Effectiveness and risk associated with infliximab alone and in combination with immunosuppressors for Crohn's disease: a systematic review and meta-analysis.
Infliximab (IFX) monotherapy and IFX combined with immunosuppressors have been used in the treatment of Crohn's disease. However, the differences between combination therapy and IFX alone remain controversial. The aim of this meta-analysis was to evaluate the effectiveness and risk associated with combination therapy and IFX monotherapy. Systematic searches were performed for randomized controlled trials with PubMed, Web of Science, OVID, and the Cochrane Library. The analyzed contents included induction of remission, short-term maintenance of remission, long-term maintenance of remission, and risks. The final results were estimated using statistical data of odds ratio (OR), relevant 95% confidence interval (CI), and P value. 6 out of 1041 citations met the selection criteria. There was no statistical difference in the effectiveness of induction and long-term maintenance of remission between two groups (P=0.07, 0.12). However, for short-term maintenance of remission, there was mild statistical difference between two groups (P=0.02, OR=1.66). For risks, apart from the difference in the aspect of reaction to infusion (OR=0.43, 95% CI=0.29-0.65, P<0.0001), there was no statistical difference. There was no significant difference in effectiveness and risks between the therapy groups. However, these outcomes should be interpreted with caution. Specific categories of combination therapy and periodic medication should be paid more attention in future studies.


Performance of the modified HEART score in an Asian population.
Chest pain is the most common potentially life-threatening presentation to the emergency department (ED). Furthermore, the identification of acute coronary syndrome (ACS) including its risk stratification and subsequent disposition can be challenging. The original HEART score was derived as a predictive tool to risk stratify patients presenting with undifferentiated chest pain (CP) and aid physician decision-making. However, it utilized conventional troponins as its cardiac biomarker component. Our study aims to assess the utility of the modified HEART score with highly sensitive troponins in an Asian setting with mixed ethnicity to determine if it corroborates the findings of another recent Chinese study by Chun-Peng et al. (Journal of Geriatric Cardiology 13:64-69, 2016). Clinical data from 413 patients presenting to the ED for evaluation of chest pain were analyzed. The predictive value of the modified HEART score for determining major adverse cardiac events (MACE) was then evaluated. A total of 49 patients (11.9%) had a MACE: 31 patients (7.5%) underwent PCI and 1 patient (0.2%) underwent CABG. There were 17 (4.1%) deaths. Three risk groups were elucidated based on MACE. In the low-risk group (0-2), there were 72 patients (17.4%), with a MACE rate of 1.4%. In the intermediate-risk group (3-5), there were 233 patients (56.4%), with a MACE rate of 5.2%. In the high-risk group (6-10), there were 108 patients (26.2%), with a MACE rate of 33.3%. The modified HEART score is an effective risk stratification tool in an ethnically diverse Asian population. Furthermore, it identifies low-risk patients who are candidates for early discharge from a local emergency department.


The prognostic and predictive value of syntactic structure analysis in serous carcinoma of the ovary.
The objective of this study was to determine whether syntactic structure analysis (SSA) can predict survival outcome and chemotherapeutic response in ovarian carcinoma. Syntactic structure analysis parameters, blindly determined in archived hematoxylin and eosin sections of 132, International Federation of Gynecology and Obstetrics (FIGO) stage I to IV serous ovarian tumors, and clinicopathologic parameters were evaluated as to their univariate and multivariate prognostic value and ability to predict chemotherapy response as measured by changes in CA125 levels. Univariate analysis revealed FIGO stage, tumor grade, preoperative CA125, presence of ascites, extent of disease residuum, and the SSA parameters minimum spanning tree (min MST), maximum MST (max MST), percent connectivity to 1, and 2 nearest neighbors to be significant predictors of overall survival and disease-free survival. Tumor grade, FIGO stage, extent of disease residuum, presence of ascites, and percent connectivity to 2 nearest neighbors were found to be significant predictors of chemotherapy response. Multivariate analysis revealed extent of disease residuum to be a significant predictor for overall survival (P <or= 0.01) and prediction of chemotherapy response (P = 0.05). International Federation of Gynecology and Obstetrics stage was a significant predictor for disease-free survival (P <or= 0.01). Syntactic structure analysis parameters did not retain independent significance. Syntactic structure analysis features can predict survival outcome and chemotherapy response in ovarian carcinoma but, with multivariate analysis, are overshadowed by FIGO stage and residual disease.


Mammographic features and correlation with biopsy findings using 11-gauge stereotactic vacuum-assisted breast biopsy (SVABB).
Mammograms are assigned a BI-RADS (Breast Imaging Reporting and Data System) category, which indicates the level of suspicion for cancer. (i) To evaluate the use of BI-RADS categories in a non-academic radiology practice based in a community hospital compared with local radiology private offices; (ii) to determine positive predictive value (PPV), sensitivity and specificity of mammograms; and (iii) to explore the correlation of BI-RAD 3-5 and lesion description with diagnosis of cancer. We performed 947 SVABBs (stereotactic vacuum-assisted breast biopsies) on 911 patients with BI-RADS 3-5. Lesions were classified as: 1=microcalcifications; 2=asymmetric density; 3=circumscribed mass; and 4=spiculated mass. BI-RADS category correlated with diagnosis of breast cancer (atypia excluded): category 3=4%; category 4=15%; and category 5=79%. The PPV of BI-RADS 4 and 5 for breast cancer or atypia was 20%, in contrast to 5% for BI-RADS 3. Sensitivity and specificity were 95% and 19%, respectively. For BI-RADS 3 without microcalcifications only 3% were positive, in contrast to 8% for remainder. First, there is a stepwise increase in cancer for each of the BI-RADS categories 3-5. Secondly, in BI-RADS 3 with microcalcifications, a biopsy is indicated according to our findings. Finally, the sensitivity of mammograms is 95% but the specificity is 19%.


Bayesian network structure for predicting local tumor recurrence in rectal cancer patients treated with neoadjuvant chemoradiation followed by surgery.
Tumor recurrence, a characteristic of malignant tumors, is the biggest concern for rectal cancer survivors. The epidemiology of the disease calls for a pressing need to improve healthcare quality and patient outcomes. Prediction models such as Bayesian networks, which can probabilistically reason under uncertainty, could assist caregivers with patient management. However, some concerns are associated with the standard approaches to developing these structures in medicine. Therefore, this study aims to compare Bayesian network structures that stem from these two techniques. A retrospective analysis was performed on 6754 locally advanced rectal cancer (LARC) patients enrolled in 14 international clinical trials. Local tumor recurrence at 2, 3, and 5-years was defined as the endpoints of interest. Five rectal cancer treating physicians from three countries elicited the expert structure. The algorithmic structure was inferred from the data with the hill-climbing algorithm. Structural performance was assessed with calibration plots and area under the curve values. The area under the curve for the expert structure on the training and validation data was above 0.9 and 0.8, respectively, for all the time points. However, the algorithmic structure had superior predictive performance over the expert structure for all time points of interest. We have developed and internally validated a Bayesian networks structure from experts' opinions, which can predict the risk of a LARC patient developing a tumor recurrence at 2, 3, and 5 years. Our result shows that the algorithmic-based structures are more performant and less interpretable than expert-based structures.


Kyphoplasty for treatment of osteoporotic vertebral fractures.
Cement reinforcement for the treatment of osteoporotic vertebral fractures is efficient mean with high success in pain release and prevention of further sintering of the reinforced vertebrae; however, the technique does not allow to address the kyphotic deformity. Kyphoplasty was designed to address the kyphotic deformity and help to realign the spine. It involves the percutaneous placement of an inflatable bone tamp into a vertebral body. Restoration of VB height and kyphosis correction is achieved by inflation of the bone tamp with liquid. After deflation, a cavity is created that eases the cement application. The potential of kyphosis reduction is given in fresh fractures with a range of 0-90% for height restoration and absolute correction of the kyphotic angle of 8.5 degrees. The cavity formation, on one hand, and the different cementing technique leads to lower risk for cement extravasation. An alternative method for kyphosis correction represents the so-called lordoplasty where the adjacent vertebrae are reinforced first and with the cannulas in place acting as a lever the reduction of the collapsed vertebra can be performed. The results with respect to kyphosis correction are superior in comparison with a kyphoplasty procedure.


GIS-based approaches on the accessibility of referral hospital using network analysis and the spatial distribution model of the spreading case of COVID-19 in Jakarta, Indonesia.
The outbreak of the novel coronavirus (COVID-19) has rapidly spread, causing million confirmed cases, thousands of deaths, and economic losses. The number of cases of COVID-19 in Jakarta is the largest in Indonesia. Furthermore, Jakarta is the capital city of Indonesia which has the densest population in the country. There is need for geospatial analysis to evaluate the demand in contrast to the capacity of Referral Hospitals and to model the spreading case of Covid-19 in order to support and organize an effective health service. We used the data from local government publicity for COVID-19 as trusted available sources. By using the verifiable data by observation from the local government, we estimated the spatial pattern of distribution of cases to estimate the growing cases. We performed service area and Origin-Destination (OD) Cost Matrix in support to existing referral hospital, and to create Standard Deviational Ellipse (SDE) model to determine the spatial distribution of COVID-19. We identified more than 12.4 million people (86.7%) based on distance-based service area, live in the well served area of the referral hospital. A total 2637 positive-infected cases were identified and highly concentrated in West Jakarta (1096 cases). The results of OD cost matrix in a range of 10 km show a total 908 unassigned cases from 24 patient's centroid which was highly concentrated in West Jakarta. Our results indicate the needs for additional referral hospitals specializing in the treatment of COVID-19 and spatial illustration map of the growth of COVID-19' case in support to the implementation of social distancing in Jakarta.


In vitro and in vivo effects of 3-bromopyruvate against Echinococcus metacestodes.
While searching for novel anti-echinococcosis drugs, we have been focusing on glycolysis which is relied on by Echinococcus for energy production and intermediates for other metabolic processes. The aim of this study was to investigate the potential therapeutic implication of glycolytic inhibitors on Echinococcus. Our results demonstrate that at an initial concentration of 40 μM, all inhibitors of glycolysis used in the current experiment [3-bromopyruvate (3-BrPA), ornidazole, clorsulon (CLS), sodium oxamate and 2,6-dihydroxynaphthalene (NA-P2)] show considerable in vitro effects against Echinococcus granulosus protoscoleces and Echinococcus multilocularis metacestodes. Among them, 3-BrPA exhibited the highest activity which was similar to that of nitazoxanide (NTZ) and more efficacious than albendazole (ABZ). The activity of 3-BrPA was dose dependent and resulted in severe ultrastructural destructions, as visualized by electron microscopy. An additional in vivo study in mice infected with E. multilocularis metacestodes indicates a reduction in parasite weight after the twice-weekly treatment of 25 mg/kg 3-BrPA for 6 weeks, compared to that of the untreated control. In particular, in contrast to ABZ, the administration of 25 mg/kg 3-BrPA did not cause toxicity to the liver and kidney in mice. Similarly, at the effective dose against Echinococcus larvae, 3-BrPA showed no significant toxicity to human hepatocytes. Taken together, the results suggest that interfering with the glycolysis of the parasite may be a novel chemotherapeutical option and 3-BrPA, which exhibited a remarkable activity against Echinococcus, may be a promising potential drug against cystic echinococcosis (CE) and alveolar echinococcosis (AE).


