Protein-enriched familiar foods and drinks improve protein intake of hospitalized older patients: A randomized controlled trial.
Adequate protein intake is important in preventing and treating undernutrition. Hospitalized older patients are recommended to consume 1.2-1.5 g of protein per kg body weight per day (g/kg/d) but most of them fail to do so. Therefore, we investigated whether a range of newly developed protein-enriched familiar foods and drinks were effective in increasing protein intake of hospitalized older patients. This randomized controlled trial involved 147 patients of ≥65 years (mean age: 78.5 ± 7.4 years). The control group (n = 80) received the standard energy and protein rich hospital menu. The intervention group (n = 67) received the same menu with various protein-enriched intervention products replacing regular products or added to the menu. Macronutrient intake on the fourth day of hospitalization, based on food ordering data, was compared between the two groups by using Independent T-tests and Mann Whitney U-tests. In the intervention group 30% of total protein was provided by the intervention products. The intervention group consumed 105.7 ± 34.2 g protein compared to 88.2 ± 24.4 g in the control group (p < 0.01); corresponding with 1.5 vs 1.2 g/kg/d (p < 0.01). More patients in the intervention group than in the control group reached a protein intake of 1.2 g/kg/d (79.1% vs 47.5%). Protein intake was significantly higher in the intervention group at breakfast, during the morning between breakfast and lunch, and at dinner. This study shows that providing protein-enriched familiar foods and drinks, as replacement of regular products or as additions to the hospital menu, better enables hospitalized older patients to reach protein intake recommendations. This trial is registered on ClinicalTrials.gov, Identifier: NCT02213393.


Acute histopathological responses of testicular tissues after different fractionated abdominal irradiation in rats.
To compare the effects of different fractionated doses of abdominal radiation therapy on acute histopathological responses of testicular tissues in rats. Thirty-three 3-week-old Wistar albino rats were randomized into 6 groups: group 1 (n = 5), control; group 2 (n = 4), hypofractionated total abdominal irradiation (TAI) of 6 Gy/1 fraction/day for 2 days; group 3 (n = 6), hypofractionated TAI of 4 Gy/1 fraction/day for 3 days; group 4 (n = 6), hypofractionated TAI of 3 Gy/1 fraction/day for 4 days; group 5 (n = 6), conventionally fractionated TAI of 2 Gy/1 fraction/day for 6 days; group 6 (n = 6), conventionally fractionated TAI of 1.7 Gy/1 fraction/day for 7 days. Mean epithelial length and diameter of seminiferous tubules of testicular tissues were determined after euthanasia. Initially, a highly significant decrease in both the mean tubular diameter and epithelial height of the seminiferous tubules was demonstrated in all irradiated rats compared with the control group. No significant differences regarding both damage parameters were found between different hypofractionated radiation therapies. Both conventional radiation therapies reduced the epithelial height and mean diameter of the seminiferous tubules to a lesser extent when compared with 6 Gy/1 fraction/day hypofractionated therapy. It was further shown that parameter values were comparable between rats that received 3 Gy/day hypofractionated therapy and rats that received either of the two conventional therapies. Furthermore, although 4 Gy/day hypofractionation decreased tubular diameter and epithelial length to a greater degree compared with the conventional therapy of 1.7 Gy/1 fraction/day, no statistically significant difference was found when compared with conventional therapy of 2 Gy/1 fraction/day. Additionally, no statistically significant difference was demonstrated between the two types of conventional radiotherapy application. The present study demonstrated that hypofractionated abdominal irradiation leads to more prominent tissue damage in the testes than conventional irradiation.


Detaching droplets in immiscible fluids from a solid substrate with the help of electrowetting.
The detachment (or removal) of droplets from a solid surface is an indispensable process in numerous practical applications which utilize digital microfluidics, including cell-based assay, chip cooling, and particle sampling. When a droplet that is fully stretched by impacting or electrowetting is released, the conversion of stored surface energy to kinetic energy can lead to the departure of the droplet from a solid surface. Here we firstly detach sessile droplets in immiscible fluids from a hydrophobic surface by electrowetting. The physical conditions for droplet detachment depend on droplet volume, viscosity of ambient fluid, and applied voltage. Their critical conditions are determined by exploring the retracting dynamics for a wide range of driving voltages and physical properties of fluids. The relationships between physical parameters and dynamic characteristics of retracting and jumping droplets, such as contact time and jumping height, are also established. The threshold voltage for droplet detachment in oil with high viscosity is largely reduced (~70%) by electrowetting actuations with a square pulse. To examine the applicability of three-dimensional digital microfluidic (3D-DMF) platforms to biological applications such as cell culture and cell-based assays, we demonstrate the detachment of droplets containing a mixture of human umbilical vein endothelial cells (HUVECs) and collagen (concentration of 4 × 10(4) cells mL(-1)) in silicone oil with a viscosity of 0.65 cSt. Furthermore, to complement the technical limitations due to the use of a needle electrode and to demonstrate the applicability of the 3D-DMF platform with patterned electrodes to chemical analysis and synthesis, we examine the transport, merging, mixing, and detachment of droplets with different pH values on the platform. Finally, by using DC and AC electrowetting actuations, we demonstrate the detachment of oil droplets with a very low contact angle (<~13°) in water on a hydrophobic surface.


Endovascular treatment of ruptured abdominal aortic aneurysms: a shift of the paradigm?
To compare endovascular aneurysm repair (EVAR) of ruptured abdominal aortic aneurysms (rAAA) to the results with open surgery. Between May 2001 and January 2004, 50 patients were diagnosed with rAAA. Fifteen (30%) patients (14 men; median age 73 years, range 58-85) underwent EVAR, while 26 (52%) patients (23 men; median age 75 years, range 60-84) had open surgery. Nine (18%) patients (5 men; median age 86 years, range 77-91) were not operated upon. Circulatory shock was defined as systolic blood pressure<80 mmHg. Mortality was defined as death within 30 days after operation; in cases where hospital stay exceeded 30 days, in-hospital mortality was registered. Five risk factors (age>76 years, loss of consciousness, hemoglobin<90 g/L, creatinine>190 micromol/L, and electrocardiographic ischemia) were analyzed. In the EVAR group, 93% (14/15) of the aneurysms were excluded from the bloodstream; there were 2 (13%) conversions: 1 intraoperatively for stent-graft migration and another owing to dissection prior to hospital discharge. Mortality after open surgery was 46% (12/26) versus 13% (2/15) in the EVAR group (p>0.05). Univariate analysis without considering variables other than mortality resulted in OR 5.4 (95% CI 0.9 to 58; p=0.07). Considering risk factors and shock, multivariate analysis resulted in OR 6.5 (95% CI 0.8 to 96; p=0.08). In the EVAR group, 60% (9/15) had complications; in the group with open surgery, the complication rate was 85% (22/26; p=0.13). It is possible to treat rAAA with EVAR. Hypotensive patients can, at least initially, be operated under local anesthesia to stabilize blood pressure utilizing a percutaneously inserted occlusion balloon. There was a trend in our study for reduced mortality and morbidity with EVAR, but further studies are required to conclude whether EVAR significantly increases survival and reduces complications.


Pain Diagnosis, Pain Coping, and Function in Individuals with Chronic Musculoskeletal Pain.
Research supports a role for coping responses in adjustment to chronic pain. However, it is likely that some coping responses play a larger role in adjustment to pain for some individuals than others. The identification of the factors that moderate the association between coping responses and pain-related outcomes has important clinical implications. This study sought to determine if musculoskeletal pain diagnosis moderates the associations between eight pain-coping responses and both pain and function. A non-probabilistic sample of 323 persons with different chronic musculoskeletal pain conditions completed measures of pain intensity, physical function, psychological function, and pain-coping responses. With only one exception, the frequency of use of pain-coping responses was not associated with pain diagnosis. Statistically significant moderation effects of pain diagnosis on the association between coping and pain outcomes were found for two coping responses: 1) support seeking when predicting pain intensity, and 2) resting when predicting both physical and psychological function. The findings indicate that coping responses tend to play a similar role in patients' pain and function across different musculoskeletal pain conditions, with some important exceptions. If the findings are found to replicate in other samples, they would have important implications for determining when psychosocial pain treatments might (and when they might not) need to be adapted for specific diagnostic groups.


A study through batch tests on the analytical determination and the fate and removal of methamphetamine in the biological treatment of domestic wastewater.
Methamphetamine (MET) is one of the most used illicit drugs in Europe and is recognized as one of the Emerging Organic Micropollutants. It is discharged into the sewerage system from different sources and then enters the wastewater treatment plants. The present study aimed at providing a better knowledge of the fate of MET through the wastewater treatment plants. The study addressed two different issues: (1) optimization of the analytical methods for MET determination in both liquid and sludge phases, focusing on the effects of potentially interfering substances and (2) investigation on the behaviour of MET in the biological treatment process, with specific concern for the biomass activity at different drug concentrations. Results of the study on issue 1 highlighted that the applied analytical method for MET determination (UPLC-MS/MS) is affected by the main components of wastewater for about 9-23%, which is comparable with the uncertainties of the method (about ± 28%). The method showed also to be repeatable and reliable (recovery > 75%; repeatability < 10-15%; bias uncertainty < 30%), and relatively easy-to-use. Therefore, it can be considered suitable for measurements on routine base in the WWTPs. Batch tests conducted to address issue 2 showed total removal of 84, 90, and 96% at 50, 100, and 200 ng/L initial MET concentration, respectively, for a contact time of 6 h. The removal process was mainly ascribed to the biological activity of both heterotrophic and autotrophic bacteria. The pseudo first-order kinetic model provided the best fitting of the experimental data of the overall biological processes at all the tested concentrations. Furthermore, the respirometric tests showed that MET does not induce any inhibition. Adsorption of MET on activated sludge was always very low.


[Severe, non-infectious mitral valve endocarditis after mitral valve reconstruction in a 32-year old female with primary antiphospholipid syndrome].
A 32-year old female with primary antiphospholipid syndrome presented 8 months after mitral valve reconstruction with progressive exertional dyspnea and echocardiographically demonstrable critical mitral stenosis and regurgitation. Tachycardia, weight loss, sleep disturbances and increasing nervosity led to the diagnosis of concomitant hyperthyroidism. After the patient stopped the oral anticoagulation by herself, a 'catastrophic antiphospholipid syndrome' with multiple microthromboembolic events in several organs developed rapidly within a few weeks. Severe respiratory failure was observed 14 days after admission at our hospital because of a pulmonary edema. Removal of the annuloplasty ring and alloplastic mitral valve replacement with a 25 mm bilifleat valve. Postoperatively, the patient was placed on oral anticoagulation. Several pre- and postoperative plasmaphereses lowered the level of antiphospholipid antibodies. The patient additionally underwent radioiodtherapy 5 months postoperatively. While hemodynamics and diuresis remained sufficient, ventilatory support with tracheostomy was necessary for 16 postoperative days to achieve stable respiration. Thirty months later, the patient is well and without further cardiac and neurological dysfunction. Secondary cardiac valve operations on patients with primary antiphospholipid syndrome may be successfully performed within a multidisciplinary approach. Oral anticoagulation remains the treatment of choice to prevent further thromboembolic events.


