A novel flow-diverting device (Tubridge) for the treatment of 28 large or giant intracranial aneurysms: a single-center experience.
The Tubridge flow diverter is a novel device developed in China and aimed at reconstructing the parent artery and occluding the aneurysm. We conducted this study to evaluate its feasibility, safety, and efficacy for the treatment of large or giant internal carotid artery aneurysms, which are still challenging with conventional therapy. The clinical and angiographic data of 28 patients with 28 large or giant internal carotid artery aneurysms treated with Tubridge flow diverters were prospectively collected and analyzed. Thirty-three Tubridge flow diverters were successfully implanted except for 1 poor midstent opening; the result was a technical success rate of 97.0% (32/33). Follow-up angiographies were available for 25 aneurysms; the mean follow-up was 9.9 months (5-24 months). Of the 25 aneurysms, 18 (72.0%) were completely occluded, 6 (24.0%) were improved, and 1 (4.0%) was unchanged. All of the visible covered branches and parent arteries were patent, with no stenosis or obliteration. During a follow-up of 6-30 months (mean, 19 months), symptoms were resolved in 13 patients, improved in 6 patients, and unchanged in 4 patients. Five patients experienced transient clinical deterioration due to a postoperative increased mass effect. Procedure-related morbidity and mortality were both zero. Our preliminary experience shows that the Tubridge flow diverter is a safe and effective tool for treating large and giant internal carotid artery aneurysms. However, multicenter randomized trials and studies involving a long-term follow-up are necessary.


Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) Magnetic Resonance Imaging Scoring to Predict Clinical Outcomes in Active Surveillance for Grade Group 1 Prostate Cancer.
To determine whether radiological change on serial multiparametric magnetic resonance imaging scored using the Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) Scoring system predicts grade reclassification (GR) at surveillance biopsy in men on active surveillance (AS) with Grade Group 1 (GG1) prostate cancer (PCa). We retrospectively reviewed records of 255 men with low-risk PCa on AS with magnetic resonance imaging (MRI)-informed diagnostic and confirmatory biopsies and studied the subset who had surveillance biopsies (n = 163) within 6months of an interval MRI. We studied 309 PRECISE scores in 255 men. 14% demonstrated radiological progression (PRECISE 4-5) on interval MRI performed within 24months, compared to 34% of those whose interval MRI was performed at a >3-year interval (P = .002). 28% (46/163) of men undergoing surveillance biopsy experienced GR to ≥ GG2 PCa. There was no significant increase in the rate of GR with increasing PRECISE score (PRECISE 1-2: 24%, PRECISE 3: 23%, PRECISE 4-5: 38%; P = .11). There was a significant increase in the rate of GR with increasing PI-RADS score (P < .05). On multivariable analysis, a PI-RADS score of 4-5 was significantly associated with GR compared to men who had a highest PI-RADS ≤3 (OR=1.98 [95% CI: 1.45-3.09, P = .01]). In a low-risk AS cohort with limited follow-up, a patient's highest PI-RADS rather than their PRECISE score on interval MRI was predictive of GR on surveillance biopsy.


28-Day repeated dose oral toxicity of recombinant human apo-lactoferrin or recombinant human lysozyme in rats.
Lactoferrin and lysozyme are important proteins of the human innate immune system. These proteins are found in breast milk and have been associated with improved infant health. Recombinant human apo-lactoferrin (apo-rhLF), 1800 and 180mg/kg bw/day, and recombinant human lysozyme (rhLZ), 360 and 36mg/kg bw/day, were orally administered to Wistar rats for 28 days. Apo-rhLF and rhLZ were expressed in rice grain, extracted, purified; the lactoferrin was iron desaturated. The animals were examined for evidence of toxicity; there were no deaths and in-life physical signs were normal. Transient differences in mean food consumption occurred in high dose apo-rhLF and low dose LZ females at week three. There were no biologically significant differences in hematological or clinical chemistry parameters. Necropsy results were normal and microscopic evaluation showed no treatment related changes in animals dosed with 1800mg/kg/day apo-rhLF or 360mg/kg/day rhLZ. The results of the 28-day oral administration demonstrate a lack of toxicity of apo-rhLF and rhLZ in rats. There were no treatment related, toxicologically relevant changes in clinical signs, growth, food consumption, hematology, clinical chemistry, organ weight and pathology. The no observed adverse effect level (NOAEL) is greater than 1800mg/kg/day for apo-rhLF and 360mg/kg/day for rhLZ.


The Persian version of the psychological flexibility in sport scale: a psychometric study.
There is a growing body of research suggesting that psychological flexibility (PF) is an important psychological construct related to psychological health and human performance. The Psychological Flexibility in Sport Scale (PFSS) is the first general scale to assess sport-related PF. So far, the PFSS has not yet been validated in other contexts than Sweden. Therefore, the current study sought to investigate a Persian version of the PFSS (P-PFSS) and extend the investigation of the psychometric properties of the PFSS in Iranian athletes. A total of 302 athletes from both team and individual sports (average age of 20.7 years, SD ± 7.5, 62.3% were female) were involved in the current study. Statistical analysis was performed on the data to test validity and reliability. The validity of the P-PFSS was tested through face and content validity, construct validity, criterion validity, and known-groups validity. The reliability of P-PFSS was verified through internal consistency and temporal stability of the scale. Results revealed that validity of the P-PFSS was satisfactory. The instrument was determined to have strong face and content validity. With modifications, the confirmatory factor analysis confirmed the scale's unidimensionality. The convergent validity of the P-PFSS was found to be acceptable (average variance extracted = 0.66) and satisfactory results were also found in the correlation matrix for the assessment of construct validity. The P-PFSS showed good criterion validity related to generic psychological flexibility and athletic-related variables. Also, the P-PFSS was able to differentiate PF between known groups. The P-PFSS was found to be reliable, with good internal consistency (Cronbach's alpha = 0.92; composite reliability = 0.92) and temporal stability on retest (intraclass correlation coefficient = 0.95). Overall, the Persian version of the PFSS showed good psychometric qualities in Iranian athletes. The current study provides additional support for the PFSS and extends the context-specific utility for practitioners and researchers in assessing sport-related PF.


The effect of termination of pregnancy on maturity of subsequent pregnancy.
Therapeutic termination of pregnancy performed during the first trimester was associated with a statistically significant increase in the incidence of second trimester abortion and of premature labour in the next pregnancy. In a series of 520 patients who had previously been aborted 8.1% suffered a mid-trimester abortion in their next pregnancy and 8.6% had premature onset of labour (compared to 2.4% (P less than 0.001) and 4.4% (P less than 0.01) respectively in a control series). The incidence of incompetence of the cervix after termination of pregnancy was 4.4%.


Patient understanding of the role of the orthopedic resident.
Patients have identified the knowledge of a physician's level of training as important. Previous studies show equally poor patient's understanding of the medical education hierarchy. Given the importance to the patient and the possible effect on patient satisfaction, it is critical to evaluate patient's understanding of the orthopedic educational hierarchy. The specific aim of this study is to evaluate patient's understanding of the role of an orthopedic resident as it pertains to their orthopedic care. Adult, English-speaking patients presenting to an outpatient academic orthopedic practice completed surveys similar to those utilized in prior research on this topic. Each questionnaire compiled demographics, questions assessing knowledge of the role of the resident in patient care, and questions to assess the patient's preferences regarding resident physician's role in their care. The knowledge section of the questionnaire was scored with 1 point given to each correct answer. The individual questions with the worst scores from the entire patient population were further evaluated to find demographic predictors of success. In addition to percent correct responses for the entire population, a linear regression model was used to evaluate the effect of age, gender, level of education, ethnicity, and number of academic visits on the knowledge section score. One hundred seventy-four (n = 174) patients completed the survey. Among them, 40% were male, 27% had a high school education or less, 82% were Caucasian, and for 18% it was their first visit to an academic hospital. The average score for the knowledge section was 10.2 (standard deviation±4.0) out of a possible of 16. Linear regression controlling for noted demographic variables revealed higher level of education to be predictive of a better score (coefficient 3.2; 95% confidence interval 1.9-4.7). The 3 worst scoring questions were regarding knowledge of (1) residents having completed medical school, (2) residents performing surgery with attending supervision, and (3) whether or not residents were actually doctors. For these questions higher level of education correlated with more correct answers (p = 0.005, p = 0.001, p = 0.000, respectively). Among the patients, 90% agreed that it was important for them to know the level of training of their physicians and 76% felt it was okay for residents to "learn" on them as long as they were supervised. Patient's knowledge of the role the resident physician provides, in their care, is variable. Higher levels of education appear predictive of better understanding. Patients have difficulty discerning where residents fit in the medical hierarchy. Despite this misunderstanding, patients find it very important that they know the physician's level of training. Given the patient's high priority of knowing the level of training of the doctors who care for them and their frequent misunderstanding of the medical hierarchy, steps should be taken to better educate patients as to who is caring for them. Besides being important for patient's informed consent, it may improve patient satisfaction.


The effects of prior knowledge on children's memory and suggestibility.
In this study, 5- and 6-year-olds were read a story and asked to recall its details. Two independent factors-prestory knowledge and poststory suggestions-were crossed to examine the effects on children's story recall. The results indicated that prestory social knowledge about the story protagonist as well as academic knowledge relating to the content of the story influenced the accuracy of children's recall immediately after the story presentation. Following the suggestive interview, children reported interviewer-provided social and academic misinformation to a greater extent when the misinformation was consistent with their prior knowledge. In contrast, children were more likely to refute misinformation that contradicted their academic knowledge. These findings are discussed in terms of the mechanisms underlying the knowledge-memory and knowledge-suggestibility linkages.


Gatifloxacin-associated corrected QT interval prolongation, torsades de pointes, and ventricular fibrillation in patients with known risk factors.
Drugs not commonly considered to be cardioactive agents have been reported to cause prolongation of the corrected QT interval with resultant torsades de pointes or ventricular fibrillation. We report 4 cases of gatifloxacin-associated cardiac toxicity in patients with known risk factors for this adverse event.


