Myocarditis after COVID-19 mRNA vaccination: A systematic review of case reports and case series.
The coronavirus disease of 2019 (COVID-19) is a global pandemic with over 266 million cases and 5 million deaths worldwide. Anti-COVID-19 vaccinations have had exceptional success in subduing the incidence, prevalence, and disease severity of COVID-19, but rare cases of myocarditis have been reported after COVID-19 vaccinations. Myocarditis occurring after COVID-19 mRNA vaccinations have distinguishable clinical characteristics. They usually have a favorable prognosis. We performed a systematic literature search on PUBMED and MEDLINE database from inception to December 5, 2021. Studies were analyzed based on predetermined eligibility criteria. A total of 57 studies containing 275 cases of COVID-19 vaccine-associated myocarditis were catalogued. Mean age was 26.7 years and male to female ratio was 14:1. For 86.9% of patients, myocarditis occurred after the second dose. Average time to onset and length of hospitalization were 3.7 and 3.9 days, respectively. Prognosis was largely benign, but there was a 1.1% reported mortality. Chest pain (95.2%), elevation of troponin (100%), and ST elevation on electrocardiography (68.5%) were common. Nonsteroidal anti-inflammatory drugs (81.4%) were the most used medication, followed by colchicine (33.1%). Patients with COVID-19 vaccine-associated myocarditis are usually younger males presenting with chest pain 3-4 days after receiving their second dose of COVID vaccine. Diagnosis is made by exclusion of all other etiologies. Given significant population benefit from COVID-19 vaccination, physicians should continue to encourage vaccination while remaining vigilant of the very rare occurrence of myocarditis following COVID-19 vaccination.


Improving day and night sleep problems in infants by changing day time sleep rhythm: a single group before and after study.
This study explores the duration and timing of day time waking periods required for sleep disturbed infants to improve day and night sleep. Seventy-nine sleep disturbed outpatients with day and night sleep problems were investigated before and two weeks after a brief sleep intervention. Data were collected by interviewing parents on their infants' day and night sleep patterns. Besides instructing the parents on night sleep regulation, they were advised to regulate day sleep. After the intervention, duration of day and night sleep increased and frequency of night waking decreased. The mean duration of the first waking period in the morning did not change, but the range decreased. The mean duration of the last waking period in the evening increased. The frequency of short and irregular day naps and the need for assistance in falling asleep decreased after the intervention. It is recommended that the last waking before night sleep is lengthened to reduce day and night sleep problems.


Pharmacokinetic profiles of significant adverse events with crizotinib in Japanese patients with ABCB1 polymorphism.
Crizotinib is a standard treatment for advanced ALK-positive non-small-cell lung cancer (NSCLC). We undertook this study to investigate the pharmacokinetics of crizotinib and clinical and pharmacogenomic factors that may increase the risk of adverse events (AEs). We defined clinically significant AEs as grade 4 hematological toxicity, grade ≥3 non-hematological toxicity, and any grade of interstitial lung disease. Eight subjects with ALK-positive NSCLC scheduled to receive crizotinib 250 mg twice daily were studied. Six patients were female and two were male, and most of the patients had low body weight with a median body weight of 46.8 kg (range, 42.4-61.0 kg). All patients developed AEs, five developing six clinically significant AEs. Six patients required dose reduction. In pharmacokinetic analysis, blood samples were obtained on days 1 and 15. The mean area under the plasma concentration-time curve from 0-12 h (AUC0-12 ) on day 15 was significantly increased in patients with clinically significant AEs (n = 5) compared with those without (n = 3) (P = 0.04). Genetic polymorphisms of ABCB1 were analyzed. One patient with the ABCB1 1236TT-2677TT-3435TT genotype was an outlier, with an AUC0-12 and peak concentrations on day 15 of 2.84× and 2.61× the mean, respectively, compared with those with other genotypes. Our results suggest that some Japanese NSCLC patients treated with crizotinib developed clinically significant toxicities that were related to altered pharmacokinetics parameters due to genotype and body weight factors.


Intraosseous synovial sarcoma of the mandible: A case report and review of the literature.
Synovial sarcoma (SS) is a malignant soft tissue tumor that usually arises in the para-articular regions of the extremities. Only nine cases of SS in the mandible have been reported to date. The present study described a case of SS arising from the left mandible. A 54-year-old woman was referred to Kyushu University Hospital (Fukuoka, Japan) with a complaint of numbness in the left mental nerve area. Computed tomography revealed replacement of the left mandibular bone marrow with soft tissue and destruction of the mandibular canal. Magnetic resonance imaging revealed an isointense mass on T1-weighted images and hyperintensity on T2-weighted images. The tumor showed homogeneous enhancement. A biopsy was performed, and monophasic SS was diagnosed based on immunohistochemical staining features and genetic analysis. Hemimandible dissection and supraomophyoid neck resection were performed with fibular osteocutaneous flap reconstruction, followed by adjuvant chemotherapy. There was no evidence of recurrence or distant metastases. The present study also reviewed the clinical, imaging, histological, and immunohistochemical features of the SS in the mandible.


Pain management intervention targeting nursing staff and general practitioners: Pain intensity, consequences and clinical relevance for nursing home residents.
Although chronic pain is common in older adults, its treatment is frequently inappropriate. This problem is particularly prevalent in nursing home residents. We therefore developed an intervention to optimize pain management and evaluated its effects on pain intensity and pain interference with function in nursing home residents in Germany. In a cluster-randomized controlled intervention, 195 residents of 12 Berlin nursing homes who were affected by pain were surveyed at three points of measurement. A modified German version of the Brief Pain Inventory was used to assess pain sites, pain intensity and pain interference with function in various domains of life. The intervention consisted of separate training measures for nursing staff and treating physicians. The primary objective of reducing the mean pain intensity by 2 points was not achieved, partly because the mean pain intensity at baseline was relatively low. However, marginal reductions in pain were observed in the longitudinal assessment at 6-month follow up. The intervention and control groups differed significantly in the intensity sum score and in the domain of walking. Furthermore, the proportion of respondents with pain scores >0 on three pain intensity items decreased significantly. Given the multifocal nature of the pain experienced by nursing home residents, improving the pain situation of this vulnerable group is a major challenge. To achieve meaningful effects not only in pain intensity, but especially in pain interference with function, training measures for nursing staff and physicians need to be intensified, and long-term implementation appears necessary. Geriatr Gerontol Int 2017; 17: 1534-1543.


A team-based multidisciplinary approach to managing peripherally inserted central catheter complications in high-risk haematological patients: a prospective study.
Use of peripherally inserted central catheters (PICCs) has markedly increased during the last decade. However, there are few studies on use of PICCs in patients with haematological malignancies (HM) receiving intensive chemotherapy. Preliminary data suggest a higher rate of PICC-related complications in these high-risk patients. This prospective observational single-centre study aimed to investigate PICC-related complications after implementation of a multidisciplinary approach to PICC care and compared it with previous literature. A total of 44 PICCs were inserted in 36 patients (27.3%, thrombocytopenia <50 × 10(9)/L at insertion) over 5045 PICC days (median duration, 114.5 days). No major insertion-related complications were observed. Major late complications were obstruction in 13.6% (1.19/1000 PICC days) of patients, catheter-related bloodstream infection in 6.8% (0.59/1000 PICC days), and catheter-related thrombosis in 4.5% (0.39/1000 PICC days). Premature PICC removal occurred in 34% (2.97/1000 PICC days) of patients. The overall rate of potentially major dangerous complications was particularly low (11.36%, 0.99/1000 PICC days) compared with previous studies. This study highlights the utility of a multidisciplinary approach for PICC care in adults with HM receiving intensive chemotherapy. We provide further data to support use of PICCs in such patient populations.


Association of left ventricular mass with all-cause mortality, myocardial infarction and stroke.
Our aim was to assess the association of left ventricular mass with mortality and nonfatal cardiovascular events. Left ventricular mass was measured by echocardiography in 40138 adult patients (mean age 61.1 ± 16.4 years, 52.5% male). The primary endpoint was all-cause mortality. Secondary endpoints included nonfatal myocardial infarction and nonfatal stroke. During a mean follow-up period of 5.6 ± 3.9 years, 9181 patients died, 901 patients had a nonfatal myocardial infarction, and 2139 patients had a nonfatal stroke. Cumulative 10-year mortality was 26.8%, 31.9%, 37.4% and 46.4% in patients with normal, mildly, moderately and severely increased left ventricular mass, respectively (p<0.001). Ten-year rates of nonfatal myocardial infarction and stroke ranged from 3.2% and 6.7% in patients with normal left ventricular mass to 5.3% and 12.7% in those with severe increase in left ventricular mass, respectively. After multivariate adjustment, left ventricular mass remained an independent predictor of all-cause mortality (hazard ratio [HR] per 100 g increase 1.21, 95% confidence interval [CI] 1.14-1-27, p<0.001 in women, and HR 1.09, 95% CI 1.04-1-13, p<0.001 in men), myocardial infarction (HR 1.60, 95% CI 1.31-1.94, p<0.001 in women and HR 1.15, 95% CI 1.02-1.29, p=0.019 in men) and stroke (HR 1.26, 95% CI 1.13-1.40, p<0.001 in women and HR 1.19, 95% CI 1.09-1.30, p<0.001 in men). Left ventricular mass has a graded and independent association with all-cause mortality, myocardial infarction and stroke.


The impact of persistent social anxiety on social functioning and health-related quality of life in young people with remitted first-episode psychosis.
Comorbid social anxiety is common in psychotic disorders and is associated with multiple negative consequences. However, the long-term effects of persistent social anxiety versus fluctuating or no anxiety on social functioning and health-related quality of life (HR-QoL) have received scant attention. Therefore, we aimed to examine the prevalence of persistent social anxiety to determine its effect on social functioning and HR-QoL in first-episode psychosis (FEP). One hundred and eight individuals with remitted FEP were classified into three groups (persistent, fluctuating or no social anxiety) according to the Social Interaction Anxiety Scale over an 18-month follow-up period. The three groups were then compared at 18 months follow-up to assess the influence of social anxiety on social functioning and HR-QoL before and after controlling for confounders. Of the 108 individuals with FEP, 25 (23.1%) had persistent social anxiety. This group presented lower social functioning and HR-QoL levels compared to the groups with fluctuating or no anxiety symptoms. The effect on HR-QoL remained significant after controlling for positive psychotic and depressive symptoms. In this study, nearly one-quarter of young people with remitted FEP experienced persistent social anxiety symptoms, which had a negative impact on HR-QoL. Thus, individuals with persistent social anxiety constitute a highly vulnerable group and may require targeted interventions to improve their social functioning and HR-QoL.


