Abortion politics in Cambodia social history, local forms and transnational issues.
Cambodia's current abortion rate and ratio could be among the highest in Southeast Asia. In 1997, the Cambodian parliament passed the first law regulating abortions. This law was adopted to contribute to reduce the high maternal mortality ratio, as a significant number of maternal deaths were believed to be related to complications of unsafe abortion. A decade later, the Ministry of Health had not yet established medical protocols for safe abortion access and women often continued to induce their own terminations or seek unsafe services. However, in 2009, the Cambodian authorities approved the importation and distribution of one manufactured abortion pill. In addition, manual vacuum abortions and medical abortion training programmes were implemented at the referral hospital level. How has this situation come about? What do we know about the local agencies of the transnational reproductive health policies related to safe abortion access in this country? This paper aims to analyse how history and intersections between global interventions, state policies, local moralities and individual strategies shape abortion policies, practices and technologies. Finally, our findings raise some issues for public health programming.


Use of in vivo induced technology to identify antigens expressed by Photobacterium damselae subsp. piscicida during infection of Senegalese sole (Solea senegalensis).
Photobacterium damselae subsp. piscicida (Phdp), the causative agent of photobacteriosis, is an important pathogen in marine aquaculture that affects many different fish species worldwide, including Solea senegalensis, an important fish species for aquaculture in the south of Europe. Bacteria express different repertoires of proteins in response to environmental conditions and when invading a host, sense in vivo environment and adapt by changing the expression of specific proteins. In the case of pathogens, identification of genes with up-regulated expression in vivo compared to in vitro conditions might give an insight into the genes relevant to the bacterial virulence. In the present work, in vivo induced antigen technology (IVIAT) has been used to search for Phdp genes only expressed or up-regulated in infected S. senegalensis. An expression library from Phdp was assayed against pooled sera from convalescent S. senegalensis specimens and 18 clones were positive, indicating that proteins encoded are expressed by Phdp during S. senegalensis infection and are immunogenic for this fish species. In addition, five proteins were reactive against adsorbed sera, indicating their in vivo induced character. Inosine-5'-monophosphate dehydrogenase, serine hydroxy methyltransferase and alanyl-tRNA synthethase, involved in aminoacid and nucleotide metabolism, the protein with antioxidant activity alkyl hydroperoxide reductase and a non-ribosomal peptide synthetase responsible for the synthesis of the siderophore piscibactin have been identified as antigens induced in Phdp during S. senegalensis infection. Proteins induced during in vivo growth of Phdp represent promising targets for the development of novel antimicrobial or prophylactic agents in the treatment and prevention of photobacteriosis.


Developmental programming of adult hyperinsulinemia, increased proinflammatory cytokine production, and altered skeletal muscle expression of SLC2A4 (GLUT4) and uncoupling protein 3.
Fetal glucocorticoid excess programs detrimental effects in the adult phenotype including hyperleptinemia and aberrant glycemic control. In this study, we determined the interactive effects of maternal dexamethasone (Dex) treatment and postnatal dietary omega-3 (n-3) fatty acids on adult proinflammatory cytokine production and skeletal muscle expression of genes central to glucose handling and fatty acid metabolism. Dex acetate was administered to pregnant rats (0.75 microg/ml drinking water) from day 13 to term. Offspring of treated and control mothers were cross-fostered to mothers on either a standard (Std) or high n-3 (Hn3) diet, and remained on these diets postweaning. Adult offspring exposed to Dex in utero exhibited fasting hyperinsulinemia when raised on the Std diet but not when raised on the Hn3 diet. Dex also programmed increased plasma tumour necrosis factor alpha and interleukin 1 beta (IL-1 beta), but the increase in IL-1 beta was also prevented by the Hn3 diet. In skeletal muscle, expression of insulin regulated Slc2a4 (formerly known as GLUT4) was elevated (up to 15-fold) after Dex in utero, and this resulted in elevated intracellular, but not membrane-associated, SLC2A4 protein. Fetal glucocorticoid excess also reduced adult skeletal muscle Ucp3 expression in all offspring, whereas skeletal muscle expression of both Ppard and Ppargc1a were increased in females but not males. In conclusion, our data show that fetal glucocorticoid excess programs adult hyperinsulinemia and increased proinflammatory cytokine production. Related changes in the skeletal muscle Slc2a4, Ucp3, and Ppard indicate that fetal glucocorticoid excess disturbs adult glucose/fatty acid transport and metabolism.


A Pilot Study for the Evaluation of PCR as a Diagnostic Tool in Patients with Suspected Dermatophytoses.
The conventional diagnostic tools for dermatophytoses suffer from several limitations including low sensitivity, specificity, and long turn-around-time. The present study was, therefore, performed to evaluate the performance of a polymerase chain reaction (PCR)-based method for the diagnosis of this condition. The study was conducted in the Dermatology outpatient department of a tertiary care teaching hospital in central India over a period of 3 months from July to September 2015. Forty participants, including 25 cases and 15 controls, were recruited in this observational study. Direct microscopy and fungal culture were performed from skin scrapings and nail clippings collected from the participants. PCR was also performed to amplify the chitin synthase 1 and internal transcribed spacer 2 genes from DNA samples extracted from the same clinical materials, using the method reported by Brillowska-Dabrowska et al. The diagnostic performance of fungal culture and PCR was compared using OpenEpi software. We observed a significant male predominance among patients with dermatophytoses. The sensitivity of fungal culture and dermatophyte PCR to diagnose dermatophytoses was 24% and 48%, respectively, whereas the specificity of the two assays was 100% and 93.3%, respectively. The likelihood ratio of a positive PCR assay was 7.2 and the negative likelihood ratio was 0.5. PCR assay also delivered a significant shortening of the time-to-diagnosis, with the mean turn-around-time being 8 hours and 14 days for PCR and culture, respectively. This study, thus, highlights the potential merits of the dermatophyte PCR assay in achieving a rapid diagnosis of dermatophytoses and underscores its utility as a complementary test to improve the sensitivity of the conventional diagnostic tools for this condition, as well as to reliably differentiate this condition from other similar skin conditions.


Hand function assessment in the first years of life in unilateral cerebral palsy: Correlation with neuroimaging and cortico-spinal reorganization.
The purpose of the present study was to correlate early hand function assessment during the first years of life with neuroimaging findings and the different patterns of cortico-motor reorganization in children with unilateral cerebral palsy (UCP). We conducted a long prospective observational study, in which 17 children with UCP (8 left-sided hemiplegia; Manual Ability Classification System level 1-3) were first assessed at a mean age of 24 months (range 18-28), and followed up by means of the Besta Scale, a new standardized protocol assessing both unimanual and bimanual hand function. They also underwent Melbourne Assessment of Unilateral Upper Limb Function (MUUL) and single-pulse Transcranial Magnetic Stimulation (TMS) at a mean age of 10 years 5 months (range 9 y 1 m-12 y 8 m). Brain MRIs of all the 17 children were independently assessed and scored by two blinded observers, according to a defined protocol. Possible correlations between hand function at first assessment, neuroimaging and TMS data were analyzed. Early hand function impairment significantly correlated with the extension of brain damage (ρ = -0.531, p = 0.028), number of involved areas (ρ = -0.608, p = 0.010), presence of radiological signs of cortico-spinal degeneration (ρ = -0.628, p = 0.007), and basal ganglia involvement (ρ = -0.485, p = 0.049). Additionally, higher hand function scores (i.e. better hand function) at first assessment significantly correlated with contralateral cortico-spinal projections, while lower scores significantly correlated with either mixed or ipsilateral cortico-spinal projections to the affected hand (χ(2)(2) = 11.418, p = 0.003; post-hoc tests: contralateral TMS group versus ipsilateral: Z = -2.943, p = 0.002 and contralateral TMS group versus mixed: Z = -2.775, p = 0.006). To our knowledge, this is the first study correlating hand function assessment in the first years of life, and its evolution over time, with neuroimaging and cortico-spinal projection patterns in children with UCP. These findings could contribute to an improved prediction of prognosis and a better delineation of therapeutic interventions in young children with UCP.


Morbidity of adjuvant treatment in early cervical cancer: a retrospective cohort study in a Latin American center.
Radical hysterectomy with pelvic lymph node assessment is the standard of treatment in early cervical cancer. Adjuvant radiotherapy or chemoradiotherapy are offered to patients with risk factors for recurrence. The objective of this study was to compare the incidence of severe (> G3) early or late morbidity related to treatment in patients with cervical cancer undergoing radical surgery with/without adjuvant treatment in a Latin American center. Retrospective cohort study of patients diagnosed with cervical cancer stage IA1 to IB1. Complications were evaluated according to Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. The cumulative incidence of severe morbidity was estimated. Risk ratios (RR) were calculated to determine the factors associated with morbidity. 239 patients were included. 133 (55.6%) received only radical surgical management and 106 (44.4%) adjuvant treatment. The incidence of early morbidity was 18.8% [95% confidence interval (CI): 12.6% to 26.5%] in the group without adjuvant treatment versus 21.7% (95% CI: 14.3% to 30.8%) in the adjuvant treatment group (p = 0.58). Late morbidity was 3% (95% CI: 1% to 7.5%) and 8.5% (95% CI: 4% to 15.5%), respectively (p = 0.063). No statistically significant differences regarding grade ≥ 3 morbidity between the groups was found (2.3% vs. 5.7%, p = 0.289). Complications during surgery is the only factor associated with postoperative morbidity related to treatment (RR = 4.1) (95% CI: 3% to 5.7%). In our study, the addition of adjuvant treatment for early cervical cancer patients who underwent radical surgery did not increase the incidence of severe early or late morbidity.


