Copper(I) Complexes Containing PCP Ligand Catalyzed Hydrogenation of Carbon Dioxide to Formate under Ambient Conditions.
The five new copper(I) complexes [Cu2(μ-Cl)2(κ1-PCPt-Bu)] (1), [Cu2(μ-Br)2(κ1-PCPt-Bu)] (2), [Cu2(μ-I)2(κ1-PCPt-Bu)] (3), [Cu2(μ-CN)2(κ1-PCPt-Bu)] (4), and [Cu4(μ3-SCN)4(κ1-PCPt-Bu)2]·CH2Cl2 (5) bearing a 1,3-bis[(di-tert-butylphosphino)methyl]benzene ligand were synthesized and characterized spectroscopically, and the molecular structures of 1, 3, and 5 were determined by single-crystal X-ray diffraction techniques. Structural studies for 1 and 3 revealed their binuclear structures with Cu···Cu separations of 2.609(3) and 2.6359(19) Å, respectively. However, 5 has a tetranuclear cubane structure with an 18-electron configuration at each copper without any metal-metal bonds. The two copper centers in 1 and 3 are bonded to one bridging PCPt-Bu ligand in a κ1-manner and two bridging (pseudo)halido ligands in a μ2-bonding mode to generate a nonplanar Cu2(μ-X)2 framework. The four copper centers in 5 are at the vertices of a tetrahedron. Each copper center has pseudo-tetrahedral coordination provided by two bridging PCPt-Bu ligands in a κ1-manner and the four bridging thiocyanate groups in a μ3-manner. These complexes were used as catalysts for the hydrogenation of CO2 to formate in the presence of DBU as a base to produce valuable energy-rich chemicals, and therefore it is a promising, safe, and simple strategy to conduct reactions under ambient pressure at room temperature. Among all of the five copper(I) complex based catalysts, 3 displayed the best catalytic performance with turnover number (TON) values of 38-8700 in 12-48 h of reaction at 25-80 °C. The outstanding catalytic performance of [Cu2(μ-I)2(κ1-PCPt-Bu)] (3) makes it a potential candidate for realizing the large-scale production of formate by CO2 hydrogenation.


Origin of mineral crystal growth in collagen fibrils.
Collagen fibrils from young turkey-leg tendons, just beginning to mineralize, were stained with uranyl acetate and examined by electron microscopy. Small needle-like mineral crystals were observed and located, in relation to the collagen banding pattern, as originating at the e band in the gap region and near the surface of the fibrils. These are evidently the sites of crystal nucleation. They lie near binding locations on collagen fibrils of two glycosylated proteins believed to be implicated in the mineralization process, as well as the sites of early crystals in embryonic fowl bones.


Retinoic acid exerts neuroprotective effects against focal cerebral ischemia by preventing apoptotic cell death.
Cerebral ischemia is a neurological disorder that leads to cognitive decline and high mortality. Retinoic acid is a metabolite of vitamin A that has anti-inflammatory and anti-apoptotic effects. This study investigated whether retinoic acid prevents neuronal cell damage on focal cerebral ischemia through modulating apoptosis signaling pathway. Middle cerebral artery occlusion (MCAO) was performed to induce focal cerebral ischemia in adult male rats. Retinoic acid (5 mg/kg) or vehicle was injected intraperitoneally for 4 days prior to MCAO. Neurological behavior deficit tests were performed 24 h after MCAO. Brain edema and infarct volume were measured, and TUNEL histochemistry was carried out. We also investigated the changes in apoptosis-related proteins including bcl-2 family proteins and caspases. MCAO injury induced severe neurological behavior deficits and brain edema. It also increased infarct volume, histopathological damages, and the number of TUNEL-positive cells in cerebral cortex. However, retinoic acid pretreatment attenuated MCAO-induced neurological behavior deficits, brain edema, and infarction. It also alleviated histopathological lesion and decreased the number of TUNEL-positive cells. Bcl-2 and bax proteins are representative bcl-2 family proteins. MCAO injury induced a decrease in bcl-2 expression and an increase in bax expression, and retinoic acid pretreatment alleviated these changes. MCAO injury caused a decrease in bcl-2/bax expression ratio in cerebral cortex, while retinoic acid restored this decrease by MCAO. Moreover, our result showed increases in caspase-9, caspase-3, PARP protein levels in MCAO-operated animals. Retinoic acid pretreatment prevented these increases. We identified the changes in cleaved forms of these proteins, similar to the changes in full-length protein. Activation of caspases and PARP proteins are considered to be representative apoptosis indicators. This study showed that retinoic acid regulates bcl-2 family proteins and caspase proteins in focal cerebral ischemia. Thus, our findings demonstrate that retinoic acid exhibits a neuroprotective effect against ischemic damage by modulating apoptosis signaling pathway.


Modulation of intracellular calcium concentration by D2-like DA receptor agonists in non-peptidergic DRG neurons is mediated mainly by D4 receptor activation.
Nociceptive stimuli attributes are codified in the periphery; at this level, D2-like dopamine (DA) receptor activation decreases the high voltage-gated Ca2+ current predominantly in mechanonociceptive neurons, which explains the presynaptic action mechanism of the antinociception produced by quinpirole when it is intrathecally administered in rats. However, the identity of D2-like DA receptor subtype that mediates this effect remains unknown. To answer this question, we used Fluo-4-based Ca2+ microfluorometry to study the depolarization-elicited [Ca2+]i increase in small non-peptidergic DRG neurons (identified by its binding to the Isolectin B4), and to test the effect of D2-like DA receptor activation by quinpirole in presence of selective antagonists for D2, D3, and D4 DA receptors. The results showed a significantly greater contribution of the D4 DA receptor in the down-modulation of depolarization-elicited [Ca2+]i increase in small non-peptidergic DRG neurons compared to the other receptors. Although the D2 and D3 receptor antagonists also slightly inhibited the effect of quinpirole, their effects were significantly weaker than those of the D4 receptor antagonist. Furthermore, we showed that quinpirole selectively inhibits the CaV2.2 Ca2+ channels. Our results suggest that the activation of the D4 DA receptors is a promising strategy for pain management at the spinal cord level.


Detection of stent fractures: a comparison of 64-slice CT, conventional cine-angiography, and intravascular ultrasonography.
We evaluated the ability of 64-slice computed tomography (CT), conventional cine-angiography, and intravascular ultrasound (IVUS) to detect stent fractures under ideal conditions. Coronary stent fracture has been implicated as one of the mechanisms of stent thrombosis and, perhaps, in-stent restenosis. However, the preferred imaging modality in detecting fractures in coronary stents has not been well established. Four different types of commonly used coronary stents (Cypher, Taxus, Vision, Hepacoat) each with three strut fractures (Cypher, 5; Taxus, 5; Vision, 4; Hepacoat, 5) were nominally deployed in polyurethane tubes and imaged with 64-slice CT, conventional cine-angiography, and IVUS. For each stent type, an unfractured control stent was also imaged. Overall accuracy (84.1% vs. 73.9%), sensitivity (80.7 vs. 77.2%), and specificity (100% vs. 58.3%) for stent fracture detection was higher with 64 multislice CT compared to conventional cine-angiography. Stent fractures were not accurately detected by IVUS. Fracture detection by multislice CT was best when the stents were imaged at 45 degrees to the z-axis. Under ideal in vitro conditions, CT has a high accuracy when used to evaluate coronary stent fractures. The overall accuracy, sensitivity, and specificity of detecting stent fractures are lower by conventional cine-angiography. Stent fractures were not detected using IVUS.


AMPA-receptor-mediated excitatory synaptic transmission is enhanced by iron-induced α-synuclein oligomers.
Aggregated α-synuclein (α-syn) is a characteristic pathological finding in Parkinson's disease and related disorders, such as dementia with Lewy bodies. Recent evidence suggests that α-syn oligomers represent the principal neurotoxic species; however, the pathophysiological mechanisms are still not well understood. Here, we studied the neurophysiological effects of various biophysically-characterized preparations of α-syn aggregates on excitatory synaptic transmission in autaptic neuronal cultures. Nanomolar concentrations of large α-syn oligomers, generated by incubation with organic solvent and Fe(3+) ions, were found to selectivity enhance evoked α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-receptor, but not NMDA-receptor, mediated synaptic transmission within minutes. Moreover, the analysis of spontaneous AMPA-receptor-mediated miniature synaptic currents revealed an augmented frequency. These results collectively indicate that large α-syn oligomers alter both pre- and post-synaptic mechanisms of AMPA-receptor-mediated synaptic transmission. The augmented excitatory synaptic transmission may directly contribute to nerve cell death in synucleinopathies. Indeed, already low micromolar glutamate concentrations were found to be toxic in primary cultured neurons incubated with large α-syn oligomers. In conclusion, large α-syn oligomers enhance both pre- and post-synaptic AMPA-receptor-mediated synaptic transmission, thereby aggravating intracellular calcium dyshomeostasis and contributing to excitotoxic nerve cell death in synucleinopathies.


Synthesis and structure-activity relationships of dual histamine H2 and gastrin receptor antagonists with noncyclic gastrin receptor antagonistic moieties.
In order to study structure-activity relationships of dual histamine H2 and gastrin receptor antagonists as well as to improve their low oral absorbability, their prototype benzodiazepine gastrin receptor antagonistic moieties were altered to a conformationally flexible noncyclic dipeptide equivalent. This skeletal modification significantly potentiated the binding affinity of hybrid compounds for the histamine H2 receptor, whereas their affinity for the gastrin receptor and receptor selectivity over the CCK-A receptor varied widely with the substituents on the gastrin moiety. Among them, [3-[3-(3-piperidin-1-ylmethylphenoxy)propylcarbamoyl]p ropyl carbamic acid 3-[3-([(3-methoxyphenyl)[(methylphenylcarbamyl)methyl]carbamoyl]me thyl)ureido]benzyl ester (7a) showed the highest dual histamine H2 and gastrin receptor antagonistic activities. It also displayed distinct gastric acid antisecretory activity in vivo for two assays, namely, Schild's rat method by i.d. administration and the rat pylorus ligation method by oral administration. With the latter case, dose-response relationships were observed for the first time, suggesting its substantially improved oral absorbability. However, 7a did not display distinct in vivo gastric acid antisecretory activity for the assay with Heidenhain pouch dogs.


