Assessment of the immune responses to Treponema pallidum Gpd DNA vaccine adjuvanted with IL-2 and chitosan nanoparticles before and after Treponema pallidum challenge in rabbits.
Syphilis is a multistage, sexually transmitted disease caused by the spirochete, Treponema pallidum (Tp). A significantly high incidence of syphilis has been reported in several countries, including China, and there is an urgent need for the development of efficacious vaccines against syphilis. DNA vaccines are a major breakthrough in the field of vaccination with several advantages over traditional vaccines. Animal model studies of Tp DNA vaccines have not been reported elsewhere but our previous reports describe the development of a single-gene Tp DNA vaccine and preclinical immunization study. In this study, chitosan (CS) nanoparticles were used as a vector and an interleukin-2 expression plasmid (pIL-2) as an adjuvant to enhance a TpGpd DNA vaccine candidate (pTpGpd) in a rabbit Tp skin challenge model. At week 8 after the first immunization, three rabbits from each group were used to determine cytokine measurements and spleen lymphocyte proliferation assay. pTpGpd in combination with pIL-2 wrapped with CS led to the greatest enhancement of anti-TpGpd antibodies and T-cell proliferation. During infection, levels of anti-TpGpd antibodies and T-cell proliferation were measured. Both the serum special IgG and IL-2, interferon-γ were significantly increased by the co-injection of the IL-2 plasmid compared with the injection of TpGpd DNA alone (P<0.05). Furthermore, IL-2 plasmid coinjection efficiently enhanced the antigen-specific lymphocyte proliferation response. Additionally, the ratios of positive skin lesions and ulcer lesions in groups immunized with pTpGpd were significantly lower than those of the pIL-2, CS or pIL-2 mixed with CS control groups (P<0.001). CS vectored and pIL-2 adjuvanted pTpGpd immunized animals exhibited the lowest rates of positive skin tests (8.33%) and ulcer lesions (4.17%) and the fastest recovery (42 d). These experiments indicate that co-injection of a pIL-2 plasmid with pTpGpd DNA vaccine wrapped with CS can significantly strengthen the long-term stability of immune response during infection, efficiently improve the protective effect against T. pallidum spirochetes infection and attenuate syphilitic lesion development.


Measurable residual disease analysis in paediatric acute lymphoblastic leukaemia patients with ABL-class fusions.
ABL-class fusions including NUP214-ABL1 and EBF1-PDGFRB occur in high risk acute lymphoblastic leukaemia (ALL) with gene expression patterns similar to BCR-ABL-positive ALL. Our aim was to evaluate new DNA-based measurable residual disease (MRD) tests detecting these fusions and IKZF1-deletions in comparison with conventional immunoglobulin/T-cell receptor (Ig/TCR) markers. Precise genomic breakpoints were defined from targeted or whole genome next generation sequencing for ABL-fusions and BCR-ABL1. Quantitative PCR assays were designed and used to re-measure MRD in remission bone marrow samples previously tested using Ig/TCR markers. All MRD testing complied with EuroMRD guidelines. ABL-class patients had 46% 5year event-free survival and 79% 5year overall survival. All had sensitive fusion tests giving high concordance between Ig/TCR and ABL-class fusion results (21 patients, n = 257 samples, r2 = 0.9786, P < 0.0001) and Ig/TCR and IKZF1-deletion results (9 patients, n = 143 samples, r2 = 0.9661, P < 0.0001). In contrast, in BCR-ABL1 patients, Ig/TCR and BCR-ABL1 tests were discordant in 32% (40 patients, n = 346 samples, r2 = 0.4703, P < 0.0001) and IKZF1-deletion results were closer to Ig/TCR (25 patients, n = 176, r2 = 0.8631, P < 0.0001). MRD monitoring based on patient-specific assays detecting gene fusions or recurrent assays for IKZF1-deletions is feasible and provides good alternatives to Ig/TCR tests to monitor MRD in ABL-class ALL.


Simultaneous saccharification and lactic acid fermentation of the cellulosic fraction of municipal solid waste using Bacillus smithii.
A primary drawback to simultaneous saccharification and fermentation (SSF) processes is the incompatibility of the temperature and pH optima for the hydrolysis and fermentation steps-with the former working best at 50-55 °C and pH 4.5-5.5. Here, nine thermophilic Bacillus and Parageobacillus spp. were evaluated for growth and lactic acid fermentation at high temperature and low pH. The most promising candidate was then carried forward to demonstrate SSF using the cellulosic fraction from municipal solid waste (MSW) as a feedstock. B. smithii SA8Eth was identified as the most promising candidate and in a batch SSF maintained at 55 °C and pH 5.0, using a cellulase dose of 5 FPU/g glucan, it produced 5.1 g/L lactic acid from 2% (w/v) MSW cellulosic pulp in TSB media. This work has both scientific and industrial relevance, as it evaluates a number of previously untrialled bacterial hosts for their compatibility with lignocellulosic SSF for lactic acid production and successfully identifies B. smithii as a potential candidate for such a process.


Progressive bulbur paralysis (Fazio-Londe disease).
Progressive bulbar paralysis of childhood is characterised by progressive paralysis of muscles innervated by cranial nerves. The authors report a case of progressive bulbar paralysis of childhood in a 12-year-old child. Child was admitted with the complaints of drooping of eyelids, difficulty in swallowing and hoarse voice. She had involvement of III, VII, IX, X, XI and XII cranial nerves and the corticospinal tracts. Electromyography revealed spontaneous activity in the form of fasciculations, giant motor unit potential and discrete recruitment of motor neurons suggestive of denervation pattern. Hearing assessment was normal. Muscle biopsy was also suggestive of neurogenic atrophy.


Organ and subcellular distribution of selenium in rats exposed to cadmium, mercury, and selenium.
Three groups of rats were given sodium selenite (Se), sodium selenite and cadmium chloride (Se + Cd), or sodium selenite, cadmium chloride, and mercuric chloride (Se + Cd + Hg), respectively. All animals received subcutaneous doses of 115CdCl2 (0.3 mg Cd/kg) every other day for a fortnight. Mercuric chloride was administered intravenously at doses of 0.5 mg Hg/kg every other day and Na2 75SeO3 intragastrically at doses of 0.1 mg Se/kg every other day for 2 weeks. The whole-body retention of selenium was slightly elevated by cadmium and increased threefold by cadmium with mercury (mainly blood, liver, and kidneys). Cadmium did not affect subcellular levels of selenium in the kidneys and slightly increased the selenium content in the soluble fraction of the liver. On the other hand, combined administration of mercury and cadmium induced a significant elevation of the selenium content in all subcellular fraction of the kidneys and in the nuclear and mitochondrial fractions of the liver. In all animal groups selenium was bound in the soluble fractions of both the liver and kidneys by high-molecular-weight proteins.


Clostridium welchii type C antitoxin in the treatment of "pig bel" (enteritis necroticans): a controlled trial in Papua New Guinea.
Enteritis necroticans remains a serious problem in the Highlands of Papua New Guinea. Earlier claims that Clostridium Welchii Type C antitoxin is effective in lowering mortality rates were subjected to a prospective controlled trial in 1972-73. Use of the antitoxin was found to be of no benefit in treatment of this disease.


Colour and size of flowers in relation to pollination of Erica species.
Data on flower colour polymorphism were recorded for 341 of some 426 species of Erica occurring in the south-western Cape, South Africa. Thirty-eight per cent of these Erica species are colour polymorphic, the incidence of polymorphism being greater than expected for ornithophilous species and lower than expected for anemophilous species. Both altitude and season of flowering are correlated with the incidence of colour polymorphism, with most polymorphs occurring in species which have relatively large altitudinal ranges and extended flowering periods. The mean corolla length for each of pink, purple and white flowers is significantly shorter than that for each of red, orange, yellow and green flowers, suggesting that these two sets of colours correspond with entomophily and ornithophily, respectively. There are no Erica species with blue flowers. We suggest that the patterns of colour polymorphism, because of their relationships with the behaviour of pollinators, may reflect patterns of speciation in the genus.


Genomic ancestry and metabolic syndrome in individuals with type 1 diabetes from an admixed population: a multicentre, cross-sectional study in Brazil.
To evaluate the relationship between self-reported colour-race, genomic ancestry, and metabolic syndrome in an admixed Brazilian population with type 1 diabetes. We included 1640 participants with type 1 diabetes. The proportions of European, African and Amerindian genomic ancestries were determined by 46 ancestry informative markers of insertion deletion. Two different sets of analyses were performed to determine whether self-reported colour-race and genomic ancestry were predictors of metabolic syndrome. Metabolic syndrome was identified in 29.8% of participants. In the first model, the factors associated with metabolic syndrome were: female gender (odds ratio 1.95, P < 0.001); diabetes duration (odds ratio 1.04, P < 0.001); family history of type 2 diabetes (odds ratio 1.36, P = 0.019); and acanthosis nigricans (odds ratio 5.93, P < 0.001). Colour-race was not a predictive factor for metabolic syndrome. In the second model, colour-race was replaced by European genomic ancestry. The associated factors were: female gender (odds ratio 1.95, P < 0.001); diabetes duration (odds ratio 1.04, P < 0.001); family history of type 2 diabetes (odds ratio 1.39, P = 0.011); and acanthosis nigricans (odds ratio 6.12, P < 0.001). Physical exercise (≥3 times a week) was a protective factor (odds ratio 0.77, P = 0.041), and European genomic ancestry was not associated with metabolic syndrome but showed an odds ratio of 1.77 (P = 0.05). Although a higher level of European genomic ancestry was observed among participants with metabolic syndrome in the univariate analysis, this association did not persist after multivariable adjustments. Further prospective studies in other highly admixed populations remain necessary to better evaluate whether the European ancestral component modulates the development of metabolic syndrome in type 1 diabetes.


Prospective multicenter study of visual outcomes following three different treatments for macular edema associated with branch retinal vein occlusion: a study by the Japanese BRVO study group.
To evaluate the visual outcomes of three different treatments for macular edema associated with a branch retinal vein occlusion. A 1-year, non-randomized study was conducted at 21 ophthalmological institutes in Japan. All of the patients received one of three treatments: medication per-oral (PO), photocoagulation (PC) or pars plana vitrectomy (PPV). Retinal hemorrhage that was lower than that shown in reference photographs was considered an inclusion criteria. Ninety-eight patients were studied. Twenty-six (26.5%) patients were in the PO, 37 (37.8%) in the PC and 35 (35.7%) in the PPV group. The mean best-corrected visual acuity (BCVA) improved significantly after 1 year in all groups (P < 0.001). There was no significant difference among those groups in the degree of the BCVA improvement. However, the BCVA in the PPV group improved significantly at 6 months, significantly earlier than in the other two groups. The BCVA at entry in the PPV group was significantly worst among patients whose eyes had a BCVA of ≥ 0.7 at 1 year (P < 0.05). PPV had a slight advantage over PC and PO, although the improvement to the BCVA did not differ significantly following any of the three treatments.


