Variation in Physician Office Visit Rates by Patient Characteristics and State, 2012.
In 2012, 74% of children and adults with a usual place to visit listed a doctor's office as their usual place for care (1,2). This report examines the rate of physician office visits by patient age, sex, and state. Visits by adults with private insurance as their expected source of payment were also examined. Estimates are based on the 2012 National Ambulatory Medical Care Survey (NAMCS), a nationally representative survey of physician office visits. State estimates for the 34 most populous states are available for the first time. State refers to the location of the physician office visit.


Nuclear migration and positioning in filamentous fungi.
Genetic analyses of nuclear distribution mutants have indicated that functions of the microtubule motor, cytoplasmic dynein, and its regulators are important for nuclear positioning in filamentous fungi. Here we review these studies and also present the need to further dissect how dynein and its associated microtubule cytoskeleton are involved mechanistically in nuclear positioning in the multinucleated hyphae.


A randomized, double-blind, placebo-controlled phase 2 study to assess safety, tolerability, and efficacy of RT001 in patients with amyotrophic lateral sclerosis.
RT001 is a deuterated synthetic homologue of linoleic acid, which makes membrane polyunsaturated fatty acids resistant to lipid peroxidation, a process involved in motor neuron degeneration in amyotrophic lateral sclerosis (ALS). We conducted a randomized, multicenter, placebo-controlled clinical trial. Patients with ALS were randomly allocated to receive either RT001 or placebo for 24 weeks. After the double-blind period, all patients received RT001 during an open-label phase for 24 weeks. The primary outcome measures were safety and tolerability. Key efficacy outcomes included the ALS Functional Rating Scale (ALSFRS-R), percent predicted slow vital capacity, and plasma neurofilament light chain concentration. In total, 43 patients (RT001 = 21; placebo = 22) were randomized. RT001 was well tolerated; one patient required dose reduction due to adverse events (AEs). Numerically, there were more AEs in the RT001 group compared to the placebo group (71% versus 55%, p = 0.35), with gastrointestinal symptoms being the most common (43% in RT001, 27% in placebo, p = 0.35). Two patients in the RT001 group experienced a serious AE, though unrelated to treatment. The least-squares mean difference in ALSFRS-R total score at week 24 of treatment was 1.90 (95% confidence interval = -1.39 to 5.19) in favor of RT001 (p = 0.25). The directions of other efficacy outcomes favored RT001 compared to placebo, although no inferential statistics were performed. Initial data indicate that RT001 is safe and well tolerated. Given the exploratory nature of the study, a larger clinical trial is required to evaluate its efficacy.


Clinical Utility of the Neutrophil-to-Bilirubin Ratio in the Detection of Disease Activity in Ulcerative Colitis.
Ulcerative colitis (UC) is a chronic relapsing remitting form of inflammatory bowel disease (IBD). Current disease monitoring includes evaluation of symptoms, fecal calprotectin, and colonoscopy. Due to limited availability of the latter two modalities in China, we sought a readily available, inexpensive, disease monitoring laboratory assessment. We recently identified a novel serological index (the neutrophil-to-bilirubin ratio, NBR) for monitoring disease activity in Crohn's disease. However, the clinical significance has not been evaluated in UC. Here, we aimed to verify the hypothesis that NBR might be useful in monitoring clinical and endoscopic activity in patients with UC. To test our hypothesis, we conducted a single-center, retrospective study including a total of 188 patients with UC and 145 non-IBD controls. NBR was calculated to determine its practical value in monitoring disease activity (including clinical and endoscopic activity). Disease activity of UC was determined by the partial Mayo score and the Mayo endoscopic score (MES) system. NBR was significantly higher in patients with UC than that in controls (12.10, IQR: 9.85-16.69 versus 5.06, IQR: 3.94-6.55; p < 0.001) and showed positive correlations with clinical and endoscopic disease activity in UC. Additionally, NBR was significantly lower in patients with endoscopic mucosal healing (MH) than that in those without endoscopic MH (8.81, IQR: 6.67-11.67 versus 13.51, IQR: 11.04-18.71; p < 0.001). Serial evaluation of NBR in a subset of patients demonstrated that NBR was significantly decreased during the MH stage compared with that during the endoscopically active stage. Our study suggests that NBR may be a promising candidate for assessing disease activity in UC, with potential for widespread clinical use and significant clinical implications.


n-3 Polyunsaturated fatty acids inhibit Fc ε receptor I-mediated mast cell activation.
In vivo models show that n-3 polyunsaturated fatty acids (PUFA) inhibit some of the processes associated with allergic inflammation but the direct effect of n-3 PUFA on mast cells, the major effector cells in allergy, is poorly understood. We sought to determine the effect and mechanism of n-3 PUFA on Fc ε receptor I (FcεRI)-mediated signal transduction and mast cell activation. Bone marrow-derived mast cells (BMMC) were differentiated from bone marrow obtained from C57BL/6 wild-type (WT) and fat-1 transgenic mice. The fat-1 mice express fatty acid n-3 desaturase and produce endogenous n-3 PUFA. For comparison, exogenous n-3 PUFA were supplemented to WT BMMC and human mast cell (LAD2) cultures. Fat-1 BMMC released less β-hexosaminidase (β-hex) and cysteinyl leukotrienes and produced less tumor necrosis factor and chemokine (C-C motif) ligand 2. n-3 PUFA supplementation reduced LAD2 and BMMC degranulation (β-hex release) following FcεRI activation. Fat-1 BMMC expressed less constitutive Lyn and linker of activated T cells (LAT), and FcεRI-mediated phosphorylation of Lyn, spleen tyrosine kinase and LAT were reduced in fat-1 BMMC. Although the expression of surface and whole cell FcεRI was similar in WT and fat-1 BMMC, unstimulated fat-1 BMMC showed reduced FcεRI localization to lipid rafts, and stimulation with antigen resulted in aberrant FcεRI shuttling to the rafts. Our results show that n-3 PUFA suppress FcεRI-mediated activation of mast cells, which results in reduced mediator release. This effect is associated with a decrease in LAT and Lyn expression as well as abnormal shuttling of FcεRI to lipid rafts.


Pneumothorax, pneumomediastinum and subcutaneous emphysema following closed percutaneous pleural biopsy: a case report.
Minimally invasive investigations, such as pleural fluid cytological assessment and closed percutaneous pleural biopsy, are often performed first in the investigation of suspected malignant pleural effusions. Malignant pleural effusions can be diagnosed with pleural fluid cytology alone in most cases; however, closed pleural biopsy is performed to increase the diagnostic yield when pleural fluid cytology is negative. This additional yield is at the expense of increased complication rates. We report a 64-year old man with a negative pleural fluid cytology but suspected malignant pleural effusion who underwent a closed pleural biopsy, which was complicated by pneumothorax, pneumomediastinum and severe subcutaneous emphysema. Pulmonary laceration by the pleural biopsy needle is the most likely aetiology of these complications. Our case report highlights an infrequent but significant complication of closed percutaneous pleural biopsy.


Some like it pungent and vile. TRPA1 as a molecular target for the malodorous vinyl disulfides from asafoetida.
Ferula assa-foetida L. is a major source of asafoetida, a foul-smelling gum-resin of dietary and medicinal relevance. Investigation of the roots and latex of F. assa-foetida yielded various mixed vinyl disulfides, including two novel asadisulfide-type esters. The reactivity of asadisulfide was investigated in the cysteamine NMR assay, where it behaved as disulfide shuffling agents due to the high mobility of the vinyl sulfide moiety. In accordance with their transthiolation capacity, these compounds potently activated TRPA1, the target of mustard oil and the pungent sulfur compounds from onion and garlic, qualifying S-alkyl-S-alkenyldisulfides, a rare class of natural products, as a novel class of dietary TRPA1 activators. These observations provide a mechanistic basis for rationalizing some of the sensory properties and potential beneficial health claims associated to the use of asafoetida as a spice and as a medicine.


The importance of chemosensory clues in Aguaruna tree classification and identification.
The ethnobotanical literature still contains few detailed descriptions of the sensory criteria people use for judging membership in taxonomic categories. Olfactory criteria in particular have been explored very little. This paper will describe the importance of odor for woody plant taxonomy and identification among the Aguaruna Jívaro of the northern Peruvian Amazon, focusing on the Aguaruna category númi (trees excluding palms). Aguaruna informants almost always place trees that they consider to have a similar odor together as kumpají - 'companions,' a metaphor they use to describe trees that they consider to be related. The research took place in several Aguaruna communities in the upper Marañón region of the Peruvian Amazon. Structured interview data focus on informant criteria for membership in various folk taxa of trees. Informants were also asked to explain what members of each group of related companions had in common. This paper focuses on odor and taste criteria that came to light during these structured interviews. Botanical voucher specimens were collected, wherever possible. Of the 182 tree folk genera recorded in this study, 51 (28%) were widely considered to possess a distinctive odor. Thirty nine of those (76%) were said to have odors similar to some other tree, while the other 24% had unique odors. Aguaruna informants very rarely described tree odors in non-botanical terms. Taste was used mostly to describe trees with edible fruits. Trees judged to be related were nearly always in the same botanical family. The results of this study illustrate that odor of bark, sap, flowers, fruit and leaves are important clues that help the Aguaruna to judge the relatedness of trees found in their local environment. In contrast, taste appears to play a more limited role. The results suggest a more general ethnobotanical hypothesis that could be tested in other cultural settings: people tend to consider plants with similar odors to be related, but say that plants with unique odors are unrelated to any other plants.


Masson's tumor in the ulnar artery.
A healthy 30-year-old woman presented to the emergency department with a pulsatile right forearm mass and numbness of her fourth and fifth fingers. Duplex scan imaging revealed an ulnar artery aneurysm with intramural thrombus. After resection, histopathology revealed intravascular papillary endothelial hyperplasia, also known as Masson's tumor, a rare but benign vascular neoplasm. Local resection of the tumor with vascular reconstruction is curative and resulted in resolution of her neurologic symptoms. To our knowledge, this is the first reported case of a Masson's tumor occurring in an ulnar artery.