Interference of thrombin in immunological assays for hirudin specific antibodies.
Recombinant hirudins (desirudin, lepirudin) are direct thrombin inhibitors administered as anticoagulants for heparin-induced thrombocytopenia (HIT) and venous thromboembolism (VTE) prophylaxis. Although these small polypeptides are widely used, concern exists over reports of antigenicity. In the largest study of r-hirudin immunogenicity to-date, we evaluated the prevalence, quantity and specificity of IgG immune responses to desirudin (15 mg SC q12h for as long as clinically required) in 245 surgical and medically-ill subjects enrolled in DESIRABLE, a multicenter, open-label, clinical trial of hospitalized patients requiring VTE prophylaxis. Sera obtained before and 30 days after desirudin administration were analyzed for IgG anti-desirudin by immunoenzymetric assay using immobilized desirudin to bind desirudin-reactive antibody and peroxidase conjugated monoclonal-anti-human IgG Fc to detect bound IgG antibody. Of 245 study subjects, 19 (7.7%) were antibody "responders" (>2-fold increase in IgG antibody levels with >50% inhibition by desirudin 30 days post-treatment). There were no differences between responders and non-responders in incidence of clinical outcomes or bleeding-related adverse events. Forty-six patients had detectable desirudin-reactive IgG antibody prior to treatment, with no significant increase in antibody levels after exposure and no increase in clinical events. The origin of pre-existing hirudin-reactive IgG antibody requires further investigation involving suspected anti-thrombin-thrombin interactions. These results indicate a low potential for immunogenicity, with <8% of patients developing IgG antibodies after desirudin administration for VTE prophylaxis. In contrast to reports on lepirudin, production of anti-hirudin antibodies to desirudin has no apparent effect on clinical events.


Partial laryngopharyngectomy in the treatment of squamous cell carcinoma of hypopharynx: analysis of the oncologic results and laryngeal preservation rate.
Partial laryngopharyngectomy (PLP) provides acceptable oncologic results and laryngeal preservation rate in selected patients with squamous cell carcinoma of the hypopharynx. Even when local recurrence develops, the chance of successful salvage is still high. To evaluate the oncologic results and laryngeal preservation rate in patients with squamous cell carcinoma of the hypopharynx who underwent PLP. The results of 39 patients who underwent PLP were compared with those of 91 patients who underwent total laryngectomy (TL). The distribution of the primary T stages were 23 (59%) pT2, 9 (23%) pT3, and 7 (18%) pT4; the pathologic stages were 8 patients (21%) stage II, 9 (23%) stage III, and 22 (56%) stage IV. All of the patients also had ipsilateral or bilateral neck dissections. Eighteen patients (46%) received postoperative adjuvant therapy. After a median follow-up of 39 months, 17 patients (44%) had recurrence, including 12 local, 2 regional, and 3 distant lesions. The 5-year overall and disease-specific survival were 44% and 56%, respectively; functional preservation was 62%. The recurrence rate was similar in patients treated with PLP and TL (44% vs 36%, p = 0.431); the local recurrence rate was higher after PLP than after TL (31% vs 8%, p = 0.001). The salvage surgery was successful in four of the six patients (67%). After salvage treatment, the 5-year overall survival (44% vs 47%) and disease-specific survival (56% vs 62%) were similar in the two groups.


Enema ion compositions for enhancing colorectal drug delivery.
Delivering drugs to the colorectum by enema has advantages for treating or preventing both local and systemic diseases. However, the properties of the enema itself are not typically exploited for improving drug delivery. Sodium ions are actively pumped out of the lumen of the colon, which is followed by osmotically-driven water absorption, so we hypothesized that this natural mechanism could be exploited to drive nanoparticles and drugs to the colorectal tissue surface. Here, we report that sodium-based, absorption-inducing (hypotonic) enemas rapidly transport hydrophilic drugs and non-mucoadhesive, mucus penetrating nanoparticles (MPP), deep into the colorectal folds to reach virtually the entire colorectal epithelial surface. In contrast, isotonic and secretion-inducing (hypertonic) vehicles led to non-uniform, poor surface coverage. Sodium-based enemas induced rapid fluid absorption even when moderately hyper-osmolal (~350 mOsm) compared to blood (~300 mOsm), which suggests that active sodium absorption plays a key role in osmosis-driven fluid uptake. We then used tenofovir, an antiretroviral drug in clinical trials for preventing HIV, to test the effects of enema composition on local and systemic drug delivery. We found that strongly hypotonic and hypertonic enemas caused rapid systemic drug uptake, whereas moderately hypotonic enemas with ion compositions similar to feces resulted in high local tissue levels with minimal systemic drug exposure. Similarly, moderately hypotonic enemas provided improved local drug retention in colorectal tissue, whereas hypertonic and isotonic enemas provided markedly reduced drug retention in colorectal tissue. Lastly, we found that moderately hypotonic enema formulations caused little to no detectable epithelial damage, while hypertonic solutions caused significant damage, including epithelial sloughing; the epithelial damage caused increased systemic drug absorption and penetration of MPP into colorectal tissue, a potential advantage in certain drug delivery applications. In summary, we illustrate that enema composition can be adjusted to maximize local versus systemic drug delivery, and that mildly hypotonic, sodium-based vehicles can provide uniform drug and MPP delivery in the colon that maximizes local drug concentrations.


Effects of positive end-expiratory pressure/recruitment manoeuvres compared with zero end-expiratory pressure on atelectasis during open gynaecological surgery as assessed by ultrasonography: a randomised controlled trial.
During general anaesthesia, most patients develop atelectasis, which promotes postoperative pulmonary complications. RCTs that investigated perioperative lung protection have failed to reduce postoperative pulmonary complications consistently. Ultrasound imaging could help confirm the effects of different protective ventilatory strategies, but this has not been tested in trials. The objective of this study was to use ultrasonography to evaluate whether lung-protective ventilation measures reduce perioperative atelectasis. We conducted a prospective, randomised patient- and assessor-blinded controlled trial in women undergoing open gynaecological surgery. Subjects were randomised to either lung protection or zero end-expiratory pressure (ZEEP; with no recruitment manoeuvres [RMs]). Lung protection entailed PEEP (7 cm H2O) and RMs every 30 min. Lung ultrasonography was undertaken at five predefined time points. The primary outcome was the difference in lung ultrasonography score (LUS) between groups before emergence; a lower LUS indicates better lung aeration. We recruited 45 women (34-85 yr old). Women randomised to lung protection had lower mean (standard deviation) LUS before emergence (6.1 [3.7]), compared with women randomised to ZEEP (11.7 [3.9]; 95% confidence interval for the difference between group means [-7.9 to -3.2]; P<0.0001). This difference did not persist after extubation, with similar mean LUSs in women who had received intraoperative lung protection (7.0 [4.1]), compared with women randomised to receive ZEEP (7.7 [3.1]). As assessed by lung ultrasonography, intraoperative PEEP/RMs decreased aeration loss during general anaesthesia. However, similar degrees of aeration loss were observed after tracheal extubation regardless of intraoperative ventilatory strategy. NCT02055807.


PLATE: A perception-latency aware estimator.
Target tracking is a popular problem with many potential applications. There has been a lot of effort on improving the quality of the detection of targets using cameras through different techniques. In general, with higher computational effort applied, i.e., a longer perception-latency, a better detection accuracy is obtained. However, it is not always useful to apply the longest perception-latency allowed, particularly when the environment does not require to and when the computational resources are shared between other tasks. In this work, we propose a new Perception-LATency aware Estimator (PLATE), which uses different perception configurations in different moments of time in order to optimize a certain performance measure. This measure takes into account a perception-latency and accuracy trade-off aiming for a good compromise between quality and resource usage. Compared to other heuristic frame-skipping techniques, PLATE comes with a formal complexity and optimality analysis. The advantages of PLATE are verified by several experiments including an evaluation over a standard benchmark with real data and using state of the art deep learning object detection methods for the perception stage.


Mammography screening: how important is cost as a barrier to use?
Recent legislation will improve insurance coverage for screening mammography and effectively lower its cost to many women. Although cost has been cited as a barrier to use, evidence of the magnitude of its effect on use is limited. Mammography use in the past 2 years among women aged 50 to 75 residing in four suburban or rural counties in Washington State was estimated from 1989 survey data. Logistic regression analysis was used to estimate the odds ratio of mammography use as a function of economic and other variables. Within a residential area, averages were used to measure the market price of mammography and the time cost to obtain a mammogram. Use was lower among women who faced a higher net price or who preferred to obtain a mammogram during weekend or evening hours and higher among women with higher incomes. Visiting no doctor regularly and smoking were predictors of failure to use mammography. The effects of economic variables on mammography use are important and stable across subsets of the population, but they are modest in size.


Is the assessment of submucosal invasion still useful in the management of early rectal cancer? A study of 91 consecutive patients.
The only studies on the prognosis of T1 tumours are old and investigate colic and rectal cancers. Very few studies use Kikuchi's classification (of dividing submucosa into three strata) to evaluate the depth of the submucosal invasion. This study aimed to assess the pathological risk factors for lymph node metastasis (LNM), and the pathological and oncological results of patients with early rectal cancer (ERC, pT1 tumour). Between 2000 and 2014, 91 consecutive patients undergoing surgery [primary total mesorectal excision (TME) or local excision (LE) alone, or LE followed by TME] for ERC were included. Eighteen patients underwent LE, 22 underwent LE followed by TME and 51 underwent primary total TME. After TME (n = 73), 16 (23%) patients had LNM. The LNM rate was 15% for Sm1 tumours, 14% for Sm2 tumours and 30% for Sm3 tumours. In multivariate analysis, lymphovascular invasion (P = 0.027) and high tumour budding (P = 0.037) were the only independent factors predictive of LNM. The depth of submucosal invasion was not associated with an increased risk of LNM. After a mean follow up of 56 ± 46 months, 5-year overall survival, specific survival and disease-free survival were, respectively, 82%, 93% and 75%. No significant difference of survival was found according to the depth of submucosal invasion or to the surgical management. Histological features seem to be stronger risk factors for LNM than depth of submucosal invasion. Considering the LNM rate, TME should be discussed after LE in terms of one of these pathological criteria.


Extracellular oxytocin in the paraventricular nucleus: hyperosmotic stimulation by in vivo microdialysis.
The effect of central osmotic stimulation on oxytocin (OT) secretion from the paraventricular nucleus (PVN) was examined using a newly developed in vivo microdialysis technique. A dialysis probe was inserted into the PVN region and microdialysis was performed in conscious animals. Hyperosmotic solutions were delivered via the dialysis probe, and perfusate and blood samples were collected. OT was consistently detected in the PVN dialysate. Hyperosmotic sodium chloride (1 M) produced a significant increase in dialysate and plasma OT, whereas D-mannitol (2 M) had no effect. These results suggest that (1) in vivo microdialysis may provide a useful technique for the evaluation of neuropeptide secretion from specific brain regions and (2) there are sodium-sensitive cells in the PVN region which respond to increases in extracellular sodium, resulting in an increase in central and peripheral oxytocin secretion.