Perinatal and Neonatal Outcomes in Immigrants From Conflict-Zone Countries: A Systematic Review and Meta-Analysis of Observational Studies.
There are controversies regarding the risk of adverse pregnancy outcomes among immigrants from conflict-zone countries. This systematic review and meta-analysis aimed to investigate the risk of perinatal and neonatal outcomes among immigrants from conflict-zone countries compared to native-origin women in host countries. A systematic search on the databases of PubMed/MEDLINE, Scopus, and Web of Science was carried out to retrieve studies on perinatal and neonatal outcomes among immigrants from Somalia, Iraq, Afghanistan, Yemen, Syria, Nigeria, Sudan, Ethiopia, Eritrea, Kosovo, Ukraine, and Pakistan. Only peer-reviewed articles published in the English language were included in the data analysis and research synthesis. The odds ratio and forest plots were constructed for assessing the outcomes of interests using the DerSimonian and Laird, and the inverse variance methods. The random-effects model and the Harbord test were used to account for heterogeneity between studies and assess publication bias, respectively. Further sensitivity analysis helped with the verification of the reliability and stability of our review results. The search process led to the identification of 40 eligible studies involving 215,718 pregnant women, with an immigration background from the conflict zone, and 12,806,469 women of native origin. The adverse neonatal outcomes of the risk of small for gestational age (Pooled OR = 1.8, 95% CI = 1.6, 2.1), a 5-min Apgar score <7 (Pooled OR = 1.4, 95% CI = 1.0, 2.1), stillbirth (Pooled OR = 1.9, 95% CI = 1.2, 3.0), and perinatal mortality (Pooled OR = 2, 95% CI = 1.6, 2.5) were significantly higher in the immigrant women compared to the women of native-origin. The risk of maternal outcomes, including the cesarean section (C-S) and emergency C-S, instrumental delivery, preeclampsia, and gestational diabetes was similar in both groups. Although the risk of some adverse maternal outcomes was comparable in the groups, the immigrant women from conflict-zone countries had a higher risk of neonatal mortality and morbidity, including SGA, a 5-min Apgar score <7, stillbirth, and perinatal mortality compared to the native-origin population. Our review results show the need for the optimization of health care and further investigation of long-term adverse pregnancy outcomes among immigrant women.


Localization of a second SigH promoter in the Bacillus subtilis sigA operon and regulation of dnaE expression by the promoter.
The presence of a second SigH promoter in the sigA operon of Bacillus subtilis was demonstrated by use of a promoter probe plasmid, a sigH deletion mutant, primer extension studies, and in vitro transcription with E sigma H holoenzyme. Both SigH promoters were expressed at low levels even during the growth phase but were expressed at higher levels during the early stationary phase. Expression from the upstream SigH promoter allowed the expression of both dnaE and sigA genes; however, expression from the downstream SigH promoter, which was located in the ribosome-binding site of the dnaE gene, resulted only in the expression of the sigA gene, since the truncated dnaE ribosome-binding site could not be used for initiating translation. Thus, promoter switching during the early stationary phase resulted not only in expression from SigH promoters but also in differential expression of the genes in the sigA operon.


Compact and modular system architecture for a nano-resonator-mass spectrometer.
Mass measurements in the mega-to giga-Dalton range are essential for the characterization of natural and synthetic nanoparticles, but very challenging to perform using conventional mass spectrometers. Nano-electro-mechanical system (NEMS) based MS has demonstrated unique capabilities for the analysis of ultra-high mass analytes. Yet, system designs to date included constraints transferred from conventional MS instruments, such as ion guides and high vacuum requirements. Encouraged by other reports, we investigated the influence of pressure on the performances of the NEMS sensor and the aerodynamic focusing lens that equipped our first-generation instrument. We thus realized that the NEMS spectrometer could operate at significantly higher pressures than anticipated without compromising particle focusing nor mass measurement quality. Based on these observations, we designed and constructed a new NEMS-MS prototype considerably more compact than our original system, and which features an improved aerodynamic lens alignment concept, yielding superior particle focusing. We evaluated this new prototype by performing nanoparticle deposition to characterize aerodynamic focusing, and mass measurements of calibrated gold nanoparticles samples. The particle capture efficiency showed nearly two orders of magnitude improvement compared to our previous prototype, while operating at two orders of magnitude greater pressure, and without compromising mass resolution.


Risk Factors for Overall Complications and Remote Infection After Gastrectomy in Elderly Gastric Cancer Patients.
A significant predictive factor for the occurrence of complications after gastrectomy in elderly gastric cancer patients is yet to be determined. We aimed to evaluate the clinical factors associated with overall complications including remote infection after gastrectomy in elderly gastric cancer patients. We retrospectively analyzed data of 101 patients aged over 80 years, who underwent curative gastrectomy. We analyzed the clinicopathological factors that were independently associated with the occurrence of overall complications or remote infection by a logistic regression model. The overall complication rate was 24.8%. We identified pneumonia as a remote infection, and the occurrence rate of remote infections was 5.9%. On multivariate analysis, hemoglobin (<11 g/dl) and operation time (>240 min) were significantly correlated with the occurrence of overall complications. Regarding the occurrence of remote infection, performing total gastrectomy and a hemoglobin level <11 g/dl were identified as significant risk factors. Preoperative anemia and intraoperative factors, including the surgical procedure, could affect the occurrence of postoperative complications in elderly patients.


Stem cells in gynecology and obstetrics.
Over the past 10 years, we have become involved in a new research effort and an increasing scientific interest in the field of stem cell-based therapy. We are therefore able to describe different areas in which stem cell research can be applied and developed in gynecology and obstetrics. I) Hematopoietic stem cells have been used to set up therapeutic strategies for the treatment of gynecological solid tumors such as ovarian cancer. In this context different autologous or allogeneic transplantation approaches have been proposed and clinically investigated. II) Umbilical cord blood, which was often considered a waste material of the delivery, actually represents a precious source of stem cells that can be used for cell-based treatments of malignancies and inherited diseases. III) A feto-maternal cell traffic has recently been demonstrated through the placental barrier during pregnancy. This cellular exchange also includes stem cells from the fetus, which can generate microchimerisms in the mother and contribute to tissue repair mechanisms in different maternal organs. IV) Stem cells can be used for prenatal transplantation to treat different severe congenital diseases of the fetus. Nevertheless, several problems need to be solved to achieve an efficient in utero stem cell transplantation. Recent reports have pointed out the importance of timing in prenatal stem cell transplantation procedures and have shown the advantage of an early stem cell injection. An ultrasound-guided intracelomic approach could allow this possibility.


Stability of Attachment Style in Adolescence: An Empirical Test of Alternative Developmental Processes.
Few studies have examined stability and change in attachment during adolescence. This 5-year longitudinal study (a) examined whether prototype or revisionist developmental dynamics better characterized patterns of stability and change in adolescent attachment (at T1, N = 176; Mage = 14.0 years, SD = 0.9), (b) tested potential moderators of prototype-like attachment stability, and (c) compared attachment stability in adolescence to stability in adulthood. The results supported the prototype model, which assumes that there is a stable, enduring factor underlying stability and change in attachment. Exploratory moderation analyses revealed that family conflict, parental separation or divorce, minority status, and male sex might undermine the prototype-like stability of adolescent attachment. Stability of attachment was lower in adolescence relative to adulthood.


Quantitative microradiography for studying dental enamel demineralization and remineralization.
A method for quantitative determination of mineral density changes in dental enamel has been developed. It utilizes the quantitative microscopy capabilities of image analysis or photometer systems. Characteristic demineralization of bovine enamel in acetate buffers containing calcium and phosphate has been used to demonstrate the results. The method together with chemical kinetic data obtained from spectrophotometric and ion-selective electrode measurements of the bulk solution for calcium, phosphate, and fluoride permit important basic studies to be conducted on demineralization and remineralization of dental enamel.


Mechanical Stress Regulates Osteogenesis and Adipogenesis of Rat Mesenchymal Stem Cells through PI3K/Akt/GSK-3β/β-Catenin Signaling Pathway.
Osteogenesis and adipogenesis of bone marrow mesenchymal stem cells (BMSCs) are regarded as being of great importance in the regulation of bone remodeling. In this study, rat BMSCs were exposed to different levels of cyclic mechanical stress generated by liquid drops and cultured in general medium or adipogenic medium. Markers of osteogenic (Runx2 and Collagen I) and adipogenic (C/EBPα, PPARγ, and lipid droplets) differentiation were detected using Western blot and histological staining. The protein levels of members of the phosphatidylinositol 3-kinase (PI3K)/Akt/glycogen synthase kinase 3β (GSK-3β)/β-catenin signaling pathway were also examined. Results showed that small-magnitude stress significantly upregulated Runx2 and Collagen I and downregulated PPARγ and C/EBPα expression in BMSCs cultured in adipogenic medium, while large-magnitude stress reversed the effect when compared with unloading groups. The PI3K/Akt signaling pathway could be strongly activated by mechanical stimulation; however, large-magnitude stress led to decreased activation of the signaling pathway when compared with small-magnitude stress. Activation of β-catenin with LiCl led to increased expression of Runx2 and Collagen I and reduction of C/EBPα and PPARγ expression in BMSCs. Inhibition of PI3K/Akt signaling partially blocked the expression of β-catenin. Taken together, our results indicate that mechanical stress-regulated osteogenesis and adipogenesis of rat BMSCs are mediated, at least in part, by the PI3K/Akt/GSK-3β/β-catenin signaling pathway.


Long Noncoding RNA MMP2-AS1 Contributes to Progression of Renal Cell Carcinoma by Modulating miR-34c-5p/MMP2 Axis.
Renal cell carcinoma (RCC) serves as a prevalent malignancy of urinary system and presents severe mortality and increasing incidence. Long noncoding RNAs (lncRNAs) have demonstrated critical roles in RCC development. Here, we were interested in the function of MMP2-AS1 during RCC progression. We observed that MP2-AS1 localized in both nucleus and cytoplasm of RCC cells using fluorescent in situ hybridization (FISH). The cell viability, proliferation, invasion, and migration of RCC cells were reduced by the depletion of MMP2-AS1. The MMP2-AS1 depletion-inhibited viability, proliferation, migration, and invasion of RCC cells were rescued by the overexpression of MMP2 in vitro. Consistently, the tumor growth of RCC cells was repressed by the depletion of MMP2-AS1 in the nude mice, while the overexpression of MMP2 could reverse this effect in vivo. Mechanically, we predicted the potential interaction of miR-34c-5p with both MMP2-AS1 and MMP2. The treatment of miR-34c-5p mimic reduced the luciferase activity of MMP2-AS1 and MMP2 3'UTR. The depletion of MMP2-AS1 enhanced miR-34c-5p expression and the expression of MMP2 was inhibited by miR-34c-5p in RCC cells. The protein levels of MMP2 were downregulated by MMP2-AS1 knockdown, while the inhibitor of miR-34c-5p rescued the expression of MMP2 in the cells. The treatment of miR-34c-5p mimic attenuated the cell viability, proliferation, invasion, and migration of RCC cells, in which MMP2 overexpression restored the phenotypes. MMP2-AS1 depletion-attenuated viability, proliferation, migration, and invasion of RCC cells were reversed by miR-34c-5p inhibitor. We concluded that MMP2-AS1 contributed to progression of renal cell carcinoma by modulating miR-34c-5p/MMP2 axis.


