Resilience of political leaders and healthcare organizations during COVID-19.
This study assesses the online societal association of leaders and healthcare organizations from the top-10 COVID-19 resilient nations through public engagement, sentiment strength, and inclusivity and diversity strength. After analyzing 173,071 Tweets authored by the leaders and health organizations, our findings indicate that United Arab Emirate's Prime Minister had the highest online societal association (normalized online societal association: 1.000) followed by the leaders of Canada and Turkey (normalized online societal association: 0.068 and 0.033, respectively); and among the healthcare organizations, the Public Health Agency of Canada was the most impactful (normalized online societal association: 1.000) followed by the healthcare agencies of Turkey and Spain (normalized online societal association: 0.632 and 0.094 respectively). In comparison to healthcare organizations, the leaders displayed a strong awareness of individual factors and generalized their Tweets to a broader audience. The findings also suggest that users prefer accessing social media platforms for information during health emergencies and that leaders and healthcare institutions should realize the potential to use them effectively.


[Videofiberscopic study of laryngeal abnormalities in patients with severe motor and intellectual disabilities].
A total of 43 patients with severe motor and intellectual disabilities were enrolled in videofiberscopic investigation of laryngeal abnormalities. Their ages ranged from 2 to 41 years (mean: 19.9 years) and all of them had severe quadriplegia due to cerebral palsy or other conditions. Thirty-two out of the 43 patients (74.4%) had laryngeal abnormalities;laryngeal stenosis including that of iatrogenic origin, hypersecretion and laryngomalacia. Direct visualization of the occurrence of aspiration could be achieved in some patients. Seven (87.5%) out of 8 patients with tracheostomy and 25 (71.4%) out of 35 patients without tracheostomy had laryngeal abnormalities, showing no significant difference. The prevalence of abnormalities was significantly higher in patients with parenteral nutrition (30/33 = 90.9%) than in those with oral feeding (2/10 = 20%). Endoscopic investigation of the larynx is important, and videofiberscopy is especially effective for evaluation of laryngeal abnormalities in severely handicapped patients.


The involvement of growth differentiation factor 5 (GDF5) and aggrecan in the epithelial-mesenchymal transition of salivary gland pleomorphic adenoma.
Pleomorphic adenoma is the most common salivary gland tumor with annual incidence of 2-3.5/100 000 in population. The histogenesis of salivary gland pleomorphic adenoma is still unclear. One concept sustains the existence of an epithelial-mesenchymal transitions (EMT) process in pleomorphic adenomas by which neoplastic epithelial cells transdifferentiate into mesenchymal cells and leading to tissue heterogeneity from this salivary gland neoplasia. Here we investigate by immunohistochemistry the expression of growth differentiation factor 5 (GDF5) and aggrecan in 15 cases of salivary gland pleomorphic adenomas. We found that both markers were present in normal salivary gland, mainly in the cells that line striated and intercalated ducts suggesting their involvement in the morphogenesis of this duct system. A constant positive reactivity for both markers was recorded in transition regions from tubular proliferative units to myxoid areas suggesting the involvement of an EMT process during the tumorigenesis of such salivary gland neoplasia. Also, both markers may be implicated in the transdifferentiation of neoplastic myoepithelial cells from the myxoid zones to lacuna cells of adjacent chondroid areas completing the morphology of this salivary gland tumor.


Parotid function and composition of parotid saliva among elderly edentulous African-American diabetics.
This study examined parotid salivary flow rate and composition in three groups of differently treated diabetics and a control group of non-diabetics. The study population was composed of edentulous African-Americans at least 65 years of age. Group A was the control, Group B insulin-dependent (Regular Iletin, U-100 qd.), Group C controlled by oral medication (Tolbutamide, 500 mg qd.), and Group D was diet controlled. All diabetic patients had serum glucose values under 250 mg/dl. Salivary flow rates, secretory IgA, electrolytes (Na+, Cl-, K+, Ca++) and total protein concentrations were evaluated. The results showed no significant differences between groups with respect to salivary flow rates, electrolytes and IgA concentrations. Additionally, all diabetic groups demonstrated a significantly lower salivary total protein concentration when compared to the controls. There appears to be no evident decrease in salivary flow rate in these three differently controlled diabetic groups compared with healthy non-diabetics.


Chemopreventive role of Coriandrum sativum against gentamicin-induced renal histopathological damage in rats.
Drug induced nephrotoxicity is one of the most common causes of renal failure. Gentamicin belongs to aminoglycosides, which elicit nephrotoxic potential. Natural antioxidants from plants demonstrate a number of biotherapeutic activities. Coriander is an important medicinal plant known for its hepatoprotective, diuretic, carminative, digestive and antihelminthic potential. This study was designed to investigate whether the extract of Coriandrum sativum ameliorates the nephrotoxicity induced by gentamicin in rats. Dried coriander powder was coarsely grinded and subjected to defatting by petroleum ether and further with ethyl acetate. The extract was filtered and subjected to phytochemical and phytoanalytical studies. Acute toxicity in Wistar rats was determined by the OECD Guideline (423). Animals were divided into four groups. The first group served as positive control, while the second group was toxic control (gentamicin treated). The third and fourth group were treated with the extract (200 and 400 mg/kg gentamicin). After 8 days, the animals were sacrificed and biochemical and histopathological studies were carried out. Phytochemical screening of the extract demonstrated Coriandrum sativum to be rich in flavonoids, polyphenolics and alkaloids. Results of acute toxicity suggested the use of 200 mg/kg and 400 mg/kg for Coriandrum sativum in the study. Coriandrum sativum extract at the dose of 400 mg/kg significantly (p<0.01) decreased creatinine levels in the animals, along with a decrease in serum urea and blood urea nitrogen. Treatment with Coriandrum sativum extract ameliorated renal histological lesions. It is concluded that Coriandrum sativum is a potential source of nephroprotective phytochemical activity, with flavonoids and polyphenols as the major components.


Immunological aspects of fresh-frozen allogeneic bone grafting for lateral ridge augmentation.
To present some immunological aspects of fresh-frozen allogeneic bone grafting for lateral bone augmentation, based on the quantitative evaluation of IL-10, IL-1β, IFN- γ and TNF- α in patients sera. Thirty-three partially or totally edentulous patients received fresh-frozen allogeneic bone (AL - 20 patients) or autologous bone onlay block grafts (AT - 13 patients) prior to oral implant placement. Blood samples were collected from each patient at various time-points during a 6 month-period (baseline, 14, 30, 90 and 180 days postoperatively). Quantitative evaluation of IL-10, IL-1β, IFN- γ and TNF- α was performed by enzyme linked immunosorbent assay (ELISA). For all evaluated markers and at all evaluated periods, inter-group comparisons showed no statistically significant differences between the groups, while the observed values were within normal levels. For AL-treated patients, intra-group evaluation showed statistically significant increase of TNF-α from baseline to 90 (P < 0.001) and 180 (P < 0.01) days, and from 14 to 90 (P < 0.01) and 180 (P < 0.05) days. IFN- γ showed intercalated results, with a decrease from baseline to 14 days (P < 0.05), and increase from 14 to 90 days (P < 0.001) and 180 (P < 0.05) days. No differences between the periods of evaluation were found for the AT group. AL grafting for lateral bone augmentation, similar to AT grafting, does not seem to challenge the immune system significantly.


Strong competition between adsorption and aggregation of surfactant in nanoscale systems.
The size-dependent behavior including surface tension, surface density (Γ), and critical micelle concentration (CMC) of a nanoscale liquid film containing surfactant has not been investigated until now. Strong competition between surface adsorption and bulk aggregation of surfactant in nanoscale systems was explored by Many-body Dissipative Particle Dynamics simulations. In nanoscale systems, as the surfactant concentration increases, Γ continues rising even after CMC is exceeded. The saturation level of Γ is achieved only when the surfactant bulk concentration is over ten times of CMC. Moreover, both surface micelles formed by adsorbed surfactant and the sublayer below the adsorbed layer are clearly identified. The former can reduce the contacts of adsorbed surfactant with water, while the latter has the surfactant concentration significantly higher than that in bulk. The strong coupling between adsorption and micellization is attributed to large surface-to-volume ratio compared to macroscopic systems, and can be simply realized by the fact that the ratio of the numbers of surfactant distributed in bulk (nbulk) and at interface (nads) is always less than unity (nbulk/nads < 1) in nanoscale systems.


[Social representations about humanization of care: ethical and moral implications].
This research aimed at identifying the ethical aspects in the social representations of clients on the humanization and to argue the implications of these for the nursing care. A qualitative study was carried out whose data collection was by means of semi-structured interview and participant observation with 24 patients hospitalized in a public institution. The social representations about humanization of care gain contours of the ethics and the moral, in the establishment of gradients of merit of the good treatment, and resolute actions, clinical evaluation and respect to the right of the client. The right to the good treatment is not equal for all, what indicates the possible differentiations in social representations about citizenship.


Insurance status and delay in orthotic treatment in children.
To determine if the type of health insurance is associated with a delay in children obtaining orthoses. The medical records of 60 children who were prescribed an ankle-foot orthosis (AFO) or thoracolumbosacral orthosis (TLSO) were retrospectively reviewed. Ten children were randomly chosen with either of 3 types of insurance (government, health maintenance organizations [HMOs], and preferred provider organizations [PPOs]) with an orthosis provided by a single supplier. The time interval between prescription and insurance company authorization was recorded, as well as the interval between prescription and procurement of the orthosis. There were significant differences in the time from prescription to authorization of orthoses between insurance types (P = 0.001) and time from authorization until brace procurement between insurance types (P = 0.01). Children with PPO insurance received authorization for an AFO faster than children with government insurance or an HMO (P < 0.05). Children with government insurance received authorization for a TLSO significantly later than children with PPO insurance (P = 0.004) or HMO insurance (P = 0.03). The difference in time between authorization and procurement of a TLSO in children with PPO insurance (36 days) was strikingly different from that of children with government insurance (123 days) (P = 0.003). This study documents that children with government insurance face delays in obtaining orthotic treatment compared with children with PPO insurance. The delay in the procurement of the more expensive brace (TLSO is approximately 4 times the cost of an AFO) correlated to more striking delays in the government-insured population.


