Ultrasound molecular imaging of angiogenesis induced by mutant forms of hypoxia-inducible factor-1α.
Targeted point mutants of hypoxia-inducible factor-1α (HIF-1α) are potential optimal agents for angiogenesis therapy. Data are limited regarding the angiogenic response of HIF-1α mutants. We aimed to compare the angiogenic effect of wild-type and mutant HIF-1α by contrast ultrasound molecular imaging (UMI) of α(v)-integrin expression. The wild-type gene of human HIF-1α, a gene with double mutations (HIF-1α(564/803)), a gene with triple mutations (HIF-1α(564/803/402)), or the LacZ gene (control) was transfected into the ischaemic hind limbs of C57BL/6 mice using an adenovirus vector. The video intensity of microbubbles targeted to α(v)-integrins in the ischaemic limbs increased along with the number of point mutations of HIF-1α. Immunohistochemical expression of endothelial α(v)-integrins was higher in the mutant HIF-1α(564/803/402) group than the other groups as was the density of both capillaries and arterioles in ischaemic muscle. Expression of both the mRNA and protein for HIF-1α and VEGF was significantly higher in the mutant HIF-1α(564/803/402) group than in the other groups. The half-life of HIF-1α and VEGF mRNA was longer in HIF-1α mutant-transfected cells than in wild-type HIF-1α or LacZ-transfected cells. HIF-1α mutants were more effective for enhancing angiogenesis in ischaemic muscle tissue than wild-type HIF-1α, and the response could be qualitatively evaluated by UMI of α(v)-integrins expression.


Viral isolation analysis of SARS-CoV-2 from clinical specimens of COVID-19 patients.
Genetic testing using reverse transcriptase real-time polymerase chain reaction (rRT-PCR) is the mainstay of diagnosis of COVID-19. However, it has not been fully investigated whether infectious viruses are contained in SARS-CoV-2 genome-positive specimens examined using the rRT-PCR test. In this study, we examined the correlation between the threshold Cycle (Ct) value obtained from the rRT-PCR test and virus isolation in cultured cells, using 533 consecutive clinical specimens of COVID-19 patients. The virus was isolated from specimens with a Ct value of less than 30 cycles, and the lower the Ct value, the more efficient the isolation rate. A cytopathic effect due to herpes simplex virus type 1 contamination was observed in one sample with a Ct value of 35 cycles. In a comparison of VeroE6/TMPRSS2 cells and VeroE6 cells used for virus isolation, VeroE6/TMPRSS2 cells isolated the virus 1.7 times more efficiently than VeroE6 cells. There was no significant difference between the two cells in the mean Ct value of the detectable sample. In conclusion, Lower Ct values in the PCR test were associated with higher virus isolation rates, and VeroE6/TMPRSS2 cells were able to isolate viruses more efficiently than VeroE6 cells.


TB and HIV Therapeutics: Pharmacology Research Priorities.
An unprecedented number of investigational drugs are in the development pipeline for the treatment of tuberculosis. Among patients with tuberculosis, co-infection with HIV is common, and concurrent treatment of tuberculosis and HIV is now the standard of care. To ensure that combinations of anti-tuberculosis drugs and antiretrovirals are safe and are tested at doses most likely to be effective, selected pharmacokinetic studies based on knowledge of their metabolic pathways and their capacity to induce or inhibit metabolizing enzymes of companion drugs must be conducted. Drug interaction studies should be followed up by evaluations in larger populations to evaluate safety and pharmacodynamics more fully. Involving patients with HIV in trials of TB drugs early in development enhances the knowledge gained from the trials and will ensure that promising new tuberculosis treatments are available to patients with HIV as early as possible. In this review, we summarize current and planned pharmacokinetic and drug interaction studies involving investigational and licensed tuberculosis drugs and antiretrovirals and suggest priorities for tuberculosis-HIV pharmacokinetic, pharmacodynamic, and drug-drug interaction studies for the future. Priority studies for children and pregnant women with HIV and tuberculosis co-infection are briefly discussed.


Multiway Decomposition Followed by Reconvolution of Fluorescence Time Decay Data.
The use of time-resolved emission spectroscopy (TRES) is increasing as these instruments become more available, and the prices are decreasing, especially with the development of cheaper LED light sources. In this article, we propose a new methodology for analyzing TRES data. It combines two existing methods: PARAFAC and reconvolution. PARAFAC is a soft modeling curve resolution technique which has been extensively applied to steady-state fluorescence data, and reconvolution is the most common method for fitting TRES data. The proposed method is compared to two well-established methods of analyzing these data, namely, global reconvolution and tail fitting. In addition, we compare our approach with the SLICING method proposed in 2021 by Devos et al. which is also based on a soft model, but does not include the reconvolution step. All of these methods follow the assumption that the measured fluorescence signal is a linear combination of the underlying fluorophores. The comparison is based on a measured TRES data set with a mixture of three fluorophores and two sets of simulated data sets with up to four fluorophores. The results show that global fitting works well as long as the signal-to-noise ratio (SNR) is high (more than 15 dB), independent of the spacing between the emission peak maxima. SLICING does not give as good estimates of the time decay, mainly due to the challenge of defining the tail. Our proposed method gives robust and accurate results, outperforming the other techniques in cases with broad instrument response functions and high noise levels with SNRs down to 5 dB.


Increased sensitivity of lymphocytes from people over 65 to cell cycle arrest and chromosomal damage.
Flow cytometry revealed that, in the presence of tritiated thymidine, a greater percentage of phytohemagglutinin-stimulated lymphocytes from old human donors were arrested in the G2 or M phase than were cells from young donors. Furthermore, lymphocytes from old donors showed significantly more chromosomal damage than did lymphocytes from young donors. Lymphocyte cultures from old or young donors not exposed to tritiated thymidine had the same percentage of cycling lymphocytes in G2 or M, although the number of lymphocytes stimulated by phytohemagglutinin to enter the cell cycle was significantly lower in cultures from old donors. Thus, the impaired incorporation of tritiated thymidine by phytohemagglutinin-exposed lymphocytes from old humans reflects both an impaired proliferative response to phytohemagglutinin and an increased sensitivity to the radiobiological effects of tritiated thymidine.


Robust Interfacial Tribofilms by Borate- and Polymer-Coated ZnO Nanoparticles Leading to Improved Wear Protection under a Boundary Lubrication Regime.
This work reports on the development of borate- and methacrylate-polymer-coated zinc oxide nanoparticles (ZnOBM) via a plasma polymerization technique to replace the harmful conventional antiwear additive zinc dialkyl dithiophosphate (ZDDP) in automotive lubricants. Here, the tribochemistry across the interfaces formed between sliding ferrous surfaces and coated and uncoated ZnO nanoparticles is thoroughly studied from the perspective of elucidating the tribofilm formation, wear, and friction performance of a novel ZnOBM-based nanolubricant. Tribological tests conducted under a boundary lubrication regime revealed that oil formulations containing only ZnOBM nanoadditives and a mixture of ZnOBM with a low amount of ZDDP (350 ppm of P) significantly improve wear performance (up to 95%) compared to the base oil. Electrical contact resistance results acquired in situ during tribological tests demonstrated that lubricants containing ZnOBM nanoparticles at sliding interfaces undergo tribochemical reactions to form stable tribofilms that reduce friction and wear. Atomic force microscopy (AFM), X-ray absorption near-edge spectroscopy (XANES), and X-ray photoelectron spectroscopy (XPS) analysis revealed that ZnOBM nanoparticles, by themselves, form patchy interfacial tribofilms containing iron borate, boron oxide, and zinc oxide and lead to superior tribological performance. Interestingly, ZnOBM nanoparticles interact synergistically with ZDDP to form a hierarchical interface of boron-doped tribofilms, with zinc-iron polyphosphates at the surface and iron oxide, zinc and iron sulfides in the bulk. These encouraging results suggest the potential effective use of the ZnOBM nanoparticles to significantly reduce harmful levels of ZDDP (350 ppm) in the engine oil without compromising the antifriction and antiwear performance and to develop eco-friendly high-performance lubricant additives.


Dexamethasone in hyperleukocytic acute myeloid leukemia.
Patients with acute myeloid leukemia and a high white blood cell count are at increased risk of early death and relapse. Because mediators of inflammation contribute to leukostasis and chemoresistance, dexamethasone added to chemotherapy could improve outcomes. This retrospective study evaluated the impact of adding or not adding dexamethasone to chemotherapy in a cohort of 160 patients with at least 50×109 white blood cells. In silico studies, primary samples, leukemic cell lines, and xenograft mouse models were used to explore the antileukemic activity of dexamethasone. There was no difference with respect to induction death rate, response, and infections between the 60 patients in the dexamethasone group and the 100 patients in the no dexamethasone group. Multivariate analysis showed that dexamethasone was significantly associated with improved relapse incidence (adjusted sub-HR: 0.30; 95% CI: 0.14-0.62; P=0.001), disease-free survival (adjusted HR: 0.50; 95% CI: 0.29-0.84; P=0.010), event-free survival (adjusted HR: 0.35; 95% CI: 0.21-0.58; P<0.001), and overall survival (adjusted HR: 0.41; 95% CI: 0.22-0.79; P=0.007). In a co-culture system, dexamethasone reduced the frequency of leukemic long-term culture initiating cells by 38% and enhanced the cytotoxicity of doxorubicin and cytarabine. In a patient-derived xenograft model treated with cytarabine, chemoresistant cells were enriched in genes of the inflammatory response modulated by dexamethasone. Dexamethasone also demonstrated antileukemic activity in NPM1-mutated samples. Dexamethasone may improve the outcome of acute myeloid leukemia patients receiving intensive chemotherapy. This effect could be due to the modulation of inflammatory chemoresistance pathways and to a specific activity in acute myeloid leukemia with NPM1 mutation.


A HPLC-MS method for profiling triterpenoid acids and triterpenoid esters in Osmanthus fragrans fruits.
Triterpenoids, as an important family of plant secondary metabolites, have important biological activities associated with health and disease prevention. In this work, we proposed a HPLC-MS method for profiling multiple groups of triterpenoid acids and triterpenoid esters differing only in one position of the hydroxyl or methyl group in O. fragrans fruits. A total of thirty-one compounds were identified, and twenty-seven components were discovered in O. fragrans fruits for the first time. The HPLC-MS profiling method was applied in the analysis of the triterpenoids of O. fragrans flowers, and the time courses of triterpenoids of O. fragrans fruits.


