Validation of pressure gradient and peripheral fractional flow reserve measured by a pressure wire for diagnosis of iliofemoral artery disease with intermediate stenosis.
To examine the pressure gradient and peripheral fractional flow reserve (pFFR) measured by a pressure wire as indicators of hemodynamic significance in iliofemoral angiographic intermediate stenosis. The utility of pressure measurements using a pressure wire with vasodilators is unclear in cases with intermediate iliofemoral stenosis. The mean pressure gradient (MPG) and mean pressure ratio (MPR) were measured at baseline and after injection of isosorbide dinitrate in 23 lesions with angiographically intermediate iliofemoral stenosis. Patients with complex lesions, infrapopliteal artery lesions, chronic total occlusion, and surgical bypass grafts were excluded. Hyperemic MPR was considered equivalent to pFFR. Changes in parameters in response to vasodilators were assessed and correlations of peak systolic velocity ratio (PSVR) with hyperemic MPG and pFFR were examined using duplex ultrasound. After injection of isosorbide dinitrate, hyperemic MPG increased significantly (from 9.0±5.7 to 16.3±6.2 mmHg; P<0.05) and hyperemic MPR (pFFR) decreased significantly (from 0.92±0.06 to 0.81±0.07; P<0.05). PSVR was significantly correlated with hyperemic MPG (R=0.52; P<0.05) and pFFR (R=-0.50; P<0.05). The optimal cut-off value of pFFR as an indicator of significant hemodynamic stenosis (PSVR >2.5) was 0.85 (area under the curve 0.72; sensitivity 94%; specificity 50%, P<0.05). pFFR measured using a pressure wire is reliable for prediction of hemodynamic significance in iliofemoral intermediate stenosis.


Compressed sodium chloride as a fast-acting antimicrobial surface: results of a pilot study.
Antimicrobial surfaces are currently being studied as an aid to reduce transmission of pathogens leading to healthcare-associated infections (HAIs). Among the most harmful and costly pathogens that cause HAIs is meticillin-resistant Staphylococcus aureus (MRSA). Currently available and previously investigated antimicrobial surface technologies that are effective against MRSA (e.g. copper alloy surfaces) take 30min to several hours to achieve significant reduction. This article presents a new antimicrobial surface technology made of compressed sodium chloride that reduces MRSA 20-30 times faster than copper alloy surfaces.


Factor structure of the Montreal Cognitive Assessment in Parkinson disease.
The Montreal Cognitive Assessment (MoCA) is a common tool for screening mild cognitive impairment (MCI) and dementia. Studies in multiple clinical groups provide evidence for various factor structures mapping to different cognitive domains. We tested the factor structure of the MoCA in a large cohort of early Parkinson disease (PD). Complete MoCA data were available from an observational cohort study for 1738 patients with recent-onset PD (64.6% male, mean age 67.6, SD 9.2). Confirmatory factor analysis (CFA) was applied to test previously defined two-factor, six-factor, and three-factor models in the full sample and in a subgroup with possible cognitive impairment (MoCA < 26). Secondary analysis used exploratory factor analysis (EFA; principal factors with oblique rotation). The mean MoCA score was 25.3 (SD 3.4, range 10-30). Fit statistics in the six-factor model (χ2 /df 17.77, root mean square error of approximation [RMSEA] 0.10, comparative fit index [CFI] 0.74, Tucker-Lewis index [TLI] 0.69, standardised root mean square residual [SRMR] 0.07) indicated poorer fit than did previous studies. Findings were similar in the two-factor and three-factor models. EFA suggested an alternative six-factor solution (short-term recall, visuospatial-executive, attention/working memory, verbal-executive, orientation, and expressive language), although CFA did not support the validity of the new model. The factor structure of the MoCA in early PD was not consistent with that of previous research. This may reflect higher cognitive performance and differing demographics in our sample. The results do not support a clear, clinically relevant factor structure in an early PD group, suggesting that the MoCA should be followed with detailed assessment to obtain domain-specific cognitive profiles.


Stability and performance of ant queue inspired task partitioning methods.
In this paper, we consider computing systems that have autonomous helper components which fulfill support functions and that possess reconfigurable hardware so that they can specialize to different types of service tasks. Several self-organized task partitioning methods are proposed that can be used by the helper components to decide how to reconfigure and which service tasks to execute. The proposed task partitioning methods are inspired by the so-called ant queue system that can be found in real ants for partitioning tasks between the individuals. The aim of this study is to investigate basic properties of the task partitioning methods, like stability and efficiency, in order to obtain basic insights into the design of task partitioning methods in self-organized service systems. More precisely, the investigations are threefold: (1) discrete event simulations are used to investigate systems, (2) for a simple version of the task partitioning system analytical stability results are obtained by means of delay differential equation systems and (3) by numerically solving initial value problems.


Disparities in pediatric cancer survivorship care: A systematic review.
Childhood cancer survivors (CCS) experience many long-term health problems that can be mitigated with recommended survivorship care. However, many CCS do not have access to survivorship care nor receive recommended survivorship care. We reviewed the empirical evidence of disparities in survivorship care for CCS. This systematic review searched PubMed, CINAHL, and PsycINFO for studies on survivorship care for CCS (PROSPERO: CRD42021227965) and abstracted the reported presence or absence of disparities in care. We screened 7945 citations, and of those, we reviewed 2760 publications at full text. A total of 22 studies reported in 61 publications met inclusion criteria. Potential disparities by cancer treatment (N = 14), diagnosis (N = 13), sex (N = 13), and current age (N = 13) were frequently studied. There was high quality of evidence (QOE) of survivorship care disparities associated with non-White race, Hispanic ethnicity, and being uninsured. Moderate QOE demonstrated disparities among CCS who were unemployed and older. Lower QOE was found for disparities based on cancer diagnosis, cancer treatment, age at diagnosis, time since diagnosis, sex, insurance type, income, educational attainment, and geographic area. We found strong empirical evidence of disparities in survivorship care for CCS associated with race, ethnicity, and insurance status. Multiple other disparate groups, such as those by employment, income, insurance type, education, cancer diagnosis, age at diagnosis, time since diagnosis, cancer treatment, geographic area, sex, and self-identified gender warrant further investigation. Prospective, multilevel research is needed to examine the role of other patient characteristics as potential disparities hindering adequate survivorship care in CCS.


Serotype discrimination of encapsulated Streptococcus pneumoniae strains by Fourier-transform infrared spectroscopy and chemometrics.
Fourier-transform infrared (FTIR) spectroscopy was evaluated as an alternative method for serotyping encapsulated Streptococcus pneumonia strains. Sixty-nine invasive strains from the Microbiology Laboratory of the Medicine Faculty of University of Lisbon were selected for the analysis. The encapsulated strains used in this work (9N, 9V, 14, 19A, 19F, 23A, 23B and 23F) were serotyped by the standard capsular reaction test using the chessboard method and specific sera. FTIR spectra were analysed with chemometric methods. Results showed that the best spectral region unveiling serotype difference is located at 1185-900 cm(-1). A partial least squares discriminant analysis model was calibrated using this spectral region against the chessboard method serotyping. FTIR spectroscopy proved to be able to correctly predict 100% of strains according to the serogroups (9, 14, 19, 23). A segregated analysis showed that it was also possible to differentiate serotypes belonging to the same serogroup although spectral differences are less pronounced as was initially expected.


A Network of microRNAs Acts to Promote Cell Cycle Exit and Differentiation of Human Pancreatic Endocrine Cells.
Pancreatic endocrine cell differentiation is orchestrated by the action of transcription factors that operate in a gene regulatory network to activate endocrine lineage genes and repress lineage-inappropriate genes. MicroRNAs (miRNAs) are important modulators of gene expression, yet their role in endocrine cell differentiation has not been systematically explored. Here we characterize miRNA-regulatory networks active in human endocrine cell differentiation by combining small RNA sequencing, miRNA over-expression, and network modeling approaches. Our analysis identified Let-7g, Let-7a, miR-200a, miR-127, and miR-375 as endocrine-enriched miRNAs that drive endocrine cell differentiation-associated gene expression changes. These miRNAs are predicted to target different transcription factors, which converge on genes involved in cell cycle regulation. When expressed in human embryonic stem cell-derived pancreatic progenitors, these miRNAs induce cell cycle exit and promote endocrine cell differentiation. Our study delineates the role of miRNAs in human endocrine cell differentiation and identifies miRNAs that could facilitate endocrine cell reprogramming.


Micro-CT evaluation of four final irrigation protocols on hard-tissue debris removal from mesial roots of mandibular molars containing isthmus.
To evaluate by means of microcomputed tomography (micro-CT), the efficacy of four final irrigation protocols in the removal of hard-tissue debris (HTD) in mesial roots of mandibular molars containing isthmus. Forty standardized mesial roots of extracted mandibular molars presenting isthmus were selected. The root canals were prepared and randomly divided into 4 groups (n = 10): EA, EndoActivator (Dentsply Sirona); EC, Easy Clean (Easy Dental Equipment, Belo Horizonte, Brazil); XPF, XP-Endo Finisher (FKG Dentaire, La Chaus-de Fonds, Switzerland); and PUI, passive ultrasonic irrigation using Irrisafe tip (Satelec Acteon, Merignac, France). Each final irrigation protocol was performed in two cycles (60 s), using, respectively, 2.5% sodium hypochlorite and 17% EDTA. Micro-CT scans were obtained pre-operatory, post-preparation, and post-irrigation. The percentage of HTD reduction was calculated. Data was analyzed statistically (ANOVA and Kruskal-Wallis, significance set at 5%). The percentage of HTD reduction was greatest for the XPF group (77.92%), followed by EA (62.92%), PUI (47.48%), and EC (32.65%). Statistical differences (p < .05) were found between XPF and EC only. A significant difference (p < .05) was found between XPF and EC in all thirds and between PUI and EC in the middle third. XPF, EA, and PUI were similarly effective in HTD reduction. However, none of the evaluated protocols was able to completely remove all the debris. Final irrigation protocols aim to clean the canal complexities that are not addressed by the shaping procedures. Micro-CT allowed to assess the removal of hard-tissue debris in the isthmus and canals of mandibular molars.


Management of Major Traumatic Upper Extremity Amputations.
Traumatic upper extremity amputation is a life-altering event, and recovery of function depends on proper surgical management and postoperative rehabilitation. Many injuries require revision amputation and postoperative prosthesis fitting. Care should be taken to preserve maximal length of the limb and motion of the remaining joints. Skin grafting or free tissue transfer may be necessary for coverage to allow preservation of length. Early prosthetic fitting within 30 days of surgery should be performed so the amputee can start rehabilitation while the wound is healing and the stump is maturing. Multidisciplinary care is essential for the overall care of the patient following a traumatic amputation of the upper limb.