Cardiac effects of ephedrine, norephedrine, mescaline, and 3,4-methylenedioxymethamphetamine (MDMA) in mouse and human atrial preparations.
The use of recreational drugs like ephedrine, norephedrine, 3,4-methylenedioxymethamphetamine (MDMA), and mescaline can lead to intoxication and, at worst, to death. One reason for a fatal course of intoxication with these drugs might lie in cardiac arrhythmias. To the best of our knowledge, their inotropic effects have not yet been studied in isolated human cardiac preparations. Therefore, we measured inotropic effects of the hallucinogenic drugs ephedrine, norephedrine, mescaline, and MDMA in isolated mouse left atrial (mLA) and right atrial (mRA) preparations as well as in human right atrial (hRA) preparations obtained during cardiac surgery. Under these experimental conditions, ephedrine, norephedrine, and MDMA increased force of contraction (mLA, hRA) and beating rate (mRA) in a time- and concentration-dependent way, starting at 1-3 µM but these drugs were less effective than isoprenaline. Mescaline alone or in the presence of phosphodiesterase inhibitors did not increase force in mLA or hRA. The positive inotropic effects of ephedrine, norephedrine, or MDMA were accompanied by increases in the rate of tension and relaxation and by shortening of time of relaxation and, moreover, by an augmented phosphorylation state of the inhibitory subunit of troponin in hRA. All effects were greatly attenuated by cocaine (10 µM) or propranolol (10 µM) treatment. In summary, the hallucinogenic drugs ephedrine, norephedrine, and MDMA, but not mescaline, increased force of contraction and increased protein phosphorylation presumably, in part, by a release of noradrenaline in isolated human atrial preparations and thus can be regarded as indirect sympathomimetic drugs in the human atrium.


Best surgical approach for splenic flexure colon cancers: Extended versus segmental resection?
The optimal surgical treatment approach for splenic flexure colon cancers remains controversial regarding the type of resection. We hypothesized that both extended and segmental resections have similar surgical and oncologic outcomes. A retrospective review of prospectively collected database was performed on all patients who had colectomy for splenic flexure colon cancer between 1996 and 2018. Of 142 patients, 119 underwent extended resection; therefore, this group was compared with the group which underwent segmental resection (n = 23). The groups were similar in age, sex, ASA scores, operative times, estimated blood loss, hospital length of stay, and postoperative complication rates (p > 0.05). Median follow-up was 9.58 years (IQR:5.46-16.48). Multivariable regression models demonstrated no significant association between resection approach and disease-free survival (HR 1.63 [95%CI:0.91-2.92]), as well as overall survival (HR 1.80 [95%CI:0.97; 3.36]). In the treatment of splenic flexure colon cancer, segmental colon resections have similar oncologic outcomes when compared to extended colectomies.


Phenotype-specific feeding behaviour of two arctic charr Salvelinus alpinus morphs.
The feeding performance of two morphs of a trophically polymorphic fish, the arctic charr Salvelinus alpinus, feeding on zooplankton, was studied in the laboratory. Limnetic morphs, with a fusiform body, terminal mouth, short pectoral fins, and relatively long and dense gill rakers, fed at significantly higher rates on Daphnia and Cyclops than did benthic morphs. The benthic morphs were characterized by a chunky body form, subterminal mouth, long pectoral fins, and relatively short and spaced-out gill rakers. The limnetic morphs attacked the prey at significantly higher rates and were more successful in capture. Benthic morphs were more reluctant to start feeding on zooplankton and reaction time was longer than in limnetic morphs. In the absence as well as presence of zooplankton food, the position of the two morphs in the aquaria differed markedly. The results agree with dietary differences found in field-collected fish. The limnetic morphs consume zooplankton, whereas benthic morphs specialize on Lymnaea gastropods. The results suggest that benthic morphs are phenotypically inferior at using the pelagic food niche. This implies that the current role of competitive or predatory interactions in segregating the morphs may be minor.


Simple and inexpensive quantification of ammonia in whole blood.
Quantification of ammonia in whole blood has applications in the diagnosis and management of many hepatic diseases, including cirrhosis and rare urea cycle disorders, amounting to more than 5 million patients in the United States. Current techniques for ammonia measurement suffer from limited range, poor resolution, false positives or large, complex sensor set-ups. Here we demonstrate a technique utilizing inexpensive reagents and simple methods for quantifying ammonia in 100 μL of whole blood. The sensor comprises a modified form of the indophenol reaction, which resists sources of destructive interference in blood, in conjunction with a cation-exchange membrane. The presented sensing scheme is selective against other amine containing molecules such as amino acids and has a shelf life of at least 50 days. Additionally, the resulting system has high sensitivity and allows for the accurate reliable quantification of ammonia in whole human blood samples at a minimum range of 25 to 500 μM, which is clinically for rare hyperammonemic disorders and liver disease. Furthermore, concentrations of 50 and 100 μM ammonia could be reliably discerned with p = 0.0001.


Assessment of extra virgin olive oil quality by miniaturized near infrared instruments in a rapid and non-destructive procedure.
Food fraud in olive oil is a major concern for consumers and authorities due to the health risks and economic impacts. Common frauds include blending with other cheaper non-olive oils, or misleading labelling. The main issue is that legislation and methods presently used in routine laboratories are not always up to date with current fraudulent practices, making detection difficult, so new analytical methods development is required. This study focuses on developing an affordable and non-destructive analysis method based on NIR spectroscopy and chemometrics for EVOO quality assessment, specifically by monitoring 7 parameters of interest in EVOO measured by official methods and used to develop calibrations through NIR data. For this, two NIR low-cost portable instruments were employed, studied in-depth and compared with a NIR benchtop instrument. Calibration results enabled detection of atypical olive oils and excellent accuracy, especially for palmitic and oleic acid predictions, demonstrating the potential of the instruments.


Fungal endophyte-induced salidroside and tyrosol biosynthesis combined with signal cross-talk and the mechanism of enzyme gene expression in Rhodiola crenulata.
Endophyte is a factor that affects the physiology and metabolism of plant. However, limited information is available on the mechanism of interaction between endophyte and plant. To investigate the effects of endophytic fungus ZPRs-R11, that is, Trimmatostroma sp., on salidroside and tyrosol accumulations in Rhodiola crenulata, signal transduction, enzyme gene expression, and metabolic pathway were investigated. Results showed that hydrogen peroxide (H2O2), nitric oxide (NO), and salicylic acid (SA) involved in fungus-induced salidroside and tyrosol accumulations. NO acted as an upstream signal of H2O2 and SA. No up- or down-stream relationship was observed, but mutual coordination existed between H2O2 and SA. Rate-limiting enzyme genes with the maximum expression activities were UDP-glucosyltransferase, tyrosine decarboxylase (TYDC), monoamine oxidase, phenylalanine ammonialyase (PAL), and cinnamic-4-hydroxylase sequentially. Nevertheless, the genes of tyrosine transaminase and pyruvate decarboxylase only indicated slightly higher activities than those in control. Thus, TYDC and PAL branches were the preferential pathways in ZPRs-R11-induced salidroside and tyrosol accumulation. Trimmatostroma sp. was a potential fungus for promoting salidroside and tyrosol accumulations. The present data also provided scientific basis for understanding complex interaction between endophytic fungus and R. crenulata.


Metallic Stent Expansion Rate at Day One Predicts Stent Patency in Patients with Gastric Outlet Obstruction.
Self-expandable metallic stent insertion has been a mainstream treatment for relieving the obstructive symptoms of malignant gastric outlet obstruction (MGOO), a late-stage complication of gastrointestinal malignancies. This study aims to investigate the predictive value of stent expansion rates in clinical outcomes in patients with MGOO. Eighty-seven patients with inoperable MGOO receiving metallic stents were reviewed retrospectively from April 2010 to December 2014. Clinical outcomes, predictors of stent patency, and survival were analyzed. The technical and clinical success rates were 100 and 94.3%, respectively. The median stent patency time was 114 days (range 13-570 days). The median survival time was 133 days (range 13-1145 days). Stent dysfunctions occurred in 28 patients (32.2%), with restenosis accounting for the majority (82%). The stent expansion rate ≥75% at Day 1 predicted the stent patency [hazard ratio (HR) 0.12, P = 0.04]. However, it did not correlate with survival. Non-gastric cancer origins (HR 2.41, P = 0.002) and peritoneal carcinomatosis (HR 2.54, P = 0.001) correlated with poor survival. However, post-stent chemotherapy (HR 0.55, P = 0.03) was related to better outcome. The comparison of clinical outcomes of first and second stent insertions showed no significant difference in the stent expansion rate either at Day 0 and Day 1 (P = 0.97 and P = 0.57). Self-expandable metallic stent insertion is a safe and effective treatment for relieving the obstructive symptoms. The stent expansion rate ≥75% at Day 1 is a novel stent-related predictor of stent patency.


Evaluation of Concomitant Orbital Floor Fractures in Patients with Head Trauma Using Conventional Head CT Scan: A Retrospective Study at a Level II Trauma Center.
Patients with head trauma may have concomitant orbital floor fractures (OFFs). The objective of our study was to determine the specific CT findings and investigate the diagnostic performance of head CT in detecting OFFs. We analyzed 3534 head trauma patients undergoing simultaneous head and facial CT over a 3-year period. The clinical data and specific head CT findings between patients with and without OFFs were compared. In our cohort, 198 patients (5.6%) had OFFs visible on CT. On head CT, orbital floor discontinuity, gas bubbles entrapped between floor fragments, inferior extraconal emphysema, and maxillary hemosinus (MHS) were more commonly observed among patients with OFFs (p < 0.001). The absence of MHS had a high negative predictive value (99.7%) for excluding OFFs. Among the different types of MHS, the pattern showing high-attenuation opacity mixed with mottled gas had the highest positive predictive value (69.5%) for OFFs and was the only independent predictor of OFFs after adjusting for the other CT variables in all patients with MHS. Head CT may serve as a first-line screening tool to detect OFFs in head trauma patients. Hence, unnecessary facial CT and additional radiation exposure may be reduced.


Correlation between gastrointestinal fungi and varying degrees of chronic hepatitis B virus infection.
This study aims to compare the diversity of intestinal fungal microbiota in patients with different degrees of chronic hepatitis B virus (HBV) infection. Culture-independent and culture-dependent methods were performed on 38 patients with hepatitis B cirrhosis, 35 patients with chronic hepatitis B, 33 HBV carriers, and 55 healthy volunteers. An overall fungal biodiversity of 37 different operational taxonomic units was found in the clone libraries; only Candida spp. and Saccharomyces cerevisiae were obtained by the culture-dependent analysis. There was a higher richness of fungal species in patients with hepatitis B cirrhosis than in patients with chronic hepatitis B, and the latter was higher than that in HBV carriers and healthy volunteers. There was little difference in enteric fungal diversity between HBV carriers and healthy volunteers. The results indicate that the diversity of enteric fungi was positively correlated with the disease progression of patients with different degrees of chronic HBV infection.


