Outcomes of combined phacoemulsification, anterior vitrectomy, and sclerectomy in nanophthalmic eyes with glaucoma.
To compare the long-term efficacy and safety of combined phacoemulsification, anterior vitrectomy, and sclerectomy (triple procedure surgery, TS); combined phacoemulsification and anterior vitrectomy (double procedure surgery, DS); and filtering surgery (FS) in nanophthalmos with angle-closure glaucoma (NACG). Retrospective cohort study. Forty patients (44 eyes) diagnosed with NACG who underwent TS, DS, and FS were included. All eyes in the TS group and seven (47%) eyes in the DS group also underwent goniosynechialysis during the surgery. The main outcome measures (intraocular pressure [IOP], best-corrected visual acuity, complications, and second surgeries) were recorded at the early- (within 1 week) and late-stage (>3 months) follow-up. The late-stage IOP was significantly lower in the TS (mean ± standard deviation: 13.29 ± 2.49 mm Hg) than in the DS (19.69 ± 6.97 mm Hg) and FS groups (27.57 ± 12.26 mm Hg, p < 0.001). More visual improvements were observed in the TS and DS groups than in the FS group at late-stage follow-up (p = 0.04). The complication rates in the TS, DS, and FS groups were 26%, 33%, and 70%, respectively (p = 0.046); the second surgery rates were 0%, 33%, and 60%, respectively (p < 0.001). In total, one, three, and six severe complications were observed in the TS, DS, and FS groups, respectively. The mean follow-up durations in the TS, DS, and FS groups were 18.89, 20.02, and 25.75 months, respectively. NACG management remains challenging. TS presented relatively good clinical efficacy and safety with better postoperative IOP outcomes, lower complications, and second surgery rates among the three groups in eyes with NACG.


Selective retrograde transport of 3H-serotonin in vagal afferents.
A new serotonergic afferent vagal component has been demonstrated in the cat by radioautography. Twenty-four hours after a bilateral injection of tritiated serotonin (3H-5-HT) into the area of the nucleus of the solitary tract (NST), heavily and lightly labelled cell bodies were observed in the nodose ganglia. After unilateral injections of 3H-5-HT into the same area, labelled ganglionar cell bodies were found in the ipsilateral nodose ganglion. Some were also found in the contralateral one, suggesting a serotonergic crossed fibers component. Dense clusters of silver grains, depicting typical labelling of neuronal varicosities, were observed in the NST. After destruction of the serotonergic terminals with 5,7-dihydroxytryptamine, followed by injection of 3H-5-HT, the number of labelled cell bodies decreased dramatically in the ipsilateral nodose ganglia and the clusters of silver grains disappeared in the NST. After ligature or section of the supranodose vagal nerve, following injection of 3H-5-HT into the NST, no radioautographic reaction was observed in the homolateral nodose ganglia. The present study demonstrates the existence of a peripheral serotonergic system in vagal afferents. The physiological implications of this new serotonergic visceral pathway remain to be studied.


Inhibition of Lincpint expression affects insulin secretion and apoptosis in mouse pancreatic β cells.
LncRNAs have been reported to maintain islet function and are associated with the development of diabetes. Here, we investigated Lincpint biological functions in mouse pancreatic β cells both in vivo and in vitro. We observed that Lincpint was highly expressed in BALB/c mouse islets and downregulated in db/db mouse islets by using qRT-PCR. Lincpint could be regulated by different concentrations of glucose in MIN6 cells. MTT and flow cytometry showed that silencing Lincpint expression in vitro increased cell apoptosis. In a GSIS assay, we detected that inhibition of the expression of Lincpint suppressed insulin synthesis and secretion. In male BALB/c mouse, blood glucose and serum insulin were decreased after knockdown of Lincpint expression as detected by IPGTT and ELISA. Immunohistochemistry indicated that positive islet area and expression of Pdx1 and Glut2 was reduced after Lincpint silencing in male BALB/c mouse. These findings suggest that Lincpint may play an important role in maintaining islet β cell function and is worthy of further investigation due to its potential in diabetes treatment.


Use of cine images in standard ultrasound imaging: a survey of sonologists.
The aim of this study was to explore how sonologists utilize cine images in their routine practice. A 10-question, multiple choice survey was distributed to members of the Society of Radiologists in Ultrasound. The survey queried respondent's routine inclusion of cines for ultrasound examinations in normal and abnormal studies in addition to questions related to respondent's practice type, geographic location, number of radiologists interpreting ultrasound examinations, and ultrasound imaging workflow. Sixty-five percent of respondents are in academic practice. Geographic location of practice, number of radiologists in the practice who interpret ultrasound, and whether the sonologist was on site where the examinations were performed was variable. Of respondents, 97% of used both static and cine images for abnormal/positive examinations and 82% used both for normal/negative studies. Nearly all respondents, who are mostly in academic practice, report using both static and cine images for all ultrasound examinations in their practice.


Cholecystectomy, peptic ulcer disease and the risk of adenocarcinoma of the oesophagus and gastric cardia.
Gastro-oesophageal reflux is a strong risk factor for oesophageal adenocarcinoma. Bile and pancreatic enzymes may be particularly carcinogenic. Cholecystectomy causes an increased gastric level of these constituents. A decreased risk of oesophageal adenocarcinoma has been observed in persons infected with cagA-positive Helicobacter pylori. There is a strong correlation between ulcer disease and Helicobacter pylori infection. The aim of this study was to determine whether previous cholecystectomy or peptic ulcer disease affects the risk of oesophageal carcinoma. Data were collected as a nationwide population-based case-control study in Sweden between 1995 and 1997. Multivariate adjusted odds ratios (ORs) were calculated with logistic regression. There was no statistically significant association between cholecystectomy and the risk of oesophageal carcinoma. Among persons with previous peptic ulcer, the adjusted OR for oesophageal adenocarcinoma was below unity (OR = 0.6, 95 per cent confidence interval 0.3-1.1). The relative risk estimates for cardia adenocarcinoma and oesophageal squamous cell carcinoma were close to unity. Cholecystectomy, despite its effect on the composition of gastric juice, does not appear to increase the risk of adenocarcinoma of the oesophagus or gastric cardia. While the data do not contradict a protective effect of H. pylori, the results are also consistent with absence of such an effect.


Immobilization of sun bears (Helarctos malayanus) with medetomidine-zolazepam-tiletamine.
A mixture of medetomidine (50.0 microg/kg, i.m.) and zolazepam-tiletamine (2.0 mg/kg, i.m.) effectively immobilized 16 sun bears (Helarctos malayanus) for more than 1 hr with good myorelaxation and minimal effects on cardiorespiratory performance during 22 immobilizations. All bears were immobilized once, except for six individuals that were immobilized twice. Atipamezole (250 microg/kg, i.v.) effectively reversed medetomidine-induced sedation and reduced recovery time significantly. Respiratory rates of immobilized bears did not change significantly over time. Rectal body temperature and heart rate decreased significantly after 10 min of immobilization. Hematologic and serum biochemical parameters did not change significantly within 30 min of induction.


A fatty acid profiling method using liquid chromatography-high resolution mass spectrometry for improvement of assisted reproductive technology.
Liquid chromatography-high resolution mass spectrometry (LC-HRMS) can be useful to improve in vitro fertilization (IVF). This study aims to find out an association between embryonic growth and embryonic uptake of free fatty acid (FFA) from culture media by using LC-HRMS. Embryos (n=55) from 15 couples undergoing IVF were studied. An embryo was cultivated for up to 6 days in a 20 μl-medium drop under mineral oil, and classified by a morphological grading system into the good-growth group (n=32; good quality blastocysts) and the poor-growth group (n=23; non-blastocysts). The control study was set up without embryo. Extracted ion chromatogram of FFAs was collected in negative-ion mode for each medium sample obtained after use. The percent change from control to sample in mass area for docosahexaenoic acid showed a decrease in the good-growth group than that in the poor-growth group (p<0.05). Decrease in %change of docosahexaenoic acid might indicate proper embryonic growth. Similar but insignificant change was observed for other essential FFAs, but not for non-essential FFAs. The proposed metabolomic approach using LC-HRMS might be a powerful tool for non-invasive evaluation of embryonic growth.


A novel SOX18 mutation uncovered in Jordanian patient with hypotrichosis-lymphedema-telangiectasia syndrome by Whole Exome Sequencing.
The SOX18 gene encodes a transcription factor that plays a notable role in certain developmental contexts such as lymphangiogenesis, hair follicle development and vasculogenesis. SOX18 mutations are linked to recessive and dominant hypotrichosis-lymphedema-telangiectasia syndrome (HLTS). In this study we report on a novel heterozygous mutation in SOX18 in a Jordanian patient suffering from HLTS that was revealed by Whole Exome Sequencing. In this case, a frameshift caused by 14-nucleotide duplication in SOX18 appeared de novo resulting in a premature translational stop at the N-terminal region of the central trans-activation domain. Here we present the clinical manifestations of the above mentioned molecular lesion in the light of what is known from published SOX18 mutations.


Potentiation of vincristine by vitamin A against drug-resistant mouse leukaemia cells.
Vitamin A has been shown to potentiate the cytotoxic action of anticancer agents like vincristine (VCR) against drug resistant mouse P388 leukaemia cells. In vitro tests showed enhancement by retinyl acetate of cytocidal activities of VCR against drug-sensitive leukaemia (P388/S) and VCR-resistant leukaemia (P388/VCR) cells in culture; retinyl acetate rather specifically potentiated VCR against cultured P388/VCR cells than P388/S cells. The cellular accumulation of radioactive VCR was significantly enhanced in cultured P388/VCR cells when retinyl acetate was present. The efflux of VCR from drug-resistant cells was blocked by retinyl acetate. The effect of the combination of vitamin A and VCR was also tested in vivo on the life-span of mice bearing P388/S or P388/VCR. Intraperitoneal administration of retinyl palmitate at 41.75 or 83.5 mg kg-1 was effective to potentiate the antileukaemic activity of VCR against P388/S bearing mice, and it also overcame vincristine-resistance in P388/VCR bearing mice.


Quantitative assessment of rabbit alveolar macrophage function by chemiluminescence.
Rabbit alveolar macrophages (RAM) were cultured for 24 hr with concentrations ranging from 3 to 12 micrograms/ml of vanadium oxide (V2O5), a known cytotoxic agent, or with high-molecular-weight organic by-products from coal gasification processes. After culture the cells were harvested and tested for functional capacity using three types of indicators: (1) luminol-amplified chemiluminescence (CL), which quantitatively detects photon emission due to respiratory burst activity measured in a newly designed instrument with standardized reagents; (2) the reduction of nitro blue tetrazolium-saturated polyacrylamide beads, a semiquantitative measure of respiratory burst activity; and (3) phagocytic efficiency, defined as percentage of cells incorporating immunoglobulin-coated polyacrylamide beads. Chemiluminescence declined linearly with increasing concentrations of V2O5 over the dose range tested. Dye reduction and phagocytic efficiency similarly decreased with increasing V2O5 concentration, but were less sensitive indicators of functional impairment than CL as measured by the amount required to reduce the response to 50% of untreated cells. The effect of coal gasification condensates on RAM function varied, but in general these tests also indicated that the CL response was the most sensitive indicator.