[Comparison of TIPS, a modified Sugiura procedure and TIPS plus a modified Sugiura procedure for portal hypertension].
Transjugular intrahepatic portosystemic shunts (TIPS), a modified Sugiura procedure and TIPS plus a modified Sugiura procedure were compared to evaluate their clinical results in treatment of portal hypertension. Ninety patients with portal hypertension respectively underwen TIPS (group I, n = 30), a modified Sugiura procedure (group II, n = 30) and TIPS plus a modified Sugiura procedure (group III, n = 30). The rates of rebleeding and encephalopathy, and the mortality of patients with portal hypertension were observed. The early postoperative complications were observed in 23.33% of the patients in group I, in 30.0% of those in group II, and in 20.0% of those in group III. The early postoperative rates of rebleeding were 6.67% in group I, 10% in group II, and 0% in group III. Hepatic encephalopathy was seen in 16.67% of the patients in group I, 0% in group II and 13.33% in group III. The early mortality was 3.33% in group I. During follow-up for 1 - 36 months, the rates of rebleeding were 34.48% in group I, 33.33% in group II, and 3.33% in group III. The rates of encephalopathy and mortality were respectively 17.20% and 20.69% in group I, 3.33% and 13.33% in group II, 3.33% and 3.33% in group III. The shunt patency in group III was higher than that in group I. Combination of TIPS and a modified Sugiura procedure can be effective to prevent and treat variceal bleeding.


Quantitative structure-activity relationships for the inhibition toxicity to root elongation of Cucumis sativus of selected phenols and interspecies correlation with Tetrahymena pyriformis.
The comparative toxicities of selected phenols to higher plants Cucumis sativus were measured and the negative logarithm molar concentration of the root elongation median inhibition (IRC50) were derived. Quantitative structure-activity relationships (QSARs) were developed to explore the toxicity influencing factors and for predictive purpose. The toxicity data, fell into two classes: polar narcosis and bio-reactive. For polar narcotic phenols, a highly significant two-parameter QSAR based on 1-octanol/water partition coefficient (logKow) and energy of the lowest unoccupied orbital (E(lumo)) was derived (IRC50 = 0.77 log Kow - 0.39E(lumo) + 2.36 n = 22 r2 = 0.89). The five bio-reactive chemicals proved to show elevated toxicity due to their typical substructure involved diverse reactive mechanisms. In an effort to model all chemicals, a robust multiple-variable QSAR combining logKow, E(lumo) and Qmax, the most negative net atomic charge, was developed (IRC50 = 0.65 logKow - 0.72E(lumo) + 0.23Qmax + 2.81 n = 27 r2 = 0.94), indicating that hydrophobicity, electrophilicity and hydrogen bond interaction contribute mainly to the phytotoxicity. The toxicological data was compared with Tetrahymena pyriformis 2-d population growth inhibition toxicity (IGC50) and excellent interspecies correlations were observed both for the polar narcotics and for five reactive chemicals (for polar narcotics: IRC50 = 0.95IGC50 + 1.07 n = 16 r2 = 0.89; for bio-reactive chemicals: IRC50 = 0.98IGC50 + 2.19 n = 5 r2 = 0.97; and for all: IRC50 = 0.93IGC50 + 1.63 n = 21 r2 = 0.87). This suggested that T pyriformis toxicity could serve as a surrogate of C. sativus toxicity for phenols and interspecies correlation also could be established for reactive chemicals.


Genotoxicity of acrylic acid, methyl acrylate, ethyl acrylate, methyl methacrylate, and ethyl methacrylate in L5178Y mouse lymphoma cells.
A series of monomeric acrylate/methacrylate esters (methyl acrylate, ethyl acrylate, methyl methacrylate, and ethyl methacrylate) as well as acrylic acid were examined for genotoxic activity in L5178Y mouse lymphoma cells without exogenous activation. All five compounds induced concentration-dependent increases in mutant frequency. Small-colony, trifluorothymidine-resistant mutants were primarily induced, which suggests that these compounds may act via a clastogenic mechanism. This prediction was confirmed by the finding that all five compounds produced gross chromosome aberrations in mouse lymphoma cells. The two acrylates were much more potent in their response than acrylic acid. Methyl acrylate (22 micrograms/ml, survival = 18%) induced 385 mutants/10(6) survivors (total mutant frequency less the spontaneous mutant frequency) and 45 chromosome aberrations/100 cells analyzed (total aberrations less the spontaneous background). Ethyl acrylate (37.5 micrograms/ml, survival = 15%) induced 683 mutants/10(6) survivors and 48 aberrations/50 cells analyzed. Acrylic acid (500 micrograms/ml, survival = 22%) induced 245 mutants/10(6) survivors and 37 aberrations/100 cells analyzed. The two methacrylates required higher concentrations to induce a positive response. Methyl methacrylate (2,799 micrograms/ml, survival = 11%) induced 230 mutants/10(6) survivors and 29 aberrations/200 cells analyzed. Ethyl methacrylate was extremely difficult to test because of a plateau in the dose response, over which the toxicity fluctuated from 2% to 37% survival. Positive responses (twice the spontaneous background) were only obtained at toxicity levels with less than approximately 20% survival. A concentration of 1,626 micrograms/ml (survival = 16%) induced 83 mutants/10(6) survivors and 11 aberrations/200 cells analyzed. The evidence suggests that the genotoxicity of these compounds is most likely due to a clastogenic mechanism.


Impact of lockdown during COVID-19 pandemic on the air quality of North Indian cities.
The World Health Organization, which proclaimed the COVID-19 a pandemic in early March 2020, imposed a partial lockdown by the Government of India on 21 March 2020. The aim of this investigation was to measure the change in air pollutants, including particulate matter (PM2.5 and PM10) and gaseous pollutants (NO2, CO and O3) during COVID-19 lockdown (25th March to 14th April 2020) across four major polluted cities in North India. In all region, PM2.5, PM10, NO2 and CO were significantly reduced while O3 has been shown mixed variation with increased in Agra and decreased in all other stations during lockdown. PM2.5 was reduced by ~20-50% and highly decreased in Noida. PM10 was most significantly decreased by 49% in Delhi. NO2 was reduced by ~10-70%, and high reduction was observed in Noida. Likewise, ~10-60% reduction was found in CO and most significantly decreased in Gurugram. However, an increased in O3 was observed in Agra by 98% while significantly reduced in other sites. Compared to the same timeframe in 2018-2019, PM2.5 and PM10 values for all sites were reduced by more than 40%.


Increased carotid intima-media thickness in rheumatoid arthritis: an update meta-analysis.
This study aims to derive a more precise estimation on carotid intima-media thickness (CIMT) level in patients with rheumatoid arthritis (RA) and related factors. Studies published from January 1, 1982 to December 31, 2014 in English, which comparing CIMT between RA group and control group were searched in PubMed, Embase, and Cochrane Library databases. Heterogeneity test was performed, and publication bias was evaluated. Stata software 12.0 was used to perform the meta-analysis. Two-thousand one hundred sixty-three articles were obtained after searching databases, and 47 studies were finally included in the meta-analysis. The result of the analysis in random effect model showed that RA group had significantly higher CIMT than control group, with the standardized mean difference (SMD) of 1.04 and 95% CI (0.81,1.27). To evaluate the stability of our results, sensitivity analyses were performed, and the results showed no significant change when any one study was excluded. Subgroup analyses showed that region, race, age, BMI, and disease duration were associated with CIMT in RA patients. In summary, CIMT in RA patients is thicker than healthy controls, and it is influenced by region, race, age, BMI, and disease duration.


Efficacy and Safety of Long-Term Thiopurine Maintenance Treatment in Japanese Patients With Ulcerative Colitis.
The long-term clinical outcomes of patients with bio-naive ulcerative colitis (UC) who maintain remission with thiopurine are unclear. The aim of this study was to assess the long-term efficacy and safety of maintenance treatment with thiopurine in UC patients. This was a retrospective observational cohort analysis conducted at a single center. Between December 1998 and August 2013, 59 of 87 patients with bio-naive UC who achieved remission after induction with treatments other than biologics were enrolled. Remission maintenance with thiopurine was defined as no concomitant treatment needed other than 5-aminosalicylate without relapse. We assessed the remission-maintenance rate, mucosal healing rate, colectomy-free rate, and treatment safety in UC patients who received thiopurine as maintenance treatment. The 84-month cumulative remission-maintenance and colectomy-free survival rates in the UC patients who were receiving maintenance treatment with thiopurine and 5-aminosalicylate were 43.9% and 88.0%, respectively. Of the 38 patients who underwent colonoscopy during thiopurine maintenance treatment, 23 (60.5%) achieved mucosal healing. Of the 59 patients who achieved clinical remission with thiopurine, 6 patients (10.2%) discontinued the thiopurine therapy because of adverse events. Our study demonstrates the long-term efficacy and safety of thiopurine treatment in patients with bio-naive UC.


[Intraoperative neuroprotection--influence of the anaesthesiological management].
Perioperative neurofunctional disorders may become clinically apparent as e.g. perioperative stroke (POS) or postoperative cognitive deficit (POCD). Newly diagnosed neuro-functional disorders are associated with worsening of postoperative outcome. Focus of this review article is on the possibilities of the intraoperative anaesthesiological management to favourably influence incidence and severity of neurological complications and to improve postoperative outcome.


Potential lung cancer risk from indoor radon exposure.
The contribution of radon daughter exposure to excess lung cancer in underground miners is universally accepted. These miners received exposures from tens to thousands of WLM in a relatively few years. Although the miners were also exposed to other noxious agents in mines, the appearance of the excess lung cancer mortality in several types of mines and the increase with increasing exposure provide convincing evidence of the role of radon as the carcinogen. It is conceivable that exposures to radon at an average concentration of one to two pCi/liter, the levels for a majority of homes, might not produce excess lung cancers. This would require that a lifetime exposure at low concentrations produce a different response from that of a few years at higher levels for the miners. This is unlikely but not impossible. The current environmental epidemiology is of varying quality. The better studies may give some answers in a few years. These studies are more likely to establish an upper limit of risk than to provide an exposure-response model. Present risk estimates cannot be used accurately in estimating the overall lung cancer risk to the US population, since there are no good data on average exposure and exposure distribution. For example, the number of homes above the EPA guideline of four pCi/liter may range from two million to 10 million. An estimate of the actual radon exposure in the US may be forthcoming from a planned EPA survey, but these data will not be available for a few years. In the conservative tradition of radiation protection, indoor radon exposures in homes are estimated to produce a number of excess lung cancers in the population. One estimate by the NCRP is about 10,000 deaths per year in the US, for an average annual estimated exposure of 0.2 WLM (about one pCi/liter). The National Academy of Sciences (BEIR IV) estimates 13,000 deaths for the same exposure, and the EPA's estimate is 5,000 to 20,000.