Histological study on transient ocular hypertension after laser iridotomy in rabbits.
We performed argon-laser iridotomy on pigmented rabbits and examined histologically the tissue of the anterior chamber angle, the iris, and the ciliary body. After laser iridotomy, 9/10 eyes showed an elevation in transient intraocular pressure. Deposits of blood plasma with fibrin were observed in the tissue of the circumferential anterior chamber angle from eyes enucleated at a period of high intraocular pressure. In the eyes in which ocular pressures returned to the baseline, the quantity of blood plasma was small. In the laser-irradiated iris and iris processes, cells constructing the vessel wall were degenerated, and blood plasma and fibrin exuded. In and around the ciliary body, fibrin was not demonstrated. These observations suggest that argon-laser irradiation to the iris leads to a breakdown of the blood-aqueous barrier mainly in the laser-treated iris, and that deposition of blood plasma with fibrin in the anterior chamber angle tissue may cause transient intraocular pressure elevations after laser iridotomy in rabbits.


The Effect of Acute Rhodiola rosea Ingestion on Exercise Heart Rate, Substrate Utilisation, Mood State, and Perceptions of Exertion, Arousal, and Pleasure/Displeasure in Active Men.
The aim of this study was to examine the effect of acute Rhodiola rosea (R. rosea) ingestion on substrate utilisation, mood state, RPE, and exercise affect. Ten males (mean age ± S.D. = 26 ± 6 years) completed two 30-minute cycling trials at an intensity of 70% of [Formula: see text] following ingestion of either 3 mg·kg(-1) body mass of R. rosea or placebo using a double-blind, crossover design. During exercise, heart rate and RPE were recorded. Participants completed measures of mood state and exercise affect before and after exercise. Expired air samples were taken during exercise to determine substrate utilisation. Repeated measures analysis of variance indicated that RPE was significantly lower at 30 minutes into exercise versus placebo (P = 0.003). Perceptions of arousal (P = 0.05) and pleasure were significantly higher after exercise with R. rosea compared to placebo (P = 0.003). Mood state scores for vigor were also higher in R. rosea condition compared to placebo (P = 0.008). There were no significant differences in energy expenditure, carbohydrate, or fat oxidation between conditions (P > 0.05). Ingestion of R. rosea favourably influenced RPE and exercise affect without changes in energy expenditure or substrate utilization during 30-minute submaximal cycling performance.


Is inadequate human immunodeficiency virus care associated with increased ED and hospital utilization? A prospective study in human immunodeficiency virus-positive ED patients.
There is a lack of data on the effect(s) of suboptimal human immunodeficiency virus (HIV) care on subsequent health care utilization among emergency department (ED) patients with HIV. Findings on their ED and inpatient care utilization patterns will provide information on service provision for those who have suboptimal access to HIV-related care. A pilot prospective study was conducted on HIV-positive patients in an ED. At enrollment, participants were interviewed regarding health care utilization. Participants were followed up for 1 year, during which time data on ED visits and hospitalizations were obtained from their patient records. Inadequate HIV care (IHC) was defined according to Infectious Diseases Society of America recommendations as less than 3 scheduled clinic visits for HIV care in the year before enrollment. Cox regression models were used to evaluate whether IHC was associated with increased hazard of health care utilization. Of 107 subjects, 36% were found to have IHC. Inadequate HIV care did not predict more frequent ED visits but was significantly associated with fewer hospitalizations (adjusted incidence rate ratio, 0.61 [95% CI: 0.43-0.86]). Inadequate HIV care did not significantly increase the hazard for earlier ED visit or hospitalization. However, further stratification analysis found that IHC increased the hazard of hospitalization for subjects without comorbid diseases (adjusted hazard ratio, 2.50 [95% CI: 1.10-5.68]). In our setting, IHC does not appear to be associated with earlier or more frequent ED visits but may lead to earlier hospitalization, particularly among those without other chronic diseases.


Disentangling the Relationship between Frailty and Intrinsic Capacity in Healthy Community-Dwelling Older Adults: A Cluster Analysis.
Frailty and intrinsic capacity (IC) are distinct but interrelated constructs. Uncertainty remains regarding how they are related and interact to influence health outcomes. We aim to understand the relationship between frailty and IC by identifying subgroups based on frailty criteria and IC domains and studying one-year outcomes. We studied 200 independent community-dwelling older adults (mean age 67.9±7.9 years, Modified Barthel Index (MBI) score 99±2.6). Frailty was defined by modified Fried criteria. Scores (range: 0-2) were assigned to individual IC domains (cognition, psychological, locomotion, and vitality) to yield a total IC score of 8. To identify subgroups, two-step cluster analysis was performed with age, frailty and IC domains. Cluster associations with one-year outcomes (frailty, muscle strength (grip strength, repeated chair stand test), physical performance (gait speed, Short Physical Performance Battery), function (MBI) and quality-of-life (EuroQol (EQ)-5D)) were examined using multiple linear regression adjusted for age, gender and education. Three distinct clusters were identified - Cluster 1: High IC/Robust (N=74, 37%); Cluster 2: Intermediate IC/Prefrail (N=73, 36.5%); and Cluster 3: Low IC/Prefrail-Frail (53, 26.5%). Comparing between clusters, IC domains, cognition, depressive symptoms, nutrition, strength and physical performance were least impaired in Cluster 1, intermediate in Cluster 2 and most impaired in Cluster 3. At one year, the proportion transitioning to frailty or remaining frail was highest in Cluster 3 compared to Cluster 2 and Cluster 1 (39% vs 6.9% vs 2.8%, P<0.001). Compared to Cluster 1, Cluster 3 experienced greatest declines in grip strength (β=-4.1, P<.001), MBI (β=-1.24, P=0.045) and EQ-5D utility scores (β=-0.053, P=0.005), with Cluster 2 intermediate between Cluster 1 and Cluster 3. Amongst independent community-dwelling older adults, IC is complementary to frailty measures through better risk-profiling of one-year outcomes amongst prefrail individuals into intermediate and high-risk groups. The intermediate group merits follow-up to ascertain longer-term prognosis.


Ethanol-extracted Cameroonian propolis: Antiproliferative effects and potential mechanism of action in prostate cancer.
The present study was conducted to evaluate in vitro and in vivo antiproliferative potential of the Cameroonian propolis and to elucidate its underlying mechanism. In vitro, ethanol-extracted propolis (EEP) was tested on cell growth, cell proliferation, cell cycle, cell death mechanism and cell migration. The cell cycle- and apoptosis-regulating proteins were assessed by Western blotting. In vivo the testosterone-induced benign prostatic hyperplasia (BPH) in Wistar rat was used to evaluate the antiproliferative potential of EEP. EEP reduced DU145 and PC3 cell survival with an IC50 of 70 and 22 μg/ml respectively. It increased the number of late apoptotic cells, the amount of cells in G0/G1 phase in DU145 and PC3 cells at 50 µg/ml. Cell cycle proteins (cdk1, pcdk1 and their related cyclins A and B) were down-regulated in both DU145 and PC3 cells, while cdk2 and pcdk2 were down-regulated only in PC3 cells. The pro-apoptotic Bax protein was up-regulated, while the anti-apoptotic Akt and pAKT, and Bcl-2 proteins were down-regulated. It increased prostate cell adhesion and chemotaxis. EEP reduced prostate weight, volume and epithelial thickness in rats. We demonstrated for the first time that Cameroonian propolis is endowed with in vitro and in vivo antiproliferative properties in the prostate.


White matter connectometry among individuals with self-reported family history of drug and alcohol use disorders.
Heredity is an important risk factor for alcoholism. Several studies have been conducted on small groups of alcohol naïve adolescents which show lowered fractional anisotropy of frontal white matter in individuals with a family history of alcohol and substance use disorder (FH+). We compare large adult FH+ and FH- groups using white matter connectometry, different from the previously used global tractography method, as it is more sensitive to regional variability. Imaging and behavioral data from the Human Connectome Project (WU-MINN HCP 1200) was analyzed. Groups of participants were positive (n = 109) and negative (n = 109) for self-reported alcohol and substance use disorders in at least one parent, and stringently matched. Connectometry was performed on diffusion MRI in DSI-Studio using q-space diffeomorphic reconstruction, and multiple regression was completed with 5000 permutations. Analyses showed decreased major tract (>40 mm) connectivity in the FH+ group in left inferior longitudinal fasciculus, bilateral cortico-striatal pathway, left cortico-thalamic pathway, and corpus callosum, compared to the FH- group. For cognitive tasks related to reward processing, inhibition, and monitoring, there were a number of interactions, such that the relationship between identified tracts and behavior differed significantly between groups. Self-reported family history was associated with decreased connectivity in reward signaling pathways, controlling for alcohol consumption and alcohol use disorder. This is the first connectometry study of FH+, and extends the neural basis of the hereditary diathesis of alcoholism beyond that demonstrated with global tractography. Regions associated with FH+ are similar to those associated with alcohol use disorder.


Challenges in the diagnosis of microbial keratitis: A detailed review with update and general guidelines.
The incidence of microbial keratitis (MK) is variable worldwide with an estimated 1.5-2 million cases of corneal ulcers in developing countries. The complications of MK can be severe and vision threatening. Therefore, proper diagnosis of the causative organism is essential for early successful treatment. Accurate sampling of microbiological specimens in MK is an important step in identifying the infective organism. Corneal scrapping, tear samples and corneal biopsy are examples of specimens obtained for the investigative procedures in MK. Ophthalmologists especially in an emergency room setting should be aware of the proper sampling techniques based on their microbiology-related basic information for each category of MK. This review article briefly describes the clinical presentation and defines in details the best updated diagnostic methods used in different types of MK. It can be used as a guide for ophthalmology trainees and general ophthalmologists who may be handling such cases at initial presentation.


The VEGFR2/mTOR/S6K1 pathway involved in the angiogenic effects of roxarsone in vitro and in vivo.
Roxarsone, an organoarsenic compound used in poultry industry to increase weight gain, is widely used as a feed additive in some developing countries. Roxarsone has a low absorption rate and is mostly excreted with feces, which could pose a risk to human health through environmental and animal food routes. Roxarsone has been demonstrated to have tumor-promoting and proangiogenic effects. Herein, we report the role of VEGFR2/mTOR/S6K1 signaling in roxarsone-promoted vessel endothelial cell growth and angiogenesis in the Matrigel plug model and the mouse B16 cell tumor transplantation model. In angiogenesis-related experiments in vitro, 1.0 μM roxarsone significantly increased the activity, proliferation, migration, and tube formation of rat vascular endothelial cells. In addition, 1.0 μM roxarsone upregulated the protein levels of mTOR, phosphorylated mTOR, S6K1, and phosphorylated S6K1 and significantly increase the expression of Mtor and S6k1 mRNA. Rapamycin and SU5416 significantly inhibited the effects of 1.0 μM roxarsone on cell growth. Furthermore, the weight, volume, and CD31 expression of B16-F10 xenografts and Matrigel plugs in mice were upregulated by 25 mg/kg roxarsone. The protein and mRNA levels of mTOR, S6K1 and its phosphorylated protein were significantly increased in the roxarsone treatment group in xenografts. SU5416 and a short hairpin RNA targeting Vegfr2 significantly reduced roxarsone-promoted xenograft and Matrigel plug growth. In summary, this study indicated that the VEGFR2/mTOR/S6K1 signaling plays a regulatory role in roxarsone-mediated promotion angiogenesis and enhanced tumor growth.


