Electricity system based on 100% renewable energy for India and SAARC.
The developing region of SAARC (South Asian Association for Regional Cooperation) is home to a large number of people living below the poverty line. In future, providing affordable, universally accessible, reliable, low to zero carbon electricity in this region will be the main aim. A cost optimal 100% renewable energy system is simulated for SAARC for the year 2030 on an hourly resolved basis. The region was divided into 16 sub-regions and three different scenarios were set up based on the level of high voltage direct current (HVDC) grid connections. The results obtained for a total system levelised cost of electricity (LCOE) showed a decrease from 71.6 €/MWh in a decentralized to 67.2 €/MWh for a centralized grid connected scenario. An additional scenario was simulated to show the benefits of integrating industrial gas production and seawater reverse osmosis desalination demand, and showed the system cost decreased by 5% and total electricity generation decreased by 1%. The results show that a 100% renewable energy system could be a reality in the SAARC region with the cost assumptions used in this research and it may be more cost competitive than nuclear and fossil carbon capture and storage (CCS) alternatives. One of the limitations of this study is the cost of land for installation of renewables which is not included in the LCOE calculations, but regarded as a minor contribution.


The impact of two workplace-based health risk appraisal interventions on employee lifestyle parameters, mental health and work ability: results of a randomized controlled trial.
Health risk appraisals (HRA) are a common type of workplace health promotion programme offered by American employers. In the United Kingdom, evidence of their effectiveness for promoting health behaviour change remains inconclusive. This randomized controlled trial examined the effects of two HRA interventions on lifestyle parameters, mental health and work ability in a UK context. A total of 180 employees were randomized into one of three groups: Group A (HRA augmented with health promotion and education activities), Group B (HRA only) and Group C (control, no intervention). After 12 months, changes in mean scoring in 10 lifestyle, mental health and work ability indices were compared, Groups A and B demonstrated non-significant improvements in 70% and 80%, respectively, compared with controls (40%). Odds ratios revealed that, compared with the control group, Group A was 29.2 (95% CI: 9.22-92.27) times more likely to report a perceived change in lifestyle behaviour; Group B 4.4 times (95% CI: 1.65-11.44). In conclusion, participation in the HRA was associated with a higher likelihood of perceived lifestyle behaviour change which was further increased in the augmented HRA group, thereby providing preliminary evidence that HRA and augmented HRA in particular may help UK employees make positive healthy lifestyle changes.


Influence of mixing regime on enzymatic saccharification of steam-exploded softwood chips.
In an attempt to elucidate the effect of reduced mixing on the enzymatic hydrolysis of lignocellulosic feedstocks, a pretreated softwood substrate was hydrolyzed under various mixing regimes using a commercial cellulase mixture. The substrate was generated by SO2-catalyzed steam explosion of Douglas fir wood chips followed by alkali-peroxide treatment to remove lignin. Three mixing regimes were tested; continuous mixing at low (25 rpm) and high (150 rpm) speeds, and mixing at low-speed interspersed with 5-min intervals of high-speed agitation at 150 rpm. At both substrate concentrations (7.5 and 10% [w/w]), the mixed-speed mixing was able to produce sufficiently high conversion rates and yields (93% after 96 h), close or slightly better than those obtained under vigorous mixing (150 rpm). The low-speed shaking produced appreciably lower conversion yields at both levels of substrate concentration. Therefore, the mixed-speed regime may be a viable process option, because it does not seem to have an adverse impact on the cellulose conversion yield and can be an effective means of reducing the mixing energy requirements of an enzymatic hydrolysis process.


White matter microstructure and connectivity changes after surgery in male adults with obstructive sleep apnea: recovery or reorganization?
Obstructive sleep apnea (OSA) is a prevalent clinical problem significantly affecting cognitive functions. Surgical treatment is recommended for those unable to use continuous positive airway pressure. We aimed to investigate the therapeutic effect of upper airway surgery on the white matter (WM) microstructure and brain connectivity in patients with OSA. Twenty-one male patients with moderate-to-severe OSA were recruited for multi-level upper airway surgery. Overnight polysomnography (PSG), neuropsychiatric tests, and brain MRI scans were acquired before and 6.1 ± 0.8 months after surgery. Nineteen male patients with untreated OSA were also included as a reference group. We calculated the longitudinal changes of diffusion tensor imaging (DTI) parameters, including fractional anisotropy (ΔFA) and mean/axial/radial diffusivity (ΔMD/AD/RD). We also assessed changes in network properties based on graph theory. Surgically treated patients showed improvement in PSG parameters and verbal memory after surgery. Globally, ΔFA was significantly higher and ΔRD was lower in the surgery group than in the untreated group. Especially ΔFA of the tracts involved in the limbic system was higher after surgery. In network analysis, higher Δbetweenness and lower Δclustering coefficients were observed in the surgical group than in the untreated group. Finally, the improvement of verbal memory after surgery positively correlated with ΔFA in superior thalamic radiation (p = 0.021), fronto aslant tracts (p = 0.027), and forceps minor tracts (p = 0.032). Surgical treatment of OSA can alleviate alterations in WM integrity and disruptions in local networks, particularly for the tracts involved in the limbic system. These findings may further explain the cognitive improvement observed after the treatment of OSA.


Photobioreactor design: Mixing, carbon utilization, and oxygen accumulation.
Photobioreactor design and operation are discussed in terms of mixing, carbon utilization, and the accumulation of photosynthetically produced oxygen. The open raceway pond is the primary type of reactor considered; however small diameter (1-5 cm) horizontal glass tubular reactors are compared to ponds in several respects. These are representative of the diversity in photobioreactor design: low capital cost, open systems and high capital cost, closed systems. Two 100-m(2) raceways were operated to provide input data and to validate analytical results. With a planktonic Chlorella sp., no significant difference in productivity was noted between one pond mixed at 30 cm/s and another mixed from 1 to 30 cm/s. Thus, power consumption or CO(2) outgassing limits maximal mixing velocities. Mixing power inputs measured in 100-m(2) ponds agreed fairly well with those calculated by the use of Manning's equation. A typically configured tubular reactor flowing full (1 cm diameter, 30 cm/s) consumes 10 times as much energy as a typical pond (20 cm deep flowing at 20 cm/s). Tubular reactors that flow only partially full would be limited by large hydraulic head losses to very short sections (as little as 2 m length at 30 cm/s flow) or very low flow velocities. Open ponds have greater CO(2) storage capacity than tubular reactors because of their greater culture volume per square meter (100-300 L/m(2) vs. 8-40 L/m(2) for 1-5-cm tubes). However, after recarbonation, open ponds tend to desorb CO(2) to the atmosphere. Thus ponds must be operated at higher pH and lower alkalinity than would be possible with tubular reactors if cost of carbon is a constraint. The mass transfer coefficient, K(L), for CO(2) release through the surface of a 100-m(2) pond was determined to be 0.10 m/h. Oxygen buildup would be a serious problem with any enclosed reactor, especially small-diameter tubes. At maximal rates of photosynthesis, a 1-cm tubular reactor would accumulate 8-10 mg O(2)/L/min. This may result in concentrations of oxygen reaching 100 mg/L, even with very frequent gas exchange. In an open pond, dissolved oxygen rises much more slowly as a consequence of the much greater volume per unit surface area and the outgassing of oxygen to the atmosphere. The maximum concentration of dissolved oxygen is typically 25-40 mg/L. The major advantage of enclosed reactors lies in the potential for aseptic operation, a product value which justifies the expense. For most products of algal mass cultivation, open ponds are the only feasible photobioreactor design capable of meeting the economic and operating requirements of such systems, provided desirable species can be maintained.


Exploratory Literature Meta-Analysis to Characterize the Relationship Between Early and Longer Term Body Weight Loss for Antiobesity Compounds.
The presented analysis was performed to characterize the relationship between treatment-related early (week 4) and longer term (3-6 months) weight loss to understand the potential utility of 4-week proof-of-mechanism studies in the early decision-making process during clinical development of new antiobesity compounds. A regression-based meta-analysis was performed leveraging publically available clinical outcomes data to (1) characterize the within-trial relationship between treatment-related early and longer term body weight loss and (2) identify and quantify key covariate effects on this relationship. Data from 89 randomized clinical trials with 209 treatment arms, representing observations from 54 461 patients and 9 treatments, were available for the meta-analysis. Results indicated that (1) there is a correlation between treatment-related early and longer term body weight loss (r > 0.9), (2) baseline body weight influences the relationship between early and longer term weight loss, whereas comorbidity such as type 2 diabetes mellitus, class of drugs including GLP-1 analogues and the antiobesity compounds lorcaserin or phentermine/topiramate showed no significant effects on this relationship. The model was externally evaluated with data from the investigational compound beloranib, for which longer term weight loss could be successfully predicted based on early response data. Based on these results, the identified strong relationship between treatment-related early and longer term weight loss appears to be independent of mechanism of action. Thus, findings from this analysis can optimize design of clinical studies and facilitate development of new anti-obesity compounds.


Alteration of the Intestinal Environment by Lubiprostone Is Associated with Amelioration of Adenine-Induced CKD.
The accumulation of uremic toxins is involved in the progression of CKD. Various uremic toxins are derived from gut microbiota, and an imbalance of gut microbiota or dysbiosis is related to renal failure. However, the pathophysiologic mechanisms underlying the relationship between the gut microbiota and renal failure are still obscure. Using an adenine-induced renal failure mouse model, we evaluated the effects of the ClC-2 chloride channel activator lubiprostone (commonly used for the treatment of constipation) on CKD. Oral administration of lubiprostone (500 µg/kg per day) changed the fecal and intestinal properties in mice with renal failure. Additionally, lubiprostone treatment reduced the elevated BUN and protected against tubulointerstitial damage, renal fibrosis, and inflammation. Gut microbiome analysis of 16S rRNA genes in the renal failure mice showed that lubiprostone treatment altered their microbial composition, especially the recovery of the levels of the Lactobacillaceae family and Prevotella genus, which were significantly reduced in the renal failure mice. Furthermore, capillary electrophoresis-mass spectrometry-based metabolome analysis showed that lubiprostone treatment decreased the plasma level of uremic toxins, such as indoxyl sulfate and hippurate, which are derived from gut microbiota, and a more recently discovered uremic toxin, trans-aconitate. These results suggest that lubiprostone ameliorates the progression of CKD and the accumulation of uremic toxins by improving the gut microbiota and intestinal environment.