Diarrhea as a Presenting Symptom of Disseminated Toxoplasmosis.
Disseminated toxoplasmosis is uncommon in both immunocompetent and immunocompromised hosts with gastrointestinal involvement being rarely described. We report a case of disseminated gastrointestinal toxoplasmosis in an immunocompromised man who presented with one month of diarrhea and abdominal pain. Imaging showed thickening of the ascending colon and cecum. Esophagogastroduodenoscopy and colonoscopy biopsies revealed Toxoplasma gondii, confirmed by immunostain. Symptoms completely resolved following treatment with pyrimethamine, sulfadiazine, and leucovorin. This case highlights the importance of including toxoplasmosis in the differential diagnosis of any immunocompromised individual presenting with gastrointestinal symptoms.


Controlling the Fiber Stress Distribution with Variable-Frequency Step Roll for Tunable Spun Yarn Structures.
The dynamic regulation of fiber stress distribution in the yarn-forming triangle area is critical for controlling variable composite yarn structures, including siro and sirofil composite yarns. In this study, comparison analyses of the variable geometric structure and stress distribution during the yarn-forming process, which involves step rolls with asymmetrical fiber control, have been carried out using ring-spinning technology. The geometric analyses show that partly staple fibers are continuously controlled while other fibers intermittently lack stress restraint, resulting in cyclically changed helical angles and wrapping density in the yarn-forming triangle area. The yarn structure model displayed that periodically distributed staple fibers occur in siro composite yarn, while sirofil composite yarn shows gradual periodic changes with uniform thickness variations, caused by cyclical changes in the stress distribution between filaments, and the strand altered the yarn-forming zone shapes from symmetrical to offset. Then, a systematic comparison of variable composite yarns with different frequencies (high, medium and low frequency) revealed that low-frequency step roll with wider grooves resulted in an intermittent output of staple fibers with less stress restraint, resulting in more pronounced structural variation in the siro and sirofil composite yarns with a slight yarn quality deterioration.


The nutritional effects of tooth loss.
In view of the high prevalence of edentulousness in developed countries, the evidence is reviewed for the effects of tooth loss on nutrition and health in the following categories of effects: mortality; food choice and nutrient intake; gastrointestinal irritation; digestion and nutrient absorption; nutritional status. The evidence indicates reduced consumption of meat, fresh fruit, and vegetables, and total energy resulting in lower Hb and vitamin C levels, increased gastrointestinal irritation and increased mortality from choking but no striking differences in digestion or nutritional status. However, most studies are not carefully controlled for other social and health factors.


Effects of the Superoxide Anionic Radicals to the Cultured Cerebral Cortex Neuron of Newborn Rat.
The effect of the superoxide anionic radicals to the cultured cerebral cortex neuron of newborn rat was investigated by using xanthine oxidase/xanthine. The results are as follows. The growth of neuron was inhibited ATPase activity decreased to 4.223 &mgr;mol/(mg.min(-1))(Pr) total cellular carbonyl increased to 295.40 &mgr;mol/g wet weight lipid peroxides(LPO) increased to 4.87 nmol/g(Pr) membrane lipid fluidity decreased (P value 0.398) in nuclear DNA, thesingle strand breaks(SSB) increased in the single cell gel assay(SCG), DNA migration was 7.35 mm ݣ subcellular structures of the neuron changed (mitochondria were swelling, etc.) and SOD gene expression of the neuron increased (the SOD activity and the SOD content increased, SOD mRNA content increased). These suggest that the superoxide anionic radicals could damage proteins, nucleic acids, lipids and subcellular structures in neurons.


Toxinotyping of Clostridium perfringens Strains Recovered from U.S. Turkeys with Necrotic Enteritis.
Necrotic enteritis (NE) is a serious disease of chickens and turkeys that causes significant economic losses to the poultry industry. On the basis of studies in chickens, Clostridium perfringens type G is considered by many to be the cause of NE in poultry. However, studies on isolates from Finnish and Italian turkeys with NE revealed that the vast majority were C. perfringens type A, and very few were C. perfringens type G. We therefore examined 74 C. perfringens isolates from U.S. turkeys with NE; 98% were type A and only 1% was type G. This result confirms that different C. perfringens types are involved in NE in turkeys when compared with chickens. We also examined the turkey isolates for other toxin genes associated with enteritis in various animal species, namely tpeL, cpb2, cpe, netE, netF, and netG. The tpeL gene, which has been associated with enhanced virulence of C. perfringens in chickens, was only found in 1% of turkey NE isolates. The cpe gene, which encodes C. perfringens enterotoxin (a major cause of food poisoning and non-foodborne C. perfringens-mediated diarrhea in humans) was also found in only 1% of our turkey NE isolates. Although cpb2, which encodes for the beta2 toxin, was found in 73% of our NE isolates, it has also been found in similar percentages of isolates from turkeys with normal intestine. The netE, netF, and netG genes were not detected among our C. perfringens isolates from turkeys.


Exploring the structure and dynamics of macromolecular complexes by native mass spectrometry.
Mass spectrometry (MS) is an effective approach for determining the mass of biomolecules with high accuracy, sensitivity and speed. Over the past 25 years, MS performed under non-denaturing conditions ("native MS") has been successfully exploited to investigate non-covalently associated biomolecules. Here we illustrate native MS applications aimed at studying protein-ligand interactions and structures of biomolecular assemblies, including both soluble and membrane protein complexes. Moreover, we review how the partial dissociation of holo-complexes can be used to determine the stoichiometry of subunits and their topology. We also describe "native top-down MS", an approach based on Fourier Transform MS (FT MS), whereby non-covalent interactions are preserved while covalent bonds are selectively fragmented. Overall, native MS plays an increasingly important role in integrative structural biology, helping researchers to elucidate the three dimensional architecture of intricate macromolecular complexes.


Feeding and digestion in low salinity in an osmoconforming crab, Cancer gracilis. I. Cardiovascular and respiratory responses.
The osmoregulatory physiology of decapod crustaceans has received extensive attention. Within this field there is a growing body of literature on cardiovascular and respiratory responses to low salinity. Most species exhibit a tachycardia coupled with an increase in ventilation rate and oxygen uptake. However, these previous experiments were conducted on animals that were starved prior to experimentation in order to avoid increases in metabolism associated with digestive processes. Because organisms are not necessarily starved prior to experiencing environmental perturbations, results from previous experiments may not represent natural physiological responses. The present study investigated how an osmoconforming decapod, the graceful crab Cancer gracilis, balanced the demands of physiological systems (prioritization or additivity of events) during feeding and digestion in a low salinity environment. Cancer gracilis exhibited a typical increase in oxygen uptake and less pronounced increases in cardiovascular variables (heart rate, stroke volume, cardiac output) during feeding in 100% seawater. In 3-day starved crabs, exposure to 65% seawater resulted in a pronounced bradycardia, with a concomitant decrease in cardiac output and haemolymph flow rates and a temporary decrease in oxygen uptake. When crabs were exposed to low salinity, 3 h and 24 h after food ingestion, heart rate increased slightly and cardiac output and ventilation rates remained stable. Although oxygen uptake decreased transiently, feeding levels were quickly regained. During a recovery phase in 100%SW there was an overshoot in parameters, suggesting repayment of an oxygen debt. Thus, it appears that feeding and digestion are prioritized in this species, allowing it to survive acute exposure to hyposaline water. Furthermore, the results show that the nutritional state of an animal is important in modulating its physiological responses to environmental perturbations. This underscores the importance of studying physiological responses at the whole organism level under conditions closely approximating those of the natural environment.


[Blood pressure change and syncope during leg phlebography].
Although syncope attacks such as black-out, faint consciousness, and cold sweat are sometimes experienced during leg phlebography, no study of their incidence and mechanism has been reported. We measured blood pressure noninvasively by using a Finapress with ECG monitor during overall examinations (21 cases, 33 limbs; male 8, female 13) following anamnesis. Age, sex, and past history of drug, syncope, leg phlebography, and other diseases were determined. All examinations were done in the upright position. Three cases (14.3%) and four limbs (12.1%) showed syncope attacks during leg phlebography. Syncope occurred after steps taken for the evaluation of venous return in two limbs, during infusion of contrast medium in one, and after infusion in the other. In all cases, the systolic blood pressure measurement during syncope was below 80 mmHg, and the sudden decrease of both systolic blood pressure (-83.0 +/- 22.0 mmHg) and heart rate (-29.5 +/- 5.0/min) suggested vasovagal reaction as a mechanism of syncope. Other causes of syncope including anaphylaxy, hyperventilation syndrome, seizure, and arrhythmia (except for bradycardia) were not found. There were also significant changes in blood pressure and heart rate in the nonsyncope group during leg phlebography that seemed to trigger vasovagal excitation. Premedication, contrast media, and position might be important factors and should be discussed further.


Renal hypoxia and lactate metabolism in hemorrhagic shock in dogs.
Central and renal hemodynamics, renal cortical and medullary oxygen tension, and renal lactate metabolism were investigated in hemorrhagic shock in dogs. During graded hemorrhage, renal tissue PO2 decreased in parallel with renal blood flow, whereas renal lactate uptake remained virtually unchanged. During shock, below a mean arterial pressure (MAP) of 72 mm Hg, renal lactate utilization declined in parallel with tissue PO2. Renal lactate was produced at an MAP of 38 mm Hg. Reinfusion of shed blood increased renal tissue PO2 above its preshock value but did not restore baseline renal oxygen consumption and lactate uptake levels. These results suggest that renal lactate utilization is not limited by oxygen delivery under moderate hemorrhagic hypotension but decreases linearly with renal tissue PO2 during shock.


Discriminant function analysis to calculate a Crohn's activity group scale to predict future inactive or active disease.
A discriminant function analysis was performed on several demographic, anthropometric, clinical, and laboratory data of 685 observations performed over 12 months on 137 patients with Crohn's disease. A Crohn's activity group scale (CAGS) was calculated. The CAGS has two advantages over the usual Crohn's disease activity index: it is objective, but more important is the fact that the values, when calculated longitudinally, have predictive value. Thus, calculation of CAGS is useful for counseling purposes and may also be useful in the design of future trials assessing therapy for Crohn's disease by allowing prerandomization stratification of patients with high or low probability of future recurrences of symptomatic disease activity.


Bicarbonate.
Bicarbonate is a laboratory value of considerable importance in emergency medicine. It is essential in the diagnosis of acid-base disorders, but must be interpreted in the context of a number of other parameters, including electrolytes, arterial blood gases, and renal function. As most laboratory evaluations, its prime importance is confirmation of impressions drawn from the history and physical examination. Still, in the emergency department, it is frequently found as an unsuspected component of a variety of pathologic processes. Except in extreme deviations from the normal range, the clinician is encouraged to seek an understanding of primary and compensatory processes before the initiation of therapy.