Molecular evidence for Neotyphodium fungal endophyte variation and specificity within host grass species.
Host specificity of Neotyphodium species symbiotic with three grass species, Festuca arundinacea, Festuca pratensis and Lolium perenne, was studied based on comparisons of amplified fragment length polymorphisms (AFLP) between hosts and their corresponding endophytes. Endophytic fungi were isolated from 24 accessions of host plants. Neotyphodium identity was determined based on morphological characteristics observed in cultures and polymerase chain reaction analysis using specific primers. The results of AFLP data analysis revealed high genetic variation in plant and fungal endophyte species. Plant AFLP genotypes from different species clustered in three distinctive groups, congruent with species. A cluster analysis of AFLP data grouped endophytic isolates according to their host species and secondarily according to their host geographic distribution. The result of the AMOVA on AFLP data accounted for a large and significant proportion of genetic variation due to differences among plant and endophyte species. Phylogenetic groups of isolates corresponded to their respective host genotypes based on maximum parsimony phylograms. Comparisons of the two phylograms illustrated a significant congruence between nodes and branches of host and endophyte clades. These results strongly suggest host specificity of Neotyphodium fungal endophytes with their geographically distant host grasses within each species.


Transcriptional regulation of cell polarity in EMT and cancer.
The epithelial-to-mesenchymal transition (EMT) is a crucial process in tumour progression providing tumour cells with the ability to escape from the primary tumour, to migrate to distant regions and to invade tissues. EMT requires a loss of cell-cell adhesion and apical-basal polarity, as well as the acquisition of a fibroblastoid motile phenotype. Several transcription factors have emerged in recent years that induce EMT, with important implications for tumour progression. However, their effects on cell polarity remain unclear. Here, we have re-examined the data available related to the effect of EMT related transcription factors on epithelial cell plasticity, focusing on their impact on cell polarity. Transcriptional and post-transcriptional regulatory mechanisms mediated by several inducers of EMT, in particular the ZEB and Snail factors, downregulate the expression and/or functional organization of core polarity complexes. We also summarize data on the expression of cell polarity genes in human tumours and analyse genetic interactions that highlight the existence of complex regulatory networks converging on the regulation of cell polarity by EMT inducers in human breast carcinomas. These recent observations provide new insights into the relationship between alterations in cell polarity components and EMT in cancer, opening new avenues for their potential use as therapeutic targets to prevent tumour progression.


Gravity delivery of laboratory specimens.
A feasible method for the safe transport by gravity of clinical laboratory specimens has been developed. In this method, specimens are delivered inside containers that closely fit the conduit in which they descend. By maintaining either end of the conduit closed, the containers descend at a constant speed that can be maintained at less than 120 cm. per sec. over a wide range of operating conditions of practical interest. The speed will increase with increasing container weight, but decrease with increasing length or diameter, or both. Heavier payloads can be accomodated at the same safe, slow speeds by increasing the size of the conduit. The system can be fabricated from standard, commercially available metal or plastic conduit.


Tetrandrine alleviates silicosis by inhibiting canonical and non-canonical NLRP3 inflammasome activation in lung macrophages.
Silicosis caused by inhalation of silica particles leads to more than ten thousand new occupational exposure-related deaths yearly. Exacerbating this issue, there are currently few drugs reported to effectively treat silicosis. Tetrandrine is the only drug approved for silicosis treatment in China, and despite more than decades of use, its efficacy and mechanisms of action remain largely unknown. Here, in this study, we established silicosis mouse models to investigate the effectiveness of tetrandrine of early and late therapeutic administration. To this end, we used multiple cardiopulmonary function test, as well as markers for inflammation and fibrosis. Moreover, using single cell RNA sequencing and transcriptomics of lung tissue and quantitative microarray analysis of serum from silicosis and control mice, our results provide a novel description of the target pathways for tetrandrine. Specifically, we found that tetrandrine attenuated silicosis by inhibiting both the canonical and non-canonical NLRP3 inflammasome pathways in lung macrophages. Taken together, our work showed that tetrandrine yielded promising results against silicosis-associated inflammation and fibrosis and further lied the groundwork for understanding its molecular targets. Our results also facilitated the wider adoption and development of tetrandirne, potentially accelerating a globally accepted therapeutic strategy for silicosis.


Neurobehavioural functioning in school-aged children with a corrected septal heart defect.
This cross-sectional study assesses neurobehavioural consequences after surgical treatment for acyanotic congenital heart defect at the age of 5 to 12 years. Fifteen school-aged children who underwent surgical intervention for a septal heart defect were examined with the short form Wechsler Intelligence Scale for Children-third Edition, Dutch Version (WISC-III-NL), and a neuropsychological assessment with the Nepsy. Performances were compared to a matched healthy control group. Parents completed the Child Behaviour Checklist and were interviewed to rate the child's cognitive and emotional functioning. Children older than eight years filled out a self-perception questionnaire. Analyses revealed significant differences between the study groups on several cognitive and behavioural domains. Estimated intelligence scores were in the average range. Domains of attention and fine motor skills, and the subtest level of language abilities, elicited significant group differences, with less favourable outcomes for the patient group. Parents of patients reported more withdrawn behaviour, social difficulties, thought problems, attentional shortcomings and lower competence for activities. These parents also indicated poor problem solving skills in everyday activities. Surgical patients displayed subtle neuropsychological difficulties concerning language and fine motor skills. Behavioural difficulties were common. Future research should address risk factors for adverse neurobehavioural manifestations in this patient group.


Del Nido cardioplegia in adult cardiac surgery: analysis of myocardial protection and post-operative high-sensitivity Troponin T.
del Nido cardioplegia has been adopted for use in adult cardiac surgery, despite a lack of robust randomised evidence supporting equivalence or superiority to conventional hyperkalaemic blood cardioplegia. We investigated the clinical surrogates of myocardial protection, and performed an extensive analysis of post-operative high-sensitivity Troponin T (hs-TnT) values in a general adult cardiac surgery population receiving del Nido, in comparison to a historical hyperkalaemic blood cohort. 171 consecutive patients of a single surgeon from between November 2018 and June 2020 received del Nido, and were compared to a historical cohort of 326 patients between January 2016 and November 2018 who received hyperkalaemic blood cardioplegia. Clinical markers of myocardial protection were compared, as were hs-TnT values at 6, 12, 24, and 72-h post-operatively. Equivalence between groups was determined using the two one-sided tests procedure. There was no difference between the groups in the incidence of post-operative low cardiac output state, inotropic support, or myocardial infarction. Del Nido patients had less defibrillation requirement, and more spontaneous resumption of normal sinus rhythm. High-sensitivity Troponin T values were similar at all time-points including in a coronary artery bypass graft subgroup, and in those patients with elevated pre-operative hs-TnT. In a broad cohort of adult cardiac surgery patients, including those undergoing coronary artery bypass surgery and those with recent myocardial infarction, del Nido provides equivalent myocardial protection and clinical outcomes when compared to hyperkalemic blood cardioplegia. Post-operative high-sensitivity Troponin T values were also equivalent between the groups.


Synthesis and Preclinical Evaluation of a Novel Fluorine-18-Labeled Tracer for Positron Emission Tomography Imaging of Bruton's Tyrosine Kinase.
Bruton's tyrosine kinase (BTK) is a target for treating B-cell malignancies and autoimmune diseases. To aid in the discovery and development of BTK inhibitors and improve clinical diagnoses, we have developed a positron emission tomography (PET) radiotracer based on a selective BTK inhibitor, remibrutinib. [18F]PTBTK3 is an aromatic, 18F-labeled tracer that was synthesized in 3 steps with a 14.8 ± 2.4% decay-corrected radiochemical yield and ≥99% radiochemical purity. The cellular uptake of [18F]PTBTK3 was blocked up to 97% in JeKo-1 cells using remibrutinib or non-radioactive PTBTK3. [18F]PTBTK3 exhibited renal and hepatobiliary clearance in NOD SCID (non-obese diabetic/severe combined immunodeficiency) mice, and the tumor uptake of [18F]PTBTK3 in BTK-positive JeKo-1 xenografts (1.23 ± 0.30% ID/cc) was significantly greater at 60 min post injection compared to the tumor uptake in BTK-negative U87MG xenografts (0.41 ± 0.11% ID/cc). In the JeKo-1 xenografts, tumor uptake was blocked up to 62% by remibrutinib, indicating the BTK-dependent uptake of [18F]PTBTK3 in tumors.


Modulational instability in large-amplitude linear laser wakefields.
We investigate the growth of ion density perturbations in large-amplitude linear laser wakefields via two-dimensional particle-in-cell simulations. Growth rates and wave numbers are found to be consistent with a longitudinal strong-field modulational instability. We examine the transverse dependence of the instability for a Gaussian wakefield envelope and show that growth rates and wave numbers can be maximized off axis. On-axis growth rates are found to decrease with increasing ion mass or electron temperature. These results are in close agreement with the dispersion relation of a Langmuir wave with an energy density that is large compared to the plasma thermal energy density. The implications for wakefield accelerators, in particular multipulse schemes, are discussed.


Characterization of the porcine FABGL gene.
The porcine major histocompatibility complex, also called swine lymphocyte antigen (SLA) complex, is of particular interest not only because of its central role in the immune response, but also because of its influence on many traits such as reproduction, fatness and meat quality. The porcine FABGL (FabG (beta-ketoacyl-[acyl-carrierprotein] reductase, Escherichia coli) like) gene, coding for a 17beta-hydroxysteroid dehydrogenase (17beta-HSD), is a candidate gene for these traits. The complete gene was sequenced and compared with human and mouse FABGL sequences. The deduced amino acid sequence showed 85 and 83% sequence identity to human and mouse sequences, respectively. Polymorphicic BbvI and DdeI restriction sites were found in the porcine FABGL gene. The promoter was compared with the promoter regions of human and mouse FABGL sequence in order to identify putative regulatory elements. The transcription profile of the porcine gene was determined and showed a widespread tissue distribution.


Mediation effects of lean mass and fat mass on the relationship between body mass index and handgrip strength.
This study aimed to assess the mediation effects of lean mass and fat mass on the relationship between body mass index (BMI) and handgrip strength (HGS) in adolescents. The sample included 118 adolescents (60 girls) aged 10-14 years. Body composition, determined from lean mass (LM) and fat mass (FM), was measured by dual-energy x-ray absorptiometry. HGS was measured using a digital dynamometer. Moderate-to-vigorous physical activity and sexual maturation, treated as covariates, were evaluated by accelerometry and pubic hair development, respectively. Spearman correlation and simple mediation analysis were used for statistical analysis. A positive relationship was observed between BMI and HGS (rho = .364, p < .001), BMI and LM (rho = .466, p < .001), LM and HGS (rho = .784, p < .001), BMI and FM (rho = .907, p < .001), and FM and HGS (rho = .291, p = .001). LM was the only significant mediator of the relationship between BMI and HGS. Only LM mediated the association between BMI and HGS, almost entirely explaining the relationship. The findings reinforce the need to include LM measurements in routine strength testing. Furthermore, strategies focused on LM development may be promising in preventing low muscle strength in adolescents.