[Laparoscopic and microsurgical varicocelectomy: comparison of the results].
Laparoscopic and microsurgical varicocelectomy were compared by clinical and cost efficacy results. Microsurgical subinguinal varicocelectomy was performed in 129 patients, laparoscopic - 167 patients. Median of the patients' age was 27 years (16-38 years). Median of follow-up in microsurgical operation was 26 months (13-60 months), in laparoscopic method - 62 months (28-71 months). By clinical criteria (time of surgical intervention, amount of analgetic drugs in the postoperative period, stay in hospital, rate of varicocele recurrence and postoperative complications), the results of microsurgical varicocelectomy proved significantly better than those of laparoscopic operations. The rate of all complications after microsurgical ligation of the testicular veins was 8 times less than after laparoscopic intervention, the rate of varicocele recurrence - 2.4 times less. Microsurgical operations were financially more effective (by 20%) than laparoscopic varicocelectomy. Thus, microsurgical varicocelectomy is more effective than laparoscopic one both clinically and financially.


Volatile Organic Compounds in Urine for Noninvasive Diagnosis of Malignant Biliary Strictures: A Pilot Study.
The use of volatile organic compounds (VOCs) in bile was recently studied and appeared promising for diagnosis of malignancy. Noninvasive diagnosis of malignant biliary strictures by using VOCs in urine has not been studied. To identify potential VOCs in urine to diagnose malignant biliary strictures. In this prospective cross-sectional study, urine was obtained immediately prior to ERCP from consecutive patients with biliary strictures. Selected-ion flow-tube mass spectrometry was used to analyze the concentration of VOCs in urine samples. Fifty-four patients with biliary strictures were enrolled. Fifteen patients had malignant stricture [six cholangiocarcinoma (CCA) and nine pancreatic cancer], and 39 patients had benign strictures [10 primary sclerosing cholangitis (PSC) and 29 with benign biliary conditions including chronic pancreatitis and papillary stenosis]. The concentration of several compounds (ethanol and 2-propanol) was significantly different in patients with malignant compared with benign biliary strictures (p < 0.05). Using receiver operating characteristic curve analysis, we developed a model for the diagnosis of malignant biliary strictures adjusted for age and gender based on VOC levels of 2-propranol, carbon disulfide, and trimethyl amine (TMA). The model [-2.4191 * log(2-propanol) + 1.1617 * log(TMA) - 1.2172 * log(carbon disulfide)] ≥ 7.73 identified the patients with malignant biliary stricture [area under the curve (AUC = 0.83)], with 93.3 % sensitivity and 61.5 % specificity (p = 0.009). Comparing patients with CCA and PSC, the model [38.864 * log(ethane) - 3.989 * log(1-octene)] ≤ 169.9 could identify CCA with 80 % sensitivity and 100 % specificity (AUC = 0.9). Measurement of VOCs in urine may diagnose malignant biliary strictures noninvasively.


Risk factors in facial hyperpigmentation in Maghrebian population - a case-control study.
Triggering factors seem to be multiple in the pathogenesis of facial hyperpigmentation (FH), as dark skin types, pregnancy, sun exposure… The aim of this study was to investigate the risk factors for FH in Maghrebian population. Patients with FH were included in a case-controlled study. Following data were recorded: age, sex, parity, phototype, FH and hormonal-related history, endocrinological features, sunlight exposure, specific cultural behaviours, use of topic corticosteroids and sunscreens. One hundred women (mean age 29.5 ± 13.7 years) were included with 200 age-matched controls. Duration of FH was 32.9 ± 42.2 months. There was a statistically significant relation between FH and hirsutism (P = 0.009), troubles of menstruations (P = 0.008), but not with acne (P = 0.23) and contraceptive oral (P = 0.06) drugs or with history of thyroid disorders (P = 0.13). For cultural factors, there were a statistical significant relation with rubbing by flannel glove (P < 0.05), use of dark soap (P = 0.009) and traditional masks (P < 0.05) but both groups were used to go to hammam. A strong relation was observed between FH and use of topical corticosteroids: 40% in the FH group vs. 5% in the control group (P < 0.05). Both groups used to apply sunscreens: 70% in the FH group and 67% in the control group where as there were no differences in the two groups for sun exposure. No statistical differences were observed regarding to age, phototypes and grade of parity. Our study demonstrated a relation between FH and hyperestrogenemia, rubbing with a friction glove, use of moroccan traditional masks and application of topical steroids. The eviction of all these triggering factors could be an adjuvant recommendation in the assessment of FH.


Gastric outlet obstruction caused by benign anastomotic stricture: treatment by fluoroscopically guided balloon dilation.
To evaluate the clinical efficacy and safety of fluoroscopically guided balloon dilation of gastric outlet obstruction caused by benign anastomotic stricture. Fluoroscopically guided balloon dilation was performed on 17 patients with gastric outlet obstruction caused by benign anastomotic stricture. Fourteen patients underwent surgery for malignant disease and three patients for complication of benign gastric ulcer. The sites of anastomotic stricture were gastrojejunal (n = 12) or gastroduodenal (n = 5). An upper gastrointestinal (UGI) series was performed just following and 1 month after balloon dilation to evaluate both the clinical success of the procedure and any complications. A dietary intake was evaluated by using the score for patients with malignant dysphagia and the pre- and postballoon dilation scores were analyzed with the Wilcoxon signed rank test. In all patients, fluoroscopically guided balloon dilation was performed in one (n = 15) or two (n = 2) sessions and was technically and clinically successful (100%). The diameters of the balloon catheters used were 15 mm (n = 4), 20 mm (n = 14), and 25 mm (n = 1 mm; mean, 19.5 mm) in a total of 19 sessions. All patients had significant improvement of their levels of dietary intake (P < .001). Two of the 17 patients required the second procedure due to recurrent symptom nine and 15 months, respectively, after initial balloon dilation. Overall, 16 patients (94%) showed good results and no recurrence during a mean follow-up period of 13.5 months (range, 5-39 months). There were no major complications associated with balloon dilation. Fluoroscopically guided balloon dilation seems to be effective and safe for patients with gastric outlet obstruction caused by benign anastomotic stricture. Achieving a luminal diameter of 20 mm seems to be necessary to prevent recurrence of symptoms.


Family satisfaction predicts life satisfaction trajectories over the first 5 years after traumatic brain injury.
Examined the influence of functional impairment, stable marital status, and family satisfaction on life satisfaction trajectories for 609 individuals (435 men, 174 women) over the first 5 years after traumatic brain injury (TBI). Participants completed the Family Satisfaction Scale (FSS), Functional Independence Measure (FIM), and the Life Satisfaction Index (LSI) at years 1, 2, 4, and 5 after sustaining a TBI. Trajectory modeling revealed that higher family satisfaction was associated with increases in life satisfaction for individuals with less functional impairment. Stable marital status was not significantly associated with life satisfaction trajectories. Family satisfaction appears to have pronounced beneficial effects on life satisfaction for persons with less functional impairment after TBI regardless of marital status. In contrast, a stable marriage appears to have no apparent benefits to self-reported life satisfaction over the first 5 years post-TBI. Theoretical and clinical implications of these results are discussed.


TBI risk stratification at presentation: a prospective study of the incidence and timing of radiographic worsening in the Parkland Protocol.
We have created a theoretical algorithm for venous thromboembolism prophylaxis after traumatic brain injury (TBI) known as the Parkland Protocol, which stratifies patients into low-, medium-, and high-risk categories for spontaneous progression of hemorrhage. This prospective study characterizes the incidence and timing of radiographic progression of the TBI patterns in these categories. Inclusion criterion was presentation with intracranial blood between February 2010 and March 2011; exclusion was receipt of only one computed tomographic scan of the head during the inpatient stay or preinjury warfarin. At admission, all patients were preliminarily categorized per the Parkland Protocol as follows: low risk (LR), patients meeting the modified Berne-Norwood criteria; moderate risk (MR), injuries larger than the modified Berne-Norwood criteria without requiring a neurosurgical procedure; high risk (HR), any patient with a craniotomy/monitor. A total of 245 patients with intracranial hemorrhage were enrolled during the 13-month study period. Of patients preliminarily classified as LR at admission (n = 136), progression was seen in 25.0%. Spontaneous worsening was seen in 7.4% of LR patients at 24 hours after injury, and no LR patients progressed at 72 hours after injury. In patients initially classified as MR at admission (n = 42), progression was seen in 42.9%, with 91.5% of patients demonstrating stable computed tomographic head scans at 72 hours after injury. In patients initially classified as HR (n = 67), 64.2% demonstrated spontaneous progression of their TBI patterns, with 10.5% continuing to progress at 72 hours after injury. Most repeat scans were performed as routinely scheduled studies (81-91%). Increases in the incidence of spontaneous worsening were seen as severities of injury progressed from the Parkland Protocol's LR to MR to HR arms. The time frames for these spontaneous worsenings seem to be such that the protocol's theoretical recommendations for venous thromboembolism prophylaxis are worth pursuing as future points of investigation.


Estimation of gas and tissue lung volumes by MRI: functional approach of lung imaging.
The purpose of this work was to assess the accuracy of MRI for the determination of lung gas and tissue volumes. Fifteen healthy subjects underwent MRI of the thorax and pulmonary function tests [vital capacity (VC) and total lung capacity (TLC)] in the supine position. MR examinations were performed at inspiration and expiration. Lung volumes were measured by a previously validated technique on phantoms. Both individual and total lung volumes and capacities were calculated. MRI total vital capacity (VC(MRI)) was compared with spirometric vital capacity (VC(SP)). Capacities were correlated to lung volumes. Tissue volume (V(T)) was estimated as the difference between the total lung volume at full inspiration and the TLC. No significant difference was seen between VC(MRI) and VC(SP). Individual capacities were well correlated (r = 0.9) to static volume at full inspiration. The V(T) was estimated to be 836+/-393 ml. This preliminary study demonstrates that MRI can accurately estimate lung gas and tissue volumes. The proposed approach appears well suited for functional imaging of the lung.