Syntheses, structures and luminescent properties of new lanthanide-based coordination polymers based on 1,4-benzenedicarboxylate (bdc).
Reaction of 1,4-benzenedicarboxylic acid (1,4-H2BDC) with EuCl(3).6H2O in MeOH in the presence of Et3N and MeCN gives a mixture of the 3-D metal-organic-framework (MOF) materials [Eu2(1,4-BDC)3(MeOH)4].8MeOH (1) and 2-D [Eu(1,4-BDC)(MeOH)4].Cl.MeOH.0.25H2O (2). Similar reactions afforded the isomorphous Gd (3) and Tb (4) analogs of 2. Reaction of 1,4-H2BDC with Ln(NO3)(3).6H2O under similar conditions gave [Ln(BDC)NO3(MeOH)2].MeCN.H2O (Ln = Eu (5) and Gd (6)), which have 2-D framework structures. The structures of 1-6 were determined by single crystal X-ray crystallographic studies and the luminescence properties of 1 and 4 in DMF solution were determined.


Sources of variability in posterior rhinomanometry.
Sources of variability in nasal airway resistance measured by posterior rhinomanometry were studied in 5 subjects tested on 5 different days and 56 subjects tested on 2 different days. On each day, a questionnaire on upper airway health and nasal symptoms was completed. The mean individual difference in nasal airway resistance between the 2 test days in the group of 56 subjects was 5.3% (SD 52.7%). Between-subject variability accounted for 74.9% and 72.5% of the total variability in the group of 5 and the group of 56 subjects, respectively. For the 5 subjects, by accounting for a change in upper airway symptoms or upper respiratory tract infection that occurred over the 5 test days, there was a significant decrease in the between-subject variability. The difference in sources of variation due to a change in upper airway symptoms was not seen in the group of 56 subjects. We conclude that the largest source of variability in nasal airway resistance is due to between-subject differences.


Vincamine prevents lipopolysaccharide induced inflammation and oxidative stress via thioredoxin reductase activation in human corneal epithelial cells.
Lipopolysaccharide (LPS) induced keratitis is a progressive infectious ocular disease in which innate inflammatory responses often cause clinical tissue damage and vision loss. In this study, the potential protective effects of vincamine, a plant alkaloid used clinically as a peripheral vasodilator, against LPS induced inflammation and oxidative stress were investigated on human corneal epithelial cells (HCECs). HCECs were treated with LPS and vincamine at various concentrations. Cell viability, reactive oxygen species (ROS) levels, and the gene expression levels of interleukin-6 (IL-6), IL-8, IL-1β, TNF-α, transforming growth factor-β (TGF-β) in HCECs, were assessed. The antioxidant potential of vincamine was evaluated by measuring the levels of malondialdehyde (MDA), total antioxidant capacity (T-AOC), and superoxide dismutase (SOD). The effects of vincamine on intracellular activities of thioredoxin reductase (TrxR) as well as other anti-oxidant proteins were also investigated in LPS treated HCECs. The results showed that vincamine protected HCECs from LPS induced cell viability reduction and ameliorated the inflammation. Vincamine exhibited a strong antioxidant activity, decreasing ROS levels and regulating the levels of SOD, T-AOC and MDA. Vincamine also exerted anti-inflammatory activities by decreasing IL-6, IL-8, IL-1β, TNF-α, TGF-β expression. Intracellular TrxR activity was significantly activated by vincamine. These findings suggest that vincamine exerts positive effects against LPS induced oxidative stress and inflammation and may be useful in protecting corneal epithelial cells from LPS induced keratitis.


Neutral endopeptidase in the heart. Neutral endopeptidase inhibition prevents isoproterenol-induced myocardial hypoperfusion in rats by reducing bradykinin degradation.
Peptide mediators may play a role in the control of myocardial perfusion. We found immunohistochemical evidence of the peptide-degrading enzyme neutral endopeptidase (NEP) in cultured rat myocytes. Therefore, we examined the effect of an NEP inhibitor, phosphoramidon, on myocardial perfusion in rats after (1) stimulating sensory nerves with capsaicin and (2) inducing myocardial hypoperfusion with isoproterenol, with or without pretreatment with selective antagonists of the substance P (NK1) and bradykinin (B2) receptors. Three to five sequential determinations of myocardial blood flow were made in anesthetized rats by injecting 100,000 radionuclide-labeled microspheres suspended in 70% dextrose into the left ventricle. Phosphoramidon doubled coronary blood flow in response to a dose of capsaicin that was ineffective in the absence of the inhibitor. Isoproterenol (50 mg/kg IP) caused an immediate fall in blood pressure and coronary blood flow; after 20 minutes, flow had returned to normal but pressure was still subnormal. Administration of phosphoramidon reduced the recovery of blood pressure but greatly increased coronary blood flow. These changes were not altered by a substance P NK1 receptor blocker but were completely abolished by a selective bradykinin B2 receptor blocker. Our data indicate that (1) NEP is present in the rat myocardium, (2) sensory nerve-induced coronary vasodilation is markedly potentiated by NEP inhibition, (3) isoproterenol-induced myocardial hypoperfusion is prevented by NEP inhibition, and (4) this effect of NEP inhibition is due to reduced degradation of bradykinin.


Study on motor learning of sternocleidomastoid muscles during ballistic voluntary opening.
Neck pain is one of the main symptoms of temporomandibular disorder. Muscle activity of the sternocleidomastoid muscle during occlusion has been clarified in recent years. We reported that when healthy individuals were instructed to chew rapidly, the activity of the sternocleidomastoid muscle responded to activity of the masseter muscle, however, during voluntary jaw opening, activity of the sternocleidomastoid muscle did not respond, but worked actively due to motor programming. The objective of the present study was to investigate the learning effects of repetitive training, that is, changes in activity mode of the neuromuscular system. The sternocleidomastoid and the anterior belly of digastric muscles in 8 healthy male adults were analyzed. In response to acoustic stimulation, each subject was instructed to open their mouth as quickly and widely as possible a total of 30 times with a break between measurements. EMG-reaction times (RT) of the sternocleidomastoid and anterior belly of digastric muscles were measured, and the length of time from the start of EMG activity of agonist to the start of actual movement was measured. In all subjects, at first measurement, EMGRT of the sternocleidomastoid muscle did not precede that of the anterior belly of digastric muscle. With each measurement, the difference in EMG-RT between the sternocleidomastoid and the anterior belly of digastric muscles decreased, and in 6 of the 8 subjects, EMG-RT of the sternocleidomastoid muscle preceded that of the anterior belly of digastric muscle. Repetitive task movement alters the start times of muscular activities, and from the perspective of EMG kinesiology, motor learning effects were confirmed with maximum ballistic voluntary jaw opening.


SUBUNIT COORDINATION IN THE FIREFLY LIGHT ORGAN.
1. Microphotographs were obtained of a firefly (Photuris sp.) light organ on cinema film at 64 frames per second with the aid of an image intensifier. 2. Analysis of the film indicates that the two light organs usually flash simultaneously, but cases of one organ leading by 32-48 msec are seen. 3. Asynchrony is also observed within the light organ during a flash. Submaximal flashes are comprised of small spots of light ("microsources") which turn on at various times throughout the flash. Their durations average 139 ± 3 (S.E.) msec (range 31-360 msec) compared with 300-425 msec for an organ flash. Microsources are of fairly uniform size and shape having an average diameter of 21.6 ± 0.3 µ. (S.E.) and a range of 11-36 µ. Microsources of this size are also seen as time functional unit of uncoordinated emission displays known as scintillation. It is suggested that the microsource is the smallest physiological unit of function in the firefly light organ. 4. Comparisons of glowing organs with histological sections demonstrate that the center portions of the "rosettes" are dark, and the centrifugal elements of the rosettes (the photocytes) emit light. 5. Microsources (21.6 µ in diameters) are somewhat smaller than the measured length of photocytes (34 µ) but larger than the width (8-10 µ). Thus the functional unit is identified as the center portions of 2 or 3 adjacent photocytes. 6. The whole organ flash is the integration of briefer staggered responses of a population of these single units which have activities of variable duration and intensities.


Isolation and characterization of an aminolevulinate-requiring Rhodobacter capsulatus mutant.
Using transposon Tn5 mutagenesis, we isolated a mutant strain of Rhodobacter capsulatus that requires aminolevulinate for growth. Southern blot analysis indicated that this strain has a single Tn5 insertion. The addition of 0.1 mM aminolevulinate to the medium allowed the mutant to grow either aerobically or photosynthetically with generation times similar to those of the parental strain. When grown photosynthetically, bacteriochlorophyll accumulation increased with increasing aminolevulinate concentration. The mutant strain had only 10% of the normal aminolevulinate synthase activity, but it had a normal level of porphobilinogen synthase activity. The requirement for aminolevulinate could be satisfied by porphobilinogen, hemin, or protoporphyrin. While the mutant grew well on agar plates containing any of these substrates, growth in liquid media containing hemin or protoporphyrin was poor. Introduction of an R' factor containing all the known R. capsulatus bch genes into the mutant strain did not relieve the requirement for aminolevulinate, suggesting that the Tn5 insertion is not within the bch region.


Multiple homonuclear band-selective decoupling NMR: Fast and unambiguous determination of diastereomeric excess.
Discrimination and quantification of chiral stereoisomers have been studied by different analytical methods, and NMR has emerged as a powerful one with the advancements in pure-shift NMR methods. In the present manuscript, an al-F1F2-MHOBS-DIAG NMR method for the quantification of diastereomeric excess ratio (dr) has been proposed and demonstrated, using hesperidin and naringin mixtures. This method enables simultaneous quantification of dr at multiple resonances, in a single experiment, and it takes only 10 min to record. The present method uses spectral aliasing and thus demands only very few indirect dwell increments. Further, the measured dr values are very reliable, because we consider several spins for the quantification.