Reversibility of D-penicillamine induced collagen alterations in rat skin and granulation tissue.
Granulation tissue was produced in rats by subcutaneous implantation of Visella sponges. D-penicillamine (D-pen) 100 or 500 mg/kg was administered daily for 42 days by gastric tubing. Pairfed, placebo treated animals were included as controls. Half of the groups were kept for additionally 28 days without medication. The inhibitory effect of D-pen on cross-link formation in newly synthesized collagen was readily reversible. By contrast, cross-link deficiency lasting beyond the observation period was observed in the higher polymeric collagen variants released by dilute acid, heat exposure or limited pepsin proteolysis as estimated by solubility, alpha/beta chain ratio and/or aldehyde content. By SDS-polyacrylamide gel electrophoresis on gels containing 3.6 M urea it was shown that purified dermal acid soluble collagen from treated animals consisted of a mixture of type I and III collagen, whereas only type I collagen was detected in controls. The band pattern was identical in reduced and unreduced collagen samples. Four weeks after D-pen discontinuance type III collagen had disappeared from the acid extract. Moreover, the ratio of type III to type I collagen in the pepsin digest from both granulation tissue and skin showed a persistent rise with D-pen. These observations indicate that D-pen destabilized type III collagen in particular by interference with its disulfide linkages. The amount of granulation tissue remained unaffected throughout the experiment, whereas the skin collagen content decreased at the higher dose level. The regeneration was not completed by the end of the observation period. Modulation of the molecular stability of granuloma collagens may be of relevance for the antirheumatoid effect of D-pen, but the sustained effect on normal tissues may imply a long standing impairment of their supportive capacity.


Within-meal gut feedback signaling.
During a meal, multiple gastrointestinal sites are stimulated by ingested nutrients and their digestion products, initiating local gastrointestinal actions and producing a variety of potential feedback signals that can contribute to meal termination. During ingestion, gastric emptying is rapid, allowing a significant portion of ingested nutrients to enter the intestine. Gastric and duodenal vagal afferent fibers increase their electrophysiological activity in relation to the mechanical presence of ingested nutrients. On reaching the duodenum, nutrients also activate vagal chemosensitive elements and stimulate the release of a variety of brain gut peptides including cholecystokinin (CCK). CCK also activates vagal afferent fibers directly and modifies the response properties of vagal mechanosensitive fibers to gastric and duodenal loads. Blocking or eliminating these feedback signals results in increased meal size demonstrating their role in meal termination.


Autogenous and efficient acceleration of energetic ions upstream of Earth's bow shock.
Earth and its magnetosphere are immersed in the supersonic flow of the solar-wind plasma that fills interplanetary space. As the solar wind slows and deflects to flow around Earth, or any other obstacle, a 'bow shock' forms within the flow. Under almost all solar-wind conditions, planetary bow shocks such as Earth's are collisionless, supercritical shocks, meaning that they reflect and accelerate a fraction of the incident solar-wind ions as an energy dissipation mechanism1,2, which results in the formation of a region called the ion foreshock3. In the foreshock, large-scale, transient phenomena can develop, such as 'hot flow anomalies'4-9, which are concentrations of shock-reflected, suprathermal ions that are channelled and accumulated along certain structures in the upstream magnetic field. Hot flow anomalies evolve explosively, often resulting in the formation of new shocks along their upstream edges5,10, and potentially contribute to particle acceleration11-13, but there have hitherto been no observations to constrain this acceleration or to confirm the underlying mechanism. Here we report observations of a hot flow anomaly accelerating solar-wind ions from roughly 1-10 kiloelectronvolts up to almost 1,000 kiloelectronvolts. The acceleration mechanism depends on the mass and charge state of the ions and is consistent with first-order Fermi acceleration14,15. The acceleration that we observe results from only the interaction of Earth's bow shock with the solar wind, but produces a much, much larger number of energetic particles compared to what would typically be produced in the foreshock from acceleration at the bow shock. Such autogenous and efficient acceleration at quasi-parallel bow shocks (the normal direction of which are within about 45 degrees of the interplanetary magnetic field direction) provides a potential solution to Fermi's 'injection problem', which requires an as-yet-unexplained seed population of energetic particles, and implies that foreshock transients may be important in the generation of cosmic rays at astrophysical shocks throughout the cosmos.


Health Sciences Students' Perspective on the Functions of Academic Advising.
Nursing and allied health students represent a significant percentage of undergraduate students. Academic advising is integral to students' success. This study aimed to identify nursing and allied-health science students' perspectives on academic advising functions and identify the demographic factors associated with these perspectives. A cross-sectional, correlational study was conducted with 252 students who completed a survey on students' perspectives on academic advising functions. Students were recruited from a large public university in western Saudi Arabia. The results revealed that 97.6% of students reported knowing their academic advisor and 80.8% reported meeting with their advisor at least once over the past year. Overall, students perceived academic advising as important (M = 4.0, SD ± 0.86). The social role of academic advising was perceived as its most important function (M = 4.1, SD ± 0.85), followed by the academic role (M = 4.0, SD ± 0.87) and the personal role (M = 3.9, SD ± 0.87). The results showed that junior students perceived academic advising as more important than their counterparts. There was a weak significant correlation between students' perception of academic advising functions and the number of meetings held with their advisors. Faculty should improve students' understanding of the academic advisor's role in academic progress. Students understanding of their academic advisor's role in supporting their academic progress should be emphasized, especially among senior students.


Pediatric medical line safety: the prevalence and severity of medical line entanglements.
The purpose of this cross-sectional study was to describe the prevalence and severity of medical line entanglements among pediatric patients (N = 486). Most patients, with ages from birth to 6 years, had at least 1 medical line (n = 444, 91%), and 294 children (60%) had 2 to 11 medical lines. Observed entanglements included lines around body parts (n = 31), lines under the body (n = 71), and lines tangled with other lines (n = 50). One third of the children were at risk for adverse events due to entanglements, and 1 patient actually experienced real harm.


Socioeconomic disparities in leisure activities over the life course of the oldest-old in China.
To identify the socioeconomic factors leading to disparities in participation in leisure activities over the life course among Chinese oldest-old people. Data are from the Chinese Longitudinal Healthy Longevity Survey (CLHLS), a sample of adults aged 80 years or older in the period 1998-2012, featuring 38 312 individuals (58 945 observations). The younger birth cohorts were found to have significantly higher levels of participation in leisure activities, with a non-linear decrease in age observed for oldest-old men and women. Higher participation levels were significantly related to higher education levels, economic independence and non-manual occupations before retirement among the Chinese oldest-old. Leisure activity participation has increased substantially in recent cohorts of Chinese oldest-olds. Those with lower socioeconomic status may represent a disadvantaged population in terms of participation in leisure activities over their life course.


Retraction: application of hybrid particle swarm and ant colony optimization algorithms to obtain the optimum homomorphic wavelet image fusion.
[This retracts the article DOI: 10.21037/atm-20-5997.].


The DNA methyltransferase-2 gene in the prawn Macrobrachium rosenbergii: characteristics and expression patterns during ovarian and embryonic development.
DNA methylation plays important roles in eukaryotic development. However, studies of DNA methylation in Crustacea are very limited. In the present study, we isolated and identified a DNA methyltransferase 2 (Mar-Dnmt2) gene from the prawn Macrobrachium rosenbergii. The cDNA of Mar-Dnmt2 contained an 1,191-bp open reading frame that encoded a putative Dnmt2 protein of 396 amino acids with the ten motifs characteristic of DNA methyltransferases and exhibiting high identities with other known Dnmt2 homologs (30%-42%). By real-time PCR, an especially high level of Mar-Dnmt2 mRNA was found in the ovary, approximately 5-16 times higher than in other tissues. Moreover, Mar-Dnmt2 mRNA obviously decreased during embryonic development. On the other hand, DNA methylation was detected in this study; about 0.05% of cytosine residues were found to be methylated in the DNA of M. rosenbergii.


Clinical trials using ascorbic acid aerosol to aid smoking cessation.
Sensory aspects of cigarette smoke are important for providing smoking satisfaction. In previous studies, we have found that substitution of the sensory cues of smoking with a citric acid aerosol significantly reduces craving for cigarettes and enhances smoking reduction and cessation with people trying to quit smoking cigarettes. In the current study, we conducted two clinical smoking cessation trials using an ascorbic acid aerosol as a sensory substitute. The cigarette substitute consisted of a cigarette-sized tube which delivered a fine aerosol of ascorbic acid (approx. 1 mg/puff, up to a maximum of 300 mg/day). Study 1 examined the overall effectiveness of the ascorbic acid smoking substitute device. One group of subjects which used the device and received clinical counseling was compared with another group which received only clinical counseling. The group using the device showed significantly greater abstinence rates at 3 weeks post-cessation. After the subjects stopped using the device, no difference in abstinence was detected. Study 2 was conducted to focus specifically on the role of tracheobronchial sensations in relieving craving for cigarettes. Two closely matched ascorbic acid delivery systems were compared. One device delivered fine particles of ascorbic acid that were targeted to reach the trachea, while the other delivered coarser particles of ascorbic acid that were not expected to reach the trachea or lower airways. An initial enhancement in smoking reduction was found for subjects using the fine particle device relative to those using the coarse particle device. However, by the end of treatment (5 weeks) both groups showed similar degrees of smoking reduction. For those who were abstinent from smoking at the end of treatment, craving for cigarettes and negative mood were both significantly lower for those using the fine particle device. Also, hunger for food was significantly lower in the fine particle device group. These results suggest that ascorbic acid delivered from a cigarette substitute may be effective in reducing smoking and promoting smoking abstinence.


Netchain coordinator services in pork supply chains including inspections according to the AMOR principle.
This paper presents a mutual inspection concept between livestock production and processing, coordinated by a netchain coordinator acting as the service provider. The concept is based on an analysis of demand and offer with respect to the coordination of livestock health status certificates. Surveys have been conducted amongst piglet producers and pig fatteners (nfarmers=206) to reflect the demand for coordination services. Another survey amongst service providers (nproviders=21) determines the availability of these services. The results show a clear demand amongst farmers for the netchain coordinator services of livestock health status certificates. It has also been found that some service providers offer audit and monitoring procedures to enable certification with highly varying degrees of service quality. Based on the surveys, the joint organisation of livestock health status certificates between producer, fattener and service provider will be presented. It will be shown that for greater efficiency, coordination should be based on the principles of Alliances for the Mutual Organisation of Risk oriented inspection strategies (AMOR). To enable the mutual organisation of inspections, four key steps have been identified to develop and test AMOR as an innovative form of cooperation: (i) inspection design, (ii) responsibilities and tasks, (iii) information and communication structures, and (iv) shared cost and benefit model.


