Survival analysis of the Wallis interspinous spacer used as an augment to lumbar decompression.
The Wallis fixed interspinous spacer may augment traditional decompression in the treatment of lumbar spinal stenosis. The aim of this study was to determine factors influencing survival of the Wallis interspinous spacer and to identify specific modes and predictors of failure. We performed a retrospective cohort study of 244 Wallis interspinous spacers implanted in 195 consecutive patients with a mean age of 56 years (range 21-87) to augment single or multi-level decompression. We examined patient demographics, indications for surgery, surgical techniques and pathology on magnetic resonance imaging (MRI). A Kaplan-Meier survival analysis was performed. Median follow-up was 4.5 years (range 2-8). Sixteen patients were lost to follow-up. Repeat MRI was performed in 98 patients (50%). A recurrent stenosis was found in 21% of patients (41/195) and occurred at a similar incidence at the level of the spacer and at adjacent spinal levels. Revision decompression was performed in 19 patients (10%) at 2.8 ± 1.8 years (range 6 months-6 years) with implant removal in 15 and conversion to fusion in 4 patients. No specific patient factors or pre-operative MRI findings predicted failure. Five-year survival was 91% (95% CI: 79-96%). The Wallis implant is generally implanted without complication when used as an adjunct to decompression with a good medium term survival. Though disc heights were maintained, the Wallis spacer did not however appear to reduce the incidence of recurrent spinal or foraminal stenosis from that expected from decompression alone.


The Gateway Hypothesis, Common Liability to Addictions or the Route of Administration Model A Modelling Process Linking the Three Theories.
The aim of this study was to describe the transitions between tobacco (T), cannabis (C) and other illicit drugs (OIDs) initiations, to simultaneously explore several substance use theories: gateway theory (GT), common liability model (CLM) and route of administration model (RAM). Data from 2 French nationwide surveys conducted in 2005 and 2010 were used (16,421 subjects aged 18-34). Using reported ages at initiations, we reconstituted a retrospective cohort describing all initiation sequences between T, C and OID. Transition probabilities between the substances were computed using a Markov multi-state model that also tested the effect of 2 latent variables (item response theory scores reflecting propensity for early onset and further substance use) on all transitions. T initiation was associated with increased likelihood of subsequent C initiation, but the reverse relationship was also observed. While the most likely initiation sequence among subjects who initiated the 3 groups of substances was the 'gateway' sequence T x2192; C x2192; OID, this pattern was not associated with substance use propensity more than alternative sequences. Early use propensity was associated with the 'gateway' sequence but also with some alternative ones beginning with T, C or OID. If the gateway sequence appears as the most likely pattern, in line with GT, the effects of early onset and substance use propensities were also observed for some alternative sequences, which is more in line with CLM. RAM could explain reciprocal interactions observed between T and C. This suggests shared influences of individual (personality traits) and environmental (substance availability, peer influence) characteristics.


Intestinal cestodes.
Cestodes infections in humans are among the most prevalent parasitosis worldwide. Although tapeworm infection is often asymptomatic, they can be associated with a range of symptoms. The landscape of cestode infections is changing with rapid diagnosis techniques and advanced molecular diagnosis aiding in identification of species specific epidemiology. Traditional descriptions of species by location have been challenged with molecular diagnostic techniques, which show variation in distribution of species, thought to be because of globalization and importation of disease. Epidemiology, molecular diagnostic techniques. Infection by tapeworms is often asymptomatic or accompanied by mild symptoms though can occasionally cause severe disease and contribute to anemia and malnutrition. Tapeworm infection is most prevalent in resource-poor countries but the distribution is worldwide. Epidemiology of infection is changing because of molecular diagnostics, which allow more accurate tracking of species.


A Very Rare Presentation of Multiple Myeloma: Unilateral Raccoon Eye.
Multiple myeloma (MM), the second most common hematological malignancy, is caused by the accumulation of monoclonal plasma cells in bone marrow. It accounts for 10-15% of deaths from hematological malignancies and approximately 2% of deaths from cancer. The median age at presentation is 70 years old. The diagnosis is incidental in 30% of cases. MM is often discovered through routine blood screening with a large gap between the total protein and the albumin levels. Two thirds of patients complain of bone pain, especially lower back pain. MM could be diagnosed after a pathologic fracture occurs in one third of patients. Presentation with symptoms related to hyperviscosity, hypercalcemia and bleeding tendency could also be observed. A rare presentation of MM is peri-orbital ecchymotic lesion (raccoon eye). Here, we report a 64 years old, male patient presented with unilateral raccoon eye and high erythrocyte sedimentation rate (ESR) to internal medicine outpatient. The patient was referred to hematology outpatient and was diagnosed with multiple myeloma.


Portal vein tumor thrombus of liver metastasis from lung cancer.
We report a case of liver metastasis of lung carcinoma with portal vein tumor thrombus (PVTT). Although the primary lesion of lung tumor remained unchanged, the patient rapidly developed wide-spread metastases and formed PVTT of liver metastasis. The primary lesion showed features of mixed Clara and bronchial surface epithelial cell component type adenocarcinoma with small foci of micropapillary pattern. Micropapillary pattern was observed in the metastatic lesions in the liver and PVTT. Micropapillary pattern lung adenocarcinoma may develop rapid metastases and cause PVTT associated with liver metastasis. We should perform a detailed examination to establish correct diagnosis.


Structure-activity relationship on (+/-)-nantenine derivatives in antiserotonergic activities in rat aorta.
A series of nine (+/-)-nantenine derivatives were synthesized and assayed for their pharmacological activities by using tension in aorta and binding experiments in rat brain membrane. Replacing a methyl group with a hydrogen ((+/-)-nornantenine) and an ethyl group at a nitrogen atom ((+/-)-ethylnornantenine) or introducing a hydroxyl group at the alpha/beta position of C-4 or displacement of a methoxy moiety at the C-1 position with a hydroxyl ((+/-)-domesticine) of (+/-)-nantenine decreased the affinity. Moreover, changing a methyl group of (+/-)-domesticine to hydrogen at a nitrogen atom ((+/-)-nordomesticine) caused loss of the activities. These results suggest that a methyl group at a nitrogen atom and a methoxy moiety at C-1 play important roles in the development of the antiserotonergic activity. Molecular modeling analysis of the interaction between the 5-HT2A receptor and (+/-)-nantenine suggested that electron lone pairs of N-6 and of the oxygen atom of the methoxy group at C-1 are important in forming a hydrogen bond to Asp155 and Asn343 of the 5-HT2A receptor, respectively.


Shift in Th1 (IL-2 and IFN-gamma) and Th2 (IL-10 and IL-4) cytokine mRNA balance within two new histological main-types of rheumatoid-arthritis (RA).
Cytokines are the main mediators of inflammation in rheumatoid arthritis (RA). Thus, Th2 cytokines--such as IL-4 and IL-10--have protective properties to this disease. In opposite, the Th1 cytokines--such as IL-2 and IFN-gamma--are supporting proinflammatory microenvironment in joints from patients with RA. The imbalance of Th1/Th2 cytokine steady state may play an important role in the pathogenesis of rheumatoid arthritis. The evaluation of this imbalance leads up to the possibility of pathohistological discrimination in this disease. In this context, we investigated Th1- (IFN-gamma, IL-2) and Th2 (IL-10, IL-4)-cell-derived cytokine mRNA expression in two novel pathohistological main-types of RA synovial membrane (SM). These main-types are characterized by different tissue-infiltrating inflammatory cells and different extent of SM destruction. Our findings showed that expression of IL-10 mRNA was an outcome of histological main-type I (p<0.001), whereas expression of IFN-gamma and IL-2 were mainly associated with pathohistological main-type II (p<0.005, p<0.05). Surprisingly, IL4 was not differential expressed and could be associated with another special T cell subset in this disease. These results suggest that Th1/Th2 balance is biased to Th2 cytokines within main-type I and Th1 cytokines in main-type II.


Factors Affecting Depression During Pregnancy and the Correlation Between Social Support and Pregnancy Depression.
Women are seriously subjected to psychiatric diseases during pregnancy and depression is the most prevailing one among these diseases. There is a relation between the social support and depression in pregnancy whose predisposing factors are genetic, psychological, biological, environmental, and hormonal. This study aimed to determine the frequency of depression symptoms, and its risk factors. Also it studied the correlation between social support and pregnancy depression. This research is a descriptive cross-sectional study. It was conducted on 266 pregnant women selected by simple random method from all pregnant women admitted at the Maternity Hospital of Trabzon, Turkey from May 21 to June 13, 2008. The data were collected with a questionnaire form, the Beck depression inventory (BDI), and the multidimensional scale of perceived social support (MSPSS). The mean BDI score of the pregnant women was 11.12 ± 6.65. According to the BDI, 46.2% of the pregnant women had no depression symptoms, 34.59% of them had mild, 13.91% had moderate, and 4.89% had severe level of depression symptoms. It was found that such factors as the educational level of the pregnant women and their husbands, having an undesired pregnancy, suffering from a chronic disease before pregnancy, presence of pregnancy-related problems, having a child with disability or having relatives whose children had disability, and smoking during pregnancy were the risk factors affecting the severity of the depression symptoms and these results were statistically significant (P < 0.05). On the other hand, the mean MSPSS score was 67.89 ± 14.26 and it was found that the pregnant women got the highest social support from their husbands. It was found that there was a significant correlation between BDI and MSPSS total score and its subscale scores (P < 0.05). According to this study, one-fifth of pregnant women were found to experience depressive symptoms, which require treatment during pregnancy, and the factors such as having no support from relatives was found to be associated with the severity of depressive symptoms during pregnancy.


Circular RNA circ-ABCB10 promotes breast cancer proliferation and progression through sponging miR-1271.
Circular RNA (circRNA) is a key regulator in the development and progression of human cancers, however its role in breast cancer tumorigenesis is not well understood. The present study aims to investigate the expression profiles and potential modulation of circRNA on breast cancer carcinogenesis. Human circRNA microarray was performed to screen for abnormally expressed circRNA in breast cancer tissue. Results found circ-ABCB10, was significantly up-regulated in breast cancer tissue. And results were replicated in a larger sample size. In vitro, loss-of-function experiments showed circ-ABCB10 knockdown suppressed the proliferation and increased apoptosis of breast cancer cells. Bioinformatics prediction program predicted the complementary sequence within circ-ABCB10 and miR-1271, which was validated by luciferase reporter assay. Finally, miR-1271 rescued the function of circ-ABCB10 on breast cancer cells, confirming the sponge effect of circ-ABCB10 on miR-1271. Overall, results identified a new functional circ-ABCB10 in breast cancer tumorigenesis, and reveal the important regulatory role of circ-ABCB10 through sponging miR-1271, providing a novel insight for breast cancer pathogenesis.