Training clinical ethics committee members between 1992 and 2017: systematic scoping review.
Clinical ethics committees (CECs) support and enhance communication and complex decision making, educate healthcare professionals and the public on ethical matters and maintain standards of care. However, a consistent approach to training members of CECs is lacking. A systematic scoping review was conducted to evaluate prevailing CEC training curricula to guide the design of an evidence-based approach. Arksey and O'Malley's methodological framework for conducting scoping reviews was used to evaluate prevailing accounts of CEC training published in six databases. Braun and Clarke's thematic analysis approach was adopted to thematically analyse data across different healthcare and educational settings. 7370 abstracts were identified, 92 full-text articles were reviewed and 55 articles were thematically analysed to reveal four themes: the design, pedagogy, content and assessment of CEC curricula. Few curricula employ consistent approaches to training. Many programmes fail to provide CEC trainees with sufficient knowledge, skills and experience to meet required competencies. Most programmes do not inculcate prevailing sociocultural, research, clinical and educational considerations into training processes nor provide longitudinal support for CEC trainees. Most CEC training programmes are not supported by host institutions threatening the sustainability of the programme and compromising effective assessment and longitudinal support of CEC trainees. While further reviews are required, this review underlines the need for host organisations to support and oversee a socioculturally appropriate ethically sensitive, clinically relevant longitudinal training, assessment and support process for CEC trainees if CECs are to meet their roles effectively.


A classification and characterization of two-locus, pure, strict, epistatic models for simulation and detection.
The statistical genetics phenomenon of epistasis is widely acknowledged to confound disease etiology. In order to evaluate strategies for detecting these complex multi-locus disease associations, simulation studies are required. The development of the GAMETES software for the generation of complex genetic models, has provided the means to randomly generate an architecturally diverse population of epistatic models that are both pure and strict, i.e. all n loci, but no fewer, are predictive of phenotype. Previous theoretical work characterizing complex genetic models has yet to examine pure, strict, epistasis which should be the most challenging to detect. This study addresses three goals: (1) Classify and characterize pure, strict, two-locus epistatic models, (2) Investigate the effect of model 'architecture' on detection difficulty, and (3) Explore how adjusting GAMETES constraints influences diversity in the generated models. In this study we utilized a geometric approach to classify pure, strict, two-locus epistatic models by "shape". In total, 33 unique shape symmetry classes were identified. Using a detection difficulty metric, we found that model shape was consistently a significant predictor of model detection difficulty. Additionally, after categorizing shape classes by the number of edges in their shape projections, we found that this edge number was also significantly predictive of detection difficulty. Analysis of constraints within GAMETES indicated that increasing model population size can expand model class coverage but does little to change the range of observed difficulty metric scores. A variable population prevalence significantly increased the range of observed difficulty metric scores and, for certain constraints, also improved model class coverage. These analyses further our theoretical understanding of epistatic relationships and uncover guidelines for the effective generation of complex models using GAMETES. Specifically, (1) we have characterized 33 shape classes by edge number, detection difficulty, and observed frequency (2) our results support the claim that model architecture directly influences detection difficulty, and (3) we found that GAMETES will generate a maximally diverse set of models with a variable population prevalence and a larger model population size. However, a model population size as small as 1,000 is likely to be sufficient.


Computed tomography of the normal feline nasal cavity and paranasal sinuses.
Computed tomography (CT) images of the feline nasal cavity and paranasal sinuses were acquired from normal adult cats. Good resolution and anatomic detail were obtained from the CT images using soft tissue formatting. A description of normal feline nasal cavity and paranasal sinus anatomy using CT is presented.


Leadership, OCB and Individual Differences: Idiocentrism and Allocentrism as Moderators of the Relationship between Transformational and Transactional Leadership and OCB.
We propose and test a framework which suggests that the relationships between leadership styles and Organizational Citizenship Behaviors (OCB) are contingent upon employee cultural-based individual differences. More specifically, we examine whether followers' idiocentrism and allocentrism moderate the relationship between transformational and transactional leadership and followers' OCB. Survey data, collected from a sample of school teachers and their principals from the Israeli kibbutzim and urban sectors, support our hypotheses. We found the relationship between transformational leadership and OCB to be positive to the extent that allocentrism increases, and negative to the extent that idiocentrism increases. We also found the relationship between transactional leadership and OCB to be positive to the extent that idiocentrism increases and negative to the extent that allocentrism increases. Implications of these findings for research and practice are discussed.


Characterization and Discrimination of Plastic Materials Using Laser-Induced Fluorescence.
The most meaningful spectral components in laser-induced fluorescence (LIF) spectra for several different commercial plastics have been individuated and used to automatically discriminate among different plastic materials and between plastics and complex organic materials, such as woods. Starting from LIF measurements on known samples, a number of significant wavelengths have been identified by principal component analysis (PCA). These have been used to produce intensity ratios functional to the discrimination. Threshold values for such ratios have been individuated in order to obtain an automatic recognition of plastics. The work done has been preparatory to the design and development of a multispectral imaging LIF system for fast detection of plastic debris in a post-blast scene.


Overexpression of PARP is an independent prognostic marker for poor survival in Middle Eastern breast cancer and its inhibition can be enhanced with embelin co-treatment.
Patients with aggressive breast cancer (BC) subtypes usually don't have favorable prognosis despite the improvement in treatment modalities. These cancers still remain a major cause of morbidity and mortality in females. This has fostered a major effort to discover actionable molecular targets to treat these patients. Poly ADP ribose polymerase (PARP) is one of these molecular targets that are under comprehensive investigation for treatment of such tumors. However, its role in the pathogenesis of BC from Middle Eastern ethnicity has not yet been explored. Therefore, we examined the expression of PARP protein in a large cohort of over 1000 Middle Eastern BC cases by immunohistochemistry. Correlation with clinico-pathological parameters were performed. Nuclear PARP overexpression was observed in 44.7% of all BC cases and was significantly associated with aggressive clinico-pathological markers. Interestingly, nuclear PARP overexpression was an independent predictor of poor prognosis. PARP overexpression was also directly associated with XIAP overexpression, with PARP and XIAP co-expression in 15.8% (159/1008) of our cases. We showed that combined inhibition of PARP by olaparib and XIAP by embelin significantly and synergistically inhibited cell growth and induced apoptosis in BC cell lines. Finally, co-treatment of olaparib and embelin regressed BC xenograft tumor growth in nude mice. Our results revealed the role of PARP in Middle Eastern BC pathogenesis and prognosis. Furthermore, our data support the potential clinical development of combined inhibition of PARP and XIAP, which eventually could extend the utility of olaparib beyond BRCA deficient cancer.


An assessment of the validity of a computer system for probabilistic record linkage of birth and infant death records in Canada. The Fetal and Infant Health Study Group.
Studies on the validity of probabilistic record linkage are sparse. We performed a probabilistic linkage to link the 1984-1994 birth records (obtained from the Canadian Birth Data Base) with 1984-1995 infant death records (from the Canadian Mortality Data Base) in Canada. We extracted the linked birth-death records for Nova Scotia and Alberta (from January 1990 to December 1991) obtained from Statistics Canada's vital registration data and compared them with corresponding records from provincial data (primarily hospital records). The results showed that over 99% of infant deaths (153/155) in the Nova Scotia provincial data were successfully located in the linked Statistics Canada file; the corresponding figure for Alberta neonatal deaths was also 99% (365/367). The distributions of gestational age and birth weight in matched cases demonstrated high agreement between the two data sources. We conclude that the computer system for probabilistic linkage developed by Statistics Canada using the available personal identifying variables in the Canadian Birth Data Base and the Canadian Mortality Data Base is valid.


Valacyclovir for prevention of recurrent herpes labialis: 2 double-blind, placebo-controlled studies.
The oral antiviral valacyclovir, which is 3 to 5 times more bioavailable than its parent compound acyclovir, is a good candidate for effective therapy to suppress recurrent herpes labialis lesions. The efficacy of oral valacyclovir in the suppression of herpes labialis has not previously been reported. Two identical, randomized, double-blind, parallel-group studies were conducted to evaluate the efficacy of oral valacyclovir 500 mg (n=49) versus placebo (n=49) once daily for 16 weeks in the suppression of herpes labialis among patients with a history of 4 or more recurrent lesions in the previous year. Data from the studies were pooled for analysis. Twenty-eight patients (60%) in the valacyclovir group compared with only 18 patients (38%) in the placebo group were recurrence-free throughout the 4-month treatment period (P=.041). The mean time to first recurrence was significantly longer with valacyclovir (13.1 weeks) compared with placebo (9.6 weeks) (P=.016). The total number of recurrences in patients using valacyclovir was 24 compared with 41 in patients using placebo. The incidence of adverse events during the 4-month treatment period was slightly lower in the valacyclovir group (22 events, 33% of patients) compared with the placebo group (29 events, 39% of patients). The results of these small double-blind, placebo-controlled studies suggest that oral valacyclovir 500 mg once daily for 4 months is effective and well tolerated for the prevention of recurrent herpes labialis. More research with larger patient numbers is warranted to corroborate and extend these findings.


Drinking water fluoride and blood pressure? An environmental study.
The relationship between intakes of fluoride (F) from drinking water and blood pressure has not yet been reported. We examined the relationship of F in ground water resources (GWRs) of Iran with the blood pressure of Iranian population in an ecologic study. The mean F data of the GWRs (as a surrogate for F levels in drinking water) were derived from a previously conducted study. The hypertension prevalence and the mean of systolic and diastolic blood pressures (SBP & DBP) of Iranian population by different provinces and genders were also derived from the provincial report of non-communicable disease risk factor surveillance of Iran. Statistically significant positive correlations were found between the mean concentrations of F in the GWRs and the hypertension prevalence of males (r = 0.48, p = 0.007), females (r = 0.36, p = 0.048), and overall (r = 0.495, p = 0.005). Also, statistically significant positive correlations between the mean concentrations of F in the GWRs and the mean SBP of males (r = 0.431, p = 0.018), and a borderline correlation with females (r = 0.352, p = 0.057) were found. In conclusion, we found the increase of hypertension prevalence and the SBP mean with the increase of F level in the GWRs of Iranian population.


