Insights into the Growth of Ternary WSSe Nanotubes in an Atmospheric CVD Reactor.

The synthesis of complex new nanostructures is challenging but also bears the potential for observing new physiochemical properties and offers unique applications in the long run. High-temperature synthesis of ternary WSe2xS2(1-x) (denoted as WSSe) nanotubes in a pure phase and in substantial quantities is particularly challenging, requiring a unique reactor design and control over several parameters, simultaneously. Here, the growth of WSSe nanotubes with the composition 0 ≤ x < 1 from W18O49 nanowhiskers in an atmospheric chemical vapor deposition (CVD) flow reactor is investigated. The oxide precursor powder is found to be heavily agglomerated, with long nanowhiskers decorating the outer surface of the agglomerates and their core being enriched with oxide microcrystallites. The reaction kinetics with respect to the chalcogen vapors varies substantially between the two kinds of oxide morphologies. Insights into the chemical reactivity and diffusion kinetics of S and Se within W18O49 nanowhishkers and the micro-oxide crystallites were gained through detailed microscopic, spectroscopic analysis of the reaction products and also through density functional theory (DFT) calculations. For safety reasons, the reaction duration was limited to half an hour each. Under these circumstances, the reaction was completed for some 50% of the nanotubes and the other half remained with thick oxide core producing new WOx@WSSe core-shell nanotubes. Furthermore, the selenium reacted rather slowly with the WOx nanowhiskers, whereas the more ionic and smaller sulfur atoms were shown to diffuse and react faster. The yield of the combined hollow and core-shell nanotubes on the periphery of the agglomerated oxide was very high, approaching 100% in parts of the reactor boat. The nanotubes were found to be very thin (∼80% with a diameter <40 nm). The optical properties of the nanotubes were studied, and almost linear bandgap modulation was observed with respect to the selenium content in the nanotubes. This investigation paves the way for further scaling up the synthesis and for a detailed study of the different properties of WSSe nanotubes.

Effect of membrane stabilizers on semen quality and sperm membrane protein expression during cryopreservation of goat semen.

BACKGROUND: Semen cryopreservation is a complex process during which there is alteration in the expression of sperm and seminal plasma proteins, molecular weight of protein or loss of membrane proteins during the process. In order to compensate for these changes, different membrane stabilizers are used in freezing semen extenders. However, there is scarcity of such studies during cryopreservation of goat semen. OBJECTIVE: To investigate the effect of membrane stabilizers on sperm membrane protein expression during cryopreservation of goat semen. MATERIALS AND METHODS: A total of 36 semen ejaculates from nine Assam Hill Goat bucks aged 2 to 2.5 years was collected by artificial vagina method. Three membrane stabilizers, each at two different concentrations viz. 50 and 80 mM sucrose, 50 and 100 mM trehalose, and 100 and 150 ng per mL IGF-1 (insulin-like growth factor 1 protein) were added to Tris-citric acid fructose egg yolk glycerol (TCFEYG) extender and semen samples were cryopreserved. The sperm membrane protein profile was studied in fresh and cryopreserved semen by SDS-PAGE. RESULTS: SDS- PAGE of sperm membrane extract of fresh semen revealed the presence of 24 protein bands with molecular weights ranging from 10 kDa to 240 kDa. Samples supplemented with 50 mM sucrose and 80 mM sucrose revealed 21 protein bands with molecular weights ranging from 10 kDa to 240 kDa. All the 21 protein bands were same as those observed in the sperm membrane of fresh spermatozoa, except that the 23 kDa, 29 kDa and 42 kDa bands were absent in frozen semen. Similarly, frozen semen extended with 50 mM trehalose and 100 mM trehalose revealed 22 protein bands with molecular weights ranging from 10 kDa to 240 kDa, but lacking the 29 kDa and 42 kDa bands. Proteins with molecular weights of 29 kDa, 130 kDa and 240 kDa were absent in frozen semen supplemented with 100 ng per mL IGF-1 and 150 ng per mL IGF-1. CONCLUSION: The present study revealed that supplementation of tris basic extender with trehalose at 100 mM and or IGF-1 at 100 ng/mL or 150 ng per mL improves the post-thaw semen characteristics and protects certain fertility related sperm membrane proteins. Doi.org/10.54680/fr23510110612.

A Meta-Analysis on Comparison of Open vs Closed Reduction of Gartland Type 3 Supracondylar Humerus Fractures in Children.