[Plasmacellular neoplasms of the head and neck: clinical status and personal experience].
In this review, the authors examine the diagnostic, prognostic and therapeutic advances in clinical management of Solitary Plasmacytoma of bone, Extramedullary Plasmacytoma and their relationship to multiple myeloma. The clinical differences among these tumors are the subject of continued studies. Oral symptoms and signs of the neoplasias are relatively common. The literature is reviewed with respect to the prevalence of oral and maxillofacial manifestations and the presence of such manifestations as the first sign and/or symptom of disease. The case of a young adult patient, with a kappa-light-chain positive extramedullary plasmacytoma of the maxillary sinus is presented. The reported case illustrates the necessity of a multidisciplinary approach using relevant immuno-hematologic, radiographic and histologic investigations in the differential diagnosis of these tumors. Factors influencing the prognosis of these neoplastic lesions are also discussed.


Machine learning-based rail corrugation recognition: a metro vehicle response and noise perspective.
Rail corrugation is a common problem in metro lines, and its efficient recognition is always an issue worth studying. To recognize the wavelength and amplitude of rail corrugation, a particle probabilistic neural network (PPNN) algorithm is developed. The PPNN is incorporated with the particle swarm optimization algorithm and the probabilistic neural network. On the basis of the above, the in-vehicle noise characteristics measured in the field are used to recognize normal rail wavelengths of 30 and 50 mm. A stepwise moving window search algorithm suitable for selecting features with a fixed order was developed to select in-vehicle noise features. Sound pressure levels at 400, 500, 630 and 800 Hz of in-vehicle noise are fed into the PPNN, and the average accuracy can reach 96.43%. The bogie acceleration characteristics calculated by the multi-body dynamics simulation model are used to recognize normal rail amplitudes of 0.1 and 0.2 mm. The bogie acceleration is decomposed by the complete ensemble empirical mode decomposition with adaptive noise, and a reconstructional signal is obtained. The energy entropy of the reconstructional signal is fed into the PPNN, and the average accuracy can reach 95.40%. This article is part of the theme issue 'Artificial intelligence in failure analysis of transportation infrastructure and materials'.


[Recent developments in internal medicine].
Whilst the practice of hospital based internal medicine is often carried out in tight collaboration with clinical specialities, in particular for deciding on the indication of interventional and diagnostic procedures, it is important to remain objective with respect to the indications and benefits of these acts. This is the case in areas such as cardiovascular medicine and nephrology. Recent studies also have the potential to modify current guidelines for the management of arterial hypertension and hypercholesterolemia. This article discusses some of these selected subjects.


Comparative study of misoprostol vs dinoprostone for induction of labour.
Various methods of induction of labour may be associated with risk and complications. Therefore, this study has been undertaken to compare the safety and efficacy of intra-vaginal misoprostol (PGE1 analogue) with intra-cervical dinoprostone (PGE2) in progress and induction of labour, the maternal side effects and the foetal outcome. 40 pregnant women aged between 16-35 years with indication of induction of labour participated in the study. Twenty patients (control) were administered 0.5 mg dinoprostone intra-cervically, 12 hourly while 20 patients (study group) were given misoprostol 100 microg, 4 hourly, intravaginally. The mean induction of labour initiation interval was 2.08 +/- 1.46 hours in study group and 2.21 +/- 1.20 hours in dinoprostone group. The Induction delivery interval was 6.92 +/- 4.01 hours in misoprostol group and 12.54 +/- 7.73 in dinoprostone group, whereas vaginal route of delivery was 95% in misoprostol group and 85% in dinoprostone group. Average dosages required were 1.55 +/- 1.02 in misoprostol group and 1.30 +/- 0.46 in dinoprostone group. All these result were statistically significant. Very few maternal side effects were reported in study group. There was no significant difference in foetal out come in either group. Therefore, it can be concluded that misoprostol is easy to administer and is cheap, effective, safe and convenient drug for induction of labour.


[Surgical management and reconstruction of petrous internal carotid artery involved in malignant tumors of lateral skull base].
To investigate the feasibility of reconstruction of internal carotid artery after ablation of malignant tumors in lateral skull base. Four male patients with malignant tumors in lateral skull base involved internal carotid artery underwent surgical treatment during Jan 2006 to Jan 2009 were retrospectively analyzed. MRI, CT and DSA were performed in all patients and showed that petrous internal carotid arteries (PICAs) were invaded, with luminal narrow. After radical dissection of tumors and the invaded PICAs, saphenous veins were used to reconstruct the PICAs. All cases were applied with postoperative concomitant radiochemotherapy. Three cases underwent total resection of temporal bone and one case underwent sub-total resection of temporal bone. Retrusion of facial nerve was performed in one case and reconstruction of facial nerve in three cases; Resection of sigmoid sinus and jugular foramen was performed in three cases. Resection and repair of meninges were performed in three cases. Free abdominal rectus and latissimus dorsi muscle myocutaneous flaps were used to repair the defect of lateral skull base and the flaps were well survived. No significant neurovascular complications occurred in the patients. Postoperative DSA showed that the reconstructed PICAs were in well conditions. Follow up showed two patients survived tumor-free for five years, one patient had recurrence three years after operation and survived with tumor, and one patient died of recurrence one year after operation. Reconstruction of PICA by saphenous vein offered the possibility of radical resection of malignant tumors in lateral skull base involved PICAs.


Coagulation-monitored, dose-adjusted catheter-directed thrombolysis or pharmaco-mechanical thrombus removal in deep vein thrombosis.
Background: Pharmaco-mechanical thrombectomy (PMT) and catheter-directed thrombolysis (CDT) are therapeutic options for selected patients with acute deep vein thrombosis (DVT) to prevent post-thrombotic syndrome (PTS). Patients and methods: We aimed to describe the clinical characteristics and outcomes of 159 patients with symptomatic iliofemoral DVT undergoing PMT alone, CDT alone, or CDT followed by PMT (bail-out) in the Swiss Venous Stent Registry. The primary outcome was the incidence of peri-interventional major and minor bleeding complications (ISTH criteria). Secondary outcomes included the incidence of PTS and stent patency after 3 years. Results: Mean age was 49±20 years and 58% were women. DVT involved the iliac veins in 99% of patients, whereas 53% had an underlying iliac vein compression. PMT alone was used in 40 patients, CDT alone in 77, and 42 received initial CDT followed by bail-out PMT due to insufficient thrombus clearance. Single-session PMT was the preferred approach in patients with iliac vein compression, patent popliteal vein, and absence of IVC thrombus. Patients treated with PMT alone received a lower r-tPA dose (median 10 mg, IQR 10-10) vs. those treated with CDT (20 mg, IQR 10-30). The rate of peri-interventional major bleeding was 0%, 1%, and 2%, whereas that of minor bleeding was 0%, 1%, and 12%, respectively, all occurring during CDT. After 3 years, PTS occurred in 6%, 9%, and 7% of patients, respectively. The primary stent patency rate was 95%, 88%, and 83%, respectively. Conclusions: The use of PMT and CDT for iliofemoral DVT was overall safe and resulted in high long-term patency and treatment success. Given the less severe presentation of DVT, single-session PMT appeared to be characterized by numerically better primary patency and lower perioperative bleeding event rates than CDT.


Idiopathic intracranial hypertension in Dubai: nature and prognosis.
To evaluate the nature and course of idiopathic intracranial hypertension (IIH) in Dubai, UAE. In a retrospective study the medical records of 50 patients with IIH were reviewed. All of them were diagnosed according to the Modified Dandy Criteria. There were 46 (92%) women. Mean age at presentation was 35.7 years. Obesity was the commonest associated factor (32%). Headache was reported in 98% followed by double vision (32%). Papilledema was present in all patients at the time of examination (100%). Perimetric study showed mild peripheral visual field constriction in 56%. Only two patients showed severe field constriction and one of them deteriorated rapidly and she became blind. The mean cerebrospinal fluid pressure was 302.5 mmH(2)O. The visual status improved significantly throughout the follow-up period. Idiopathic intracranial hypertension has relatively benign course in this part of the world and more aggressive treatment is not recommended.


Unusual presentation of large B cell lymphoma: a case report and review of literature.
Diffuse large B cell lymphoma (DLBCL) is the largest subtype of non-Hodgkin's lymphomas (NHLs) and is characterized by relatively frequent extranodal presentation. In these cases, the most common extranodal localizations are stomach, CNS, bone, testis and liver. Simultaneous detection of multiple extranodal involvement at presentation is quite uncommon, with the majority of these cases characterized by gastric or intestinal disease localization. Retrospective analysis concerning multifocal extranodal NHLs never pointed out disease features such as those described here. We report a patient with an unusual presentation of DLBCL, characterized by adrenal and renal involvement, associated with symptoms and signs of the cold agglutinin disease and a hypercoagulable state. Subsequently, computed tomography (CT) and fluorodeoxyglucose-positron emission tomography (FDG-PET) scanning disclosed a rapidly extensive spread to nodes and bones. Cytofluorimetric analysis of a renal specimen showed medium-to-large lympho-monocytoid elements positive for CD20 with monoclonal expression of immunoglobulin kappa light chain. Histopathological examination confirmed a renal CD20 positive DLBCL localization.


Hormonal and immunological characterization of the cell-associated plasminogen activators produced by cultured rat granulosa cells.
The hormonal induction and immunological reactivities of the cell-associated plasminogen activators (PAs) produced by granulosa cells obtained from the ovaries of diethylstilbestrol-implanted immature rats were studied. FSH and other cAMP-inducing ligands, including cholera toxin, forskolin, and 8-bromo-cAMP, elevated the PA activity of granulosa cells in a concentration-dependent manner during a 4-h culture, with an approximate 10-fold maximal increase in PA activity compared to control cells. Negligible levels of PA activity were observed in the extracellular medium in the absence or presence of hormones. The PA induced by FSH or cAMP in intact cells was progressively neutralized during the 4-h culture by increasing amounts of antibodies to the tissue-type PA (tPA), but not by an IgG fraction against the urokinase-type PA (UK-PA). However, solubilization of granulosa cells with Triton X-100 revealed the presence of intracellular UK-PA activity in both FSH-treated and control cells that consisted of about 20% of the total cellular PA activity. Electrophoretic analysis of extracts from solubilized granulosa cells indicated the presence of three peaks of PA activity. A PA with a Mr of 70,000 was induced by FSH, was completely inactivated by tPA antibodies, and required fibrin for full activity. A 40,000 Mr fibrin-independent PA was also stimulated by FSH and was partially inhibited by UK-PA antibodies, but not by anti-tPA immunoglobulin G. A third peak of PA activity comigrated with a human UK-PA standard at a Mr of 33,000, was fully neutralized by UK-PA antibodies, and was largely present only in control cells. These results suggest that during the first hours of granulosa cell development, FSH via cAMP induces the production of a cell-surface tPA, while both FSH-treated and control cells synthesize intracellular UK-PAs. Hormonal regulation of the production and activities of these cellular enzymes may allow the expression of specific differentiated functions of developing granulosa cells.