Body mass index, smoking, and risk of death between 40 and 70 years of age in a Norwegian cohort of 32,727 women and 33,475 men.
Overweight-obesity and smoking are two main preventable causes of premature death. Because the relationship between smoking and body mass index (BMI) complicates the interpretation of associations between BMI and death risks, direct estimates of risks associated with joint exposures are helpful. We have studied the relationships of BMI and smoking to middle age (40-69 years) death risk-overall and by causes-in a Norwegian cohort of 32,727 women and 33,475 men who were 35-49 years old when baseline measurements and lifestyle information were collected in 1974-1988. Individuals with a history of cancer, cardiovascular disease or diabetes at baseline were excluded. Mortality follow-up was through 2009. The relationship between BMI and middle age death risk was U-shaped. Overall middle age death risks were 11% in women and 21 % in men. The combination of obesity and heavy smoking resulted in fivefold increase in middle age death risks in both women and men: For women middle age death risk ranged from 6 % among never smokers in the 22.5-24.9 BMI group to 31% (adjusted 28%) in obese (BMI > 30 kg/m(2)) heavy smokers (≥20 cigarettes/day). The corresponding figures in men were 10% and 53% (adjusted 45%). Obese never smokers and light (1-9 cigarettes/day) smokers in the 22.5-24.9 BMI groups both experienced a twofold increase in middle age risks of death. For women, cancer (56%) was the most common cause of death followed by cardiovascular disease (22%). In men, cardiovascular disease was most common (41%) followed by cancer (34%). Cardiovascular disease deaths were more strongly related to BMI than were cancer deaths.


Heparin therapy as adjuvant treatment for profound idiopathic sudden sensorineural hearing loss.
This study aimed to provide evidence of whether unfractionated heparin used as adjuvant therapy in conjunction with systemic corticosteroid therapy improves hearing recovery in patients with profound idiopathic sudden sensorineural hearing loss (ISSNHL), and to compare the effect of this treatment with those of additional intratympanic corticosteroid therapy. Retrospective chart review. Eighty-seven patients with profound ISSNHL (≥90 dB) and who had been admitted at a tertiary referral center between 2010 and 2018 were retrospectively reviewed, 67 patients for additional intratympanic corticosteroid injection (ITSI) (ITSI group) and 21 for adjuvant heparin therapy (heparin group). Hearing recovery was evaluated by grade assessment according to the American Academy of Otolaryngology-Head and Neck Surgery criteria. Of the patients in the heparin group, 42.8% recovered serviceable hearing, which was significantly higher than the recovery rates (19.7%) of those in the ITSI group. Particularly, in patients with pretreatment hearing level of 90 to 100 dB, adjuvant heparin therapy enhanced therapeutic effects with a significant hearing recovery rate of 80%. However, in patients with initial hearing level >100 dB, the rates of significant hearing recovery in the two groups were roughly equal and remained unsatisfactory (8.1% in the ITSI group and 9.1% in the heparin group). The results of this study suggest that the treatment of profound ISSNHL with adjuvant heparin therapy, in combination with systemic steroid therapy, results in higher hearing recovery rates when compared to combined local and systemic corticosteroid therapy, without serious complications. 3b Laryngoscope, 130:1310-1315, 2020.


Mathematical learning disability in girls with Turner syndrome: a challenge to defining MLD and its subtypes.
Turner syndrome is a common disorder with a prevalence of 1:2,500 live female births. Although not associated with mental retardation, there is an increased risk of learning difficulties in this population. In particular, mathematical learning difficulties among girls with Turner syndrome are prevalent, significant, and persistent. As such, the study of mathematical performance in girls with Turner syndrome presents opportunities to advance our knowledge of mathematics ability, disability, and disability subtypes. Moreover, the Turner syndrome phenotype illustrates the challenges faced when defining mathematical learning disability (MLD) and characterizing MLD subtypes because the cognitive phenotype is aligned with several proposed MLD subtypes. There is some evidence linking MLD in Turner syndrome with spatial deficits, with executive dysfunction, and with deficient numerosity skills. Yet there is also conflicting evidence as to whether any of these explanations underlies MLD in Turner syndrome. Most mathematical difficulties in girls with Turner syndrome, as a group, occur on timed tests or on complex problems. On untimed tests, achievement test scores may be age appropriate. Therefore, the inclusion of MLD in the Turner syndrome cognitive phenotype reminds us that we cannot rule out MLD solely on the basis of performance on an untimed calculations subtest, and it poses a challenge to the widespread practice in which many researchers engage, that is, defining MLD on the basis of broad mathematics achievement test outcomes.


Coding and decoding in a point-to-point communication using the polarization of the light beam.
A new technique for coding and decoding of optical signals through the use of polarization is described. In this technique the concept of coding is translated to polarization. In other words, coding is done in such a way that each code represents a unique polarization. This is done by implementing a binary pattern on a spatial light modulator in such a way that the reflected light has the required polarization. Decoding is done by the detection of the received beam's polarization. By linking the concept of coding to polarization we can use each of these concepts in measuring the other one, attaining some gains. In this paper the construction of a simple point-to-point communication where coding and decoding is done through polarization will be discussed.


Clostridium difficile-associated cecitis in guinea pigs exposed to penicillin.
Penicillin treatment resulted in lethal hemorrhagic cecitis in seven of eight guinea pigs. Cecal contents at necropsy from all seven animals contained a cytopathic toxin which was neutralized by Clostridium sordellii and C difficile antitoxins. Bacteriologic cultural examinations of these specimens yielded penicillin-sensitive strains of C difficile which produced a similar or identical cytotoxin in vitro. Stools obtained before penicillin administration and cecal contents from control animals lacked a cytotoxin and cultures failed to yield C difficile. Intracecal injection of cell-free supernatant of C difficile broth cultures reproduced the lesion noted with penicillin treatment. These results implicate C difficile as an agent of penicillin-induced lethal hemorrhagic cecitis in guinea pigs.


Pulmonary vein stenosis and the pathophysiology of "upstream" pulmonary veins.
Surgical and catheter-based interventions on pulmonary veins are associated with pulmonary vein stenosis (PVS), which can progress diffusely through the "upstream" pulmonary veins. The mechanism has been rarely studied. We used a porcine model of PVS to assess disease progression with emphasis on the potential role of endothelial-mesenchymal transition (EndMT). Neonatal piglets underwent bilateral pulmonary vein banding (banded, n = 6) or sham operations (sham, n = 6). Additional piglets underwent identical banding and stent implantation in a single-banded pulmonary vein 3 weeks postbanding (stented, n = 6). At 7 weeks postbanding, hemodynamics and upstream PV pathology were assessed. Banded piglets developed pulmonary hypertension. The upstream pulmonary veins exhibited intimal thickening associated with features of EndMT, including increased transforming growth factor (TGF)-β1 and Smad expression, loss of endothelial and gain of mesenchymal marker expression, and coexpression of endothelial and mesenchymal markers in banded pulmonary vein intimal cells. These immunopathologic changes and a prominent myofibroblast phenotype in the remodeled pulmonary veins were consistently identified in specimens from patients with PVS, in vitro TGF-β1-stimulated cells isolated from piglet and human pulmonary veins, and human umbilical vein endothelial cells. After stent implantation, decompression of a pulmonary vein was associated with reappearance of endothelial marker expression, suggesting the potential for plasticity in the observed pathologic changes, followed by rapid in-stent restenosis. Neonatal pulmonary vein banding in piglets recapitulates critical aspects of clinical PVS and highlights a pathologic profile consistent with EndMT, supporting the rationale for evaluating therapeutic strategies designed to exploit reversibility of upstream pulmonary vein pathology.


Medication use by persons with chronic fatigue syndrome: results of a randomized telephone survey in Wichita, Kansas.
Chronic fatigue syndrome (CFS) is characterized by profound fatigue, which substantially interferes with daily activities, and a characteristic symptom complex. Patients use a variety of prescribed and self-administered medications, vitamins, and supplements for relief of their symptoms. The objective of this study was to describe utilization of medications and supplements by persons with CFS and non-fatigued individuals representative of the general population of Wichita, Kansas. We used a random-digit dialing telephone survey to identify persons with CFS in the general population of Wichita, Kansas. Subjects who on the basis of telephone interview met the CFS case definition, and randomly selected non-fatigued controls, were invited for a clinic evaluation that included self-reported use of medications and supplements. Sex-adjusted odds ratios and 95% confidence interval were estimated to measure the association between CFS and use of various drug categories. We clinically evaluated and classified 90 subjects as CFS during the study and also collected clinical data on 63 who never described fatigue. Subjects with CFS reported using 316 different drugs compared to 157 reported by non-fatigued controls. CFS subjects were more likely to use any drug category than controls (p = 0.0009). Pain relievers and vitamins/supplements were the two most common agents listed by both groups. In addition CFS persons were more likely to use pain relievers, hormones, antidepressants, benzodiazepines, gastro-intestinal, and central nervous system medications (Sex-adjusted odds ratios range = 2.97 - 12.78). Although the reasons for increased use of these agents were not elucidated, the data indicated the CFS patients' need for symptom relief.


Patterns of subnet usage reveal distinct scales of regulation in the transcriptional regulatory network of Escherichia coli.
The set of regulatory interactions between genes, mediated by transcription factors, forms a species' transcriptional regulatory network (TRN). By comparing this network with measured gene expression data, one can identify functional properties of the TRN and gain general insight into transcriptional control. We define the subnet of a node as the subgraph consisting of all nodes topologically downstream of the node, including itself. Using a large set of microarray expression data of the bacterium Escherichia coli, we find that the gene expression in different subnets exhibits a structured pattern in response to environmental changes and genotypic mutation. Subnets with fewer changes in their expression pattern have a higher fraction of feed-forward loop motifs and a lower fraction of small RNA targets within them. Our study implies that the TRN consists of several scales of regulatory organization: (1) subnets with more varying gene expression controlled by both transcription factors and post-transcriptional RNA regulation and (2) subnets with less varying gene expression having more feed-forward loops and less post-transcriptional RNA regulation.


Factors Associated with Apathy in Alzheimer's Disease: A Cross-Sectional Analysis of the Texas Alzheimer's Research and Care Consortium (TARCC) Study.
Apathy is among the most frequent neuropsychiatric syndromes in Alzheimer's disease (AD). To determine the prevalence of apathy and the associated clinical and laboratorial parameters (focus on inflammatory biomarkers) in patients with dementia enrolled at the Texas Alzheimer's Research and Care Consortium (TARCC) study. This is a cross-sectional analysis of TARCC baseline. Participants were evaluated through different clinical tools, including the Mini-Mental State Examination (MMSE) and the Lawton-Brody Instrumental Activities of Daily Life (IADL)/Physical Self-Maintenance Scale (PSMS). Apathy was defined by a positive response to the respective item in the Neuropsychiatric Inventory-Questionnaire applied to caregivers. Serum levels of 16 biomarkers were determined by HumanMap multiplex immunoassay. Comparisons between apathy versus non-apathy groups were carried out with non-parametric tests. Logistic regression and the least absolute shrinkage and selection operator (LASSO) were used to separately model apathy as a function of each biomarker, adjusted for the potential confounders. From 1,319 patients with AD (M/F: 579/740, mean age ± SD: 75.3 ± 8.4), 373 (28.3%) exhibited apathy. When categorized according to the presence of apathy, the groups had significant differences in sex, diabetes diagnosis, and tobacco use. The apathy group also had worse cognitive performance and daily functioning than the non-apathy group as assessed, respectively, by MMSE and IADL/PSMS. Higher levels of interleukin-6, interleukin-10, and leptin were associated with higher odds of apathy. Apathy is associated with cognitive and functional status in AD. The association between apathy and peripheral inflammatory mediators deserves further investigation.


