The Association between 25-Hydroxyvitamin D and Hemoglobin A1c Levels in Patients with Type 2 Diabetes and Stage 1-5 Chronic Kidney Disease.
Aim. To examine the relationship between plasma 25-hydroxyvitamin D (25(OH)D) levels and blood hemoglobin A1c (HbA1c) levels in diabetic patients at various stages of chronic kidney disease (CKD). Methods. We screened for data collected between 2003 and 2012. The correlation between 25(OH)D and HbA1c levels was studied in patients categorized according to the severity of CKD and their vitamin D status. A multivariate linear regression model was used to determine whether 25(OH)D and HbA1c levels were independently associated after adjustment for a number of covariates (including erythrocyte metformin levels). Results. We identified 542 reports from 245 patients. The mean HbA1c value was 6.7 ± 1.0% in vitamin D sufficiency, 7.3 ± 1.5% in insufficiency, and 8.4 ± 2.0% in deficiency (P < 0.0001). There was a negative correlation between 25(OH)D and HbA1c levels for the population as a whole (r = -0.387, P < 0.0001) and in the CKD severity subgroups (r = -0.384, P < 0.0001 and r = -0.333, P < 0.0001 for CKD stages 1-3 and 4-5, resp.). In the multivariate analysis, the 25(OH)D level was the only factor associated with HbA1c (P < 0.0001). Conclusion. 25(OH)D levels were negatively correlated with HbA1c levels independently of study covariates.


Anatomical reconstruction of first ray instability hallux valgus with a medial anatomical TMTJ1 plate.
First tarsometatarsal joint (TMTJ1) arthrodesis is a powerful tool for hallux valgus correction. Past criticism of the TMTJ1 arthrodesis has focused on high non-union rates, and consequent need for delayed weightbearing as prevention. In this study we present a selection and treatment protocol to minimise non-union while allowing early weightbearing. All TMTJ1 arthrodesis procedures for hallux valgus performed by the senior surgeon over the period June, 2016 to July, 2019 were included. An anatomically-designed, medial TMTJ1 plate and screw compression was utilised for TMTJ1 arthrodesis. The construct was augmented with synthetic intermetatarsal stabilisation. All patients were kept non-weightbearing for 2 weeks, followed by progressive weightbearing as tolerated for 4 weeks. Minimum follow-up was 1 year. 300 modified Lapidus procedures were performed for hallux valgus with mean IMA 17° (Range: 14-29). Mean age was 58 years, with 93% female. 284 (94%) had an Akin osteotomy, while 222 cases (74%) were associated with another forefoot procedure. Patients began progressive weight bearing as tolerated from 2 weeks. All were fully weight bearing by 8 weeks post-operatively. There was a 100% union rate in this group. Mean AOFAS Hallux MTP-IP scores rose from 59 pre-operatively to 97 post-operatively. One plate was removed due to tibialis anterior impingement. There were no recurrences at final follow-up. We describe a selection and treatment protocol for TMTJ1 arthrodesis for hallux valgus. This yields high union rates while allowing early weight bearing. 4.


Creativity and modelling the measurement process of the Higgs self-coupling at the LHC and HL-LHC.
This paper provides an account of the nature of creativity in high-energy physics experiments through an integrated historical and philosophical study of the current and planned attempts to measure the self-coupling of the Higgs boson by two experimental collaborations (ATLAS and CMS) at the Large Hadron Collider (LHC) and the planned High Luminosity Large Hadron Collider (HL-LHC). A notion of creativity is first identified broadly as an increase in the epistemic value of a measurement outcome from an unexpected transformation, and narrowly as a condition for knowledge of the measurement of the self-coupling of the Higgs. Drawing upon Tal's model-based epistemology of measurement (2012) this paper shows how without change to 'readings' (or 'instrument indicators') a transformation to the model of the measurement process can increase the epistemic value of the measurement outcome. Such transformations are attributed to the creativity of the experimental collaboration. Creativity, in this context, is both a product, a creative and improved model, and the distributed collaborative process of transformation to the model of the measurement process. For the case of the planned measurements at the HL-LHC, where models of the measurement process perform the epistemic function of prediction, creativity is included in the models of the measurement process, both as projected quantified creativity and as an assumed property of the future collaborations.


An Asymmetric Layer Structure Enables Robust Multifunctional Wearable Bacterial Cellulose Composite Film with Excellent Electrothermal/Photothermal and EMI Shielding Performance.
Highly robust flexible multifunctional film with excellent electromagnetic interference shielding and electrothermal/photothermal characteristics are highly desirable for aerospace, military, and wearable devices. Herein, an asymmetric gradient multilayer structured bacterial cellulose@Fe3 O4 /carbon nanotube/Ti3 C2 Tx (BC@Fe3 O4 /CNT/Ti3 C2 Tx ) multifunctional composite film is fabricated with simultaneously demonstrating fast Joule response, excellent EMI shielding effectiveness (EMI SE) and photothermal conversion properties. The asymmetric gradient 6-layer composite film with 40% of Ti3 C2 Tx possesses excellent mechanical performance with exceptional tensile strength (76.1 MPa), large strain (14.7%), and good flexibility. This is attributed to the asymmetric gradient multilayer structure designed based on the hydrogen bonding self-assembly strategy between Ti3 C2 Tx and BC. It achieved an EMI SE of up to 71.3 dB, which is attributed to the gradient "absorption-reflection-reabsorption" mechanism. Furthermore, this composite film also exhibits excellent low-voltage-driven Joule heating (up to 80.3 °C at 2.5 V within 15 s) and fast-response photothermal performance (up to 101.5 °C at 1.0 W cm-2 within 10 s), which is attributed to the synergistic effect of heterostructure. This work demonstrates the fabrication of multifunctional bacterial cellulose@Fe3 O4 /carbon nanotube/Ti3 C2 Tx composite film has promising potentials for next-generation wearable electronic devices in energy conversion, aerospace, and artificial intelligence.


Characterization of dental pulp stem cells isolated from a patient diagnosed with Crouzon syndrome.
Stem cells isolated from patients with rare diseases are important to elucidate their pathogeny and mechanisms to enable regenerative therapy. However, the mechanisms underlying tissue regeneration using patient-derived dental pulp stem cells (DPSCs) are unclear. In this study, we investigated the levels of mRNA and protein expression related to cellular differentiation of Crouzon syndrome patient-derived DPSCs (CS-DPSCs) with a Gly338Arg fibroblast growth factor receptor 2 mutation. Multipotency-related gene expression levels were equivalent in both healthy donor DPSCs and CS-DPSCs. CS-DPSCs showed higher osteocalcin (OCN) expression than healthy donor DPSCs. CS-DPSCs showed a lower increase in the rate of OCN expression among phorbol 12-myristate 13-acetate (PMA)-treated cells than healthy donor DPSCs compared with untreated control cells. CS-DPSCs showed a lower phosphorylation rate of p38 and p44/42 in PMA-treated cells than healthy donor DPSCs compared with untreated control cells. These results demonstrate that CS-DPSCs have higher OCN expression and lower PMA stimulation-responsiveness than healthy donor DPSCs.


Canonical Thyroid Hormone Receptor β Action Stimulates Hepatocyte Proliferation in Male Mice.
3,5,3'-L-triiodothyronine (T3) is a potent inducer of hepatocyte proliferation via the Wnt/β-catenin signaling pathway. Previous studies suggested the involvement of rapid noncanonical thyroid hormone receptor (TR) β signaling, directly activating hepatic Wnt/β-catenin signaling independent from TRβ DNA binding. However, the mechanism by which T3 increases Wnt/β-catenin signaling in hepatocytes has not yet been determined. We aimed to determine whether DNA binding of TRβ is required for stimulation of hepatocyte proliferation by T3. Wild-type (WT) mice, TRβ knockout mice (TRβ KO), and TRβ mutant mice with either specifically abrogated DNA binding (TRβ GS) or abrogated direct phosphatidylinositol 3 kinase activation (TRβ 147F) were treated with T3 for 6 hours or 7 days. Hepatocyte proliferation was assessed by Kiel-67 (Ki67) staining and apoptosis by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay. Activation of β-catenin signaling was measured in primary murine hepatocytes. Gene expression was analyzed by microarray, gene set enrichment analysis (GSEA), and quantitative reverse transcription polymerase chain reaction. T3 induced hepatocyte proliferation with an increased number of Ki67-positive cells in WT and TRβ 147F mice (9.2% ± 6.5% and 10.1% ± 2.9%, respectively) compared to TRβ KO and TRβ GS mice (1.2% ± 1.1% and 1.5% ± 0.9%, respectively). Microarray analysis and GSEA showed that genes of the Wnt/β-catenin pathway-among them, Fzd8 (frizzled receptor 8) and Ctnnb1 (β-catenin)-were positively enriched only in T3-treated WT and TRβ 147F mice while B-cell translocation gene anti-proliferation factor 2 was repressed. Consequently, expression of Ccnd1 (CyclinD1) was induced. Instead of directly activating Wnt signaling, T3 and TRβ induce key genes of the Wnt/β-catenin pathway, ultimately stimulating hepatocyte proliferation via CyclinD1. Thus, canonical transcriptional TRβ action is necessary for T3-mediated stimulation of hepatocyte proliferation.


Tuning of the o-C(arom)-N bond-formation reactivity of aniline using ruthenium(II) templates.
Chemical reactions of aniline with two face-capped ruthenium(II) templates viz. CpRu(II)Cl(PPh(3))(2) and (Bnz)(2)Ru(II)(2)Cl(4) have been studied to develop an insight into the role of the metal template for the rare type of o-C(arom)-N bond-forming reaction in aniline.


[Management of COPD exacerbations: from primary care to hospitalization].
The Société de pneumologie de langue française defines acute exacerbation of chronic obstructive pulmonary disease (AE COPD) as an increase in daily respiratory symptoms, basically duration ≥ 48h or need for treatment adjustment. Etiology of EA COPD are mainly infectious, viral (rhinovirus, influenzae or parainfluenzae virus, coronavirus, adenovirus and respiratory syncytial virus) or bacterial (Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis). Pollutant exposure can also lead to AE COPD, such as NO2, SO2, ozone or particulates (PM10 and PM2.5). In 30% the etiology remains unknown. Differential diagnoses of AE COPD include infectious pneumonia, pneumothorax, acute heart failure and pulmonary embolism. Presences of signs of severity impose hospitalization: signs of respiratory distress, shock, acute confusion but also fragile patients, insufficient home support or absence of response to initial treatment. AE COPD treatments consist on increase in bronchodilators, chest physiotherapy, and antibiotics if sputum is frankly purulent. Systemic corticosteroids should not be systematic. Recommended dose is 0.5 mg/kg on short course (5-7 days). During hospitalization, oxygen supplementation and thromboprophylaxis could be prescribed. The main interest in non-invasive ventilation is persistent hypercapnia despite optimal medical management. During ambulatory management or hospitalization, clinical assessment at 48-72 h is mandatory.