Aortic valve prolapse with aortic regurgitation assessed by Doppler color-flow echocardiography.
The incidence of and the Doppler color-flow echocardiographic characteristics of aortic valve prolapse with nonrheumatic aortic regurgitation were examined. Aortic valve prolapse was observed in 21 of 243 patients (15 men and 6 women) with aortic regurgitation as detected by Doppler color-flow echocardiography (rheumatic, 112; nonrheumatic, 131) in 1247 consecutive patients. Patients with aortic valve prolapse included three patients with essential hypertension and one with annuloaortic ectasia. The remaining 17 patients (7% of those with aortic regurgitation) had no other associated cardiovascular disease (idiopathic aortic valve prolapse). Prolapse of the mitral or the tricuspid valve or both was associated with aortic valve prolapse in seven patients. Aortic regurgitation jet was markedly deviated from the axis of left ventricular outflow tract toward the anterior mitral leaflet or the interventricular septum in 17 of 21 (81%) patients with aortic valve prolapse, whereas 28 of 110 (25%) patients with nonrheumatic aortic regurgitation without prolapse and 17 of 112 (15%) patients with rheumatic aortic regurgitation without prolapse showed the deviation of regurgitant jet (p < 0.001). In conclusion, idiopathic aortic valve prolapse is one of the significant causes of aortic regurgitation, and a marked deviation of regurgitant jet is a characteristic Doppler color-flow echocardiographic finding of aortic regurgitation that results from aortic valve prolapse.


Multifunctional Bi2S3/PLGA nanocapsule for combined HIFU/radiation therapy.
A multifunctional organic-inorganic hybrid nanocapsule based on Bi2S3-embedded poly (lactic-co-glycolic acid) (PLGA) nanocapsule has been elaborately designed to combine the merits of both polymeric shell structure and Bi2S3 nanoparticles. Hydrophobic Bi2S3 nanoparticles were successfully introduced into the PLGA nanocapsules via a facile and efficient water/oil/water (W/O/W) emulsion strategy. The elastic polymeric PLGA shell provides the excellent capability of ultrasound contrast imaging to the Bi2S3/PLGA. Meanwhile, the potential of these microcapsules to enhance the high intensity focused ultrasound (HIFU) therapy was demonstrated. Importantly, this research provided the first example of both in vitro and in vivo to demonstrate the radiosensitization effect of Bi2S3-embedded PLGA hybrid nanocapsules against prostate cancer under external X-ray irradiation. Thus, the successful integration of the Bi2S3 and PLGA nanocapsules provided an alternative strategy for the highly efficient ultrasound guided HIFU/RT synergistic therapy.


Clinico-demographic and survival profile of people living with HIV on antiretroviral treatment.
To assess the demographic, clinical, and survival profile of people living with HIV. A retrospective cohort study was conducted among patients enrolled at a single antiretroviral therapy center in North Karnataka. A total of 11,099 were recruited from April 2007 to January 2020, out of which 3,676 were excluded and the final 7,423 entries were subjected to analysis. The outcome of interest was the time to death in months of people living with HIV on antiretroviral therapy (ART). The clinical and demographic characteristics were examined as potential risk factors for survival analysis. To investigate the factors that influence the mortality of patients using ART, univariate and multivariate Cox regression were performed. Hazard ratio (HR), 95% confidence interval (CI), and p-values were presented to show the significance. The log-rank test was used to determine the significance of the Kaplan-Meier survival curve. Out of 7,423 HIV-positive people, majority were female (51.4%), heterosexual typology (89.2%), and in the age group 31-45 years (45.5%). The risk of death in male patients was 1.24 times higher (95% CI: 1.14-1.35) than female patients. Patients with age >45 were 1.67 times more likely to die than patients ≤30 (95% CI: 1.50-1.91). In the multivariable analysis, the hazards of mortality increased by 3.11 times (95% CI: 2.09-2.79) in patients with baseline CD4 count ≤50 as compared to those who had baseline CD4 count >200. The risk of death in patients who were diagnosed with TB was 1.30 times more (95% CI: 1.19-1.42) than in those who did not have TB. The survival probabilities at 3 and 90 months were more in female patients (93%, 70%) compared with male patients (89, 54%), respectively. This study proved that age, sex, baseline CD4 count, and tuberculosis (TB) status act as risk factors for mortality among people with HIV. Prevention strategies, control measures, and program planning should be done based on the sociodemographic determinants of mortality.


Cutaneous metastasis of castration-resistant prostate cancer: A rare case report and review of literature.
Carcinoma prostate is the second most common malignancy in males. It starts with a relatively indolent course and maybe asymptomatic during the initial stages. However, metastasis is highly common in Carcinoma prostate. The sites of metastases include bone, lung, liver, pleura and adrenals with cutaneous metastasis being one of the rarest sites being less than 1%. In our case report we present one such rare finding of Carcinoma prostate with cutaneous metastasis.


Characterization of organic cation/carnitine transporter family in human sperm.
Spermatozoan maturation, motility, and fertility are, in part, dependent upon the progressive increase in epididymal and spermatozoal carnitine, critical for mitochondrial fatty acid oxidation, as sperm pass from the caput to the cauda of the epididymis. We demonstrate that the organic cation/carnitine transporters, OCTN1, OCTN2, and OCTN3, are expressed in sperm as three distinct proteins with an expected molecular mass of 63 kDa, using Western blot analysis and our transporter-specific antibodies. Carnitine uptake studies in normal control human sperm samples further support the presence of high-affinity (OCTN2) carnitine uptake (K(m) of 3.39+/-1.16 microM; V(max) of 0.23+/-0.14 pmol/min/mg sperm protein; and mean+/-SD; n=12), intermediate-affinity (OCTN3) carnitine uptake (K(m) of 25.9+/-14.7 microM; V(max) of 1.49+/-1.03 pmol/min/mg protein; n=26), and low-affinity (OCTN1) carnitine uptake (K(m) of 412.6+/-191 microM; V(max) of 32.7+/-20.5 pmol/min/mg protein; n=18). Identification of individuals with defective sperm carnitine transport may provide potentially treatable etiologies of male infertility, responsive to L-carnitine supplementation.


Knowledge, practices and compliance related to COVID-19 among Nepalese population in Province 2, Nepal.
The study aimed to access the knowledge, practice, and compliance related to COVID-19 among people residing in Province 2, Nepal. A descriptive cross-sectional study was conducted from October 2020 to March 2021. A total of 457 participants of eight districts of Province 2 were enrolled after obtaining consent. Data were collected by face-to-face interviews with participants. A total of 31 validated pre-structured questionnaires were asked to participants in which 11 questions were for knowledge, 12 questions were for practices, and 8 questions were for compliance related to COVID-19. For tool validation, pre-testing was done in 10.0% of individuals of the targeted study population of Mahottari district. Out of 457 participants, 353(77.2%) were male. The majority of the participants were unmarried (68.3%), had only school-level education (26.5%), Hindu by religion (89.7%), farmers (23.0%), and businessmen (23.0%). More than 75.0% of individuals had knowledge about the causative agent of COVID-19 symptoms and the purpose of isolation. About 53.8% of participants had good knowledge of social distancing, 31.1% had knowledge of masks, and 39.3% knew about sanitizer. Moreover, 94.3% of the respondents had good knowledge of hand-washing practice with soap-water and use of sanitizer, 89.1% had good knowledge of wearing masks and 82.9% followed social distancing. Compliance with standard procedures of sneezing was recorded in 43.1%, washing hands with soap water/sanitizer was 82.3%, and disposal of masks was 53.6%. A significant association was observed between gender with knowledge and compliance (p < 0.05). District-wise association with knowledge, practice and compliance was found to be significant (p < 0.05). The findings suggest that participants have a good level of knowledge; however, the practice and compliances are considerably low related to COVID-19.


Mating behaviour in mixed infections of Schistosoma haematobium and S. mattheei.
In mixed infections of Schistosoma haematobium and S. mattheei, homospecific and heterospecific pairs are formed, with a preponderance of homospecific pairs indicating the existence of a mate preference system. S. haematobium apparently exhibits a greater specific mate recognition system than does S. mattheei. In sequential infections when mice are exposed to S. mattheei 4 weeks after infection with S. haematobium, S. haematobium males are better at pairing with S. mattheei females than are S. mattheei males. Hence, genetic exchanges between S. haematobium and S. mattheei giving rise to viable hybrids poses the problem of the genetic identity of these species of schistosomes. The most important reproductive isolating mechanisms are definitive host specificity, S. haematobium being primarily a parasite of man, whereas S. mattheei is a parasite of domestic stock and wild ungulates, and the preference for homospecific pairings in simultaneous infections. In contrast, when S. haematobium is the older infection, S. haematobium males are better than S. mattheei males at pairing with females of either species. Hybridisation is the likely outcome of such interactions. The lack of viability of S. mattheei male X S. haematobium female indicates genetic differences between the two species. Occurrences of natural hybridisation between S. haematobium and S. mattheei may lead to a change in the response of the parasite to chemotherapeutic treatment.


Fiber-in-tube solid-phase microextraction with molecularly imprinted coating for sensitive analysis of antibiotic drugs by high performance liquid chromatography.
An on line fiber-in-tube solid-phase microextraction (SPME) method was developed by longitudinally packing molecularly imprinted fibers (MIP-fibers) into PEEK tube as the online extraction unit. The obtained device therefore offers a reduced back pressure and rapid kinetics for its longitudinal channels, as well as possesses improved extraction capacity compared with traditional SPME method thanks to the increase of coating volume. In addition, the extraction of analytes was specific by using molecularly imprinted coatings, which greatly reduced the interference of sample matrix. To evaluate the new strategy, the PEEK tube was firstly packed with multiple ofloxacin imprinted fibers (OFL-MIP-fibers) for the analysis of four fluoroquinolones in animal-producing food samples. The extraction yields were significantly increased with the enrichment factors from 69 to 136. Sensitive results were achieved with the limits of detection as low as 0.016-0.11 μg/L (S/N=3). This method was applied successfully to analysis of fluoroquinolones in pork liver and chicken samples with good repeatability (RSDs less than 7.2%). To expand the method, the PEEK tube was then filling with two different fibers imprinted by ofloxacin and sulfamethazine respectively in order to obtain simultaneous extraction of these two categories of antibiotic drugs. Preliminary results showed the hybrid packing strategy could simultaneously enrich the target analytes from complicated samples. The possibility of applying the method to pork liver sample spiked with fluoroquinolones and sulfonamides was also studied.


Averaging is not everything: the saccade global effect weakens with increasing stimulus size.
When two elements are presented closely aligned, the average saccade endpoint will generally be located in between these two elements. This 'global effect' has been explained in terms of the center of gravity account which states that the saccade endpoint is based on the relative saliency of the different elements in the visual display. In the current study, we tested one of the implications of the center of gravity account: when two elements are presented closely aligned with the same size and the same distance from central fixation, the saccade should land on the intermediate location, irrespective of the stimulus size. To this end, two equally-sized elements were presented simultaneously and participants were required to execute an eye movement to the visual information presented on the display. Results showed that the strongest global effect was observed in the condition with smaller stimuli, whereas the saccade averaging was weaker when larger stimuli were presented. In a second experiment, in which only one element was presented, we observed that the width of the distribution of saccade endpoints is influenced by stimulus size in that the distribution is broader with smaller stimuli. We conclude that perfect saccade averaging is not always the default response by the oculomotor system. There appears to be a tendency to initiate an eye movement towards one of the visual elements, which becomes stronger with increasing stimulus size. This effect might be explained by an increased uncertainty in target localization for smaller stimuli, resulting in a higher probability of the merging of two stimulus representations into one representation.