Clinical superiority of a new nonionic contrast agent (iopamidol) for cardiac angiography.
The hemodynamic and electrophysiologic alterations induced by ionic contrast agents during cardiac angiography are well described. Recently nonionic contrast agents have become available for cardiac angiography. To evaluate the safety of these new agents, a double-blind randomized study was performed comparing a new nonionic agent (iopamidol) with a commonly used ionic contrast agent (Renografin-76). Eighty-one patients undergoing left ventriculography and coronary angiography were included; 41 received iopamidol and 40 received sodium meglumine diatrizoate (Renografin-76). After left ventriculography, there was a decrease in the arterial pressure with both contrast agents. However, the severity and the duration of hypotension were both significantly greater with Renografin-76 compared with the new nonionic agent (p less than 0.001). After selective injections of the coronary arteries, electrocardiographic analysis demonstrated that the increase in the QT interval (p less than 0.0002) and the changes in both the ST segment and T wave amplitude (p less than 0.001) were significantly greater in the Renografin-76 group compared with the iopamidol group. During coronary angiography, 8 of the 40 patients receiving Renografin-76 required temporary pacing for sinus pauses of 2.5 seconds or more, and 2 of the 40 also developed ventricular fibrillation. None of the 41 patients receiving iopamidol had these complications. This report demonstrates that the electrocardiographic changes, the severity and duration of hypotension and the incidence of serious arrhythmias are significantly greater with Renografin-76 than with iopamidol. Thus, this new nonionic agent appears to enhance the safety of cardiac angiography.


Integrating compound-specific stable isotope and enantiomer-specific analysis to characterize the isomeric and enantiomeric signatures of hexachlorocyclohexanes (HCHs) in paddy soils.
Organic pollutants in paddy fields may undergo different processes from those in dryland due to the anaerobic environment. The integrated use of compound-specific stable isotope analysis (CSIA) and enantiomer-specific analysis is a promising technique for understanding the behavior and fate of organic pollutants in soils. In this study, soil samples were collected from paddy fields in three major rice cultivation regions of China, spanning a transect of 4000 km. The mean concentrations of ƩHCHs in paddy soils from the Taihu Plain were the highest (1.44 ng/g). The ratios of α-HCH/β-HCH (all below 11.8) and α-HCH/γ-HCH (92% below 4.64), as well as the enantiomeric fractions (EFs) of chiral α-HCH (mean of 0.81), reflected that the distribution of HCHs was affected by the use of both technical HCHs and lindane. The preferential depletion of (-)-α-HCH and pronounced carbon isotope fractionation of α-HCH (δ13C of -28.22 ± 0.92‰ -23.63 ± 1.89‰) demonstrated its effective transformation. Factors such as altitude, soil temperature, soil pH, soil conductivity and soil organic matter significantly influenced the fate and transformation of HCHs. The current study highlights the integrated application of CSIA and enantiomer-specific analysis to provide multiple lines of evidence for the transformation of HCHs in soils.


Light-quality regulation of freezing tolerance in Arabidopsis thaliana.
To acquire freezing tolerance, higher plants require a period of low temperature (usually <4 degrees C) termed cold acclimation. Upon transfer of plants to low temperature, increased expression of the CRT/DRE binding factor (CBF) family of transcriptional activators leads to the upregulation of genes containing a C-repeat/drought-responsive (CRT/DRE) promoter element and metabolic changes that enhance tolerance to subzero temperatures. Here, we show that a low red to far-red ratio (R/FR) light signal increases CBF gene expression in Arabidopsis thaliana in a manner dependent on the circadian clock. This light quality-dependent increase in CBF expression is sufficient to confer freezing tolerance at temperatures higher than those required for cold acclimation. Furthermore, the use of light-quality signals to stimulate CBF expression has revealed ambient temperature-dependent coupling of CBF transcription factors to downstream COLD REGULATED (COR) genes, providing evidence for a second temperature-regulated step in this pathway.


Subcellular localization and capacity of beta-oxidation and aldehyde dehydrogenase in porcine liver.
Porcine hepatocyte organelles were separated by isopycnic sucrose gradient centrifugation from livers of 6-month-old Yorkshire pigs. The presence of a peroxisomal palmitoyl-CoA oxidizing system and a peroxisomal NAD:aldehyde dehydrogenase (ALDH) with high Km for acetaldehyde was demonstrated. Peroxisomal palmitate oxidizing capacity was found to be equal to that of the surviving mitochondria. The high Km isozyme of ALDH was mainly located in the mitochondria (54%), with a significant portion in the peroxisome (32%). Remaining activity is distributed among the microsomes (8.3%) and cytosol (4.6%). The low Km isozyme was confined almost exclusively to the mitochondria. ALDH may exist in the peroxisome as a detoxification mechanism and contribute to shorter half-lives of reactive aldehydes in the cell. Species differences are discussed.


Breast cancer incidence by age at discovery of mammographic abnormality in women participating in French organized screening campaigns.
Statistical modeling was already predicted the occurrence/prognosis of breast cancer from previous radiological findings. This study predicts the breast cancer risk by the age at discovery of mammographic abnormality in the French breast cancer screening program. This was a cohort study. The study included 261,083 women who meet the inclusion criteria: aged 50-74 years, living in French departments (Ain, Doubs, Haute-Saône, Jura, Territoire-de-Belfort, and Yonne), with at least two mammograms between January 1999 and December 2017, of which the first was 'normal/benign'. The incidence of each abnormality (microcalcifications, spiculated mass, obscured mass, architectural distortion, and asymmetric density) was first estimated, then the breast cancer risk was predicted secondly according to the age at discovery of each mammographic abnormality, using an actuarial life table and a Cox model. Overall breast cancer (6326 cases) incidence was 3.3 (3.0; 3.1)/1000 person-years. The breast cancer incidence increased proportionally with the discovery age of the speculated mass and microcalcifications. The incidence was twice as high when the spiculated mass age of discovery was ≥70 (12.2 [10.4; 14.4]) compared with age 50-54 years (5.8 [5.1; 6.7]). Depending on the spiculated mass discovery age, the breast cancer risk increased by at least 40% between the age groups 55-59 years (1.4 [1.0; 1.8]) and ≥70 years (2.4 [1.9; 3.3]). Whatever the abnormality, the incidence of breast cancer was higher when it was present in only one breast. The study highlights a stable incidence of breast cancer between successive mammograms, an increased risk of breast cancer with the finding age of spiculated mass and microcalcifications. The reduced delay between the abnormality discovery date and the breast cancer diagnosis date would justify a specific follow-up protocol after the finding of these two abnormalities.


Progressive Obstruction of Inferior Vena Cava by Ameroid Constrictor: The Canine Model of Revealing Hemodynamic and Compensatory Patterns of Tumor Thrombus Formation at the Renal Hilus Level.
Background: To develop an efficient and stable canine model of inferior vena cava (IVC) progressive obstruction at the renal hilus level. Methods: The model was established in two beagles by encircling an ameroid constrictor (AC) on the IVC at the renal hilus level. Abdominal wall varicosity and animal weight variations were observed weekly after operation. Ultrasound examination was performed weekly after surgery to observe the AC position, the diameter, and the velocity in the IVC. Six weeks after surgery, IVC angiography and CT scan were performed to observe the collateral circulation establishment and internal organ variation. Blood samples were taken regularly to monitor for variation in critical biochemical parameters. Renal biopsy was performed at 0, 2, 4, and 6 weeks after surgery. Results: Superficial varicose veins were observed on the abdominal wall at 2 weeks after surgery. Four weeks after operation, the IVC diameter increased by ∼30%, whereas the IVC velocity decreased by more than 50%. Collateral circulation was observed by IVC angiography at 6 weeks through multiple dilated veins along with neovascularization. CT scan showed congestive alteration in the kidney. The body weight, kidney, and liver function were not significantly affected. Chronic congestive renal injury was detected in the renal tubular epithelium by kidney biopsy after surgery. Conclusions: A canine model of IVC progressive obstruction at the renal hilus level was stably and safely established for the first time by using an AC, which may be helpful for preserving pivotal collateral circulation and nontumor-side kidney function in the IVC thrombus surgery.


Does overweight in infancy persist through the preschool years? An analysis of CDC Pediatric Nutrition Surveillance System data.
To determine whether overweight in infancy (0-11 months) and young childhood (12-35 months) persists through the preschool years. Analysis of longitudinal surveillance data for 380 518 low-income children monitored in the U.S. Pediatric Nutrition Surveillance System from birth to age 59 months. Overweight was defined as weight-for-height > or = 95th percentile. We determined the proportion of the children (overweight vs non-overweight) above or below the 95th percentile of weight-for-height at the later ages. The relative risk (RR) for overweight among overweight infants (vs non-overweight infants) at 1, 2, 3 and 4 years old was 4.3, 3.5, 3.3, and 2.9, respectively. 62.5% of overweight 3-year-old was still overweight a year later, but only 4.1% non-overweight 3-year-old became overweight a year later (RR = 15.2). However, low birth weight children had the highest RR to remain overweight after they became overweight compared to normal and high birth weight children. Overweight during infancy persists through the preschool years. Tracking of overweight appears to become stronger as children get older and is more pronounced among low birth weight children than normal or high birth weight children. Monitoring preschoolers' height and weight status should be a strategy for preventing of obesity in adolescence and adulthood.


Pediatric Allergic Contact Dermatitis: Lessons for Better Care.
Allergic contact dermatitis (ACD) is an immune-mediated condition that is likely underrecognized in children. ACD is the result of primary sensitization and secondary elicitation by allergy-provoking haptens. A detailed clinical history and physical examination may yield diagnosis. Patch testing is the criterion standard diagnostic tool for confirming the diagnosis of ACD in both children and adults. Herein, we present an overview of pediatric ACD, an analysis of relevant current literature on the topic, focused management recommendations, and a discussion of existing knowledge gaps that must be addressed by future research.


Potential role of JAK2 in cerebral vasospasm after experimental subarachnoid hemorrhage.
The Janus kinase (JAK) proteins are key regulators for transducing signals from the cell surface to the nucleus in response to cytokines to orchestrate the appropriate cellular response. Previous studies have demonstrated that JAK1 is activated in the basilar artery after subarachnoid hemorrhage (SAH), however it has not been investigated whether, and to what degree, JAK2 is induced by SAH and also the role of JAK2 in the pathogenesis of cerebral vasospasm following SAH remains unknown. Experiment 1 aimed to investigate the time-course of the JAK2 activation in the basilar artery after SAH. In Experiment 2, we chose the maximum time point of JAK2 activation and assessed the effect of AG490 (a specific JAK2 inhibitor) on regulation of cerebral vasospasm and endothelial apoptosis. All SAH animals were subjected to injection of autologous blood into cisterna magna twice on day 0 and day 2. As a result, the elevated expression of activated JAK2 was detected in the basilar artery after SAH and peaked on day 3. After AG490 intracisternal administration, the vasospasm was markedly aggravated and the apoptosis index of endothelial cells was also significantly increased in the basilar arteries. Anti-apoptotic genes such as bcl-2 and bcl-xL were down-regulated after the injections of AG490. Our results suggest that JAK2 is activated in the arterial wall after SAH, playing a beneficial role to vasospasm development, possibly through protecting endothelial cells and up-regulating anti-apoptotic genes.