The health seeking process: an approach to the natural history of illness.
Anthropological research on health-related behaviors in the United States has tended to emphasize folk illnesses among particular subcultural groups, obscuring the heterogeneity of popular culture health beliefs and practices in the lay health system. The development of theoretical models for this complex society will require research that stresses similarity as well as diversity within and between population groups. The health seeking process is proposed in this paper as a means to document natural histories of illness in any subculture. Concepts from medical anthropology and medical sociology are related to five components of health seeking -- symptom definition, illness-related shifts in role behavior, lay consultation and referral, treatment actions, and adherence. Illustrative propositions to guide further research are proposed.


[Smoking and mortality fro ischemic heart disease. Comparative study in capitals of Brazilian metropolitan regions, 1988].
An ecological study was performed to test the association between coronary heart disease (CHD) mortality and smoking in Brazil. Lung cancer mortality was used as a surrogate for smoking habit. The mortality rate for CHD (ICD-9:410-414) and lung cancer (ICD-9: 162) were determined in the following metropolitan areas: Belém, Recife, Salvador, Belo Horizonte, Rio de Janeiro, São Paulo, Curitiba and Porto Alegre for males and females between 30 and 69 year old. ANOVA test was used to compare both age-adjusted mortality rates. A positive association by ANOVA was determined only for males ages 60-69 and to age-adjusted rates. The relationship between smoking and CHD mortality as determined in Brazilian cities, among men, mainly in the older ages, is a proof that tobacco control would contribute to downward trends in CHD mortality rates.


Hiding in plain view: genetic profiling reveals decades old cross contamination of bladder cancer cell line KU7 with HeLa.
KU7 is a popular urothelial carcinoma cell line that was isolated from the bladder of a patient at Keio University in 1980. It has subsequently been widely used in laboratories around the world. We describe how routine cell line authentication revealed that KU7 was cross contaminated almost 30 years ago with HeLa, a cervical carcinoma cell line. Presumed KU7 clones dating from 1984 to 1999 were provided by M.D. Anderson Cancer Center, Vancouver Prostate Centre, Kyoto University, Tokyo Medical University and Keio University. HeLa was obtained from ATCC. Genomic DNA was isolated and short tandem repeat analysis was performed at the M.D. Anderson Cancer Center Characterized Cell Line Core Facility, Johns Hopkins University Fragment Analysis Facility and RIKEN BioResource Center, Ibaraki, Japan. Comparative genomic hybridization was performed on a platform (Agilent Technologies, Santa Clara, California) at Vancouver Prostate Centre. The short tandem repeat profile of all KU7 clones was an exact match with that of HeLa. Comparative genomic hybridization of all samples revealed an abundance of shared chromosomal aberrations. Slight differences in some genomic areas were explained by genomic drift in different KU7 clones separated by many years. Our analysis identified that cross contamination of KU7 with HeLa occurred before 1984 at the source institution. All KU7 clones in the urological literature should be considered HeLa and experimental results should be viewed in this light. Our results emphasize the need to authenticate cell lines in oncological research.


Short-term differences in cardiac function following controlled exposure to cookstove air pollution: The subclinical tests on volunteers exposed to smoke (STOVES) study.
Exposure to household air pollution from solid fuel combustion for cooking and heating is an important risk factor for premature death and disability worldwide. Current evidence supports an association of ambient air pollution with cardiovascular disease but is limited for household air pollution and for cardiac function. Controlled exposure studies can complement evidence provided by field studies. To investigate effects of short-term, controlled exposures to emissions from five cookstoves on measures of cardiac function. Forty-eight healthy adults (46% female; 20-36 years) participated in six, 2-h exposures ('treatments'), including emissions from five cookstoves and a filtered-air control. Target fine particulate matter (PM2.5) exposure-concentrations per treatment were: control, 0 µg/m3; liquefied petroleum gas, 10 µg/m3; gasifier, 35 µg/m3; fan rocket, 100 µg/m3; rocket elbow, 250 µg/m3; and three stone fire, 500 µg/m3. Participants were treated in a set (pre-randomized) sequence as groups of 4 to minimize order bias and time-varying confounders. Heart rate variability (HRV) and cardiac repolarization metrics were calculated as 5-min means immediately and at 3 h following treatment, for analysis in linear mixed-effects models comparing cookstove to control. Short-term differences in SDNN (standard deviation of duration of all NN intervals) and VLF (very-low frequency power) existed for several cookstoves compared to control. While all cookstoves compared to control followed a similar trend for SDNN, the greatest effect was seen immediately following three stone fire (β = -0.13 ms {%}; 95% confidence interval = -0.22, -0.03%), which reversed in direction at 3 h (0.03%; -0.06, 0.13%). VLF results were similar in direction and timing to SDNN; however, other HRV or cardiac repolarization results were not similar to those for SDNN. We observed some evidence of short-term, effects on HRV immediately following cookstove treatments compared to control. Our results suggest that cookstoves with lower PM2.5 emissions are potentially capable of affecting cardiac function, similar to stoves emitting higher PM2.5 emissions.


The impact on rural livelihoods and ecosystem services of a major relocation and settlement program: A case in Shaanxi, China.
China's largest-ever resettlement program is underway, aiming to restore ecosystems and lift ecosystem service providers out of the poverty trap and into sustainable livelihoods. We examine the impact of the relocation and settlement program (RSP) to date, reporting on an ecosystem services (ES) assessment and a 1400-household survey. The RSP generally achieves the goals of ES increase and livelihood restore. In biophysical terms, the RSP improves water quality, sediment retention, and carbon sequestration. In social terms, resettled households so far report transformation of livelihoods activities from traditional inefficient agricultural and forest production to non-farm activities. Increased income contributes to decrease the poverty rate and improve resettled households' living condition and standard. Meanwhile, the RSP decreases households' dependence on ES in terms of provisioning services. Difficulty and challenge also showed up subsequently after relocation. A major current challenge is to enable poorer households to move, while providing greater follow-up support to relocated households. While the program is unique to China, it illuminates widespread opportunities for addressing environmental and poverty-related concerns in a rapidly changing world.


Cysteine and methionine oxidation in thrombotic disorders.
Thrombosis is the leading cause of death in many diseased conditions. Oxidative stress is characteristic of these conditions. Yet, the mechanisms through which oxidants become prothrombotic are unclear. Recent evidence suggests protein cysteine and methionine oxidation as prothrombotic regulators. These oxidative post-translational modifications occur on proteins that participate in the thrombotic process, including Src family kinases, protein disulfide isomerase, β2 glycoprotein I, von Willebrand factor, and fibrinogen. New chemical tools to identify oxidized cysteine and methionine proteins in thrombosis and hemostasis, including carbon nucleophiles for cysteine sulfenylation and oxaziridines for methionine, are critical to understanding why clots occur during oxidative stress. These mechanisms will identify alternative or novel therapeutic approaches to treat thrombotic disorders in diseased conditions.


Identification of an immunotherapy-responsive molecular subtype of bladder cancer.
Although various molecular subtypes of bladder cancer (BC) have been investigated, most of these studies have focused on muscle-invasive BC (MIBC). A few studies have investigated non-muscle-invasive BC (NMIBC) or NMIBC and MIBC together, but none has classified progressive NMIBC or immune checkpoint inhibitor (ICI)-based therapeutic responses in early-stage BC patients. A total of 1,934 samples from seven patient cohorts were used. We performed unsupervised hierarchical clustering to stratify patients into distinct subgroups and constructed a classifier by applying SAM/PAM algorithms. We then investigated the association between molecular subtypes and immunotherapy responsiveness using various statistical methods. We explored large-scale genomic datasets encompassing NMIBC and MIBC, redefining four distinct molecular subtypes, including a subgroup containing progressive NMIBC and MIBC with poor prognosis that would benefit from ICI treatment. This subgroup showed poor progression-free survival with the distinct features of high mutation load, activated cell cycle, and inhibited TGFβ signalling. Importantly, we verified that BC patients with this subtype were significantly responsive to an anti-PD-L1 agent in the IMvigor210 cohort. Our results reveal an immunotherapeutic option for ICI treatment of highly progressive NMIBC and MIBC with poor prognosis. This research was supported by the National Research Foundation of Korea grant funded by the Korean government, a grant from the Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea, and a grant from the KRIBB Research Initiative Program.


[Fear Avoidance Beliefs and physical function in elderly individuals with chronic low back pain].
Fear Avoidance Beliefs and physical function in elderly individuals with chronic low back pain This analysis assessed how fear avoidance beliefs (FABs) affected subjective and objective functional parameters as well as pain in elderly individuals. The study comprised 152 elderly patients with low back pain, which was attributed to spondylosis in almost half of the cases. Their average age was 70.1 years (SD=4.3, range 65-84). All of the patients participated in a physiotherapeutic program including data acquisition before treatment (t1), immediately after its completion (t2), and 6 months later (t3). FABs were assessed by a five-item scale with satisfying psychometric properties. The primary outcome criterion was function, which was evaluated as a subjective measure using the Hannover functional disability scale and as an objective measure based on the anteflexion determined by ultrasound topometry. Secondary outcome criteria were pain parameters. At the time o the first measurement (t1), the patients were classified into three groups with strong, intermediate, or weak FABs. Analyses of variance reveal an improvement of subjective functional capacity in every FAB group between t1 and t2. At t3, there is a decline of these values only in the group of the high fear avoiders. High fear avoiders also show lower values in the objective measure at all three measurement points. No influence of the FABs on the pain parameters could be determined. It would be expected that the efficacy of physiotherapy could be improved if the patients' FABs are taken into consideration when planning the treatment regimen.


Consolidative Thoracic Radiation Therapy After First-Line Chemotherapy and Immunotherapy in Extensive-Stage Small Cell Lung Cancer: A Multi-Institutional Case Series.
Survival for patients with extensive-stage small cell lung cancer (ES-SCLC) remains poor. Consolidative thoracic radiation therapy (cTRT) and upfront immunotherapy with chemotherapy have each incrementally improved patient outcomes, but have not yet been combined in clinical trials. We sought to characterize outcomes and toxicities after first-line chemotherapy and immunotherapy followed by cTRT. Patients with ES-SCLC who were treated with first-line chemotherapy and immunotherapy followed by cTRT were identified at 2 institutions. Patient outcomes including overall survival (OS), progression-free survival, local progression-free survival, distant progression free-survival, and toxicity were assessed. Twenty patients were included in our data set treated from 2018 to 2021 with a median follow-up of 12 months. Median OS in this cohort was 16 months with 6-month OS of 94.7% and 12-month OS of 77.5% (comparable to historical controls). There were also low rates of toxicity, including 0% grade 3+ toxicity, 0% grade 2 pneumonitis, and 5% grade 2 esophagitis. Treatment of ES-SCLC with first-line chemoimmunotherapy followed by cTRT appears to be safe and to have outcomes comparable to published modern clinical trials. Further studies are warranted to determine the therapeutic effect of cTRT after chemoimmunotherapy.