Distal and proximal actions of peptide pheromone M-factor control different conjugation steps in fission yeast.
Mating pheromone signaling is essential for conjugation between haploid cells of P-type (P-cells) and haploid cells of M-type (M-cells) in Schizosaccharomyces pombe. A peptide pheromone, M-factor, produced by M-cells is recognized by the receptor of P-cells. An M-factor-less mutant, in which the M-factor-encoding genes are deleted, is completely sterile. In liquid culture, sexual agglutination was not observed in the mutant, but it could be recovered by adding exogenous synthetic M-factor, which stimulated expression of the P-type-specific cell adhesion protein, Map4. Exogenous M-factor, however, failed to recover the cell fusion defect in the M-factor-less mutant. When M-factor-less cells were added to a mixture of wild-type P- and M-cells, marked cell aggregates were formed. Notably, M-factor-less mutant cells were also incorporated in these aggregates. In this mixed culture, P-cells conjugated preferentially with M-cells secreting M-factor, and rarely with M-factor-less M-cells. The kinetics of mating parameters in liquid culture revealed that polarized growth commenced from the contact region of opposite mating-type cells. Taken together, these findings indicate that M-factor at a low concentration induces adhesin expression, leading to initial cell-cell adhesion in a type of "distal pheromone action", but M-factor that is secreted directly in the proximity of the adhered P-cells may be necessary for cell fusion in a type of "proximal pheromone action".


Serendipitous Discovery of a Guanine-rich DNA Molecule with a Highly Stable Structure in Urea.
We have made an accidental discovery of an unusual, single-stranded, guanine-rich DNA molecule that is capable of adopting a folded structure in 7 M urea (7MU) known to denature nucleic acid structures. The folding of this molecule requires Na+ and Mg2+ and the folded structure remains stable when subjected to denaturing (7MU) polyacrylamide gel electrophoresis. Results from sequence mutagenesis, DNA methylation, and circular dichroism spectroscopy studies suggest that this molecule adopts an intramolecular guanine-quadruplex structure with 5 layers of guanine tetrads. Our finding indicates that DNA has the ability to create extremely stable structural folds despite its limited chemical repertoire, making it possible to develop DNA-based systems for unconventional applications.


Hypersensitivity Pneumonitis Due to Metalworking Fluid Aerosols.
This review summarises the clinical knowledge of hypersensitivity pneumonitis in workers exposed to aerosols of metalworking fluid, reviewing published outbreaks and clinical cases. Metalworking fluid exposure has become the commonest recognised cause of occupational hypersensitivity pneumonitis, having been rare before 2000. There are many possible agents in the metalworking fluid which may be the cause of disease including bacteria, mycobacteria, fungae, biocides, emulsifiers, reodorants and dissolved chrome and cobalt. Causes are likely to be different in different outbreaks. Mycobacteria growing in the metalworking fluid have generated immune responses in some workers, but their role in disease causation is not yet established. Many outbreaks have been identified in large workplaces using common sumps. It is not possible to prevent microbial contamination of metalworking fluids in use. Disease prevention should focus on stopping inhalation of aerosols, particularly by re-engineering to remove recirculation.


Phylogeny of Symbiotic Genes and the Symbiotic Properties of Rhizobia Specific to Astragalus glycyphyllos L.
The phylogeny of symbiotic genes of Astragalus glycyphyllos L. (liquorice milkvetch) nodule isolates was studied by comparative sequence analysis of nodA, nodC, nodH and nifH loci. In all these genes phylograms, liquorice milkvetch rhizobia (closely related to bacteria of three species, i.e. Mesorhizobium amorphae, Mesorhizobium septentrionale and Mesorhizobium ciceri) formed one clearly separate cluster suggesting the horizontal transfer of symbiotic genes from a single ancestor to the bacteria being studied. The high sequence similarity of the symbiotic genes of A. glycyphyllos rhizobia (99-100% in the case of nodAC and nifH genes, and 98-99% in the case of nodH one) points to the relatively recent (in evolutionary scale) lateral transfer of these genes. In the nodACH and nifH phylograms, A. glycyphyllos nodule isolates were grouped together with the genus Mesorhizobium species in one monophyletic clade, close to M. ciceri, Mesorhizobium opportunistum and Mesorhizobium australicum symbiovar biserrulae bacteria, which correlates with the close relationship of these rhizobia host plants. Plant tests revealed the narrow host range of A. glycyphyllos rhizobia. They formed effective symbiotic interactions with their native host (A. glycyphyllos) and Amorpha fruticosa but not with 11 other fabacean species. The nodules induced on A. glycyphyllos roots were indeterminate with apical, persistent meristem, an age gradient of nodule tissues and cortical vascular bundles. To reflect the symbiosis-adaptive phenotype of rhizobia, specific for A. glycyphyllos, we propose for these bacteria the new symbiovar "glycyphyllae", based on nodA and nodC genes sequences.


Cardiovascular effects of low-dose dexamethasone in very low birth weight neonates with refractory hypotension.
Administration of hydrocortisone and relatively high doses of dexamethasone increase blood pressure in volume- and pressor-resistant hypotensive preterm infants. However, little is known about the temporal relationship of dexamethasone administration and the improvement in blood pressure and the weaning of pressors/inotropes. Furthermore, there are no sufficient data available on whether a smaller dose of dexamethasone would also be effective in treating refractory hypotension. To study the cardiovascular responses to low-dose dexamethasone in very low birth weight neonates with volume- and pressor-resistant hypotension. Retrospective database review. Twenty-four preterm neonates (gestational age 26 (23-34) weeks; birth weight 801 (457-1,180) g; postnatal age 2 (1-24) days, medians (ranges)) who remained hypotensive despite volume administration and combined dopamine and dobutamine treatment at >or=30 microg/kg/min received dexamethasone 0.1 mg/kg followed by 0.05 mg/kg intravenously every 12 h for 5 additional doses if still on pressors >or=8 microg/kg/min. Two hours after the first dose of dexamethasone the mean blood pressure increased from 30 +/- 5 to 34 +/- 6 mm Hg (p < 0.001) and remained elevated at 4, 6, 12, and 24 h after treatment was started (p < 0.001). Six hours after the initial dose of dexamethasone the pressor/inotrope requirement decreased from 34 +/- 9 to 24 +/- 13 microg/kg/min (p = 0.001) and continued to decrease at 12 and 24 h (p < 0.001). Urine output also increased significantly during the first 6 h after dexamethasone (p < 0.001). Low-dose dexamethasone rapidly increases blood pressure and decreases pressor requirements in very low birth weight neonates with volume- and pressor-resistant hypotension.


Clinical trials with 1-acetyl-2-picolinoylhydrazine (NSC-68626) in children.
Thirty-seven children with various malignant neoplasms were treated with 1-acetyl-2-picolinoylhydrazine. Complete regressions were documented in one child with embryonal rhabdomyosarcoma, in one child with generalized histiocytosis-X, and in one child with Hodgkin's disease. One patient had renal failure while receiving the drug but no conclusive cause and effect relationship could be established. Toxic effects otherwise were mild and consisted primarily of nausea and vomiting.


[Detection of β-Lactamase Produced by Klebsiella pneumoniae Using High Performance Liquid Chromatography].
In order to develop a new method to detect β-lactamase, we determined degradation of β-lactam antibiotics, ampicillin sodium (ABPC) and cefotaxime sodium (CTX), by β-lactamase-producing Klebsiella pneumoniae (K. pneumoniae) in terms of high performance liquid chromatography (HPLC). Using HPLC with an ODS column and an eluent composed of phosphate buffer and methanol, we could detect ABPC and CTX within 10 min. After cultured with K. pneumoniae, ABPC and CTX were degraded. The degradation rate corresponding to the rate of peak area incubated with and without bacteria increased with increasing McFarland No. of bacterial suspension and incubation time. Under the culture condition of McFarland No. 3.0 and 90-min incubation, the degradation rate of ABPC and CTX was 52.6 and 70.8% by K. pneumoniae, whereas it was less than 10% by susceptible bacteria. Consequently, these results confirmed that β-lactamase produced by ABPC- and CTX-resistant bacteria could be detected within about 120 min through HPLC measurement.


The relationship between the pan-immune-inflammation value and long-term prognoses in patients with hypertension: National Health and Nutrition Examination Study, 1999-2018.
Direct antihypertensive therapy in hypertensive patients with a high CVD risk can reduce the incidence of cardiovascular death but increase adverse cardiovascular events, so additional ways to identify hypertensive patients at high risk may be needed. Studies have shown that immunity and inflammation affect the prognoses of patients with hypertension and that the pan-immune-inflammation value (PIV) is an index to assess immunity and inflammation, but few studies have applied the PIV index to patients with hypertension. To explore the relationship between the PIV and long-term all-cause and cardiovascular mortality in patients with hypertension. Data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018 with a mortality follow-up through December 31, 2019, were analyzed. A total of 26,781 participants were evaluated. The patients were grouped based on PIV levels as follows: T1 group (n = 8,938), T2 group (n = 8,893), and T3 group (n = 8,950). The relationship between the PIV and long-term all-cause and cardiovascular death was assessed by survival curves and Cox regression analysis based on the NHANES recommended weights. The PIV was significantly associated with long-term all-cause and cardiovascular mortality in patients with hypertension. After full adjustment, patients with higher PIV have a higher risk of all-cause [Group 3: HR: 1.37, 95% CI: 1.20-1.55, p < 0.001] and cardiovascular [Group 3: HR: 1.62, 95% CI: 1.22-2.15, p < 0.001] mortality. Elevated PIV was associated with increased all-cause mortality and cardiovascular mortality in hypertensive patients.


Her-2 Over-Expression in Gastric Carcinoma:A 5-Year Retrospective Study in A Lagos Cohort Population.
Gastric cancer is the fifth most common cancer and the prognosis has remained poor over the decades due to a high percentage of advanced stage presentation. To determine the frequency of HER-2 over-expression in gastric carcinoma in a Lagos cohort population, comparing it with known clinico-pathologic and prognostic factors. Data on 54 patients with gastric carcinoma were retrieved from the Histopathology Department of Lagos University Teaching Hospital. Haematoxylin and Eosin slides were made from the patients' paraffin blocks. These were reviewed for confirmation of diagnosis and determination of pathological prognostic factors. HER-2 over-expression was assessed using immunohistochemistry. The data was analyzed using SPSS 16. Forty-two gastric biopsies and twelve gastrectomy specimens were available for study from the 54 patients. The ages ranged from 30 to 83 years (mean = 55.96 years). The male to female ratio was 3.2:1. Majority of the carcinomas were intestinal type (83.3%), with diffuse, mixed and indeterminate types accounting for 13%, 1.9% and 1.9% respectively. About 44% of the cases were moderately-differentiated grade and patients who had gastrectomies presented mostly with stage T3 disease (75%). HER-2 was over-expressed in 13% of cases, with one equivocal case. There were no statistically significant associations between HER-2 over-expression and the prognostic factors. HER-2 over-expression occurs in a small percentage of gastric carcinoma in Lagos and is independent of most of the pathological parameters. Further work, with larger cohort, is needed to better characterize the possible prognostic benefits of targeted anti-HER-2 therapy in gastric carcinomas.