Intelligent Albumin-MnO2 Nanoparticles as pH-/H2 O2 -Responsive Dissociable Nanocarriers to Modulate Tumor Hypoxia for Effective Combination Therapy.
A unique type of pH/H2 O2 dual-responsive intelligent nanoscale delivery system based on albumin-coated MnO2 is presented, which is capable of modulating the tumor microenvironment (TME) by relieving hypoxia. Additionally, TME-responsive size changes enable effective intratumor diffusion. A highly effective combined photodynamic and chemotherapy is realized with these nanoparticles in a mouse tumor model.


A computational study of the chlorination and hydroxylation of amines by hypochlorous acid.
The reactions of hypochlorous acid (HOCl) with ammonia, (di)methylamine, and heterocyclic amines have been studied computationally using double-hybrid DFT methods (B2PLYP-D and BK-PLYP) and a G3B3 composite scheme. In the gas phase the calculated energy barriers for N- and/or C-hydroxylation are ca. 100 kJ mol(-1) lower than the barrier for N-chlorination of amines. In the model solvent, however, the latter process becomes kinetically more favored. The explicit solvent effects are crucial for determination of the reaction mechanism. The N-chlorination is extremely susceptible to the presence of explicit water molecules, while no beneficial solvation effect has been found for the N- or C-hydroxylation of amines. The origin of the observed solvent effects arises from differential solvation of the respective transition states for chlorine- and oxygen-transfers, respectively. The nature of solvation of the transition state structures has been explored in more detail by classical molecular dynamics (MD) simulation. In agreement with the quantum mechanical approach, the most stable structural motif, which includes the amine, HOCl, and two reactive waters, has been identified during the MD simulation. The inclusion of 5 or 6 explicit water molecules is required to reproduce the experimental barriers for HOCl-induced formation of N-chloramines in an aqueous environment.


PAX6 and congenital eye malformations.
The PAX6 gene is a paradigm for our understanding of the molecular genetics of mammalian eye development. Twelve years after its identification it is one of the most intensively studied genes, both in terms of its diverse and complex functions during oculogenesis and its role in an ever-increasing variety of human congenital eye malformations. The PAX6 field has benefited greatly from the continued input of clinicians, human geneticists and developmental biologists. This review summarizes the latest data on the PAX6 mutation spectrum and recent insights into Pax6 function from the mouse.


[ParC-10 cells for modelling parotid gland tissue reorganization].
Salivary gland hypofunction, which may occur in head and neck cancers following therapeutic irradiation or in Sjogren's syndrome, drastically impair the patient's quality of life. Conventional treatments do not provide a satisfactory solution to the problem, therefore it is becoming increasingly urgent to develop completely new management approaches in particular, the challenge of restoring the function of acini. Many biologically based interventions studied, thus "reprogramming" with gene therapy of survivor ducts or regeneration potential of progenitor cells in the salivary gland. Our research group has been working on several models, which have shown that by using appropriate media containing extracellular proteins (e.g. BME, basal membrane extract) can be achieved acinar differentiation. A significant proportion of in vitro models of salivary gland are submandibular of origin, which however is different from the development and function of parotid. Our research group aimed to model the potential treatment options for salivary gland hypofunction, the carrier or bioactive molecules directed differentiation, as well as the potential of gene therapy on rat parotid-derived cell line (Par-C10). In our experiments, we have studied the morphological changes of Par-C10 cells cultured on permeable polyester membrane, or in three-dimensional cultures, using varying concentrations of BME. In addition, we have tested the use of recombinant adenovirus vectors that could modify Par-C10 cells and make them useful in gene therapy models. Our data suggest that Par-C10 cell line is suitable for modelling parotid gland tissue organization and may also serve as a useful gene therapy model system.


Specificity of practice, visual information, and intersegmental dynamics in rapid-aiming limb movements.
The authors tested the specificity of practice hypothesis on intersegmental dynamics of rapid-aiming limb movements. During acquisition, 20 participants performed an aiming task as quickly and accurately as possible either with or without vision. Following moderate (140 trials) and extensive (560 trials) practice, participants completed 20 transfer test trials in a no-vision condition. Overall, the acquisition-phase findings revealed that vision improved aiming accuracy performance but had only a slight impact on movement time and intersegmental dynamics. After 560 trials of practice, however, withdrawal of vision resulted in specificity of practice effects on intersegmental dynamics at the shoulder as well as on aiming accuracy. Taken together, those findings support and extend the specificity of practice hypothesis


Physiological oxygen culture reveals retention of metabolic memory in human induced pluripotent stem cells.
Reprogramming somatic cells to a pluripotent cell state (induced Pluripotent Stem (iPS) cells) requires reprogramming of metabolism to support cell proliferation and pluripotency, most notably changes in carbohydrate turnover that reflect a shift from oxidative to glycolytic metabolism. Some aspects of iPS cell metabolism differ from embryonic stem (ES) cells, which may reflect a parental cell memory, or be a consequence of the reprogramming process. In this study, we compared the metabolism of 3 human iPS cell lines to assess the fidelity of metabolic reprogramming. When challenged with reduced oxygen concentration, ES cells have been shown to modulate carbohydrate use in a predictably way. In the same model, 2 of 3 iPS cell lines failed to regulate carbohydrate metabolism. Oxygen is a well-characterized regulator of cell function and embryo viability, and an inability of iPS cells to modulate metabolism in response to oxygen may indicate poor metabolic fidelity. As metabolism is linked to the regulation of the epigenome, assessment of metabolic responses of iPS cells to physiological stimuli during characterization is warranted to ensure complete cell reprogramming and as a measure of cell quality.


Suppressive effects of histamine skin reactivity by a nonsedating antihistamine-mequitazine.
The suppressive activity of mequitazine (MQZ) on histamine skin reactivity was evaluated in 29 healthy subjects (age 22-25 years) in a single-blind study. Fifteen subjects received MQZ, at a dosage of 5 mg BID, for 7 days while 14 served as controls. A prick skin test with saline or histamine hydrochloride (1 mg/ml and 10 mg/ml) was performed in duplicate, on both forearms, starting from the baseline day and continuing for 4 days after medication had been discontinued (total of 11 days). The skin-test subject and the reader was unaware of the randomization process. Mean diameters of wheal and flare as well as the skin index scores (after Voorhost) were used in the analysis. Maximal flare suppression (as compared to the baseline values) was observed on day 6 (97% suppression for 1 mg/ml and 54% suppression for 10 mg/ml, p less than 0.01). Suppression of wheal size was significant (19% for 1 mg/ml and 28% for 10 mg/ml) but was not clinically relevant. Suppression of skin index scores was maximal on day 6 (71% for 1 mg/ml and 43% for 10 mg/ml, p less than 0.01). After MQZ had been discontinued, all measurements gradually returned to baseline values and were not different therefrom within 3 days. However, final measurements of wheal and flare were smaller than baseline values (60-94% of baselines). We conclude that MQZ, at the manufacturers's recommended dose of 5 mg BID, significantly suppressed flare size of histamine skin tests and recommend that MQZ be discontinued for at least 3 days prior to performing allergy skin tests.


A community outbreak of echovirus infection associated with an outdoor swimming pool.
Forty-six people became ill with vomiting, diarrhoea and headache within days of an outdoor swimming pool opening for the summer season in a small seaside village. During the weekend of the outbreak, 185 tickets to the pool had been sold. It was found that 34 bathers were ill, and one subject had vomited into the pool. All other cases arose after this incident. The risk of infection was greatest among those who swallowed pool water (24/28 versus 10/17, p = 0.07). Echovirus 30 was isolated from the case who vomited into the pool and from six other cases. Normal chlorine levels had not been adequate to contain the infection risk from vomitus, and, in future, pool attendants witnessing such incidents should consider closing the pool to the public and seeking advice on superchlorination.


[Are botulinum toxin type A preparations really the same medication? A comparison of three botulinum toxin A for variations in labelled neurological indications].
Recently, the list of clinical applications of botulinum toxin type A (BTX-A) enlarged. This medication is used not only by neurologists, but also by medical rehabilitation specialists, urologists, proctologists, and migraine and aesthetic medicine specialists. Currently, there are three commercially available BTX-A preparations available: Botox, Dysport and Xeomin. They have similar mechanisms of action but their chemical formulation, clinical potency, migration and diffusion as well as safety profile seem to be different. This may result in problems of bioequivalence, not only clinical but also economic ones. The authors reviewed the available clinical and laboratory studies on neurological indications labelled in Poland. Each BTX-A formulation should be treated as a different medication and used cautiously according to the individual range of dosages established in clinical trials.


GOLIAH (Gaming Open Library for Intervention in Autism at Home): a 6-month single blind matched controlled exploratory study.
To meet the required hours of intensive intervention for treating children with autism spectrum disorder (ASD), we developed an automated serious gaming platform (11 games) to deliver intervention at home (GOLIAH) by mapping the imitation and joint attention (JA) subset of age-adapted stimuli from the Early Start Denver Model (ESDM) intervention. Here, we report the results of a 6-month matched controlled exploratory study. From two specialized clinics, we included 14 children (age range 5-8 years) with ASD and 10 controls matched for gender, age, sites, and treatment as usual (TAU). Participants from the experimental group received in addition to TAU four 30-min sessions with GOLIAH per week at home and one at hospital for 6 months. Statistics were performed using Linear Mixed Models. Children and parents participated in 40% of the planned sessions. They were able to use the 11 games, and participants trained with GOLIAH improved time to perform the task in most JA games and imitation scores in most imitation games. GOLIAH intervention did not affect Parental Stress Index scores. At end-point, we found in both groups a significant improvement for Autism Diagnostic Observation Schedule scores, Vineland socialization score, Parental Stress Index total score, and Child Behavior Checklist internalizing, externalizing and total problems. However, we found no significant change for by time × group interaction. Despite the lack of superiority of TAU + GOLIAH versus TAU, the results are interesting both in terms of changes by using the gaming platform and lack of parental stress increase. A large randomized controlled trial with younger participants (who are the core target of ESDM model) is now discussed. This should be facilitated by computing GOLIAH for a web platform. Trial registration Clinicaltrials.gov NCT02560415.