[Comparative analysis of affinity modification of several aminoacyl-tRNA synthetases with gamma-(p-azidoanilide)-ATP].
The inhibitory action of gamma-(p-azidoanilide)-ATP on the reactions of tRNA aminoacylation catalysed by several aminoacyl-tRNA synthetases was investigated. This compound was shown to be a competitive inhibitor with respect to ATP in the case of arginyl-, valyl-, isoleucyl-, leucyl-, threonyl-, phenylalanyl-tRNA synthetases of E. coli MRE-600 and tryptophanyl-tRNA synthetase of beef pancreas. The Ki value of this analog changes from 3 x 10(-5) up to 4 x 10(-3) M depending on the enzyme specificity. In the case of methionyland lysyl-tRNA synthetases from E. coli the non-competitive and mixed inhibition accordingly was observed. The activity of isoleucyl-, valyl-, leucyl-, threonyl-, phenyl-alanyl- and tryptophanyl-tRNA synthetases in the reaction of tRNA aminoacylation is decreased as a result of UV-irradiation of the enzymes in the presence of gamma-(p-azidoanilide)-ATP. ATP and aminoacids protect these enzymes against irreversible inactivation. These results confirm the affinity labelling of the substrate binding sites of these enzymes. However, the appreciable inactivation of enzymes with UV-irradiation in the presence of gamma-(p-azidoanilide)-ATP was not detected in the cases of hystidyl-, lysyl-, methionyl-, seryl-, tyrosyl- and phenylalanyl-tRNA synthetases of E. coli MRE-600. The data obtained enable one to suggest the difference in the structure of the amino acid activating sites of different aminoacyl-tRNA synthetases.


A homologue of the rabbit kappa-chain allotype b9 ON IgG from a cottontail rabbit.
Eight out of 12 anti-b9 antisera tested strongly bound 125IgG of only one of four individual cottontail rabbits (Sylvilagus floridanus). In addition to this apparent polymorphism of a b9 homologue in cottontail rabbits, a polymorphism defined by some anti-b5 antisera was found. Three of 15 anti-b5 antisera reacted with IgG from only two of the four cottontail rabbits. Reactions with anti-b4 and anti-b6 were similar to those with hare IgG. Most anti-b4 and anti-b6 antisera bound the IgG from each animal. The cottontails we tested also resembled the hare with respect to their weak reactivity with some anti-a2 antisera (Vh allotype) and strong reactivity with anti-15 (an allotype localized in the Fc portion of rabbit gamma-chains).


Terahertz Laser Pulse Boosts Interlayer Spin Transfer in Two-Dimensional van der Waals Magnetic Heterostructures.
Light-induced ultrafast dynamics in two-dimensional (2D) magnetic systems demonstrate substantial advancements in spintronics. Here, using the real-time time-dependent density functional theory (rt-TDDFT), we applied laser pulses with various frequencies, from terahertz (THz) to optical pulse, to systematically study the interlayer spin transfer dynamics in 2D van der Waals nonmagnetic-ferromagnetic heterostructures, including graphene-Fe3GeTe2 (Gr/FGT) and silicene-Fe3GeTe2 (Si/FGT). Our results demonstrate that low-frequency THz pulses are particularly effective in facilitating interlayer spin injection from the ferromagnetic FGT layers to the Si or Gr layers. On the contrary, high-frequency optical pulses exhibit a minimal influence on this process. Such an effect is attributed to the low-frequency THz pulses inducing in-phase oscillations of the electron charge density around atomic centers, leading to a highly efficient interlayer spin transfer. Our results provide a new insight into ultrafast THz radiation control intralayer spin transfer and magnetic proximity dynamics in the 2D limit.


Arch reconstruction without circulatory arrest: current clinical applications and results of therapy.
Laboratory and clinical data have confirmed the deleterious effects of deep hypothermic circulatory arrest. Long-term data and rigorous neuropsychiatric data are currently sparse, but that which are available show adverse outcomes following circulatory arrest, and therefore support the use of continuous perfusion techniques. There are no available long-term data on continuous perfusion techniques with respect to neurologic outcomes, but using these techniques the incidence of postoperative seizures or other neurologic events is rare. Currently available bypass systems and microsurgical techniques have allowed continuous flow and regional perfusion to become practical alternatives. Several innovative techniques for avoiding circulatory arrest during neonatal aortic arch reconstruction for univentricular and biventricular hearts are described. It would appear prudent and desirable to provide continuous perfusion now that long-term survival after repair of even the most complex cardiac anomalies including single ventricle defects is commonplace.


Role of prostaglandins in delayed cerebral ischemia after subarachnoid hemorrhage.
Prostaglandin E2, thromboxane B2, and 6-oxo-prostaglandin F1 alpha were assayed in blood and cerebrospinal fluid samples from patients after subarachnoid hemorrhage (SAH) and from a control population. The levels found in samples obtained from patients after SAH were compared with those found in controls and were also correlated with a number of clinical and radiological variables, many of which are either significantly associated with or represent evidence of cerebral ischemia. The levels of prostaglandin E2, thromboxane B2, and 6-oxo-prostaglandin F1 alpha in blood samples from patients after SAH and from controls were below the level of sensitivity of the assays. Levels of prostaglandin E2, thromboxane B2, and 6-oxo-prostaglandin F1 alpha in cerebrospinal fluid from patients after SAH were significantly elevated when compared with those found in control samples. There was no significant correlation, however, between the level of each prostaglandin measured and the following variables: clinical grade on admission as assessed by the Glasgow Coma Score and the World Federation of Neurological Surgeons grading system; the amount of subarachnoid blood seen on computed tomographic scan; the occurrence of ischemic deterioration; the occurrence of low density change on computed tomographic scan; the presence of vasospasm on angiography; clinical outcome as assessed by the Glasgow Coma Score 3 months after the ictus; and the incidence of ischemia as a cause of death or disability as assessed 3 months after the ictus. A primary role for prostaglandins in the etiology of delayed cerebral ischemia after SAH is not therefore confirmed.


Interctions between potassium ions and glycine transport in the yeast Saccharomyces carlsbergensis.
A study has been made of the effects of both varying the pH and extracellular [K(+)] on the initial rate of uptake of glycine (v) by a strain of Saccharomyces carlsbergensis that concentrated the amino acid, with respect to the extracellular phase, by up to 1400 times. When no other substrate than glycine was provided and [glycine] was relatively small (</=0.2mm) (1) v increased fivefold when the pH was lowered from 7 to 4.5; (2) v fell by up to about 80% as [K(+)] rose, K(+) behaving as a non-competitive inhibitor of the system, with K(i) 0.33mequiv./l at pH7; (3) the absorption of glycine caused up to about 2 or 3 equiv. of K(+) to leave the yeast cells. These three phenomena were each less evident when glucose was present. An analogy is drawn between the respective interactions of H(+) and K(+) with the yeast system and the well recognized effects of Na(+) and K(+) on amino acid transport in certain mammalian systems.


Associations of alleles of the esterase-1 locus with gene arrangements of the left arm of the second chromosome in Drosophila robusta.
Evidence of strong associations of Est-1 alleles with the 2L, 2L1 and 2L3 gene arrangements of the left arm of the second chromosome in D. robusta is presented. Each gene arrangement is polymorphic for three to four Est-1 alleles. The allele frequencies differ in the 2L3 and 2L arrangements; the allele Est-1(.92) is 8% in the 2L3 arrangement (n=203)-this allele is 82% in the 2L arrangement (n=203); the allele Est-1(1.0) is 66% and 14.8% in the 2L3 and 2L arrangements, respectively. There are no differences in allele frequencies in 2L3 arrangements from any of the widely separated seven different populations; similarly the allele frequencies in the 2L arrangement are alike in all five widely separated populations studied. The allele frequencies in the 2L1 arrangement are intermediate to those observed in the 2L3 and the 2L arrangements and show north-south clinal change. These associations between Est-1 alleles and gene arrangements of the left arm of the second chromosome are due to natural selection favoring different allele frequencies in different gene arrangements, as a result of epistatic interactions between the Est-1 locus and the loci on the gene arrangements. As expected, we observe that the proportion of heterozygotes is greater in the inversion heterokaryotypes than in the homokaryotypes.


Mechanical phenotype of cancer cells: cell softening and loss of stiffness sensing.
The stiffness sensing ability is required to respond to the stiffness of the matrix. Here we determined whether normal cells and cancer cells display distinct mechanical phenotypes. Cancer cells were softer than their normal counterparts, regardless of the type of cancer (breast, bladder, cervix, pancreas, or Ha-RasV12-transformed cells). When cultured on matrices of varying stiffness, low stiffness decreased proliferation in normal cells, while cancer cells and transformed cells lost this response. Thus, cancer cells undergo a change in their mechanical phenotype that includes cell softening and loss of stiffness sensing. Caveolin-1, which is suppressed in many tumor cells and in oncogene-transformed cells, regulates the mechanical phenotype. Caveolin-1-upregulated RhoA activity and Y397FAK phosphorylation directed actin cap formation, which was positively correlated with cell elasticity and stiffness sensing in fibroblasts. Ha-RasV12-induced transformation and changes in the mechanical phenotypes were reversed by re-expression of caveolin-1 and mimicked by the suppression of caveolin-1 in normal fibroblasts. This is the first study to describe this novel role for caveolin-1, linking mechanical phenotype to cell transformation. Furthermore, mechanical characteristics may serve as biomarkers for cell transformation.


Rethinking Timing of First Sex and Delinquency.
The relation between timing of first sex and later delinquency was examined using a genetically informed sample of 534 same-sex twin pairs from the National Longitudinal Study of Adolescent Health, who were assessed at three time points over a 7-year interval. Genetic and environmental differences between families were found to account for the association between earlier age at first sex and increases in delinquency. After controlling for these genetic and environmental confounds using a quasi-experimental design, earlier age at first sex predicted lower levels of delinquency in early adulthood. The current study is contrasted with previous research with non-genetically informative samples, including Armour and Haynie. Results suggest a more nuanced perspective on the meaning and consequences of adolescent sexuality than is commonly put forth in the literature.