Patient experiences of inpatient hospital care: a department matter and a hospital matter.
To examine the added value of measuring and possibly presenting patient experiences at the department level, in addition to the hospital level, and to explore the possibility that patient experiences differ according to the 'type' of hospital department. Secondary analysis of data from a widely used survey on patient experiences of Dutch inpatient hospital care [Consumer Quality Index (CQI) Inpatient Hospital Care]. Inpatient hospital care experience survey of patients of 78 Dutch hospitals. A total of 15 171 randomly selected inpatients from 78 Dutch hospitals, who had at least one night of hospitalization between October 2006 and October 2007. Explained variance in patient experiences at the department level, compared with the explained variance at the hospital level. Significant differences in patient experiences between types of departments, expressed in regression coefficients. Patient experiences were measured using validated quality indicators, calculated from specific survey items. Adding the department level to the analyses of patient experiences is statistically worthwhile for a number of quality indicators of the CQI Inpatient Hospital Care, and will enable the presentation of more detailed results within hospitals. Furthermore, the results indicated that there are some systematic differences in patient experiences between specific types of hospital departments across hospitals. However, the proportion of variance in experiences explained by both department and hospital is limited (max. 14%). Analyses of quality information on patient experiences of inpatient hospital care should not only take the hospital level, but also at the more specific department level into account.


Circulating Androgen Concentrations and Risk of Incident Heart Failure in Older Men: The Cardiovascular Health Study.
Background Circulating androgen concentrations in men decline with age and have been linked to diabetes and atherosclerotic cardiovascular disease (ASCVD). A similar relationship has been reported for low total testosterone and incident heart failure (HF) but remains unstudied for free testosterone or the more potent androgen dihydrotestosterone (DHT). We hypothesized that total/free testosterone are inversely related, sex hormone-binding globulin is positively related, and total/free DHT bear a U-shaped relationship with incident HF. Methods and Results In a sample of men from the CHS (Cardiovascular Health Study) without atherosclerotic cardiovascular disease or HF, serum testosterone and DHT concentrations were measured by liquid chromatography-tandem mass spectrometry, and sex hormone-binding globulin by immunoassay. Free testosterone or DHT was calculated from total testosterone or total DHT, sex hormone-binding globulin, and albumin. We used Cox regression to estimate relative risks of HF after adjustment for potential confounders. In 1061 men (aged 76±5 years) followed for a median of 9.6 years, there were 368 HF events. After adjustment, lower calculated free testosterone was significantly associated with higher risk of HF (hazard ratio [HR], 1.14 [95% CI, 1.01-1.28]). Risk estimates for total testosterone (HR, 1.12 [95% CI, 0.99-1.26]), total DHT (HR, 1.10 [95% CI, 0.97-1.24]), calculated free dihydrotestosterone (HR, 1.09 [95% CI, 0.97-1.23]), and sex hormone-binding globulin (HR, 1.07 [95% CI, 0.95-1.21]) were directionally similar but not statistically significant. Conclusions Calculated free testosterone was inversely associated with incident HF, suggesting a contribution of testosterone deficiency to HF incidence among older men. Additional research is necessary to determine whether testosterone replacement therapy might be an effective strategy to lower HF risk in older men.


Sleep hygiene education: efficacy on sleep quality in working women.
Although sleep hygiene education represents a promising approach for patients with poor sleep quality, little research has been devoted in understanding the sleep hygiene behavior and knowledge of working women. The purpose of this study was to investigate the efficacy of a short-term sleep hygiene education program on working women with poor sleep quality. This pilot study was a prospective and an exploratory intervention study. The intervention was tested on 37 selected working women with poor sleep quality in the community. The Pittsburgh Sleep Quality Index (score > 5) was used to identify working women with poor sleep quality. After a pretest to assess sleep quality, researchers implemented a 5-week sleep hygiene education program that addressed good sleep environments/habits, emotional stress, the influence of diet/alcohol/tobacco on sleep, exercise, and alternative therapies. Tests administered midway through the program and after program completion provided the data used to analyze effective sleep quality changes. Results showed sleep hygiene education to improve participant sleep quality significantly (p < .001). The sleep quality of all participants improved over both the 3- and the 5-week education program. The six components of the Pittsburgh Sleep Quality Index (i.e., subjective sleep quality, sleep latency, sleep duration, sleep disturbances, use of sleeping medication, and daytime dysfunction) also improved. A brief and effective sleep hygiene education program delivered by a nurse can improve sleep quality in working women with sleeping problems.


Chemoattractant-mediated transient activation and membrane localization of Akt/PKB is required for efficient chemotaxis to cAMP in Dictyostelium.
Chemotaxis-competent cells respond to a variety of ligands by activating second messenger pathways leading to changes in the actin/myosin cytoskeleton and directed cell movement. We demonstrate that Dictyostelium Akt/PKB, a homologue of mammalian Akt/PKB, is very rapidly and transiently activated by the chemoattractant cAMP. This activation takes place through G protein-coupled chemoattractant receptors via a pathway that requires homologues of mammalian p110 phosphoinositide-3 kinase. pkbA null cells exhibit aggregation-stage defects that include aberrant chemotaxis, a failure to polarize properly in a chemoattractant gradient and aggregation at low densities. Mechanistically, we demonstrate that the PH domain of Akt/PKB fused to GFP transiently translocates to the plasma membrane in response to cAMP with kinetics similar to those of Akt/PKB kinase activation and is localized to the leading edge of chemotaxing cells in vivo. Our results indicate Akt/PKB is part of the regulatory network required for sensing and responding to the chemoattractant gradient that mediates chemotaxis and aggregation.


Characteristics of paraspinal muscle fat infiltration in asymptomatic Chinese adults: a cross-sectional study.
Paraspinal muscle fat infiltration is closely related to the occurrence and development of lumbar spine disorders and postoperative complications. This study aimed to explore the effects of age, sex, muscle, and level on paraspinal muscle fat infiltration among Chinese adults to identify the best single level of assessing whole-level paraspinal muscle fat infiltration and to define the standardized identification thresholds for paraspinal muscle fat infiltration by means of magnetic resonance imaging. This was a single-center, cross-sectional study conducted on 336 asymptomatic Chinese volunteers aged 20 to 69 years recruited from Beijing and surrounding communities through designed advertisements from May 2022 to October 2022. The fat signal fraction of multifidus (FSFMF), erector spinae (FSFES), psoas major (FSFPM), and the sum of multifidus, erector spinae, and psoas major (FSFTotal) at lumbar levels L1-L5 were measured with magnetic resonance imaging. The Student t-test and Mann-Whitney test were performed, and Pearson correlations and intraclass correlation coefficients were determined. Subgroups were compared using analysis of variance followed by a post hoc Bonferroni test or Kruskal-Wallis test. FSFTotal (14.02%±4.71% vs. 10.34±4.08%; P<0.001), FSFMF (21.14%±6.77% vs. 16.21%±6.26%; P<0.001), and FSFES (15.97%±5.56% vs. 12.37%±4.80%; P<0.001) were higher in females than in males and increased with age and lumbar level, whereas FSFPM did not significantly differ by age (all P values >0.05) or sex (P=0.12) and showed a decreasing trend from L1 to L5. The FSFTotal at L4 showed both the strongest correlation (Pearson correlation coefficient =0.95; P<0.001) and agreement (intraclass correlation coefficient =0.92; P<0.001) with the whole-level FSFTotal. Pathological paraspinal muscle fat infiltration identification thresholds of FSFTotal, FSFMF, FSFES, and FSFPM were 10.0-33.9%, 19.2-47.4%, 16.2-43.6%, and 4.8%, respectively, in each age (range, 20-69 years) and sex group. In asymptomatic Chinese adults, paraspinal muscle fat infiltration can be influenced by age, sex, muscle type, and location. The L4 level can serve as an optimal substitution in whole-level fat infiltration measurement. We present the first data concerning the identification thresholds of pathological paraspinal muscle fat infiltration, which will provide a valuable resource for researchers in the field.


The case of the elusive androgen.
To describe a case of androgen excess and discuss the important factors in diagnosis and management. A case report is presented of a postmenopausal woman who had had severe hirsutism for 18 months. Her history, clinical and laboratory findings, treatment, and outcome are chronicled. The pertinent literature--especially that related to the differential diagnosis of hyperandrogenism--is also reviewed. A 62-year-old woman had progressive hirsutism of the face, back, and abdomen as well as alopecia of the scalp, for which spironolactone therapy had proved ineffective. Laboratory studies showed a testosterone level of 644 ng/dL. Preoperative evaluation pointed to an ovarian source of testosterone. After total abdominal hysterectomy and bilateral oophorectomy, histologic examination of the ovaries showed bilateral hilar cell hyperplasia. Three months later, the serum testosterone level remained high (556 ng/dL), and repeated computed tomography of the abdomen disclosed a previously unseen 9-mm adenoma of the left adrenal gland, which was removed laparoscopically. Because of a persistently high testosterone value (546 ng/dL), the patient underwent dexamethasone suppression studies, followed by adrenal stimulation with corticotropin; no pathologic findings were demonstrated. Finally, gonadotropin suppression with nafarelin, 200 mg intranasally daily for 6 weeks, yielded a prompt and sustainable decrease in the testosterone level. This result was associated with dramatic clinical improvement. It is speculated that the patient had residual testosterone-producing tissue originating from primitive mesenchymal cells from the urogenital ridge, which was responsive to gonadotropins, in an unidentified abdominal or pelvic site.