Hsa_circ_0005576 promotes osimertinib resistance through the miR-512-5p/IGF1R axis in lung adenocarcinoma cells.
Osimertinib is a third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) for lung adenocarcinoma (LUAD) harboring activating mutations, but patients ultimately develop acquired resistance. Circular RNAs are involved in EGFR-TKI resistance, while the role of hsa_circ_0005576 in the osimertinib resistance of LUAD remains unknown. In this study, we demonstrated that hsa_circ_0005576 could facilitate osimertinib-resistant LUAD cells. Briefly, knockdown of hsa_circ_0005576 not only suppressed the proliferation and promoted the apoptosis of resistant LUAD cells, but also increased their sensitivity to osimertinib. Mechanistically, hsa_circ_0005576, serving as an miRNA sponge, could directly interact with miR-512-5p and subsequently upregulate the miR-512-5p-targeted insulin-like growth factor 1 receptor. Rescue assays indicated that miR-512-5p inhibition could reverse the effects of hsa_circ_0005576 knockdown in LUAD cells resistant to osimertinib. Overall, our study revealed that hsa_circ_0005576 regulates proliferation and apoptosis through miR-512-5p/IGF1R signaling, which contributes further to the resistance of LUAD cells to osimertinib. In addition, this study provides a novel insight into the mechanisms underlying osimertinib resistance of LUAD.


Acute and maintenance ECT with flupenthixol in refractory schizophrenia: sustained improvements in psychopathology, quality of life, and social outcomes.
To determine the effects of ECT combined with antipsychotic medication therapy on psychopathology, quality of life, and social functioning in patients with refractory schizophrenia. An open acute (Phase I) and maintenance (Phase II) study of the combination of ECT and flupenthixol in the treatment of 46 schizophrenic patients who were nonresponsive to antipsychotic medication from at least two different classes. Scales used: the Brief Psychiatric Rating Scale (BPRS), the Quality of Life Scale (QLS), Social and Occupational Functioning Assessment Scale (SOFAS), Global Assessment of Functioning (GAF), and Mini-Mental State Exam (MMSE). The duration of Phase II was 1 year. In Phase I, there were marked reductions in the BPRS scores, and substantial increases in the QLS, SOFAS, GAF, and MMSE scores. During Phase II, the BPRS negative symptoms worsened but remained improved from baseline. Changes in other outcome measures were negligible. ECT and MECT combined with flupenthixol were effective in improving psychopathology in patients refractory to antipsychotic medication alone. Ratings of psychopathology, quality of life, and social functioning all improved in Phase I and were generally sustained during Phase II in patients who had remitted.


Other potential medical therapies: the use of antiviral agents to investigate and treat primary ciliary cirrhosis.
A human betaretrovirus has been characterized in patients with primary biliary cirrhosis (PBC) and the related mouse mammary tumor virus linked with autoimmune biliary disease in the NOD.c3c4 mouse model. Translational studies have been performed in patients who have PBC to investigate the role of viral infection in disease. Patients treated with Combivir experienced significant improvements in hepatic biochemistry, clinical symptoms, and histology with evidence of reversal of ductopenia. Preliminary studies suggest that the NOD.c3c4 mouse model of PBC provides a good model to test safer and more potent drug regimens for future use in trials for patients who have PBC.


Cis-acting and trans-acting regulatory mutations define two types of promoters controlled by the qa-1F gene of Neurospora.
The function of the qa-1F positive regulatory gene of Neurospora has been studied by mapping the initiation sites for transcription of the clustered qa structural genes in wild type, in qa-1F mutants, and in cis-acting activator protein-independent mutants of qa-2 (qa-2ai mutants). Each structural gene under qa-1F control has two to four promoters. The qa-2ai mutations, which include point mutations and small (68-84 bp) duplications 5' to qa-2, allow qa-1F-independent transcription from surrounding qa promoters independently of the orientations and positions (up-stream or downstream) of teh mutations relative to the promoters. However, one subset of promoters was not reactivated by the enhancer-like elements created by these mutations, and qa-1F mutants selectively deficient in the activation of these promoters have been identified. Therefore, the qa-1F regulatory gene appears to control two types of promoters that have different requirements for activation.


De novo whole-genome assembly in an interspecific hybrid table grape, 'Shine Muscat'.
The first genome sequence of an interspecific grape hybrid (Vitis labruscana × Vitis vinifera), 'Shine Muscat', an elite table grape cultivar bred in Japan, is presented. The resultant genome assemblies included two types of sequences: a haplotype-phased sequence of the highly heterozygous genomes and an unphased sequence representing a 'pseudo-haploid' genome. The unphased sequences, assembled to the chromosome level with Hi-C reads, spanned 488.97 Mb in length, 99.1% of the estimated genome size, with 4,595 scaffold sequences and a 23.9-Mb N50 length. The phased sequences had 15,650 scaffolds spanning 1.0 Gb and a 4.2-Mb N50 length. 32,827 high-confidence genes were predicted on the unphased genomes. Clustering analysis of the 'Shine Muscat' gene sequences with three other Vitis species and Arabidopsis indicated that 11,279 orthologous gene clusters were common to Vitis spp. and Arabidopsis, 4,385 were Vitis specific, and 234 were 'Shine Muscat' specific. Whole-genome resequencing was also performed for the parental lines of 'Shine Muscat', Akitsu-21 and 'Hakunan', and parental-specific copy number variations were identified. The obtained genome resources provide new insights that could assist in cultivation and breeding strategies to produce high-quality table grapes.


Inhibition of constitutive NF-κB activity induces platelet apoptosis via ER stress.
Platelets are anucleate cells, known for their pivotal roles in hemostasis, inflammation, immunity, and disease progression. Being anuclear, platelets are known to express several transcriptional factors which exert nongenomic functions, including the positive and negative regulation of platelet activation. NF-κB is one such transcriptional factor involved in the regulation of genes for survival, proliferation, inflammation and immunity. Although, the role NF-κB in platelet activation and aggregation is partially known, its function in management of platelet survival and apoptosis remain unexplored. Therefore, two unrelated inhibitors of NF-κB activation, BAY 11-7082 and MLN4924 were used to determine the role of NF-κB in platelets. Inhibition of NF-κB caused decreased SERCA activity and increased cytosolic Ca2+ level causing ER stress which was determined by the phosphorylation of eIF2-α. Further, there was increased BAX and decreased BCl-2 levels, incidence of mitochondrial membrane potential depolarization, release of cytochrome c into cytosol, caspase activation, PS externalization and cell death in BAY 11-7082 and MLN4924 treated platelets. The obtained results demonstrate the critical role played by NF-κB in Ca2+ homeostasis and survival of platelets. In addition, the study demonstrates the potential side effects associated with NF-κB inhibitors employed during inflammation and cancer therapy.


Key aspects of analytical method validation and linearity evaluation.
Method validation may be regarded as one of the most well-known areas in analytical chemistry as is reflected in the substantial number of articles submitted and published in peer review journals every year. However, some of the relevant parameters recommended by regulatory bodies are often used interchangeably and incorrectly or are miscalculated, due to few references to evaluate some of the terms as well as wrong application of the mathematical and statistical approaches used in their estimation. These mistakes have led to misinterpretation and ambiguity in the terminology and in some instances to wrong scientific conclusions. In this article, the definitions of various relevant performance indicators such as selectivity, specificity, accuracy, precision, linearity, range, limit of detection, limit of quantitation, ruggedness, and robustness are critically discussed with a view to prevent their erroneous usage and ensure scientific correctness and consistency among publications.


Factors Associated with Low Flow in Aortic Valve Stenosis.
Low-flow low-gradient aortic stenosis (AS) is a predictor of worse outcome compared with normal-flow AS. Although depressed left ventricular ejection fraction (LVEF) is associated with low flow, there is less evidence to support the role of other indices of cardiac structure and function. Clinical and echocardiographic data from patients with native AS and valve areas ≤ 1.0 cm(2) were retrospectively analyzed to identify characteristics that are associated with low-flow low-gradient AS. In total, 941 patients were included. On multivariate analysis, factors independently associated with low flow (stroke volume index < 35 mL/m(2)) included worse right ventricular systolic function, atrial fibrillation, lower LVEF, and higher left ventricular mass, with moderate or severe mitral regurgitation independently associated with low flow in the 694 patients (74%) with preserved LVEFs. Right ventricular dysfunction and atrial fibrillation are independently associated with low-flow low-gradient AS, while moderate or severe MR is independently associated with low flow in patients with preserved LVEF. These associations with low flow in AS are clinically important to recognize, to avoid underestimation of AS severity.


Long-term correction of canine hemophilia B by gene transfer of blood coagulation factor IX mediated by adeno-associated viral vector.
Hemophilia B is a severe X-linked bleeding diathesis caused by the absence of functional blood coagulation factor IX, and is an excellent candidate for treatment of a genetic disease by gene therapy. Using an adeno-associated viral vector, we demonstrate sustained expression (>17 months) of factor IX in a large-animal model at levels that would have a therapeutic effect in humans (up to 70 ng/ml, adequate to achieve phenotypic correction, in an animal injected with 8.5x10(12) vector particles/kg). The five hemophilia B dogs treated showed stable, vector dose-dependent partial correction of the whole blood clotting time and, at higher doses, of the activated partial thromboplastin time. In contrast to other viral gene delivery systems, this minimally invasive procedure, consisting of a series of percutaneous intramuscular injections at a single timepoint, was not associated with local or systemic toxicity. Efficient gene transfer to muscle was shown by immunofluorescence staining and DNA analysis of biopsied tissue. Immune responses against factor IX were either absent or transient. These data provide strong support for the feasibility of the approach for therapy of human subjects.


Nonlinear mechanical response of DNA due to anisotropic bending elasticity.
The response of a short DNA segment to bending is studied, taking into account the anisotropy in the bending rigidities caused by the double-helical structure. It is shown that the anisotropy introduces an effective nonlinear twist-bend coupling that can lead to the formation of kinks and modulations in the curvature and/or in the twist, depending on the values of the elastic constants and the imposed deflection angle. The typical wavelength for the modulations, or the distance between the neighboring kinks is found to be set by half of the DNA pitch.