[Pharmacodynamics study of suanzaoren decoction extracted by different technological process].
To select the optimal technological process for Suanzaoren decoction. The effects of extracts from different technological processes on spontaneous motion and sleep time in mice induced by pentobarbital sodium (subthreshold dosage) were studied. Both the decoction and 95% alcohol extract of Suanzaoren possess sedative and hypnotic effects. Suanzaoren aqueous decoction was selected as the optimal technological process.


Return to Work after Laparoscopic Hysterectomy
In Australia, return to work and full activity after abdominal hysterectomy is routinely delayed until the seventh postoperative week. We conducted a telephone survey of 100 women who had undergone laparoscopic-assisted hysterectomy inquiring, among other questions, when they had returned to full duties as well as when they felt they could have returned, if these were different. The mean time to return to full activity was markedly less than the standard 6 weeks. By changing the public perception and expectations regarding recovery after laparoscopic hysterectomy, we believe the procedure can be explained better by practitioners and will appear even more attractive to patients.


Molecular characterization and different expression patterns of the FABP gene family during goat skeletal muscle development.
The FABP (adipocyte fatty acid-binding protein) genes play an important role in intracellular fatty acid transport and considered to be candidate genes for fatness traits in domestic animal. In this study, we cloned the cDNA sequences of goat FABP family genes and their expression patterns were detected by semi-quantitative RT-PCR and quantitative real time RT-PCR. Expression analysis showed that goat FABP1 gene was predominantly expressed in liver, kidney and large intestine. While FABP4 was widely expressed in many tissues with a high expression level was observed in the fat, skeletal muscle, stomach and lung. Notably, FABP2 gene was expressed specifically in small intestine. Moreover, goat FABP3 was expressed at 60 day with the highest level, then significantly (p < 0.01) decreased at the 90 day. No significant expression differences were observed in longissimus dorsi muscles among 3 day, 30 day and 60 day. Goat FABP4 was expressed at 3 day with the lowest level, then significantly (p < 0.01) increased to a peak at the 60 day. In addition, a significant relationship between FABP3 mRNA expression levels and intramuscular fat (IMF) content was observed. These results suggest that the FABP3 and FABP4 may be important genes for meat quality and provides useful information for further studies on their roles in skeletal muscle IMF deposit.


Strong intramolecular hydrogen bonding in confined amino acids.
Intramolecular hydrogen bonding is evaluated in three different amino acids encapsulated in C60 fullerene in the context of electron density analysis. While conventional intramolecular hydrogen bonding in isolated amino acids are dominated by electrostatic character, it is shown that strong intramolecular hydrogen bonding can be formed in confined amino acids so that in two cases covalent intramolecular hydrogen bonding is appeared in the confined species. Also, results show that zwitterionic amino acids are stable in confined state, where no implicit or explicit solvation is applied. Covalent character for intramolecular hydrogen bonding in amino acids have not yet been reported.


Prevalence and associated risk factors of bovine trypanosomosis in tsetse suppression and non-suppression areas of South Omo Zone, Southwestern Ethiopia.
A cross-sectional study aimed to elucidate the prevalence of bovine trypanosomosis and its potential risk factors was conducted in tsetse suppression and non-suppression areas of South Omo Zone, Southern Ethiopia from November 2018- May 2019. A total of 1284 blood samples from local zebu cattle (642 each in dry and wet season) were examined by using buffy coat technique and thin blood smear method. The overall prevalence was 11.05 % with 14.33 % in dry and 7.78 % in wet season. According to multiple logistic regression analysis of tsetse suppression areas, higher prevalence in female than male (OR = 0.48, 95 % CI: 0.27, 0.83), in poor (OR = 3.25, 95 % CI: 1.26, 11.09) and medium (OR = 2.07, 95 % CI: 0.74, 7.37) than good body conditioned animals was recorded. Moreover, tethered animals (OR = 2.07, 95 % CI: 1.06, 3.92) were more likely to be infected than communal grazers and also higher prevalence in dry season than wet season (OR = 0.52, 95 % CI: 0.30, 0.87). Similarly, in tsetse non-suppression areas, higher prevalence in female than male (OR = 0.48, 95 % CI: 0.27, 0.85) and in wet season (OR = 0.41, 95 % CI: 0.23, 0.7) than dry season was recorded. Trypanosoma congolense and Trypanosoma vivax were found in cattle with the former more prevalent in both areas. Overall pooled mean packed cell volume (PCV) of parasitaemic animals (23.57 ± 3.13) was significantly lower than aparasitaemic animals (27.80 ± 4.95). Similarly, parasitaemic animals from tsetse suppression areas and tsetse non-suppression areas had significantly lower mean PCV than their aparasitaemic counterparts. Mean PCV of T. congolense (23.59 ± 3.22) infected animals was not different (P > 0.05) from T. vivax infected animals (23.26 ± 3.31). It was also indicated that the probability of anaemic animals to be parasitaemic was significantly higher (P < 0.05) than non-anaemic animals in both areas. In conclusion, the prevalence of trypanosomosis revealed its endemicity which bottlenecked the livestock production and productivity in the study area despite of tsetse suppression activities. Therefore, integrated parasite and vector control approach should be undertaken to curve the disease.


2-{5,5-Dimethyl-3-[2-(pyridin-2-yl)ethen-yl]cyclo-hex-2-enyl-idene}propane-dinitrile.
The mol-ecule of the title compound, C(18)H(17)N(3), with the exception of the -C(CH(3))(2) group, is nearly planar [maximum deviation: 0.208 (4), r.m.s. deviation 0.099 (6) Å] and the disubstituted C atom is displaced by 0.679 (2) Å from the mean plane through the remaining non-H atoms. In the crystal, the packing is stabilized by weak C-H⋯π inter-actions.


The effects of self-administered alcohol-induced 'hangover' in a naturalistic setting on psychomotor and cognitive performance and subjective state.
To examine in as naturalistic a setting as possible whether having an alcohol-induced 'hangover' impairs psychomotor and cognitive performance. The sample consisted of 71 male and female social drinkers who were tested twice, once at baseline and once after exposure to the study condition. They were randomized into a control group who returned for testing on a prearranged date (n = 33), and a group who were instructed to make arrangements to return the day after a self-determined heavy drinking session (n = 38). Of the 'hangover' group, 13 participants still had a blood alcohol concentration of >1 mg/100 ml at the time of testing and these were analysed separately. All participants were students. Psychomotor performance was assessed by means of a battery of psychomotor tasks, rate of information processing was tested by the Speed and Capacity of Language Processing Test (SCOLP) and subjective state was assessed by questionnaire measures. All participants in the 'hangover' group reported subjective and physical symptoms of hangover on the second testing session. Performance was significantly impaired on the hits-key components of the vigilance task, was less accurate on the primary and secondary reaction time tasks and showed greater dispersion in range of ability for participants in the 'acute and hangover' compared to 'control'. Probe memory revealed no significant group effect. Ratings of subjective state revealed significant group differences for the variables 'ability to drive', 'concentrate' and 'react quickly' as well as 'tiredness'. There were no group differences for performance on the SCOLP. Hangover had negative effects on self-reported subjective and physical state and subtle effects on performance.


Postoperative acute kidney injury after volatile or intravenous anesthesia: a meta-analysis.
Postoperative acute kidney injury (AKI) is a common complication after surgery. The pathophysiology of postoperative AKI is complex. One potentially important factor is anesthetic modality. We, therefore, conducted a meta-analysis of the available literature regarding anesthetic modality and incidence of postoperative AKI. Records were retrieved until January 17, 2023, with the search terms ("propofol" OR "intravenous") AND ("sevoflurane" OR "desflurane" OR "isoflurane" OR "volatile" OR "inhalational") AND ("acute kidney injury" OR "AKI"). A meta-analysis for common effects and random effects was performed after exclusion assessment. Eight records were included in the meta-analysis with a total of 15,140 patients (n = 7,542 propofol and n = 7,598 volatile). The common and random effects model revealed that propofol was associated with a lower incidence of postoperative AKI compared with volatile anesthesia [odds ratio: 0.63 (95% confidence interval: 0.56-0.72) and 0.49 (95% confidence interval: 0.33-0.73), respectively]. In conclusion, the meta-analysis revealed that propofol anesthesia is associated with a lower incidence of postoperative AKI compared with volatile anesthesia. This may motivate choosing propofol-based anesthesia in patients with increased risk of postoperative AKI due to preexisting renal impairment or surgery with a high risk of renal ischemia.NEW & NOTEWORTHY This study analyzed the available literature on anesthetic modality and incidence of postoperative AKI. The meta-analysis revealed that propofol is associated with lower incidence of AKI compared with volatile anesthesia. It might therefore be considerable to use propofol anesthesia in surgeries with increased susceptibility for developing renal injuries such as cardiopulmonary bypass and major abdominal surgery.


Metatranscriptomic analysis of ammonia-oxidizing organisms in an estuarine bacterioplankton assemblage.
Quantitative PCR (qPCR) analysis revealed elevated relative abundance (1.8% of prokaryotes) of marine group 1 Crenarchaeota (MG1C) in two samples of southeastern US coastal bacterioplankton, collected in August 2008, compared with samples collected from the same site at different times (mean 0.026%). We analyzed the MG1C sequences in metatranscriptomes from these samples to gain an insight into the metabolism of MG1C population growing in the environment, and for comparison with ammonia-oxidizing bacteria (AOB) in the same samples. Assemblies revealed low diversity within sequences assigned to most individual MG1C open reading frames (ORFs) and high homology with 'Candidatus Nitrosopumilus maritimus' strain SCM1 genome sequences. Reads assigned to ORFs for ammonia uptake and oxidation accounted for 37% of all MG1C transcripts. We did not recover any reads for Nmar_1354-Nmar_1357, proposed to encode components of an alternative, nitroxyl-based ammonia oxidation pathway; however, reads from Nmar_1259 and Nmar_1667, annotated as encoding a multicopper oxidase with homology to nirK, were abundant. Reads assigned to two homologous ORFs (Nmar_1201 and Nmar_1547), annotated as hypothetical proteins were also abundant, suggesting that their unknown function is important to MG1C. Superoxide dismutase and peroxiredoxin-like transcripts were more abundant in the MG1C transcript pool than in the complete metatranscriptome, suggesting an enhanced response to oxidative stress by the MG1C population. qPCR indicated low AOB abundance (0.0010% of prokaryotes), and we found no transcripts related to ammonia oxidation and only one RuBisCO transcript among the transcripts assigned to AOB, suggesting they were not responding to the same environmental cues as the MG1C population.