Trans-10, cis-12 conjugated linoleic acid induced cell death in human colon cancer cells through reactive oxygen species-mediated ER stress.
Dietary conjugated linoleic acids (CLA) are fatty acid isomers with anticancer activities produced naturally in ruminants or from vegetable oil processing. The anticancer effects of CLA differ upon the cancer origin and the CLA isomers. In this study, we carried out to precise the effects of CLA isomers, c9,t11 and t10,c12 CLA, on mechanisms of cell death induction in colon cancer cells. We first showed that only t10,c12 CLA treatment (25 and 50μM) for 72h triggered apoptosis in colon cancer cells without affecting viability of normal-derived colon epithelial cells. Exposure of colon cancer cells to t10,c12 CLA activated ER stress characterized by induction of eIF2α phoshorylation, splicing of Xbp1 mRNA and CHOP expression. Furthermore, we evidenced that inhibition of CHOP expression and JNK signaling decreased t10,c12 CLA-mediated cancer cell death. Finally, we showed that CHOP induction by t10,c12 CLA was dependent on ROS production and that the anti-oxidant N-acetyl-cysteine reduced CHOP induction-dependent cell death. These results highlight that t10,c12 CLA exerts its cytotoxic effect through ROS generation and a subsequent ER stress-dependent apoptosis in colon cancer cells.


Zearalenone formation byFusarium crookwellense /Burgess, Nelson and Toussoun/ isolates from Poland and their pathogenicity towards cereals.
Fusarium crookwellense /B.N. and T./ isolated from affected cereals in Poland formed zearalenone on wheat grain up to 602 mg/kg. Tested isolates have been found strong to severe pathogens of wheat, rye, triticale and barley seedlings and corn ears with pathogenicity similar to that ofF. culmorum andF. graminearum.


Associations between body height, body composition and cholesterol levels in middle-aged men. the coronary risk factor study in southern Sweden (CRISS).
Short body height is associated with increased risk for coronary heart disease; however, mechanisms are not fully explained. In this study, associations between body height and serum cholesterol, non-high-density lipoprotein (non-HDL cholesterol) and high-density lipoprotein (HDL cholesterol) were investigated. Prospective cohort study of middle-aged men from Helsingborg, Sweden starting 1990. Two birth-year cohorts were invited at 37, 40 and 43 years of age; participation at baseline was 991 (68%). Serum and HDL cholesterol, systolic and diastolic blood pressure, weight, height, waist and hip circumferences were measured. Non-HDL cholesterol, body mass index (BMI) and waist/ hip ratio (WHR) were calculated. The participants completed a questionnaire covering lifestyle variables. There were statistically significant inverse correlations between body height and serum cholesterol (-0.11) and non-HDL cholesterol (-0.12). One standard deviation, 6.7 cm, taller body height was associated with a lower serum cholesterol (-0.12 mmol/l) and a lower non-HDL cholesterol (-0.13 m mol/l; p < 0.001). These associations remained when adjusted for BMI and WHR. Men with serum cholesterol equal to or above 6.5 mmol/l were significantly shorter (mean 178.71 cm) than men with serum cholesterol below 6.5 mmol/l (mean 179.71 cm). In addition, BMI and WHR were positively associated with serum and non-HDL cholesterol and inversely associated with HDL cholesterol. The change in cholesterol levels over the six-year follow-up was significantly associated to the change in BMI and WHR. Body height had an independent and inverse relation to serum cholesterol and non-HDL cholesterol in middle-aged men, and the lipid pattern suggests that the underlying mechanism might be different from the traditional association between lipids and the metabolic syndrome. Although the direct clinical implication is limited, our results may help to explain the association between short height and risk of myocardial infarction.


Role of K+ channels in EDHF-dependent relaxation induced by acetylcholine in canine coronary artery.
To identify the K+ channels responsible for endothelium-derived hyperpolarizing factor (EDHF)-dependent relaxation, we studied the effects of various K+ channel blockers on acetylcholine-induced relaxation, which persists even in the presence of both an inhibitor of nitric oxide synthase and that of cyclooxygenase, in canine coronary artery rings. A nonselective K+ channel blocker, tetrabutylammonium (TBA), a large and intermediate conductance Ca2+-activated K+ channel blocker, charybdotoxin (CTX), and a voltage-dependent K+ channel blocker, 4-aminopyridine (4-AP), significantly inhibited this residual relaxation. A combined treatment with CTX and 4-AP almost completely blocked the relaxation. Neither a large (iberiotoxin) nor a small (apamin) conductance Ca2+-activated K+ channel blocker blocked the relaxation. We also investigated effects of K+ channel blockers on basal tone to determine whether or not EDHF is involved in regulating basal tone. TBA and CTX substantially raised basal tone to a greater degree in endothelium-intact preparations than in endothelium-denuded preparations. These results indicate that EDHF may exert its relaxing action through intermediate conductance Ca2+-activated and voltage-dependent K+ channels in canine coronary arteries. In addition, EDHF may play a role in maintaining basal vascular tone.


Toxoplasma gondii Prevalence in Hunter-Killed Mourning Doves (Zenaida macroura) and Rock Pigeons (Columba livia) from East Tennessee, USA.
We molecularly examined brains from 186 hunter-killed Mourning Doves (Zenaida macroura) and 11 Rock Pigeons (Columba livia) from eastern Tennessee, USA for Toxoplasma gondii. Two doves (1%) were PCR- and sequence-positive, whereas all pigeons were PCR-negative.


Influence and Impact of Cognitive Trajectories on Outcome in Patients Undergoing Radical Cystectomy: An Observational Study.
To evaluate cognitive trajectories after radical cystectomy and their impact on surgical outcomes, including urinary continence. Ninety patients received cognitive testing using the Mini Mental State Examination before open radical cystectomy as well as 3 days and 2 weeks after surgery. Based on the Mini Mental State Examination changes ≥3 points between the three time points, five cognitive trajectories emerged (stable cognition, persistent or transient deterioration, or persistent or transient improvement). Surgical outcomes were assessed 90 days, 6 months, and 1 year postoperatively. Mean age was 67.9 ± 9.3 years (range 40-88 years). Sixty-six patients (73.3%) had stable cognition, 9 patients (10.0%) had persistent deterioration and 7 patients (7.8%) had transient deterioration, 5 patients (5.6%) had persistent improvement and 3 patients (3.3%) had transient improvement. An impaired preoperative cognition was the only significant risk factor of short-term cognitive deterioration (odds ratio adjusted for age and sex 9.4, 95% confidence interval 1.6-56.5, P = .014). Cognition showed no associations with 1-year mortality, 90-day complication rate, cancer progression, or duration of in-hospital stay. Patients with transient or persistent cognitive deterioration had an increased risk for nighttime incontinence (odds ratio adjusted for age and sex 5.1, 95% confidence interval 1.1-22.4, P = .032). In this study, the majority of patients showed stable cognition after major abdominopelvic surgery. Cognitive deterioration occurred in a small subgroup of patients, and an impaired preoperative cognition was the only significant risk factor. Postoperative cognitive deterioration was associated with nighttime incontinence.


[The dynamics of thymalin localization in human thymus cells in embryogenesis].
Immunofluorescence methods were applied to study the localization of the thymalin-containing cells in human thymic epithelium of 6-23-wk-old fetus and 2-3-yr-old infants. The study of the fetal thymus (6 weeks) showed the presence of thymalin in reticuloepithelial framework. These cells were present in both in the cortex (in subcapsular regions) and in the medulla; Thymalin-containing cells presence--in the Hassall's corpuscles (23 weeks). The same results were obtained with the infants thymus (3-yr-old).


Isolation and characterization of calmodulin in the pheromone gland of the silkworm, Bombyx mori.
Production of the sex pheromone bombykol in the silkworm, Bombyx mori, is regulated by a neurohormone termed pheromone biosynthesis activating neuropeptide (PBAN). It has been suggested that the external signal of PBAN in this species is transmitted to the intracellular cascade reactions consisting of Ca2+/calmodulin (CaM) complex and phosphoprotein phosphatase. To demonstrate the molecular mechanisms regulated by PBAN, we attempted to characterize CaM in the pheromone gland of B. mori. By using ion-exchange and RP-HPLC, B. mori CaM was purified from the cytosolic fraction of the pheromone gland. The primary structure was deduced by composition/sequence analysis and mass spectrometric analysis of the fragment peptides obtained from enzymatic and chemical fragmentations. The amino acid sequence of B. mori CaM was identical with Drosophila CaM deduced from the CaM gene of D. melanogaster, suggesting that insects have well conserved the molecule of CaM.


Genetic polymorphisms in early-onset myocardial infarction in a sample of Iraqi patients: a pilot study.
Early-onset myocardial infarction constitutes nearly one third of cases of myocardial infarction among Iraqis, which is rather higher than the proportions reported in many Western countries. Thus this study was initiated to investigate the role of some genetic polymorphisms, as well as acquired risk factors in this condition. A total of 102 Iraqi patients with first myocardial infarction aged 50 years, and 77 matched controls were enrolled. The DNAs of participants were screened for nine polymorphisms, namely: β-Fibrinogen (- 455G > A), Factor XIII (V34L), Plasminogen Activator inhibitor-1 (PAI-1, 4G/5G), Human Platelet Antigen-1 (HPA1a/b), 5,10-Methylenetetrahydrofolate Reductase MTHFR (C677T) and MTHFR (A1298C), Angiotensin-Converting Enzyme (ACE) 287 bp insertion/deletion (I/D), Apolipoprotein-B (ApoB: R3500Q), and Apolipoprotein-E (Apo E: E2/E3/E4), using PCR and reverse hybridization technique. Among traditional risk factors, univariate analysis revealed that smoking (OR 2.86 [95%CI 1.53-5.34]), hyperlipidemia (OR 5.23 [95%CI 2.66-10.29]), and diabetes mellitus (OR 4.05 [95% CI 1.57-10.41]) were significantly higher among patients compared to controls (P<0.001, <0.001 and 0.002 respectively), while none of the nine genetic polymorphisms reached significance. Multivariate Logistic regression, however, revealed that only smoking and hyperlipidemia retained significance (P of < 0.001 each). The need to initiate further studies on larger cohorts is paramount to understand the higher than expected frequency of early-onset myocardial infarction in our population.