Age at symptom onset is not associated with reduced action cancelation in adults with obsessive-compulsive disorder.
The aim of the current study was to examine the association between age at symptom onset and action cancelation in adults with obsessive-compulsive disorder (OCD). Performance on the stop-signal task was compared among adult patients with early-onset OCD (n=63, onset age ≤19), late-onset OCD (n=33, onset age ≥20), and healthy controls (n=51). Stop-signal reaction time (SSRT) was significantly longer in both OCD groups compared to the control group. However, no significant differences were found between the two OCD groups. In addition, age at symptom onset was not associated with response inhibition performance in adults with OCD. The study findings support the existence of reduced performance on action cancelation in patients with OCD compared to healthy controls with no difference between early- and late-onset OCD subtypes.


Comparative Evaluation of Fresh Aloe barbadensis Plant Extract and Mineral Trioxide Aggregate as Pulpotomy Agents in Primary Molars: A 12-month Follow-up Study.
The purpose of this study was to compare the clinical and radiographic outcomes of fresh Aloe vera barbadensis plant extract and mineral trioxide aggregate (MTA) as pulpotomy agents in primary molar teeth. Pulpotomy procedure was performed in sixty primary molar teeth which were randomly allocated to two groups, i.e., Aloe vera pulpotomy (Group A) and MTA pulpotomy (Group B). All the pulpotomized teeth were evaluated clinically and radiographically at 1, 3, 6, 9, and 12 months of time interval using predetermined criteria. The success rates between Groups A and B at the end of the 1st month were 24.1% and 96.4%, at the end of 3rd month were 57.1% and 100%, at the end of 6th month were 75% and 100%, at the end of 9th month were 66.6% and 100%, and at the end of 12 months were 100% and 100% respectively. The overall success rates at the end of 12-month follow-up period were 6.9% and 71.4%, respectively, after taking dropout patients into consideration, and the difference was statistically significant (P < 0.001). MTA pulpotomy was found to be superior when compared to fresh A. barbadensis plant extract pulpotomy in primary molars.


Using machine learning to impute legal status of immigrants in the National Health Interview Survey.
We describe a novel machine learning method of imputing legal status for immigrants using nationally representative survey data from the Survey of Income and Program Participation (SIPP) and the National Health Interview Survey (NHIS). K-nearest Neighbor (KNN) classifier and Random Forest (RF) Algorithm machine learning were described as novel imputation methods compared to established regression-based imputation. After validating the imputation methods using sensitivity, specificity, positive predictive value (PPV) and accuracy statistics, the Random Forest Algorithm was more accurate in identifying undocumented immigrants and minimized bias in both socio-demographic variables included in the imputation, and unobserved health variables relative to regression-based imputation and KNN.•We developed a new machine learning method of imputing legal status for immigrants that can be used with nationally representative, publicly available data.•Our findings indicate that using machine learning to impute legal status of immigrants, specifically the Random Forest Algorithm, was more accurate in identifying undocumented immigrants and minimized bias relative to other imputation methods.


Visualization of the Third Ventricle, the Future Cavum Septi Pellucidi, and the Cavum Veli Interpositi at 11+3 to 13+6 Gestational Weeks on 3D Transvaginal Ultrasound Including Normative Data.
To show the development of the third ventricle, commissural plate, future cavum septi pellucidi, and cavum veli interpositi in weeks 12-14 by transvaginal 3D ultrasound. This is a prospective transvaginal 3D study carried out to define the third ventricle and the diencephalic midline structures surrounding it. 93 of 387 fetuses in which the commissural plate with the future cavum septi pellucidi, cavum veli interpositi, and the roof of the third ventricle could be well visualized, were selected with the choroid plexus of the third ventricle and the pituitary gland serving as leading structures. In a small number of fetuses, the optic chiasm could also be displayed. In addition, the following measurements were performed: third ventricle craniocaudal and anteroposterior, roof of the third ventricle/cavum veli interpositi, and fcsp. The sonomorphologic characteristics of the commissural plate, the future cavum septi pellucidi, and the cavum veli interpositi are described IN 9% OF THE FETUSES examined. Measurements of the third ventricle, cavum veli interpositi, and the roof of the third ventricle show the following results: 3rd V cc = 3.895 + 0.091*CRL mm; 3rd V ap = 4.175 + 0.036*CRL mm; CVI ap = 2.223 + 0.029*CRL mm; CVI cc = 0.139 + 0.02*CRL mm. Transvaginal neurosonography enables visualization and measurement of the normal fetal third ventricle at 12-14 weeks of gestation including visualization of the future cavum septi pellucidi and the cavum veli interpositi. BEFORE USE IN PATIENTS CAN BE CONSIDERED, FURTHER SCIENTIFIC WORK IS REQUIRED.


Characterization and Risk Assessment of Heavy Metals in River Sediments on the Western Bank of Taihu Lake, China.
In this study, nine heavy metals (Cd, Cr, As, Hg, Pb, Cu, Ni, Be, and Sb) in the sediments of 17 typical rivers on the western bank of Taihu Lake were determined. Several statistical methods were applied to analyze the distribution, sources, pollution status, and potential ecological risk of these metals. The mean concentrations of heavy metals in sediments other than Be exceeded their local background values. Geoaccumulation index and potential ecological risk index analyses demonstrated that most sediment samples were contaminated and may pose ecological risks, especially those from the Taihu Lake estuary. In particular, Cd concentrations indicated moderate contamination and potentially serious to severe ecological risk. Principal component, cluster, and correlation analyses demonstrated that Ni, Sb, Cr, and Cu were derived from industrial sources, whereas the other metals had complex origins.


Oligodeoxynucleotide-directed mutagenesis using the yeast transformation system.
In this report we describe a highly efficient method for site-specific mutagenesis using the yeast transformation system. The method is based on the observation that Saccharomyces cerevisiae can be transformed at high frequency with single-stranded circular DNA vectors [Singh et al., Gene 20 (1982) 441-449]. The model system studied was the TRP1 gene of S. cerevisiae cloned into a derivative of the phage M13mp9 vector containing the yeast URA3 gene. ARS1, located adjacent to the TRP1 gene, allows the plasmid to replicate autonomously in yeast. Synthetic 5'P-oligodeoxynucleotides, 19 and 35 nucleotides (nt) in length, designed to produce an A----T transversion mutation within the TRP1 gene, were annealed to ss DNA of the M13 vector at a molar ratio of 30:1 and directly transformed into yeast. The intended single nt mutation was obtained at frequencies of 24 and 43%, respectively. The latter approaches the theoretical limit of 50%. In the absence of the 5'-terminal phosphate, both the transformation frequency and the efficiency of mutagenesis by the synthetic oligodeoxynucleotide (oligo) were decreased by 2-4 fold. This procedure completely obviates the need for any enzymatic manipulations in vitro after forming the heteroduplex with the oligo primer containing the desired mutation. For yeast genes, direct phenotypic selection is possible in the recipient strain.


Peptidylglycine monooxygenase activity of monomeric species of growth hormone.
C-terminal α-amidation of peptides is an important event in the course of pro-hormone and neuropeptide processing; it is a modification that contributes to the biological activity and stability of about 25 peptides in neural and endocrine systems. This laboratory has shown that bovine growth hormone (bGH) also has a catalytic function, i.e. peptidylglycine monooxygenase activity, which is the first step in the alpha-amidation of glycine-extended peptides. We report here that the peptidylglycine monooxygenase activity of monomeric bovine pituitary GH, in the presence of ascorbate, is stimulated by combination with oligomeric forms of bGH one of which is a hetero-oligomer with metallothionein. Three species of recombinant monomeric GH (bovine, human and chicken) also catalyze this monooxygenase reaction. Tetrahydrobiopterin also functions as a reductant - with a significantly greater turnover than achieved with ascorbate. These findings clarify the role of GH in peptidylglycine monooxygenation and provide an explanation for earlier observations that peptide amidation is not totally obliterated in the absence of ascorbate, in cultured pituitary cells or in vivo. The evolution of bifunctional GH is also discussed, as are some of the significances of the peptidylglycine monooxygenase activity of human GH in relation to peptides such as oxytocin, glucagon-like peptide-1 and peptide PYY.


Rapid exposure monitoring of six bisphenols and diethylstilbestrol in human urine using fabric phase sorptive extraction followed by high performance liquid chromatography - photodiode array analysis.
A novel fabric phase sorptive extraction protocol is developed for rapid exposure monitoring of six bisphenol analogues, including bisphenol A, bisphenol S, bisphenol F, bisphenol E, bisphenol B, bisphenol C, and diethylstilbestrol (DES) from human urine prior to high-performance liquid chromatography-photodiode array analysis. FPSE sample pretreatment protocol ensures the harmonization of the proposed method with the principles of Green Analytical Chemistry (GAC). Among eighteen evaluated FPSE membranes, sol-gel poly (ethylene glycol) (PEG) coated cellulose FPSE membrane resulted in the most efficient extraction. This polar FPSE membrane effectively exploits a number of advantageous features inherent to FPSE including sponge-like porous architecture of the sol-gel sorbent coating, favorable surface chemistry, flexibility and built-in permeability of cellulose fabric substrate, high primary contact surface area for rapid sorbent-analyte interaction, expanded pH, solvent and thermal stability as well as reusability of the FPSE membrane. Optimization was centered on the evaluation of critical parameters, namely the size of the FPSE membrane, the elution solvent mixture, the volume of the sample, the extraction time, the elution time, the kind of the external agitation mechanical stimulus, the ionic strength and the pH of the sample. The chromatographic separation was achieved on a Spherisorb C18 column and a gradient elution program with mobile phase consisted of 0.05 ammonium acetate solution and acetonitrile. The total analysis time was 17.4 min. The developed method was validated in terms of linearity, sensitivity, selectivity, precision, accuracy, stability, and ruggedness. The limits of detection and quantification varied from 0.26-0.62 ng/mL and 0.8-1.9 ng/mL, respectively. The relative recoveries were calculated between 90.6 and 108.8%, while the RSD values were <10% in all cases. The effectiveness of the proposed method was confirmed by its successful implementation in the bioanalysis of real urine samples.