Factors contributing to learning satisfaction with blended learning teaching mode among higher education students in China.
Blended learning has increasingly grown in importance as a method of classroom instruction in Chinese higher education classrooms in the context of fast-evolving network information technology, higher standards of educational informatization, and growing attention to the reform of teaching modes in higher education. The efficiency of blended learning can be increased by better understanding the students' learning satisfaction and its key influencing factors. Based on the theories of constructivism and phenomenology, the study constructs an index system of student satisfaction with blended learning in higher education, and conducts a questionnaire survey on 650 students with blended learning experience in 6 universities in Sichuan Province, China, obtaining 598 valid questionnaires after reviewing the collected questionnaires for missing values. This study uses descriptive statistical analysis (DSA), one-way ANOVA, Pearson correlation analysis, and multiple linear regression (MLR) to analyze the effects of each factor in the index system on satisfaction. Results indicate that the overall level of student satisfaction with blended learning in universities is moderately high, with students' self-satisfaction being the lowest, and that substantial disparities exist in the evaluation of satisfaction with blended learning on various online resources, online teaching forms, and offline teaching methods. This study applies multiple linear regression (MLR) to conclude that students' learning attitudes, curriculum design, and teachers' teaching methods are the most important factors influencing satisfaction with blended learning in universities. Results indicate that a blended learning system be built from the three dimensions of students, teachers, and curriculum, offering a theoretical foundation and point of reference for the ongoing reform of blended learning in higher education. The study is of great significance in optimizing teaching quality and deepening the reform of blended learning.


Optimal strategy in chemotherapy for a Gompertzian model of cancer growth.
The problem of optimal cancer chemotherapy is reconsidered. For the assumed result of the therapy the cumulative negative toxic effect of the drug is minimized. The unknown function to be optimized is the time-dependent dose of the drug. The Gompertzian model of cell population growth is employed. The formulated problem of the calculus of variations is solved using the method of Miele (the method of extremization of linear integrals via Green's theorem). The optimal solution is unique and of "bang-bang" type with one switching point.


Bone morphogenetic proteins regulate neural tube closure by interacting with the apicobasal polarity pathway.
During neural tube closure, specialized regions called hinge points (HPs) display dynamic and polarized cell behaviors necessary for converting the neural plate into a neural tube. The molecular bases of such cell behaviors (e.g. apical constriction, basal nuclear migration) are poorly understood. We have identified a two-dimensional canonical BMP activity gradient in the chick neural plate that results in low and temporally pulsed BMP activity at the ventral midline/median hinge point (MHP). Using in vivo manipulations, high-resolution imaging and biochemical analyses, we show that BMP attenuation is necessary and sufficient for MHP formation. Conversely, BMP overexpression abolishes MHP formation and prevents neural tube closure. We provide evidence that BMP modulation directs neural tube closure via the regulation of apicobasal polarity. First, BMP blockade produces partially polarized neural cells, which retain contact with the apical and basal surfaces but where basolateral proteins (LGL) become apically localized and apical junctional proteins (PAR3, ZO1) become targeted to endosomes. Second, direct LGL misexpression induces ectopic HPs identical to those produced by noggin or dominant-negative BMPR1A. Third, BMP-dependent biochemical interactions occur between the PAR3-PAR6-aPKC polarity complex and phosphorylated SMAD5 at apical junctions. Finally, partially polarized cells normally occur at the MHP, their frequencies inversely correlated with the BMP activity gradient in the neural plate. We propose that spatiotemporal modulation of the two-dimensional BMP gradient transiently alters cell polarity in targeted neuronal cells. This ensures that the neural plate is flexible enough to be focally bent and shaped into a neural tube, while retaining overall epithelial integrity.


Sensorimotor transduction of time information is preserved in subjects with cerebellar damage.
The cerebellar contribution to motor entrainment through rhythmic auditory stimuli was analyzed by comparing rhythmic motor responses in subjects with cerebellar pathologies and in healthy controls. Eleven patients with cerebellar lesions and eight healthy subjects tapped in synchrony with an auditory rhythmic stimulus using a hand-held pencil-shaped electrode connected to a PC. A 60-stimulus sequence was delivered with an ISI of 500 ms and changed at random to a new ISI value with either consciously perceived (+/-50 ms) or unperceived tempo changes (+/-10 ms). Synchronization patterns for both groups were computed based on the timing of inter-response intervals (IRIs) and synchronization errors (SE). Variability of IRI as well as the timing of adaptation patterns after the tempo changes were modeled and analyzed mathematically using a logistic/sigmoid function. Healthy subjects performed with significantly lower IRI variability than cerebellar patients. Patients with focal lesions performed with significantly lower IRI variability than patients with atrophic lesions. Asymptote parameters during isochronous synchronization as well as slope angles and symmetry points of the adaptation curves after tempo perturbation showed no significant differences between groups. Present data indicate that temporal variability of rhythmic motor responses is differentially affected by distinct cerebellar pathologies but that motor entrainment to auditory rhythms is not affected by lesion of the cerebellar circuits.


[Effectiveness of Dispersible Forms of Perindipril in Patients With Uncontrolled Arterial Hypertension in Clinical Practice].
The study was aimed at evaluating the efficacy and usability of a dispersible form of perindopril in patients with arterial hypertension (HT) in clinical practice. The study enrolled 52 patients with newly diagnosed or uncontrolled HT of grade 1-2. The baseline assessment consisted of physical examination, instrumental and laboratory tests, including electrocardiography, clinical and biochemical blood tests, measurement of daily albuminuria, and estimation of glomerular filtration rate (GFR). The assessment was repeated at 12 weeks of treatment. The patients were asked to complete questionnaires at the first visit, in order to determine the potential need for administration of dispersible tablets, and at the last visit, to evaluate the convenience of their use. Depending on the baseline blood pressure (BP) and the risk for cardiovascular events, patients were treated with perindopril dispersible form 10 mg/daily in monotherapy, or with combination of perindopril 10 mg/daily in the dispersible form and indapamide retard 1.5 mg/daily. The interim assessments of the treatment efficacy and safety were carried out at 2 and 4 weeks, and the final assessment was performed at 12 weeks from inclusion. The target BP was achieved in 22 (42.3%) patients at 2 weeks, 35 (67.3%) patients at 4 weeks, and 50 (96.2%) patients at 12 weeks of treatment. The reductions in systolic and diastolic BP, assessed by office BP measurements and BP self-control, as well as reduction in heart rate became significant (<0.001) as earlier as after 2 weeks of treatment, and this trend continued up to 12 weeks. In addition, the treatment was associated with by a significant reduction in daily albuminuria, serum creatinine, and increase in GFR. According to the survey data, 71.4% of patients preferred dispersible form of perindopril to the ordinary one, considering it as more convenient, effective and applicable in various everyday situations. In patients with HT, the dispersible form of perindopril in monotherapy and in combination with a diuretic provides a rapid and substantial BP reduction, as well as the achievement of target BP values in the majority of cases. In addition, such a treatment is associated with a significant positive effect on the heart rate, as well as on the renal function. Treatment with a soluble form of perindopril is well tolerated by patients and is estimated by them as a convenient and effective one.


Are polymorphisms in MTRR A66G and MTHFR C677T genes associated with congenital heart diseases in Iranian population?
The 5, 10-methyleneterahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) are two essential enzymes involved in folate metabolism. The relationship between genetic polymorphisms and congenital heart defects (CHDs) is inconsistent. Our aim was to investigate the association between two well-known polymorphisms of MTHFR and MTRR genes, C677T and A66G, respectively, and CHDs in Iranian patients. We enrolled 74 patients with ventricular septal defect (VSD) and 79 with tetralogy of fallot (TOF) along with 147 healthy controls. C677T and A66G polymorphisms were detected using tetra-primer ARMS (amplification refractory mutation system) PCR. Individuals carrying homozygote mutant (TT) genotype of C677T polymorphism represented the highest risk for CHDs (OR=7.3, 95% CI: 0.8-61, P=0.06). Also, significantly increased risk of VSD was observed in individuals with TT genotype (OR=10, 95% CI: 1-92.2, P=0.04). However, the frequency for variant allele (T) of C677T polymorphism was not statistically different between cases and controls (16.3% and 20.9%, respectively). For A66G polymorphism, we found that AG and GG genotypes had higher frequencies in the patients (48.4% and 21.6% respectively) than controls (42.9% and 15.6%, respectively). In line with this, combined AG+GG genotype represented with significantly elevated risk of CHDs (OR=1.6; 95% CI: 1-2.6, P=0.03). AG+GG combination was also identified as a risk factor for TOF (OR=1.8, 95% CI: 1-3.3, P=0.04). We demonstrated that C677T polymorphism of MTHFR gene was significantly associated with VSD in our patients. Our study also suggested that A66G polymorphism of MTRR gene may contribute to the development of TOF in Iranians.


Phosphoenolpyruvate carboxykinase and pyruvate carboxylase in developing rat liver.
1. Phosphoenolpyruvate carboxykinase and pyruvate carboxylase were measured in foetal, newborn and adult rat liver extracts by a radiochemical assay involving the fixation of [(14)C]bicarbonate. 2. Pyruvate-carboxylase activity in both foetal and adult liver occurs mainly in mitochondrial and nuclear fractions, with about 10% of the activity in the cytoplasm. 3. Similar studies of the intracellular distribution of phosphoenolpyruvate carboxykinase show that more than 90% of the activity is in the cytoplasm. However, in the 17-day foetal liver about 90% of the activity is in mitochondria and nuclei. 4. Pyruvate-carboxylase activity in both particulate and soluble fractions is very low in the 17-day foetal liver and increases to near adult levels before birth. 5. Phosphoenolpyruvate-carboxykinase activity in the soluble cell fraction increases 25-fold in the first 2 days after birth. This same enzyme in the mitochondria has considerable activity in the foetal and adult liver and is lower in the newborn. 6. Kinetic and other studies on the properties of phosphoenolpyruvate carboxykinase have shown no differences between the soluble and mitochondrial enzymes. 7. It is suggested that the appearance of the soluble phosphoenolpyruvate carboxykinase at birth initiates the rapid increase in overall gluconeogenesis at this stage.


Indices of impaired self-awareness in traumatic brain injury patients with focal frontal lesions and executive deficits: implications for outcome measurement.
In patients with moderate to severe traumatic brain injury (TBI), impairments of self-awareness are frequently found and associated with worse functional outcome and poor compliance with rehabilitation. The aim of this study was to investigate whether indications of impaired self-awareness could be found in TBI patients with frontal lesions and executive function deficits. Twenty-two TBI patients with focal frontal injuries were compared to 29 TBI patients without focal frontal injuries visible on neuroimaging. No differences were found on several outcome measures, including the Glasgow Outcome Scale-Extended (GOS-E), the Differential Outcome Scale (DOS), and return to work (RTW), although the frontal injury patients were more severely injured as indicated by the Glasgow Coma Scale (GCS) and duration of post-traumatic amnesia (PTA), and had impaired performance on a neuropsychological test of executive functioning. Even more so, the frontal injury group had a significantly lower score on the Sickness Impact Profile (SIP), indicating that they had fewer complaints than the patients without frontal injury, and scored significantly higher on the percentage of recovery (PoR) score, which expresses the extent of recovery as a percentage of their previous level of functioning. In contrast to the non-frontal-injury group, their PoR scores were not related to RTW, reflecting an erroneous perception of their actual working status. The positive results on these different outcome measures, which are partly or entirely self-reported, were seen as an indication of an impaired self-evaluative ability in the frontal injury patients. To determine outcome in a patient with frontal injuries and executive dysfunction, the judgment of several relevant other persons in the patient's life (e.g., partners, therapists, and employers) of the patient's daily life functioning should be sought.