Emotional valence of self-defining memories in older adults: A longitudinal study.
The present study aimed to evaluate the pleasantness bias and fading affect bias in self-defining memories (SDMs) and to examine the relationship between their emotional valence of SDMs and cognitive function and serotonin transporter polymorphisms (5-HTTLPR) with a prospective longitudinal method. Ninety-two older adults recalled SDMs twice at an interval of one year (T1 and T2). The results showed a pleasantness bias and a fading affect bias in SDMs. The higher the working memory was, the higher the vividness of SDMs and the higher the concordance rate of SDMs between T1 and T2. Meanwhile, cognitive performance had no effect on the emotional valence of SDMs. Additionally, the repeatedly recalled SDMs in the S/S allele carriers of the 5-HTTLPR polymorphism changed with a lower negative valence at T2 than at T1. The 5-HTTLPR polymorphism may be a plasticity factor that predicts positive outcomes in positive situations.


Simulation study of a D-shape PET scanner for improved sensitivity and reduced cost in whole-body imaging.
Much research effort is being made to increase the sensitivity and improve the imaging performance of positron emission tomography (PET) scanners. Conventionally, sensitivity can be increased by increasing the number of detector rings in the axial direction (but at high cost) or reducing the diameter of the scanner (with the disadvantages of reducing the space for patients and degrading the spatial resolution due to the parallax error). In this study, we proposed a PET scanner with a truncated ring and an array of detectors that can be arranged in a straight line below the bed. We called this system 'D-PET' as it resembles the letter 'D' when it is rotated by 90° in the counterclockwise direction. The basic design idea was to cut the unused space under the patient's bed; this area is usually not in use in clinical diagnosis. We conducted Monte Carlo simulations of the D-PET scanner and compared its performance with a cylindrical PET scanner. The scanners were constructed from 4-layer depth-of-interaction detectors which consisted of a 16 × 16 × 4 LYSO crystal array with dimensions of 2.85 × 2.85 × 5 mm3. The results showed that the D-PET had an increase in sensitivity and peak-NECR of 30% and 18%, respectively. The D-PET had low noise in the reconstructed images throughout the field-of-view compared to the cylindrical PET. These were achieved while keeping sufficient space for the patient, and also without a severe effect on the spatial resolution. Furthermore, the number of detectors (and hence the cost) of the D-PET scanner was reduced by 12% compared to the cylindrical PET scanner.


Validation and comparison of luminex multiplex cytokine analysis kits with ELISA: determinations of a panel of nine cytokines in clinical sample culture supernatants.
Analyses of the expression pattern of multiple cytokines are frequently required for characterization of the status of the immune system as it pertains to Th type bias and intrinsic levels of inflammation. Classically, analysis of cytokine expression patterns has been performed by enzyme-linked immunosorbent assays (ELISA) for each separate analyte. A new technology, Luminex MAP, facilitates the simultaneous evaluation of multiple immune mediators with advantages of higher throughput, smaller sample volume, and lower cost. Validation of this technology has been limited to small sample sets, limited use of clinical study specimens, and use of non-commercial reagents. Ninety-six specimens from women over the course of their respective pregnancies were evaluated for cytokine concentrations using commercially available ELISA kits and commercially available Luminex MAP kits according to the manufacturers' directions. Correlations between data sets were evaluated using Pearson's correlation coefficient (r). Excellent correlations were demonstrated for IL-1 beta, IL-4, IL-5, IL-6, IL-10, IFN gamma, and TNF alpha, in contrast to IL-12 p 70 and IL-13. Luminex multiplex technology has distinct advantages and is a valid alternative method to ELISA for the evaluation of the majority of cytokines tested and for the characterization of immune system status.


Ventricular arrhythmia incidence in the rat is reduced by naloxone.
This study characterized the antiarrhythmic effects of the opioid receptor antagonist naloxone in rats subject to electrically induced and ischemic arrhythmias. Naloxone (2, 8 and 32 μmol/kg/min) was examined on heart rate, blood pressure, and the electrocardiogram (EKG) as well as for effectiveness against arrhythmias produced by occlusion of the left anterior descending coronary artery or electrical stimulation of the left ventricle. Naloxone reduced blood pressure at the highest dose tested while heart rate was dose-dependently reduced. Naloxone dose-dependently prolonged the P-R and QRS intervals and increased the RSh amplitude indicative of effects on cardiac sodium (Na) channels. Naloxone prolonged the Q-T interval suggesting a delay in repolarization. Naloxone effects were comparable to the comparator quinidine. Naloxone (32 μmol/kg/min) reduced ventricular fibrillation (VF) incidence to 38% (from 100% in controls). This same dose significantly increased the threshold for induction of ventricular fibrillation (VFt), prolonged the effective refractory period (ERP) and reduced the maximal following frequency (MFF). The patterns of ECG changes, reduction in ischemic arrhythmia (VF) incidence and changes in electrically induced arrhythmia parameters at high doses of naloxone suggest that it directly blocks cardiac Na and potassium (K) ion channels.


Patients with benign prostatic hyperplasia show shorter leukocyte telomere length but no association with telomerase gene polymorphisms in Han Chinese males.
Benign prostatic hyperplasia (BPH) is an age-related disease, occurring in >70% of men of age >60. Because telomeres and telomerase play a key role in aging and age-related diseases, and certain telomerase gene single nucleotide polymorphisms (SNPs) are shown to be associated with the susceptibility to age-related diseases, we wanted to determine the relationship between BPH and leukocyte telomere length (LTL) and telomere length-related single nucleotide polymorphisms (SNPs) of the telomerase holoenzyme genes. Peripheral blood was collected from both BPH patients and age-matched healthy male controls and genomic DNA was extracted. rs2736100 and rs2736098 at the TERT and rs12696304 at the TERC locus were analysed using pre-designed TaqMan SNP genotyping assay kits. LTL was determined using qPCR. Patients with BPH had significantly shorter LTL (1.231 ± 0.532 vs 0.899 ± 0.322, P < 0.001). The genotyping results show similar frequencies in rs2736100, rs2736098 and rs12696304 between healthy and BPH individuals. Shorter telomeres but not telomerase SNPs at the TERT and TERC loci, are associated with BPH. Short telomeres may promote senescence of a fraction of prostatic epithelial cells, while senescent cells in turn facilitate epithelial and stromal cell proliferation by the senescence-associated secretory phenotype mechanism, thereby eventually leading to BPH development.


Identification of RET fusions in a Chinese multicancer retrospective analysis by next-generation sequencing.
Fusion of RET with different partner genes has been detected in papillary thyroid, lung, colorectal, pancreatic, and breast cancer. Approval of selpercatinib for treatment of lung and thyroid cancer with RET gene mutations or fusions calls for studies to explore RET fusion partners and their eligibility for RET-based targeted therapy. In this study, RET fusion patterns in a large group of Chinese cancer patients covering several cancer types were identified using next-generation sequencing. A total of 44 fusion patterns were identified in the study cohort with KIF5B, CCDC6, and ERC1 being the most common RET fusion partners. Notably, 17 novel fusions were first reported in this study. Prevalence of functional RET fusions was 1.05% in lung cancer, 6.03% in thyroid cancer, 0.39% in colorectal cancer, and less than 0.1% in gastric cancer and hepatocellular carcinoma. Analysis showed a preference for fusion partners in different tumor types, with KIF5B being the common type in lung cancer, CCDC6 in thyroid cancer, and NCOA4 in colorectal cancer. Co-occurrence of EGFR mutations and RET fusions with rare partner genes (rather than KIF5B) in lung cancer patients was correlated with epidermal growth factor receptor-tyrosine kinase inhibitor resistance and could predict response to targeted therapies. Findings from this study provide a guide to clinicians in determining tumors with specific fusion patterns as candidates for RET targeted therapies.


Generating co-management at Kasha Katuwe Tent Rocks National Monument, New Mexico.
Collaborative planning theory and co-management paradigms promise conflict prevention and the incorporation of indigenous knowledge into plans. Critics argue that without devolved power to culturally legitimate institutions, indigenous perspectives are marginalized. Co-management practice in North America is largely limited to treaty-protected fish and wildlife because federal agencies cannot devolve land management authority. This paper explores why the Pueblo de Cochiti, a federally recognized American Indian Tribe, and the U.S. Bureau of Land Management sustained an rare joint management agreement for the Kasha-Katuwe Tent Rocks National Monument in New Mexico despite a history of conflict over federal control of customary tribal lands that discouraged the Pueblo from working with federal agencies. Based on the participant interviews and documents, the case suggests that clear agreements, management attitudes, and the direct representation of indigenous forms of government helped achieve presumed co-management benefits. However, parties enter these agreements strategically. We should study, not assume, participant goals in collaborative processes and co-management institutions and pay special attention to the opportunities and constraints of federal laws and institutional culture for collaborative resource management with tribal and local communities.


Metabolism of aldosterone in the colostomized duck (Anas platyrhynchos): partial characterization of urinary metabolites.
1. Chronically colostomized ducks were injected with [4-14C]-aldosterone to study the metabolism of aldosterone and the pattern of metabolite excretion via the kidney. 2. Nearly half of the injected dose was excreted as radiometabolites during the first 24 hr; the largest amounts being excreted during the first 3 hr after injection. 3. Ion-exchange chromatography showed that monosulfate, disulfate, glucuronide, acidic, and neutral metabolites were excreted during each collection period, and that their relative proportions changed with time after injection of [4-14C]-aldosterone. 4. HPLC analysis of the neutral radiometabolites revealed 15 major peaks with retention times corresponding to both polar and reduced derivatives of aldosterone. 5. Only small quantities of unaltered labelled aldosterone were excreted. 6. Treatment of the birds with SKF 525-A caused a decrease in the total quantity of radiometabolite excreted and a change in the proportions of neutral and acidic metabolites in the cloacal fluid. 7. The decreases that occurred in the absolute amounts of some of the polar metabolites excreted by the birds treated with SKF-525A suggests that they may be hydroxylated and at least part of the aldosterone metabolizing system in the duck is cytochrome P450 dependent.