What Factors Do Clinicians, Coaches, and Athletes Perceive Are Associated With Recovery From Low Back Pain in Elite Athletes? A Concept Mapping Study.
OBJECTIVE: Identify factors that elite sport clinicians, coaches, and athletes perceive are associated with low back pain (LBP) recovery. DESIGN: Concept mapping methodology. METHOD: Participants brainstormed, sorted (thematically), and rated (5-point Likert scales: importance and feasibility) statements in response to the prompt, "What factors are associated with the recovery of an elite athlete from low back pain?" Data cleaning, analysis (multidimensional scaling, hierarchical cluster analysis, and descriptive statistics), and visual representation (cluster map and Go-Zone graph) were conducted following concept mapping guidelines. RESULTS: Participants (brainstorming, n = 56; sorting, n = 34; and rating, n = 33) comprised 75% clinicians, 15% coaches, and 10% athletes and represented 13 countries and 17 sports. Eighty-two unique and relevant statements were brainstormed. Sorting resulted in 6 LBP recovery-related themes: (1) coach and clinician relationships, (2) inter-disciplinary team factors, (3) athlete psychological factors, (4) athlete rehabilitation journey, (5) athlete non-modifiable risk factors, and (6) athlete physical factors. Participants rated important recovery factors as follows: athlete empowerment and psychology, coach-athlete and athlete-clinician relationships, care team communication, return-to-sport planning, and identifying red flags. CONCLUSION: Factors perceived as important to LBP recovery in elite athletes align with the biopsychosocial model of community LBP management. Clinicians should consider that an athlete's psychology, relationships, care team communication, and rehabilitation plan may be as important to their LBP recovery as the formulation of a diagnosis or the medications or exercises prescribed. J Orthop Sports Phys Ther 2023;53(10):1-16. Epub 10 August 2023. doi:10.2519/jospt.2023.11982.


Changes in utilization of robotic bariatric surgery and effect on patient outcomes from 2015-2020.
Robotic surgery is an increasingly popular alternative to laparoscopy for performing bariatric operations. To describe changes in utilization and complication rates of this technique over the last six years an analysis of the 2015-2020 Metabolic and Bariatric Surgery Accreditation and Quality Improvement Program participant use files (MBSAQIP PUF) was performed. All patients who underwent laparoscopic or robotic bariatric surgery from 2015 to 2020 were included. 1,341,814 robotic and laparoscopic bariatric operations were included. Both the number and proportion performed robotically increased from 2015 (n = 9866, 5.87%) to 2019 (n = 54,356, 13.16%). In 2020, although the number of cases decreased, the proportion performed robotically still increased (17.37%). Yet, there has been no significant change in 30 day risk of death (p = 0.946) or infection (p = 0.721). In fact, the risk of any complication has decreased from 8.21% in 2015 to 6.43% in 2020 (p = 0.001). Robotic cases are being increasingly performed on high-risk patients with 77.06% of patients being American Society of Anesthesiologists (ASA) class 3 or higher in 2015 versus 81.03% (p = 0.001) in 2020. Robotic cases are also more likely to be revision operations than laparoscopic cases (12.16% vs 11.4%, p = 0.001). From 2015 to 2020 robotic bariatric surgery became more prevalent yet both complication rates and length of operation decreased suggesting it is an increasingly safe option. The risk of robotic complications remains higher than laparoscopy, however there are significant differences in the patient populations suggesting there may be specific patients and/or operations in which robotic bariatric surgery is being used.


Linkage between serum cholinesterase 2 (CHE2) and gamma-crystallin gene cluster (CRYG): assignment to chromosome 2.
Serum cholinesterase 2 (CHE2) was examined in a Danish material of normal families that has been tested earlier for 70-78 classical marker systems and 25 RFLP systems. DNA for RFLP typing was provided by transforming 16-year-old frozen lymphocytes. The frequency of allele CHE2*C5+ in the Danish population was found to be 0.0430. The highest lod score was between CHE2 and the gamma-crystallin gene cluster (CRYG) (zeta = 4.21 at theta = 0.00 in females). The scores were from a single family with 15 children. CHE2 may, accordingly, be assigned to the location of CRYG: chromosome 2, bands q33-q35.


[Determination of Ca2+ content in human enamel by electroprobe after polypeptide tooth paste usage].
The purpose of this study was to investigate the capability of polypeptide tooth paste for remineralization of human enamel. 8 enamel slabs,which were taken from extracted tooth for orthodontics reason, were immersed in artificial cariogenic solution for 0.5h. Then,the slabs were treated by tooth paste with polypeptide and tooth paste without polypeptide for 5 min. After tooth paste were washed away by warm water, the slabs were immersed in artificial saliva. The experiment were carried out twice per day for 15 days. Two slabs were taken from test group(treated by tooth paste with polypeptide) and control group (treated by tooth paste without polypeptide) on the twelfth day and fifteenth day, respectively. The Ca(2+) content in enamel slabs were determined by electroprobe and analyzed by image process. The content of Ca(2+) in test group was higher than that in control group significantly. The polypeptide tooth paste has certain capability of inhibiting demineralization for human enamel.


Computed tomography appearance of fused (horseshoe) kidney.
Horseshoe kidneys occur approximately once in every 400-500 births. We present three cases of renal fusion anomalies with their computed tomography scans. In patients with little retroperitoneal fat the presence of a renal fusion anomaly can mimic a retroperitoneal mass. Horseshoe kidneys can be suspected by the characteristic anteromedial placement of the renal hilar structures and by enhancement after contrast infusion. An intravenous pyelogram will confirm the finding.


Activated carbon-based electrodes for two-steps catalytic/ electrocatalytic reduction of glycerol in Amberlyst-15 mediator.
Redox mediators supply an effective way to promote electrons (and protons) transport between the electrode and substrate without being in direct physical contact with the electrode. Here, the carbon-based electrodes with Amberlyst-15 as the redox mediator were used in the electrocatalytic reduction to investigate their ability to indirectly convert glycerol into 1,2-propanediol. The process aims to study the influence of different activated carbon compositions (60%, 70%, 80%, and 90% of total weight) in the activated carbon composite (ACC) electrodes on the electrochemical properties, reaction mechanisms, and selectivity of the yielded products. Their electrochemical behavior and physicochemical properties were determined by cyclic voltammetry (CV) and chronoamperometry (CA), followed by FESEM-EDX for the selected ACC electrode. Electroactive surface area (EASA) plays a role in glycerol mass transport and electrons transfer. EASA of 60ACC, 70ACC, 80ACC, and 90ACC (geometrical surface area of 0.50 cm2) were 19.62, 24.50, 36.74 and 30.83 cm2, respectively. With the highest EASA, 80ACC enhanced the mass transport and electrons transfer process that eventually improved its electrocatalytic activity. It outperformed other ACC electrodes by generating Amberlyst-15 radicals (A-15•-) with high current density at low potential (-0.5 V vs. Ag/AgCl). A-15•- served as the electron-donor for the homogeneous redox reaction with glycerol in delivering highly reactive glycerol radical for further intermediates development and generated 1,2-propanediol at -2.5 V vs. Ag/AgCl (current density of -0.2018 A cm-2). High activated carbon content portrayed a dominant role in controlling EASA and favored consecutive acetol-1,2-propanediol production through the C-O bond breakage. From the galvanostatic electrolysis, 1,2-propanediol selectivity was higher on 80ACC (88.6%) compared to 60ACC (61.4%), 70ACC (70.4%) and 90ACC (72.5%). Diethylene glycol formation was found to be the side reaction but preferred low activated carbon percentage in 60ACC and 70ACC.


Delayed ischaemic preconditioning in the presence of galectin-9 protects against renal ischaemic injury through a regulatory T-cell dependent mechanism.
Renal ischaemia/reperfusion injury (IRI) is a complication of major surgeries. Regulatory T cells (Tregs) can suppress immunologic damage in the renal IR. Previous studies indicated that delayed ischaemic preconditioning (IPC) partially attenuates IR by inducing Treg expansion. Galectin-9 also attenuates inflammation-related organ injury by expanding Tregs, but it was not used in renal IR yet. Our aim was to test whether IPC combined with galectin-9 has an increased renoprotective effect. Mice were divided into five treatment groups (n = 6 per group): (i) IR group: renal ischaemia/reperfusion group; (ii) IPC-IR group: IPC followed by renal IR; (iii) IPC-Gal9-IR group: Gal-9 injections during the time between IPC and IR; (iv) IPC-Gal9-PC61-IR group: anti-CD25 antibody administration apart from IPC, Gal-9 and IR; (v) sham-sham group. We assessed the renal function, histopathological scores, and percentages of Tregs and interferon-γ (IFN-γ) cells in peripheral bood, spleen, and kidney and compared these values among the different groups. Serum creatinine measured was significantly lower after IPC and even lower in combination with Gal-9 injection. The histopathological scores for tubulo-interstitial injury were decreased following IPC and markedly lower after the addition of Gal-9. The number of kidney infiltrating neutrophils and IFN-γ secreting CD4+ T cells was diminished in the IPC/Gal9 combination group, while the percentage of Treg cells in the peripheral blood, spleen, and kidney of animals from the IPC-Gal9-IR group was also markedly increased. The renoprotective effect of delayed IPC combined with galectin-9 was superior to IPC alone, through a mechanism related to expansion of regulatory T cells.


First record of the parasitic barnacle Anelasma squalicola Darwin, 1852 (Pollicipedomorpha: Pollicipedidae) in the Eastern Pacific Ocean and a new host report: Etmopterus benchleyi Vsquez, Ebert amp; Long, 2015 (Squaliformes: Etmopteridae).
Anelasma squalicola is a parasitic barnacle of members of the deep-water shark families Etmopteridae, Pentanchidae and Scyliorhinidae. We report the first published confirmation of this species in the Eastern Pacific Ocean, based on material collected off Costa Rica, its first record as a parasite of the Ninja lantern shark, Etmopterus benchley (Etmopteridae), and a new size record for the host. The information presented herein expands the knowledge (distribution and host usage) of this enigmatic species.