A pilot assessment of parental practices and attitudes regarding risk disclosure and clinical research involving children in Huntington disease families.
To characterize parental practices of informing children of risk for Huntington disease (HD), and to understand the attitudes of parents concerning childhood participation in HD research. An anonymous Internet survey was accessed by individuals of HD families. The survey probed for data regarding individual risk for HD, as well as when or if children had been informed of the disease. Respondents expressed their attitudes concerning childhood participation in HD clinical research. Two hundred forty-nine individuals responded (approximately 80% female), and 84% had never participated in an HD clinical trial. Seventy-five percent of respondents were parents; nearly two thirds of them had provided some information about HD to their children. There was overwhelming support for affected, at-risk, and unaffected adults in terms of HD research participation, but there was a statistically significant disparity by gene status, with gene negative and symptomatic gene positive adults being more inclined to participate than at-risk or asymptomatic/gene positive adults. More than 50% of respondents supported childhood participation, but typically in late adolescence (15-18 years). Gene negative and symptomatic adults were statistically more likely to agree with childhood inclusion than at-risk or asymptomatic/gene positive adults. These results serve as pilot data for further investigations to address childhood participation in HD research. In addition, these findings will inform ongoing studies as to appropriate practices to undertake to include minors.


A comprehensive untargeted metabolomics study in zebrafish embryos exposed to perfluorohexane sulfonate (PFHxS).
Perfluorohexane sulfonate (PFHxS) is one of the short-chain perfluoroalkyl substances (PFASs), and frequently detected in the environment, humans, and wildlife, but a detailed mechanism of toxicity has been not studied yet. In this study, a comprehensive set of polar metabolites was determined in i) the developing zebrafish embryo (4, 24, 48, 72, and 120 h post fertilization (hpf)), and ii) in the developing zebrafish after exposure to four concentrations of PFHxS (0.3, 1, 3, and 10 μM) from 24to 120 hpf. The temporal (developmental stages) distribution of individual metabolites (541 metabolites) in zebrafish provided comprehensive information about the biological roles of various metabolites in developing vertebrates such as genetic processes, energy metabolism, protein metabolism, and glycerophospholipid metabolism. PFHxS in zebrafish embryo showed time- and concentration- dependent bioaccumulation, and no baseline toxicity was expected at the test concentrations. However, effects on many metabolites were already observed at the lowest tested concentration (0.3 μM), and these effects were more pronounced at later stages of developmental (72 and 120 hpf). In addition to oxidative stress, the effects of PFHxS on zebrafish embryos were related to the disruption of the fatty acid oxidation (FAO), sugar metabolism, and other metabolic pathways. This study gave new and comprehensive information on the underlying mechanism of the toxicity of PFHxS.


Air pollution and arterial hypertension. A new risk factor is in the air.
Air pollution is one of the greatest environmental threats and has been implicated for several adverse cardiovascular effects including arterial hypertension (HTN). However, the exact relationship between air pollution exposure and HTN is still unclear. Air contamination provokes oxidative stress, systemic inflammation, and autonomic nervous system imbalance that subsequently induce endothelial dysfunction and vasoconstriction leading to increased blood pressure. The aim of this review was to describe the potential mechanisms by which air pollution contributes to HTN and to summarize the consequences of short- and long-term exposure.


Artificial intelligence tool detection of intravenous contrast enhancement using spleen attenuation.
To assess the ability of an automated AI tool to detect intravenous contrast material (IVCM) in abdominal CT examinations using spleen attenuation. A previously validated automated AI tool measuring the attenuation of the spleen was deployed on a sample of 32,994 adult (age ≥ 18) patients (mean age, 61.9 ± 14.7 years; 13,869 men, 19,125 women) undergoing 65,449 supine position CT examinations (41,020 with and 24,429 without IVCM by DICOM header) from January 1, 2000 to December 31, 2021. After exclusions, receiver operating characteristic (ROC) curve analysis was performed to determine the optimal threshold for binary classification of IVCM status (non-contrast vs IVCM enhanced), which was then applied to the sample. Discordant examinations (i.e., IVCM status determined by AI tool did not match DICOM header) were manually reviewed to establish ground truth. Repeat ROC curve and contingency table analysis were performed to assess AI tool performance. ROC analysis of the initial study sample of 61,783 CT examinations yielded AUC of 0.970 with Youden index suggesting an optimal spleen attenuation threshold of 65 Hounsfield units (HU). Manual review of 2094 discordant CT examinations revealed discordance due to DICOM header error in 1278 (61.0%) and AI tool misclassification in 410 (19.6%), with 406 (9.4%) meeting exclusion criteria. Analysis of 61,377 CT examinations in the final study sample yielded AUC of 0.999 with accuracy of 99.3% at the 65 HU threshold. Error rate for DICOM header information was 2.1% (1278/61,377) versus 0.7% (410/61,377) for the AI tool. The automated spleen attenuation AI tool was highly accurate for detection of IVCM at a threshold of 65 HU.


American Society of Hypertension position paper: central blood pressure waveforms in health and disease.
A number of devices are available which noninvasively estimate central aortic blood pressure using a variety of approaches such as tonometry or oscillometry. In this position paper, we discuss how the central pressure waveform is generated and measured, how central pressure waveforms appear in health and disease, the predictive value of central blood pressure measurements, the effects of interventions on waveforms, and areas of future need in this field of clinical and research endeavor.


Extent of Surgery for Follicular Thyroid Carcinoma.
To examine the association between the extent of surgery and overall survival in follicular thyroid cancer (FTC) patients. Retrospective analysis of the National Cancer Database (NCDB). Patients who underwent surgical intervention for FTC from 2004 to 2015 were selected. Patients were >18 years old, with tumor size 1-4 cm, no other malignancies, and >0 follow up time. Patients were divided into two cohorts based on extent of surgery: lobectomy (≥1 lobe resected) and thyroidectomy (total or near total resection). Pearson's chi-squared analysis was used to compare cohorts. Kaplan-Meier survival and Cox hazards models were utilized to determine overall survival between two cohorts with p < 0.05 used for significance. A total of 6871 patients were identified with FTC, of which 1507 patients underwent lobectomy and 5364 patients underwent total thyroidectomy. There were no significant differences in patient demographics, comorbidity index, local spread, or tumor grade. Patients undergoing lobectomy had mean survival of 12.94 versus 12.71 years for those undergoing thyroidectomy. Extent of surgery was not associated with a significant difference in survival (5 years OS = 96% in lobectomy and 95.5% in total thyroidectomy, p = 0.08). Stratification by tumor grade resulted in no significant difference in survival between lobectomy and thyroidectomy. Survival time was not significantly different in patients with more extensive resection of FTC. 3 Laryngoscope, 133:993-999, 2023.


Organically modified silica: synthesis and applications due to its surface interaction with organic molecules.
Silica gels can be chemically modified using organic precursors producing organically modified silica (ORMOSIL), a class of novel materials for hosting varieties of organic and inorganic substrates. Ormosil matrixed materials show an enhanced activity during catalysis, photochemical activities like absorption and emission, electrochemical sensitivities, sensing of gases, solvents, pH of solution and biomolecules, etc. Ormosil-based materials can be used as efficient protective coatings and can be utilized in designing wave guides that can carry out excellent photonic transmission of information. The synthetic and chemical modification of ormosil and some of the above applications have been discussed.


[Toward innovative hospital care].
For healthcare financing to remain profitable and to continue to function, the care system must be innovative in terms of patient care. Work organisation has changed with the pricing system for medical acts. The system of enhanced recovery after surgery helps to reduce hospitalisation times and to reflect on organisation. Nurses are on the front line.


Cloning, Expression, Characterization, and Mutagenesis of a Thermostable Exoinulinase From Kluyveromyces cicerisporus.
Inulinase is an enzyme that belongs to glycoside hydrolase family 32. It converts inulin into high-fructose syrups and fructoligosaccharides, both of which are widely used in pharmaceutical and food industries. In this study, the kcINU1 gene (GenBank accession number AF178979) encoding an exoinulinase was cloned from Kluyveromyces cicerisporus CBS4857 and expressed in Pichia pastoris X-33, yielding a maximum of 45.2 ± 0.6 U mL(-1) of inulinase activity of culture supernatant. The expressed inulinase was purified and characterized. The enzyme had an optimum temperature of 55 °C and an optimum pH of 4.5. It had a K m of 0.322 mM and a V max of 4317 μM min(-1) mg(-1) protein when inulin was used as a substrate. It retained nearly 90 % of the maximal activity after pre-incubation at 50 °C for 1 h or at pH ranging from 3.0 to 6.0 at 4 °C for 24 h, demonstrating that KcINU1 was stable at high temperature and low pH. Moreover, we constructed two KcINU1 mutants, Asp30Ala and Glu215Ala, by site-directed mutagenesis and confirmed via zymogram analysis that Asp-30 and Glu-215 of the enzyme were the catalytic active center. The present study has provided important information for understanding the catalytic mechanism of exoinulinase.


The effect of tooth borne versus skeletally anchored Alt-RAMEC protocol in early treatment of Class III malocclusion: a single-centre randomized clinical trial.
This was a randomized, controlled trial designed to compare outcomes between the use of dental and skeletal anchorage, using the Face mask/Alternate Rapid Maxillary Expansion and Contraction (FM/Alt-RAMEC) protocol. The study was carried out at Mater Dei Hospital, Malta and included prepubertal skeletal Class III malocclusion patients where the aetiology was primarily maxillary hypoplasia. Two groups were assigned. Group I was treated with FM/Alt-RAMEC and group II was treated with skeletally anchored FM/Alt-RAMEC. Wear-time (WT) of the FM was monitored using TheraMon microsensors. Patients were instructed to wear the FM for 12-14 hours/day for 9 months. Changes were evaluated with lateral cephalograms and analysed with Wilcoxon and Mann-Whitney U tests. ANOVA was used to analyse the effect of gender on compliance parameters. Spearman's correlation coefficient was used to assess the correlation between compliance and skeletal changes. To compare the skeletal and dentoalveolar changes in patients treated with these two protocols. The primary outcome was to assess skeletal and dentoalveolar outcomes in patients treated with skeletally anchored FM/RME and tooth-borne FM/RME; utilizing Alt-RAMEC protocol. The secondary outcome was compliance rate and adherence to FM wear among patients. Randomizer software and the sealed envelope technique were used to randomly allocate patients 1:1 into either group I (tooth-borne FM/Alt-RAMEC) or group II (skeletally anchored FM/Alt-RAMEC). It was not possible to blind to treatment allocation, but blinding was used when assessing the outcomes. Numbers randomized and analysed. Thirty-five patients were allocated. Group I consisted of 18 subjects and group II consisted of 17 subjects. One patient in group I dropped out due to illness, so 17 subjects in each group completed the study. Post-treatment changes in group I showed significant increases in SNA (2.10°), ANB (3.90°), Wits (4.70 mm), and overjet (5.40 mm). Group II showed significant increases in ANB (3.10°), Wits (3.20 mm), and overjet (4.50 mm). Wearing time for group I patients was 7.87 ± 2.88 hours/day and for group II was 6.98 ± 2.68 hours/day, with no significant difference between the groups. Lack of long-term follow-up post-treatment, making the conclusion applicable only in the short term. No harm was observed in both groups. Despite the large difference between the measured and the patient-reported daily WT, both tooth-borne and skeletally anchored FM/Alt-RAMEC showed positive, similar, skeletal and dental effects. ISRCTN12197405.