Investigation on the interaction of Rutin with serum albumins: Insights from spectroscopic and molecular docking techniques.
The binding interaction of Rutin, a flavonoid, with model transport proteins, bovine serum albumin (BSA) and human serum albumin (HSA), were investigated using different spectroscopic techniques, such as fluorescence, time-resolved single photon counting (TCSPC) and circular dichroism (CD) spectroscopy as well as molecular docking method. The emission studies revealed that the fluorescence quenching of BSA/HSA by Rutin occurred through a simultaneous static and dynamic quenching process, and we have evaluated both the quenching constants individually. The binding constants of Rutin-BSA and Rutin-HSA system were found to be 2.14 × 106 M-1 and 2.36 × 106 M-1 at 298 K respectively, which were quite high. Further, influence of some biologically significant metal ions (Ca2+, Zn2+ and Mg2+) on binding of Rutin to BSA and HSA were also investigated. Thermodynamic parameters justified the involvement of hydrogen bonding and weak van der Waals forces in the interaction of Rutin with both BSA and HSA. Further a site-marker competitive experiment was performed to evaluate Rutin binding site in the albumins. Additionally, the CD spectra of BSA and HSA revealed that the secondary structure of the proteins was perturbed in the presence of Rutin. Finally protein-ligand docking studies have also been performed to determine the probable location of the ligand molecule.


Dopaminergic involvement in the estrogen-induced suppression of frequency of pulsatile luteinizing hormone secretion in the ovariectomized rat.
This experiment examined whether various catecholaminergic synthesis inhibitors and receptor blockers affect the inhibitory effect on the frequency of pulsatile luteinizing hormone (LH) secretion induced by local application of estradiol benzoate (EB) into the preoptic suprachiasmatic area (POSC) of ovariectomized rats. Ovariectomized rats were pretreated with either alpha-methyl-p-tyrosine (AMPT; tyrosine hydroxylase inhibitor), AMPT plus threo-dihydroxyphenylserine (DOPS; norepinephrine precursor), diethyldithiocarbamate (DDC; dopamine-beta-hydroxylase inhibitor), pimozide (dopaminergic receptor blocker), phenoxybenzamine (alpha-adrenergic receptor blocker), propranolol (beta-adrenergic receptor blocker), or their vehicles. EB implantation into the POSC reduced the frequency of existing pulsatile LH secretion in vehicle-treated rats. Pretreatment of the rat with AMPT, AMPT plus DOPS, or pimozide did not affect the basal pulsatile LH secretion but eliminated the suppressive effect of EB implantation on the LH pulse frequency. In rats pretreated with DDC or phenoxybenzamine, basal pulsatile LH secretion was significantly inhibited, and EB implantation did not lower serum LH further in these rats. Propranolol had no obvious effect on either basal pulsatile LH secretion or EB-induced suppression of LH pulse frequency. These findings suggest that, in addition to the alpha-adrenergic involvement in maintaining the basal pulsatile LH secretion, the intact dopaminergic system is required for the suppression of the frequency of LH pulses induced by estrogen.


It's about who they are and what they can do: Māori perspectives on frailty in later life.
This study aimed to explore Māori (the indigenous people of Aotearoa New Zealand) understandings of frailty. Focus groups were held with older Māori in supported living, health professionals working with older Māori and a rural community. A qualitative thematic analysis was conducted. Two interlinked, overarching themes emerged: (1) Frailty is a multidimensional experience, not simply a physical one. (2) The experience of frailty is a balance between deficits and strengths. The Waikare o te Waka o Meihana model provided a useful framework for structuring the thematic results. Culturally appropriate and comprehensive support and care for older Māori with frailty will be facilitated by a rounded strength-based approach and listening skills.


Learning curve of liver stiffness measurement using a new hybrid machine composed of transient elastography interfaced with ultrasound.
To assess the learning curve for performing reliable liver stiffness measurements using a new hybrid machine composed of transient elastography (TE) interfaced with an ultrasound device for radiographers and radiologists with different levels of expertise in ultrasound imaging. Ten novice operators who had never performed TE measurements were prospectively evaluated from April to October 2018: senior radiologists, young radiologists, fellows, radiographers, and residents, with different levels of experience in abdominal ultrasound imaging. All operators had a short theoretical training followed by a training session under supervision in three patients. Then, each operator had to perform TE in 50 consecutive patients with chronic liver disease, using beforehand ultrasound examination to select measurement area in the right liver lobe, and if needed, the XL probe. Percentages of failures and reliable measurements were compared. The rates of failures of measurements, poorly reliable, reliable, and very reliable results, were of 4.2% (21/500), 2.4% (12/500), 47.6% (238/500), and 45.8% (229/500), respectively. The rates of reliable plus very reliable results were excellent, ranging from 91 to 96% among all the subgroups. The rates of very reliable, reliable, and unreliable results did not differ between operator subgroups and especially between junior radiologists, senior radiologists, and radiographers. No breaking point was observed in the interquartile range/median values over time. TE interfaced with ultrasound in this hybrid machine presents no learning curve effect. After a short initial training session, a novice observer is able to perform high rates of reliable and very reliable TE measurements. • When performing liver stiffness measurements using a new hybrid machine composed of transient elastography interfaced with ultrasound, the rate of failures of measurements is very low, below 5%. • After a short training session and using ultrasound planning, a novice operator, whatever its expertise in ultrasound imaging, is capable of performing high rates of reliable and very reliable measurements. • No learning curve is needed for performing reliable liver stiffness measurements using this new hybrid machine.


A single-strip mini-paper chromatographic method for rapid purity-control of 99mTc-labeled radiopharmaceuticals.
A single-strip miniaturized paper chromatographic method (Mini-PC) was developed using 80%-90% acetone solvent for rapid purity-control of 99mTc-radiopharmaceuticals. Routine 99mTc-radiopharmaceuticals (eight kinds of "kit" made agents) and diluted agents (in which radiochemical impurities might be formed) were analyzed by Mini-PC and other methods. This showed that, compared with the other methods, the Mini-PC technique is useful for the simple and rapid routine analysis of radiochemical impurities of "kit" made 99mTc-radiopharmaceuticals.


Bacterial infection and semen quality.
We have analyzed two infertile male cohorts with (n=39) and without genital tract infection (n=14) comparing their selected seminological parameters with healthy controls (n=30). Genital tract infection (GTI) has been defined by the presence of leukocytes and pathological bacterial strains identified with Bio-Merieux tests. We have found statistically significant deteriorated semen volume, sperm concentration, motility, morphology and vitality in ejaculated samples of patients with genital tract infection in comparison to healthy controls. Statistically significant negative influence towards sperm reproductive potential has been revealed in case of Escherichia coli, Ureaplasma urealyticum and Staphylococcus aureus.


Case management in the Community Psychiatric Nursing Service in Hong Kong: describing the process.
To explore the roles, functions, and work practices of case managers and their perceptions on the implementation of case management in the Community Psychiatric Nursing Services. A qualitative descriptive approach was used. Data were collected from daily reports, field observations, reflective diaries, and small group interviews. The study showed the work practices of case managers were more intensive compared to the conventional community psychiatric nursing practice, and there was more involvement of clients and their family in the treatment process. Case managers identified liaison, coordination, supportive and family counseling, and teaching practical living skills as their important roles. This study provides valuable information in understanding the process of case management and contributed to the development of case management as a care delivery model in Hong Kong.


Synthesis and antibacterial and antifungal activities of 5-nitro-2-furfurylidene polyhalophenoxyacethydrazides VIII.
Fifteen 5-nitro-2-furfurylidene phenoxyacethydrazides were synthesized, and the antibacterial and antifungal activities of the compounds prepared were determined against different microorganisms. The o-methoxy derivative was found to be the most active compound.


Sustainable utilization of foundry waste: Forecasting mechanical properties of foundry sand based concrete using multi-expression programming.
Waste Foundry sand (WFS), a major solid waste from metal casting industry, is posing a significant environmental threat owing to its disposal to landfills. In this research, an innovative artificial intelligence technique i.e. Multi-Expression Programming (MEP) is applied to model the split tensile strength (ST) and modulus of elasticity (E) of concrete containing waste foundry sand (CWFS). The presented formulations correlate mechanical properties with four input variables i.e. w/c, foundry sand content, superplasticizer content and compressive strength. The results of statistical analysis validate the model accuracy as evident by the low values of objective function (0.033 for E and 0.052 for ST). Moreover, the average error in the predicted values is significantly low i.e. 0.287 MPa and 1.75 GPa for ST and E model, respectively. Parametric study depicts that the models are well trained to accurately predict the trends of mechanical properties with variation in mix parameters. The prediction models can promote the usage of WFS in green concrete thereby preventing waste disposal and contributing towards and sustainable construction.


Flurbiprofen sodium microparticles and soft pellets for nose-to-brain delivery: Serum and brain levels in rats after nasal insufflation.
Neuroinflammation in Alzheimer's disease (AD) revamped the role of a preventive therapeutic action of non steroidal anti-inflammatory drugs; flurbiprofen could delay AD onset, provided its access to brain is enhanced and systemic exposure limited. Nasal administration could enable direct drug access to central nervous system (CNS) via nose-to-brain transport. Here, we investigated the insufflation, deposition, dissolution, transmucosal permeation, and in vivo transport to rat brain of flurbiprofen from nasal powders combined in an active device. Flurbiprofen sodium spray-dried microparticles as such, or soft pellets obtained by agglomeration of drug microparticles with excipients, were intranasally administered to rats by the pre-metered insufflator device. Blood and brain were collected to measure flurbiprofen levels. Excipient presence in soft pellets lowered the metered drug dose to insufflate. Nevertheless, efficiency of powder delivery by the device, measured as emitted fraction, was superior with soft pellets than microparticles, due to their coarse size. Both nasal powders resulted into rapid flurbiprofen absorption. Absolute bioavailability was 33% and 58% for microparticles and pellets, respectively. Compared to intravenous flurbiprofen, the microparticles were more efficient than soft pellets at enhancing direct drug transport to CNS. Direct Transport Percentage index evidenced that more than 60% of the intranasal dose reached the brain via direct nose-to-brain transport for both powders. Moreover, remarkable drug concentrations were measured in the olfactory bulb after microparticle delivery. Bulb connection with the entorhinal cortex, from where AD initiates, makes flurbiprofen sodium administration as nasal powder worth of further investigation in an animal model of neuroinflammation.