Research needs in taeniasis-cysticercosis.
This Memorandum discusses the epidemiology of taeniasis-cysticercosis, particularly the survival of taeniid eggs in nature, and goes on to consider diagnostic procedures (parasitological and serological), resistance to infection, pathogenesis and clinical pathology, chemotherapy, and the economic and social consequences of infection. Topics requiring further research are listed, and recommendations are made concerning the approach to the problem.


Reduction of 5-hydroxytryptamine (5-HT)(1A)-mediated temperature and neuroendocrine responses and 5-HT(1A) binding sites in 5-HT transporter knockout mice.
The aim of the present study was to determine whether alterations in 5-hydroxytryptamine (5-HT)(1A) receptors would be found in knockout mice lacking the serotonin transporter (5-HTT). Hypothermic and neuroendocrine responses to the 5-HT(1A) agonist 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) were used to examine the function of 5-HT(1A) receptors. Initial studies evaluated the dose-response and time course of 8-OH-DPAT-induced hypothermia and hormone secretion in normal CD-1 mice (the background strain of the 5-HTT knockout mice). 8-OH-DPAT dose-dependently produced hypothermic responses that peaked at 20 min postinjection. 8-OH-DPAT-induced hypothermia was blocked by the 5-HT(1A) antagonist WAY-100635. 8-OH-DPAT dose-dependently increased the concentrations of plasma oxytocin, corticotropin, and corticosterone. In the 5-HTT knockout (-/-) mice, the hypothermic response to 8-OH-DPAT (0.1 mg/kg s.c.) was completely abolished. Furthermore, 5-HTT-/- mice had significantly attenuated plasma oxytocin and corticosterone responses to 8-OH-DPAT. No significant changes in the hypothermic or hormonal responses to 8-OH-DPAT were observed in heterozygous (5-HTT+/-) mice. [(3)H]8-OH-DPAT- and [(125)I]MPPI [4-(2'-methoxyphenyl)-1-[2'-[N-(2"-pyridinyl)-iodobenzamido]ethyl] pip erazine]-binding sites in the hypothalamus and [(125)I]MPPI-binding sites in the dorsal raphe were significantly decreased in 5-HTT-/- mice. The results indicate that lack of the 5-HTT is associated with a functional desensitization of 5-HT(1A) receptor responses to 8-OH-DPAT, which may be a consequence, at least in part, of the decrease in density of 5-HT(1A) receptors in the hypothalamus and dorsal raphe of 5-HTT-/- mice.


Leaky sodium channels from voltage sensor mutations in periodic paralysis, but not paramyotonia.
Hypokalemic periodic paralysis (HypoPP) is associated with mutations in either the Ca(V)1.1 calcium channel or the Na(V)1.4 sodium channel. Some Na(V)1.4 HypoPP mutations have been shown to cause an anomalous inward current that may contribute to the attacks of paralysis. Herein, we test whether disease-associated Na(V)1.4 mutations in previously untested homologous regions of the channel also give rise to the anomalous current. The functional properties of mutant Na(V)1.4 channels were studied with voltage-clamp techniques in an oocyte expression system. The HypoPP mutation Na(V)1.4-R1132Q conducts an anomalous gating pore current, but the homologous R1448C mutation in paramyotonia congenita does not. Gating pore currents arising from missense mutations at arginine residues in the voltage sensor domains of Na(V)1.4 are a common feature of HypoPP mutant channels and contribute to the attacks of paralysis.


[Apparatus for the synchronous measurement of pressure distribution and components of the resulting force under the human footsole (author's transl)].
The presented stationary apparatus enables to make measurements of qualitative and quantitative pressure distribution under the barefooted human footsole. With a film camera the pressure distribution is recorded on 35 mm black-and-white negative film with 60 pictures/sec during the unrolling of the foot. With a duration of 0.5 sec at a walking speed of 5 km/h the unrolling is recorded by about 30 separate pictures. Besides the illustration of pressure distribution each of the pictures shows: a pressure comparing unit, the side-view of the unrolling foot, the actual recording time in units of 1/100 sec and statements about the test person. Each of the recorded pictures in then scanned by a black-and-white-TV-camera. By means of electronic hardware coloured isobares of the pressure distribution given by the different foot deformities are computed and shown on a colour monitor screen. By strain gages, the three components of the resulting force (weight) are registered synchronously.


Excitatory Effects of Dopamine on the Cardiac Ganglia of the Crabs Portunus Sanguinolentus and Podophthalmus Vigil.
1. Dopamine, a cardioexcitor in decapod crustaceans, increased the frequency and/or duration of bursts of action potentials in the semi-isolated cardiac ganglia of two species of crabs. The number of motoneurone action potentials in each burst was increased, which in the intact heart would increase the force and amplitude of heart contraction. 2. The effects were concentration-dependent, with a threshold concentration of 10-8M or lower when dopamine was applied by continuous perfusion. At 5×10-6M, dopamine increased burst frequency by 200%. 3. The main site of dopamine action was the group of four posterior small interneurones which normally function as the pacemaker for the cardiac ganglion system. Effects on the five large motoneurones occurred at higher concentrations. This regional difference in sensitivity was demonstrated by selective applications of dopamine to different parts of the cardiac ganglion and by the use of preparations in which the two ends of the ganglion had been functionally separated by a ligature around the ganglionic trunk. 4. In the small neurones, dopamine was found to stimulate the slow tetrodotoxin-resistant regenerative depolarizations known as driver potentials. The effects on driver potential frequency and train duration were concentration dependent. In one of the two species of crabs, in which electrotonic connections between small and large neurones are strong, large neurone driver potentials were indirectly induced by dopamine. 5. In the tetrodotoxin-treated large motoneurones, dopamine, at a concentration about ten-fold higher than needed to activate the small neurones, decreased the threshold for current-induced driver potentials, and slightly reduced membrane resistance. 6. We suggest that the excitatory action of dopamine on the untreated cardiac ganglion can in large part be accounted for by its action on driver potential production in the small neurones.


Thrombotic thrombocytopenic purpura directly linked with ADAMTS13 inhibition in the baboon (Papio ursinus).
Thrombotic thrombocytopenic purpura (TTP) is the prototypical microangiopathy characterized by disseminated microthromboses, hemolytic anemia, and ultimately organ dysfunction. A link with deficiency of the von Willebrand factor-cleaving protease (ADAMTS13) has been demonstrated, but additional genetic and/or environmental triggers are thought to be required to incite acute illness. Here we report that 4 days of ADAMTS13 functional inhibition is sufficient to induce TTP in the baboon (Papio ursinus), in the absence of inciting triggers because injections with an inhibitory monoclonal antibody (mAb) consistently (n = 6) induced severe thrombocytopenia (< 12 × 10(9)/L), microangiopathic hemolytic anemia, and a rapid rise in serum lactate dehydrogenase. Immunohistochemical staining revealed the characteristic disseminated platelet- and von Willebrand factor-rich thrombi in kidney, heart, brain, and spleen but not lungs. Prolonged inhibition (14 days, n = 1) caused myocardial ischemic damage and asplenia but not death. Control animals (n = 5) receiving equal doses of a noninhibitory anti-ADAMTS13 mAb remained unaffected. Our results provide evidence for a direct link between TTP and ADAMTS13 inhibition and for a mild disease onset. Furthermore, we present a reliable animal model of this disease as an opportunity for the development and validation of novel treatment strategies.


The architecture of amyloid-like peptide fibrils revealed by X-ray scattering, diffraction and electron microscopy.
Structural analysis of protein fibrillation is inherently challenging. Given the crucial role of fibrils in amyloid diseases, method advancement is urgently needed. A hybrid modelling approach is presented enabling detailed analysis of a highly ordered and hierarchically organized fibril of the GNNQQNY peptide fragment of a yeast prion protein. Data from small-angle X-ray solution scattering, fibre diffraction and electron microscopy are combined with existing high-resolution X-ray crystallographic structures to investigate the fibrillation process and the hierarchical fibril structure of the peptide fragment. The elongation of these fibrils proceeds without the accumulation of any detectable amount of intermediate oligomeric species, as is otherwise reported for, for example, glucagon, insulin and α-synuclein. Ribbons constituted of linearly arranged protofilaments are formed. An additional hierarchical layer is generated via the pairing of ribbons during fibril maturation. Based on the complementary data, a quasi-atomic resolution model of the protofilament peptide arrangement is suggested. The peptide structure appears in a β-sheet arrangement reminiscent of the β-zipper structures evident from high-resolution crystal structures, with specific differences in the relative peptide orientation. The complexity of protein fibrillation and structure emphasizes the need to use multiple complementary methods.


Theoretical evidence for the significance of certain types of DNA secondary structure in the genomes of phi X174, G4, fd, SV40 and the plasmid pBR322.
The significance of certain types of DNA secondary structure was assessed on a purely theoretical basis by analyzing their distribution over the entire genomes of bacteriophages phi X174, G4, fd, the eucaryotic virus SV40 and the E. coli plasmid pBR322. A computer program was designed to search the translated and non-translated (intercistronic) regions of these genomes for the potential of forming perfect hairpins (perfectly base paired stems: no G-T pairing; no interruptions) with small loops. The number of found occurrences was then compared to the statistically expected number. The results reveal a significant excess in each genome of perfect hairpins with stem length greater than 7 and end loops less than or equal to 20 over that expected given their nucleotide composition. For stem length of 5 to 7 the same observation holds true for the intercistronic regions, but for translated regions the number of such structures is below expectation. This suggests an evolutionary selection for these structures.