Cortical superficial siderosis and first-ever cerebral hemorrhage in cerebral amyloid angiopathy.
To investigate whether cortical superficial siderosis (cSS) is associated with increased risk of future first-ever symptomatic lobar intracerebral hemorrhage (ICH) in patients with cerebral amyloid angiopathy (CAA) presenting with neurologic symptoms and without ICH. Consecutive patients meeting modified Boston criteria for probable CAA in the absence of ICH from a single-center cohort were analyzed. cSS and other small vessel disease MRI markers were assessed according to recent consensus recommendations. Patients were followed prospectively for future incident symptomatic lobar ICH. Prespecified Cox proportional hazard models were used to investigate cSS and first-ever lobar ICH risk adjusting for potential confounders. The cohort included 236 patients with probable CAA without lobar ICH at baseline. cSS prevalence was 34%. During a median follow-up of 3.26 years (interquartile range 1.42-5.50 years), 27 of 236 patients (11.4%) experienced a first-ever symptomatic lobar ICH. cSS was a predictor of time until first ICH (p = 0.0007, log-rank test). The risk of symptomatic ICH at 5 years of follow-up was 19% (95% confidence interval [CI] 11%-32%) for patients with cSS at baseline vs 6% (95% CI 3%-12%) for patients without cSS. In multivariable Cox regression models, cSS presence was the only independent predictor of increased symptomatic ICH risk during follow-up (HR 4.04; 95% CI 1.73-9.44, p = 0.001), after adjusting for age, lobar cerebral microbleeds burden, and white matter hyperintensities. cSS is consistently associated with an increased risk of future lobar ICH in CAA with potentially important clinical implications for patient care decisions such as antithrombotic use.


Long-term management of chronic heart failure patients in internal medicine.
Chronic heart failure (CHF) is one of the main disabilities in elderly patients requiring frequent hospitalizations with high health care costs. We studied the outcome of CHF outpatient management in reducing hospitalization after discharge from a division of Internal Medicine at a large 3rd referral regional Hospital. 147 CHF inpatients (M:F: 63:84; mean age 76 ± 9.6 years) admitted for acute exacerbation of CHF were followed up as outpatients at 1, 6, 12 and 24 months after discharge. At baseline, patients underwent: laboratory tests, ECG, echocardiogram and a dedicated-intensive health care educational program involving also their families. The rate of hospitalization in the same group of patients was compared with data from the previous 24 months, a period when patients had been seen elsewhere without disease management programs. Patients had high prevalence of comorbidities and the majority was in NYHA class III or IV. Hypertension and valvular heart disease were the most common causes for CHF. Systolic function was preserved (LVEF ≥ 50%) in 61.9% of cases. Functional NYHA class improved significantly after 6 months and remained stable at 24 months. There was a significant increase in the use of the renin-angiotensin system blockers, beta-blockers and diuretics compared to admission to the ward. At 24 months, hospital readmissions were decreased by 42% as compared to the previous 24 months. Risk factors for re-hospitalizations were anemia, NYHA class III or IV and previous hospitalizations. Establishing an intensive outpatient management program for CHF patients leads to long-term beneficial effects with improved clinical parameters and decreased hospitalization in the setting of Internal Medicine.


Macular amelanotic melanoma in situ.
This report aims at directing the attention to the rare entity of amelanotic melanoma in situ, as exemplified in a patient who had an amelanotic lentigo maligna 10 years ago and a recurrent lesion of identical clinical and histological (except for pagetoid tumor cells in the epidermis) appearance 4 years ago. Amelanotic melanomas in situ appear as inconspicuous reddish macules, which can hardly be diagnosed or even suspected on clinical grounds.


Improving aerobic power in primary school boys: a comparison of continuous and interval training.
The purpose of this study was to assess whether the magnitude of change in aerobic power was different in boys (mean age 10.25 +/- 0.50 y) who followed a high-intensity interval training protocol, compared to those who followed a moderate-intensity continuous training protocol. Boys were assigned to either a control group (n = 15), a continuous training group (n = 10), or an interval training group (n = 10). They completed peak oxygen uptake tests at baseline and following an 8-week training period. The control group continued with normal activity habits, whilst the continuous training group followed a 20-minute steady-state cycle protocol at 80-85 % of the maximal heart rate, and the interval training group completed 30-s sprints on a cycle ergometer, interspersed with active rest periods. The two training protocols were designed to incur similar cardiovascular work over the 20 minutes of each training session. Significant increases (p < 0.05) in peak oxygen uptake were noted for both the interval and continuous training groups. The interval training group showed marked pre- to post-increases in both peak oxygen pulse, oxygen pulse at the ventilatory threshold, and ventilatory threshold that were not apparent in the continuous group boys. It would appear that a high-intensity interval protocol confers a different training effect in comparison to continuous steady-state training in boys. Possible mechanisms that underpin these adaptations may include increased blood volume and a concomitant adjustment in stroke volume.


Sustainable hydroxypropyl methylcellulose/xyloglucan/gentamicin films with antimicrobial properties.
Hydroxypropyl methylcellulose (HPMC) and xyloglucan (XG) crosslinked with citric acid over a range of HPMC/XG weight ratios formed sustainable blend films characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis, scanning electron microscopy, tensile tests, circular dichroism and determination of inhibitory activity against Staphylococcus aureus and Escherichia coli. Both in solution and in the crosslinked films, HPMC chains lost the original ordered conformation upon interacting with XG, giving rise to an entropic gain. The highest values of tensile strength (25MPa) and Young's modulus (689MPa) occurred for the 50:50 HPMC/XG blend films. In vitro loading of gentamicin sulfate (GS) in the films amounted to 0.18±0.05 -0.37±0.05g of GS per g polymer. At pH 7.4 and 37°C, the GS release kinetics from the films fitted with the Korsmeyer-Peppas model revealed a non-Fickian release mechanism with diffusional coefficient n∼0.7. The cross-linked films of HPMC, XG and their blends loaded with GS showed outstanding antibacterial activity against Staphylococcus aureus and Escherichia coli, disclosing their potential for novel biomedical applications.


Perioperative morbidity and mortality from major gynecologic surgery in the elderly woman.
To report perioperative morbidity and mortality rates in elderly women who underwent major gynecologic surgery. The charts of 110 women between 80 and 91 years of age who underwent major gynecologic surgery between July 1995 and May 2003 were retrospectively reviewed. The mean age was 83.1 years. Forty-nine procedures (44.1%) were performed for cancer, 32 (28.8%) for a mass and 23 (20.7%) for pelvic organ prolapse or urinary incontinence. Sixty-nine (62.7%) procedures were performed abdominally, 36 (32.4%) vaginally and 5 (4.5%) laparoscopically. Fifty (44.6%) patients experienced a postoperative complication, and 9 (8.1%) experienced a major one. Major complications included serious morbidity, in 5 (4.5%) patients, and mortality, in 4 (3.6%). Advanced age (> 85 years) was not associated with any of the outcomes of interest, while prior surgical history was significantly associated with a decreased hospital stay (p < 0.001). Increased hospital stay was associated with a moderate or severe medical history (p < 0.05) and laparotomy/laparoscopy vs. vaginal surgery (p < 0.01). Postoperative complications occurred frequently among women > 80 years of age who underwent gynecologic surgery. The increased perioperative morbidity in the elderly should be considered when performing surgery on women in that age group.


Carcass and meat characteristics from farm-raised and wild fallow deer (Dama dama) and red deer (Cervus elaphus): A review.
Deer species are utilised for food, hunting and other products throughout the world. Consumers are typically exposed to venison derived predominantly from both farm-raised or wild fallow (Dama dama) and red deer (Cervus elaphus). The production of venison under farm conditions, compared to the meat of deer hunted in the wild, allows for a regular supply of a consistently good meat. It is lean, tasty, and rich in proteins and minerals, with a low content of fat and cholesterol. Overall, the worldwide demand for meat is still growing, and both the potential of farming deer species and their use as meat producers have led to an increased interest in venison. The current knowledge about various factors (e.g. nutrition, age, sex, condition, season) affecting venison and game meat has significantly increased during past decades but information regarding the interaction between production system or pre- and post-slaughter handling and ultimate deer meat quality are still very limited.


How affect modulates conversational meanings: a review of experimental research: invited review.
Affect has been found to play important role in word and sentence processing. What is less understood is the role it plays in the process by which interlocutors arrive at what speakers mean. In the present review, the way affect modulates how we comprehend what others mean is examined. This is done by reviewing studies that have employed experimental methods using both written materials and spoken utterances. The goal of the present review is to better understand how the inferential process is framed by affective factors and to propose ways of integrating affectivity into pragmatics. In Part 1, the motivation for the present review is explicated. In Part 2, experimental evidence is presented and suggestions are offered about how to best operationalise variables crucial for disentangling affect from other mechanisms that contribute to utterance interpretation. In Part 3, central notions of pragmatics are discussed with regard to affectivity, which it is proposed that, if construed as a goal-oriented activity that serves interpersonal configuration, can account for several pragmatic phenomena.


ERCP subsequent to retroperitoneal perforation caused by endoscopic sphincterotomy.
Perforation occurs after endoscopic sphincterotomy in 0.4% of cases. With recognition of a perforation, the procedure usually is aborted and further attempts at ERCP are thought to be precluded by the complication. The aim of this study was to determine the timing and the outcome of ERCP after retroperitoneal perforation caused by endoscopic sphincterotomy when the initial ERCP was incomplete. A total of 1787 patients underwent endoscopic sphincterotomy during a period of 29 months. A type II duodenal perforation was recognized in 15 patients, whereupon the ERCP, including further intervention, was halted. Eight patients agreed to undergo a second therapeutic ERCP to complete the treatment of the primary disease. Therapeutic ERCP was repeated in all patients from 11 to 15 days after the perforation. Treatment was successfully completed in all patients without complication. Therapeutic ERCP may be repeated and has a high success rate in patients who sustain a perforation caused by endoscopic sphincterotomy.