Systemic Inflammation and Autoimmunity in Women with Chronic Endometritis.
To determine in women with recurrent pregnancy loss (RPL) and/or implantation failure (RIF) the prevalence of chronic endometritis (CE), systemic inflammation and autoimmunity, and whether they relate. This retrospective study examined inflammatory (adiponectin, CRP, leptin, and IL6) and autoimmune (total immunoglobulins, ANA, thyroid antibodies, antiphospholipid antibodies) markers in a group of 55 women with RPL/RIF. A diagnosis of CE was reached by endometrial biopsy, demonstrating CD138-positive plasma cells on histology. The prevalence of markers of systemic inflammation and autoimmunity was compared between women with and without CE. Among all RPL/RIF patients, 32.7% demonstrated at least one positive inflammatory marker, 61.8% at least one autoimmune marker, and 45.5% CE. Moreover, CE patients did not differ in systematic inflammatory or autoimmune profiles from those without CE. Endometritis and elevated inflammatory and autoimmune markers are common in women with RPL/RIF, but endometritis cannot be predicted based on either peripheral inflammatory or autoimmune markers.


Comparison of safety, efficacy, and outcome of successful versus unsuccessful percutaneous coronary intervention in "true" chronic total occlusions.
Despite improving techniques for opening chronic total occlusions (CTOs), the benefit of successful recanalization of the artery remains unclear. The aims of this study were to investigate the safety and efficacy of percutaneous coronary intervention for "true" CTO, defined by Thrombolysis In Myocardial Infarction (TIMI) flow grade 0 and duration > or =3 months, and to compare the outcome of successful versus failed procedures. A cohort of 172 consecutive patients with de novo CTOs of native vessels confirmed by angiographic review in which percutaneous coronary interventions were attempted was studied. End points included angiographic success, in-hospital complications, and long-term major adverse cardiac events. Technical success was obtained in 73.8% of CTO lesions (127 of 172). No deaths or nonfatal Q-wave myocardial infarctions occurred in the hospital. Repeat percutaneous coronary interventions in the hospital were required in 1.6% of patients (2 of 127) in whom the CTOs were initially opened. Perforation during the initial failed attempts occurred in 6.7% of patients (3 of 45). One patient required operative repair. After an average follow-up period of 2 years, patients with successful procedures experienced similar incidences of cardiac death and nonfatal Q-wave myocardial infarctions as did patients with failed procedures (5.3% and 4.9%, respectively, p = 0.3). Patients with successfully opened arteries required target vessel revascularization more frequently, but this did not reach statistical significance (18.8% vs 0%, p = 0.06). In conclusion, attempts to open CTOs with the devices available at the time of this registry were accompanied by a significant risk for perforation. Furthermore, successful recanalization did not translate into a reduction in 2-year mortality or nonfatal Q-wave myocardial infarctions compared with patients with failed procedures.


Towards Organs on Demand: Breakthroughs and Challenges in Models of Organogenesis.
In recent years, functional three-dimensional (3D) tissue generation in vitro has been significantly advanced by tissue-engineering methods, achieving better reproduction of complex native organs compared to conventional culture systems. This review will discuss traditional 3D cell culture techniques as well as newly developed technology platforms. These recent techniques provide new possibilities in the creation of human body parts and provide more accurate predictions of tissue response to drug and chemical challenges. Given the rapid advancement in the human induced pluripotent stem cell (iPSC) field, these platforms also hold great promise in the development of patient-specific, transplantable tissues and organs on demand.


Effective tools for the trace element characterization of tissues: neutron activation analysis and voltammetry.
The National Biomonitoring Specimen Bank at the National Institute of Standards and Technology applies a variety of techniques for extensive characterization of banked samples. To determine a large number of trace elements in small samples at low levels, instrumental neutron activation analysis has been combined with voltammetry. The two methods produce high quality data for thirty pollutant and biological trace elements. Results on archived specimens of human livers and intercomparisons of the two methods are reported.


Interaction of curcumin with intravenous immunoglobulin: a fluorescence quenching and Fourier transformation infrared spectroscopy study.
The interaction of curcumin with intravenous immunoglobulin (IVIG) mainly composed of immune gamma globulin (IgG) was studied in vitro by spectroscopic methods including fluorescence spectroscopy and Fourier transformation infrared (FTIR) spectroscopy. Docking was used to calculate the interaction mode between curcumin and IVIG. The binding parameters for the reaction were calculated according to the Sips equation, which suggested that the binding of IVIG to curcumin was characterized by two binding sites with the average affinity constant K(o) at 1.170 x 10(4) M(-1) (296 K), and it was a non-specific and weak drug-protein interaction. The secondary structure compositions of free IVIG and its curcumin complexes were calculated by the FTIR difference spectra, self-deconvolution, second derivative resolution enhancement and the curve-fitting procedures of amide I band. The observed spectral changes indicate a partial unfolding of the protein structure, but the typical beta structural conformation of IVIG is still retained. The average binding distance between curcumin and the chromophore of IVIG (5.57 nm) was obtained using the theory of Förster energy transfer. IVIG can serve as transport protein (carrier) for curcumin.


Direct Endovascular Thrombectomy or With Prior Intravenous Thrombolysis for Acute Ischemic Stroke: A Meta-Analysis.
Background and purpose: It is unclear whether endovascular thrombectomy alone compared with intravenous thrombolysis combination with endovascular thrombectomy can achieve similar neurological outcomes in patients with acute large vessel occlusion stroke. We aimed to perform a systematic review and meta-analysis of randomized controlled trials to compare endovascular thrombectomy alone or intravenous thrombolysis plus endovascular thrombectomy in this population. Methods: We systematically searched PubMed, Embase, and ClinicalTrials.gov. We restricted our search to randomized clinical trials that examined the clinical outcomes of endovascular thrombectomy alone vs. intravenous thrombolysis plus endovascular thrombectomy. The Cochrane risk of bias tool was used to assess study quality. Random-effects meta-analyses were used for evaluating all outcomes. Results: Total three randomized controlled trials with 1,092 individuals enrolled were included in the meta-analysis, including 543 (49.7%) who received endovascular thrombectomy alone and 549 (50.3%) who received intravenous thrombolysis plus endovascular thrombectomy. The primary outcome of 90-day functional independence (modified Rankin scale (mRS) score ≤ 2) was 44.6% (242/543) in the endovascular thrombectomy alone group vs. 42.8% (235/549) in the alteplase with endovascular thrombectomy group (odds ratio (OR), 1.08 [95% CI, 0.85-1.38]; P = 0.0539). Among pre-specified secondary outcomes, no significant between-group differences were found in excellent outcome (mRS score ≤ 1) (OR, 1.12 [95% CI, 0.85-1.47]; P = 0.418), mortality at 90 days (OR, 0.93 [95% CI, 0.68-1.29]; P = 0.673), successful reperfusion (thrombolysis in cerebral infarction 2b-3) (OR, 0.75 [95% CI, 0.54-1.05]; P = 0.099), and symptomatic intracranial hemorrhage (OR, 0.72 [95% CI, 0.45-1.15]; P = 0.171). Conclusions: Among patients with acute ischemic stroke in the anterior circulation within 4.5 h from the onset, endovascular thrombectomy alone was non-inferior to combined intravenous thrombolysis and endovascular thrombectomy.


[Reversible brain damage following acute poisoning with an organic solvent determined by magnetic resonance].
Acute exposure to the effects of volatile solvents is characterized by the abrupt onset of symptoms and signs of poisoning, and relatively fast recovery in the majority of cases. We report a 24-year-old patient with an acute, accidental poisoning with a mixture of volatile organic solvents (most probably toluene, styrene and xylene), which led to the development of upward gaze paresis, diplopia, hemiparesis, ataxic gate, and the late onset truncal ataxia episodes. After 6 weeks, he recovered completely, while his extensive brain MRI lesions in the caudate nuclei, laterobasal putaminal regions, bilateral anterior insular cortex, central midbrain tegmental area) withdrew completely after 4 months. Acute toxic encephalopathy should be a part of the differential diagnosis in any patient with acute neurobehavioral and neurological deficit.


Induction of graft-versus-autoimmune (GVA) disease effect against refractory psoriasis by complete donor-type chimerism and graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
A 67-year-old man with AML, who had a 21-year history of psoriasis without remission, received a reduced-intensity transplantation from an HLA-identical sibling. The preparative regimen consisted of busulfan and fludarabine. Graft-versus-host-disease (GVHD) prophylaxis was cyclosporine and methotrexate. Psoriasis was completely resolved on day 18. The subsequent clinical course was uneventful until day 42, when psoriasis recurred at the same sites as before RIST. Peripheral blood examined on day 63 showed mixed chimerism with 54% recipient type. Cyclosporine was rapidly tapered off over the next 2 weeks. On day 90, 100% donor-type chimerism was confirmed. Subsequently, psoriasis improved simultaneously with the occurrence of mucositis and rash as a manifestation of GVHD. Scattered erythematous patches of psoriasis disappeared again by day 105. We initiated 0.5 mg/kg prednisolone on day 119, and resumed cyclosporine on day 133. At 7 months after RIST, he still suffers from chronic GVHD, but his psoriasis remains in remission for the first time in 21 years. The anti-psoriasis effect of the conditioning is mild and transient, while the graft-versus-autoimmunity effect, related to the induction of complete donor-type chimerism and GVHD, is more profound and persisting. A graft-versus-autoimmunity effect lies in the delicate balance between alloimmunity and immunosuppressant used for GVHD prophylaxis/treatment.