Evaluation of the influence of inlet boundary conditions on computational fluid dynamics for intracranial aneurysms: a virtual experiment.
Inlet boundary conditions (BCs) are important inputs of computational fluid dynamics (CFD) in intracranial aneurysms (IAs). We performed sensibility analysis of CFD to different inlet BCs applied to illustrative patient-specific aneurysm-vessel geometry. BCs corresponding to generic and patient-specific pulsatile flow curves were applied to three vascular geometry models of carotid ophthalmic aneurysm-vessel geometry, in which the inlet lengths were different. CFD outcomes were compared to high frame rate Digital Subtraction Angiography (DSA) sequences. The streamlines were found to match contrast agent (CA) motion pattern in the case where the non-truncated inlet vessel model was coupled to generic Womersley BC solution. Even though dynamic pressure loss (55%) was equal for all models and different BCs, the minimum distance to wall of the fastest velocity fields for the non-truncated model was significantly larger (p=0.002) and mean vorticity sign was different. Significant difference in spatial distributions of wall shear stress (WSS) and oscillating shear stress index (OSI) was found in aneurysm between Womersley and Plugflow BC conditions, only. Reliable CFD for carotid ophthalmic aneurysm would require avoiding truncation of the inlet vessel to be independent of the solution applied to generate CFD.


Exposure therapy leads to enhanced late frontal positivity in 8- to 13-year-old spider phobic girls.
Neurobiological studies have demonstrated that psychotherapy is able to alter brain function in adults, however little exists on this topic with respect to children. This waiting-list controlled investigation focused on therapy-related changes of the P300 and the late positive potential (LPP) in 8- to 13-year-old spider phobic girls. Thirty-two patients were presented with phobia-relevant, generally disgust-inducing, fear-inducing, and affectively neutral pictures while an electroencephalogram was recorded. Participants received one session of up to 4h of cognitive-behavioral exposure therapy. Treated children showed enhanced amplitudes of the LPP at frontal sites in response to spider pictures. This result is interpreted to reflect an improvement in controlled attentional engagement and is in line with already existing data for adult females. Moreover, the girls showed a therapy-specific reduction in overall disgust proneness, as well as in experienced arousal and disgust when viewing disgust pictures. Thus, exposure therapy seems to have broad effects in children.


Chest pain with diffuse coronary ischaemia.
An 80-year-old male with a medical history of hypertension, diabetes and moderate calcific aortic stenosis, presented with ischaemic chest pain at rest. Cardiovascular examination revealed soft systolic murmur only. ECG (see online supplementary figure S1) demonstrated inferolateral ST segment depression with ST elevation in lead aVR, suggesting diffuse subendocardial ischaemia possibly consistent with a threatening left main or proximal left anterior descending (LAD) coronary lesion. Emergency coronary angiography demonstrated tandem smooth stenoses in the proximal left circumflex (LCx) and LAD arteries (figure 1A), which persisted throughout the cardiac cycle, and after 200 mcg bolus of intracoronary nitrate. Aortogram is shown (figure 1B). What diagnosis underlies the cause of this patient's symptoms? Congenital coronary artery anomaly.Coronary artery vasospasm.Myocardial bridging.Obstructive coronary artery disease.Unruptured left sinus of Valsalva aneurysm.


Response of F. arundinacea seed germination to temperatures, water potentials, and priming treatments using hydro- and thermal-time models.
The germination process and seedling development are the determining steps in the plant lifecycle that are the most sensitive to adverse environmental conditions. Therefore, this study was conducted to explore the effects of temperature and osmotic potential on germination responses using threshold models and to establish an optimal priming protocol for improving tolerance responses against osmotic stress in early growth stages. The results demonstrated that osmotic stress of - 0.8 MPa significantly influenced the extent, timing, and speed of seed germination. In addition, priming treatments led to an enhanced performance of early growth stages in response to osmotic stress. Based on thermal-time and hydro-time models, the predicted physiological parameters of the median thermal-time at sub-optimal temperature ( θ T 50 = 909.09 ∘ C h), the median ceiling temperature for 50% germination (Tc(50) = 39.29 °C), the common base temperature (Tb = 7.88 °C), the constant thermal-time at supra-optimal temperature ( θ T = 805.96 °C h), the threshold water potential (Ψb(50) = - 1.13 MPa), and the hydro-time constant ( θ H = 56.09 MPa h) quantitatively describe the tolerance threshold of the germination process under different osmotic and temperature conditions. The results also showed that the efficiency of seed treatments depended on the priming conditions, including temperature, duration, and also concentration of the priming agent. However, the treatments of gibberellic acid (5 days, 10 °C, 100 ppm), salicylic acid (5 days, 10 °C, 50 ppm), calcium chloride (3 days, 10 °C, 10 mM), potassium nitrate (3 days, 10 °C, 100 mM), and hydro-priming (3 days, 10 °C) were optimal protocols of each priming method, resulting in an increased seed vigor under osmotic stress. Hence, the predicted biological parameters could easily be applied to determine the physiological changes of germination under environmental factors over time. Also, results suggest that recommended osmo-, hydro-, and hormonal-priming treatments could be efficient methods for ameliorating the osmotic tolerance in the post-priming stages of this plant, especially in arid lands. The online version contains supplementary material available at 10.1007/s12298-022-01229-w.


Compression generated by cortical screws in an artificial bone model of an equine medial femoral condylar cyst.
Determine compression generated by lag and neutral screws over 12 h using two bone analogs. Experimental study. Bone analogs were made of composite synthetic bone (CSB) or three-dimensional printed polylactic acid (PLA). Analogs had a 2 mm exterior shell with a 10 mm thick internal layer of open-cell material. Bone analogs were opposed, making a 4-sided box with open ends. A central channel contained the sensor and the screws passed through it to engage both paired analogs. Four screw/analog conditions were tested: neutral and lag screw with bicortical engagement, neutral and lag screw with unicortical engagement. All screws were tightened to 2 Nm torque and compression values recorded at 0, 0.5, 1, 2, 6, and 12 h (six trials per condition). Medians were compared across groups for statistical significance. There was no difference in median compression between lag and neutral bicortical screws. For PLA, greater median compression was generated by neutral (median 437 N) and lag (median 379 N) bicortical screws compared to neutral unicortical screws (median 208 N, p < .001); lag bicortical screws generated greater median compression than lag unicortical screws (median 265 N, p = .012). For CSB, lag bicortical screws (median 293 N) generated greater median compression than neutral unicortical screws (median 228 N, p = .008). Lag and neutral screws generated similar compression. Bicortical screws had higher median compression than unicortical screws in bone analogs. Neutral screws generate compression in cancellous bone analogs that can be increased with bicortical bone engagement.


Wzi is an outer membrane lectin that underpins group 1 capsule assembly in Escherichia coli.
Many pathogenic bacteria encase themselves in a polysaccharide capsule that provides a barrier to the physical and immunological challenges of the host. The mechanism by which the capsule assembles around the bacterial cell is unknown. Wzi, an integral outer-membrane protein from Escherichia coli, has been implicated in the formation of group 1 capsules. The 2.6 Å resolution structure of Wzi reveals an 18-stranded β-barrel fold with a novel arrangement of long extracellular loops that blocks the extracellular entrance and a helical bundle that plugs the periplasmic end. Mutagenesis shows that specific extracellular loops are required for in vivo capsule assembly. The data show that Wzi binds the K30 carbohydrate polymer and, crucially, that mutants functionally deficient in vivo show no binding to K30 polymer in vitro. We conclude that Wzi is a novel outer-membrane lectin that assists in the formation of the bacterial capsule via direct interaction with capsular polysaccharides.


Water, K+, H+, lactate and glucose fluxes during cell volume regulation in perfused rat liver.
The present study has been performed to test for ion release from isolated perfused rat liver exposed to hypotonic perfusates. Replacement of 40 mmol/l NaCl in perfusate by 80 mmol/l raffinose leads to slight alkalinization and slight decrease of liver weight. Subsequent decrease of perfusate osmolarity by omission of raffinose results in an increase of liver weight and a parallel increase of effluent sodium, chloride and potassium activity pointing to net uptake of solute free water. While effluent chloride and sodium activities approach perfusate activities within less than 2 min, a second, 6 min lasting increase of effluent potassium activity is observed, pointing to potassium release by the liver. This transient increase of effluent potassium activity is paralleled by a decrease of liver weight. Throughout exposure to hypotonic perfusates, lactate, pyruvate and glucose release by the liver is significantly decreased and effluent pH is rendered alkaline. Readdition of 80 mmol/l raffinose leads to rapid decrease of liver weight and a parallel decrease of effluent sodium, chloride and potassium activities followed by a 10-20 min lasting decrease of effluent potassium activity, pointing to net uptake of potassium, which almost matches the net release observed before. The transient decrease of potassium activity is paralleled by an increase of liver weight, an increase of effluent glucose, lactate and pyruvate concentration and an acidification of the effluent. Similar decrease of effluent potassium activity, acidification of effluent and increase of effluent glucose, lactate and pyruvate concentration are observed, if perfusates are made hypertonic by addition of raffinose.(ABSTRACT TRUNCATED AT 250 WORDS)


Effective control of hypertension: a project of the Hungarian Society of Hypertension, baseline data.
The aim of the project is to assess the quality and improve the preventive and curative practices at the primary care level in Hungary. A total of 50 general practitionaires were selected on a voluntary basis in Budapest, Hungary, and from them, 30 were randomized to the intervention (I) group and 20 to the reference (R) group. The members in the I group have been trained for the official hypertension guideline and their everyday work is monitored. Those in the R group have only been monitored to measure the efficacy of the training. In all, 10% from the known hypertensive persons (N=10,799) and 5% of the remaining (nonhypertensive) patients (N=60,341) were selected randomly from the GP's computer files and invited for screening investigation performed by trained medical students. They measured the blood pressure of patients, assessed the cardiovascular risk status and the quality of education of patients by standardized questionnaires. In total, 4083 patients were invited, but only 39.2% attended the screening visit. The prevalence of undetected hypertension was 34.6%. This prevalence was significantly higher in the older (>60 years: 46.8%) than in the younger (<50 years: 20.8%, P<0.0001) age group and it was higher in men (41.5%) than in women (30.1%, P<0.001). The proportion of H patients on drug treatment was 85.3% and the frequency of patients under effective blood pressure control (eg<140/90 mmHg) was 27.8%. Counselling to patients for a healthier lifestyle (exercise, smoking, alcohol consumption, diet) was very rare. In conclusion, our data represent the primary care of Budapest and may not be relevant to the whole country. As a consequence of this study, education of primary care physicians and patients is a must for further improvement of hypertension care.


CT and MRI findings in infantile vanishing white matter.
Infantile vanishing white matter disease is an uncommon cause of developmental delay and seizures in children. Presented here is a case of vanishing white matter disease diagnosed at 6 months of age. Imaging findings demonstrated widespread white matter abnormalities throughout the supratentorial and infratentorial brain. The diagnosis of infantile vanishing white matter disease was confirmed via molecular analysis which revealed a rare mutation in the gene responsible for this disorder.