Qualitative profile of degummed guar (Cyamopsis tetragonoloba L.) seeds grown in a Mediterranean area for use as animal feed.
Guar (Cyamopsis tetragonoloba L.) is an interesting summer legume multipurpose crop used for the extraction of seed gum, due to its galactomannan content, and the high-protein by-product, (germ and hull) used for animal feed. The aim of this study was to assess qualitative traits of degummed seeds, named guar meal, of six guar varieties from India, South Africa and USA, grown in a Mediterranean environment (Sicily, Southern Italy), in order to explore their suitability for livestock, and comparing them with the marketed Indian products of guar meals, Churi and Korma. After harvest, seeds were manually degummed and proximate composition was analysed using the official method of analyses, total phenols and tannins by UV spectrophotometry and fatty acids by GC-FID. Qualitative profile of degummed guar seeds (DGS) was significantly (p < .05) influenced by the genotype. Among DGS, Matador showed a high (p < .05) content of protein (518 g/kg), lipids (59.4 g/kg) and the lowest (p < .05) NDF level (181 g/kg) compared to the other varieties. Total phenol content of DGS showed similar values among varieties (2.57 mg gallic acid/g, on average) and with those of guar meal Korma 50%-53% (2.89 mg gallic acid/g) and Korma 56%-58% (2.94 mg gallic acid/g). Tannins were below the instrumental limit of quantification (1.5 mg/g of catechin equivalents) in DGS, as well as in the marketed products. Fatty acid composition was significantly influenced (p < .05) by the genotype. Matador showed the significant highest content of polyunsaturated fatty acids (PUFA) of the n6 series (45.2 g/100 g), whereas India showed the significant (p < .05) highest content of PUFA of the n3 series (3.55 g/100 g), and the significant (p < .05) highest level of n3/n6 PUFA ratio (0.08), and the best (p < .05) Atherogenic Index (0.19) and Thrombogenic Index (0.46). This study shows the interesting nutritional characteristics of degummed guar seeds, underlining that, if the future of the guar gum industries depends largely on the utilization of guar seed meal, this product can be considered a valuable feed resource and a way to increase the income of guar production.


[Formation of ionol complexes with free fatty acids].
UV spectrophotometry and high-resolution NMR spectrometry have demonstrated the formation of the complexes of ionol and fatty acids. This formation occurs as a result of the two types of interactions: 1/hydrogen bond formation between ionol OH-group and the carboxylic group of a fatty acid; 2/van der Waals interactions between the hydrogen chain of a fatty acid and tret -butyl groups of ionol. The latter interaction becomes more powerful with increase in fatty acid unsaturation. The molecular structure of the complexes of ionol with fatty acids is suggested.


Correlation between electroretinogram findings and molecular analysis in the Duchenne muscular dystrophy phenotype.
Fifteen consecutive patients with the Duchenne muscular dystrophy (DMD) phenotype were studied. Each patient was asked to undergo an ophthalmic examination, an electroretinogram (ERG), and to donate a blood sample for molecular diagnosis. All 15 patients had a normal ophthalmic examination. Electroretinography was successful in 14/15 patients. The ERG tracings were normal in seven patients, abnormal in seven, and unreliable in one. Blood for molecular analysis was obtained in 12/15 patients. In the seven patients with a normal ERG, five underwent molecular analysis, and in these five no deletion was detected in the dystrophin gene. In the seven patients with an abnormal ERG, six had molecular analysis available, and all six were found to have a deletion. These results suggest that patients with a classic DMD phenotype are genetically heterogeneous, and that this heterogeneity is reflected in the ERG.


Taxonomic re-evaluation of the monotypic genus Pararhabdophis Bourret, 1934 (Squamata: Colubridae: Natricinae) with discovery of its type species, P. chapaensis, from China.
The Asian monotypic genus Pararhabdophis Bourret, 1934 has long been known from a single holotype of the type species Pararhabdophis chapaensis Bourret, 1934 only. The limited available information hampered the identification of the natricine species. On the basis of eight newly collected specimens of P. chapaensis from the type locality in Sa Pa, Lao Cai Province, Vietnam and from Pingbian, Yunnan Province in southwestern China, the taxonomic position of the genus Pararhabdophis was re-evaluated using both morphological and molecular datasets for the first time. Pararhabdophis chapaensis is nested within the genus Hebius Thompson, 1913 with strong support, and morphologically indistinguishable from the latter genus. As a consequence, we herein synonymize the genus Pararhabdophis with Hebius and discuss about the existing paraphyly of some Hebius species. In addition we report Hebius chapaensis for the first time from China and provide redescription and natural history data of this poorly known species. To facilitate future taxonomic work, an identification key to all known natricine genera from China and Vietnam is also provided.


Hyperreactio luteinalis associated with pregnancy induced hypertension.
This is a unique case of hyperreactio luteinalis associated with partial HELLP syndrome, chronic superimposed hypertension, and intrauterine growth restriction. The cysts were managed conservatively. A caesarean section was performed at 34 weeks due to the deterioration of liver function tests, and intrauterine growth restriction. Multiple tissue biopsies of the ovaries were taken which showed theca leutein cysts. Her postoperative recovery was uneventful. The size of the cysts subsequently regressed to normal in 3 months postpartum.


Catalytic Dienylation: An Emergent Strategy for the Stereoselective Construction of Conjugated Dienes and Polyenes.
Stereoselective construction of conjugated dienes and polyenes has remained an enduring synthetic problem, due to the central roles they play in natural product synthesis, methodology, and medicine. This review focuses on the recent developments in dienylation as an emerging strategy for the direct installation of unsaturated four carbon atom units of conjugated π-systems, outlining the regio- and stereoselectivity, as well as the synthetic scope of reactions with various dienylating reagents and the mechanistic implications of the catalytic cross-coupling processes that are used to enable dienylation.


On Dipole Moments and Hydrogen Bond Identification in Water Clusters.
It is demonstrated that the localized orbitals calculated for a water cluster have small delocalization tails along the hydrogen bonds, that are crucial in determining the resulting dipole moments of the system. (By cutting them, one gets much smaller dipole moments for the individual monomers-close to the values one obtains by using a Bader-type analysis.) This means that the individual water monomers can be delimited only in a quite fuzzy manner, and the electronic charge density in a given point cannot be assigned completely to that or another molecule. Thus, one arrives to the brink of breaking the concept of a water cluster consisting of individual molecules. The analysis of the tails of the localized orbitals can also be used to identify the pairs of water molecules actually forming hydrogen bonds.


Calculation of converged rovibrational energies and partition function for methane using vibrational-rotational configuration interaction.
The rovibration partition function of CH4 was calculated in the temperature range of 100-1000 K using well-converged energy levels that were calculated by vibrational-rotational configuration interaction using the Watson Hamiltonian for total angular momenta J = 0-50 and the MULTIMODE computer program. The configuration state functions are products of ground-state occupied and virtual modals obtained using the vibrational self-consistent field method. The Gilbert and Jordan potential energy surface was used for the calculations. The resulting partition function was used to test the harmonic oscillator approximation and the separable-rotation approximation. The harmonic oscillator, rigid-rotator approximation is in error by a factor of 2.3 at 300 K, but we also propose a separable-rotation approximation that is accurate within 2% from 100 to 1000 K.


Periampullary carcinoma with bilateral ovarian cystadenoma in pregnancy.
We report a 30-year-old woman with periampullary cancer and a large left ovarian cystadenoma presenting during pregnancy with features of duodenal obstruction. She had a right benign ovarian tumor removed a year back. She delivered an intrauterine-growth-retarded live baby. Laparotomy in the postpartum period revealed an unresectable periampullary growth with hepatic metastasis and a left ovarian cystadenoma. The ovarian tumor was removed and a palliative gastrojejunostomy performed.


Birth prevalence of Down syndrome in Singapore from 1993 to 1998.
To examine the livebirth prevalence rate of Down Syndrome in Singapore from 1993 to 1998. Index cases for the National Birth Defects Register were obtained from all neonatal nurseries in Singapore, all hospital discharge summaries, cytogenetic and pathology reports from all pathology laboratories in Singapore and from the compulsory reporting of all termination of pregnancy cases and stillbirths delivered. Information for the Register was obtained from case notes retrieved from the medical record offices, antenatal clinics, cytogenetic laboratories, pathology departments and the Registry of Births and Deaths. All foetuses with Trisomy 21 diagnosed prenatally together with livebirths and stillbirths with Down Syndrome diagnosed at or after birth were identified from the Registry database. Prevalence of Down Syndrome From 1993 to 1998, there were 295 Down Syndrome livebirths, four stillbirths and 197 Down Syndrome foetuses aborted. There has been an increasing number of Down Syndrome foetuses diagnosed antenatally ending in termination and this is accompanied by a falling trend in the Down Syndrome livebirth rate in the same years from 1.17 to 0.89 per 1000 total live births. This is despite an expected increase in Down Syndrome livebirth rate obtained by modelling maternal Down Syndrome age-related risks on the maternal age distribution over the years. The livebirth prevalence of Down Syndrome in Singapore has fallen over the years from 1.17/1000 livebirths in 1993 to 0.89/1000 livebirths in 1998 due to antenatal diagnosis and selective termination.


Associations among Metabolism, Circadian Rhythm and Age-Associated Diseases.
Accumulating epidemiological studies have implicated a strong link between age associated metabolic diseases and cancer, though direct and irrefutable evidence is missing. In this review, we discuss the connection between Warburg effects and tumorigenesis, as well as adaptive responses to environment such as circadian rhythms on molecular pathways involved in metabolism. We also review the central role of the sirtuin family of proteins in physiological modulation of cellular processes and age-associated metabolic diseases. We also provide a macroscopic view of how the circadian rhythm affects metabolism and may be involved in cell metabolism reprogramming and cancer pathogenesis. The aberrations in metabolism and the circadian system may lead to age-associated diseases directly or through intermediates. These intermediates may be either mutated or reprogrammed, thus becoming responsible for chromatin modification and oncogene transcription. Integration of circadian rhythm and metabolic reprogramming in the holistic understanding of metabolic diseases and cancer may provide additional insights into human diseases.