Accelerated increase in vegetation carbon sequestration in China after 2010: A turning point resulting from climate and human interaction.
China has increased its vegetation coverage and enhanced its terrestrial carbon sink through ecological restoration since the end of the 20th century. However, the temporal variation in vegetation carbon sequestration remains unclear, and the relative effects of climate change and ecological restoration efforts are under debate. By integrating remote sensing and machine learning with a modelling approach, we explored the biological and physical pathways by which both climate change and human activities (e.g., ecological restoration, cropland expansion, and urbanization) have altered Chinese terrestrial ecosystem structures and functions, including vegetation cover, surface heat fluxes, water flux, and vegetation carbon sequestration (defined by gross and net primary production, GPP and NPP). Our study indicated that during 2001-2018, GPP in China increased significantly at a rate of 49.1-53.1 TgC/yr2 , and the climatic and anthropogenic contributions to GPP gains were comparable (48%-56% and 44%-52%, respectively). Spatially, afforestation was the dominant mechanism behind forest cover expansions in the farming-pastoral ecotone in northern China, on the Loess Plateau and in the southwest karst region, whereas climate change promoted vegetation cover in most parts of southeastern China. At the same time, the increasing trend in NPP (22.4-24.9 TgC/yr2 ) during 2001-2018 was highly attributed to human activities (71%-81%), particularly in southern, eastern, and northeastern China. Both GPP and NPP showed accelerated increases after 2010 because the anthropogenic NPP gains during 2001-2010 were generally offset by the climate-induced NPP losses in southern China. However, after 2010, the climatic influence reversed, thus highlighting the vegetation carbon sequestration that occurs with ecological restoration.


Epidemiological study of asymptomatic inflammatory bowel disease: the identification of cases during a screening programme for colorectal cancer.
An asymptomatic population of 37,000 people in the Nottingham area were offered faecal occult blood tests in a screening study for colorectal cancer. Seventeen thousand nine hundred and thirty people completed the tests and 481 individuals with positive tests underwent full investigation of the colon. Eight people with previously undiagnosed inflammatory bowel disease were identified. In five cases there was total ulcerative colitis; in one a proctitis and in two Crohn's disease. Two further patients with ulcerative colitis were identified; they had been lost to follow up for 25 and 45 years respectively. The combined prevalence of inflammatory bowel disease was 56/10(5) and it is likely that current studies of the epidemiology of these conditions may underestimate the true prevalence by between 27% and 38%.


Rapid desensitization protocols for patients with cardiovascular disease and aspirin hypersensitivity in an era of dual antiplatelet therapy.
To review the available protocols for rapid desensitization of patients with aspirin hypersensitivity and apply the data for use in patients with cardiovascular disease who would benefit from the dual antiplatelet therapy. A literature search was conducted via MEDLINE from 1966 to December 2006. Main search terms included: aspirin sensitivity, aspirin allergy, aspirin desensitization, aspirin-induced asthma, aspirin therapy, and aspirin intolerance syndrome. Articles describing rapid aspirin desensitization protocols were selected for review. Literature pertaining to aspirin hypersensitivity, drug desensitization, and the use of aspirin and dual antiplatelet therapy was also examined. Three rapid desensitization protocols were identified and evaluated. While landmark studies demonstrated that dual antiplatelet therapy with aspirin and clopidogrel significantly reduces mortality and morbidity in acute coronary syndromes and coronary stenting, patients with aspirin hypersensitivity are frequently managed with clopidogrel alone with no supporting data. Approximately 10% of the population experiences hypersensitivity to aspirin, which can manifest as asthma exacerbations, rhinorrhea, angioedema, urticaria, and anaphylaxis. The hypersensitivity reaction is mediated through aspirin-directed antibodies or by excessive leukotriene production. The desensitization process involved depletion of these mediators, as well as down-regulation of leukotriene receptors. Two groups of investigators developed rapid protocols to desensitize patients with aspirin hypersensitivity safely and effectively. The rapid protocol developed by Wong provides benefits over other protocols with its low starting dose and completion in less than 3 hours, low incidence of adverse effects, and high success rate in aspirin desensitization. The Wong protocol is an attractive option for the rapid desensitization of patients requiring dual antiplatelet therapy with aspirin and clopidogrel in the perimyocardial infarction period.


Synthesis of some novel analogues of 4-(1-Pyrrolidinyl) Piperidine and their effect on plasma glucose level.
In the present study some compounds of 4-(1-Pyrrolidinyl) Piperidine (I) have been synthesized. Structures of compounds were confirmed by using HNMR, IR, Mass and UV spectrophotometer techniques. All the derivatives (II, III, IV and V) and the parent compound (I) at the dose of 100 mg/kg were evaluated for their effect on plasma glucose level. Compound (II) was the only derivative which showed effect on plasma glucose level.


Impaired fibrinolysis and increased protease levels in gastric and duodenal mucosa of patients with active duodenal ulcer.
Cathepsin B and L (cysteine proteases), urokinase- and tissue-type plasminogen activators (serine proteases), and type-1 inhibitor are involved in gastric mucosal injury. We determined tissue protease levels in duodenal ulcer and their relationship to ulcer phase, bleeding tendency, Helicobacter pylori infection, and use of H2-blockers. Endoscopic biopsies of antral and duodenal mucosa were obtained from 61 patients with active or healed duodenal ulcer and control subjects. Antigen concentrations were measured by ELISA. Significantly higher levels of cathepsins, urokinase-type plasminogen activator, type-1 inhibitor, and significantly lower levels of tissue-type plasminogen activator were found in active ulcers. Bleeders had the highest cathepsins and urokinase-type plasminogen activator levels. Higher levels of urokinase-type plasminogen activator, cathepsin B, and type-1 inhibitor were observed in Helicobacter pylori-positive patients. Our results suggest that impaired fibrinolysis (tissue-type plasminogen activator), intramucosal proteases (cathepsins), tissue remodeling, and angiogenesis (urokinase-type plasminogen activator and type-1 inhibitor) are involved in duodenal ulcer formation and healing.


PD-1 blockade with nivolumab in relapsed/refractory primary central nervous system and testicular lymphoma.
Primary central nervous system (CNS) lymphoma (PCNSL) and primary testicular lymphoma (PTL) are rare extranodal large B-cell lymphomas with similar genetic signatures. There are no standard-of-care treatment options for patients with relapsed and refractory PCNSL and PTL, and the overall prognosis is poor. PCNSLs and PTLs exhibit frequent 9p24.1 copy-number alterations and infrequent translocations of 9p24.1 and associated increased expression of the programmed cell death protein 1 (PD-1) ligands, PD-L1 and PD-L2. The activity of PD-1 blockade in other lymphomas with 9p24.1 alterations prompted us to test the efficacy of the anti-PD1 antibody, nivolumab, in 4 patients with relapsed/refractory PCNSL and 1 patient with CNS relapse of PTL. All 5 patients had clinical and radiographic responses to PD-1 blockade, and 3 patients remain progression-free at 13+ to 17+ months. Our data suggest that nivolumab is active in relapsed/refractory PCNSL and PTL and support further investigation of PD-1 blockade in these diseases.


Contamination risk of synovial biopsy cultures in total hip arthroplasty: a prospective review of 100 cases.
Cultures of deep synovial biopsies remain an important tool in diagnosing periprosthetic joint infection, a devastating complication following total hip arthroplasty (THA). Recent reports of unexpected positive intraoperative cultures in aseptic revision arthroplasty, however, challenge the validity and interpretation of these cultures. The aim of this study was to evaluate the contamination risk of synovial biopsy cultures collected intraoperatively during primary THA of healthy subjects. Synovial biopsies for culture were collected during primary total hip arthroplasty procedures from 100 consecutive cases. The synovial biopsies were taken within the first 15 minutes after skin incision. Biopsy specimen were cultured on 4 different media for 8 or 15 days. Positive cultures were identified using Maldi-Tof spectrometry. 16 cultures yielded a bacterium, suggesting a false positive result of 16%. The mean time for the cultures to become positive was 6.29 days (standard deviation [SD] 3.90) with a maximum of 15 days. Proprionibacterium acnes and Staphylococcus epidermidis were most commonly cultured with 6 positive results for both bacteria. Our study yielded a 16% false positive rate in cultures of synovial biopsy taken during primary total hip arthroplasty of healthy subjects, suggesting that contamination risk of these synovial biopsy cultures may be larger than assumed by clinicians.


Small Molecule and Peptide Recognition of Protein Transmembrane Domains.
Membrane proteins play vital roles in cell signaling, molecular transportation, and cell adhesion. The interactions of transmembrane domains are much less well understood than those of their water-soluble counterparts, and they have been deemed "undruggable" despite their important biological functions such as protein anchoring, signal transduction, and ligand recognition. Nevertheless, continual developments in this area have revealed useful probes for investigating and regulating these membrane proteins. This review summarizes and evaluates the strategies available for discovering small molecules and peptides that recognize the protein transmembrane domains of membrane proteins, with a particular focus on rational design and library screening.


Assessing Procedural Competence: Validity Considerations.
Simulation-based medical education (SBME) offers opportunities for trainees to learn how to perform procedures and to be assessed in a safe environment. However, SBME research studies often lack robust evidence to support the validity of the interpretation of the results obtained from tools used to assess trainees' skills. The purpose of this paper is to describe how a validity framework can be applied when reporting and interpreting the results of a simulation-based assessment of skills related to performing procedures. The authors discuss various sources of validity evidence because they relate to SBME. A case study is presented.


Salmonella kingabwa meningitis in a neonate.
A 23-day-old male baby was admitted with 1 day history of high temperature, irritability and poor feeding. His general examination was unremarkable. Salmonella species grew from CSF culture and subsequent identification revealed Salmonella kingabwa, a serotype which rarely causes human illness. The child lived with his parents and regularly visited his grandmother for 4 h every day. Grandmother kept five snakes and five water dragons as pets. They lived in tanks and crawled freely around the house. For decades the reptiles have been known to carry Salmonella, which can be transmitted directly or indirectly to humans through ingestion of the bacteria, which causes subsequent infection. Reptile exposure is a rare but significant risk factor for Salmonella illness in England and contact with reptiles should be avoided by children less than 5 years old, pregnant ladies, older and those with impaired immunity.