Dual role of inflammatory mediators in cancer.
Inflammation is the body's response to noxious stimuli such as infectious, physiological or chemical agents, it releases various inflammatory mediators via immune cells such as neutrophils, macrophages, and lymphocytes. These inflammatory mediators are growth factors, chemokines, and cytokines. Reactive oxygen species (ROS) and nitrogen species (RNS) activate transcriptional factors (NF-KB, STAT-3) and bring about cellular proliferation, genomic instability, angiogenesis, resistance to apoptosis, invasion, and metastasis. The presence of inflammatory mediators in the tumour microenvironment inhibits or promotes inflammation-induced cancer, depending on various stages of immune surveillance of the tumor i.e. by immunoediting, immunoprocessing, and immunoevasion. Myeloid derived suppressor cells are immature myeloid progenitor cells. They are the major immune-suppressor cells in the tumour inflammatory microenvironment that activate transcriptional factor NF-KB, STAT-3 to bring about tumour progression. Another gene which the micro RNA's are noncoding RNA molecules is found to have a link with inflammation and cancer. This article discusses the roles of inflammatory mediators involved in antitumour or protumour activity within the context of the tumour microenvironment.


Drug-eluting balloon angioplasty versus uncoated balloon angioplasty in patients with femoropopliteal arterial occlusive disease.
The optimal percutaneous treatment for femoropopliteal arterial occlusive disease has yet to be assessed. This systematic review and meta-analysis assessed the efficacy of drug-eluting balloons (DEBs) compared with uncoated balloons (UCBs) for the treatment of femoropopliteal arterial occlusive disease. We used Preferred Reporting Items for Systematic Reviews and Meta-Analysis Statement (PRISMA) standards to systematically search the electronic databases of MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) for trials comparing DEBs vs UCBs in the femoropopliteal arteries. All articles were critically assessed for relevance, validity, and availability of data regarding patient and lesion characteristics and outcomes. All data were systematically pooled, and meta-analysis was performed on binary restenosis, late lumen loss (LLL), target lesion revascularization (TLR), major amputation, mortality, and changes in the ankle-brachial index and the Rutherford-Baker classification. From 364 screened articles, we included nine trials, all of which had a low risk of bias. We found a significant reduction of binary restenosis at 6 months (14.3% vs 40.1%; P < .0001), binary restenosis at 1 year (26.6% vs 47.4%; P = .008), LLL at 6 months (-0.80 mm; P < .00001), TLR at 1 year (10.4% vs 26.9; P = .0008), and TLR at 2 years (13.8% vs 40.7%; P = .0003) after DEB angioplasty compared with UCB angioplasty. The difference in amputation rate and mortality was not significant. Definitions on changes in ankle-brachial index and Rutherford classifications were heterogeneous and, therefore, could not be pooled in sufficient numbers. Compared with UCB angioplasty, the use of DEBs increases the durability of the treatment effect in femoropopliteal arterial disease, expressed by a significant decrease of binary restenosis, LLL, and TLR at short-term and midterm follow-up.


Comparative study of 2 oral care protocols in intensive care units.
The quality of oral care is important in limiting the emergence of ventilator-associated pneumonia (VAP) in intubated patients. Our main objective was to measure the quality improvement in oral care following the implementation of a new oral care protocol. We also monitored VAP rates. This was a cohort study of patients in 5 adult ICUs covering different specialties. During period 1, caregivers used a foam stick for oral care and during period 2 a stick and tooth brushing with aspiration. Oral chlorhexidine was used during both periods. The caregivers rated improvement in oral health on the basis of 4 criteria (tongue, mucous membranes, gingivae, and teeth). Caregiver satisfaction was also assessed. The incidence of VAP was monitored. A total of 2,030 intubated patients admitted to intensive care units benefited from oral care. The patient populations during the 2 periods were similar with regard to demographic data and VAP potential risk factors. Oral health was significantly better from the third day of oral care in period 2 onward (period 1, 6.4 ± 2.1; period 2, 5.6 ± 1.8; P = .043). Caregivers found the period 2 protocol easier to implement and more effective. VAP rates decreased significantly between the 2 periods (period 1, 12.8%; period 2, 8.5%; P = .002). Our study showed that the implementation of a simple strategy improved the quality of oral care of patients in intensive care units, and decreased VAP rates.


Exploiting social influence to magnify population-level behaviour change in maternal and child health: study protocol for a randomised controlled trial of network targeting algorithms in rural Honduras.
Despite global progress on many measures of child health, rates of neonatal mortality remain high in the developing world. Evidence suggests that substantial improvements can be achieved with simple, low-cost interventions within family and community settings, particularly those designed to change knowledge and behaviour at the community level. Using social network analysis to identify structurally influential community members and then targeting them for intervention shows promise for the implementation of sustainable community-wide behaviour change. We will use a detailed understanding of social network structure and function to identify novel ways of targeting influential individuals to foster cascades of behavioural change at a population level. Our work will involve experimental and observational analyses. We will map face-to-face social networks of 30 000 people in 176 villages in Western Honduras, and then conduct a randomised controlled trial of a friendship-based network-targeting algorithm with a set of well-established care interventions. We will also test whether the proportion of the population targeted affects the degree to which the intervention spreads throughout the network. We will test scalable methods of network targeting that would not, in the future, require the actual mapping of social networks but would still offer the prospect of rapidly identifying influential targets for public health interventions. The Yale IRB and the Honduran Ministry of Health approved all data collection procedures (Protocol number 1506016012) and all participants will provide informed consent before enrolment. We will publish our findings in peer-reviewed journals as well as engage non-governmental organisations and other actors through venues for exchanging practical methods for behavioural health interventions, such as global health conferences. We will also develop a 'toolkit' for practitioners to use in network-based intervention efforts, including public release of our network mapping software. NCT02694679; Pre-results.


Case Report: Calcium sensing receptor gene gain of function mutations: a case series and report of 2 novel mutations.
Autosomal dominant hypocalcemia (ADH1) is a genetic disorder characterized by low serum calcium and low or inappropriately normal levels of parathyroid hormone. The disease is caused by a heterozygous activating mutation of the calcium-sensing receptor (CaSR) gene, encoding a G-Protein-coupled cell membrane sensor of extracellular calcium concentration mainly expressed by parathyroid glands, renal tubules, and the brain. ADH1 has been linked to 113 unique germline mutations, of which nearly 96% are missense mutations. There is often a lack of a clear genotype/phenotype correlation in the reported literature. Here, we described a case series of 6 unrelated ADH1 probands, each one bearing a gain-of-function CaSR mutation, and two children of one of these cases, matching our identified mutations to the same ones previously reported in the literature, and comparing the clinical and biochemical characteristics, as well as the complication profile. As a result of these genetic and clinical comparisons, we propose that a genotype/phenotype correlation may exist because our cases showed similar presentation, characteristics, and severity, with respect to published cases with the same or similar mutations. We also contend that the severity of the presentation is highly influenced by the specific CaSR variant. These findings, however, require further evaluation and assessment with a systematic review.


Platelet retraction force measurements using flexible post force sensors.
Platelets play an important role in hemostasis by forming a thrombotic plug that seals the vessel wall and promotes vascular healing. After platelets adhere and aggregate at the wound site, their next step is to generate contractile forces through the coordination of physicochemical interactions between actin, myosin, and alpha(IIb)beta(3) integrin receptors that retract the thrombus' size and strengthen its adhesion to the exposed matrix. Although platelet contractile forces (PCF) are a definitive feature of hemostasis and thrombosis, there are few approaches that can directly measure them. In this study, we describe the development of an approach to measure PCF in microthrombi using a microscopic flexible post force sensor array. Quasi-static measurements and live microscopic imaging of thrombin-activated platelets on the posts were conducted to assay the development of PCF to various hemostatic conditions. Microthrombi were observed to produce forces that monotonically increased with thrombin concentration and activation time, but forces subsided when thrombin was removed. PCF results were statistically similar on arrays of posts printed with fibronectin or fibrinogen. PCF measurements were combined with clot volume measurements to determine that the average force per platelet was 2.1 +/- 0.1 nN after 60 min, which is significantly higher than what has been measured with previous approaches. Overall, the flexible post arrays for PCF measurements are a promising approach for evaluating platelet functionality, platelet physiology and pathology, the impacts of different matrices or agonists on hemostatic responses, and in providing critical information regarding platelet activity that can guide new hemostatic or thrombotic strategies.


Study of the uptake of non-steroid anti-inflammatory drugs in wheat and soybean after application of sewage sludge as a fertilizer.
Non-steroid anti-inflammatory drugs (NSAIDs) are frequently occurring in sludge and waters from sewage treatment plants (STPs). Sludge obtained from sewage treatment is often applied as a fertilizer in agriculture and not many studies about the uptake of pharmaceuticals into crops can be found. In this paper, we present a greenhouse experiment to study the presence of four NSAIDs (naproxen, ketoprofen, diclofenac and ibuprofen) in two different crops (soybean and wheat) after application of sludge as a fertilizer. Two different amounts of sludge were added to the soil; the recommended amount (with respect to phosphorus content) and the double recommended amount. One treatment without sludge was also included as a blank. The crops were harvested after 60 as well as 110 days. Only diclofenac and ibuprofen were detected in the sludge in concentrations of 22 and 217 ng g(-1) dry weight, respectively. None of the NSAIDs were detected in the crops from any of the treatments. Compared to the amounts applied to the soil, detection limits correspond to an uptake of less than 2% for diclofenac and 0.8% for ibuprofen.


Volumetric tissue changes following combined surgical therapy of peri-implantitis: A 2-year follow-up analysis. A prospective case series.
To assess volumetric tissue changes following combined surgical therapy of peri-implantitis over a follow-up period of 24 months. A total of 20 patients (n = 28 implants) were diagnosed with peri-implantitis and underwent access flap surgery, implantoplasty, and augmentative therapy at intrabony components (ie, combined therapy) using a natural bone mineral and a native collagen membrane. The peri-implant region of interest (ROI) was intraorally scanned pre-operatively (S0), and after 12 (S3) and 24 (S4) months. Digital files were superimposed for the assessment of volumetric changes between the referred time points. The change in thickness was assessed at a standardized ROI, segmented into two equidistant sections (ie, marginal and apical). Peri-implant tissues exhibited a nonsignificant mean thickness loss of 0.16 (95% CI: -4 to 0.06) and 0.17 mm (95% CI: -0.05 to 0.4) at S3 and S4, respectively. S0-S3 dimensional thickness changes at marginal and apical areas were -0.24 (95% CI: -0.48 to 0.002) and -0.19 mm (95% CI: -0.36 to -0.2), respectively. Dimensional changes from S0 to S4 amounted to -0.22 mm (95% CI: -0.46 to 0.02) and -0.07 mm (95% CI: -0.09 to 0.2), respectively. The thickness changes at marginal and apical ROIs were significant from S0 to S3. Clinical parameters (ie, plaque index, bleeding on probing, and probing depth) significantly improved over the 24-month follow-up period. Linear regression analyses revealed no significant association between baseline bone loss (%), width of keratinized mucosa, and mucosal recession scores and thickness changes. Peri-implant tissues revealed minor volumetric changes at 12 and 24 months after combined surgical therapy.