Preoperative predictors of lateral neck lymph node metastasis in papillary thyroid microcarcinoma.
Lateral lymph node metastasis (LNM) is not uncommon in papillary thyroid microcarcinoma (PTMC). Our present study aimed to investigate the risk factors associated with lateral LNM in PTMC.We retrospectively collected data pertaining to 366 patients with PTMC who underwent surgery at our center from 2010 to 2015. These patients were divided into the following 2 groups: a lateral LNM-positive group and a lateral LNM-negative group. Clinical and ultrasound data were compared between the 2 groups to determine the risk factors associated with lateral LNM.Univariate and multivariate analyses indicated that capsule invasion (OR = 3.995, 95% CI, 2.148-7.430) and upper portion location (OR = 4.541, 95% CI, 2.444-8.438) were significant risk factors for lateral LNM of PTMC and that capsule invasion (AUC = 0.666) and upper portion location (AUC = 0.678) could be used to predict lateral LNM of PTMC. Moreover, the patients in lateral LNM positive group exhibited significantly higher rates of tumor recurrence or metastasis than the patients in lateral LNM negative group (P = 0.027).Patients with PTMC located in the upper portion or exhibiting capsule invasion should receive meticulous preoperative evaluations for lateral LNM, prophylactic lateral LND may be considered.


Lamin A/C and Vimentin as a Coordinated Regulator during Amoeboid Migration in Microscale Confined Microenvironments.
Cell migration occurs in confined microenvironments, which plays a vital role in the process of tumor metastasis. However, it is challenging to study their behaviors in vivo. Here we developed a cell squeeze system that can be scaled down to micrometers to mimic native physical confined microenvironments, wherein degrees of surface adhesion and mechanical constraints could be manipulated in order to investigate cell-migrating behaviors. Based on the microscale cell squeeze system, we found the synergistic role of lamin A/C and vimentin in cell transition and migration under strong confinement. The dynamic variations in lamin A/C and vimentin expression establish a positive feedback loop in response to confinement, effectively promoting amoeboid migration by modulating nuclear deformability while ensuring cell viability. This work shed light on modulating cell response to microenvironments by altering the expression of lamin A/C and/or vimentin, which may be a more efficient way of inhibiting cancer metastasis.


Placental Stem Cells from Domestic Animals: Translational Potential and Clinical Relevance.
The field of regenerative medicine is moving toward clinical practice in veterinary science. In this context, placenta-derived stem cells isolated from domestic animals have covered a dual role, acting both as therapies for patients and as a valuable cell source for translational models. The biological properties of placenta-derived cells, comparable among mammals, make them attractive candidates for therapeutic approaches. In particular, stemness features, low immunogenicity, immunomodulatory activity, multilineage plasticity, and their successful capacity for long-term engraftment in different host tissues after autotransplantation, allo-transplantation, or xenotransplantation have been demonstrated. Their beneficial regenerative effects in domestic animals have been proven using preclinical studies as well as clinical trials starting to define the mechanisms involved. This is, in particular, for amniotic-derived cells that have been thoroughly studied to date. The regenerative role arises from a mutual tissue-specific cell differentiation and from the paracrine secretion of bioactive molecules that ultimately drive crucial repair processes in host tissues (e.g., anti-inflammatory, antifibrotic, angiogenic, and neurogenic factors). The knowledge acquired so far on the mechanisms of placenta-derived stem cells in animal models represent the proof of concept of their successful use in some therapeutic treatments such as for musculoskeletal disorders. In the next future, legislation in veterinary regenerative medicine will be a key element in order to certify those placenta-derived cell-based protocols that have already demonstrated their safety and efficacy using rigorous approaches and to improve the degree of standardization of cell-based treatments among veterinary clinicians.


Binge alcohol consumption by non-alcohol-dependent women during pregnancy affects child behaviour, but not general intellectual functioning; a prospective controlled study.
Effects of binge ethanol consumption during early gestation on child neurodevelopment have not been elucidated. To study whether binge drinking affects cognitive abilities and behavior of exposed children, a prospective observational study comparing 51 children exposed to binge drinking during the first trimester of pregnancy to 51 children not exposed to any teratogens was conducted. The children's physical development, intelligence, language abilities and behavior were assessed. Temperament test results showed that children exposed in utero to maternal binge drinking displayed a greater degree of disinhibited behavior and that this behavior was associated with early drinking variables. Although binge alcohol drinking by non-alcohol-dependent women during the first trimester of pregnancy does not appear to affect intelligence or cognitive and language development of young children, binge drinking in pregnancy does increase the likelihood of certain behavioral characteristics that might predispose these children to later behavioral dysfunction.


Evaluation of Susceptibility Testing Methods for Aztreonam and Ceftazidime-Avibactam Combination Therapy on Extensively Drug-Resistant Gram-Negative Organisms.
Carbapenem-resistant Enterobacterales (CRE) and Pseudomonas aeruginosa (CR-PA) producing metallo-β-lactamases (MBLs) cause severe nosocomial infections with no defined treatment. The combination of aztreonam (ATM) with ceftazidime-avibactam (CZA) is a potential therapeutic option, but there is no approved, feasible testing method for use in clinical laboratories to assess the activity of two antimicrobials in combination. Here, we evaluate the performance of four ATM-CZA combination testing methods, as follows: broth disk elution (DE), disk stacking (DS), strip stacking (SS), and strip crossing (SX). We used 10 clinical, representative Enterobacterales and 6 P. aeruginosa isolates harboring MBL, Guiana extended-spectrum beta-lactamase (GES), or non-MBL enzymes. Four of these isolates were from clinical cases treated by ATM-CZA. All CRE producing NDM and CR-PA producing GES that were resistant to ATM and CZA alone were susceptible to the ATM-CZA combination. P. aeruginosa generating NDM or VIM remained resistant to ATM-CZA, likely due to non-β-lactamase mechanisms, and all other isolates were susceptible to ATM or CZA alone. The most accurate, precise, and reproducible methods of low complexity were disc elution and both strip methods (SX and SS) using MIC test strips (MTS) , all with 100% sensitivity and specificity, followed by Etest with SX (95.83% sensitivity, 100% specificity) and SS (87.5% sensitivity, 100% specificity). DS had the lowest performance. DE is particularly valuable in low-resource settings that routinely use disks. MTS yielded higher categorical agreements by SX (94%) and SS (84%), relative to Etest by SX (90%) and SS (82%). P. aeruginosa results yielded the majority of the errors. These methods may allow laboratories to inform clinical decision making like combination therapy for severe infections caused by extensively drug-resistant Enterobacterales.


Electrospinning of polymer nanofibers with ordered patterns and architectures.
Nanofibers with ordered patterns and architectures are critically important for many applications, including nanoscale device fabrication and tissue regenerations. During electrospinning process, the charge on a depositing nanofiber will become constant after the volatilization of solvent complete, which happens when the nanofibers get close to a collector that usually has a certain distance from the spinneret. In this case, the component forces acting on the depositing nanofibers that are arriving to a collector surfaces can be relatively analyzed based on the simulation results of the electrical field distribution on the collector. By using finite element method (FEM), in this study, the nanofiber deposition behavior including the orientation and alignment of nanofibers that are approaching to a collector were simulated and systematically investigated in term of the effects of electrostatic field applied to the collector. Based on the simulation results, we have experimentally demonstrated that Poly(epsilon-caprolactone) (PCL) nanofibers with various desired patterns and ordered architectures were prepared using predesigned collectors.


Proteomic profiling of cancer of the gingivo-buccal complex: Identification of new differentially expressed markers.
Tobacco-related oral cancer is the most common cancer among Indian males, gingivo-buccal complex (GBC) being the most affected subsite due to the habit of chewing tobacco. Proteins from the lysates of microdissected normal and transformed epithelium from clinically well-characterized tissue samples of the GBC were separated by two-dimensional gel electrophoresis to identify differentially expressed proteins. Eleven protein spots showed differential expression, which could withstand the stringency of statistical evaluation. The observations were confirmed with additional tissues. Nine of these differentiators were identified by MS as lactate dehydrogenase B, α-enolase, prohibitin, cathepsin D, apolipoprotein A-I, tumor protein translationally controlled-1, an SFN family protein, 14-3-3σ and tropomyosin. Cluster analysis indicated that these proteins, as a coexpressed set, could distinguish normal and transformed epithelium. Functionally, these differentiator molecules are relevant to the pathways and processes that have been previously implicated in oral carcinogenesis and could therefore be investigated further as a panel of markers for management of cancer of the GBC.


The acetylcholinesterase ichthyotoxin is a common component in the extracellular products of Vibrionaceae strains.
In previous work, it was reported that a strain of Aeromonas hydrophila (B32) produces the most potent lethal toxin with neurotoxic activity described so far for fish. In the present study, the presence and distribution of this acetylcholinesterase toxin lethal for fish were determined in extracellular products (ECP) of 42 Vibrionaceae strains using both immunological and colorimetric methods. This neurotoxin was shown to be present in the majority of the ECP from the Aeromonas and Vibrio strains tested and is responsible for the specific acetylcholinesterase activity. Also, although the Western blot and Ouchterlony techniques are valid as qualitative methods for the detection of this toxin, the Western blot procedure was 100-fold more sensitive than the Ouchterlony technique.


Adult immunization. Summary of the National Vaccine Advisory Committee Report.
In January 1994 the National Vaccine Advisory Committee adopted a report that reviewed the status of adult immunization in the United States. Vaccine-preventable infections of adults represent a continuing cause of morbidity and mortality. Their major impact is among older persons. Effective and safe vaccines against these diseases are available, but they are poorly used. Several reasons account for low immunization levels among adults, including inadequate awareness by health care providers and the public of the importance and benefits of vaccination. Health care providers often fail to take advantage of opportunities to immunize adults during office, clinic, and hospital contacts and fail to organize programs in medical settings that ensure adults are offered the vaccines they need. Inadequate reimbursement for adult immunization by public and private health insurers and a lack of federal programs to support vaccine delivery are also major problems. The National Vaccine Advisory Committee's report includes five goals and 18 recommendations for improving adult immunization. To reach the Public Health Service adult immunization goals for the year 2000, the Committee recommends (1) improvements in public and provider education; (2) major changes in clinical practice; (3) increased financial support by public and private health insurers; (4) improved surveillance of vaccine-preventable diseases and vaccine production and delivery; and (5) support for research on vaccine-preventable diseases, new and improved vaccines, immunization practices, and international programs for adult immunization.


