Celiac disease in children with short stature.
The aim of the present study was to determine the prevalence of celiac disease in children with short stature. In all children with short stature (height more than 2 SD below the mean for age and sex) and normal physical examination, attending Motahary pediatric clinic in Shiraz, Iran, from 2003 till 2005, work-ups were made to find a cause for their short stature and of course their serum was assayed for IgG anti-tissue transglutaminase (TTG) antibody by ELISA test, as a marker for CD. There were 26 girls and 46 boys with mean age of 9.8 years. Routine work-up showed microcytic hypochromic anemia in four children (5.6%) and giardiasis in five (6.9%). GH stimulation test revealed GH deficiency in five children (6.9%). Elevated IgG anti-TTG antibody level was detected in two children (2.8%). Duodenal biopsies of these children were in favor of celiac disease. Although, the prevalence of CD in this study was not significantly different (P value = 0.14) from the prevalence rate in healthy blood donors in Iran, the findings emphasize the fact that CD must be considered in a child with short stature, especially if the height is more than 3 SD below the mean for sex and age, even in the absence of gastrointestinal symptoms. In conclusion, the measurement of anti-TTG antibody should be included in the diagnostic evaluation of children with short stature.


A systematic approach to protein glycosylation analysis: a path through the maze.
Protein glycosylation is an important post-translational modification. It is a feature that enhances the functional diversity of proteins and influences their biological activity. A wide range of functions for glycans have been described, from structural roles to participation in molecular trafficking, self-recognition and clearance. Understanding the basis of these functions is challenging because the biosynthetic machinery that constructs glycans executes sequential and competitive steps that result in a mixture of glycosylated variants (glycoforms) for each glycoprotein. Additionally, naturally occurring glycoproteins are often present at low levels, putting pressure on the sensitivity of the analytical technologies. No universal method for the rapid and reliable identification of glycan structure is currently available; hence, research goals must dictate the best method or combination of methods. To this end, we introduce some of the major technologies routinely used for structural N- and O-glycan analysis, describing the complementary information that each provides.


Economic evaluation of sunitinib malate in second-line treatment of metastatic renal cell carcinoma in Finland.
Cytokine therapy is currently used as first-line treatment of metastatic renal cell carcinoma (mRCC). Until recently, treatments with proven efficacy after the failure of first-line cytokine therapy were not available. In recent clinical trials, sunitinib has been associated with good response rates in patients with mRCC. The aim of this study was to analyze the cost-effectiveness of sunitinib as second-line therapy for cytokine-refractory mRCC compared with current routine clinical practice in Finland (ie, best supportive care [BSC], including palliative biochemotherapy). A probabilistic decision-analytic model was developed to estimate the cost-effectiveness of sunitinib. Data were gathered from clinical trials, literature sources, and expert opinions, as well as from a local sample (n = 39) from 2 university hospitals in Finland. Clinical experts treating patients with mRCC in Finland provided the information on care practices of prescribing sunitinib. The analysis was conducted from the perspective of the health care payer in Finland. According to estimated incremental cost-effectiveness ratios (ICERs), 1 progression-free month gained cost euro4802 (2005 Euros); 1 life-year gained cost euro30,831; and 1 quality-adjusted life-year (QALY) gained cost euro43,698, compared with BSC, in the treatment of mRCC. The expected mean cost in BSC was euro5543. When parameter uncertainty was considered, the probability of sunitinib being the more cost-effective choice of treatment was ~70% at the willingness-to-pay level of euro45,000/QALY gained. Based on the results of this cost-effectiveness analysis, sunitinib is potentially cost-effective as a second-line treatment of mRCC compared with the treatment currently practiced in Finnish hospitals. The ICER (euro/QALY gained) obtained in the present study was less than the value considered suitable for novel oncology treatments.


[Effect of low intensity electromagnetic radiation on coagulation and fibrinolytic properties of blood in vitro].
It is shown that new hypotheses concerning the mechanism of low-intensity mm-wave radiation effect on plasma and thrombosis haemocoagulation and fibrinolitic system. It is supposed that plasma and thrombosis factors in the area of irradiation can be primary receptor that transfer external radiation onto primary physiological targets.


