of factual material was good up to 18 months post-program. Participants developed positive attitudes toward lifestyle development and volunteerism. The program is recommended for supplementation of school health promotion curricula.


Laparoscopic treatment of celiac axis compression syndrome (CACS) and hiatal hernia: Case report with bleeding complications and review.
Median arcuate ligament (MAL) malposition is a rare cause of celiac axis compression syndrome (CACS) or Dunbar syndrome. A 26-year-old female presented with severe postprandial epigastric pain, weight loss, heartburn and regurgitation unresponsive to medical therapy. CT angiography and duplex ultrasound demonstrated the MAL crossing anterior to the celiac artery (CA). Reconstructions demonstrated CA compression, while the superior mesenteric artery (SMA) was normal. The MAL was laparoscopically divided, releasing the celiac axis. A concomitant Nissen fundoplication was performed. At 3-months follow-up, the CT-scan demonstrated no evidence of CACS with complete symptom resolution. Dunbar's syndrome can be treated with endovascular surgery, laparoscopic MAL division or vascular surgery.Six anatomical and morphologic variations of aortic and esophageal hiatus are described. The result of the analysis of these anatomical data leads to the conclusion that hiatus hernia, Dunbar's syndrome and GERD have a common etiopathogenesis and physiopathology. Laparoscopic treatment is useful and feasible in centers with experience in majorlaparoscopic surgery with reduced invasiveness, better cosmetic effect and shorter postoperative course.


Monitoring occupational exposure to carcinogens: detection by 32P-postlabelling of aromatic DNA adducts in white blood cells from iron foundry workers.
Blood samples were volunteered by workers in a Finnish iron foundry who were occupationally exposed to polycyclic aromatic hydrocarbons and from control subjects not known to be occupationally exposed to this class of chemical carcinogens. DNA was isolated from peripheral white blood cells and digested with micrococcal nuclease, spleen phosphodiesterase and nuclease P1. The DNA digest was then incubated with [gamma-32P]ATP and polynucleotide kinase. Aromatic adducts present in the digest that were resistant to nuclease P1 were thus 32P-labelled while unmodified nucleotides were not. The 32P-labelled adducts were resolved by t.l.c. and detected by autoradiography. Foundry workers were classified as belonging to high, medium or low exposure groups according to their exposure to airborne benzo[a]pyrene (high greater than 0.2, medium 0.05-0.2, low less than 0.05 microgram BP/m3 air). Aromatic adducts were found to be present in DNA from 3/4 samples from the high exposure group, 8/10 samples from the medium exposure group. 4/18 samples from the low exposure group and 1/9 samples from the unexposed controls. The levels of adducts found in the high and medium group samples ranged up to 1 adduct in 10(7) nucleotides but the levels formed in the low exposure group samples were not significantly different from those in unexposed controls. No differences related to the smoking habits of the subjects were observed. Most of the DNA adducts detected had chromatographic mobilities distinct from those formed when the 7,8-diol 9,10-oxide of BP reacted with DNA. The results indicate that highly-exposed individuals are more likely to contain aromatic DNA adducts in their white blood cells, but large interindividual variations were evident. In addition, multiple samples from the same subjects indicate that qualitative and quantitative changes in adduct patterns occur with time. This pilot study suggests that 32P-postlabelling may be useful in monitoring human exposure to known and to previously unidentified environmental genotoxic agents.