Effect of remifentanil with and without atropine on heart rate variability and RR interval in children.
Remifentanil can cause bradycardia either by parasympathetic activation or by other negative chronotropic effects. The high frequency (HF) component of heart rate variability (HRV) is a marker of parasympathetic activity. This study aimed to evaluate the effect of remifentanil on RR interval and on HRV in children. Forty children ASA I or II were studied after approval by the human studies committee and informed parental consent was obtained. After stabilisation at sevoflurane 1 MAC, they were randomly divided into two groups: one received a 20 microg.kg(-1) atropine injection (AT + REMI) and the other ringer lactate solution (REMI). Three minutes later, a 1 microg.kg(-1) bolus of remifentanil was administered over 1 min, followed by a continual infusion at 0.25 microg.kg(-1).min(-1) for 10 min increased to 0.5 microg.kg(-1).min(-1) for a further 10 min. A time varying, autoregressive analysis of RR sequences was used to estimate classical spectral parameters: low (0.04-0.15 Hz; LF) and high (0.15-0.45 Hz; HF) frequency, whereas the root mean square of successive differences of RR intervals (rmssd) was derived directly from the temporal sequence. Statistical analyses were conducted by means of the multiple correspondence analysis and with non parametrical tests. Remifentanil induced an RR interval lengthening, i.e. bradycardia, in both groups compared to pretreatment values and was associated with an increase of HF and rmssd only for the REMI group. The parasympathetic inhibition by atropine did not totally prevent remifentanil's negative chronotropic effect. A direct negative chronotropic effect of remifentanil is proposed.


A cell-free scaffold-based cartilage repair provides improved function hyaline-like repair at one year.
Bone marrow stimulation techniques in cartilage repair such as drilling are limited by the formation of fibrous to hyaline-like repair tissue. It has been suggested such techniques can be enhanced by covering the defect with scaffolds. We present an innovative approach using a polyglycolic acid (PGA)-hyaluronan scaffold with platelet-rich-plasma (PRP) in drilling. We asked whether (1) PRP immersed in a cell-free PGA-hyaluronan scaffold improves patient-reported 1-year outcomes for the Knee injury and Osteoarthritis Score (KOOS), and (2) implantation of the scaffold in combination with bone marrow stimulation leads to the formation of hyaline-like cartilage repair tissue. We reviewed 52 patients who had arthroscopic implantation of the PGA-hyaluronan scaffold immersed with PRP in articular cartilage defects of the knee pretreated with Pridie drilling. Patients were assessed by KOOS. At 9 months followup, histologic staining was performed in specimens obtained from five patients to assess the repair tissue quality. The KOOS subscores improved for pain (55 to 91), symptoms (57 to 88), activities of daily living (69 to 86), sports and recreation (36 to 70), and quality of life (38 to 73). The histologic evaluation showed a homogeneous hyaline-like cartilage repair tissue. The cell-free PGA-hyaluronan scaffold combined with PRP leads to cartilage repair and improved patient-reported outcomes (KOOS) during 12 months of followup. Histologic sections showed morphologic features of hyaline-like repair tissue. Long-term followup is needed to determine if the cartilage repair tissue is durable. Level IV, therapeutic study. See the Guidelines for Authors for a complete description of levels of evidence.


Evaluation of ER, PgR, HER-2, Ki-67, cyclin D1, and nm23-H1 as predictors of pathological complete response to neoadjuvant chemotherapy for locally advanced breast cancer.
The purpose of this study was to evaluate the importance of biological markers to predict pathologic complete response (pCR) to neoadjuvant docetaxel plus epirubicin combination chemotherapy in patients with locally advanced breast cancer (LABC). Two hundred and twenty consecutive patients with LABC who had received neoadjuvant chemotherapy (NCT) with docetaxel and epirubicin from March 2006 to March 2009 were included in this retrospective study. The pre- and post-neoadjuvant chemotherapy (NCT) treatment expression levels and changes of Ki-67 proliferation index, estrogen receptor (ER), progesterone receptor (PgR), epidermal growth factor receptor 2 (HER-2), cyclin D1, and nm23-H1 were detected by immunohistochemistry (IHC). The pCR rate was 9.1% (95% CI, 5.3-12.9%). In univariate analysis, poor tumor differentiation, OR after 2 cycles of NCT, both negative of ER/PgR, negative HER-2, positive cyclin D1, and positive nm23-H1 were found to be significantly predictive of a pCR. Histological grade and ER/PgR status were significant for pCR on multivariate analysis (P = 0.023 and 0.003, respectively). The expression levels of cyclin D1 (median, 8% vs. 9%; P = 0.016) after NCT treatment increased significantly, while the median Ki-67 proliferation index was dramatically decreased after NCT treatment from 35 to 15% (P = 0.036). However, after a Bonferroni adjustment, only the difference of Ki-67 proliferation index was still significant (P = 0.026). Histological grade and ER/PgR status are independent predictive factors of pCR to neoadjuvant docetaxel plus epirubicin combination chemotherapy in locally advanced breast cancer. Expression of HER-2, Ki-67, cyclin D1, and nm23-H1 were not predictive for pCR.


Low-to-High Cross-Frequency Coupling in the Electrical Rhythms as Biomarker for Hyperexcitable Neuroglial Networks of the Brain.
One of the features used in the study of hyperexcitablility is high-frequency oscillations (HFOs, >80 Hz). HFOs have been reported in the electrical rhythms of the brain's neuroglial networks under physiological and pathological conditions. Cross-frequency coupling (CFC) of HFOs with low-frequency rhythms was used to identify pathologic HFOs in the epileptogenic zones of epileptic patients and as a biomarker for the severity of seizure-like events in genetically modified rodent models. We describe a model to replicate reported CFC features extracted from recorded local field potentials (LFPs) representing network properties. This study deals with a four-unit neuroglial cellular network model where each unit incorporates pyramidal cells, interneurons, and astrocytes. Three different pathways of hyperexcitability generation-Na - ATPase pump, glial potassium clearance, and potassium afterhyperpolarization channel-were used to generate LFPs. Changes in excitability, average spontaneous electrical discharge (SED) duration, and CFC were then measured and analyzed. Each parameter caused an increase in network excitability and the consequent lengthening of the SED duration. Short SEDs showed CFC between HFOs and theta oscillations (4-8 Hz), but in longer SEDs the low frequency changed to the delta range (1-4 Hz). Longer duration SEDs exhibit CFC features similar to those reported by our team. First, Identifying the exponential relationship between network excitability and SED durations; second, highlighting the importance of glia in hyperexcitability (as they relate to extracellular potassium); and third, elucidation of the biophysical basis for CFC coupling features.


Chronic mild diarrhoea, stunted growth and neuromuscular abnormalities.
This report describes a 3 year-old girl with signs of ventricular hypertrophy, short stature, and persistent diarrhoea (without steatorrhoea or creatorrhoea) which was resistant to therapy. There was no clinical evidence of myopathy but a myopathic pattern was found on electromyography. Biochemical studies revealed no abnormalities. Routine histological studies of biopsied muscle showed no obvious structural abnormalities. Examination of 1 micrometer tissue sections revealed groups of atrophic fibers. Electronmicroscopy revealed widened spaces between the myofibrils with disruption of filament arrangement. The mitochondria in the motor end-plates were very distended and almost devoid of cristae.


Studies on phosphatidylcholine model membranes. I. Iodine permeability measurement by specific ion electrode.
An iodide specific ion electrode was used to measure iodide released from egg phosphatidylcholine liposomes after passage through an ion exchange column. The permeation process was shown to be a sum of two separate first order processes. The method permits linear initial rates of iodide release to be determined for the first 5 min of permeation. Iodide permeability in the absence of Tris buffer was found to be a decreasing function of pH. In the presence of Tris, iodide permeability went through a minimum ofrom ph 7.3-8.5. the permeability was found to decrease when cholesterol was incorporated into the liposomes.


Expression relationship and significance of NEAT1 and miR-27a-3p in serum and cerebrospinal fluid of patients with Alzheimer's disease.
To explore the expression relationship and significance of long chain non-coding RNA nuclear-enriched abundant transcript 1 (LncRNA NEAT1) and miR-27a-3p in serum and cerebrospinal fluid of patients with Alzheimer's disease (AD). Sixty-six AD patients received by the Department of Neurology of our hospital from October 2019 to September 2021 were gathered, according to the Clinical Dementia Rating Scale (CDR) score, they were grouped into mild group (≤1 point, n = 41) and moderate-to-severe group (> 1 point, n = 25). Another 32 cases of serum and cerebrospinal fluid samples from outpatient physical examination personnel were regarded as the control group. The general materials on all subjects was recorded and cognition was assessed;real-time quantitative PCR was performed to measure the expression levels of miR-27a-3p and NEAT1 in serum and cerebrospinal fluid;enzyme-linked immunosorbent assay was performed to measure the protein levels of β-amyloid precursor protein cleaving enzyme 1 (BACE1), β-amyloid (Aβ) 40 and Aβ42 in cerebrospinal fluid;Spearman's method was performed to analyze the correlation of serum miR-27a-3p and NEAT1 levels with MMSE and MoCA scores;Pearson method was performed to analyze the correlation between serum miR-27a-3p and NEAT1 levels and Aβ deposition standard uptake value ratio (SUVR) and cerebrospinal fluid miR-27a-3p, NEAT1, BACE1, Aβ42 and Aβ40 levels. The MMSE score, MoCA score, serum miR-27a-3p level, cerebrospinal fluid miR-27a-3p, Aβ42 levels and Aβ42/Aβ40 ratio of AD patients in mild group and moderate-to-severe group were all lower than those in the control group, and the moderate-to-severe group were lower than the mild group (all P < 0.05);the serum NEAT1 level, SUVR, and cerebrospinal fluid NEAT1 and BACE1 levels were higher than those in the control group, and the moderate-to-severe group were higher than the mild group (all P < 0.05). Serum NEAT1 level in AD patients was positively correlated with SUVR, cerebrospinal fluid NEAT1 and BACE1 (r = 0.350, 0.606, 0.341, all P < 0.05);serum miR-27a-3p level was positively correlated with cerebrospinal fluid miR-27a-3p level (r = 0.695, P < 0.05), and negatively correlated with SUVR and cerebrospinal fluid BACE1 level (r = - 0.521, - 0.447, both P < 0.05). The expression trends of NEAT1 and miR-27a-3p in the serum and cerebrospinal fluid of AD patients are consistent, the level of NEAT1 is increased, and the level of miR-27a-3p is decreased. The levels of the two are negatively correlated, which is related to the degree of Aβ deposition in the brain of AD patients and is involved in the progression of AD.


Measurement of IgE on rat mast cells: relation to serum IgE and allergen-induced histamine release.
IgE antibodies against trinitrophenylated ovalbumin (TNP-OVA) were raised in Brown Norway rats by a highly reproducible immunization procedure. With these rats, the kinetics of the IgE response was studied, both for free circulating and cell-bound IgE. Cell-bound IgE was dissociated from peritoneal cell suspensions at acid pH; TNP-specific and total IgE in serum and in eluates of peritoneal cells were determined by radioimmunoassay. Both for total and TNP-specific IgE, a significant correlation was found between the serum IgE level and the amount of IgE molecules per mast cell. One day before TNP hapten could induce histamine release from mast cells, TNP-specific IgE appeared in the circulation and on the cells. These results suggest that also in active sensitization, there is a lag time for sensitization of mast cells.


