Associations of Dietary Cholesterol, Serum Cholesterol, and Egg Consumption With Overall and Cause-Specific Mortality: Systematic Review and Updated Meta-Analysis.
Despite substantial research highlighting the importance of exogenous dietary cholesterol intake and endogenous serum cholesterol level in human health, a thorough evaluation of the associations is lacking. Our study objective was to examine overall and cause-specific mortality in relation to dietary and serum cholesterol, as well as egg consumption, and conduct an updated meta-regression analysis of cohort studies. We conducted a prospective analysis of 27 078 men in the ATBC Study (Alpha-Tocopherol, Beta-Carotene Cancer Prevention). Multivariable-controlled cause-specific Cox proportional hazards regression models were used to calculate hazard ratios and 31-year absolute mortality risk differences. A systematic review and meta-analysis of cohort studies was also performed (PROSPERO [URL: https://www.crd.york.ac.uk/prospero/; Unique identifier: CRD42021272756]). Based on 482 316 person-years of follow-up, we identified 22 035 deaths, including 9110 deaths from cardiovascular disease (CVD). Greater dietary cholesterol and egg consumption were associated with increased risk of overall and CVD-related mortality. Hazard ratios for each additional 300 mg cholesterol intake per day were 1.10 and 1.13 for overall and CVD-related mortality, respectively; for each additional 50-g egg consumed daily, hazard ratios were 1.06 and 1.09, respectively, for overall and CVD-related mortality (all P values<0.0001). After multivariable adjustment, higher serum total cholesterol concentrations were associated with increased risk of CVD-related mortality (hazard ratios per 1 SD increment, 1.14; P<0.0001). The observed associations were generally similar across cohort subgroups. The updated meta-analysis of cohort studies on the basis of 49 risk estimates, 3 601 401 participants, and 255 479 events showed consumption of 1 additional 50-g egg daily was associated with significantly increased CVD risk (pooled relative risk, 1.04 [95% CI, 1.00-1.08]; I2=80.1%). In the subgroup analysis of geographic regions (Pinteraction=0.02), an increase of 50-g egg consumed daily was associated with a higher risk of CVD in US cohorts (pooled relative risk, 1.08 [95% CI, 1.02-1.14]) and appeared related to a higher CVD risk in European cohorts with borderline significance (pooled relative risk, 1.05), but was not associated with CVD risk in Asian cohorts. In this prospective cohort study and updated meta-analysis, greater dietary cholesterol and egg consumption were associated with increased risk of overall and CVD-related mortality. Our findings support restricted consumption of dietary cholesterol as a means to improve long-term health and longevity.


Feasibility and safety of laparoscopic management of hydatid disease of the liver.
Laparoscopic treatment of hydatid disease of the liver produces encouraging results, though its feasibility and safety have been questioned. We evaluated the feasibility and safety of laparoscopic management of hydatid disease of the liver. Consecutive patients with this disease reporting to our department from August 1998 to January 2002 were offered laparoscopic management. Our protocol included preoperative albendazole for 4 weeks, laparoscopic cyst evacuation after its sterilization, and deroofing and suction drainage of the cavity, addition of omentoplasty if required, and a follow-up exceeding 6 months. Eighteen patients (M11:F7) with 22 liver hydatid cysts underwent laparoscopic surgery. The mean cyst size was 7.4 cm (range, 5.6 cm to 16.6 cm). Two patients needed conversion to an open operation. Spillage of cyst contents occurred in 5 patients. True recurrence of hydatid disease occurred in the original site in 2 patients (11%), and false recurrence was seen in 2 patients (11%), all within 6 months. With proper patient selection, laparoscopic management of hydatid cysts of the liver is a feasible option with low rates of conversion. Both true and false recurrences are common with conservative laparoscopic options, and undetected ectocysts may be the cause of true cyst recurrence.


Molecularly imprinted polymer film grafted from porous silica for efficient enrichment of steroid hormones in water samples.
Steroid hormones as endocrine disrupting compounds can interfere with the functioning of hormonal systems of organisms and thus affect the health and reproduction of humans and wildlife. Unfortunately, these types of harmful endocrine disrupting compounds have been found in a variety of environmental samples at very low concentrations. Therefore, a simple, fast, and efficient method for enrichment of water samples is needed. A molecularly imprinted solid-phase extraction combined with high performance liquid chromatography coupled with diode array detection was developed for the determination of six steroid hormones, such as estrone, 17-β-estradiol, estriol, 17-α-ethinylestradiol, progesterone, and testosterone in water samples. The recoveries obtained in the proposed method were in the range of 78.7-101.3%. Matrix effect below 20% suggests that the quantitative and qualitative results of the analysis were not significantly affected by the matrix. The results show that molecularly imprinted polymers based on spherical silica gel had the potential to be a highly innovative and selective sorbent. The proposed method was proved to be applicable for molecularly imprinted solid-phase extraction in selective and reliable extraction and enrichment of steroid hormones in environmental water samples.


Choline Triggers Exacerbations of Chronic Obstructive Pulmonary Disease in Patients Infected with Pseudomonas aeruginosa.
Although exacerbations of chronic obstructive pulmonary disease produced by Pseudomonas aeruginosa infections are a major cause of death, the molecular mechanism that produces them is not well known. Here we focused on the energetic basis of dyspnoea, hypercapnia and acidosis symptoms. We used an in vivo exacerbation model exposing mice to cigarette smoke and LPS, to mimic emphysema and infections, and choline challenges to trigger exacerbations, that showed 31% increased in the airway resistance for naïve mice and 250% for smoke/LPS treatment. Tissue resistance was increased 32%, in naïve mice, and 169% for smoke/LPS treatment. A decreased tissue elastance, was confirmed by decreased collagen content and increased alveoli chord length. Consequently, the O2 demanded was 260% greater for smoke/LPS treated mice, to provide the energy required to pump the same volume of air then for naïve mice. The extra CO2 produced per ml of air pumped caused hypercapnia and acidosis by 4% decrease in pH.In addition, the bacteria grown with choline had a decrease of 67% in phosphate, 23% ATP and 85% phospholipids with an increase of 57% in polyphosphates, 50% carbohydrates, 100% LPS, consuming 45% less energy relative to the bacteria grown with succinate. choline, released by P. aeruginosa, triggers exacerbation symptoms by increasing lung resistance, O2 consumption and producing more pCO2 in blood with dyspnea, hypercapnia and acidosis. The energetic shift of decreased O2 bacterial demand and increased lung demand benefits the infection, thus restoring the energetic balance on the host will favor P. aeruginosa eradication.


Integrative analysis of key candidate genes and signaling pathways in acute coronary syndrome related to obstructive sleep apnea by bioinformatics.
Although obstructive sleep apnea (OSA) has been clinically reported to be associated with acute coronary syndrome (ACS), the pathogenesis between the two is unclear. Herein, we analyzed and screened out the prospective molecular marker. To explore the candidate genes, as well as signaling cascades involved in ACS related to OSA, we extracted the integrated differentially expressed genes (DEGs) from the intersection of genes from the Gene Expression Omnibus (GEO) cohorts and text mining, followed by enrichment of the matching cell signal cascade through DAVID analysis. Moreover, the MCODE of Cytoscape software was employed to uncover the protein-protein interaction (PPI) network and the matching hub gene. A total of 17 and 56 integrated human DEGs in unstable angina (UA) and myocardial infarction (MI) group associated with OSAs that met the criteria of |log2 fold change (FC)|≥ 1, adjusted P < 0.05, respectively, were uncovered. After PPI network construction, the top five hub genes associated with UA were extracted, including APP, MAPK3, MMP9, CD40 and CD40LG, whereas those associated with MI were PPARG, MAPK1, MMP9, AGT, and TGFB1. The establishment of the aforementioned candidate key genes, as well as the enriched signaling cascades, provides promising molecular marker for OSA-related ACS, which will to provide a certain predictive value for the occurrence of ACS in OSA patients in the future.


Evolving Antithrombotic Treatment Patterns for Patients With Nonvalvular Atrial Fibrillation and Acute Coronary Syndrome or Underwent Percutaneous Coronary Intervention in China: A Cross-Sectional Study.
Antithrombotic therapy in patients with nonvalvular atrial fibrillation (NVAF) concomitant with the acute coronary syndrome (ACS) or underwent percutaneous coronary intervention (PCI) is challenging and has evolved in recent years. However, real-world data on this issue about antithrombotic regimens at discharge and its evolving trend were relatively scarce, especially in China. A total of 2,182 patients with NVAF and ACS/PCI were enrolled from 2017 to 2019. A total of 1,979 patients were finally analyzed and divided in three sequential cohorts: cohort 1 (2017), n = 674; cohort 2 (2018), n = 793; and cohort 3 (2019), n = 512. Baseline characteristics and antithrombotic therapy at discharge were analyzed by cohort. In our cross-sectional study, the majority of patients (59.6%) received dual antiplatelet therapy (DAPT). Over the 3 years, DAPT prescription reduced from nearly 70% to <50% (P trend < 0.001), while triple therapy (TT)/double therapy (DT) increased from 27.2 to 50.0% (P trend < 0.001). This trend was also seen in different subgroups stratified by CHA2DS2-VASc score, HAS-BLED score, coronary artery disease type, or management type, and was validated after multivariate adjustment. Persistent atrial fibrillation and history of congestive heart failure, hypertension, diabetes mellitus, and stroke/transient ischemic attack/systemic embolism were the independent predictors of TT/DT use, while ACS, PCI, or advanced chronic kidney disease was related with more DAPT prescription. There is a shift of antithrombotic regime at discharge for patients with NVAF with recent ACS/PCI with reducing DAPT prescription and increasing TT/DT prescription. While the appropriate antithrombotic regimen for patients with NVAF having ACS/PCI is still underused in China.