Protocol of BRICS: Brazilian multicentric pragmatic randomised trial of surgical interventions for displaced diaphyseal clavicle fracture study: MIPO versus ORIF for the treatment of displaced midshaft clavicle fractures.
Fractures of the diaphysis of the clavicle are common; however, treatment guidelines for this condition are lacking. Surgery is associated with a lower risk of non-union and better functional outcomes but a higher risk of complications. Open reduction and internal fixation with plates and screws are the most commonly performed techniques, but they are associated with paraesthesia in the areas of incisions, extensive surgical exposure and high rates of implant removal. Minimally invasive techniques for treating these fractures have a lower rate of complications. The aim of this study is to evaluate which surgical treatment option (minimally invasive osteosynthesis or open reduction and internal fixation) has better prognosis in terms of complications and reoperations. The study proposed is a multicentric, pragmatic, randomised, open-label, superiority clinical trial between minimally invasive osteosynthesis and open reduction and internal fixation for surgical treatment of patients with displaced fractures of the clavicle shaft. In the proposed study, 190 individuals with displaced midshaft clavicle fractures, who require surgery as treatment, will be randomised. The assessment will occur at 2, 6, 12, 24 and 48 weeks, respectively. The primary outcome of the study will be the number of complications and reoperations. For sample size calculation, a moderate effective size between the techniques was considered in a two-tailed test, with 95% confidence and 90% power. Complications include cases of infection, hypertrophic scarring, non-union, refracture, implant failure, hypoesthesia, skin irritation and shoulder pain. Reoperations are defined as the number of surgeries for pseudoarthrosis, implant failure, infection and elective removal of the implant. Study approved by the institutional ethics committee (number 34249120.9.0000.5505-V.3). The results will be disseminated by publications in peer-reviewed journals and presentations in medical meetings. RBR-3czz68)/UTN U1111-1257-8953.


Reduced estradiol synthesis by letrozole, an aromatase inhibitor, is protective against development of pentylenetetrazole-induced kindling in mice.
Neurosteroids, such as testosterone and their metabolites, are known to modulate neuronal excitability. The enzymes regulating the metabolism of these neurosteroids, thus, may be targeted as a noval strategy for the development of new antiepileptic drugs. The present work targeted two such enzymes i,e aromatase and 5α-reductase in order to explore the potential of letrozole (an aromatase inhibitor) on pentylenetetrazole (PTZ)-induced kindling in mice and the ability of finasteride (a 5α-reductase inhibitor) to modulate any such effects. PTZ (30 mg/kg, i.p.), when administered once every two days (for a total of 24 doses) induced kindling in Swiss albino mice. Letrozole (1 mg/kg, p.o.), administered prior to PTZ, significantly reduced the % incidence of kindling, delayed mean onset time of seizures and reduced seizure severity score. Letrozole reduced the levels of plasma 17β-estradiol after induction of kindling. The concurrent administration of finasteride and letrozole produced effects similar to letrozole on PTZ-kindling and on estradiol levels. This implies that the ability of letrozole to redirect the synthesis of dihydrotestosterone (DHT) and 5α-androstanediol from testosterone doesn't appear to play a significant role in the protective effects of letrozole against PTZ kindling. Letrozole, however, increased the levels of 5α-DHT in mice plasma. The aromatase inhibitors, thus, may be exploited for inhibiting the synthesis of proconvulsant (17β-estradiol) and/or redirecting the synthesis of anticonvulsant (DHT and 5α-androstanediol) neurosteroids.


The effects of actors vocal exercises for relaxation on fluency: A preliminary study.
To determine the efficacy of treatment based on Kristin Linklater's technique for vocal preparation for performance for use with people who stutter. A protocol for a treatment for stuttering involving breathing exercises, relaxation techniques, and focus on awareness was designed by the first author from Linklater's published exercises in her book Freeing the Natural Voice (2006). Four adults who stutter participated in a 12-week, single-case reversal design study. Treatment efficacy was determined by baseline and post-treatment measures on the OASES, self-report naturalness, tension and severity scale, and percentage of stuttering-like disfluency (SLD). Qualitative measures included a daily tension and practice log, a program completion questionnaire, and accounts from the clinicians administering the treatment protocol. Three of four participants scored lower on the OASES post-treatment, suggesting that the impact of stuttering on their daily lives had decreased. All four experienced a reduction in the number of SLD counted throughout treatment sessions compared to baseline data. A treatment for stuttering based on Linklater's work including regulation of breathing, relaxation, and awareness of breath may be effective in improving fluency and decreasing the impact of stuttering and warrants further study.


Tooth wear as a result of pica.
This paper reports a case of tooth surface loss as a result of the eating disorder pica. Background to the condition is discussed and the clinical findings and treatment of the patient outlined. The case illustrates a rare cause of wear which should be considered when patients present with an unusual pattern of tooth surface loss.


