In Hong Kong, smokers are butting out in record numbers.
Thanks to a partial ban on tobacco advertising and a concerted effort by antismoking advocates and hospitals, more than 100,000 people have quit smoking in Hong Kong in the last 3 years, giving the British territory one of the world's lowest smoking rates. This article examines initiatives behind the successful trend and identifies how Hong Kong is addressing the challenge of reducing smoking rates among youth, women and poor people.


Comparison of Unmanned Aerial Vehicle Technology Versus Standard Practice in Identification of Hazards at a Mass Casualty Incident Scenario by Primary Care Paramedic Students.
IntroductionThe proliferation of unmanned aerial vehicles (UAV) has the potential to change the situational awareness of incident commanders allowing greater scene safety. The aim of this study was to compare UAV technology to standard practice (SP) in hazard identification during a simulated multi-vehicle motor collision (MVC) in terms of time to identification, accuracy and the order of hazard identification. A prospective observational cohort study was conducted with 21 students randomized into UAV or SP group, based on a MVC with 7 hazards. The UAV group remained at the UAV ground station while the SP group approached the scene. After identifying hazards the time and order was recorded. The mean time (SD, range) to identify the hazards were 3 minutes 41 seconds (1 minute 37 seconds, 1 minute 48 seconds-6 minutes 51 seconds) and 2 minutes 43 seconds (55 seconds, 1 minute 43 seconds-4 minutes 38 seconds) in UAV and SP groups corresponding to a mean difference of 58 seconds (P=0.11). A non-parametric permutation test showed a significant (P=0.04) difference in identification order. Both groups had 100% accuracy in hazard identification with no statistical difference in time for hazard identification. A difference was found in the identification order of hazards. (Disaster Med Public Health Preparedness. 2018;12:631-634).


Breast cancer in Iran: a survival analysis.
A prospective study was undertaken to examine survival in Iranian breast cancer patients. One hundred and sixty-seven breast cancer patients diagnosed in 1997 were entered into the study and followed up for five years. The mean age of the patients at diagnosis was 47.2 (SD = 13.5), ranging from 24 to 81 years. A total of 39 patients were lost in the follow-up period, leaving 128 for analysis of data. Of these, 79 were alive and 49 were dead after five years. Most patients (61%) presented with advanced disease. Using life table analysis, the overall relative 5-year survival rate was found to be 62% (SE = 0.04). In addition, after adjustment for age at diagnosis, initial treatment (mastectomy, breast conserving surgery, and neo-adjuvant therapy), and disease stage, using Cox's regression model, it was found that receiving neo-adjuvant therapy as the initial treatment was an independent predictor of poorer survival (Hazard ratio = 4.56, 95% CI 2.20-9.44, P<0.0001). The other variables (older age and late stage disease), although associated with high hazards rates, were not significant. The study findings suggest that overall relative survival rate in Iranian breast cancer patients stands between western and eastern European countries and needs to be improved. It seems that early detection and better management using standard guidelines might contribute considerably to improvement of survival in women experiencing breast cancer.


Poly (ɛ-caprolactone)-chitosan-poly (vinyl alcohol) nanofibrous scaffolds for skin excisional and burn wounds in a canine model.
Poly (ɛ-caprolactone)-chitosan-poly (vinyl alcohol) (PCL: Cs: PVA) nanofibrous blend scaffolds were known as useful materials for skin wound healing and would help the healing process about 50% faster at the final time point. From the previous studies by the authors, PCL: Cs: PVA (in 2: 1: 1.5 mass ratio) nanofibres showed high efficacy in healing on rat models. In this study, the scaffolds were examined in burn and excision wounds healing on dogs as bigger models. The scaffolds were applied on dorsum skin wounds (n = 5) then macroscopic and microscopic investigations were carried out to measure the wounds areas and to track healing rate, respectively. Macroscopic results showed good aspect healing effect of scaffolds compared with control wounds especially after 21 days post-operating for both cutting and burn wounds. Pathological studies showed that the healing rates of the wounds covered with PCL: Cs: PVA nanofibrous scaffolds were much rapid compared to untreated wounds in control group. The immunogenicity of the scaffolds in canine model was also investigated. The findings showed that nanofibrous blend scaffolds was not immunogenic in humoural immune responses. All these results indicated that PCL: Cs: PVA nanofibrous web could be considered as promising materials for wounds healings.


Education as an Antidote to Cynicism: A Longitudinal Investigation.
Although cynical beliefs about human nature yield numerous adverse consequences for individuals' life outcomes and well-being, very little is known about factors that counteract the development of cynical beliefs. Drawing from the literature on the "education effect" describing the importance of education in overcoming close-mindedness and negative views of others, we propose that education can represent an antidote to cynicism. The results of two large-scale longitudinal studies showed that education was associated with lower levels of cynicism over time spans of 4 and 9 years. Longitudinal mediation analyses underscored the role of individual differences in perceived constraints, a facet of personal control, as the psychological mechanism underlying the education effect: Higher education is associated with a reduced perception of constraints, which is in turn related to less endorsement of cynical beliefs.


Characteristics of the tomato chromoplast revealed by proteomic analysis.
Chromoplasts are non-photosynthetic specialized plastids that are important in ripening tomato fruit (Solanum lycopersicum) since, among other functions, they are the site of accumulation of coloured compounds. Analysis of the proteome of red fruit chromoplasts revealed the presence of 988 proteins corresponding to 802 Arabidopsis unigenes, among which 209 had not been listed so far in plastidial databanks. These data revealed several features of the chromoplast. Proteins of lipid metabolism and trafficking were well represented, including all the proteins of the lipoxygenase pathway required for the synthesis of lipid-derived aroma volatiles. Proteins involved in starch synthesis co-existed with several starch-degrading proteins and starch excess proteins. Chromoplasts lacked proteins of the chlorophyll biosynthesis branch and contained proteins involved in chlorophyll degradation. None of the proteins involved in the thylakoid transport machinery were discovered. Surprisingly, chromoplasts contain the entire set of Calvin cycle proteins including Rubisco, as well as the oxidative pentose phosphate pathway (OxPPP). The present proteomic analysis, combined with available physiological data, provides new insights into the metabolic characteristics of the tomato chromoplast and enriches our knowledge of non-photosynthetic plastids.


Genetic heterogeneity in Italian families with IgA nephropathy: suggestive linkage for two novel IgA nephropathy loci.
IgA nephropathy (IgAN) is the most common glomerulonephritis worldwide, but its etiologic mechanisms are still poorly understood. Different prevalences among ethnic groups and familial aggregation, together with an increased familial risk, suggest important genetic influences on its pathogenesis. A locus for familial IgAN, called "IGAN1," on chromosome 6q22-23 has been described, without the identification of any responsible gene. The partners of the European IgAN Consortium organized a second genomewide scan in 22 new informative Italian multiplex families. A total of 186 subjects (59 affected and 127 unaffected) were genotyped and were included in a two-stage genomewide linkage analysis. The regions 4q26-31 and 17q12-22 exhibited the strongest evidence of linkage by nonparametric analysis (best P=.0025 and .0045, respectively). These localizations were also supported by multipoint parametric analysis, in which peak LOD scores of 1.83 ( alpha =0.50) and 2.56 ( alpha =0.65) were obtained using the affected-only dominant model, and by allowance for the presence of genetic heterogeneity. Our results provide further evidence for genetic heterogeneity among families with IgAN. Evidence of linkage to multiple chromosomal regions is consistent with both an oligo/polygenic and a multiple-susceptibility-gene model for familial IgAN, with small or moderate effects in determining the pathological phenotype. Although we identified new candidate regions, replication studies are required to confirm the genetic contribution to familial IgAN.


Determinants of utilization of Tay-Sachs screening.
To identify the characteristics of patients associated with optimal utilization of Tay-Sachs screening. Medical records of patients undergoing amniocentesis for genetic diagnosis were reviewed. Three hundred twenty-nine of 537 charts evaluated were from individuals at risk for Tay-Sachs heterozygosity. Among these, 213 couples had previously been screened for Tay-Sachs. In 116 couples, neither member of the couple had been screened before amniocentesis. A concurrent reference group consisted of 208 couples without an indication for Tay-Sachs screening. Patient characteristics, including ethnicity, genetic screening history, parental ages, and pregnancy history, were reviewed for each group. Analysis of variance and likelihood chi 2 test were used for statistical analysis. There were no significant differences in maternal age or reproductive history among the groups. The most common indication for amniocentesis was advanced maternal age for all three groups. However, the previously screened group was more than twice as likely to self-refer because of a positive family history or patient anxiety than was the unscreened group (P = .006). Conversely, the unscreened group was more than twice as likely as screened couples to be referred because of a positive high or positive low maternal serum alpha-fetoprotein level (P = .002). Despite 2 decades of professional and lay education, many couples are unaware of their individual risk for Tay-Sachs heterozygosity. Additional education, most likely at the professional level, is needed to maximize informed participation.


A preliminary study on ultrasound-guided percutaneous microwave ablation for palliative treatment of advanced head and neck malignancies.
To evaluate the safety and efficacy of ultrasound (US)-guided percutaneous microwave ablation (UgPMWA) for palliative treatment of advanced head and neck malignancies. This study includes 18 consecutive patients with advanced head and neck malignancies (n = 24), who have undergone UgPMWA for palliative treatment at our institution from December 2016 to April 2020. The maximum diameter and volume of the tumor were assessed by US, CT or MRI before microwave ablation (MWA), 1, 3 and 6 months after MWA and every 6 months thereafter. The quality of life was clinically assessed by the University of Washington Head and Neck Quality of Life questionnaire (UW-QOl). The success rate of tumor-targeting microwave antenna placement was 100%. No nerve injury and serious complications or death occurred during the perioperative period. The follow-up duration varied from 1 month to 38 months (11.56 ± 10.23 months) among patients. By the last follow-up before submission, the value of maximum diameter (5.00 ± 2.90 vs 3.28 ± 2.11 cm. p < 0.05) and tumor volume decreased significantly(74.35 ± 46.88 vs 47.45 ± 24.08 cm3. p < 0.05)respectively after palliative treatment with UgPMWA. UW-QOl of the patients was improved (59.24 ± 11.51 vs 69.84 ± 8.12, p < 0.05). UgPMWA is safe and effective for the palliative treatment of head and neck malignancies. Ultrasonic guidance can indicate an accurate location of the microwave antenna. It can also monitor the ablation area in real-time during the operation to avoid damage to surrounding normal tissues.