High-intensity focused ultrasound in prostate cancer; a systematic literature review of the French Association of Urology.
We discuss the efficacy and safety of high-intensity focused ultrasound (HIFU) in patients with prostate cancer, to define the best indications for HIFU in daily clinical practice as primary therapy. We searched Medline and Embase for clinical studies evaluating the efficacy and safety of HIFU in prostate cancer (July 2007), and abstracts presented at the 2005-2007 annual meetings of the European Association of Urology and American Urological Association were screened. In all, 37 articles/abstracts were selected. As the data on HIFU as salvage therapy were limited, we focused on HIFU as primary therapy. Studies consisted of case series only. Included patients were approximately 70 years old with T1-T2 N0M0 disease, Gleason Score <or=7, a prostate-specific antigen (PSA) level of <or=28 ng/mL and a prostate volume of <or=40 mL. Negative biopsy rates with the Ablatherm device (EDAP TMS S.A., Vaulx-en-Velin, France) were 64-93%, and a PSA nadir of <or=0.5 ng/mL was achieved in 55-84% of patients. The 5-year actuarial disease-free survival rates were 60-70%. The most common complications were stress urinary incontinence, urinary tract infection, urethral/bladder neck stenosis or strictures, and erectile dysfunction. For the Ablatherm device, the rate of complications has been significantly reduced over the years, due to technical improvements in the device and the use of transurethral resection of the prostate before HIFU. In conclusion, HIFU as primary therapy for prostate cancer is indicated in older patients (>or=70 years) with T1-T2 N0M0 disease, a Gleason score of <7, a PSA level of <15 ng/mL and a prostate volume of <40 mL. In these patients HIFU achieves short-term cancer control, as shown by a high percentage of negative biopsies and significantly reduced PSA levels. The median-term survival data also seem promising, but long-term follow-up studies are needed to further evaluate cancer-specific and overall survival rates before the indications for primary therapy can be expanded.


Comparison of the effectiveness of anchoring needles and coils in localizing multiple nodules in the lung.
Recently, a new type of pulmonary nodule positioning needle has been adopted clinically. We aimed to evaluate the efficacy and safety of a new type of localization needles compared with coils for the simultaneous localization of multiple pulmonary nodules guided by computed tomography (CT) prior to video-assisted thoracoscopic surgery (VATS). From January 2021 to March 2022, 87 pulmonary nodules from 40 patients were localized using the new localization needle. From January 2020 to December 2020, 68 pulmonary nodules in 31 patients were localized using coils. The relative outcomes were compared. The success rate of pulmonary nodule localization in the needle group was 97.7% while that in the coil group was 98.5%. In the needle group, the time needed to locate the first nodule was significantly shorter than in the coil group (10.9 min vs. 17.2 min, P = 0.001). Moreover, the time needed per patient was also significantly shorter for the needle group compared with the coil group (23.7 min vs. 30 min, P = 0.017). The incidence of pneumothorax in the needle group was 25.0% vs. 12.9% in the coil group (P = 0.204). The rate of pulmonary hemorrhage in the needle group was 40.0% vs. 32.3% in the coil group (P = 0.502). The success rate of VATS wedge resection was 100% in both groups. Both disposable pulmonary nodule localization needles and coils are safe and effective for CT-guided localization of multiple pulmonary nodules of the same stage prior to VATS. However, the use of needles is time-saving compared with the use of coils. The coil localization may exhibit better safety than needle localization.


Presence and axonal transport of cholinoceptor, but not adrenoceptor sites on a cat noradrenergic neurone.
1. Noradrenaline release and radioligand binding studies were carried out in the cat hypogastric nerve ligated in vito 2 cm distal to the inferior mesenteric ganglion for different time periods, and in different effector organs.2. Large quantities of noradrenaline and dopamine beta-hydroxylase (DBH) accumulated in the segments of nerve immediately proximal (P(1)) and distal (D(1)) to the ligation, with rates of about 100 and 25 mm/24 hr for the orthograde and retrograde transport, respectively.3. Nicotine evoked the release of noradrenaline from P(1) and atrial slices; the secretory response to nicotine was completely antagonized by mecamylamine. [(3)H]alpha-bungarotoxin biding to membranes from P(1) allowed the estimation of a K(D) of 2.97 nm and a B(max) of 1639 f-mole/mg protein.4. Acetylcholine inhibited the release of endogenous noradrenaline evoked by high K(+) stimulation in atrial slices, but not in P(1) segments. Similarly, carbachol decreased [(3)H]noradrenaline release induced by electrical stimulation (twenty-six shocks, 2 Hz, 5 msec) in the atrium but not in P(1).5. [(3)H]Quinuclydinilbenzylate ([(3)H]QNB) specifically binds to membranes from P(1) and vas deferens, following a saturation curve. In the case of P(1) segments taken 48 hr after ligation a K(D) of 0.35 nm and a B(max) of 129 f-mole/mg protein were found.6. The fact that the B(max) in P(1) and D(1) increased with the time of ligation suggests that orthograde and retrograde axonal transports of muscarinic binding sites exist in this nerve, with approximate rates of transport of 15 and 8 mm/24 hr, respectively.7. As far as adrenoceptors are concerned, we observed that yohimbine or phentholamine did not modify transmitter release from P(1), evoked by high K(+) or electrical stimulation. However, yohimbine enhanced the release of [(3)H]noradrenaline induced by electrical stimulation from splenic slices of the same animals.8. [(3)H]Clonidine, [(3)H]dihydroergocryptine or [(3)H]dihydroalprenolol ([(3)H]DHA) did not specifically bind to membranes from P(1), in spite of the fact that they showed typical saturation curves for specific binding in cortex and atrial membranes from the same cats.9. In conclusion, these data (a) further show that the ligated hypogastric nerve is a good model of noradrenergic nerve terminal free of effector cell; (b) provide direct evidence for the neural location of nicotinic receptors whose activation trigger noradrenaline release from noradrenergic neurones; (c) demonstrate the neural location and axonal transport of muscarinic receptor sites, but leave certain doubts about its functional role in this noradrenergic neurone; and (d) do not support the hypothesis that alpha and beta-adrenoceptors which modulate noradrenaline release from peripheral noradrenergic nerve terminals are neurally (or prejunctionally) located.


Quantitative PCR for glucose transporter and tristetraprolin family gene expression in cultured mouse adipocytes and macrophages.
Quantitative real-time PCR (qPCR) such as TaqMan and SYBR Green qPCR are widely used for gene expression analysis. The drawbacks of SYBR Green assay are that the dye binds to any double-stranded DNA which can generate false-positive signals and that the length of the amplicon affects the intensity of the amplification. Previous results demonstrate that TaqMan assay is more sensitive but generates lower calculated expression levels than SYBR Green assay in quantifying seven mRNAs in tung tree tissues. The objective of this study is to expand the analysis using animal cells. We compared both qPCR assays for quantifying 24 mRNAs including those coding for glucose transporter (Glut) and mRNA-binding protein tristetraprolin (TTP) in mouse 3T3-L1 adipocytes and RAW264.7 macrophages. The results showed that SYBR Green and TaqMan qPCR were reliable for quantitative gene expression in animal cells. This result was supported by validation analysis of Glut and TTP family gene expression. However, SYBR Green qPCR overestimated the expression levels in most of the genes tested. Finally, both qPCR instruments (Bio-Rad's CFX96 real-time system and Applied Biosystems' Prism 7700 real-time PCR instrument) generated similar gene expression profiles in the mouse cells. These results support the conclusion that both qPCR assays (TaqMan and SYBR Green qPCR) and both qPCR instruments (Bio-Rad's CFX96 real-time system and Applied Biosystems' Prism 7700 real-time PCR instrument) are reliable for quantitative gene expression analyses in animal cells but SYBR Green qPCR generally overestimates gene expression levels than TaqMan qPCR.


Bolus pharmacokinetics: moving beyond mass-based dosing to guide drug administration.
Despite the common approach of bolus drug dosing using a patient's mass, a more tailored approach would be to use empirically derived pharmacokinetic models. Previously, this could only be possible though the use of computer simulation using programs which are rarely available in clinical practice. Through mathematical manipulations and approximations, a simplified set of equations is demonstrated that can identify a bolus dose required to achieve a specified target effect site concentration. The proposed solution is compared against simulations of a wide variety of pharmacokinetic models. This set of equations provides a near-identical solution to the simulation approach. A boundary condition is established to ensure the derived equations have an acceptable error. This approach may allow for more precise administration of medications with the use of point of care technology and potentially allows for pharmacokinetic dosing in artificial intelligence problems.


Potential use of barks of woody vascular plants in bone mending: A review.
The use of synthetic drugs to overcome bone ailments causes severe side effects, but the application of herbals is helpful in maintaining bone health and accelerating bone mending. Currently, there is no oral allopathic medicine to hasten bone healing, though folk and traditional practices have adopted herbal to fasten the recovery from bone ailments. Earliest recovery is a universally desired phenomenon, especially for elderly people where many more cases of traumatic injuries are common along the compromised body immunity. The computerized database search engines, such as Google Scholar, PubMed, ScienceDirect, Springer Link, etc., and textbooks were used to collect all relevant information about barks for bone mending activity published from 1990 onwards using certain keywords such as bark, folklore/ traditional bone healing practices, and phytopharmacology. The results obtained were compiled to make this review and related information is tabulated herewith. Traditional herbal bone healing exists in every society in the world. The plant barks of a few species (e.g., Ficus religiosa, Prunus cerasoides, Terminalia arjuna, etc.) have outstanding significance for bone healing because of their special chemical composition and novel properties to reduce swelling, pain, soreness, and speedy recovery of functions. Mostly bark extracts are rich in polyphenols, and minerals, represented with antioxidant, immunostimulatory, antibacterial properties, etc. There is a diversity of bark utilization for bone healing from different plant species, globally, of which only a few have been phytopharmacologically deciphered. Validated bark ingredients as medicine or food supplements are more useful due to the least side effects. Entrepreneurs have a scope to use bioactive obtained from plant barks that have not been scientifically screened till now. The research focused on the commercial application of plant barks as green medicine needs fingerprints of bioactive and clinically validated data including the concentration of biomarkers in the blood (IC50) for reducing the healing period. Phytopharmacological screening of barks used in folk medicine and synthesizing the therapeutics at mega quantities in industries is an array of hopes for sustainable utilization of natural resources. The bio-stimulating knowledge of certain herbal ingredients will be helpful in the development of synergistic formulations for rapid bone mending.