Conformational and phase transitions in DNA--photosensitive surfactant solutions: Experiment and modeling.
DNA binding to trans- and cis-isomers of azobenzene containing cationic surfactant in 5 mM NaCl solution was investigated by the methods of dynamic light scattering (DLS), low-gradient viscometry (LGV), atomic force microscopy (AFM), circular dichroism (CD), gel electrophoresis (GE), flow birefringence (FB), UV-Vis spectrophotometry. Light-responsive conformational transitions of DNA in complex with photosensitive surfactant, changes in DNA optical anisotropy and persistent length, phase transition of DNA into nanoparticles induced by high surfactant concentration, as well as transformation of surfactant conformation under its binding to macromolecule were studied. Computer simulations of micelles formation for cis- and trans-isomers of azobenzene containing surfactant, as well as DNA-surfactant interaction, were carried out. Phase diagram for DNA-surfactant solutions was designed. The possibility to reverse the DNA packaging induced by surfactant binding with the dilution and light irradiation was shown.


Human diphyllobothriasis: reports from Rio de Janeiro, Brazil.
This paper reports the occurrence of diphyllobothrid operculated eggs with abopercular knob, found in stool samples from 5 adult humans from Rio de Janeiro, who usually ate raw fish as sushi and sashimi, and presented gastrointestinal disturbances.


Validation of the use of 32P-orthophosphate as a probe for monitoring DNA replication in pancreatic islet cells.
This study aims at validating the use of 32P-orthophosphate as a probe for monitoring DNA replication instead of [3H]-thymidine where the specific activity of the latter is affected by perturbation of the cellular environment. It was found that to obtain a clean DNA fraction for determining the incorporation of the label, protein must be removed by the use of Proteinase K, and RNA by alkaline hydrolysis. Alkaline hydrolysis of RNA was found superior to RNAse digestion in not leaving behind large RNA fragments that may contaminate the DNA fraction.


Rehospitalizations, early revisions, infections, and hospital resource use in the first year after hip and knee arthroplasties.
We examined 3 negative outcomes for 58 351 hip and knee arthroplasty patients: rehospitalization, revision and infection, and their impact on resource use in the year after surgery. In the year before surgery, 12.9% of elective hip and 10.2% of knee patients were hospitalized. In the year after, 14.8% of elective hip and 15.5% of knee patients were hospitalized, representing a 15% and 52% increase, respectively. Twenty-eight percent of emergent hip patients were hospitalized at least once preoperatively; this did not change after surgery. Revision occurred in 2.0% of emergent hip, 1.7% of elective hip, and 0.9% of knee patients. Joint infection was diagnosed in 1.3% of patients. The increased hospitalization after the elective hip and knee procedures represents an incremental cost of 10% over the index hospital stay.


Q fever is underestimated in the United States: a comparison of fatal Q fever cases from two national reporting systems.
Two national surveillance systems capturing reports of fatal Q fever were compared with obtained estimates of Q fever underreporting in the United States using capture-recapture methods. During 2000-2011, a total of 33 unique fatal Q fever cases were reported through case report forms submitted to the Centers for Disease Control and Prevention and through U.S. death certificate data. A single case matched between both data sets, yielding an estimated 129 fatal cases (95% confidence interval [CI] = 62-1,250) during 2000-2011. Fatal cases of Q fever were underreported through case report forms by an estimated factor of 14 and through death certificates by an estimated factor of 5.2.


Minimal promoter for the NAD+-specific glutamate dehydrogenase gene of Neurospora crassa.
The expression of the NAD+-specific glutamate dehydrogenase (NAD-GDH) gene of Neurospora crassa is subject to catabolite repression. To identify the minimal sequence necessary for promoter function, the 5'-flanking region of the NAD-GDH gene was screened for potential protein-binding sites. Fragments of DNA, containing sequences upstream from the ATG initiation codon, were employed as probes of Southwestern blots of total cellular protein from cells grown in media promoting repression and induction of NAD-GDH. Two polypeptides interacted differentially with a promoter probe; one was present in greater abundance in repressed cells and a higher relative level of the second was witnessed in induced cells. Electrophoretic mobility shift assays with labeled promoter fragments exhibited preferential interaction with proteins in the induced cultures. The upstream sequence containing the putative protein-binding sites was fused with the coding sequence of the green fluorescent protein (GFP). The resulting plasmid was introduced into the microconidia of an albino mutant of N. crassa by electroporation. Stable integration of the plasmid and_expression of GFP in the hyphae and conidia of the transformants were demonstrated by Southern and Western blot analysis and fluorescence microscopy.


Treatment of new-onset ulcerative colitis and ulcerative proctitis: a retrospective study.
Although guidelines recommend use of oral 5-aminosalicylates (5-ASAs) as first-line therapy in patients with mild to moderate ulcerative colitis (UC) and ulcerative proctitis (UP) and steroids with or without 5-ASAs in those more severely ill, little is known about how UC and UP are actually treated. To document treatment of new-onset UC and UP in routine clinical practice. Using a large US health insurance database, we identified all persons with new-onset UC or UP between 1 January 2005 and 31 December 2007, based on: (i) initial receipt of an oral 5-ASA, mesalazine (mesalamine) suppository, 5-ASA enema, steroid, antimetabolite, budesonide or TNF inhibitor; (ii) sigmoidoscopy/colonoscopy in prior 30 days resulting in a new diagnosis of UC or UP and (iii) no prior encounters for Crohn's disease. We examined patterns of pharmacotherapy over 1 year. We identified 1516 UC patients and 636 UP patients who met study entry criteria. In UC, initial therapies most frequently used were oral 5-ASAs (53% of patients), oral 5-ASAs and systemic steroids (12%), systemic steroids (8%) and mesalazine suppositories (6%); in UP, mesalazine suppositories (42%) and oral 5-ASAs (19%) were most often used, followed by combination therapy (14%), mesalazine enema (11%) and rectal steroids (10%). Few patients received maintenance therapy, and there was limited use of antimetabolites and biological agents. Oral 5-ASAs and systemic steroids are the mainstay of treatment in patients with new-onset ulcerative colitis; in those with new-onset ulcerative proctitis, it is mesalazine suppositories. Care of these patients appears consistent with treatment guidelines.


Influence of the target delay and duration on the prediction of a moving stimulus future position.
In a linear-motion prediction study an immobile target with different duration and delay with respect to the onset of the visible motion determined the motion extrapolation distance. The subject's task was to press a key at the moment when the moving stimulus would reach the position of the target if it continued its motion on the screen. The subject's response time was measured between the moment of the moving stimulus disappearance and the moment of key pressing. A linear relationship between the response time and the concealment time was obtained under all experimental conditions. It was demonstrated that the duration of the target did not affect the linear regression equation constants. The delay of the target presentation with respect to the onset of the visible motion was found to influence the free term of the linear relationship. When the target was presented with a great delay (0.56 s before the moving stimulus disappearance) the intercept in the linear relationship significantly decreased. The present results suggest that the organization of the response in the motion prediction conditions influences the temporal characteristics of the subject's performance. This influence is manifested in alternation of the free term in the linear relationship between the response time and concealment time.


Prevention of cerebral ischaemic reperfusion injury by intra-arterial administration of superoxide dismutase in the rat.
An experimental test was performed to determine whether superoxide dismutase, an oxygen-free radical scavenger, reduces neurological dysfunction after transient global cerebral ischaemia. Three groups of 13 rats each were used. Group 1 served as normal controls. Groups 2 and 3 were subjected to transient global cerebral ischaemia. Before ischaemia, the right carotid bifurcation was isolated and the right external carotid artery was retrogradely cannulated, with the catheter tip positioned near the origin of the internal carotid artery. Once global cerebral ischaemia was complete, either isotonic saline (group 2) or superoxide dismutase solution (group 3) was injected through the above-mentioned catheter, before, during and after reperfusion. Consequently, the injected solutions were distributed through the circle of Willis to all of the ischaemic brain tissue. Somatosensory evoked potentials were registered in the three groups of animals and were used as a measure of neuronal function. In control animals (group 1) mean P1 latency was 8.1 msec and while the mean P1 latency was 11.9 msec in the isotonic saline treated animals (group 2), it was reduced to 8.8 msec in rats treated with the superoxide dismutase solution (group 3). P1 latency was significantly higher in group 2 than in groups 1 and 3 (P less than 0.001). As evaluated by somatosensory evoked potentials, we have concluded that the intra-arterial injection of superoxide dismutase to the ischaemic tissue improves neuronal function in rats subjected to transient global cerebral ischaemia.


A short isoform of STIM1 confers frequency-dependent synaptic enhancement.
Store-operated Ca2+-entry (SOCE) regulates basal and receptor-triggered Ca2+ signaling with STIM proteins sensing the endoplasmic reticulum (ER) Ca2+ content and triggering Ca2+ entry by gating Orai channels. Although crucial for immune cells, STIM1's role in neuronal Ca2+ homeostasis is controversial. Here, we characterize a splice variant, STIM1B, which shows exclusive neuronal expression and protein content surpassing conventional STIM1 in cerebellum and of significant abundance in other brain regions. STIM1B expression results in a truncated protein with slower kinetics of ER-plasma membrane (PM) cluster formation and ICRAC, as well as reduced inactivation. In primary wild-type neurons, STIM1B is targeted by its spliced-in domain B to presynaptic sites where it converts classic synaptic depression into Ca2+- and Orai-dependent short-term synaptic enhancement (STE) at high-frequency stimulation (HFS). In conjunction with altered STIM1 splicing in human Alzheimer disease, our findings highlight STIM1 splicing as an important regulator of neuronal calcium homeostasis and of synaptic plasticity.


Immunohistochemical prognostic markers in bladder cancer.
The management of superficial bladder cancer is characterized by early recognition of recurrence and the prevention of progression. Biological markers must provide additional information to that provided by multiplicity, size and grade. So, the identification of new prognostic biomarkers for bladder cancer could be used to divide patients into risk groups determining treatment and follow-up schemes. The transformation of a normal cell into a malignant cell is a multistep mechanism, which involves various alterations on the molecular and genetic level. Transitional-cell carcinoma (TCC) is believed to arise through a series of genetic changes. One mechanism of these changes is the mutation of normal genes to oncogenes, which allows cells to escape the regulation of cellular growth control. In addition, tumour growth is regulated by a balance between proliferation, growth arrest and programmed cell death. The control of growth arrest and apoptosis plays key roles in the development of human cancer and in cancer treatment. Tumours present a complex ecosystem in which interactions between tumour cells, extracellular matrix and host cells may lead to reciprocal influences resulting in tumour promotion, invasion and metastasis. Tumour invasion is considered to be a dynamic complex process, which involves a number of steps. During these steps, a lot of critical molecules are involved, the expression of which may offer useful information about the biological behavior of bladder cancer. This review article summarizes the most promising immunohistochemical prognostic factors which have been considered to be involved in the complex and multistep process of bladder carcinogenesis, and in the process of invasion and metastasis.