Cross injection analysis: concept and operation for simultaneous injection of sample and reagents in flow analysis.
This work presents a new flow injection strategy, called 'cross injection analysis' or CIA, an alternative cost-effective approach in flow analysis. The flow platform is made from a rectangular acrylic block, approximately 5×3×1.5 cm (x×y×z), with crossing cylindrical channels drilled out along the x- and y-axis of the block. The outlet from the single x-axis channel is connected to a detector flow cell. This channel is filled with the carrier solution. The flow in the x-axis channel is driven by a computer controlled single-channel peristaltic pump. The multiple y-axis channels, running perpendicular to the x-channel, are connected to a multi-channel peristaltic pump. These channels contain the sample and reagent solutions that flow across the intersection zones of the channels. To mix the sample and reagent with subsequent detection of the reaction zone, flow is applied along the x-axis channel, while flow in the y-axis channels is stopped. We successfully demonstrated the validity of the CIA technique by the spectrometric determination of Fe(II) using 1,10-phenanthroline and the speciation of Fe(II) and Fe(III). To place the CIA technique within the context of flow analysis, a brief overview of the evolution of flow injection analysis and its later innovative development is included.


Natural products as potent inhibitors of hypoxia-inducible factor-1α in cancer therapy.
Hypoxia is a prominent feature of tumors. Hypoxia-inducible factor-1α (HIF-1α), a major subunit of HIF-1, is overexpressed in hypoxic tumor tissues and activates the transcription of many oncogenes. Accumulating evidence has demonstrated that HIF-1α promotes tumor angiogenesis, metastasis, metabolism, and immune evasion. Natural products are an important source of antitumor drugs and numerous studies have highlighted the crucial role of these agents in modulating HIF-1α. The present review describes the role of HIF-1α in tumor progression, summarizes natural products used as HIF-1α inhibitors, and discusses the potential of developing natural products as HIF-1α inhibitors for the treatment of cancer.


Prevalence of overweight and obesity and its associated factors: findings from National Nutrition and Health Survey in Taiwan, 1993-1996.
To report the overall and regional prevalence of obesity/overweight in Taiwan and to study its associated risk factors. A total of 3046 adults > or = 20 years of age collected in National Nutrition and Health Survey in Taiwan, 1993-1996. Prevalence rates of overweight and obesity were 21.1 and 4.0% under the current WHO definition. The prevalence rates of overweight and obesity, using the Taiwanese definition (BMI = 24-26.99 kg/m(2) and > or = 27 kg/m(2), respectively), were 22.9 and 10.5% for males and 20.3 and 13.2% for females, respectively. The highest prevalence rates of obesity were found in the mountainous areas. In addition to age and residing location, education level in women and metabolic equivalent (MET) score and alcohol consumption in men were correlates of obesity. Effects of nutrition/health-related behaviors might be in part explained by education level and residing location of the subjects. The prevalence of obesity defined by WHO criteria among people in Taiwan was moderate, with considerable regional variation. The regional differences in obesity prevalence could not be completely accounted for by the sociodemographic and lifestyle factors studied.


Neural network functional connectivity during and after an episode of delirium.
Delirium is a common and potentially life-threatening clinical syndrome. The authors investigated resting-state functional connectivity in patients with delirium to elucidate possible neural mechanisms underlying this disorder. Twenty-two patients underwent initial functional MRI at rest during an episode of delirium. Of these patients, 14 completed follow-up scans after the episode resolved. Twenty-two comparison subjects without delirium also underwent scanning. The authors assessed cortical functional connectivity using the seed region of the posterior cingulate cortex and functional connectivity strengths between a priori subcortical regions related to acetylcholine and dopamine on data from 20 initial and 13 follow-up scans. Dorsolateral prefrontal cortex activity and posterior cingulate cortex activity were inversely correlated in comparison subjects but strongly correlated in patients during an episode of delirium as indicated by increased functional connectivity between the two regions. Although precuneus activity was positively correlated with posterior cingulate cortex activity in comparison subjects, the correlation was further increased in patients during an episode of delirium, and the increment was associated with less severity and shorter duration of delirium. Functional connectivity strengths of the intralaminar thalamic and caudate nuclei with other subcortical regions were reduced during an episode of delirium but recovered after resolution of the episode. These findings suggest that the disruption in reciprocity of the dorsolateral prefrontal cortex with the posterior cingulate cortex and reversible reduction of functional connectivity of subcortical regions may underlie the pathophysiology of delirium. In addition, enhanced integration in the posteromedial cortices may account for facilitating the rapid improvement of delirium.


Harnessing technology and molecular analysis to understand the development of cardiovascular diseases in Asia: a prospective cohort study (SingHEART).
Cardiovascular disease (CVD) imposes much mortality and morbidity worldwide. The use of "deep learning", advancements in genomics, metabolomics, proteomics and devices like wearables have the potential to unearth new insights in the field of cardiology. Currently, in Asia, there are no studies that combine the use of conventional clinical information with these advanced technologies. We aim to harness these new technologies to understand the development of cardiovascular disease in Asia. Singapore is a multi-ethnic country in Asia with well-represented diverse ethnicities including Chinese, Malays and Indians. The SingHEART study is the first technology driven multi-ethnic prospective population-based study of healthy Asians. Healthy male and female subjects aged 21-69 years old without any prior cardiovascular disease or diabetes mellitus will be recruited from the general population. All subjects are consented to undergo a detailed on-line questionnaire, basic blood investigations, resting and continuous electrocardiogram and blood pressure monitoring, activity and sleep tracking, calcium score, cardiac magnetic resonance imaging, whole genome sequencing and lipidomic analysis. Outcomes studied will include mortality and cause of mortality, myocardial infarction, stroke, malignancy, heart failure, and the development of co-morbidities. An initial target of 2500 patients has been set. From October 2015 to May 2017, an initial 683 subjects have been recruited and have completed the initial work-up the SingHEART project is the first contemporary population-based study in Asia that will include whole genome sequencing and deep phenotyping: including advanced imaging and wearable data, to better understand the development of cardiovascular disease across different ethnic groups in Asia.


Corn cob fusariosis - Natural infection of various genotypes in 1985 and 1986.
Corn cob fusariosis symptoms were observed at four localities of Poland: Radzikow /Central region/, Kobierzyce /South West/, Swadzim /Central West/ and Smolice /Central South/, during the 1985 and 1986 growing season. SpeciesF. subglatinans was found as dominating, causing in about 95% of affected cobs symptoms of "pink ear rot". The other important species ofFusarium which infected corn cobs wereF. culmorum, F. graminearum, F. sporotrichioides, F. avenaceum, F. moni1i forme. A first time in Poland was found the speciesF. crookhiellense. The intensity of particular genotypes fusariosis was expressed as fusariosis index /Fi/ ranging from 0 to 500. Susceptibility to Fusarium ear rot differed significantly between examined corn hybrids and varieties from 0 to 245 Fi, it let to eliminate hybrids very susceptible toFusaria infection of cob.


Incidence, impact and risk factors for multidrug-resistant organisms (MDRO) in patients with major trauma: a European Multicenter Cohort Study.
The burden of MDRO in health systems is a global issue, and a growing problem. We conducted a European multicenter cohort study to assess the incidence, impact and risk factors for multidrug-resistant organisms in patients with major trauma. We conducted this study because the predictive factors and effects of MDRO in severely injured patients are not yet described. Our hypothesis is that positive detection of MDRO in severely injured patients is associated with a less favorable outcome. Retrospective study of four level-1 trauma centers including all patients after major trauma with an injury severity score (ISS) ≥ 9 admitted to an intensive care unit (ICU) between 2013 and 2017. Outcome was measured using the Glasgow outcome scale (GOS). Of 4131 included patients, 95 (2.3%) had a positive screening for MDRO. Risk factors for MDRO were male gender (OR 1.73 [95% CI 1.04-2.89]), ISS (OR 1.01 [95% CI 1.00-1.03]), PRBC's given (OR 1.73 [95% CI 1.09-2.78]), ICU stay > 48 h (OR 4.01 [95% CI 2.06-7.81]) and mechanical ventilation (OR 1.85 [95% CI 1.01-3.38]). A positive MDRO infection correlates with worse outcome. MDRO positive cases GOS: good recovery = 0.6%, moderate disability = 2.1%, severe disability = 5.6%, vegetative state = 5.7% (p < 0.001). MDRO in severely injured patients are rare but associated with a worse outcome at hospital discharge. We identified potential risk factors for MDRO in severely injured patients. Based on our results, we recommend a standardized screening procedure for major trauma patients.


Treatment Outcomes and Effects of Ethanol Sclerotherapy on Systemic Coagulation Profile of Patients with Venous Malformation.
Venous malformations (VMs) and sclerotherapy may disrupt the normal systemic coagulation profile in individuals. This study investigated a correlation between the clinical efficacy of sclerotherapy in the treatment of VMs and the changes in coagulation indexes to provide data that will inform the future application of this therapy. From September 2019 to September 2020, 61 patients were enrolled in this study to receive sclerotherapy with absolute alcohol. The clinical outcomes and the coagulation profile were assessed. Sclerotherapy induced increasing fibrin (original) degradation products (FDP) and D-dimer (D-D) levels. The changes in FDP and D-D level pretreatment and posttreatment were positively correlated with treatment outcomes. Moreover, a repeated treatment with absolute alcohol may restore normal levels of FDP and D-D. Upregulation of FDP and D-D levels after sclerotherapy results in good therapeutic outcomes. Therefore, monitoring changes in FDP and D-D levels in patients with VMs undergoing sclerotherapy may reflect the effects of sclerotherapy.


Investigations of step-growth thiol-ene polymerizations for novel dental restoratives.
The goal of this work was to investigate the feasibility of formulating novel dental restorative materials that utilize a step-growth thiol-ene photopolymerization. Particularly, we are aiming to significantly reduce the polymerization shrinkage and shrinkage stress while retaining adequate physical properties as compared to current dimethacrylatre-based systems. The thiol-ene system is composed of a 4:3 molar mixture of triallyl-1,3,5-triazine-2,4,6-trione (TATATO) and pentaerythritol tetramercaptopropionate (PETMP). The simultaneous measurement of shrinkage stress and functional group conversion was performed. Solvent extraction of unreacted monomers and dynamic mechanical analysis on the polymer networks that were formed were also studied. Flexural strength was measured for both filled and unfilled PETMP/TATATO and Bis-GMA/TEGDMA systems. Photopolymerization of PETMP/TATATO occurs at a much higher rate, with the maximum polymerization rate six times faster, than Bis-GMA/TEGDMA cured under the identical conditions. The results from the simultaneous measurement of shrinkage stress and conversion showed that the onset of shrinkage stress coincides with the delayed gel point conversion, which is predicted to be 41% for the 3:4 stoichiometric PETMP/TATATO resin composition. The maximum shrinkage stress developed for PETMP/TATATO was about 0.4 MPa, which was only approximately 14% of the maximum shrinkage stress of the Bis-GMA/TEGDMA system. Adequate flexural strength and flexural modulus values were obtained for both filled and unfilled PETMP/TATATO systems. The dramatically reduced shrinkage stress, increased polymerization rate, significance increased functional group conversion, and decreased leachable species are all benefits for the use-of thiol-ene systems as potential dental restorative materials.