Classics revisited: Dietrich Starck on comparative embryology and placentation.
Dietrich Starck (1908-2001) was a German embryologist who wrote extensive reviews on comparative placentation. Starck's embryology textbook and his comprehensive review of comparative embryology and placentation give excellent insights into the foundational literature and are extensively referenced. The many original illustrations include placentas from species that are not well described elsewhere. These resources are especially valuable as a portal to the early literature on comparative placentation.


New high O2 carrying perfluorochemical emulsions: toxicity, radiosensitivity of GM-CFC and development of metastases in mice.
The effects of two new concentrated perfluorochemical emulsions based on F-66E and PFOB, which carry significantly more oxygen than Fluosol-DA 20%, were tested on normal tissues (toxicity and radiation response) and on the development of metastases from Lewis Lung Carcinoma (3LL) in female C57 BL/6 mice. Twenty one days after injection of F-66E or PFOB emulsions (15 ml/kg body weight), the spleen and liver weights were significantly increased but had returned to normal after 2-3 months. Splenomegaly already observed in 3LL bearing mice was significantly increased by F-66E emulsion injection. The radiosensitivity of GM-CFC was not altered when unanesthetized GM-CFC was not altered when unanesthetized mice were pretreated with F-66E emulsions and/or carbogen 1 hr prior to and during irradiation. The rate of tumor take and the period before detection of tumors were not modified when an emulsion of F-66E was injected simultaneously or 10 days after 3LL cells. Mean survival of mice, and the number of metastases on lung surfaces were similar in F-66E injected mice and control mice.


Interplay between C1-inhibitor and group IIA secreted phospholipase A2 impairs their respective function.
High levels of human group IIA secreted phospholipase A2 (hGIIA) have been associated with various inflammatory disease conditions. We have recently shown that hGIIA activity and concentration are increased in the plasma of patients with hereditary angioedema due to C1-inhibitor deficiency (C1-INH-HAE) and negatively correlate with C1-INH plasma activity. In this study, we analyzed whether the presence of both hGIIA and C1-INH impairs their respective function on immune cells. hGIIA, but not recombinant and plasma-derived C1-INH, stimulates the production of IL-6, CXCL8, and TNF-α from peripheral blood mononuclear cells (PBMCs). PBMC activation mediated by hGIIA is blocked by RO032107A, a specific hGIIA inhibitor. Interestingly, C1-INH inhibits the hGIIA-induced production of IL-6, TNF-α, and CXCL8, while it does not affect hGIIA enzymatic activity. On the other hand, hGIIA reduces the capacity of C1-INH at inhibiting C1-esterase activity. Spectroscopic and molecular docking studies suggest a possible interaction between hGIIA and C1-INH but further experiments are needed to confirm this hypothesis. Together, these results provide evidence for a new interplay between hGIIA and C1-INH, which may be important in the pathophysiology of hereditary angioedema.


Theory of planned behavior and intention to exercise: effects of setting.
To explore whether setting type (structured versus unstructured) might moderate the relationship between specific theory of planned behavior (TPB) constructs and exercise intention. It was hypothesized that perceived behavioral control (PBC) would predict intention only in an unstructured setting. Students (N=122) completed a questionnaire that assessed TPB constructs and exercise intention for a structured (sign up) or unstructured setting (no sign up). Simple slopes analysis of the significant interaction revealed PBC was a predictor of intention only in the unstructured setting. This provides support for the suggestion that the effect of PBC on exercise intention would be moderated by setting.


Membrane protein thiol cross-linking associated with the permeabilization of the inner mitochondrial membrane by Ca2+ plus prooxidants.
In a previous report (Macedo, D.V., Ferraz, V. L., Pereira-da-Silva, L., and Vercesi, A. E. (1988) in Integration of Mitochondrial Functions (Lemasters, J. J., et al., eds) pp. 535-542, Plenum Publishing Corp., New York), we proposed that the alterations in the inner mitochondrial membrane permeability caused by Ca2+ plus prooxidants could be the consequence of membrane protein sulfhydryl-disulfide transitions. In this study, we show that Ca2+ plus diamide, a thiol oxidant, significantly decrease the ability of beef heart submitochondrial particles to build up and sustain a membrane potential generated by succinate oxidation. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of solubilized membrane proteins indicates that these effects on the membrane potential are associated with the production of protein aggregates due to thiol cross-linking. Evidence is also presented that these protein aggregates can be produced in mitoplasts previously loaded with Ca2+ and that this is potentiated by the presence of either diamide or t-butylhydroperoxide. Furthermore, dithiothreitol, a disulfide reductant, was found to be much more effective than NAD(P)+ reductants in reversing Ca2+ efflux induced by prooxidants. It is concluded that the perturbation of the inner mitochondrial membrane caused by Ca2+ plus prooxidants is associated with protein polymerization due to thiol cross-linking, resulting in the production of high molecular mass protein aggregates.


Transarterial embolization for hepatocellular carcinoma. Antibiotic prophylaxis and clinical meaning of postembolization fever.
The aim of this prospective randomized controlled trial was to investigate the need for prophylactic antibiotherapy in patients with cirrhosis and hepatocellular carcinoma who underwent transarterial embolization and to establish the parameters that determine the development of fever > 38 degrees C after this procedure. Sixty-one consecutive patients with cirrhosis undergoing 75 procedures were randomized into Group I [(n = 37) allocated to receive prophylactic antibiotics (Cefotaxime + Metronidazole)] and Group II [(n = 38) allocated to receive no antibiotic treatment]. Twelve of the 37 patients (32%) in Group I and 13 of the 38 patients (34%) in Group II developed fever > 38 degrees C after treatment. However, none of them developed bacterial infection, and all biological fluid cultures were negative. A logistic regression analysis disclosed that the obtention of an extensive tumor necrosis was the unique parameter independently associated with the development of fever. Antibiotic prophylaxis is therefore not necessary in patients with cirrhosis and hepatocellular carcinoma undergoing transarterial embolization. The appearance of fever after this procedure does not indicate bacterial infection; it rather represents a clinical marker of extensive tumor necrosis and thus of a favorable response to treatment.


Techniques for hazard analysis and their use at CERN.
CERN, The European Organisation for Nuclear Research is situated near Geneva and has its accelerators and experimental facilities astride the Swiss and French frontiers attracting physicists from all over the world to this unique laboratory. The main accelerator is situated in a 27 km underground ring and the experiments take place in huge underground caverns in order to detect the fragments resulting from the collision of subatomic particles at speeds approaching that of light. These detectors contain many hundreds of tons of flammable materials, mainly plastics in cables and structural components, flammable gases in the detectors themselves, and cryogenic fluids such as helium and argon. The experiments consume high amounts of electrical power, thus the dangers involved have necessitated the use of analytical techniques to identify the hazards and quantify the risks to personnel and the infrastructure. The techniques described in the paper have been developed in the process industries where they have been to be of great value. They have been successfully applied to CERN industrial and experimental installations and, in some cases, have been instrumental in changing the philosophy of the experimentalists and their detectors.


Effects of arsenic disulfide on proliferation, cytokine production, and frequencies of CD4(+), CD8(+), and regulatory T cells in mitogen-activated human peripheral blood mononuclear cells.
Influence of arsenic disulfide (As2S2) on human immune cells has little been investigated. Effects of As2S2 on proliferation, cytokine production, and frequencies of CD4(+) T, CD8(+) T and CD4(+)CD25(+)Foxp3(+) regulatory T cells in mitogen-activated human peripheral blood mononuclear cells were examined. Anti-proliferative effects of As2S2 on peripheral blood mononuclear cells activated by T-cell mitogen were assessed by a colorimetric assay. Cytokine concentrations in the culture medium were measured with beads-array procedures followed by flow cytometry. CD4(+) T cells, CD8(+) T cells and CD4(+)CD25(+)Foxp3(+) regulatory T cells were stained with fluorescence-labeled specific antibodies followed by flow cytometry analysis. As2S2 at 1-10μM significantly suppressed mitogen-activated proliferation of peripheral blood mononuclear cells (p<0.05). As2S2 at 10μM inhibited production of IL-6, -10, -17A, tumor necrosis factor-α, and interferon-γ from the activated peripheral blood mononuclear cells, though the effects were not statistically significant. As2S2 at 10μM significantly suppressed the frequencies of CD4(+) T and CD8(+) T cells (p<0.05), whereas significantly enhanced the frequency of CD4(+)CD25(+)Foxp3(+) regulatory T cells (p<0.05). The data suggest that As2S2 attenuates T cell-mediated immunity by not only suppressing the proliferation of T cells and cytokine release but also increasing the frequency of regulatory T cells. T cell-mediated autoimmunity contributes to bone marrow failure in myelodysplastic syndrome (MDS), and thus the above As2S2 effects are beneficial for the treatment of MDS patients.


LINC00689 induces gastric cancer progression via modulating the miR-338-3p/HOXA3 axis.
LINC00689 acts one critical regulatory role in several tumors. However, the functional, regulatory mechanism and expression of LINC00689 remains unknown in gastric cancer. LINC00689 and miR-338-3p levels were determined using a quantitative reverse transcriptase-polymerase chain reaction analysis and an enzyme-linked immunoassay and a cell-counting kit-8 assay were utilized to detect interleukin (IL)-8, IL-6 and IL-1β expression and cell proliferation, respectively. We found that LINC00689 and HOXA3 are overexpressed and miR-338-3p is decreased in gastric cancer cells. Compared to control specimens, LINC00689 is overexpressed in gastric cancer specimens and the level of LINC00689 was up-regulated in 32 cases (32/40; 80.0%) compared to control samples. LINC00689 increased cell growth, epithelial-mesenchymal transition (EMT) development and secretion of inflammatory factors in gastric cancer. Compared to control specimens, miR-338-3p expression was decreased in gastric cancer specimens and a Pearson's correlation assay revealed that miR-338-3p was negatively correlated with LINC00689 expression in gastric cancer specimens. HOXA3 was identified as one target gene of miR-338-3p and Ectopic expression of LINC00689 suppressed miR-338-3p and enhanced HOXA3 expression in HGC-27 cells. LINC00689 enhanced cell growth, EMT development and secretion of inflammatory factors by promoting HOXA3. LINC00689 may present a potential future target for gastric cancer treatment.