A genome-wide association study reveals additive and dominance effects on growth and fatness traits in large white pigs.
The dominance effect is a kind of non-additive effect due to the interaction between alleles at the same locus. Quantitative traits such as growth traits in farm animals have been found to be influenced by dominance effects. However, dominance effects are usually ignored in the genome-wide association study (GWAS) of complex traits for farm animals. In this study, we performed GWAS and genetic parameters estimation for the two traits age at 100 kg (AGE) and backfat thickness at 100 kg (BF) of 3572 Large White pigs. The pigs were from three breeding farms of China and were genotyped by an in-house designed 50k SNP chip. Our results showed significant non-zero variance for the dominance effect of AGE, while the dominance effect of BF was not significant. Using a GWAS model accounting for both additive and dominance effects, we identified three additive and two dominance significant SNPs for the trait AGE. For the trait BF, three genome-wide significant additive SNPs were detected, but no significant SNP was found for the dominance effect. In total, six important functional genes (NPAS3, USP16, PARN, ARL15, GPC3, ABHD4) near significant SNPs were identified as candidate genes associated with AGE or BF. Notably, ARL15 and PARN were associated with AGE near the dominance association signals. Overall, the newly detected SNPs and newly identified candidate genes in our study added new information about the genetic architectures of growth and fatness traits in pigs, and have the potential to be applied to the pig breeding program in the future.


A shared short-term memory system for stimulus duration and stimulus frequency.
Recent research has suggested the existence of a modality-independent memory system that is responsible for storing representations of simple, scalar stimulus attributes, such as the frequency of an auditory pure tone or the duration of a stimulus. In the present study, we modify an existing computational model of short-term memory (STM) for stimulus frequency to allow it to perform STM tasks for both stimulus frequency and stimulus duration, supporting the notion of a common scalar STM system. We further demonstrate the utility of the model by showing that it can reproduce the subjective shortening effect, a classic finding in the psychophysical literature.


Orodispersible films: Towards drug delivery in special populations.
Orodispersible films (ODF) hold promise as a novel delivery method, with the potential to deliver tailored therapies to different patient populations. This article reviews the current strides of ODF technology and some of its unmet quality and manufacturing aspects. A topic highlights opportunities and limitations of inkjet printed ODF as a population-specific drug delivery. Overall, this article aims to stimulate further research to fill the current knowledge gap between manufacturing and administration requirements of ODF targeting specific patient subpopulations such as geriatrics.


Using peer, self, and counselor ratings to evaluate treatment progress.
It is generally recognized that the evaluation of treatment progress requires multiple methods of assessment. To provide a basis for supplementing existing measures, the current study investigated the use of a peer rating methodology for evaluating the treatment progress of 381 probationers admitted to a four-month residential drug abuse facility. Self ratings of "working the program" (i.e., conscientiously participating in treatment) were compared with ratings by peers in the program and with ratings by counselors. Peer and counselor ratings were more highly correlated with each other than with client self ratings. Peer as well as self ratings detected differences between enhanced and standard counseling, and were related to individual difference measures known to be associated with treatment progress. In addition, peer midterm ratings of "working the program" were related to both self and counselor ratings of clients' endterm participation, and counselor ratings of the likelihood of remaining clean and sober. These findings support the use of peer ratings as additional indicators of treatment progress.


Protective factors for psychosocial outcomes following cumulative childhood adversity: systematic review.
The long-term cumulative impact of exposure to childhood adversity is well documented. There is an increasing body of literature examining protective factors following childhood adversity. However, no known reviews have summarised studies examining protective factors for broad psychosocial outcomes following childhood adversity. To summarise the current evidence from longitudinal studies of protective factors for adult psychosocial outcomes following cumulative exposure to childhood adversity. We conducted a formal systematic review of studies that were longitudinal; were published in a peer-reviewed journal; examined social, environmental or psychological factors that were measured following a cumulative measure of childhood adversity; and resulted in more positive adult psychosocial outcomes. A total of 28 studies from 23 cohorts were included. Because of significant heterogeneity and conceptual differences in the final sample of articles, a meta-analysis was not conducted. The narrative review identified that social support is a protective factor specifically for mental health outcomes following childhood adversity. Findings also suggest that aspects of education are protective factors to adult socioeconomic, mental health and social outcomes following childhood adversity. Personality factors were protective for a variety of outcomes, particularly mental health. The personality factors were too various to summarise into meaningful combined effects. Overall GRADE quality assessments were low and very low, although these scores mostly reflect that all observational studies are low quality by default. These findings support strategies that improve connection and access to education following childhood adversity exposure. Further research is needed for the roles of personality and dispositional factors, romantic relationship factors and the combined influences of multiple protective factors.


Synthesis of Substituted 1,6-Diarylnaphthalenes via a Tandem Claisen Rearrangement and Ene Reaction Protocol.
In this work, we developed a concise synthetic route for the synthesis of polysubstituted naphthalenes starting from commercially available isovanillin and its derivatives. Reaction with styryl bromide via O-styrylation, Claisen rearrangement, ene reaction, and O-alkylation occurred in high yields. The key structures were confirmed by single-crystal X-ray diffraction.


KATP channels in vascular smooth muscle.
ATP sensitive potassium channels (KATP channels) appear widely distributed in the vascular system. At the single channel level, channels with both small and large conductance have been described, though the former appear to be activated by potassium channel openers or ATP depletion in whole cell studies. KATP channels are inhibited by cytoplasmic ATP, and may be activated by intracellular nucleotide diphosphates. Regulation by intracellular metabolites confers a degree of sensitivity of the channel to the metabolic status of the cell, and there is evidence that KATP currents are activated during metabolic inhibition. In general, activation of KATP channels will lead to membrane hyperpolarisation and so to vasorelaxation. The functional role of the channel is being intensively studied at present. The channel may form a target for a number of endogenous vasodilators, and may be inhibited by some vasoconstrictors. It may be involved in the vasodilator response to hypoxia, and may contribute to the resting membrane potential of smooth muscle in some blood vessels.


Influence of different midsole foam in advanced footwear technology use on running economy and biomechanics in trained runners.
Ethylene and vinyl acetate (EVA) and polyether block amide (PEBA) are recently the most widely used materials for advanced footwear technology (AFT) that has been shown to improve running economy (RE). This study investigated the effects of these midsole materials on RE and biomechanics, in both fresh and worn state (after 450 km). Twenty-two male trained runners participated in this study. Subjects ran four 4-min trials at 13 km‧h-1 with both fresh EVA and PEBA AFT and with the same models with 450 km of wear using a randomized crossover experimental design. We measured energy cost of running (W/kg), spatiotemporal, and neuromuscular parameters. There were significant differences in RE between conditions (p = 0.01; n2 = 0.17). There was a significant increase in energy cost in the worn PEBA condition compared with new (15.21 ± 1.01 and 14.87 ± 0.99 W/kg; p < 0.05; ES = 0.54), without differences between worn EVA (15.13 ± 1.14 W/kg; p > 0.05), and new EVA (15.15 ± 1.13 w/kg; ES = 0.02). The increase in energy cost between new and worn was significantly higher for the PEBA shoes (0.32 ± 0.38 W/kg) but without significant increase for the EVA shoes (0.06 ± 0.58 W/kg) (p < 0.01; ES = 0.51) with changes in step frequency and step length. The new PEBA shoes had lower energy cost than the new EVA shoes (p < 0.05; ES = 0.27) with significant differences between conditions in contact time. There is a clear RE advantage of incorporating PEBA versus EVA in an AFT when the models are new. However, after 450 km of use, the PEBA and EVA shoes had similar RE.


Postjunctional vascular smooth muscle alpha-2 adrenoreceptors in human autonomic failure.
Animal studies have suggested that vasoconstrictor alpha-2 adrenoreceptors exist on vascular smooth muscle cells. We tested this hypothesis in a patient with severe autonomic failure who demonstrated a pressor response to oral clonidine (a selective alpha-2 adrenoreceptor partial agonist). After clonidine 0.8 mg orally, mean arterial pressure rose by 54 mm Hg. After pretreatment with prazosin (a selective alpha-1 adrenoreceptor antagonist) and confirmation of alpha-1 blockade, clonidine 0.8 mg still raised mean arterial pressure by 43 mm Hg. After pretreatment with yohimbine (a selective alpha-2 adrenoreceptor antagonist), clonidine 0.8 mg elevated mean arterial pressure by 13 mm Hg. Since alpha-1 antagonism does not block, and alpha-2 antagonism does not block the pressor effect of clonidine, we conclude that clonidine raised blood pressure in this severely affected autonomic failure patient by vascular alpha-2 adrenoreceptor stimulation. Thus, this provides pharmacological evidence that postjunctional vascular smooth muscle alpha-2 adrenoreceptors exist in man and can modulate blood pressure.


Comparative study of the fertility potential of men with only one testis.
The fertility potential of 54 men aged between 19 and 42 years, who had undergone unilateral orchidectomy was evaluated. In all cases the remaining testis was of normal volume and consistency. The patients were divided into four groups according to the cause of the orchidectomy: group I--cryptorchism (n = 19), group II--testicular torsion (n = 14), group III--testicular cancer (n = 12) and group IV--accidental (n = 9). The time between orchidectomy and seminal analysis varied from 6 months to 30 years (median 5 years). All semen samples were examined at the same laboratory, and no differences in sperm concentration were found among the groups. 53% in group I, 57% in group II, 50% in group III, and 56% in group IV had sperm counts of less than 20 million/ml. Our results suggest that unilateral orchidectomy leads to a considerable decrease in fertility potential, whatever the reason for it.


Blood lead levels in Noranda children following removal of smelter-contaminated yard soil.
In 1979, children two to five years of age living in Rouyn-Noranda, QC, in an urban district located within 1 km from a copper smelter had mean (geometric) blood lead levels (BLL) of 21 micrograms/dL. Afterwards, stack emissions were lowered. In 1989, mean (geom.) BLL were reduced to 11 micrograms/dL; 50% of the district children had BLL less than 10 micrograms/dL. In 1990-91, a $3 million top soil removal operation took place; residential lots having more than 500 ppm soil lead were decontaminated. In 1991, BLL were reduced to 7 micrograms/dL; 75% of the children had less than 10 micrograms/dL. Geographic analysis of the 1991 results showed that children with the highest BLL lived nearest to the smelter, where atmospheric dustfall to the ground reached 36 mg/m2/month. Follow-up pediatric blood lead campaigns are planned in 1993 and 1995, to evaluate the effects of an ongoing program for further reduction of atmospheric smelter emissions.