Surgery as a Viable Alternative First-Line Treatment for Prolactinoma Patients. A Systematic Review and Meta-Analysis.
The improved remission and complication rates of current transsphenoidal surgery warrant reappraisal of the position of surgery as a viable alternative to dopamine agonists in the treatment algorithm of prolactinomas. To compare clinical outcomes after dopamine agonist withdrawal and transsphenoidal surgery in prolactinoma patients. Eight databases were searched up to July 13, 2018. Primary outcome was disease remission after drug withdrawal or surgery. Secondary outcomes were biochemical control and side effects during dopamine agonist treatment and postoperative complications. Fixed- or random-effects meta-analysis was performed to estimate pooled proportions. Robustness of results was assessed by sensitivity analyses. A total of 1469 articles were screened: 55 (10 low risk of bias) on medical treatment (n = 3564 patients) and 25 (12 low risk of bias) on transsphenoidal surgery (n = 1836 patients). Long-term disease remission after dopamine agonist withdrawal was 34% (95% confidence interval [CI], 26-46) and 67% (95% CI, 60-74) after surgery. Subgroup analysis of microprolactinomas showed 36% (95% CI, 21-52) disease remission after dopamine agonist withdrawal, and 83% (95% CI, 76-90) after surgery. Biochemical control was achieved in 81% (95% CI, 75-87) of patients during dopamine agonists with side effects in 26% (95% CI, 13-41). Transsphenoidal surgery resulted in 0% mortality, 2% (95% CI, 0-5) permanent diabetes insipidus, and 3% (95% CI, 2-5) cerebrospinal fluid leakage. Multiple sensitivity analyses yielded similar results. In the majority of prolactinoma patients, disease remission can be achieved through surgery, with low risks of long-term surgical complications, and disease remission is less often achieved with dopamine agonists.


Evaluation and costs of volunteer telephone cessation follow-up counseling for Veteran smokers discharged from inpatient units: a quasi-experimental, mixed methods study.
The Reach, Effectiveness, Adoption, Implementation, and Maintenance (RE-AIM) framework was used to evaluate the volunteer telephone smoking cessation counseling follow-up program implemented as part of the inpatient Tobacco Tactics intervention in a Veterans Affairs (VA) hospital. This was a quasi-experimental, mixed methods design that collected data through electronic medical records (EMR), observations of telephone smoking cessation counseling calls, interviews with staff and Veterans involved in the program, and intervention costs. Reach: Of the 131 Veterans referred to the smoking cessation telephone follow-up program, 19% were reached 0-1 times, while 81% were reached 2-4 times. Effectiveness: Seven-day point-prevalence 60-day quit rates (abstracted from the EMR) for those who were reached 2-4 times were 26%, compared to 8% among those who were reached 0-1 times (p = 0.06). Sixty-day 24-hour point-prevalence quit rates were 33% for those reached 2-4 times, compared to 4% of those reached 0-1 times (p < 0.01). Adoption and Implementation: The volunteers correctly followed protocol and were enthusiastic about performing the calls. Veterans who were interviewed reported positive comments about the calls. The cost to the hospital was $21 per participating Veteran, and the cost per quit was $92. Maintenance: There was short-term maintenance (about 1 year), but the program was not sustainable long term. Quit rates were higher among those Veterans that had greater participation in the calls. Joint Commission standards for inpatient smoking with follow-up calls are voluntary, but should these standards become mandatory, there may be more motivation for VA administration to institute a hospital-based, volunteer telephone smoking cessation follow-up program. ClinicalTrials.Gov NCT01359371.


An emerging player in the adaptive immune response: microRNA-146a is a modulator of IL-2 expression and activation-induced cell death in T lymphocytes.
Activation of the T cell-mediated immune response has been associated with changes in the expression of specific microRNAs (miRNAs). However, the role of miRNAs in the development of an effective immune response is just beginning to be explored. This study focuses on the functional role of miR-146a in T lymphocyte-mediated immune response and provides interesting clues on the transcriptional regulation of miR-146a during T-cell activation. We show that miR-146a is low in human naive T cells and is abundantly expressed in human memory T cells; consistently, miR-146a is induced in human primary T lymphocytes upon T-cell receptor (TCR) stimulation. Moreover, we identified NF-kB and c-ETS binding sites as required for the induction of miR-146a transcription upon TCR engagement. Our results demonstrate that several signaling pathways, other than inflammation, are influenced by miR-146a. In particular, we provide experimental evidence that miR-146a modulates activation-induced cell death (AICD), acting as an antiapoptotic factor, and that Fas-associated death domain (FADD) is a target of miR-146a. Furthermore, miR-146a enforced expression impairs both activator protein 1 (AP-1) activity and interleukin-2 (IL-2) production induced by TCR engagement, thus suggesting a role of this miRNA in the modulation of adaptive immunity.


Singapore in international comparisons of birthweight and perinatal mortality.
The position of Singapore as regards birthweight distribution and perinatal mortality has been compared with six countries in the 1973 WHO study namely, Austria, Cuba, Hungary, Japan, New Zealand and Sweden. Birthweight distribution and perinatal mortality reflect both the social and health conditions of a population and the standards of obstetric and paediatric care, and seeing where a country ranks in the international comparison of them may play a role in the formulation of health policy for that country. Singapore was well placed for the proportion of very low birthweight babies (less than 1,500 grams), ranking 2nd for both live births (0.5%) and total births (0.7%). It was however not so well placed for proportion of low birthweight babies (less than 2,500 grams), ranking 5th for both live births (8.8%) and total births (9.2%). With regard to perinatal mortality Singapore at 20.0 per 1,000 total births ranked 4th and this improved to 3rd after standardizing for birthweight and in fact was little different from Hungary (1st) and Sweden (2nd). Given that standardization for birthweight largely removes the effect of "socioeconomic and demographic factors" so that remaining differences to a large extent reflect medical care, this indicates a relatively high standard of perinatal care in Singapore. The problems of interpretation, the implications of the findings and suggestions for improving birth statistics in Singapore are discussed.


Position of the Society for Nutrition Education and Behavior: The Importance of Including Environmental Sustainability in Dietary Guidance.
It is the position of the Society for Nutrition Education and Behavior that environmental sustainability should be inherent in dietary guidance, whether working with individuals or groups about their dietary choices or in setting national dietary guidance. Improving the nutritional health of a population is a long-term goal that requires ensuring the long-term sustainability of the food system. Current environmental trends, including those related to climate change, biodiversity loss, land degradation, water shortages, and water pollution, threaten long-term food security and are caused in part by current diets and agricultural practices. Addressing these problems while producing more food for a growing population will require changes to current food systems. Dietary choices have a significant role in contributing to environmental impacts, which could be lessened by consuming fewer overconsumed animal products and more plant-based foods while reducing excess energy intake and the amount of food wasted. Discussion of sustainability within governmental dietary guidance is common in many countries, is consistent with previous US guidelines, and is within the scope of authorizing legislation. Dietary choices are a personal matter, but many American consumers are motivated by a concern for the environment and would welcome sound advice from credentialed nutrition professionals. More opportunities are needed for developing such interdisciplinary knowledge among nutritionists.


Effect of alpha-methylphenylalanine and phenylalanine on brain polyribosomes and protein synthesis.
A chronic hyperphenylalanemia was effectively produced in developing mice by daily administrations of phenylalanine (2 mg/g body wt) and a phenylalanine hydroxylase inhibitor alpha-methyl-D,L-phenylalanine (0.43 mg/g body wt). The presence of alpha-methylphenylalanine in newborn mice inhibited 65-70% of hepatic phenylalanine hydroxylase activity within 12 h. Since this maximum inhibition persisted for 24 h or longer, decreased enzyme activity was maintained by daily administrations. Whereas concentrations of phenylalanine increased approximately 40-fold in both plasma and brain following injection of alpha-methylphenylalanine and phenylalanine, plasma levels of tyrosine were not altered significantly. Concomitant with changes in phenylalanine concentrations we observed the brain polyribosomes' disaggregation, which reached a maximum 3 h after injection and persisted as long as 18 h. Polyribosomes did not become refractory to as many as 10 daily injections of alpha-methylphenylalanine and phenylalanine. In addition to polyribosome disaggregation, chronic hyperphenylalanemia reduced the rates of polypeptide chain elongation on polyribosomes isolated from brain homogenates.


Missed diagnoses in African Americans with obsessive-compulsive disorder: the structured clinical interview for DSM-IV Axis I disorders (SCID-I).
Research on the utility of structured interviews in assessing OCD is scarce, and even more so, in its use for OCD in African Americans. The purpose of this study was to examine the utility of the Structured Clinical Interview for DSM-IV Axis I Disorders (SCID-I) in detecting OCD in African Americans when used by well-trained, culturally competent clinicians. Seventy-four African American adults with OCD were assessed with the SCID-I and additional measures of OCD. Results revealed the poor diagnostic utility of the SCID OCD section (SCID-OCD), with 66.2% (N = 49) correctly identified and 33.8% (N = 25) incorrectly diagnosed. Participants receiving the correct diagnosis were more likely to endorse compulsive behaviors, specifically ordering compulsions, and experience greater symptom severity. The lack of sensitivity for identification of OCD is discussed as the SCID-OCD seems to often miss a true diagnosis of OCD in African Americans.


Pediatric glaucoma surgery: a report by the American Academy Of Ophthalmology.
To review the current published literature to evaluate the success rates and long-term problems associated with surgery for pediatric glaucoma. Literature searches of the PubMed and Cochrane Library databases were last conducted in May 2012. The search yielded 838 potentially relevant citations, of which 273 were in non-English languages. The titles and abstracts of these articles were reviewed by the authors, and 364 were selected for possible further review. Members of the Ophthalmic Technology Assessment Committee Glaucoma Panel reviewed the full text of these articles and used the 36 that met inclusion and exclusion criteria for this Ophthalmic Technology Assessment. There were no studies on the topic that provided level I evidence. The assessment included only level II and level III studies. Surgeons treat pediatric glaucoma most commonly with goniotomy, trabeculotomy, trabeculectomy, combined trabeculotomy and trabeculectomy, tube shunt surgery, cyclodestruction, and deep sclerectomy. Certain surgical options seem better for specific diagnoses, such as primary congenital glaucoma, aphakic glaucoma, and glaucomas associated with other ocular or systemic anomalies. There are many surgical options for the treatment of the pediatric glaucomas. The relative efficacy of these various procedures for particular diagnoses and clinical situations should be weighed against the specific risks associated with the procedures for individual patients.


[Pathogenesis of infraclusions].
Any case of infraclusion should be considered to be a defect of the vertical adaptation of the dental system, i.e. as a local alveolar disturbance. Two types of pathogenesis can be proposed: an interposition between the dental arches of an obstacle which prevents the egression of the teeth and, the lesser known pathogenesis, the pressure exerted simultaneously on the vestibular and lingual surfaces of the incisors can, because of the oblique surface of contact, result in a system of forces which results in the arrest of dental eruption.