Constitutive expression of PPARγ inhibits proliferation and migration of gastric cancer cells and down-regulates Wnt/β-Catenin signaling pathway downstream target genes TERT and ENAH.
Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the PPAR nuclear hormone receptor superfamily, which plays a crucial role in carcinogenesis. Wnt/β-Catenin signaling pathway has been well certified to contribute to the progression of gastric malignancies. β-Catenin mediates transcriptional regulation by forming a complex with LEF/TCF transcription factors, resulting in activation of downstream target genes such as TERT, ENAH. In this study, we aimed at detecting the effect of PPARγ on TERT, ENAH and explaining the further mechanisms of PPARγ on tumor suppression. The pEGFP-N1-PPARγ recombinant plasmid has already been constructed by researchers in our laboratory. We stably transfected it into three gastric cancer (GC) cell lines (MKN-28, SGC-7901 and BGC-823). CCK-8 and transwell assay were employed to analyze the capability of cell proliferation and metastasis. The mRNA and protein levels were evaluated by real-time PCR and western blot analysis. After transfected with PPARγ overexpression plasmid, the ability of cell proliferation and migration declined significantly (p<0.05). The expression of PPARγ increased (p<0.05) and β-Catenin was inhibited obviously (p<0.05) in the group of pEGFP-N1-PPARγ plasmid transfection. Meanwhile, the mRNA or protein levels of TERT and ENAH were suppressed (p<0.05) in pEGFP-N1-PPARγ plasmid transfection group compared with control groups. PPARγ might inhibit the proliferation and migration of GC cell lines through suppressing the expression of TERT and ENAH. PPARγ played an important role as a physiological regulator and might be a target for the treatment of GC.


Pharmacology and subcellular distribution of [3H]rilmenidine binding sites in rat brain.
We have previously reported that in rat brain membranes, [3H]rilmenidine, in addition to labelling alpha2-adrenoceptors and the I2B-subtype of imidazoline receptor binding site (I2B-RBS), may label an additional I-RBS population, distinct from previously classified I1-RBS and I2-RBS. In this study, using crude or fractionated rat brain membranes we examined the possible association of [3H]rilmenidine-labelled I-RBS with the A- and B-isoforms of monoamine oxidase (MAO) by studying the inhibition of [3H]rilmenidine binding by a number of MAO inhibitors; and comparing the maximal binding density (Bmax) and subcellular distribution of [3H]rilmenidine binding sites with that of MAO-A and MAO-B catalytic sites labelled by [3H]RO41-1049 and [3H]RO19-6327 and 12-RBS labelled by [3H]2-BFI. Inhibition of [3H]rilmenidine binding by all MAO inhibitors tested produced very shallow curves (slope 0.29-0.56). Clorgyline and moclobemide (selective MAO-A inhibitors) displayed moderate affinities (60-140 nM), while pargyline (non-selective MAO-inhibitor), RO41-1049 (selective MAO-A inhibitor) and RO19-6327 (selective MAO-B inhibitor) exhibited very low affinities (> 2 microM) for 50-75% of [3H]rilmenidine-labelled I-RBS in crude brain membranes and even lower affinity for the remaining binding. Under identical buffer conditions, the Bmax of [3H]rilmenidine-labelled I-RBS (1.45+/-0.14 pmol/mg protein) was considerably lower than those of MAO-A (13.10+/-0.15 pmol/mg) and MAO-B (10.35+/-0.50 pmol/mg) sites. These results suggest that [3H]rilmenidine does not interact directly with the active catalytic site of either MAO enzyme and could at best only associate with a subpopulation of MAO molecules. Binding studies on five fractions of rat cortex homogenates-nuclear (N), heavy (M) and light (L) mitochondrial, microsomal non-mitochondrial (P), and soluble cytosolic (S) fractions-revealed that 45% of total [3H]rilmenidine binding was present in the P fraction cf. 20 and 23% in the M and L fractions, in contrast to [3H]RO19-6327 and [3H]2-BFI which bound 11-13% in the P fraction and 36-38% and 35-44% in the M and L fractions, respectively. Binding of all ligands in the N fraction was 6-15% of total. These studies reveal that [3H]rilmenidine-labelled I-RBS, unlike the I2-RBS, are not predominantly associated with mitochondrial fractions containing the MAO enzymes (and cytochrome oxidase activity), but appear to be distributed in both the mitochondrial and plasma membrane fractions in rat cerebral cortex.


Supratentorial extra-axial RELA fusion-positive ependymoma misdiagnosed as meningioma by intraoperative histological and cytological examinations: a case report.
Dura-attached supratentorial extra-axial ependymoma is a very rare type of tumor, with only nine reported cases. Preoperative diagnosis of dura-attached supratentorial extra-axial ependymoma is difficult and often radiologically misdiagnosed as a meningioma. We report a case of dura-attached supratentorial extra-axial ependymoma that was misdiagnosed using intraoperative histological and cytological examinations. A 26-year-old Japanese man with headache and nausea was referred to our medical facility. Magnetic resonance imaging revealed a cystic mass of 70 × 53 × 57 mm in the left temporoparietal lobe. A peritumoral band with hyperintensity on T2-weighted imaging was observed at the periphery of the lesion, suggesting an extra-axial lesion with no apparent connection to the ventricle. A dural tail sign was also noted on the gadolinium-enhanced T1-weighted image. Preoperative clinical diagnosis was meningioma. Proliferated tumor cells in sheets with intermingled branching vessels were observed in the frozen tissue. Perivascular rosettes were inconspicuous, and the tumor cells had rhabdoid cytoplasm. The tumor was intraoperatively diagnosed as a meningioma, suspected to be a rhabdoid meningioma. Perivascular rosettes were evident in the formalin-fixed paraffin-embedded tissues, suggesting ependymoma. The tumor cells had eosinophilic cytoplasm without a rhabdoid appearance. Anaplastic features, such as high tumor cellularity, increased mitotic activity, microvascular proliferation, and necrosis, were observed. Ependymal differentiation was confirmed on the basis of ultrastructural analysis. Molecular analysis detected C11orf95-RELA fusion gene. The final diagnosis was RELA fusion-positive ependymoma, World Health Organization grade III. Owing to its unusual location, dura-attached supratentorial extra-axial ependymomas are frequently misdiagnosed as meningiomas. Neuropathologists should take great precaution in intraoperatively diagnosing this rare subtype of ependymoma to avoid misdiagnosis of the lesion as other common dura-attached tumors.


Inhibition of c-Jun N-terminal kinase pathway attenuates cerebral vasospasm after experimental subarachnoid hemorrhage through the suppression of apoptosis.
Recent studies have demonstrated that apoptosis in cerebral arteries could play an essential role in cerebral vasospasm after subarachnoid hemorrhage (SAH) and that SP600125, an inhibitor of c-Jun N-terminal kinase (JNK) could suppress apoptosis. The present study examined whether SP600125 could reduce cerebral vasospasm through the suppression of apoptosis. Fifteen dogs were assigned to 3 groups: control, SAH, and SAH + SP600125 (30 micromol/l). SAH was induced by the injection of autologous blood into the cisterna magna on day 0 and day 2. Angiograms were evaluated on day 0 and day 7. The activation of the JNK pathway and caspase-3 were also evaluated using Western blot. To determine the distribution, TUNEL staining and immunohistochemistry for phosphorylated c-jun and cleaved caspase-3 were performed. Severe vasospasm was observed in the basilar artery of the SAH dogs. SP600125 reduced angiographic and morphological vasospasm and reduced the expression of cleaved caspase-3, thereby suppressing apoptosis. These results demonstrate that SP600125 attenuates cerebral vasospasm through the suppression of apoptosis, which may provide a novel therapeutic target for cerebral vasospasm.


Predicting orally disintegrating tablets formulations of ibuprophen tablets: an application of the new SeDeM-ODT expert system.
This article provides a new innovative tool for pharmaceutical preformulation to predict whether a disintegrant excipient or mixture of powder containing API+excipients is suitable to obtain a bucodispersible tablet by direct compression or not. This innovative tool is the new model SeDeM-ODT that provides the Index of Good Compressibility and Bucodispersibility (IGCB index), which is based on the previous SeDeM expert system that indicates the aptitude of a powder to be compressed. The IGCB index is composed of six main factors (from 15 pharmaceutical raw parameters), which indicate whether a mixture of powder has the aptitude to be compressed by direct compression and at the same time indicates whether these tablets are suitable to be used as a bucodispersible tablet (disintegration time lower than 3 min).


Dental and Orofacial Injuries.
Oral and facial injuries are very common in sport, and can be very expensive to treat. Many of these injuries are preventable with proper pre-competition assessment and suitable well-designed protection. Prompt sideline identification and management of orofacial injuries and appropriate follow-up are crucial to successful outcomes. There have been significant recent advances in both trauma management and mouth guard design and fabrication techniques. Athletes have a unique set of challenges-including collisions, finances, travel and training, dehydration, sport beverages, and high carbohydrate diets-that may compromise their oral health.


Computed tomography of the orbit with special emphasis on coronal sections.
Computed tomography (CT) is an extremely valuable noninvasive method for evaluating orbital soft-tissue structures. The possibility of scanning in the coronal plane has added a new dimension to the study. Direct enlargement viewing of scans on the display console has disclosed minute anatomic and pathologic details.


Stoma creation for fecal diversion: is the laparoscopic technique appropriate?
This study assessed the results of laparoscopic stoma creation for fecal diversion. All patients who underwent elective laparoscopic stoma creation as the sole procedure were evaluated prospectively. Univariate analysis was performed to determine whether previous abdominal surgery, age, gender, body mass index, indication, or surgeons' experience has an effect on the outcome. Between November 1992 and May 1998, 42 patients (17 males, 25 females) with a mean age of 62.1 years (range 17-91) underwent laparoscopic stoma formation. Fecal diversion included loop ileostomy (n = 7), loop sigmoid colostomy (n = 32), and end-sigmoid colostomy (n = 3). Most common indications were unresectable rectal cancer, rectal obstruction caused by advanced pelvic tumors and benign disorders such as perianal Crohn's disease, and fecal incontinence. Of the 42 procedures 41 were completed laparoscopically (97.6%). Complications occurred in four patients (9.5%) requiring reoperation in two (4.8%). Mean length of surgery was 74.4 min (range 30-200). First bowel movements resumed on the 3rd day (range 2nd-7th) after surgery and patients were discharged from hospital after 13 days (range 6-47). Short-term results (> 30 days-1 year) indicated that no further stoma-related complications occurred. Analyzing factors potentially predictive of outcome, no statistically significant differences were documented in relation to previous abdominal surgery, age, gender, body mass index, indication, or surgeons' experience (P > 0.05). Laparoscopic stoma creation is appropriate to achieve fecal diversion because it is technically feasible and can be performed with low morbidity. In addition to the benefits of the minimally invasive technique for the patients, laparoscopic stoma formation can be ideal for the surgeon as basic and initial step to perform laparoscopic colorectal procedures.


Immunofluorescence localization of plasma protein synthesis in cultured chick hepatocytes.
Fibrinogen, albumin and the major apoprotein of high density lipoprotein (apoprotein A) were localized in a primary embryonic chick liver cell culture by indirect immunofluorescence staining. Changes in the pattern of plasma protein synthesis under a variety of conditions, as measured by the accumulation of secreted plasma proteins in the culture medium, could be studied at the cellular level because relative fluorescence intensities were shown to reflect synthetic rates. In all cases studied, the immunofluorescence of the hepatic parenchymal cells was of a similar intensity throughout the monolayers, indicating that the cells in culture constitute a homogeneous population with respect to the synthesis of these plasma proteins.