S[+] Apomorphine is a CNS penetrating activator of the Nrf2-ARE pathway with activity in mouse and patient fibroblast models of amyotrophic lateral sclerosis.
Compelling evidence indicates that oxidative stress contributes to motor neuron injury in amyotrophic lateral sclerosis (ALS), but antioxidant therapies have not yet achieved therapeutic benefit in the clinic. The nuclear erythroid 2-related-factor 2 (Nrf2) transcription factor is a key regulator of an important neuroprotective response by driving the expression of multiple cytoprotective genes via its interaction with the antioxidant response element (ARE). Dysregulation of the Nrf2-ARE system has been identified in ALS models and human disease. Taking the Nrf2-ARE pathway as an attractive therapeutic target for neuroprotection in ALS, we aimed to identify CNS penetrating, small molecule activators of Nrf2-mediated transcription in a library of 2000 drugs and natural products. Compounds were screened extensively for Nrf2 activation, and antioxidant and neuroprotective properties in vitro. S[+]-Apomorphine, a receptor-inactive enantiomer of the clinically approved dopamine-receptor agonist (R[-]-apomorphine), was identified as a nontoxic Nrf2 activating molecule. In vivo S[+]-apomorphine demonstrated CNS penetrance, Nrf2 induction, and significant attenuation of motor dysfunction in the SOD1(G93A) transgenic mouse model of ALS. S[+]-apomorphine also reduced pathological oxidative stress and improved survival following an oxidative insult in fibroblasts from ALS patients. This molecule emerges as a promising candidate for evaluation as a potential neuroprotective agent in ALS patients in the clinic.


Dual-Cross-Linked Supramolecular Polysiloxanes for Mechanically Tunable, Damage-Healable and Oil-Repellent Polymeric Coatings.
Polymeric coatings that show tunable mechanical strength, healing ability of mechanical damage, and proper liquid repellency will be promising in various areas across life and industry. However, the exploitation of such coating materials is largely limited by their molecular design. In this work, polymeric coatings with ion-controlled mechanics and coloration and damage-healing and oil-sliding properties have been demonstrated based on a supramolecular design of dual-cross-linked polysiloxanes. The coating color and mechanical properties can be adjusted by coordinative metal ions with various metal-ligand binding abilities. Dense and dynamic hydrogen bonds and coordination bonds lead to the ready healing ability and high durability of the coating. The extreme smoothness of the flat silicone coating facilitates not only the sliding of impinging oil but also the restoration of topological integrity from mechanical damage. The coating can be selectively patterned and applied to large-scale substrates by diverse coating operations, making it feasible for versatile applications.


L-leucine, L-methionine, and L-phenylalanine share a Na(+)/K (+)-dependent amino acid transporter in shrimp hepatopancreas.
Hepatopancreatic brush border membrane vesicles (BBMV), made from Atlantic White shrimp (Litopenaeus setiferus), were used to characterize the transport properties of (3)H-L-leucine influx by these membrane systems and how other essential amino acids and the cations, sodium and potassium, interact with this transport system. (3)H-L-leucine uptake by BBMV was pH-sensitive and occurred against transient transmembrane concentration gradients in both Na(+)- and K(+)-containing incubation media, suggesting that either cation was capable of providing a driving force for amino acid accumulation. (3)H-L-leucine uptake in NaCl or KCl media were each three times greater in acidic pH (pH 5.5) than in alkaline pH (pH 8.5). The essential amino acid, L-methionine, at 20 mM significantly (p < 0.0001) inhibited the 2-min uptakes of 1 mM (3)H-L-leucine in both Na(+)- and K(+)-containing incubation media. The residual (3)H-L-leucine uptake in the two media were significantly greater than zero (p < 0.001), but not significantly different from each other (p > 0.05) and may represent an L-methionine- and cation-independent transport system. (3)H-L-leucine influxes in both NaCl and KCl incubation media were hyperbolic functions of [L-leucine], following the carrier-mediated Michaelis-Menten equation. In NaCl, (3)H-L-leucine influx displayed a low apparent K M (high affinity) and low apparent J max, while in KCl the transport exhibited a high apparent K M (low affinity) and high apparent J max. L-methionine or L-phenylalanine (7 and 20 mM) were competitive inhibitors of (3)H-L-leucine influxes in both NaCl and KCl media, producing a significant (p < 0.01) increase in (3)H-L-leucine influx K M, but no significant response in (3)H-L-leucine influx J max. Potassium was a competitive inhibitor of sodium co-transport with (3)H-L-leucine, significantly (p < 0.01) increasing (3)H-L-leucine influx K M in the presence of sodium, but having negligible effect on (3)H-L-leucine influx J max in the same medium. These results suggest that shrimp BBMV transport (3)H-L-leucine by a single L-methionine- and L-phenylalanine-shared carrier system that is enhanced by acidic pH and can be stimulated by either Na(+) or K(+) acting as co-transport drivers binding to shared activator sites.


Pyrite and sulfur-coupled autotrophic denitrification system for efficient nitrate and phosphate removal.
The inefficiency of nitrogen removal in pyrite autotrophic denitrification (PAD) and the low efficiency of PO43--P removal in sulfur autotrophic denitrification (SAD) limit their potential for engineering applications. This study examined the use of pyrite and sulfur coupled autotrophic denitrification (PSAD) in batch and column experiments to remove NO3--N and PO43--P from sewage. The effluent concentration of NO3--N was 0.32 ± 0.11 mg/L, with an average Total nitrogen (TN) removal efficiency of 99.14%. The highest PO43--P removal efficiency was 100% on day 18. There was a significant correlation between pH and the efficiency of PO43--P removal. Thiobacillus, Thiomonas and Thermomonas were found to be dominant at the bacterial genus level in PSAD. Additionally, the abundance of Thermomonas in the PSAD was greater than that observed in the SAD reactor. This result indirectly indicates that the PSAD system has more advantages in reducing N2O.


Standardizing dosimetry in esophageal PDT: an argument for use of centering devices and removal of misleading units.
A simple standardization of esophageal photodynamic therapy light dosimetry is proposed. Calculations of the effect on local treatment dose of using non-centered diffusing fibers have been made and the methods of calculating light energy dose to the treatment area within a centering balloon are discussed. A requirement for centering devices and standard units of Joules per cm(2) of treatment area are indicated.


Flap endonuclease-1 rs174538 G>A polymorphisms are associated with the risk of esophageal cancer in a Chinese population.
Esophageal cancer has a high mortality rate, particularly in Asia, and there are obvious racial differences in regard to incidence. The purpose of our study was to assess the genetic susceptibility of functional single nucleotide polymorphisms in flap endonuclease-1 (FEN1) in esophageal squamous cell carcinoma ESCC. Clinical blood samples of 629 ESCC cases and 686 control samples were collected. The ligation detection reaction method was used to determine FEN 1 rs174538 G>A genotypes. A significantly decreased risk of ESCC was associated with FEN1 rs174538 GA genotypes among patients under 63 years old. Our results suggest that functional polymorphism FEN1 rs174538 G>A might affect personal susceptibility to ESCC. This result provides a solid theoretical foundation for further clinical study using larger sample sizes.


National Cooperative Crohn's Disease Study: extraintestinal manifestations and perianal complications.
Among 569 patients with Crohn's disease, 24% had a history of at least one extraintestinal manifestation and 36% had a history of perianal disease before randomization. Multiple extraintestinal manifestations occurred in the same patient more frequently than would be expected by chance. Seventy-six percent of patients with ileocolitis had perianal disease, extraintestinal manifestations, or both. This was significantly greater than the 58% incidence in patients with disease confined to the small bowel. Perianal complications alone were significantly more common in patients with colitis or ileocolitis than in those with disease of only the small bowel. This was true also of internal fistulization. There was a significant positive association between perianal disease and the presence of extraintestinal features. Perianal abscess appeared to respond to sulfasalazine and anal fissure to prednisone or azathioprine. These results require confirmation in larger series of patients.


The Effects of APP-Based Intervention for Depression Among Community-Dwelling Individuals With Spinal Cord Injury: A Randomized Controlled Trial.
To assess the effect of a self-management intervention delivered by mobile application (APP) for depression among community-dwelling individuals with spinal cord injury (SCI). Randomized controlled trial. General communities in China. Community-dwelling individuals with SCI who were diagnosed within 2 years were recruited in this study (N=98). It was a convenience sample with an average age of 41.71, 82.7% participants were men. Participants in the intervention group (n=49) received 5 sessions on self-management training provided by nurse-led multidisciplinary team via APP at the second, fourth, sixth, eighth, and 12th weeks, respectively, after they discharge from hospitals. Participants in the control group (n=49) received routine telephone counselling provided by follow-up nurses at the 12th week after they discharge. The outcome of this study is depression, which is not the primary outcomes in the registration of this program. Depression was measured by version 2 of Beck Depression Inventory at discharge (T0), the 12th week after discharge from hospitals (T1), and the 24th week after discharge from hospitals (T2). There were 98 participants (49 in the intervention group and 49 in the control group) completing the intervention and data collection. Compared with the control group, the intervention group had lower level of depression at T2 (B=-5.76; 95% CI=-9.97, -1.54; P=.007). Small to moderate effect sizes on depression favoring the intervention were demonstrated at T1 (Cohen's d=-.178) and T2 (Cohen's d=-.535). APP-based self-management support can be a potential intervention to reduce depression among community-dwelling individuals with SCI.


Development and validation of a high performance liquid chromatography assay for 17alpha-methyltestosterone in fish feed.
17alpha-Methyltestosterone (MT) is used to manipulate the gender of a variety of fish species. A high performance liquid chromatography (HPLC) internal standard method for the determination of 17alpha-methyltestosterone in fish feed using 3beta-methoxy-17beta-hydroxyandrost-5-en-7-one as internal standard (IS) has been developed. The method has been validated for the quantitation of MT in fish feed using 245 nm UV absorbance as the parent wavelength and 255 nm as a qualifier wavelength. The method was validated in the concentration range of 15.0-120 mg/kg of 17alpha-methyltestosterone in fish feed. Method was also found to be suitable for other feeds.