Modulation of isolation-induced fighting by N- and C-terminal analogs of substance P: evidence for multiple recognition sites.
Substance P (SP) significantly reduced fighting in mice made aggressive by prolonged isolation. The N-terminal heptapeptide fragment SP (1-7) also reduced fighting. The C-terminal fragment SP(4-11) was without activity, while the shorter C-terminal fragment analog less than E-SP(7-11) significantly increased isolation-induced fighting. The aggression-enhancing effect of less than E-SP(7-11) was antagonized by naloxone, which by itself had no significant effect. The aggression-reducing effect of SP(1-11) was significantly enhanced by naloxone, while the effect of SP(1-7) was unchanged. These results demonstrate that a behavioral effect of SP may be duplicated by an N-terminal fragment of the SP molecule, and that peptide fragments or analogs of the N- and C-terminal portions of the SP molecule can exert opposing effects on a specific behavior. These findings represent a structure/activity relationship that is strikingly different from any previously described for SP. The differing effects of naloxone on N- and C-terminal fragment analogs suggest that these two effects may be mediated by different mechanisms.


Quantifying transcription factor binding dynamics at the single-molecule level in live cells.
Progressive, technological achievements in the quantitative fluorescence microscopy field are allowing researches from many different areas to start unraveling the dynamic intricacies of biological processes inside living cells. From super-resolution microscopy techniques to tracking of individual proteins, fluorescence microscopy is changing our perspective on how the cell works. Fortunately, a growing number of research groups are exploring single-molecule studies in living cells. However, no clear consensus exists on several key aspects of the technique such as image acquisition conditions, or analysis of the obtained data. Here, we describe a detailed approach to perform single-molecule tracking (SMT) of transcription factors in living cells to obtain key binding characteristics, namely their residence time and bound fractions. We discuss different types of fluorophores, labeling density, microscope, cameras, data acquisition, and data analysis. Using the glucocorticoid receptor as a model transcription factor, we compared alternate tags (GFP, mEOS, HaloTag, SNAP-tag, CLIP-tag) for potential multicolor applications. We also examine different methods to extract the dissociation rates and compare them with simulated data. Finally, we discuss several challenges that this exciting technique still faces.


Short-term representatives of daytime and night-time ambulatory blood pressures.
To see whether measurements of ambulatory blood pressure during short-term daytime and night-time periods can represent complete daytime and night-time pressures accurately. Short-term measurements would be less uncomfortable for patients, easier to perform and could lead to fewer missing values, outliers or artefacts than full-day measurements, especially when repeated monitorings are required. Ambulatory blood pressure was measured every 15 min for 24 h in 254 subjects with normal or borderline office blood pressure. Each pressure profile included at least 80 valid readings. Mean blood pressures for different 1-, 2-, 3-, 4-, 5- and 6-h spans were calculated and compared with mean daytime and night-time values using paired Student's t-test. One or two-hour spans of daytime blood pressure poorly represented mean daytime pressure. In contrast, 4-h readings, selected between 1000-2200 h represented daytime blood pressure with good accuracy. Over the total sample, 4-h mean blood pressure readings from 1000-2200 h differed from daytime readings by less than 2 mmHg and 2-h mean readings from 0300-0700 h differed from mean night-time readings by less than 1 mmHg. We suggest that 4-h measurements of ambulatory blood pressure during the daytime and 2-h measurements at night (with time spans selected as indicated as above) may be of value.


The umbilical cord twist: origin, direction, and relevance.
The purpose of this study was to evaluate the origin, direction, and relevance of the umbilical cord twist. We initially hypothesized that the direction of the helix or twist of the human umbilical cord at birth correlated with the eventual handedness of the child. Among 2801 singleton placentas in this study, only 5% had no twist, and the left twist outnumbered the right twist by 7 to 1, a ratio that is strikingly similar to the predominance of right-handed persons to non-right-handed persons in the general population. Forty-five 3- and 4-year-old children with previously documented cord twists were evaluated with respect to hand preference and performance. The direction of the cord twist was independent of the handedness of the child as well as the mother. We have documented an increased incidence of absent twist and right twist in association with single umbilical artery, suggesting that the impetus for the cord twist is independent on hemodynamic forces in the umbilical cord itself. We further document an increased incidence of absent twist among intrauterine fetal deaths and twins, suggesting that decreased fetal movement can impede the forces leading to normal twisting of the umbilical cord. Absence of cord twist may be associated with adverse prognosis.


Moving from peanut extract to peanut components: towards validation of component-resolved IgE tests.
Replacement of peanut extracts by recombinant peanut components is an important step in allergy serologic testing. Criteria are needed for the unbiased inclusion of patients into a study to validate such a replacement. Plasma samples from 64 peanut-positive children (42 reactors, 22 nonreactors in a double-blind, placebo-controlled food challenge) were used to compare IgE reactivity to six recombinant peanut allergens with reactivity to natural peanut proteins extracted at neutral or low pH. We tested the hypothesis that poor extractability of Ara h 9 and other basic allergens at neutral pH leads to under-representation of patients with such sensitization. IgE reactivity to the components did not fully explain IgE reactivity to peanut extract in 5 of 32 reactors with IgE to peanut extract ≤100 kUA /l. IgE reactivity to components was stronger than to the extract in 11 plasma samples, which was largely due to a low Ara h 8 reactivity of the extract. IgE reactivity to Ara h 9 was much lower than reactivity to other basic proteins, some of which bound IgE well in the RAST, but lost IgE reactivity upon immunoblotting. Conventional peanut extracts are deficient in significant IgE-binding components. The inclusion of patients for a validation study should be based on serology performed with improved peanut reagents to avoid a bias against these under-represented, potentially important allergens. To judge clinical relevance of an allergen, the reagent used for inclusion of patients needs to be efficient in detecting IgE to this component.


A Novel Decision-Support Tool (IniCT Score) for Repeat Head Computed Tomography in Pediatric Mild Traumatic Brain Injury.
The necessity of computed tomography (CT) has been questioned in pediatric mild traumatic brain injury (mTBI) because of concerns related to radiation exposure. Distinguishing patients with lower and higher risk of clinically important TBI (ciTBI) is paramount to the optimal management of these patients. This study aimed to analyze the imaging predictors of ciTBI and develop an algorithm to identify patients at low and high risk for ciTBI to inform clinical decision making using a large single-center cohort of pediatric patients with mTBI. We retrospectively identified pediatric patients with mTBI with repeat CT within 48 hours of injury using an institutional database. Among 3867 pediatric patients, 219 patients with mTBI with repeat CT were included. Thirty-eight had ciTBI (17%), 16 (7%) required intensive care unit admission, and 6 (3%) underwent surgery. Median time interval between initial and repeat CT was 7 hours (range, 4-10). Clinical worsening and radiologic progression were evident in 36 (16%) and 24 (11%) patients, respectively. Multivariate analysis showed that 5 pathologic findings (depressed skull fracture, pneumocephalus, epidural hematoma, subdural hematoma, and contusion) on initial CT and radiologic progression on repeat CT were independent predictors of ciTBI. A new scoring system based on these 5 factors on initial CT (IniCT [Initial CT scoring system] score) had excellent discrimination for ciTBI, need for intensive care unit admission, and neurosurgery (area under the curve >0.8). The IniCT scoring system can successfully differentiate low-risk and high-risk patients based on initial CT scan. Zero score can eliminate the need for a routine repeat CT, whereas scores ≥2 should prompt serial neurologic examinations and/or repeat CT depending on the clinical situation.


Conversion of sewage sludge into biochar: A potential resource in water and wastewater treatment.
Production of biochar from sewage sludge (SS) is consistent with the goal of sustainable resource recovery and promotes a wastewater-based circular economy. Thermochemical conversion of SS to biochar resolves two major issues simultaneously as it minimizes the cost of disposal and acts as a resource to eliminate the toxic contaminants from water and wastewater. The reusability and ready availability of the biochar, irrespective of the season, makes it an economically viable material for wastewater treatment. In this review, explicit insights into the production, modification and usage of SS derived biochar are provided including (i) the production yield, (ii) characteristic features such as physical, chemical, electrochemical and morphological aspects, and (iii) impact on contaminant removal through adsorption, catalytic and electrochemical processes. Particular attention is given to the use of SS derived biochar as an adsorbent for contaminants present in wastewaters, the potential use of biochar as a catalyst and support material in advanced oxidation processes and the use of biochars as an electrode material. The effect of pyrolysis conditions and co-pyrolysis with other materials on biochar properties is explored and insight is provided into the toxicity of biochar components present at different process conditions.


[Construction and characterization of hSef recombinant adenoviral vectors].
Sef (similar expression to fgf genes) was identified as a feedback antagonist of FGF signaling in zerbrafish, mouse and human. To construct recombinant adenoviral vectors expressing hSef-L and hSef-S, the coding sequences of the two isoforms were amplified and ligated into pAdTrack-CMV, forming shuttle vectors pAdTrack-CMV/hSef-L-Myc and pAdTrack-CMV/hSef-S-Myc. After sequence confirmation, these two shuttle vector plasmids were linearized by Pme I and then co-transformed respectively with the adenoviral genome vector pAdEasy-1 into E. coli BJ5183. The successful recombinants were selected by Kanamycin and confirmed by Pac I digestion. The recombinant vectors Ad-hSef-L-Myc and Ad-hSef-S-Myc were finally digested with Pac I and transfected into HEK293 cells to pack into viral particles. The virus were amplified in 293 cells and used to infect MEF cells. Western blotting analysis was used to demonstrate the expression of hSef-L-Myc and hSef-S-Myc proteins. The inhibitory effects of the adenovirus mediated Sef expression on FGF signaling was further evaluated by Elk luciferase reporter assay. Our results indicated the constructed virus could produce effectively the proteins and then inhibit FGF signaling in MEF cells.


Priming of associative long-term depression in the dentate gyrus by theta frequency synaptic activity.
Associative long-term synaptic depression (LTD) was investigated utilizing negatively correlated activity patterns in the medial and lateral perforant path inputs to the dentate gyrus in anesthetized rats. Normally only nonassociative, or heterosynaptic, LTD is elicited in naive pathways. We report here, however, that associative LTD in the lateral path is readily induced after being "primed" by a brief period of lateral path synaptic activity at a theta rhythm frequency (5 Hz). Priming of associative LTD lasts at least 2 hr and is not seen following priming activity at non-theta frequencies (1 and 15 Hz). N-methyl-D-aspartate receptor activation is critical for establishing the priming effect, but not for the subsequent induction of the associative LTD. These data suggest that theta rhythm activity in the dentate gyrus may predispose the system to a specific form of synaptic plasticity, associative LTD.