GPCR Signaling Regulation in Dictyostelium Chemotaxis.
GPCR signaling is the most prevailing molecular mechanism for detecting ambient signals in eukaryotes. Chemotactic cells use GPCR signaling to process chemical cues for directional migration over a broad concentration range and with high sensitivity. Dictyostelium discoideum is a classical model, in which the molecular mechanism underlying eukaryotic chemotaxis has been well studied. Here, we describe protocols to evaluate the spatiotemporal chemotactic responses of Dictyostelium discoideum by different microscopic observations combined with biochemical assays. First, two different chemotaxis assays are presented to measure the dynamic concentration ranges for different cell strains or chemotactic parameters. Next, live-cell imaging and biochemical assays are provided to detect the activities of GPCR and its partner heterotrimeric G proteins upon chemoattractant stimulation. Finally, a method for detecting how a cell deciphers chemical gradients is described.


The first Canadian indigenous case of bovine spongiform encephalopathy (BSE) has molecular characteristics for prion protein that are similar to those of BSE in the United Kingdom but differ from those of chronic wasting disease in captive elk and deer.
Brain tissue from a case of bovine spongiform encephalopathy (BSE) from Alberta was subjected to a Western immunoblotting technique to ascertain the molecular profile of any disease-specific, abnormal prion protein, that is, prion protein that is protease-resistant (PrP(res)). This technique can discriminate between isolates from BSE, ovine scrapie, and sheep experimentally infected with BSE. Isolates of brain tissue from the BSE case in Alberta, 3 farmed elk with chronic wasting disease (CWD) from different parts of Saskatchewan, and 1 farmed white-tailed deer with CWD from Edmonton, Alberta, were examined alongside isolates of brain tissue from BSE, ovine scrapie, and sheep experimentally infected with BSE from the United Kingdom (UK). The molecular weights of PrP(res) and the cross reactions to 2 specific monoclonal antibodies (mAbs) were determined for each sample. The BSE isolates from Canada and the UK had very similar PrP(res) molecular weights and reacted with only 1 of the 2 mAbs. The PrP(res) isolated from both elk and white-tailed deer with CWD had a higher molecular weight profile than did the corresponding PrP(res) from the scrapie and BSE isolates. The PrP(res) from CWD cases cross reacted with both mAbs, a property shared with PrP(res) in isolates from scrapie but not with PrP(res) isolates from BSE or sheep experimentally infected with BSE. The results from this study seem to confirm that the PrP(res) isolated from the BSE case in Alberta has similar molecular properties to the PrP(res) isolated from a BSE case in the UK, and that it differs in its molecular and immunological characteristics from the CWD and scrapie cases studied.


Latrophilin-3 disruption: Effects on brain and behavior.
Latrophilin-3 (LPHN3), a G-protein-coupled receptor belonging to the adhesion subfamily, is a regulator of synaptic function and maintenance in brain regions that mediate locomotor activity, attention, and memory for location and path. Variants of LPHN3 are associated with increased risk for attention deficit hyperactivity disorder (ADHD) in some patients. Here we review the role of LPHN3 in the central nervous system (CNS). We describe synaptic localization of LPHN3, its trans-synaptic binding partners, links to neurodevelopmental disorders, animal models of Lphn3 disruption in different species, and evidence that LPHN3 is involved in cognition as well as activity and attention. The evidence shows that LPHN3 plays a more significant role in neuroplasticity than previously appreciated.


Comparison of prevention of parent-to-child HIV transmission programme & national biennial HIV sentinel surveillance data for tracking HIV epidemic in India.
HIV sentinel surveillance (HSS) among antenatal women in India has been used to track the epidemic for many years. However, reliable tracking at the local level is not possible as ANC sentinel sites are limited in number and cover a smaller sample size at each site. Prevention of parent-to-child-transmission (PPTCT) programme data has a potential advantage due to better geographical coverage, which could provide more precise HIV case estimates; therefore, we compared HSS ANC data with PPTCT programme data for HIV tracking. Out of the 499 surveillance sites, where HSS and PPTCT programme was being conducted in 2015, 210 sites (140 urban and 70 rural) were selected using a stratified random sampling method. HSS (n=72,981) and PPTCT (n=112,832) data records were linked confidentially. The sociodemographic characteristics of HSS and PPTCT attendees were compared. HIV prevalence from HSS ANC was compared with the PPTCT programme data using Chi-square test. State- and site-level correlation of HIV prevalence was also done. Concordance between HSS and PPTCT HIV positivity was estimated using kappa statistics. The age distribution of HSS and PPTCT attendees was similar (range: 23 to 27 yr); however, HSS ANC participants were better educated, whereas PPTCT recorded a higher proportion of homemakers. The correlation of HIV prevalence between HSS and PPTCT was high (r=0.9) at the State level and moderate at the site level (r=0.7). The HIV positivity agreement between HSS ANC and PPTCT was good (kappa=0.633). A similar prevalence was reported across 26 States, whereas PPTCT had a significantly lower prevalence than HSS in three States where PPTCT coverage was low. Overall HIV prevalence was 0.31 per cent in HSS and 0.22 per cent in PPTCT (P<0.001). High-quality PPTCT programme data can provide reliable HIV trends in India. An operational framework for PPTCT-based surveillance should be pilot-tested in a phased manner before replacing HSS with PPTCT.


The Müller-Lyer contrast illusion: a computational approach.
When a temporal delay is interposed between the contextual elements (wings) and the focal element (central axis) of the Müller-Lyer figures, the usual assimilation illusion changes to an illusion of contrast; that is, judged axis length is contrasted away from rather than assimilated toward the context provided by parallel extents between wings. Presentation time for the preceding contextual wings on the order of 1 sec or more was needed to produce contrast effects in judgments of the following focal axis (Experiment 3) and, given sufficient presentation time, these contrast effects were largely unaffected by the length of the temporal delay between contextual and focal elements, appearing equally strong for delays between 0 and 2 sec (Experiments 1 and 2). These results are consistent with a representational basis for these contrast effects that is high-level and long-lived. The Müller-Lyer contrast illusion may reflect the inadvertent error arising from basing judgments about particular objects on information about attribute differences among objects. Such judgmental errors may be the natural consequence of constrained computations that make explicit information required for certain common tasks, but at the expense of obscuring information required for less common tasks.


HSPB1 influences mitochondrial respiration in ER-stressed beta cells.
Beta-cell death and dysfunction are involved in the development of type 1 and 2 diabetes. ER-stress impairs beta-cells function resulting in pro-apoptotic stimuli that promote cell death. Hence, the identification of protective mechanisms in response to ER-stress could lead to novel therapeutic targets and insight in the pathology of these diseases. Here, we report the identification of proteins involved in dysregulated pathways upon thapsigargin treatment of MIN6 cells. Utilizing quantitative proteomics we identified upregulation of proteins involved in protein folding, unfolded protein response, redox homeostasis, proteasome processes associated with endoplasmic reticulum and downregulation of TCA cycle, cellular respiration, lipid metabolism and ribosome assembly processes associated to mitochondria and eukaryotic initiation translation factor components. Subsequently, pro-inflammatory cytokine treatment was performed to mimic pathological changes observed in beta-cells during diabetes. Cytokines induced ER stress and impaired mitochondrial function in beta-cells corroborating the results obtained with the proteomic approach. HSPB1 levels are increased by prolactin on pancreatic beta-cells and this protein is a key factor for cytoprotection although its role has not been fully elucidated. Here we show that while up-regulation of HSPB1 was able to restore the mitochondrial dysfunction induced by beta-cells' exposure to inflammatory cytokines, silencing of this chaperone abrogated the beneficial effects promoted by PRL. Taken together, our results outline the importance of HSPB1 to mitigate beta-cell dysfunction. Further studies are needed to elucidate its role in diabetes.


Etiology and outcome of crescentic glomerulonephritis.
To determine the etiology, course and predictors of outcome in children with crescentic glomerulonephritis (GN). Retrospective, descriptive study. Pediatric Nephrology Clinic at a referral center in Northern India. Clinic records of patients aged <18 year with crescentic GN diagnosed from 2001 - 2010 and followed at least 12 months were reviewed. Crescentic GN, defined as crescents in ≥50% glomeruli, was classified based on immunofluorescence findings and serology. Risk factors for renal loss (chronic kidney disease stage 4-5) were determined. Of 36 patients, (median age 10 yr) 17 had immune complex GN and 19 had pauci-immune crescentic GN. The etiologies of the former were lupus nephritis (n=4), postinfectious GN (3), and IgA nephropathy, Henoch Schonlein purpura and membranoproliferative GN type II (2 each). Three patients with pauciimmune GN showed antineutrophil cytoplasmic antibodies (ANCA). Rapidly progressive GN was present in 33 patients, and required dialysis in 12. At median 34 (19-72) months, 2 patients with immune complex GN and 8 with pauciimmune GN showed renal loss. Renal survival was 94.1% at 3 yr, and 75.3% at 8 yr in immune complex GN; in pauciimmune GN survival was 63.2% and 54.1%, respectively (P=0.054). Risk factors for renal loss were oliguria at presentation (hazards ratio, HR 10.50; P=0.037) and need for dialysis (HR 6.33; P=0.024); there was inverse association with proportion of normal glomeruli (HR 0.91; P=0.042). Pauci-immune GN constitutes one-half of patients with crescentic GN at this center. Patients with pauciimmune GN, chiefly ANCA negative, show higher risk of disease progression. Renal loss is related to severity of initial presentation and extent of glomerular involvement.


Polarotaxis in non-biting midges: female chironomids are attracted to horizontally polarized light.
Non-biting midges (Chironomidae, Diptera) are widely distributed aquatic insects. The short-living chironomid adults swarm in large numbers above water surfaces, and are sometimes considered a nuisance. They are vectors of certain bacteria, and have a key-role in benthic ecosystems. Optical cues, involving reflection-polarization from water, were found to be important in the habitat selection by three Mediterranean freshwater chironomid species. In this work we report on our multiple-choice experiments performed in the field with several other European freshwater chironomid species. We show that the investigated non-biting midges are positively polarotactic and like many other aquatic insects their females are attracted to horizontally polarized light. Our finding is important in the visual ecology of chironomids and useful in the design of traps for these insects.