Case report: myelopathy secondary to congenital osteopetrosis of the cervical spine.
A rare occurrence of osteopetrosis involving cervical vertebrae and producing a compressive myelopathy is described. Clinical and radiographic findings are presented, and the pathophysiology of this unusual entity is discussed.


The detection of internal mammary lymph nodal chain metastases in breast cancer using radiolabelled colloids.
The authors report their studies of 39 lymphoscintigraphies performed on patients with breast cancer. They point out that interpretation of scintigraphic imaging must take into account the morphologic variations of the lymph nodes of the internal mammary chains (i.e. single central chain, single central lymph node) and the morphological difference in the symmetry of lymph nodes considered non-pathologic to avoid false positives. The authors retain that lack of visualization of a chain, conspicuous increase in size of a lymph node, asymmetry of pathologic development, or reduced uptake by one or more lymph nodes of the internal mammary chains must be interpreted as a sign of metastatic spread. The authors recommend lymphoscintigraphy as an effective technique in the screening of breast cancer patients for staging, follow-up, restaging, and planning of radiotherapy.


Pediatric Respiratory Emergencies.
Respiratory emergencies are 1 of the most common reasons parents seek evaluation for the their children in the emergency department (ED) each year, and respiratory failure is the most common cause of cardiopulmonary arrest in pediatric patients. Whereas many respiratory illnesses are mild and self-limiting, others are life threatening and require prompt diagnosis and management. Therefore, it is imperative that emergency clinicians be able to promptly recognize and manage these illnesses. This article reviews ED diagnosis and management of foreign body aspiration, asthma exacerbation, epiglottitis, bronchiolitis, community-acquired pneumonia, and pertussis.


Update in the Management of Idiopathic Intracranial Hypertension.
Idiopathic intracranial hypertension is a syndrome of increased intracranial pressure of unknown cause that most often occurs in women of childbearing age. Most patients are overweight or obese with a history of recent weight gain. Following a brief review of the symptoms and signs, we discuss the approach to assessment and monitoring of this condition. We then present a practical approach to treatment. Because patients frequently struggle with weight loss and can also have refractory headaches and coexisting psychosocial issues, we emphasize the importance of a multidisciplinary approach to the management of this common condition.


Structured alarm systems for the operating room.
The administration of anesthesia may be viewed as a closed-loop control system consisting of three major components: the anesthesia system, the patient, and the system operator. A monitoring and alarm system during anesthesia should not be limited to only one of the three major components but must include monitoring of the patient, the performance of the anesthesia system, and the action of the system operator. For an alarm system to be successful when an adverse condition occurs, an alarm must be generated and identified, the problem identified and corrected, and the patient stabilized before injury results. The authors describe the characteristics of a structured alarm system that maximizes the time available to correct a potential problem before injury begins, that clearly identifies the cause of the problem, and that prioritizes alarms according to the urgency of the required response. Alarms should be easy to temporarily silence, have built-in alarm default settings to prevent the inadvertant use of settings meant for a previous patient, and have a graphic display that enables the operator to detect problems or trends before an alarm sounds.


ART uptake and adherence among women who use drugs globally: A scoping review.
To assess the state of peer-reviewed literature surrounding uptake and adherence of antiretroviral therapy (ART) among HIV-positive women who use drugs (WWUD). Consistent with PRISMA-ScR guidelines, we conducted a scoping literature review on ART uptake and adherence among WWUD, searching PubMed, Embase, CINAHL, PsycInfo, and Sociological Abstracts. Eligibility criteria included: reporting at least one ART uptake or adherence related result among WWUD aged 18 or older; peer-reviewed; published in English between 1996-2018. Our search identified 6735 studies; 86 met eligibility requirements. ART uptake ranged from 30 % to 76 % and adherence ranged from 27 % to 95 %. Substance use, co-morbid psychiatric disorders, and side effects emerged as the primary ART uptake and adherence barriers among this population. Few facilitators were identified. This study is the first scoping review to look at ART uptake and adherence among WWUD globally. The wide range in uptake and adherence outcomes indicates the need for gold standard assessments, which may differ between high and low resource settings. This study offers rich insight into uptake and adherence barriers and facilitators, primarily at the intrapersonal level. More research is needed to examine interventions that focus on additional levels of the SEM (e.g., community and policy levels). These review findings can inform ART interventions, future research, and offer guidance to other support services with WWUD, such as PrEP interventions.


Carvedilol: a review of its use in chronic heart failure.
Carvedilol (Dilatrend) blocks beta(1)-, beta(2)- and alpha(1)-adrenoceptors, and has antioxidant and antiproliferative effects. Carvedilol improved left ventricular ejection fraction (LVEF) in patients with chronic heart failure (CHF) in numerous studies. Moreover, significantly greater increases from baseline in LVEF were seen with carvedilol than with metoprolol in a double-blind, randomised study and in a meta-analysis. Carvedilol also reversed or attenuated left ventricular remodelling in patients with CHF and in those with left ventricular dysfunction after acute myocardial infarction (MI). Combined analysis of studies in the US Carvedilol Heart Failure Trials Program (patients had varying severities of CHF; n = 1094) revealed that mortality was significantly lower in carvedilol than in placebo recipients. In addition, the risk of hospitalisation for any cardiovascular cause was significantly lower with carvedilol than with placebo. Mortality was significantly lower with carvedilol than with metoprolol in patients with mild to severe CHF in the Carvedilol Or Metoprolol European Trial (COMET) [n = 3029]. The Carvedilol Prospective Randomised Cumulative Survival (COPERNICUS) trial (n = 2289) demonstrated that compared with placebo, carvedilol was associated with significant reductions in all-cause mortality and the combined endpoint of death or hospitalisation for any reason in severe CHF. All-cause mortality was reduced in patients who received carvedilol in addition to conventional therapy compared with those who received placebo plus conventional therapy in the Carvedilol Post-Infarct Survival Control in LV Dysfunction (CAPRICORN) trial (enrolling 1959 patients with left ventricular dysfunction following acute MI). Carvedilol was generally well tolerated in patients with CHF. Adverse events associated with the alpha- and beta-blocking effects of the drug occurred more commonly with carvedilol than with placebo, whereas placebo recipients were more likely to experience worsening heart failure. In conclusion, carvedilol blocks beta(1)-, beta(2)- and alpha(1)-adrenoceptors and has a unique pharmacological profile. It is thought that additional properties of carvedilol (e.g. antioxidant and antiproliferative effects) contribute to its beneficial effects in CHF. Carvedilol improves ventricular function and reduces mortality and morbidity in patients with mild to severe CHF, and should be considered a standard treatment option in this setting. Administering carvedilol in addition to conventional therapy reduces mortality and attenuates myocardial remodelling in patients with left ventricular dysfunction following acute MI. Moreover, mortality was significantly lower with carvedilol than with metoprolol in patients with mild to severe CHF, suggesting that carvedilol may be the preferred beta-blocker.


Sensory innervation of the external and internal genitalia of the female rat.
Using a whole-nerve recording method, the genitalia of the female rat were found to receive afferent innervation as follows. Pelvic nerve: vagina, cervix, and perineal skin; hypogastric nerve: cervix and proximal three fifths of the uterus; pudendal nerve: skin of perineum, inner thigh, and clitoral sheath. It is probable that the pudendal and pelvic nerves are activated during copulation, and that all 3 nerves are activated during parturition.


Rubber band ligation for piles can be disastrous in HIV-positive patients.
We report a patient with haemorrhoids treated with rubber band ligation who developed a huge supralevator abscess. A diverting sigmoidostomy had to be established as surgical drainage via the rectum was not adequate. Eventually the patient accepted the HIV-testing which proved positive. Six months later the sigmoidostomy was still needed as the abscess cavity remained large. We conclude that rubber band ligation in HIV-positive patients should be abandoned.


Trps1 deficiency enlarges the proliferative zone of growth plate cartilage by upregulation of Pthrp.
We have reported that elongation of the columnar proliferative zone of long bone growth plates in Trps1-/- mice during the late fetal stage in the previous study [1]. Since expression of Trps1 protein was found to overlap with that of mRNAs for Indian hedgehog (Ihh), PTH/PTHrP receptor (PPR), and PTHrP, we hypothesized that Trps1 may inhibit the hypertrophic differentiation of chondrocytes by interacting with the Ihh/PTHrP feedback loop. To investigate whether Trps1 has a role in this Ihh/PTHrP feedback loop, we compared the growth plates of Trps1-/- mice and wild-type (Trps1+/+) mice. Immunohistochemistry showed that Trps1 protein was strongly expressed in the periarticular and prehypertrophic zones of the fetal growth plate in wild-type mice on embryonic day 18.5 (E18.5). On the other hand, Ihh, PPR, and PTHrP mRNAs were predominantly expressed in the prehypertrophic zone at this stage of development. While expression of Ihh and PPR by prehypertrophic chondrocytes was unaffected in the growth plates of Trps1-/- mice, the range of PTHrP expression was expanded toward the proliferating zone in these mice. Quantitative real-time PCR analysis demonstrated upregulation of PTHrP in the epiphyseal growth plates of Trps1-/- mice. Furthermore, promoter analysis combined with the chromatin immunoprecipitation (ChIP) assay demonstrated that direct binding of Trps1 to the PTHrP promoter suppressed the transcription of PTHrP. Finally, organ culture of E14.5 tibiae in the absence or the presence of Pthrp revealed that the proliferative zone of the tibial growth plate was elongated by culture with Pthrp compared to that of control tibiae. Taken together, these data provide the first genetic evidence that lack of Trps1 leads to overexpression of PTHrP, and that Trps1 is required to maintain the normal organization of chondrocytes in the growth plate.


Chiral Aniline Synthesis via Stereospecific C(sp3)-C(sp2) Coupling of Boronic Esters with Aryl Hydrazines.
An enantiospecific coupling between alkylboronic esters and lithiated aryl hydrazines is described. The reaction proceeds under transition-metal-free conditions and is promoted by acylation of a hydrazinyl arylboronate complex, which triggers a N-N bond cleavage with concomitant 1,2-metalate rearrangement. Judicious choice of the acylating agent enabled the synthesis of ortho- and para-substituted anilines with essentially complete enantiospecificity from a wide range of boronic ester substrates.


Cyclization of an Achiral Flipping Panel to Homochiral Tubes Exhibiting Circularly Polarized Luminescence.
Macrocyclization of the bendable 2,7-dimethoxythianthrene with methylene linkages afforded a pair of homochiral macrocycles featuring a hex-nut-like geometry. Their structures were fully characterized by NMR spectroscopy, mass spectrometry, and single-crystal X-ray diffraction analysis. Their stable planar chirality facilitates efficient resolution of the pair of enantiomers which could be readily derivatized. Installing phenylethynyl groups on their rims leads to luminescent tubular macrocycles exhibiting circularly polarized luminescence with a large dissymmetry value |glum | of 5×10-3 . Supramolecular binding of electron-deficient guests by the tube results in fluorescence quenching, which proved its potential for the future development of switchable chiroptical systems.