PURPOSE OF THE STUDY Although there are numerous studies on outcomes and comparison of open and closed reduction but there is no clarity on relationship between outcomes and complications with type of surgical intervention done for Type 3 Gartland supracondylar humerus fracture. The aim of this study is to compare the outcomes and complications of closed vs open reduction in Type 3 Gartland supracondylar humerus fractures. MATERIAL AND METHODS Electronic literature searches of Embase, MEDLINE and the Cochrane Library was conducted in February 2022 using the terms "supracondylar", "humerus", "fracture", "Gartland type 3" and synonymous. The data extracted included the study details, demographic data, procedure performed, final functional and cosmetic outcome according to Flynn criteria and complications of included studies. RESULTS Pooled data analysis revealed no significant difference in mean satisfactory outcome rate according to Flynn cosmetic criteria in open group (97%, 95% CI 95.5%-98.5%), as compared to closed group (97.5%, 95% CI 96.3%-98.7%), although a statistically significant difference in mean satisfactory rate according to Flynn functional criteria in open group (93.4%, 95% CI 90.8%- 96.1%) as compared to closed group (98.5%, 95% CI 97.5%-99.4%) was noted. On separate comparison of the two-arm studies, closed reduction favoured better functional outcomes (RR 0.92, 95% CI 0.86-0.99). CONCLUSIONS Closed reduction and percutaneous fixation have better functional outcome than open reduction with K-wire fixation. But there was no significant difference in cosmetic outcomes, overall complication rate and nerve injury with either open or closed reduction. The threshold of converting a closed reduction to an open reduction in supracondylar humerus fractures of children should be high. Key words: supracondylar humerus, open reduction, percutaneous pinning, Flynn criteria.

Metabolic transitions define spermatogonial stem cell maturation.

STUDY QUESTION: Do spermatogonia, including spermatogonial stem cells (SSCs), undergo metabolic changes during prepubertal development? SUMMARY ANSWER: Here, we show that the metabolic phenotype of prepubertal human spermatogonia is distinct from that of adult spermatogonia and that SSC development is characterized by distinct metabolic transitions from oxidative phosphorylation (OXPHOS) to anaerobic metabolism. WHAT IS KNOWN ALREADY: Maintenance of both mouse and human adult SSCs relies on glycolysis, while embryonic SSC precursors, primordial germ cells (PGCs), exhibit an elevated dependence on OXPHOS. Neonatal porcine SSC precursors reportedly initiate a transition to an adult SSC metabolic phenotype at 2 months of development. However, when and if such a metabolic transition occurs in humans is ambiguous. STUDY DESIGN, SIZE, DURATION: To address our research questions: (i) we performed a meta-analysis of publicly available and newly generated (current study) single-cell RNA sequencing (scRNA-Seq) datasets in order to establish a roadmap of SSC metabolic development from embryonic stages (embryonic week 6) to adulthood in humans (25 years of age) with a total of ten groups; (ii) in parallel, we analyzed single-cell RNA sequencing datasets of isolated pup (n = 3) and adult (n = 2) murine spermatogonia to determine whether a similar metabolic switch occurs; and (iii) we characterized the mechanisms that regulate these metabolic transitions during SSC maturation by conducting quantitative proteomic analysis using two different ages of prepubertal pig spermatogonia as a model, each with four independently collected cell populations. PARTICIPANTS/MATERIALS, SETTING, METHODS: Single testicular cells collected from 1-year, 2-year and 7-year-old human males and sorted spermatogonia isolated from 6- to 8-day (n = 3) and 4-month (n = 2) old mice were subjected to scRNA-Seq. The human sequences were individually processed and then merged with the publicly available datasets for a meta-analysis using Seurat V4 package. We then performed a pairwise differential gene expression analysis between groups of age, followed by pathways enrichment analysis using gene set enrichment analysis (cutoff of false discovery rate < 0.05). The sequences from mice were subjected to a similar workflow as described for humans. Early (1-week-old) and late (8-week-old) prepubertal pig spermatogonia were analyzed to reveal underlying cellular mechanisms of the metabolic shift using immunohistochemistry, western blot, qRT-PCR, quantitative proteomics, and culture experiments. MAIN RESULTS AND THE ROLE OF CHANCE: Human PGCs and prepubertal human spermatogonia show an enrichment of OXPHOS-associated genes, which is downregulated at the onset of puberty (P < 0.0001). Furthermore, we demonstrate that similar metabolic changes between pup and adult spermatogonia are detectable in the mouse (P < 0.0001). In humans, the metabolic transition at puberty is also preceded by a drastic change in SSC shape at 11 years of age (P < 0.0001). Using a pig model, we reveal that this metabolic shift could be regulated by an insulin growth factor-1 dependent signaling pathway via mammalian target of rapamycin and proteasome inhibition. LARGE SCALE DATA: New single-cell RNA sequencing datasets obtained from this study are freely available through NCBI GEO with accession number GSE196819. LIMITATIONS, REASONS FOR CAUTION: Human prepubertal tissue samples are scarce, which led to the investigation of a low number of samples per age. Gene enrichment analysis gives only an indication about the functional state of the cells. Due to limited numbers of prepubertal human spermatogonia, porcine spermatogonia were used for further proteomic and in vitro analyses. WIDER IMPLICATIONS OF THE FINDINGS: We show that prepubertal human spermatogonia exhibit high OXHPOS and switch to an adult-like metabolism only after 11 years of age. Prepubescent cancer survivors often suffer from infertility in adulthood. SSC transplantation could provide a powerful tool for the treatment of infertility; however, it requires high cell numbers. This work provides key insight into the dynamic metabolic requirements of human SSCs across development that would be critical in establishing ex vivo systems to support expansion and sustained function of SSCs toward clinical use. STUDY FUNDING/COMPETING INTEREST(S): This work was funded by the NIH/NICHD R01 HD091068 and NIH/ORIP R01 OD016575 to I.D. K.E.O. was supported by R01 HD100197. S.K.M. was supported by T32 HD087194 and F31 HD101323. The authors declare no conflict of interest.