Pharmacological and analytical aspects of alkannin/shikonin and their derivatives: An update from 2008 to 2022.
Alkannin/shikonin (A/S) and their derivatives are naturally occurring naphthoquinones majorly found in Boraginaceae family plants. They are integral constituents of traditional Chinese medicine Zicao (roots of Lithospermum erythrorhizon). In last two decades significant increase in pharmacological investigations on alkannin/shikonin and their derivatives has been reported that resulted in discovery of their novel mechanisms in various diseases and disorders. This review throws light on recently conducted pharmacological investigations on alkannin/shikonin and their derivatives and their outputs. Various analytical aspects are also discussed and brief summary of patent applications on inventions containing alkannin/shikonin and its derivatives is also provided.


The contribution of fungal enzymes to the digestion of leaves by Gammarus fossarum Koch (Amphipoda).
Gut extracts of Gammarus fossarum liberated reducing substances (at pH values ≤7) and amino acids (pH≥7) from freshly shed oak leaves only after removal of soluble leaf phenols. When carboxymethylcellulose was used at a concentration equal to that of leaf cellulose, release of reducing substances was considerably higher. Fungal enzymes extracted from decomposing leaves were active against structural carbohydrates but showed no proteolytic activity. At low pH values, they retained their full activity in the presence of gut enzymes of G. fossarum, at higher pH values they were inhibited. Conditioned leaves released larger amounts of reducing substances and amino acids when exposed to gut enzymes. The improvement varies with the fungal species used for conditioning and with the length of the conditioning period. The digestibility of leaf carbohydrates and proteins reached separate peaks and then declined. Fungal carbohydrases ingested by G. fossarum retained some activity for up to 4h.


[Piety, fashion and business: positions of ethical/aesthetic femininity in muslim lifestyle-vlogs].
The article discusses empirical findings on the construction of models of Muslim femininity in German-speaking lifestyle vlogs on YouTube, in which faithful Muslim women appear as influencers and stage their everyday routines and practices in a mostly idealized way and with references to religious knowledge. Applying a post-structuralist theoretical framework, I consider those models as subject positions of a specific discourse of Muslim femininity promoting certain modes of self-understanding, self-conduct and related ways of affection. After a brief discussion of Muslim and secular discourses of femininity in which my data can be located, I present results from a discourse analysis of videos from two German-speaking channels: I suggest that the producers constitute a hybrid model of Muslim subjectivity which encompasses templates of a successful Muslim life in a secular society. In this context, producers seek to dissolve everyday contradictions and tensions between Western consumer and popular culture on the one, and Muslim religiosity on the other hand. By doing so, they produce a position of ethical/aesthetical Muslim femininity that brings together ideals of fashionable expressivity with religious self-conceptions and (neo-)liberal discourses of female autonomy and self-entrepreneurship.


Perforated retrocecal appendicitis presenting with lung abscess-A case report.
Retrocecal appendicitis usually presents with atypical signs and symptoms which may lead to delayed diagnosis, perforation and serious complications. Development of a large lung abscess secondary to perforation of retrocecal appendicitis in an adolescent patient is an extremely rare entity and to the best of our knowledge has not been described in literature. We present a 15-year-old boy with complaint of chest pain, cough, fever, vague abdominal pain and raised inflammatory markers who underwent CT examination. On CT, a collection with focal calcification was noted in the right iliac fossa that extended along the right retroperitoneum through the retrocrural space in the right lung base communicating with a cavitary pulmonary lesion with air-fluid level. A diagnosis of perforated retrocecal appendicitis with retroperitoneal and right lung abscesses was made. The patient underwent appendectomy and the entire retroperitoneal and lung abscesses were drained. A lung abscess as a complication of perforated retrocecal appendicitis should be in consideration in septic patients with thoracoabdominal infectious manifestations.


A systematic review and meta-analysis assessing antiretroviral therapy for treatment-experienced HIV adult patients using an optimized background therapy approach: is there evidence enough for a standardized third-line strategy?
The World Health Organization (WHO) has identified the need for evidence on third-line antiretroviral therapy (ART) for adults living with HIV/AIDS, given that some controversy remains as to the best combinations of ART for experienced HIV-1-infected patients. Therefore, we conducted a systematic review and meta-analysis to (i) assess the efficacy of third-line therapy for adults with HIV/AIDS based on randomized controlled trials (RCT) that adopted the "new antiretroviral (ARV) + optimized background therapy (OBT)" approach and (ii) address the key issues identified in WHO's guidelines on the use of third-line therapy. MEDLINE, EMBASE, LILACS, ISI Web of Science, SCOPUS, and Cochrane Central Register of Controlled Trials were searched for RCTs assessing third-line ARV therapy that used an OBT approach between 1966 and 2015. Data was extracted using an Excel-structured datasheet based on the Consolidated Standards of Reporting Trials (CONSORT) recommendations. The primary outcome of this meta-analysis was the proportion of patients reaching undetectable HIV RNA levels (< 50 copies/mL) at 48 weeks of follow-up. Included studies were evaluated using the Cochrane's Risk of Bias assessment tool. Summarized evidence was rated according to the GRADE approach. Eighteen trials assessing 9 new ARV + OBT combinations defined as third-line HIV therapy provided the efficacy data: 7 phase IIb trials and 11 phase III trials. Four of the 18 trials provided extension data, thus resulting in 14 trials providing 48-week efficacy data. In the meta-analysis, considering the outcome regarding the proportion of patients with a viral load below 50 copies/ml at 48 weeks, 9 out of 14 trials demonstrated the superiority of the new combination being studied (risk difference = 0.18, 95% CI 0.13-0.23). The same analysis stratified by the number of fully active ARVs demonstrated a risk difference of 0.29 (95% CI 0.12-0.46), 0.28 (95% CI 0.17-0.38) and 0.17 (95% CI 0.10-0.24) respectively from zero, one, and two or more active drugs strata. Nine of the 18 trials were considered to have a high risk of bias. Efficacy results demonstrated that the groups of HIV-experienced patients receiving the new ARV + OBT were more likely to achieve viral suppression when compared to the control groups. However, most of these trials may be at a high risk of bias. Thus, there is still not enough evidence to stipulate which combinations are the most effective for therapeutic regimens that are to be used sequentially due to documented multi-resistance.


Aerobic exercise and the post myocardial infarction patient: a review of the literature.
Meta analyses of randomized controlled tests of cardiac rehabilitation after myocardial infarction demonstrate that regular exercise reduces the risk of overall mortality and cardiovascular mortality. In patients with established coronary artery disease, exercise is associated with improved activity tolerance, modification of risk factors, and improvement in quality of life. Randomized controlled tests demonstrate that whereas older patients after coronary events are substantially less fit than younger patients, they obtain a similar relative improvement of aerobic capacity with a graded conditioning program. However, older adults are enrolled in such programs at a lower rate than other age groups. Despite similar clinical profiles to men, women are less likely to participate in exercise rehabilitation. In this article we discuss the principles of program development, guidelines for monitoring of patients, and facilitation of exercise programs in the Australian context.


Characterization and inhibition study of MurA enzyme by capillary electrophoresis.
A capillary electrophoresis-based enzyme assay for UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is described. This method, based on UV detection, provides baseline separation of one of the reaction products, enolpyruvyluridine 5'-diphospho-N-acetylglucosamine (EP-UDP-GlcNAc), from substrates phosphoenolpyruvate (PEP) and uridine 5'-diphospho-N-acetylglucosamine (UDP-GlcNAc) within 4 min. The other product, phosphate, is not detectable by UV at 200 nm. Quantitation of individual components, substrates or product, can be accomplished based on the separated peaks. This methodology was used to determine the Michaelis constant, Km, and product formation rate constant, Kcat, for MurA. Additionally, the CE method was used to evaluate the inhibition effects on MurA using one specific compound as an example. By following similar procedures, the apparent Km values in the presence of different inhibitor concentrations were determined. The inhibition constant, Ki, can be determined from these apparent Km values. In addition, this CE method can be used to study the inhibition mechanism. The principle of this approach is generally applicable to other enzyme studies.


Macrophage Kdm6b controls the pro-fibrotic transcriptome signature of foam cells.
In order to identify regulators of foam cells, we studied the H3K27 demethylase Kdm6b (also known as Jmjd3), a known regulator of macrophages, in controlling the transcriptional profile of foam cells. Foam cells from Kdm6b-deleted or Kdm6b wild-type mice were isolated and used for RNA-sequencing analysis. Pathway analysis revealed that pro-fibrotic pathways were strongly suppressed in Kdm6b-deleted foam cells. Analysis of published datasets showed that foam cell formation induces these pro-fibrotic characteristics. Overlay of both datasets indicated that fibrotic genes which are induced upon foam cell formation, are reduced in the absence of Kdm6b. These data suggest that foam cell formation induces a pro-fibrotic gene signature in a Kdm6b-dependent manner. We identified Kdm6b as a novel regulator of the pro-fibrotic signature of peritoneal foam cells.


Cholesterol diet counteracts repeated anesthesia/infusion-induced cognitive deficits in male Brown Norway rats.
A variety of cardiovascular and cerebrovascular diseases are associated with alterations in cholesterol levels and metabolism. Moreover, convincing evidence shows that high cholesterol diet can lead to learning and memory impairments. On the other hand, a significant body of research has also demonstrated that learning is improved by elevated dietary cholesterol. Despite these conflicting findings, it is clear that cholesterol plays an important role in these cognitive properties. However, it remains unclear how this blood-brain barrier (BBB)-impenetrable molecule affects the brain and under what circumstances it provides either detrimental or beneficial effects to learning and memory. The aim of this study was to characterize the effects of 5% cholesterol diet on six-month-old inbred Brown Norway rats. More important, we sought to examine the role that cholesterol can play when repeated anesthesia and intravenous infusion disrupts cognitive function. This present study supports previous work showing that enriched cholesterol diet leads to significant alterations in neuroinflammation and BBB disruption. Following repeated anesthesia and intravenous infusion of saline we observe that animals under normal diet conditions exhibit significant deficiencies in spatial learning and cholinergic neuron populations compared to animals under enriched cholesterol diet, which do not show such deficiencies. These findings indicate that cholesterol diet can protect against or counteract anesthesia/infusion-induced cognitive deficits. Ultimately, these results suggest that cholesterol homeostasis serves an important functional role in the brain and that altering this homeostasis can either exert positive or negative effects on cognitive properties.