Natural Resources of Medicinal and Cosmetic Plants.
This Special Issue (SI) of Plants is devoted to medicinal and cosmetic plants [...].


The safety and biocompatibility of direct aesthetic restorative materials.
Restorative dental materials are among the most important medical devices in terms of the numbers of patients who benefit and the technical sophistication of the products. Many though contain toxic or noxious substances, including potentially sensitising resin monomers, photoinitiators, acidic polymers and glass or ceramic filler particles. Despite this, dental materials are among the safest medical devices in use today, with very few reports of adverse reactions or injuries among both patients or the dental team. This paper considers the potential for adverse reactions to dental materials, current evidence for harm and finally examines the reasons why in real-world clinical use the likelihood of an adverse event is extremely low. Medical devices regulations, responsible manufacture and clinical vigilance all appear to play important roles in ensuring that dental materials do not cause or present a risk to patients. While this excellent in-practice safety record is welcome, there is now increasing interest in the 'macro' scale biocompatibility of dental materials and their packaging in the environment, subjects that have been relatively neglected until recently. It was concluded that this should be a priority for future research and development and support is needed from governments alongside the manufacturing industry and the profession.


Powdered chitin agar as a selective medium for enumeration of actinomycetes in water and soil.
Agar media made with 0.4% colloidal chitin plus mineral salts and adjusted to pH 8.0 was superior to four other commonly used media for the isolation and enumeration of actinomycetes from water samples. More actinomycetes developed on chitin agar, and the development of bacteria and fungi was suppressed. Frozen and vacuum-dried chitin from aqueous colloidal suspensions was finely divided and gave results comparable to those obtained with media prepared from colloidal suspensions.


Overview of nonrandomized studies of laparoscopic hernia repair.
Laparoscopic techniques have become established in the field of general surgery. Whereas there is general agreement that laparoscopic cholecystectomy has advantages over the open surgical operation, laparoscopic herniorrhaphy or hernioplasty remains controversial. This report looks at a representation of the available literature to date concentrating on nonrandomized studies.


[Optimization of Extracting Technology of Saponins in Steamed Panax notoginseng by Box-Behnken Design and Response Surface Methodology].
To optimize the extraction process of saponins in steamed Panax notoginseng by Box-Behnken design-response surface methodology. On the basis of single factor screening, Box-Behnken experimental design was employed,the content of saponins and dry extract rate of overall desirability( OD) were as the evaluation index,and the extraction time( X1),solvent multiple( X2),solvent concentration( X3) and extraction times were used as independent variables. Optimum experimental condition were selected from the stationary point of the response surfaces. By Box-Behnken design-response surface methodology and prognostic scoring system optimized scheme,the preferred processing condition were as follows, the right amount of steamed Panax notoginseng,added 16 times of 70% ethyl alcohol,extracted three times,and each time extracted for 2. 5 h. The calculated value of the process condition was basically consistent with the theoretical value,with less deviation. The extraction technology of saponins optimized by Box-Behnken design is practical and rational,which can better predict the content of saponins and dry extract rate and other indicators in steamed Panax notoginseng.


Disparities in healthcare utilization by insurance status among patients with symptomatic peripheral artery disease.
Peripheral artery disease (PAD) is a common circulatory disorder associated with increased hospitalizations and significant health care-related expenditures. Among patients with PAD, insurance status is an important determinant of health care utilization, treatment of disease, and treatment outcomes. However, little is known about PAD-costs differences across different insurance providers. In this study we examined possible disparities in length of stay and total charge of inpatient hospitalizations among patients with PAD by insurance type. We conducted a cross-sectional analysis of length of stay and total charge by insurance provider for all hospitalizations for individuals with PAD in South Carolina (2010-2018). Cross-classified multilevel modeling was applied to account for the non-nested hierarchical structure of the data, with county and hospital included as random effects. Analyses were adjusted for patient age, race/ethnicity, county, year of admission, admission type, all-patient refined diagnostic groups, and Charlson comorbidity index. Among 385,018 hospitalizations for individuals with PAD in South Carolina, the median length of stay was 4 days (IQR: 5) and the median total charge of hospitalization was $43,232 (IQR: $52,405). Length of stay and total charge varied significantly by insurance provider. Medicare patients had increased length of stay (IRR = 1.08, 95 CI%: 1.07, 1.09) and higher total charges (β: 0.012, 95% CI: 0.007, 0.178) than patients with private insurance. Medicaid patients also had increased length of stay (IRR = 1.26, 95% CI: 1.24,1.28) but had lower total charges (β: -0.022, 95% CI: -0.003. -0.015) than patients with private insurance. Insurance status was associated with inpatient length of stay and total charges in patients with PAD. It is essential that Medicare and Medicaid individuals with PAD receive proper management and care of their PAD, particularly in the primary care settings, to prevent hospitalizations and reduce the excess burden on these patients.


Expression of high levels of tubulin and microtubule-associated protein 2d in the neurohypophysial astrocytes of adult rat.
The hypothalamo-neurohypophysial system, containing arginine vasopressin and oxytocin, is well known to show reversible morphological reorganization for both neurons and glial cells during chronic physiological stimulation. To determine the molecular background for these morphological changes, we investigated the expression of tubulin and microtubule-associated protein (MAP) 2d in the neurohypophysial astrocytes, pituicytes of adult rats by using reverse transcription-polymerase chain reaction, western blot, and immunohistochemistry. The mRNA of MAP2d was expressed at higher levels than that of MAP2c in the neurohypophysis, cerebral cortex, and cerebellum. In contrast, predominant expression of mRNA of MAP2c was detected in the olfactory bulb. Western blot analysis showed the presence of MAP2d in the neurohypophysis, however the amount was below the detection level in the cerebral cortex and cerebellum. A double labeling study using a confocal laser scanning microscope showed intense tubulin immunoreactivity in the glial fibrillary acidic protein (GFAP)-positive pituicytes of the intact neurohypophysis. Almost no tubulin immunoreactivity was observed in the astrocytes of the intact cerebral cortex, cerebellum, and supraoptic nucleus, in contrast to strong tubulin immunoreactivity in neuronal dendrites and somata. Interestingly, intense tubulin immunoreactivity was also observed in the GFAP-positive reactive astrocytes in the immediate vicinity of the artificial lesion of the cerebral cortex. Electron microscopic observation further demonstrated the presence of a lot of microtubules in the pituicytes of intact rats.The present results demonstrate that pituicytes in the adult rat neurohypophysis expresses high levels of tubulin and MAP2d compared with normal brain astrocytes, and suggest that the ability of astrocytic morphological alteration may be at least partly ascribed to this high expression of microtubule proteins.


Establishing generalization effects among autistic children.
Although elusive, generalization of behavior change in autistic children is essential to obtaining maximum treatment effects. Using behaviorally based treatment and teachers and parents as trainers, generalization effects between home and school were measured on four behaviors: following instructions, washing, wiping bottom, and sharing toys. The results indicate that both settings were effective in establishing generalization. Behaviors treated in one setting generalized to another when children were provided with an opportunity for daily practice. Treatment with practice in other settings is possible in contrast to providing treatment on the same behavior in both settings.


BIO 300, a nanosuspension of genistein, mitigates pneumonitis/fibrosis following high-dose radiation exposure in the C57L/J murine model.
BIO 300 nanosuspension (Humanetics Corporation) is being developed as a medical countermeasure (MCM) for the mitigation of the delayed effects of acute radiation exposure, specifically pneumonitis and fibrosis of the lung. The objective of this study was to determine the best dose and treatment duration of BIO 300 to mitigate lung injury and improve the likelihood for survival in C57L/J mice exposed to whole thorax lung irradiation (WTLI). Age- and sex-matched C57L/J mice received a single dose of 11.0 or 12.5 Gy WTLI. BIO 300 (200 or 400 mg·kg-1 , oral gavage) was administered daily starting 24 h post-exposure for a duration of 2, 4, 6 or, in some cases, 10 weeks. Non-treated controls were included for comparison in both sexes. Animals were observed daily for signs of major morbidity. Respiratory function was assessed biweekly. Lungs were collected, weighed and paraffin embedded for histological evaluation post mortem. BIO 300 administered at an oral dose of 400 mg·kg-1 for 4 to 6 weeks starting 24 h post-WTLI reduced morbidity associated with WTLI. The improvement in survival correlated with reduced respiratory frequency and enhanced pause. The irradiated lungs of mice treated with BIO 300 (400 mg·kg-1 ) for 4 to 6 weeks displayed less morphological damage and airway loss due to oedema, congestion and fibrotic scarring than the untreated, irradiated controls. BIO 300 is a promising MCM candidate to mitigate pneumonitis/fibrosis when administered daily for 4-6 weeks starting 24 h post-exposure.


Identification of serotonergic and sympathetic neurons in medullary raphe nuclei.
The purpose of the present study was to identify midline medullary serotonin (5-HT) neurons and to determine if these neurons were distinct from previously identified sympathoinhibitory and sympathoexcitatory neurons. Identification of medullary 5-HT neurons was based on electrophysiological and pharmacological similarities to dorsal raphe 5-HT neurons. Sympathoinhibitory and sympathoexcitatory neurons were characterized by an irregular discharge pattern which was temporally related to inferior cardiac sympathetic nerve discharge (SND) and to the cardiac cycle. Sympathoinhibitory neurons increased their discharge rate and the discharge of sympathoexcitatory neurons decreased during baroreceptor reflex activation. A third type of neuron fired in an extremely regular fashion (as judged by interspike interval analysis), fired at a rate of 1.1 spikes/s and had spike durations of approximately 2 ms. The discharges of regularly firing neurons were not temporally related to SND and were not affected during baroreceptor reflex activation. Regularly firing neurons and sympathoinhibitory neurons could be antidromically activated by electrical stimulation of the intermediolateral cell column of the spinal cord. Axonal conduction velocity of sympathoinhibitory neurons (2.4 m/s) was significantly greater than that for regularly firing neurons (1.3 m/s). Regularly firing neurons were completely inhibited by low doses of the 5-HT1A agonist 8-hydroxy-dipropylamino-tetralin (8-OH-DPAT) (i.e. 2 micrograms/kg, i.v.) while much higher doses of the drug failed to affect the discharges of sympathoinhibitory and sympathoexcitatory neurons. Microiontophoretic application of 5-HT and 8-OH-DPAT profoundly depressed the firing of regularly discharging neurons. Based on the striking similarities between regularly firing medullary neurons and dorsal raphe 5-HT neurons it is concluded that the regularly firing neurons were 5-HT-containing neurons. Furthermore, these medullary 5-HT neurons are distinct from sympathoinhibitory and sympathoexcitatory neurons.