Safety, quality and efficiency of intra-operative imaging for treatment decisions in patients with suspected choledocholithiasis without pre-operative magnetic resonance cholangiopancreatography.

INTRODUCTION: Cholecystectomy is the accepted treatment for patients with symptomatic gallstones. In this study, we evaluate a simplified strategy for managing suspected synchronous choledocholithiasis by focussing on intra-operative imaging as the primary decision-making tool to target common bile duct (CBD) stone treatment. METHODS: All elective and emergency patients undergoing laparoscopic cholecystectomy (LC) for gallstones with any markers of synchronous choledocholithiasis were included. Patients unfit for surgery or who had pre-operative proof of choledocholithiasis were excluded. Intra-operative imaging was used for evaluation of the CBD. CBD stone treatment was with bile duct exploration (LCBDE) or endoscopic retrograde cholangiopancreatography (LC + ERCP). Outcomes were safety, effectiveness and efficiency. RESULTS: 506 patients were included. 371 (73%) had laparoscopic ultrasound (LUS), 80 (16%) had on-table cholangiography (OTC) and 55 (11%) had both. 164 (32.4%) were found to have CBD stones. There was no increase in length of surgery for LC + LUS compared with average time for LC only in our unit (p = 0.17). 332 patients (65.6%) had clear ducts. Imaging was indeterminate in 10 (2%) patients. Overall morbidity was 10.5%. There was no mortality. 142 (86.6%) patients with stones on intra-operative imaging proceeded to LCBDE. 22 (13.4%) patients had ERCP. Sensitivity and specificity of intra-operative imaging were 93.3 and 99.1%, respectively. Success rate of LCBDE was 95.8%. Effectiveness was 97.8%. CONCLUSIONS: Eliminating pre-operative bile duct imaging in favour of intra-operative imaging is safe and effective. When combined with intra-operative stone treatment, this method becomes a true 'single-stage' approach to managing suspected choledocholithiasis.

Bioactive phytocompound mulberroside C and endophytes of Morus alba as potential inhibitors of HIV-1 replication: a mechanistic evaluation.