No association between pulmonary artery catheter use and postoperative complications in off-pump coronary artery bypass grafting: a single-center pilot study.
A pulmonary artery catheter is often used in cardiac surgery despite its uncertain effectiveness. The aim of this pilot study was to investigate the associations between the use of a pulmonary artery catheter and clinical outcomes in off-pump coronary artery bypass grafting. Patients over 20 years of age who had undergone off-pump coronary artery bypass grafting between December 2018 and November 2021 were enrolled in this single-center retrospective pilot study. The propensity score of pulmonary artery catheterization was calculated. Multivariate analysis including the propensity score as a covariate was performed to assess clinical outcomes. The primary outcome was the composite outcome of in-hospital death, unplanned intraoperative conversion to cardiopulmonary bypass, resuscitated cardiac arrest, mechanical circulatory support, myocardial infarction, stroke, new initiation of renal replacement therapy, inhaled nitric oxide, re-intubation and tracheostomy. Among the 315 patients who were enrolled, 298 were included in the final analysis. A pulmonary artery catheter was inserted in 131 patients. There were 50 patients with the composite outcome including two in-hospital deaths. Multivariate logistic regression analysis showed that pulmonary artery catheterization was not significantly related to the composite outcome. Clinical outcomes worsened significantly as the number of anastomoses increased (odds ratio: 1.450, 95% confidence interval: 1.040-2.040, P=0.029). Pulmonary artery catheterization did not improve the clinical outcomes in off-pump coronary artery bypass grafting in this pilot study.


Lumbar synovial cysts.
Synovial spinal cysts are typically found in the lumbar spine, most often at the L4-L5 level. Magnetic resonance imaging is the diagnostic imaging of choice in the workup of suspected synovial cysts. This study consisted of 24 patients with lumbar synovial cysts treated by cyst excision and nerve root decompression through partial or complete facetectomy and primary posterolateral fusion. The most common location of the cysts was the L4-L5 segment. Synovial tissue was found in histological sections of 18 cysts. At a mean follow-up of 12 (range, 8 to 24) months, 20 patients (83%) had excellent or good results; two patients (8.3%) had fair and two patients (8.3%) had poor improvement. Operative complications included dural tear in two patients and postoperative wound dehiscence in one patient, which were treated accordingly. To eliminate the risk of recurrence synovial cyst excision through partial or complete facetectomy is required. In addition, since synovial cysts reflect disruption of the facet joint and some degree of instability, primary spinal fusion is recommended.


Inhibition of STAT3 reduces astrocytoma cell invasion and constitutive activation of STAT3 predicts poor prognosis in human astrocytoma.
Astrocytoma cells characteristically possess high invasion potentials. Recent studies have revealed that knockdown of signal transducers and activators of transcription 3 (STAT3) expression by RNAi induces apoptosis in astrocytoma cell. Nevertheless, the distinct roles of STAT3 in astrocytoma's invasion and recurrence have not been elucidated. In this study, we silenced STAT3 using Small interfering RNAs in two human glioblastoma multiforme (GBM) cell lines (U251 and U87), and investigated the effect on GBM cell adhesion and invasion. Our results demonstrate that disruption of STAT3 inhibits GBM cell's adhesion and invasion. Knockdown of STAT3 significantly increased E-cadherin but decreased N-cadherin, vascular endothelial growth factor, matrix metalloproteinase 2 and matrix metalloproteinase 9. Additionally, expression of pSTAT3(Tyr705) correlates with astrocytoma WHO classification, Karnofsky performance status scale score, tumor recurrence and survival. Furthermore, pSTAT3(Tyr705) is a significant prognostic factor in astrocytoma. In conclusion, STAT3 may affect astrocytoma invasion, expression of pSTAT3(Tyr705) is a significant prognostic factor in tumor recurrence and overall survival in astrocytoma patients. Therefore, STAT3 may provide a potential target for molecular therapy in human astrocytoma, and pSTAT3(Tyr705)could be an important biomarker for astrocytoma prognosis.


Functional studies of human decidua in spontaneous early pregnancy loss: effect of soluble factors and purified CD56+ lymphocytes on killing of natural killer- and lymphokine-activated killer-sensitive targets.
Inappropriate leukocyte activation and disturbance of the delicate cytokine balance within the uterus during early human pregnancy may initiate spontaneous abortion. The purpose of the present study was to assess whether decidual soluble factors from women suffering sporadic spontaneous early pregnancy loss could enhance the cytotoxic activity of peripheral blood lymphocytes (PBL), and to investigate the lytic activity of endometrial granulated lymphocytes (eGL) purified from decidua against natural killer (NK)- and lymphokine-activated killer (LAK)-sensitive targets. Decidual cell culture supernatants from sporadic spontaneous abortion cases did not have any effect on PBL cytotoxic activity against the NK-sensitive target cells K562. Endometrial GL purified from decidua of spontaneous aborters were unable to lyse the LAK-sensitive target cells Raji and, in contrast with eGL from decidua of first-trimester therapeutic aborters, approximately 50% of the cases also failed to kill K562 cells. These results do not provide evidence to implicate either cell-mediated or cytokine-mediated cytolytic mechanisms in early spontaneous pregnancy loss, thus strengthening the possibility that other damaging effects are operating. Nevertheless, the deficient cytotoxic activity in a proportion of spontaneous abortion decidua merits further investigation.


METTL3 Inhibitors for Epitranscriptomic Modulation of Cellular Processes.
The methylase METTL3 is the writer enzyme of the N6 -methyladenosine (m6 A) modification of RNA. Using a structure-based drug discovery approach, we identified a METTL3 inhibitor with potency in a biochemical assay of 280 nM, while its enantiomer is 100 times less active. We observed a dose-dependent reduction in the m6 A methylation level of mRNA in several cell lines treated with the inhibitor already after 16 h of treatment, which lasted for at least 6 days. Importantly, the prolonged incubation (up to 6 days) with the METTL3 inhibitor did not alter levels of other RNA modifications (i. e., m1 A, m6 Am , m7 G), suggesting selectivity of the developed compound towards other RNA methyltransferases.


Nuclear factor-kappa B1 is associated with gastric cancer in a Chinese population.
Activated nuclear factor-κB (NF-κB) is associated with the pathogenesis of numerous cancers, such as gastric cancer (GC). Genetic polymorphisms in the genomic region containing nuclear factor-κB1 (NFKB1) have a plausible role in modulating the risk of GC. To identify markers contributing to the genetic susceptibility to GC, we analyzed 15 single nucleotide polymorphisms (SNPs, rs28362491, rs3774932, rs1598856, rs230531, rs230530, rs230528, rs230521, rs230498, rs230539, rs1005819, rs3774956, rs4648055, rs3774964, rs4648068, and rs3774968) in the genomic region containing NFKB1. The participants included 401 patients with GC and 433 healthy controls. The allelic or genotypic frequencies of the rs28362491 (located in the promoter region of NFKB1), rs230521 (NFKB1 intron 4), and rs4648068 (NFKB1 intron 12) polymorphisms in the patients with GC were significantly different from those in the healthy controls. Strong linkage disequilibrium was observed in 4 blocks (D'>0.9). Significantly more A-T haplotypes (block 1, P=0.0005), A-C haplotypes (block 2, P=0.0001) and G-A-A haplotypes (block 4, P=0.016) were found in the patients with GC. Significantly more A-C haplotypes (block 1, P=0.005) and A-G haplotypes (block 2, P=0.0004) were found in the healthy controls. These findings suggest a role for NFKB1 polymorphism in GC among a Han Chinese population and may be informative for future genetic studies on gastric cancer.


Effect of iacP mutation on flagellar phase variation in Salmonella enterica serovar typhimurium strain UK-1.
Flagella are surface appendages that are important for bacterial motility and invasion of host cells. Two flagellin subunits in Salmonella enterica serovar Typhimurium, FliC and FljB, are alternatively expressed by a site-specific DNA inversion mechanism called flagellar phase variation. Although this inversion mechanism is understood at the molecular level, the key factor controlling the expression of the two flagellin subunits has not been determined. In this study, we found that a putative acyl carrier protein, IacP, affects flagellar phase variation in S. Typhimurium strain UK-1 under Salmonella pathogenicity island 1 (SPI1)-inducing conditions. Liquid chromatography-mass spectrometry analysis of the secreted proteins from S. Typhimurium determined that the amount of FljB secreted was significantly higher in the iacP mutant strain, a finding confirmed by Western blot analysis. Northern blotting, quantitative PCR, and microarray data showed that the level of FljB in the iacP mutant strain was regulated at the transcriptional level, although the transcription and expression of the fliC gene were independent of IacP. FljB production was abolished by the deletion of the Hin DNA invertase but could be restored by the introduction of a plasmid carrying the hin gene. We also found that in the iacP mutant strain, the orientation of the invertible H segment is in the FljB-expressing phase. Furthermore, electron microscopy observations indicated that the iacP mutant strain had more flagella per cell than the wild-type strain. These results suggest that IacP is associated with flagellar phase switching under SPI1-inducing conditions.


HE4 (WFDC2) gene overexpression promotes ovarian tumor growth.
Selective overexpression of Human epididymal secretory protein E4 (HE4) points to a role in ovarian cancer tumorigenesis but little is known about the role the HE4 gene or the gene product plays. Here we show that elevated HE4 serum levels correlate with chemoresistance and decreased survival rates in EOC patients. HE4 overexpression promoted xenograft tumor growth and chemoresistance against cisplatin in an animal model resulting in reduced survival rates. HE4 displayed responses to tumor microenvironment constituents and presented increased expression as well as nuclear translocation upon EGF, VEGF and Insulin treatment and nucleolar localization with Insulin treatment. HE4 interacts with EGFR, IGF1R, and transcription factor HIF1α. Constructs of antisense phosphorothio-oligonucleotides targeting HE4 arrested tumor growth in nude mice. Collectively these findings implicate increased HE4 expression as a molecular factor in ovarian cancer tumorigenesis. Selective targeting directed towards the HE4 protein demonstrates therapeutic benefits for the treatment of ovarian cancer.