4-Hy-droxy-N'-(4-hy-droxy-3-nitro-benzyl-idene)benzohydrazide.
The mol-ecule of the title compound, C(14)H(11)N(3)O(5), assumes an E configuration with respect to the methyl-idene unit. An intra-molecular O-H⋯O hydrogen bond is present in the mol-ecule. The dihedral angle between the mean planes of the two benzene rings is 5.46 (15)°. The crystal structure is stabilized by inter-molecular O-H⋯O, O-H⋯N, and N-H⋯O hydrogen bonds.


Nonsense suppressors partially revert the decrease of the mRNA level of a nonsense mutant allele in yeast.
suc2 degrees is a naturally occurring amber mutant allele of the yeast invertase structural gene SUC2. Strains carrying suc2 degrees had only 10% of the wild type invertase-specific mRNA level. Amber suppressors, which allowed suc2 degree strains to ferment sucrose caused an increase of the SUC-specific mRNA level.


Specificity and reactivity of human leukocyte elastase, porcine pancreatic elastase, human granulocyte cathepsin G, and bovine pancreatic chymotrypsin with arylsulfonyl fluorides. Discovery of a new series of potent and specific irreversible elastase inhibitors.
The reactivity and specificity of a series of substituted benzenesulfonyl fluorides with human leukocyte (HL) elastase, cathepsin G, porcine pancreatic (PP) elastase, and bovine chymotrypsin A alpha are reported. Benzenesulfonyl fluorides with 2-fluoroacyl substituents were found to be potent and specific inhibitors of elastase. HL elastase was inhibited most rapidly by 2--(CF3CF2CONH)--C6H4SO4F (kobs/[I] = 1700 M-1 s-1) which is slightly better than our best peptide chloromethyl ketone inhibitor of this enzyme. PP elastase was most rapidly inhibited by 2--(CF3CONH)--C6H4-SO2F (kobs/[I] = 2300 M-1S-1). The 2--(CF3CF2CF2CONH) and 2--(CF3SNH) derivatives were quite selective for HL elastase and inhibited PP elastase, cathepsin G, and chymotrypsin A alpha quite slowly. A specific and potent chymotrypsin inhibitor (2--(Z--Gly--NH)--C6H4SO2F) was also discovered. A model for the elastase inhibition reaction is proposed which involves interaction of the fluroacyl group of the inhibitor with the primary substrate recognition site S1 of the enzyme. Hydrogen bonding also occurs between the inhibitor NH and a backbone peptide carbonyl group, probably from residue 214. The 2-fluoroacyl group plays the dual role of binding in the hydrophobic S1 pocket and through electronic effects, increasing the strength f the hydrogen bond. The results of this study demonstrate that it is possible to construct simple organic molecules which are specific inhibitors of HL elastase, PP elastase, or chymotrypsin.


Closed-set automatic speaker identification using multi-scale recurrent networks in non-native children.
Children may benefit from automatic speaker identification in a variety of applications, including child security, safety, and education. The key focus of this study is to develop a closed-set child speaker identification system for non-native speakers of English in both text-dependent and text-independent speech tasks in order to track how the speaker's fluency affects the system. The multi-scale wavelet scattering transform is used to compensate for concerns like the loss of high-frequency information caused by the most widely used mel frequency cepstral coefficients feature extractor. The proposed large-scale speaker identification system succeeds well by employing wavelet scattered Bi-LSTM. While this procedure is used to identify non-native children in multiple classes, average values of accuracy, precision, recall, and F-measure are being used to assess the performance of the model in text-independent and text-dependent tasks, which outperforms the existing models.


Overexpression of the regulator of G-protein signalling protein enhances ABA-mediated inhibition of root elongation and drought tolerance in Arabidopsis.
Regulator of G-protein signalling (RGS) proteins identified recently in Arabidopsis have been involved in the regulation of several physiological processes, but largely nothing is known about their roles at both the physiological and the molecular level. In the experiments reported here, the overexpression approach was used to present evidence that RGS1 protein plays critical roles in plant development and in modulating abscisic acid (ABA) and drought stress signal transduction. RGS1 affected the shapes of leaves, the development of floral buds, the elongation of stems, siliques, and hypocotyls, and the time of flowering. Post-germination growth was inhibited by 1 microM ABA, and root growth was hypersensitive to ABA for 35S-RGS1 transgenic plants. RGS1 overexpression conferred more drought tolerance to transgenic plants, as compared with the wild type (Columbia). Reverse transcription-PCR (RT-PCR) results indicated that RGS1 overexpresssion significantly stimulated the expression of NCED and ABA2, that encode two key enzymes catalysing ABA biosynthesis. Furthermore, the expression of several stress-regulated genes was either up- or down-regulated in RGS1-overexpressing transgenic plants. Combining the results above with previous results, it is suggested that RGS1 exerted its effects on plant responsiveness to ABA and drought tolerance largely through changing the expression either of genes responsible for ABA biosynthesis, which leads to changes in endogenous ABA levels, or of stress-responsive genes.


Selection of Mice for Object Permanence Cognitive Task Solution.
The selection of mice for high ("plus") and low ("minus") scores in the puzzle-box test was performed over five generations. This test evaluates the success (or failure) in finding the underpass, leading to the dark part of the box, when it is blocked. This means that the mouse is either able or unable to operate the "object permanence rule" (one of the index's cognitive abilities). For the "+" strain, animals were bred who solved the test when the underpass test blocked with a plug; the "-" strain comprised those who were unable to solve this task. In mice of the "+" strain, the proportion of animals that was able to solve "plug" stages of the test was higher than in the "-" strain and in the non-selected genetically heterogeneous population. The "+" mice ate significantly more new food in the hyponeophagia test. Animals of both strains demonstrated the ability to "manipulate" the plug blocking the underpass, touching the plug with their paws and muzzle, although the majority of "-" mice were unable to open the underpass effectively. Thus, mice of both selected strains demonstrated that they were able to understand that the underpass does exist, but only "+"-strain animals (at least the majority of them) were able to realize the solution. The selection for plug-stage solution success affected the mouse's ability to open the hidden underpass.


Ergoline derivatives with oral, prolonged, alpha-adrenolytic activity.
The alpha-adrenolytic activity of 1-methyl-10-methoxydihydrolysergol 2-(3,5-dimethyl)pyrrolcarboxylate (XV, formula II) is, both in vitro and parenterally, quite similar to that of dihydroergotamine. By oral route the new compound is more active, and longer lasting than dihydroergotamine.


Community-Based Risk Communication Survey: Risk Prevention Behaviors in Communities during the H1N1 crisis, 2010.
The present study aimed to investigate the prevalence of and factors associated with H1N1 preventive behaviors in a community-based population. A cross-sectional study was conducted in three urban and two rural communities in Korea. Interviews were conducted with 3462 individuals (1608 men and 1854 women) aged ≥ 19 years during February-March 2010. Influenza-related information including anxiety, preventive behaviors and their perceived effectiveness, vaccination status, past influenza-like illness symptoms, and sources of and trust in information was obtained. Among 3462 participants, 173 reported experiencing influenza-like illness symptoms within the past 12 months. The mean H1N1 preventive behavior score was 25.5 ± 5.5 (out of a possible 40). The percent of participants reporting high perceived effectiveness and high anxiety was 46.2% and 21.4%, respectively. After controlling for potential confounders, H1N1 preventive behavior scores were predicted by a high (β = 3.577, p < 0.001) or moderate (β = 2.529, p < 0.001) perception of their effectiveness. Similarly, moderate (β = 1.516, p < 0.001) and high (β = 4.103, p < 0.001) anxiety scores predicted high preventive behavior scores. Effective methods of promoting population behavior change may be nationwide campaigns through mass media, as well as education and promotion by health care providers and broadcasters.


Impaired sweating as an exocrine manifestation in Sjögren's syndrome.
To examine the prevalence of hypohidrosis and to quantitate sweating as an exocrinopathy in Sjögren's syndrome (SS), 49 patients with SS (primary form, 38; secondary form, 11) were studied. Sweating was induced by mental stimulation such as deep breathing or hand grasping. Statistically significant reductions of sweat volume were seen in SS (P < 0.005). Patients under 50 years old showed impaired sweat function compared with normal controls (P < 0.0005). In a control study, only haemodialysis patients showed impairment of sweating and this was greater than in patients with SS aged under 50 years. These results suggest that patients with SS develop impaired sweating as an exocrine manifestation in addition to the known symptoms of xerostomia and xerophthalmus.


Influence of extracellular polymeric substances on the heteroaggregation between CeO2 nanoparticles and soil mineral particles.
Interaction with soil mineral particles (SMPs) and organic matters can significantly determine the fate of nanoparticles (NPs) in the environment such as waters, sediments, and soils. In this study, the heteroaggregation of CeO2 NPs with different soil minerals (kaolinite, montmorillonite, goethite and hematite) and the influence of extracellular polymeric substance (EPS) were studied. The obvious heteroaggregation between CeO2 NPs with different SMPs were demonstrated via co-settling and aggregation kinetics experiments. The variety in the heteroaggregation between CeO2 NPs with different SMPs is mainly induced by the difference in their surface properties, such as surface charge, specific surface areas and surface complexation. The presence of EPS can result in great inhibition on the heteroaggregation between CeO2 NPs with the positive charged goethite by enhancing the electrostatic repulsion between NPs and mineral colloids. However, the influence of EPS on the interaction between CeO2 NPs with negative charged SMPs is more dependent on the steric stabilization. The presence of EPS may promote the migration of CeO2 NPs in environment and then increase their risks to human health and ecosystems. These findings contribute to better understanding interactions between NPs and SMPs and have important implications on predicting the behaviors and risks of NPs in the natural environment.


Mild clinical expression of Lambert-Eaton myasthenic syndrome in a patient with HIV infection.
Neuromuscular complications of HIV are related to immunodeficiency, direct cytotoxicity of the virus or side effect of the treatments. Autoimmune disorders involving the nervous system, including Guillain-Barre syndrome, myositis and vasculitis, have been described in association with HIV. Neuromuscular junction autoimmune diseases such as myasthenia gravis have been occasionally reported in patients with HIV, whereas the Lambert-Eaton myasthenic syndrome (LEMS) has never been described. We report an unusual case of paucisymptomatic LEMS in a patient with HIV infection.