OBJECTIVES: Despite considerable advancement in antiretroviral therapy, development of safe, effective, and multi-targeted drugs for HIV still remains a big challenge. Endophytes are untouched and, hence, an important and novel sources in drug discovery endeavours. The present study was conducted to identify the anti-HIV compounds from Morus alba and endophytes isolated from it. METHODS: The extracts of isolated endophytes were screened using high-performance liquid chromatography (HPLC). Further, all samples were analysed for their cytotoxicity using a thiazolyl blue tetrazolium bromide assay. Subsequently, anti-HIV activity was performed using cell-based and cell-free assay. At the end, potential endophytes were identified using gene sequencing. RESULTS: A total of 27 endophytes were isolated from the eight stem bark samples of M. alba. Of the 27 endophytes, extracts of total of four endophytes showed a profile similar to the M. alba plant when analysed by HPLC. Further experimentation with extracts of these four endophytes, along with an extract of M. alba stem bark and its bioactive molecule, mulberroside C, revealed that all these six samples have good inhibitory potential for HIV. Among them, mulberroside C and two endophytic fungal extracts showed very potent anti-HIV activity. Subsequently, mechanistic studies at the molecular level showed that out of six test samples, three acted as protease inhibitors. Further, all four potential endophytes were identified using gene sequencing. CONCLUSIONS: The overall findings of these studies can help in the development of a novel anti-HIV candidate from mulberroside C, an extract of stem bark of M. alba and extracts of these endophytes. However, further validation and clinical studies are required to develop an anti-HIV drug.

Comparative evaluation of the conventional tube test and column agglutination technology for ABO antibody titration in healthy individuals: a report from India.

Determination of accurate anti-A/-B titers is important for treatment selection in ABO-incompatible stem cell and solid-organ transplants. The standard method for ABO antibody titration is the conventional tube test (CTT). Dithiothreitol (DTT) is commonly used to inactivate the IgM antibody component. The aim of this study was to compare six different methods for ABO antibody titration and to observe the effectiveness of DTT on antibody estimation. A total of 90 healthy voluntary blood donors were enrolled in this study, including 30 each for blood groups A, B, and O. Antibody titrations were performed and tested using the CTT-immediate spin (IS), CTT-antihuman globulin (AHG) with and without DTT, column agglutination technology (CAT)-IS, and CAT-AHG with and without DTT methods. Bead-CAT was used, and the positive cutoff value was set to 1+ for each method to determine the endpoint of the titer. The median values of anti-A/-B titers by IS were found to be higher than those values by AHG in CTT and CAT among group B and A individuals, whereas no statistically significant differences were observed in values from group O individuals for IS and AHG anti-A/-B titers, estimated by each method. Although there was positive correlation between the anti-A/-B titer results obtained using the CTT and CAT in all blood groups, testing using AHG showed poor agreement with and without DTT pretreatment (kappa value of 0.11 and 0.20, respectively). Moderate agreement was observed between CTT-IS and CAT-IS (kappa value of 0.46). Median anti-A/-B AHG titers were reduced by the use of DTT in all blood group samples. Significant differences in the interpretability of anti-A/-B titers were observed among different methods. A uniform approach for selecting the method for ABO antibody titration is highly recommended, and DTT pretreatment of plasma to neutralize IgM activity should be considered to obtain precise values of IgG anti-A/-B titers. Immunohematology 2021;37:25-32 .Determination of accurate anti-A/-B titers is important for treatment selection in ABO-incompatible stem cell and solid-organ transplants. The standard method for ABO antibody titration is the conventional tube test (CTT). Dithiothreitol (DTT) is commonly used to inactivate the IgM antibody component. The aim of this study was to compare six different methods for ABO antibody titration and to observe the effectiveness of DTT on antibody estimation. A total of 90 healthy voluntary blood donors were enrolled in this study, including 30 each for blood groups A, B, and O. Antibody titrations were performed and tested using the CTT-immediate spin (IS), CTT-antihuman globulin (AHG) with and without DTT, column agglutination technology (CAT)-IS, and CAT-AHG with and without DTT methods. Bead-CAT was used, and the positive cutoff value was set to 1+ for each method to determine the endpoint of the titer. The median values of anti-A/-B titers by IS were found to be higher than those values by AHG in CTT and CAT among group B and A individuals, whereas no statistically significant differences were observed in values from group O individuals for IS and AHG anti-A/-B titers, estimated by each method. Although there was positive correlation between the anti-A/-B titer results obtained using the CTT and CAT in all blood groups, testing using AHG showed poor agreement with and without DTT pretreatment (kappa value of 0.11 and 0.20, respectively). Moderate agreement was observed between CTT-IS and CAT-IS (kappa value of 0.46). Median anti-A/-B AHG titers were reduced by the use of DTT in all blood group samples. Significant differences in the interpretability of anti-A/-B titers were observed among different methods. A uniform approach for selecting the method for ABO antibody titration is highly recommended, and DTT pretreatment of plasma to neutralize IgM activity should be considered to obtain precise values of IgG anti-A/-B titers. Immunohematology 2021;37:25­32 .