Treatment of grade III and IV astrocytoma with high-dose irradiation: schedule and chemotherapy.
From October 1978 to June 1981, 35 consecutive patients with grade III-IV malignant glioma were treated with a concentrated course of radiotherapy (two cycles of 17 Gy in two sessions over a 3-day period) with a cobalt unit, followed by chemotherapy with vincristine and BCNU. In the 30 evaluable patients, no complete remission, seven partial remissions, 23 stable disease, and no progression were encountered. Median duration of response was 6 months (range 4-11+). Median survival time was 9 months (range 7-19); radically resected patients survived longer than those with inoperable tumor. Toxicity of treatment was acceptable; however, two patients with brain stem tumors had acute neurologic toxicity following the first radiotherapy session.


Protective role of Punica granatum (pomegranate) peel and seed oil extracts on diethylnitrosamine and phenobarbital-induced hepatic injury in male rats.
The present study is an attempt to reveal the protective role of Punica granatum peel and seed oil extracts against diethylnitrosamine (DEN) and phenobarbital (PB) induced hepatic injury in rats. DEN administration increased the levels of malondialdehyde (MDA), DNA fragmentation, caspase-3 and glutathione reductase (GSR) activities, while the level of reduced glutathione (GSH) and the activities of superoxide dismutase (SOD), glutathione S-transferase (GST) and total glutathione peroxidase (t-GPx) were decreased compared with the control. Treatment with peel and seed oil extracts pre, during and post DEN administration improved liver functions, decreased the levels of MDA, DNA fragmentation, caspase-3 and GSR activities with an elevation in levels of GSH, SOD, GST and t-GPx activities. This indicates that these extracts reduced the oxidative stress and apoptosis induced by DEN. Also the effect of administration of PE and SOE separately for a long time (23 weeks) on healthy rats was studied.


[Role of uropontin in calcium oxalate lithogenesis].
The formation of calcium oxalate stones involves four phases: nucleation, growth, aggregation and retention. Stone formation is a complex, multifactorial phenomenon involving, among other factors, proteins, some of which play an inhibitory role, while others play a promoting role. The authors studied the role of uropontin. Uropontin is the urinary form of osteopontin. Osteopontin is essentially involved in the mineralisation of bone tissue. Uropontin is secreted in the kidney by epithelial cells of the distal convoluted tubule and loop of Henle. Uropontin has an inhibitory action on the four phases of calcium oxalate crystal formation and is also one of the main constituents of the calcium oxalate stone matrix. A reduction of uropontin expression in epithelial cells induces a reduction of calcium oxalate stone formation. Uropontin is a protein largely involved in the lithogenesis of urinary stones, but its mechanism of action has not yet been fully elucidated.


MicroRNA-204 may participate in the pathogenesis of hypoxic-ischemic encephalopathy through targeting KLLN.
Hypoxic-ischemic encephalopathy (HIE) is a common neonatal disease that can lead to high neonatal mortality rates. Previous studies have indicated that microRNAs (miRs) may be involved in the pathogenesis of HIE; however, the specific mechanisms underlying their involvement require further investigation. The aim of the present study was to investigate the roles of miR-204 and its target gene killin p53 regulated DNA replication inhibitor (KLLN) in HIE using rat HIE models. Brain injury was induced by surgery and incubation of hypoxic incubator brain using 10-day-old pup rats. On day 3, rats were sacrificed, and the infarct size of the brain was determined using a tetrazolium chloride assay. Terminal deoxynucleotidyl transferase UTP nick-end labeling staining was performed to detect the cell death rate in the brain tissue. Following this, the brain tissues were collected, and reverse transcription-quantitative polymerase chain reaction, western blot analysis and immunohistochemistry assays were performed to examine the expression levels of miR-204 and KLLN. Furthermore, neurons were cultured and transfected with miR-204 inhibitors or mimics, and the effect of miR-204 on the proliferation and apoptosis of neurons was examined using MTT and flow cytometric assays. Finally, a dual-luciferase reporter assay was performed to confirm whether KLLN is a direct target of miR-204. The expression of miR-204 was significantly downregulated and the expression of KLLN was significantly increased in the brain tissue of HIE rats (P<0.001). In addition, the transfection with miR-204 inhibitors significantly decreased the proliferation rates and significantly increased the apoptosis rate of neurons; however, transfection with miR-204 mimics prompted the opposite results. The dual-luciferase reporter assay also confirmed that KLLN is a direct target of miR-204. Taken together, the results of the present study demonstrated that miR-204 was downregulated in HIE and that miR-204 may serve important roles in the pathogenesis of HIE through targeting KLLN.


Kidney transplantation among identical twins: therapeutic dilemmas.
A case of the successful kidney transplantation among two homozygous twins is presented here. Prior to the familial kidney transplantation from the identical twins, the patient underwent peritoneal and haemodialyses as well as cadaveric kidney transplant from an unrelated donor. In this patient, vascular accessibility was poor and the second familial transplantation was performed urgently. Transplanted kidney function proved excellent; however, the issues of the best immunosuppressant to be selected are under consideration. Decision on the use or withdrawal of immunosuppressant drugs requires careful review of the disease status, concomitant disease and other factors influencing the final outcome.


Inhibitory effect of prednisone on insulin secretion in man: model for duplication of blood glucose concentration.
Treatment with oral prednisone (15 mg every 6 h) for 1 day plus a 4-h glucose infusion at 2.8 mg/min kg body weight to 5 normal, healthy individuals raised their blood glucose to 137 +/- 4.5 mg per 100 ml (mean +/- SEM). In order to evaluate the effects of steroid-induced hyperglycemia on insulin responses, a model for the duplication of blood glucose concentration in serial studies was developed. During glucose infusion at 5.7 mg/min kg body weight, the fractional uptake of glucose at the end of infusion (KG) was 2.08 +/- 0.2%/min and the apparent volume of distribution (V) was 285 +/- 10.5 ml/kg. Further increase in the rate of glucose infusion did not affect KG and V. Based on these parameters, KG and V, the stable blood glucose achieved during the prednisone study (C) was duplicated both after short (4 h) and prolonged (28 h) glucose infusions (138 +/- 4.5 and 146 +/- 4.5 mg/100 ml, respectively) at rates calculated as the product of KG.C.V. The effects of prednisone treatment on insulin secretion were examined (1) during fasting, (2) at identical glucose concentrations during glucose infusions at constant rates, and (3) in response to glucose pulse (0.1 g/kg) during the infusions. During fasting, there was a significant elevation of mean blood glucose with prednisone (99 +/- 1.8 mg/100 ml) compared with that in the control study (88 +/- 1.7 mg/100 ml). The plasma IRI, however, remained unchanged (10 +/- 2.3 vs 10 +/- 1.6 muU/ml). During glucose infusions in the presence of similar blood glucose levels, the IRI was lower after prednisone treatment (18 +/- 1.5 muU/ml) than during the short and prolonged glucose infusions (42 +/- 5.1 and 63 +/- 7.0 muU/ml). The insulin response to the glucose pulse also was significantly lower during steroid treatment. Thus, prednisone apparently has an early inhibitory effect on the insulin response to glucose.


[Nanostructured RNA for RNA interference].
RNA interference (RNAi) is a potent and highly specific gene-silencing phenomenon which is initiated or triggered by double-stranded RNAs (dsRNAs). Shortly after the development of RNAi, small interfering RNAs (siRNAs) that are 21 nucleotides in length with a 3' nucleotide overhang were shown to be very effective in mammalian cells. Much effort has been dedicated to the application of siRNAs, both as biological tools and as therapeutic agents. Currently, synthetic siRNA would be the method of choice for clinical purposes. However, natural RNA strands are quickly degraded in biological fluids. Chemically synthesized unnatural nucleotides have been developed and introduced into the siRNA strand. For example, modification of the ribose moiety with a 2'-deoxy, 2'-O-methyl, or 2'-fluoro group, or modification of the phosphate backbone have been examined. Although these modifications improve the stability of siRNA in serum, they often cause a decrease in RNAi activity. There is also concern that unnatural RNA derivatives are toxic in the human body. A method to stabilize nontoxic natural RNA strands should be very useful for applications in RNAi technology. We came up with an idea that nano-structural design stabilizes natural RNA. We tested several new designs such as dumbbell RNA, double stranded circular RNA, or branched RNA in biological stability and RNA interference activity. Consequently, dumbbell or branched design offered prolonged RNAi effect due to high biological stability.


The impact of the COVID-19 pandemic on infertility patients and endometriosis patients in the Netherlands.
How do infertility patients, endometriosis patients and health-care providers rate virtual care as an alternative to physical consultations during the first lockdown of the coronavirus disease 2019 (COVID-19) pandemic in the Netherlands, and how does this influence quality of life and quality of care? Infertility patients and endometriosis patients from a university hospital and members of national patient organizations, as well as healthcare providers in infertility and endometriosis care, were asked to participate between May and October 2020. The distributed online questionnaires consisted of an appraisal of virtual care and an assessment of fertility-related quality of life (FertiQol) and patient-centredness of endometriosis care (ENDOCARE). Questionnaires were returned by 330 infertility patients, 181 endometriosis patients and 101 healthcare providers. Of these, 75.9% of infertility patients, 64.8% of endometriosis patients and 80% of healthcare providers rated telephone consultations as a good alternative to physical consultations during the COVID-19-pandemic. Only 21.3%, 14.8% and 19.2% of the three groups rated telephone consultations as a good replacement for physical consultations in the future. A total of 76.6% and 35.9% of the infertility and endometriosis patients reported increased levels of stress during the pandemic. Infertility patients scored lower on the FertiQol, while the ENDOCARE results care seem comparable to the reference population. Virtual care seems to be a good alternative for infertility and endometriosis patients in circumstances where physical consultations are not possible. Self-reported stress is especially high in infertility patients during the COVID-19-pandemic. Healthcare providers should aim to improve their patients' ability to cope.