Reducing the sink/source ratio of on-date palm plants during fruit growth has physiological and biochemical impacts on the shift in source-sink limitations.
The present study examined the impact of reducing the 'sink' on the 'source' in On-palms with a bunch number greater than eight. The capacity of leaves and fruit, as well as assimilate loading and unloading in phloem, restrict plant growth and yield. The study evaluated yield components, as well as photosynthetic and hormonal feedback, resulting from source-sink relationships. During the mid-Kimri, removing bunches from On-trees stabilized yield components and fruit size, suggesting that On-trees have a sink limitation. Bunch thinning boosted these indicators compared to normal trees with a bunch number between six and eight inclusive, indicating that On-trees had source limitations. In mid-Khalal, the treatments presented a type of source and sink limitation that is opposite to mid-Kimri. The thinning techniques addressed the source-sink limitation by adjusting the additional carbon allocation. This resulted in an increase of non-reducing sugars and starch in different organs, whereas reducing sugars decreased. These adjustments were made to reduce sucrose-phosphate synthase and sucrose synthase activity, raising invertase activity, lowering indole-3-acetic acid, zeatin, gibberellin, and abscisic acid hormone levels in fruits, as well as lowering trehalose production in organs. Levels of hormones, enzymes, and trehalose showed less variation during bunch thinning and source limitation compared to bunch removal and sink limitation. At Rutab, thinning types demonstrated the source limitation of On-trees. Bunch removal and bunch thinning by removing the source-sink limitation had the greatest effect on increasing yield components and fruit size, respectively. To improve the quality and quantity of fruit, it is important to use both thinning techniques simultaneously. © 2023 Society of Chemical Industry.


IgG4-related tubulointerstitial nephritis: A prospective analysis.
Immunoglobulin-G4 (IgG4)-related tubulo-interstitial nephritis (IgG4TIN) could be the first presentation of IgG4-related systemic disease. Most of the data is from the West or Japan and retrospective, with good patient outcome. This study was carried out from April 2011 to July 2013. We report a prospective follow-up of 11 patients who presented with renal dysfunction and had histological diagnosis of IgG4TIN followed for a minimum period of 1 year or until end-stage renal disease. IgG4TIN constituted 0.28% of total renal biopsies and 6.5% of all tubulointerstitial nephritis. Patient ages ranged between 21 and 71 years with a male predominance. All the patients had renal dysfunction at presentation with a mean serum creatinine of 5.12 mg/dL. Proteinuria was subnephrotic except when there was coexisting membranous glomerulonephritis (36.4%). The mean 24-h urine protien excretion was 1.8 g. Serum IgG4 levels were elevated in 10 (90.9%) patients. Ten (90.9%) patients had renomegaly and one (9.1%) had focal renal mass. Extra-renal manifestations were present in seven (63.6%). Renal histology showed pattern A in five (45.5%), pattern B in four (36.3%) and pattern C in two (18.1%) patients. All but one patient (90.9%) received immunosuppressive therapy. Four (36.3%) achieved complete remission and three (27.2%) progressed to end stage renal disease. Two patients died due to infections while on steroid therapy. One patient with a mass had end stage renal disease for 12 months and did not improve with steroid therapy, and one (pattern C) had progressive chronic kidney disease on follow-up. IgG4TIN in an Indian cohort most often presents with rapidly progressive renal failure and less often has extra-renal organ involvement. On follow-up, patients can experience a more aggressive course with progression to end stage renal disease.


Hybrid Minimally Invasive Esophagectomy for Carcinoma Oesophagus: Experience at Tertiary Care Centre in North Karnataka.
Surgery remains the mainstay for curative treatment of carcinoma of midthoracic and lower thoracic oesophagus. In the twentieth century, open esophagectomy was the standard of care. In the twenty-first century, treatment for carcinoma oesophagus has revolutionized with incorporation of neoadjuvant treatment and application of various minimally invasive techniques for esophagectomy. At present, there is no consensus about the optimum position to perform minimally invasive esophagectomy (MIE). We share our experience of MIE with modification in the port position in this article.


The effect of functional remission and cognitive insight on criminal behavior in patients with schizophrenia.
OBJECTıVE: This study was planned to determine the relationship of functional remission with a criminal history and determine its effect on criminal behavior in patients with schizophrenia. This cross-sectional study was conducted with 132 patients with schizophrenia (66 with and 66 without a criminal history). Data were collected between November 2020 and April 2021 using a personal information form, the Functional Remission of General Schizophrenia (FROGS), the Taylor Crime Violence Rating Scale, the Beck Cognitive Insight Scale, and the Positive and Negative Syndrome Scale (PANSS) was used to collect data. In terms of all scale variables, there were significant differences between the groups with and without a criminal history (p < 0.05). These differences were mostly clearly observed in the FROGS-social functionality (effect size: 16.79), PANSS-positive (effect size: 2.62) and FROGS-health and treatment (effect size: 2) subscales. In this study, it was determined that as the symptoms of the illness increased in schizophrenia, the patients' functional remission and insight decreased, and their tendency to commit crimes increased. Psychiatric nurses can plan therapeutic interventions to increase the functionality and insight levels of patients with schizophrenia.


Colorectal endoscopic mucosal resection with submucosal injection of epinephrine versus hypertonic saline in patients taking antithrombotic agents: propensity-score-matching analysis.
Endoscopic mucosal resection (EMR) to remove colon polyps is increasingly common in patients taking antithrombotic agents. The safety of EMR with submucosal saline injection has not been clearly demonstrated in this population. The present study aimed to evaluate the efficacy and safety of submucosal injection of saline-epinephrine versus hypertonic saline in colorectal EMR of patients taking antithrombotic agents. This study enrolled 204 patients taking antithrombotic agents among 995 consecutive patients who underwent colonic EMR from April 2012 to March 2018 at Ureshino Medical Center. Patients were divided into two groups according to the injected solution: saline-epinephrine or hypertonic (10%) saline (n = 102 in each group). Treatment outcomes and adverse events were evaluated in each group and risk factors for immediate and post-EMR bleeding were investigated. There were no differences between groups in patient or polyp characteristics. The main antithrombotic agents were low-dose aspirin, warfarin, and clopidogrel. Propensity-score matching created 80 matched pairs. Adjusted comparisons between groups showed similar en bloc resection rates (95.1% with saline-epinephrine vs. 98.0% with hypertonic saline). There were no significant differences in adverse events (immediate EMR bleeding, post-EMR bleeding, perforation, or mortality) between groups. Multivariate analyses revealed that polyp size over 10 mm was associated with an increased risk of immediate EMR bleeding (odds ratio 12.1, 95% confidence interval 2.0-74.0; P = 0.001). Two tested solutions in colorectal EMR were considered to be both safe and effective in patients taking antithrombotic agents.


Caspase-7 mediates caspase-1-induced apoptosis independently of Bid.
Inflammasomes are innate immune mechanisms that activate caspase-1 in response to a variety of stimuli, including Salmonella infection. Active caspase-1 has a potential to induce two different types of cell death, depending on the expression of the pyroptosis mediator gasdermin D (GSDMD); following caspase-1 activation, GSDMD-sufficient and GSDMD-null/low cells undergo pyroptosis and apoptosis, respectively. Although Bid, a caspase-1 substrate, plays a critical role in caspase-1 induction of apoptosis in GSDMD-null/low cells, an additional mechanism that mediates this cell death independently of Bid has also been suggested. This study investigated the Bid-independent pathway of caspase-1-induced apoptosis. Caspase-1 has been reported to process caspase-6 and caspase-7. Silencing of caspase-7, but not caspase-6, significantly reduced the activation of caspase-3 induced by caspase-1, which was activated by chemical dimerization, in GSDMD/Bid-deficient cells. CRISPR/Cas9-mediated depletion of caspase-7 had the same effect on the caspase-3 activation. Moreover, in the absence of GSDMD and Bid, caspase-7 depletion reduced apoptosis induced by caspase-1 activation. Caspase-7 was activated following caspase-1 activation independently of caspase-3, suggesting that caspase-7 acts downstream of caspase-1 and upstream of caspase-3. Salmonella induced the activation of caspase-3 in GSDMD-deficient macrophages, which relied partly on Bid and largely on caspase-1. The caspase-3 activation and apoptotic morphological changes seen in Salmonella-infected GSDMD/Bid-deficient macrophages were attenuated by caspase-7 knockdown. These results suggest that in addition to Bid, caspase-7 can also mediate caspase-1-induced apoptosis and provide mechanistic insights into inflammasome-associated cell death that is one major effector mechanism of inflammasomes.


The influence of age on prognosis in carcinoma of the cervix.
Of 385 new patients with invasive carcinoma of the cervix FIGO stages IB-IV treated between 1970-1984 inclusive, 11% (43 patients) were aged less than or equal to 35 years. During the period studied there was a gradual rise in the proportion of such young women from 2% for the triennium 1970-1972 to 18% for 1982-1984. In women aged less than or equal to 35 years early stage disease predominated, 72% presenting with stage IB disease, compared with 29% in the older age group. For FIGO stage IB there was no significant difference in actuarial survival between younger and older patients (P greater than 0.1), both age groups having a 5-year survival rate of 81%. Similarly for FIGO stage II there was no difference in actuarial survival (P greater than 0.1) between younger and older patients who had 5-year survival rates of 66% and 63% respectively. In our experience the incidence of invasive carcinoma of the cervix in young women is rising, but stage for stage their survival is similar to that of older women.


Ultrafast deposition of faceted lithium polyhedra by outpacing SEI formation.
Electrodeposition of lithium (Li) metal is critical for high-energy batteries1. However, the simultaneous formation of a surface corrosion film termed the solid electrolyte interphase (SEI)2 complicates the deposition process, which underpins our poor understanding of Li metal electrodeposition. Here we decouple these two intertwined processes by outpacing SEI formation at ultrafast deposition current densities3 while also avoiding mass transport limitations. By using cryogenic electron microscopy4-7, we discover the intrinsic deposition morphology of metallic Li to be that of a rhombic dodecahedron, which is surprisingly independent of electrolyte chemistry or current collector substrate. In a coin cell architecture, these rhombic dodecahedra exhibit near point-contact connectivity with the current collector, which can accelerate inactive Li formation8. We propose a pulse-current protocol that overcomes this failure mode by leveraging Li rhombic dodecahedra as nucleation seeds, enabling the subsequent growth of dense Li that improves battery performance compared with a baseline. While Li deposition and SEI formation have always been tightly linked in past studies, our experimental approach enables new opportunities to fundamentally understand these processes decoupled from each other and bring about new insights to engineer better batteries.