Therapeutic Effect of Curcumin in Women with Polycystic Ovary Syndrome Receiving Metformin: A Randomized Controlled Trial.
Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility, for which the insulin sensitizer metformin has been used therapeutically. It has been shown that curcumin also exhibits insulin-sensitizing properties. Given that metformin acts as an ovulation inducing agent and both curcumin and metformin can reduce insulin resistance, the aim of the current study was to evaluate the effect of metformin with and without curcumin nanomicelles in the treatment of women with polycystic ovary syndrome. This clinical trial was conducted on 100 women with PCOS, diagnosed according to the Rotterdam criteria, who were sequentially recruited and randomly divided into two groups (n = 50 each). Group 1 received 500 mg metformin three times daily and group 2 received 80 mg/day capsule of curcumin nanomicelle and 500 mg metformin three times a day for 3 months. After collecting fasting blood samples, biochemical parameters including triglycerides, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol, plasma glucose, alanine amino transferase (ALT) and aspartate aminotransferase (AST) were evaluated based on enzymatic methods. Hormonal parameters were assessed using immunoassay kits. Insulin resistance (HOMA-IR) and insulin-sensitivity check index (QUICKI) were also assessed. After treatment, fasting insulin, HOMA-IR, and total testosterone in group 2 were significantly lower than those in group 1 (p < 0.05). Post-treatment LDL-C levels in groups 1 and 2 were 117.9 ± 24 and 91.12 ± 19.46 mg/dL, respectively (p < 0.01). In addition, HDL-C levels were increased with curcumin (group 1: 38.1 ± 4.36 mg/dL; group 2: 44.12 ± 7.3 mg/dL, p < 0.05). Total cholesterol was decreased with curcumin level (group 1: 207.9 ± 39.84 mg/dL; group 2; 159.7 ± 48.43 mg/dL, p < 0.05), with a decrease in triglycerides levels (group 1: 141.6 ± 9.57; group 2: 97.5 ± 8.8 mg/dL, p < 0.01). This study showed that curcumin has a synergistic effect with metformin in the improvement of insulin resistance and lipid profile in patients with PCOS. Therefore, the combined use of metformin and curcumin may have therapeutic utility in patients with PCOS.


Molecular Link in Flavonoid and Amino Acid Biosynthesis Contributes to the Flavor of Changqing Tea in Different Seasons.
The present study was aimed to elucidate the flavor formation mechanism of Changqing tea. High-performance liquid chromatography (HPLC) analysis showed that the total catechins of Changqing tea was 65-160 mg/g, with 16-34 mg/g non-galloyated catechins and 49-126 mg/g galloylated catechins. Tea polyphenols and free amino acids account for 286-312 mg/g and 35-89 mg/g, respectively. Transcriptome of Changqing tea during different seasons revealed 316, 130 and 12 DEGs in comparisons of spring vs. autumn, spring vs. summer, and summer vs. autumn, respectively. Compared to spring, the genes involved in flavonoid biosynthesis and bitter imparted amino acids were up-regulated in summer and autumn. Metabolome analysis was conducted by using HPLC-MS; the result indicated that umami and kokumi contributing amino acids were decreased in summer and autumn compared with spring. It could be concluded that the coordination of flavonoid biosynthesis and amino acids biosynthesis resulted in the special flavor of Changqing tea.


The influence of traumatic intrusion of primary teeth on their permanent successors. A radiographic and histologic study in monkeys.
Intrusion of maxillary central primary incisors was performed in 18 green vervet monkeys (Cercopithecus aethiops) with the purpose of studying early and late histologic changes in odontogenesis of permanent tooth germs and the effect of treatment of primary tooth injury. Immediate changes were studied in five monkeys where both maxillary central primary incisors were intruded. The monkeys were sacrificed 10-15 min after intrusion. The immediate changes in the permanent tooth germ consisted of contusion and displacement of the reduced enamel epithelium and slight displacement of the hard dental tissue in relation to the cervical loop, or Hertwig's epithelial root sheath. Late changes and effect of treatment were studied in 13 monkeys where both maxillary central incisors were intruded. One central primary incisor was removed 1 hour after intrusion while the other incisor was allowed to remain in the jaw. The monkeys were sacrificed 6 weeks after injury and the anterior portion of the maxilla was examined histometrically. The late changes consisted of metaplasia of the reduced enamel epithelium into a stratified squamous epithelium and, in most cases, changes in morphology of the dentin and enamel matrices. On the side where the injured tooth was preserved, significantly larger areas of epithelial metaplasia of the reduced enamel epithelium were present compared with the extraction side. Changes in morphology of the enamel matrix and dentin were found with the same frequency in the two groups, but tended to be less severe in the extraction group. It is concluded that more studies are needed on the effect of metaplasia of the reduced enamel epithelium on complete mineralization of the enamel before an optimal treatment of intruded primary incisors can be determined.


Sleep in multiple sclerosis and neuromyelitis optica spectrum disorder-the SEMN study.
This study aimed to (1) evaluate in patients with multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) the presence of sleep disorders such as hypersomnia, fatigue, risk of apnea, and the presence of restless legs syndrome/Willis-Ekbom disease (RLS/WED); (2) evaluate quality of sleep in patients with MS and NMOSD; and (3) correlate them with clinical and imaging data. The study was cross-sectional and was carried out in the sector of demyelinating diseases of the neurology service of HUGV-UFAM, Manaus, Brazil, from January 2017 to December 2020. Our sample consisted of 60 patients, 41 with MS and 19 with NMOSD. We found that patients with MS and NMOSD have poor sleep quality (65%) and hypersomnia (53% in MS; 47% in NMOSD), but low risk of apnea by STOP-BANG. The frequency of RLS/WE found was 14% in MS, and 5% in NMOSD. No correlation existed between sleep quality, number of relapses, and sleep quality for the Expanded Disability Status Scale (EDSS), i.e., fatigue/illness duration. Patients with MS and NMOSD have poor sleep quality, excessive sleepiness, and are at low risk for OSA, yet the frequency of RLS/WED is like that of the general population. There does not seem to be a significant difference between these sleep disorders in these demyelinating diseases of the CNS.


Charge Transport in Organic Semiconductors: The Perspective from Nonadiabatic Molecular Dynamics.
Organic semiconductors (OSs) are an exciting class of materials that have enabled disruptive technologies in this century including large-area electronics, flexible displays, and inexpensive solar cells. All of these technologies rely on the motion of electrical charges within the material and the diffusivity of these charges critically determines their performance. In this respect, it is remarkable that the nature of the charge transport in these materials has puzzled the community for so many years, even for apparently simple systems such as molecular single crystals: some experiments would better fit an interpretation in terms of a localized particle picture, akin to molecular or biological electron transfer, while others are in better agreement with a wave-like interpretation, more akin to band transport in metals.Exciting recent progress in the theory and simulation of charge carrier transport in OSs has now led to a unified understanding of these disparate findings, and this Account will review one of these tools developed in our laboratory in some detail: direct charge carrier propagation by quantum-classical nonadiabatic molecular dynamics. One finds that even in defect-free crystals the charge carrier can either localize on a single molecule or substantially delocalize over a large number of molecules depending on the relative strength of electronic couplings between the molecules, reorganization, or charge trapping energy of the molecule and thermal fluctuations of electronic couplings and site energies, also known as electron-phonon couplings.Our simulations predict that in molecular OSs exhibiting some of the highest measured charge mobilities to date, the charge carrier forms "flickering" polarons, objects that are delocalized over 10-20 molecules on average and that constantly change their shape and extension under the influence of thermal disorder. The flickering polarons propagate through the OS by short (≈10 fs long) bursts of the wave function that lead to an expansion of the polaron to about twice its size, resulting in spatial displacement, carrier diffusion, charge mobility, and electrical conductivity. Arguably best termed "transient delocalization", this mechanistic scenario is very similar to the one assumed in transient localization theory and supports its assertions. We also review recent applications of our methodology to charge transport in disordered and nanocrystalline samples, which allows us to understand the influence of defects and grain boundaries on the charge propagation.Unfortunately, the energetically favorable packing structures of typical OSs, whether molecular or polymeric, places fundamental constraints on charge mobilities/electronic conductivity compared to inorganic semiconductors, which limits their range of applications. In this Account, we review the design rules that could pave the way for new very high-mobility OS materials and we argue that 2D covalent organic frameworks are one of the most promising candidates to satisfy them.We conclude that our nonadiabatic dynamics method is a powerful approach for predicting charge carrier transport in crystalline and disordered materials. We close with a brief outlook on extensions of the method to exciton transport, dissociation, and recombination. This will bring us a step closer to an understanding of the birth, survival, and annihiliation of charges at interfaces of optoelectronic devices.


Self-relevance modulates brain responses to angry body expressions.
In a social context, the direction of the body of surrounding agents indicates whether one is the potential target of an impending action or simply an observer, and thus influences the way one processes and reacts to their emotional expressions. The present functional magnetic resonance imaging experiment investigated how self-relevance influences anger processing in the brain by independently manipulating target (oriented to self or to other) and emotion (neutral and anger). The perception of body expression of anger elicits activity in a previously identified network that includes the amygdala, the fusiform gyrus, the superior temporal sulcus and the premotor cortex. Activity within this network is independent of body direction and is parametrically modulated by the intensity of the bodily emotional expression. Moreover, the ventromedial prefrontal cortex and somatosensory cortices responded preferentially to anger expressions oriented to self. We suggest that these brain areas may participate in the selection of specific behavioural strategies when one is the potential target of someone's anger.


The effects of vasoactive agents, platelet agonists and anticoagulation on thrombelastography.
Platelet activation is a critical step in primary hemostasis and clot formation. We tested a hypothesis that platelet stimulating effects of vasoactive agents or platelet agonists could be shown using thrombelastography (TEG) as faster onset or increased clot strength. We further examined if TEG could be modified to evaluate activated platelets as a reversal of anticoagulation in the presence of partial thrombin inhibition. Blood samples were obtained from 126 non-cardiac surgical patients. Effects of vasoactive agents on TEG and aggregometry were examined using epinephrine, norepinephrine, vasopressin, desmopressin acetate, milrinone and olprinone (Experiment I). Platelet agonists (epinephrine, ADP and collagen) were separately tested on TEG (Experiment II). Effects of platelet agonists (ADP and collagen) on TEG under anticoagulation in the absence or presence of abciximab were studied (Experiment III). We also tested antiplatelet effects of milrinone and olprinone in the presence of anticoagulants on TEG (Experiment IV). Neither vasoactive agents nor platelet agonists affected TEG or aggregometry results except for milrinone and olprinone on aggregometry (Experiment I, II). Platelet agonists facilitated clotting in the presence of anticoagulants (Experiment III). Abciximab-treated platelets still exhibited procoagulant effects in the presence of heparin, while not in the presence of argatroban (Experiment III). Platelet inhibition on the modified TEG was more extensive with milrinone than olprinone, and it was dose dependent (Experiment IV). Modified TEG using heparin or argatroban might delineate the procoagulant effects of platelets by adding platelet specific agonist.