Chaos and Quantum Scars in Bose-Josephson Junction Coupled to a Bosonic Mode.

We consider a model describing Bose-Josephson junction (BJJ) coupled to a single bosonic mode exhibiting quantum phase transition (QPT). Onset of chaos above QPT is observed from semiclassical dynamics as well from spectral statistics. Based on entanglement entropy, we analyze the ergodic behavior of eigenstates with increasing energy density which also reveals the influence of dynamical steady state known as π-mode on it. We identify the imprint of unstable π-oscillation as many body quantum scar (MBQS), which leads to the deviation from ergodicity and quantify the degree of scarring. Persistence of phase coherence in nonequilibrium dynamics of such initial state corresponding to the π-mode is an observable signature of MBQS which has relevance in experiments on BJJ.

The role of imaging in malignant pleural mesothelioma: an update after the 2018 BTS guidelines.

Malignant pleural mesothelioma (MPM) is a primary malignancy of the pleura and is associated with a poor outcome. The symptoms and signs of malignant mesothelioma present late in the natural history of the disease and are non-specific, making the diagnosis challenging and imaging key. In 2018, the British Thoracic Society (BTS) updated the guideline on diagnosis, staging, and follow-up of patients with MPM. These recommendations are discussed in this review of the current literature on imaging of MPM. It is estimated MPM will continue to cause serious morbidity and mortality in the UK late into the 21st century, and internationally, people continue to be exposed to asbestos. We aim to update the reader on current and future imaging strategies, which could aid early diagnosis of pleural malignancy and provide an update on staging and assessment of tumour response.

An observational analysis of low-dose thalidomide in recalcitrant prurigo nodularis.

Thalidomide has been used as an effective treatment for prurigo nodularis (PN) with a median dose of 200 mg, but the risk of peripheral neuropathy precludes long-term use. We analysed the efficacy of low-dose thalidomide (< 100 mg) in 17 patients with recalcitrant PN. Patients were initiated on thalidomide 50 mg on alternate days, and the dose was increased (doubled) in a stepwise manner, if needed, until a ≥ 50% reduction in score (partial response; PR) on a visual analogue scale (VAS) was achieved. Thalidomide then was continued at the same dose for 4 weeks to achieve ≥ 90% decrease in VAS score; if this was not achieved, the dose was increased to a maximum of 100 mg and continued until complete resolution of lesions (complete response; CR). Four patients discontinued thalidomide due to adverse effects. Four patients achieved PR, while 9 patients (n = 2 with 50 mg, n = 7 with 100 mg) achieved CR. No patient developed neuropathy. In addition, complete responders achieved an earlier ≥ 50% reduction in VAS score. Two patients relapsed after 12 months but responded to thalidomide 50 mg.

OssDsign cranioplasty in children: a single-centre experience.

INTRODUCTION: OssDsign have developed a new type of cranioplasty plate, consisting of calcium phosphate reinforced with titanium. Currently, there is little known about the cosmetic outcomes and infection rate when OssDsign cranioplasty plates are implanted into paediatric patients. METHODS: A retrospective case series was performed to include all paediatric patients who received an OssDsign cranioplasty at a single centre, Sheffield Children's Hospital. The cosmetic outcomes were subjectively reported by the parents of the children. RESULTS: We identified seven paediatric patients where OssDsign cranioplasty was performed. This included two bifrontal and five hemicranioplasties. However, there was failure to implant an OssDsign hemicranioplasty in one patient where a titanium plate was subsequently used. The median duration of follow-up was 15 months. The infection rate was zero. The parents of the patients who successfully received OssDsign cranioplasties were pleased with the cosmetic outcomes. There were cosmetic complaints from the parents of the one patient who received a titanium plate. CONCLUSION: Our early experience with OssDsign cranioplasty in paediatric patients indicates that it may potentially be associated with a low rate of infection and good cosmetic outcomes.

A comparison between flow-regulated and adjustable valves used in hydrocephalus during infancy.