Performance Effect of Adjusting Insulin Sensitivity for Model-Based Automated Insulin Delivery Systems.
Model predictive control (MPC) has become one of the most popular control strategies for automated insulin delivery (AID) in type 1 diabetes (T1D). These algorithms rely on a prediction model to determine the best insulin dosing every sampling time. Although these algorithms have been shown to be safe and effective for glucose management through clinical trials, managing the ever-fluctuating relationship between insulin delivery and resulting glucose uptake (aka insulin sensitivity, IS) remains a challenge. We aim to evaluate the effect of informing an AID system with IS on the performance of the system. The University of Virginia (UVA) MPC control-based hybrid closed-loop (HCL) and fully closed-loop (FCL) system was used. One-day simulations at varying levels of IS were run with the UVA/Padova T1D Simulator. The AID system was informed with an estimated value of IS obtained through a mixed meal glucose tolerance test. Relevant controller parameters are updated to inform insulin dosing of IS. Performance of the HCL/FCL system with and without information of the changing IS was assessed using a novel performance metric penalizing the time outside the target glucose range. Feedback in AID systems provides a certain degree tolerance to changes in IS. However, IS-informed bolus and basal dosing improve glycemic outcomes, providing increased protection against hyperglycemia and hypoglycemia according to the individual's physiological state. The proof-of-concept analysis presented here shows the potentially beneficial effects on system performance of informing the AID system with accurate estimates of IS. In particular, when considering reduced IS, the informed controller provides increased protection against hyperglycemia compared with the naïve controller. Similarly, reduced hypoglycemia is obtained for situations with increased IS. Further tailoring of the adaptation schemes proposed in this work is needed to overcome the increased hypoglycemia observed in the more resistant cases and to optimize the performance of the adaptation method.


Modular glass chip system measuring the electric activity and adhesion of neuronal cells--application and drug testing with sodium valproic acid.
We developed a modular neurochip system by combining a small (16x16 mm2) glass neurochip (GNC) with a homemade head stage and commercial data acquisition hardware and software. The system is designed for the detection of the electric activity of cultivated nerve or muscle cells by a 52-microelectrode array (MEA). In parallel, cell adhesion can be registered from the electric impedance of an interdigitated electrode structure (IDES). The GNC was tested with various cell lines and primary cells. It is fully autoclavable and re-useable. Murine embryonic primary cells were used as a model system to correlate the electric activity and adhesion of neuronal networks in a drug test with sodium valproic acid. The test showed the advantage of the parallel IDES and MEA measurements, i.e. the parallel detection of cytotoxic and neurotoxic effects. Toxic exposure of the cells during neuronal network formation allows for the characterization of developmental neurotoxic effects even at drug concentrations below the EC50-value for acute neurotoxic effects. At high drug concentrations, the degree of cytotoxic damage can still be assessed from the IDES data in the event that no electric activity develops. The GNC provides optimal cell culture conditions for up to months in combination with full microscopic observability. The 4'' glass wafer technology allows for a high precision of the GNC structures and an economic production of our new system that can be applied in general and developmental toxicity tests as well as in the search for neuro-active compounds.


Increase in intra-abdominal pressure raises brain venous pressure, leads to brain ischaemia and decreases brain magnesium content.
Intra-abdominal hypertension (IAH) may increase brain venous pressure, which may lead to brain injury. The aim of the present study was to analyse the effect of IAH on brain venous pressure and brain total and ionised magnesium (tMg and iMg), calcium (Ca) and zinc (Zn) contents in rats. Forty four adult Wistar rats were examined. Animals were divided into two groups: control, and IAH: rats with intra-abdominal pressure (IAP) elevated to 25 mmHg. IAP was measured directly in the abdominal cavity. After retrograde cannulation of the jugular vein, the jugular venous pressure (JVP) was measured as the brain venous pressure. JVP and IAP were noted after induction of anaesthesia, immediately following induction of IAH and 90 min after induction of IAH. In all rats, brains were removed for biochemical and histological analysis. Biochemical analysis was performed in 30 rats, histological visualisation in 14. IAP elevated to 25 mmHg increased JVP in the IAH group. After 90 min, JVP decreased; however, its value was still higher compared with pre-IAH. In the IAH group, tMg and iMg were significantly lower than in the control group. Moreover, Ca and Zn levels were higher in the IAH group compared with the control group. The histological examination showed changes indicative of ischaemic neuronal cell stress. Firstly, increase in IAP elevates JVP. Secondly, raised JVP decreases tMg and iMg. Thirdly, raised JVP increases the Ca and Zn content in the rat brain. Fourthly, IAH leads to changed characteristics of brain ischaemia.


Atypical Clinical Presentations of Pediatric Acute Immune-Mediated Polyneuropathy.
Guillain-Barré syndrome (GBS) is the most common cause of acute flaccid paralysis in children. During the acute phase, the disorder can be life-threatening by involving the respiratory muscles and the autonomic nervous system. Nevertheless, the prognosis is good, and most children achieve full recovery. The aim of this study was to characterize the clinical and electrophysiologic findings in children with Guillain-Barré syndrome referred to a tertiary center in Israel. A retrospective database review from 2009 to 2015 identified 39 children. Data on clinical presentation, respiratory complications, and long-term neurologic outcomes were collected. Atypical clinical findings at admission included asymmetric weakness in 23%, nonascending weakness in 30%, and normal deep tendon reflexes in 28%. Eight children were later diagnosed with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Electrophysiologic findings, available in 12 patients with Guillain-Barré syndrome, revealed acute inflammatory demyelinating polyradiculoneuropathy (AIDP) in 4 (33.5%), AIDP with secondary axonal changes in 3 (25%), and acute motor axonal neuropathy (AMAN) subtype in 4 (33.5%); 8% had no abnormal findings. On follow-up, 71% of the children with Guillain-Barré syndrome fully recovered compared to 14% of the children with CIDP. Corresponding rates of neurologic sequelae were 29% and 86%. Clinicians should be alert to the atypical presenting symptoms of Guillain-Barré syndrome, which occur in a significant proportion of children.


Gendered Expectations: Examining How Peers Shape Female Students' Intent to Pursue STEM Fields.
Building on prior psychological and sociological research on the power of local environments to shape gendered outcomes in STEM fields, this study focuses on the critical stage of adolescence to explore the potential negative impact of exposure to exclusionary messages from peers within girls' science classrooms, as well as the positive potential impact of inclusionary messages. Specifically, utilizing longitudinal data from a diverse sample of adolescent youth, analyses examine how the presence of biased male peers, as well as confident female peers, shape girls' subsequent intentions to pursue different STEM fields, focusing specifically on intentions to pursue the male-dominated fields of computer science and engineering, as well as more gender equitable fields. Results reveal that exposure to a higher percentage of 8th grade male peers in the classroom who endorsed explicit gender/STEM stereotypes significantly and negatively predicted girls' later intentions to pursue a computer science/engineering (CS/E) major. Yet results also reveal that exposure to a higher percentage of confident female peers in the science classroom positively predicted such intentions. These results were specific to CS/E majors, suggesting that peers are an important source of messages regarding whether or not girls should pursue non-traditional STEM fields. This study calls attention to the importance of examining both positive and negative sources of influence within the local contexts where young people live and learn. Limitations and directions for future research are also discussed.


Impression techniques for removable partial dentures.
This article concerns a subject that has been very perplexing to dentists attempting to provide superior removable prosthetic services. The techniques in this article have been developed, tried, and proven over 42 years of clinical practice. Adequate impressions for partial denture construction when crowns that have been fitted to the mouth are included as part of the master cast. The dilemma of having already cemented crowns with attachments on them can be a problem. An easy technique has been developed for analog production in these cases.


Effect of microencapsulation of Lactobacillus plantarum 25 into alginate/chitosan/alginate microcapsules on viability and cytokine induction.
Lactobacillus plantarum 25 (LP25) encapsulated into alginate/chitosan/alginate (ACA) microcapsules (LP25-ACA MCs) prepared by an extrusion methods were characterized to assess their efficacy in oral delivery. The particle sizes of LP25-ACA MCs were 1.11 +/- 0.32 mm. The loading content of LP25 was 1.11 x 10(7) colony forming unit (cfu)/microcapsule and encapsulation efficiency was above 98%. The viability of LP25 in ACA MCs was more than 65% in simulated gastric fluid (SGF, pH 2.0) and 75% in simulated small intestinal fluid (SIF, pH 7.2) up to 2 h. Encapsulated LP25 were completely released from LP25-ACA MCs in SIF and simulated colon fluid (SCF, pH 6.0) within 12 h and 8 h respectively. The viability of LP25 in ACA MCs till 5 weeks was above 58%, whereas viability of free LP25 stored at room temperature up to 5 weeks was zero. Besides, LP25-ACA MCs induced the secretion of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) from macrophages and dendritic cells showing the immunomodulatory effect of LP25. These findings demonstrate that the encapsulation of LP25 by ACA is a suitable strategy for oral delivery of probiotics.


[Orthodontic studies in children with stunted growth].
Biometrical studies on a group of 43 children with stunted growth showed that stunted growth is associated with smaller dimensions of the upper dental arch. The lower dental arch is not involved. The relationship between the variations in the characteristics under examination are explained with the aid of three basic factors of growth which had been established mathematically. The crown diameters of the permanent teeth are not smaller as in children with normal growth.


Development of mucus-penetrating iodine loaded self-emulsifying system for local vaginal delivery.
The major goal of this project was to formulate iodine-based self nano-emulsifying drug delivery system to provide improve antimicrobial activity and enhanced mucosal residence time via mucus penetration. Iodine SNEDDS (Self nano-emulsifying drug delivery system) with different concentration were formulated using castor oil as the oil phase, cremophor ethoxylated (CrEL) as a surfactant and after screening a number of vehicles, PEG 400 was employed as co-surfactant. Self-emulsification time, thermodynamic stability tests, robustness to dilution, percent transmittance, droplet size, and drug release were measured. Ternary phase diagrams were plotted to determine the area of emulsification. When compared to the commercial formulation, dissolving experiments revealed that the iodine from the SNEDDS enhanced aqueous solubility. In-vitro iodine release was determined to be around 15% per hour, with muco-adhesive and, muco-penetrating characteristics showing a 38-fold improvement. Furthermore, SNEDDS demonstrated significant antibacterial efficacy against Escherichia coli and Staphylococcus aureus. Similarly, when compared to marketed drugs, in-vitro drug absorption profile from the manufactured SNEDDS shown to be much higher. According to these results iodine containing SNEDDS could be a useful new formulation for iodine mucosal usage.