A Novel Coenzyme A Analogue in the Anaerobic, Sulfate-Reducing, Marine Bacterium Desulfobacula toluolica Tol2T.
Coenzyme A (CoA) thioesters are formed during anabolic and catabolic reactions in every organism. Degradation pathways of growth-supporting substrates in bacteria can be predicted by differential proteogenomic studies. Direct detection of proposed metabolites such as CoA thioesters by high-performance liquid chromatography coupled with high-resolution mass spectrometry can confirm the reaction sequence and demonstrate the activity of these degradation pathways. In the metabolomes of the anaerobic sulfate-reducing bacterium Desulfobacula toluolica Tol2T grown with different substrates various CoA thioesters, derived from amino acid, fatty acid or alcohol metabolism, have been detected. Additionally, the cell extracts of this bacterium revealed a number of CoA analogues with molecular masses increased by 1 dalton. By comparing the chromatographic and mass spectrometric properties of synthetic reference standards with those of compounds detected in cell extracts of D. toluolica Tol2T and by performing co-injection experiments, these analogues were identified as inosino-CoAs. These CoA thioesters contain inosine instead of adenosine as the nucleoside. To the best of our knowledge, this finding represents the first detection of naturally occurring inosino-CoA analogues.


Nanomaterial-based therapeutics for antibiotic-resistant bacterial infections.
Antibiotic-resistant bacterial infections arising from acquired resistance and/or through biofilm formation necessitate the development of innovative 'outside of the box' therapeutics. Nanomaterial-based therapies are promising tools to combat bacterial infections that are difficult to treat, featuring the capacity to evade existing mechanisms associated with acquired drug resistance. In addition, the unique size and physical properties of nanomaterials give them the capability to target biofilms, overcoming recalcitrant infections. In this Review, we highlight the general mechanisms by which nanomaterials can be used to target bacterial infections associated with acquired antibiotic resistance and biofilms. We emphasize design elements and properties of nanomaterials that can be engineered to enhance potency. Lastly, we present recent progress and remaining challenges for widespread clinical implementation of nanomaterials as antimicrobial therapeutics.


Analysis of a 42.5 kb DNA sequence of chromosome X reveals three tRNA genes and 14 new open reading frames including a gene most probably belonging to the family of ubiquitin-protein ligases.
We have sequenced a 42,500 bp stretch located on chromosome X of Saccharomyces cerevisiae between the genes MET3 and CDC8. This stretch contains 24 open reading frames (ORFs) of at least 100 amino acids. Ten of these correspond to previously published sequences, whereas of the 14 remaining ORFs, only one, GTD892, has significant similarity to proteins from yeast or other organisms. It may belong to the family of ubiquitin-protein ligases and be involved in the ubiquitin-dependent proteolytic pathway. In addition, three tRNA genes were recognized, two of which had not been hitherto localized.


OsTCP19 influences developmental and abiotic stress signaling by modulating ABI4-mediated pathways.
Class-I TCP transcription factors are plant-specific developmental regulators. In this study, the role of one such rice gene, OsTCP19, in water-deficit and salt stress response was explored. Besides a general upregulation by abiotic stresses, this transcript was more abundant in tolerant than sensitive rice genotypes during early hours of stress. Stress, tissue and genotype-dependent retention of a small in-frame intron in this transcript was also observed. Overexpression of OsTCP19 in Arabidopsis caused upregulation of IAA3, ABI3 and ABI4 and downregulation of LOX2, and led to developmental abnormalities like fewer lateral root formation. Moreover, decrease in water loss and reactive oxygen species, and hyperaccumulation of lipid droplets in the transgenics contributed to better stress tolerance both during seedling establishment and in mature plants. OsTCP19 was also shown to directly regulate a rice triacylglycerol biosynthesis gene in transient assays. Genes similar to those up- or downregulated in the transgenics were accordingly found to coexpress positively and negatively with OsTCP19 in Rice Oligonucleotide Array Database. Interactions of OsTCP19 with OsABI4 and OsULT1 further suggest its function in modulation of abscisic acid pathways and chromatin structure. Thus, OsTCP19 appears to be an important node in cell signaling which crosslinks stress and developmental pathways.


Concurrent validity and discriminative ability of Dutch performance-based motor tests in 5 to 6 years old children.
To assess the concurrent validity and discriminative ability of total, gross and fine motor (TM, GM and FM) scores of Dutch performance-based motor tests, the Baecke-Fassaert Motor Test (BFMT) and the 8- and 4-Skills Scan (SkSc) with the Movement Assessment Battery (MABC) for children at age 5. 116 Dutch children (40.3% boys) were included. Spearman's rho correlations and area under the curves (AUC) were assessed. Correlations between the TM scores of the tests were strong (absolute values from 0.58 to .65); the correlations between the GM scores and the FM scores between and within tests were weaker (absolute values from 0.30 to 0.45). Related to the cut-off (15th percentile) of the MABC, the AUC of the BFMT, 8- and 4-SkSc, the AUC was 0.853 (95% CI: 0.757-0.949), 0.905 (95% CI: 0.837-0.972) and 0.844 (95% CI: 0.730-0.957), respectively. At optimal cut-offs, the sensitivity and specificity of the BFMT, the 8- and 4-SkSc were 78.6 and 78.4%, 92.2 and 73.2%, 78.6 and 76.3%, respectively. All tests had a reasonably high discriminative ability, but validation with the MABC-2 and adaptations are needed to meet the requirements for screening (i.e. sensitivity ≥80% and specificity ≥90%). The relatively weak correlation between GM and FM scores implies that tests should be normalized and validated for GM and FM ability, separately.


Are extracellular microRNAs involved in type 2 diabetes and related pathologies?
MicroRNAs (miRNAs) are a class of evolutionary conserved non-coding RNAs of 19-22 nucleotides that function as negative regulators of gene expression. Originally discovered in C. elegans, miRNAs regulate fundamental cellular processes in diverse organisms, including the control of metabolic pathways involved in fat metabolism, adipocyte differentiation, energy homeostasis, glucose-stimulated insulin secretion and inflammation. Several miRNAs have been identified as having a physiological role in tissues in which type 2 diabetes (T2DM) complications occur (liver, pancreas, adipose tissue and skeletal muscle). In addition, previous studies in animal models or in human tissues have demonstrated altered expression of microRNAs in insulin-sensitive tissues of T2DM patients suggesting a potential role for these small RNA molecules in the complications associated with the diabetic condition. However all these data assume that miRNAs reside and elicit their regulatory action within the producing cells. However, studies in the last 5years have demonstrated that miRNAs are not only found intracellularly, but are also detectable outside cells, including in various body fluids. This phenomenon raises questions about the biological functions of such extracellular miRNAs. The aim of the present review is to summarize the current knowledge of the impact of extracellular miRNAs on the development of obesity-associated T2DM, and its related complications including endothelial and vascular smooth muscle cell dysfunction. It also considers the possible use of blood miRNAs as biomarkers for the detection of T2DM, classification of the disease and detection of associated pathologies.


Local actin-dependent endocytosis is zygotically controlled to initiate Drosophila cellularization.
In early Drosophila embryos, several mitotic cycles proceed with aborted cytokinesis before a modified cytokinesis, called cellularization, finally divides the syncytium into individual cells. Here, we find that scission of endocytic vesicles from the plasma membrane (PM) provides a control point to regulate the furrowing events that accompany this development. At early mitotic cycles, local furrow-associated endocytosis is controlled by cell cycle progression, whereas at cellularization, which occurs in a prolonged interphase, it is controlled by expression of the zygotic gene nullo. nullo mutations impair cortical F-actin accumulation and scission of endocytic vesicles, such that membrane tubules remain tethered to the PM and deplete structural components from the furrows, precipitating furrow regression. Thus, Nullo regulates scission to restrain endocytosis of proteins essential for furrow stabilization at the onset of cellularization. We propose that developmentally regulated endocytosis can coordinate actin/PM remodeling to directly drive furrow dynamics during morphogenesis.


Effects of thermal therapy on rehabilitation after total knee arthroplasty. A prospective randomized study.
The role of local heat or cold therapy used in conjunction with exercise in the rehabilitation of total knee arthroplasty patients was investigated. Thirty-six osteoarthritic patients were analyzed. Parameters evaluated were range of motion, swelling about the knee, and pain. All patients received the total condylar knee prosthesis and began range of motion rehabilitation fourteen days after operation. Results showed that temperature alteration does not augment passive range of motion after total knee arthroplasty. It was also shown that cold application decreases swelling as compared with heat. Additionally, the application of cold partially alleviates the discomfort of the rehabilitation process in certain patients.


Fibromyalgia severity according to age categories: results of a cross-sectional study from a large national database.
The role of age in influencing the severity of fibromyalgia (FM) is still controversial. The aim of this study is to define the contribution of age in the severity of FM from data from a large national database. This cross-sectional study included adult patients with FM diagnosed according to the 2010/2011 American College of Rheumatology criteria. Disease severity was assessed with the revised Fibromyalgia Impact Questionnaire (FIQR) and the modified Fibromyalgia Assessment Status (FAS 2019mod). Patients were grouped into five age categories (between 18-40 years, between 41-50 years, between 51-60 years, between 61-70 years, and ≥71 years). Differences in disease severity between groups were assessed by one-way analysis of variance (ANOVA). The study included 2889 patients (199 males and 2690 females), mean age of 52.58 (±11.82) years, with a mean FIQR score of 59.22 (±22.98) and a mean FAS 2019mod of 25.50 (±8.66). Comparing the mean values of the various indices between age categories, there were no statistically significant differences between the groups for FIQR total score and FAS 2019mod. However, the 60-70 years category showed the lowest scores for both scales. The main difference emerged for the FIQR physical function subscale, where the ≥71 years category showed significantly higher scores (p<0.05) compared the 18-40 years category. The severity of FM has a significant level of stationarity according to age categories. Patients between 60-70 years have a lower disease burden. Physical function is the health domain with the most significant difference between the groups.


Understanding Dalit equity: a critical analysis of primary health care policy discourse of Kerala in the context of 'Aardram' mission.
The Government of Kerala in 2017 launched the Aardram Mission with the aim to revamp public health delivery in the State. A key strategy under the mission was its focus on comprehensive primary health care to achieve equitable health care delivery through the Family Health Centre (FHC) initiative. Given this, the current study aims to examine the primary health care policy discourse for their perspectives on caste-driven inequities. The study undertook a Critical Discourse Analysis (CDA) of the primary health care policy discourse in Kerala. This included CDA of spoken words by senior health policy actors and policy texts on Aardram Mission and FHC. Though equity was a major aspirational goal of the Mission, related policy discourse around equity failed to acknowledge caste as a potential axis of health marginalisation in the State. The dismissal of caste manifested in three major ways within the policy discourse. One, the 'invisibilisation' of caste-driven inequities through strategies of (un)conscious exclusion of Dalit issues and 'obliteration' of caste differences through the construction of abstract and homogenous groups that invisibilise Dalits. Secondly, locating caste as a barrier to primary health care initiatives and health equity in the state, and finally through the maintenance of an 'apoliticised' social determinants discourse that fails to recognize the role of caste in shaping health disparities, specifically among Dalits in Kerala. Given Kerala's renewed commitment to strengthening its public health provisioning, the acknowledgment of caste-driven inequities is invariable in its path toward health equity and social justice.