Mechanical properties and water vapour permeability of film from Haruan (Channa striatus) and fusidic acid spray for wound dressing and wound healing.
Aerosol is a new dosage form for wound dressing and wound healing. Concentrate of aerosols which were prepared for wound dressing and wound healing will produced films after sprayed onto the surface of wounds. The aim of this study is to evaluate the mechanical and water vapour permeability properties of the films from the aerosol concentrates. Film forming dispersions contained Haruan extract and Fusidic acid as the active ingredients, hydroxypropyl methylcellulose (HPMC) as polymer and polyethylene glycol (PEG) 400, glycerin and propylene glycol as plasticizers. Haruan extract is used to promote healing and Fusidic acid is added in formula as antibiotic to prevent the infections. The films were prepared by using casting technique. Based on the results, it is concluded that films produced from Formula E1, E2 and F4 possessed good elongation at break but low tensile strength. All Formula E, Formula F4 and F5 were permeable but Formula F5 was brittle and would peel off by themselves from the Petri dish.


Single-cycle rituximab-induced immunologic changes in children: Enhanced in neuroimmunologic disease?
To investigate the immunologic impact of a single cycle of rituximab (RTX) in children and adolescents with immune-mediated disorders, we evaluated B cells and immunoglobulin levels of 20 patients with neuroimmunologic, nephrologic, dermatologic, and rheumatologic disorders treated under recommended guidelines. Retrospective study of immunologic changes in children (aged ≤18 years) diagnosed with immune-mediated disorders in which RTX was prescribed between June 2014 and February 2019. Patients were excluded if they had prior diagnosis of malignant disease or primary immunodeficiency. Patients were clinically and immunologically followed up every 3 months. Only patients having received a single cycle of RTX and with a follow-up greater than 12 months were included in the analysis of persistent dysgammaglobulinemia. Twenty children were included. Median age at RTX treatment was 12.8 years (interquartile range [IQR] 6.6-15.5 years). Median follow-up was 12.6 months (IQR 10.2-24 months). Of the 14 patients eligible for persistent dysgammaglobulinemia analysis (3 had received RTX retreatment, 2 had <12 months post-RTX follow-up, and in 1 data for this time point was missing), 2/14 (14%) remained with complete B-cell depletion, and 5/14 (36%) had dysgammaglobulinemia. Patients with dysgammaglobulinemia were younger (7.8 vs 15.6 years, p = 0.072), had more underlying neuroimmunologic diseases (5/5 vs 0/9, p < 0.001), and had received more frequently concentrated doses of RTX (3/5 vs 1/9, p = 0.05) than patients without dysgammaglobulinemia. Kinetics of immunoglobulins in the 20 patients revealed a decrease as early as 3 months after RTX in patients with neuroimmunologic disorders. In our cohort, single-cycle RTX-induced dysgammaglobulinemia was enhanced in patients with neuroimmunologic diseases. Further studies are needed to confirm this observation.


Fluorescence, polarized fluorescence, and Brewster angle microscopy of palmitic acid and lung surfactant protein B monolayers.
Fluorescence, polarized fluorescence, and Brewster angle microscopy reveal that human lung surfactant protein SP-B and its amino terminus (SP-B[1-25]) alter the phase behavior of palmitic acid monolayers by inhibiting the formation of condensed phases and creating a new fluid protein-rich phase. This fluid phase forms a network that separates condensed phase domains at coexistence and persists to high surface pressures. The network changes the monolayer collapse mechanism from heterogeneous nucleation/growth and fracturing processes to a more homogeneous process through isolating individual condensed phase domains. This results in higher surface pressures at collapse, and monolayers easier to respread on expansion, factors essential to the in vivo function of lung surfactant. The network is stabilized by a low-line tension between the coexisting phases, as confirmed by the observation of extended linear domains, or "stripe" phases, and a Gouy-Chapman analysis of protein-containing monolayers. Comparison of isotherm data and observed morphologies of monolayers containing SP-B(1-25) with those containing the full SP-B sequence show that the shortened peptide retains most of the native activity of the full-length protein, which may lead to cheaper and more effective synthetic replacement formulations.


Deletions fusing the hisG and hisD genes in Salmonella typhimurium.
Frameshift mutation hisD497 occurs in the operator-proximal portion of the Salmonella typhimurium gene coding for the dimeric protein, L-histidinol dehydrogenase (HDH). Rare revertants of hisD497 are deletions fusing the hisD gene to the adjacent preceding structural gene, hisG (adenosine 5'-triphosphate-PR transferase). HDH purified from one revertant, hisGD4908, contains subunits of approximately normal molecular weight but with no clearly demonstrable unique amino-terminal sequence. We propose that a combined inactive G-D polypeptide is synthesized and then cleaved at a number of closely juxtaposed sites by endoproteolytic activity. At least some of the resulting fragments then participate in formation of active HDH dimers.


CD4 T Cell-Dependent and -Independent Roles for IFN-γ in Blood-Stage Malaria.
Production of IFN-γ by CD4 T cells is widely theorized to control Plasmodium parasite burden during blood-stage malaria. Surprisingly, the specific and crucial mechanisms through which this highly pleiotropic cytokine acts to confer protection against malarial disease remain largely untested in vivo. Here we used a CD4 T cell-restricted Cre-Lox IFN-γ excision mouse model to test whether and how CD4 T cell-derived IFN-γ controls blood-stage malaria. Although complete absence of IFN-γ compromised control of the acute and the chronic, recrudescent blood-stage infections with P. c. chabaudi, we identified a specific, albeit modest, role for CD4 T cell-derived IFN-γ in limiting parasite burden only during the chronic stages of P. c. chabaudi malaria. CD4 T cell IFN-γ promoted IgG Ab class switching to the IgG2c isotype during P. c. chabaudi malaria in C57BL/6 mice. Unexpectedly, our data do not support gross defects in phagocytic activity in IFN-γ-deficient hosts infected with blood-stage malaria. Together, our data confirm CD4 T cell-dependent roles for IFN-γ but suggest CD4 T cell-independent roles for IFN-γ in immune responses to blood-stage malaria.


Ethanol and diet interactions in male rhesus monkeys.
Development of alcohol-related liver and other diseases appears to be modified by host and environmental factors that include diet and nutritional status, exposure to other drugs and toxins, and infection. The relative importance of alcohol toxicity and malnutrition in the induction of fatty liver and cirrhosis, the subject of this report, has been debated. Male rhesus (M mulatta) monkeys were fed purified liquid diets, adequate or marginally deficient in lipotropes (choline, methionine, and folate), containing ethanol to supply 40-50% of calories for 1.5-4.5 years. Controls, fed the diets with sucrose and fat isocalorically substituted for ethanol, grew well and were clinically normal. Ethanol-fed monkeys in both diet groups failed to gain weight and were slightly anemic, with mild derangements of serum electrolytes and small amounts of fat in their livers. None had fibrosis or cirrhosis until the severity of the lipotrope-deficiency was increased; then two of four deficient animals developed cirrhosis and one developed fibrosis. (The severe deficiency induced weight loss and fatty liver, but not fibrosis, in one of two controls.) We conclude that alcohol does not induce hepatic fibrosis or cirrhosis in rhesus monkeys fed a nutritionally complete diet, a result supported by studies in rats and another monkey, M radiata. Alcohol does induce cirrhosis when fed in combination with a lipotrope-deficient diet that is not, by itself, cirrhogenic.


[Expression of FABP7 in mouse placenta tissue and human trophoblast HTR-8/Svneo cells].
To detect the expression of FABP7 in the placenta of pregnant mice and in HTR-8/Svneo cells. Real-time PCR and immunofluorescence were used to detect FABP7 mRNA and protein expressions in the uterine and placental tissue of pregnant mice at different days of gestation. FABP7 expression was also detected in cultured HTR-8/Svneo cells using immunofluorescence assay. The mice were treated with E2, P4 or their combination for 6 and 24 h and Fabp7 mRNA level in the uterus was detected with real-time PCR. At 7.5-10.5 days of gestation, the pregnant mice showed positive expressions of Fabp7 mRNA in the uterus and placenta, and FABP7 protein was detected in the decidualized cells and trophoblast giant cells. The expressions of FABP7 were detected at both the mRNA and protein levels in cultured HTR-8/Svneo cells. In mice treated with P4 alone or with E2+P4 for 6 and 24 h, the expression level of Fabp7 mRNA was upregulated in the uterus. Fabp7 upregulation was observed in mice at 24 h following E2 treatment but not at 6 h. FABP7 is expressed in trophoblast giant cells and decidual cells in the placental tissue of mice and in cultured HTR-8/Svneo cells, suggesting the involvement of FABP7 in placental development and in maintenance of pregnancy. E2 and P4 can regulate the expression of FABP7 in mouse uterus.


Primary thromboprophylaxis in the palliative care setting: a qualitative systematic review.
Symptomatic venous thromboembolism (VTE) occurs in 15% of patients with advanced malignancy. Primary thromboprophylaxis using low-molecular-weight heparin (LMWH) is supported by Level 1A evidence but is under-utilized in the palliative setting. A systematic search was performed of Medline, Cochrane Library, EMBASE, AMED, and Web of Science for papers published between 1960 and January 2010 using search terms: 'palliative', 'thromboprophylaxis', 'thromboembolism', 'heparin', and 'advanced cancer'. Forty-two citations were obtained, of which 34 were excluded as they dealt with treatment of VTE, novel anticoagulants, or LMWH as a cancer treatment. Eight original articles were reviewed independently by two authors. Data was extracted according to a predetermined questionnaire. Studies examined practice in specialist palliative care (SPC) units, and attitudes held by a total of 32 physicians and 198 patients. Patients find LMWH acceptable, particularly patients who experienced a sudden decline in performance status. Reluctance to prescribe LMWH is based on physicians' concerns regarding negative impact on quality of life, and lack of evidence specific to the palliative care setting. In conclusion, LMWH prophylaxis should be implemented in patients with a previously good performance status who have a transiently increased risk of VTE and no contraindications. Further research is required using outcome measures specific to palliative care.