Construction of three new Gateway® expression plasmids for Trypanosoma cruzi.
We present here three expression plasmids for Trypanosoma cruzi adapted to the Gateway® recombination cloning system. Two of these plasmids were designed to express trypanosomal proteins fused to a double tag for tandem affinity purification (TAPtag). The TAPtag and Gateway® cassette were introduced into an episomal (pTEX) and an integrative (pTREX) plasmid. Both plasmids were assayed by introducing green fluorescent protein (GFP) by recombination and the integrity of the double-tagged protein was determined by western blotting and immunofluorescence microscopy. The third Gateway adapted vector assayed was the inducible pTcINDEX. When tested with GFP, pTcINDEX-GW showed a good response to tetracycline, being less leaky than its precursor (pTcINDEX).


Timing of initial cereal exposure in infancy and risk of islet autoimmunity.
Dietary exposures in infancy have been implicated, albeit inconsistently, in the etiology of type 1 diabetes mellitus (DM). To examine the association between cereal exposures in the infant diet and appearance of islet autoimmunity (IA). Birth cohort study conducted from 1994 to 2002 with a mean follow-up of 4 years. Newborn screening for HLA was done at St Joseph's Hospital in Denver, Colo. First-degree relatives of type 1 DM individuals were recruited from the Denver metropolitan area. We enrolled 1183 children at increased type 1 DM risk, defined as either HLA genotype or having a first-degree relative with type 1 DM, at birth and followed them prospectively. We obtained exposure and outcome measures for 76% of enrolled children. Participants had variable lengths of follow-up (9 months to 9 years). Blood draws for the detection of insulin autoantibody, glutamic acid decarboxylase autoantibody, or IA-2 autoantibody were performed at 9, 15, and 24 months and annually thereafter. Children with IA (n = 34) were defined as those testing positive for at least 1 of the autoantibodies on 2 or more consecutive visits and who tested positive or had diabetes on their most recent visit. Children initially exposed to cereals between ages 0 and 3 months (hazard ratio [HR], 4.32; 95% confidence interval [CI], 2.0-9.35) and those who were exposed at 7 months or older (HR, 5.36; 95% CI, 2.08-13.8) had increased hazard of IA compared with those who were exposed during the fourth through sixth month, after adjustment for HLA genotype, family history of type 1 DM, ethnicity, and maternal age. In children who were positive for the HLA-DRB1*03/04,DQB8 genotype, adjusted HRs were 5.55 (95% CI, 1.92-16.03) and 12.53 (95% CI, 3.19-49.23) for initial cereal exposure between ages 0 to 3 months and at 7 months or older, respectively. There may be a window of exposure to cereals in infancy outside which initial exposure increases IA risk in susceptible children.


Myths and realities of the cardiac vagus.
There is continuing belief that cardiac parasympathetic postganglionic fibres are sparse or absent from the ventricles. This review of the literature shows that the supposition is a myth. Early studies considered that fine silver-stained fibres coursing amongst ventricle myocardial cells were most likely cardiac parasympathetic postganglionic fibres. The conclusions were later supported by acetyl cholinesterase staining using a method that appeared not to be associated with noradrenaline nerve fibres. The conclusion is critically examined in the light of several recent histological studies using the acetyl cholinesterase method and also a more definitive technique (CHAT), that suggest a widespread location of parasympathetic ganglia and a relatively dense parasympathetic innervation of ventricular muscle in a range of mammals including man. The many studies demonstrating acetylcholine release in the ventricle on vagal nerve stimulation and a high density of acetylcholine M2 receptors is in accord with this as are tests of ventricular performance from many physiological studies. Selective control of cardiac functions by anatomically segregated parasympathetic ganglia is discussed. It is argued that the influence of vagal stimulation on ventricular myocardial action potential refractory period, duration, force and rhythm is evidence that vagal fibres have close apposition to myocardial fibres. This is supported by clear evidence of accentuated antagonism between sympathetic activity and vagal activity in the ventricle and also by direct effects of vagal activity independent of sympathetic activity. The idea of differential control of atrial and ventricular physiology by vagal C and vagal B preganglionic fibres is examined as well as differences in chemical phenotypes and their function. The latter is reflected in medullary and supramedullary control. Reference is made to the importance of this knowledge to understanding the normal physiology of cardiac autonomic control and significance to pathology.


A facile method for the stereoselective Horner-Wadsworth-Emmons reaction of aryl alkyl ketones.
Excellent Z or E selectivity was observed in the Horner-Wadsworth-Emmons (HWE) reactions of methyl bis(2,2,2-trifluoroethyl)phosphonoacetate or ethyl 2-fluoro-2-diethylphosphonoacetate with aryl alkyl ketones bearing substituents on an aromatic moiety employing Sn(OSO2CF3)2 in the presence of N-ethylpiperidine.


Dissociation of NSC606985 induces atypical ER-stress and cell death in prostate cancer cells.
Castration-resistant prostate cancer (CRPC) is a major cause of prostate cancer (Pca) death. Chemotherapy is able to improve the survival of CRPC patients. We previously found that NSC606985 (NSC), a highly water-soluble camptothecin analog, induced cell death in Pca cells via interaction with topoisomerase 1 and activation of the mitochondrial apoptotic pathway. To further elucidate the role of NSC, we studied the effect of NSC on ER-stress and its association with NSC-induced cell death in Pca cells. NSC produced a time- and dose-dependent induction of GRP78, CHOP and XBP1s mRNA, and CHOP protein expression in Pca cells including DU145, indicating an activation of ER-stress. However, unlike conventional ER-stress in which GRP78 protein is increased, NSC produced a time- and dose-dependent U-shape change in GRP78 protein in DU145 cells. The NSC-induced decrease in GRP78 protein was blocked by protease inhibitors, N-acetyl-L-leucyl-L-leucylnorleucinal (ALLN), a lysosomal protease inhibitor, and epoxomicin (EPO), a ubiquitin-protease inhibitor. ALLN, but not EPO, also partially inhibited NSC-induced cell death. However, both 4-PBA and TUDCA, two chemical chaperons that effectively reduced tunicamycin-induced ER-stress, failed to attenuate NSC-induced GRP78, CHOP and XBP1s mRNA expression and cell death. Moreover, knockdown of NSC induction of CHOP expression using a specific siRNA had no effect on NSC-induced cytochrome c release and NSC-induced cell death. These results suggest that NSC produced an atypical ER-stress that is dissociated from NSC-induced activation of the mitochondrial apoptotic pathway and NSC-induced cell death in DU145 prostate cancer cells.


Knowledge, attitude, and practice of medication among Haikou residents.
Our study aims to explore the knowledge, attitude, and practice (KAP) and its influencing factors of medication among residents in Haikou, the capital city of Hainan Province, and inform the development of interventions to reduce residents' medication errors. A cross-sectional questionnaire survey was conducted to investigate the KAP of medication among Haikou residents and its influencing factors from March to September 2019. A total of 471 valid questionnaires were collected (245 online and 226 offline), with an effective recovery rate of 94.2%. The average score of KAP of medication were 52.2±13.08, 27.34±8.14, and 51.54±9.22, respectively. The knowledge score reached "good" in the evaluation criteria of the questionnaire, and the attitude and practice scores were "fair". Multiple linear regression analysis revealed the medication knowledge increased with age; a lower education degree was associated with less knowledge and more medication errors, and a higher education level was associated with more access to medication knowledge. Education on rational drug use should be performed via multiple ways to promote rational drug use and reduce risky medication behaviors, particularly among residents with low education degrees, e.g., drug counseling and guidance, regularly push medication science popularization, public welfare lecture on rational drug use, organize and compile popular science books.


Analysis of volatile organic compounds and metabolites of three cultivars of asparagus (Asparagus officinalis L.) using E-nose, GC-IMS, and LC-MS/MS.
Asparagus (A. officinalis L.) is a perennial herb of the genus Asparagus that is rich in nutrients. This study aimed to distinguish three cultivars of asparagus (Paladin, Grace, and Jinggang red) based on their volatile organic compounds (VOCs) and metabolic profiles. VOCs in the three cultivars were separated and identified using electronic nose (E-nose) and gas chromatography-ion mobility spectrometry (GC-IMS). Differences in metabolites among the three cultivars were analyzed using liquid chromatography-tandem mass spectrometry (LC-MS/MS). E-nose and GC-IMS showed that the VOCs in asparagus differed significantly among the three groups. E-nose result showed that purple asparagus (Jinggang red) was connected to a stronger earthy odor; green asparagus (Paladin and Grace) were shown characteristic dill flavor. Moreover, 50 VOCs were detected by using GC-IMS. Ketones and alcohols were most abundant in Paladin; methyl benzoate and dimethyl sulfide were most abundance in Grace; aldehydes and acids were most abundance in Jinggang red. Moreover, 130 and 71 different metabolites were detected in the positive and negative modes among three cultivars, such as quercetin and rutin. Functional analysis revealed that these metabolites were involved in beta-alanine metabolism and ATP-binding cassette (ABC) transporters. In summary, E-nose combined with GC-IMS and LC-MS/MS methods has good application prospects in evaluating and identifying VOCs and metabolites of different cultivars of asparagus. The identified VOCs and metabolites can provide guidelines for the development of functional asparagus products.


Liquid-crystal-based fiber laser sensor for non-invasive gas detection.
This Letter reports a new optical fiber gas sensor for measuring breath acetone. The sensor is based on photonic bandgap (PBG) mode laser emission sensing technology using liquid crystal (LC), which is combined with silica fiber and chiral nematic liquid crystal (CNLC), thus providing an ultra-compact, fast-response and simple-to-produce sensing system with a fast response that can accurately and quantitatively determine the concentration of respiratory acetone within the normal oral temperature range (35-38°C). Since LCs are affected by temperature, we propose a method that eliminates the influence of the temperature to solve the problem of the temperature influence when measuring gas. The detection of acetone leads to splitting of the dual laser peaks, with a linear correlation of 0.99. The sensor has a limit of detection of 65 ppm for acetone vapor and thus is suitable for breath acetone detection in diabetic patients.