Concurrent validity and between-unit reliability of a foot-mounted inertial measurement unit to measure velocity during team sport activity.
The concurrent validity and between-unit reliability of a foot-mounted inertial measurement unit (F-IMU) was investigated during linear and change of direction running drills. Sixteen individuals performed four repetitions of two drills (maximal acceleration and flying 10 m sprint) and five repetitions of a multi-directional movement protocol. Participants wore two F-IMUs (Playermaker) and 10 retro-reflective markers to allow for comparisons to the criterion system (Qualisys). Validity of the F-IMU derived velocity was assessed via root-mean-square error (RMSE), 95% limits of agreement (LoA) and mean difference with 95% confidence interval (CI). Between-unit reliability was assessed via intraclass correlation (ICC) with 90% CI and 95% LoA. The mean difference for instantaneous velocity for all participants and drills combined was -0.048 ± 0.581 m ∙ s-1, the LoA were from -1.09 to -1.186 m ∙ s-1 and RMSE was 0.583 m ∙ s-1. The ICC ranged from 0.84 to 1, with LoA from -7.412 to 2.924 m ∙ s-1. Differences were dependent on the reference speed, with the greatest absolute difference (-0.66 m ∙ s-1) found at velocities above 7 m ∙ s-1. Between-unit reliability of the F-IMU ranges from good to excellent for all locomotor characteristics. Playermaker has good agreement with 3D motion capture for velocity and good to excellent between-unit reliability.


Peritraumatic distress: its relationship to posttraumatic stress and complicated grief symptoms in sudden death survivors.
Although sudden death has been linked to posttraumatic stress disorder (PTSD), its role in complicated grief (CG) and sudden death survivors is unknown. This questionnaire study investigated the role of peritraumatic distress in PTSD and CG symptoms in adults (n = 125) an average of 28.37 months (SD = 3.12) after a loved one's sudden death. The Peritraumatic Distress Inventory, Impact of Event Scale-Revised, and Inventory of Complicated Grief were administered to assess symptoms of peritraumatic distress, PTSD, and CG, respectively. Peritraumatic distress was the strongest correlate of both PTSD (β = .42, p < .001) and CG (β = .39, p < .001) symptoms, in a model containing current distress (Hopkins Symptom Checklist-21). Peritraumatic distress may be a key mechanism in the development of both PTSD and CG, therefore suddenly bereaved individuals reporting higher peritraumatic distress may be at risk of both adverse trauma and grief reactions.


K-wire fixation for extraarticular transverse/short oblique fractures of the shaft of the middle phalanx associated with extensor tendon injury.
In a prospective study, 22 cases of extraarticular transverse/short oblique fractures of the shaft of the middle phalanx associated with extensor tendon injury had fixation of the fracture as well as immobilisation of the distal interphalangeal joint using a K-wire. Mobilisation of the proximal interphalangeal and metacarpophalangeal joints was started immediately after surgery. The wires were removed after 6 weeks. No post-operative complications were noted. At final follow-up (mean = 15 weeks, range = 12-24 weeks), 18 of 22 patients obtained excellent and good total active motion (TAM) scores. Stiffness was confined to the distal interphalangeal joint, and hence when the results were re-analysed for motion at that joint only, only 11 patients had excellent and good outcomes.


New sample carrier systems for thermogravimetric analysis under forced flow conditions and their influence on microkinetic results.
For thermogravimetric analysis, it has been shown that, depending on the type of sample container, different kinetic results could be obtained despite regarding the same reaction under constant conditions. This is due to limiting macrokinetic effects which are strongly dependant on the type of sample carrying system. This prompted the need for sample containers which deliver results minimally limited by diffusive mass transport. In this way, two container systems were developed, both characterized by a forced flow stream through a solid, porous bed: one from bottom to top (counter-current flow) and one from top to bottom (co-current flow). Optical test measurements were performed, the results indicating that reaction proceedings are almost fully independent of the geometrical shape of the sample containers. The Boudouard reaction was investigated with a standard crucible and the new developed systems; the reaction rates determined differed significantly, up to a factor of 6.2 at 1373 K.


Induction of dendritic spines by β2-containing nicotinic receptors.
Glutamatergic synapses are located mostly on dendritic spines in the adult nervous system. The spines serve as postsynaptic compartments, containing components that mediate and control the synaptic signal. Early in development, when glutamatergic synapses are initially forming, waves of excitatory activity pass through many parts of the nervous system and are driven in part by a class of heteropentameric β2-containing nicotinic acetylcholine receptors (β2*-nAChRs). These β2*-nAChRs are widely distributed and, when activated, can depolarize the membrane and elevate intracellular calcium levels in neurons. We show here that β2*-nAChRs are essential for acquisition of normal numbers of dendritic spines during development. Mice constitutively lacking the β2-nAChR gene have fewer dendritic spines than do age-matched wild-type mice at all times examined. Activation of β2*-nAChRs by nicotine either in vivo or in organotypic slice culture quickly elevates the number of spines. RNA interference studies both in vivo and in organotypic culture demonstrate that the β2*-nAChRs act in a cell-autonomous manner to increase the number of spines. The increase depends on intracellular calcium and activation of calcium, calmodulin-dependent protein kinase II. Absence of β2*-nAChRs in vivo causes a disproportionate number of glutamatergic synapses to be localized on dendritic shafts, rather than on spines as occurs in wild type. This shift in synapse location is found both in the hippocampus and cortex, indicating the breadth of the effect. Because spine synapses differ from shaft synapses in their signaling capabilities, the shift observed is likely to have significant consequences for network function.


Effect of low body temperature on associative interference in conditioned taste aversion.
When two novel conditioned stimuli precede an unconditioned stimulus (US), the interval between the two conditioned stimuli (CS1 and CS2) influences the magnitude of the CS-US associability of each CS. As the interval between CS1 and CS2 increases, the associability of CS1 with the US decreases due to interference by CS2 and the associability of CS2 increases, given its temporal proximity to the US. Because hypothermia has been reported to increase the interval at which conditioned taste aversions can be formed, its influence was examined on the above relationship, i.e., how interference from CS2 affects the associability of CS1 with the US. Rats received a conditioned taste aversion procedure where CS1 and CS2 were presented either one after the other or separated by an 80-min. delay. For all subjects, the US or pseudo-US was presented immediately after CS2. When hypothermia was interpolated between the two flavor stimuli that were spaced 80 min. apart, CS2-interference with the CS1-US association was greatly attenuated. We propose that hypothermia modifies internal timing mechanisms such that the externally timed 80-min. CS1-CS2 interval was perceived as much shorter for rats made hypothermic. As a result of this perceived shortened inter-CS interval, CS2 produced less interference for the CS1-US association than would be expected for such a relatively long delay between CS1 and CS2.


Comparative study of the ability of Leishmania mexicana promastigotes and amastigotes to alter macrophage signaling and functions.
Leishmania alternates between two morphologically different stages, promastigotes and amastigotes. While the majority of reports focused on how the promastigote form can alter macrophage (Mphi) signaling and function, fewer reports investigated signaling alterations mediated by amastigotes, and there is a lack of comparative studies. In this study, we performed a comparison between the ability of both forms of the parasite to alter Mphi signaling and functions. Here, we show that both promastigotes and amastigotes were able to rapidly activate host protein tyrosine phosphatases (PTPs), importantly the Src homology 2 domain-containing PTP (SHP-1). However, we found that PTP-1B is specifically activated by promastigote but not amastigote infection and that lmcpb(-/-) promastigotes were no longer able to activate PTP-1B. We also show a similarity in the way promastigotes and amastigotes inactivate the transcription factors (TFs) STAT-1alpha and AP-1, but we show differences in the modulation of NF-kappaB, with promastigotes cleaving the p65 subunit, generating a smaller p35 subunit, and amastigotes fully degrading the p65 subunit with no p35 production. Importantly, we show that the cysteine proteinase LmCPb plays a key role in the alteration of NF-kappaB, STAT-1alpha, and AP-1 by promastigote and amastigote infections, ultimately leading to the inability of these TFs to translocate to the nucleus in response to gamma interferon (IFN-gamma) stimulation and thus contributing to the ability of both parasite forms to effectively block IFN-gamma-mediated nitric oxide (NO) production in Mphis.


Biosynthesis of vitamin B6 in Rhizobium: in vitro synthesis of pyridoxine from 1-deoxy-D-xylulose and 4-hydroxy-L-threonine.
Pyridoxine (vitamin B6) in Rhizobium is synthesized from 1-deoxy-D-xylulose and 4-hydroxy-L-threonine. To define the pathway enzymatically, we established an enzyme reaction system with a crude enzyme solution of R. meliloti IFO14782. The enzyme reaction system required NAD+, NADP+, and ATP as coenzymes, and differed from the E. coli enzyme reaction system comprising PdxA and PdxJ proteins, which requires only NAD+ for formation of pyridoxine 5'-phosphate from 1-deoxy-D-xylulose 5-phosphate and 4-(phosphohydroxy)-L-threonine.


Evaluation of Organogel Nanoparticles as Drug Delivery System for Lipophilic Compounds.
The purpose of the study was to evaluate organogel nanoparticles as a drug delivery system by investigating their stability, according to the formulation strategy, and their release profile. The gelled nanoparticles were prepared by hot emulsification (above the gelation temperature) of an organogel in water, and cooling at room temperature. In the first step, we used DLS and DSC to select the most suitable formulations by optimizing the proportion of ingredients (HSA, PVA, castor oil) to obtain particles of the smallest size and greatest stability. Then, two lipophilic drug models, indomethacin and ketoconazole were entrapped in the nanoparticles made of castor oil gelled by 12-hydroxystearic acid. Thermal studies (DSC) confirmed that there was no significant alteration of gelling due to the entrapped drugs, even at 3% w/w. Very stable dispersions were obtained (>3 months), with gelled oil nanoparticles presenting a mean diameter between 250 and 300 nm. High encapsulation efficiency (>98%) was measured for indomethacin and ketoconazole. The release profile determined by in vitro dialysis showed an immediate release of the drug from the organogel nanoparticles, due to rapid diffusion. The study demonstrates the interest of these gelled oil nanoparticles for the encapsulation and the delivery of lipophilic active compounds.