Double origin of the posterior inferior cerebellar artery: association with intracranial aneurysm on catheter angiography.
Double origin of the posterior inferior cerebellar artery (PICA) is a congenital anomaly in which the PICA forms from two separate vessels arising from the vertebral artery. The prevalence of double origin of the PICA on catheter angiography is unknown because only four case reports have been published. Because some congenital intracranial vascular oddities are associated with an elevated incidence of aneurysm formation, we sought to determine the association between intracranial aneurysm and double origin of the PICA and to measure the prevalence of double origin of the PICA on catheter angiography. A retrospective review was done over a 27-month period to identify patients with double origin of the PICA. Patients were excluded if both PICAs were not adequately visualized on catheter angiography. The cohort was then divided into two groups consisting of patients with and those without intracranial aneurysm. A total of 207 patients (101 males, 106 females) met the inclusion criteria. One or more cerebral aneurysms were found in 35.3% and double origin of the PICA in 1.45% of the patients. Double origin of the PICA was present in 4.1% of the patients with an aneurysm, and none of the patients without an aneurysm had double origin of the PICA (p = 0.043). A majority of the seven known cases of double origin of the PICA described by angiography in the peer-reviewed literature have associated intracranial aneurysm disease. Our data show that double origin of the PICA is seen in 4.1% of patients with intracranial aneurysm and on 1.45% of catheter angiograms. Double origin of the PICA has an increased association with intracranial aneurysmal disease and may represent a risk factor for subsequent development of intracranial aneurysm.


Surgical management of amiodarone-induced thyrotoxicosis in a patient with Eisenmenger's syndrome: literature review and case report.
We present a patient with a rare combination of amiodarone-induced thyrotoxicosis and Eisenmenger's syndrome. Case report and review of the world literature regarding the morbidity and mortality of surgical management of amiodarone-induced thyrotoxicosis and the potential hazards of non-cardiac surgery in patients with Eisenmenger's syndrome. Failure of maximal medical therapy necessitated surgical management to treat amiodarone-induced thyrotoxicosis which, in this particular patient, carried significant risks. Total thyroidectomy was performed leading to rapid resolution of thyrotoxicosis, and the patient made an uncomplicated recovery. We present this case because of its rarity and the potentially hazardous nature of surgical intervention in patients with Eisenmenger's syndrome. The pathogenesis of amiodarone-induced thyrotoxicosis and the differing approaches of medical and surgical management are discussed. Based on our findings, we propose that surgical management should be considered earlier in the treatment algorithm (or possibly as first-line therapy) for amiodarone-induced thyrotoxicosis.


Cardiovascular effects of aspidofractinine-type alkaloids from Kopsia.
Intravenous injection of the aspidofractinine alkaloid, kopsingine (1, 0.2-10.0 mg/kg) from Kopsia teoi, produced dose-related decreases in the mean arterial blood pressure and heart rate in anesthetized spontaneously hypertensive rats, which were similar to those seen in normotensive controls. Minor modifications in the molecular structure of kopsingine, as in kopsaporine (2, the 12-demethoxy derivative of kopsingine) and 14,15-dihydrokopsingine (4), did not significantly alter the hypotensive responses, whereas a more drastic change in the structure, as in the heptacyclic kopsidine A (3) and the 3-to-17 oxo-bridged compound 5, resulted in an increase in blood pressure. The antihypertensive effects of kopsingine (1) and its congeners (2 and 4) along with the pressor effects produced by the heptacyclic oxo-bridged compounds (5 and 3) could be ascribed to central as well as peripheral actions.


Digital imaging for the general dental practitioner: 1. Getting started.
Clinical photography has been used in dental practices all over the world for many years, although it has generally been the keen amateur photographer or enthusiastic practitioner who undertook clinical photography, often with specialized equipment. Understanding the equipment, and how to use it successfully, have caused many hours of frustration, culminating in an anxious wait for the results to be returned (or lost) by the processors.


Novel Coronavirus (2019-nCoV) in Disguise.
Novel coronavirus (2019-nCoV) pandemic is currently one of the most influential topics as it not only impacts the field of medicine but most importantly, it affects the lives of many individuals throughout the world. We report an interesting 2019-nCoV case in a tertiary community hospital with the initial concern of acute pyelonephritis without respiratory symptoms that ultimately led to the quarantine of a number of healthcare providers. This case emphasizes the importance of radiological evidence in diagnosing 2019-nCoV in the setting of an initial atypical presentation. It also serves as an example of how healthcare providers may need to increase their suspicion for COVID-19 to ensure self-protection and prompt diagnosis in the era of an ongoing pandemic.


Lung cancer incidence among world trade center rescue and recovery workers.
Many World Trade Center disaster (WTC) rescue and recovery workers (WTC RRWV) were exposed to toxic inhalable particles. The impact of WTC exposures on lung cancer risk is unclear. Data from the WTC Health Program General Responders Cohort (WTCGRC) were linked to health information from a large New York City health system to identify incident lung cancer cases. Incidence rates for lung cancer were then calculated. As a comparison group, we created a microsimulation model that generated expected lung cancer incidence rates for a WTC- and occupationally-unexposed cohort with similar characteristics. We also fitted a Poisson regression model to determine specific lung cancer risk factors for WTC RRWV. The incidence of lung cancer for WTC RRWV was 39.5 (95% confidence interval [CI]: 30.7-49.9) per 100,000 person-years. When compared to the simulated unexposed cohort, no significant elevation in incidence was found among WTC RRWV (incidence rate ratio [IRR] 1.34; 95% CI: 0.92-1.96). Predictors of lung cancer incidence included age, smoking intensity, and years since quitting for former smokers. In adjusted models evaluating airway obstruction and individual pre-WTC occupational exposures, only mineral dust work was associated with lung cancer risk (IRR: 2.03; 95% CI: 1.07-3.86). In a sample from a large, prospective cohort of WTC RRWV we found a lung cancer incidence rate that was similar to that expected of a WTC- and occupationally-unexposed cohort with similar individual risk profiles. Guideline-concordant lung cancer surveillance and periodic evaluations of population-level lung cancer risk should continue in this group.


Responsiveness of the DASH questionnaire for surgically treated tennis elbow.
This study evaluates if the Disabilites of the Arm, Shoulder and Hand (DASH) questionnaire is an adequately responsive outcome measure in lateral extensor release for tennis elbow. To measure responsiveness (sensitivity to clinical change), 21 patients with operated tennis elbow completed the DASH questionnaire pre-operatively and again postoperatively. The effect size (2.03) and standardized response (1.54) mean that, as well as the correlation with patient satisfaction and the Roles & Maudsley score (10), the DASH questionnaire is a useful tool to evaluate the outcome of surgical treatment of tennis elbow.


3D culture increases pluripotent gene expression in mesenchymal stem cells through relaxation of cytoskeleton tension.
Three-dimensional (3D) culture has been shown to improve pluripotent gene expression in mesenchymal stem cells (MSCs), but the underlining mechanisms were poorly understood. Here, we found that the relaxation of cytoskeleton tension of MSCs in 3D culture was critically associated with the expressional up-regulation of Nanog. Cultured in spheroids, MSCs showed decreased integrin-based cell-matrix adhesion but increased cadherin-based cell-cell interaction. Different from that in 2D culture, where MSCs exhibited branched and multiple-directed F-actin stress bundles at the cell edge and strengthened stress fibres transversing the cell body, MSCs cultured in spheroids showed compact cell body, relaxed cytoskeleton tension with very thin cortical actin filament outlining the cell, and increased expression of Nanog along with reduced levels of Suv39h1 (H3K9 methyltransferase) and H3K9me3. Notably, pharmaceutical inhibition of actin polymerization with cytochalasin D or silencing Suv39h1 expression with siRNA in 2D-cultured MSCs elevated the expression of Nanog via H3K9 demethylation. Thus, our data suggest that 3D culture increases the expression of Nanog through the relaxation of actin cytoskeleton, which mediates reduced Suv39h1 and H3K9me3 levels.


Determinants of Slow Flow in Percutaneous Coronary Intervention to the Culprit Lesion of Non-ST Elevation Myocardial Infarction.
Slow flow is a serious complication in percutaneous coronary intervention (PCI) and is associated with poor clinical outcomes. Our previous study revealed that the ratio of stent diameter to vessel diameter was the determinant of slow flow in intravascular ultrasound (IVUS)-guided PCI to the culprit lesion of ST elevation myocardial infarction (STEMI). The purpose of this study was to verify whether the ratio of stent diameter to vessel diameter is the determinant of slow flow in IVUS-guided PCI to the culprit lesion of non-STEMI (NSTEMI). We included 150 NSTEMI patients and divided into the slow flow group (n = 17) and the non-slow flow group (n = 133). The ratio of stent diameter to vessel diameter was significantly larger in the slow flow group (0.77 ± 0.11) than the non-slow flow group (0.71 ± 0.11) (P = 0.03). Multivariate logistic regression analysis revealed that the ratio of stent diameter to vessel diameter (per 0.1 increase: OR 2.06, 95% CI 1.23-3.46, P = 0.006) was the determinant of slow flow after controlling covariates. In conclusion, the ratio of stent diameter to vessel diameter was the determinant of slow flow in IVUS-guided PCI to the culprit lesion of NSTEMI. Unlike other parameters, the ratio of stent diameter to vessel diameter is the modifiable parameters. We may consider the modest stent expansion strategy rather than the aggressive stent expansion strategy in IVUS-guided PCI to the culprit lesion of NSTEMI.


Direct comparison of CGCRYODERM and DermACELL in the same patient for outcomes in bilateral implant-based breast reconstruction: a retrospective case series.
The use of acellular dermal matrix (ADM) has been popularized in implant-based breast reconstruction (IBR). However, it is still controversial if ADM-associated complication rates differ with varying types of ADM products. The aim of this study was to compare postoperative complications between CGCRYODERM and DermACELL. A retrospective chart review was performed on 32 patients (64 breasts) who underwent bilateral prosthetic breast reconstruction between June 2015 and December 2019. All patients received two different ADMs in each breast during the surgery. Demographic variables, operative characteristics, and postoperative outcomes were compared between the cryopreserved and pre-hydrated ADM. The overall major and minor postoperative complications developed in 7 and 1 out of 32 patients, respectively. Seroma and infection were the most common complications. There were no cases that infection and/or seroma involved both breasts in one individual. No significant differences were observed in terms of seroma, infection, hematoma, mastectomy flap necrosis, or drainage period between the CGCRYODERM and DermACELL groups (P=0.5637, 0.1797, 1.0000, 0.3173, and 0.2925, respectively). There was no case of reconstruction failure leading to explantation. There were no statistically significant differences in postoperative complications between the two breasts reconstructed with CGCRYODERM and DermACELL in the same patient who underwent bilateral IBR. This is the first study to compare cryopreserved and pre-hydrated ADMs. We suggest that CGCRYODERM is a suitable option with a comparable safety profile for IBR.