Enhanced hematopoietic protection from radiation by the combination of genistein and captopril.
The hematopoietic system is sensitive to radiation injury, and mortality can occur due to blood cell deficiency and stem cell loss. Genistein and the angiotensin converting enzyme (ACE) inhibitor captopril are two agents shown to protect the hematopoietic system from radiation injury. In this study we examined the combination of genistein with captopril for reduction of radiation-induced mortality from hematopoietic damage and the mechanisms of radiation protection. C57BL/6J mice were exposed to 8.25Gy (60)Co total body irradiation (TBI) to evaluate the effects of genistein and captopril alone and in combination on survival, blood cell recovery, hematopoietic progenitor cell recovery, DNA damage, and erythropoietin production. 8.25Gy TBI resulted in 0% survival after 30days in untreated mice. A single subcutaneous injection of genistein administered 24h before TBI resulted in 72% survival. Administration of captopril in the drinking water, from 1h through 30days postirradiation, increased survival to 55%. Genistein plus captopril increased survival to 95%. Enhanced survival was reflected in a reduction of radiation-induced anemia, improved recovery of nucleated bone marrow cells, splenocytes and circulating red blood cells. The drug combination enhanced early recovery of marrow progenitors: erythroid (CFU-E and BFU-E), and myeloid (CFU-GEMM, CFU-GM and CFU-M). Genistein alone and genistein plus captopril protected hematopoietic progenitor cells from radiation-induced micronuclei, while captopril had no effect. Captopril alone and genistein plus captopril, but not genistein alone, suppressed radiation-induced erythropoietin production. These data suggest that genistein and captopril protect the hematopoietic system from radiation injury via independent mechanisms.


A descriptive qualitative study of perceptions of parents on their child's vaccination.
To explore the perceptions of parents on their child's vaccination in Singapore. Vaccination is a key part of health care, and the management of vaccination for children has gained increasing interest globally. Previous studies found that parents had multiple concerns and low confidence in making vaccination decisions for their children. As no study in this area has been conducted in Singapore, the views and needs of parents regarding their child's vaccination remain unknown. Descriptive qualitative study. Purposive sampling was used to recruit 19 parents of children undergoing routine vaccination in a clinic in Singapore. Semistructured face-to-face or telephone interviews were conducted using an interview guide and were audiorecorded. Thematic analysis was used to analyse the data. The thematic analysis generated four themes from 15 subthemes. Theme 1 summarised the factors promoting vaccination uptake, theme 2 was factors impeding vaccination compliance, theme 3 described parents' supportive roles before, during and after the vaccination, and theme 4 was about parents' need for improvement in vaccination services, information and communication with healthcare professionals. This study provided insight into parental views, experiences and needs regarding their child's vaccination. The results suggest a need for developing intervention programmes addressing information needs and pain management strategies to improve parents' experiences regarding their children's vaccination. Healthcare professionals and policymakers should take actions to improve parents' experiences regarding their child's vaccination by minimising the impeding factors and improving services, information provided and communications with parents.


Imatinib induced melasma-like pigmentation: Report of five cases and review of literature.
Imatinib mesylate is a cytotoxic agent that targets tyrosine kinase. Common side effects of this drug include nausea, edema and maculopapular rash. Hypopigmentation is a commonly reported side effect of this drug while hyperpigmentation has rarely been described. We describe five cases of melasma-like pigmentation induced by this anti-cancer drug. Four of the patients were diagnosed with gastrointestinal stromal tumor while one had chronic myeloid leukemia. Patients received imatinib mesylate in a dose of 400 mg daily. Over an average period of 3 months, well defined hyperpigmented macules appeared over the convexities of the face. One of the patients also developed similar pigmentation on the forearm. Other causes of hyperpigmentation were excluded in each patient.


[Antiphospholipid syndrome. Proposition for management].
Antiphospholipid antibodies (antiprothrombinase and anticardiolipin) carry with them for mothers the risks of repeated fetal loss and of disorders of the blood clotting mechanism both before and after delivery. All the same screening does not have to be carried out routinely but should be reserved for patients who have already lost one fetus (intrauterine death after 12 weeks of amenorrhoea) and/or venous or arterial thrombosis. The diagnosis depends on a strict methodology and strict criteria for making a positive diagnosis. The treatment of these antibodies (with corticosteroids and intravenous immunoglobulin) or the prevention of possible thrombotic complications (using platelet antiaggregation/heparin) has to be decided taking into account the level of antibodies, previous obstetric and thrombotic history and the lupus symptomatology as shown by the patients. The overall success rate of treatment is between 53 and 81%.


Evaluation of different treatment modalities for fractured and non-fractured simple bone cyst: A single-center review of 68 patients.
Simple bone cysts (SBCs) occur most frequently in the proximal aspect of the humerus and femur in growing age and are associated with intercurrent pathological fractures in up to 87%. Therapeutic management of SBCs remains controversial. The aim of this study was to examine the outcome of conservative and various surgical treatment modalities considering the specific anatomic location and integrity of the SBC.In this retrospective study, we analyzed 68 cases of SBCs who underwent a conservative or surgical treatment between 2009 and 2020 with a mean follow-up of 30.1 months. The epidemiological characteristics, complications, clinical, and radiographic outcome after conservative or surgical treatment were assessed.The study includes 50 male (73.5%) and 18 female (26.5%) patients with a mean age of 9.1 years. The most common locations were the proximal humerus (69.2%, n = 47) and femur (16.2%, n = 11). In 43 cases (63.2%; upper limb n = 40, lower limb n = 3) a pathological fracture occurred. Fifty patients (73.5%; upper limb n = 40, lower limb n = 10) underwent a conservative treatment. In 11 cases (16.2.1%; upper limb n = 4, lower limb n = 7) an intralesional curettage and defect reconstruction with bone substitute without stabilization were performed. Five patients (7.3%; upper limb n = 4, lower limb n = 1) received an osteosynthesis, in two cases (2.9%; upper limb 1; lower limb 1) combined with an intralesional curettage and defect reconstruction with bone substitute. All 32 pathological fractures treated conservatively (upper limb n = 31, lower limb n = 1) healed within 6 weeks; 17/43 patients (39.5%) suffered at least one second fracture. After intralesional curettage and defect reconstruction with bone substitute local recurrence was observed in 5/13 cases (38.5%). Spontaneous consolidation, at least partially, was observed in three cases (4.4%) following conservative treatment after fracture. No relevant secondary angular or torsional deformity was observed after treatment.The majority of SBCs can be treated conservatively, especially in the upper extremity. However, if a fracture is completely dislocated, joint affecting, unstable or open, surgical treatment is necessary. Load-dependent pain or the inability to mobilize timely after fracture can necessitate surgical treatment in SBCs affecting the lower extremity. Spontaneous resolution, especially after fracture, can be seen in rare cases.


[Problems of gastrointestinal angiography].
The subject of abdominal angiography is discussed, for informational rather than technical reasons, on the basis of seven years personal experience. The method used to prepare the patient for angiography and emergency treatment of the various episodes of reaction to the contrast medium or of complications of arterial catheterism are illustrated and some of the most significant aspects of abdominal angiographic symptomatology described.


Dynamic expression of Runx1 in skin affects hair structure.
The three mammalian Runx transcription factors, some of which are known to be involved in human genetic diseases and cancer, are pivotal players in embryo development and function as key regulators of cell fate determination and organogenesis. Here, we report the expression of Runx1 during the development of hair and other skin appendages in the mouse and describe the effect of Runx1 on the structural hair output. In hair follicles, where the three Runx proteins are expressed, Runx1 expression is most prominent in both mesenchymal and epithelial compartments. The epithelial expression includes the hair keratin forming layers of the hair shaft and the bulge, where interestingly, Runx1 is co-expressed with keratin 15, a putative hair follicle stem cell marker. In the hair mesenchyme, during early stages of hair morphogenesis, Runx1 is expressed in a discrete dermal sub-epithelial layer, while at later stages it is found in a hair cycle dependent pattern in the dermal papilla. To elucidate the function of Runx1 in the hair follicle we have generated a Runx1 epidermal conditional knockout and found that the mutant mice display a remarkable structural deformation of the zigzag hair type. The data delineate Runx1 as a novel specific marker of several hair follicle cell types and sheds light on its role in hair morphogenesis and differentiation.


Characterization of Aroma-Active Compounds in Italian Tomatoes with Emphasis on New Odorants.
An aroma distillate was prepared by solvent extraction and subsequent SAFE distillation from Italian vine-ripe tomatoes eliciting an intense overall aroma. Application of gc/olfactometry and the aroma extract dilution analysis revealed 44 odor-active compounds, 42 of which could be identified. The highest odor activity value of 2048 was established for the green, grassy (Z)-3-hexenal, the metallic smelling trans-4,5-epoxy-(E)-2-decenal, the potato-like 3-(methylthio)propanal, and the caramel-like 4-hydroxy-2,5-dimethyl-3(2H)-furanone. Of the further odorants, 13 compounds have previously not been reported as tomato odorants. Although most of these showed lower FD-factors, in particular, the coconut/dill-like smelling wine lactone ((3S,3aS,7aR)-3a,4,5,7a-tetrahydro-3,6-dimethylbenzofuran-2(3H)-one) appeared with a quite high FD factor. In addition, a fruity, almond-like odorant (6) with an FD factor of 1024 was detected. By application of high resolution mass spectrometry and polarity considerations, the structure of a methyl-2-ethoxytetrahydropyran isomer was suggested for 6. Four of the five possible isomers, the 3-methyl-, 4-methyl-, 5-methyl-, and 6-methyl-2-ethoxytetrahydropyran were synthesized and showed similar mass spectrometric patterns. However, these were excluded by their different retention indices. Although the synthesis of the remaining 2-methyl-2-ethoxytetrahydropyran resulted in only small yields, which were not sufficient for NMR measurements, this structure is very likely for 6. This compound was never reported as a food constituent before. Finally, quantitation of 23 odorants by stable isotope dilution assays allowed for the preparation of an aroma recombinate resembling the overall aroma of the tomatoes.


Cost-Effectiveness Analysis of Different Genetic Testing Strategies for Lynch Syndrome in Taiwan.
Patients with Lynch syndrome (LS) have a significantly increased risk of developing colorectal cancer (CRC) and other cancers. Genetic screening for LS among patients with newly diagnosed CRC aims to identify mutations in the disease-causing genes (i.e., the DNA mismatch repair genes) in the patients, to offer genetic testing for relatives of the patients with the mutations, and then to provide early prevention for the relatives with the mutations. Several genetic tests are available for LS, such as DNA sequencing for MMR genes and tumor testing using microsatellite instability and immunohistochemical analyses. Cost-effectiveness analyses of different genetic testing strategies for LS have been performed in several studies from different countries such as the US and Germany. However, a cost-effectiveness analysis for the testing has not yet been performed in Taiwan. In this study, we evaluated the cost-effectiveness of four genetic testing strategies for LS described in previous studies, while population-specific parameters, such as the mutation rates of the DNA mismatch repair genes and treatment costs for CRC in Taiwan, were used. The incremental cost-effectiveness ratios based on discounted life years gained due to genetic screening were calculated for the strategies relative to no screening and to the previous strategy. Using the World Health Organization standard, which was defined based on Taiwan's Gross Domestic Product per capita, the strategy based on immunohistochemistry as a genetic test followed by BRAF mutation testing was considered to be highly cost-effective relative to no screening. Our probabilistic sensitivity analysis results also suggest that the strategy has a probability of 0.939 of being cost-effective relative to no screening based on the commonly used threshold of $50,000 to determine cost-effectiveness. To the best of our knowledge, this is the first cost-effectiveness analysis for evaluating different genetic testing strategies for LS in Taiwan. The results will be informative for the government when considering offering screening for LS in patients newly diagnosed with CRC.