A decrease in cell size accompanies a loss of docosahexaenoate in the rat hippocampus.
Rats raised on n-3 essential fatty acid deficient diets demonstrate spatial memory deficits. To investigate neuroanatomical correlates of these deficits, morphological analysis of the hippocampus were carried out. Adult, female rats were raised for three generations on n-3 deficient or n-3 supplemented diets. Two n-3 deficient diets contained adequate linoleic acid (LA), or high linoleic acid (high LA), and two supplemented diets contained LA supplemented with alpha-linolenic acid (+LNA), or linoleic supplementation with alpha-linolenic and docosahexaenoic acids (+LNA/DHA). The total fatty acid composition of the hippocampus revealed a profound loss (90%) in docosahexaenoic acid (DHA) in the hippocampi of LA and high LA animals compared to those on +LNA and +LNA/DHA diets with a reciprocal increase in docosapentaenoic acid (DPAn-6) in all phospholipid species. The volume, density, total number, and cell body size of neurons in CA1-3, granular and hilar layers of the hippocampus were measured at septal and temporal locations using unbiased stereology. No differences were detected in any of these measures except for in cell body size; CA1 pyramidal neurons in the LA group were significantly (p < 0.04) smaller than neurons in the +LNA/DHA group at the septal location.


Impact of drying on solid state modifications and drug distribution in ibuprofen-loaded calcium stearate pellets.
Drying is a common pharmaceutical process, whose potential to alter the final drug properties-even at relatively low temperatures-is often neglected. The present study addresses the impact of drying at 20 and 50 °C on wet-extruded calcium stearate (CaSt) pellets. Drying at 20 °C caused the majority of ibuprofen to accumulate at the pellet surface due to a strong convective flow from the pellet's center to the surface. In contrast, pellets dried at 50 °C still contained ibuprofen in the pellet's interior due to the higher drying rate and the associated film breakage during drying. Moreover, the higher drying temperature caused CaSt to form a second lamellar phase and ibuprofen to convert (partly) into its amorphous state. Overall, the drying process affected the solid state and the spatial ibuprofen distribution within the pellet. Knowledge of these effects can aid in tailoring advanced multipellet formulations.


An Ethnographic Assessment of COVID-19‒Related Changes to the Risk Environment for People Who Use Drugs in Tijuana, Mexico.
Objectives. To characterize the effects of the onset of the COVID-19 pandemic on the risk environment of people who use drugs (PWUD) in Tijuana, Mexico. Methods. We used intensive participant-observation ethnography among street-based PWUD and key informants, such as frontline physicians and harm reductionists. Results. PWUD described an unprecedented cessation of police violence and extortion during the initial pandemic-related lockdown, though this quickly reversed and police violence worsened. Government-provided housing and medical treatment with methadone were temporarily provided to PWUD in a dedicated clinic, yet only for PWUD with COVID-19 symptoms. Concurrently, non‒COVID-19‒related hospital care became virtually inaccessible, and many PWUD died of untreated, chronic illnesses, such as hepatitis C, and soft-tissue infections. Border closures, decreases in social interaction, and reduced drug and sex tourism resulted in worsening food, income, and housing insecurity for many PWUD. By contrast, potent illicit drugs remained easily accessible in open-air drug markets. Conclusions. The pandemic exacerbated health risks for PWUD but also offered profound glimpses of beneficial structural changes. Efforts are needed in Tijuana and elsewhere to institutionalize positive pandemic-related shifts and ameliorate novel harms for PWUD. (Am J Public Health. 2022;112(S2):S199-S202. https://doi.org/10.2105/AJPH.2022.306796).


[Effect of compound coarse grain food on insulin resistance and expression of PPARgamma in rat].
To explore the effect of compound coarse grain food on insulin resistance (IR) in rats. Forty Sprague-Dawley rats were randomly divided into normal control group (n=10) and model group (n=30), provided regular diet and high fat diet separately. After 6 weeks, the model group were divided into high fat diet group, rice flour group and coarse grain group, and provided the corresponding feed. After feeding 9 weeks, the fasting blood glucose, insulin and the expression of PPAR-gamma mRNA in rats were measured. IR was successfully induced by 6-weeks high fat diet. The body weight and insulin resistance index (HOMA-IR) in coarse grain group were significantly lower than high fat diet group and rice flour group. The expression of PPAR-gamma mRNA in coarse grain group was significantly higher than other three groups (P < 0.05). The coarse grain food can reduce the concentration of blood glucose and insulin in rat with insulin resistance induced by high-fat dietary, and improve insulin sensitivity. The possible mechanism is the over-expression of PPAR-gamma.


Templated fabrication of fiber-basket polymersomes via crystallization-driven block copolymer self-assembly.
Immobilizing uniform nanostructures on a mesoscale substrate is a promising approach to prepare nanometer to micrometer sized materials with new functionalities. The hierarchical structures formed depend on both the nature of the substrate and the components deposited. In this paper, we describe the use of colloidal polystyrene microbeads as a sacrificial template to create a nanofibrous network coating consisting of elongated block copolymer micelles. This network has a secondary structure very different from that of conformal coatings obtained by other methods. In addition, the fibers of the network could be elongated by crystallization-driven self-assembly. The network was locked in place by cross-linking the micelles through in situ generation of small Pt nanoparticles. Subsequent removal of the sacrificial template gave an open vesicular structure. To demonstrate further transformation of the membrane, we showed that the cross-linked micelles could also be used to embed silver nanoparticles. The sacrificial template contained known amounts of Tb and Tm ions, allowing us to estimate via atomic mass spectrometry that 85% of the template surface was covered with micelle seeds. This approach to fabricating hierarchical coating structures expands the generality and scope of template-assisted synthesis to build advanced hierarchical materials with precise morphological control.


Breeding systems and continuing evolution in the endemic Sorbus taxa on Arran.
The Arran whitebeams Sorbus arranensis and S. pseudofennica are two endemic woody plant taxa that have evolved on Arran through hybridisation. S. arranensis is a triploid hybrid between the widespread diploid S. aucuparia and the rare tetraploid S. rupicola. S. pseudofennica is a tetraploid formed by crossing between S. arranensis and S. aucuparia. In order to determine the mating systems of the two endemic species six maternal trees of each taxon together with 10-12 of their seed offspring were scored for their phenotype at three microsatellite loci and one nuclear intron locus. All seeds of S. arranensis were identical in phenotype to their maternal parents. In S. pseudofennica, 17.5% of all seeds differed in marker phenotype from their maternal parent. The proportion of seed with nonmaternal phenotypes varied significantly among maternal trees of S. pseudofennica. The results suggest that the triploid S. arranensis is an obligate apomict, whereas the tetraploid S. pseudofennica is a facultative apomict. Molecular marker analysis of three trees from Arran with an unusual leaf morphology indicates that they are the product of sexual reproduction by S. pseudofennica, and may originate from hybridisation with S. aucuparia. This research demonstrates that the Sorbus taxa on Arran are participants in an active evolutionary process generating novel biodiversity. Conservation programmes for these taxa should aim to preserve this evolutionary process rather than the individual taxonomic entities that it produces.


[Secretion of gonadotropins during sleep. Changes during secondary amenorrheas].
4 females with secondary amenorrheas underwent sleep polygraphic recordings together with blood samples for measurements of LH, FSH and GH, 3 normal females served as controls. Among normal subjects LH and FSH secretion showed a pulsating pattern around the time of ovulation, appearing as secretory episodes throughout the night, without any relationship with sleep stages. In amenorrheas, 3 types of abnormalities could be identified: the first was a lack of secretory episodes of LH and FSH associated with an abnormal pattern of GH (9 subjects). The second was an hypersecretion of LH and a decrease of FSH secretion together with a normal secretion of GH in 4 subjects with a Stein-Leventhal syndrome. The last one was an hypersecretion of LH and FSH together with a normal pattern of GH in a subject with an early menopause. These results are discussed according to the present data on the part of neurotransmission in the regulation of ovulation and the 2 types of sleep. Furthermore secretory abnormalities of LH and FSH together with a disconnection between GH secretion and the stages of sleep lead to question the possibility of interrelationships in the secretory mechanisms of these different hormones.


A study of prevalence and correlates of nonadherence to immunosuppressive medications in renal transplant recipients of South Indian population and their impact on long-term graft function.
Nonadherence to immunosuppressant medications leading onto poor graft outcome is frequent among renal transplant recipients. In this study, we sought to assess the prevalence and correlates of nonadherence to immunosuppressants and its impact on graft function. A singlecenter, retrospective cum cross-sectional study of renal transplant recipients of age >18 years and who had completed at least six months after transplantation was performed. Nonadherence was assessed based on the Immunosuppressant Therapy Adherence Scale questionnaire. Factors attributed to nonadherence were assessed based on the Immunosuppressant Therapy Barriers Scale (ITBS) questionnaire. Social, economic, demographic data, and all transplant related information were recorded. Two hundred and seventy-nine patients were included in the study, of whom 78% were male. Median follow-up period was 46 months (interquartile range - 24 months to 82 months). Seventy-four patients (26.5%) admitted nonadherence to immunosuppressants. The nonadherence was significantly related to the male gender, late acute rejection episodes, rise in serum creatinine from > 0.5 mg/dL from nadir level, lower blood levels of calcineurin inhibitor, and higher ITBS scores. Refill rates and use of alarm reminders were not significantly associated with better adherence.


[Quality assurance for histodiagnosis and cytodiagnosis with a model of proficiency testing].
A quality assurance (QA) program for histopathology and cytology has not yet been completed although an inhouse quality control for technical standardization is being tested. The fact that a strict Performance Improvement Program of CAP (College of American Pathologists) for cytology is required separately from other laboratory tests emphasizes the importance of cytology, since erroneous cytology reports would directly cause incorrect clinical diagnosis. The results of questionnaires gathered by the QA Committee of the Japan Association of Registered Clinical Laboratories on preparation techniques, workload limits of pathologists and technologists, double diagnostic systems, error detection programs, and specialization of personnel are presented. In addition to pathology and cytology proficiency testing provided by CAP survey, a model of blind QC (quality control) in our laboratory is discussed; for diagnostic standardization of histopathology, reexamination of randomly selected cases by another pathologist and reexamination of previously diagnosed cases by the same doctor are periodically performed. For error detection of cytoscreening, cytologists are obligated to reexamine random samples of 1 to 10% of negative gynecological slides. Evaluation of sufficiency of slides as required by the Bethesda System is referred to diagnostic interpretation.