Flexible Intramedullary Nailing of Forearm Fractures at the Distal Metadiaphyseal Junction in Adolescents.
The purpose of this study was to analyze the radiographic and functional outcomes of flexible intramedullary (IM) nailing in adolescent patients with forearm fractures at the diaphysis or at the metadiaphyseal junction (MDJ). We retrospectively reviewed the results of 40 patients who underwent IM nailing for pediatric forearm fractures. Thirty males and 10 females were followed for an average of 16 months (range, 12 to 20 months). Their average age was 11 years (range, 10 to 16 years). The average duration from the onset of trauma to surgery was 3.8 days (range, 1 to 36 days). Fracture sites were located at the MDJ of the radius in 8 patients (MDJ group) while 32 patients had middle-third fractures (D group). We assessed the magnitude and location of the maximum radial bow and range of movements. Functional outcomes were evaluated using Daruwalla criteria. Open reduction was carried out in 8 cases. Union was achieved at an average of 8.3 weeks postoperatively. The results were classified as good in 38 and excellent in 2 according to Daruwalla criteria with restoration of forearm rotation. The mean angulation at the last follow-up was 1.8° on the anteroposterior radiograph and 3.3° on the lateral radiograph (MDJ group: 1.8° and 2.1°, respectively; D group: 1.9° and 2.8°, respectively). There was no significant difference in the mean angulation between the groups. The mean magnitude of maximal radial bow was 5.7% ± 1.8% (MDJ group, 5.2% ± 0.8%; D group, 5.9% ± 1.9%). The mean location of maximal radial bow was 58.0% ± 8.8% (MDJ group, 56.4% ± 8.9%; D group, 58.6% ± 8.9%). The differences in the mean magnitude and location of maximal radial bow with the normal contralateral arms (7.0% ± 1.2% and 50.9% ± 6.0%, respectively) were not significantly different between the groups. Complications included superficial infection (2), delayed union (1), and refracture (1). IM nail fixation provided satisfactory results and maintained adequate stability for both forearm bone fractures in adolescents, even though the fracture was located at the MDJ of the radius.


Abscisic acid associated with key enzymes and genes involving in dynamic flux of water soluble carbohydrates in wheat peduncle under terminal drought stress.
Remobilization of stem water soluble carbohydrates (WSC) can supply crucial carbon resources for grain filling under drought stress, while the regulatory metabolism associated with abscisic acid (ABA) is still limited. Two cultivars, LJ196 (drought-tolerant) and XD18 (drought-prone), were pot-grown under well-watered (WW) and drought-stressed (DS) conditions. Concentrations of WSC components and ABA, and fructan metabolizing enzymes and genes were investigated in peduncle after anthesis. When compared with those under the WW, LJ196 remained higher grain yield and grain-filling rate than XD18 under the DS. During the early period of grain filling (0-14 DAA), DS increased concentrations of total WSC and its components, but thereafter substantially reduced them. The gene expression levels and enzymatic activities of fructan 1-exohydrolases (1-FEH) and fructan 6-exohydrolases (6-FEH) showed similar trends, whereas those of fructan: fructan 1-fructosyltransferase (1-FFT), and sucrose: fructan 6-fructosyltransferase (6-SFT) were depressed and declined over the period of examination. LJ196 still showed higher levels of ABA and fructan metabolizing. The ABA concentration under the DS was positively and significantly correlated with total WSC and fructan concentration, and expression levels of these enzymes and genes as well, with more prominently with those of 6-FEH. Presumably, ABA could enhance fructan hydrolysis by strongly up-regulating the gene expression and enzymatic activity of 6-FEH to accelerate WSC remobilization. However, stem WSC induced by DS could be not fully remobilized to grains, due to its weaker correlation with grain-filling rate and finally indicating lower grain yield. The findings would provide useful information for wheat production under water-deficit environments.


Coexistence of homochiral and heterochiral adenine domains at the liquid/solid interface.
In this work, the self-assembly of the DNA base molecule adenine (A) is imaged with high-resolution scanning tunneling microscopy (STM) at the liquid (1-octanol)/solid (HOPG) interface at room temperature. Rather surprisingly, the STM results reveal, for the first time, the spontaneous formation of two coexisting distinct (homo- and heterochiral) domains of adenine, which are formed at the liquid/solid interface without changing any experimental conditions. Ab initio density functional theory (DFT) calculations support our STM findings and suggest the existence of various A networks of nearly similar stability that all are constructed from the most stable A dimer.


Granulocyte colony-stimulating factor and differentiation-induction in myeloid leukemic cells.
The granulocyte colony-stimulating factor (G-CSF) belongs to a family of hemopoietic growth factors regulating the production of granulocytes and macrophages. Murine G-CSF stimulates the proliferation and differentiation of precursors of neutrophilic granulocytes and is also able to stimulate the functional activities of mature neutrophils. Among the hemopoietic growth factors, G-CSF has an outstanding capacity to induce terminal differentiation and suppression of self-renewal in myeloid leukemic cells. Murine and human G-CSF's show complete biological cross-reactivity across species and bind equally well to G-CSF receptors of either species. Specific receptors for G-CSF exist on all normal neutrophilic cells and have not been lost in the generation of primary human myeloid leukemias. This data indicates that G-CSF may be a useful reagent in the treatment of myeloid leukemia, in hemopoietic regeneration and in increasing resistance against infections.


Analysis of power in medical decision-making: an argument for physician autonomy.
Two of the patient's rights in a Uniform Act for the Terminally Ill should be a) the right to be treated if there is reasonable doubt of the patient's wishes until it becomes clear that the treatment is not beneficial and that the patient is indeed terminally ill, and b) the right not to be subjected to treatment with no medical benefit. A physician with appropriate supporting independent opinions would be the logical individual to whom the responsibility of protecting those rights should be given. This is particularly true when the patient is incapable of his or her own medical decisions and has left no instructions regarding his or her personal goals in medical care in the event of severe illness. Two cases and an analysis of power in medical decision-making illustrate these points.


Use of gel filtration to examine the distribution of calcium among serum proteins.
Gel filtration of serum by use of dextran bisacrylamide beads ("Sephacryl S-200," fractionation range: 5000-250 000 daltons), separates the serum proteins into three distinct peaks. We used an eluent containing (per liter) 140 mmol of sodium, 1.10 mmol of calcium, 0.50 mmol of magnesium, and 10 mmol of 2-([2-hydroxy-1, 1-bis(hydroxymethyl)ethyl]amino)ethanesulfonate buffer (pH 7.43 at 37 degrees C) to provide the physiological conditions necessary to maintain the equilibrium of bound calcium in serum. We examined the calcium binding by each of the three protein groups. Calculating the calcium bound per gram of protein in each peak, we found that proteins in the first peak (alpha2-macroglobulin, IgM, haptoglobins) bind about the same amount of calcium per gram as does albumin. The proteins of the second peak (largely IgG and IgA) bind less calcium than does albumin, which is the protein accounting for 90% or more of the third peak. We also were able to calculate intrinsic association constants for calcium/albumin under physiological conditions.


[Characterization of Salmonella typhimurium multidrug resistance and the reversal of antimicrobial resistance].
Salmonella typhimurium 17Y, isolated from one diseased pig that was clinically diagnosed as pig salmonellosis, was a multiresistance strain with resistance to 14 antibiotics among tested 19 antibiotics. In this study, the resistance to 11 antimicrobials was reversed by high temperature and high concentration (0.5%) of SDS, resulting in the sensitive strain 17S1. PCR results showed that the resistant genes BlaTEM, blaOXA-1, cat 1, tet (B), aacC2 located on the plasmid. Furthermore, PCR detected the class I integron which carries dhfrX II for trimethoprim resistance, aadA18b for aminoglycoside resistance and sull for sulfamethoxazole resistance. The integron was identified to exist in the plasmid. Because the target genes gyrA and parC for quinolone category were detected by PCR from both resistant and sensitive strains, it was determined that the genes gyrA and parC were located in the bacterial genome. The gene sequencing of gyrA and parC revealed that a point mutation AAC --> GAC resulting in one amino acid replacement of N87D in gyrA occurred for the sensitive strain 17S1. It was demonstrated that the amino acid 87 was a hot point for mutation in quinolone resistance determining region (QRDR). The finding suggests that the amino acid replacement of N87D is responsible for the quinolone susceptibility. In addition, the 100 continuous passages of the sensitive strain showed that the drug sensitive status was stable. However, when the drug pressure maintained for a long time, the resistance was induced again. Meanwhile, 6 salmonella plasmid virulence genes (spvA-D, R and rck) were eliminated with the resistance reversal, indicating that the virulence plasmid was cured. Reasonably, the bacterial virulence decreased shown by 10- fold increase of LD50 for the sensitive strain, and the statistical significant decline of in vivo spread and growth (P < 0.05) in mice. Taken altogether, the multidrug resistance of Salmonella typhimurium was determined by its plasmid. The plasmid elimination with SDS reversed most of the resistance (11/14) and decreased the bacterial virulence. Therefore, strategy to eliminate the plasmids would be an effective way to deal with the multiresistance issue. However, drug control in routine clinical practice would not be neglected at any time.


Computational approaches for the discovery of cysteine protease inhibitors against malaria and SARS.
Cysteine proteases are implicated in a variety of human physiological processes and also form an essential component of the life cycle of a number of pathogenic protozoa and viruses. The present review highlights the drug design approaches utilized to understand the mechanism of inhibition and discovery of inhibitors against protozoal cysteine protease, falcipain (a cysteine protease of P. falciparum which causes malaria), and viral cysteine protease, SARS-CoV M(pro) (a cysteine protease of severe acute respiratory syndrome corona virus). The article describes rational approaches for the design of inhibitors and focuses on a variety of structure as well as ligand-based modeling strategies adopted for the discovery of the inhibitors. Also, the key features of ligand recognition against these targets are accentuated. Although no apparent similarities exist between viral and protozoal cysteine proteases discussed here, the goal is to provide examples of rational drug design approaches adopted to design inhibitors against these proteases. The current review would be of interest to scientists engaged in the development of drug design strategies to target the cysteine proteases present in mammals and other lower order organisms.