Brain perfusion in Alzheimer's disease with and without apathy: a SPECT study with statistical parametric mapping analysis.
Alzheimer's disease (AD) is clinically characterized by cognitive symptoms that, in combination with behavioral disturbances, significantly interfere with activities of daily living. These behavioral disorders contribute to the clinical heterogeneity of the disease and probably express different pathophysiological processes. Apathy is one of the most frequent behavioral disorders in AD. The aim of this study was to evaluate brain perfusion of AD patients with and without apathy (as determined by the Neuropsychiatric Inventory) compared with that in healthy elderly subjects. A total of 15 AD patients without apathy (AD/NA; mean age 76.6) and 15 AD patients with apathy (AD/A; mean age 77.6) were studied. Brain perfusion was measured by 99mTc-labeled bicisate (ECD) single-photon emission tomography (ECD SPECT). The images of the two AD subgroups were compared by means of statistical parametric mapping (SPM 99) to corresponding images of 11 healthy elderly control subjects (obtained from the Society of Nuclear Medicine database). Compared with the healthy elderly subjects, the apathy-free AD subgroup had significantly lower perfusion of inferior temporal regions (left fusiform gyrus, left parahippocampal area) and occipital regions (left gyrus lingualis). The apathy subgroup had significantly decreased perfusion of the left anterior cingulate, the right inferior and medial gyrus frontalis, the left orbitofrontal gyrus and the right gyrus lingualis. The differences in the brain areas with reduced perfusion between the apathy-free subjects (mainly the posterior regions) and the apathetic subjects (mainly the anterior regions) indicate that behavioral disorders such as apathy participate in the heterogeneity of brain perfusion in AD.


A hybrid NIR-soft sensor method for real time in-process control during continuous direct compression manufacturing operations.
Near Infrared (NIR) spectroscopy is commonly utilized for continuous manufacturing as Process Analytical Technology (PAT) tool. This paper focus on a continuous direct compression manufacturing process, in which an NIR PAT probe is integrated into the tablet press feed frame and into the tablet diversion control system to ensure continuous monitoring of the potency and homogeneity of the blend within the process line. The quantification of NIR spectra is achieved through Partial Least-Squares (PLS) modeling, calibrated with offline analyzed tablet cores at different potency levels. Because the NIR measurements are often sensitive to sample physical properties caused by raw materials or process conditions, etc., adopting a data-driven approach will require a large amount of representative data throughout the method lifecycle. During the early stages of process development, whenever new uncaptured source of variability in the model space are encountered, the chemometric predictions can deviate from the offline reference, requiring frequent model updates. These deviations can be reduced by integrating process and physico-chemical knowledge in the on-line potency estimation. This paper presents a novel hybrid method combining the online NIR PLS and a potency soft sensor estimation, enabling a robust potency prediction whilst minimizing maintenance downtimes and facilitating cross-site method transfer.


Predictors of cardiovascular death in patients with a left ventricular restrictive filling pattern of the mitral inflow.
The survival, clinical and echocardiographic variables and the predictors of cardiovascular death were determined for a group of 168 patients (mean age 63+/-13 years; 65 females; mean left ventricular ejection fraction 32+/-10%) with restrictive filling of the left ventricle and depressed systolic function after a mean follow-up period of 2.7+/-1 years. Shorter deceleration time (DT) of the mitral inflow was the only variable significantly different between survivors and nonsurvivors (p<0.05) and the only predictor of death found by multivariate logistic regression analysis (odds ratio 2.2, 95% confidence interval 1.7-3.6). In this patient population, a DT of the early wave of the mitral inflow <140 ms identified the patients with the highest risk of cardiac death. DT is a practical echocardiographic parameter for risk stratification of patients with significant left ventricular systolic dysfunction and restrictive filling of the left ventricle.


Serial inoculation of sheep with two bluetongue virus types.
Groups of sheep inoculated with bluetongue virus type 4 were challenged at various intervals after inoculation (from seven to 70 days) with bluetongue virus type 3. Examination of the clinical and serological response showed that animals were protected from challenge with a second bluetongue virus for up to 14 days after the inoculation of the first virus type. An adoptive transfer experiment in monozygotic sheep involving both antibody and T lymphocytes was carried out. Only partial protection was observed against heterologous virus challenge, indicating that although the T cell response has a cross-protective component, antibody is not involved. These observations indicate that current vaccination procedures should be reappraised, particularly in terms of revaccination with multiple bluetongue virus type.


Pharmacokinetics of alkylating metabolites of cyclophosphamide in different strains of mice.
Determination of the amount of alkylating (NBP) metabolites of cyclophosphamide (CP) in blood serum of BALB/c and DBA/2 mice has revealed that the shape of the curve describing the accumulation of NBP-metabolites, depends on the administered drug dose and animals' genotype. The experimental data obtained made it possible to suggest an improved pharmacokinetic model which takes into account a possible switching in of factors conditioning non-linear changes in the intensity of the accumulation processes in blood and elimination of CP alkylating metabolites from blood. The effect of different CP alkylating metabolite kinetics in BALB/c and DBA/2 mice on a different sensitivity of these mice to the immunodepressive action of CP in vivo, has been discussed.


Venous thromboembolism rates in patients with bone and soft tissue sarcoma of the extremities following surgical resection: A systematic review.
Patients undergoing an orthopedic surgery for bone or soft tissue sarcoma are at increased venous thromboembolism (VTE) risk. Unfortunately, there is a lack of thromboprophylaxis guidelines in this population. The purpose of this systematic review was to determine the soft tissue and bone sarcoma VTE rate and to explore the thromboprophylaxis regimens used. The databases MEDLINE, EMBASE, and CENTRAL were queried using keywords related to VTE and long bone malignancy requiring surgical intervention to 2020. Included studied reported VTE rate in patients with surgically managed extremity sarcoma. Descriptive statistics and weighted mean totals were calculated. A total of 2082 studies were screened and 23 studies were included. The overall VTE rate was 2.9%, with a rate of 3.7% and 1.4% in patients with bone and soft tissue sarcomas, respectively. Low-molecular-weight heparin was the most commonly used chemoprophylaxis. There is a high VTE rate following sarcoma surgery. The VTE rate is higher in bone sarcoma surgery, which may be attributed to differences in surgery and postoperative recovery. There was no consensus on the duration or type of thromboprophylaxis used. Future research is needed to determine the most effective thromboprophylaxis regimen in patients with sarcoma and whether individualized thromboprophylaxis is required.


Positive psychological constructs and association with reduced risk of mild cognitive impairment and dementia in older adults: A systematic review and meta-analysis.
Understanding factors associated with dementia risk is important for informing future interventions aimed at dementia prevention. There is accumulating evidence for the association between depression and risk of dementia, however less is known about the association between positive psychological factors and dementia incidence. This review aims to synthesise evidence regarding the association between positive psychological constructs (PPCs) and later risk of MCI and dementia in adults aged 50 and over. Literature searches were conducted in Medline, PsycINFO, and Scopus until March 2021. Papers reporting on the association between at least one PPC and later risk of MCI or dementia in people aged 50 + without cognitive impairment at baseline were included. Results from the meta-analyses revealed that purpose in life was significantly associated with a reduced risk of dementia (HR = 0.81, 95% CI [0.78, 0.85], p < .001), however results for positive affect were non-significant (HR = 0.94, 95% CI [0.76, 1.15], p = .54). Results for other PPCs are described narratively. Mixed findings for different PPCs highlight the importance of investigating these factors individually. Understanding which factors may play a protective role in their association with risk of mild cognitive impairment and dementia could have important implications for informing dementia prevention interventions.


Putative targeting of matrix metalloproteinase-8 in atherosclerosis.
There is compelling evidence indicating that some members of the matrix metalloproteinase (MMP) family play important roles in the pathogenesis of atherosclerosis and related vascular and cardiac conditions such as atherosclerotic plaque rupture leading to myocardial infarction, heart failure after myocardial infarction, neointima formation following angioplasty, and abdominal aortic aneurysm. Studies have shown that administration of MMP inhibitors can deter some of these conditions in experimental animal models, but few pertinent human clinical trials have been reported to date. Clinical studies of broad-spectrum MMP inhibitors in cancers and arthritis, however, have reported considerable side effects that are likely to be related to the lack of selectivity of these inhibitors. Since different members of the MMP family can have divergent and even opposing functions, it is believed that selective MMP inhibitors that specifically target particular MMPs that are key in the disease pathogenesis will likely have greater efficacy and less adverse effects. In recent years there has been accumulating evidence indicating an important role of MMP8 in atherosclerosis and the associated conditions mentioned above. This article will review findings from studies examining MMP8 in relation to these conditions and discuss rationale of targeting MMP8 as a potential therapeutic strategy.


Mutated NDUFS6 is the cause of fatal neonatal lactic acidemia in Caucasus Jews.
NADH:ubiquinone oxidoreductase (complex I; EC 126.96.36.199), the largest respiratory chain complex is composed of 45 proteins and is located at the mitochondrial inner membrane. Defects in complex I are associated with energy generation disorders, of which the most severe is congenital lactic acidosis. We report on four infants from two unrelated families of Jewish Caucasus origin with fatal neonatal lactic acidemia due to isolated complex I deficiency. Whole genome homozygosity mapping, identified a 2.6 Mb region of identical haplotype in the affected babies. Sequence analysis of the nuclear gene encoding for the NDUFS6 mitochondrial complex I subunit located within this region identified the c.344G>A homozygous mutation resulting in substitution of a highly evolutionary conserved cysteine residue by tyrosine. This is the second report of NDUFS6 mutation in humans. Both reports describe three diverse homozygous mutations with variable consequential NDUFS6 protein defects that result in similar phenotype. Our study further emphasizes that NDUFS6 sequence should be analyzed in patients presenting with lethal neonatal lactic acidemia due to isolated complex I deficiency.


Soluble IL-18 receptor complex: a new star in the firmament of rheumatoid arthritis diagnosis?
It has long been recognized that laboratory tests are useful in the diagnosis of disease and to monitor treatment outcome. Their performance has become even more demanding with the development of personalized medicine. In patients with rheumatoid arthritis (RA) the standard biochemical tests measure serological markers of disease, such as C-reactive protein, and RA-associated auto-antibodies, such as rheumatoid factor and anti-citrullinated protein antibodies. The information obtained from these markers does not, however, provide a complete picture of the disease and treatment efficacy. New biomarkers based on cytokine receptor complexes are promising for RA theragnostics.


Effectiveness of policies maintaining or restricting days of alcohol sales on excessive alcohol consumption and related harms.
Local, state, and national laws and policies that limit the days of the week on which alcoholic beverages may be sold may be a means of reducing excessive alcohol consumption and related harms. The methods of the Guide to Community Preventive Services were used to synthesize scientific evidence on the effectiveness for preventing excessive alcohol consumption and related harms of laws and policies maintaining or reducing the days when alcoholic beverages may be sold. Outcomes assessed in 14 studies that met qualifying criteria were excessive alcohol consumption and alcohol-related harms, including motor vehicle injuries and deaths, violence-related and other injuries, and health conditions. Qualifying studies assessed the effects of changes in days of sale in both on-premises settings (at which alcoholic beverages are consumed where purchased) and off-premises settings (at which alcoholic beverages may not be consumed where purchased). Eleven studies assessed the effects of adding days of sale, and three studies assessed the effects of imposing a ban on sales on a given weekend day. The evidence from these studies indicated that increasing days of sale leads to increases in excessive alcohol consumption and alcohol-related harms and that reducing the number of days that alcoholic beverages are sold generally decreases alcohol-related harms. Based on these findings, when the expansion of days of sale is being considered, laws and policies maintaining the number of days of the week that alcoholic beverages are sold at on- and off-premises outlets in local, state, and national jurisdictions are effective public health strategies for preventing excessive alcohol consumption and related harms.