Phosphorylation of Neurogenin2 specifies the migration properties and the dendritic morphology of pyramidal neurons in the neocortex.
The molecular mechanisms specifying the dendritic morphology of different neuronal subtypes are poorly understood. Here we demonstrate that the bHLH transcription factor Neurogenin2 (Ngn2) is both necessary and sufficient for specifying the dendritic morphology of pyramidal neurons in vivo by specifying the polarity of its leading process during the initiation of radial migration. The ability of Ngn2 to promote a polarized leading process outgrowth requires the phosphorylation of a single tyrosine residue at position 241, an event that is neither involved in Ngn2 direct transactivation properties nor its proneural function. Interestingly, the migration defect observed in the Ngn2 knockout mouse and in progenitors expressing the Ngn2(Y241F) mutation can be rescued by inhibiting the activity of the small-GTPase RhoA in cortical progenitors. Our results demonstrate that Ngn2 coordinates the acquisition of the radial migration properties and the unipolar dendritic morphology characterizing pyramidal neurons through molecular mechanisms distinct from those mediating its proneural activity.


Tomato plant leaf disease segmentation and multiclass disease detection using hybrid optimization enabled deep learning.
Production of crops is increasing day by day in agriculture sectors. The insecurity of food is a main reason of plant disease and is a main global issue that humans face these days. With the design of contemporary environmental agriculture, more focus is devised for yielding the crop and elevating its quality. The occurrence of crops has elevated in years and the kind of disease has become more and more complex. The disease in plants and the pernicious insects are the major risks in agriculture field. Thus, earlier discovery and treatment of this disease are imperative. The major design of Deep Learning (DL) model helped in detecting the plant disease and grants a dynamic tool with accurate results. This paper presents DL-assisted technique for detecting and classifying the tomato disease and used deep batch-normalized eLu Alex Net (DbneAlexnet) for classifying the tomato plant leaves. Initially, tomato plant leaf images are taken as an input from specific dataset represented and it is subjected to preprocessing phase to eliminate unwanted distortions using anisotropic filtering. Then, the segmentation is carried out using U-net, which is trained by Gradient-Golden search optimization (Gradient-GSO) Algorithm and it is incorporation of both Golden search optimization (GSO) and Gradient concept. Thereafter the segmented image is given to image augmentation process, where position augmentation and color augmentation are considered. Finally, the multiclass plant leaf disease is classified using DbneAlexnet and is trained using proposed Gradient Jaya- Golden search optimization (GJ-GSO). Here, the GJ-GSO is devised with the integration of Gradient concept, Jaya algorithm, and GSO algorithm. The proposed GJ-GSO-based DbneAlexnet outperformed highest accuracy of 92.4%, True positive rate (TPR) of 91.9%, True negative rate (TNR) of 92.2% and smallest False Positive Rate (FPR) of 0.078. Hence, the technique with unified segmentation and classification is effectual for identifying the plant disease and the empirical research verifies the benefits of the developed model.


MiR-485-3p serves as a biomarker and therapeutic target of Alzheimer's disease via regulating neuronal cell viability and neuroinflammation by targeting AKT3.
Numerous microRNAs (miRNAs) have been identified as functional molecules in Alzheimer's disease (AD) pathogenesis. This study aimed to investigate the diagnostic value of microRNA-485-3p (miR-485-3p) in AD patients, evaluate the effect of miR-485-3p on neuronal viability and neuroinflammation, as well as the underlying molecular mechanisms. Quantitative Real-Time PCR was used to estimate expression of miR-485-3p and AKT3. A ROC analysis was used to evaluate the diagnostic value of miR-485-3p. The correlation of miR-485-3p with patients' MMSE score and inflammatory response was analyzed. Using Aβ-treated SH-SY5Y and BV2 cells models, the effects of miR-485-3p on neuronal proliferation, apoptosis, and neuroinflammation were explored. A luciferase reporter assay was used to confirm the target gene of miR-485-3p in both SH-SY5Y and BV2 cells. Serum miR-485-3p expression was significantly upregulated in AD patients and cell models, which had a high diagnostic accuracy and correlated with MMSE score and inflammatory response in AD patients. The knockdown of miR-485-3p in SH-SY5Y and BV2 cells was found to significantly reverse the effect of Aβ treatment on neuronal viability and neuroinflammation. AKT3 was determined as a target of miR-485-3p, which might mediate the biological function of miR-485-3p in AD pathogenesis. All the data indicated that increased serum miR-485-3p serves as a diagnostic biomarker in AD patients, and knockdown of miR-485-3p exerts a neuroprotective role by improving neuronal viability and weakening neuroinflammation, which may be mediated by AKT3. This study may provide a novel biomarker and therapeutic target for AD therapy.


Small and large fixed ratios with the same unit price.
Key pressing of rats was maintained under multiple and discrete-trial choice schedules with reinforcer units of 45 mg food pellets or 3.5 s dips of sucrose solution. Both smaller and larger fixed ratio (FR) schedules were associated with the same unit price in a manner, for example, that each of eight iterations of FR120 was associated with delivery of a single reinforcer unit and one instance of FR960 was associated with eight reinforcer units. FR requirement varied between 20 and 1560 per aggregate reinforcer and unit price varied between 20 and 240 per reinforcer unit. During multiple schedules with food reinforcers, rates and patterns of responding were comparable over nearly a 50-fold range of FR requirements (20-1380) when unit price was 20; over nearly a six-fold range of FR requirements (120-720) when unit price was 120; and was only marginally maintained when unit price was 240. Demand for food pellets was comparatively inelastic at FRs between 20 and 120, during which subjects did not receive supplemental feeding outside experimental sessions, but was elastic at FRs greater than 240, when subjects sometimes did receive supplemental feeding. In a discrete-trial choice procedure with a constant unit price of 120 for sucrose solution, subjects were indifferent between smaller FRs and alternative FRs as large as 480, but began switching away from larger FRs that were 600 or greater. Because responding had been comparably maintained under both FR120 and FRs as large as 960 in the multiple schedule, results from the choice procedure indicated that choice performance was influenced by variables other than FR requirement and unit price. Because aggregate reinforcers were the same for smaller and larger FRs, the most likely reason for preferring smaller FRs was the nearness in time to some reinforcer.


A Bibliometric Analysis of the Top 100 Most Influential Articles on Cerebral Cavernous Malformations.
Cerebral cavernous malformations (CCMs) or cavernomas, are low-flow sinusoidal vascular anomalies of the central nervous system comprised of capillary networks filled with blood in various stages of thrombosis. This bibliometric analysis summarizes the most-cited articles on CCM and highlights the contributing articles to today's evidence-based practice. In the execution of this bibliometric-based review article, the Scopus database was used to perform a title-specific, keyword-based search for all publications until June 2022. The keyword "cerebral cavernous malformations" OR "cerebral cavernous hemangioma" OR "cerebral cavernous angioma" OR "cerebral cavernoma." was used. Our results were arranged in descending order based on the article's citation count. The 100 most-cited articles were selected for analysis. Parameters included the following: title, citation count, citations per year, authors, specialty of first author, institution, country of origin, publishing journal, Source Normalized Impact per Paper, and Hirsch index were collected. The keyword-based search showed that 806 articles were published between 1974 and 2022 on CCMs. The top 100 articles were published between 1980 and 2018. The top 100 most cited articles collected a total of 12,928 citations with an average of 129.3 citations per paper. The rate of self-citations accounted for an average of 2.79% of the total number of citations. The bibliometric analysis provides a quantitative overview of how medical topics and interventions are analyzed in academic medicine. In the present study, we evaluated the global trends in CCMs by analyzing the top 100 most cited papers.


The investigation of the correlation between metabolic syndrome and Chinese medicine constitution types in senior retired military personnel of the People's Liberation Army.
To investigate the incidence of metabolic syndrome (MS) and the distribution of constitutional pattern in elderly retired personnel of the People's Liberation Army. Adopting the method of cross-sectional field investigation, from June to December in 2008, the investigation questionnaires were completed by the aged over 60 and collected from 69 military retired residences in the 4 cities of Shanghai, Nanjing, Hangzhou and Qingdao. Other data, including demographic characteristics, physiological characteristics, life style and former medical history, were collected and analyzed. The statistical analysis for the database was drawn up by the software Epidata 3.0. A total of 4,502 people were included in this study, and 35.3% of them were diagnosed with MS. There was no obvious difference in mobility among ages (60 to 69, 70 to 79 and over 80, P>0.05). Referring to the MS patients in the 70s age group, both the phlegm-dampness and dampness-heat constitutional types were evidently higher than those in the 60s age group (P=0.019, P=0.008); while MS patients in 80s and older showed a significantly lower incidence of dampness-heat constitution than those in the 60s (P=0.00); and ql-deficiency constitution was obviously higher in the 80s age group than those in the other two groups (P=0.00). The top 3 constitutions in MS people were, respectively, phlegm-dampness, dampness-heat and qi-deficiency constitution; while in non-MS people, the top 3 constitutions were gentleness, qi-deficiency and phlegm-dampness. When the patient's body mass index (BMI) was more than 25 kg/m(2), the rate of phlegm-dampness and dampness-heat constitution significantly increased, while the rate of qi-deficiency constitution declined; the discrepancy was significant (P=0.00). The prevalence rate of MS in military senior people was 35.3%, which did not vary among the three age groups. Phlegm-dampness, dampness-heat and qi-deficiency constitution were the three dominant constitutional types seen in the MS patients. The distribution of constitution formation was different in MS people and non-MS people. For different dimensions of BMI, the proportion of each kind of constitutions was varied.


Responding to the emotions of others: dissociating forms of empathy through the study of typical and psychiatric populations.
Empathy is a lay term that is becoming increasingly viewed as a unitary function within the field of cognitive neuroscience. In this paper, a selective review of the empathy literature is provided. It is argued from this literature that empathy is not a unitary system but rather a loose collection of partially dissociable neurocognitive systems. In particular, three main divisions can be made: cognitive empathy (or Theory of Mind), motor empathy, and emotional empathy. The two main psychiatric disorders associated with empathic dysfunction are considered: autism and psychopathy. It is argued that individuals with autism show difficulties with cognitive and motor empathy but less clear difficulties with respect to emotional empathy. In contrast, individuals with psychopathy show clear difficulties with a specific form of emotional empathy but no indications of impairment with cognitive and motor empathy.