Relationships between urinary inositol excretions and whole-body glucose tolerance and skeletal muscle insulin receptor phosphorylation.
This study assessed the relationships of urinary D-chiro-inositol and myo-inositol excretions to indices of whole-body glucose tolerance and total content and tyrosine phosphorylation of the insulin receptor (activation) in skeletal muscle of older nondiabetic subjects. Fifteen adults (age, 65 +/- 8 years; body mass index, 27.9 +/- 3.3 kg/m(2) [mean +/- SD]) completed duplicate assessments of oral (75-g oral glucose tolerance test [OGTT]) and intravenous (300 mg/kg body weight intravenous glucose tolerance test) glucose tolerance challenges and 24-hour urinary D-chiro-inositol and myo-inositol excretions. Skeletal muscle (vastus lateralis) biopsies were obtained at minute 60 of the OGTTs. Subjects with higher urinary D-chiro-inositol excretion had higher insulin (rho = 0.51, P < or = .05) and C-peptide (rho = 0.56, P < or = .05) area under the curves, and lower insulin sensitivity index (rho = -0.60, P < or = .05) during the intravenous glucose tolerance test. The urinary myo- to D-chiro-inositol ratio was also inversely related to insulin area under the curve (rho = -0.59, P < or = .05). Urinary D-chiro-inositol (rho = -0.60, P < or = .05) and myo-inositol (rho = -0.60, P < or = .05) were inversely related to tyrosine phosphorylation of the insulin receptor (phosphotyrosine 1162/1163), but not total content of the insulin receptor during the OGTT. The apparent relationships were modestly weakened when adjustments were made for sex. These findings support previous research linking higher urinary D-chiro-inositol excretion with a progressive decline in whole-body glucose tolerance. This is the first report to link higher urinary D-chiro-inositol excretion to a blunted activation of skeletal muscle insulin receptor signaling in older nondiabetic subjects.


Modelling changes in clinical attachment loss to classify periodontal disease progression.
The goal of this study was to identify progressing periodontal sites by applying linear mixed models (LMM) to longitudinal measurements of clinical attachment loss (CAL). Ninety-three periodontally healthy and 236 periodontitis subjects had their CAL measured bi-monthly for 12 months. The proportions of sites demonstrating increases in CAL from baseline above specified thresholds were calculated for each visit. The proportions of sites reversing from the progressing state were also computed. LMM were fitted for each tooth site and the predicted CAL levels used to categorize sites regarding progression or regression. The threshold for progression was established based on the model-estimated error in predictions. Over 12 months, 21.2%, 2.8% and 0.3% of sites progressed, according to thresholds of 1, 2 and 3 mm of CAL increase. However, on average, 42.0%, 64.4% and 77.7% of progressing sites for the different thresholds reversed in subsequent visits. Conversely, 97.1%, 76.9% and 23.1% of sites classified as progressing using LMM had observed CAL increases above 1, 2 and 3 mm after 12 months, whereas mean rates of reversal were 10.6%, 30.2% and 53.0% respectively. LMM accounted for several sources of error in longitudinal CAL measurement, providing an improved method for classifying progressing sites.


[Comparative analysis of proteins in seminal plasma of non-obstructive azoospermia patients and healthy fertile males].
To analyse protein alterations in the seminal plasma of non-obstructive azoospermia patients. Semen samples were collected from 11 healthy fertile and 6 azoospermia male volunteers respectively and tested by SELDI-TOF-MS with CM10 protein chip to get protein spectra maps, which were automatically treated with the special softwares of Ciphergen Inc. The mean peak heights of 28 proteins expressed in the seminal plasma of the azoospermia patients were statistically different from those of the healthy fertile males (P < 0.05 ), of which 24 were of lower contents than in the normal controls, 4 with remarkably significant difference, M/Z 7 196.058, 7 630.573, 7 547.610 and 7 709.833 (P < 0.01). The seminal plasma proteins of the azoospermia patients were significantly different from those of the healthy fertile males, with decreased contents of most of the different proteins, which might be significantly correlated with the development of azoospermia.


Mutagenic DNA repair in Escherichia coli. XVI. Mutagenesis by ultraviolet light plus delayed photoreversal in recA strains.
Mutagenesis was demonstrable after delayed photoreversal of UV-irradiated strains carrying a recA deletion indicating that RecA protein is not essential for the misincorporation process that is revealed by delayed photoreversal. Moreover, the data suggest that RecA protein actually depresses misincorporation to varying extents depending on the recA allele. No delayed photoreversal was demonstrable in reA1 or recA56 bacteria unless the lexA102(ind-) allele was also present. It is suggested that the level of these RecA proteins may be lower in the lexA102(ind-) strains thus minimising their depressive effect. Delayed photoreversal mutagenesis in strains carrying the recA441 allele was not affected by either adenine or guanosine plus cytidine, substances which affect the proteolytic activity of RecA441 protein.


Transport and biological activities of bile acids.
Bile acids have emerged as important biological molecules that support the solubilization of various lipids and lipid-soluble compounds in the gut, and the regulation of gene expression and cellular function. Bile acids are synthesized from cholesterol in the liver and eventually released into the small intestine. The majority of bile acids are recovered in the distal end of the small intestine and then returned to the liver for reuse. The components of the mechanism responsible for the recycling of bile acids within the enterohepatic circulation have been identified whereas the mechanism for intracellular transport is less understood. Recently, the ileal lipid binding protein (ILBP; human gene symbol FABP6) was shown to be needed for the efficient transport of bile acids from the apical side to the basolateral side of enterocytes in the distal intestine. This review presents an overview of the transport of bile acids between the liver and the gut as well as within hepatocytes and enterocytes. A variety of pathologies is associated with the malfunction of the bile acid transport system.


The effects of cephem antibiotics and related compounds on the aldehyde dehydrogenase in rat liver mitochondria.
The effects of cephem antibiotics and their related compounds on aldehyde dehydrogenase obtained from rat liver mitochondria were studied. A pH of 8.8 and reaction temperature 24 degrees were the conditions for measurement of enzyme activity. The apparent Michaelis constant Km values for NAD, acetaldehyde and propionaldehyde were 3.8 X 10(-5) M, 4.0 X 10(-5) M and 2.5 X 10(-5) M, respectively. Cefamandole, cefoperazone and cefmetazole, having a 1-methyl-5-thiotetrazol group at position 3 of the cephem ring, caused a relatively potent inhibition of aldehyde dehydrogenase. Cefmetazole and cefoperazone also showed a significant inhibition on highly purified yeast aldehyde dehydrogenase; the extent of inhibition on yeast enzyme was almost the same as that on rat mitochondrial aldehyde dehydrogenase. The decrease in enzyme activity effected by 1-methyl-1H-tetrazol-5-thiol (MTT) was greater than those of 1H-tetrazol (TZ), 1H-tetrazol-5-thiol and 1-(2-dimethylaminoethyl)-1H-tetrazol-5-thiol, but was, of course, less than that of disulfiram. Cefamandole, cefmetazole and MTT showed competitive inhibition with NAD, while TZ was uncompetitive inhibitor with respect to both NAD and acetaldehyde. Enzyme inhibition caused by disulfiram, cefmetazole and MTT increased time-dependently and the addition of 2-mercaptoethanol into the medium effectively and completely restored enzyme inhibition. These results suggest that thiol group at position 5 of 1H-tetrazol ring is responsible for the type of inhibition with NAD, and methyl group at position 1 of 1H-tetrazol ring is important to exhibit a potent inhibition on aldehyde dehydrogenase.


The etiology of neurosensory hearing defects in preterm infants.
We retrospectively investigated the influence of gestational age, perinatal risk, and the duration of incubator care periods in 193 surviving preterm infants with a gestational age between 28 and 36 weeks raised in our intensive care nursery incubators from 1965--1967. 24 (12.4%) of the children showed definite neurosensory hearing defects, which were particularly encountered in the high frequencies. No correlation could be substantiated between hearing difficulties and hyperbilirubinemia, streptomycin application and gestational age. This study does not support the assumption that the duration of noise exposure in currently used incubators is a major determinant for the development of deafness in otherwise healthy preterm infants. Our study did show, however, a strong correlation between the sum of all perinatal risk factors and neurosensory hearing loss.


Value co-creation with family caregivers to people with dementia through a tailor-made mHealth application: a qualitative study.
Digitalization has been recognized as an efficient and cost-effective solution to address the increasing need for care due to the ageing population and the rise in people with dementia. This has subsequently increased the need to also care for family caregivers in community settings. Another benefit of digitalization is the introduction of new service concepts within service-dominant logic namely, value co-creation, which is changing the dynamics in healthcare, transitioning from a provider-centric to a customer-centric approach. The literature indicates that this transition is a slow process in healthcare due to the complex service context consisting of multi-stakeholders, with a fragmented decision-making process. This has resulted in limited research on how individuals co-create value through technology. The study aimed to explore how family caregivers to people with dementia living at home, as consumers of healthcare services co-create value in a multi-stakeholder context through a tailormade mHealth application. A qualitative explorative design was used. Data were collected through semi-structured interviews with 12 family caregivers of people with dementia living at home. The data were analyzed deductively using qualitative content analysis. The findings show how family caregivers to people with dementia as healthcare consumers, engaged with a mHealth application and other actors in their service network through different levels of value co-creation activities. This paper showed a willingness among family caregivers to people with dementia living at home, who mostly consisted of older people, to implement new technology to assist them with their caregiving tasks. The different value co-creation activities adopted by the family caregivers generated different levels of experiential value such as support, knowledge, and increased access to healthcare.


Clustered arg genes on a BamHI segment of the Escherichia coli chromosome.
BamHI cleavage of DNAs from transducing phages gamma darg13 (ppc, argECBH, bfe), gamma darg14 (ppc, argECBH) and gamma darg23 (argECBH) yields three purely gamma DNA segments (and, in one case, a fourth), as well as several Excherichia coli-DNA-containing segments. The length (in kilobases, kb) of the segments, determined by electron microscopy and ararose gel electrophoresis is 4.2, 7.5, 8.4, 6.2, 6.9, and 6.4 kb for gamma darg13; 13.0, 7.5, 4.7, 6.2, 6.9, and 6.4 kb for gamma darg 14: and 5.3, 11.0, 4.7, 6.2, 6.9, and 6.4 kb for gamma darg23. Ordering of the segments (in relation to the gamma genetic map and with the direction from left to right corresponding to the clockwise orientation of the E. coli genetic map and to each of the numerical sequences given) reveals, on 26 kb of bacterial DNA, two cleavage sites defining the 7.5-kb segment obtainable from the DNA of either gamam darg13 or gamma darg14. These and analogous findings with argEC and argCB deletion-bearing strains, together with results from heteroduplex experiments, locate argE, argC, argB, and presumably argH on the 7.5-kb segment.