In situ gelling gelrite/alginate formulations as vehicles for ophthalmic drug delivery.
The objective of this study was to develop an ion-activated in situ gelling vehicle for ophthalmic delivery of matrine. The rheological properties of polymer solutions, including Gelrite, alginate, and Gelrite/alginate solution, were evaluated. In addition, the effect of formulation characteristics on in vitro release and in vivo precorneal drug kinetic of matrine was investigated. It was found that the optimum concentration of Gelrite solution for the in situ gel-forming delivery systems was 0.3% (w/w) and that for alginate solution was 1.4% (w/w). The mixture of 0.2% Gelrite and 0.6% alginate solutions showed a significant enhancement in gel strength at physiological condition. On the basis of the in vitro results, the Gelrite formulations of matrine-containing alginate released the drug most slowly. For each tested polymer solution, the concentration of matrine in the precorneal area was higher than that of matrine-containing simulated tear fluid (STF) almost at each time point (p < 0.05). The area under the curve of formulation 16 (0.2%Gelrite/0.6%alginate) was 4.65 times greater than that of containing matrine STF. Both the in vitro release and in vivo pharmacological studies indicated that the Gelrite/alginate solution had the better ability to retain drug than the Gelrite or alginate solutions alone. The tested formulation was found to be almost non-irritant in the ocular irritancy test. The overall results of this study revealed that the Gelrite/alginate mixture can be used as an in situ gelling vehicle to enhance ocular retention.


Duration of hepatitis B immunity in low risk children receiving hepatitis B vaccinations from birth.
The duration of protection after hepatitis B vaccination of infants is unknown. We determined antibody to hepatitis B surface antigen (anti-HBs) at 4-13 years of age in 363 low risk children who had been vaccinated starting at birth with hepatitis B vaccine. Those with nonprotective titers (<10 mIU/mL) received a booster dose. We similarly followed 16 children of hepatitis B surface antigen (HBsAg)-positive mothers. Of low risk infants receiving a plasma-derived vaccine, 41% (42 of 102) of those whose primary response was unknown and 24% (4 of 17) who had initially responded retained protective titers (> or = 10 mIU/mL) of anti-HBs at 9 and 13 years, respectively. Of those who did not have protective antibody titers, 61% (33 of 54) and 67% (8 of 12), respectively, responded to a booster dose. In children of HBsAg-positive mothers, 31% retained protective anti-HBs at 12 years, and 90% (9 of 10) with nonprotective titers responded to a booster. In low risk children initially receiving a recombinant vaccine, 12.5% (26 of 208) and none (0 of 36) retained protective anti-HBs titers at 5 and 7 years of age, respectively. Of those who did not have protective titers, 90% (120 of 134) and 91% (32 of 35), respectively, responded to a booster. Anti-HBs disappeared by 5 years of age in most children who were vaccinated with hepatitis B vaccine from birth. Although most children showed immunologic memory, one-third failed to demonstrate an anamnestic response to a booster dose. Additional long term studies of low risk infants are needed to determine duration of protection and the necessity for or timing of booster doses.


Attitudes towards, and wishes for, euthanasia in advanced cancer patients at a palliative medicine unit.
Most studies on attitudes towards euthanasia and physician-assisted suicide (PAS) have been conducted in healthy populations. The aim of this study is to explore and describe attitudes towards, and wishes for, euthanasia/PAS in cancer patients with short life expectancy. Semi-structured interviews with 18 cancer patients with a life expectancy of less than nine months. All patients were recruited from an inpatient palliative medicine unit. Patients holding a positive attitude towards euthanasia/PAS do not necessarily want euthanasia/PAS for themselves. Wishes are different from requests for euthanasia/PAS. Fear of future pain and a painful death were the main reasons given for a possible wish for euthanasia/PAS. Worries about minimal quality of life and lack of hope also contributed to such thoughts. Wishes for euthanasia/PAS were hypothetical; they were future oriented and with a prerequisite that intense pain, lack of quality of life and/or hope had to be present. Additionally, wishes were fluctuating and ambivalent. The wish to die in these patients does not seem to be constant. Rather, this wish is more appropriately seen as an ambivalent and fluctuating mental 'solution' for the future. Health care providers should be aware of this when responding to utterances regarding euthanasia/PAS.


[Injury of rat blood vessels caused by acute ozone exposure and its mechanism].
To investigate the vascular damage effects and possible mechanism of acute exposure to ozone (O3) in male Wistar rats. One hundred and twenty male Wistar rats were randomly divided into six groups, 20 in each group. The experimental animals were placed in a gas poisoning cabinet, the control group was exposed to filtered air, and the treatment group was exposed to ozone at concentrations of 0.12 ppm, 0.5 ppm, 1.0 ppm, 2.0 ppm, and 4.0 ppm, respectively, for 4 hours. Arterial blood pressure data were obtained by PC-lab medical physiological signal acquisition system. Blood rheology indicators and blood biochemical indicators were detected by Tianjin Dean Diagnostic Laboratory. Serum endothelin-1 (ET-1), homocysteine (HCY), von Willebrand factor (vWF), 8-hydroxydeoxyguanosine (8-OhdG), interleukin (IL-6) and tumor necrosis factor alpha (TNF-α) were detected by enzyme-linked immunosorbent assay (ELISA) microplate assay. Oxidative stress indicators superoxide dismutase (SOD) activity and malondialdehyde (MDA) were determined by xanthine oxidase method, thiobarbituric acid (TBA) method, reduced glutathione (GSH) and nitric oxide (NO) were tested by using microplate colorimetry. Paraffin sections were prepared from thoracic aorta tissue, and vascular structure was observed by HE staining. Acute exposure to 0.12 ppm ozone could cause a significant increase in arterial systolic blood pressure (SBP). Exposure to different concentrations of ozone could cause a significant increase in plasma viscosity, and the K value of the ESR equation was significantly increased in the 1.0 ppm ozone exposure group. Both the relative and reduced viscosities were significantly reduced at ozone concentrations of 0.5 ppm and 4.0 ppm, while the red blood cell deformation index was increased significantly at ozone concentrations of 0.12 ppm, 0.5 ppm, 1.0 ppm, and 2.0 ppm. Acute ozone exposure resulted in the decrease of total cholesterol content. The content of high-density lipoprotein cholesterol (HDL-C) was significantly reduced in the 0.12 ppm ozone exposure group. When the ozone concentration was higher than 1.0 ppm, the body may also had an inflammatory reaction (increased TNF-α) and oxidative stress (increased MDA, decreased GSH). Acute exposure to ozone could lead to elevated levels of ET-1 in the blood, with significant differences in the 4.0 ppm concentration group, while HCY levels were decreased firstly and then increased, reaching the highest in the 1.0 ppm concentration group. No obvious pathological changes were observed in the thoracic aorta. Acute ozone exposure can affect arterial blood pressure, blood rheology and cholesterol metabolism in rats. The possible mechanism is that ozone exposure leads to inflammatory reaction and oxidative stress reaction, causing vascular endothelial function damage, and vascular endothelial cells increase with ozone exposure concentration.


One Ferroptosis-Related Gene-Pair Signature Serves as an Original Prognostic Biomarker in Lung Adenocarcinoma.
Lung adenocarcinoma is the most common histological subtype of lung cancer which causes the largest number of deaths worldwide. Exploring reliable prognostic biomarkers based on biological behaviors and molecular mechanisms is essential for predicting prognosis and individualized treatment strategies. Ferroptosis is a recently discovered type of regulated cell death. We downloaded ferroptosis-related genes from the literature and collected transcriptome profiles of lung adenocarcinoma from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) to construct ferroptosis-related gene-pair matrixes. Then, we performed the least absolute shrinkage and selection operator regression to build our prognostic ferroptosis-related gene-pair index (FRGPI) in TCGA training matrix. Our study validated FRGPI through ROC curves, Kaplan-Meier methods, and Cox hazard analyses in TCGA and GEO cohorts. The optimal cut-off 0.081 stratified patients into low- and high-FRGPI groups. Also, the low-FRGPI group had a significantly better prognosis than the high-FRGPI group. For further study, we analyzed differentially expressed ferroptosis-related genes between high- and low-FRGPI groups. Gene set enrichment analysis (GSEA) enrichment maps indicated that "cell cycle," "DNA replication," "proteasome," and "the p53 signaling pathway" were significantly enriched in the high-FRGPI group. The high-FRGPI group also presented higher infiltration of M1 macrophages. Meanwhile, there were few differences in adaptive immune responses between high- and low-FRGPI groups. In conclusion, FRGPI was an independent prognostic biomarker which might be beneficial for guiding individualized tumor therapy.


Boophilus microplus tick larvae, a rich source of Kunitz type serine proteinase inhibitors.
Serine proteinase inhibitors from Boophilus microplus tick larvae (BmTIs) were purified by affinity chromatography on a trypsin-Sepharose column. BmTIs presented molecular weight between M(r) 6200 and 18,400 and inhibitory activity for trypsin, HuPK (human plasma kallikrein) and neutrophil elastase. Using ion exchange chromatography, BmTIs were separated in several protein pools named BmTI-A to BmTI-F and BmTI-1 to BmTI-7. All BmTI forms presented inhibitory activity for trypsin with apparent dissociation constants (K(i)) in the nM range. In this work, we describe the purification of BmTI-D, BmTI-2, and BmTI-3. These three inhibitors affected neutrophil elastase and HuPK with K(i) also in nM range. BmTI-D proved to be the best HuPK inhibitor, while BmTI-3 was more efficient for neutrophil elastase with dissociation constants (K(i)) of 12 and 0.5 nM, respectively. BmTI-D, BmTI-2, and BmTI-3 N-terminal amino acid sequences allowed us to include them into the BPTI-Kunitz type serine proteinase inhibitor family. BmTIs purified on trypsin-Sepharose were also used in a bovine immunization assay, resulting in antibody (anti-BmTIs) production.


[Evaluation of genotoxicity by DNA damages].
A great number of genotoxins are known to be present in the environment. These genotoxins induce many kinds of DNA damage, and may cause changes in genetic information and cancer. Therefore, evaluation of such DNA damage is important to keep genetic information stable and to prevent cancer. We reviewed here methods used to assay the damage and the importance of this DNA damage in mutation. DNA damage is categorized into two groups, strand breaks and base modifications. To assay DNA strand breaks, the alkaline elution method, pulsed-field gel electrophoresis and single-cell gel assay are being used. The alkaline elution method determines both single- and double-strand breaks sensitively and quantitatively. Pulsed-field gel electrophoresis preferentially determines double-strand breaks, and the results of the method appeal to the eye as an electrophoretogram. The single-cell gel assay could determine both single- and double-strand breaks even in a single cell, and could evaluate susceptibility to the damage in individual cells. To assay base modifications, methods to detect differences in the physicochemical properties of the damage (physicochemical methods), immunoassays and the 32P-postlabeling method are being used. Physicochemical methods are suitable for chemically minor and abundant modifications such as those in 8-hydroxyguanine, using high-performance liquid chromatography or gas chromatography/mass spectroscopy. Immunoassays, by the use of specific antibodies against DNA damage, are highly sensitive to DNA damage such as changes in O6-methylguanine and thymine glycol, and simple once the assay systems have been established.(ABSTRACT TRUNCATED AT 250 WORDS)


ALDH3B2 Polymorphism Is Associated with Colorectal Cancer Susceptibility.
Colorectal cancer (CRC) is the 5th leading cancer in China. Alcohol consumption has been reported to be one of the risk factors of CRC. However, it remains unclear whether genetic variants of alcohol metabolic genes are associated with CRC risk. In this study, we tested the coding variants in the alcohol metabolic genes and the risk of CRC, by using 485 cases and 516 controls. A total of 16 germline coding variants in 10 alcohol metabolic genes were genotyped. We identified that rs3741178 in ALDH3B2 was significantly associated with CRC risk with odds ratio being 2.13 (95% CI: 1.24-3.68, P=0.0064). Further functional annotation suggested that this variant may damage the protein function of ALDH3B2. Our results suggested that ALDH3B2 in the alcohol metabolism pathway contributed to the development of CRC, which may contribute to the prevention of this disease in the future.