The human long noncoding RNA lnc-IL7R regulates the inflammatory response.
Long noncoding RNAs (lncRNAs), once thought to be transcriptional noise, have been recently shown to regulate a variety of biological processes. However, there is not much knowledge regarding their roles in the inflammatory response. In this study, we performed human lncRNA microarray assays and identified a number of lncRNAs that demonstrated altered expression in response to LPS stimulation. Of these lncRNAs, lnc-IL7R, which overlaps with the 3'untranslated region (3'UTR) of the human interleukin-7 receptor α-subunit gene (IL7R) gene, was significantly upregulated in LPS-treated cells. Functionally, lnc-IL7R was capable of diminishing the LPS-induced inflammatory response, demonstrated by elevated expression of LPS-induced E-selectin, VCAM-1, IL-6, and IL-8 in lnc-IL7R knockdown cells. Mechanistically, we found that lnc-IL7R knockdown diminished trimethylation of histone H3 at lysine 27 (H3K27me3), a hallmark of silent transcription, at the proximal promoters of the inflammatory mediators. Our data suggest that lnc-IL7R contributes another layer of complexity in regulation of the inflammatory response.


Effect of carrageenan on the non-specific resistance of mice to injected syngeneic tumour cells, alone or in mixtures.
The mechanisms of non-specific resistance to syngeneic methylcholanthrene-induced fibrosarcomas of mice were investigated. Results showed that a small tumour graft of 0.05 X 10(5) cells is greatly enhanced in growth when admixed with large numbers of cell fragments, killed cells or viable non-replicating cells. The enhancement of small tumour grafts in cell mixtures was found to be non-specific. Carrageenan, a known anti-macrophage agent, significantly increased tumour growth in normal mice. However, it did not enhance the increased tumour growth of 0.05 X 10(5) cells mixed with 10(6) viable, non-replicating mitomycin C-treated tumour cells. The latter observation indicates that carrageenan and admixed cells interfere with the same tumour-inhibitory mechanism and therefore cannot produce additive effects. The results give support to the concept of a non-specific macrophage "surveillance" system which appears crucial in controlling tumour growth, since it determines the establishment of small numbers of tumour cells while they can still be easily destroyed.


Detection of c-fms protooncogene in early mouse embryos by whole mount in situ hybridization indicates roles for macrophages in tissue remodelling.
The c-fms protoncogene which encodes the receptor for macrophage colony-stimulating factor (CSF-1) was localized in the developing mouse embryo by whole in situ hybridization. c-fms was expressed first in placental trophoblasts. Around 9.5 dpc, isolated c-fms-positive cells became detectable in the yolk sac and by 10.5 dpc large numbers were detectable throughout the embryo. The localization of c-fms expression was consistent with its restriction to macrophages, and with the location of those macrophages in sites of tissue turnover and extensive cell death.


Short-term effect of COVID-19 pandemic on cryptocurrency markets: A DCC-GARCH model analysis.
This research examines the impact of the coronavirus index on the returns and volatility of ten major cryptocurrencies during the COVID-19 pandemic. For this purpose, we applied a multivariate volatility GARCH model with an integrated dynamic conditional correlation (DCC) approach to daily cryptocurrency values observed data during the January-December, 2020 period. Moreover, we used the Granger causality test to study return-volume correlations. The findings indicate that cryptocurrency volatility declined after the World Health Organization declared on March 11, 2020, that the coronavirus was a pandemic. Unlike most of the relevant previous studies, we found that the COVID-19 crisis did not have a long-term effect on cryptocurrency returns and volatility but only presented a short-term effect. Our results have implications for investors who need to determine an optimal portfolio for a scenario other than the base.


Improved efficiency of butanol production by absorbent fermentation with a renewable carrier.
Biobutanol production is still not economically competitive because of some principal drawbacks including high cost in feedstock consumption, low butanol concentration in the fermentation broth caused by severe product inhibition. An alternative fermentation mode is becoming an urgent requirement to solve these problems. Biobutanol production by absorbent fermentation with a renewable carrier, i.e. pretreated straw materials, is studied in this paper. Compared with other types of porous media, alkali-treated steam-exploded straw was proved to be a suitable carrier for absorbent fermentation of butanol. The Acetone-Butanol-Ethanol (ABE) concentration increased by 52% compared with submerged culture at an initial glucose concentration of 65 g/L. The adsorption of ABE solvent on substrate and increased bacterial concentration alleviated the end product inhibition and partly explained this positive effect. The steam pretreatment conditions, solid-liquid ratio, substrate types and substrate concentration were also investigated. Steam-explosion at 1.1 MPa for 4 min and solid-liquid ratio of 1:10 was shown to be the optimum. Glucose showed a great advantage over xylose, and higher glucose content was more conducive to biobutanol production. However, the yield of solvent decreased with the increased initial sugar concentration. Considering comprehensively, 100 g/L initial glucose was considered to be the optimum. This work demonstrated an effective approach of improved butanol fermentation and its probable mechanisms of this positive effect, i.e. the adsorption of ABE solvent and the adhesion of bacteria on porous substrate accounted for the production improvement and the proportional variation of solvent constituents.


Molecular phylogeny of the fern family Blechnaceae (Polypodiales) with a revised genus-level treatment.
Blechnaceae, a leptosporangiate fern family nested within eupolypods II, comprises 200-250 species, typically divided among seven to nine genera. Despite recent molecular studies of the family, it still lacks a modern taxonomic update based on broad sampling from the two centres of diversity-the Neotropics and Australasia/Oceania. To test generic circumscriptions, we have assembled the broadest dataset thus far, from three plastid regions (rbcL, rps4-trnS, trnL-trnF) and with taxonomic sampling focused on both major diversity centres. Our sampling includes 156 taxa and 178 newly generated sequences. We recognize three subfamilies, each corresponding to a highly supported clade across all analyses (maximum parsimony, Bayesian inference and maximum likelihood). The genera Salpichlaena, Stenochlaena and Telmatoblechnum are monophyletic, while Blechnum is polyphyletic, because Brainea, Doodia and Sadleria all nest within it. We outline and explain a plan to resolve the polyphyly of Blechnum by recognizing additional, monophyletic, segregate genera.


Risk factors associated with pre-eclampsia in pregnancies conceived by ART.
What are the factors associated with the increased incidence of pre-eclampsia in pregnancies conceived through IVF using autologous oocytes? A nested case-control study from the combined cohort of three multicentre randomized trials comparing fresh to frozen embryo transfer, including women who achieved clinical pregnancy after the first embryo transfer. Multivariable logistic regression was used to assess the effect of baseline characteristics, ovarian response parameters, type of fertilization, type of embryo transfer, and number of gestational sacs on the risk of pre-eclampsia. There were 2965 clinical pregnancies and 90 women were diagnosed with pre-eclampsia. Twin gestations (odds ratio [OR] 2.34, 95% confidence interval [CI] 1.50-3.66), mean arterial pressure (OR 1.04, 95% CI 1.01-1.07), frozen embryo transfer (OR 2.06, 95% CI 1.27-3.35), body mass index (BMI) (OR 1.10, 95% CI 1.02-1.18), progesterone level on the day of human chorionic gonadotrophin trigger (OR 1.53, 95% CI 1.07-2.20), and the total dose of gonadotrophin (OR 0.999, 95% CI 0.999-1.000, P = 0.037) were associated with the risk of pre-eclampsia. When the analysis was confined to women who underwent frozen embryo transfer, twin gestations (OR 2.44, 95% CI 1.43-4.18), BMI (OR 1.13, 95% CI 1.03-1.23) and the total dose of gonadotrophin (OR 0.999, 95% CI 0.999-1.000, P = 0.014) were still related to the risk of pre-eclampsia. The embryo stage at transfer was not included in the final models. Frozen embryo transfer was an independent risk factor of pre-eclampsia in assisted reproductive technology. The high ovarian response may also increase the risk of pre-eclampsia. The embryo stage at transfer was not related to the risk of pre-eclampsia.


Dichotomy of Dosage Compensation along the Neo Z Chromosome of the Monarch Butterfly.
Mechanisms of sex chromosome dosage compensation (SCDC) differ strikingly among animals. In Drosophila flies, chromosome-wide transcription is doubled from the single X chromosome in hemizygous (XY) males, whereas in Caenorhabditis nematodes, expression is halved for both X copies in homozygous (XX) females [1, 2]. Unlike other female-heterogametic (WZ female and ZZ male) animals, moths and butterflies exhibit sex chromosome dosage compensation patterns typically seen only in male-heterogametic species [3]. The monarch butterfly carries a newly derived Z chromosome segment that arose from an autosomal fusion with the ancestral Z [4]. Using a highly contiguous genome assembly, we show that gene expression is balanced between sexes along the entire Z chromosome but with distinct modes of compensation on the two segments. On the ancestral Z segment, depletion of H4K16ac corresponds to nearly halving of biallelic transcription in males, a pattern convergent to nematodes. Conversely, the newly derived Z segment shows a Drosophila-like mode of compensation, with enriched H4K16ac levels corresponding to doubled monoallelic transcription in females. Our work reveals that, contrary to the expectation of co-opting regulatory mechanisms readily in place, the evolution of plural modes of dosage compensation is also possible along a single sex chromosome within a species.


'So few fat ones grow old': diet, health, and virtue in the golden age of rising life expectancy.
Life expectancy and chronic disease rates both rose dramatically in the United States during the first third of the twentieth century. As a result of this concurrence, Americans in this era increasingly thought about things they could do to extend their own lives, especially eating less, exercising more, and limiting stress, all factors thought to reduce chronic disease. New recognition of the correlation between daily physical habits and long lives made longevity look like a sign of virtue. At the same time, amidst discussions about the relationship between individual longevity and national vitality, this correlation also contributed to Americans' moralization of diet, exercise, and emotional self-control.


Twist1 homodimers enhance FGF responsiveness of the cranial sutures and promote suture closure.
Haploinsufficiency of the transcription factor TWIST1 is associated with Saethre-Chotzen Syndrome and is manifested by craniosynostosis, which is the premature closure of the calvaria sutures. Previously, we found that Twist1 forms functional homodimers and heterodimers that have opposing activities. Our data supported a model that within the calvaria sutures Twist1 homodimers (T/T) reside in the osteogenic fronts while Twist1/E protein heterodimers (T/E) are in the mid-sutures. Twist1 haploinsufficiency alters the balance between these dimers, favoring an increase in homodimer formation throughout the sutures. The data we present here further supports this model and extends it to integrate the Twist1 dimers with the pathways that are known to regulate cranial suture patency. This data provides the first evidence of a functional link between Twist1 and the FGF pathway, and indicates that differential regulation of FGF signaling by T/T and T/E dimers plays a central role in governing cranial suture patency. Furthermore, we show that inhibition of FGF signaling prevents craniosynostosis in Twist1(+/-) mice, demonstrating that inhibition of a signaling pathway that is not part of the initiating mutation can prevent suture fusion in a relevant genetic model of craniosynostosis.