Development and validation of a novel survival model for head and neck squamous cell carcinoma based on autophagy-related genes.
In view of the critical role of autophagy-related genes (ARGs) in the pathogenesis of various diseases including cancer, this study aims to identify and evaluate the potential value of ARGs in head and neck squamous cell carcinoma (HNSCC). RNA sequencing and clinical data in The Cancer Genome Atlas (TCGA) were analyzed by univariate Cox regression analysis and Lasso Cox regression analysis model established a novel 13- autophagy related prognostic genes, which were used to build a prognostic risk model. A multivariate Cox proportional regression model and the survival analysis were used to evaluate the prognostic risk model. Moreover, the efficiency of prognostic risk model was tested by receiver operating characteristic (ROC) curve analysis based on data from TCGA database and Gene Expression Omnibus (GEO). Besides, the other independent datasets from Human Protein Atlas dataset (HPA) also applied. 13 ARGs (GABARAPL1, ITGA3, USP10, ST13, MAPK9, PRKN, FADD, IKBKB, ITPR1, TP73, MAP2K7, CDKN2A, and EEF2K) with prognostic value were identified in HNSCC patients. Subsequently, a prognostic risk model was established based on 13 ARGs, and significantly stratified HNSCC patients into high- and low-risk groups in terms of overall survival (OS) (HR = 0.379,95% CI: 0.289-0.495, p < 0.0001). The multivariate Cox analysis revealed that this model was an independent prognostic factor (HR = 1.506, 95% CI = 1.330-1.706, P < 0.001). The areas under the ROC curves (AUC) were significant for both the TCGA and GEO, with AUC of 0.685 and 0.928 respectively. Functional annotation revealed that model significantly enriched in many critical pathways correlated with tumorigenesis, including the p53 pathway, IL2 STAT5 signaling, TGF beta signaling, PI3K Ak mTOR signaling by gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA). In addition, we developed a nomogram shown some clinical net could be used as a reference for clinical decision-making. Collectively, we developed and validated a novel robust 13-gene signatures for HNSCC prognosis prediction. The 13 ARGs could serve as an independent and reliable prognostic biomarkers and therapeutic targets for the HNSCC patients.


Polyphosphoestered Nanomedicines with Tunable Surface Hydrophilicity for Cancer Drug Delivery.
The surface hydrophilicity of nanoparticles has a major impact on their biological fates. Ascertaining the correlation between nanoparticle surface hydrophilicity and their biological behaviors is particularly instructive for future nanomedicine design and their antitumor efficacy optimization. Herein, we designed a series of polymeric nanoparticles based on polyphosphoesters with well-controlled surface hydrophilicity in the molecular level and systemically evaluated their biological behaviors. The results demonstrated that high surface hydrophilicity preferred lower protein absorption, better stability, longer blood circulation, and higher tumor accumulation but lower cellular uptake. Upon encapsulation of drugs, nanoparticles with high hydrophilicity showed an excellent antitumor therapeutic efficacy in both primary and metastatic tumors as compared to the relatively hydrophobic ones. Further analyses revealed that the superior antitumor outcome was attributed to the balance of tumor accumulation and cellular uptake, demonstrating the particular importance of nanoparticle surface hydrophilicity regulation on the antitumor efficacy. Our work provides a potent guideline for a rational designation on the surface hydrophilicity of nanoparticles for cancer treatment optimization.


Dioscin induces cancer cell apoptosis through elevated oxidative stress mediated by downregulation of peroxiredoxins.
Dioscin has been shown to promote anticancer activity against several forms of cancers. However, its detailed molecular mechanisms have not been clearly clarified.In this study, we demonstrate that dioscin induces apoptosis in cancer cells through the induction of oxidative stress. Treatment with cancer cells in vitro with dioscin resulted in rapid generation of reactive oxygen species (ROS) and the induction of mitochondrial pathway apoptosis in human esophageal cancer cell line Kyse510. Inhibition of oxidative stress by the antioxidant N-acetylcysteine blocked the induction of apoptosis by dioscin, indicating that ROS generation is the primary mechanism responsible for the proapoptotic activity of dioscin. Proteomic analysis and protein gel blotting further revealed peroxiredoxins 1 and 6 (PRDX 1 and 6), which are implicated in ROS metabolism and apoptosis, were associated with the anticancer effects of dioscin. Meanwhile, overexpression of PRDX 1 and 6 significantly blocked the elevated ROS and apoptosis induced by dioscin. In conclusion, we suggest that PRDX1 and PRDX6 are key targets in the process of dioscin-induced apoptosis that involves intracellular elevated ROS.


Effectiveness of a community-based integrated care ward (CICW) on 90-day readmission among the elderly people: a retrospective cohort study of a rural area in Japan.
Objective: Community-based integrated care wards (CICW) play a role in supporting the return of patients to their homes. However, studies investigating the readmission risk associated with CICW are lacking. To investigate the influence of CICW on readmission, we conducted a retrospective cohort study among Japanese elderly people. Materials and Methods: This study used data from the Diagnosis Procedure Combination (DPC) and medical records of the Hamada Medical Center, Shimane Prefecture in 2014-2019. The number of subjects and readmission in each hospitalization case (general ward only [GW] and CICW) were 1,521 and 416 subjects and 152 and 49 cases, respectively. We selected the hospitalization cases for heart failure (I30-I52), ischemic heart disease (I20-I25), pneumonia (J09-J18), chronic lower respiratory tract diseases (J40-J47), intestinal diseases (K55-K64), cerebrovascular disease (I60-I69), gallbladder, bile duct, and pancreatic diseases (K80-K87) from the International Statistical Classification of Diseases and Related Health Problems (ICD-10). The hazard ratios (HRs) and 95% confidence intervals (CIs) for readmission via a CICW were estimated using a multivariate Cox proportional hazards model. Results: The HRs for readmission associated with CICW were not different between the shorter and longer durations, considering the percentage of CICW stay. Compared with GW cases, the HR of CICW cases was 0.40 (95% CI, 0.17-0.92) in coordination with outside agencies of hospital discharge support. While the HR of GW cases was 2.35 (95% CI 1.01-5.47), a significantly increased risk was observed in people living alone. A similar risk was not observed in CICW cases with the HR of 0.56 (95% CI 0.15-2.07). Conclusion: The present study observed decreased risk of readmission among the patients discharged from CICW, compared to GW. Further research is required to clarify the causal factors for this decreased risk.


COVID-19 pandemia and inherited cardiomyopathies and channelopathies: a short term and long term perspective.
Inherited heart disease represent a very heterogenous group of cardiac disorders, characterized by inherited, acquired, and often rare disorders affecting the heart muscle (cardiomyopathies) or the cardiac electrical system (ion channel disease). They are often familial diseases, and are among the leading cause of juvenile sudden death and heart failure. The aim of this paper is to give a perspective on how to run a clinical service during an epidemic or pandemic emergency and to describe the potential COVID-19 associated risks for patients affected by inherited heart diseases.


Behavioral symptoms in community-dwelling elderly Nigerians with dementia, mild cognitive impairment, and normal cognition.
Few studies have examined the neuropsychiatric status of patients with dementia and cognitive impairment in the developing world despite the fact that current demographic trends suggest an urgent need for such studies. To assess the level of neuropsychiatric symptoms in community-dwelling individuals with dementia, cognitive impairment no dementia and normal cognition. Subjects were from the Ibadan site of Indianapolis-Ibadan Dementia Project with stable diagnoses of normal cognition, cognitive impairment, no dementia/mild cognitive impairment (CIND/MCI), and dementia. Informants of subjects made ratings on the neuropsychiatric inventory and blessed dementia scale; subjects were tested with the mini mental state examination. One hundred and eight subjects were included in the analytic sample, 21 were cognitively normal, 34 were demented, and 53 were CIND/MCI. The diagnostic groups did not differ in age, per cent female, or per cent with any formal education. The most frequent symptoms among subjects with CIND/MCI were depression (45.3%), apathy (37.7%), night time behavior (28.3%), appetite change (24.5%), irritability (22.6%), delusions (22.6%), anxiety (18.9%), and agitation (17.0%). Depression was significantly more frequent among the CIND/MCI and dementia (44.1%) groups compared with the normal cognition group (9.5%). Distress scores were highest for the dementia group, lowest for the normal cognition group, and intermediate for the CIND/MCI group. Significant neuropsychiatric symptomatology and distress are present among cognitively impaired persons in this community-based study of older adults in this sub-Saharan African country. Programs to assist family members of cognitively impaired and demented persons should be created or adapted for use in developing countries.


N-acetylcysteine-conjugated pyrrole identified in rat urine following administration of two pyrrolizidine alkaloids, monocrotaline and senecionine.
This report demonstrates that an Ehrlich-reagent-positive metabolite of monocrotaline and senecionine is excreted in the urine of male rats as an N-acetylcysteine conjugate of (+/-)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (NAC-DHP). Isolation of the metabolite employed an initial organic extraction followed by HPLC separation of remaining urinary components using a reverse-phase, polymer-based, PRP-1 column. Fast-atom-bombardment tandem mass spectrometry was used to identify the metabolite. This finding suggests that reactive metabolites of pyrrolizidine alkaloids generated in the liver can survive the aqueous environment of the circulatory system as glutathione conjugates or mercapturic acids.


The OPTIMIZE trial: Rationale and design of a randomized controlled trial of motivational enhancement therapy to improve adherence to statin medication.
Statins are a class of medications that are particularly effective for lowering cholesterol and reducing cardiovascular morbidity and mortality. Despite a range of benefits, non-adherence to statin medication is prevalent with 50% to 75% of patients failing to adhere to treatment within the first 2-years. A previous review on interventions to improve adherence to cholesterol lowering medication concluded that rigorous trials were needed with emphasis on the patient's perspective and shared decision making. Motivational interviewing (MInt) is a promising patient-centered approach for improving adherence in patients with chronic diseases. This manuscript describes the rational and design of a randomized controlled trial (RCT) testing the efficacy of MInt in improving adherence to statin medication. Patients filling their first statin prescription will be recruited to complete a 6-month observation run-in period (phase-1) after which medication possession ratio (MPR) will be assessed. Patients meeting criteria for non-adherence (MPR≤60%) will be invited to participate in the trial. 336 non-adherent new statin users will undergo a fasting lipid panel, complete baseline questionnaires, and be randomly allocated to receive four sessions of adherence education delivered using MInt (EdMInt) or to an education control (EC) delivered at 3-month intervals. Final assessments will occur 12-months after the first EdMInt or EC session. The primary outcome is change in MPR adherence to statin medication from baseline to 12-months. Secondary outcomes include within-patient change in self-reported medication adherence, stage of change and self-efficacy for medication adherence, motivation to adhere to statin medication, and lipid profile.