Pyrrole-based EGFR inhibitors for the treatment of NCSLC: Binding modes and SARs investigations.
The treatment of advanced non-small cell lung cancer (NSCLC) has made substantial progress due to the rapid development of small molecule targeted therapy, with dramatically prolonged survival. As an effective drug for the treatment of NSCLC, epidermal growth factor receptor (EGFR) inhibitors are currently experiencing issues like severe adverse events and drug resistance. It is urgent to develop novel types of EGFR inhibitors to overcome the abovementioned limitations. Pyrrole always works well as a probe for the creation of novel medication candidates for hard-to-treat conditions like lung cancer. Although the design, synthesis, and biological assays of pyrrole derivatives have been reported, their inhibitory actions against the receptor tyrosine kinase (RTK) EGFR have not been in-depthly studied. This review highlights the small molecule EGFR inhibitors containing pyrrole heterocyclic pharmacophores in recent years, and the research on their mechanism, biological activity, and structure-activity relationship (SAR).


HSPB8 counteracts tumor activity of BRAF- and NRAS-mutant melanoma cells by modulation of RAS-prenylation and autophagy.
Cutaneous melanoma is one of the most aggressive and lethal forms of skin cancer. Some specific driver mutations have been described in multiple oncogenes including BRAF and NRAS that are mutated in 60-70% and 15-20% of melanoma, respectively. The aim of this study was to evaluate the role of Small Heat Shock Protein B8 (HSPB8) on cell growth and migration of both BLM (BRAFwt/NRASQ61R) and A375 (BRAFV600E/NRASwt) human melanoma cell lines. HSPB8 is a member of the HSPB family of chaperones involved in protein quality control (PQC) system and contributes to chaperone assisted selective autophagy (CASA) as well as in the regulation of mitotic spindle. In cancer, HSPB8 has anti- or pro-tumoral action depending on tumor type. In melanoma cell lines characterized by low HSPB8 levels, we demonstrated that the restoration of HSPB8 expression causes cell growth arrest, reversion of EMT (Epithelial-Mesenchymal Transition)-like phenotype switching and antimigratory effect, independently from the cell mutational status. We demonstrated that HSPB8 regulates the levels of the active prenylated form of NRAS in NRAS-mutant and NRAS-wild-type melanoma cell lines. Consequently, the inhibition of NRAS impairs the activation of Akt/mTOR pathway inducing autophagy activation. Autophagy can play a dual role in regulating cell death and survival. We have therefore demonstrated that HSPB8-induced autophagy is a crucial event that counteracts cell growth in melanoma. Collectively, our results suggest that HSPB8 has an antitumoral action in melanoma cells characterized by BRAF and NRAS mutations.


Tranexamic acid reduces allogeneic red cell transfusions in patients undergoing total knee arthroplasty: results of a meta-analysis of randomized controlled trials.
The delayed bleeding associated with total knee arthroplasty (TKA) may be a result of a tourniquet-induced imbalance of the procoagulant and fibrinolytic systems. There are conflicting results in the literature about tranexamic acid (TA) infusion in reducing postoperative blood loss and the number of transfused red cells (RBC) units. A meta-analysis was performed to summarize the results of different research studies. Randomized controlled trials reported through October 2004 were retrieved, and nine studies met the criteria for meta-analysis. Summary odds ratio (OR) of allogeneic transfusion and a weighted mean difference (WMD) of transfusions per patient in TA-treated group versus placebo group were calculated across studies. The use of TA significantly reduced the proportion of patients requiring blood transfusion (summary OR, 0.10; 95% CI, 0.06-0.18; p < 0.00001) and the number of RBC transfusions per patient (WMD, -1.72; 95% CI, -2.11 to -1.33; p < 0.00001) when compared with patients who received placebo. Our meta-analysis shows that the use of TA for patients undergoing TKA is effective in reducing the requirements of allogeneic blood transfusion.


Mapping a resistance gene in wheat cultivar Yangfu 9311 to yellow mosaic virus, using microsatellite markers.
Wheat yellow mosaic disease, which is caused by wheat yellow mosaic bymovirus (WYMV) and transmitted by soil-borne fungus, results in severe damage on wheat (Triticum aestivum L.) production in China. For development of resistant cultivars to reduce wheat yield losses due to wheat yellow mosaic disease, resistance test and genetic analysis indicated that a single dominant gene in wheat cultivar Yangfu 9311 contributed to the resistance. Bulk segregant analysis was used to identify microsatellite markers linked to the resistance gene in an F(2) population derived from the cross Yangfu 9311 (resistant) x Yangmai 10 (susceptible). Microsatellite markers Xwmc41, Xwmc181, Xpsp3039, and Xgwm349 were co-dominantly or dominantly linked with the gene responsible for WYMV resistance at a distance of 8.1-11.6 cM. Based on the wheat microsatellite consensus map and the results from amplification of the cultivar Chinese Spring nulli-tetrasomic stocks, the resistance gene to wheat yellow mosaic disease derived from Yangfu 9311, temporarily named as YmYF, was thus mapped on the long arm of chromosome 2D (2DL).


A new astrocytic cell line which is able to induce a blood-brain barrier property in cultured brain capillary endothelial cells.
Astrocytes, a member of the glial cell family in the central nervous system, are assumed to play a crucial role in the formation of the blood-brain barrier (BBB) in vertebrates. It was shown that astrocytes induce BBB-properties in brain capillary endothelial cells (BCEC) in vitro. We now established an astroglial cell line of non-tumoral origin. The cloned cell line (A7) shows a highly increased proliferation rate and expresses the astrocytic marker glial fibrillary acidic protein. Furthermore, the clone A7 expresses S-100-protein and vimentin, which are also expressed by primary cultured astrocytes. This cell line therefore shows general astrocytic features. In addition, we were able to show that A7 cells re-induce the BBB-related marker enzyme alkaline phosphatase in BCEC, when these two cell types are co-cultured. Thus we have a cell line which can be readily cultured in large quantities, shows common astrocyte properties and is able to influence BCEC with respect to a BBB-related feature.


Combustion Synthesis and Photoluminescence Properties of Novel Bi2Al4O9:Eu3+ Phosphor for n-UV w-LEDs.
The combustion procedure was used to synthesize Bi2Al4O9:Eu3+ phosphors. The XRD and photoluminescence properties are investigations. The XRD patterns consist of an orthorhombic crystal structure. At 395 nm, the maximum excitation intensity was obtained. Following 395 nm excitation, two different emission peaks at 593 and 615 nm were observed. Concentration quenching occurred at 0.5 mol % Eu3+ ions. The CIE coordinates for the Bi2Al4O9 phosphor with Eu3+ ion doped are 615 nm (x = 0.680, y = 0.319) falling in the red region. According to the photoluminescence results, Bi2Al4O9:Eu3+ phosphors might be useful in the fields of near UV-excited w-LEDs.


Salinization and wastewater effects on the growth and some cell contents of Scenedesmus bijugatus.
The aim of this study is to determine the effect of salinization and wastewater stresses on the growth, some cellular contents (total soluble proteins, total soluble carbohydrates, nucleic acids, and amino acids composition) and ultrastructure using TEM of unicellular green alga Scenedesmus bijugatus. Treatment of S. bijugatus by NaCl at 10 and 50 mg L-1 significantly increased the growth of this alga and its cellular macro-molecules. While, treatment above this concentration with NaCl significantly inhibited the growth and cellular macro-molecules. On the other hand, treatment by NaCl at the pre-lethal concentration (300 mg L-1) had different effects on its detected amino acids. Whereas, Asp. Acid, Pro, Cys, Val, Iso-leu, leu, Phe.ala and Lys were slightly stimulated with salinization treatment. On contrast the levels of amino acids: Thr, Ser, Glu.acid, Gly, Ala, Mth, His and Arg were markedly inhibited. Ultrastructure examination of treated S. bijugatus by 300 mg L-1 of NaCl for 8 days showed increase of starch granules, shrinkage of cell contents and thickening of cell wall. The recorded data indicated also that treatment by wastewater with all concentrations led to stimulatory effects on their growth and cellular macro-molecules except at 100% wastewater which had inhibitory effects on Asp., Gly., Thr., Ser., Pro., Glu., Ala., Meth., and Cyst., of S. bijugatus. Also, wastewater induced a slight change in the treated S. bijugatus as elevation in starch granules and presence of thylakoid membranes although not clear as in the control.


Spirituality and optimism: a holistic approach to component-based, self-management treatment for HIV.
For people living with HIV (PLWH), spirituality and optimism have a positive influence on their health, can slow HIV disease progression, and can improve quality of life. Our aim was to describe longitudinal changes in spirituality and optimism after participation in the SystemCHANGE™-HIV intervention. Upon completion of the intervention, participants experienced an 11.5 point increase in overall spiritual well-being (p = 0.036), a 6.3 point increase in religious well-being (p = 0.030), a 4.8 point increase in existential well-being (p = 0.125), and a 0.8 point increase in total optimism (p = 0.268) relative to controls. Our data suggest a group-based self-management intervention increases spiritual well-being in PLWH.


Long-lasting afterdischarge of alpha-motoneurons after muscle vibration or electrical stimulation of group I afferent fibers in the anemically decerebrated cat.
Experiments were performed on anemically decerebrated cats. Motoneuronal activity in the spinal cord was intracellularly or extracellulary recorded and muscle vibration or electrical stimulation of the peripheral nerve was applied for 1 s every 2 s. Such stimulation elicited monosynaptic responses and afterdischarge, a response which lasts after cessation of the stimuli. Stimulus frequencies from 50 to 200 Hz were effective in eliciting the afterdischarge, while frequencies higher or lower than this range of stimulation were ineffective. The interspike intervals of the motoneuron afterdischarge were almost constant and did not correspond to the stimulus frequency. The mean intervals obtained from the motoneurons examined ranged from 70 to 120 ms. Power spectrum analysis of the membrane potential ripples recorded immediately after stimulation revealed increased activity at 38 and 62 Hz components. Since the spike interval of the afterdischarge in this motoneuron was 80 ms, the interval was almost equal to 5- and 3-fold the cyclic time of the increased frequency components. This indicates that the interval of afterdischarge was determined by the specifically increased frequency components of the membrane potential ripples.