Identification of a new turncurtovirus in the leafhopper Circulifer haematoceps and the host plant species Sesamum indicum.
Turncurtoviruses (family: Geminiviridae; genus: Turncurtovirus) appear to have a high degree of genetic variation in Iran. Leafhoppers of the species Circulifer haematoceps (Mulsant and Rey, 1855) (family: Cicadellidae) were collected in 2014 from three geographical regions in south-eastern Iran (Orzoeyeh, Jiroft and Sirjan; Kerman province) and screened for the presence of turncurtoviruses using a combination of PCR and rolling circle amplification (RCA) methods. Eleven genomes of turncurtovirus were recovered and sequenced. Leafhoppers were sampled off sesame (S. indicum L.) and turnip (Brassica rapa sub sp. rapa). Thus, we identified three symptomatic sesame plants (yellowing, boat-shaped leaf curling, vein swelling on the lower leaf surfaces) from sesame farms in Jiroft. In these samples, we identified the same turncurtovirus as in the leafhoppers and have named it sesame curly top virus (SeCTV). Collectively, these SeCTV share > 98% genome-wide pairwise identity and ~ 87.3% to a recently identified turncurtovirus (sesame yellow mosaic virus; SeYMV) from sesame in Pakistan (GenBank accession MF344550). The SeCTV and SeYMV sequences share < 70% genome-wide pairwise identity with isolates of Turnip curly top virus and Turnip leaf roll virus, the two species in the genus Turncurtovirus. Based on the pairwise identities and phylogenetic analysis, SeCTV (n = 12) and SeYMV (n = 1) represent two strains of a new species in the genus Turncurtovirus.


3D luminescent concentrators.
A solution to develop high-brightness incoherent sources consists in luminescent concentration. Indeed, the absorption/emission process in a high index medium allows us to circumvent the brightness conservation law by the confinement of the light in 1 or 2 dimensions. In practice, Ce-doped luminescent concentrators pumped with InGaN LED exceed LED's brightness by one order of magnitude. This work shows how light confinement in 3 dimensions increases the brightness by an additional order of magnitude. Thanks to an analytical approach validated by experimental results, this concept gives new degrees of freedom for the design of luminescent concentrators and paves the way to a generation of incoherent sources among the brightest ever designed.


Comparison of surface structures of corundum Cr2O3(0 0 0 1) and V2O3(0 0 0 1) ultrathin films by x-ray photoelectron diffraction.
Thin Cr2O3(0 0 0 1) layers are formed by oxidation of a Cr(1 1 0) single crystal. This surface is further modified by growing an epitaxial ultrathin V2O3(0 0 0 1) film by reactive vapor deposition. Synchrotron based soft-x-ray photoemission spectroscopy and x-ray photoelectron diffraction are used to characterize the surface layers of these two corundum-structured oxides. By comparison of experimental XPD patterns with simulated electron multiple scattering calculations, two distinctively different surface terminations are extracted for the two oxides. While for V2O3 we confirm the previously proposed vanadyl-terminated surface structure, we propose a new surface structure for Cr2O3 that consists of excess chromium atoms occupying interstitial sub-surface sites.


Natural Hazard Management from a Coevolutionary Perspective: Exposure and Policy Response in the European Alps.
A coevolutionary perspective is adopted to understand the dynamics of exposure to mountain hazards in the European Alps. A spatially explicit, object-based temporal assessment of elements at risk to mountain hazards (river floods, torrential floods, and debris flows) in Austria and Switzerland is presented for the period from 1919 to 2012. The assessment is based on two different data sets: (1) hazard information adhering to legally binding land use planning restrictions and (2) information on building types combined from different national-level spatial data. We discuss these transdisciplinary dynamics and focus on economic, social, and institutional interdependencies and interactions between human and physical systems. Exposure changes in response to multiple drivers, including population growth and land use conflicts. The results show that whereas some regional assets are associated with a strong increase in exposure to hazards, others are characterized by a below-average level of exposure. The spatiotemporal results indicate relatively stable hot spots in the European Alps. These results coincide with the topography of the countries and with the respective range of economic activities and political settings. Furthermore, the differences between management approaches as a result of multiple institutional settings are discussed. A coevolutionary framework widens the explanatory power of multiple drivers to changes in exposure and risk and supports a shift from structural, security-based policies toward an integrated, risk-based natural hazard management system.


Involvement of cholinergic neurons in the release of dopamine elicited by stimulation of mu-opioid receptors in striatum.
The involvement of striatal cholinergic neurons in the release of dopamine (DA) elicited by the mu-opioid receptor agonist DAGO ([D-Ala2, NMePhe4-Gly5(ol)]enkephalin) was explored. The striatal release of DA was measured by microdialysis in rats anesthetized with chloral hydrate. When infused in the striatum, through the microdialysis probe, DAGO increased the extracellular levels of DA. The previous injection in striatum of AF 64-A, a toxin for cholinergic neurons, or the concomitant infusion of the M2-muscarinic antagonist methoctramine abolished the effect of DAGO on the DA release. It is concluded that stimulation of mu-opioid receptors, by inhibiting the acetylcholine release which stimulates tonically M2-muscarinic receptors likely associated with dopaminergic nerve endings, indirectly increases the striatal DA release.


[Buzhong yiqi decoction containing serum reversed resistance of A549/DDP to cisplatin and its effect on the expression of survivin: an experimental research ].
To analyze the reversal effect of Buzhong Yiqi Decoction (BYD) on multidrug resistance of human adenocarcinoma of lung cell line A549/DDP, and to study its effect on the expression of survivin by using serum pharmacological methods in vitro. Methods Totally 24 SD rats were divided into the high, medium and low dose groups, and the blank control group by randomized controlled method. The high dose BYD containing serum (1. 134 g/mL, 2 mL), the middle dose BYD containing serum (0.576 g/mL, 2 mL), and the low dose BYD containing serum (0.284 g/mL, 2 mL) were prepared. The inhibitory effects of different dose and concentrations BYD on the proliferation of A549 and A549/DDP cells were detected by MTT assay, and the drug resistance reversal fold was calculated. The expression of Survivin in the two cell strains were detected respectively by immunohistochemical assay, Western blot, and immunofluorescence method. BYD containing serum showed obvious inhibitory effect on the growth of A549 and 549/DDP. The inhibition rates of 10% dose groups were higher than those of 5% dose groups. Besides, it gradually increased along with increased concentrations. Compared with 10% blank control group, the inhibition rate increased in 10% middle and low dose groups (P <0.05). After acted with 10% middle dose BYD containing serum, IC50, of A549 and A549/DDP were both reduced (P <0.05), reversal fold (RF) both increased. Its reversal ratio on A549/DDP cells was 2. 46, decreasing the resistance of A549/DDP to DDP. Compared with A549 in the same group, the expression of Survivin was detected to decrease by immunocytochemical assay, Western blot, and immunofluorescence method (P<0.05). Compared with 10% blank control group, the inhibition rate decreased in 10% middle dose group (P <0. 05). 10% middle dose BYD containing serum could significantly inhibit the apoptosis of A549 and A549/DDP. Besides, it could moderately reverse the multidrug resistance of A549/DDP cells to DDP possibly through reducing the intracellular expression of Survivin and enhancing the sensitivity 549/DDP to chemotherapeutics.


Aqueous Synthesis of Protein-Encapsulated ZnSe Quantum Dots and Physical Significance of Semiconductor-Induced CuII Ion Sensing.
In view of their promising bio-applicability, we have synthesized water-soluble bovine serum albumin (BSA)-encapsulated ZnSe quantum dots (QDs) with visible emission with longer average luminescence lifetimes of approximately 125 ns at ambient conditions. BSA-ZnSe QDs are shown to be efficient selective copper ion probes in the presence of physiologically important metal ions through luminescence quenching with a high Stern-Volmer constant (3.3×105 m-1 ). The mechanism of sensing has been explained in terms of electron transfer processes and the apparent rate of electron transfer (Ket ) from ZnSe QDs to Cu2+ has been calculated to be 2.8×108 s-1 . It is demonstrated that the negative conduction band potential plays a major role in the feasibility of the electron transfer process, which is reflected in the higher efficacy of ZnSe QDs in sensing copper(II) ions over other group II-VI quantum dots, namely, CdSe, ZnS, or CdS. The results observed with cysteine-capped QDs are almost identical to those with BSA-encapsulated QDs and this presumably negates the possible reason of CuII ion induced quenching ascribed to its binding with surface groups or replacement of metal sites as proposed by several groups previously.


Prevalence of alcoholism in a family practice center.
One hundred forty-seven adult patients seeking care at a university family practice center were screened for alcoholism. Approximately one half were given the Michigan Alcoholism Screening Test (MAST), and the rest were interviewed by a trained interviewer who administered the MAST and a shorter questionnaire (the CAGE) and used her overall clinical impression to gauge their likelihood of being alcoholic. The two groups were demographically similar, as were the results of the screening. There were 28 patients (19.1 percent) with a MAST score greater than 5, and 24 patients (16.3 percent) were thought to be alcoholic. The prevalence of alcoholism was much higher in men (P less than .001), but no other demographic differences were found. Twenty-four clinic charts of patients with alcoholism identified in the study were reviewed for evidence of physician awareness of alcohol abuse, but in only 12 was alcohol use mentioned at all, and in only two was alcoholism diagnosed. These findings are consistent with prior published reports of incidence of alcoholism in other settings.