The impact of a state criminal HIV exposure law on residents living with HIV in the U.S.A.
The United States of America has, by far, the highest number of cases of and convictions for HIV transmission or exposure in the world. Little is known, however, about the impact of this phenomenon on people living with HIV/AIDS (PHAs). In this article, based on an oral abstract presentation at AIDS 2010, Carol Galletly provides information on research into the impact on PHAs of the HIV exposure law of the state of Michigan.


Acute retrobulbar optic neuritis with anti-myelin oligodendrocyte glycoprotein antibody-associated disease complicated with microscopic polyangiitis: A case report.
Anti-myelin oligodendrocyte protein antibody-associated disease (MOGAD) is a new disease entity with various clinical phenotypes. MOGAD often present with recurrent optic neuritis (ON), and it can also develop as a compartment of neuromyelitis optica spectrum disorder (NMOSD). Moreover, multiple autoantibodies such as an anti-myeloperoxidase antineutrophil cytoplasmic antibody (MPO-ANCA) had been reported in the serum of patients with NMOSD. We report an 86-year-old woman with a 2-year history of microscopic polyangiitis (MPA). The patient had a rapid loss of vision in her left eye. No abnormal findings were observed on her left fundus, and she tested negative for MPO-ANCA upon admission. However, anti-MOG antibodies were observed in the patient's serum and cerebrospinal fluid. A diagnosis of MOGAD complicated with MPA was made. The patient received twice steroid pulse therapy and oral azathioprine as maintenance therapy. Her vision rapidly recovered, and no subsequent relapse was observed during the 8-month observation period. To the best of our knowledge, this is the first case of MOGAD complicated with MPA, and steroid pulse therapy and azathioprine therapy were effective for ON caused by MOGAD.


GPR35: from enigma to therapeutic target.
The orphan G-protein-coupled receptor 35 (GPR35), although poorly characterised, is attracting considerable interest as a therapeutic target. Marked differences in pharmacology between human and rodent orthologues of the receptor and a dearth of antagonists with affinity for mouse and rat GPR35 have previously restricted the use of preclinical disease models. The development of improved ligands, novel transgenic knock-in mouse lines, and detailed analysis of the disease relevance of single-nucleotide polymorphisms (SNPs) have greatly enhanced understanding of the key roles of GPR35 and have stimulated efforts towards disease-targeted proof-of-concept studies. In this opinion article, new information on the biology of the receptor is considered, whilst insight into how GPR35 is currently being assessed for therapeutic utility - in areas ranging from inflammatory bowel diseases to nonalcoholic steatohepatitis and various cancers - is also provided.


The myocardial recovery mode after cold storage for transplantation with Collins' solution and cardioplegic solution. A functional and metabolic study in the rat heart.
Mechanisms and kinetics of the effects of the ionic composition of two different storage solutions, an intracellular type and an extracellular type, were analyzed by examining the myocardial functional and metabolic recovery processes during the early reperfusion periods after 3 hours of cold storage using an isolated perfused working rat heart model. The hearts were stored either in our own cardioplegic solution (group 1) or in Collins' solution (group 2) for 3 hours at 4 degrees C and were then reperfused. The electromechanical activity in group 1 was elevated, as indicated by a higher incidence of ventricular fibrillation at 5 minutes of reperfusion (group 1: 5/6; group 2: 0/5; p < 0.05). The coronary flow rate in group 2 was significantly lower, at least for the first 15 minutes after reperfusion, than that of group 1, suggesting the possible existence of vasoconstriction in group 2. Although myocardial oxygen uptake during this period was smaller in group 2, the recovery of myocardial high-energy phosphate levels was better and creatine kinase leakage was less in group 2. The recovery of aortic flow after 30 minutes of reperfusion was significantly better in group 2 (group 1, 59.1 +/- 5.8%; group 2, 71.7 +/- 6.0%; p < 0.01), although the early recovery was somewhat worse in group 2. These data suggest that the heart stored in an intracellular-type solution, compared with one stored in an extracellular-type solution, recovers in an electromechanically suppressed fashion during the early reperfusion phase, associated with a better metabolic recovery and a slower but larger functional recovery. The disadvantage of the intracellular-type solution, however, may be its effect on the increase of coronary vascular resistance during the early reperfusion period.


Assessing the convergence of self-report and informant measures for adults with autism spectrum disorder.
Self-report measures are frequently used for research and clinical assessments of adults with autism spectrum disorder. However, there has been little research examining agreement between self-report and informant-report in this population. Valid self-report measures are essential for conducting research with and providing high quality clinical services for adults with autism spectrum disorder. This study collected measures from 40 pairs of adults with autism spectrum disorder and their caregivers on measures of symptom severity, daily living skills, quality of life, and unmet service needs. Caregiver and self-report responses were highly associated with one another on all measures, though there were significant gaps between scores on the measures of daily living skills and quality of life. It is also important to understand how each informant's responses relate to outcomes in the areas of employment and independent living. Using self-report and caregiver-report together better predicted outcomes for the adult with autism spectrum disorder than scores from either individual reporter alone. These findings show that there is unique and valuable information provided by both adults with autism spectrum disorder and their caregivers; a multi-informant approach is important for obtaining the most comprehensive picture of current functioning, identifying unmet service needs, and creating treatment plans. This research also highlights the importance of including and prioritizing self-report perspectives in shaping service planning.


Cronkhite-Canada syndrome associated with carcinoma of the sigmoid colon: report of a case.
Cronkhite-Canada syndrome is generally accepted as being a benign disorder. We herein present a 66-year-old-male patient with Cronkhite-Canada syndrome who had a carcinoma of the sigmoid colon along with multiple colonic polyps, which included juvenile-type polyps, adenomas, and hyperplastic polyps. In the world literature, there have been 34 cases of Cronkhite-Canada syndrome associated with colorectal carcinoma among the 280 reported cases of this syndrome. This report thus adds to the growing evidence that Cronkhite-Canada syndrome may be a premalignant condition for colorectal carcinoma. A periodic examination of the colon is therefore advised in order to detect any development of colorectal carcinoma at an early stage.


Systematic review and meta-analysis of tick-borne disease risk factors in residential yards, neighborhoods, and beyond.
Exposure to blacklegged ticks Ixodes scapularis that transmit pathogens is thought to occur peri-domestically. However, the locations where people most frequently encounter infected ticks are not well characterized, leading to mixed messages from public health officials about where risk is highest. We conducted a systematic review and meta-analysis on spatial risk factors for tick-borne disease and tick bites in eastern North America. We examined three scales: the residential yard, the neighborhood surrounding (but not including) the yard, and outside the neighborhood. Nineteen eligible studies represented 2741 cases of tick-borne illness and 1447 tick bites. Using random effects models, we derived pooled odds ratio (OR) estimates. The meta-analysis revealed significant disease risk factors at the scale of the yard (OR 2.60 95% CI 1.96 - 3.46), the neighborhood (OR 4.08 95% CI 2.49 - 6.68), and outside the neighborhood (OR 2.03 95% CI 1.59 - 2.59). Although significant risk exists at each scale, neighborhood scale risk factors best explained disease exposure. Analysis of variance revealed risk at the neighborhood scale was 57% greater than risk at the yard scale and 101% greater than risk outside the neighborhood. This analysis emphasizes the importance of understanding and reducing tick-borne disease risk at the neighborhood scale. Risk-reducing interventions applied at each scale could be effective, but interventions applied at the neighborhood scale are most likely to protect human health. The study was registered with PROSPERO: CRD42017079169 .


Histone variants in metazoan development.
Embryonic development is regulated by both genetic and epigenetic mechanisms, with nearly all DNA-templated processes influenced by chromatin architecture. Sequence variations in histone proteins, core components of chromatin, provide a means to generate diversity in the chromatin structure, resulting in distinct and profound biological outcomes in the developing embryo. Emerging literature suggests that epigenetic contributions from histone variants play key roles in a number of developmental processes such as the initiation and maintenance of pericentric heterochromatin, X-inactivation, and germ cell differentiation. Here, we review the role of histone variants in the embryo with particular emphasis on early mammalian development.


Chitosan-based nanocomplexes for simultaneous loading, burst reduction and controlled release of doxorubicin and 5-fluorouracil.
In this work, nanocomplexes based on chitosan grafted by carboxy-modified polylactic acid (SPLA) were prepared with the aim of loading simultaneously two anticancer drugs - doxorubicin and 5-fluorouracil, as well as to control their release, reduce the initial burst and boost cytotoxicity. The SPLA was prepared by a polycondensation reaction, using pentetic acid as the core molecule, and linked to the chitosan backbone through a coupling reaction. Nanocomplexes loaded with both drugs were formulated by the polyelectrolyte complexation method. The structure of the SPLA was characterized by 1H NMR, while the product CS-SPLA was analyzed by FTIR-ATR to prove the occurrence of the reaction. Results showed that the diameters and ζ-potential of the nanocomplexes fall in the range 120-200nm and 20-37mV, respectively. SEM and TEM analysis confirmed the spherical shape and dimensions of the nanocomplexes. The presence of hydrophobic side chain SPLA did not influence the encapsulation efficiency of the drugs but strongly reduced the initial burst and prolonged release over time compared to unmodified chitosan. MS analysis showed that no degradation or interactions between the drugs and carrier were exhibited after loading or 24h of release had taken place, confirming the protective role of the nanocomplexes. In vitro tests demonstrated an increase in the cytotoxicity of the drugs when loaded in the prepared carriers.


Host-symbiont recognition in the environmentally transmitted sepiolid squid-Vibrio mutualism.
Associations between environmentally transmitted symbionts and their hosts provide a unique opportunity to study the evolution of specificity and subsequent radiation of tightly coupled host-symbiont assemblages [3, 8, 24]. The evidence provided here from the environmentally transmitted bacterial symbiont Vibrio fischeri and its sepiolid squid host (Sepiolidae: Euprymna) demonstrates how host-symbiont specificity can still evolve without vertical transmission of the symbiont [1]. Infection by intraspecific V. fischeri symbionts exhibited preferential colonization over interspecific V. fischeri symbionts, indicating a high degree of specificity for the native symbiotic strains. Inoculation with symbiotic bacteria from other taxa (monocentrid fish and loliginid squids) produced little or no colonization in two species of Euprymna, despite their presence in the same or similar habitats as these squids. These findings of host specificity between native Vibrios and sepiolid squids provides evidence that the presence of multiple strains of symbionts does not dictate the composition of bacterial symbionts in the host.