CRMP4 CpG Hypermethylation Predicts Upgrading to Gleason Score ≥ 8 in Prostate Cancer.
This study determined the predictive value of CRMP4 promoter methylation in prostate tissues collected by core needle biopsies for a postoperative upgrade of Gleason Score (GS) to ≥8 in patients with low-risk PCa. A retrospective analysis of the clinical data was conducted from 631 patients diagnosed with low-risk PCa by core needle biopsy at multiple centers and then underwent Radical Prostatectomy (RP) from 2014-2019. Specimens were collected by core needle biopsy to detect CRMP4 promoter methylation. The pathologic factors correlated with the postoperative GS upgrade to ≥8 were analyzed by logistic regression. The cut-off value for CRMP4 promoter methylation in the prostate tissues collected by core needle biopsy was estimated from the ROC curve in patients with a postoperative GS upgrade to ≥8. Multivariate logistic regression showed that prostate volume, number of positive cores, and CRMP4 promoter methylation were predictive factors for a GS upgrade to ≥8 (OR: 0.94, 95% CI: 0.91-0.98, P=0.003; OR: 3.16, 95% CI: 1.81-5.53, P<0.001; and OR: 1.43, 95% CI: 1.32-1.55, P<0.001, respectively). The positive predictive rate was 85.2%, the negative predictive rate was 99.3%, and the overall predictive rate was 97.9%. When the CRMP4 promoter methylation rate was >18.00%, the low-risk PCa patients were more likely to escalate to high-risk patients. The predictive sensitivity and specificity were 86.9% and 98.8%, respectively. The area under the ROC curve (AUC) was 0.929 (95% CI: 0.883-0.976; P<0.001). The biochemical recurrence (BCR)-free survival, progression-free survival (PFS), and cancer-specific survival (CSS) were worse in patients with CRMP4 methylation >18.0% and postoperative GS upgrade to ≥8 than in patients without an upgrade (P ≤ 0.002). A CRMP4 promoter methylation rate >18.00% in prostate cancer tissues indicated that patients were more likely to escalate from low-to-high risk after undergoing an RP. We recommend determining CRMP4 promoter methylation before RP for low-risk PCa patients.


[Chronic pain in the elderly].
Chronic pain is a common problem for the aged. Aim of the study was to evaluate prevalence, characteristics and influence on functional parameters of chronic pain in the elderly. Our study included 105 patients (mean age 82.2 +/- 9 yr). Chronic pain, tested by using the McGill Pain Questionnaire, was present in 87 patients (82.9%); it lasted more than 2 years and it was continuous in half of them (49.4%). Our study shows that chronic pain in the elderly has a strong affective component. Its intensity, evaluated by specific tests such as analogical visual and verbal scales, influences old patient's quality of life.


Scalable Screening of Soft Matter: A Case Study of Mixtures of Ionic Liquids and Organic Solvents.
Room-temperature ionic liquids (RTILs) are a class of organic salts that are liquid at room temperature. Their physiochemical properties, including low vapor pressure and wide electrochemical stability window, have driven their use as electrolytes in many electrochemical applications; however, the slow transport properties of many RTILs have limited their utility in some applications. This issue is often mitigated by solvating ionic liquids in neutral organic solvents. To date, however, solvent interactions have only been explored for a small number of solvents, particularly acetonitrile and propylene carbonate, at only a few compositions. In this work, we use molecular dynamics simulations in the context of a computational screening approach to study mixtures of ionic liquids in many different solvents at a range of concentrations. Building on prior work, we again find that ionic liquid diffusivity increases monotonically with greater solvent concentration. In contrast to prior work, we find that pure solvent diffusivity, not polarity, is the most influential solvent property on mixture behavior. We also explore the concentration dependence of ionic conductivity and find maxima at intermediate concentrations. Experimental conductivity measurements, inspired by the computational screening study, support this observation with qualitatively consistent results. These results can further guide the selection of solvents for electrochemical applications of RTILs.


Posttraumatic stress disorder with secondary psychotic features (PTSD-SP): Diagnostic and treatment challenges.
Trauma exposure leads to various psychiatric disorders including depression, anxiety, bipolar disorders, personality disorders, psychotic disorders, and trauma related disorders, especially posttraumatic stress disorder (PTSD). There are some overlapping symptoms of both PTSD and psychosis that make diagnosis challenging. Despite this overlap, the evidence of PTSD with comorbid psychosis as a distinct entity lies in the research showing biologic, genetic and treatment management differences between psychotic PTSD, non-psychotic PTSD, psychotic disorders and healthy controls. There is emerging evidence that PTSD with secondary psychotic features (PTSD-SP) might be a discrete entity of PTSD with known risk factors that increase its prevalence. This review has presented evidence for individuals with PTSD-SP being distinct in genetics and neurobiological factors. Individuals with PTSD and comorbid psychosis can benefit from evidence based psychotherapy (EBT). There is not enough evidence to recommend second generation antipsychotics (SGA) for PTSD-SP given that risperidone and quetiapine are the only SGAs studied in randomized controlled trials. Hence, developing an operational diagnostic criteria and treatment framework for clinical and research use is critical.


Hematopoiesis and Mast Cell Development.
Hematopoietic stem cells (HSCs) are defined based on their capacity to replenish themselves (self-renewal) and give rise to all mature hematopoietic cell types (multi-lineage differentiation) over their lifetime. HSCs are mainly distributed in the bone marrow during adult life, harboring HSC populations and a hierarchy of different kinds of cells contributing to the "niche" that supports HSC regulation, myelopoiesis, and lymphopoiesis. In addition, HSC-like progenitors, innate immune cell precursors such as macrophages, mast cells, natural killer cells, innate lymphoid cells, and megakaryocytes and erythrocyte progenitor cells are connected by a series of complex ontogenic relationships. The first source of mast cells is the extraembryonic yolk sac, on embryonic day 7. Mast cell progenitors circulate and enter peripheral tissues where they complete their differentiation. Embryonic mast cell populations are gradually replaced by definitive stem cell-derived progenitor cells. Thereafter, mast cells originate from the bone marrow, developing from the hematopoietic stem cells via multipotent progenitors, common myeloid progenitors, and granulocyte/monocyte progenitors. In this review article, we summarize the knowledge on mast cell sources, particularly focusing on the complex and multifaceted mechanisms intervening between the hematopoietic process and the development of mast cells.


Childhood sexual abuse, teenage pregnancy, and partnering with adult men: exploring the relationship.
Although the mechanism by which early victimization, specifically sexual abuse, increases the risk of adolescent pregnancy is unclear, a relationship between previous victimization and adolescent pregnancy has been demonstrated. While partnering with an older man may initially offer the means necessary to escape a neglectful or violent family of origin, this protection be accompanied by an imbalance of power and control. Both adolescent mothers partnered with adult men and adolescent mothers partnered with male peers reported sexual abuse perpetrated by family members, family friends, strangers, and peers. Policies developed to protect young people from victimization, including mandatory reporting and statutory rape laws, should be evaluated for their consistent application to all children, regardless of age, race, gender, or pregnancy status.


In Situ Generation of Azonia-Containing Polyelectrolytes for Luminescent Photopatterning and Superbug Killing.
Polyelectrolytes play an important role in both natural biological systems and human society, and their synthesis, functional exploration, and profound application are thus essential for biomimicry and creating new materials. In this study, we developed an efficient synthetic methodology for in situ generation of azonia-containing polyelectrolytes in a one-pot manner by using readily accessible nonionic reactant in the presence of commercially available cheap ionic species. The resulting polyelectrolytes are emissive in the solid state and can readily form luminescent photopatterns with different colors. The azonia-containing polyelectrolytes possess extraordinary potency of reactive oxygen species (ROS) generation, enabling them to impressively kill methicillin-resistant Staphylococcus aureus (MRSA), a drug resistant superbug, both in vitro and in vivo.


Short Communication: HIV-1 Transmission Networks Across South Korea.
Molecular epidemiology can help clarify the properties and dynamics of HIV-1 transmission networks in both global and regional scales. We studied 143 HIV-1-infected individuals recruited from four medical centers of three cities in South Korea between April 2013 and May 2014. HIV-1 env V3 sequence data were generated (337-793 bp) and analyzed using a pairwise distance-based clustering approach to infer putative transmission networks. Participants whose viruses were ≤2.0% divergent according to Tamura-Nei 93 genetic distance were defined as clustering. We collected demographic, risk, and clinical data and analyzed these data in relation to clustering. Among 143 participants, we identified nine putative transmission clusters of different sizes (range 2-4 participants). The reported risk factor of participants were concordant in only one network involving two participants, that is, both individuals reported homosexual sex as their risk factor. The participants in the other eight networks did not report concordant risk factors, although they were phylogenetically linked. About half of the participants refused to report their risk factor. Overall, molecular epidemiology provides more information to understand local transmission networks and the risks associated with these networks.


Consequences of Weight Cycling: An Increase in Disease Risk?
Research indicates that weight cycling, or "yo-yo dieting" is a common occurrence in overweight and obese populations. The long term negative health consequences of weight cycling are debated and it is unclear whether or not this weight change pattern poses a greater disease risk compared to obesity maintenance. This review discusses the prevalence of weight cycling and physiological alterations occurring during weight loss that promotes weight regain. We also discuss the effect weight regain has upon adipose tissue in terms of rate and type of accumulation. Also within this review are discussions surrounding the previously published literature based upon human and rodent research. We focus on previous limitations and difference in experimental design that have perhaps resulted in mixed findings concerning independent effects of weight cycling on health parameters. The final purpose of this review is to discuss future directions in evaluating the pro-inflammatory response to weight cycling in order to compare the disease risk compared to obesity maintenance.


The efficacy and safety of two different doses of caffeine in respiratory function of preterm infants.
Caffeine is widely used for prevention of apnea and helps successful extubation from mechanical ventilation. It facilitates the transition from invasive to noninvasive support and reduces duration of continuous positive airway pressure (CPAP) in preterm infants. The optimum caffeine dose in preterm infants has not been well-studied in terms of benefits and risks. We compared efficacy and safety of once versus twice-daily caffeine dose in premature infants. This study was a randomized clinical trial conducted in Bu-Ali Sina Teaching Hospital, Sari. Patients with gestational age of <37 weeks were included. Both groups received 20 mg/kg loading dose of caffeine intravenously followed by maintenance dose of 5 mg/kg/day in group 1 or 2.5 mg/kg every 12 hours in group 2. Extubation failure, CPAP failure and possibly adverse reactions were evaluated. The mean of gestational age and birth weight were 32.27±3.23 (weeks) and 1824.5±702.54 (gr), respectively. The rate of extubation and CPAP failure and length of NICU stay were lower in twice-daily-group with no statistically significant difference. The means of O2 saturations on the first three days of caffeine therapy were higher in twice-daily-group. Caffeine was generally safe and well tolerated. This study, which assayed short-term effects of caffeine, showed that twice daily caffeine maintenance dose was related to more benefits in facilitating extubation or prevention of CPAP failure in preterm infants. However, there was not statistically significant difference between two groups.