Immunoperoxidase assay for the detection of specific IgG antibodies to Hantaan virus.
A technique, using indirect immunoperoxidase antibody (IPA), was developed for the detection of IgG antibody to Hantaan virus. The same protein A-peroxidase conjugate was used with mouse, rat and human sera. The IPA technique employs glass slides with air-dried gamma-ray-inactivated and acetone-fixed Hantaan-infected Vero-E6 cells. Antibody titers detected by IPA was comparable to those detected by the indirect fluorescent antibody technique.


The underling mechanism of bacterial TetR/AcrR family transcriptional repressors.
Bacteria transcriptional regulators are classified by their functional and sequence similarities. Member of the TetR/AcrR family is two-domain proteins including an N-terminal HTH DNA-binding motif and a C-terminal ligand recognition domain. The C-terminal ligand recognition domain can recognize the very same compounds as their target transporters transferred. TetRs act as chemical sensors to monitor both the cellular environmental dynamics and their regulated genes underlying many events, such as antibiotics production, osmotic stress, efflux pumps, multidrug resistance, metabolic modulation, and pathogenesis. Compounds targeting Mycobacterium tuberculosis ethR represent promising novel antibiotic potentiater. TetR-mediated multidrug efflux pumps regulation might be good target candidate for the discovery of better new antibiotics against drug resistance.


Faecal carriage of extended-spectrum β-lactamase-producing Enterobacteriaceae among humans in Java, Indonesia, in 2001-2002.
To characterise commensal Escherichia coli and other Enterobacteriaceae with reduced susceptibility to cefotaxime that were collected in a large survey carried out among 3995 patients and healthy persons in two urban regions on Java, Indonesia, in 2001-2002. The putative extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae were analysed using double-disk synergy tests, isoelectric focusing, PCR assays, DNA sequencing, and pulsed-field gel electrophoresis (PFGE). On the day of discharge after five or more days of hospitalisation, at least 95 of 999 (9.5%) patients carried ESBL-positive Enterobacteriaceae as dominant faecal flora. Six patients were simultaneously colonised with E. coli and Klebsiella pneumoniae isolates with ESBL activity. On admission, only 6 of 998 (0.6%) patients were colonised. Faecal carriage of ESBL-producing Enterobacteriaceae among healthy persons or persons visiting a public health centre was not detected. The 107 ESBL-positive strains included 68 E. coli, 35 K. pneumoniae, and four other Enterobacteriaceae. bla(CTX-M-15) was the most prevalent ESBL in both E. coli (47.1%) and K. pneumoniae (45.7%), but the E. coli O25b-ST131 clone was virtually absent. Other ESBL types found were: SHV-2, -2a, -5, -12, CTX-M-3, -9, -14, and TEM-19. PFGE revealed extensive genetic diversity among the isolates. In 2001-2002, faecal carriage of ESBL-producing Enterobacteriaceae as dominant flora in Indonesia was almost exclusively hospital-associated. The presence of various bla(ESBL) genes and the extensive genetic diversity among isolates argue against a single/dominant strain outbreak.


Directional discrimination of motion in depth based on changing target vergence.
Difference limens for the apparent direction of motion in depth were measured in eight observers. Two points of light were presented dichoptically in an otherwise dark field. Their lateral motion (changing target-vergence stimulus) mimicked the oscillation of an object in depth along different paths. All seven paths of 100 cm length had a common distant position in the median plane 150 cm from the observer. The directions of the paths were equidistant; the second and sixth paths were directed toward the left and right eye of the observer, respectively. Discrimination of direction was best for motion along the median plane and deteriorated toward the periphery. There was no indication of local minima of the difference limen for motions toward the eyes as has been observed with changing-disparity stimuli.


A worldwide survey of management practices in laboratory animal allergy.
A questionnaire survey of laboratory animal facilities sought to determine employer practices and policies regarding allergy to laboratory animals. Information from 159 American institutions and 93 facilities from 20 other nations indicates that an effective program to control the problem of occupational allergy to laboratory animals remains to be developed.


Thermodynamics of carbohydrate-lipid interactions.
Thermodynamic analyses of carbohydrate-lipid interactions were performed by investigating the effects of a series of carbohydrates, including monosaccharides, disaccharides, and trisaccharides, on the phase-transition properties of aqueous dispersions of 1,2-dipalmitoyl phosphatidylcholine (DPPC). The temperature of the lipid's main phase transition from the gel to liquid-crystalline phase is essentially unchanged in the presence of carbohydrate. The change in the free energy (delta G) of the transition is zero when a carbohydrate is added to aqueous dispersions of DPPC, while the enthalpy (delta H) and the entropy of the melting of DPPC are decreased. The thermodynamic information was used to examine carbohydrate-lipid interactions. Such interactions were elucidated according to our knowledge of the specific properties of carbohydrates in aqueous solutions and the previously proposed hydrophobic interaction involving hydrocarbon tails of the lipid in aqueous dispersions.


Pigment epithelium-derived factor regulates early pancreatic fibrotic responses and suppresses the profibrotic cytokine thrombospondin-1.
Pigment epithelium-derived factor (PEDF) is important for maintaining the normal extracellular matrix. We hypothesized that the initiation of pancreatic fibrosis is dependent on the loss of PEDF. Pancreatic PEDF expression was assessed in wild-type mice fed either a control or ethanol diet using an intragastric feeding model. Pancreatitis responses were elicited with either a single episode or a repetitive cerulein-induced (50 μg/kg, 6 hourly i.p. injections) protocol in wild-type and PEDF-null mice. Quantitative real-time PCR and immunoblotting were performed to assess fibrogenic responses. In wild-type animals, PEDF expression increased with pancreatitis and was more pronounced in mice fed ethanol. Compared with wild-type mice, α-smooth muscle actin staining and expression levels of fibrogenic markers (eg, transforming growth factor-β1, platelet-derived growth factor, collagen I, and thrombospondin-1) were higher in PEDF-null mice at baseline. Sirius red staining revealed more fibrosis in PEDF-null versus wild-type pancreas 1 week after pancreatitis. Differences in tissue fibrosis resolved with longer recovery periods. PEDF overexpression suppressed thrombospondin-1 levels in vitro. Ethanol feeding and experimental pancreatitis increased PEDF expression in wild-type mice. PEDF-null mice, however, demonstrated enhanced early fibrotic responses compared with wild-type mice with pancreatitis. These findings indicate that PEDF acts as a compensatory antifibrotic cytokine in pancreatitis.


Inhibition of EZH2 ameliorates hyperoxaluria-induced kidney injury through the JNK/FoxO3a pathway.
Enhancer of zeste homolog 2 (EZH2), a histone H3 lysine 27 methyltransferase, has been shown to play a role in kidney diseases. However, its role in hyperoxaluria-induced renal tubular epithelial cells (TECs) injury remains unclear. A hyperoxaluria rat model was established by providing 0.5% ammonium chloride and drinking water containing 1% ethylene glycol. TECs were exposed to oxalate stress. The 3-DZNeP, a selective EZH2 inhibitor, was administered in vivo and in vitro. Cell viability, ROS production, and apoptosis ratio were evaluated. Crystal deposition was detected by Von Kossa staining and kidney tissue injury was detected by HE staining and TUNEL. EZH2, H3K27me3, cleaved-caspase3, IL-6, and MCP-1 were examined by western blot or immunohistochemistry. Inhibition of EZH2 by 3-DZNeP significantly attenuated hyperoxaluria-induced oxidative and inflammatory injury and CaOx crystal deposition in vivo. Similarly, inhibition of EZH2 using 3-DZNeP or shRNA restored cell viability, suppressed LDH release and the production of intracellular ROS in vitro. Furthermore, the MAPK signaling pathway and FoxO3a levels were activated or elevated in TECs exposed to oxalate. EZH2 inhibition using 3-DZNeP blocked these effects. CC90003 (ERK inhibitor) or SB203580 (p38 inhibitor) did not significantly affect the expression of FoxO3a in TECs treated with 3-DZNeP and oxalate; only SP600125 (JNK inhibitor) significantly decreased FoxO3a expression. EZH2 inhibition protects against oxalate-induced TECs injury and reduces CaOx crystal deposition in the kidney may by modulating the JNK/FoxO3a pathway; EZH2 may be a promising therapeutic target in TECs injury.


The potential therapeutic effect of statins in multiple sclerosis: beneficial or detrimental effects.
Multiple sclerosis (MS) is a chronic progressive disabling disease of the central nervous system (CNS) characterized by demyelination and neuronal injury. Dyslipidemia is observed as one of the imperative risk factors involved in MS neuropathology. Also, chronic inflammation in MS predisposes to the progress of dyslipidemia. Therefore, treatment of dyslipidemia in MS by statins may attenuate dyslipidemia-induced MS and avert MS-induced metabolic changes. Therefore, the present review aimed to elucidate the possible effects of statins on the pathogenesis and outcomes of MS. Statins adversely affect the cognitive function in MS by decreasing brain cholesterol CoQ10, which is necessary for the regulation of neuronal mitochondrial function. However, statins could be beneficial in MS by shifting the immune response from pro-inflammatory Th17 to an anti-inflammatory regulatory T cell (Treg). The protective effect of statins against MS is related to anti-inflammatory and immunomodulatory effects with modulation of fibrinogen and growth factors. In conclusion, the effects of statins on MS neuropathology seem to be conflicting, as statins seem to be protective in the acute phase of MS through anti-inflammatory and antioxidant effects. However, statins lead to detrimental effects in the chronic phase of MS by reducing brain cholesterol and inhibiting the remyelination process.


Preparation of meta-amidino-N,N-disubstituted anilines as potent inhibitors of coagulation factor Xa.
The serine protease factor Xa is a critical enzyme in the blood coagulation cascade. Recently, the inhibition of factor Xa has begun to emerge as an attractive strategy for the discovery of novel antithrombotic agents. Here we describe a series of meta-amidino-N,N-disubstituted anilines as structurally simple and very potent inhibitors of factor Xa.