Proton nuclear magnetic resonance study on the roles of histidine residues in the binding of polypeptide chain elongation factor Tu from Thermus thermophilus with aminoacyl transfer ribonucleic acid and guanine nucleotides.
Proton nuclear magnetic resonance (1H NMR) spectra were measured of the polypeptide chain elongation factor Tu (EF-Tu) from an extreme thermophile, Thermus thermophilus HB8 [Nakano, A., Miyazawa, T., Nakamura, S., & Kaziro, Y. (1979) Arch. Biochem. Biophys. 196, 233-238], in order to elucidate the environment around functionally important histidine residues. In the present study, the behavior of five histidine C2 proton signals was studied in more detail. A hydrogen-deuterium exchange experiment was carried out on the histidine C2 protons of free EF-Tu, and the previous assignments of C2 proton signals were revised in part. An analysis of the 1H NMR spectra of EF-Tu photooxidized under various conditions indicates that a histidine residue is located in the aminoacyl-tRNA binding site and is probably essential for the binding with aminoacyl-tRNA. A solvent-accessible histidine residue is found to lie near the aminoacyl-tRNA binding site. Furthermore, the effect of paramagnetic hexacyanochromate(III) ion on the 1H NMR spectra of free EF-Tu suggests that another histidine residue lies near the guanine nucleotide binding site.


Reversible Photocontrol of Microtubule Stability by Spiropyran-Conjugated Tau-Derived Peptides.
Spatiotemporal modulation of microtubules by light has become an important aspect of the biological and nanotechnological applications of microtubules. We previously developed a Tau-derived peptide as a binding unit to the inside of microtubules. Here, we conjugated the Tau-derived peptide to spiropyran, which is reversibly converted to merocyanine by light, as a reversible photocontrol system to stabilize microtubules. Among the synthesized peptides with spiropyran/merocyanine at different positions, several peptides were bound to the inside of microtubules and stabilized the structures of microtubules. The peptide with spiropyran at the N-terminus induced polymerization and stabilization of microtubules, whereas the same peptide with the merocyanine form did not exert these effects. Reversible formation of microtubules/tubulin aggregates was achieved using the peptide with spiropyran conjugated at the N-terminus and irradiation with UV and visible light. Spiropyran-conjugated Tau-derived peptides would be useful for spatiotemporal modulation of microtubule stability through reversible photocontrol of binding.


Angiogenesis and bone regeneration by mesenchymal stem cell transplantation with danshen in a rabbit model of avascular necrotic femoral head.
The present study aimed to explore the potential of combined treatment with mesenchymal stem cells (MSCs) and danshen for angiogenesis and bone regeneration in a rabbit model of avascular necrosis of femoral head (ANFH). A rabbit model of ANFH was established using the Shwartzman reaction with methylprednisolone and Escherichia coli endotoxin injection. Magnetic resonance imaging (MRI) and histopathological examination were used to evaluate the rabbit model of ANFH. The rabbits were randomly divided into the danshen group, the MSCs group, the danshen combined with MSCs group and the model group (treated with physiological saline). The expression level of monocyte chemoattractant protein-1 (MCP-1) and stromal cell-derived factor-1 (SDF-1) were determined by reverse transcription polymerase chain reaction (RT-PCR). The expression level of bone morphogenetic protein-2 (BMP-2) and vascular endothelial growth factor (VEGF) were detected by immunofluorescence and the mRNA expression of BMP-2 and VEGF were detected by RT-PCR. Typical osteonecrosis occurred in the rabbit model of ANFH, which indicated that the model was successfully established. MCP-1 and SDF-1 were significantly increased in the model group compared with the normal group (P<0.05). Following the administration of MSCs and Salvia miltiorrhiza (danshen), MSCs labeled with 5-bromo-2-deoxyuridine were observed to be gathered in the necrotic area. The increased migration of MSCs to the necrotic area may be due to the upregulated expression of the chemokines MCP-1 and SDF-1. ANFH treated with danshen combined with MSCs may promote revascularization by increasing the expression of VEGF and BMP-2 in the femoral head, promoting re-ossification and revascularization. Danshen combined with the transplantation of MSCs may be regarded as a novel therapy for the treatment of ANFH in a clinical setting.


Nanometer-scale modification and welding of silicon and metallic nanowires with a high-intensity electron beam.
We demonstrate that a high-intensity electron beam can be applied to create holes, gaps, and other patterns of atomic and nanometer dimensions on a single nanowire, to weld individual nanowires to form metal-metal or metal-semiconductor junctions, and to remove the oxide shell from a crystalline nanowire. In single-crystalline Si nanowires, the beam induces instant local vaporization and local amorphization. In metallic Au, Ag, Cu, and Sn nanowires, the beam induces rapid local surface melting and enhanced surface diffusion, in addition to local vaporization. These studies open up a novel approach for patterning and connecting nanomaterials in devices and circuits at the nanometer scale.


Prevalence of Mycoplasma genitalium in asymptomatic men in Japan.
We aim to clarify the prevalence of Mycoplasma genitalium in asymptomatic men in Japan. First-catch urine specimens were obtained from 187 asymptomatic Japanese men and examined for the presence of M. genitalium using a polymerase chain reaction (PCR)-based assay. Two (1.1%) of 187 first-catch urine specimens were positive for M. genitalium. The prevalence of M. genitalium in urine specimens of asymptomatic men in Japan is lower than that in asymptomatic men in the UK (6%) and Denmark (9%).


Reducing contrast dose using virtual monoenergetic imaging for aortic CTA.
Three-dimensional computed tomographic angiography (3D-CTA) is widely used to evaluate the inner diameters of vessels and the anatomical vascular structure prior to endoscopic aortic surgery or transcatheter valve implantation. Virtual monoenergetic imaging (VMI) is a new application in dual-energy CT (DECT). We evaluated the potential for contrast dose reduction in preoperative aortic CTA using VMI. To evaluate performance in terms of image quality and vessel shape, we quantified the contrast-to-noise ratio (CNR) and the vessel diameter using a cylinder phantom we developed, and used volume rendering to assess visual quality. All VMI had improved CNR values compared with conventional 120 kVp images at an iodine content of 15 mgI/mL. In each image, a virtual mono-energy of 40 keV yielded the highest CNR value, and an iodine content of 9 mgI/mL was comparable to that of conventional images with an iodine content of 15 mgI/mL. The circularity indices (CI) of the vascular model at 15, 12, and 9 mgI/mL were similar to those of the reference condition using conventional voltages; however, CI was degraded at iodine contents of 6 and 3 mgI/mL with VMI. In the case of iodine content of 15 mgI/mL, VMI was superior, with conventional image by visual evaluation. In the cases of iodine contents of 12 and 9 mgI/mL, image quality was judged to be almost the same level when comparing 12 and 9 mgI/mL to conventional images. In the case of 6 and 3 mgI/mL, reference image using conventional technique was superior to that of VMI. We demonstrated in that decreasing contrast iodine content is possible using VMI with an energy of 40 keV for preoperative aortic 3D-CTA.


Yeast two-hybrid screens to identify Drosophila PP1-binding proteins.
Protein phosphatase type 1 (PP1) is one of the major classes of serine/threonine protein phosphatases and has been found in all eukaryotic cells examined to date. Metazoans from Drosophila to humans have multiple genes encoding catalytic subunits of PP1 (PP1c), which are involved in a wide range of biological processes. Studies in the fruit fly Drosophila melanogaster have revealed some of the essential functions of the PP1c genes. However, the PP1c isoforms have pleiotropic and overlapping functions, making it difficult to characterize their many biological roles and identify their specific in vivo substrates. Regulatory subunits of PP1 provide the key to understanding the role of PP1, as they are responsible for directing PP1c to different intracellular locations and/or affecting their activity or substrate specificity. The existence of isoform-specific PP1 regulatory subunits might also help to explain the unique roles of different PP1 catalytic subunits. Drosophila is an excellent model organism in which to characterize the role of PP1 catalytic and regulatory subunits, because it combines molecular and biochemical approaches with powerful genetics, in a well-characterized animal model. In this chapter, we will describe how the two-hybrid system can be used to identify Drosophila PP1c-interacting proteins and study their interactions with different PP1c isoforms and variants. With the appropriate bait and library constructs, this method should also be equally applicable to identifying binding subunits of related phosphatases or PP1c from other organisms.


Upper thoracic spinal cord herniation after traumatic nerve root avulsion. Case report and review of the literature.
Transdural herniation of the spinal cord, a rare but well-documented entity, has been reported sporadically for more than 25 years as a possible cause for various neurological signs and symptoms ranging from isolated sensory or motor findings to myelopathy and Brown-Séquard syndrome. The authors report, to the best of their knowledge, the first case of upper thoracic spinal cord herniation occurring after traumatic nerve root avulsion.


Older Patients' Worries in Connection With General Anesthesia and Surgery-A Qualitative Study.
To examine anxiety and what older patients worry about related to anesthesia and colorectal surgery, and their perceptions regarding nurses' ability to ease preoperative worry. Qualitative individual face-to-face interviews. The study included 18 patients aged between 62 and 91 years with lower abdominal tumors. The study was conducted in two day-surgery wards in Sweden. Interview data were analyzed with Malterud's systematic text condensation. Four themes were identified: (1) losing control of one's body, leaving one's life in someone else's hands, and the feeling that there is no going back, (2) claustrophobia and anticipated pain in an unknown environment, (3) unknown and frightening vocabulary concerning the surgery, and (4) what can happen if something goes wrong. Patients worry about a number of things. If preoperative worry could be identified, actions taken to reduce worry could be personalized and patients' own strategies to reduce worries may be helpful for them.


Validation of contralateral premolars as the substrate for endodontic comparison studies.
To use micro-CT technology and metrology software to validate the use of contralateral premolars as samples in endodontic comparison studies by comparing them before and after canal instrumentation with one instrumentation system. Furthermore, to determine whether contralateral premolar roots (CPRs) will yield non-significantly different outcomes regarding shaping ability (volume), degree of twisting and three-dimensional shape changes. The null-hypothesis (H0 ) is that there are no differences between the CPRs pre- or post-instrumentation. Twenty-eight extracted human contralateral premolars (n = 44 contralateral roots) from 12 donor patients were scanned with microcomputed tomography before and after instrumentation. Root canal lengths (RCLs) were measured visually using a dental-operating microscope, electronic apex locator and micro-CT scans. Data were analysed statistically for differences between pre- and post-instrumentation. Instrumentation increased the volume of the canals significantly (P < 0.05). Degree of twisting for a majority (83%) of the contralateral roots pairs did not change significantly (P > 0.05). There was no significant difference (P > 0.05) in the shape deviation analysis between contralateral pairs. There was no significant difference (P > 0.05) for RCL between the contralateral pairs for any of the three endometric methods. Contralateral premolar root canals were associated with similar changes in terms of volume, three-dimensional shape and degree of twisting from pre- to post-instrumentation. There was no difference between the CPR pairs pre- and post-instrumentation, and the study validates contralateral premolars as samples for root canal comparison studies. The null-hypothesis (H0 ) could not be rejected.