Sustained moderate-to-high disease activity and higher Charlson score are predictors of incidental serious infection events in RA patients treated with conventional disease-modifying anti-rheumatic drugs: a cohort study in the treat-to-target era.
Rheumatoid arthritis (RA) guidelines have moved toward intensive treatment aimed at remission. Treatment and disease activity are predictors of infections; patients from developing countries have additional predictors that may further impact the infection spectrum. Our aim was to describe serious infection events (SIEs), predictors and impact on RA outcomes, in a cohort of Mexican Mestizo patients. Up to February 2015, charts from 176 early RA patients were reviewed by a single data abstracter. SIEs were defined according to strict criteria. RA patients with ≥1 SIE up to last follow-up were considered cases. Descriptive statistics were used; cases and paired controls (no SIE up to last follow-up) were compared by uni-variate analysis and multiple logistic regression. The cohort contributed to 948 patient-years of follow-up. There were 34 SIEs in 15 patients, at a (mean±SD) follow-up of 5±4 years. Incidence rate of SIE was 8.7 infections per 100 patient-years. Twenty-four isolated SIE were present in 14 patients. The most frequent SIEs were complicated urinary tract infections and pneumonia (each, n=8) and soft-tissue infections (n=7). In the case-control analysis, higher Charlson score (OR: 2.04, 95%CI: 1.001-4.164, p=0.05) and higher cumulative DAS28 (OR: 3.08, 95%CI: 1.91-4.98, p=0.000) were predictors of SIE; in patients with at least moderate disease activity, risk of SIE increased with higher level of cumulative disease activity. However, SIEs did not impact subsequent DAS28, HAQ and SF-36. Comorbidity and cumulative disease activity increased serious infection risk in early RA patients treated with conventional drugs, but SIEs did not impact disease outcomes.


Mechanisms of complement activation and effects of C1-inhibitor on the meconium-induced inflammatory reaction in human cord blood.
Meconium aspiration syndrome has a complex pathophysiology. Meconium activates the complement system and meconium-induced cytokine formation is differentially mediated by complement and CD14. C1-inhibitor (C1-INH) regulates complement and contact-system activation mainly by protease inhibition, but may reduce inflammation by other mechanisms as well. The aim of the study was to investigate the initial mechanisms of meconium-induced complement activation and to study the effect of C1-INH on the meconium-induced inflammatory reaction. Human serum from five donors was preincubated with an anti-MBL monoclonal antibody and then incubated with meconium for 30 min at 37 degrees C. Human cord whole blood, anticoagulated with lepirudin, from six donors was preincubated with C1-INH and then incubated with meconium for 30 min and 4h at 37 degrees C. Complement activation products specific for the different pathways were measured by ELISAs: classical pathway C1rs/C1-INH complexes, classical and lectin pathway C4d, alternative pathway C3bBbP, and terminal pathway sC5b-9 complex (TCC). A Bio-Plex Array Reader was used to measure 27 inflammatory mediators. The anti-MBL monoclonal antibody significantly reduced meconium-induced formation of C4d by 63% (p=0.0159) and TCC by 27% (p=0.0079). C1-INH dose-dependently inhibited meconium-induced formation of C1rs/C1-INH complexes, C4d, C3bBbP, and TCC compared to albumin (p<0.002 for all). C1-INH induced a dose-dependent and substantial inhibition of meconium-induced formation of the proinflammatory cytokines TNFalpha, IL-1 beta, IL-6 and IFN-gamma (p<0.01 for all), the chemokines IL-8, MCP-1, MIP-1 alpha, MIP-1 beta, and eotaxin (p<0.02 for all), the growth factors G-CSF, GM-CSF, basic FGF, and PDGFbb (p<0.05 for all), and the anti-inflammatory cytokine IL-1ra (p<0.001). Meconium activated the lectin complement pathway as well as the alternative pathway. C1-INH efficiently reduced a broad spectrum of inflammatory mediators even at the lowest concentration. Administration of C1-INH may thus reduce the inflammatory response in MAS.


Identification of novel candidate biomarkers for acute myocardial infarction by the Olink proteomics platform.
Both pathological and normal processes depend on proteins. In this study, plasma protein profiles were analyzed by a novel proximity extension assay (PEA) to identify potential pathogenic mechanisms and diagnostic biomarkers in patients diagnosed with acute myocardial infarction (AMI). In this study, we identified a total of 92 plasma proteins using the Olink Target 96 Cardiovascular III panel in a cohort consisting of 30 healthy controls (HC), 28 patients with unstable angina (UA) and 30 patients with AMI. Subsequently, we conducted a differential expression analysis to identify protein molecules that were specifically expressed in patients with AMI. To gain insights into the potential functional mechanisms of these differentially expressed molecules, we performed Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. Following that, the utilization of least absolute shrinkage and selection operator (LASSO) regression facilitated the identification of potential protein biomarkers, enabling the differentiation between AMI and UA. A diagnostic model was subsequently developed through logistic regression, and the effectiveness of these markers was assessed using receiver operating characteristic (ROC) analysis. Ultimately, the diagnostic capabilities of these potential biomarkers were validated in an independent validation cohort consisting of 30 UA cases and 30 AMI cases. In this study, a comprehensive analysis of plasma proteins identified a total of 92 proteins. Further analysis using analysis of variance revealed that 25 proteins exhibited specific expression in the AMI group compared to the HC and UA groups. Additionally, KEGG enrichment analysis indicated that these differentially expressed proteins were primarily associated with the activation of cytokine-cytokine receptor interaction, PI3K-Akt signaling pathway, and GnRH signaling pathway. AGRP, TGM2, IL6, GH1, and CA5A were identified through LASSO regression as prospective protein biomarkers for distinguishing between UA and AMI. The diagnostic model comprising these five proteins exhibited exceptional performance in both the discovery and validation datasets, surpassing AUC values of 0.9. The findings of our study provide additional insights into the involvement of the inflammatory response and AKT cascade response in the development of AMI. Moreover, we have identified potential protein markers that could be utilized for the accurate diagnosis of AMI. These results offer a fresh perspective for clinical decision-making in the context of AMI.


Detection of trace tetracycline in fish via synchronous fluorescence quenching with carbon quantum dots coated with molecularly imprinted silica.
A novel fluorescence-based sensor combining synchronous fluorescence spectroscopy (SFS) with molecularly imprinted polymers (MIPs) was fabricated with reverse microemulsion method. Tetracycline (TC), (3-aminopropyl) triethoxysilane (APTES), tetraethyl orthosilicate (TEOS) and carbon quantum dots (CDs) were used as template, functional monomer, cross-linker and signal sources respectively in the probe preparation. A synchronous fluorescence emission (λem) at 355nm was observed for the prepared MIP-coated CDs (MIP@CDs) particles when the wavelength interval (Δλ) was set as 70nm, and the synchronous fluorescence intensity could be rapidly and efficiently quenched by TC based on inner filter effect (IFE). The quenching efficiencies of synchronous fluorescence intensity was linearly fitted with tetracycline (TC) concentrations ranging from 0.1 to 50μmolL-1 with a detection limit (DL) of 9nmolL-1 (3σ, n=9). The MIP@CDs was used as a probe to detect TC in fish samples with the recoveries ranging from 98.4% to 103.1% and the relative standard deviation less than 6.0%. The results illustrated that the as-prepared MIP@CDs could be applied to the detection of trace TC in fish samples with rapidity, high sensitivity and accuracy.


Generalized fuzzy variable precision rough sets based on bisimulations and the corresponding decision-making.
Recently, the classical rough set has been extended in many ways. However, some of them are based on binary relations which only excavate "one step" information to distinguish objects. The "one step" in the binary relation means that the ordered pair of the starting and end points of the step belongs to the relation. Faced with some complex data sets, the "one step" information may be not feasible. Motivated by the notion of bisimulation in computer science, three types of bisimulation-based generalized fuzzy variable precision rough set (BGFVPRS) models are constructed. Different from many existed rough set models which are based on binary relations, the BGFVPRS models can distinguish objects by excavating the "multi-step" information of underlying relations. The related properties and relationships of BGFVPRS models are investigated. The uncertainty measure of BGFVPRS models and the reduction of fuzzy bisimulations are also discussed. Furthermore, learning from the PROMETHEE II method and combining it with our presented BGFVPRS models, a novel multiple-attribute decision-making method is provided. This method can effectively deal with complex problems including attribute data and relational data. The flexibility and effectiveness of our decision-making method are illustrated by comparative analysis and sensitivity analysis in the Zachary karate club network.


Automatic Dissolution Testing with High-Temporal Resolution for Both Immediate-Release and Fixed-Combination Drug Tablets.
Dissolution testing plays many important roles throughout the pharmaceutical industry, from the research and development of drug products to the control and evaluation of drug quality. However, it is a challenging task to perform both high-efficient separation and high-temporal detection to achieve accurate dissolution profile of each active ingredient dissolved from a drug tablet. In our study, we report a novel non-manual-operation method for performing the automatic dissolution testing of drug tablets, by combining a program-controlled sequential analysis and high-speed capillary electrophoresis for efficient separation of active ingredients. The feasibility of the method for dissolution testing of real drug tablets as well as the performance of the proposed system has been demonstrated. The accuracy of drug dissolution testing is ensured by the excellent repeatability of the sequential analysis, as well as the similarity of the evaluation of dissolution testing. Our study show that the proposed method is capable to achieve simultaneous dissolution testing of multiple ingredients, and the matrix interferences can be avoided. Therefore it is of potential valuable applications in various fields of pharmaceutical research and drug regulation.


Characterization of Two Recombinant 3-Hexulose-6-Phosphate Synthases from the Halotolerant Obligate Methanotroph Methylomicrobium alcaliphilum 20Z.
Two key enzymes of the ribulose monophosphate (RuMP) cycle for formaldehyde fixation, 3-hexulose-6-phosphate synthase (HPS) and 6-phospho-3-hexulose isomerase (PHI), in the aerobic halotolerant methanotroph Methylomicrobium alcaliphilum 20Z are encoded by the genes hps and phi and the fused gene hps-phi. The recombinant enzymes HPS-His6, PHI-His6, and the two-domain protein HPS-PHI were obtained by heterologous expression in Escherichia coli and purified by affinity chromatography. PHI-His6, HPS-His6 (2 × 20 kDa), and the fused protein HPS-PHI (2 × 40 kDa) catalyzed formation of fructose 6-phosphate from formaldehyde and ribulose-5-phosphate with activities of 172 and 22 U/mg, respectively. As judged from the kcat/Km ratio, HPS-His6 had higher catalytic efficiency but lower affinity to formaldehyde compared to HPS-PHI. AMP and ADP were powerful inhibitors of both HPS and HPS-PHI activities. The two-domain HPS-PHI did not show isomerase activity, but the sequences corresponding to its HPS and PHI regions, when expressed separately, were found to produce active enzymes. Inactivation of the hps-phi fused gene did not affect the growth rate of the mutant strain. Analysis of annotated genomes revealed the separately located genes hps and phi in all the RuMP pathway methylotrophs, whereas the hps-phi fused gene occurred only in several methanotrophs and was absent in methylotrophs not growing under methane. The significance of these tandems in adaptation and biotechnological potential of methylotrophs is discussed.