Incidence of clinical atrial fibrillation and related complications using a screening algorithm at a nationwide level.
In a recent position paper, the European Heart Rhythm Association (EHRA) proposed an algorithm for the screening and management of arrhythmias using digital devices. In patients with prior stroke, a systematic screening approach for atrial fibrillation (AF) should always be implemented, preferably immediately after the event. Patients with increasing age and with specific cardiovascular or non-cardiovascular comorbidities are also deemed to be at higher risk. From a large nationwide database, the aim was to analyse AF incidence rates derived from this new EHRA algorithm. Using the French administrative hospital discharge database, all patients hospitalized in 2012 without a history of AF, and with at least a 5-year follow-up (FU) (or if they died earlier), were included. The yearly incidence of AF was calculated in each subgroup defined by the algorithm proposed by EHRA based on a history of previous stroke, increasing age, and eight comorbidities identified via International Classification of Diseases 10th Revision codes. Out of the 4526 104 patients included (mean age 58.9 ± 18.9 years, 64.5% women), 1% had a history of stroke. Among those with no history of stroke, 18% were aged 65-74 years and 21% were ≥75 years. During FU, 327 012 patients had an incidence of AF (yearly incidence 1.86% in the overall population). Implementation of the EHRA algorithm divided the population into six risk groups: patients with a history of stroke (group 1); patients > 75 years (group 2); patients aged 65-74 years with or without comorbidity (groups 3a and 3b); and patients < 65 years with or without comorbidity (groups 4a and 4b). The yearly incidences of AF were 4.58% per year (group 2), 6.21% per year (group 2), 3.50% per year (group 3a), 2.01% per year (group 3b), 1.23% per year (group 4a), and 0.35% per year (group 4b). In patients aged < 65 years, the annual incidence of AF increased progressively according to the number of comorbidities from 0.35% (no comorbidities) to 9.08% (eight comorbidities). For those aged 65-75 years, the same trend was observed, i.e. increasing from 2.01% (no comorbidities) to 11.47% (eight comorbidities). These findings at a nationwide scale confirm the relevance of the subgroups in the EHRA algorithm for identifying a higher risk of AF incidence, showing that older patients (>75 years, regardless of comorbidities) have a higher incidence of AF than those with prior ischaemic stroke. Further studies are needed to evaluate the usefulness of algorithm-based risk stratification strategies for AF screening and the impact of screening on major cardiovascular event rates.


Chemical structures of constituents from the flowers of Osmanthus fragrans var. aurantiacus.
Three new megastigmane glycosides named floraosmanosides I-III and a new γ-decalactone named floraosmanolactone I together with 16 known constituents were isolated from the flowers of Osmanthus fragrans var. aurantiacus cultivated in Guangxi Zhuang Autonomous Region, China. The chemical structures of the new compounds were elucidated on the basis of chemical and physicochemical evidence. Among them, ligustroside and (+)-pinoresinol significantly inhibited nitric oxide production in lipopolysaccharide-activated RAW264.7 macrophages.


Treatment of Status Epilepticus: What Are the Guidelines and Are We Following Them?
Status epilepticus (SE) is associated with high morbidity and mortality. The American Epilepsy Society (AES) has established guidelines regarding proper dosing of antiepileptic drugs (AEDs). There are also recommendations for appropriate weaning off anesthetic agents in SE. Our aim was to determine the frequency with which guidelines were being followed during routine clinical care. A retrospective chart review was completed for patients with a diagnosis of SE within the last 10 years. All patients with SE on anesthetic agents were included when analyzing AED dosing. Patients with anoxic brain injury were excluded when reviewing anesthetic wean times. Seventy-six patients were identified on anesthetic agents. Five patients had anoxic brain injury and were excluded from the anesthetic weaning analysis. Medications were under dosed as follows: lorazepam 0.05 mg/kg (N=51), midazolam 0.07 mg/kg (N=14), fosphenytoin 17.9 mg/kg (N=47), levetiracetam 21.7 mg/kg (N=42), valproate sodium 16.7 mg/kg (N=12), phenobarbital 4.1 mg/kg (N=4), lacosamide 215 mg (N=13), and topiramate 333 mg (N=3). Anesthetic agents were weaned as follows: <24 hours 32/71 (45%), 24 to 48 hours 11/71 (15%), 48 to 72 hours 12/71 (17%), and >72 hours 11/71 (15%). Seizure recurrence rates were: 8/32 (25%) <24 hours, 2/11 (18%) 24 to 48 hours, 1/12 (8.3%) 48 to 72 hours, and 1/11 (9%) at >72 hours. This retrospective review demonstrates how guidelines and recommendations for SE are not consistently followed. Under dosing of AEDs and aggressive weaning of anesthetic agents may result in higher morbidity and mortality.


Antarctic and New Zealand Byblisoides (Amphipoda: Ampeliscidae) with a key to the world species.
The family Ampeliscidae is a species diverse family ranging from shallow waters to over 4000 m depth. Within this family, however, one genus, Byblisoides has few species and is generally found in deep water. The conservative morphology of other species of Byblisoides is also evident in the new species described here. This study extends the known species composition of the genus from seven species to nine. A key to world species is updated.


Significance of CD4+ T-cell count in the management of appendicitis in patients with HIV.
Identification of complicated appendicitis (CA) is critical to the management of appendicitis. However, previous studies have not investigated indicators of CA among patients with HIV or whether it is safe to use conservative treatment for appendicitis in these patients. Among 322 patients with appendicitis, we identified 14 who had HIV. Six of them were operated and 8 were treated with antibiotics; CA was diagnosed in 4. Patients with HIV and CA had a significantly lower CD4+ T-cell count than those with uncomplicated appendicitis. A white blood cell count lower than 7.4 × 10(9)/L was observed exclusively in patients with CA. No patient with HIV whose appendicitis was treated conservatively died or experienced a recurrence. We discuss our findings, which suggest the possibility of conservative treatment of appendicitis in patients with HIV and identification of CA by low CD4+ T-cell count.


Pharmacologic stimulation of erythrocyte 2,3-diphosphoglycerate production in vivo.
The ability of phosphate alone and in combination with sodium bicarbonate, vitamin C and pyruvate to elevate 2,3-diphosphoglycerate (DPG) levels was examined in normal human subjects in vivo. Statistically significant increases in DPG levels were noted (P less than .001) for all regimens pooled. Average rise in DPG levels reached 6% above pretreatment levels after 2 to 3 days of treatment. No changes in DPG levels were detectable in a group of control subjects over the same time period. Variation among pharmacologic trials and among subjects within trials in the actual magnitude of DPG build-up was marked. Significant differences could not be detected among the pharmacologic regimens in their ability to produce DPG increases. Previous reports suggested the use of these agents to stimulate red cell glycolysis but it seems that their effects and the mechanisms of glycolytic control in vivo are considerably more complex than has been previously suggested.


A Case of Ischemia-Induced Perianal Ulceration Mimicking Pyoderma Gangrenosum.
A 68-year-old woman, with a 75-pack-year smoking history and a history of chronic excess alcohol intake, presented with a 5-week history of worsening perianal pain and ulceration. She recently had an inpatient admission with back pain and urinary tract infection during which she developed diarrhea and fecal incontinence. Initially, the perianal ulceration was diagnosed as severe irritant contact dermatitis and treated with barrier creams and topical clobetasone 17-butyrate 0.05% weight for weight, oxytetracycline 3.0% weight for weight and nystatin cream (Trimovate®). Despite this, the ulceration progressed, resulting in hospital readmission 1 month later. There was no history of consumption of nicorandil (an antianginal therapy), of recurrent oral ulcers, or of inflammatory bowel disease. On examination, there were multiple areas of deep, sloughy ulceration bilaterally around the perianal and buttock regions with erythematous and violaceous edges (Figure 1). Complete blood count, blood film, rheumatoid factor, autoimmune and vasculitic profile, hepatitis screen, immunoglobulins and plasma protein electrophoresis were all normal. Punch biopsy revealed scanty dermal perivascular inflammatory cell infiltrate and occasional neutrophils (Figure 2). No evidence of granulomata, dysplasia, malignancy, or Langerhans histiocytes was identified, and periodic acid-Schiff staining was negative.


Optimization of image-forming optics for transmission optical projection tomography.
A new optical system for transmission optical projection tomography (TOPT) is presented to reduce the divergence of the projection data from the true parallel projections. This is performed by introducing an iris at the back focus of the objective lens. The influence of the defocusing on TOPT is demonstrated by computational simulations and experiments. We compare the performances of the new and conventional TOPT systems in order to optimize the optical system for three-dimensional imaging of the embryos of small animals. The optimal imaging performance is given by the new system with numerical apertures between 0.007 and 0.014, with which the spatial resolution of 25 microm is achieved. The optimal configuration is validated by TOPT of a phantom sample and a fixed five-day chick embryo.


Electrothermally driven flows in ac electrowetting.
Mixing within sessile drops can be enhanced by generating internal flow patterns using ac electrowetting. While for low ac frequencies, the flow patterns have been attributed to oscillations of the drop surface, we provide here the driving mechanism of the hitherto unexplained high-frequency flows. We show that: (1) the electric field in the liquid bulk becomes important, leading to energy dissipation due to Joule heating and a temperature increase of several degrees Celsius, and (2) the fluid flow at these frequencies is generated by electrothermal effect, i.e., gradients in temperature give rise to gradients in conductivity and permittivity, the electric field acting on these inhomogeneities induces an electrical body force that generates the flow. We solved numerically the equations for the electric, temperature and flow fields. The temperature is obtained from a convection-diffusion equation where Joule heating is introduced as a source term. From the solution of the electric field and the temperature, we compute the electrical force that acts as a body force in Stokes equations. Our numerical results agree with previous experimental observations.