Selective targeting of pigmented retinal pigment epithelial (RPE) cells by a single pulsed laser irradiation: an in vitro study.
This work describes the selective targeting of pigmented retinal pigment epithelial (RPE) cells by a single pulsed laser irradiation. We observed: (1) single pulsed laser irradiation caused cellular damages on pigmented, and not on non-pigmented RPE cells at laser radiant exposure up to 2550 mJ/cm(2); (2) in the mixture of pigmented and non-pigmented RPE cells, single pulsed laser-induced damage was confined to pigmented RPE cells. This study demonstrates that the pigmented RPE cells can be selectively damaged, using a single pulsed laser irradiation, without thermal coagulation to adjacent non-pigmented RPE cells.


Influence of quercetin on amiodarone pharmacokinetics and biodistribution in rats.
Amiodarone (AMD), a drug of choice to treat cardiac arrhythmias, has a narrow therapeutic index (NTI). It inhibits CYP3A4, CYP2C9, and CYP2D6 enzymes. Quercetin (QUE), a pharmacologically important bioflavonoid in vegetables and fruits, is important in treating cardiovascular comorbidities. QUE alters the bioavailability of drugs used concurrently by dual inhibition of P-glycoproteins (P-gp) and cytochrome (CYP) enzyme systems. The current study aimed to investigate the pre-treatment and co-administration effect of QUE on AMD pharmacokinetics in rats. Two separate animal trials (I and II) were planned to probe the effect of QUE on AMD pharmacokinetics by following previously cited studies. The pre-treatment group received oral doses of QUE for 14 days, and a single dose of AMD on the 15th day. Rats were administered single doses of QUE (20 mg/kg) and AMD (50 mg/kg) concurrently in a carboxymethylcellulose (CMC) in the co-administration study. Blood was collected at pre-determined time points. AMD was quantified by HPLC, and data was analyzed by PK solver software. In the pre-treated group, peak plasma concentration (Cmax) and area under the curve (AUC0-∞) of AMD were increased by 45.52% and 13.70%, respectively, while time to achieve maximum concentration (tmax), half-life (t1/2) and clearance (CL) were declined by 35.72%, 16.75%, and 11.0% respectively compared to the control. In the co-administered group, compared to controls, Cmax and AUC0-∞ were elevated to 12.90% and 7.80%, respectively, while tmax, t1/2, and CL declined by 16.70%, 2.35%, and 13.40%. Further, AMD was increased in lung tissue of both treated groups, relative to the respective controls. A notable pharmacokinetic drug interaction between QUE and AMD was observed in rats and warrants possible drug interaction study in humans, suggesting AMD dose adjustment specifically in patients with arrhythmia having a pre-treatment history and simultaneous administration of QUE-containing products.


How motivated are patients with type 2 diabetes to change their lifestyle? A survey among patients and healthcare professionals.
It is unknown to what extend patients with type 2 diabetes mellitus (T2DM) in primary care are motivated to change their lifestyle. We assessed the level of motivation to change lifestyle and the agreement for that level between patients and healthcare professionals. Patients with T2DM (150) filled in a questionnaire to assess the level of motivation to change their lifestyle, using a single question with three answer options. We investigated the agreement for this level between these patients and their healthcare professionals (12 professionals). In addition, we investigated and compared the level of physical activity as indicated by the patients and the healthcare professionals. A large part of the patients reported to have a deficient physical activity level (35% according to patients, 47% according to healthcare professionals, kappa 0.32) and were not motivated to change their lifestyle level (29% according to patients, 43% according to healthcare professionals, kappa 0.13). Patients tended to overestimate their physical activity and their motivation to change in comparison with their healthcare professionals. Patients with T2DM in primary care should increase their physical activity level. Healthcare professionals often do not know whether patients are motivated to change their lifestyle, and should therefore assess motivation regularly to optimize lifestyle management.


Future aspects of psychoneuroimmunology - lymphocyte peptides reflecting psychiatric disorders studied by mass spectrometry.
We have investigated whether cytoplasmatic and nuclear extracts of human peripheral blood lymphocytes contain arginine vasopressin (AVP), of importance for memory functions, in samples from healthy controls and patients diagnosed as depressed. It is the first time as AVP, AVP-fragments and chemically modified AVP-forms have been demonstrated in lymphocyte/nuclear extracts. This was performed by an HPLC-purification step, followed by a second immunoprecipitation step before identification by mass spectrometry. We are developing new methods using a combination of high-resolution mass spectrometry and separation techniques such as capillary electrophoresis and nano liquid chromatography. We have named this methodological approach when studying endogenous peptides -Peptidomics.


Later-Life Disability in Environmental Context: Why Living Arrangements Matter.
Household social and environmental context are key elements of the disablement process, yet few studies explicitly examine the relationship between household composition, housing type, and disability progression. This study investigates the risk of older adults' disability progression by type of living arrangement (e.g., household composition, housing type) and whether the relationship varies by socioeconomic status. We used Health and Retirement Study data (waves 1998-2012; n = 41,467 total observations) and fit time-series logistic regression models to estimate increases in activities of daily living (ADLs) and instrumental activities of daily living (IADLs) limitations. Because living arrangements are influenced by financial resources, we also stratified analyses by wealth. Disability rates were highest among those living alone or with nonfamily others and in self-described fair/poor quality housing. Overall, disability risk was more strongly associated with wealth than living arrangements. For more affluent older adults, living alone was associated with a decreased risk of IADL disability; for the least affluent older adults, living alone had the opposite association-increased risk of both ADL and IADL disability. Later-life disability progression should be understood in the context of both household environment and wealth. Household composition and housing characteristics were associated with disability progression and the risk of increasing disability was consistently higher for those in the lowest wealth quintile. These findings identify where older adults with disabilities live and that comprehensive interventions to reduce disability progression should consider household social and environmental context, as well as wealth.


Evaluation of Physical Activity and Lifestyle Interventions Focused on School Children with Obesity Using Accelerometry: A Systematic Review and Meta-Analysis.
Despite the existence of global recommendations for physical activity and lifestyle to avoid childhood obesity, there are no specific recommendations for school-age children. The aim of this meta-analysis was to measure the effects of current interventions with a physical activity component on body mass index (BMI) Z-score and on the moderate and vigorous physical activity (MVPA) time, measured by accelerometry, and focused on children with obesity. Randomized controlled trial studies (RCTs) based on physical activity interventions focused on children with obesity (6 to 12 years old) from January 1991 to August 2018 were included. The post-intervention mean and standard deviation of the BMI Z-score and MVPA engaged time were extracted to calculate the results using random effects models. Of a total of 229 studies considered potentially eligible, only 10 RCTs met the inclusion criteria. There were improvements in the BMI Z-score for physical activity intervention groups, compared with non-intervention children in addition to a significant increase in time engaged in MVPA. In conclusion, interventions with a physical activity component in school-children with obesity seem to be effective at reducing BMI and producing an increase in time spent engaged in physical activity. Therefore, interventions based on physical activity should be considered one of the main strategies in treating childhood obesity.


Correlation of PD-L1 Surface Expression on Leukemia Cells with the Ratio of PD-L1 mRNA Variants and with Electrophoretic Mobility.
The expression on the surface of tumor cells of ligands for the PD-1 inhibitory receptor prevents the antitumor immune response and is considered to be a negative prognostic factor in a variety of solid tumors as well as in hematologic malignancies. To determine if it were possible to analyze PD-L1 with PCR-based methods, we assessed the expression of PD-L1 in primary samples from patients with acute myeloid leukemia, in healthy donors, and in a panel of cell lines, by means of flow cytometry, RT-PCR, and Western blotting. Although the surface density of the protein was not correlated with the amount of expressed full-length mRNA, we found a statistically significant positive correlation between PD-L1 surface density and the ratio of two transcript variants (variant 1/variant 2). Our PCR-based method allows for retrospective examination of PD-L1 surface expression from frozen cDNA samples, without the need for a reference gene. Our results also suggest that variant 2, which is produced by alternative splicing, negatively regulates PD-L1 protein expression on the cell surface. In addition, PD-L1 exposition on the cell surface is clearly associated with a shift of electrophoretic mobility, observed on Western blots. This finding can explain the relatively large variability in PD-L1 apparent molecular weight reported in the literature and offers an alternate means for the assessment of PD-L1 surface expression. Cancer Immunol Res; 4(10); 815-9. ©2016 AACR.


Intra-household mosquito net use in Ethiopia, Ghana, Mali, Nigeria, Senegal, and Zambia: are nets being used? Who in the household uses them?
Mosquito net ownership is rising in sub-Saharan Africa but will substantially reduce malaria only if nets are used and the most vulnerable household members sleep under them. We used data from 9 large-scale household surveys conducted in 6 African countries from 2000 to 2004 that enumerated all household members and nets owned, analyzing only net-owning households. Across countries, women of reproductive age and children under 5 (without gender bias) were most likely to use the net; least likely were children of age 5-14 and adult males. Nets commonly covered 2-3 people. If a baby net was used, fewer people used the family net. Pregnant women were more likely to use a net in 2004 than in 2000. In several countries, a sizable minority of nets owned were not used. Understanding intra-household net-use patterns helps malaria control programs more effectively direct their efforts to increase their public health impact.


The effects of IL-17 upon human natural killer cells.
These experiments were designed to investigate the effects of IL-17 upon the phenotype and function of human Natural Killer (NK) cells. Peripheral blood mononuclear cells from healthy subjects were cultured in the presence or absence of different combinations of IL-17s and changes in relative numbers and cell surface phenotype of NK cells and CD56+CD3+ cells measured by flow cytometry. Real time PCR was used to measure changes in expression of the cytotoxicity-related genes perforin A and granzymes A and B and IL-17 receptors. A chromium release assay was used to measure cytotoxic function against K562 tumour cells. IL-17D, IL-17A, IL-17F or the combination of both of the latter had little effect upon NK cell surface expression of Killer Immunoglobulin-like Receptors, although IL-17A modestly increased NK cell numbers. Slight but not significant increases in expression of perforin and granzymes were induced by IL-17A and/or IL-17F. Both IL-17A and D significantly increased cytotoxic function of NK cells at some E:T ratios. Similarly, numbers of NK cells induced to express CD107a after interaction with K562 cells were increased, but not significantly, by all combinations of IL-17s tested. IL-17RC was not found at the NK cell surface but was expressed at the message level and the protein detected intracellularly. NK cells are known to produce IL-17 but here we report that there is little response to this cytokine although some isoforms may moderately enhance cytotoxic function. There may therefore be some enhancement of NK cell function resulting from Th17 cell activation.