Validation of a 4D-PET maximum intensity projection for delineation of an internal target volume.
The delineation of internal target volumes (ITVs) in radiation therapy of lung tumors is currently performed by use of either free-breathing (FB) (18)F-fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET/CT) or 4-dimensional (4D)-CT maximum intensity projection (MIP). In this report we validate the use of 4D-PET-MIP for the delineation of target volumes in both a phantom and in patients. A phantom with 3 hollow spheres was prepared surrounded by air then water. The spheres and water background were filled with a mixture of (18)F and radiographic contrast medium. A 4D-PET/CT scan was performed of the phantom while moving in 4 different breathing patterns using a programmable motion device. Nine patients with an FDG-avid lung tumor who underwent FB and 4D-PET/CT and >5 mm of tumor motion were included for analysis. The 3 spheres and patient lesions were contoured by 2 contouring methods (40% of maximum and PET edge) on the FB-PET, FB-CT, 4D-PET, 4D-PET-MIP, and 4D-CT-MIP. The concordance between the different contoured volumes was calculated using a Dice coefficient (DC). The difference in lung tumor volumes between FB-PET and 4D-PET volumes was also measured. The average DC in the phantom using 40% and PET edge, respectively, was lowest for FB-PET/CT (DCAir = 0.72/0.67, DCBackground 0.63/0.62) and highest for 4D-PET/CT-MIP (DCAir = 0.84/0.83, DCBackground = 0.78/0.73). The average DC in the 9 patients using 40% and PET edge, respectively, was also lowest for FB-PET/CT (DC = 0.45/0.44) and highest for 4D-PET/CT-MIP (DC = 0.72/0.73). In the 9 lesions, the target volumes of the FB-PET using 40% and PET edge, respectively, were on average 40% and 45% smaller than the 4D-PET-MIP. A 4D-PET-MIP produces volumes with the highest concordance with 4D-CT-MIP across multiple breathing patterns and lesion sizes in both a phantom and among patients. Freebreathing PET/CT consistently underestimates ITV when compared with 4D PET/CT for a lesion affected by respiration.


In vivo action of phosphatidylserine, amitriptyline and stress on the binding of [3H]imipramine to membranes of the rat cerebral cortex.
Liposomes of bovine brain phosphatidylserine and of phosphatidylcholine were prepared and injected i.p. into rats for 5 days. Another group received i.p. injections of amitriptyline in addition to phosphatidylserine. Subgroups of control and phosphatidylserine-injected rats were submitted to an acute swimming stress for 15 min. The number of [3H]imipramine binding sites in the phosphatidylserine-injected rats, decreased 23% whereas there was no change in the phosphatidylcholine-injected rats. The combination of amitriptyline and phosphatidylserine produced a more marked reduction in [3H]imipramine binding (-47%). Control rats undergoing acute stress showed a 30% decrease in [3H]imipramine binding whereas the stress did not significantly change the control values of the phosphatidylserine-treated animals. These findings are discussed in relation to the known action of phosphatidylserine on several neurotransmitter systems and on the potentiation of antidepressant effects.


Ablation for Atrial Fibrillation: Termination of Atrial Fibrillation is Not the End Point.
Permanent pulmonary vein isolation constitutes the main procedural goal of current approaches to atrial fibrillation (AF) catheter ablation, with established effectiveness as a stand-alone procedure in most patients with paroxysmal AF. In patients with AF of longer duration, however, the definition of the optimal procedural end point is still controversial. Based on analysis of data from 16 studies that have assessed the value of AF termination in predicting long-term procedural success, it is concluded that AF termination clearly represents an unreliable procedural end point during ablation of nonparoxysmal AF.


Changes in excitability in motor cortex (representation of foreleg) of the dog depending on signal signification of flexor reaction during elaboration of transswitching.
Excitability in a cortical representation of a foreleg was determined during elaboration of transswitching in dogs in three variations depending upon the stimulus used as a Conditioned stimulus (CS). If the flexor reaction to direct stimulation of the motor cortex was used as a CS, excitability changes of opposite signs appeared in the cortical representation of the foreleg, the threshold of flexion decreased in the alimentary situation and increased in the defense situation. Such changes in excitability were observed during instrumental conditioned transswitching. If subthreshold stimulation of the motor cortex was used as the CS, the threshold of flexion increased in both situations in approximately equal degree.


Endovascular occlusion of iatrogenic lumbar artery pseudoaneurysm using liquid embolic agent: Case report.
We describe a case of iatrogenic pseudoaneurysm of the fourth lumbar artery as a complication after transpedicular screw fixation in the lumbar spine. The lesion was succesfully occluded with endovascular liquic embolic agent infusion and the patient was fully recovered.


Functional organization of the human first and second somatosensory cortices: a neuromagnetic study.
Multichannel neuromagnetic recordings were used to differentiate signals from the human first (SI) and second (SII) somatosensory cortices and to define representations of body surface in them. The responses from contralateral SI, peaking at 20-40 ms, arose mainly from area 3b, where representations of the leg, hand, fingers, lips and tongue agreed with earlier animal studies and with neurosurgical stimulations and recordings on convexial cortex in man. Representations of the five fingers were limited to a cortical strip of approximately 2 cm in length. Responses from SII peaked 100-140 ms after contra- and ipsilateral stimuli and varied considerably from one subject to another. Signs of somatotopical organization were seen also in SII. Responses of SII were not fully recovered at interstimulus intervals of 8 s.


Syndecan-1 in multiple myeloma: relationship to conventional prognostic factors.
Syndecan-1 (CD138) mediates myeloma cell adhesion, and loss of syndecan-1 from the cell surface may contribute to myeloma cell proliferation and dissemination and influence the prognosis in patients with multiple myeloma (MM). In order to test this hypothesis, we have evaluated syndecan-1 expression on the surface of malignant plasma cells and soluble forms of syndecan-1 in the serum of 25 newly diagnosed MM patients by flow cytometry and immunosorbent assay. Soluble syndecan-1 levels were significantly higher in MM as compared to controls (P<0.001). Cellular and soluble syndecan-1 was significantly inversely correlated (r=-0.89, P<0.001). The soluble syndecan-1 was significantly higher in non- responders to chemotherapy when compared to responders (P<0.01), and in non- survivors as compared to survivors (P<0.001). In contrast, cellular syndecan-1 expression was significantly lower in non- responders when compared to responders (P<0.01), and in non- survivors as compared to survivors (P<0.05). The levels of soluble syndecan-1 increased from stage I through stage II to stage III, whereas cellular syndecan-1 expression were decreased from high levels in stage III down to a low in stage I, with a statistically significant difference (P<0.01, P<0.05, respectively). There was a significant positive correlation between soluble syndecan-1 and plasma cell count (r=0.079, P<0.001), beta2 microglobulin (r=0.85, P<0.001), serum creatinine (r=0.84, P<0.001), C-reactive protein (r=0.082, P<0.001), alkaline phosphatase (r=0.58, P<0.05) and serum calcium (r=0.77, P<0.01) and a negative correlation with hemoglobin level (r=-0.78, P<0.01), platelets count (r=-0.82, P<0.01) and Albumin level (r=-0.64, P<0.01). Cox regression analysis using soluble syndecan-1 at mean-2SD of the controls could correctly classify patient outcome in 84.0%. The addition of beta2 microglobulin to soluble syndecan-1 increased the predictability of the patients' outcome to 96.7%. We conclude that soluble syndecan-1 levels are negatively correlated to the cellular form and that high levels of soluble syndecan-1 and lower expression of cellular syndecan-1 at diagnosis are negative prognostic factors. Assessment of soluble syndecan-1 and beta2 microglobulin at diagnosis is an independent prognostic system for MM.


TRPV1 agonism inhibits endothelial cell inflammation via activation of eNOS/NO pathway.
Transient receptor potential vanilloid type 1 channel (TRPV1) is found to be expressed in endothelial cells (ECs) and activate endothelial nitric oxide synthase (eNOS). Recent studies implicate TRPV1 in attenuating inflammatory responses. However, the mechanisms underlying the beneficial effects remain unclear. In this study, we investigated whether TRPV1 suppresses inflammatory responses of ECs via eNOS/NO pathway. Human umbilical vein endothelial cells (HUVECs) and renal microvascular endothelial cells (MVECs) isolated from deoxycorticosterone (DOCA)-salt hypertensive mice were cultured in the presence of capsaicin (CAP, a specific TRPV1 agonist) with or without the specific inhibitor of TRPV1, NOS, or Ca2+-dependent phosphatidylinositol 3-kinase (PI3K)/Akt pathway, before lipopolysaccharide (LPS) stimulation. NO metabolites, protein expression, and inflammatory molecules were evaluated by Griess assay and immune assay-based multiplex analysis, respectively. Monocyte adhesion was determined by measuring the fluorescently labeled human monocytes attached to LPS-stimulated ECs. In HUVECs, treatment with CAP increased NO production, and CAP-induced NO production was accompanied by increased eNOSser1177 phosphorylation. Additionally, CAP attenuated LPS-induced cytokine and chemokine production, adhesion molecule expression, activation of NF-κB, and monocyte adhesion in HUVECs, and these effects were abrogated by the inhibition of TRPV1, NOS, or Ca2+-dependent PI3K/Akt pathway. Moreover, these protective actions of TRPV1 were also observed in renal MVECs isolated from DOCA-salt hypertensive mice. Our results indicate that TRPV1 activation suppresses the inflammatory response of ECs via the activation of Ca2+/PI3K/Akt/eNOS/NO pathway, the protective effects are also documented in ECs derived from salt-sensitive hypertensive mice.


Different responses of the retinal and cutaneous microcirculation to transient dysmetabolic conditions.
This study evaluated the responses of the retinal and cutaneous microcirculation to acute hyperlipidemia and hyperhomocysteinemia. Twenty-five clinically healthy men (mean age 24 ± 2 years) were studied four times in a randomized order, with intervals of at least one week between the two dietary interventions always preceded by a day for baseline assessment. The two interventions consisted of either 0.1 g/kg l-methionine to induce hyperhomocysteinemia or of 500 ml whipping cream (30% fat) to induce hyperlipidemia. Microvascular vasodilator responses to flickering-light and to cutaneous acetylcholine iontophoresis were assessed by retinal vessel analysis and laser Doppler flowmetry respectively. The fat load produced significant increases in triglycerides and total cholesterol which was accompanied by a reduction of the retinal arterial flicker response. Methionine administration induced a threefold increase in homocysteine levels and a concomitant decrease in retinal venous flicker response. Acute hyperlipidemia and hyperhomocysteinemia had no effect on cutaneous microvascular vasodilator responses to acetylcholine. The inter- and intra-subject reproducibility was higher for retinal vessel analysis as compared to laser Doppler flowmetry. The retinal microcirculation is more sensitive to metabolic changes than the cutaneous microcirculation and can be reliably assessed by retinal vessel analysis. Reproducibility of retinal vessel analysis may be enhanced by multi-vessel assessment.