Immunomodulation and Intestinal Morpho-Functional Aspects of a Novel Gram-Negative Bacterium Rouxiella badensis subsp. acadiensis.
A novel bacterium (Rouxiella badensis subsp. acadiensis) isolated from the microbiota of wild blueberry fruit was investigated for its immunomodulation capabilities and intestinal morpho-functional aspects. The whole-genome shotgun sequencing of this bacterium led to its new taxonomy and showed absence of pathogenicity genes. Although the bacterium was used for blueberry-fermentation and enhancing its anti-inflammatory effects on neurodegeneration, diabetes, and cancer, no study has assessed the effect of the bacterium on health. In this study, we used several in vitro and in vivo assays to evaluate the interaction of R. badensis subsp. acadiensis with the intestinal mucosa and its impact on the localized immune response. The strain antibiotic susceptibility has been investigated as well as its tolerance to gastric and intestinal environment and ability to attach to human intestinal epithelial cells (Caco-2 and HT-29). In addition, Balb/c mice were used to explore the immune-modulatory characteristics of the live bacterium at the intestinal level and its impact on the morpho-functional aspects of the intestinal mucosa. In vitro assays revealed the ability of R. badensis subsp. acadiensis to survive the gastric and intestinal simulated conditions and to satisfactorily adhere to the human intestinal epithelial cells. The bacterium was shown to be sensitive to an array of antibiotics. Immuno-modulation studies with mice orally administered with R. badensis subsp. acadiensis showed a higher number of IgA positive cells in the small intestine, a higher concentration of the anti-inflammatory cytokine IL-10 in the intestinal mucosa, as well as an increase in the number of goblet cells. The anti-inflammatory cytokine miR146a was found to be increased in the ileum and brain. Furthermore, it increases the number of goblet cells which contribute to intestinal barrier integrity. Taken together, our findings reflect the ability of the tested bacterium to modulates the intestinal homeostasis and immune response. Detailed safety unpublished studies and genome data support our finding. The strain Rouxiella badensis subsp. acadiensis has been filed in a provisional patent; a U.S. Provisional Application No. 62/916,921 entitled "Probiotics Composition and Methods." Future studies are still needed to validate the potential utilization of this strain as functional food and its potential probiotic effect.


Inhibition of vascular endothelial growth factor with a sequence-specific hypoxia response element antagonist.
Vascular endothelial growth factor (VEGF) and its receptors have been implicated as key factors in tumor angiogenesis that are up-regulated by hypoxia. We evaluated the effects of DNA-binding small molecules on hypoxia-inducible transcription of VEGF. A synthetic pyrrole-imidazole polyamide designed to bind the hypoxia response element (HRE) was found to disrupt hypoxia-inducible factor (HIF) binding to HRE. In cultured HeLa cells, this resulted in a reduction of VEGF mRNA and secreted protein levels. The observed effects were polyamide-specific and dose-dependent. Analysis of genome-wide effects of the HRE-specific polyamide revealed that a number of hypoxia-inducible genes were down-regulated. Pathway-based regulation of hypoxia-inducible gene expression with DNA-binding small molecules may represent a new approach for targeting angiogenesis.


Global gene expression analysis of cellular death mechanisms induced by mesoporous silica nanoparticle-based drug delivery system.
Mesoporous silica nanoparticles (MSNs), as one of the most promising inorganic drug carriers, have attracted ever increasing attention due to their unique structural, physicochemical, and biochemical features. Drug delivery systems (DDSs) based on MSNs could easily escape from endosomes after endocytosis and protect the loaded drugs from bioerosion by stable MSN carriers, efficiently deliver drugs intracellularly in a sustained release way, and consequently kill cancer cells at enhanced efficacy. However, the underlying pathways and mechanisms of cancer cell death induced by MSN-mediated drug delivery have not been well explored. In this study, we introduce gene expression analyses to evaluate the pathways and mechanisms of cancer cell death induced by a MSN-based drug delivery system. Unique changes in gene expressions and gene ontology terms, which were caused only by the MSN-based DDS (DOX-loaded MSNs, DOX@MSNs) but not by free drug doxorubicin (DOX) and/or the carrier MSNs, were discovered and proposed to be responsible for the varied cell death mechanisms, including the greatly enhanced necrosis due to amplified oxidative stress and the apoptosis related with DNA/RNA synthesis and cell cycle inhibitions. By virtue of a certain kind of synergetic biological effect between the drug and the carrier, the DOX@MSNs DDS was found capable of increasing the intracellular levels of reactive oxygen species and triggering the mitochondria-related autophagic lysosome pathway, consequently activating a specific pathway of necrosis, which is different from those by the free drug and the carrier.


Mood disorders in the female patient.
Disruptive changes in mood and low energy level are among the most common reasons women consult a physician. Usually no clear physiological explantation for these changes can be found. Many physicians feel uncomfortable dealing with patients with these complaints. The purpose of this paper is to discuss a practical approach to helping women with such conditions. A variety of terms have been utilized to refer to the situation in which a female patient has decreased energy or labile mood. Premenstrual Syndrome (PMS) and chronic fatigue syndrome (CFS) are currently popular terms. An association of low mood with menstrual cycle phase is undoubted, with the late luteal-early premenstrual phase most commonly associated with depression and irritability. It seems likely that women with PMS and those without it do not differ in circulating hormone levels during their cycles but rather in the brain response to these. Estrogen and progesterone receptors exist in the brain and change during the cycle. Elaborate diagnostic efforts are rarely rewarding in managing mood and energy disorders. Of more value is a careful history particularly concerned with the pattern of mood changes and with life stresses, accompanied by a thorough physical examination and laboratory tests. In most cases, changes in mood and energy are a variant of clinical depression. Changes in energy and sleep may be more evident than low affect. Treatment with an appropriate antidepressant, usually a selective serotonin re-uptake inhibitor (SSRI), benefits most of these patients. Allowing the patient to express concerns about stressful life situations is often of great value.


Impact of Canadian tobacco packaging policy on use of a toll-free quit-smoking line: an interrupted time-series analysis.
A policy for new pictorial health warning labels on tobacco packaging was introduced by Health Canada in 2012. The labels included, for the first time, a prominently displayed toll-free number for a quit-smoking line. We used data from the Ontario provincial quitline to investigate the call volume and number of new callers receiving treatment in the months before and after the new policy was introduced. We used an interrupted time-series analysis to examine trends in the overall call volume and number of new callers receiving treatment (≥ 1 telephone counselling session) through Ontario's quitline (Smokers' Helpline) between January 2010 and December 2013. We analyzed data using Box-Jenkins autoregressive integrated moving-average models; we adjusted the models for a major campaign promoting the quitline, a seasonality (January) effect and tobacco pricing. We found a relative increase of 160% in the average monthly call volume during the 7 months after the introduction of the new labels (870 calls per month at baseline and 1391 additional calls per month on average after the policy change; standard error [SE] 108.94, p < 0.001), and a sustained increase of 43% in subsequent months. We observed a relative increase of 174% in the number of new callers receiving treatment (153 new callers per month at baseline and 267 additional new callers per month after the policy change; SE 40.03, p < 0.001) and a sustained increase of 80% in subsequent months. The effect was significant even after controlling for a major promotion campaign and the January effect. We found a significant increase in the monthly overall call volume and number of new callers receiving treatment per month after the introduction of the new tobacco health warning labels, with a sustained increase in overall calls and new callers beyond the first 7 months. Our findings add to the body of evidence on the benefit of including a toll-free quitline number on tobacco packaging.


Deep Brain Stimulation-Possible Treatment Strategy for Pathologically Altered Body Weight?
The treatment of obesity and eating disorders such as binge-eating disorder or anorexia nervosa is challenging. Besides lifestyle changes and pharmacological options, bariatric surgery represents a well-established and effective-albeit invasive-treatment of obesity, whereas for binge-eating disorder and anorexia nervosa mostly psychotherapy options exist. Deep brain stimulation (DBS), a method that influences the neuronal network, is by now known for its safe and effective applicability in patients with Parkinson's disease. However, the use does not seem to be restricted to these patients. Recent preclinical and first clinical evidence points towards the use of DBS in patients with obesity and eating disorders as well. Depending on the targeted area in the brain, DBS can either inhibit food intake and body weight or stimulate energy intake and subsequently body weight. The current review focuses on preclinical and clinical evidence of DBS to modulate food intake and body weight and highlight the different brain areas targeted, stimulation protocols applied and downstream signaling modulated. Lastly, this review will also critically discuss potential safety issues and gaps in knowledge to promote further studies.


Electrolytes in hypertensive cardiovascular disease.
Nonpharmacologic measures have been increasingly applied to the management of patients with essential hypertension (EH). In this report, we review the published literature concerning dietary factors and blood pressure. Specifically, the impact of manipulations of dietary sodium, potassium, magnesium, and calcium on blood pressure are considered. The data support a beneficial role for calcium supplementation and sodium restriction and lesser roles for potassium supplementation in at least some hypertensive individuals. At this time, no dietary alteration can be recommended for broad application to the population as a whole.


Additive protection of aprotinin, protease inhibitor to cold cardioplegia from ischemic myocarium.
Protective action of aprotinin froom ischemic myocardial damage was evaluated in 9 patients compared to non-treated 18 patients, who underwent open heart surgery (22 ACB, 3 AVR and 2 MVR) with respect to the alterations of beta-glucronidase, acid-phosphatase, MB-CPK and m-GOT. Cold cardioplegia with glucose-insulin-potassium solution was used in this investigation. Average arrest time was 78.6 +/- 4.9 minutes associated with hypothermia between 25 and 28 degrees C in rectal temperature. Aprotinin was administered in 9 patients intravenously with 5,000 KIU/Kg 30 minutes prior to CPB and then 5,000 KIU/Kg in the prime solution. Activity of beta-glucronidase was significantly suppressed in the aprotinin-treated group compared to the non-treated group following cardioplegia and in the reperfusion period up to 6 hours, however, acid-phosphatase failed to demonstrate significant difference among two groups. Serum MB-CPK and m-GOT levels in the aprotinin-treated group did not elevate the beginning of reperfusion following cardioplegia. These data suggest that aprotinin add myocardial protection to cold cardioplegia.


Three regions of the pRB pocket domain affect its inactivation by human papillomavirus E7 proteins.
A critical event in papillomavirus transformation of human cells is the inactivation of pRB by the E7 protein. E7, like many other viral oncoproteins, possesses a well-characterized LXCXE peptide motif that interacts with the pocket domain of pRB. Disruption of the LXCXE-binding cleft on pRB renders it resistant to E7 binding and inactivation. Such binding cleft mutants of pRB are capable of inducing a G(1) arrest in the human papillomavirus 18-transformed HeLa cell line. We show here that the efficient inactivation of pRB in HeLa cells does not simply depend on the integrity of the LXCXE-binding cleft. Multiple site-directed mutants that alter conserved surfaces of the pRB pocket domain cause HeLa cells to accumulate in G(1). We divide these mutants into two classes: those that can be bound by E7 and those that cannot. The E7 interacting mutants include changes in conserved residues that lie in a groove between the A and B halves of the pocket. Surprisingly, none of these mutants show a clear defect in any of the known mechanisms for pRB inactivation by E7. Analysis of mutants that are compromised for E7 binding reveals that this interaction depends on both the LXCXE-binding cleft and on a conserved group of lysines adjacent to the cleft. These basic amino acids on pRB define a discrete interaction point with E7. These residues most likely form ionic interactions with conserved acidic amino acids on E7 since a stable pRB/E7 interaction was restored when the lysine residues on pRB and the acidic residues on E7 were interchanged.