INTRODUCTION: Ventriculoperitoneal shunt insertion during the neonatal period and early infancy is associated with a high rate of shunt failure when compared to the adult population. Furthermore, the function of flow-regulated valves and differential pressure valves may be different in neonatal hydrocephalus. METHODS: A retrospective case series of all primary shunt procedures carried out during or immediately following the neonatal period, from August 2011 to February 2018 at Sheffield Children's Hospital. The total sample size was 55. This included 34 patients with adjustable valves (Miethke ProGav) and 21 with flow-regulated valves (Orbis-Sigma); however, only 53 had adequate follow-up. RESULTS: The overall 1 year shunt survival was 34% (18/53), and there was no significant difference depending on which shunt valve was implanted. The primary shunt infection rate was 11% (6/53) with S. aureus being the most common causative organism. During the first year of life, clinical signs of shunt overdrainage were seen more frequently in patients with adjustable valves than in those with flow-regulated valves (59% [19/32] versus 24% [5/21], p = 0.02). Furthermore, 2 patients in the adjustable valve group developed sagittal craniosynostosis secondary to shunt overdrainage. CONCLUSION: Shunt failure is high when inserted during or immediately following the neonatal period. Overdrainage may be less common in patients with flow-regulated valves. However, if overdrainage is observed, adjusting the setting of a differential pressure valve can effectively treat the overdrainage without the need for invasive shunt revision surgery.

Evaluating sensitivity of hyperspectral indices for estimating mangrove chlorophyll in Middle Andaman Island, India.

Mangroves are the highly productive and extensive ecosystem in the tropical coasts. Chlorophyll is the key foliar determinant of mangrove productivity. Optical characteristics of mangrove markedly differ from land vegetation; hence, defining narrowband spectral indices most sensitive to mangrove chlorophyll is crucial, in view of their importance to the coastal environment and mounting biotic pressures. We assessed the sensitivity of a set of satellite hyperspectral remote sensing indices to mangrove canopy chlorophyll in Middle Andaman Island, India, and propose most robust spectral indices for mangrove chlorophyll estimation. We generated simple, modified simple, normalized difference vegetation, and non-linear indices from all possible two band combinations of EO-1 Hyperion bands in the 500-900 nm spectral range. The strength of correlation between each pair of spectral indices to mangrove chlorophyll was analyzed in 2D correlograms and validated using k-fold cross-validation technique. Results show that 549 nm, 559 nm (green) and 702 nm, 722 nm, 742 nm, and 763 nm (red-edge) wavelengths are the most sensitive to mangrove chlorophyll. We report performance of traditional chlorophyll indices and new indices with higher predictive capability for mangrove chlorophyll prediction. Simple ratio (559 nm/885 nm) offered the strongest correlation with mangrove chlorophyll (R2-0.75, RMSE-0.60, p < 0.05). Study findings will help researchers in deciding suitable chlorophyll indices for mangrove productivity and stress assessment. The best calibrated index was used to prepare mangrove chlorophyll spatial variability map of the study area.

One-Dimensional Quasicrystals with Power-Law Hopping.

One-dimensional quasiperiodic systems with power-law hopping, 1/r^{a}, differ from both the standard Aubry-André (AA) model and from power-law systems with uncorrelated disorder. Whereas in the AA model all single-particle states undergo a transition from ergodic to localized at a critical quasidisorder strength, short-range power-law hops with a>1 can result in mobility edges. We find that there is no localization for long-range hops with a≤1, in contrast to the case of uncorrelated disorder. Systems with long-range hops rather present ergodic-to-multifractal edges and a phase transition from ergodic to multifractal (extended but nonergodic) states. Both mobility and ergodic-to-multifractal edges may be clearly revealed in experiments on expansion dynamics.

Effects of saxagliptin on adipose tissue inflammation and vascular function in overweight and obese people: a placebo-controlled study.