Natural anticoagulants: A missing link in mild to moderate bleeding tendencies.
There is a growing interest in natural anticoagulants as a cause of mild to moderate bleeding disorders (MBDs), particularly in patients with bleeding of unknown cause (BUC), which is defined as having a mild to moderate bleeding phenotype without a definite diagnosis despite exhaustive and repeated laboratory investigations. Recently, abnormalities in two natural anticoagulant pathways, thrombomodulin (TM), and tissue factor pathway inhibitor (TFPI), were identified in single patients or families as the underlying cause for a bleeding tendency. The objective of this review is to discuss the current understanding of the role of natural anticoagulants in MBDs using available clinical and translational data. A Cochrane Library and PubMed (MEDLINE) search focusing on selected natural anticoagulants and their role in MBDs was conducted. Data on the influence of natural anticoagulants including protein C, protein S, antithrombin, TM, and TFPI or factors with anticoagulant properties like fibrinogen gamma prime (γ') on MBDs are scarce. Observations from sepsis treatment and from translational research highlight their importance as regulators of the haemostatic balance, especially via the activated protein C-related pathway, and suggest a role in some MBDs. Similar to the distinct genetic variants of natural anticoagulants linked to thrombosis, we hypothesize that novel variants may be associated with a bleeding tendency and could be identified using next generation sequencing.


EZH2-mediated H3K27me3 promotes autoimmune hepatitis progression by regulating macrophage polarization.
Autoimmune hepatitis (AIH) is a chronic progressive liver disease related to abnormal immune stimulation, leading to liver cirrhosis, liver cancer and liver failure. There is an urgent need to find novel biomarkers and potential drug targets for effective treatment of the disease. Although previous studies have shown that EZH2, as a histone methyltransferase, plays critical roles in tumor and autoimmune diseases, its role in autoimmune hepatitis remains largely unknown. In this study, we reported that the EZH2 and H3K27me3 expression level was significantly upregulated in liver tissues during the progression of AIH. High expression of EZH2 enhanced autoimmune hepatitis, immune response and liver fibrosis through H3K27me3. EZH2 inhibition induced the phenotype of hepatic macrophages to switch from M1 to M2 in the development of AIH. These findings indicated that EZH2-mediated H3K27me3 promoted autoimmune hepatitis by regulating the polarization of hepatic macrophages. EZH2 may be a promising therapeutic target for the prevention or treatment of autoimmune hepatitis.


Activation of collagenase production in a rat macrophage-like cell line.
Collagenase activity from a rat macrophage line, AK-5, has been studied. The enzyme is present in these cells and its release is stimulated by Con A, LPS and a lymphokine preparation from rat spleen cells. Collagenase activity from these cells is inhibited by EDTA, cysteine or dithiothreitol, thereby suggesting it to be similar to other mammalian collagenases.


Lack of spirometry use in Danish patients initiating medication targeting obstructive lung disease.
Research indicates that a large proportion of patients using medication targeting obstructive lung disease have no history of spirometry testing. To investigate the use of spirometry when initiating pulmonary medication targeting obstructive lung disease and to explore possible patient characteristics associated with undergoing spirometry. Population-based cohort study. Three Danish National registers were linked enabling a retrieval of data on all primary and secondary healthcare services provided in the time period 2007-2010. In 2008 a total of 40,969 patients were registered as first time users of pulmonary medication targeting obstructive lung disease. The mean age of the study cohort was 55.6 yrs (SD 18.7). Spirometry test had been performed in 20,262 (49.5%) of the study cohort in the period from 6 months before to 12 months after their first prescription. Just above one third of the cohort, 14,275 (34.8%), had undergone spirometry in the two-month period close to redemption of their first prescription. Women and patients in the oldest age categories were less likely to have spirometry performed. Many patients initiate medication targeting obstructive pulmonary disease without having airway obstruction confirmed through spirometry. Only one third of the study cohort had a spirometry performed when initiating medication and half had still not undergone spirometry after a year. There should be an increased focus on confirming airway obstruction when initiating medication.


Raf-induced vascular endothelial growth factor augments Kaposi's sarcoma-associated herpesvirus infection.
Recombinant green fluorescent protein encoding Kaposi's sarcoma-associated herpesvirus (rKSHV.152) infection of beta-estradiol stimulated human foreskin fibroblasts (HFF) or HFF/DeltaB-Raf([FF]):ER (expressing a weaker form of B-Raf) could be enhanced to levels comparable to that of HFF/DeltaB-Raf([DD]):ER cells by pretreating cells with soluble vascular endothelial growth factor (VEGF). Conversely, VEGF expression and infection efficiency typically observed in beta-estradiol stimulated HFF/DeltaB-Raf([DD]):ER cells could be lowered significantly by treating with VEGF small interfering RNA. In addition, we observed enhancement of the KSHV infection in HFF cells transfected with human VEGF(121). These results confirm the ability of Raf-induced VEGF to augment KSHV infection of cells.


Intracellular protein topogenesis.
Concurrently with or shortly after their synthesis on ribosomes, numerous specific proteins are unidirectionally translocated across or asymmetrically integrated into distinct cellular membranes. Thereafter, subpopulations of these proteins need to be sorted from each other and routed for export or targeted to other intracellular membranes or compartments. It is hypothesized here that the information for these processes, termed "protein topogenesis," is encoded in discrete "topogenic" sequences that constitute a permanent or transient part of the polypeptide chain. The repertoire of distinct topogenic sequences is predicted to be relatively small because many different proteins would be topologically equivalent-i.e., targeted to the same intracellular address. The information content of topogenic sequences would be decoded and processed by distinct effectors. Four types of topogenic sequences could be distinguished: signal sequences, stop-transfer sequences, sorting sequences, and insertion sequences. Signal sequences initiate translocation of proteins across specific membranes. They would be decoded and processed by protein translocators that, by virtue of their signal sequence-specific domain and their unique location in distinct cellular membranes, effect unidirectional translocation of proteins across specific cellular membranes. Stop-transfer sequences interrupt the translocation process that was previously initiated by a signal sequence and, by excluding a distinct segment of the polypeptide chain from translocation, yield asymmetric integration of proteins into translocation-competent membranes. Sorting sequences would act as determinants for posttranslocational traffic of subpopulations of proteins, originating in translocation-competent donor membranes (and compartments) and going to translocation-incompetent receiver membranes (and compartments). Finally, insertion sequences initiate unilateral integration of proteins into the lipid bilayer without the mediation of a distinct protein effector. Examples are given for topogenic sequences, either alone or in combination, to provide the information for the location of proteins in any of the intracellular compartments or for the asymmetric orientation of proteins and their location in any of the cellular membranes. Proposals are made concerning the evolution of topogenic sequences and the relationship of protein topogenesis to the precellular evolution of membranes and compartments.


The effects of lisuride and some other dopaminergic agonists on receptor binding in human brain.
The effect of lisuride, bromocriptine, CQ 32-084 and CU 32-085 on the specific binding of radiolabelled spiperone to homogenates of human putamen taken post-mortem has been investigated. In addition, the binding of 3H-lisuride to such preparations has been studied. Lisuride is found to inhibit spiperone binding to the dopamine receptor at very low concentrations and to bind to the beta-adrenergic receptor at somewhat higher levels. Lisuride binding to the dopamine receptor was found to be antagonist-like. A measure of the in vivo effect of lisuride was obtained from investigations of brain tissue taken from a patient treated with the drug before death.


Characterization of unique functionalities in c-Src domains required for osteoclast podosome belt formation.
Deletion of c-Src, a ubiquitously expressed tyrosine kinase, results in osteoclast dysfunction and osteopetrosis, in which bones harden into "stone." In contrast, deletion of the genes encoding other members of the Src family kinase (SFK) fails to produce an osteopetrotic phenotype. This suggests that c-Src performs a unique function in the osteoclast that cannot be compensated for by other SFKs. We aimed to identify the molecular basis of this unique role in osteoclasts and bone resorption. We found that c-Src, Lyn, and Fyn were the most highly expressed SFKs in WT osteoclasts, whereas Hck, Lck, Blk, and Fgr displayed low levels of expression. Formation of the podosome belt, clusters of unique actin assemblies, was disrupted in src-/- osteoclasts; introduction of constitutively activated SFKs revealed that only c-Src and Fyn could restore this process. To identify the key structural domains responsible, we constructed chimeric Src-Hck and Src-Lyn constructs in which the unique, SH3, SH2, or catalytic domains had been swapped. We found that the Src unique, SH3, and kinase domains were each crucial to establish Src functionality. The SH2 domain could however be substituted with Lyn or Hck SH2 domains. Furthermore, we demonstrate that c-Src's functionality is, in part, derived from an SH3-proximal proline-rich domain interaction with c-Cbl, leading to phosphorylation of c-Cbl Tyr700. These data help clarify Src's unique functionality in the organization of the cytoskeleton in osteoclasts, required for efficient bone resorption and explain why c-Src cannot be replaced, in osteoclasts, by other SFKs.


HPLC purification of the main allergen of Parietaria judaica pollen.
A two-step purification procedure of Par j I from the whole Parietaria judaica pollen extract is described. The first step consisted of gel filtration HPLC using a TSKG 3000 SW column, and 0.1% trifluoroacetic acid as the eluant. By this method, proteins were separated from the highly colored material present in the extract. Then, Par j I-containing fractions were chromatographed on a reversed-phase HPLC column (Vydac C4) using an acetonitrile gradient. This second step yielded pure Par j I as assessed by SDS-PAGE and CIE. Previously reported microheterogeneity was still observed, but amino acid analysis of various RP-HPLC fractions suggested that the heterogeneity of Par j I might not be due to changes in its primary structure. Allergenic activity of Par j I was shown to be retained after the purification procedure by several immunochemical techniques.


Nuclear factor-kappaB bioluminescence imaging-guided transcriptomic analysis for the assessment of host-biomaterial interaction in vivo.
Establishment of a comprehensive platform for the assessment of host-biomaterial interaction in vivo is an important issue. Nuclear factor-kappaB (NF-kappaB) is an inducible transcription factor that is activated by numerous stimuli. Therefore, NF-kappaB-dependent luminescent signal in transgenic mice carrying the luciferase genes was used as the guide to monitor the biomaterials-affected organs, and transcriptomic analysis was further applied to evaluate the complex host responses in affected organs in this study. In vivo imaging showed that genipin-cross-linked gelatin conduit (GGC) implantation evoked the strong NF-kappaB activity at 6h in the implanted region, and transcriptomic analysis showed that the expressions of interleukin-6 (IL-6), IL-24, and IL-1 family were up-regulated. A strong luminescent signal was observed in spleen on 14 d, suggesting that GGC implantation might elicit the biological events in spleen. Transcriptomic analysis of spleen showed that 13 Kyoto Encyclopedia of Genes and Genomes pathways belonging to cell cycles, immune responses, and metabolism were significantly altered by GGC implants. Connectivity Map analysis suggested that the gene signatures of GGC were similar to those of compounds that affect lipid or glucose metabolism. GeneSetTest analysis further showed that host responses to GGC implants might be related to diseases states, especially the metabolic and cardiovascular diseases. In conclusion, our data provided a concept of molecular imaging-guided transcriptomic platform for the evaluation and the prediction of host-biomaterial interaction in vivo.