Genetic basis for the cooperative bioactivation of plant lignans by Eggerthella lenta and other human gut bacteria.
Plant-derived lignans, consumed daily by most individuals, are thought to protect against cancer and other diseases1; however, their bioactivity requires gut bacterial conversion to enterolignans2. Here, we dissect a four-species bacterial consortium sufficient for all five reactions in this pathway. A single enzyme (benzyl ether reductase, encoded by the gene ber) was sufficient for the first two biotransformations, variable between strains of Eggerthella lenta, critical for enterolignan production in gnotobiotic mice and unique to Coriobacteriia. Transcriptional profiling (RNA sequencing) independently identified ber and genomic loci upregulated by each of the remaining substrates. Despite their low abundance in gut microbiomes and restricted phylogenetic range, all of the identified genes were detectable in the distal gut microbiomes of most individuals living in northern California. Together, these results emphasize the importance of considering strain-level variations and bacterial co-occurrence to gain a mechanistic understanding of the bioactivation of plant secondary metabolites by the human gut microbiome.


Relevance of philosophy of life and optimism for psychological distress among individuals in a stage where death is approaching.
The purpose was to investigate the relevance of philosophy of life as well as optimism for the psychological distress among Swedish individuals in a stage where death is approaching. Sixty-nine persons were included; of these were 42 patients newly diagnosed with advanced gastrointestinal cancer and 26 were partners to these patients. The participants' philosophy of life was studied through a semi-structured interview. The interview statements were subjected to content analysis. Optimism was measured by the Life Orientation Test and psychological distress by the Hospitality and Depression Scale. The results showed that optimistic respondents had less psychological distress. Two aspects of philosophy of life had relevance for such distress. These were wondering about why the cancer had occurred and having a feeling of being able to live a good life having or living near a person with advanced cancer. In conclusion, the above-mentioned aspects of philosophy of life as well as optimism have relevance for psychological distress among these individuals, which stress the importance that health-care staff address both patients' and their partners' concerns about their philosophy of life.


Steroid phobia and adherence--problems, solutions, impact on benefit/risk profile.
Adherence is important with all medications. It can be more difficult with inhaled steroids in light of concern about adverse effects. Although the degree of fear regarding inhaled steroids is difficult to quantify, it appears to be an important factor in adherence. These fears exist for several reasons, including misinformation obtained from such sources as the Internet. To improve adherence and decrease morbidity and mortality, it is vital that health care providers are aware of potential barriers to adherence. Measures such as simplifying and properly explaining medication regimens are helpful. Just as important is the establishment of a strong patient-provider relationship. This makes it easier to convince patients of the need for recommended medications. If the provider is able to effectively communicate and convince the patient of the benefit/risk ratio of steroids, improved patient outcomes can be achieved.


Effects of rosiglitazone on body fat distribution and insulin sensitivity in Korean type 2 diabetes mellitus patients.
The objective of the study was to investigate the effects of rosiglitazone (RSG), a thiazolidinedione derivative, on body fat distribution and insulin sensitivity in Korean subjects with type 2 diabetes mellitus. This study was a phase IV, multicenter, single-blind, positive-controlled parallel group study. Eighty-nine patients with type 2 diabetes mellitus, aged 30 to 75 years, were enrolled in this study. Their fasting plasma glucose levels ranged from 126 to 270 mg/dL, and subjects had hemoglobin A1c levels of greater than 7.0%. We compared the effect of the treatment with glibenclamide plus RSG 4 mg/d (increased to 8 mg/d after 6 months) with glibenclamide plus placebo on body fat distributions, which were determined by computed tomography scanning and glycemic and insulinemic responses to oral glucose load. During the 12-month treatment period, the difference between the changes in the ratio of the intraabdominal adipose tissue (IAAT) to abdominal subcutaneous adipose tissue areas (SAT) between treatment groups was significant (from 1.13 +/- 0.53 to 1.00 +/- 0.40 in the RSG group and from 0.92 +/- 0.54 to 0.96 +/- 0.62 in the placebo group, P = .0351). The glycemic responses to oral glucose load (area under the curve, millimoles per liter per hour) were improved in the RSG group with 12 months of treatment (from 4.88 +/- 1.10 to 4.38 +/- 1.35 in 1 hour and from 13.78 +/- 2.83 to 12.16 +/- 2.52 in 2 hours), and the difference between the changes of the glycemic response showed statistical significance between groups (RSG group vs placebo group: -0.53 +/- 1.42 vs 0.38 +/- 1.31, difference in 1 hour; -0.76 +/- 2.98 vs 1.43 +/- 2.58, difference in 2 hours). However, there was no difference between insulin responses from baseline to follow-up and no differences in the change in insulin response between groups. In Korean subjects with type 2 diabetes mellitus, 12 months of treatment with RSG may increase SAT, but may have a neutral effect on IAAT, resulting in a decrease in the IAAT:SAT ratio. The RSG treatment improved the glucose control in type 2 diabetes mellitus. However, it is important to determine whether the glucose-lowering effect of RSG occurs mainly through direct enhancement of insulin sensitivity.