An alternate procedure for making a remount cast for a locking type removable partial denture.
This procedure describes the use of silicone impression material to make an index that will correctly position a hinge and latch removable partial denture when a remount cast is being made. This procedure ensures that the partial denture can be retrieved with the index without stressing the retentive components of the partial denture and the remaining dentition. Recovering the remount cast is easier because the latch can be released before the impression index is separated from the cast.


Epidemiology of influenza under the coronavirus disease 2019 pandemic in Nanjing, China.
Since the pandemic of coronavirus disease-19 (COVID-19), the incidence of influenza has decreased significantly, but there are still few reports in the short period before and after the pandemic period. This study aimed to explore influenza activity and dynamic changes before and during the pandemic. A total of 1 324 357 influenza-like illness (ILI) cases were reported under the ILI surveillance network from January 1, 2018, to September 5, 2021, in Nanjing, of which 16 158 cases were detected in a laboratory. Differences in ILI and influenza were conducted with the χ2 test. The number of ILI cases accounted for 8.97% of outpatient and emergency department visits. The influenza-positive ratio (IPR) was 7.84% in ILI cases. During the COVID-19 pandemic, ILI% and IPR dropped by 6.03% and 11.83% on average, respectively. Besides this, IPR rose slightly in Week 30-35 of 2021. Not only differences in gender, age, and employment status, but also the circulating strains had changed from type A to B through the COVID-19 pandemic. The level of influenza activity was severely affected by COVID-19, but it seems that it is inevitable to be vigilant against the co-circulation in the future.


Type IV collagen immunoreactivity of basement membrane in inflammatory-regenerative and dysplastic lesions of the flat colonic mucosa.
The aim of this research is to establish by immunohistochemistry if there is a change in the expression of collagen type IV, as a substitute of basement membrane, in development of epithelial dysplasia in chronically inflamed colon mucosa. Biopsy specimens from 270 patients were examined: 74 were classified as inflammatory-regenerative and 196 as dysplastic lesions. There were 108 cases of mild dysplasia, 58 cases of moderate and 30 cases severe dysplasia, respectively. Visualisation of collagen IV and its way of expression within basement membrane of glandular crypts was performed by immunohistochemistry and then compared with findings in normal colon mucosa and colon adenocarcinoma tissue. Changes in the expression of collagen IV comprised of its focal irregularities, diffuse thinning and/or thickening, focal interruptions or its complete absence. Significant changes in the expression of collagen IV in relation to normal mucosa already occur in inflammatory-regenerative mucosa. In mild dysplasia, these changes are more intensive in relation to those in inflammatory altered mucosa as well as at severe dysplasia in relation to moderate dysplasia. Changes in the expression of collagen IV in severe dysplasia are significantly more serious than in moderate dysplasia but are identical to those in colon adenocarcinoma tissue. These findings suggest that change in the expression of collagen IV is in correlation to a degree of epithelial dysplasia that developed in flat chronically inflamed colon mucosa.


Mammalian galectins: structure, carbohydrate specificity, and functions.
Galectins are a family of beta-galactoside binding lectins, homological by a sequence of the carbohydrate-binding site. In this review literature data about structure and carbohydrate specificity of galectins are discussed. The role of galectins in the regulation of cell adhesion in immune response, inflammation, and cancer progression is considered.


Quality control in a National Program for the Early Detection of Breast Cancer: women's satisfaction with the mammography process.
The experience of the mammography testing process and related satisfaction influence women's willingness to undergo the test again. The study goal was to assess women's overall satisfaction with the mammography examination service provided by participating units in the National Program for the Early Detection of Breast Cancer in Israel. Between August 2003 and March 2004, a random sample of 3,295 women from 38 mammography units nationwide was drawn. Women were interviewed within 48 hours of their mammography, regarding their assessment of the examination process: discomfort, overall satisfaction, and intention to rescreen. Overall satisfaction and process items were measured on an ordinal scale ranging from 1 (lowest) to 6 (highest). Multivariate binomial regression was performed to identify significant predictors of being less satisfied and to estimate the associated relative risks with 95% confidence interval (CI). A response of "very satisfied" (score 6), indicating overall satisfaction with the mammography process, was reported by 77% (95% CI, 73%-80%) of the women, 19% (95% CI, 17%-21%) said they were satisfied. Willingness to rescreen was reported by 95%. Negative assessment of staff attitude was the most influential predictor of being less satisfied. Twenty-six percent of women reported experiencing very discomforting pain. This response was associated with a diagnostic test indication, and with process items directly related to the test (technician's attitude toward the patient; information provided by her; privacy during the test). Women's satisfaction was high, as was intention to rescreen. The gap between intention and rescreening begs further investigations as to other types of barriers preventing women from adherence to rescreening.


Comorbid diseases associated with pemphigus: a case-control study.
Pemphigus has been associated with physical and psychiatric comorbid diseases. This study aims to further investigate these associations in patients with pemphigus, and to analyze the relationships of comorbid conditions with sex and age, pemphigus disease area index score, diagnostic delay and cutaneous/mucous involvement. Patients with pemphigus were matched by age, gender and area of residence with eight controls each. The odds of comorbid conditions in patients vs. matched controls was determined using univariate conditional logistic regression models. Comorbid diseases significantly associated with the diagnosis of pemphigus at P < 0.05 in univariate models were subsequently included in a multivariable conditional logistic regression model with a forward procedure. The study sample included 163 patients with pemphigus. Cardiovascular diseases, hyperlipidemia, autoimmune thyroid disorders, dermatological autoimmune/inflammatory conditions and cancer were the most prominent conditions at the time of diagnosis. In the multiple conditional regression analysis, the two diagnoses independently associated with patients with pemphigus were cancer and dermatological autoimmune/inflammatory conditions. In sensitivity analyses excluding four patients with paraneoplastic pemphigus, these associations were still significant. Cancer and dermatological autoimmune/inflammatory conditions may represent possible triggering conditions for pemphigus and should be considered as early warning signs for the disease.


Effect of imidacloprid on hepatotoxicity and nephrotoxicity in male albino mice.
Imidacloprid (IC) is a systemic insecticide related to the tobacco toxin nicotine. IC is a toxic substance frequently used into combat insects, rodents and plants pests and other creatures that can pose problems for agriculture. We, therefore, planned this study to assess risk factors, biochemical and histological alterations associated with hepatotoxicity and nephrotoxicity. Forty-eight adult male albino mice were divided into four groups of 12 animals each. All the animals were given standard synthetic pellet diet. One group served as control, and the other three were served as experimental groups. Decrease in the body weight of the high dose group was observed at 15 mg/kg/day, and no mortality occurred during the treatment period. High dose of imidacloprid caused a significant elevation of serum clinical chemistry parameters, serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvate kinase (SGPT), alkaline phosphatase (ALP) and total bilirubin (TBIL). Histology of liver and kidney indicates hepatotoxicity and nephrotoxicity at a high dose of imidacloprid. Based on the morphological, biochemical and histopathological analysis, it is evident that imidacloprid induced toxicological effects at 15 mg/kg/day to mice. The results of the present study demonstrate that IC had significant effects on body weight, liver functions and kidney (p < 0.05) at a dose of 15 mg/kg body weight. IC treatment 5 and 10 mg/kg/day may be considered as no observed adverse effect level (NOAEL) for mice. It was concluded that IC can cause hepatotoxicity and nephrotoxicity at a dose much lower than the LD50 (131 mg/kg body weight) in mice.


Accuracy of reduction of femoral subcapital fractures.
Fifty-four patients with recent subcapital fractures of the femur underwent a Flynn reduction manoeuvre and are compared with 68 patients who were treated by a different method of reduction. Analysis of the postoperative radiographs showed no significant difference in the accuracy of reduction (0.1 greater than P greater than 0.05). The Flynn reduction manoeuvre is recommended as a method which compares favourably with other manoeuvres.


Evaluation of Intratumoral Response Heterogeneity in Metastatic Colorectal Cancer and Its Impact on Patient Overall Survival: Findings from 10,551 Patients in the ARCAD Database.
Metastatic colorectal cancer (mCRC) is a heterogeneous disease that can evoke discordant responses to therapy among different lesions in individual patients. The Response Evaluation Criteria in Solid Tumors (RECIST) criteria do not take into consideration response heterogeneity. We explored and developed lesion-based measurement response criteria to evaluate their prognostic effect on overall survival (OS). Patients enrolled in 17 first-line clinical trials, who had mCRC with ≥ 2 lesions at baseline, and a restaging scan by 12 weeks were included. For each patient, lesions were categorized as a progressing lesion (PL: > 20% increase in the longest diameter (LD)), responding lesion (RL: > 30% decrease in LD), or stable lesion (SL: neither PL nor RL) based on the 12-week scan. Lesion-based response criteria were defined for each patient as follows: PL only, SL only, RL only, and varied responses (mixture of RL, SL, and PL). Lesion-based response criteria and OS were correlated using stratified multivariable Cox models. The concordance between OS and classifications was measured using the C statistic. Among 10,551 patients with mCRC from 17 first-line studies, varied responses were noted in 51.6% of patients, among whom, 3.3% had RL/PL at 12 weeks. Among patients with RL/SL, 52% had stable disease (SD) by RECIST 1.1, and they had a longer OS (median OS (mOS) = 19.9 months) than those with SL only (mOS = 16.8 months, HR (95% CI) = 0.81 (0.76, 0.85), p < 0.001), although a shorter OS than those with RL only (mOS = 25.8 months, HR (95% CI) = 1.42 (1.32, 1.53), p < 0.001). Among patients with SL/PL, 74% had SD by RECIST 1.1, and they had a longer OS (mOS = 9.0 months) than those with PL only (mOS = 8.0 months, HR (95% CI) = 0.75 (0.57, 0.98), p = 0.040), yet a shorter OS than those with SL only (mOS = 16.8 months, HR (95% CI) = 1.98 (1.80, 2.18), p < 0.001). These associations were consistent across treatment regimen subgroups. The lesion-based response criteria showed slightly higher concordance than RECIST 1.1, although it was not statistically significant. Varied responses at first restaging are common among patients receiving first-line therapy for mCRC. Our lesion-based measurement criteria allowed for better mortality discrimination, which could potentially be informative for treatment decision-making and influence patient outcomes.