Examining the link between emotional childhood abuse and social relationships in midlife: The moderating role of the oxytocin receptor gene.
A single nucleotide polymorphism (SNP), rs53576, of the oxytocin receptor gene (OXTR) has been associated with fundamental aspects of social processes and behaviors. Compared to A carriers, GG individuals have enhanced social competencies and tend to elicit more positive responses from social partners. However, the G allele of the OXTR rs53576 has also been associated with greater social sensitivity. The current study examined the unique influence of emotional childhood abuse on positive and negative aspects of different types of social relationships (e.g., family, spouse/partner, and friends) in midlife and whether genetic variations of OXTR rs53576 moderated these associations. A total of 614 participants in midlife (aged 40-65), recruited for a large-scale study of Phoenix metropolitan residents (AS U Live Project), answered self-report questionnaires and provided blood samples for DNA genotyping. Hierarchical multiple regression analyses tested whether emotional childhood abuse predicted social support and strain for each relationship type and whether these potential linkages differed by OXTR genotype (GG versus AA/AG). Overall, individuals with a history of emotional childhood abuse had less supportive and more strained relationships in midlife. For supportive family relationships, the effect of emotional childhood abuse was moderated by OXTR rs53576 (p < .001). Under conditions of experiencing more emotional abuse in childhood, GG individuals had more supportive family relationships in midlife compared to A carriers. Overall, genetic variations of OXTR rs53576 may be an important candidate in understanding the development of social functioning within the context of emotional childhood abuse.


Ciliary body edema after scleral buckling surgery for rhegmatogenous retinal detachment.
Choroidal detachment and anterior chamber (AC) shallowing develop in some cases after scleral buckling surgery for rhegmatogenous retinal detachment (RD). Postoperative angle-closure glaucoma has been reported to occur in 4% of cases. It is supposed that compression by the local scleral buckling induces ciliary body edema and angle narrowing. This study aimed to evaluate quantitatively the time course of changes in ciliary body thickness and AC depth (ACD) before and after the scleral buckling procedure using ultrasound biomicroscopy. Prospective consecutive case series. Forty-six eyes of 44 patients (43.7+/-18.1 years old [mean +/- standard deviation]) undergoing rhegmatogenous RD surgery. Ciliary body thickness and ACD were measured before and 3, 7, 14, and 28 days after the procedure. Ultrasound biomicroscopy was used to evaluate ACD and ciliary body thickness. Time course of changes in ciliary body thickness and ACD. The surgery caused significant increases in ciliary body thickness at 3, 7, and 14 days postoperatively (P<0.0001, Bonferroni multiple comparison). Ciliary body edema reached its peak 3 days after surgery, followed by a gradual decrease thereafter. Ciliary body thickness in the encircling group was statistically greater than in the segmental buckling group at 3 and 7 days postoperatively (P<0.001, Student's t test). The ciliary body was significantly thicker in the direction of buckling than on the opposite side 3 days after surgery (P = 0.0079). In the encircling group, retinal reattachment surgery significantly decreased ACD 3 days after surgery (P = 0.018), whereas no significant fluctuations were found in the buckling group. Even without apparent choroidal detachment and a shallow AC, subclinical ciliary edema existed in all directions of all eyes for at least 1 month after the scleral buckling procedure. The ciliary body in the direction of scleral buckling showed greater edema than the other areas. Eyes treated with the encircling band showed greater ciliary edema than those treated with segmental buckling alone.


Magnesium ferrite-reinforced polypyrrole hybrids as an effective adsorbent for the removal of toxic ions from aqueous solutions: Preparation, characterization, and adsorption experiments.
Contaminated waters with high contents of toxic anions are detrimental to the human health and wildlife. Thus, the quality of drinking water should be carefully monitored. Adsorption technique has been determined to be a reasonable strategy out of several methods used to remove toxic anions from water. Novel MgFe2O4-reinforced polypyrrole (Ppy@x%MgFe2O4) (x = 1%, 2%, and 5% of MgFe2O4) hybrids were synthesized from a pyrrole monomer and MgFe2O4 using a simple chemical oxidation method. The fabricated hybrids were studied for their capability to remove PO43-, NO3-, and Cr(VI) from aqueous solutions. The results showed that PO43-, NO3-, and Cr(VI) removal was highly pH-dependent. The adsorption isotherms of hybrids were fitted well by the Langmuir model, with the maximum adsorption efficiency of 116.90, 76.14, and 138.60 mg/g for PO43-, NO3-, and Cr(VI), respectively. In addition, the above-mentioned toxic anions could be efficiently desorbed from spent Ppy@x%MgFe2O4 using a 0.1 M NaOH solution, and the hybrids exhibited good regenerability. The prepared materials are promising candidates for PO43-, NO3-, and Cr(VI) removal and exhibit high adsorption efficiency, rapid adsorption-desorption behavior, and appropriate recovery from the aqueous medium under external magnetic field.


Successful treatment of Prototheca peritonitis complicating continuous ambulatory peritoneal dialysis.
We describe the second reported case of peritonitis caused by the alga Prototheca wickerhamii in a patient on continuous ambulatory peritoneal dialysis (CAPD). This organism, which grows slowly on agar media, is recognised as a race cause of other infections. The condition is clinically similar to cases of fungal peritonitis, but there are important differences, particularly when choosing the best treatment.


Genome-wide linkage analysis is a powerful prenatal diagnostic tool in families with unknown genetic defects.
Genome-wide linkage analysis is an established tool to map inherited diseases. To our knowledge it has not been used in prenatal diagnostics of any genetic disorder. We present a family with a severe recessive mental retardation syndrome, where the mother wished pregnancy termination to avoid delivering another affected child. By genome-wide scanning using the Affymetrix (Santa Clara, CA, USA) 10k chip we were able to establish the disease haplotype. Without knowing the exact genetic defect, we excluded the condition in the fetus. The woman finally gave birth to a healthy baby. We suggest that genome-wide linkage analysis--based on either SNP mapping or full-genome sequencing--is a very useful tool in prenatal diagnostics of diseases.


Changes in the tegumental surface of Schistosoma haematobium during development in the mammalian host.
The development of surface of Schistosoma haematobium in the mammalian host was studied by scanning electron microscopy, beginning with lung stages obtained at 7 days, and at various intervals thereafter to completion of development. The major changes observed were similar to those previously seen in Schistosoma mansoni.


Long-term benefits of inhaled corticosteroids in asthma: the propensity score method.
The aim of this study was to apply a propensity score approach to assess the long-term benefits of inhaled corticosteroids (ICS) on respiratory health in asthma. This analysis was conducted on adults with persistent asthma from the Epidemiological study on the Genetics and Environment of Asthma, a 12-year follow-up study. ICS exposure was assessed by questionnaire. Change in lung function over the follow-up period, asthma control, and health-related quality of life (asthma quality of life questionnaire) were assessed by standardized and validated methods. Among 245 adults with persistent asthma, 78 (31.8%) were regularly/continuously exposed to ICS (≥6 months/year, ICS++ ) and 167 never/irregularly exposed to ICS (<6 months/year, ICS+/- ) over the follow-up period. Compared with ICS+/- subjects, a nonsignificant trend for a slower lung function decline (mL/year) was observed in ICS++ subjects (β [95%CI] = -11.4 [-24.9; 2.0]). The ICS++ subjects did not have better controlled asthma and higher health-related quality of life as compared with ICS+/- subjects. Applying a propensity score method did not offer evidence of a statistical significant long-term benefit of ICS on respiratory health in adults with persistent asthma regularly or continuously exposed to ICS over a long period.


Enhanced solar light photocatalytic performance of Fe-ZnO in the presence of H2O2, S2O82-, and HSO5- for degradation of chlorpyrifos from agricultural wastes: Toxicities investigation.
This study reported Fe doped zinc oxide (Fe-ZnO) synthesis to degrade chlorpyrifos (CPY), a highly toxic organophosphate pesticide and important sources of agricultural wastes. Fourier transform infrared, X-ray diffraction, scanning electron microscope, and energy-dispersive X-ray spectroscopic analyses showed successful formation of the Fe-ZnO with highly crystalline and amorphous nature. Water collected from agricultural wastes were treated with Fe-ZnO and the results showed 67% degradation of CPY by Fe-ZnO versus 39% by ZnO at 140 min treatment time. Detail mechanism involving reactive oxygen species production from solar light activated Fe-ZnO and their role in degradation of CPY was assessed. Use of H2O2, peroxydisulfate (S2O82-) and peroxymonosulfate (HSO5-) with Fe-ZnO under solar irradiation promoted removal of CPY. The peroxides yielded hydroxyl (OH) and sulfate radical () under solar irradiation mediated by Fe-ZnO. Effects of several parameters including concentration of pollutant and oxidants, pH, co-existing ions, and presence of natural organic matter on CPY degradation were studied. Among peroxides, HSO5- revealed to provide better performance. The prepared Fe-ZnO showed high reusability and greater mineralization of CPY. The GC-MS analysis showed degradation of CPY resulted into several transformation products (TPs). Toxicity analysis of CPY as well as its TPs was performed and the formation of non-toxic acetate imply greater capability of the treatment technology.


13C and 1H NMR study of the metabolic degradation of 4-pentenoate in different dog nephron segments.
The metabolism of 4-pentenoate in isolated kidney tubules has been investigated by 1H and 13C NMR. The 4-pentenoate metabolite, 3-keto-4-pentenoyl-CoA, accumulated in proximal tubules only and its formation could be competitively inhibited by octanoate. 4-Pentenoate was metabolized in thick ascending limbs but not in papillary collecting ducts.


Microbiota assembly, structure, and dynamics among Tsimane horticulturalists of the Bolivian Amazon.
Selective and neutral forces shape human microbiota assembly in early life. The Tsimane are an indigenous Bolivian population with infant care-associated behaviors predicted to increase mother-infant microbial dispersal. Here, we characterize microbial community assembly in 47 infant-mother pairs from six Tsimane villages, using 16S rRNA gene amplicon sequencing of longitudinal stool and tongue swab samples. We find that infant consumption of dairy products, vegetables, and chicha (a fermented drink inoculated with oral microbes) is associated with stool microbiota composition. In stool and tongue samples, microbes shared between mothers and infants are more abundant than non-shared microbes. Using a neutral model of community assembly, we find that neutral processes alone explain the prevalence of 79% of infant-colonizing microbes, but explain microbial prevalence less well in adults from river villages with more regular access to markets. Our results underscore the importance of neutral forces during microbiota assembly. Changing lifestyle factors may alter traditional modes of microbiota assembly by decreasing the role of neutral processes.