Assembly and Trafficking of Homomeric and Heteromeric Kainate Receptors with Impaired Ligand Binding Sites.
Kainate receptors (KARs) are a subfamily of ionotropic glutamate receptors (iGluRs) mediating excitatory synaptic transmission. Cell surface expressed KARs modulate the excitability of neuronal networks. The transfer of iGluRs from the endoplasmic reticulum (ER) to the cell surface requires occupation of the agonist binding sites. Here we used molecular modelling to produce a range of ligand binding domain (LBD) point mutants of GluK1-3 KAR subunits with and without altered agonist efficacy to further investigate the role of glutamate binding in surface trafficking and activation of homomeric and heteromeric KARs using endoglycosidase digestion, cell surface biotinylation and imaging of changes in intracellular Ca2+ concentration [Ca2+]i. Mutations of conserved amino acid residues in the LBD that disrupt agonist binding to GluK1-3 (GluK1-T675V, GluK2-A487L, GluK2-T659V and GluK3-T661V) reduced both the total expression levels and cell surface delivery of all of these mutant subunits compared to the corresponding wild type in transiently transfected human embryonic kidney 293 (HEK293) cells. In contrast, the exchange of non-conserved residues in the LBD that convert antagonist selectivity of GluK1-3 (GluK1-T503A, GluK2-A487T, GluK3-T489A, GluK1-N705S/S706N, GluK2-S689N/N690S, GluK3-N691S) did not alter the biosynthesis and trafficking of subunit proteins. Co-assembly of mutant GluK2 with an impaired LBD and wild type GluK5 subunits enables the cell surface expression of both subunits. However, [Ca2+]i imaging indicates that the occupancy of both GluK2 and GluK5 LBDs is required for the full activation of GluK2/GluK5 heteromeric KAR channels.


Peptides of 2-aminopimelic acid: antibacterial agents that inhibit diaminopimelic acid biosynthesis.
Succinyl-CoA:tetrahydrodipicolinate-N-succinyltransferase is a key enzyme in the biosynthesis of diaminopimelic acid (DAP), a component of the cell wall peptidoglycan of nearly all bacteria. This enzyme converts the cyclic precursor tetrahydrodipicolinic acid (THDPA) to a succinylated acyclic product. L-2-Aminopimelic acid (L-1), an acyclic analogue of THDPA, was found to be a good substrate for this enzyme and was shown to cause a buildup of THDPA in a cell-free enzyme system but was devoid of antibacterial activity. Incorporation of 1 into a di- or tripeptide yielded derivatives that exhibited antibacterial activity against a range of Gram-negative organisms. Of the five peptide derivatives tested, (L-2-aminopimelyl)-L-alanine (6) was the most potent. These peptides were shown to inhibit DAP production in intact resting cells. High levels (30 mM) of 2-aminopimelic acid were achieved in the cytoplasm of bacteria as a result of efficient uptake of the peptide derivatives through specific peptide transport systems followed, presumably, by cleavage by intracellular peptidases. Finally, the antibacterial activity of these peptides could be reversed by DAP or a DAP-containing peptide. These results demonstrate that the peptides containing L-2-aminopimelic acid exert their antibacterial action by inhibition of diaminopimelic acid biosynthesis.


More accurate cancer-related excess mortality through correcting background mortality for extra variables.
Relative survival methods used to estimate the excess mortality of cancer patients rely on the background (or expected) mortality derived from general population life tables. These methods are based on splitting the observed mortality into the excess mortality and the background mortality. By assuming a regression model for the excess mortality, usually a Cox-type model, one may investigate the effects of certain covariates on the excess mortality. Some covariates are cancer-specific whereas others are variables that may influence the background mortality as well. The latter should be taken into account in the background mortality to avoid biases in estimating their effects on the excess mortality. Unfortunately, the available life table might not include such variables and, consequently, might provide inaccurate values of the background mortality. We propose a model that uses multiplicative parameters to correct potentially inaccurate background mortality. The model can be seen as an extension of the frequently used Estève model because we assume a Cox-type model for the excess mortality with a piecewise constant baseline function and introduce additional parameters that multiply the background mortality. The original and the extended model are compared, first in a simulation study, then in an application to colon cancer registry data.


Molecular arrangements of self-assembled surfactant films: characterization from atomic force microscopy data.
The adsorbed surfactant film molecular arrangement with thickness of approximately 5 nm is determined by measurements of the film dielectric permittivity. Before the advent of atomic force microscopy the dielectric permittivity was a macroscopic parameter, appropriate only for describing uniform environments since its profile was difficult to measure for local intermolecular interactions and its spatial distribution was frequently settled without experimental justification. Here, we show that atomic force microscopy made it possible to measure the dielectric permittivity profile in a scale below 5 nm for adsorbed layers of self-assembled surfactant films in water. The measured values of the film's dielectric permittivity and the film's thickness determine the compactness of the adsorbed film and consequently the presence of water molecules in the film and the conformal structure of the adsorbed molecules.


Social and physical anhedonia and valence and arousal aspects of emotional experience.
Two studies examined whether self-reported anhedonia is associated with 2 facets of emotional experience, valence and arousal. In Study 1, in multiple assessments of emotional experience (e.g., naturalistic and lab contexts and social and nonsocial situations), people with elevated social anhedonia (n = 40) reported less intensity of positive affect than both controls (n = 30) and people with elevated perceptual aberration-magical ideation (n = 29). Social anhedonia was also associated with providing less emotional content when describing what it is like to experience positive situations. In contrast, both social anhedonia and perceptual aberration-magical ideation were associated with increased frequency of negative affect for their daily experiences. Moreover, social anhedonia was not associated with a decrease specifically in high-arousal emotions. In Study 2 (n = 339), social and physical anhedonia (but not perceptual aberration-magical ideation) were again associated with decreased self-reported positive affect to lab stimuli. In these studies, results were not statistically accounted for by personality, current mood, or current distress. Overall, results suggest anhedonia may be associated with a general decrease in self-reported positive affect intensity.


Evaluation of two commercial methods for the detection of Listeria sp. and Listeria monocytogenes in a chicken nugget processing plant.
This study measures the detection performances of two rapid test systems (Listeria Rapid Test Clearview and Bax system) for the screening of Listeria sp. and Listeria monocytogenes, respectively. A total of 413 samples from different sources (product from (i) different stages of processing, (ii) different environments, and (iii) different food handlers), collected from a chicken nugget processing plant, were analysed by both rapid methods and a cultural method consisting of pre-enrichment, enrichment, and isolation onto selective agars (PALCAM, LPM, and HCLA). Overall, results showed an excellent correlation between data obtained using Clearview and the cultural method, with Clearview presenting an efficiency of 99%. Bax showed a lower correlation using the cultural method, with an efficiency of 71.1%. The type of sample did not affect the efficiency of Clearview, which varied from 98.1% for product samples to 100% for environmental and food handler samples, while for Bax it had a marked influence. Efficiency of Bax varied from as high as 100% for food handlers to 37.9% for product samples.


CD25+CD4+ cells contribute to Th2 polarization during helminth infection by suppressing Th1 response development.
Mice infected with Schistosoma mansoni develop polarized Th2 responses in which Th1 responses are prevented by IL-10-mediated suppression of IL-12 production. We show that dendritic cells from infected mice are primed to make IL-12 in response to CD40 ligation, and that IL-10 acts by inhibiting this process. In infected mice, two subpopulations of CD4(+) cells, separable by their expression of CD25, make IL-10. CD25(+)CD4(+) cells expressed forkhead box P3, inhibited proliferation of CD4(+) T cells, and made IL-10, but little IL-5. In contrast, CD25(-)CD4(+) cells failed to express forkhead box P3 or to inhibit proliferation and accounted for all the IL-5, IL-6, and IL-13 produced by unseparated splenic populations. Thus, CD25(+) and CD25(-) subpopulations could be characterized as regulatory T cells (Treg cells) and Th2 cells, respectively. Consistent with their ability to make IL-10, both CD25(+) and CD25(-)CD4(+) T cells from infected mice were able, when stimulated with egg Ag, to suppress IL-12 production by CD40 agonist-stimulated dendritic cells. Additionally, in adoptive transfer experiments, both CD4(+) subpopulations of cells were able to partially inhibit the development of Th1 responses in egg-immunized IL-10(-/-) mice. The relationship of Treg cells in infected mice to natural Treg cells was strongly suggested by the ability of CD25(+)CD4(+) cells from naive mice to inhibit Th1 response development when transferred into egg-immunized or infected IL-10(-/-) mice. The data suggest that natural Treg cells and, to a lesser extent, Th2 cells play roles in suppressing Th1 responses and ensuring Th2 polarization during schistosomiasis.


Postweaning multisystemic wasting syndrome (PMWS) in pigs in Croatia: detection and characterisation of porcine circovirus type 2 (PCV2).
The objective of this study was to characterise porcine circovirus type 2 (PCV2) from pigs with naturally occurring postweaning multisystemic wasting syndrome (PMWS) in Croatia, and to determine the epizootiological, clinical and pathomorphological features of the disease. During a systematic health monitoring programme conducted in the period from January 2002 to June 2003, PMWS was suspected on eight different pig-producing farms in Croatia. The diagnosis of PMWS met all three key criteria: the presence of compatible clinical signs, the presence of the characteristic microscopic lymphoid lesions, and the detection of PCV2 within the lesions by polymerase chain reaction (PCR) and by in situ hybridisation (ISH). Moreover, PCV2 DNA from swine tissues was extracted and sequenced. The phylogenetic analysis of 4 Croatian PCV2 strains showed close relationship to PCV2 strains isolated in Slovenia, France, the Netherlands, the United Kingdom, China and Hungary. PCV2 was also demonstrated by electron microscopy in the lymph node of an affected animal. This is the first demonstration of PMWS in Croatia based on all scientifically accepted diagnostic criteria.


Pathological and parasitological characterization of infection by trematodes (Paramphistomatidae) in the large intestine of capybaras.
Gross and histological lesions caused by an intestinal parasite were described in three capybaras. The parasites presented a mean length of 14 mm and width of 7 mm, were round to oval or piriform, reddish and pedunculated, and adhered strongly to the mucosa of the large intestine. The intestinal mucosa at the parasite attachment site presented loss of surface epithelium and most glands, with replacement by fibrovascular proliferation that protruded from the mucosa and was involuted by the ventral sucker of the parasite. The lamina propria presented cellular debris, eosinophils, macrophages and plasma cells. The morphological characteristics, observed using serial histological sections, made it possible to classify the parasite as a trematode (Paramphistomatidae), compatible with Taxorchis schistocotyle. One capybara also harbored many ciliated protozoa in the large intestine (at the site of attachment of the parasite) and inside the caeca of the trematodes. In conclusion, this study described a multifocal necrotizing colitis associated with T. schistocotyle parasitism in capybaras.