AIMS: To test the effect of the dipeptidyl peptidase-4 inhibitor saxagliptin on adipose tissue inflammation and microvascular function, and whole-body postprandial endothelial function. METHODS: A randomized, double-blind, placebo-controlled, parallel study was conducted between June 2013 and November 2016 in 44 overweight or obese people without diabetes (saxagliptin, n=28; placebo, n=16). Subcutaneous abdominal adipose tissue biopsies, a 4-h fat-enriched meal test and peripheral arterial tonometry for measurement of endothelial function were performed at baseline and after 6 weeks of treatment with saxagliptin (5 mg/day) or matching placebo. RESULTS: Forty participants were analysed (saxagliptin, n=26; placebo, n=14). Secretion of interleukin-8 from adipose tissue explants was reduced after saxagliptin (median fold-change from baseline: 0.8 saxagliptin vs 3.3 placebo; P=0.02). Adipose tissue expression of thioredoxin-inhibitory protein (TxNIP) was lower after saxagliptin (0.75 vs 1.0; P=0.02), while there were no significant differences in adipose tissue secretion of interleukin-1b, interleukin-6 or macrophage chemoattractant protein 1 (MCP-1), adipose tissue macrophage content, adipose tissue mRNA levels of mcp1, cd36, cd68, il6, il8, txnip and adpq, and activation of adipose tissue inflammatory pathways [extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK) and nuclear factor-κB (NF- κB)] or insulin-induced vasodilation of adipose tissue arterioles. Postprandial plasma glucose was slightly lower (by an estimated 0.3 mmol/l; P=0.01), while postprandial insulin, triglyceride levels and endothelial function were unchanged after saxagliptin. CONCLUSIONS: The effect of saxagliptin on adipose tissue inflammation was relatively modest, with many inflammatory markers unchanged. We also found no evidence that saxagliptin therapy improved adipose tissue arteriole vasodilation or postprandial endothelial function.

Magnitude of unreported kala-azar cases in a highly endemic district of Bihar, India: A positive impact of Indian elimination programme.

BACKGROUND & OBJECTIVES: In India, kala-azar surveillance is weak and no public-private partnership exists for disease containment. Estimate of disease burden is not reliably available and still cases are going to private providers for the treatment. The present study aimed to assess the magnitude of kala-azar cases actually detected and managed at private set-up and unreported to existing health management information system. METHODS: Institution based cross-sectional prospective pilot study was conducted. List of facilities was created with the help of key informants. The information about incidence of kala-azar cases were captured on monthly basis from July 2010 to June 2011. Rapid diagnostic strip test (rk-39) or bone marrow/splenic puncture were applied as laboratory methods for the diagnosis of kala-azar. Descriptive statistics as well as chi-square test for comparison between proportions was conducted. RESULTS: Overall availability of private practitioners (PPs) was 4.59/1,00,000 population and maximum PPs (46; 93.9%) were from qualified category. The median years of medical practice was 25 yr (inter quartile-range [18, 28]). Interestingly, only a small proportion (240; 19%) of cases was managed by PPs. Amongst the PPs, only low proportion (32; 18.2%) managed >2 cases per month. The mean number of kala-azar suspects and cases identified varied significantly between different PPs' professions with p <0.048 and p <0.032, respectively. A highly significant difference (p <0.0001) was observed for kala-azar case load between qualified and unqualified practitioners. A small proportion (38; 15.8%) of kala-azar cases was not present in the public health system record. INTERPRETATION & CONCLUSION: Still sizeable proportions of cases are going to PPs and unrecorded into government surveillance system. A mechanism need to be devised to involve at least qualified PPs in order to reduce treatment delay and increase case detection in the region.

Quantitative Characterization of the Nanoscale Local Lattice Strain Induced by Sr Dopants in La_{1.92}Sr_{0.08}CuO_{4}.

The nanometer scale lattice deformation brought about by the dopants in the high temperature superconducting cuprate La_{2-x}Sr_{x}CuO_{4} (x=0.08) was investigated by measuring the associated x-ray diffuse scattering around multiple Bragg peaks. A characteristic diffuse scattering pattern was observed, which can be well described by continuum elastic theory. With the fitted dipole force parameters, the acoustic-type lattice deformation pattern was reconstructed and found to be of similar size to lattice thermal vibration at 7 K. Our results address the long-term concern of dopant introduced local lattice inhomogeneity, and show that the associated nanometer scale lattice deformation is marginal and cannot, alone, be responsible for the patched variation in the spectral gaps observed with scanning tunneling microscopy in the cuprates.

First-time-in-human randomized clinical trial in healthy volunteers and haemodialysis patients with SNF472, a novel inhibitor of vascular calcification.