Lumos: a statewide linkage programme in Australia integrating general practice data to guide system redesign.
With ageing of the Australian population, more people are living longer and experiencing chronic or complex health conditions. The challenge is to have information that supports the integration of services across the continuum of settings and providers, to deliver person-centred, seamless, efficient and effective healthcare. However, in Australia, data are typically siloed within health settings, precluding a comprehensive view of patient journeys. Here, we describe the establishment of the Lumos programme-the first statewide linked data asset across primary care and other settings in Australia and evaluate its representativeness to the census population. Records extracted from general practices throughout New South Wales (NSW), Australia's most populous state, were linked to patient records from acute and other settings. Innovative privacy and security technologies were employed to facilitate ongoing and regular updates. The marginal demographic distributions of the Lumos cohort were compared with the NSW census population by calculating multiple measures of representation to evaluate its generalisability. The first Lumos programme data extraction linked 1.3 million patients' general practice records to other NSW health system data. This represented 16% of the NSW population. The demographic distribution of patients in Lumos was >95% aligned to that of the NSW population in the calculated measures of representativeness. The Lumos programme delivers an enduring, regularly updated data resource, providing unique insights about statewide, cross-setting healthcare utilisation. General practice patients represented in the Lumos data asset are representative of the NSW population overall. Lumos data can reliably be used to identify at-risk regions and groups, to guide the planning and design of health services and to monitor their impact throughout NSW.


[Can endogenous and neurotic depression be psychopathologically differentiated? Results of statistical analyses].
The concordant results of 54 studies in statistical classification of depressive states are investigated. It is ascertained, that the most trials to classificate depression by multivariate data analysis were not resulting in the discrimination of two syndromes, which were interpreted as endogenous versus neurotic. Much more, the statistical analyses of syndromes of depression succeeded in several classes of depressive symptoms. However, one can differentiate two types of such classes, one of clear-cut classes with especially psychotic symptoms, consistent in different investigations, and another of diffuse, unstable symptom clusters. It is presumed that competitive principles form the depressive states. In addition to etiological factors such as endogenous or neurotic processes, these principles are the severity of the illness, the defense mechanisms of the patient, and the topics of deficit experience.


Experiences of Women with Postpartum Depression Participating in a Support Group Led by Mental Health Providers.
The purpose of this study was to explore experiences of women currently with or at high risk for developing postpartum depression (PPD) who were participating in a postpartum support group facilitated by mental health providers. Using a qualitative design, women ≥18 years of age, who had given birth within the past 2 years, and who were currently attending, or had attended the PPD support group within the past year were invited to participate. The women provided demographic data and participated in a semistructured face-to-face interview. Data were analyzed using qualitative content analysis. Seven women between 27 and 38 years of age participated. Most were married and college educated. At time of the interviews, participants were between 5 months and 2 years postpartum and all reported taking antidepressant medications for their symptoms. Qualitative content analysis revealed three overall themes: attendance, impact, and medication adherence, with associated subthemes. Women attending a PPD support group facilitated by mental health providers felt supported, were more likely to disclose their symptoms to other women in the same situation, and were able to share their feelings without fear of judgment. Having concerns about antidepressant medication addressed at each meeting promoted medication adherence. Nurses working with childbearing women should be aware of community support services available for women at risk for developing PPD.


[Curriculum "patient safety" for undergraduate medical students at the department of surgery, University of Greifswald].
Risk reducing measures like the surgical checklist have been proven to reduce effectively adverse events and improve patient safety and teamwork among surgical staff members. Nevertheless, many physicians still refuse to use even simple safety tools like the WHO checklist. A progress in patient safety can only be achieved by changing the operating proceedings and mentality of medical students. This is best performed by teaching patient safety already very early in the medical education. The present study demonstrates the implementation and evaluation of the curriculum "patient safety" for undergraduate medical students in the 4th year of medical school at the Department of Surgery, University of Greifswald. 141 students evaluated a total of six lectures from April to October 2011. The results indicate that young medical students show great enthusiasm in safety matters and are willing to adopt the principles. Especially the importance of the issue and the didactic design were evaluated as being very high. The curriculum "patient safety" as part of the training program in medical school is a powerful and effective educational tool that is able to raise the student's awareness of patient safety affairs. Thereby it is crucial to start early within medical education during the phase of socialisation. We recommend the general implementation of a patient safety curriculum in medical school.


Electrophysiologic and antiarrhythmic effects of phentolamine in experimental coronary artery occlusion and reperfusion in the dog.
We studied the electrophysiologic and antiarrhythmic effects of phentolamine on ventricular arrhythmias seen after acute coronary artery occlusion and reperfusion in the anesthetized dog. One group of animals underwent proximal left circumflex artery occlusion for 1 hr followed by 4 hr of reperfusion. One-half received phentolamine, 0.25 mg/kg bolus, 30 min before occlusion, followed by continuous intravenous infusion of 0.15 mg/kg/min throughout the experiment, while the other half received saline and served as controls. Phentolamine reduced the number of premature ventricular contractions (PVCs) during the reperfusion period but had no effect on postocclusion arrhythmias. Another group of dogs underwent ligation of two consecutive left anterior descending diagonal branches for 1 hr followed by reperfusion. Effective refractory periods and ventricular activation times were measured before occlusion, every 10 min during occlusion, and every 10 min during reperfusion in both normal and ischemic zones. In this model, phentolamine reduced both the number of PVCs and the complexity of ventricular ectopy seen in the first 10 min after reperfusion. Compared to control, phentolamine decreased the shortening of ischemic zone refractory period seen after occlusion and prevented the overshoot seen after reperfusion. Phentolamine had no effect on ventricular activation times or mean blood pressure. Phentolamine is effective in preventing reperfusion ventricular arrhythmias and may act by decreasing the dispersion of refractoriness between normal and ischemic zones during coronary occlusion and reperfusion and by preventing the rapid increase in refractory period after reperfusion.


Organically directed iron sulfate chains: structural diversity based on hydrogen bonding interactions.
Six organically directed 1-D iron sulfates hydrated and hydrolyzed to different extents have been prepared hydrothermally. [C2H10N2]1.5[Fe(SO4)(3)].2H2O (I), [C2H10N2][Fe(SO4)2(OH)].H2O (II), [C6H18N2]0.5[Fe(SO4)2(H2O)2] (III), and [C6H18N2]0.5[Fe2(SO4)(H2O)4(OH)].H2O (V) possess the linear topological structures observed in ferrinatrite, sideronatrite, kröhnkite, and copiapite minerals, respectively. [C4H12N2][Fe2(SO4)3(OH)2(H2O)2].H2O (IV) shows a novel linear structure that can be regarded as a hybrid of the tancoite and butlerite types. [C6N4H22]0.5[Fe(SO4)2(OH)].2H2O (VI) adopts a cis configuration, compared with II, to give a rare inorganic helical iron sulfate chain which is a new member of the organically directed transitional metal sulfates. The results reveal that the starting molar proportion of the reactants and the type of amines are critical for the structural motif. There is an obvious relationship between the constitution of chains and the type of amino groups, involving the amount of N-H...O hydrogen bonds.


Purification and Characterization of Ethyl 2-Methyl-3-oxobutanoate Reductase from Klebsiella pneumoniae IF03319.
An enzyme that catalyzes a reduction of ethyl 2-methyl-3-oxobutanoate (1) to ethyl (2R,3S) 3-hydroxy- 2-methylbutanoate was found in Klebsiella pneumoniae IFO 3319 cells. The enzyme was isolated from the cells and purified 250-fold by ammonium sulfate fractionation, ion exchange chromatography, affinity chromatography, and gel filtration. The purified enzyme was found to be a monomer protein with a molecular weight of approximately 31,000 and an isoelectric point of 6.2. It was NADPH-dependent and had maximum activity at pH 7.0 and 45°C for the reduction and at pH 10.0 and 45°C for oxidation. The Km's at pH 7.0 were 5.6 mM for 1 and 12.5 mM for benzyl 2-methyl-3-oxobutanoate, respectively. Esters of 2-oxocycloalkane carboxylic acids as well as esters of 2-methyl-3-oxobutanoic acid served as substrates, and the corresponding reduced products were obtained with high stereoselectivity.


Photosensitizing medications and photocarcinogenesis.
Photosensitivity is an exaggerated or abnormal response to ultraviolet (UV) or visible light exposure. Many current medications are known photosensitizers; however, the effects of the sensitization can be subclinical and go unnoticed by the person affected. While some of these drugs are used for short and defined periods, others are used indefinitely for the treatment of chronic disease. The question of whether either of these practices translates into an increased risk of skin cancer is an important one. Numerous medications have real, distinct and well-elucidated mechanisms that potentiate the development of skin cancer, while with some medications the mechanism for the observed carcinogenesis remains unclear. In this article we will discuss the clinical, mechanistic and epidemiological evidence supporting photochemical genotoxicity and carcinogenesis.


Neuromusculoskeletal torque-generation process has a large destabilizing effect on the control mechanism of quiet standing.
The delay of the sensory-motor feedback loop is a destabilizing factor within the neural control mechanism of quiet standing. The purposes of this study were 1) to experimentally identify the neuromusculoskeletal torque-generation process during standing posture and 2) to investigate the effect of the delay induced by this system on the control mechanism of balance during quiet standing. Ten healthy adults participated in this study. The ankle torque, ankle angle, and electromyograms from the right lower leg muscles were measured. A ground-fixed support device was used to support the subject at his/her knees, without changing the natural ankle angle during quiet standing. Each subject was asked to mimic the ankle torque fluctuation by exerting voluntary ankle extension while keeping the supported standing posture. Using the rectified soleus electromyogram as the input and the ankle torque as the output, a critically damped, second-order system (twitch contraction time of 0.152 +/- 0.027 s) successfully described the dynamics of the torque-generation process. According to the performed Bode analysis, the phase delay induced by this torque-generation process in the frequency region of spontaneous body sway during quiet standing was considerably large, corresponding to an effective time delay of about 200 to 380 ms. We compared the stability of the balance control system with and without the torque-generation process and demonstrated that a much smaller number of gain combinations can stabilize the model with the torque-generation process than without it. We concluded that the phase delay induced by the torque-generation process is a more destabilizing factor in the control mechanism of quiet standing than previously assumed, which restricts the control strategies that can stabilize the entire system.