Optimizing post-operative imaging: a retrospective cohort study comparing two methods of lateral hip radiography after cephalomedullary nail surgery.
Currently, there is no consensus on the most appropriate technique for obtaining lateral hip radiographs after cephalomedullary nail (CMN) surgery. The aim of this study was to investigate the distribution of two commonly used postoperative lateral hip radiographic methods (classic lateral view and modified lateral view) and try to find out which one is better suited for this situation. A retrospective analysis was conducted on 146 patients who underwent surgical fixation for extracapsular hip fractures between January 2018 and June 2022. The main outcome measured was the angle between the straight part of the CMN and the lag screw/blade on hip lateral X-rays (CMNA). The lateral hip radiographs were categorized into two groups based on different lateral hip radiographic methods. CMNA, patient age, gender, fracture classification based on the 2018 AO classification, nail length (short/long), surgical side (left/right), height, weight, BMI, preoperative waiting time, postoperative imaging interval were collected and compared between the two groups. The distribution trend of CMNA significantly differs between two types of hip joint lateral radiographic methods. Specifically, the classic lateral method exhibits a significantly bimodal and skewed distribution with a median (p25, p75) of -21.6° (-31.2°, -8°), whereas the modified lateral method presents a normal distribution with a mean ± SD of +7.57° ± 14.4°. The difference in the Mean Rank between the classic (47.10) and the modified (102.96) lateral methods is statistically significant (P < 0.001). The CMNA method is an excellent tool for studying the lateral distribution.We recommend using the modified lateral view as the preferred option for obtaining lateral hip radiographs after CMN surgery due to its superior distribution of CMNA and greater patient-friendliness.


HAM/TSP-derived HTLV-1-infected T cell lines promote morphological and functional changes in human astrocytes cell lines: possible role in the enhanced T cells recruitment into Central Nervous System.
The mechanisms through which HTLV-1 leads to and maintains damage in the central nervous system of patients undergoing HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) are still poorly understood. In recent years, increasing evidence indicates that, not only lymphocytes but also glial cells, in particular astrocytes, play a role in the pathophysiology of HAM/TSP. In this study we used a model of co-culture between human HTLV-1-infected (CIB and C91PL) and non-infected (CEM) T lymphocyte cell lines and astrocyte (U251 and U87) cell lines to mimic the in vivo T cell-astrocyte interactions. We first observed that CIB and C91PL adhere strongly to cultured astrocytes cell lines, and that co-cultures of HTLV-1 infected and astrocyte cell lines cells resulted in rapid syncytium formation, accompanied by severe morphological alterations and increased apoptotic cell death of astrocyte cells. Additionally, cultures of astrocyte cell lines in presence of supernatants harvested from HTLV-1-infected T cell cultures resulted in significant increase in the mRNA of CCL2, CXCL1, CXCL2, CXCL3, CXCL10, IL-13, IL-8, NFKB1, TLR4, TNF, MMP8 and VCAM1, as compared with the values obtained when we applied supernatants of non-infected T- cell lines. Lastly, soluble factors secreted by cultured astrocytic cell lines primed through 1-h interaction with infected T cell lines, further enhanced migratory responses, as compared to the effect seen when supernatants from astrocytic cell lines were primed with non-infected T cell lines. Collectively, our results show that HTLV-1 infected T lymphocyte cell lines interact strongly with astrocyte cell lines, leading to astrocyte damage and increased secretion of attracting cytokines, which in turn may participate in the further attraction of HTLV-1-infected T cells into central nervous system (CNS), thus amplifying and prolonging the immune damage of CNS.


Platorchestiinae subfam. nov. (Amphipoda, Senticaudata, Talitridae) with the description of three new genera and four new species.
A new subfamily, Platorchestiinae, is established for fifteen genera of talitrid amphipods of which three: Cocorchestia gen. nov.; Demaorchestia gen. nov. and Insularorchestia gen. nov. are new. Four new species are described: Demaorchestia hatakejima sp. nov.; D. mie sp. nov.; D. pseudojoi sp. nov. and Insularorchestia susorum sp. nov..


Adsorption of Cu(II), Cd(II) and Ni(II) ions by cross-linked magnetic chitosan-2-aminopyridine glyoxal Schiff's base.
The adsorption of Cu(II), Cd(II) and Ni(II) ions from aqueous solution by cross-linked magnetic chitosan-2-aminopyridine glyoxal Schiff's base resin (CSAP) was studied in a batch adsorption system. Cu(II), Cd(II) and Ni(II) removal is pH dependent and the optimum adsorption was observed at pH 5.0. The adsorption was fast with estimated initial rate of 2.7, 2.4 and 1.4 mg/(g min) for Cu(2+), Cd(2+) and Ni(2+) respectively. The adsorption data could be well interpreted by the Langmuir, Freundlich and Temkin model. The maximum adsorption capacities obtained from the Langmuir model were 124±1, 84±2 and 67±2 mg g(-1) for Cu(2+), Cd(2+) and Ni(2+) respectively. The adsorption process could be described by pseudo-second-order kinetic model. Thermodynamic parameters revealed the feasibility, spontaneity and exothermic nature of adsorption. The sorbents were successfully regenerated using EDTA and HCl solutions.


Comparison of 2 Different Paclitaxel-Coated Balloons in Coronary In-Stent Restenosis: A Randomized Controlled Trial.
Drug-coated balloons (DCBs) offer an effective treatment for in-stent restenosis (ISR). The Genoss DCB is a novel paclitaxel-coated balloon with a shellac plus vitamin E excipient that enhances drug delivery to the target lesion, minimizing restenosis. This study aimed to investigate the angiographic efficacy, clinical safety, and effectiveness of the novel shellac plus vitamin E-based DCB in a randomized controlled trial designed to enable regulatory approval of this new device in South Korea. This noninferiority trial randomized patients experiencing their first ISR to the novel shellac plus vitamin E-based DCB or the reference SeQuent Please iopromide-based DCB in a 1:1 ratio. All patients underwent planned angiographic and clinical follow-up at 6 months. The study was powered for the primary endpoint of 6 months in-segment late lumen loss (LLL). A total of 82 patients from 7 centers were randomized to either the novel shellac plus vitamin E-based DCB group (n = 41) or the reference iopromide-based DCB group (n = 41). The 6-month in-segment LLL was 0.15 ± 0.43 mm with the novel DCB compared with 0.24 ± 0.39 mm with the reference device. The 1-sided 97.5% upper confidence limit of the difference was 0.13 mm, lower than the noninferiority limit of 0.29 mm, achieving noninferiority (P for noninferiority = 0.001). Major cardiovascular events were comparable between 2 groups at 6 months (7.7% for the novel DCB vs 10.3% for the reference DCB; P = 0.692). In this multicenter, head-to-head comparison randomized trial, the novel shellac plus vitamin E-based DCB showed a comparable result to the reference iopromide-based device for the primary endpoint of 6-month in-segment LLL for the treatment of coronary ISR. (Compare the Safety and Efficacy of Genoss® DCB and SeQuent® Please in Korean Patient With Coronary In-stent Restenosis; NCT04405063).


Prostate-specific antigen immunosensing based on mixed self-assembled monolayers, camel antibodies and colloidal gold enhanced sandwich assays.
Prostate-specific antigen (PSA) is a valuable biomarker for prostate cancer screening. We developed a PSA immunoassay on a commercially available surface plasmon resonance biosensor. Our PSA receptor molecule consists of a single domain antigen-binding fragment, cAbPSA-N7, derived from dromedary heavy-chain antibodies and identified after phage display. It binds PSA with a high k(on) value of 1.9x10(6) M-1 s-1, and was covalently immobilised on a gold substrate via a mixed self-assembled monolayer (SAM) of alkanethiols by using carbodiimide-coupling chemistry in 10mM acetate buffer pH 5.5 to obtain an optimal pre-concentration. The best performing and optimised mixed SAM consisted of (10%) 16-mercapto-1-hexadecanoic acid (16-MHA) for covalent cAbPSA-N7 immobilisation and (90%) 11-mercapto-1-undecanol (11-MUOH) to minimise non-specific adsorption of the analyte. In this way, two advantages are incorporated in a single coupling layer. Up to 28 fmol/mm2 of cAbPSA-N7 could be immobilised and 30% of its binding sites participate actively in PSA interaction. In addition, the optimised layer showed also optimal performance to assess physiological samples. Although PSA concentrations as low as 10 ng/ml could be detected directly, this detection limit could be enhanced to PSA levels in the sub ng/ml range by introducing a sandwich assay involving a biotinylated secondary antibody and streptavidin modified gold nanoparticles. This approach realizes the PSA detection at clinical relevant concentrations.


[Utilization of a multiparametric technique for analysis of specificity of different inhibitors of various forms of cyclic nucleotide phosphodiesterases].
Multiple enzymes and compounds were used to study relationship between chemical structure and enzymatic affinity. Reduction of multidimensional data, by mathematical methods, as factorial correspondence analysis (FCA), with simple graphical representation allows to define the relative specificity of various molecules for different enzymatic targets. Using a significative sample of molecule tests and their biological responses it would be possible for each new compound to determine its typology inside its molecular family and to give insight for pharmacological modulation. Papaverine analogues reference drugs and three isolated cyclic nucleotide phosphodiesterase forms were used as experimental model in this analysis.


Effects of daily levels of fatigue and acutely induced fatigue on the visual evoked magnetic response.
Fatigue is a common complaint in modern society. As photosensitivity is associated with fatigue, this study aimed to clarify the relationship between neural response to visual stimuli and fatigue using a 160-channel whole-head-type magnetoencephalographic system. Twelve healthy male volunteers were enrolled. Participants were randomly assigned to two groups in a single-blinded, crossover fashion to perform acute fatigue-inducing mental task sessions, i.e., 0-back or 2-back test for 30 min. Visual evoked magnetic field (VEF) intensities were evaluated by standardized low-resolution brain electromagnetic tomography modified for a quantifiable method. VEF consisted of two phases, and although acute fatigue did not alter the VEF intensities and the intensities before the acute fatigue-inducing mental task sessions were not correlated with the Chalder's Fatigue Scale scores in either of the two phases, the intensities after the 0-back test trials for 30 min in Phase 1 and those after the 2-back test trials in Phase 2 were significantly correlated with the fatigue scale scores. The daily level of fatigue was related to VEF intensity after the acute mental fatigue loads. Our findings provide new perspectives to evaluate our daily level of fatigue as well as to clarify the neural mechanisms underlying it.