Examining the linkages between maternity services and postpartum modern contraceptive adoption among young women in India: Insights from the 2015-16 and 2019-21 National Family Health Survey.
The adoption of maternity services and postpartum modern contraception are the two most crucial components that help in reducing maternal and infant mortality; still, India is consistently struggling with it. This paper, therefore, aimed to examine the linkages between use of maternity services and postpartum modern contraceptive adoption. The required reproductive calendar data were extracted from the 2015-16 and 2019-21 National Family Health Survey (NFHS) datasets. The assessment was made based on a sample of currently married women aged 15-24 years who had given most recent childbirth in five years preceding the survey. For the analysis, a time-to-event approach was applied using the Kaplan-Meier survival statistic, Log-Rank Chi-square test and Cox-Proportional Hazard (Cox-PH) models. The results revealed that the proportion of postpartum modern contraceptive uptake among young users increased by 9%, from 33% in 2015-16 to 42% in 2019-21. The Cox-PH models revealed that, in both NFHS waves, the associations between various components of maternity services and postpartum modern contraceptive uptake were strongly significant, even after controlling for selected socio-economic and demographic correlates. The findings of this study reinforced urgent need for implementing integrated maternal-child health and family planning programmes and for boosting effective family planning counselling by health professionals to promote and motivate young women with a desire to early adoption of modern contraception in subsequent months after a recent childbirth.


Novel fluorescent probe for highly sensitive bioassay using sequential enzyme-linked immunosorbent assay-capillary isoelectric focusing (ELISA-cIEF).
This paper presents a novel rhodamine diphosphate molecule that allows highly sensitive detection of proteins by employing sequential enzyme-linked immunosorbent assay and capillary isoelectric focusing (ELISA-cIEF). Seven-fold improvement in the immunoassay sensitivity and a 1-2 order of magnitude lower detection limit has been demonstrated by taking advantage of the combination of the enzyme-based signal amplification of ELISA and the concentration of enzyme reaction products by cIEF.


Quality of life and non-motor symptoms in Parkinson's disease patients with subthreshold depression.
The role of subthreshold depression (subD) in Parkinson's Disease (PD) is not clear. The present study aimed to compare the quality of life (QoL) in PD patients with subD vs patients with no depressive disorder (nonD). Factors related to subD were identified. PD patients and controls recruited from the COPPADIS cohort were included. SubD was defined as Judd criteria. The 39-item Parkinson's disease Questionnaire (PDQ-39) and the EUROHIS-QOL 8-item index (EUROHIS-QOL8) were used to assess QoL. The frequency of depressive symptoms was higher in PD patients (n = 694) than in controls (n = 207) (p < 0.0001): major depression, 16.1% vs 7.8%; minor depression, 16.7% vs 7.3%; subD, 17.4% vs 5.8%. Both health-related QoL (PDQ-39; 18.1 ± 12.8 vs 11.6 ± 10; p < 0.0001) and global QoL (EUROHIS-QOL8; 3.7 ± 0.5 vs 4 ± 0.5; p < 0.0001) were significantly worse in subD (n = 120) than nonD (n = 348) PD patients. Non-motor Symptoms Scale (NMSS) total score was higher in subD patients (45.9 ± 32 vs 29.1 ± 25.8;p < 0.0001). Non-motor symptoms burden (NMSS;OR = 1.019;95%CI 1.011-1.028; p < 0.0001), neuropsychiatric symptoms (NPI; OR = 1.091; 95%CI 1.045-1.139; p < 0.0001), impulse control behaviors (QUIP-RS; OR = 1.035; 95%CI 1.007-1063; p = 0.013), quality of sleep (PDSS; OR = 0.991; 95%CI 0.983-0.999; p = 0.042), and fatigue (VAFS-physical; OR = 1.185; 95%CI 1.086-1.293; p < 0.0001; VAFS-mental; OR = 1.164; 95%CI 1.058-1.280; p = 0.0001) were related to subD after adjustment to age, disease duration, daily equivalent levodopa dose, motor status (UPDRS-III), and living alone. SubD is a frequent problem in patients with PD and is more prevalent in these patients than in controls. QoL is worse and non-motor symptoms burden is greater in subD PD patients.


Association between genetic polymorphism of GSTT1 and depression score in individuals chronically exposed to natural sour gas.
In order to investigate the association between effects of genetic polymorphisms of GSTT1 and GSTM1 and depression score of individuals chronically exposed to natural sour gas containing sulfur compounds, the present cross-sectional study was done. The study was performed on 124 healthy females living in the polluted area of Masjid-i-Sulaiman (MIS; Khozestan province, southwest of Iran). The GSTT1 and GSTM1 genotypes were determined using a polymerase chain reaction (PCR)-based method. Depression and hopelessness scores were determined by means of Beck's depression inventory (BDI) and Beck's hopelessness scale (BHS), respectively. The BHS score was positively correlated to the depression score (beta=0.687, t=10.474, p<0.001). The GSTT1 active genotype decreased the BDI score (beta=-0.161, t=-2.451, p=0.016). Polymorphism of GSTM1 may not be a good predictive factor for BDI (beta=-0.056, t=-0.857, p=0.393). There is no evidence for additive effect of GSTM1 and GSTT1 polymorphisms on BDI score. It is supposed that chronic exposure to natural sour gas may positively associated with DNA strand breaks and apoptosis in brain, especially in GSTT1 null genotype persons; finally living in the contaminated areas of MIS is associated with high BDI score.


Growth and reactivity of silver clusters in amino polycarboxylic acid solutions.
Reduction and subsequent aggregation of silver ions in the presence of various chelating agents such as trans-1,2-diaminocyclohexanetetraacetic acid (DCTA) 1,2-propylenediaminetetraacetic acid (PDTA), diethylenetriaminepentaacetic acid (DTPA), and triethylenetetraaminehexaacetic acid (TTHA) have been studied by pulse radiolysis. Rate constants of formation and transient absorption spectra for the ligand-complexed Ag(0) and Ag(2)(+) have been determined. The redox potential of Ag(+)(L)/Ag(0)(L) becomes more negative than that of Ag(+)/Ag(0). Growth and reactivity of silver clusters were also studied in the presence of methyl viologen (MV(2+)). The kinetics of formation of the MV(+*) radical, produced by the same pulse as in the case of silver atoms, confirms the catalytic electron transfer toward super critical silver clusters in the presence of ligands. The results suggest that catalytic electron transfer activity of silver clusters depends on the ligand.


[Use of social media by French urologists: Results from a study of the National French Urological Association].
Social Media (SoMe) have changed the face of modern medicine. Our purpose was to make an inventory on the use of SoMe within urologists members of the French Urological Association (AFU). A 15 questions-survey was sent by email 2 months to urologists AFU members before the 108th French Congress of Urology (#CFU2014). At the same time, the activity of urologists using Twitter was analyzed over the period of the national conference with the symplur software (www.symplur.com). Overall, 270 (17.3%) surveys were completed. Only 50% of responders had an online SoMe account. The most commonly used social media platforms were: Facebook (36.1%) followed by LinkedIn (28.2%), Google+ (19.6%), YouTube (18.7%) and Twitter (17.4%). The use of SoMe was higher in the age groups 30-40 and 40-50 years than in older age groups (83% versus 36%). Only 38.7% of respondents reported using SoMe in a professional field. At the congress #CFU2014, there were over 1000 tweets generated by 173 different contributors. Only a minority of French urologists have reported to be connected to SoMe and a predominantly personal use. The emergence of Twitter in French urological conferences is very new but seems promising. Further studies are needed, especially within the members of the residents French urological association to better characterize the true impact of SoMe in urology. 4.


Feasibility of strain and strain rate imaging for the assessment of regional left atrial deformation: a study in normal subjects.
There are no data on the use of Myocardial Velocity Imaging (MVI) to study the left atrium (LA) wall deformation. The aims of this study were to assess the feasibility of measuring regional longitudinal strain/strain rate (epsilon/SR) profiles in the LA wall, to define the normal values and to validate these measurements. MVI data were recorded in 40 healthy young individuals using a GE Vivid7 for the lateral, anterior and inferior LA walls. The peak epsilon/SR values and total epsilon values during the contractile, reservoir and conduit LA phases were measured. For the LA lateral wall, the total epsilon values were correlated with the LA volumetric indicators (LA active emptying fraction: LA AEF; LA expansion index: LA EI; and LA passive emptying fraction: LA PEF). The correlations were significant for all three periods: contractile (total epsilon vs. LA AEF, r=-0.78, P<0.001), reservoir (total epsilon vs. LA EI, r=0.43, P<0.01) and conduit (total epsilon vs. LA PEF, r=-0.46, P<0.005). SR/epsilon imaging for the quantification of longitudinal myocardial LA deformation was shown to be feasible and the normal values were reported and validated. These data may improve the understanding of the LA pathophysiology.


A summary of the effects of antihypertensive medications on measured blood pressure.
Epidemiologic analysis of family data on blood pressure (BP) is often compromised by the effects of antihypertensive medications. A review of numerous clinical trials that investigated the effects of BP-lowering medications is summarized here. Published clinical trials, including 137 clinical trials with monodrug therapies and 28 clinical trials of combination drug therapies with a total of 11,739 participants, were reviewed from PubMed. Six major classes/groups of antihypertensive medications were categorized by ethnicity, including angiotensin-converting enzyme (ACE) inhibitors, alpha1-blockers, cardioselective beta-blockers (beta1-blockers), calcium channel blockers, thiazide and thiazide-like diuretics, and loop diuretics. Using sitting or supine BP, for ethnic groups combined, monodrug therapy with ACE inhibitors showed a weighted average effect of lowering the systolic and diastolic BP by 12.5/9.5 mm Hg; alpha1-blockers by 15.5/11.7 mm Hg; beta1-blockers by 14.8/12.2 mm Hg; calcium channel blockers by 15.3/10.5 mm Hg; thiazide diuretics by 15.3/9.8 mm Hg; and loop diuretics by 15.8/8.2 mm Hg. However, ACE inhibitors, alpha1-blockers, and beta1-blockers were less effective in African Americans than in non-African Americans, whereas calcium channel blockers, thiazide diuretics, and loop diuretics were more effective in African Americans than in non-African Americans. For two-drug combination therapy with ethnic groups combined, the BP-lowering effect of the second medication, when compared to its effect as monodrug therapy, was 84% and 65% for systolic and diastolic BP, respectively. The BP-lowering effects reported here may be used to impute the pretreatment BP levels, which can improve the information content and hence the power of epidemiologic analysis in studies where use of antihypertensive medications is a confounding factor in the BP measurements.


[Quality Assurance of Screening Colonoscopy in Austria and Europe].
Screening colonoscopy, an efficient tool for reducing the incidence and mortality of colorectal cancer, is only effective if it is performed under high quality standards. The European Society for Gastrointestinal Endoscopy has identified the following key performance measures for screening: adenoma detection rate, cecal intubation rate, and adequate bowel preparation rate. The Quality Certificate for Colorectal Cancer Screening-which was launched as a quality assurance program on a voluntary basis by the Austrian Society of Gastroenterology and Hepatology together with the umbrella organization of Austrian social insurance carriers and the Austrian Cancer Aid for endoscopists throughout Austria-monitors these quality parameters. The aim is to achieve the highest standards of colorectal cancer screening in order to achieve the best outcomes for patients. Interest in quality-assured screening colonoscopy is also high throughout Europe: many countries, e.g., the Netherlands, Norway, and the United Kingdom, have programs to monitor and improve the quality of screening.