A case of CD3+, CD4-, CD8-, WT31- acute T-cell leukemia.
The article reports a case of acute T-cell leukemia (T-ALL) with the unusual CD3+, WT31 phenotype. On surface marker analysis, the blast cells were found to be CD7+, CD2-, CD5-, CD1-, CD4-, CD8-, CD3+ and negative for B-lymphoid and myeloid lineage. The cells had both TCR beta and TCR gamma gene rearrangement but had negative results with the monoclonal antibody WT31, which reacts with a framework epitope on the T alpha/beta heterodimer (Ti) of the conventional T-cell receptor (TCR). This suggests an association of the CD3 molecular complex with a different polypeptide (the alternate TCR gamma). In two similar reported cases of T-ALL (WT31-, CD3+, CD4-, CD8-), the CD3 molecular complex was found to be associated with a product of the T gamma gene.


DAF-16/FOXO and EGL-27/GATA promote developmental growth in response to persistent somatic DNA damage.
Genome maintenance defects cause complex disease phenotypes characterized by developmental failure, cancer susceptibility and premature ageing. It remains poorly understood how DNA damage responses function during organismal development and maintain tissue functionality when DNA damage accumulates with ageing. Here we show that the FOXO transcription factor DAF-16 is activated in response to DNA damage during development, whereas the DNA damage responsiveness of DAF-16 declines with ageing. We find that in contrast to its established role in mediating starvation arrest, DAF-16 alleviates DNA-damage-induced developmental arrest and even in the absence of DNA repair promotes developmental growth and enhances somatic tissue functionality. We demonstrate that the GATA transcription factor EGL-27 co-regulates DAF-16 target genes in response to DNA damage and together with DAF-16 promotes developmental growth. We propose that EGL-27/GATA activity specifies DAF-16-mediated DNA damage responses to enable developmental progression and to prolong tissue functioning when DNA damage persists.


[Psychiatric comorbidity in medical inpatients - prevalence and effect on the length of stay].
In the course of a year the prevalence of psychiatric comorbidity as well as the effect of psychiatric comorbidity on the length of stay on two internal medical wards we investigated. When examined by separate methods, the prevalence of psychiatric comorbidity reached 36 % (ICD-10 diagnosis) in a sample of 511 medical inpatients of a university hospital. The study shows that patients with psychiatric comorbidity have a significantly longer length of stay - up to 8.2 days compared with inpatients with mere internal diagnosis. This association was not influenced by the length and the severity of the illness. The findings lead to the conclusion that psychiatric comorbidity is a central contributor to one of the most important factors of medical costs - the length of stay.


Esophageal contractions, bolus transit and perception of transit after swallows of liquid and solid boluses in normal subjects.
Esophageal dysphagia is the sensation that the ingested material has a slow transit or blockage in its normal passage to the stomach. It is not always associated with motility or transit alterations. To evaluate in normal volunteers the possibility of perception of bolus transit through the esophagus after swallows of liquid and solid boluses, the differences in esophageal contraction and transit with these boluses, and the association of transit perception with alteration of esophageal contraction and/or transit. The investigation included 11 asymptomatic volunteers, 4 men and 7 women aged 19-58 years. The subjects were evaluated in the sitting position. They performed swallows of the same volume of liquid (isotonic drink) and solid (macaroni) boluses in a random order and in duplicate. After each swallow they were asked about the sensation of bolus passage through the esophagus. Contractions and transit were evaluated simultaneously by solid state manometry and impedance. Perception of bolus transit occurred only with the solid bolus. The amplitude and area under the curve of contractions were higher with swallows of the solid bolus than with swallows of the liquid bolus. The difference was more evident in swallows with no perception of transit (n = 12) than in swallows with perception (n = 10). The total bolus transit time was longer for the solid bolus than for the liquid bolus only with swallows followed by no perception of transit. The results suggest that the perception of esophageal transit may be the consequence of inadequate adaptation of esophageal transit and contraction to the characteristics of the swallowed bolus.


Embryonic mortality and intrauterine growth retardation (IUGR) associated with placental alterations in pregnant rats treated with methyl methanesulfonate (MMS) at the peri-implantation stage.
Embryonic mortality and intrauterine growth retardation (IUGR) are induced by exposure of rodents to xenobiotic agents during the pregastrulation period of development. We examined the time course of the effects of methyl methanesulfonate (MMS), an alkylating agent, on conceptus development in order to clarify the relative roles of the embryo and the placenta in their induction. Pregnant rats were treated orally with a single dose of MMS (200 mg/kg) in the morning of gestation day (GD) 6 (peri-implantation stage). Embryonic mortality was increased on GD12 and thereafter by MMS treatment, with newly dead embryos showing placental hypoplasia at GD12. Embryo or fetal weight was also smaller for MMS-treated dams than for control dams from GD14 to GD20. The labyrinth zone and junctional zone (JZ) of the placenta were thinner in MMS-treated rats from GD12 to GD17 and from GD12 to GD20 (except for GD17), respectively. Furthermore, MMS-treated dams showed a smaller number of glycogen cells in the JZ on GD14. In contrast, the placental glycogen concentration was higher and the expression of glucose transporter 1 in the JZ remained at GD20. These results indicate that exposure of pregnant rats to MMS at the peri-implantation stage of embryogenesis affects placental development and growth. The placental impairment induced by MMS was likely responsible for the embryonic death observed 6 days after exposure of dams to this agent as well as for the IUGR of surviving embryos or fetuses throughout the gestation period.


A novel model for biofilm initiation in porous media flow.
Bacteria often form biofilms in porous environments where an external flow is present, such as soil or filtration systems. To understand the initial stages of biofilm formation, one needs to study the interactions between cells, the fluid and the confining geometries. Here, we present an agent based numerical model for bacteria that takes into account the planktonic stage of motile cells as well as surface attachment and biofilm growth in a lattice Boltzmann fluid. In the planktonic stage we show the importance of the interplay between complex flow and cell motility when determining positions of surface attachment. In the growth stage we show the applicability of our model by investigating how external flow and biofilm stiffness determine qualitative colony morphologies as well as quantitative measurements of, e.g., permeability.


Mechanistic Insights Into Trehalose-Mediated Cold Stress Tolerance in Rapeseed (Brassica napus L.) Seedlings.
Cold stress (CS) severely affects several physiological, biochemical, and molecular mechanisms and limits the growth and production of rapeseed (Brassica napus L.). Trehalose (Tre) acts as a growth modulator, which is extensively used to improve the tolerance to multiple plant stresses. Further, Tre also serves as an external force in inducing plant signaling molecules, regulating the expression of stress-responsive genes, and enhancing the CS tolerance in plants. Nevertheless, the importance of exogenous Tre in improving the CS tolerance in rapeseed is still unclear. Therefore, the current study was designed to get mechanistic insights into Tre-mediated CS tolerance in rapeseed seedlings. To explore the Tre role, we designed four treatments [control (CK), CK + 20 mM L-1 Tre, Cold, and Cold + 20 mM L-1 Tre] and three CS conditions (4, 0, and -4°C). The results showed that Tre treatments significantly mitigated the adverse effects of CS on the seedlings and increased the survival rate of Tre-treated seedlings under CS conditions. The exogenous Tre dramatically increased the contents of osmoprotectants, including the soluble sugar (SS), soluble protein (SP), and proline (Pro), and the activities of antioxidant enzymes, such as catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), and ascorbate peroxidase (APX) were also increased under CS conditions. Additionally, Tre decreased the malondialdehyde (MDA) contents to protect the rapeseed seedlings. Moreover, Tre also remarkably augmented the expression levels of antioxidant genes (CAT12, POD34, and FSD7), CS-responsive marker genes (CBF1, CBF2, CBF4, COR6.6, COR15, COR25, COL1, and KIN1), and Tre-biosynthesis genes (TPS4, TPS8, and TPS9). Briefly, exogenous Tre not only regulates the antioxidant and osmotic balance, but it also significantly participates in Tre metabolism and signaling network to improve the CS tolerance in rapeseed. Thus, Tre-induced supervisory connections between physiological or/and biochemical attributes provide information to dissect the mechanisms of Tre-mediated CS tolerance.


Ankylosing spondylitis combined with angioimmunoblastic T cell lymphoma.
The authors present the report of an ankylosing spondylitis combined with angioimmunoblastic T cell lymphoma after the anti-tumour necrosis factor treatment.


Impact of stepwise sodium and ultra filtration profiles and dialysis solution flow rate profile on dialysis adequacy.
Inadequate dialysis is one of the main causes of mortality of the patients undergoing hemodialysis. The methods that lead to improvement of dialysis adequacy in these patients are of great importance due to them causing an improvement of quality of life. As numerous factors can play a role in improvement of dialysis adequacy, the present study aimed to investigate the level of impact of stepwise sodium and ultra filtration profiles and dialysis solution flow rate profile on dialysis adequacy. This is a cross-over clinical trial conducted on 32 patients selected from two hemodialysis centers in Isfahan in 2013. The patients were assigned to two identical groups through random allocation, and each patient in group 1 underwent hemodialysis for four routine dialysis sessions, four stepwise sodium and ultra filtration profile sessions, and four sessions by stepwise dialysis solution flow rate profile. The patients in group 2 underwent hemodialysis for four sessions of stepwise dialysate flow rate profile, four sessions of stepwise sodium and ultra filtration profiles, and four sessions of routine dialysis method. Dialysis adequacy was on line calculated by Kt/V ratio in each session, and was analyzed by repeated measure analysis of variance (ANOVA), least significant difference (LSD) post-hoc test, and independent t-test. Means of dialysis adequacies were 1.239 (0.25) in the routine method, 1.407 (0.26) in stepwise sodium and ultra filtration profiles, and 1.414 (0.26) in dialysis solution flow rate profile. There was a significant difference between the routine method and the other two profiles (P < 0.05), but the difference in dialysis adequacy means in the two profile methods was not significant (P > 0.05). Mean scores of dialysis adequacy in the three treatment methods in the two groups showed that the sequence of methods had no effect on treatment outcome (P > 0.05). Stepwise sodium and ultra filtration profiles and stepwise dialysis solution flow rate profile are suggested as they can increase dialysis adequacy compared to the routine method.