AIMS: SNF472 is a calcification inhibitor being developed for the treatment of cardiovascular calcification in haemodialysis (HD) and in calciphylaxis patients. This study investigated the safety, tolerability and pharmacokinetics (PK) of intravenous (IV) SNF472 in healthy volunteers (HV) and HD patients. METHODS: This is a first-time-in-human, double-blind, randomized, placebo-controlled Phase I study to assess the safety, tolerability and PK of SNF472 after ascending single IV doses in HV and a single IV dose in HD patients. A pharmacodynamic analysis was performed to assess the capability of IV SNF472 to inhibit hydroxyapatite formation. RESULTS: Twenty HV and eight HD patients were enrolled. The starting dose in HV was 0.5 mg kg-1 and the dose ascended to 12.5 mg kg-1 . The dose selected for HD patients was 9 mg kg-1 . Safety analyses support the safety and tolerability of IV SNF472 in HD patients and HV. Most treatment-emergent adverse events were mild in intensity. No clinically significant effects were observed on vital signs or laboratory tests. PK results were similar in HD patients and HV and indicate a lack of significant dialysability. Pharmacodynamic analyses demonstrated that SNF472 administration reduced hydroxyapatite crystallization potential in HD patients who received IV SNF472 9 mg kg-1 by 80.0 ± 2.4% (mean ± standard error of the mean, 95% CI, 75.3-84.8) compared to placebo (8.7 ± 21.0%, P < 0.001, 95% CI, -32.4 to 49.7). CONCLUSION: The results from this study showed acceptable safety and tolerability, and lack of significant dialysability of IV SNF472. It is a potential novel treatment for cardiovascular calcification in end-stage renal disease and calciphylaxis warranting further human studies.

Pre-freezing Treatment with Butylated Hydroxytoluene and Cholesterol-loaded Methyl-ß-cyclodextrin Improves Quality of Cryopreserved Boar Semen.

BACKGROUND: Pre-freezing treatment of boar sperm with additives improves the quality of post-thaw sperms. OBJECTIVES: The study aimed to determine the efficacy of butylated hydroxy-toluene (BHT) and cholesterol-loaded methyl-ß-cyclodextrin (CLC) for the improvement of the frozen-thawed boar sperm quality. METHODS: Split samples of 30 ejaculates from six boars were cryopreserved in lactose-egg yolk-glycerol extender containing BHT (0.2 mM), CLC (5 mg/ 200-240 x 106 sperm) or BHT (0.2 mM) plus CLC (5 mg per 200-240 x 106 sperm). Semen samples were evaluated for motility, membrane integrity, acrosomal status, mitochondrial membrane potential (MMP), DNA integrity and lipid peroxidation after equilibration and after freezing. RESULTS: The addition of BHT and CLC into the extender significantly improved (P<0.05) plasma membrane integrity and decreased (P<0.05) lipid peroxidation after freezing. Post-thaw motility and live intact acrosome were significantly (P<0.05) higher in the extenders with BHT or BHT plus CLC. The post-thaw MMP of viable spermatozoa and DNA integrity were not affected. BHT plus CLC showed a significant (P<0.05) improvement on motility as compared to BHT and CLC alone. CONCLUSION: Treatment of boar spermatozoa with BHT and CLC improved post-thaw sperm quality.

Effect of Reduced Glutathione, Water Soluble Vitamin E Analogue and Butylated Hydroxytoluene on the Post Thaw Characteristics of Boar Spermatozoa.

BACKGROUND: Antioxidant in freezing extender of boar semen improved post thaw sperm function. OBJECTIVE: The study compared the effects of reduced glutathione (GSH), water soluble vitamin E analogue Trolox and butylated hydroxytoluene (BHT) on quality of cryopreserved boar spermatozoa. MATERIALS AND METHODS: Using split sample technique three different antioxidants namely, GSH (1 mM), vitamin E (0.2 mM) and BHT (0.2 mM) were added to the freezing medium of lactose-egg yolk-glycerol extender, and samples were frozen using controlled freezing rate of 40°C/min from -6 to -140°C. Samples were evaluated for sperm motility, acrosomal status, plasma membrane integrity, mitochondrial membrane potential, lipid peroxidation and sperm DNA integrity after equilibration and after freezing. RESULTS: The supplementation of GSH, vitamin E and BHT resulted in significantly higher post thaw motility, live intact acrosome and plasma membrane intact sperm. The incidence of post thaw sperm lipid peroxidation was significantly reduced after addition of antioxidants. However, antioxidants treatment neither significantly improved mitochondrial membrane potential of live sperm sub-population nor sperm DNA integrity after freezing. There was no significant difference of the post thaw sperm characteristics among three antioxidants. Protective effect of GSH, vitamin E and BHT are comparable on cryopreserved boar spermatozoa.