Anti-c-Mpl antibodies in immune thrombocytopenia suppress thrombopoiesis and decrease response to rhTPO.
Anti-TPO receptor (anti-c-Mpl) antibodies exist and could affect rhTPO treatment in ITP. Anti-c-Mpl autoantibodies and TPO levels were measured in serum from 187 ITP patients and 59 healthy controls. The anti-c-Mpl-antibody-positive (anti-c-Mpl+) and anti-c-Mpl-antibody-negative (anti-c-Mpl-) IgG from ITP patients were assessed on megakaryocyte proliferation, polyploidy, apoptosis, and platelet release with rhTPO treatment. Anti-c-Mpl antibodies were detected in 54/187 ITP patients but in none of the controls. ITP patients with anti-c-Mpl antibodies had higher serum TPO levels, but lower megakaryocyte and platelet counts compared with anti-c-Mpl- patients. Antibodies targeting platelet glycoprotein (GP) were also more frequently identified in anti-c-Mpl+ ITP patients. Moreover, patients with anti-c-Mpl antibodies were less responsive to rhTPO treatment than patients without anti-c-Mpl antibodies. Additionally, the anti-c-Mpl antibody titer decreased in ITP patients following treatment. In vitro study, lower megakaryopoiesis, platelet generation and percent of polyploidy were observed in anti-c-Mpl+ group compared with the anti-c-Mpl- group in the presence of rhTPO. Our findings demonstrated that the anti-c-Mpl antibody represents a novel indicator of poor prognosis and may be a potential therapeutic target in ITP.


A Case of Pulmonary Hypertension Due to Fistulas Between Multiple Systemic Arteries and the Right Pulmonary Artery in an Adult Discovered for Occulted Dyspnoea.
Pulmonary hypertension (PH) can be caused by a fistula between the systemic and pulmonary arteries. Here, we report a case of PH due to multiple fistulas between systemic arteries and the right pulmonary artery where the ventilation/perfusion scan showed no perfusion in the right lung. A 32-year-old male patient was hospitalised for community-acquired pneumonia. After treatment with antibiotics, the pneumonia was alleviated but dyspnoea persisted. Pulmonary hypertension was diagnosed using right heart catheterisation, which detected the mean pulmonary artery pressure as 37mmHg. The anomalies were confirmed by contrast-enhanced CT scan (CT pulmonary angiography), systemic arterial angiography and pulmonary angiography. Following embolisation of the largest fistula, the haemodynamics and oxygen dynamics did not improve, and even worsened to some extent. After supportive therapy including diuretics and oxygen, the patient's dyspnoea, WHO function class and right heart function by transthoracic echocardiography all improved during follow-up. Pulmonary hypertension can be present even when the right lung perfusion is lost. Closure of fistulas by embolisation, when those fistulas act as the proliferating vessels, may be harmful.


[Secretion of free hydrochloric acid after organ-saving surgery for duodenal ulcer].
Secretory function of the operated stomach was studied in 188 patients after trunk and selective vagotomy with distal resection and pyloroplasty of various extent. Under conditions of vagotomy the preservation of the whole stomach essentially fails to increase residual secretion of free hydrochloric acid.


Some physiological correlates to regular and irregular phonation at the end of an utterance.
This article examines respiratory and acoustic events at the ends of utterances that coincide with the end of a breath. All utterances end with a vowel. Between the start of the final fall in signal amplitude and the end of phonation, the alveolar pressure falls by 1.2-2.6 cm H2O, on average, and glottal area increases by a factor of 4.0 (median). The mean glottal area at the end of phonation ranges from 9.6 to 13.5 mm2 across subjects. Physiological correlates are examined for utterances that end with regular and with irregular phonation. Irregular phonation is usually produced with brief intervals of adduction followed by longer intervals of abduction and/or with incomplete closure of the folds. This physiological correlate to irregular phonation is not consistent with descriptions of vocal fry or creaky voice in which the vocal folds are tightly adducted over most of the cycle. The rise in average glottal area and drop in alveolar pressure were similar for utterances that ended with regular phonation and those that ended with irregular phonation. These data suggest that a similar phonation-ending gesture underlies both groups of utterances. This gesture includes abduction of the vocal folds and a drop in alveolar pressure.


Hepatitis C virus core protein selectively inhibits synthesis and accumulation of p21/Waf1 and certain nuclear proteins.
By using a vaccinia virus-T7 expression system, possible effects of hepatitis C virus (HCV) core protein on synthesis and accumulation of host cellular proteins transiently expressed in cultured cells were analyzed. Immunoblot and immunofluorescence analyses revealed that synthesis and accumulation of certain nuclear proteins, such as p21/Waf1, p53, proliferating cell nuclear antigen and c-Fos, were strongly inhibited by HCV core protein. On the other hand, synthesis and accumulation of cytoplasmic proteins, such as 2'-5'-oligoadenylate synthetase (2'-5'-OAS), RNase L and MEK1, were barely affected by HCV core protein. Northern blot analysis showed that the degrees of mRNA expression for those proteins did not differ between HCV core protein-expressing cells and the control, suggesting that the inhibition occurred at the post-transcription level. Pulse-labeling analysis suggested that HCV core protein strongly inhibited synthesis of p21/Waf1 at the translation level. Once being accumulated in the nucleus, p21/Waf1 stability was not significantly affected by HCV core protein. Mutants of HCV core protein C-terminally deleted by 18 or 41 amino acids (aa), which were localized almost exclusively in the nucleus, lost their ability to inhibit synthesis/accumulation of p21/Waf1 whereas another mutant C-terminally deleted by 8 aa still maintained the same properties (subcellular localization and the inhibitory effect) as the full-length HCV core protein of 191 aa. Taken together, our present results suggest that expression of HCV core protein in the cytoplasm selectively inhibits synthesis of p21/Waf1 and some other nuclear proteins at the translation level.


Induction of the antigen receptor expression on B lymphocytes results in rapid competence for signaling of SLP-65 and Syk.
The binding of antigen to the B cell antigen receptor (BCR) results in the activation of protein tyrosine kinases (PTKs) such as Lyn and Syk, and the phosphorylation of several substrate proteins including HS1 and SLP-65. How these signaling elements are connected to the BCR is not well understood. Using an expression vector for a tamoxifen-regulated Cre recombinase, we have developed a method that allows the inducible expression of the BCR. Disruption of the VH leader reading frame of the immunoglobulin heavy chain by two loxP sites is overcome by Cre-mediated DNA recombination and results in the cell surface expression of the BCR starting 4 h after exposure of transfected B cells to tamoxifen. This method can, in principle, be employed for the inducible expression of any secreted or type I transmembrane protein. By monitoring the activation of signaling elements in pervanadate-stimulated B cells expressing different levels of the BCR, we show here that phosphorylation of SLP-65 and Syk, but not of Lyn, is strictly dependent on the expression of the BCR on the cell surface. These data suggest that the BCR reorganizes its signaling molecules as soon as it appears on the cell surface.


Knowledge across networks: how to build a global neuroscience collaboration.
The International Brain Laboratory (IBL) is a collaboration of ∼20 laboratories dedicated to developing a standardized mouse decision-making behavior, coordinating measurements of neural activity across the mouse brain, and utilizing theoretical approaches to formalize the neural computations that support decision-making. In contrast to traditional neuroscientific practice, in which individual laboratories each probe different behaviors and record from a few select brain areas, IBL aims to deliver a standardized, high-density approach to behavioral and neural assays. This approach relies on a highly distributed, collaborative network of ∼50 researchers - postdocs, graduate students, and scientific staff - who coordinate the intellectual, administrative, and sociological aspects of the project. In this article, we examine this network, extract some lessons learned, and consider how IBL may represent a template for other team-based approaches in neuroscience, and beyond.


Impact of repeat flooding on mental health and health-related quality of life: a cross-sectional analysis of the English National Study of Flooding and Health.
To assess the association between flooding/repeat flooding and: (1) psychological morbidity (anxiety, depression, post-traumatic stress disorder (PTSD)) and (2) health-related quality of life (HRQoL) at 6 months post-flooding. Cross-sectional analysis of data from the English National Study of Flooding and Health. Cumbria, England. Questionnaires were sent to 2500 residential addresses at 6 months post-flooding; 590 people responded. Probable depression was assessed using the Patient Health Questionnaire, probable anxiety using the Generalised Anxiety Disorder scale and probable PTSD using the short-form PTSD checklist (PCL-6). HRQoL was assessed using the EQ-5D-5L. Mental health outcomes were analysed using logistic regression; HRQoL dimensions using ordinal regression; and summary index/Visual Analogue Scale scores using linear regression. One hundred and nineteen participants had been flooded, over half of whom were experiencing a repeat flooding event (54%; n=64). Mental health outcomes were elevated among flooded compared with unaffected participants (adjusted OR for probable depression: 7.77, 95% CI: 1.51 to 40.13; anxiety: 4.16, 95% CI: 1.18 to 14.70; PTSD: 14.41, 95% CI: 3.91 to 53.13). The prevalence of depression was higher among repeat compared with single flooded participants, but this was not significant after adjustment. There was no difference in levels of anxiety or PTSD. Compared with unaffected participants, those flooded had lower EQ-5D-5L index scores (adjusted coefficient: -0.06, 95% CI: -0.12 to -0.01) and lower self-rated health scores (adjusted coefficient: -6.99, 95% CI: -11.96 to -2.02). There was, however, little difference in HRQoL overall between repeat and single flooded participants. Interventions are needed to help minimise the impact of flooding on people's mental health and HRQoL.


Development of a field test for evaluating aerobic fitness.
The purpose of this study was to investigate the reproducibility and utility of a standardised and externally paced field test (15-m Incremental Shuttle Walk and Run Test [15 mISWRT]) to assess aerobic fitness in middle-aged adults. 14 middle-aged participants performed the 15-m ISWRT 3 times within one week (Test 1, Test 2, Test 3). Reproducibility of the 15-m ISWRT was tested by comparing 15-m ISWRT performance (distance completed), HRmax, and VO 2max for each test. The utility of the 15-m ISWRT for evaluating VO 2max over a wide range in middle-aged adults was tested by comparing the range of VO 2max obtained from the portable expired gas analyzer with the VO 2max reference values and ranges for health promotion published by Japan's Ministry of Health, Labour and Welfare. A multiple comparison of distance completed in the 15-m ISWRT Test 1, Test 2, and Test 3 found no significant difference between Test 2 and Test 3. The ICC was 0.99 for Test 2 vs. Test 3. VO 2max measured from the 15-m ISWRT in Test 3 had a minimum value of 22.8 ml/kg/min and a maximum value of 38.7 ml/kg/min. In conclusion, the 15-m ISWRT is reliable and useful for evaluating VO 2max in middle-aged adults.