Depression in pregnancy. Prevalence and associated factors.
To evaluate the occurrence of depression during pregnancy and its associated factors. Epidemiological, quantitative, descriptive and cross-sectional study, conducted from January to May 2013 with 209 pregnant women in the city of Alfenas, State of South Minas Gerais, Brazil. The Hospital Anxiety and Depression Scale (HASD) of Zigmond y Snaith and a form for characterization of participants were used for data collection. Depression was present in 14.8% of the pregnant women and was more frequent during the second trimester of pregnancy. Depression during pregnancy was significantly associated with number of births, number of children, ranking as the number of pregnancies, family support, amount of cigarettes smoked per day, consumption of alcohol, use of daily medications, history of mental disorder, presence of striking events in the last 12 months and history of domestic violence. The evaluation of depression showed that this disorder is common during pregnancy, and the risk is higher among primigravidae women, women who use alcohol, use daily medications, have history of mental disorder, have experienced a striking event in the last 12 months and who have suffered domestic violence. Knowledge of the factors associated with occurrence of depression allows early adoption of interventions to monitor the mental health of women throughout pregnancy, preventing this and other disorders.


X-ray zooming microscopy with two Fresnel zone plates.
We propose a variable-magnification full-field x-ray microscope using two Fresnel zone plates (FZPs). By moving the positions of the two FZPs, the magnification can be continuously changed even if the sample and camera positions are fixed. It was demonstrated that the magnification can be changed in the range of 25-150× using a hard x-ray beam at 14.4 keV. Using the first FZP as a convex lens and the second FZP as a concave lens, high magnification can be achieved at a short camera length. Even under the condition of a camera length of about 7 m, a magnification higher than 300× was achieved, and a line and space pattern with a pitch of 40 nm was observed at 10 keV. By inserting a knife edge at an appropriate position in the optical system, a phase-contrast image can be easily obtained, which is useful for soft-tissue observation of biological samples.


Post-translational alterations of the tyrosine kinase p56lck in response to activators of protein kinase C.
We have found in different human cells of lymphoid and non-lymphoid origin that the 56 kilodalton (kDa) lck protein is rapidly converted to a product migrating at approximately 60 kDa (designated p60lck) in response to the phorbol ester 4 alpha-phorbol 12 beta-myristate (PMA) as well as the diacylglycerol analogue 1,2-dioctanoyl-sn-glycerol (diC8). This conversion is associated with an increase in serine phosphorylation within the amino-terminal 18 kDa portion of the lck protein. The serine phosphorylation modification and diminished electrophoretic mobility of the lck protein appear to be completely reversible within 60 min following treatment with diC8. The changes in p56lck phosphorylation and gel mobility in response to activators of protein kinase C are also associated with a small but reproducible decrease in the ability of the lck protein to be phosphorylated in immune complex kinase assays. While these alterations of the lck gene product may play an important role in antigen-mediated activation of T-lymphocytes, we demonstrated that they can also be induced independently of T-cell activation suggesting that they are not necessarily implicative of this process.


Coordinated control of lumen size and collective migration in the salivary gland.
The Drosophila embryonic salivary gland is a powerful system to analyze the cellular and molecular mechanisms of tubulogenesis in vivo. The secretory portion of the salivary gland (referred to here as the salivary gland), is a pair of elongated epithelial tubes with a single central lumen, that is formed by the invagination and collective migration of gland cells from the ventral surface of the embryo. ( 1) (,) ( 2) As the salivary gland elongates during migration, the central lumen elongates and narrows at the proximal end. ( 3) A number of genes are known to regulate salivary gland migration and/or lumen size (Table 1); however, it is only recently that we have begun to analyze how control of salivary gland migration is coordinated with control of lumen size. To understand coordinated control of salivary gland migration and lumen size, we analyzed the role of the single Drosophila Rho GTPase, Rho1, in salivary gland tubulogenesis. In addition to the requirement of Rho1 in salivary gland invagination and migration (Xu et al., 2008), our recent studies show that Rho1 controls salivary gland lumen width and length during the migration process (Fig. 1). These studies reveal that Rho1-mediated processes at the proximal end of the migrating salivary gland, such as cell shape change, cell rearrangement and apical domain elongation, contribute to collective migration, and narrowing and elongation of the lumen. ( 4).


Human clinical studies of tea polyphenols in allergy or life style-related diseases.
Many previous epidemiological studies have revealed that green tea or green tea catechins contributed to the preveintion of lifestyle-related diseases. Several cohort studies on the relationship between green tea consumption and cardiovascular disease (CVD) risk/type 2 diabetes mellitus risk have been conducted. The results showed that green tea consumption (5 or more cups/day) was inversely associated with mortality from CVD and all causes. Within CVD mortality, the strongest inverse association was observed for stroke mortality. Furthermore, consumption of green tea, coffee, and total caffeine was associated with a reduced risk for type 2 diabetes. On the other hand, the analysis of randomized clinical trial (RCT) studies showed that the administration of green tea beverages or extracts resulted in significant reductions in serum total cholesterol and LDL-cholesterol concentrations, but had no apparent effect on HDL-cholesterol. Green tea reduced fasting blood glucose levels in a small intervention trial, although no improvements in HbA1c levels were seen. Continuous intake of green tea containing catechins and caffeine (5 or more cups per day) may be beneficial for body weight management, vascular disease risk reduction via LDL-cholesterol improvement, and type 2 diabetes risk reduction through the lowering of fasting blood glucose levels. Epigallocatechin-3-O-(3-O-methyl) gallate (EGCG3"Me) isolated from cv. "Benifuuki" green tea has been shown to strongly inhibit mast cell activation and histamine release after FcepsilonRI cross-linking through the suppression of tyrosine phosphorylation (Lyn) of cellular protein kinase, and the suppression of myosin light chain phosphorylation and high-affinity IgE receptor expression via the binding to 67 kDa laminin receptors. A double-blind clinical study on subjects with Japanese cedar pollinosis was carried out. At the eleventh week after starting intake, which was coincident with the most severe period of cedar pollen-scattering, symptoms such as nose blowing and eye itching were significantly relieved in the Benifuuki group compared with the placebo group. Six weeks of intake of Benifuuki green tea containing O-methylated catechins was useful for reducing some of the symptoms derived from Japanese cedar pollinosis, and did not affect any of the normal immune responses in the subjects with Japanese cedar pollinosis. Based on an investigation into the effects of the cultivars, tea seasons of crops and manufacturing methods, it was concluded that green or semi-fermented tea made from fully-matured Benifuuki in the second crop season should be consumed.


Doomscrolling Scale: its Association with Personality Traits, Psychological Distress, Social Media Use, and Wellbeing.
Doomscrolling is a fairly new concept in mental health research which has attracted significant attention in recent years. This paper consists of three separate studies examining doomscrolling. In Study I (N = 378), both 15-item and 4-item forms of Doomscrolling Scale (DS) were confirmed by confirmatory factor analysis. Item Response Analysis demonstrated that all items had strong discriminative power. Different reliability coefficients supported the high reliability of DS. In Study II (N = 419), both correlation and network analysis indicated that doomscrolling was significantly associated with big five personality traits, social media addiction, fear of missing out, and some features of social media usage. In Study III (N = 460), the relationship of doomscrolling with psychological distress and wellbeing indicators -life satisfaction, mental well-being and harmony in life- were investigated. Structural equation modeling indicated that the relationship between doomscrolling and wellbeing indicators were mediated by psychological distress. This comprehensive and pioneering study on doomscrolling has highlighted the individual and social impacts of doomscrolling.


Isolated cerebral mucormycosis that looks like stroke and brain abscess: A case report and review of the literature.
Cerebral mucormycosis is an infectious disease of the brain caused by fungi of the order Mucorales. These infections are rarely encountered in clinical practice and are often misdiagnosed as cerebral infarction or brain abscess. Increased mortality due to cerebral mucormycosis is closely related to delayed diagnosis and treatment, both of which present unique challenges for clinicians. Cerebral mucormycosis is generally secondary to sinus disease or other disseminated disease. However, in this retrospective study, we report and analyze a case of isolated cerebral mucormycosis. The constellation of symptoms including headaches, fever, hemiplegia, and changes in mental status taken together with clinical findings of cerebral infarction and brain abscess should raise the possibility of a brain fungal infection. Early diagnosis and prompt initiation of antifungal therapy along with surgery can improve patient survival.


Predictors of Micrometastases in Patients with Barcelona Clinic Liver Cancer Classification B Hepatocellular Carcinoma.
Transarterial chemoembolization (TACE) is indicated for Barcelona Clinic Liver Cancer (BCLC) B hepatocellular carcinoma (HCC). Whether TACE provides any long-term survival benefits remains unclear. We aimed to investigate micrometastases predictors with which to identify patients who would benefit from surgical resection (SR). First, we analyzed risk factors of micrometastases, microvascular invasion, and poor histologic grade in 38 patients with newly diagnosed resectable BCLC stage B HCC limited to one or two segments with well-preserved liver function and who underwent SR between January 2006 and December 2013. Second, we validated identified risk factors in 54 newly diagnosed resectable BCLC B HCC patients with well-preserved liver function who underwent TACE during the same period to determine their influence on survival. Risk factors of micrometastases in SR patients were α-fetoprotein (AFP) ≥110 [hazard ratio (HR)=5.166; 95% confidence interval (CI), 1.031-25.897; p=0.046] and prothrombin induced by vitamin K absence-II (PIVKA-II) ≥800 (HR=5.166; 95% CI, 1.031-25.897; p=0.046). The cumulative probability of tumor recurrence (p=0.009) after SR differed according to levels of AFP and PIVKA-II. After validation of these risk factors in the TACE group, patients with SR and AFP <110 and PIVKA-II <800 had superior survival outcomes than other patients (HR=0.116; 95% CI, 0.027-0.497; p=0.004). AFP and PIVKA-II levels predict micrometastases and survival. Therefore, they should be considered when selecting SR for BCLC B HCC.


Comfort assessment of personal protection systems during total joint arthroplasty using a novel multi-dimensional evaluation tool.
A number of studies have assessed the usefulness of surgical gowns and exhaust suits with regards to barrier function and protection afforded to healthcare workers from blood strike-through, splashes and aerosols. We have performed a comfort assessment comparison between the Charnley exhaust suit, disposable gown plus visor and the Stryker Steri-Shield system using a newly developed objective multidimensional ergonomic tool designed to measure wearable comfort across the dimensions of emotion, attachment, harm, perceived change, movement and anxiety. The total mean Comfort Rating Scale value for a disposable gown plus visor was 16.1 with a mean dimensional score of 2.7 (range, 0.2-8.4), for the Charnley system the values were 51.4 and 8.6 (range, 5.9-12.8), respectively, and for the Stryker Steri-Shield 15.4 and 2.6 (range, 0.8-5.6). The Steri-Shield system provides the least variation in comfort and, as such, may offer the best combination of comfort, protective qualities and form or style of personal protection equipment for lower limb arthroplasty operations.