The efficacy of implant surface decontamination using chemicals during surgical treatment of peri-implantitis: A systematic review and meta-analysis.
To answer the following PICOS question: "In adult patients with peri-implantitis, what is the efficacy of surgical therapy with chemical surface decontamination of implant surfaces in comparison with surgical therapy alone or surgery with placebo decontamination, on probing pocket depth (PD) reduction and bleeding on probing (BoP)/suppuration on probing (SoP), in randomized controlled clinical trials (RCTs) and non-RCTs with at least 6 months of follow-up?" Six databases were searched from their inception up to 20 May 2022. Data on clinical outcome variables were pooled and analysed using mean differences (MDs), risk ratios (RRs), or risk differences (RDs) as appropriate, 95% confidence intervals (CIs), and prediction intervals (PIs) in the case of significant heterogeneity. Primary outcomes were determined as changes in PD and BoP/SoP. Secondary outcomes were radiographic marginal bone loss (MBL), implant loss, and disease resolution. PROSPERO registration number: CRD42022325603. Six RCTs-two with moderate, three with high, and one with low risk of bias (RoB)-were included. These studies test the adjunctive effect of photodynamic therapy (PDT), chlorhexidine (CHX), and administration of local antibiotics (LAbs) during surgery on the clinical outcome. In a single 12-month study, the adjunctive use of local antibiotics showed a clinically relevant reduction of PD [MD = 1.44; 95%CI (0.40 to -2.48)] and MBL [MD = 1.21; 95%CI (0.44-1.98); one trial, 32 participants]. PDT showed a small but significant reduction in BoP [MD = 7.41%; 95%CI (0.81-14.00); p = 0.028; two trials; 42 participants]. Treatment with CHX resulted in no significant changes in PD, BoP, or MBL compared to placebo (saline solution). None of the interventions affected disease resolution and implant loss. Certainty of the evidence was very low for all outcome measures assessed. Within the limitations of this systematic review and the meta-analysis, adjunctive use of chemicals such as PDT, CHX, and LAbs for surface decontamination during surgery of peri-implantitis cannot be recommended as superior to standard debridement procedures (mechanical debridement with or without saline).


De Novo Malignancies After Kidney Transplant: Where Do We Stand and Does the Head and Neck Region Require More Caution?
The aim of this study was to investigate the characteristics of de novo malignancies arising in kidney transplant recipients followed in a tertiary hospital in Turkey and to examine the tumors in the head and neck region as a subgroup. Data from kidney transplant recipients treated at our institution between January 2010 and July 2022 were retrospectively analyzed in this single-center study. Data regarding malignancies were noted according to the pathologists' reports. In situ malignancies and those arising after graft loss were not evaluated. The study population comprised 231 patients (165 men; 71.4%) with a median follow-up of 11 years (2853 patient-years). The recipients had a higher cancer risk than the general population (standardized incidence rate = 3.04; 95% CI, 1.82-4.26). Thirty de novo malignant tumors were detected in 24 patients (10.4%). The mean age at diagnosis of cancer was 54.88 ± 11.44 years. The median time from transplant to cancer diagnosis was 11.5 years (range, 7-18.8 y). Nonmelanoma skin cancers (56.7% of all tumors) were the most common malignancies. Twenty-two lesions (73.3%) that developed in 17 patients (7.4%) were localized to the head and neck region: 15 (68.2%) were cutaneous and 7 (31.8%) were noncutaneous. The median time from transplant to head and neck cancer diagnosis was 12 years (range, 7.5-17.5 y). Mortality rate was higher in cancer patients (10 [41.7%] vs 17 [8.2%]; P < 0.01). The incidence of de novo malignancy in kidney transplant recipients was relatively higher compared with previous data. Nonmelanoma skin cancers were the most common type. Three-quarters of all lesions were in the head and neck region, and two-thirds were of cutaneous origin.


Herpes virus infection, an unusual source of adult respiratory distress syndrome.
We report a patient with Herpes Simplex Virus induced diffuse interstitial pneumonia associated with ARDS. A dramatic improvement in the respiratory function seems to have followed acyclovir administration.


Multilevel models for longitudinal variables prognostic for survival.
The issue of modelling the joint distribution of survival time and of prognostic variables measured periodically has recently become of interest in the AIDS literature but is of relevance in other applications. The focus of this paper is on clinical trials where follow-up measurements of potentially prognostic variables are often collected but not routinely used. These measurements can be used to study the biological evolution of the disease of interest; in particular the effect of an active treatment can be examined by comparing the time profiles of patients in the active and placebo group. It is proposed to use multilevel regression analysis to model the individual repeated observations as function of time and, possibly, treatment. To address the problem of informative drop-out--which may arise if deaths (or any other censoring events) are related to the unobserved values of the prognostic variables--we analyse sequentially overlapping portions of the follow-up information. An example arising from a randomized clinical trial for the treatment of primary biliary cirrhosis is examined in detail.


Dietary Intake Assessment, Severity of Symptoms, and Pain in Women with Fibromyalgia.
A cross-sectional study was conducted to assess dietary intake in 92 FMS compared to 96 healthy control patients and to examine the potential associations between daily intake and pain and the severity of symptoms in women with FMS. The tender point count (TPC), the Visual Analog Scale (VAS), and the Revised Fibromyalgia Impact Questionnaire (FIQR) were assessed. FIQ-R correlated negatively with phosphorus (r = -.230, p = .028), iron (r = -.320, p = 0.002), zinc (r = -.238, p = .023), vitamin B1 (r = -.218, p = .038), vitamin B6 (r = -.123, p = .012), folic acid (r = -.250, p = .017), and vitamin C (r = -.217, p = .039). A negative correlation was also found between VAS pain and the intake of vitamin B6 (r = -.322, p = .002). Lower intakes of certain micronutrients correlated with higher scores in FIQ-R and a lower intake of vitamin B6 correlated with higher scores in VAS pain, supporting the potential relevance of these micronutrients in the severity of symptoms and in levels of global pain in FMS women.


Unilateral Venous Approach to Contralateral or Bilateral Carotid Cavernous Shunts.
Cavernous carotid fistulas (CCF) are anatomically complex vascular lesions. Treatment via the venous approach has been previously described and is highly dependent on the patency of the drainage pathways. The use of a unilateral approach to contralateral or bilateral shunts is technically challenging and not commonly described. We present our experience with the unilateral across-the-midline approach to both cavernous sinuses to treat shunts according to anatomic compartments to achieve anatomic cure. Patients included in this study presented with either bilateral or unilateral shunts with unilateral venous drainage. We used a transarterial guiding catheter for road mapping and control angiography. A venous triaxial system was used to achieve support for distal navigation across the midline via the coronary sinus to the contralateral cavernous sinus. Coils were favored for embolization, with occasional complementary liquid embolic material. Five patients underwent complete occlusion in a single session. One patient required additional complementary transarterial embolization. Despite a successful unilateral approach to bilateral cavernous sinuses, 1 patient needed an additional ipsilateral transophthalmic venous approach to obliterate the anterior compartment of the cavernous sinus. No complications were encountered. Complete angiographic cure was observed in all patients by the end of the final procedures, with persistent occlusion in their follow-up imaging. Careful inspection of the venous anatomy and fistulization sites is critical when treating unilateral or bilateral carotid cavernous shunts. The contralateral venous route can serve as a safe approach when visualized. Crossing the midline via the anterior or posterior coronary sinuses is feasible and efficacious.


Corrigendum.
Endovascular Stroke Therapy - A New Era Michael D. Hill, Mayank Goyal, and Andrew M. Demchuk In the paper of Hill et al. (1) published in the April 2015 issue of the International Journal of Stroke, the authors would like to clarify that the word stentriever, which is a trademarked term, mentioned several times throughout the text should be replaced with the generic term retrievable stent. We apologize for these errors. Reference 1 Hill MD, Goyal M, Demchuk AM. Endovascular stroke therapy - a new era. Int J Stroke 2015; 10:278-9.


[Along the road with François].
It was at the Pasteur Institute, in François Gros' laboratory, that I had the opportunity to discover the world of research. An opportunity in more ways than one, first because of the nature of the subject, myogenesis, which lent itself particularly well to cellular and genetic approaches to development and differentiation in vertebrates. An opportunity also because the head of the laboratory, François Gros, who was responsible for the choice of this topic, had created an environment in which researchers could develop their projects with great confidence and freedom.


Vascular protective potential of the total flavanol glycosides from Abacopteris penangiana via modulating nuclear transcription factor-κB signaling pathway and oxidative stress.
"Sanxuelian", the rhizome of Abacopteris penangiana (AP), is traditionally used in Chinese medicine for the treatment of blood circulation stasis, hemorheology barriers, edema and inflammation for patients of metabolic syndrome. This study was to investigate the protective effect of the total flavanol glycosides from AP (FAP) on diabetic vascular impairments by measuring the extents of oxidative stress and inflammatory response in mice. The experimental aortic pathology in diabetic mice was induced by fed on high-fat diet and injected with streptozotocin. The activities of FAP on attenuating aortas injuries, hypoglycemic, hypolipidemic, inhibiting oxidative stress and anti-inflammation were investigated. Additionally, the aortic expressions of nuclear transcription factor-κB (NFκB) were determined by western blot and immunohistochemistry analysis. Furthermore, the effects of FAP on human umbilical vein endothelia cells (HUVECs) were studied. In animal study, the results showed that FAP enhanced the activities of antioxidant enzymes and attenuated the levels of proinflammatory cytokines. The plasma lipid profiles and glucose level in FAP treated groups were significantly decreased along with the vascular impairments were alleviated. Moreover, the aortic expression of NFκB was decreased. In cellular experiment, FAP could inhibit the apoptosis of HUVECs induced by H(2)O(2). The results indicated that FAP had hypolipidemic, hypoglycemic and vascular protective activities and represented a potential herb for the treatment of aortic pathology involved with metabolic syndrome.


Longitudinal melanonychia with spreading pigmentation in Laugier-Hunziker syndrome: a report of two cases.
We present two cases of Laugier-Hunziker syndrome with longitudinal melanonychia and Hutchinson's sign, associated with essential melanotic pigmentation of the mouth and lips.