Proteome analysis in dystrophic mdx mouse muscle reveals a drastic alteration of key metabolic and contractile proteins after chronic exercise and the potential modulation by anti-oxidant compounds.
Weakness and fatigability are typical features of Duchenne muscular dystrophy patients and are aggravated in dystrophic mdx mice by chronic treadmill exercise. In the present study, we describe, the pattern of differentially abundant spots that is associated to the worsening of dystrophy phenotype induced by chronic exercise. Our proteomic analysis pointed out 34 protein spots with different abundance between sedentary and exercised mdx mice. These proteins belong mostly to glucose metabolism, energy production and sarcomere structure categories. Interestingly exercise induced an increase of typical fast twitch fiber proteins (Troponin T fast skeletal muscle, Troponin I fast skeletal muscle and Myozenin-1) combined with an increase of several glycolytic enzymes. Concerning energy transfer, Adenylate kinase, showed a marked decrease when compared with non-exercised mdx. The decline of this enzyme correlates with increased Creatin kinase enzyme, suggesting that a compensatory energy metabolism mechanism could be activated in mdx mouse skeletal muscle following exercise. In addition, we analysed muscles from exercised mdx mice treated with two natural anti-oxidant compounds, apocynin and taurine, that in our previous study, were proved to be beneficial on some pathology related parameters, and we showed that these compounds can counteract exercise-induced changes in the abundance of several proteins. Mdx mouse model of Duchenne muscular dystrophy shows a phenotype of the disorder milder than in human sufferers. This phenotype can be worsened by a different protocols of chronic exercise. These protocols can mimic the muscle progressive damage observed in humans, can allow studying the effects of inadequate training on dystrophic muscles and have been largely used to assess the ability of a drug to reduce the damage induced by exercise. In this study, we describe for the first time, the pattern of protein variation associated with the worsening of dystrophy phenotype induced by chronic exercise. Our proteomic analysis pointed out 34 protein spots with different amount between sedentary and exercised mdx mice. These proteins belong mostly to glucose metabolism, energy production and sarcomere structure categories and their variation indicates that mdx exercised muscle are not able to carry out the metabolic changes associated to fast-to-slow transition typically observed in aerobically trained muscle.


Theoretical investigations of the IR spectroscopy of Ni(C(2)S(2)H(2))(2). A case study of the P_VMWCI(2) algorithm including anharmonic effects.
The near infrared (NIR) spectra of bis(ethylene-1,2-dithiolato)nickel, Ni(C(2)S(2)H(2))(2) are fully interpreted here by applying a method developed for efficient automatic computation of both the infrared wave numbers and the intensities. The employed procedure uses parallel variational multiple window configuration interaction wave functions, the so-named P_VMWCI(2) algorithm, which incorporates both the mechanical and the electric anharmonic effects. It is shown that inclusion of anharmonicities is crucial for correctly assigning the fundamental, combination, and overtone vibrational frequencies in the infrared spectrum of the target system, for which conflicting assignments are found in literature.


Chitosan: A compound for drug delivery system in gastric cancer-a review.
Gastric cancer is known as the fourth most common cancer and the second main cause of cancer-related deaths. Gastric cancer has some characteristics including high incidence rates of metastasis and mortality as well as low rates of early diagnosis, radical resection and 5-year survival. Radical surgery and following chemotherapy has been done for patients with early gastric cancer leading to 90 % survival rate in 5-year after operation. Besides, in advanced stage some cases don't have the chance of surgery as well as the risk of metastasis is high in these patients overally leading to poor prognosis. In recent years, finding a suitable drug delivery system for chemotherapeutic drugs in gastric cancer is an considerable subject for researchers. Chitosan is known as an appropriate compound for chemo-drug delivery in cancer treatment due to its high biodegradability and biocompatibility. Moreover, trans-mucosal drug delivery is facilitated by chitosan via its mucoadhesive and cationic features enhancing interaction with mucous membrane. In addition, a large amount of experimental evidence has reported the efficacy of chitosan for drug delivery in gastric cancer. Thus, the aim of this article was to review this evidence as well as new chitosan-based drug delivery systems investigated in gastric cancer.


Infection by Leishmania amazonensis in mice: a potential model for chronic hypoxia.
Hypoxia is a common feature of injured and infected tissues. Hypoxia inducible factors 1α and 2α (HIF-1α, HIF-2α) are heterodimeric transcription factors mediating the cellular responses to hypoxia and also the vascular endothelial growth factor (VEGF). VEGF is a cytokine which can be induced by hypoxia, whose pathogenic mechanisms are still unclear and which is the subject of debate. Murine cutaneous lesions during Leishmania amazonensis parasite infection are chronic, although they are small and self-controlled in C57BL/6 mice and severe in BALB/c mice. In the present study we examined the presence of hypoxia, HIF-1α, HIF-2α and VEGF during the course of infection in both mouse strains. Hypoxia was detected in lesions from BALB/c mice by pimonidazole marking, which occurred earlier than in lesions from C57Bl/6 mice. The lesions in the BALB/c mice showed HIF-1α and HIF-2α expression in the cytoplasm of macrophages and failed to promote any VEGF expression, while lesions in the C57BL/6 mice showed HIF-2α nuclear accumulation and subsequent VEGF expression. In conclusion, the animal models of leishmaniasis demonstrated a diversity of patterns of expression, cell localization and activity of the main transducers of hypoxia and may be useful models for studying the pathogenic mechanisms of HIF-1α and HIF-2α during chronic hypoxic diseases.


Long Term Outcomes of Intratympanic Dexamethasone in Intractable Unilateral Meniere's Disease.
To evaluate the long term effect of Intratympanic dexamethasone in intractable Meniere's disease. 30 patients with refractory Meniere's disease which did not respond to the standard medical management, were treated with Intratympanic dexamethasone injections. Post treatment hearing outcome and dizziness scores were compared with the pretreatment values respectively. The mean dizziness handicap inventory (DHI) score was reduced from 91.58 (range 80-100) to be 31.00 (p = 0.00) at 3 months of treatment. With the successive follow-up periods, the mean DHI scores were reduced to 51.50, 46.6, and 50.90 at the end of, 6, 12, and 24 months (p = 0.04, 0.35, and 0.49 respectively). Again at the end of 24 months, 23.80% of patients were free of vertigo (p = 0.01). No patient had improvement in the hearing (> 10 dB) in any of the follow-up periods and 6.6% demonstrated deterioration in hearing. There were no major intraoperative or postoperative complications detected. Intratympanic injection of steroid is a safe and effective method for treating intractable Meniere's disease. Although short term improvement in the vertigo is well documented, still in 23% of the patients were found to be free of vertigo at even the end of 24 months. There was no significant improvement in hearing noticed, either in short term or in long term.


Profiling an electrospray plume by laser-induced fluorescence and Fraunhofer diffraction combined to mass spectrometry: influence of size and composition of droplets on charge-state distributions of electrosprayed proteins.
We investigated how physico-chemical properties of charged droplets are affected by the electrospray process, using simultaneous in situ measurements by laser-induced fluorescence (LIF), Fraunhofer diffraction and mass spectrometry. For this purpose, we implemented a laser-induced-fluorescence profiling setup in conjunction with a fast, high-resolution particle sizing scheme on a modified Agilent Jet Stream electrospray source coupled to a single quadrupole mass analyser. The optical setup permits us to profile the solvent fractionation and the size of the droplets as they evaporate in an electrospray plume by measuring both the angular scattering pattern and emission spectra of a solvatochromic fluorescent dye. Mass spectra are recorded simultaneously. These mass spectrometry and optical spectroscopy investigations allow us to study the relation between the observed charge-state distributions of protein anions and physico-chemical properties of evaporating droplets in the spray plume. By mixing water with methanol, a refolding of cytochrome C is observed as the water percentage increases in the plume due to the preponderant evaporation of volatile methanol.


Bovine neutrophils recruited by endotoxin to a teat cistern continuously produce oxygen radicals and show increased phagocytosis and extracellular chemiluminescence.
Bovine neutrophils were harvested from a teat cistern following endotoxin infusion and were compared with blood neutrophils by measurements of chemiluminescent and phagocytic activity towards C3- and IgG-opsonized and unopsonized yeast particles. Both phagocytosis and luminol-dependent chemiluminescence elicited by all three particles were enhanced in the teat cells. The increase in the luminol-dependent chemiluminescence towards C3- and IgG-opsonized particles was due to an enhanced extracellular release of myeloperoxidase. The observed increase in phagocytosis of unopsonized yeast was shown to reflect the interaction between up-regulated CR3 receptors on the surface of the teat neutrophils and the yeast particles. A high chemiluminescent activity of the teat neutrophils in both the luminol- and lucigenin-dependent systems in the absence of a phagocytic prey indicated that the NADPH oxidase was permanently active and that myeloperoxidase was continuously released by the cells. Treatment of neutrophils with cytochalasin B showed that the chemiluminescence and phagocytosis of teat neutrophils were less sensitive to this drug than that of blood neutrophils. These results indicate that the teat neutrophils have up-regulated their receptors for IgG- and C3-opsonized and unopsonized yeast on the cell surface by the action of actin. The cells also have a permanently active NADPH oxidase dependent on the association with actin and show a higher tendency than blood neutrophils to secrete the content of their primary granules during phagocytosis.


Salvage of thrombosed arteriovenous fistulae of patients on hemodialysis: report on the experience of a Brazilian center.
Hemodialysis vascular access thrombosis is an acute event that can interrupt the dialytic treatment. A timely management can restore access patency, avoiding the use of central venous catheters and their complications. To present the experience from a Brazilian Interventional Nephrology Center (INC) in the salvage of arteriovenous fistula (AVF) and grafts for hemodialysis. A retrospective study was performed to evaluate the primary and secondary patencies of 41 hemodialysis accesses with thrombosis confirmed by ultrasound and submitted to endovascular salvage procedures. We considered clinical success the use of the access for at least 3 subsequent hemodialysis sessions. The procedures were done in an outpatient center by interventional nephrologists. Patients were followed for up to 18 months with Doppler every 3 months. Forty-five salvage procedures were performed in 41 accesses of 40 hemodialysis patients with native AVF or grafts. Of these, 90% were AVF, mostly upper arm, and 10% were grafts. Clinical success rate was 60% (27 procedures). Primary patency at 12 months was 39% and secondary was 52%. Gender of the patient, diabetes, and location of the access did not correlate statistically with outcomes. There were 3 major complications (anastomosis rupture, grade 3 hematoma, and anaphylactic shock). The majority of thrombosed accesses can be successfully treated, maintaining its long-term patency. The need of repeated intervention is frequent.