Correction to: Taurine Ameliorates High Glucose Induced Apoptosis in HT-22 Cells.
Affiliations of authors Muhammad Shahbaz and Shahid Alam were incorrect in the published book. This has now been corrected as below.


Expression of neuronal nitric oxide synthase in the pancreas of the sheep.
In numerous mammals, nitric oxide (NO) influences the activity of the exocrine and endocrine pancreas. In this study, immunocytochemistry was utilized to investigate the expression of neuronal nitric oxide synthase (nNOS) in the pancreas of sheep. In double immunocytochemical staining, the co-localization of nNOS with vasoactive intestinal polypeptide (VIP), neuropeptide Y (NPY) or substance P (SP) was studied. The presence of nNOS was confined to the intrapancreatic neurones (9.6 +/- 1.3%) as well as to nerve fibres of the endocrine pancreas and intrapancreatic ganglia. nNOS-immunoreactive (IR) neurones were round and oval in shape and predominantly (83.3 +/- 2.6%) belonged to the middle-size group (25-50 mum). Numerous, fine islets supplying nNOS-IR nerve terminals were devoid of VIP, SP or NPY. Moderately numerous, non-varicose nNOS-IR nerve fibres of intrapancreatic ganglia frequently expressed VIP or NPY, but not SP; 2.2 +/- 0.6% of nNOS-IR intrapancreatic neurones displayed lack of VIP, whereas 7.5 +/- 0.8% were VIP-IR. All nNOS-IR neurones were devoid of SP. The frequencies of nNOS-IR/NPY-IR and nNOS-IR/NPY-negative intrapancreatic neurones were 2.2 +/- 0.4% and 6.1 +/- 1.1%, respectively. Comparison with other mammals indicated that nitrergic innervation of the ovine pancreas is species-determined and may be a reflection of the ruminants' digestion specificity. The possible origin of nNOS-IR nerve fibres and functional significance of NO in the pancreas of sheep were discussed.


Per Oral Endoscopic Myotomy for the Management of Achalasia in a Patient with Prior Lap Band, Sleeve Gastrectomy, and Roux-en-Y Gastric Bypass.
Achalasia after bariatric surgery is a rare pathological entity. Nonetheless, several cases have been described in literature. Per oral endoscopic myotomy has recently emerged as the preferred approach for the management of esophageal motility disorders. We report a video case of POEM performed in a female patient with prior multiple bariatric surgical procedures. In her past medical history, she underwent to laparoscopic lap band, sleeve gastrectomy, and Roux-Y-gastric bypass. POEM was carried out without complication. Myotomy was performed only for 1 cm below the cardias due to the presence of the gastro-jejunal anastomosis. Post-operative course was uneventful and oral diet was restarted after one day. At 2 months follow-up, the patient is asymptomatic with no weight regain. We report the first case of POEM after three different bariatric surgical procedure. Fibrosis due to prior interventions did not hampered POEM procedure, and the shorter myotomy due to the presence of small gastric pouch did not reduced its efficacy.


Amino acids substitutions in σ1 and μ1 outer capsid proteins of a Vero cell-adapted mammalian orthoreovirus are required for optimal virus binding and disassembly.
In a recent study, the serotype 3 Dearing strain of mammalian orthoreovirus was adapted to Vero cells; cells that exhibit a limited ability to support the early steps of reovirus uncoating and are unable to produce interferon as an antiviral response upon infection. The Vero cell-adapted virus (VeroAV) exhibits amino acids substitutions in both the σ1 and μ1 outer capsid proteins but no changes in the σ3 protein. Accordingly, the virus was shown not to behave as a classical uncoating mutant. In the present study, an increased ability of the virus to bind at the Vero cell surface was observed and is likely associated with an increased ability to bind onto cell-surface sialic acid residues. In addition, the kinetics of μ1 disassembly from the virions appears to be altered. The plasmid-based reverse genetics approach confirmed the importance of σ1 amino acids substitutions in VeroAV's ability to efficiently infect Vero cells, although μ1 co-adaptation appears necessary to optimize viral infection. This approach of combining in vitro selection of reoviruses with reverse genetics to identify pertinent amino acids substitutions appears promising in the context of eventual reovirus modification to increase its potential as an oncolytic virus.


Edge Distance-based Topological Indices of Strength-weighted Graphs and their Application to Coronoid Systems, Carbon Nanocones and SiO2 Nanostructures.
The edge-Wiener index is conceived in analogous to the traditional Wiener index and it is defined as the sum of distances between all pairs of edges of a graph G. In the recent years, it has received considerable attention for determining the variations of its computation. Motivated by the method of computation of the traditional Wiener index based on canonical metric representation, we present the techniques to compute the edge-Wiener and vertex-edge-Wiener indices of G by dissecting the original graph G into smaller strength-weighted quotient graphs with respect to Djoković-Winkler relation. These techniques have been applied to compute the exact analytic expressions for the edge-Wiener and vertex-edge-Wiener indices of coronoid systems, carbon nanocones and SiO2 nanostructures. In addition, we have reduced these techniques to the subdivision of partial cubes and applied to the circumcoronene series of benzenoid systems.


Age and sex dependent alteration in presenilin expression in mouse cerebral cortex.
(1) Presenilin (PS) expression is regulated by several cellular and extracellular factors which change with age and sex. Both age and sex are key risk factors for Alzheimer's disease (AD), which is linked to mutations in PS genes. (2) We have analyzed the effect of age and sex on PS expression by northern hybridization and western blot analysis using the cerebral cortex of adult (24 +/- 2 weeks) and old (65 +/- 5 weeks) mice. (3) Our results demonstrate that PS1 was downregulated and PS 2 was upregulated in old mice of both sexes. The level of PS 1 was relatively higher and that of PS 2 was lower in female than male mice of same age group. Taken together, these findings show age and sex dependent alteration in PS expression, which in turn may influence the signal transduction pathways and consequently brain functions.


Post-translational modification of MALT1 and its role in B cell- and T cell-related diseases.
Mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a multifunctional protein. MALT1 functions as an adaptor protein to assemble and recruit proteins such as B-cell lymphoma 10 (BCL10) and caspase-recruitment domain (CARD)-containing coiled-coil protein 11 (CARD11). Conversely it also acts as a paracaspase to cleave specified substrates. Because of its involvement in immunity, inflammation and cancer through its dual functions of scaffolding and catalytic activity, MALT1 is becoming a promising therapeutic target in B cell- and T cell-related diseases. There is growing evidence that the function of MALT1 is subtly modulated via post-translational modifications. This review summarized recent progress in relevant studies regarding the physiological and pathophysiological functions of MALT1, post-translational modifications of MALT1 and its role in B cell- and T cell- related diseases. In addition, the current available MALT1 inhibitors were also discussed.


Leucocyte adherence inhibition: a microassay demonstrating antigen recognition in cattle.
Calves, sensitised by cutaneous application of dinitrochlorobenzene, developed lesions of delayed hypersensitivity at the sites of application nine to 14 days later. Leucocytes from sensitised calves, collected 10 to 16 days after sensitisation, reacted in an in vitro leucocyte adherence inhibition test with the same hapten in water soluble form, dinitrobenzenesulphonate. The leucocyte adherence inhibition microtest which was simple, rapid, reproducible and amenable to rigorous statistical analysis, should find use in many areas of bovine immunology.


Melphalan, Etoposide, and Carboplatin Megatherapy with Autologous Stem Cell Transplantation in Children with Relapsing or Therapy-Resistant Extracranial Germ-Cell Tumors-A Retrospective Analysis.
Pediatric germ cell tumors (GCTs) are a group of chemosensitive malignancies with a 90% curability rate. We report a series of children with relapsing or therapy-resistant GCT treated with melphalan-etoposide-carboplatin high-dose chemotherapy (HDCT) and autologous stem cell transplantation. This consisted of 18 children, either with GCTs after relapse (nine patients) or with an unsatisfactory response to first-line chemotherapy (nine patients), who underwent HDCT. The HDCT regimens MEC1 (carboplatin 1500 mg/m2, etoposide 1800 mg/m2, and melphalan 140 mg/m2) and MEC2 (carboplatin 800 mg/m2, etoposide 800 mg/m2, and melphalan 140 mg/m2) were each used in nine patients. The median observation time was 81 months, the 5-year overall survival (OS) was 76%, and the event-free survival (EFS) was 70.8%. Non-relapse mortality was 0%, and four patients died after HDCT due to progression of the malignancy. No difference in OS or EFS was noted between the MEC1 and MEC2 protocols. The 5-year OS and 5-year EFS were higher in children treated with autologous stem cell transplantation before the age of four years. The presence of metastatic disease or time of HDCT consolidation during first/subsequent line chemotherapy did not affect patient survival. The melphalan-etoposide-carboplatin protocol is feasible in pediatric GCT, but is associated with potentially life-threatening complications. In conclusion, the use of HDCT must be examined in well-designed clinical trials, and the identification of patients who can benefit from this approach is critical to avoid overtreatment.


Expression control of the AMPK regulatory subunit and its functional significance in yeast ER stress response.
AMP-activated protein kinase (AMPK) is an evolutionarily conserved heterotrimeric kinase complex consisting of a catalytic subunit, α, and two regulatory subunits, β and γ. Previously, we demonstrated that Snf1, the Saccharomyces cerevisiae ortholog of AMPK, negatively regulates the unfolded protein response (UPR) pathway and the Hog1 MAP kinase pathway in ER stress response. However, it remains unclear how the alternate three β subunits, Sip1, Sip2, and Gal83, of the Snf1 complex participate in ER stress response. Here, we show that Gal83 plays a major role in Snf1-mediated downregulation of the UPR and Hog1 pathways. Gal83 is the most abundant β subunit in the normal state and further induced by ER stress. This induction is mediated via activation of the GAL83 promoter by the UPR. When expressed under the control of the GAL83 promoter, Sip2 exhibits potent functional activity equivalent to Gal83. Our results suggest that the functional significance of the β subunit of Snf1 AMPK in ER stress response is defined by modulation of the expression level through regulation of the promoter activity.