An Electrically and Thermally Erasable Liquid Crystal Film Containing NIR Absorbent Carbon Nanotube.
Carbon nanotubes (CNTs) coated by a poly(vinylpyrrolidone) (PVP) layer were doped in bistable cholesteric liquid crystal (ChLC) film to provide electric, thermal, or optical erasability controllable films. The CNT/PVP formed a compatible NIR-absorbing film that can generate heat to switch ChLC film from a planar texture to a focal conic texture. The appropriate content of CNT/PVP is provided to achieve a fast thermal response, satisfactory dispersion, and clear display brightness. The ChLC film containing CNT/PVP @ 0.8 (wt.%) saves 51% time at thermal erasing, compared to the ChLC mixture without NIR absorbent. The hybrid organic-inorganic bistable ChLC material reported here extends and offers new applications of ChLC writing tablets.


Interpenetrating network expansion sponge based on chitosan and plasma for ultrafast hemostasis of arterial bleeding wounds.
Preventing arterial hemorrhage by intervening within the first few minutes is critical to the patient's life. Hemostatic materials have been developed over the last decades to address this issue, nevertheless these materials alone do not contribute to improve the survival effects in many extreme conditions, which is usually caused by penetrating arterial bleeding wounds that are incompressible and deep arterial bleeding with irregularly shapes. It is well known that, after calcium ion stimulation, many intriguing changes occurred in the major components of plasma, including the activation of several coagulation factors, such as the conversion of fibrinogen to fibrin, prothrombin to thrombin, and so on. Therefore, we constructed an expansion sponge with interpenetrating network based on chitosan and plasma, while various activated coagulation factors in plasma were also loaded into the pore structure of chitosan sponges. The prepared CS-PG sponge is capable of providing a simpler and more efficient method for treating high-pressure arterial bleeding wounds, which includes three steps: Rapid sealing and adhension, Thrombin catalysis and Activated autocoagulation. As the next generation bioactive materials, compared to conventional hemostatic materials, CS-PG sponge demonstrated superior hemostatic characteristics in both rabbit femoral artery damage and rat liver injury models.


A single micromanipulated stem cell gives rise to multiple T-cell receptor gene rearrangements in the thymus in vitro.
The extensive range of specificities of T-cell receptors is generated, as for immunoglobulins, by rearrangement of genetic information. Much valuable information about rearrangement processes has been inferred by comparing DNA from (monoclonal) lymphoid lines with germ-line DNA and, for B cells, from rearrangements in some Abelson murine leukaemia virus-transformed cell lines. However, because it is difficult to isolate and grow precursor populations, it has not proved possible to study rearrangements occurring in normal untransformed cells in vitro. Here we show that a single T-cell precursor colonizing an alymphoid thymus lobe in organ culture can generate multiple receptor beta-chain gene rearrangements. These observations provide unequivocal evidence for the intra-thymic diversification of the T-cell repertoire. They also offer the possibility of investigating rearrangement and its control in the clonal progeny of a single normal T-cell precursor without the perturbations involved in the use of viral transformation or the production of T-cell hybridomas.


An open-label study of high-dose intravenous immunoglobulin in severe childhood asthma.
Eight pediatric patients with severe steroid-dependent asthma were enrolled in an open-label trial of high-dose intravenous immunoglobulin (IVIG) in an attempt to decrease their steroid requirements. Monthly therapy with high-dose IVIG resulted in a threefold decrease in both maintenance oral corticosteroid dose and in extra oral corticosteroids needed for control of exacerbations of asthma. This was accompanied by significant improvements in peak expiratory flow rates and in symptom-score rating. An immunomodulatory effect of IVIG was suggested by the changes in immediate skin test reactivity. Seven of the eight patients demonstrated one or more reactions to a panel of allergens before therapy. During the course of the trial, there was a progressive diminution in skin test reactivity with a 100-fold reduction in sensitivity at the completion of 6 months of therapy. In this preliminary study, the reduction in steroid requirements, improvement in symptoms and peak flow measurements, and diminution in immediate skin test reactivity support a potential role for IVIG in the treatment of severe steroid-dependent asthma. A larger, randomized trial now appears warranted.


Association of WNK1 exon 1 polymorphisms with essential hypertension in Hani and Yi minorities of China.
The association of polymorphisms in exon 1 of the WNK1 gene with essential hypertension in the minority groups of Hani and Yi of China was investigated in the case-control study. The sequence of 1257bp containing the WNK1 gene exon 1 was determined in 1307 individuals (649 essential hypertension subjects and 658 controls) to identify SNPs in Hani and Yi minority groups. Four of eleven previously known SNPs (rs3168640, rs11885, rs11554421 and rs34880640) were identified. The SNP analysis indicated that SNPs rs11885 and rs11554421 were significantly associated with hypertension in both Hani and Yi populations, and rs34880640 was significantly associated with hypertension in Hani but not in Yi population, adjusted for covariates. Haplotype analysis indicated that the haplotype H1 significantly decreased the risk of hypertension in both populations. These results suggested that WNK1 polymorphisms were involved in the predisposition of essential hypertension in Hani and Yi populations and its effects showed a clear population specificity. This finding supported the importance of population specificity in determining the genetic factors associated with diseases and thus disease treatment.


Incidence of Listeria monocytogenes in fresh foods in Barcelona (Spain).
From September 1989 to March 1990, a study of Listeria spp. was carried out on 311 samples of raw foodstuffs from markets and other establishments in the city of Barcelona. These foodstuffs included vegetables (103 samples), minced meats from pork, beef and poultry (168 samples) and bivalve molluscs (40 samples). L. monocytogenes was isolated in 7.8% of the vegetable samples, 17.3% of the minced meats and in 7.5% of bivalve molluscs. The most frequent serovars were 1/2 and 4. Other species isolated were L. innocua, L. welschimeri and L. seeligeri.


A dedicated C-6 β-hydroxyacyltransferase required for biosynthesis of the glycolipid anchor for Vi antigen capsule in typhoidal Salmonella.
Vi antigen is an extracellular polysaccharide produced by Salmonella enterica Typhi, Citrobacter freundii, and some soil bacteria belonging to the Burkholderiales. In Salmonella Typhi, Vi-antigen capsule protects the bacterium against host defenses, and the glycan is used in a current glycoconjugate vaccine to protect against typhoid. Vi antigen is a glycolipid assembled in the cytoplasm and translocated to the cell surface by an export complex driven by an ABC transporter. In Salmonella Typhi, efficient export and cell-surface retention of the capsule layer depend on a reducing terminal acylated-HexNAc moiety. Although the precise structure and biosynthesis of the acylated terminus has not been resolved, it distinguishes Vi antigen from other known glycolipid substrates for bacterial ABC transporters. The genetic locus for Vi antigen-biosynthesis encodes a single acyltransferase candidate (VexE), which is implicated in the acylation process. Here, we determined the structure of the VexE in vitro reaction product by mass spectrometry and NMR spectroscopy to reveal that VexE catalyzes β-hydroxyacyl-ACP dependent acylation of the activated sugar precursor, uridine-5'-diphospho-GlcNAc, at C-6 to form UDP-6-O-[β-hydroxymyristoyl]-α-d-GlcNAc. VexE belongs to the lysophosphatidyl acyltransferase family, and comparison of an Alphafold VexE model to solved lysophosphatidyl acyltransferase structures, together with modeling enzyme:substrate complexes, led us to predict an enzyme mechanism. This study provides new insight into Vi terminal structure, offers a new model substrate to investigate the mechanism of glycolipid ABC transporters, and adds biochemical understanding for a novel reaction used in the synthesis of an important bacterial virulence factor.


The effect of paclitaxel plus carboplatin chemotherapy on subclinical cardiotoxicity in patients with non-small cell lung cancer: A speckle tracking echocardiography-based study.
Although chemotherapy-induced cardiotoxicity is an emerging problem, limited information is available on the effects of chemotherapy on left ventricular (LV) mechanical functions in patients with non-small cell lung cancer (NSCLC). We aimed to explore chemotherapy-induced alterations in cardiac mechanical functions in patients with NSCLC using speckle tracking echocardiography (STE). Seventy-one patients with NSCLC and 34 age and sex matched control subjects were consecutively included. Based on their good performance status (Eastern Cooperative Oncology Group performance status), 39 patients were treated with paclitaxel plus carboplatin (PC) regimen and 32 patients were treated with vinorelbine plus cisplatin (VC) regimen. All patients and controls underwent conventional two-dimensional echocardiography and STE at baseline to assess their LV functions. The echocardiographic examinations of NSCLC patients were repeated after the chemotherapy regimens. None of the NSCLC patients developed any signs or symptoms of clinical heart failure during or after the chemotherapy. There were not any significant differences in LV ejection fraction between NSCLC patients and controls before and after chemotherapy. There were not any significant differences in baseline LV global longitudinal strain (GLS), radial strain (RS), and circumferential strain (CS) between NSCLC patients and controls. However, all LV GLS, RS and CS significantly decreased in patients treated with the PC regimen resulting in a significant difference compared to both VC group and controls while no significant decreases were observed in strain measures in VC group. Paclitaxel plus carboplatin, but not VC, may induce subclinical cardiotoxicity in patients with NSCLC, which may be detected by STE.


Effect of fixation time on measurement of 2'-deoxyribonucleoside 5'-triphosphate pools in the rat embyro.
Values for the concentrations of deoxyribonucleoside triphosphates in rat embryos on day 12 of gestation, determined by high-pressure liquid chromatography, were artifactually two to three times as high in embryos fixed by cooling in ice/water followed by freezing on solid CO2, in 20s, as in those more rapidly/fixed in liquid N2, in 1 s.


Splanchnic buffering of metabolic acid during early endotoxemia.
We sought to determine the sites of metabolic acid production and clearance during acute endotoxemia. In 10 pentobarbital-anesthetized dogs, flow was measured (ultrasonic probes) for the protal vein, hepatic artery, and renal artery. Catheters were inserted into the hepatic vein, pulmonary artery, renal vein and portal vein. Measurements of blood gases and strong ions were obtained from each site during control conditions and after 30 minutes of intravenous infusion of 1 mg/kg of Escherichia coli endotoxin. The total metabolic acid flux across each organ was calculated using the standard base excess formula and the effective strong ion difference method. PaCO2 was maintained by controlled ventilation. Mean arterial pH decreased from 7.34 to 7.22 with acute endotoxemia. Although transvisceral pH gradients revealed net acid release, the source of this was purely respiratory (carbon dioxide). During early endotoxemia, the gut significantly increased metabolic acid uptake (36.60 +/- 6.60 mmol/h, P < .05). We conclude that during early endotoxemia in the dog, the gut is a major site of metabolic acid removal.