Optimisation of enzymatic hydrolysis of apple pomace for production of biofuel and biorefinery chemicals using commercial enzymes.
Apple pomace, a waste product from the apple juice industry is a potential feedstock for biofuel and biorefinery chemical production. Optimisation of hydrolysis conditions for apple pomace hydrolysis using Viscozyme L and Celluclast 1.5L was investigated using 1 L reaction volumes. The effects of temperature, pH, β-glucosidase supplementation and substrate feeding regimes were determined. Hydrolysis at room temperature using an unbuffered system gave optimal performance. Reactors in batch mode resulted in a better performance (4.2 g/L glucose and 16.8 g/L reducing sugar, 75 % yield for both) than fed-batch (3.2 g/L glucose and 14.6 g/L reducing sugar, 65.5 and 73.1 % yield respectively) in 72 h. The addition of Novozyme 188 to the core mixture of Viscozyme L and Celluclast 1.5L resulted in the doubling of glucose released. The main products (yield %) released from apple pomace hydrolysis were galacturonic acid (78 %), glucose (75 %), arabinose (90 %) and galactose (87 %). These products are potential raw materials for biofuel and biorefinery chemical production.


A social network intervention to improve connectivity and burnout among psychiatry residents in an academic institution: a quasi-experimental study.
Burnout is common among residents, which could be associated with their professional network characteristics. This study aimed to assess the social networks of psychiatry residents and develop an intervention to improve their network characteristics, burnout, and perception of the educational environment. We recruited a cohort of 17 PGY-2 residents and assessed their social networks, burnout, and perception of the educational environment. After the baseline survey, we held a focus group with PGY-2 residents to discuss the results, their network characteristics, and interventions that can improve their relationships. The PGY-2 residents indicated that offering extracurricular opportunities to facilitate friendly interactions among the residents and faculty members would be the most feasible and acceptable intervention. Therefore, four "interest groups" for extracurricular activities were established. Residents and faculty members were invited to participate in interest groups to improve the network characteristics. Some PGY-2 residents and faculty members agreed to moderate interest group sessions (active members). After the intervention, active residents improved significantly in the perceived personal accomplishment subscale of the burnout inventory and their perception of the educational environment. Active faculty members also had a significant increase in their relationships with PGY-2 residents in one domain of social networks. Enhancing relationships between residents and faculty members through participatory intervention and extracurricular activities can improve faculty-resident connectivity and residents' perception of personal accomplishment and educational environment quality.


Purification and characterization of mouse glucose 6-phosphate dehydrogenase.
Glucose-6-phosphate dehydrogenase was purified to homogeneity from testes and kidneys of the inbred strain of mice (DBA/2J) by a simple two-step affinity column procedure. This involved the sequential application of 8-(6-aminohexyl)-amino-AMP- and -2', 5'-ADP-Sepharose columns and biospecific elution with NADP+ in both steps. The molecular and biochemical properties of the purified enzyme were studied in detail. These include the molecular weight determination, amino acid composition, steady-state kinetics, inactivation by high temperature, urea and iodoacetate, and immunology. The purified enzyme from mouse kidneys or testes was shown to be a tetramer with a molecular weight of 220,000. The enzyme is highly specific for glucose-6-phosphate, exhibits almost no activity with NAD+ as a coenzyme and is little inhibited by AMP or ATP. Michaelis constants for glucose-6-phosphate and NADP+ were determined to be 50 microM and 10 microM respectively. NADPH is a competitive inhibitor of NADP+ and has a Ki of 18 microM. Rabbit antisera against glucose-6-phosphate dehydrogenase were raised. The antisera also cross-react with the same enzyme from human and guinea pig.


Interaction between home and community-based services and PM2.5 on cognition: A prospective cohort study of Chinese elderly.
PM2.5 and home and community-based services (HCBSs) had been shown to affect cognition, but the evidence on their joint effects was limited. Aimed to study the joint effects of HCBSs and PM2.5 on cognition, we utilized the follow-up data of participants in the Chinese Longitudinal Health Longevity Survey (CLHLS) who were 65 years of age or older and had normal cognitive function at baseline for the 2008-2018, 2011-2018, and 2014-2018 waves. 16,954, 9,765, and 7192 participants from each of these three waves were initially recruited, respectively. The PM2.5 concentration data of each province in China from 2008 to 2018 was obtained from the Atmospheric Composition Analysis Group. Participants were asked what kind of HCBSs were available in their community. The cognitive status of the participants was evaluated by the Chinese version of Mini-Mental State Examination (CMMSE). We applied the Cox proportional hazard regression model to investigate the joint effects of HCBSs and PM2.5 on cognition and further stratified the analysis according to HCBSs. Hazard ratio (HR) and 95% confidence interval (95% CI) were calculated based on Cox models. During a median follow-up period of 5.2 years, 911 (8.8%) participants with normal baseline cognitive function developed cognitive impairment. Compared to participants without HCBSs and exposed to the highest level of PM2.5, those with HCBSs and exposed to the lowest level of PM2.5 had a significantly reduced risk of developing cognitive impairment (HR = 0.428, 95% CI: 0.303-0.605). The results from the stratified analysis revealed that the detrimental effect of PM2.5 on cognition was more pronounced in participants without HCBSs (HR = 3.44, 95% CI: 2.18-5.41) compared with those with HCBSs (HR = 1.42, 95% CI: 0.77-2.61). HCBSs may attenuate the harmful impact of PM2.5 on cognitive status in the elderly Chinese and the government should further promote the application of HCBSs.


Again, what the philosophy of biology is not.
There are many things that philosophy of biology might be. But, given the existence of a professional philosophy of biology that is arguably a progressive research program and, as such, unrivaled, it makes sense to define philosophy of biology more narrowly than the totality of intersecting concerns biologists and philosophers (let alone other scholars) might have. The reasons for the success of the "new" philosophy of biology remain poorly understood. I reflect on what Dutch and Flemish, and, more generally, European philosophers of biology could do to improve the situation of their discipline locally, regionally, and internationally, paying particular attention to the lessons to be learned from the "Science Wars."


Medial pivot prosthesis has a better functional score and lower complication rate than posterior-stabilized prosthesis: a systematic review and meta-analysis.
We aimed to compare the postoperative clinical efficacy and safety of medial pivot (MP) prosthesis and posterior-stabilized (PS) prosthesis in the treatment of knee osteoarthritis (KOA). All studies involving MP and PS prosthesis in PubMed, EMBASE, Cochrane Library, and Web of Science were searched since the establishment of the database. The included outcomes were knee range of motion (ROM), functional score, radiographic results, complication rate, and revision rate. Studies were independently evaluated by the Newcastle-Ottawa Scale for case-control studies and the assessment tool of the Cochrane Collaboration for randomized controlled trials. I2 was used to test the heterogeneity, and fixed- or random-effects models were selected for meta-analysis according to the heterogeneity results. A total of 19 studies, consisting of 3592 patients and 3783 knees (MP: 1811 knees, PS: 1972 knees), were included in the meta-analysis. The WOMAC (MD = - 1.11, 95% CI - 1.98 to - 0.23; P = 0.01) and HSS (MD = - 4.32, 95% CI - 8.30 to - 0.34; P = 0.03) in the MP group were significantly lower compared with the PS group, and the complication rate (OR 0.53, 95% CI 0.33-0.87; P = 0.01) was also lower compared with the PS group. There was no significant difference in ROM, radiographic results, and revision rate between the two groups (P > 0.5). The existing literature provided evidence to support better clinical effect and lower complication rate of MP prosthesis compared to PS prosthesis. These results provide a reference for clinicians when choosing a suitable prosthesis.


Isotachophoretic determination of mobility and pKa by means of computer simulation. V. Evaluation of mo and pKa of twenty-eight dipeptides and assessment of separability.
Isotachophoretic qualitative indices, RE, for twenty-eight dipeptides were measured in the range pH 7.4-9.6. The absolute mobility, mo, and pKa values were evaluated by the use of the least-squares method, utilizing a simulation of the isotachophoretic steady state. The mo values were newly evaluated and the pKa values were in good agreement with literature values. By comparison of the evaluated mo and pKa values of the dipeptides with those of the constituent amino acids, simple relationships were found which may be used to estimate the mo and pKa values of other dipeptides. The separability of the dipeptides was also evaluated by considering the differences between their simulated effective mobilities. It is concluded that isotachophoresis is very convenient for the separation of dipeptides and their constituent amino acids.


Stability of milk fatty acid profile during simulated shipping for analysis by gas chromatography.
Milk fat trans-10 C18:1 can be used in diagnosing low milk fat production on dairy farms because it is a specific marker of biohydrogenation-induced milk fat depression. Individual fatty acids (FA), including the trans C18:1 isomer, can be determined only by gas-liquid chromatography. The analysis is currently available at a limited number of laboratories and often requires long-distance shipping. Expedited shipping with dry ice or ice packs is expensive. Therefore, the objective of this study was to determine the effect of heat treatment before shipping, shipping temperature, and shipping time on milk FA profile. Samples were collected from 3 farms on 2 occasions and stored in a polystyrene foam cooler with an ice pack, at room temperature, or at 37°C for 1, 2, 3, and 7 d. Heating the sample before shipping, shipping temperature, and shipping time had very little effect on any FA analyzed. Differences observed were of small magnitude and not of practical importance, demonstrating that milk FA profile is expected to be very stable during shipping. Based on this, we propose that freezing samples and shipping in a sealed bag by second-day shipment is appropriate and demonstrated that this had little effect on FA profile of 48 milk samples. Importantly, these methods are recommended only for gas-liquid chromatography analysis of FA profile. Freezing is not appropriate for shipping for analysis by mid-infrared spectrometry-based methods or methods quantifying compounds per unit of milk because it is difficult to homogenize samples after freezing or extended shipping that results in denaturization of proteins and breaking of fat globules.


Fas-mediated apoptosis of peripheral blood mononuclear cells in patients with hepatitis C.
In the present study, we demonstrated that a close relationship exists between hepatitis C virus (HCV) infection of peripheral blood mononuclear cells (PBMCs) and cell-surface Fas expression in patients with hepatitis C, and showed the possibility of PBMCs apoptosis via a Fas-mediated system. The expression of Fas on PBMCs was found by flowcytometric analysis to be significantly increased in these patients. In addition, the treatment of patients' PBMCs with anti-Fas antibody induced cell death, with nuclear condensation and fragmentation and cellular DNA fragmentation. These data indicate that the patients' PBMCs expressed a large amount of functional Fas on the cell surface and were susceptible to stimulation against Fas, causing apoptotic cell death. We then quantified the serum-soluble Fas ligand (sFasL), which was known to bind to Fas and induce the apoptotic signals into the sensitized cells. The patients' serum sFasL levels were significantly higher than those of normal subjects and showed a good negative correlation with their PBMC number. To demonstrate the correlation between Fas expression and HCV infection, nested reverse transcriptase polymerase chain reaction (RT-PCR) was performed to detect HCV RNA. Interestingly, HCV RNA was preferentially detected from Fas-positive cells but not from Fas-negative cells, which had been isolated from PBMCs by magnetic beads. These results suggest that HCV infection of PBMCs might induce Fas expression and additional stimulation such as sFasL might induce apoptosis in these Fas-expressing cells. These mechanisms, in addition to hypersplenism, may explain the decrease in the number of PBMCs observed in patients with chronic hepatitis C.