Co-transport of H+/Cl- by a synthetic prodigiosin mimic.
An amidopyrrole with appended imidazole group can bind and co-transport H+/Cl- across vesicle membranes much more effectively than an analogue with an appended pyridyl group.


Dendritic immune cell densities in the central cornea associated with soft contact lens types and lens care solution types: a pilot study.
The purpose of this study was to assess whether differences in central corneal dendritic immune cell densities associated with combinations of soft contact lenses and lens care solutions could be detected by in vivo confocal microscopy. Participants were adults naïve to contact lens wear (n = 10) or who wore soft contact lenses habitually on a daily-wear schedule (n = 38) or on a study-assigned schedule for 30 days with daily disposable silicone hydrogel lenses (n = 15). Central corneas were scanned using an in vivo confocal microscope. Cell densities were compared among groups by demographic parameters, lens materials, and lens care solutions (polyhexamethylene biguanide [PHMB], polyquaternium-1 and myristamidopropyl dimethylamine [PQ/MAPD], peroxide, or blister pack solution [for daily disposable lenses]). Among lens wearers, no associations were observed between immune cell densities and age, gender, or years of lens-wearing experience. Mean cell density was significantly lower (P < 0.01) in nonwearers (29 ± 23 cells/mm(2), n = 10) than in lens wearers (64 ± 71 cells/mm(2), n = 53). Mean cell density was lower (P = 0.21) with traditional polymer lenses (47 ± 44 cells/mm(2), n = 12) than with silicone hydrogel lenses (69 ± 77 cells/mm(2), n = 41). Lowest to highest mean density of immune cells among lens wearers was as follows: PQ/MAPD solution (49 ± 28 cells/mm(2)), blister pack solution (63 ± 81 cells/mm(2)), PHMB solution (66 ± 44 cells/mm(2)), and peroxide solution (85 ± 112 cells/mm(2)). In this pilot study, in vivo confocal microscopy was useful for detecting an elevated immune response associated with soft contact lenses, and for identifying lens-related and solution-related immune responses that merit further research.


Assessing nonlinearities and heterogeneity in debt sustainability analysis: a panel spline approach.
This paper empirically studies public debt sustainability with the penalized panel splines approach for 25 EU economies from 2000 to 2019 by estimating the response of the primary surplus to lagged debt relative to GDP, respectively. A positive coefficient on average indicates sustainable policies, which is supported by all our results. Moreover, we show that this relationship is not homogeneous across the distribution of the debt ratios but varies with the magnitude of public debt to GDP. The estimations reveal a strongly increasing reaction for small and high debt ratios while it is rather flat for intermediate levels. This holds for normal times, too, whereas during years of economic crisis a monotonously increasing response can be observed. Additionally, for a cluster consisting of smaller EU economies, there is an indication of 'fiscal fatigue', meaning that the effort of active fiscal counter-steering peters out for high ratios of public debt to GDP. The same effect can be observed for the whole sample and a sample including the large EU economies, once Greece is removed.


Short synthesis of a broadly Reactive, cell permeable serine hydrolase Fluorophosphonate-Alkyne probe.
An abbreviated synthesis of the cell permeable fluorophosphonate-alkyne probe (FP-alkyne) for the broad assessment of serine hydrolase activity has been developed. While FP-alkyne has proven pivotal in numerous chemical biology studies access has relied on a lengthy preparation over nine steps. We have developed a four-step synthesis, starting from commercially available compounds, with three purification steps to provide a new expedited route allowing easy access to a useful tool compound for exploring serine hydrolases chemistry and biology. This route was used in our own studies to generate FP-alkyne which in turn was used to identify the enzyme responsible for Fatty Acid Esters of Hydroxy Fatty Acids (FAHFA) biosynthesis. The use of this route can enable the syntheses of new tool compounds in addition to improving accessibility to FP-alkyne.


Towards high performance dielectric microwave resonators for X-band EPR spectroscopy.
Microwave (MW) resonators in Electron Paramagnetic Resonance (EPR) spectroscopy concentrate the MW magnetic field (B1) at the sample and separate the MW electric field from the sample. There are numerous experimental methods in EPR spectroscopy which all impose different requirements on MW resonators (e.g. high or low quality factor, MW conversion, and B1-field homogeneity). Although commercial spectrometers offer standardized MW resonators for a broad application range, newly emerging and highly-specialized research fields push these spectrometers to or beyond their sensitivity limits. Optimizing the MW resonator offers one direct approach to improve the sensitivity. Here we present three low-cost optimization approaches for a commercially available X-band (9-10 GHz) MW resonator for three experimental purposes (continuous-wave (CW), transient and pulse EPR). We obtain enhanced MW conversion factors for all three optimized resonators and higher quality factors for two optimized resonators. The latter is important for CW and transient EPR. Furthermore, we fabricated a resonator which features an extended area of homogeneous B1-field and, hence, improved pulse EPR performance. Our results demonstrate that small changes to a commercial MW resonator can enhance its performance in general or for specific applications.


Validation of algorithms to estimate gestational age at birth in the Medicaid Analytic eXtract-Quantifying the misclassification of maternal drug exposure during pregnancy.
Accurate ascertainment of gestational age (GA) has been a challenge in perinatal epidemiologic research. To date, no study has validated GA algorithms in Medicaid Analytic eXtract (MAX). We linked livebirths of mothers enrolled in Medicaid ≥30 days after delivery in 1999-2010 MAX to state birth certificates. We used clinical/obstetric estimate of gestation on the birth certificates as gold standard to validate claims-based GA algorithms. We calculated the proportions of deliveries with algorithm-estimated GA within 1-/2-weeks of the gold standard, the sensitivity, specificity, and positive/negative predictive value (PPV/NPV) of exposure to select medications during specific gestation windows, and quantified the impact of exposure misclassification on hypothetical relative risk (RR) estimates. We linked 1 336 495 eligible deliveries. Within 1-week agreement was 77%-80% overall and 47%-56% for preterm deliveries. The trimester-specific drug exposure status had high sensitivities and PPVs (88.5%-98.5%), and specificities and NPVs (>99.0%). Assuming a hypothetical RR of 2.0, bias associated with exposure misclassification during first trimester ranged from 10% to 40% under non-differential/differential misclassification assumptions. Claims-based GA algorithms had good agreement with the gold standard overall, but lower agreement among preterm deliveries, potentially resulting in biased risk estimated for pregnancy exposure evaluations.


A simple guide to the terminology and application of leucocyte monoclonal antibodies.
This review aims to provide a simple guide and quick reference to the terminology and diagnostic applications of leucocyte monoclonal antibodies. The differentiation cluster terminology, where applicable, is used throughout.


Design and Development of Novel 4-(4-(1H-Tetrazol-5-yl)-1H-pyrazol-1-yl)-6-morpholino-N-(4-nitrophenyl)-1,3,5-triazin-2-amine as Cardiotonic Agent via Inhibition of PDE3.
The classical phosphodiesterase 3A (PDE3A) inhibitors provide relaxation of the vasculature system via increasing the cellular level of cyclic adenosine monophosphate (cAMP) and proved to be useful in the management of congestive heart failure. Consequently, the present paper deals with the development of novel pyrazole derivatives tethered with substituted 1,3,5-triazine derivatives in search for novel PDE3 inhibitors. The synthesis of designed inhibitors was realized in a multi-step reaction and the structures were ascertained with the help of various spectroscopic techniques. Subsequently, these analogs were tested for their inhibitory activities against PDE3 enzymes, where they exhibited considerable inhibition, revealing 9g as the most promising inhibitor of the class. In a docking study, the morpholine fragment of compound 9g was efficiently engulfed in the small pocket of the active site lined by Gly940 and Pro941. The substituted aromatic ring of the core scaffold was found to be positioned deep in the cavity bordered by Tyr829, Asn830, Leu850, Glu851, and Thr893. Moreover, it considerably improved the contractility of cardiac muscles without altering the heart beat frequency in experimental subjects.


Syphilis infection and epidemiological characteristics in Haidian District, Beijing, China, 2013-2018.
This study aimed to investigate the epidemiological characteristics of syphilis between 2013 and 2018 in the Haidian District of Beijing in China. In addition, this study suggests potential strategies to control the spread of syphilis infection. Observational study. Data were collected from the Infectious Disease Reporting System at medical institutions within the Haidian District of Beijing between 2013 and 2018. Epidemiological methods, combined with Chi-squared test, were used to analyse the distribution of syphilis in terms of time, region, population and development stage. In total, 3048 patients with syphilis were reported in the Haidian District between 2013 and 2018, with an average annual prevalence of 14.26 per 100,000 population. The prevalence of syphilis was higher in rural than urban regions, and the sex ratio of male-to-female was 1.52:1. Patients aged 20-29 years accounted for 22.60% (689/3048) of the total cases. In terms of occupational distributions, the highest proportion (30.61%; 933/3048) was seen in individuals who were homemakers or unemployed. Latent syphilis was present in 66.83% (2037/3048) of patients and accounted for an increased proportion of syphilis cases each year. Syphilis was epidemic in the Haidian District of Beijing between 2013 and 2018. High prevalence was seen in young and middle-aged males living in urban areas. The prevalence of syphilis has been increasing since 2016; thus, public health policies and intervention strategies need to be strengthened to curb the spread of infection.


Artificial vascular graft for inferior vena cava reconstruction in living donor liver transplantation: a case report.
Artificial grafts are not recommended because of the high incidence of thrombogenic effects. However, in some situations, such as emergency or when no vascular bank is available, an artificial graft must be used. We present a case in which a polytetrafluoroethyline graft was used as a conduit to reconstruct the retrohepatic vena cava severed during living donor liver transplantation (LDLT). A 48-year-old woman had end-stage primary biliary cirrhosis for 5 years received a right lobe liver graft from her son. The retrohepatic vena cava was divided and ligated in several sequences. The upper end of the severed retrohepatic vena cava retracted into the liver parenchyma. The lower end of the severed vena cava was distended, with multiple stitches. A 16-mm artificial graft was used as a conduit to replace the inferin vena cava for outflow reconstruction. The patient tolerated the complicated procedure well. No anticoagulant was used throughout the entire course. The patient has been well with excellent liver function after follow-up for more than 5 years. Magnetic resonance imaging and Doppler ultrasonographic studies showed good patency of the cava with no evidence of thrombosis. We suggest use of an artificial graft in living donor liver transplantation, in particular in urgent situations when autologous or allogeneic vessels are not available.