Preventive activity of Copaifera langsdorffii Desf. leaves extract and its major compounds, afzelin and quercitrin, on DNA damage in in vitro and in vivo models.
Copaifera langsdorffii Desf. is a plant found in South America, especially in Brazil. Oleoresin and the leaves of this plant is used as a popular medicinal agent. However, few studies on the chemical composition of aerial parts and related biological activities are known. This study aimed to examine the cytotoxic, genotoxic, and antigenotoxic potential of C. langsdorffii aerial parts hydroalcoholic extract (CLE) and two of its major compounds afzelin and quercitrin. The cytotoxic and antigenotoxic potential of CLE was determined as follows: 1) against genotoxicity induced by doxorubicin (DXR) or methyl methanesulfonate (MMS) in V79 cells; 2) by direct and indirect-acting mutagens in Salmonella typhimurium strains; and 3) by MMS in male Swiss mice. The protective effects of afzelin and quercitrin against DXR or MMS were also evaluated in V79 and HepG2 cells. CLE was cytotoxic as evidenced by clonogenic efficiency assay. Further, CLE did not induce a significant change in frequencies of chromosomal aberrations and micronuclei; as well as number of revertants in the Ames test demonstrating absence of genotoxicity. In contrast, CLE was found to be antigenotoxic in mammalian cells. The results also showed that CLE exerted inhibitory effect against indirect-acting mutagens in the Ames test. Afzelin and quercitrin did not reduce genotoxicity induced by DXR or MMS in V79 cells. However, treatments using afzelin and quercitrin decreased MMS-induced genotoxicity in HepG2 cells. The antigenotoxic effect of CLE observed in this study may be partially attributed to the antioxidant activity of the combination of major components afzelin and quercitrin.


CT-demonstrated transcalvarial channels diagnostic of dural arteriovenous fistula.
MR imaging-evident intraosseous channels associated with the presence of a dural arteriovenous fistula have been described in the literature. We describe these channels in relation to a case of dural arteriovenous fistula seen on CT. The presence of this subtle sign should be sought, and the area reviewed in all CT evaluations of patients with pulsatile tinnitus.


Summary measure of discrimination in survival models based on cumulative/dynamic time-dependent ROC curves.
Assessments of the discriminative performance of prognostic models have led to the development of several measures that extend the concept of discrimination as evaluated by the receiver operating characteristics curve and the area under the receiver operating characteristic curve (AUC) of diagnostic settings. Thus, several time-dependent-receiver operating characteristic curve and AUC(t) have been proposed. One of the most used, the cumulative/dynamic AUCC,D(t) is the probability that, given two randomly chosen patients, one having failed before t and the other having failed after t, the prognostic marker will be correctly ranked. In this paper, we propose a weighted AUCC,D(t) with time- and data-dependent weights as a summary measure of the mean AUCC,D(t), restricted to a finite time range to ensure its clinical relevance. A simulation study shows that estimated restricted mean AUC increased with the strength of association of the covariate with the outcome, with low impact of censoring, and adequate coverage of bootstrap confidence intervals. We illustrate this methodology to two real datasets from two randomized clinical trials to assess the prognostic factors of the overall mortality in patients who have compensated cirrhosis and to assess the prognostic factors of event-free survival in patients who have acute myeloid leukemia.


[A brief introduction to the disease-syndrome names in bamboo slips of Qin Dynasty].
There are plenty of names of disease-syndrome from the four kinds of unearthed Qin bamboo slips, namely Fangmatan, Shuihudi, Zhoujiatai, and Liye. Altogether, these names number to 85. According to statistics, nomenclature of 34 disease-syndromes are derived from the location of the lesion, 8 from symptoms, 1 from etiology, 12 from location of lesion plus symptom, 3 from location plus etiology, and 25 are for special diseases. Through comparison of these names, with those from oracle bones and Han bamboo slips, Prescriptions for Hundred Kinds of Disease, it is summarized that, as time passes, nomenclature simply named by the location of the lesion was gradually reduced, and named by etiology and special diseases gradually increased. To some extent, it reflects the historical process of knowledge of the disease gradually deepened in ancient times.


Nocturnal Desaturation is Associated With Atrial Fibrillation in Patients With Ischemic Stroke and Obstructive Sleep Apnea.
Both atrial fibrillation (AF) and obstructive sleep apnea (OSA) are risk factors for ischemic stroke. Previous studies suggested that OSA is associated with AF in individuals who have not had a stroke. For better secondary prevention of stroke, this study determined the association between OSA and AF among patients with ischemic stroke. This cross-sectional study recruited consecutive patients with subacute ischemic stroke admitted for neurorehabilitation. The baseline and clinical data were collected, and standard polysomnography was performed in a sleep center. The 47 women and 111 men enrolled in this study were divided into two groups according to the presence of AF. The AF group (n = 26) had a significantly older age (72.2 versus 60.1 years, P = .016), significantly more disability (Barthel index: 35 versus 45, P = .045), and marginally higher mean oxygen desaturation (6.7% versus 5.6%, P = .079) compared to the non-AF group. The two groups did not significantly differ in sex, body mass index, prevalence of hyperthyroidism, and other parameters of OSA. The multivariate logistic regression analysis revealed that mean desaturation was significantly associated with AF after adjusting for age, neck circumference, Barthel index and high-density lipoprotein level (odds ratio = 1.19 (95% confidence interval 1.05-1.35), P = .008). Nocturnal hypoxia due to OSA is an independent predictor of AF in patients with subacute ischemic stroke. The use of overnight pulse oximeter to assess nocturnal hypoxia and predict paroxysmal AF in patients with cryptogenic stroke needs further evaluation. A commentary on this article appears in this issue on page 667.


Primitive neuroectodermal tumor/Ewing's sarcoma in adult uro-oncology: A case series from a developing country.
Peripheral primitive neuroectodermal tumor/Ewing's sarcoma (PNET/EWS) is primarily a tumor of soft tissues and bones. Primary localization of PNET/EWS in genitourinary organs is rare. No data on this localization of PNET/EWS are available in literature from Pakistan. We searched our adult uro-oncology records from 1994 till date and identified all cases of adult genitourinary and adrenal PNET/EWS diagnosed on histology and immunohistochemistry. Their case records were reviewed to obtain data on demographics, presentation, pathologic features, management and outcome. Six cases were found; all were young and had aggressive disease at presentation. Four had renal PNET/EWS. One case each of prostate and adrenal PNET/EWS was seen. Surgery and chemotherapy formed the mainstay of management. Three patients (50%) died during treatment, two were lost to follow-up and one case with renal PNET/EWS showed good initial response to chemotherapy but was later on lost to follow-up. In conclusion, PNET/EWS should be considered in the differential diagnosis of genitourinary malignant tumors in young patients. These tumors are aggressive with poor outcome.


An over-the-counter omission.
Despite the widespread use of over-the-counter (OTC) medications, their utilization is rarely ascertained at hospital admission. Presented here is an interesting case of acute renal failure and hemolytic anemia attributable to a commonly utilized OTC medication. The chronic use of phenazopyridine accounted for all of these findings. Upon discontinuation, everything normalized within one month. Although the differential diagnosis for renal failure and hemolytic anemia is extensive, scleral icterus, normal bilirubin, and orange-colored urine raised the suspicion of phenazopyridine use. This case report highlights overuse of common OTC medications, as well as a lack of knowledge of potential adverse reactions. With history-taking vigilance and patient education, adverse events from OTC medications can be minimized.


The National Health Service (NHS) at 70: some comparative reflections.
As the National Health Service (NHS) turns 70, it bears comparison with another universal system celebrating an anniversary this year: Canada's 50-year-old medicare model. Each system is iconically popular, and each revolves around a profession-state accommodation. Both the popularity and the central axis of each system have been tested by external shocks in the form of periodic fiscal cycles of investment and austerity, and internal stresses generating organizational cycles of centralization and decentralization. In addition, the English NHS has undergone periodic bursts of major policy change, which have arguably moved the system closer to the Canadian single-payer model.


Contractile acto-myosin network on nuclear envelope remnants positions human chromosomes for mitosis.
To ensure proper segregation during mitosis, chromosomes must be efficiently captured by spindle microtubules and subsequently aligned on the mitotic spindle. The efficacy of chromosome interaction with the spindle can be influenced by how widely chromosomes are scattered in space. Here, we quantify chromosome-scattering volume (CSV) and find that it is reduced soon after nuclear envelope breakdown (NEBD) in human cells. The CSV reduction occurs primarily independently of microtubules and is therefore not an outcome of interactions between chromosomes and the spindle. We find that, prior to NEBD, an acto-myosin network is assembled in a LINC complex-dependent manner on the cytoplasmic surface of the nuclear envelope. This acto-myosin network remains on nuclear envelope remnants soon after NEBD, and its myosin-II-mediated contraction reduces CSV and facilitates timely chromosome congression and correct segregation. Thus, we find a novel mechanism that positions chromosomes in early mitosis to ensure efficient and correct chromosome-spindle interactions.


Mechanisms of basolateral base transport in the renal proximal tubule.
Renal proximal tubules absorb HCO3- by secretion of H+ into the tubular lumen. This paper focuses on the mechanisms of HCO3- exit across the basolateral cell membrane. The major exit pathway is rheogenic sodium bicarbonate co-transport. This system transports Na+ and HCO3-, but not Cl-, in obligatory coupling at a fixed overall stoichiometry of three HCO3- to one Na+. The fact that HCO3- flux is reduced after inhibition of cytoplasmic and/or membrane-bound peritubular carbonic anhydrase indicates that HCO3- is not transported as such but is split during permeation into its buffer subspecies from which it is regenerated on the other side of the membrane. Since flow of OH- or of H+ (in opposite directions) can be excluded, it appears most likely that one HCO3- and one CO3(2-) move together with one Na+. Besides carbonic anhydrase inhibitors, disulphonic stilbenes and harmaline are known to block the co-transporter. In addition to rheogenic Na+ (HCO3-)3 co-transport, Na+-dependent and Na+-independent electroneutral Cl-/HCO-3 exchange have been identified. The latter mechanisms are particularly important in S3 segments of proximal tubule where Na+ (HCO3-)3 co-transport is missing. Further mechanisms which operate in parallel, but at lower rates, are electroneutral SO4(2-)/HCO3- exchange and, in some species, lactate/HCO3- exchange. Moreover, there may be some uncoupled OH- flux and it is reasonable to assume that OH- (or H+) flux is involved in the transport of dicarboxylic acids across the basolateral cell membrane.