The development of hypophosphataemic osteomalacia with myopathy in two patients with HIV infection receiving tenofovir therapy.
We report two cases in which osteomalacia developed in patients on tenofovir-containing highly active antiretroviral therapy (HAART) in the context of Fanconi syndrome with hypophosphataemia. Bone pain was the presenting feature and myopathy followed in one case. Disability was reversed with withdrawal of the drug and with mineral supplementation. The cases highlight the importance of considering the diagnosis of osteomalacia in patients treated with tenofovir. A possible association with incipient acute renal failure, particularly during nonsteroidal anti-inflammatory drug (NSAID) use, needs further investigation.


Postprandial oxidative stress is modulated by dietary fat in adipose tissue from elderly people.
We have investigated whether dietary fat modifies the postprandial oxidative stress in adipose tissue of elderly people. Twenty participants received three diets for 4 weeks each: SFA-rich diet, Mediterranean (Med) diet enriched in MUFA with virgin olive oil, and a low-fat, high-carbohydrate diet enriched in n-3 PUFA (α-linolenic acid from plant origin) (CHO-PUFA diet). After 12 h of fasting, volunteers received a breakfast reflecting the fatty acid composition of the diet ingested in the preceding dietary period. Med diet induced higher postprandial SOD2 and TrxR mRNA levels, and CHO-PUFA diet induced higher GPx1 and TrxR mRNA levels compared with SFA-rich diet. Med and CHO-PUFA breakfasts induced a postprandial increase in plasma reduced glutathione (GSH), and a greater postprandial GSH/oxidized glutathione ratio compared to the SFA-rich diet. Our study suggests that the consumption of Med and CHO-PUFA diets may reduce postprandial oxidative stress compared to an SFA-rich diet, which may be due to higher antioxidant enzymes gene expression in adipose tissue.


Experimental and theoretical study of light scattering by individual mature red blood cells by use of scanning flow cytometry and a discrete dipole approximation.
Elastic light scattering by mature red blood cells (RBCs) was theoretically and experimentally analyzed by use of the discrete dipole approximation (DDA) and scanning flow cytometry (SFC), respectively. SFC permits measurement of the angular dependence of the light-scattering intensity (indicatrix) of single particles. A mature RBC is modeled as a biconcave disk in DDA simulations of light scattering. We have studied the effect of RBC orientation related to the direction of the light incident upon the indicatrix. Numerical calculations of indicatrices for several axis ratios and volumes of RBC have been carried out. Comparison of the simulated indicatrices and indicatrices measured by SFC showed good agreement, validating the biconcave disk model for a mature RBC. We simulated the light-scattering output signals from the SFC with the DDA for RBCs modeled as a disk-sphere and as an oblate spheroid. The biconcave disk, the disk-sphere, and the oblate spheroid models have been compared for two orientations, i.e., face-on and rim-on incidence, relative to the direction of the incident beam. Only the oblate spheroid model for rim-on incidence gives results similar to those of the rigorous biconcave disk model.


Pediatric Insomnia.
Insomnia is the most common sleep disorder among all ages; unfortunately, however, child and adolescent insomnia is infrequently addressed. Given the importance of adequate sleep for proper brain development, pediatric populations are particularly vulnerable to the negative effects of insomnia. Therefore, proper clinical assessment and treatment of pediatric insomnia is crucial. This article is the result of a comprehensive literature review and serves as a guide to the disorder and how it presents differently across child development.


Putting risk in its place: methodological considerations for investigating extreme event health risk.
Health is affected by the places in which people live, work and interact, yet many epidemiological studies overlook the characteristics of places and instead focus solely on the people who inhabit them. Place-based investigations of disparities in health outcomes are concerned with the healthiness of places and not merely the healthiness of the populations in these places. A place-based approach has been used within medical geography and medical sociology, typically in the study of health differentials associated with long-term, cumulative exposures to a wide range of environmental variables. This approach has rarely been extended, however, to health research that looks at the effects of extreme events (such as industrial accidents or hurricanes). The purpose of this paper is to incorporate a place-based framework into extreme event health research. The paper first discusses methodological considerations for a place-based approach and then illustrates the use of spatial analysis techniques as the first step in identifying place-based risk factors in mortality associated with heat waves. The study centers on St. Louis, Missouri, a city where heat waves are frequent and heat-related mortality is high. The results show that heat-related mortality rates during the most severe heat waves were generally higher in the warmer, less stable and more disadvantaged areas of St. Louis and lower in the cooler and more affluent parts of the city. During the milder years analyzed, there was little evidence of a relationship between place-based characteristics and the distribution of heat-related mortality. These findings about extreme event mortality risk would not have been evident from a population-based analysis. Ongoing dialog between epidemiologists and social scientists can help to bring place into the arena of extreme event research and to increase understanding of the role of place in risk.


Memory consolidation of Pavlovian fear conditioning requires nitric oxide signaling in the lateral amygdala.
Nitric oxide (NO) has been widely implicated in synaptic plasticity and memory formation. In studies of long-term potentiation (LTP), NO is thought to serve as a 'retrograde messenger' that contributes to presynaptic aspects of LTP expression. In this study, we examined the role of NO signaling in Pavlovian fear conditioning. We first show that neuronal nitric oxide synthase is localized in the lateral nucleus of the amygdala (LA), a critical site of plasticity in fear conditioning. We next show that NO signaling is required for LTP at thalamic inputs to the LA and for the long-term consolidation of auditory fear conditioning. Collectively, the findings suggest that NO signaling is an important component of memory formation of auditory fear conditioning, possibly as a retrograde signal that participates in presynaptic aspects of plasticity in the LA.


Impulsivity and sleep and circadian rhythm disturbance predict next-day mood symptoms in a sample at high risk for or with recent-onset bipolar spectrum disorder: An ecological momentary assessment study.
Impulsivity and sleep and circadian rhythm disturbance are core features of bipolar spectrum disorders (BSDs) that are antecedents to onset and persist even between mood episodes; their pervasive presence in BSD suggests that they may be particularly relevant to understanding BSD onset and course. Considerable research demonstrates bidirectional associations between impulsivity and sleep disturbance in healthy individuals; thus, it is important to examine how these features interact to impact BSD symptomatology. Young adults (N = 107, 55% female, M age = 21.82 years) at high risk for developing BSD (based on high self-reported reward sensitivity) or with recent-onset BSD participated in ecological momentary assessment (EMA) to examine relationships between impulsivity, sleep and circadian rhythm alterations, and mood symptoms in everyday life. Impulsivity was measured via self-report/behavioral task, sleep was measured via actigraphy, circadian rhythms were measured via dim light melatonin onset (DLMO) time, and mood symptoms were measured three times daily via self-report. Multi-level modeling revealed that less total sleep time predicted increased next-day mood symptoms. Moreover, DLMO, total sleep time, and sleep onset latency moderated the relationship between impulsivity and EMA-assessed mood symptoms. Fewer minutes of sleep and later DLMO strengthened the positive relationship between impulsivity and mood symptoms. Mood symptoms in our sample were mild; future studies should replicate findings in populations with more severe mood symptoms. This multi-method assessment of dynamic relationships revealed novel associations between impulsivity, sleep and circadian rhythm disturbance, and symptoms within individuals at high-risk for or with recent-onset BSD.


Deep infection after hip fracture surgery: predictors of early mortality.
This study analysed the predictors of mortality in patients who are diagnosed with deep infection following hip fracture surgery. Data were prospectively collected for 3 years from all patients undergoing hip fracture surgery and who had developed a subsequent deep infection. Infection was defined as positive microbiology culture from deep tissue or fluid samples. Demographic data, treatment, complications and subsequent surgeries were analysed. Potential predisposing factors including chronic medical co-morbidities, American Society of Anesthesiologists (ASA) grade, alcohol excess and smoking were assessed. The main outcome measures were 30-day and 1-year mortality. There were 2718 consecutive operations performed for a fracture of the proximal femur over a 3-year period. Forty-three (1.6%) patients had a deep postoperative infection diagnosed on fluid and/or tissue sampling. The mean age was 73 years (25-94) and 65% were female. Of the 43 patients who developed deep infection, the primary procedure in 25 (58%) patients was reduction and internal fixation, with 18 (42%) undergoing hemi-arthroplasty. The most common causative organism was Staphylococcus epidermidis (n=13, 30%), with methicillin-resistant Staphylococcus aureus (MRSA) accounting for 23% (n=10). The 30-day mortality was significantly higher than that of patients with no deep infection (19% vs. 6.5%; p=0.004). On univariate analysis, increasing age, dementia and diabetes were predictive of both 30-day and 1-year mortality (all p<0.05). S. aureus (sensitive or resistant) was approaching significance at 1 year (p=0.065). On multivariate analysis, dementia and diabetes were independent predictors of 30-day mortality, with dementia and S. aureus predictive at 1 year. The 30-day mortality rate in patients diagnosed with deep infection following hip fracture surgery is higher than those without infection. Dementia, diabetes and S. aureus infection are independent predictors of mortality following deep infection.


Assessing blood-brain barrier function using in vitro assays.
The impermeability of the blood-brain barrier (BBB) is due to a number of properties including tight junctions on adjoining endothelial cells, absence of pinocytic vesicles, and expression of multidrug transporters. Although the permeability of many chemicals can be predicted by their polarity, or oil/water partition coefficient, many lipophilic chemicals are not permeable because of multidrug transporters at the luminal and abluminal membranes. In contrast, many nutrients, which are usually polar, cross the BBB more readily than predicted by their oil/water partition coefficients due to the expression of specific nutrient transporters. In vitro models are being developed because rodent models are of low input and relatively expensive. Isolated brain microvessels and cell culture models each offers certain advantages and disadvantages. Isolated brain microvessels are useful in measuring multidrug drug transporters and tight junction integrity, whereas cell culture models allow the investigator to measure directional transport and can be genetically manipulated. In this chapter, we describe how to isolate large batches of brain microvessels from freshly slaughtered cows. The different steps in the isolation procedure include density gradient centrifugations and filtering. Purity is determined microscopically and by marker enzymes. Permeability is assessed by measuring the uptake of fluorescein-labeled dextran in an assay that has been optimized to have a large dynamic range and low inter-day variability. We also describe how to evaluate transendothelial cell electrical resistance and paracellular transport in cell culture models.