Putting Patient Autonomy in its Proper Place; Professional Norm-Guided Medical Decision-Making.
The recommended model for patient participation in medical decision-making is the shared decision-making model (SDM). That model is ambiguous as to how much physician influence on patient decision-making is desirable or permissible. Most discussants suggest that physician influence on medical decisions, while allowable, should be limited. Empirical studies of medical decision-making have shown that much medical practice does not conform to the SDM. The author recommends a different model for medical decision-making, "professional norm-guided medical decision-making," which, he suggests, much medical practice actually follows. This model does not defer to patient autonomy to the extent usually recommended by the SDM and permits a greater degree of physician influence on patient medical decisions than usual versions of that model. Having described the working of the the professional norm-guided decision-making model, the author specifies the form of patient autonomy respected by it and offers a case for preferring this model of medical decision-making to the SDM.


The effect of spraying bacterial and fungal solutions on Korean pine Pinus koraiensis Sieb. et Zucc. cone development and seed quality when sprayed during the flowering phase.
Korean pine is an economically essential afforestation species limited by the unreasonable collection of cones, indiscriminate use of chemical pesticides and pest damage. This study aimed to determine whether spraying bacterial or fungal solutions affected insect pests, cone development, and the seed quality of Korean pine Pinus koraiensis Sieb. et Zucc. The experiment was conducted in a forest plantation in Linkou County (Heilongjiang, China) in 2019. Four fungal strains and one bacterial strain were applied during the flowering phase of Korean pine. The results after a year and a half of study indicated that a high concentration of Bacillus thuringiensis 223176 promoted cone development, increased seed weight, and reduced the proportion of damaged cones. Under this treatment, there were 15.873% damaged cones; the seed weight reached 0.829 g, and there were 82.738% fully developed cones. Trees treated with the second most effective strain, Beauveria bassiana 122077, had 30.556% damaged cones and an average seed weight of 0.810 g. Leucanicillium antillanum 01 performed the worst in this study. The seed weight was only 0.775 g, and the damaged and fully developed cones were 52.444 and 41.773%, respectively. In summary, spraying bacterial or fungal solutions during the flowering stage of Korean pine positively impacted seed quality and effectively decreased damage by the lepidopteran species that feed on the cones and seeds in this study.


Comparison of three instruments assessing the quality of economic evaluations: a practical exercise on economic evaluations of the surgical treatment of obesity.
The increasing use of full economic evaluations has led to the development of various instruments to assess their quality. The purpose of this study was to compare the frequently used British Medical Journal (BMJ) check-list and two new instruments: the Consensus Health Economic Criteria (CHEC) list and the Quality of Health Economic Studies (QHES) instrument. The analysis was based on a practical exercise on economic evaluations of the surgical treatment of obesity. The quality of nine selected studies was assessed independently by two health economists. To compare instruments, the Spearman rank correlation coefficient was calculated for each assessor. Moreover, the test-retest reliability for each instrument was assessed with the intraclass correlation coefficient (ICC) (3,1). Finally, the inter-rater agreement for each instrument was estimated at two levels: comparison of the total score of each article by the ICC(2,1) and comparison of results per item by kappa values. The Spearman's rank correlation coefficient between instruments was usually high (rho > 0.70). Furthermore, test-retest reliability was good for every instruments, that is, 0.98 (95 percent CI, 0.86-0.99) for the BMJ check-list, 0.97 (95 percent CI, 0.73-0.98) for the CHEC list, and 0.95 (95 percent CI, 0.75-0.99) for the QHES instrument. However, inter-rater agreement was poor (kappa < 0.40 for most items and ICC(2,1) < or = 0.5). The study shows that the results of the quality assessment of economic evaluations are not so much influenced by the instrument used but more by the assessor. Therefore, quality assessments should be performed by at least two independent experts and final scoring based on consensus.


Consecutive borylcupration/C-C coupling of γ-alkenyl aldehydes towards diastereoselective 2-(borylmethyl)cycloalkanols.
Copper(i) catalyzes the borylative cyclization of γ-alkenyl aldehydes through chemo- and regioselective addition of Cu-B to C[double bond, length as m-dash]C and concomitant intramolecular 1,2-addition of Cu-C on C[double bond, length as m-dash]O. The products are formed in an exclusive diastereoselective manner and computational analysis identifies the key points for the observed chemo- and diastereoselectivity.


Galectin-3 interacts with the cell-surface glycoprotein CD146 (MCAM, MUC18) and induces secretion of metastasis-promoting cytokines from vascular endothelial cells.
The galactoside-binding protein galectin-3 is increasingly recognized as an important player in cancer development, progression, and metastasis via its interactions with various galactoside-terminated glycans. We have shown previously that circulating galectin-3, which is increased up to 30-fold in cancer patients, promotes blood-borne metastasis in an animal cancer model. This effect is partly attributable to the interaction of galectin-3 with unknown receptor(s) on vascular endothelial cells and causes endothelial secretion of several metastasis-promoting cytokines. Here we sought to identify the galectin-3-binding molecule(s) on the endothelial cell surface responsible for the galectin-3-mediated cytokine secretion. Using two different galectin-3 affinity purification processes, we extracted four cell membrane glycoproteins, CD146/melanoma cell adhesion molecule (MCAM)/MUC18, CD31/platelet endothelial cell adhesion molecule-1 (PECAM-1), CD144/VE-cadherin, and CD106/Endoglin, from vascular endothelial cells. CD146 was the major galectin-3-binding ligand and strongly co-localized with galectin-3 on endothelial cell surfaces treated with exogenous galectin-3. Moreover, galectin-3 bound to N-linked glycans on CD146 and induced CD146 dimerization and subsequent activation of AKT signaling. siRNA-mediated suppression of CD146 expression completely abolished the galectin-3-induced secretion of IL-6 and G-CSF cytokines from the endothelial cells. Thus, CD146/MCAM is the functional galectin-3-binding ligand on endothelial cell surfaces responsible for galectin-3-induced secretion of metastasis-promoting cytokines. We conclude that CD146/MCAM interactions with circulating galectin-3 may have an important influence on cancer progression and metastasis.


Limits on volume changes in the mushroom bodies of the honey bee brain.
The behavioral maturation of adult worker honey bees is influenced by a rising titer of juvenile hormone (JH), and is temporally correlated with an increase in the volume of the neuropil of the mushroom bodies, a brain region involved in learning and memory. We explored the stability of this neuropil expansion and its possible dependence on JH. We studied the volume of the mushroom bodies in adult bees deprived of JH by surgical removal of the source glands, the corpora allata. We also asked if the neuropil expansion detected in foragers persists when bees no longer engage in foraging, either because of the onset of winter or because colony social structure was experimentally manipulated to cause some bees to revert from foraging to tending brood (nursing). Results show that adult exposure to JH is not necessary for growth of the mushroom body neuropil, and that the volume of the mushroom body neuropil in adult bees is not reduced if foraging stops. These results are interpreted in the context of a qualitative model that posits that mushroom body neuropil volume enlargement in the honey bee has both experience-independent and experience-dependent components.


Microwave absorption behavior of core-shell structured poly (3,4-ethylenedioxy thiophene)-barium ferrite nanocomposites.
The present paper reports the complex permittivity, permeability, and microwave absorption properties of core shell type poly (3,4-ethylenedioxy thiophene) (PEDOT) nanocomposite with barium ferrite, synthesized by in situ emulsion polymerization, in the 12.4-18 GHz frequency range. High-resolution transmission electron microscopy (HRTEM) studies reveal the formation of core-shell type morphology with ferrite particles (60-80 nm) as the center while the polymer (PEDOT) formulates the outer shell of the composite. The presence of barium ferrite nanoparticles in the polymer matrix includes the magnetic losses, which mainly arise from the magnetic hysteresis, domain-wall displacement, and eddy current loss. The higher dielectric (epsilon'' = 23.5) and magnetic loss (micro'' = 0.22) contributes to the microwave absorption value of 22.5 dB (>99% attenuation) and are found to increase with the amount of ferrite constituents. The polymer was further characterized through Fourier transform infrared spectroscopy (FTIR), energy dispersive X-ray spectroscopy (EDS), and X-ray diffraction (XRD).


Functionalizable Sol-Gel Silica Coatings for Corrosion Mitigation.
Corrosion is constantly a major problem of the world economy in the field of metal products, metal processing and other areas that utilise metals. Previously used compounds utilizing hexavalent chromium were amongst the most effective materials for corrosion protection but regulations have been recently introduced that forbid their use. Consequently, there is a huge drive by engineers, technologists and scientists from different disciplines focused on searching a new, more effective and environmentally-friendly means of corrosion protection. One novel group of materials with the potential to solve metal protection problems are sol-gel thin films, which are increasingly interesting as mitigation corrosion barriers. These environmentally-friendly and easy-to-obtain coatings have the promise to be an effective alternative to hexavalent chromium compounds using for anti-corrosion industrial coatings. In this review the authors present a range of different solutions for slow down the corrosion processes of metallic substrates by using the oxides and doped oxides obtained by the sol-gel method. Examples of techniques used to the sol-gel coating examinations, in terms of anti-corrosion protection, are also presented.


A mouse B-cell alloantigen determined by gene(s) linked to the major histocompatibility complex.
Antibodies cytotoxic for only a subpopulation of C57Bl/10 lymph node and spleen cells were detected when rat antiserum against B10.D2 was exhaustively absorbed with B10.A lymphocytes. Antibodies of similar specificity were also detected in B10.A anti-B10.D2 and in B10.A anti-C57Bl/10 alloantisera. Reactions with recombinant strains of mice indicate that the cell-surface antigen(s) responsible for this specificity is determined by gene(s) in or to the left of the Ir-1 region of the major histocompatibility complex. A variety of criteria implicate B cells as the subpopulation of lymphocytes bearing this antigen. In view of these data and the recent report by others of a T-cell alloantigen determined by gene(s) in the major histocompatibility complex, it seems possible that there may be a variety of H-2-linked alloantigens expressed preferentially on subclasses of lymphocytes.