Integrating flexibility and interactivity in bioinformatics visual programming tools with Focus+Context algorithm.
An improved bioinformatics visual programming prototype system VBP that aims to visualise highly complicated bioinformatical data is described. In this paper, we describe the integration of Focus+Context algorithm and bio-visual programming to show the dynamic adjusting of Focusing on details without losing the context simultaneously. Because of this flexible and interactive architecture, VBP makes an ideal bio-visual programming tool for future bioinformatics or systems biology research.


Apolipoprotein E gene polymorphisms and risk for coronary artery disease in Chinese Xinjiang Uygur and Han population.
To examine the relationship between apolipoprotein E (Apo E) gene polymorphism and risk of coronary artery disease (CAD), analyzing association of polymorphism with classical risk factors. A total of 124 patients (including 84 Han population and 40 Uygur population) with angiographically verified CAD or myocardial infarction were prospectively evaluated. Data referring to hypertension, diabetes, and tobacco consumption were recorded. The levels of total cholesterol (TC), high density lipoprotein (HDL) cholesterol, Apo A1 and B, and triglycerides (TG) were determined. DNA was obtained from 124 patients and 70 controls. In order to determine Apo E genotypes, DNA was PCR amplified and digested with HhaI. The genetic polymorphism of Apo E is due to three common alleles, epsilon (epsilon) 2, epsilon3, epsilon4, at a single autosomal gene locus. These alleles determine the six phenotypes E2/2, E3/3, E4/4, E4/2, E4/3, and E3/2. In Uygur population, the frequency of the epsilon2, epsilon3, and epsilon4 was 0.155, 0.648, and 0.197 respectively. In Han population, the frequency of the epsilon2, epsilon3, and epsilon4 was 0.081, 0.772, and 0.146 respectively. In the patient group, the frequency of the epsilon2, epsilon3, and epsilon4 was 0.060, 0.758, and 0.182 respectively. In the control group, the frequency of the epsilon2, epsilon3, and epsilon4 was 0.193, 0.671, and 0.136 respectively. epsilon2 frequency of Uygur' patients and controls was 0.050 and 0.290 respectively. Serum low density lipoprotein (LDL) cholesterol, TC, and TG values tended to decrease from the Apo E-4 phenotypes to Apo E-2 phenotypes. When deletion polymorphism of epsilon2 was compared with the common risk factors for CAD, its risk ratio (RR) is 4.38. These studies confirm and find that Apo E phenotype distribution in Uygur population differs significantly from that in Han population in Xinjiang. CAD patients have significantly lower epsilon2 allele and slightly higher epsilon3 or epsilon4 allele frequency than controls, especially in Uygur population. It shows protective effects of epsilon2 on CAD.


Sialoglycopeptides isolated from human arteriosclerotic tissue.
Sclerotic and non-sclerotic tissues of intima-media of human aorta were digested with pronase, after preliminary extraction of saline (1%)-soluble substances and fat. Subsequently, sialoglycopeptide fractions were obtained from the pronase digests by fractionation with CPC (cetylpyridinium chloride). Complete separation of sialoglycopeptides was achieved by chromatography on a DEAE-Sephadex A-25 column at pH 7.2, followed by repeated chromatography on the same Sephadex column at pH 5.2. The purified sialoglycopeptides thus obtained showed heterogeneity of their carbohydrate chains, although they contained the same monosaccharides (galactose, mannose, glucose, glucosamine, galactosamine, fucose, and sialic acid). Heterogeneity was also observed in their peptide chains. The contents of hydroxyamino acids and alkali-sensitive linkages of these preparations indicated that the fractions eluted from the DEAE-Sephadex A-25 column at higher molarity of the eluting salt at pH 5.2 contained many more O-glycosidic linkages between hydroxyamino acis(s) and sugar(s) than those eluted at lower molarity. The present data indicate that the concentration of sialoglycoproteins in intimamedia of human aorta increases significantly in arteriosclerosis in terms of defatted dry tissue. Moreover, the chemical nature of the sialoglycoproteins was modified slightly in the disease.


Endodermal sinus tumour of stomach--a case report.
This is a case report of an endodermal sinus tumour arising in the stomach of a 1 1/2 years male child. The tumour occupied full thickness of fundus and part of the body of the stomach. H&E sections of the tumour tissue showed endodermal sinus tumour with predominantly reticular and endodermal sinus patterns. Elevated level of alpha-fetoprotien was detected in the serum of the patient and within the tumour tissue by immunohistochemical technique.


Plaque color analysis by the conventional yellow-color grading system and quantitative measurement using LCH color space.
Yellow plaques of higher color grades are regarded as more vulnerable. We tried to elucidate the characteristics of yellow color that are regarded as the sign of vulnerable plaques by an objective and quantitative plaque color analysis. The color of yellow plaques was quantitatively analyzed using LCH color space and was presented by the maximum values of lightness (Lmax), chroma (Cmax), and hue (Hmax). Effect of light intensity on these parameters was experimentally examined (five plaque models, six light intensities). Relation between conventional yellow-color grade and LCH parameters was examined (31 plaques). Color analysis with LCH color space was applied (1) to compare the culprit lesions of unstable angina (eight patients) and of stable effort angina (nine patients) and (2) to evaluate the regression of yellow plaque by 80-week statin treatment (four patients, 19 plaques). Cmax and Hmax were not influenced by light intensity so far as it was within appropriate range. Cmax (13 +/- 3, 25 +/- 5, and 28 +/- 4) became higher and Hmax (178 +/- 26, 134 +/- 10, and 91 +/- 16) became lower as the grade became higher (P < 0.0001). Culprit lesions of unstable angina had higher Cmax (22.8 +/- 7.9 vs 14.8 +/- 7.5, P = 0.04) and lower Hmax (73.3 +/- 19.7 vs 168.0 +/- 71.5, P = 0.002) than stable effort angina. Statin treatment reduced Cmax (21.3 +/- 9.6 vs 14.6 +/- 3.1, P = 0.004) and increased Hmax (82.6 +/- 25.8 vs 142.3 +/- 54.1, P = 0.0005). Plaque color was consistently and quantitatively measurable using LCH color space uninfluenced by light intensity of appropriate range. Vulnerable yellow color had high chroma and low hue, indicating vivid and reddish-yellow color.


Nonpalpable lymph nodes of the neck: assessment with US and US-guided fine-needle aspiration biopsy.
Ultrasound (US) and US-guided fine-needle aspiration biopsy (FNA) were performed in 91 nonpalpable neck nodes of 70 patients, 98% of which had known malignancy. Various sonographic findings were evaluated for predicting malignancy. The accuracy of US-guided FNA for detecting malignancy was 88%, with 96% sensitivity and 94% specificity. The ratio of minimal to maximal axial diameters of a node was most valid for predicting malignancy with US. A ratio of more than 0.55 yielded the highest accuracy (80%) (92% sensitivity, 63% specificity). Addition of any other factors to this criterion did not improve its accuracy. US and US-guided FNA are accurate for the assessment of nonpalpable neck nodes. Lymph nodes with a round configuration should be biopsied in patients with known malignancy.


A simple approach to assess the cancer risk of occupational exposure to genotoxic drugs in healthcare settings.
Several drugs for human use possess genotoxic properties as a necessary consequence of their intended therapeutic effect (e.g. antineoplastics). Health workers may be exposed to these chemicals in various occupational settings such as dose preparation and administration. To date, there are no quantitative risk assessment models to estimate the cancer risk of health workers due to the handling of genotoxic drugs. We therefore developed a quantitative risk assessment model to assess the cancer risk of occupational exposure to genotoxic drugs in healthcare settings based on the threshold of toxicological concern (TTC) concept. This model was used to evaluate the cancer risk of health workers due to the handling of genotoxic drugs in modern health care facilities. We modified the threshold of toxicological concern (TTC) concept to fit the purpose of occupational cancer risk assessment. The risk model underlying ICH guideline M7 (R1): "assessment and control of DNA reactive (mutagenic) impurities in pharmaceuticals to limit potential carcinogenic risk" was used as a starting point for our model. We conducted a short review of studies on the occupational exposure of health workers to genotoxic drugs. These occupational exposure data were compared to the acceptable exposure levels resulting from our TTC based risk model. Based on the threshold of toxicological concern (TTC) concept, we defined an acceptable daily intake (ADI) of 4 μg/day as threshold of no concern for the exposure of health workers to genotoxic drugs. Regarding the dermal exposure of health workers to genotoxic drugs, we derived a corresponding acceptable surface contamination level (ASCL) of 20 ng/cm2. Both ADI and ASCL are usually not exceeded in modern healthcare settings. Current safety precautions provide sufficient protection to health workers. The application of our model indicates that workers in modern healthcare facilities are not at risk of developing work related cancer above widely accepted cancer risk levels due to the occupational exposure to genotoxic drugs. Hence, the present study may assist employers and public authorities to make informed decisions concerning the need for (further) protective measures and during risk communication to health workers.


Calcium kinetics are altered in clinically stable girls with cystic fibrosis.
Reduced bone mass in individuals with cystic fibrosis (CF) may result from alterations in calcium metabolism. Bone calcium deposition and resorption rates, calcium balance, and markers of bone turnover were assessed using stable isotopes of calcium in 22 prepubertal and pubertal girls with CF. Bone calcium deposition was associated with the availability of dietary calcium, total serum osteocalcin, and leptin concentrations. Reduced bone mass in individuals with CF may result from inadequate bone calcium (Ca) deposition, and excessive resorption, although these parameters have not been directly assessed in children with CF. We used stable Ca isotopes to measure rates of bone Ca deposition (Vo+), resorption, and retention in 22 clinically stable girls with CF (aged 7-18 yr). Rates of bone Ca deposition were determined by mathematically modeling the disappearance of iv Ca stable isotope ((42)Ca) for 6 d post dosing. Indirect markers of bone turnover and hormones associated with pubertal development were also assessed. Rates of bone Ca deposition and retention were highest during early puberty (Tanner stages 2 and 3). Calcium deposition rates in prepubertal (Tanner 1) and postmenarchal girls (Tanner stages 4 and 5) did not support substantial bone Ca retention. Net absorption of dietary Ca and serum osteocalcin and leptin concentrations were positively associated with Vo+. Time post menarche and serum leptin concentrations explained 91% of the variability in Vo+ (P = 0.0007). Serum total osteocalcin was low (10.9 +/- 5.4 ng/ml), and a substantial percentage of osteocalcin was undercarboxylated (54.3 +/- 11.8%). We concluded that increased calcium absorption and serum leptin concentrations were significantly associated with rates of bone Ca deposition, demonstrating an impact of nutritional status on this process. Rates of bone Ca deposition were lower than typically reported in healthy children, as were indirect markers of bone formation. These alterations in bone turnover contribute to reduced bone mass in girls with CF.