Absorption and distribution of radioactivity from suppositories containing 3H-benzocaine in rats.
The effects of the suppository vehicle, drug concentration, and nonionic surfactants on in vitro benzocaine dialysis through a cellulose membrane and on rectal absorption in rats of total radioactivity following administration of 3H-benzocaine were investigated. In vitro dialysis correlated quite well with in vivo absorption, and drug release was greater from water-soluble vehicles than from oleaginous vehicles. Inclusion of a nonionic hydrophilic or lipophilic surfactant in cocoa butter resulted in a statistically significant increase for in vitro drug release, while a lipophilic surfactant showed little effect in vivo and a hydrophilic surfactant depressed release in vivo. Both types of surfactant had small effects on release from polyethylene glycol. In vitro release of benzocaine from some commercially available suppositories was compared with experimental preparations. Variation in blood radioactivity following administration of the same concentration of 3H-benzocaine in the same dosage form in male and female rats is reported.


[Preoperative chemotherapy of squamous cell carcinoma of the head and neck with V-T-M schedule (author's transl)].
13 patients with far advanced squamous cell carcinoma of the head and neck were treated with a low dose combination chemotherapy of Vincristine, Bleomycin and Methrotrexate during 7--8 weeks prior to surgery or radio-therapy. V-B-M was given as an out- patient regimen. 9 patients were treated the first time ever, 4 patients suffered of tumor-recurrence. 5 patients i.e. 38% achieved complete remission of all measurable disease, a total of 9 patients i.e. 69% achieved a partial remission of more than 50%. Prior treatment or localisation of tumor did not influence the results. Competent application warranted, toxicity was mild. The significance of pre-operatively achieved complete remission is discussed. Short-term follow up does not yet permit any statement upon survival.


Randomized Clinical Trial: Probiotics Alleviated Oral-Gut Microbiota Dysbiosis and Thyroid Hormone Withdrawal-Related Complications in Thyroid Cancer Patients Before Radioiodine Therapy Following Thyroidectomy.
Thyroid hormone withdrawal (THW) in postoperative thyroid cancer patients who need always accompanied by complications (e.g., dyslipidemia and constipation). At present, there are no effective and safe means to alleviate these complications. We aimed to assess the oral-gut microbiota profiles in THW patients then investigate whether probiotics could alleviating alleviate THW related complications and investigate whether these therapeutic effects were associated with the oral-gut microbiota state. Fifty eligible thyroid carcinoma patients undergoing thyroidectomy were randomly assigned to receive probiotics or placebo during THW. Complications were assessed through validated questionnaires and plasma lipid indicators. The complex probiotics preparation was composed of Bifidobacterium infantis, Lactobacillus acidophilus, Enterococcus faecalis, and Bacillus cereus. Probiotics alleviated lack of energy, constipation, weight gain, and dry mouth and decreased the levels of fecal/serum LPS and plasma lipid indicators (total cholesterol, triglycerides, low-density lipoprotein, and apolipoprotein A) (P < 0.05). Gut and oral microbial diversity were significantly decreased after THW, while an increased microbial dysbiosis index (MDI) was observed. Probiotics distinctly restored the gut and oral microbial diversity. Increased Holdemanella, Enterococcus, and Coprococcus_2, while decreased Fusobacterium, Eubacterium_ruminantium_group, Ruminococcus_1, and Parasutterella in the gut were found after probiotics intervention. Lack of energy, constipation, weight gain, and dyslipidemia were seen to be related to the above microbiota. In addition, probiotics reduced oral Prevotella_9, Haemophilus, Fusobacterium, and Lautropia, which were positively correlated with the occurrence of dry mouth. Probiotics reduce the incidence of complications in patients after THW, which may be related to modifying the oral and gut microbiota. [https://clinicaltrials.gov/], identifier America Clinical Trial Registry NCT03574051.


A vinylcyclobutane substrate designed as a cyclopropylcarbinyl radical probe.
Appending a spirocyclopropane linkage to bicyclo[3.2.0]hept-2-ene is achieved by selective kinetic cyclopropanation of 6-methylenebicyclo[3.2.0]hept-2-ene. The resultant vinylcyclobutane undergoes [1,3] migration as the dominant thermal process. A minor cyclopropylcarbinyl (CPC) rearrangement product clearly implicates a diradical transition structure. The presence and absence of other potential thermal products have enabled us to construct a detailed mechanistic proposal to account for all viable dynamic processes.


Development of a novel task for investigating decision making in a social context following traumatic brain injury.
Examination of social cognition as a target for assessment and intervention is beginning to gain momentum in a number of illnesses and acquired disorders. One facet of social cognition is decision making within interpersonal situations. This skill forms an important part of our everyday lives and is commonly impaired in those with neurological and mental health conditions. A novel task was developed to allow the assessment of decision making specifically within a social context and was examined within a group known to experience this difficulty. Participants with severe traumatic brain injury (TBI) were compared to healthy control participants on the Social Decision Making Task (SDMT), which required the participant to learn who the "friendly" players were in a game of toss. Participants also completed a nonsocial decision-making task, the Iowa Gambling Task (IGT) as well as a battery of neuropsychological tests and social cognition tasks. Current social functioning was also examined. Consistent with predictions, the TBI group made poorer decisions on the SDMT than the control group; however, group differences were not evident on the IGT. No significant relationships were observed between the SDMT and either measures of executive functioning (including working memory and reversal learning) or social cognition (including emotion recognition and theory of mind). Performance on the SDMT and the IGT were not associated, suggesting that the two tasks measure different constructs. The SDMT offers a novel way of examining decision making within a social context following TBI and may also be useful in other populations known to have specific social cognition impairment. Future research should aim to provide further clarification of the mechanisms of action and neuroanatomical correlates of poor performance on this task.


Staying in Motion After a Stroke: A Growing Number of Technologies Can Provide a Range of Options to Help Stroke Survivors Get Moving Again.
After suffering a stroke-perhaps a blood clot gets lodged in the brain or a blood vessel near the brain bursts-a person may suddenly not be able to hear, talk, or see. He or she might have trouble walking or exhibit a speech impediment. In fact, one of the greatest challenges of treating patients affected by stroke is that it's a heterogeneous condition, says Joel Stein, a physiatrist specializing in physical medicine and rehabilitation at Columbia University and Weill Cornell Medical College in New York City (Figure 1). "It can affect any area of the brain," he explains. "There are large and small strokes. There are strokes that bleed into the brain, or block blood vessels, so it's reasonable to believe that the recovery and treatment may not be the same for all these types of strokes."


[Mechanosensitivity of gramicidin A channels in semispherical bilayer membranes at constant tension].
Mechanoelectrical transduction in gramicidin A channels was studied in macroscopic planar lipid bilayer membranes bulged at constant tension. We found a supralinear increase in the single channel activity, which was proportional to the square of membrane radius but could not be accounted for by the increase in membrane surface area or by recruitment of new channels. When being extrapolated to biological membranes, these observations may suggest that the activity of permeability of ion channels can be influenced simply by changing the shape of the membrane, with or without stretching.


The Diagnosis Value of a Novel Model with 5 Circulating miRNAs for Liver Fibrosis in Patients with Chronic Hepatitis B.
Differential expression of five selected miRNAs (hsa-mir-1225-3p, hsa-mir-1238, hsa-miR-3162-3P, hsa-miR-4721, and hsa-miR-H7) was verified by qRT-PCR in the plasma of 83 patients and 20 healthy controls. The relative expression of these miRNAs was analyzed in different groups to screen target miRNA. A logistic regression analysis was performed to assess factors associated with fibrosis progression. The receiver operating characteristic (ROC) curve and discriminant analyses validated the ability of these predicted variables to discriminate the nonsignificant liver fibrosis group from the significant liver fibrosis group. Furthermore, the established models were compared with other prediction models to evaluate the diagnostic efficiency. These five tested miRNAs all had signature correlations with hepatic fibrotic level (p < 0.05), and the upregulation trends were consistent with miRNA microarray analysis previously. The multivariate logistic regression analysis identified that a model of five miRNAs (miR-5) had a high diagnostic accuracy in discrimination of different stages of liver fibrosis. The ROC showed that the miR-5 has excellent value in diagnosis of fibrosis, even better than the Forns score, FIB-4, S index, and APRI. GO functions of different miRNAs mainly involved in various biological processes were markedly involved in HBV and revealed signaling pathways dysregulated in liver fibrosis of CHB patients. It was validated that the combination of these five miRNAs was a new set of promising molecular diagnostic markers for liver fibrosis. The diagnosis model (miR-5) can distinguish significant and nonsignificant liver fibrosis with high sensitivity and specificity.


Toxin-antitoxin systems are ubiquitous and plasmid-encoded in vancomycin-resistant enterococci.
Vancomycin-resistant enterococci (VRE) are common hospital pathogens that are resistant to most major classes of antibiotics. The incidence of VRE is increasing rapidly, to the point where over one-quarter of enterococcal infections in intensive care units are now resistant to vancomycin. The exact mechanism by which VRE maintains its plasmid-encoded resistance genes is ill-defined, and novel targets for the treatment of VRE are lacking. In an effort to identify novel protein targets for the treatment of VRE infections, we probed the plasmids obtained from 75 VRE isolates for the presence of toxin-antitoxin (TA) gene systems. Remarkably, genes for one particular TA pair, the mazEF system (originally identified on the Escherichia coli chromosome), were present on plasmids from 75/75 (100%) of the isolates. Furthermore, mazEF was on the same plasmid as vanA in the vast majority of cases (>90%). Plasmid stability tests and RT-PCR raise the possibility that this plasmid-encoded mazEF is indeed functional in enterococci. Given this ubiquity of mazEF in VRE and the deleterious activity of the MazF toxin, disruption of mazEF with pharmacological agents is an attractive strategy for tailored antimicrobial therapy.