[Comparison of the efficacy of propafenone and hydroquinidine in stabilized extrasystolic ventricular arrhythmia by means of dynamic electrocardiographic Holter monitoring].
The aim of our study has been to evaluate the efficacy of Propafenon by a reliable experimental method. We have compared the efficacy of Propafenon (300 mg three times daily) with that of Dihydroquinidine Chloride at an elevated dose (300 mg six times daily). Twelve patients, with chronic arrhythmia (at least 1500 premature ventricular beats - PVBs - during a preliminary 24-hour dynamic electrocardiographic Holter monitoring), have been studied. The study has been performed in a double-blind cross-over fashion, and the drugs were administered according to a randomized sequence by the double dummy technique for 4 days. Placebo administration periods of similar duration were established before, after and between the two periods of drug administration. At the end of each Propafenon Dihydroquinidine Chloride and Placebo administration period a 48-hour Holter monitoring was performed. The number of PVBs/hour measured during the 3 periods of Placebo administration (714 +/- 418, 804 +/- 422, 779 +/- 433 respectively) confirmed the chronic nature of the ventricular arrhythmia and the absence of spontaneous variations during the study. Treatment with Propafenon and Dihydroquinidine Chloride significantly reduced the number of PVBs/hour to 87 +/- 130 and to 216 +/- 453 respectively. The reduction observed during Propafenon administration was more than observed during Dihydroquinidine Chloride administration, but it was not statistically significant because of the different behaviour of the individual patients. All patients but one had an over 65% reduction of PVBs/h; only 8/12 patients showed a reduction greater than 65% during Dihydroquinidine Chloride administration.(ABSTRACT TRUNCATED AT 250 WORDS)


Direct provisional restoration technique.
A technique has been presented for the efficient fabrication of a temporary or provisional restoration with emphasis on esthetics, proper contour, and marginal integrity. Attention to details in these procedures can be most rewarding to both the patient and the dentist.


Newly discovered role of the heterotrophic nanoflagellate Katablepharis japonica, a predator of toxic or harmful dinoflagellates and raphidophytes.
Heterotrophic nanoflagellates are ubiquitous and known to be major predators of bacteria. The feeding of free-living heterotrophic nanoflagellates on phytoplankton is poorly understood, although these two components usually co-exist. To investigate the feeding and ecological roles of major heterotrophic nanoflagellates Katablepharis spp., the feeding ability of Katablepharis japonica on bacteria and phytoplankton species and the type of the prey that K. japonica can feed on were explored. Furthermore, the growth and ingestion rates of K. japonica on the dinoflagellate Akashiwo sanguinea-a suitable algal prey item-heterotrophic bacteria, and the cyanobacteria Synechococcus sp., as a function of prey concentration were determined. Among the prey tested, K. japonica ingested heterotrophic bacteria, Synechococcus sp., the prasinophyte Pyramimonas sp., the cryptophytes Rhodomonas salina and Teleaulax sp., the raphidophytes Heterosigma akashiwo and Chattonella ovata, the dinoflagellates Heterocapsa rotundata, Amphidinium carterae, Prorocentrum donghaiense, Alexandrium minutum, Cochlodinium polykrikoides, Gymnodinium catenatum, A. sanguinea, Coolia malayensis, and the ciliate Mesodinium rubrum, however, it did not feed on the dinoflagellates Alexandrium catenella, Gambierdiscus caribaeus, Heterocapsa triquetra, Lingulodinium polyedra, Prorocentrum cordatum, P. micans, and Scrippsiella acuminata and the diatom Skeletonema costatum. Many K. japonica cells attacked and ingested a prey cell together after pecking and rupturing the surface of the prey cell and then uptaking the materials that emerged from the ruptured cell surface. Cells of A. sanguinea supported positive growth of K. japonica, but neither heterotrophic bacteria nor Synechococcus sp. supported growth. The maximum specific growth rate of K. japonica on A. sanguinea was 1.01 d-1. In addition, the maximum ingestion rate of K. japonica for A. sanguinea was 0.13ngC predator-1d-1 (0.06 cells predator-1d-1). The maximum ingestion rate of K. japonica for heterotrophic bacteria was 0.019ngC predator-1d-1 (266 bacteria predator-1d-1), and the highest ingestion rate of K. japonica for Synechococcus sp. at the given prey concentrations of up to ca. 107 cells ml-1 was 0.01ngC predator-1d-1 (48 Synechococcus predator-1d-1). The maximum daily carbon acquisition from A. sanguinea, heterotrophic bacteria, and Synechococcus sp. were 307, 43, and 22%, respectively, of the body carbon of the predator. Thus, low ingestion rates of K. japonica on heterotrophic bacteria and Synechococcus sp. may be responsible for the lack of growth. The results of the present study clearly show that K. japonica is a predator of diverse phytoplankton, including toxic or harmful algae, and may also affect the dynamics of red tides caused by these prey species.


Catastrophic neurologic syndrome with dramatic ECG changes.
Cerebrogenic ECG abnormalities, especially prominent T wave inversions and prolongation of the QT(U) interval, are well-described. Brady- and tachyarrhythmias, including polymorphic VT, have been also described in the setting of neurologic injury. We report an unusual case of a 22-year-old man who presented with idiopathic acute encephalopathy. His hospital course was complicated by persistent fevers, along with refractory seizures treated with propofol. Serial ECG findings included marked ventricular repolarization prolongation with bursts of torsade de pointes, diffuse ST elevations simulating extensive myocardial ischemia or infarction, as well as a Brugada-like pattern. To our knowledge, this case is the first reported with the combination of such findings in a patient with a catastrophic neurologic syndrome.


Emergent symbolic relations in speakers and nonspeakers.
Eight adults with developmental disabilities and four typically developing preschool children participated in an experiment studying emergent stimulus-stimulus relations after match-to-sample instruction. Participants were taught to match lexigrams (arbitrary graphic stimuli) to objects. Each object was functionally related to another object in the teaching set. For example, brush and comb were members of the teaching set. Most participants were able to select objects when the objects were named in pretests. Postteaching probes assessed emergent relations between spoken names and lexigrams. In addition, we included probes to detect emergent relations between related lexigrams. That is, would participants select the lexigram for comb when the experimenter displayed the lexigram for brush (without explicit teaching)? Two preschool children and five adults with developmental disabilities showed emergent relations between lexigrams and spoken words. However, only two preschool children showed the emergent lexigram to related lexigram relations.


MRI during radiotherapy of glioblastoma : Does MRI allow for prognostic stratification?
To evaluate the role of magnetic resonance imaging (MRI) as a predictor for the clinical course in patients with glioblastoma. In 64 patients with glioblastoma undergoing (chemo)radiotherapy MRI studies were obtained before radiation, after 30 gray (Gy), after 60 Gy and during follow-up. MRI findings were assigned to categories: definite progression, questionable progression, no change. Patients were followed clinically. At 30 Gy, 23 of 64 patients (36 %) demonstrated definite (dp; n = 15) or questionable (qp; n = 8) progression; in 41/64 (64 %) no change was found compared with preradiation MRI. After radiotherapy at 60 Gy, 26 of 64 (41 %) patients showed dp (n = 18) or qp (n = 8). In 2 cases with qp at the 30 Gy MRI, progress was unquestionable in the 60 Gy MRI study. In the 64 patients, 5 of the 60 Gy MRIs showed dp/qp after being classified as no change at the 30 Gy MRI, 2 of the 30 Gy MRIs showed qp, while the 60 Gy MRI showed tumour regression and 3 fulfilled the criteria for pseudoprogression during ongoing radiotherapy. The 30 Gy study allowed for prognostic stratification: dp/qp compared to stable patients showed median survival of 10.5 versus 20 months. MR follow-up after 30 Gy in patients undergoing (chemo)radiotherapy for glioblastoma allows prognostic appraisal. Pseudoprogression has to be taken into account, though rare in our setting. Based on these findings, early discussion of treatment modification is possible.


Enhancement of TiO₂ NPs Activity by Fe₃O₄ Nano-Seeds for Removal of Organic Pollutants in Water.
The enhancement of the photocatalytic activity of TiO₂ nanoparticles (NPs), synthesized in the presence of a very small amount of magnetite (Fe₃O₄) nanoparticles, is here presented and discussed. From X-ray diffraction (XRD) and differential scanning calorimetry (DSC) analyses, the crystallinity of TiO₂ nanoparticles (NPs) seems to be affected by Fe₃O₄, acting as nano-seeds to improve the tetragonal TiO₂ anatase structure with respect to the amorphous one. Photocatalytic activity data, i.e., the degradation of methylene blue and the Ofloxacin fluoroquinolone emerging pollutant, give evidence that the increased crystalline structure of the NPs, even if correlated to a reduced surface to mass ratio (with respect to commercial TiO₂ NPs), enhances the performance of this type of catalyst. The achievement of a relatively well-defined crystal structure at low temperatures (Tmax = 150 °C), preventing the sintering of the TiO₂ NPs and, thus, preserving the high density of active sites, seems to be the keystone to understand the obtained results.


Historical correlates of genital herpes simplex virus type 2 infection in men attending an STD clinic.
While nearly one in four Americans has antibodies to HSV-2, only one of 40 reports a history of genital herpes (GH). The goal of this study was to correlate questions designed to elicit a GH history with serological evidence of HSV-2 in male STD clinic attendees. Consecutive males were enrolled in a study of the epidemiology of GH. Consenting men answered questionnaires regarding their histories of possible GH and underwent serological testing for HSV-1 and HSV-2. Association statistics between response to each question and HSV-2 serological status were calculated. Of 328 men enrolled, 148 (46%) had HSV-2 antibodies. 14 (4.3%) reported a history of GH when queried as part of a list of other STD (sensitivity (S) 0.08). 17 (5.2%) reported a history of GH when asked directly "Do you have genital herpes?" (S 0.09). 75 (21.1%) participants reported a history of a recurring genital sore, ulcer, or zipper cut (S 0.32). Overall, 64.2% of HSV-2 seropositive men answered "no" to all three questions. A "yes" response to any of the questions was only 36% sensitive for predicting HSV-2 infection. Few HSV-2 infected men report either a history of GH or are aware that they are infected. Asking about a history of recurrent genital sores was a more sensitive historical marker of HSV-2 infection than asking about a history of "genital herpes."