[Differences in the clinical feature of Sjögren syndrome in the presence and absence of rheumatoid arthritis].
In our study, we investigated the clinical features of sicca syndrome in the presence and absence of rheumatoid arthritis. Twenty patients with sicca syndrome alone and 22 patients with sicca syndrome accompanied by rheumatoid arthritis were examined. The average onset age of the sicca syndrome alone is 12 years younger than the syndrome associated with rheumatoid arthritis. Moreover, rheumatoid arthritis tended to antecede the clinical onset of the sicca syndrome in the latter group. Relevant to the clinical investigative data, frequent lower values of CH 50 and positive reactions to the anti-nuclear antibody were noted in the sicca syndrome alone group. In this group, a lowering of cell-mediated immunity and a decrease in lysozyme density in lacrimal fluid were also noted. Relevant to the clinical manifestation, a high frequency of recurrence of parotitis, purpura and lymphadenopathy was also noted. Related to the joint findings, 45% of the patients with sicca syndrome alone disclosed clinical evidence for arthritis, however, no significant radiographic findings were observed. It is clear that there were distinct differences in clinical figures in both groups, while continuity of the clinical figures between them was also confirmed. When we take the known pathological and molecular genetic findings into consideration, it may be assumed that the differences in the clinical figures between these two entities could result from the difference of the causative mechanism of the conditions. Furthermore, we may safely say that the sicca syndrome alone may reflect the essential pathophysiologic figure of this particular syndrome.


Geoepidemiology and Immunologic Features of Autoinflammatory Diseases: a Comprehensive Review.
The knowledge on systemic autoinflammatory disorders (SAID) is expanding rapidly and new signalling pathways are being decrypted. The concept of autoinflammation has been proposed since 1999, to define a group of diseases with abnormal innate immunity activation. Since then, more than 30 monogenic SAID have been described. In this review, we first describe inflammasomopathies and SAID related to the interleukin-1 pathway. Recent insights into the pathogenesis of familial Mediterranean fever and the function of Pyrin are detailed. In addition, complex or polygenic SAID, such as Still's disease or PFAPA syndrome, are also discussed. Then, major players driving autoinflammation, such as type-1 interferonopathies (including the recently described haploinsuffiency in A20 and otulipenia), TNF-associated periodic syndromes, defects in ubiquitination, and SAID with overlapping features of autoimmunity or immunodeficiency. Discoveries of the pathogenic role of mosaicism, intronic defects coupled to the likelihood to identify digenic or polygenic diseases are providing new challenges for physicians and geneticists. This comprehensive review depicts the various SAID, presenting them according to their predominant pathophysiological mechanism, with a particular emphasis on recent findings. Epidemiologic data are also presented. Finally, we propose a practical diagnostic approach to the most common monogenic SAID, based on the most characteristic clinical presentation of these disorders.


TLR-1, TLR-2, and TLR-6 MYD88-dependent signaling pathway: A potential factor in the interaction of high-DNA fragmentation human sperm with fallopian tube epithelial cells.
The DNA integrity of spermatozoa that attach to fallopian tube (FT) cells is higher than spermatozoa that do not attach. FT epithelial cells can distinguish normal and abnormal sperm chromatin. This study investigated the effects of sperm with a high-DNA fragmentation index (DFI) from men with unexplained repeated implantation failure (RIF) on the Toll-like receptor (TLR) signaling pathway in human FT cells in vitro. Ten men with a RIF history and high-DFI and 10 healthy donors with low-DFI comprised the high-DFI (>30%) and control (<30%) groups, respectively. After fresh semen preparation, sperm were co-cultured with a human FT epithelial cell line (OE-E6/E7) for 24 hours. RNA was extracted from the cell line and the human innate and adaptive immune responses were tested using an RT2 profiler polymerase chain reaction (PCR) array. The PCR array data showed significantly higher TLR-1, TLR-2, TLR-3, TLR-6, interleukin 1α (IL-1α), IL-1β, IL-6, IL-12, interferon α (IFN-α), IFN-β, tumor necrosis factor α (TNF-α), CXCL8, GM-CSF, G-CSF, CD14, ELK1, IRAK1, IRAK2, IRAK4, IRF1, IRF3, LY96, MAP2K3, MAP2K4, MAP3K7, MAP4K4, MAPK8, MAPK8IP3, MYD88, NFKB1, NFKB2, REL, TIRAP, and TRAF6 expression in the high-DFI group than in the control group. These factors are all involved in the TLR-MyD88 signaling pathway. The MyD88-dependent pathway through TLR-1, TLR-2, and TLR-6 activation may be one of the main inflammatory pathways activated by high-DFI sperm from men with RIF. Following activation of this pathway, epithelial cells produce inflammatory cytokines, resulting in neutrophil infiltration, activation, phagocytosis, neutrophil extracellular trap formation, and apoptosis.


Clinical Variability in a Family with an Ectodermal Dysplasia Syndrome and a Nonsense Mutation in the TP63 Gene.
Mutations in the TP63 gene have been associated with a variety of ectodermal dysplasia syndromes, among which the clinically overlapping Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) and the Rapp-Hodgkin syndromes. We report a multiplex nonconsanguineous family of Ashkenazi-Jewish descent, in which the index patient presented with a persistent scalp skin lesion, dystrophic nails and light thin hair. Further evaluation revealed over 10 affected individuals in the kindred, over four generations, exhibiting varying degrees of ectodermal involvement. Analysis of the TP63 gene from four of the patients and from two healthy individuals of the same family was performed. Gene sequencing of the patients revealed a nonsense mutation leading to a premature termination codon (PTC) (p.Gln16X). The same mutation was found in all tested affected individuals in the family, but gave rise to marked phenotypic variability with minor clinical manifestations in some individuals, underscoring the clinical heterogeneity associated with the recently described PTC-causing mutations.


Hepatitis C virus upregulates B-cell receptor signaling: a novel mechanism for HCV-associated B-cell lymphoproliferative disorders.
B-cell receptor (BCR) signaling is essential for the development of B cells and has a critical role in B-cell neoplasia. Increasing evidence indicates an association between chronic hepatitis C virus (HCV) infection and B-cell lymphoma, however, the mechanisms by which HCV causes B-cell lymphoproliferative disorder are still unclear. Herein, we demonstrate the expression of HCV viral proteins in B cells of HCV-infected patients and show that HCV upregulates BCR signaling in human primary B cells. HCV nonstructural protein NS3/4A interacts with CHK2 and downregulates its activity, modulating HuR posttranscriptional regulation of a network of target mRNAs associated with B-cell lymphoproliferative disorders. Interestingly, the BCR signaling pathway was found to have the largest number of transcripts with increased association with HuR and was upregulated by NS3/4A. Our study reveals a previously unidentified role of NS3/4A in regulation of host BCR signaling during HCV infection, contributing to a better understanding of the molecular mechanisms underlying HCV-associated B-cell lymphoproliferative disorders.


Attachment and growth of mammalian cells on microcarriers with different ion exchange capacities.
In the design of microcarriers for animal cell growth, the exchange capacity has been considered a critical factor. However, charge densities of microcarriers under culture conditions are not the same as the exchange capacities. Furthermore, the charge density requirement for optimum attachment is not necessarily the same as that required for optimum growth. We demonstrate that charge is not the sole factor affecting the attachment and growth of animal cells on microcarriers. We also show that supplemental serum in the growth medium has a negative effect on cell attachment to microcarriers.


Temple syndrome diagnosed in an adult patient with clinical autism spectrum disorder.
Temple syndrome (TS14) leads to growth failure, precocious puberty, and diabetes mellitus. However, the long-term prognosis, including the development of social behavior in TS14 patients, remains unclarified. We report the clinical course of a male patient with autism spectrum disorder that received a diagnosis of TS14 at 33 years of age.


Visual object agnosia as a problem in integrating parts and part relations.
Current models of vision generally assume that the recognition of visual objects is achieved by encoding their component parts, as well as the spatial relations among parts. The current study examined how the processing of parts and their configurations may be affected in visual agnosia due to brain damage. Both a visual agnosic patient (AR) and healthy control subjects performed a visual search task in which they had to discriminate between targets and distractors that varied according to whether they shared their parts and/or their configuration. The results show that AR's visual search rates are disproportionally slow when targets and distractors share the same configuration than when they have different configurations. AR is also found to be disproportionately slow in discriminating targets and distractors that share identical parts when the targets and distractors share the same configuration. With differently configured targets and distractors, AR shows no part sharing effect. For controls, in contrast, the part and configuration sharing effects occur independently of one another. It is concluded that AR's object recognition deficit arises from difficulties in discriminating objects that share their configuration, and from an abnormal dependency of part information processing upon object configuration.


Measuring Patient Mobility in the ICU Using a Novel Noninvasive Sensor.
To develop and validate a noninvasive mobility sensor to automatically and continuously detect and measure patient mobility in the ICU. Prospective, observational study. Surgical ICU at an academic hospital. Three hundred sixty-two hours of sensor color and depth image data were recorded and curated into 109 segments, each containing 1,000 images, from eight patients. None. Three Microsoft Kinect sensors (Microsoft, Beijing, China) were deployed in one ICU room to collect continuous patient mobility data. We developed software that automatically analyzes the sensor data to measure mobility and assign the highest level within a time period. To characterize the highest mobility level, a validated 11-point mobility scale was collapsed into four categories: nothing in bed, in-bed activity, out-of-bed activity, and walking. Of the 109 sensor segments, the noninvasive mobility sensor was developed using 26 of these from three ICU patients and validated on 83 remaining segments from five different patients. Three physicians annotated each segment for the highest mobility level. The weighted Kappa (κ) statistic for agreement between automated noninvasive mobility sensor output versus manual physician annotation was 0.86 (95% CI, 0.72-1.00). Disagreement primarily occurred in the "nothing in bed" versus "in-bed activity" categories because "the sensor assessed movement continuously," which was significantly more sensitive to motion than physician annotations using a discrete manual scale. Noninvasive mobility sensor is a novel and feasible method for automating evaluation of ICU patient mobility.


Access to care for children with fractures.
Earlier studies have found that children with fractures and PPO insurance have no access problems to orthopaedic care, but children with Medicaid have problems with access to orthopaedic care. Fifty randomly selected orthopaedic offices in each of the 2 counties served by a children's hospital were telephoned to seek an appointment for a fictitious 10-year-old boy with a forearm fracture. Each office was called twice, 1 time reporting that the child had PPO insurance and 1 time that he was having Medicaid. In the second arm of the study, data including insurance status were prospectively collected on all patients with fractures seen in the emergency department of children's hospital. Of the 100 offices telephoned, 8 offices gave an appointment within 1 week to the child with Medicaid insurance. Thirty-six of the 100 offices gave an appointment within 1 week to the child with PPO insurance. For the 2210 pediatric fractures seen in the emergency department, the payer mix for patients presenting initially to our facility (1326 patients) was 41% Medicaid, 9% selfpay, and 50% commercial. For the patients presenting to our emergency department after being seen at an outside facility first (884 patients), the payer mix was 47% Medicaid, 13% self-pay, and 40% commercial. The percentages between these two groups were similar but did have a statistically significant difference (P=0.021). To the best of our knowledge, this is the first study that reports a majority (64/100) of orthopaedic offices in the region would not care for a child with a fracture regardless of insurance status. Consistent with earlier studies, children with Medicaid have less access to care. The similar insurance status of children sent to the emergency department from other facilities compared with those presenting directly suggests that children in this study are sent to a children's hospital for specialized care rather than for economic reasons. Level II.