KAGIANA: an excel-based tool for retrieving summary information on Arabidopsis genes.
Various public databases provide Arabidopsis gene information via the internet. It is useful to abstract information obtained from such databases. We have developed the KAGIANA tool, which allows a user to retrieve summary information obtained from selective databases and to access pages for a gene of interest in those databases. The tool is based on Microsoft Excel and provides several macro programs for gene expression analyses. It can assist plant biologists in accessing omics information for plant biology. The KAGIANA tool is freely available at http://pmnedo.kazusa.or.jp/kagiana/.


Feasible time-bin entanglement purification based on sum-frequency generation.
High quality time-bin entanglement is widely exploited to achieve the purposes of fundamental tests of physics and the implementation of quantum communication protocols both in free space and optical fiber propagation. However, the imperfect approaches of generating time-bin entangled state will degrade its quality and limit its practical application. Entanglement purification is to distill high quality entangled states from low quality entangled states. In this paper, we present the first entanglement purification protocol (EPP) for time-bin entanglement. We first explain this EPP for two-photon time-bin entangled state and then extend it to the system of multi-photon time-bin entangled state. We also design a possible realization of this EPP with practical spontaneous parametric down conversion (SPDC) source. Differ from the conventional EPPs, this EPP does not require the sophisticated controlled-not (CNOT) gate or similar operations, and it uses the feasible sum-frequency generation (SFG) to perform the purification. Moreover, the double-pair noise emitted from the SPDC source can be eliminated automatically which is the other advantage of this EPP. If we combine with the faithful entanglement swapping, this EPP may have potential to be a part of full quantum repeaters.


[Dextran and hemodilution in the prevention of postoperative venous thrombo-embolism (author's transl)].
A retrospective study was made to evaluate the effects of two preventive measures on deep venous thrombosis. The first group consists of 147 patients operated upon for biliary tract disease and 118 operative at the hip. The prophylactic measures consisted of dextran and ASA. The second group comprises 52 patients who underwent biliary tract surgery and 40 a hip intervention. During the operation they were submitted to a moderate normovolemic hemodilution (Hemat. 27%) only. During the postoperative period this group received no other prophylactic measures or therapy except for routine physical therapy. This study suggests that moderate normovolemic hemodilution is the best prophylaxis for deep venous thrombosis. Indeed, in the first group 10% of those operated upon for biliary tract disease developed a deep venous thrombosis as detected by the fibrinogen-I 25 test and phlebography (0,68% massive lethal pulmonary embolism). The incidence was 37,2% after hip surgery (1,6% massive lethal pulmonary embolism). Of those operated with moderate normovolemic hemodilution no deep venous thrombosis was detected in the biliary surgery group and only 10% in the hip surgery group. None of them died of a pulmonary embolus. The mechanisms by which normovolemic moderate hemodilution prevents the development of deep venous thrombosis are discussed.


Damage and inflammation in muscular dystrophy: potential implications and relationships with autoimmune myositis.
This review provides an updated evaluation of the role of inflammation in muscular dystrophy, and presents findings which suggest that non-immunological factors promote idiopathic inflammatory myopathies. Recent findings are summarized which indicate that immune-targeted interventions may provide useful approaches to treat muscular dystrophy. Elevated expression of the cytotoxic T-lymphocyte derived cytolytic molecule, perforin, and the inducible costimulatory molecule have been identified in muscles of Duchenne muscular dystrophy patients, which strengthens evidence that a cellular immune response contributes to dystrophinopathy. Conversely, new findings implicate non-immune factors in inflammatory myopathy pathogenesis. Muscles from healthy individuals expressed autoantigens typically present in inflammatory myopathies, and autoantigen expression increased along with elevated major histocompatibility complex class I expression at sites of muscle regeneration in inflammatory myopathies. Those observations suggest that regeneration could render conditions sufficient for an autoimmune response in inflammatory myopathies. Further studies of corticosteroids or tumor necrosis factor blockade in treating dystrophinopathy indicate that immunological interventions may yield improved therapies for muscular dystrophy. In addition, advancements in understanding the involvement of chemokines in muscular dystrophy and inflammatory myopathies suggest that targeting specific chemokines has potential therapeutic value. Our developing understanding of the pathogenesis of muscular dystrophies and inflammatory myopathies shows complex interactions between immunological and non-immunological features of these diseases that can affect disease onset and course. Among the muscular dystrophies, the best evidence for an immunological component to disease pathogenesis exists for dystrophinopathies. Conversely, muscle damage leading to regeneration may promote some inflammatory myopathies, although much remains to be learned concerning the identity and pathological significance of non-immunological features of inflammatory myopathies.


Enhancing Aerobic Exercise with a Novel Virtual Exercise Buddy Based on the Köhler Effect.
Research on active videogames (AVGs) has demonstrated the motivation-boosting power of the Köhler effect (a motivating force for "weak links" in groups based on group principles of upward social comparison and indispensability) with software-generated partners (SGPs), but the effect has yet to be examined over time. We tested the viability of the Köhler effect in an AVG with an SGP over 12 exercise sessions using a cycle ergometer and whether a fatiguing partner (FP) could further boost the effect. A repeated-measures design was used to assess mean changes in exercise persistence over time. Participants were randomly assigned to one of three game conditions: AVG alone (individual-control [IC]), AVG with a consistently superior partner (CSP), or AVG with a superior partner who showed signs of fatigue (FP). Assessments were conducted on 82 participants (42 college students and 40 adults from the community) in a laboratory over 12 experimental sessions. The main outcome measure was exercise persistence (minutes of gameplay cycling at 75% HRmax). Data yielded significant improvements in exercise duration for men in the FP condition when compared with men in the IC condition (Mdiff = 12:32 minutes, SEdiff = 4:54). Women showed no change in exercise persistence over time and no condition differences. Exercising in an AVG with a superior SGP, who shows signs of fatigue over time, improved exercise persistence for men but not for women under present experimental conditions.


Cerebellar lesions in tuberous sclerosis complex: neurobehavioral and neuroimaging correlates.
We assessed the structural and functional imaging features of cerebellar lesions and their neurobehavioral correlates in a large cohort of patients with tuberous sclerosis complex. A consecutive series of 78 patients with tuberous sclerosis complex underwent magnetic resonance imaging (MRI) and positron emission tomography (PET) studies with [(18)F]fluorodeoxyglucose (FDG) and alpha-[(11)C]methyl-l-tryptophan (AMT) as part of their evaluation for epilepsy surgery. Neurobehavioral assessment included the Gilliam Autism Rating Scales (GARS) and the Vineland Adaptive Behavior Scales (VABS). Twenty-one patients (27%) had cerebellar lesions (10 boys; mean age 9 +/- 8 years; 9 had right-sided, 10 had left-sided, and 2 had bilateral cerebellar lesions). The lesions showed decreased glucose metabolism (0.79 +/- 0.10) and increased (1.04 +/- 0.10) AMT uptake compared with the normal (nonlesional) cerebellar cortex. Comparisons between patients with (n = 20) and without (n = 57) a cerebellar lesion on neurobehavioral functioning, controlling for the number and location of cortical tubers, revealed that the cerebellar lesion group had higher overall autistic symptomatology. Within-group analyses of the cerebellar lesion group revealed that children with right-sided cerebellar lesions had higher social isolation and communicative and developmental disturbance compared with children with left-sided cerebellar lesions. The side of the cerebellar lesion was not related to adaptive behavior functioning. These findings provide additional empiric support for a role of the cerebellum in autistic symptomatology. Further investigation of the potential role of the right cerebellum in autism, particularly with regard to the dentatothalamofrontal circuit, is warranted.


Long-Term Effect of Guided Implant Surgery on Clinical Outcomes and Peri-Implantitis of Maxillary Implants-An Observational Cohort Study.
(1) Although the accuracy of static computer-aided implant surgery (sCAIP) is well reported, information on its long-term effect on peri-implant health and complications is scarce. (2) Twenty-six patients initially treated were recalled. Implant survival, radiographic bone level, peri-implant health, and complications were registered. A multilevel regression model was applied to study the relationship between the research variables. (3) Sixteen patients participated in this study (average age 58.5 years; range 27.8-73.8). The mean follow-up time was 9.1 years (range 7.3-11.3). Two implants failed, resulting in a survival rate of 97.1%. The mean bone level change corresponded to a loss of 0.63 mm (SD 1.90) for the whole group, 0.17 mm (SD 1.46), and 0.91 mm (SD 2.09) for tooth- and mucosa-supported guides, respectively. The mean PPD for the total group was 4.24 mm (SD 1.25), and 3.79 mm (SD 0.97) and 4.51 mm (SD 1.33) for the tooth- and mucosa-supported guides, respectively. Four implants (6.3%) were diagnosed with peri-implantitis. Coronal deviation was slightly associated with having a negative impact on bone level at follow-up, but this was not statistically significant. Seven patients (43.8%) experienced technical complications. Biological complications were seen in 3/16 patients (18.75%). (4) SCAIP may contribute to more predictable implant placement; the long-term clinical outcome is similar to conventional nonguided surgery.


Confirmation of a Rare Genetic Leukoencephalopathy due to a Novel Bi-allelic Variant in RPIA.
Ribose 5-phosphate isomerase deficiency is a rare genetic leukoencephalopathy caused by pathogenic sequence variants in RPIA, that encodes ribose 5-phosphate isomerase, an enzyme in the pentose phosphate pathway. Till date, only three individuals with ribose 5-phosphate isomerase deficiency have been described in literature. We report on a subject with RPIA associated progressive leukoencephalopathy with elevated urine arabitol and ribitol levels and a novel missense variant c.770T > C p.(Ile257Thr) in exon 8 of RPIA. We also compare the phenotypes of all the four subjects. Our report confirms the phenotype and the genetic cause of this condition.