Robertsonian translocations: an overview of a 30-year experience in a single tertiary medical center in Taiwan.
Advanced maternal age (AMA) is the most frequent indication for amniocentesis in predicting balanced reciprocal translocations, and abnormal ultrasound findings are indications in predicting unbalanced reciprocal translocations; however, to date, no studies have focused on Robertsonian translocations. A retrospective review was conducted on 16,749 pregnant women who underwent midtrimester amniocentesis between January 1981 and December 2010. Robertsonian translocations were identified in 39 cases. The percentage of Robertsonian translocations in all amniocentesis cases was 0.23% (39/16,749); 31 were balanced and eight were unbalanced. De novo abnormality occurred in 17 cases, or in 43.6% of all Robertsonian translocations. The two major indications for amniocentesis with a diagnosis of Robertsonian translocations were AMA (41.0%, n = 16) and a parent with abnormal karyotypes (18.0%, n = 7). The highest percentage of Robertsonian translocations was found in parents with abnormal karyotypes (2.8%, 7/252), but neither of the indications were clearly superior for detecting de novo Robertsonian translocations. Although AMA is an indication for amniocentesis in approximately two-fifths of cases with Robertsonian translocations, the indication of parent with abnormal karyotypes was more likely to lead to the detection of non-de novo Robertsonian translocations, suggesting that parents with abnormal karyotypes need careful prenatal consultation.


Cefotaxime treatment for women with community-acquired pelvic abscesses.
Forty-one women with pelvic abscesses complicating salpingitis were treated with parenteral cefotaxime, a newer cephalosporin. Abscesses ranged in size from 4 by 4 to 13 by 15 cm, and in 10 women (24%) they were greater than or equal to 10 cm. Neisseria gonorrhoeae was recovered from the endocervix in 17 women (41%). A mean of 26.7 gm of cefotaxime was given over a mean of 6.5 days, and operation was not required during initial therapy. Only two women (5%) required the addition of another antimicrobial. Chronic pelvic pain and recurrent infection were infrequent during the 31- to 43-month follow-up period. Five women (12%) were readmitted for elective surgical therapy because of persistent or recurrent adnexal mass 1 to 33 months following study entry. Six (15%) women became pregnant and were delivered of their infants a mean of 25 months following cefotaxime therapy.


Failure of azithromycin therapy in gonorrhea and discorrelation with laboratory test parameters.
Azithromycin is efficacious in the treatment of chlamydial genital tract infection but less so in gonorrhea. However, MICs of azithromycin for gonococci from previously reported azithromycin treatment failures were consistently below the 'susceptible' MIC level of 2 mg/L. To examine gonococci not eliminated with 1 g azithromycin therapy to establish treatment outcome/MIC correlates in gonorrhea. The MICs and phenotypes of gonococci isolated from five cases of treatment failure after 1 g azithromycin therapy were determined and compared with the MICs of a systematic sample of routine isolates. Azithromycin MICs of gonococci from five cases of failed 1 g azithromycin treatment were 0.125 or 0.25 mg/L, well within the current 'susceptible' MIC range. None of the isolates were of the mtr phenotype. The MIC90 of a systematic sample of 219 gonococcal isolates was 0.25 mg/L. The antibiotic MIC/treatment outcome correlates that are usually found in gonorrhea do not apply for azithromycin. Current MIC criteria do not accurately define susceptibility or resistance of gonococci to azithromycin and by themselves do not predict the likely outcome of therapy. Pharmacokinetic factors may decrease the predictive value of MIC data.


Studies on the mechanism of Tris-induced inactivation of oxygen evolution.
A study was made of the inactivation by Tris of O2 evolution in chloroplasts and the subsequent reactivation of O2 evolution. We conclude: 1. At concentrations of Tris sufficient to inhibit O2 evolution directly, a slow rate (t 1/2 approximately 20--25 min) of inactivation occurs; 2. Inactivation is accelerated (t 1/2 approximately 2 min) by weak light absorbed by system II and is rate limited by a dark step with a half-time of about 200 s; 3. Minimally one quantum event within System II is sufficient to inactive 50--70% of the O2 evolving centers; 4. This process is 3-(3,4-dichlorophenyl)-1,1-dimethylurea insensitive but is inhibited by reduced dichlorophenol indophenol and phenazine methosulfate, carbonylcyanide-p-trifluoromethoxyphenylhydrazone, 2-(3-chloro-4-trifluoromethyl)-anilino-3,5-dinitrothiophene and tetraphenylboron; 5. Partial reactivation of inactive O2 evolving centers is affected by the use of the same reagents inhibiting the light induced inactivations; 6. The life-time (t 1/2 approximately 1 to 3 h) of the activable state is correlated with diffusion across thylakoids of the larger manganese pool released from binding sites and remaining in thylakoids following inactivation of O2 evolution.


Structural Basis for High-Affinity Trapping of the NaV1.7 Channel in Its Resting State by Tarantula Toxin.
Voltage-gated sodium channels initiate electrical signals and are frequently targeted by deadly gating-modifier neurotoxins, including tarantula toxins, which trap the voltage sensor in its resting state. The structural basis for tarantula-toxin action remains elusive because of the difficulty of capturing the functionally relevant form of the toxin-channel complex. Here, we engineered the model sodium channel NaVAb with voltage-shifting mutations and the toxin-binding site of human NaV1.7, an attractive pain target. This mutant chimera enabled us to determine the cryoelectron microscopy (cryo-EM) structure of the channel functionally arrested by tarantula toxin. Our structure reveals a high-affinity resting-state-specific toxin-channel interaction between a key lysine residue that serves as a "stinger" and penetrates a triad of carboxyl groups in the S3-S4 linker of the voltage sensor. By unveiling this high-affinity binding mode, our studies establish a high-resolution channel-docking and resting-state locking mechanism for huwentoxin-IV and provide guidance for developing future resting-state-targeted analgesic drugs.


Vaccine hesitancy among working-age adults with/without disability in the UK.
To estimate levels of COVID-19 vaccine hesitancy among working-age adults with disabilities in the United Kingdom. Cross-sectional survey. Secondary analysis of data collected on a nationally representative sample of 10,114 respondents aged 16-64 years. The adjusted relative risk for hesitancy among respondents with a disability was 0.92 (95% CI 0.67-1.27). There were stronger associations between gender and hesitancy and ethnic status and hesitancy among participants with a disability. The most common reasons cited by people with disabilities who were hesitant were: concern about the future effects of the vaccine, not trusting vaccines and concern about the side effects of vaccination. The higher rates of vaccine hesitancy among women with disabilities and among people from minority ethnic groups with disabilities are concerning.


Differentiating between Transient and Enduring distress on the Edinburgh Depression Scale within screening contexts.
Research has shown that women screened as being 'possibly depressed' on the Edinburgh Depression Scale consist of two distinct duration types: those with Transient distress, and those with Enduring distress. This paper reports on the exploration of antenatal data to ascertain if information from the initial EDS screening can help determine which women may have Transient, and which Enduring, distress after just a few weeks. Data from three antenatal studies were explored, where the EDS had been given twice within a psychosocial screening setting. Repeat testing of the EDS, together with a diagnostic interview, was conducted 2-5 weeks later. Women with Enduring distress (those scoring high on both occasions) were significantly more likely to meet criteria for a depressive disorder than those with Transient distress. They also scored significantly and clinically meaningfully higher on their initial EDS, though no cut-off score was optimal in discriminating between the two duration categories. Differentiation could also not be made from the endorsement of the self-harm question, but was best when women were asked to predict how they would be feeling, and why. The data come from three studies just with English-speaking women with slightly different methodologies, producing information on a fairly small number of women with Transient (n=12-29) and Enduring (n=14-25) distress. In addition the EDS re-test interval of between 2 and 5 weeks was quite wide. Clinical implications are that women who score high initially on the EDS are most likely to continue to score high (have Enduring distress) if they themselves think this will be the case, or if they only give wishful thinking as the reason as to why they think they will feel better. Research studies should also therefore analyse their data taking into account this duration category.


Randomized clinical trial of moxonidine in patients undergoing major vascular surgery.
Myocardial ischaemia is the leading cause of perioperative morbidity and mortality after surgery in patients with coronary artery disease. The aim of this study was to evaluate the effects of moxonidine, a centrally acting sympatholytic agent, on perioperative myocardial ischaemia and 1-year mortality in patients undergoing major vascular surgery. In this double-blind, placebo-controlled two-centre trial, 141 patients were randomly assigned to receive moxonidine or placebo on the morning before surgery and on the following 4 days. Levels of cardiac troponin I (cTnI) were analysed before surgery and on days 1, 2, 3 and 7 thereafter. Holter electrocardiograms were recorded for 48 h starting before the administration of the study drug. Patients were followed daily during admission and by telephone interview 12 months after surgery. The incidence of raised perioperative cTnI levels or alteration in the ST segment in the Holter electrocardiogram or both was 40 per cent in the moxonidine group and 37 per cent in the placebo group (P = 0.694). All-cause mortality rates within 12 months were 10 per cent in the moxonidine group and 11 per cent in the placebo group (P = 0.870). Small oral doses of moxonidine did not reduce the incidence of perioperative myocardial ischaemia and had no effect on mortality in patients undergoing vascular surgery. NCT00244504 (http://www.clinicaltrials.gov).


The influence of some antidepressant drugs on the nuclear volume of rat cingular cortex cells in culture.
The changes in the volume of cell nuclei of the rat cingular cortex were investigated in culture after incubation with some antidepressant drugs. Two-week incubation of the cingular cortex culture with both tricyclic (desipramine, imipramine, amitryptyline) and non-tricyclic (mianserin) antidepressants in concentration of 3 X 10(-6) M resulted in a decrease of the volume of the cell nuclei. Because the size of the nucleus is regarded as a criterion of the cell metabolic activity, our results may point to a diminished activity of metabolic processes of the cells.