Tobacco use and associated mental symptoms and health risk behaviours amongst individuals 15 years or older in South Africa.
Tobacco use may deteriorate mental health and increase health risk behaviours. The aim of this investigation was to identify associations between tobacco use and mental illness symptoms and health risk behaviours in individuals 15 years or older in South Africa. Community-based national population sample in South Africa. Cross-sectional data were analysed from the 'South African National Health and Nutrition Examination Survey (SANHANES-1) 2012', using a sample of 15 310 individuals 15 years or older (median age 33 years). Measures included information on tobacco use, sociodemographic factors, mental symptoms and health risk behaviour. Compared to non-tobacco users, daily tobacco users were associated with psychological distress and post-traumatic stress disorder (PTSD) in adjusted logistic regression analysis, and with sleeping problems in unadjusted analysis. Past tobacco use, less than daily, and daily tobacco use were highly associated with a drinking problem. In terms of dietary variables, less than daily and daily tobacco use increased the odds of inadequate fruit intake and salty food intake, and daily tobacco use decreased the odds of fast food consumption. Past tobacco use, less than daily, and daily tobacco use were inversely associated with physical inactivity, and daily tobacco use was associated with not always washing hands before eating. The study showed that compared to non-tobacco users, daily tobacco users had significantly poorer mental health (psychological distress and PTSD) and increased odds for several health risk behaviours (drinking problem, inadequate fruit intake, salty food consumption and not always washing hands before eating) as compared to non-tobacco users.


Phrase-level speech simulation with an airway modulation model of speech production.
Artificial talkers and speech synthesis systems have long been used as a means of understanding both speech production and speech perception. The development of an airway modulation model is described that simulates the time-varying changes of the glottis and vocal tract, as well as acoustic wave propagation, during speech production. The result is a type of artificial talker that can be used to study various aspects of how sound is generated by humans and how that sound is perceived by a listener. The primary components of the model are introduced and simulation of words and phrases are demonstrated.


Respiratory muscle dysfunction in systemic lupus erythematosus.
An assessment of pulmonary mechanics revealed weakness of inspiratory and expiratory muscles as cause of the restrictive ventilatory defect (vital capacity: 47 +/- 10 percent predicted) in seven (ages 33 to 62 years) out of 26 consecutive patients with systemic lupus erythematosus (SLE). Maximal inspiratory transdiaphragmatic pressures were reduced mainly due to the markedly increased (more positive) esophageal pressures. During maximal expiratory efforts, esophageal and gastric pressures were grossly decreased. These abnormalities probably may be considered part of a more generalized, yet subclinical muscle disorder due to the SLE with, however, predominant involvement of the respiratory muscles. The abnormalities were not related to the use of corticosteroids or generalized inanition. The static expiratory lung compliance was reduced in all patients (55 +/- 18 percent predicted), but normalized immediately following passive inflation of the lungs to transpulmonary pressures of more than 30 cm H2O in two of the three subjects tested. The volume restriction was not progressive over a period of 38.5 patient-years.


Guidelines for genetic study of aniridia.
Aniridia is a panocular disorder which occurs in 1/50,000 to 1/100,000 live births and can appear either in isolated form or in the context of a syndrome. Isolated aniridia is inherited as an autosomal dominant condition and is caused by mutations of the PAX6 gene. A variety of techniques and methodologies within molecular genetics and cytogenetics are used to study these mutations. To identify the different aspects of this disease and to provide a guide for proper genetic diagnosis leading to improved clinical management of the disease. Aniridia is an autosomal dominant disease that primarily affects the iris, though it can impact most of the ocular structures. The disease is mainly caused by mutations in the PAX6 gene located on chromosome 11p13 which encodes a transcription factor that is involved in the development of the eye. Genetic analysis of aniridia is complex and requires the use of both molecular genetics and cytogenetics techniques. These procedures are indicated in all cases of aniridia. It is important bear certain clinical and technical aspects in mind prior to starting analysis or providing genetic counseling for patients and their families. The use of molecular genetic techniques in the genetic diagnosis of aniridia enables patients and their families to receive better clinical management.


A nuclear target for interleukin-1alpha: interaction with the growth suppressor necdin modulates proliferation and collagen expression.
There is growing evidence for the intracellular role of cytokines and growth factors, but the pathways by which these activities occur remain largely obscure. Previous work from our laboratory identified the constitutive, aberrant expression of the 31-kDa IL-1 alpha precursor (pre-IL-1 alpha) in the nuclei of fibroblasts from the lesional skin of patients with systemic sclerosis (SSc). We established that pre-IL-1 alpha expression was associated with increased fibroblast proliferation and collagen production. Further investigation has led to the identification of a mechanism by which nuclear expression of pre-IL-1 alpha affects fibroblast growth and matrix production. By using a yeast two-hybrid method, we found that pre-IL-1 alpha binds necdin, a nuclear protein with growth suppressor activity. We mapped the region of pre-IL-1 alpha responsible for necdin binding and found it to be localized near the N terminus, a region that is present on pre-IL-1 alpha, but not the mature 17-kDa cytokine. Expression studies demonstrated that pre-IL-1 alpha associates with necdin in the nuclei of mammalian cell lines and regulates cell growth and collagen expression. Our results provide the first evidence, to our knowledge, of a nuclear target for pre-IL-1 alpha. Based on these findings, we propose that the constitutively up-regulated expression of pre-IL-1 alpha in the nuclei of SSc fibroblasts up-regulates proliferation and matrix production of SSc fibroblasts through binding necdin, and by counteracting its effects on cell growth and collagen production.


Seasonal sugarcane harvesters of Gujarat: trapped in a cycle of poverty.
Based on primary data collected from the households of Dangs district in South Gujarat, India, the paper shows that every year a third of young adults migrate to Surat district and neighbouring areas for half a year to work as sugarcane harvesters. The data show that they live in temporary shelters in harsh conditions with bare minimum necessities and amenities. A large share of their earnings, much lower than the minimum wage rate for agricultural labour, is used to pay the labour contractors who provide cash advances during the lean post-monsoon months. Paying back the principal amount with hefty interest on it traps generations of migrant workers in the vicious cycle of poverty and indebtedness.


Relationship of high leptin levels with an adverse lipid and insulin profile in 6-8 year-old children in Spain.
Leptin, an adipokine elevated in obesity, may be related to an adverse cardiovascular risk profile in childhood. However, evidence for this relationship in pre-pubertal children is scarce. We aimed to analyze the relationship between leptin levels and lipid and insulin profiles in Spanish children. Our population-based sample included 389 males and 369 females aged 6-8 years. Lipid levels were determined by standard methods, insulin by radioimmunoassay and leptin by sandwich ELISA. Leptin levels were higher in girls (8.6 ng/ml) than boys (4.7 ng/ml) (p < 0.001). Leptin increased from ages 6 to 8 in girls, but remained steady in boys. In both sexes, leptin increased significantly (p < 0.001) across weight category from normal weight to obese. Children in the highest tertile of leptin concentration showed significantly (p < 0.01) lower levels of HDL-cholesterol (HDL-C) and apolipoprotein-AI (apo-AI) and significantly higher triglyceride (TG) levels than children in lower tertiles. However, in linear regression analysis, after adjustment for body mass index (BMI), leptin only accounted for 1.5% of the variance of HDL-C in boys, and 2.6% of the variance of apo-AI in girls. Leptin was strongly and positively correlated with insulin and HOMA. Upon regression analysis, leptin contributed to over 20% of the variability in insulin and HOMA, independent of BMI. Leptin levels show sex differences in pre-pubertal children. In this age group, leptin levels are strongly related to insulin, and affect lipid profile -namely HDL-C, apo-AI and TG- particularly when leptin levels are high.


Cardiac Fabry's disease: an unusual cause of left ventricular hypertrophy.
A 64-year-old male was observed as an outpatient with atypical, non-exercise-induced chest pain and palpitations. He had arterial hypertension and marked concentric left ventricular hypertrophy. After 2.5 years of antihypertensive drug therapy the patient's blood pressure had returned to normal, but his left ventricular hypertrophy was unchanged. Electrocardiography, transthoracic echocardiography, myocardial perfusion scintigraphic imaging, measurement of alpha-galactosidase A activity, gene sequencing, brain MRI, carotid artery ultrasonography, biochemical renal evaluation and cardiac Doppler tissue imaging. Cardiac Fabry's disease. Losartan, hydrochlorothiazide, low-dose aspirin and bisoprolol. The patient is expected to begin enzyme replacement therapy.


Accumulation and transfer of Hg, As, Se, and other metals in the sediment-vegetation-crab-human food chain in the coastal zone of the northern Brazilian state of Pará (Amazonia).
The high consumption of crabs (Ucides cordatus) stimulated interest in the present study on the northern coast of Brazil, which encompasses a preserved area of mangrove forest. The objective was to describe and quantify the transfer of metals from the muddy sediments to the leaves of the Rhizophora mangle, and thence the crabs and humans. The samples were collected along two transects, while samples of hair were obtained from local habitants. The pH, interstitial salinity, Eh (mV) were measured, the granulometry and mineralogical and multi-element chemical analyses were run, and the organic material determined. The sediments are silty-clayey, composed of quartz, kaolinite, iron oxides, and illite, as well as smaller portions of smectite, pyrite, halite, and high levels of SiO2 (56.5 %), Al2O3 (18.5 %), and Fe2O3 (7 %). The elements Zn, Sr, As, and Zr are concentrated in the leaves, while the bioaccumulation of Zn, Se, Sr, and As was recorded in the crabs, of which, Se is the most concentrated in the tissue of the muscles and the hepatopancreas. The concentrations of nutrient and toxic elements were similar in all age groups (hair samples), with only Hg presenting an increasing concentration between infants and adults. The highest rates of transfer were recorded for the elements Zn and Se in the crabs and Hg in leaves and hair. The accumulation of metals in the leaves and crabs reflects the chemical composition of the sediments and low rates of sediment-vegetation-crab transfer, with the exception of Hg, which accumulated in the hair.


Diagnostic value of hand X-rays in Turner's syndrome.
Previously described radiological signs of Turner's syndrome were evaluated in X-rays of the left hand from 17 patients with Turner's syndrome (age 10.4--15.3 years) and 17 age-matched girls with constitutional short stature. While none of the signs clearly distinguished between the two groups, ballooning of the tips of the terminal phalanges with a high ratio between the tip and mid-shaft diameters seemed to be the most useful of Turner's syndrome. Disproportionately long phalanges in the 4th finger and the presence of a coarse reticular pattern in the carpal bones appeared to be the next most useful signs. The presence of a short 4th metacarpal or a narrow carpal angle, and assessment for Madelung's deformity were of little value in distinguishing between the two groups.