Quality of life after hepatectomy in patients with hepatocellular carcinoma: implication of change in hepatic protein synthesis.
Surgical removal has been accepted as a therapeutic option for hepatocellular carcinoma. However, little is known about the quality of life after hepatectomy for hepatocellular carcinoma. In this report, we describe the risk factors most affecting impaired quality of life after partial hepatectomy in patients with hepatocellular carcinoma. Ninety-six patients who received curative resections 12-60 months previously, answered our original questionnaire, mailed to them. The questions consisted of 14 items concerning physical function, social function, psychological function, physical sensation, and recognition of the disease, with a scoring system of 1, 2, and 3. Based on the pre- and postoperative serum alanine aminotransferase or cholinesterase levels at 3-month intervals during the follow-up period, the changes were classified into three types: those staying in the favorable or unfavorable range at one year (no change, Type 1 or Type 3), and those entering the unfavorable range postoperatively (Type 2). Total quality of life score: the sum of scores to questions 1-12, displayed two peaks of normal distribution. Based on a point of intersection of the two curves: i.e., score of 22, the patients were classified into 2 groups: those with preserved quality of life (n = 75) i.e., total quality of life scores of 12-21, and impaired quality of life, scores of 22 or more (n = 21). Older age (> or = 65 y) at hepatectomy, in the course of treatment for recurrence, and Type 2 change of serum cholinesterase level were associated with the impaired quality of life. Multivariate analysis revealed that Type 2 change of serum cholinesterase levels was an independent risk factor for an impaired quality of life. Furthermore, the patients exhibiting Type 2 change of serum cholinesterase levels were clearly impaired in their physical and social functions compared to the other patients. Hepatitis-related or cancer-related factors showed no correlation with the deterioration of the quality of life. The quality of life after hepatectomy in patients with hepatocellular carcinoma was impaired in cases of aged patients, treatment for recurrence, and Type 2 change of the serum cholinesterase level. Postoperative maintenance of protein synthesis including cholinesterase is one measure to preserve a satisfactory quality of life after hepatectomy.


Engineered viral nanoparticles for flow cytometry and fluorescence microscopy applications.
Viral nanoparticles (VNPs) are attractive platforms for use in the biotechnology and biomedical fields because of their biological nature. A wide variety of these particles, labeled with fluorescent reporters, have been characterized using flow cytometry and cellular imaging techniques. Fluorescence microscopy allows the direct observation of VNPs on the cell surface or inside the membrane as well as the cellular localization of the nanoparticles while flow cytometry allows the statistical quantification of nanoparticle uptake and targeting specificity. These techniques are essential when characterizing the properties of VNPs and provide information toward the use of VNPs for targeting, imaging, and/or cargo delivery.


Detecting single quantum dot motion with nanometer resolution for applications in cell biology.
Quantum dots (QDs), semiconductor particles of nanometer dimension, have emerged as excellent fluorescent analogs in tracer experiments with single molecule sensitivity for bioassays. Cell imaging greatly benefits from the remarkable optical and physical properties of these inorganic nanocrystals: QDs are much brighter and exhibit a higher resistance to photobleaching than traditional fluorophores, and their narrow emission spectrum and flexible surface chemistry make them particularly suitable for multiplex imaging. Here, we have demonstrated the achievement of a nanometer spatial resolution on the position of a single QD in a simple optomechanical instrument using a high-sensitivity low-noise detector, an intensified CCD camera. Furthermore, nanometer variations in the amplitude of a QD's sinusoidal oscillations could be quantitatively distinguished after fast Fourier transform (FFT) based data processing. As confirmed by experiments where QDs were attached to the surface of bovine aortic endothelial cells, this method can be exploited in biology to assess molecular and subcellular contributions to responses such as motility, intracellular trafficking, and mechanotransduction, with high resolution and minimal disturbance to cells.


Antiproliferative effects of two hydrosoluble derivatives of oxysterols on cultured lymphoma cells.
The antitumor effects of two new hydrosoluble derivatives of oxygenated sterols: JB69 and JC40 have been evaluated in vitro on a panel of lymphoma and leukemia cells from human and murine origins. These compounds result from the combination of a nucleotide with 7 beta-hydroxycholesterol (JB69) or 7 beta,25-dihydroxycholesterol (JC40). Both derivatives exhibit a significant cytotoxic activity against the different tumor cell lines tested, with some degree of difference between them. On the whole, the concentrations needed to inhibit the cell growth were found to be higher than those required for their parent compounds. However, two interesting features appeared in our experiments. (1) In a serum-free culture medium, cell lysis occurred within the first hours of incubation and seemed to result from the detergent-like properties possessed by this type of compounds. (2) In a culture medium supplemented with serum, we noted, that at high concentrations of JB69 (40 microM or 20 microM) and only with this oxysterol derivative, an important increase of incorporation of tritiated thymidine and uridine into DNA and RNA by viable cells. The origin of this effect is as yet unknown, but it strongly suggests a possible action on nucleic acids synthesis and metabolism. Taken together, these results emphasize the diversity and the complexity of the mechanisms involved in the cytotoxicity of these derivatives of oxysterols.


Endothelin-1 Gene Polymorphism and Its Level Predict the Risk of Venous Thromboembolism in Male Indian Population.
Genes related to endothelial function are responsible for the regulation of vascular functions. The aim of this study is to investigate whether endothelial gene-associated polymorphism and their plasma levels can be used to predict the risk for venous thromboembolism (VTE). We studied 133 patients with VTE and 164 healthy controls. Endothelin (EDN) G8002A, EDN T1370G, EDN 3A/4A, eNOSG894T, angiotensin-converting enzyme I/D, vascular endothelial growth factor C936T, and endothelial cell protein C receptor A6936G polymorphism was genotyped by restriction fragment length polymorphism. Plasma levels of endothelin 1 (EDN1), endothelial nitric oxide synthase, and angiotensin-converting enzyme were measured by enzyme-linked immunoassay kit. The genotype and allele frequency between control and patients with VTE were significantly altered only for EDN T1370G polymorphism. The plasma EDN1 concentration was relatively higher in patients with VTE ( P = .0017) compared to healthy controls and showed an association with the EDN1 gene polymorphism in male Indian population. Logistic regression model analysis for EDN T1370G indicated a significant association between EDN G allele and occurrence of VTE. The EDN1 gene polymorphism may play a significant role in predicting individual's susceptibility toward VTE and its clinical progression.


Androgen receptor binding sites identified by a GREF_GATA model.
Changes in transcriptional regulation can be permissive for tumor progression by allowing for selective growth advantage of tumor cells. Tumor suppressors can effectively inhibit this process. The PMEPA1 gene, a potent inhibitor of prostate cancer cell growth is an androgen-regulated gene. We addressed the question of whether or not androgen receptor can directly bind to specific PMEPA1 promoter upstream sequences. To test this hypothesis we extended in silico prediction of androgen receptor binding sites by a modeling approach and verified the actual binding by in vivo chromatin immunoprecipitation assay. Promoter upstream sequences of highly androgen-inducible genes were examined from microarray data of prostate cancer cells for transcription factor binding sites (TFBSs). Results were analyzed to formulate a model for the description of specific androgen receptor binding site context in these sequences. In silico analysis and subsequent experimental verification of the selected sequences suggested that a model that combined a GREF and a GATA TFBS was sufficient for predicting a class of functional androgen receptor binding sites. The GREF matrix family represents androgen receptor, glucocorticoid receptor and progesterone receptor binding sites and the GATA matrix family represents GATA binding protein 1-6 binding sites. We assessed the regulatory sequences of the PMEPA1 gene by comparing our model-based GREF_GATA predictions to weight matrix-based predictions. Androgen receptor binding to predicted promoter upstream sequences of the PMEPA1 gene was confirmed by chromatin immunoprecipitation assay. Our results suggested that androgen receptor binding to cognate elements was consistent with the GREF_GATA model. In contrast, using only single GREF weight matrices resulted in additional matches, apparently false positives. Our findings indicate that complex models based on datasets selected by biological function can be superior predictors as they recognize TFBSs in their functional context.


[Influence of process methods on contents of chemical component Radix Polygoni Multiflori].
Different methods of processing Radix Polygoni Multiflori and the change of chemical components including emodin, physcion, 2,3,5,4'-stilbene glucoside, and tannin were investigated. The dried roots of polygoni were processed in different ways, such as, steamed with black bean sauce, steamed with water, stewed with black bean sauce, and stewed with black bean sauce at high pressure, for h and 36 h, respectively. The process stewing with black bean sauce was also investigated for 12, 24, 36 h, and 48 h, respectively. The results indicated that 2,3,5,4'-stilbene glucoside and total free anthraquinones varied in different processes. In the process of black bean sauce stewing, the content of 2,3,5,4'-stilbene glucoside decreased with processing time, reached 17% of original at 48 h. The content of tannin and combined and free anthraquinones also decreased with processing time. It was concluded, therefore, that the processing of Radix Polygoni Multiflori should be standardized to avoid significant variation of chemical contents.


Hollow CoS/C Structures for High-Performance Li, Na, K Ion Batteries.
Alkali ion (Li, Na, and K) batteries as a new generation of energy storage devices are widely applied in portable electronic devices and large-scale energy storage equipment. The recent focus has been devoted to develop universal anodes for these alkali ion batteries with superior performance. Transition metal sulfides can accommodate alkaline ions with large radius to travel freely between layers due to its large interlayer spacing. Moreover, the composite with carbon material can further improve electrical conductivity of transition metal sulfides and reduce the electron transfer resistance, which is beneficial for the transport of alkali ions. Herein, we designed zeolitic imidazolate framework (ZIF)-derived hollow structures CoS/C for excellent alkali ion (Li, Na, and K) battery anodes. The porous carbon framework can improve the conductivity and effectively buffer the stress-induced structural damage. The ZIF-derived CoS/C anodes maintain a reversible capacity of 648.9, and 373.2, 224.8 mAh g-1 for Li, Na, and K ion batteries after 100 cycles, respectively. Its outstanding electrochemical performance is considered as a universal anode material for Li, Na, and K ion batteries.