Allogenic Blood Transfusion Is an Independent Predictor of Poorer Peri-operative Outcomes and Reduced Long-Term Survival after Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: a Review of 936 Cases.
There is a paucity of data on the impact of allogenic blood transfusion (ABT) on morbidity and survival outcomes after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC). Nine hundred and thirty-five consecutive CRS/HIPEC procedures were performed between 1996 and 2016 at a high-volume institution in Sydney, Australia. Of these, 337(36%) patients required massive ABT (MABT) (≥5 units). Peri-operative complications were graded according to the Clavien-Dindo classification. The association of concomitant MABT with 21 peri-operative outcomes and overall survival (OS) was assessed using univariate and multivariate analyses. In-hospital mortality was 1.8%. Patients requiring MABT had more extensive disease as reflected by a higher peritoneal cancer index (≥17) (70 vs. 29%, p < 0.001) and longer operative times (≥9 h) (82 vs. 35%, p < 0.001). After accounting for confounding factors, MABT was associated with in-hospital mortality (relative risk (RR), 7.72; 95% confidence interval (CI), 1.35-10.11; p = 0.021) and grade III/IV morbidity (RR, 2.05; 95% CI, 1.42-2.95; p < 0.001). MABT was associated with an increased incidence of prolonged hospital stay (≥28 days) (RR, 1.86; 95% CI, 1.26-2.74; p = 0.002) and intensive care unit stay (≥4 days) (RR, 1.83; 95% CI, 1.24-2.70, p = 0.002). It was also associated with a significant OS in patients with colorectal cancer peritoneal carcinomatosis (RR 4.49; p < 0.001) and pseudomyxoma peritonei (RR, 4.37; p = 0.026), but not appendiceal cancer (p = 0.160). MABT is an independent predictor for poorer peri-operative outcomes including in-hospital mortality and grade III/IV morbidity. It may also compromise long-term survival, particularly in patients with colorectal cancer peritoneal carcinomatosis.


[Analysis of volatile components from the flowers of Chrysanthemum morifolium by GC-MS with solid-phase microextraction].
To study a method for extraction and analysis of volatile components from Chrysanthemum morifolium 'gonghuangjv' cv. nov (CM GHJ) and C. morifolium 'gongbaijv' cv. nov (CM GBJ) by solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS). The volatile components were extracted in different temperature, different balance period and different extraction fiber using head space solid-phase microextraction (HS-SPME), and were identified by CGC-MS. The variety in integral area of each component was observed in different conditions and its relative content was determined by normalization of area. The better condition of SPME for C. morifolium was that the sample was extracted using 100 microm polydimethylsiloxane (PDMS) extraction fiber after it had been balanced for 6 hours at 75 degrees C. 53 components from CM GHJ and CM GBJ were identified, and there were 35 same components in CM GHJ and CM GBJ. HS-SPME-GC-MS is convenient, rapid and reliable for analysis of volatile components in C. morifolium.


Screening and identification of yeast sequences that cause growth inhibition when overexpressed.
To isolate genes that negatively regulate cell growth, we constructed a galactose-inducible expression library with partially digested Saccharomyces cerevisiae genomic DNA fragments inserted downstream of the GAL10 promoter. In all, 240,000 yeast transformants were screened for lethality on galactose medium. From 17 such transformants identified, 16 nonoverlapping DNA sequences were obtained. Restriction mapping and determination of DNA sequences adjacent to the GAL10 promoter indicated that the inserts encoded part or all of the URA2, RBP1, TPK3, SAC7, BOI1, and BNI1 genes, and also open reading frames (ORFs) from chromosomes IV, V, IX, XI, and XIII. Some of the identified sequences lacked the amino-terminal sequences of the ORFs, suggesting that truncated forms of the proteins might be necessary for growth inhibition. The sequence of the pGA108 insert was highly homologous to the telomeric X-element and contained an ARS consensus sequence, suggesting a possible growth inhibitory effect of an RNA molecule. Overexpression of the BNI1 deltaN and BOI1 deltaN genes, which lacked amino-terminal sequences, was associated with phenotypes similar to those of mutants defective in bud formation. Overexpression of the GIN4 and GIN12 sequences induced elongated buds and a G2/M arrest-like phenotype, respectively. The phenotypes induced by the overexpression of our cloned sequences could result from either a dominant-positive or a dominant-negative effect and, unexpectedly, in one case from an effect of an RNA.


Frequency of Toxocariasis among Patients Clinically Suspected to Have Visceral Toxocariasis: A Retrospective Descriptive Study in Sri Lanka.
Human toxocariasis is caused by several species of the nematode Toxocara. Two common clinical syndromes are ocular and visceral larva migrans. To determine the Toxocara antibody positivity in clinically suspected VLM patients and to describe demographic factors and clinical manifestations of seropositive patients. 522 clinically suspected patients were studied between 1993 and 2014. Relevant data was gathered from referral letters. Serum samples were subjected to Toxocara antigen ELISA. Overall, seropositivity was 50.2% (262), of which 109 (40.8%) were positive at high level of Toxocara antibody carriage and 153 (58.4%) were positive at low levels. The seropositives ranged from 3 months to 70 years (mean = 7.8). Younger age group had higher levels of seropositivity and it was statistically significant. Majority of children under 5 years were seropositive (47.7%, n = 125). Seropositivity was common in males (55.3%, n = 145). Clinical manifestations of seropositives include lymphadenopathy (24.1%) skin rash (22.5%), dyspnoea (21.7%), fever (21%), hepatosplenomegaly (9.2%), and abdominal pain (3.8%). 197 (75.2%) seropositive cases had eosinophilia. These symptoms were not statistically significant. This study confirms toxocariasis as an important cause of childhood ill health identifying common clinical symptoms recommending preventive measures to limit transmission.


Sex difference in normal thymic appearance in adults 20-30 years of age.
To determine whether there is a sex difference in the appearance of the normal thymus in 20-30-year-old men and women. This retrospective study was approved by the institutional review board and was compliant with HIPAA. The requirement for informed consent was waived. Images and medical records of 238 consecutive subjects without known thymic disease (175 men, 63 women) who underwent chest computed tomography with intravenous contrast material in 2008 were reviewed. Average thymic region of interest (ROI), subjective assessment of thymic attenuation by using a scale of grades 0-3, thymic anteroposterior measurement, and mean maximal thymic lobe thickness were recorded by two independent thoracic radiologists, blinded to subject age and sex. Thymic morphologic characteristics were assessed in consensus. The two-sided Wilcoxon rank-sum test, Student t test, test for linear regression, analysis of covariance, two-way factorial analysis of variance, and continuity-adjusted χ(2) test were used for statistical analysis. There was a significant sex difference in thymic attenuation as measured objectively by using mean thymic ROI measurement (P < .0001) and subjectively by using a scale of grades 0-3 (P < .0001), which held true when corrected for age (P < .0001). A sex difference was also found in regard to the rate of decrease in mean thymic attenuation with age, with men's thymuses exhibiting a significant decrease in attenuation during the decade, unlike women (P = .0479). There was no significant sex difference in mean maximal thymic lobe thickness (P = .8697). A quadrilateral, as opposed to triangular, configuration of the thymus was more common in women than men (P = .0034). There is a significant sex difference in normal thymic appearance in 20-30-year-old men and women. The thymus of 20-30-year-old women typically exhibits higher attenuation and more commonly exhibits a quadrilateral configuration.


Development of the Brussels Infant and Toddler Stool Scale ('BITSS'): protocol of the study.
The Bristol Stool Form Scale (BSS) which consists of 7 photographs of different stool forms allows assessment of stool consistency (scale 1 for hard lumps to scale 7 for watery stools), in an objective manner in adults. The BSS is also sometimes used to characterise the stools of infants and young children. Despite its use, there is general agreement among paediatric gastroenterologists that the BSS is not adequate to be used in infants and young children who wear diapers; thus, a new scale specifically designed for this population is needed. Our aim is to develop a paediatric stool scale, the Brussels Infant and Toddler Stool Scale ('BITSS'), and to evaluate the interobserver agreement of stool assessment with the BITSS between the patient's parent and healthcare providers (physicians and nurses). This study has two phases. In the first phase, 11 key-opinion leaders in the field of paediatric gastroenterology representing different areas of the world selected seven coloured photographs of infants and/or young children wearing diapers to match the original descriptors of the BSS. The selected photographs were used to create a new scale in which the drawings of stools of the BSS were replaced by infant/toddlers stool photographs. In phase II, we aim at demonstrating that parents, nurses and primary healthcare physicians interpret the stool-pictures of the BITSS with a high degree of consensus and that the agreement is independent of whether it is a parent or a healthcare provider. Interobserver variability of stool assessment with the BITSS between the patient's parent and healthcare providers will be assessed. The study will be approved by the Ethics Committee of the participating centres. The findings of this study will be submitted to a peer-reviewed journal. Abstracts will be submitted to national and international conferences. NCT02913950.


[Parenting skills situation and need assessment among parents of primary school pupils].
To investigate parenting skills and need among parents of primary school pupils and to explore influencing factors. A total of 1 394 parents of rural and urban primary school pupils were recruited by multistage stratified random clustered sampling method. They were asked to complete a self-report questionnaire regarding demographic and socioeconomic backgrounds, parenting scale, parenting need assessment, parent-to-child interaction attitudes, social support, physical/mental maltreatment experiences in childhood and so forth. Apart from TV/film/broadcasting, rural parents' utilization of other parenting deliveries was less than that of urban parents. Urban and rural parents both had high needs for parenting skills. Parents' physical/mental maltreatment experiences in childhood were risk factors for dysfunctional parenting. Positive parent-to-child interaction attitudes and high social support were protective factors against dysfunctional parenting. Mothers, parents of boys, middle/low family incomes, and parents with positive parent-to-child interaction attitudes had higher demands for parenting skills. We should make full use of mass media, interpersonal communication to meet the needs of parenting for parents, especially rural parents. More attention should be paid to parents with childhood maltreatment experiences, low social support and less positive parent-to-child interaction attitudes.


Vasoactive intestinal polypeptide induces tyrosine hydroxylase in PC12 cells.
Physiological stress induces tyrosine hydroxylase, the rate-limiting enzyme for catecholamine biosynthesis, via trans-synaptic mechanisms within the adrenal medulla. Previous studies have implicated cAMP as a second messenger capable of inducing tyrosine hydroxylase; however, it is unclear whether any receptor coupled to adenylate cyclase mediates tyrosine hydroxylase induction. Recently, vasoactive intestinal polypeptide, whose receptor is coupled to adenylate cyclase in many tissues, has been shown to meet many of the criteria for a neuromodulator within the adrenal medulla. We therefore undertook a series of studies to determine whether vasoactive intestinal polypeptide may induce tyrosine hydroxylase in PC12 cells, a cell line derived from rat adrenal medulla. Here we report that vasoactive intestinal polypeptide produces a transient, time- and concentration-dependent increase in tyrosine hydroxylase mRNA levels which is followed by a stable increase in tyrosine hydroxylase protein. The increase in tyrosine hydroxylase mRNA does not occur in a mutant PC12 cell line deficient in cAMP-dependent protein kinase activity, indicating that the effect of vasoactive intestinal polypeptide is mediated through the cAMP second messenger pathway. This is the first report demonstrating that a neuromodulator which acts on an adenylate cyclase-coupled receptor can induce tyrosine hydroxylase.