Correlation with Platelet Parameters and Genetic Markers of Thrombophilia Panel (Factor II g.20210G>A, Factor V Leiden, MTHFR (C677T, A1298C), PAI-1, β-Fibrinogen, Factor XIIIA (V34L), Glycoprotein IIIa (L33P)) in Ischemic Strokes.
An important type of arterial thrombosis, ischemic stroke is associated with increased mortality risk, severe disability and life quality impairment. In this study, we analyzed mean platelet volume, platelet count values and genetic thrombophilia markers of patients who have ischemic stroke history and searched the relationship with genetic predisposition of ischemic strokes and platelet parameters. A retrospective, clinical trial was performed by reviewing the ischemic stroke history (except cryptogenic events) of 599 patients and 100 controls. The results of the genetic thrombophilia panel were used to classify the study group and control group into low and high risk for thrombophilia groups. The high-risk group included patients homozygous/heterozygous for Factor II g.20210G>A or Factor V Leiden mutations with/without any other polymorphism. The low-risk group included patients heterozygous or homozygous for MTHFR (C677T, A1298C), PAI-1, β-fibrinogen, Factor XIIIA (V34L) and glycoprotein IIIa (L33P) polymorphisms or negative in terms of both mutations and polymorphisms. The results of study showed us that high-risk group mutations are important risk factors for ischemic stroke but low-risk group polymorphisms are not significant. According to platelet parameters, although there was a significant difference between MPV and PLT values of ischemic stroke and control group, thrombophilia mutations and polymorphisms have not a significant effect on MPV and PLT values in ischemic stroke patients.


Protective antibodies against a sphingomyelinase D from Loxosceles intermedia spider venom elicited in mice with different genetic background.
In the present investigation we used a recombinant LiD1 toxin, named rLiD1his, from Loxosceles intermedia brown spider to elicit specific antibodies in mice carrying different Human Leukocyte Antigens class II (HLAII) {DRB1.0401 (DR4), DQB1.0601 (DQ6) and DQB1.0302 (DQ8)} as well as in BALB/C and C57BL/6 control mice. All mice strains produced high antibody titers against rLiD1his but DR4 mice antibodies (the lower responder mice) were not able to recognize L. intermedia crude venom. The anti-rLiD1his sera, except from DR4 mice, were able to neutralize dermonecrotic, hemorrhagic and edematogenic effects of rLiD1his in naïve rabbits. Overlapping peptides from the amino acid sequence of LiD1 toxin were prepared by SPOT method and differences in LiD1 epitope recognition were observed using different mice anti-rLiD1his sera. The region (160)DKVGHDFSGNDDISDVGK(177) was recognized by transgenic DQ8 and DQ6 mice sera. Other epitopes were recognized by at least two different animals' sera including (10)MGHMVNAIGQIDEFVNLG(27), (37)FDDNANPEYTYHGIP(51), (70)GLRSATTPGNSKYQEKLV(87) and (259)AAYKKKFRVATYDDN(273). Among these epitopes, the epitopes 37-51 and 160-177 have already been shown in previously studies as good candidates to be used alone or combined with other peptides to induce protective immune response against Loxosceles venoms. The results presented here highlight the importance of HLAII in antibody response and recognition of specific B-cell epitopes of rLiD1his spider toxin according to HLAII type and impact in the epitopic vaccine development against this spider.


[Faced with conjugal violence, the need for a global care].
Domestic violence is a public health and societal problem that must be treated in three ways: the perpetrator, the victim and the children. The treatment of this violence is multidisciplinary. It requires the commitment of everyone in the interest of all the protagonists of the family unit. Networking is essential for health professionals, social workers, police forces and the justice system.


Degradation of three fungicides following application on strawberry and a risk assessment of their toxicity under greenhouse conditions.
The health risk to humans of pesticide application on minor crops, such as strawberry, requires quantification. Here, the dissipation and residual levels of three fungicides (pyraclostrobin, myclobutanil, and difenoconazole) were studied for strawberry under greenhouse conditions using high-performance liquid chromatography (HPLC)-tandem mass spectrometry after Quick, Easy, Cheap, Effective, Rugged, and Safe extraction. This method was validated using blank samples, with all mean recoveries of these three fungicides exceeding 80%. The residues of all three fungicides dissipated following first-order kinetics. The half-lives of pyraclostrobin, myclobutanil, and difenoconazole were 1.69, 3.30, and 3.65 days following one time application and 1.73, 5.78, and 6.30 days following two times applications, respectively. Fungicide residue was determined by comparing the estimated daily intake of the three fungicides against the acceptable daily intake. The results indicate that the potential health risk of the three fungicides was not significant in strawberry when following good agricultural practices (GAP) under greenhouse conditions.


Heterogeneous effects of cytotoxic chemotherapies for platinum-resistant ovarian cancer.
Single-agent chemotherapy with or without bevacizumab (Bev) is a standard therapy for platinum-resistant ovarian cancer (PR-OC). However, there is a lack of literature on chemotherapy agent selection in heterogenous PR-OC. Therefore, we aimed to clarify the heterogeneous treatment effects of each chemotherapy agent. Patients who underwent single-drug chemotherapy agents or Bev combination therapy for PR-OC between January 2009 and June 2022 were included in this study. We assessed the impact of each chemotherapy agent on the time to treatment failure (TTF) according to histological type, platinum-free interval (PFI), and Bev usage. A total of 158 patients received 343 different chemotherapy regimens. In patients with clear cell carcinoma/mucinous carcinoma (CC/MC), gemcitabine (GEM) had the strongest effect with a median TTF of 5.3 months, whilst nedaplatin (NDP) had the lowest effect with a median TTF of 1.4 months. In contrast, in the non-CC/MC group, irinotecan (CPT-11) and NDP had a better TTF than GEM and pegylated liposomal doxorubicin (PLD). There were notable differences in the treatment efficacy of NDP according to PFI. Specifically, NDP prolonged the TTF in patients with a PFI ≥ 3 months. Compared with GEM alone, GEM + Bev tended to prolong the TTF more effectively; however, an additive effect was not observed with PLD + Bev. This study demonstrated that the effect of chemotherapy agents differed according to the tumor and background characteristics of the patient. Our findings will improve selection of effective therapies for patients with PR-OC by considering their background characteristics.


Long-term effects of early environment on the brain: Lesson from rodent models.
The postnatal period is characterized by extensive neuronal plasticity, synaptic organization, and remodeling. High neuroplasticity renders the brain sensitive to the remodeling effects induced by environmental factors, such as exposure to adversity, which can imprint neurochemical, neuroendocrine, morphological, and behavioral changes. Early experiences that influence developmental trajectories during maturation of the brain can have a wide range of long-lasting effects, modulating stress-coping strategies in adult life and inducing vulnerability or resilience to psychopathologies, depending on the gene×later experience interplay. Future studies will clarify how manipulation of the early environment induces these effects acting on genetic and epigenetic factors.


Biochemical evaluation of the inflammatory changes in cardiac, hepatic and renal tissues of adriamycin-administered rats and the modulatory role of exogenous heparin-derivative treatment.
The aim of the present work is to evaluate the role of a heparin derivative, low molecular weight heparin (LMWH), certoparin on the inflammatory changes in adriamycin (ADR) cytotoxicity on a biochemical basis. Male Wistar rats (140+/-10g) were divided into four groups: untreated control, ADR group (a single dose intravenous injection of 7.5 mg/kg ADR), LMWH control (300 microg/(day rat) s.c. for 1 week) and ADR plus LMWH group (7.5 mg/kg ADR on day 1 of study period followed by LMWH treatment, 300 microg/(day rat) commencing on day 8 and continued for 1 week). At the end of the 2-week experimental period, biochemical assessment of the inflammatory status was carried out in the plasma, cardiac, hepatic and renal tissues. Increased concentrations of plasma C-reactive protein (CRP) and fibrinogen indicated severe inflammation in the ADR cytotoxic rats. These acute-phase inflammatory markers diminished significantly in the LMWH treated group, when compared with the cytotoxic group (p<0.001). Tissue damage was marked by elevated levels of plasma and tissue hexose, hexosamine, hexuronic acid and sialic acid, which were reversed on LMWH administration (p<0.001). The activities of lysosomal enzymes was measured in the experimental groups, and it was observed that the ADR induced rats showed a marked increase in the enzymic activities, while LMWH treated rats revealed normal activities. The present study throws light on the inflammatory changes in the ADR-challenged heart, liver and kidney tissues, and projects the biochemical basis for the anti-inflammatory property of the LMWH, certoparin.


Effect of diabetic retinopathy and diabetes on the intraocular straylight in pseudophakic eyes.
The aim of this study was to prove the relationship between the intraocular straylight level and diabetic retinopathy (DR) according to disease severity. Also, we aimed to evaluate whether diabetes mellitus (DM) per se could be a risk factor of increased intraocular straylight although we did not rely on a definite sign of DR in this study. In this prospective comparative study, ninety three eyes were enrolled and divided into four groups as follows: Group 1 (26 eyes), without DR or DM; Group 2 (25 eyes), with DM but without DR; Group 3 (21 eyes), mild to moderate non-proliferative DR; and Group 4 (21 eyes), severe non-proliferative DR. To measure the intraocular straylight in an objective manner, the C-quant straylight meter was used to preoperatively and 2 months postoperatively in all patients who underwent phacoemulsification surgery. All the patients also underwent a macular optical coherence tomography and hemoglobin A1c (HbA1c) analysis. A comparison of straylight levels adjusted by age among four groups was performed postoperatively. The postoperative level of intraocular straylight was statistically significantly different among four groups (P <0.05). When adjusted for ages, Group 4 showed the highest straylight level when compared with Group 3 and the other two groups (P <0.05). Group 1 showed the lowest straylight level in comparison with Group 2 and the other two groups (P <0.05). There was no significant correlation between HbA1c level, duration of diabetes and postoperative straylight level. The level of intraocular straylight at 2 months postoperatively had a tendency to increase as the severity of DR increased. Additionally, the straylight level was higher in DM patients without DR than in patients without DM. Therefore, the severity of DR seemed to influence the intraocular straylight level. Although there is no definite sign of DR, DM per se can be a risk factor for increasing intraocular straylight. In conclusion, the level of intraocular straylight seems to be a sensitive test for detecting early retinal damage secondary to DM.