Variability of neuronal responses in the posterior superior temporal sulcus predicts choice behavior during social interactions.
Recent studies have shown that neural activity in a well-defined patch in the posterior superior temporal sulcus (the "gaze-following patch," GFP) of the primate brain is strongly modulated when the other's gaze attracts the observer's attention to locations/objects, the other is looking at. Changes of the mean discharge rate of neurons in the monkey GFP indicate that they are involved in two distinct computations: the allocation of spatial attention guided by the other's gaze vector and the suppression of gaze following if inappropriate in a given situation. Here, we asked if and how the discharge variability of neurons in the GFP is related to the task and if it carries information on behavioral performance. To this end, we calculated the Fano factor as a measure of across-trial discharge variability as a function of time. Our results show that all neurons exhibiting a task-related discharge-rate modulation also exhibit a stimulus onset-dependent drop in the Fano factor. Furthermore, the amplitude of the Fano factor reduction is modulated by task condition and the neuron's selectivity in this regard. We found that these effects are directly related to the monkeys' behavioral performance in that the Fano factor is predictive about upcoming correct or wrong decisions. Our results indicate that neuronal discharge variability as gauged by the Fano factor, hitherto primarily studied in the context of visual perception or motor control, is an informative measure also in studies of the neural underpinnings of complex social behavior.NEW & NOTEWORTHY Quenching of neural variability following stimulus onset is a widely accepted phenomenon. However, the relevance of quenching for the shaping of complex social behaviors remains to be explored. Here, we show that task selective neurons in the GFP exhibit a higher degree of variability quenching than their neighboring unselective neurons. Furthermore, we demonstrate that behavioral errors are not only associated with lower firing rates but also less variability quenching, suggesting that both facilitate optimal performance.


Validation of ultrasound methods to monitor gastric volume changes in preterm infants.
The aim of this study was to validate 4 sonographic methods of estimating stomach volume for the purpose of monitoring changes in gastric volume over time and to describe the echogenic characteristics of milk feeds. Twenty-four infants were monitored during a single intragastric tube feed, with 2 ultrasound images of the entire stomach and an image of the antral cross-sectional area (ACSA) before, during, and after the feed. Raw measurements, 3 stomach volume calculations, and ACSA were tested for intra- and interrater agreement. Calculated stomach volumes and ACSA were compared with delivered feed volumes, and characteristics of stomach image echogenicity graded at each time point. Spheroid calculation of stomach volume was the most reliable and valid measure of stomach volume. Fortified breast milk feeds were more echogenic than unfortified breast milk feeds. Residual stomach volumes (median 2.12 mL, range 0.59-9.27 mL) were identified in 18 of 24 infants. Direct ultrasound stomach measurement (spheroid) will provide a useful research tool and a potential clinical tool for assessing gastric emptying and feeding intolerance in preterm infants.


Pre-existing pulmonary fibrosis is associated with adverse outcomes after lung resection.
Pulmonary fibrosis is a risk factor for the development of lung cancer. However, the low incidence of the pathology means that it is not well represented in thoracic surgery risk scoring systems. We aimed to assess whether short and long-term outcomes after lung resection for primary lung cancer were worse in patients with pre-existing pulmonary fibrosis. A total of 5029 consecutive patients undergoing lung resection for primary lung cancer between 2012 and 2018 in two UK centres were included. Primary outcomes were 90-day & 1-year mortality, post-operative complications and overall survival. Univariable analyses were used to compare outcomes between patients with and without pre-existing pulmonary fibrosis. In total, 0.7% (n = 33) of patients had a pre-existing diagnosis of pulmonary fibrosis (idiopathic pulmonary fibrosis 48.5%, non-specific interstitial pneumonia 6.1%, unknown 45.5%). Overall, 90-day and 1-year mortality were all significantly higher amongst patients with fibrosis (90-day: 18.2% vs 3.6%, p < 0.001; 1-year: 36.4% vs 10.7%, p < 0.001). The rate of reintubation was significantly higher for patients with fibrosis (9.1% vs 2.9%, p = 0.038) yet there was no difference in post-operative length of stay between groups (fibrosis: 6 days [IQR 4-9 days] vs non-fibrosis: 5 days [IQR 4-8 days], p = 0.675). Overall survival was also significantly reduced for patients with pulmonary fibrosis (log-rank analysis, p < 0.001). Despite its small size, this study suggests that short and long-term outcomes after lung resection are worse for patients with pre-existing pulmonary fibrosis. Segmental resections could be considered in these patients where oncologically appropriate to minimise peri-operative risk.


The Aymara of Western Bolivia. IV. Gene frequencies for eight blood groups and 19 protein and erythrocyte enzyme systems.
A total of 315 individuals, mainly of Aymara origin, from western Bolivia were examined for genetic variation at eight red cell antigen and 19 serum protein and red cell enzyme loci. The gene frequencies for polymorphic loci and the discovery of several rare variants are discussed in terms of previous work among the Aymara and the closely related Quechua. The effect of inclusion of related individuals in the sample on gene frequency, variance of gene frequency and genetic distance, is discussed.


Opioid peptides excite pyramidal neurons and evoke epileptiform activity in hippocampal transplants in oculo.
The effect of opiate peptide administration on the electrical activity of intraocular hippocampal transplants was studied. Similar to observations in situ, the administration of beta-endorphin or methionine enkephalin produces a concentration-dependent increase in the firing rate of identified pyramidal neurons within hippocampal formation transplants. In addition, these peptides elicit a profound increase in 'EEG' amplitude, which ultimately develops into epileptiform activity. The ability of naloxone to either reverse or prevent the peptide-induced changes in both single unit and EEG activity supports the hypothesis that the excitatory response of the hippocampus to opioid peptides is mediated via an opiate receptor. The results of this study also suggest that the excitatory response to the opiate peptides in hippocampus is the result of alterations in intrinsic neuronal circuitry and is not dependent upon extra-hippocampal afferents.


Finding centre: ocular and fMRI investigations of bisection and landmark task performance.
The line bisection task is used as a bedside test of spatial neglect patients who typically bisect lines to the right of true centre. To disambiguate the contribution of perceptual from motor biases in bisection, previous research has used the landmark task in which participants determine whether a transection mark is left or right of centre. One recent study using stimuli that reliably leads to leftward perceptual biases in healthy individuals, found that ocular judgements of centre were biased to the right of centre, whereas manual bisections were biased leftwards. Here we used behavioural measures and functional MRI in healthy individuals to investigate ocular and perceptual judgements of centre. Ocular judgements were made by having participants fixate the centre of a horizontal bar that was dark at one end and light at the other (i.e., a 'greyscale' stimulus), whereas perceptual responses were made by having participants indicate whether a transection mark on the greyscales stimuli was to the left or right of centre. Behavioural data indicated a leftward bias in the first, second and longest fixations for bisection. Moreover, greyscale orientation (i.e., dark extremity to the right or to the left), and stimulus position modulated fixations. In contrast, for the landmark task, initial fixations were attracted towards the transection mark, whereas subsequent fixations were closer to veridical centre. Imaging data showed a large bilateral network, including superior parietal and lingual cortex, that was active for bisection. The landmark task activated a predominantly right hemisphere network including superior and inferior parietal cortices. Taken together these results indicate that very different strategies and underlying neural networks are invoked by the bisection and landmark tasks.


Transhepatic inferior vena cava filter retrieval due to chronic occlusion of jugular and subclavian veins.
Retrieval of inferior vena cava filters is routinely performed via an internal jugular venous access. We present a case of a 55-year-old woman with myeloproliferative disorder, complicated by venous thrombosis. She was referred to interventional radiology for removal of an inferior vena cava filter, which had been placed 5 months prior for mechanical prophylaxis in the setting of femoral orthopedic surgery. Due to the patient's chronic occlusion of the bilateral jugular and subclavian veins, a transhepatic approach was used to retrieve the filter successfully without immediate complications.


Interaction of folate - Linked silica nanoparticles with HeLa cells: Analysis and investigation the effect of polymer length.
This work is a continuance to our previous findings on silica nanoparticles (NPs) modified with diamine polymer, carboxymethyl-β-cyclodextrin (CM-β-CD) and folic acid (FA), respectively. When four different polymer lengths (D230, D400, D2000 and D4000) were analyzed, the release rate of anticancer agents was inversely related to the polymer length while the cell toxicity was directly related to the length. We investigate here the effect of polymer length on the extent of cellular interaction with HeLa cells. The mean particle size, the polydispersity (PD) and the zeta potential of the NPs were measured using dynamic light scattering (DLS), the quantitative analysis of the extent of NPs' interaction was studied using fluorescence microscopy and transmission electron microscopy (TEM) was used to qualitatively visualize them. The particle size increased by increasing the polymer length, the PD values were within the acceptable ranges (0.3-0.5) and the zeta potential was in the range of (-16 to -20 mV). A direct relation was observed between the fluorescence intensity and the length. All modified NPs were capable of entering the cells, however a greater number of NPs with long polymers was observed compared to short polymers. Thus, the direct relation of polymer length to the cell toxicity is due to the release rate behavior and the enhanced interaction of NPs which possess long polymers.


Dispersion of knee helical axes during walking in young and elderly healthy subjects.
Knee joint rotation center displacement can be estimated in vivo through the analysis of helical axis (HAs) dispersion. HAs can be analyzed during walking, providing information on joint stability. The study aim was to describe knee HAs dispersion during walking in dominant and non-dominant legs of young and elderly healthy subjects. Twenty young (YG: age 23.3 ± 2.4 years) and twenty elderly (EG: age 69.3 ± 4.6 years) healthy subjects were asked to walk on a treadmill at a self-selected speed with reflective markers placed bilaterally on thighs and shanks to detect HAs dispersion and knee kinematics with an optoelectronic system. HAs dispersion was described during the following four phases of gait cycle: (1) flexion from 95% of the previous gait cycle to 10% of the subsequent gait cycle, (2) extension from 10% to 40%, (3) flexion from 40% to 75% and (4) extension from 75% to 95% of the gait cycle. Mean Distance (MD) and Mean Angle (MA) were used as HAs dispersion indexes during each gait phase. Participants showed greater MD and MA in sagittal and frontal planes during the first and second phases. EG revealed higher MD (p = 0.001) and MA (p < 0.001) during the first phase and higher MA (p = 0.001) during the fourth phase in both dominant and non-dominant legs on the sagittal plane. HAs dispersion could be related to the amount of forces acting on knee (first two phases) and knee degeneration (elderly). These results may be used as reference data in further studies on HAs dispersion in presence of knee pathologies or after knee surgery or rehabilitation.


Teaching foundational perspective-taking skills to children with autism using the PEAK-T curriculum: single-reversal "I-You" deictic frames.
We taught basic perspective-taking tasks to 3 children with autism and evaluated their ability to derive mutually entailed single-reversal deictic relations of those newly established perspective-taking skills. Furthermore, we examined the possibility of transfers of perspective-taking function to novel untrained stimuli. The methods were taken from the PEAK-T training curriculum, and results yielded positive gains for all 3 children to learn basic perspective taking as well as for 2 of the 3 to derive untrained single-reversal I relations following direct training of single-reversal You relations. All participants demonstrated a transfer of stimulus function to untrained stimuli after the single-reversal deictic relations had been mastered.