The long-term stability of metallic materials for use in joint endoprostheses.
In orthopedic implants, metals are permanently incorporated into bones and tissue. Usually the metals are not in the electrochemical equilibrium state immediately after implantation. The metal oxide forms itself only after hours up to weeks. In the meantime the metal releases ions into the tissue, much more than in the equilibrium state. On the other hand a passive layer can interchange mechanically with bones and implanted components. The resulting destruction of the surface leads equally to an increasing release of ions. As a consequence of these facts, perfect metals for application in implants must have a short repassivation period and mechanically indestructible surface oxides. To what extent the applied metals perform these conditions is tested for the stainless steel type 316 L, the multiphase alloy MP-35 N and TiAIV. A comparison of the rates of corrosion resulting from damage to, or destruction of, the passivating oxide layers, with the rates that can occur in connection with local forms of corrosion, shows that in joint implants, it is merely the repassivation properties of the metals employed that determine the concentration of ions in the tissue.


Rheumatoid arthritis activity scores in patients with and without fibromyalgia syndrome.
Fibromyalgia syndrome (FM) is a systemic disease of unknown etiology, which can cause widespread musculoskeletal pain. In patients with rheumatoid arthritis (RA), FM can cause an additional symptom burden, which can affect some variables on the RA disease activity score 28 (DAS28), a tool that evaluates 28 joints in RA patients. Compare the results of four different versions of the DAS28 and the parameters used to determine disease activity scores in RA patients with and without FM, and determine whether there are treatment differences between RA patients with and without FM. Retrospective, cross-sectional. Tertiary hospital. We identified patients diagnosed with RA between 1 September 2016 and 1 February 2020 and identified patients with and without FM. Differences between variables in the DAS28 calculations (tender joint count [TJC], patient global assessment [PGA], and others), between patients with and without FM, and differences between patients with and without FM who were using or not using biological agents. 381, including 322 females (84.5%). The frequency of FM in RA patients was 25.7% (89 females, 24.6%). In RA patients with FM, the TJC and PGA median values were significantly higher than in patients without FM (P<.05). The use of corticosteroids and biological therapy in patients with FM was more frequent than in patients without FM (P<.05). Compared to patients without FM, patients with FM switched treatment more often because of non-response to treatment (P=.01) Median values of the DAS28 scores (calculated by four different versions of the instrument) in RA patients with FM were higher than in patients without FM (P<.05). The presence of FM in RA patients may affect the subjective variables in different versions of DAS28 scores, causing the disease activity to score higher on the instrument, erroneously indicating worse disease than is actually present. A single center, retrospective study. None.


Normal modes and frequencies from covariances in molecular dynamics or Monte Carlo simulations.
We propose a simple method to obtain normal modes (NMs) and their characteristic frequencies from molecular dynamics or Monte Carlo simulations at any temperature. The resulting NM are consistent with the vibrational density of states (DOS) (every feature of the DOS can be attributed to one or few NMs). At low temperatures they coincide with the ones obtained from the Hessian matrix. We define the NMs (rho(i)) by imposing the condition that their velocities be uncorrelated to each other: rho(i)(t)rho(j)(t) proportional, variant delta(ij), where denotes time average and delta(ij) is Kronecker's delta. With this definition the modes are the eigenvectors of the matrix K(ij)(v)=1/2<square root of (m(i)m(j))v(i)v(j)> [i, j=1,...,3N (N being the number of atoms); m are masses and v atomic velocities]. The eigenvalues of K(ij)(v), lambda(i)(v), represent the kinetic energy in each NM. The ratio between the eigenvalues (lambda(i)(v)) and those obtained using positions (lambda(i)(r)), accelerations (lambda(i)(a)) in K(ij)(v) instead of velocities are a very good approximation to the mode frequencies: 2pinu(i) approximately (lambda(i)(v)/lambda(i)(x))((1/2)) approximately (lambda(i)(a)/lambda(i)(x))((1/4)). We demonstrate the new method using with two cases: an isolated water molecule and a crystalline polymer.


Interactions of insulin-like growth factors I and II and multiplication-stimulating activity with receptors and serum carrier proteins.
Insulin-like growth factors (IGFs) I and II, purified from human plasma, and multiplication-stimulating activity (MSA), purified from media conditioned by the BRL 3A rat liver cell line, are polypeptides with similar biological and biochemical properties. We have compared the interaction of 125I-labeled and unlabeled MSA, IGF-I, and IGF-II with four intact cell or cell membrane preparations previously shown to possess MSA receptors: rat liver plasma membranes, chick embryo fibroblasts, human fibroblasts, and BRL 3A2 cells. In each case, specific binding of 125I-labeled IGF-I and IGF-II was demonstrated. With each 125I-labeled peptide, significant inhibition of binding and parallel dose-response curves were observed with unlabeled IGF-I, IGF-II, and MSA. Striking differences were noted, however, in the relative potencies of the unlabeled peptides as competitive inhibitors of binding. We conclude that the different specificities of binding inhibition reflect a significant heterogeneity among IGF receptors. A similar heterogeneity appears to occur among somatomedin carrier proteins in rat and human sera.


The Role of Bromodomain Testis-Specific Factor, BRDT, in Cancer: A Biomarker and A Possible Therapeutic Target.
Cancer cells have recently been shown to activate hundreds of normally silent tissue-restricted genes, including a specific subset associated with cancer progression and poor prognosis. Within these genes, a class of testis-specific genes designed as cancer/testis, attracted special attention because of their oncogenic roles as well as their potential use in immunotherapy. Here we focus on one of these genes encoding the testis-specific member of the bromodomain and extra-terminal (BET) family, known as BRDT. Aberrant activation of BRDT was first detected in lung cancers. In this study, we report that the frequency of BRDT's aberrant activation in lung cancer varies according to the histological subtypes and in contrast with other cancer/testis genes, it is rarely expressed in other solid tumours. The functional characterization of BRDT in its physiological setting in male germ cells is now painting a clear portrait of its normal activity and also suggests possible underlying oncogenic activities, when the gene is ectopically activated in cancers. Also, these functional studies of BRDT point to specific anti-cancer therapeutic strategies that could be used to "high-jack" BRDT's action and turn it against cancer cells, which express this gene. Finally, BRDT's expression could be used as a biomarker for cell sensitivity to BET bromodomain inhibitors, which have become newly available as anti-cancer drugs.


Antivenom preclinical efficacy testing against Asian snakes and their availability in Asia: A systematic review.
Cross-neutralizing strategy has been applied to improve access to antivenoms, a key to reducing mortality and disability of snakebite envenoming. However, preclinical studies have been conducted to identify antivenoms' cross-neutralizing ability when clinical studies may not be considered ethical. Therefore, this study aimed to identify and summarize scattered evidence regarding the preclinical efficacy of antivenoms against Asian snakes. In this systematic review, we searched for articles published until May 30, 2022, in PubMed, Scopus, Web of Science, and Embase. Preclinical studies that reported the available antivenoms' neutralizing ability against Asian snake lethality were included. Quality assessment was performed using the Systematic Review Centre for Laboratory animal Experimentation's risk of bias tool and the adapted the Animal Research Reporting In Vivo Experiments guidelines. The availability of effective antivenoms against Asian snakes was analyzed by comparing data from included studies with snakebite-information and data platforms developed by the World Health Organization. Fifty-two studies were included. Most studies assessed the antivenom efficacy against snakes from Southeast Asia (58%), followed by South Asia (35%) and East Asia (19%). Twenty-two (49%) medically important snakes had antivenom(s) with confirmed neutralizing ability. Situation analyses of the availability of effective antivenoms in Asia demonstrated that locally produced antivenoms did not cover all medically important snakes in each country. Among countries without local antivenom production, preclinical studies were conducted only in Bangladesh, Sri Lanka, and Malaysia. Risk of bias assessment was limited in some domains because of unreported data. Cross-neutralizing of antivenoms against some medically important snakes in Asia was confirmed. This strategy may improve access to geographically effective antivenoms and bypass investment in novel antivenom development, especially in countries without local antivenom production. A database should be developed to aid the development of a snakebite-information system.


Discovery of type 2 diabetes mellitus with correlation and optimization driven hybrid deep learning approach.
Diabetes mellitus is a severe condition that has the potential to impair strength. The disease known as diabetes mellitus, which is a chronic condition, is brought on by a significant rise in blood glucose levels. The diagnosis of this condition is made using a variety of chemical and physical testing. Diabetes, however, can harm the organs if it goes undetected. This study develops a hybrid deep-learning technique to recognize Type 2 diabetes mellitus. The data is cleaned up at the pre-processing stage using a data transformation technique based on the Yeo-Jhonson transformation. The tanimoto similarity is used in the feature selection process to select the best features from the data. To prepare data for future processing, data augmentation is performed. The Deep Residual Network and the Rider-based Neural Network are recommended and trained separately for the T2DM identification using the Competitive Multi-Verse Rider Optimizer. The outputs generated by the RideNN and DRN classifiers are blended using correlation-based fusion. The suggested CMVRO-based NN-DRN has shown improved performance with the highest accuracy of 91.4%, sensitivity of 94.8%, and specificity of 90.1%.


Disclosure of sexual victimization: the effects of Pennebaker's emotional disclosure paradigm on physical and psychological distress.
Research suggests that many sexual assault survivors do not disclose their experience, which may increase associated distress. Pennebaker's emotional disclosure paradigm has been shown to ameliorate psychological and physical distress in individuals exposed to stressful events. The current study assessed the effectiveness of this paradigm with sexual assault survivors (N = 74). College women with a history of sexual assault wrote about their most severe victimization or about how they spend their time (control). Then 73 women (98.6%) completed a 1-month follow-up assessment. Results indicated that across writing sessions, the disclosure group reported greater reductions in negative mood immediately post-writing. However, both groups showed significant reductions in physical complaints, psychological distress, and traumatic stress symptoms at the 1-month follow-up, suggesting no added benefit to disclosure of a sexual assault using a brief written paradigm.