Changes in thermoviscoelastic and biochemical properties of Atroncau blancu and roxu Afuega'l Pitu cheese (PDO) during ripening.
Thermoviscoelastic and biochemical properties of Afuega'l Pitu cheese blancu (B) and roxu (R), a Spanish acid-curd cheese made from cow's milk, were determined at 3, 15, 30 and 60 days of ripening. The contents of fat (>45 g/100 g total solids, TS) and NaCl (<3 g/100 g TS) were similar between varieties and did not change with ripening. Total solids, pH, nitrogen fractions and fat acidity increased with ripening time in B and R samples. Lactose content was higher in B than in R cheeses at 3 d, was degraded gradually throughout ripening but did not disappear totally in both cheeses at 60 d. Viscoelastic parameters were determined in the linear viscoelastic region (LVER) by stress sweeps (6.3 rad/s, 20 °C): the stress amplitude (σmax) and complex modulus (G*) increased, while strain amplitude (γmax) decreased up to 60 d. Mechanical spectra were also determined, in the LVER, at 20 °C, 50 °C and 75 °C, showing that all samples behaved as "true gels" (elastic modulus, G' > viscous modulus, G''), irrespective of temperature. The best gel properties (low values of loss factor, tanδ = G''/G', and minor frequency dependence, i.e., low n', n'' exponents), were observed at 20 °C for B30 and R30. The viscoelastic parameters (G0' and G0'') increased with ripening time, irrespective of the temperature, and for a fixed ripening time they were lower at higher temperature. At 75 °C, all samples exhibited notable frequency dependence (n'' ≫ n'), resulting in shear-induced gelation at low frequencies (high oscillation times) which was consistent with data in thermal profiles from 70 °C to 90 °C.


The EULAR Scleroderma Trials and Research Group (EUSTAR): an international framework for accelerating scleroderma research.
Systemic sclerosis has a complex pathogenesis and a multifaceted clinical spectrum without a specific treatment. Under the auspices of the European League Against Rheumatism, the European League Against Rheumatism Scleroderma Trials And Research group (EUSTAR) has been founded in Europe to foster the study of systemic sclerosis with the aim of achieving equality of assessment and care of systemic sclerosis patients throughout the world according to evidence-based principles. EUSTAR created the minimal essential data set, a simple two-page form with basic demographics and mostly yes/no answers to clinical and laboratory parameters, to track patients throughout Europe. Currently, over 7000 patients are registered from 150 centres in four continents, and several articles have been published with the data generated by the minimal essential data set. A commitment of EUSTAR is also to teaching and educating, and for this reason there are two teaching courses and a third is planned for early in 2009. These courses have built international networks among young investigators improving the quality of multicentre clinical trials. EUSTAR has organized several rounds of 'teach the teachers' to further standardize the skin scoring. EUSTAR activities have extended beyond European borders, and EUSTAR now includes experts from several nations. The growth of data and biomaterial might ensure many further fruitful multicentre studies, but the financial sustainability of EUSTAR remains an issue that may jeopardize the existence of this group as well as that of other organizations in the world.


[Various parameters of lipid metabolism after intra-arterial injections of ozone in patients with ischemia of the lower extremities and diabetes mellitus].
In 50 subjects with arteriosclerotic ischaemia of the lower extremities and 41 subjects with diabetes mellitus ozone was applied intra-arterially. Before and after the treatment serum lipids concentration was examined. In the group with arteriosclerotic ischemia significant decrease in cholesterol level and both his fractions was seen. Whereas in the group with diabetes the cholesterol LDL was significantly reduced. In both groups total lipids level serum was decreased. It suggests that ++ozone therapy set back the arteriosclerosis progress, normalized some parameters of lipid metabolism and improved HDL to LDL cholesterol fractions relationship.


Microstructure and mechanical properties of Ti-15Zr alloy used as dental implant material.
Ti-Zr alloys have recently started to receive a considerable amount of attention as promising materials for dental applications. This work compares mechanical properties of a new Ti-15Zr alloy to those of commercially pure titanium Grade4 in two surface conditions - machined and modified by sand-blasting and etching (SLA). As a result of significantly smaller grain size in the initial condition (1-2µm), the strength of Ti-15Zr alloy was found to be 10-15% higher than that of Grade4 titanium without reduction in the tensile elongation or compromising the fracture toughness. The fatigue endurance limit of the alloy was increased by around 30% (560MPa vs. 435MPa and 500MPa vs. 380MPa for machined and SLA-treated surfaces, respectively). Additional implant fatigue tests showed enhanced fatigue performance of Ti-15Zr over Ti-Grade4.


Erythrophagocytosis in phenylhydrazine induced acute anaemia in chickens.
Acute anaemia was experimentally induced in chickens with a single subcutaneous injection of phenylhydrazine-hydrochloride. The birds were necropsied at fixed intervals. Liver, spleen and red bone marrow (from middle of tibia) were promptly dissected out. Impression smears were stained and examined under dry high power. Erythrophagocytosis was massive in the liver, moderate in the spleen and less conspicuous in bone marrow. Extensive erythrophagocytosis by the mononuclear cells might be associated with extravascular haemolysis. This appeared to be a major factor in the induction of anaemia.


Collaborative care for comorbid depression and diabetes: a systematic review and meta-analysis.
The collaborative care model is recommended for depression in adults with a chronic physical health problem like diabetes. We sought to systematically assess the effect of collaborative care on depression and glycaemia in adults with comorbid depression and diabetes to inform guidelines and practice. Systematic review and meta-analysis. We searched PubMed, Scopus, Cochrane Library, CINAHL, Health Source Nursing, MEDLINE, PsychINFO and reference lists of retrieved articles published before August 2013. Randomised controlled trials (RCTs) on collaborative care (ie, coordinated multidisciplinary model of care) for depression that reported the effects on depression and glycaemic outcomes in adults with comorbid clinically relevant depression and diabetes were eligible. Data on the mean difference in depression and glycaemic outcomes were extracted and pooled using random effects meta-analysis. Seven RCTs included for review reported effects on depression outcomes in 1895 participants, and glycated haemoglobin (HbA1c) level in 1556 participants. Collaborative care significantly improved the depression score (standardised mean difference was -0.32 (95% CI -0.53 to -0.11); I(2)=79%) and HbA1c level (weighted mean difference was -0.33% (95% CI -0.66% to -0.00%); I(2)=72.9%) compared with control conditions. Depression remission did not predict better glycaemic control across studies. Limited evidence from short-to-medium term RCTs predominantly conducted in the USA suggests that collaborative care for depression significantly improves both depression and glycaemia outcomes, independently, in people with comorbid depression and diabetes.


Light and scanning electron microscopic imaging of leaf transverse sections of indigenous fodder grasses of central Punjab, Pakistan.
The significance of grasses as fodder is enormous. However, it has been observed that different fodder grasses are identified locally with the similar vernacular names. Even same species recognized with different names. This happened due to their reduced and overlapped morphological characters. Hence comprehensive taxonomic keys were required to provide authentic identification of this grass flora. Current study established microscopic identification tools on the basis of leaf transverse anatomical features. Results demonstrated a great diversity in ribs and furrows arrangement among all studied grass members. Lolium temulentum, Phalaris minor, Poa annua, Arundo donax, Aristida adscensionis, Desmostachya bipinnata, Cenchrus biflorus and Digitaria ciliaris possessed ribs and furrows only at adaxial surfaces whereas all other species possessed this feature abaxially. Generally all the species contain three types of vascular bundles i.e. small, medium and large. Therefore, this qualitative feature is valuable only at family level, however, it found insignificant in taxa identification. Diversity was observed in bundle sheath type which could be taxonomically significant. Generally bundle sheath was found complete in most of species but in Bromus japonicus Thunb., Dactylis glomerata L., Acrachne racemosa (Heyne ex Roth) Ohwi, Chrysopogon aucheri (Boiss.) Stapf, Dichanthium annulatum (Forssk.) Stapf, Heteropogon contortus (L.) P Beauv. Ex. Roem & Schult. Eragrostis minor Host. and in Agrostis gigantea Roth. had incomplete type of sheath. Results reported great diversity in characters which could be taxonomically viable. RESEARCH HIGHLIGHTS: This research highlighted the significance of microscopic examination of leaf transverse anatomical features in field of taxonomy. Established anatomical tools would be of great importance for the identification of studied species.


The extract based on the Kampo formula daikenchuto (Da Jian Zhong Tang) induces Bdnf expression and has neurotrophic effects in cultured cortical neurons.
Reductions in brain-derived neurotrophic factor (BDNF) expression levels have been reported in the brains of patients with neurological disorders such as Alzheimer's disease. Therefore, upregulating BDNF and preventing its decline in the diseased brain could help ameliorate neurological dysfunctions. Accordingly, we sought to discover agents that increase Bdnf expression in neurons. Here, we screened a library of 42 Kampo extracts to identify those with the ability to induce Bdnf expression in cultured cortical neurons. Among the active extracts identified in the screen, we focused on the extract based on the Kampo formula daikenchuto. The extract of daikenchuto in the library used in this study was prepared using the mixture of Zingiberis Rhizoma Processum (ZIN), Zanthoxyli Piperiti Pericarpium (ZAN), and Ginseng Radix (GIN) without Koi. In this study, we defined DKT as the mixture of ZIN, ZAN, and GIN without Koi (DKT extract means the extract prepared from the mixture of ZIN, ZAN, and GIN without Koi). DKT extract significantly increased endogenous Bdnf expression by mediated, at least in part, via Ca2+ signaling involving L-type voltage-dependent Ca2+ channels in cultured cortical neurons. Furthermore, DKT extract significantly improved the survival of cultured cortical neurons and increased neurite complexity in immature neurons. Taken together, our findings suggest that DKT extract induces Bdnf expression and has a neurotrophic effect in neurons. Because BDNF inducers are expected to have therapeutic potential for neurological disorders, re-positioning of Kampo formulations such as daikenchuto may lead to clinical application in diseases associated with reduced BDNF in the brain.


Uptrend of cervical and sacral fractures underlie increase in spinal fractures in the elderly, 2003-2017: analysis of a state-wide population database.
Traumatic spinal injuries can be life-threatening conditions. Despite numerous epidemiological studies, reports on specific spinal regions affected are lacking. We hypothesized that fractures at specific regions, such as the cervical spine (including the axis segment), have been affected to a greater degree. We also hypothesized that advanced age may be a significant contributing factor. To longitudinally analyze trend of spine fractures and specific fracture subtypes. Longitudinal trend analysis of discharged patient state database. Discharged patient's data from 15 years (2003-2017) METHODS: We retrieved pertinent ICD-9 and 10 codes depicting fractures involving the entire spine and specific subtypes. To assess possible association with age, we analyzed the trend of the average age in patients discharged with and without spinal fractures as well as in specific fracture subtypes. Similar analysis was performed for other common fragility fractures. FDA device/drug status: The manuscript submitted does not contain information about medical device(s) or drug(s). We found that within 15 years, the overall proportion of spinal fractures has increased by 64% (from 0.47 to 0.77% of all discharged patients) with the greatest increase noted in fractures of the cervical spine (123%) and specifically of the second cervical vertebra (84%). Age was found to have increased more in patients with spinal fractures than in the general discharged population. Surprisingly, other non-spinal fractures among patients above 60 remained relatively stable, demonstrating a spine-specific effect. Our findings confirm a recent increase in all spinal fractures and in the cervical and sacral regions in particular. Advanced age may be an important underlying factor.