A comparison of neurotransmitter-specific and neuropeptide-specific neuronal cell types present in the dorsal cortex in turtles with those present in the isocortex in mammals: implications for the evolution of isocortex.
Although it seems highly likely that mammalian isocortex evolved from a structure resembling reptilian telencephalic cortex, it has been uncertain if this occurred by the laminar differentiation of three-layered reptilian cortex into six-layered mammalian isocortex without the addition of new cell types or by laminar differentiation with the addition of new cell types. To distinguish between these two possibilities, immunohistochemical techniques were used to study turtles to see if the same major neuronal cell types, as defined by neurotransmitter or neuropeptide content, present in mammalian isocortex are also present in the specific part of reptilian cortex thought to be the forerunner of at least parts of isocortex, namely the dorsal cortex. Neurons containing the following substances are the major transmitter-specific types of neurons known to be present in mammalian isocortex: cholecystokinin-8 (CCK8), vasoactive intestinal polypeptide (VIP), acetylcholine, substance P (SP), neuropeptide Y (NPY), somatostatin (SS), LANT6, enkephalin, GABA and glutamate (GLUT). In turtles, only those of the above substances that are found in large numbers of neurons in layers V-VI in mammalian isocortex, irrespective of whether they are also present in layers II-IV (i.e. SP, NPY, SS, LANT6, GABA and GLUT), were present in neurons in dorsal cortex. The neurons containing these substances in dorsal cortex in turtles were generally highly similar in morphology to their counterparts in mammalian isocortex. In contrast, neurons labeled for CCK8, VIP or acetylcholine, which are mainly found in neurons of layers II-IV of mammalian isocortex, were absent or extremely rare in dorsal cortex. The absence or paucity of neurons labeled for these latter substances in dorsal cortex in turtles did not reflect an overall staining failure of the antisera used since the same antisera yielded excellent labeling of neurons, fibers and terminals in many other brain regions in turtles. Thus, dorsal cortex in turtles appears to lack several of the major cell types characteristic of layers II-IV of mammalian isocortex, but possesses a number of the major cell types characteristic of layers V-VI of isocortex. The findings support and extend a previous suggestion by Ebner [1976], based on hodological data, that dorsal cortex in turtles may lack the types of neurons found in the more superficial layers of mammalian isocortex.(ABSTRACT TRUNCATED AT 400 WORDS)


Substrate binding to a nitrite reductase induces a spin transition.
The multiheme enzyme nitrite reductase catalyzes a 6-electron reduction of nitrite to ammonia. The reaction is initiated by substrate binding to the free axial position of the high spin penta-coordinated heme active site. The spin configuration of the resulting complex is crucial for discrimination between the heterolytic vs homolytic character of the cleavage of the N-O bond and, therefore, subsequent steps of the catalytic cycle. Here, we report the first experimental evidence, based on resonance Raman spectroscopy, that nitrite binding to the enzyme from D. vulgaris induces a transition from the high spin to the low spin configuration in the catalytic heme, thereby favoring the heterolytic route.


Recent developments in dental plaque disclosants.
The use of erythrosin and fluorescein for disclosing dental plaque in 81 children aged 11-14 years and in 17 young men is reported. Erythrosin stained all plaque. When fluroescein was used, plaque, whether mature or recently exposed to sugars was disclosed under ultra-violet light. In the children, the erythrosin stained approximately twice as extensively as fluorescein.


Dynamic contour tonometry: principle and use.
Interindividual variability of central corneal thickness has been found to be a source of error for conventional Goldmann applanation tonometry. The dynamic contour tonometer represents a potentially new technology for non-invasive and direct intraocular pressure (IOP) measurement, and has been proposed to accurately measure the true IOP irrespective of the corneal thickness. It is based on the principle that when the tip of the device exactly matches the contour of the cornea, the pressure measured by a transducer placed on its tip is an accurate indicator of the true IOP. This device is also capable of measuring the ocular pulse amplitude, a variable that has controversial significance in the diagnosis and management of glaucoma. Even though this technique seems to be very promising, further studies are required to conclusively determine the effectiveness of the dynamic contour tonometer in patients having an abnormal or irregular corneal contour.


Chemical analysis of complex organic mixtures using reactive nanospray desorption electrospray ionization mass spectrometry.
Reactive nanospray desorption electrospray ionization (nano-DESI) combined with high-resolution mass spectrometry was utilized for the analysis of secondary organic aerosol produced through ozonolysis of limonene (LSOA). Previous studies have shown that LSOA constituents are multifunctional compounds containing at least one aldehyde or ketone groups. In this study, we used the selectivity of the Girard's reagent T (GT) toward carbonyl compounds to examine the utility of reactive nano-DESI for the analysis of complex organic mixtures. In these experiments, 1-100 μM GT solutions were used as the working solvents for reactive nano-DESI analysis. Abundant products from the single addition of GT to LSOA constituents were observed at GT concentrations in excess of 10 μM. We found that LSOA dimeric and trimeric compounds react with GT through a simple addition reaction resulting in formation of the carbinolamine derivative. In contrast, reactions of GT with monomeric species result in the formation of both the carbinolamine and the hydrazone derivatives. In addition, several monomers did not react with GT on the time scale of our experiment. These molecules were characterized by relatively high values of the double bond equivalent and low oxygen content. Furthermore, because addition of a charged GT tag to a neutral molecule eliminates the discrimination against the low proton affinity compounds in the ionization process, reactive nano-DESI analysis enables quantification of individual compounds in the complex mixture. For example, we were able to estimate for the first time the amounts of dimers and trimers in the LSOA mixture. Specifically, we found that the most abundant LSOA dimer was detected at the ~0.5 pg level and the total amount of dimers and trimers in the analyzed sample was ~11 pg. Our results indicate that reactive nano-DESI is a valuable approach for examining the presence of specific functional groups and for the quantification of compounds possessing these groups in complex mixtures.


Mechanisms shaping the slow nicotinic synaptic current at the motoneuron-renshaw cell synapse.
In spinal cord slices from newborn mice we have analyzed the kinetics of the EPSCs mediated by heteromeric nicotinic receptors at the motoneuron-Renshaw cell (MN-RC) synapse. The miniature EPSCs decay with a time constant of 13.0 ± 1.1 ms whereas the decay of the evoked EPSCs (eEPSCs) is biphasic, with time constants of 15.6 ± 0.8 and 124.8 ± 9.0 ms. The slow component becomes prominent during a repetitive stimulation, but its time constant is unchanged. It is selectively reduced by the addition of acetylcholinesterase (AChE), and thus appears to involve ACh spillover. The constancy of the slow time constant during a train is best explained by a local spillover activating high-affinity receptors. In many cells a fraction of the eEPSC originates in neighboring RCs and is transmitted by the low-pass filter of the gap junctions. The component transmitted electrically can be eliminated by meclofenamic acid, a blocker of gap junctions. The local spillover produced by a repetitive stimulation was compared with the long-range spillover produced by inactivation of AChE. The pharmacological inactivation of AChE by neostigmine caused the appearance of an ultra-slow (second range) decay component in eEPSCs and also a continuous inward current interpreted as resulting from a continuous ACh presence. In animals lacking functional AChE in the CNS (PRiMA(-/-) mice) the EPSCs resembled those observed in neostigmine but the steady inward current was much smaller, suggesting an adaptation to the absence of AChE.


Analysis of matrisome expression patterns in murine and human dorsal root ganglia.
The extracellular matrix (ECM) is a dynamic structure of molecules that can be divided into six different categories and are collectively called the matrisome. The ECM plays pivotal roles in physiological processes in many tissues, including the nervous system. Intriguingly, alterations in ECM molecules/pathways are associated with painful human conditions and murine pain models. Nevertheless, mechanistic insight into the interplay of normal or defective ECM and pain is largely lacking. The goal of this study was to integrate bulk, single-cell, and spatial RNA sequencing (RNAseq) datasets to investigate the expression and cellular origin of matrisome genes in male and female murine and human dorsal root ganglia (DRG). Bulk RNAseq showed that about 65% of all matrisome genes were expressed in both murine and human DRG, with proportionally more core matrisome genes (glycoproteins, collagens, and proteoglycans) expressed compared to matrisome-associated genes (ECM-affiliated genes, ECM regulators, and secreted factors). Single cell RNAseq on male murine DRG revealed the cellular origin of matrisome expression. Core matrisome genes, especially collagens, were expressed by fibroblasts whereas matrisome-associated genes were primarily expressed by neurons. Cell-cell communication network analysis with CellChat software predicted an important role for collagen signaling pathways in connecting vascular cell types and nociceptors in murine tissue, which we confirmed by analysis of spatial transcriptomic data from human DRG. RNAscope in situ hybridization and immunohistochemistry demonstrated expression of collagens in fibroblasts surrounding nociceptors in male and female human DRG. Finally, comparing human neuropathic pain samples with non-pain samples also showed differential expression of matrisome genes produced by both fibroblasts and by nociceptors. This study supports the idea that the DRG matrisome may contribute to neuronal signaling in both mouse and human, and that dysregulation of matrisome genes is associated with neuropathic pain.


Reducing exposure risk in the operating room.
The purpose of this article is to evaluate and recommend current best practices related to safe handling of sharp instruments in reducing transmission of blood borne pathogens, specifically HIV, in the operating suite. 1) To identify the risk of exposure to bloodborne pathogens from sharps in the OR suite. 2) To identify practices to reduce the risk of exposure to bloodborne pathogens in the OR suite.


Agr typing of Staphylococcus aureus species isolated from clinical samples in training hospitals of Isfahan and Shahrekord.
As an opportunistic pathogen, Staphylococcus aureus is associated with serious nosocomial infections and growing antimicrobial resistance against beta-lactams among S. aureus strains has become a global challenge. The current study was designed to investigate the presence of agr genes among S. aureus strains recovered from clinical samples in university hospitals of Isfahan and Shahrekord. A total of 150 S. aureus isolates were screened by Disk diffusion method (DDM) and conventional PCR. The minimum (17.3%) and maximum (46%) antibiotic resistance rates were found in vancomycin and cefoxitin, respectively. The majority of our isolates were classified as agr type I followed by type II, type IV, and type III. The statistical analysis showed a significant correlation between agr type I and antibiotic resistance against cefoxitin and erythromycin (p = 0.04 and p = 0.03, respectively). Based on our findings, the agr typing could be considered an effective approach for molecular tracking of S. aureus infections.


Medical student experience with AIDS and needle disposal behaviour.
A survey of medical students at Columbia University, College of Physicians and Surgeons, was conducted to investigate needle-handling behaviour with HIV positive patients. Recapping a used needle increases the students' risk of a needle stick. There were 160 responses, yielding a response rate of 27.6%. Students placed used needles in the sharps container without recapping the needle significantly more often if they had experience with a patient with AIDS. There was no correlation between personal exposure to contaminated material (being stuck or exposure to other contaminated material) and correct needle disposal behaviour. Women students (single or married) only used increased precautions during sex about one-third of the time, a figure similar to women psychiatric patients. Single male students used increased precautions 41.5% of the time, while married male students used increased precautions 8.7% of the time.