[Main food intake prediction of Chinese residents based on grey model].
To predict the main food intake trend of the China's urban and rural residents from 2022 to 2030. Data was collected from the China Health and Nutrition Survey(CHNS), which was carried out on a stratified, multistage, clustered, and random sampling method. And the average daily food intake in the survey was continuously collected by a 24-hour dietary review method for 3 consecutive days. The sample sizes aged 20 years or older of seven rounds survey were 9794, 9425, 9313, 9726, 12 760, 15 446 and 15 051, respectively. Based on the seven rounds of average food intake, the main food intake of urban and rural residents in China from 2022 to 2030 was predicted by the Grey model. (1)The mean absolute percentage error of average food intake prediction in urban and rural ranged from 1.6% to 38.4%. (2)In terms of the trends of food intake from 2022 to 2030, the grain and vegetable average intake of plant food in urban and rural residents showed a decreasing trend, while the average intake of fruits showed an increasing trend. The average intake of animal food, such as poultry and aquatic products in urban, livestock, poultry, eggs in rural areas showed an upward trend. Meanwhile, the average intake of animal food, such as livestock and eggs in urban and aquatic products in rural showed a downward trend. (3)Compared with the 2018, the fruits, poultry and aquatic product intake of urban and rural residents in 2030 will increase by 60.7%, 29.4% and 6.6%, the intake of grain, vegetables, livestock and eggs in urban areas will decrease by 36.9%, 19.4%, 8.7% and 12.4%, respectively. In 2030, the intake of fruits, livestock, poultry and eggs of rural residents will increase by 88.9%, 31.8%, 71.9% and 9.2%, respectively. While the intake of grain, vegetables and aquatic products of rural residents will decrease by 32.5%, 24.8% and 2.2%, respectively. (4)By 2030, the average intake of poultry in urban and rural areas will be within the recommended range of dietary guidelines. But the average intake of grain, vegetables, fruits, eggs and aquatic products in urban and rural areas will remain below dietary recommendations. While the livestock average intake will be far higher than the recommendations. The model accuracy is different when applied to different kinds of food. According to the prediction result of the grey model, residents should be guided to maintain the current grain intake level and increase the intake of vegetables, fruits, poultry, eggs and aquatic products in order to get balanced diet, while reducing the intake of livestock.


Factors influencing the success of ICP projects.
In order to evaluate ICPs, criteria for success must be identified. The key areas to consider are quality of patient care, staff and patient satisfaction, documentation and cost. Commitment, resources, desire and need, facilitation and management also have an impact. The role of the ICP facilitator is vital to a project's success.


Protective effect of resveratrol on kidney in rats with diabetic nephropathy and its effect on endoplasmic reticulum stress.
Diabetic nephropathy (DN) can cause chronic renal insufficiency and significantly reduce the life quality of patients with diabetes mellitus, and may eventually lead to death. The study investigated the expression of endoplasmic reticulum stress-related factors, which have important roles in the progress of DN and to explore effects of resveratrol on DN and the possible mechanism. Specific pathogen free (SPF) grade healthy male Sprague Dawley (SD) rats were divided into different groups for different treatments. The diabetic rat model was established by intraperitoneal injection of low-dose streptozotocin (STZ) (40 mg/kg). The normal rats and diabetes model rats were divided into four groups including normal control group (N), normal control + resveratrol (N+R), model group (M), and model + resveratrol group (M+R) for different treatments. The changes of renal histology were observed by immunohistochemistry. Glucose oxidase/peroxidase method was used to measure FPG, UP 24 h content was measured by bicinchoninic acid (BCA) assay, BUN, Scr and Cys C content were measured by automatic biochemical analyzer. The expressions of 78 kDa glucose-regulated protein (GRP78), protein kinase RNA-like endoplasmic reticulum kinase (PERK), and activating transcription factor 4 (ATF4) and C/EBP-homologous protein (CHOP) were analyzed by Western blot. Resveratrol treatment significantly reduced the fasting blood glucose level, urinary protein level and renal pathological damage. The phosphorylation of PERK in the kidney of rats with diabetes was up-regulated, while resveratrol treatment reduced this change. The expression of p- PERK, GRP78, ATF4, and CHOP was significantly increased in rats with diabetes, while resveratrol treatment can reduce the increased level of those endoplasmic reticulum stress related factors. Resveratrol has a good therapeutic effect on DN in rats without side effect. The mechanism may be related to the regulation of endoplasmic reticulum stress response.


Science Signaling Podcast for 7 June 2016: Modeling signal integration.
This Podcast features an interview with Kevin Janes, senior author of a Research Article that appears in the 7 June 2016 issue of Science Signaling, about a statistical modeling method that can extract useful information from complex data sets. Cells exist in very complex environments. They are constantly exposed to growth factors, hormones, nutrients, and many other factors that influence cellular behavior. When cells integrate information from multiple stimuli, the resulting output does not necessarily reflect a simple additive effect of the responses to each individual stimulus. Chitforoushzadeh et al employed a statistical modeling approach that maintained the multidimensional nature of the data to analyze the responses of colonic epithelial cells to various combinations of the proinflammatory cytokine TNF, the growth factor EGF, and insulin. As the model predicted, experiments confirmed that insulin suppressed TNF-induced proinflammatory signaling through a mechanism that involved the transcription factor GATA6.Listen to Podcast.


Cd isotope fractionation during tobacco combustion produces isotopic variation outside the range measured in dietary sources.
Cadmium production has risen 1000-fold in the past 100 years, from under 20 to over 20,000 tons per year, causing anthropogenically-mobilized Cd to overwhelm natural sources in global cycling. Cadmium has no known biological function in humans, yet has biochemical behaviors similar to zinc and manganese, making exposure detrimental to human health. Identifying and quantifying the sources of Cd for human sub-populations is key to reducing exposures. Cadmium stable isotopes may provide a method for tracing Cd sources throughout the environment and the human body, but at present the limited database for high precision Cd isotopic compositions is inadequate to support such an analysis. Here, we provide new Cd isotope data on dietary sources, cigarette smoking components, and environmentally relevant standard reference materials. Results indicated that minor but significant variations are observed in food products (e.g., peanuts, sunflower seeds, spinach, kale, lettuce, cocoa powder; ~0.9‰ at 4 amu) that may be useful for tracing contamination in agricultural soils. In contrast, Cd isotope fractionation during smoking is larger (~6‰ at 4 amu) and has implications for tracing cadmium sources from tobacco combustion in the environment and throughout the human body. The primary inhaled component of cigarette smoke contains highest delta values (δ116/112Cd or δ114/110Cd ~5.2‰), while the second-hand smoke and cigarette ash have the lowest delta values (δ116/112Cd or δ114/110Cd ~-0.9‰). Used cigarette butts have δ114/110Cd ~2.4‰, in between the values measured in ash/s hand smoke and the inhaled smoke components. The high delta values of the inhaled smoke indicate that Cd isotopes may be used to determine the extent of Cd exposure due to smoking in human biological samples. This study provides new data for previously uncharacterized isotopic reservoirs that can be included in future studies of Cd source-exposure tracing.


Retinal Neuron Is More Sensitive to Blue Light-Induced Damage than Glia Cell Due to DNA Double-Strand Breaks.
Blue light is a major component of visible light and digital displays. Over-exposure to blue light could cause retinal damage. However, the mechanism of its damage is not well defined. Here, we demonstrate that blue light (900 lux) impairs cell viability and induces cell apoptosis in retinal neurocytes in vitro. A DNA electrophoresis assay shows severe DNA damage in retinal neurocytes at 2 h after blue light treatment. γ-H2AX foci, a specific marker of DNA double-strand breaks (DSBs), is mainly located in the Map2-posotive neuron other than the glia cell. After assaying the expression level of proteins related to DNA repair, Mre11, Ligase IV and Ku80, we find that Ku80 is up-regulated in retinal neurocytes after blue light treatment. Interestingly, Ku80 is mainly expressed in glia fibrillary acidic protein (GFAP)-positive glia cells. Moreover, following blue light exposure in vivo, DNA DSBs are shown in the ganglion cell layer and only observed in Map2-positive cells. Furthermore, long-term blue light exposure significantly thinned the retina in vivo. Our findings demonstrate that blue light induces DNA DSBs in retinal neurons, and the damage is more pronounced compared to glia cells. Thus, this study provides new insights into the mechanisms of the effect of blue light on the retina.


Salt tolerance of Triticum monococcum L., T. dicoccum (Schrank) Schubl., T. durum Desf. and T. aestivum L. seedlings.
Responses to salt stress of diploid wheat Triticum monococcum L., tetraploid wheats T. dicoccum (Schrank) Schubl. and T. durum Desf. cv. Grandur, and hexaploid wheats T. aestivum L. cvs. Begra and Gama were studied. Seeds were germinated on filter paper in Petri dishes, moistened in Hoagland medium containing 0 (control), 10, 20, 50, 100 and 200 mM NaCl. Index of tolerance to salt treatments was calculated on the basis of shoot length. Increase in salt concentration led to decrease in seed germination and inhibition of shoot and root elongation. Hexaploid and diploid wheats were more tolerant to salt stress than tetraploid wheats.


Magnetic Gel Composites for Hyperthermia Cancer Therapy.
Hyperthermia therapy is a medical treatment based on the exposition of body tissue to slightly higher temperatures than physiological (i.e., between 41 and 46 °C) to damage and kill cancer cells or to make them more susceptible to the effects of radiation and anti-cancer drugs. Among several methods suitable for heating tumor areas, magnetic hyperthermia involves the introduction of magnetic micro/nanoparticles into the tumor tissue, followed by the application of an external magnetic field at fixed frequency and amplitude. A very interesting approach for magnetic hyperthermia is the use of biocompatible thermo-responsive magnetic gels made by the incorporation of the magnetic particles into cross-linked polymer gels. Mainly because of the hysteresis loss from the magnetic particles subjected to a magnetic field, the temperature of the system goes up and, once the temperature crosses the lower critical solution temperature, thermo-responsive gels undergo large volume changes and may deliver anti-cancer drug molecules that have been previously entrapped in their networks. This tutorial review describes the main properties and formulations of magnetic gel composites conceived for magnetic hyperthermia therapy.