Cloning and sequence analysis of cDNA encoding the bovine testis-derived male-enhanced antigen (Mea).
A full-length cDNA encoding the bovine male enhanced antigen (Mea) has been cloned from a bovine testicular cDNA library and sequenced. The primary structure of the bovine Mea peptide deduced from this nucleotide sequence has 174 amino acid residues and is highly homologous to human (95.9%, 165/172) and mouse (92.5%, 161/174) Mea gene products. It is located on an autosome, and is expressed highly in the testes.


Ventilation strategy during urological and gynaecological robotic-assisted surgery: a narrative review.
Robotic-assisted surgery has improved the precision and accuracy of surgical movements with subsequent improved outcomes. However, it requires steep Trendelenburg positioning combined with pneumoperitoneum that negatively affects respiratory mechanics and increases the risk of postoperative respiratory complications. This narrative review summarises the state of the art in ventilatory management of these patients in terms of levels of positive end-expiratory pressure (PEEP), tidal volume, recruitment manoeuvres, and ventilation modes during both urological and gynaecological robotic-assisted surgery. A review of the literature was conducted using PubMed/MEDLINE; after completing abstract and full-text review, 31 articles were included. Although different levels of PEEP were often evaluated within a protective ventilation strategy, including higher levels of PEEP, lower tidal volume, and recruitment manoeuvres vs a conventional ventilation strategy, we conclude that the best PEEP in terms of lung mechanics, gas exchange, and ventilation distribution has not been defined, but moderate PEEP levels (4-8 cm H2O) could be associated with better outcomes than lower or highest levels. Recruitment manoeuvres improved intraoperative arterial oxygenation, end-expiratory lung volume and the distribution of ventilation to dependent (dorsal) lung regions. Pressure-controlled compared with volume-controlled ventilation showed lower peak airway pressures with both higher compliance and higher carbon dioxide clearance. We propose directions to optimise ventilatory management during robotic surgery in light of the current evidence.


A fast and efficient metal-mediated oxidation of isoniazid and identification of isoniazid-NAD(H) adducts.
It is currently believed that isoniazid (INH) is oxidised inside Mycobacterium tuberculosis to generate, by covalent attachment to the nicotinamide ring of NAD(H) (beta-nicotinamide adenine dinucleotide), a strong inhibitor of InhA, an enzyme essential for mycolic acid biosynthesis. This work was carried out to characterise the InhA inhibitors (named INH-NAD(H) adducts) which are generated, in the presence of the nicotinamide coenzyme NAD+, by oxidation of INH with manganese(III) pyrophosphate, a nonenzymatic and efficient oxidant used to mimic INH activation by the catalase-peroxidase KatG inside M. tuberculosis. The oxidation process is almost complete in less than 15 minutes (in comparison to the slow activation obtained in the KatG-dependent process (2.5 hours) or in the nonenzymatic O2/Mn(II)-dependent activation (5 hours)). The alkylation of NAD+ by the postulated isonicotinoyl radical generates, in solution, a family of INH-NAD(H) adducts. Analyses with liquid chromatography/electrospray ionisation mass spectrometry (LC/ESI-MS) and experiments performed with 18O- and 2H-labelled substrates allowed us to propose two open and four hemiamidal cyclised dihydropyridine structures as the main forms present in solution; these result from the combination of the isonicotinoyl radical and the nicotinamide part of NAD+. A small amount of a secondary oxidation product was also detected. Structural data on the forms present in solution should help in the design of inhibitors of enzymes involved in the biosynthesis of mycolic acids to act as potential antituberculosis drugs.


Impaired autoregulation of cerebral blood flow in the distressed newborn infant.
Cerebral blood flow was measured, using the 133Xe clearance technique, a few hours after birth in 19 infants with varying degrees of respiratory distress syndrome. Ten of these infants had had asphyxia at birth. The least affected infants with normotension (systolic blood pressure 60 to 65 mm Hg) had CBF values of about 40 ml/100 gm/minute. Hypotensive infants with asphyxia at birth or RDS or both had values for CBF of about 20 ml/100 gm/minute, or less. CBF was strongly correlated with the arterial blood pressure, showing a linear relationship that was identical in infants with asphyxia at birth and infants with RDS only. CBF varied considerably with spontaneous variations in blood pressure, suggesting that autoregulation was lacking. This finding may explain why distressed premature infants are prone to develop massive capillary bleeding in the germinal layer with penetration to the ventricles.


Superconductivity above 30 K in alkali-metal-doped hydrocarbon.
The recent discovery of superconductivity with a transition temperature (T(c)) at 18 K in K(x)picene has extended the possibility of high-T(c) superconductors in organic materials. Previous experience based on similar hydrocarbons, like alkali-metal doped phenanthrene, suggested that even higher transition temperatures might be achieved in alkali-metals or alkali-earth-metals doped such polycyclic-aromatic-hydrocarbons (PAHs), a large family of molecules composed of fused benzene rings. Here we report the discovery of high-T(c) superconductivity at 33 K in K-doped 1,2:8,9-dibenzopentacene (C(30)H(18)). To our best knowledge, it is higher than any T(c) reported previously for an organic superconductor under ambient pressure. This finding provides an indication that superconductivity at much higher temperature may be possible in such PAHs system and is worthy of further exploration.


Functional neuroimaging during altered states of consciousness: how and what do we measure?
The emergence of functional neuroimaging has extended the doctrine of functional specificity of the brain beyond the primary stages of perception, language, and motor systems to high-level cognitive, personality, and affective systems. This chapter applies functional magnetic resonance imaging to another high-level realm of cognition and neurology to characterize cortical function in patients with disorders of consciousness. At first pass, this objective appears paradoxical because conventional investigations of a cognitive process require experimental manipulation. For example, to map the location of language-sensitive cortex, a language-related task is performed according to a temporal sequence that alternates the task with rest (no-task) periods. Application of this approach to the study of consciousness would require that levels of consciousness be similarly varied, this is an unlikely technique. Alternatively, another strategy is presented here where the focus is on functional brain activity elicited during various passive stimulations of patients who are minimally conscious. Comparisons between patients with altered states of consciousness due to brain injury and healthy subjects may be employed to infer readiness and potential to sustain awareness. As if a behavioral microscope, fMRI enables a view of occluded neural processes to inform medical practitioners about the health of the neurocircuity-mediating cognitive processes. An underlying point of view is that assessment of recovery potential can be enhanced by neuroimaging techniques that reveal the status of residual systems specialized for essential cognitive and volitional tasks for each patient. Thus, development of imaging techniques that assess the functional status of individual unresponsive patients is a primary goal. The structural integrity of injured brains is often compromised depending on the specific traumatic event, and, therefore, images cannot be grouped across patients, as is the standard practice for investigations of cognitive systems in healthy volunteers. This chapter addresses these challenges and discusses technique adaptations associated with passive stimulation, paradigm selection, and individual patient assessments, where there is "zero tolerance for error," and confidence in the results must meet the highest standards of care. Similar adaptations have been previously developed for the purpose of personalized planning for neurosurgical procedures by mapping the locations of essential functional systems such as language, perception, and sensory-motor functions for each individual patient. Rather than addressing the question of "how does the brain do consciousness" with these techniques, this chapter presents methods for assessment of neurocognitive health in specific patients with disorders of consciousness.


Big Gods: Extended prosociality or group binding?
Big Gods are described as having a "prosocial" effect. However, this conflates parochialism (group cohesion) with cooperation extended to strangers or out-group members. An examination of the cited experimental studies indicates that religion is actually associated with increased within-group parochialism, rather than extended or universal prosociality, and that the same general mechanisms underlie both religious and secular effects.


GC-MS confirmation of xylazine (Rompun), a veterinary sedative, in exchanged needles.
In order to assess the extent of xylazine (Xyz) injection in Puerto Rico, two waves of used-syringe collections were performed. In the first, syringes were gathered, anonymously and without additional information; in the second, a short interview, also anonymous, was administered. We found Xyz in 37.6% of the collected syringes; the majority of the Xyz-containing syringes came from ranching communities. Syringes containing Xyz more frequently also contained "speedball" than those without (90.6% and 66.7%, respectively). Self-reports of Xyz injection deviated markedly from actual detection: only 50% (self-described users) and 22% (self-described non-users) of the collected syringes contained the drug. With a high prevalence of skin ulcers (38.5% vs. 6.8%; p<0.001), Xyz users were more likely to be in poor health compared to non-users. Surprisingly, though a higher percentage of Xyz users than non-users had college-level educations (23.1% vs. 5.5%), they were more likely to be homeless (64.1% vs. 37%).


Osteopenia in pregnancy during long-term heparin treatment: a radiological study post partum.
Osteopenia, sometimes with compression fractures of the spine, is a side-effect of long-term heparin treatment. The frequency is unknown. In this study, 70 women were given subcutaneous heparin as therapy for, or prophylaxis against, thromboembolism during pregnancy. All, except two, were examined by X-ray of the spine and hip first week post partum. The duration of treatment and the dosage of heparin varied. There were 12 (17%) with obvious osteopenia, including two women with multiple fractures of the spine (3%). Re-examination 6-12 months post partum showed that the changes were reversible in most cases. Another 18 women were examined about three years after heparin treatment during pregnancy. No obvious osteopenia was found among them or in a control group of 30 women examined in the first week post partum. The degree of osteopenia was not correlated with either the heparin dose or the duration of treatment. Women treated with heparin in consecutive pregnancies do not seem to have an increased risk of osteopenia.


Stress tolerance in entomopathogenic nematodes: Engineering superior nematodes for precision agriculture.
Entomopathogenic nematodes (EPNs) are soil-dwelling parasitic roundworms commonly used as biocontrol agents of insect pests in agriculture. EPN dauer juveniles locate and infect a host in which they will grow and multiply until resource depletion. During their free-living stage, EPNs face a series of internal and environmental stresses. Their ability to overcome these challenges is crucial to determine their infection success and survival. In this review, we provide a comprehensive overview of EPN response to stresses associated with starvation, low/elevated temperatures, desiccation, osmotic stress, hypoxia, and ultra-violet light. We further report EPN defense strategies to cope with biotic stressors such as viruses, bacteria, fungi, and predatory insects. By comparing the genetic and biochemical basis of these strategies to the nematode model Caenorhabditis elegans, we provide new avenues and targets to select and engineer precision nematodes adapted to specific field conditions.


Biophysics in Membrane of Cells.
The membrane of a cell, often compared to a dynamic city border, carries out an intricate dance of controlling entry and exit, guarding the valuable life processes occurring inside [...].