Exploring the role of peer density in the self-reported oral health outcomes of older adults: a kernel density based approach.
Previous research has documented that oral health is inextricably linked with overall health and is an important component of successful aging. Additionally, peer social interactions are known to improve older adults' general well-being by increasing social opportunities and knowledge of local resources. This study examines the relationship between peer density of participants aged 50 and older in the ElderSmile program and self-reported oral health in northern Manhattan. Results from logistic regression models found that higher peer kernel density estimation values are associated with better self-reported oral health. This reinforces the need for place-based health interventions, and provides new evidence of the importance of peer communities for older adults.


Triaxially Woven Hydrogen-Bonded Chicken Wires of a Tetrakis(carboxybiphenyl)ethene.
Interpenetration of low-dimensional networked structural motifs crucially affects porosity, stability, and properties of the whole reticular framework. However, varying and controlling the manner of interpenetration is still challenging. Herein, a porous hydrogen-bonded organic framework (HOF) with wvm-like weave constructed by triaxially woven chicken wires of X-shaped tetra-armed tetrakis(carboxybiphenyl)ethene CBPE, formally 4',4''',4''''',4'''''''-(ethene-1,1,2,2-tetrayl)tetrakis(1,1'-biphenyl-4-carboxylic acid), is reported. The structure is a contrast to a non-interpenetrated layered framework composed of tetrakis(4-carboxyphenyl)ethene CPE. This exotic framework of CBPE is due to the disproportionate conformation of the outer four phenylene rings in the peripheral biphenyl arms. The activated framework CBPE-1a exhibits thermal stability up to 220 °C and a BET surface area of 555 m2 g-1 . Additionally, the HOF shows mechanochromic behavior in terms of fluorescence color and quantum efficiency. The achievement of the present HOFs can provide insight into constructing a new type of functional porous organic materials with interwoven network structures.


MbIDGF, a novel member of the imaginal disc growth factor family in Mamestra brassicae, stimulates cell proliferation in two lepidopteran cell lines without insulin.
Imaginal disc growth factor (IDGF) is a soluble polypeptide growth factor that was first identified from the conditioned medium of Drosophilia imaginal disc C1.8+ cells. Working with insulin, IDGF stimulated the growth of cultured imaginal disk cells, which suggested that IDGF might function as a cofactor of Drosophila insulin or insulin like peptide. Here we report a new member of the IDGF family, named MbIDGF, from the cabbage armyworm, Mamestra brassicae. Using a cloned cDNA of MbIDGF, recombinant MbIDGF protein was expressed in baculovirus-infected Sf9 cells and purified. Without insulin, the recombinant MbIDGF protein stimulated cell growth of SES-MaBr-4 and NIAS-MaBr-93 cell lines that were derived from the fat bodies and hemocytes of M. brassicae, in a dose-dependent manner. The saturation of growth stimulation by MbIDGF was attained for the two types of cells at 80 ng/ml (0.8 nM) and 300 ng/ml (6 nM), respectively. The results suggest that MbIDGF may stimulate the growth of lepidopteran cells by a new mechanism without associating with the insulin pathway.


Level of Knowledge About COPD Among Patients and Caregivers.
Chronic obstructive pulmonary disease (COPD) represents a major health burden worldwide. COPD-specific education may positively affect the emotional distress associated with the disease and may contribute to the patients' poor health-related quality of life. Studies have shown that education regarding COPD is lacking among disease sufferers. The aim of our study was to evaluate the knowledge of COPD among patients and caregivers. We used the Bristol COPD Knowledge Questionnaire in hospitalized and nonhospitalized patients with COPD and other pulmonary diseases, their caregivers, and healthy volunteers. Mean total knowledge score of patients with COPD was 24.27 ± 8.44, of patients with other respiratory diseases 25.53 ± 7.93, of caregivers of patients with COPD 21.80 ± 5.32, of caregivers of patients with other pulmonary diseases 23.50 ± 8.79, and of healthy subjects 25.85 ± 9.27 (p = 0.071). Our data further indicate the lack of knowledge of COPD among patients and their carers and emphasize the need of education programs.