Complete genome sequence of Syntrophobacter fumaroxidans strain (MPOB(T)).
Syntrophobacter fumaroxidans strain MPOB(T) is the best-studied species of the genus Syntrophobacter. The species is of interest because of its anaerobic syntrophic lifestyle, its involvement in the conversion of propionate to acetate, H2 and CO2 during the overall degradation of organic matter, and its release of products that serve as substrates for other microorganisms. The strain is able to ferment fumarate in pure culture to CO2 and succinate, and is also able to grow as a sulfate reducer with propionate as an electron donor. This is the first complete genome sequence of a member of the genus Syntrophobacter and a member genus in the family Syntrophobacteraceae. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 4,990,251 bp long genome with its 4,098 protein-coding and 81 RNA genes is a part of the Microbial Genome Program (MGP) and the Genomes to Life (GTL) Program project.


Highly effective ashless and non-corrosive dimercaptobenzothiadiazole as multifunctional lubricant additives in naphthenic base oil.
The conventional medium chain chlorinated paraffin (MCCP) and zinc dialkyl dithiophosphate (ZDDP) additives have greatly enhanced the extreme pressure (EP) and anti-wear (AW) performance of the metalworking fluids. However, chlorine- and zinc-containing additives are restricted in use due to eco-toxicity issue. Herein, ashless and non-corrosive dimercaptobenzothiadiazole derivatives, namely bis-2,5-benzylsulfanyl-[1,3,4]thiadiazole (BBST) and bis-2,5-octylsulfanyl-[1,3,4]thiadiazole (BOST) consist of three sulfur atoms have been synthesized and evaluated. The performance of BBST shows a weld load (PD) of 3089 N and AW value of 5 mm2, which represents an improvement of 3.1 and 7.4 folds over naphthenic base oil (NBO). In addition, BBST also outperformed BOST, MCCP, and ZDDP in terms of its weld load and AW properties. Based on XPS analysis and molecular electrostatic potential maps (MEPS), BBST exhibits superior tribology performance due to the interaction between the sulfur (S), nitrogen (N), and π-electrons of the benzene ring with the metal surface. The formation of FeS, Fe2O3 and Fe⋯N coordinate bonds contributes to the creation of an excellent tribofilm.


Magnetic resonance cholangiopancreatography: a meta-analysis of test performance in suspected biliary disease.
Magnetic resonance cholangiopancreatography (MRCP) is one of many newer noninvasive tests that can image the biliary tree. To precisely estimate the overall sensitivity and specificity of MRCP in suspected biliary obstruction and to evaluate clinically important subgroups. MEDLINE search (January 1987 to March 2003) for studies in English or French, bibliographies, and subject matter experts. Studies were included if they allowed construction of 2x2 contingency tables of MRCP compared with a reasonable gold standard for at least 1 of the following: the presence, level, or cause of biliary obstruction. Two independent observers graded study quality, which included consecutive enrollment, blinding, use of a single (versus composite) gold standard, and nonselective use of the gold standard. Logistic regression was used to examine the influence of publication year, quality score, proportion of patients having a "direct" gold standard, and clinical context on diagnostic performance. Of 498 studies identified, 67 were included (4711 patients). Mixed-effect models were used to estimate the sensitivity and specificity, and quantitative receiver-operating characteristic analysis was performed. Magnetic resonance cholangiopancreatography had a high overall pooled sensitivity (95% [+/-1.96 SD: spread of SD, 75% to 99%]) and specificity (97% [spread of SD, 86% to 99%]). The procedure was less sensitive for stones (92%; odds ratio, 0.51 [CI, 0.35 to 0.75]) and malignant conditions (88%; odds ratio, 0.28 [CI, 0.18 to 0.44]) than for the presence of obstruction. In addition, diagnostic performance was higher in studies that were larger, did not use consecutive enrollment, and did not use gold standard assessment for some patients. Magentic resonance cholangiopancreatography is a noninvasive imaging test with excellent overall sensitivity and specificity for demonstrating the level and presence of biliary obstruction; however, it seems less sensitive for detecting stones or differentiating malignant from benign obstruction.


Acute histopathological changes induced by methyl isocyanate in lungs, liver, kidneys & spleen of rats.
Methyl isocyanate (MIC), inhaled or administered subcutaneously (sc) at lethal concentration/dose caused essentially similar histopathological changes in all the viscera except for the lungs. The observed congestion of the viscera, foci of hepatocellular necrosis with widening of Disse's spaces in the liver and tubulo-rhexis with degeneration in the kidneys are attributable mostly to the initial shock. In addition, the lungs revealed more distinct route specific patterns of histopathological lesions. Inhaled MIC caused acute eosinophilic necrosis of the bronchial epithelium and frank alveolar edema, while MIC administered sc led to prominent vascular endothelial damage and severe interstitial pneumonitis with normal bronchial epithelium. The differential loci of damage in the lungs may be attributed to the immediate contact surface available for interaction with MIC.


[The effect of procyanidin on periprosthetic osteolysis caused by TCP wear particles in the mouse calvaria and its mechanism].
To investigate the protective effects of procyanidin on periprosthetic osteolysis caused by tricalcium phosphate (TCP) wear particles in the mouse calvaria and its mechanism. Forty-eight male ICR mice were randomly divided into sham group, TCP group, and procyanidin (0.2 mg/kg, 1 mg/kg, 5 mg/kg)-treated group (n=12). A periprosthetic osteolysis model in the mouse calvaria was established by implanting 30 mg of TCP wear particles onto the surface of bilateral parietal bones following removal of the periosteum. On the 2nd day post-operation, procyanidin (1 mg/kg, 5 mg/kg) was locally injected to the calvaria under the periosteum every other day. After 2 weeks, all the mice were sacrificed to collect the blood samples and the calvaria. Periprosthetic osteolysis and osteoclastogenesis in the mouse calvaria were observed by tartrate resistant acid phosphatase (TRAP) staining and HE staining. mRNA levels of TRAP, capthesin K, c-Fos and NFATc1 in the periprosthestic bone tissue were examined by real-time fluorescence quantitative PCR. Serum contents of total anti-oxidation capacity (T-AOC) and MDA, and superoxide dismutase (SOD) activity were determined by chemical colorimetry. Protein expressions of autophagic biomarkers such as Beclin-1 and LC-3 in periprosthetic bone tissue of the calvaria were examined by Western blot. Compared with sham group, periprosthetic osteolysis, osteoclastogenesis, mRNA levels of TRAP, capthesin K, c-Fos and NFATc1, and serum MDA content were increased significantly in the TCP group (P<0.05), whereas serum T-AOC level and SOD activity were decreased. The protein expressions of Beclin-1 and LC-3, and the conversion of LC3-II from LC3-I were both up-regulated markedly in the mouse calvaria of TCP group (P<0.05). Compared with TCP group, osteolysis, osteoclastogenesis, mRNA levels of TRAP, capthesin K, c-Fos and NFATc1 and serum MDA content were decreased obviously in the procyanidine group (P<0.05), serum T-AOC level and SOD activity were increased, the expressions of Beclin-1 and LC-3, and the conversion of LC3-II from LC3-I were down-regulated obviously in the mouse calvaria of procyanidin group (P<0.05). Procyanidin has a protective effect of periprosthetic osteolysis caused by TCP wear particles in the mouse calvaia, its mechanism may be mediated by inhibition of oxidative stress and autophagy.


Guillain-Barre Syndrome in Postpartum Period: Rehabilitation Issues and Outcome - Three Case Reports.
We report three females who developed Guillain-Barre Syndrome in postpartum period (within 6 weeks of delivery) and were admitted in the Neurological Rehabilitation Department for rehabilitation after the initial diagnosis and treatment in the Department of Neurology. The first case, axonal variant (acute motor axonal neuropathy [AMAN]) had worst presentation at the time of admission, recovered well by the time of discharge. The second case, acute motor sensory axonal neuropathy variant and the third case, AMAN variant presented at the late postpartum period. Medical treatment was sought much later due to various reasons and both the patients had an incomplete recovery at discharge. Apart from their presentations, rehabilitation management is also discussed in some detail.


Realization of the Einstein-Podolsky-Rosen paradox using momentum- and position-entangled photons from spontaneous parametric down conversion.
We report on a momentum-position realization of the EPR paradox using direct detection in the near and far fields of the photons emitted by collinear type-II phase-matched parametric down conversion. Using this approach we achieved a measured two-photon momentum-position variance product of 0.01 variant Planck's over 2pi (2), which dramatically violates the bounds for the EPR and separability criteria.


Endoscopic band ligation: beyond prevention and management of gastroesophageal varices.
Endoscopic band ligation (EBL) is the preferred endoscopic technique for the endoscopic treatment of acute esophageal variceal bleeding. EBL has also been used to treat nonvariceal bleeding. Recently, Han et al demonstrated that EBL can be a feasible and safe alternate technique for the management of iatrogenic gastric perforation especially in cases in which closure with endoclips is difficult. EBL is technically simpler to perform than other methods and provides a good view of the lesions under direct pressure and suction from the transparent ligation cap. EBL can be used even if the diameter of the perforation is greater than 10 mm or if there is a severe tangential angle. In this commentary, we discuss the efficacy and safety of EBL for the closure of iatrogenic gastrointestinal perforation. We also discuss the advantages and disadvantages of EBL for the treatment of nonvariceal bleeding.


Quality of life and self-esteem in children treated for idiopathic short stature.
Changes in health-related quality of life (HRQOL) and self-esteem were studied in children with idiopathic short stature (ISS) participating in a study on the effect of growth hormone treatment. Prepubertal children (n = 36) with ISS were randomly assigned to a treatment or control group. Children with ISS, their parents, and the pediatrician completed HRQOL and self-esteem questionnaires 3 times in 2 years. At the start, children with ISS did not have lower scores than the norm population, except for social functioning HRQOL. The pediatrician reported an improvement of HRQOL in the treatment group, the parents reported no change, and the children in the treatment group reported the same, or sometimes even worse, HRQOL or self-esteem than the control group. Changes related to the child's satisfaction with height and hardly to growth itself. The assumption that growth hormone treatment improves HRQOL in children with ISS could not be supported in this study.