Effectiveness of Integrated Care on Delaying Progression of stage 3-4 Chronic Kidney Disease in Rural Communities of Thailand (ESCORT study): a cluster randomized controlled trial.
In developing countries, renal specialists are scarce and physician-to-patient contact time is limited. While conventional hospital-based, physician-oriented approach has been the main focus of chronic kidney disease (CKD) care, a comprehensive multidisciplinary health care program (Integrated CKD Care) has been introduced as an alternate intervention to delay CKD progression in a community population. The main objective is to assess effectiveness of Integrated CKD Care in delaying CKD progression. We carried out a community-based, cluster randomized controlled trial. Four hundred forty-two stage 3-4 CKD patients were enrolled. In addition to the standard treatments provided to both groups, the patients in the intervention group also received "Integrated CKD Care". This was delivered by a multidisciplinary team of hospital staff in conjunction with a community CKD care network (subdistrict healthcare officers and village health volunteers) to provide group counseling during each hospital visit and quarterly home visits to monitor compliance with the treatment. Duration of the study was 2 years. The primary outcome was difference of mean eGFR between the intervention and the control groups over the study period. The mean difference of eGFR over time in the intervention group was significantly lower than the control group by 2.74 ml/min/1.73 m2 (95%CI 0.60-4.50, p = 0.009). Seventy composite clinical endpoints were reported during the study period with significantly different incidences between the control and the intervention groups (119.1 versus 69.4 per 1000 person-years; hazard ratio (HR) 0.59, 95% CI 0.4-0.9, p = 0.03). Integrated CKD Care can delay CKD progression in resource-limited settings. ( NCT01978951 ). Prospectively registered as of December 8, 2012.


Sexual size and shape dimorphism, and allometric scaling in the pupal and adult traits of Eristalis tenax.
The patterns and amount of variation in size, shape, and/or life history traits between females and males are fundamentally important to gain the comprehensive understanding of the evolution of phenotypic diversity. In addition, the covariation of phenotypic traits can significantly contribute to morphological diversification and sexual dimorphism (SD). Using linear and geometric morphometrics, 237 Eristalis tenax specimens sampled from five populations were, therefore, comparatively assessed for the variation in sexual size dimorphism (SSD), sexual shape dimorphism (SShD), and life history traits, as well as for trait covariation (ontogenetic and static allometry). Pupal body, adult wing, and body mass traits were analyzed. Female-biased SSD was observed for pupal length, width, and centroid size, adult wing centroid size, mass, wing loading, and wing area. Conversely, pupal length/width ratio, developmental time, and mass were not found to be sexually dimorphic. Next, wing SShD, but not pupal body SShD was revealed, while allometry was found to be an important "determinant of SD" at the adult stage, with only a minor impact at the pupal stage. By comparing the patterns of covariance (based on allometric slope and intercept) between respective body mass and morphometric traits of pupae and adults, greater variation in allometric slopes was found in adult traits, while static allometries of the two stages significantly differed, as well. Finally, the results indicate that changes in the allometric intercept could be an important source of intraspecific variation and SD in drone fly adults.


Authors who have an impact on candidates' training: cultural differences and theoretical languages.
The authors consider the influence that a sense of geographical and cultural ties of candidates from different regions has on their theoretical interests. They question the way that this is taken into consideration in psychoanalytic training. The function of theory, both in terms of its transmission and the creation of new knowledge, is explored from this perspective. The results of an Internet survey are presented. The candidate sample for this survey (N = 250) was drawn from Europe, Latin America and North America, and candidates were asked to indicate their degree of interest for each of the 55 authors in a given list. The results showed that there were significant differences in the areas of theoretical interest of the candidates depending on the geographical region. Furthermore, what is also significant is how these differences in areas of theoretical interest were linked to those authors who had developed their work in the same geographical region as the candidates. These differences are shown to be connected to the candidates' sense of regional belonging. Data are also presented about which authors have the greatest impact in a given region, along with the influence values of the authors in relation to each one of the regions. Finally, the candidates' interest in each of the authors is specified in terms of a general mean rank and a regional mean rank, thus showing which authors candidates find most interesting in each of the regions. The study concludes by arguing that the results of the investigation enable us to question how psychoanalytic theory is transmitted, and, more specifically, how it is transmitted within institutions at a regional level. It is also suggested that the means be found to uncover the inconsistencies linked to cultural ties. It is proposed that further research be conducted to look more deeply into how cultural differences play a part in the different theoretical languages in the training of psychoanalysts.


The role of maximal oxygen uptake in exercise performance.
The maximal ability to deliver oxygen to the tissues of the body establishes the upper limit of endurance performance; however, the ability of the skeletal muscles to utilize a high oxygen load for a sustained period of time is also of great importance. The fatigue that limits endurance is due to a local limitation of oxygen or substrate, which leads to excessive anaerobic metabolism or decreased energy production. The peripheral adaptation from specific and intense training may further improve endurance performance.


Glucose-6-phosphate dehydrogenase activity measured by spectrophotometry and associated genetic variants from the Oromiya zone, Ethiopia.
The study aimed to gain first data on the prevalence of G6PD enzyme deficiency measured by spectrophotometry and associated genetic variants in Jimma and surroundings, Ethiopia. The area is a Plasmodium vivax endemic region, but 8-aminoquinolines such as primaquine are not recommended as G6PD testing is not available. Healthy volunteers were recruited at Jimma University, Ethiopia. Enzyme activity was tested by spectrophotometry at the University of Ulm, Germany. A G6PD RDT (Binax NOW® G6PD, Alere, USA) was additionally performed. The G6PD gene was analysed for polymorphisms in a sub-population. Tests for haemoglobinopathies and the presence of malaria parasites were conducted. No severe or moderate (cut-off 60%) G6PD deficiency was found in 206 volunteers. Median male activity was 6.1 U/g Hb. Eleven participants (5.4%) showed activities between 70 and 80%. No haemoglobinopathy was detected. None of the subjects showed asymptomatic parasitaemia. One G6PD-A+ variant (A376G) and one new non-synonymous mutation (G445A) were found. As the prevalence of G6PD deficiency seems low in this area, the use of 8-aminoquinolines should be encouraged. However, reliable G6PD testing methods have to be implemented and safe cut-off levels need to be defined.


Biosensors for Screening Kinase Inhibitors.
For successful drug discovery it is important to understand the fundamentals of the underlying causes and consequences of the diseases for which the drug is being developed. One such physiological process in eukaryotic cells is protein phosphorylation, which is the main post-translational modification of proteins responsible for the onset or progression of Alzheimer's disease, diabetes and various cancers. Protein phosphorylation is facilitated by kinases and inhibitors of kinases act as drugs in controlling or curing these diseases by reducing protein phosphorylation. This review discusses the technologies capable of detecting kinase activity and screening candidate compounds to identify novel inhibitors of protein kinases.


Xanthorrhizol induces apoptosis via the up-regulation of bax and p53 in HeLa cells.
Xanthorrhizol is a sesquiterpenoid compound extracted from Curcuma xanthorrhiza, which is known locally as Temulawak. Traditionally, C. xanthorrhiza was found to have antibacterial, anticancer and anti-inflammatory activity. The rhizome has also been used to treat inflammation in postpartum uterine bleeding. An antiproliferative assay using methylene blue staining revealed that xanthorrhizol inhibited the proliferation of the cervical cancer cell line HeLa with an EC50 value of 6.16 microg/ml. Xanthorrhizol significantly increased apoptosis in HeLa cells, as evaluated by the Tdt-mediated dUTP nick end-labelling (TUNEL) assay and nuclear morphology by Hoechst 33258 staining. Western blot analysis, which was further confirmed by the immunostaining results, implied an up-regulation of tumor suppressor protein p53 and the pro-apoptotic protein Bax, following the treatment with xanthorrhizol. Xanthorrhizol, however, did not affect the expression of the anti-apoptotic protein, Bcl-2 and the viral oncoprotein, E6. Hence, xanthorrhizol is a promising antiproliferative and anticancer agent which induces p53 and Bax-dependent apoptosis in HeLa cervical cancer cells.


Time-course microarrays reveal early activation of the immune transcriptome in a choline-deficient mouse model of liver injury.
Choline-deficient diet is extensively used as a model of nonalcoholic fatty liver disease (NAFLD). In this study, we explored genes in the liver for which the expression changed in response to the choline-deficient (CD) diet. Male CD-1 mice were divided into two groups and fed a CD diet with or without 0.2% choline bitartrate for one or three weeks. Hepatic levels of choline metabolites were analyzed by using liquid chromatography mass spectrometry and hepatic gene expression profiles were examined by DNA microarray analysis. The CD diet lowered liver choline metabolites after one week and exacerbated fatty liver between one and three weeks. We identified >300 genes whose expression was significantly altered in the livers of mice after consumption of this CD diet for one week and showed that liver gene expression profiles could be classified into six distinct groups. This study showed that STAT1 and interferon-regulated genes was up-regulated after the CD diet consumption and that the Stat1 mRNA level was negatively correlated with liver phosphatidylcholine level. Stat1 mRNA expression was actually up-regulated in isolated hepatocytes from the mouse liver with the CD diet. This study provides insight into the genomic effects of the CD diet through the Stat1 expression, which might be involved in NAFLD development.


Changes in maternal peripheral T helper 1-type and T helper 2-type immunity during labor.
The percentages of Th1 and Th2 cells and the Th1:Th2 ratios in peripheral blood from 22 patients with a singleton pregnancy at 30 and 36 weeks' gestation, on admission for the spontaneous onset of labor pains, at 1 minute after placental delivery and on day 7 after delivery were determined using flow cytometry. The percentages of Th1 and Th2 cells and the ratio of Th1:Th2 did not markedly change during 30 weeks' gestation and 1 minutes after placental delivery. However, the percentage of Th2 cells had decreased significantly at 7 days after delivery. In addition, the Th1:Th2 cell ratios were significantly elevated on day 7 after delivery. Thus, the termination of pregnancy may not be associated with a change in maternal Th1:Th2-immunity.


Expanding M NET: lessons from the development of a referring physician computer network.
M NET, the University of Michigan Medical Center's statewide referring physician computer network, was implemented as a pilot project in 1990. After three years of design, development and implementation, M NET has progressed from its pilot project status to a production system within the institution's strategic plan for hospital networking. This paper describes the evolution of M NET from a small pilot project to its current production status encompassing all clinical departments and hundreds of physicians across the state. The lessons learned from the pilot, the requirements of both the referring physicians and the Medical Center, and the development of a flexible and robust network architecture to allow network expansion are addressed.