Association between relative handgrip strength and hypertension in Chinese adults: An analysis of four successive national surveys with 712,442 individuals (2000-2014).
This study aimed to identify the 15-year trends of handgrip strength-to-weight (relative HS) and assess the association between relative HS and hypertension among Chinese adults aged 20-69. Using a complex, stratified, multistage probability cluster sampling, we analyzed data collected from 712,442 adults aged 20-69 years in four successive national surveys (2000-2014). We used a handheld dynamometer to measure strength and divided by body weight to calculate the relative HS. Blood pressure was recorded with a sphygmomanometer and hypertension was defined as resting systolic blood pressure at least 140 mmHg or diastolic at least 90 mmHg. The Mann-Kendall trend test examined trends in relative HS over time. We also computed odd ratios (OR) and 95% confidence intervals (95% CI) by tertile of relative HS and examined the association between relative HS and hypertension. The relative HS level decreased with the increase of age in both male and females (p trend <0.001). In each of four surveys, one interquartile decrease in relative HS was associated with an increased risk of hypertension by 44% (OR = 1.44, 95%CI: 1.40-1.47), 58% (OR = 1.58, 95%CI: 1.54-1.62), 48% (OR = 1.48, 95%CI: 1.45-1.52), 43% (OR = 1.43, 95%CI: 1.40-1.47), respectively. In the Chinese adult population, the relative HS level decreased from 2000 to 2014 across all ages in both males and females. A lower relative HS was associated with a higher risk of hypertension. The findings provided evidence for the association between muscle strength and hypertension in large-scaled population.


Clinical and angiographic outcomes after use of 90Strontium/90Yttrium beta radiation for the treatment of in-stent restenosis: results from the Stents and Radiation Therapy 40 (START 40) registry.
To evaluate the safety and efficacy of a 40-mm 90Strontium/90Yttrium source train in the management of in-stent restenosis within native coronary arteries. This multicenter, prospective registry was designed to compare the results of patients with in-stent restenosis treated with a 40-mm source train to the placebo arm of the previously reported randomized Stents and Radiation Trial (START). All patients entered in the registry were treated with repeat balloon angioplasty followed by intravascular brachytherapy. Radiation dose was prescribed based on vessel size. 18 Gy was delivered at 2 mm for vessel diameters between 2.75 and 3.35 mm, and 23 Gy was used for vessels between 3.36 and 4.0 mm. The efficacy endpoints for the START 40 registry included a reduction in the target lesion revascularization (TLR) rate, target vessel revascularization rates, and target vessel failure (TVF) at 8 months. Secondary angiographic efficacy endpoints were binary restenosis at 8 months, in-stent minimum luminal diameter (MLD), and late loss. The safety endpoints included major adverse cardiac events as well as late aneurysm formation. The registry was designed to allow a statistically valid comparison of these results to the placebo group of the START 30 trial. Quantitative angiographic analysis was performed on the 8-month follow-up examination. Rates of restenosis were evaluated for various segments of the treated vessel. A separate analysis was performed to evaluate the relationship between vessel injury length and the radiated segment. A total of 207 patients were entered into the START 40 registry. The postprocedure angiographic results, including the postprocedure MLD and percent diameter stenosis, were similar between the START 40 patients and the placebo group from the START trial in the stented segment of the treated vessel. Eight-month angiographic follow-up was available on 150 patients from the registry. The TLR rate was significantly reduced when compared to the placebo group (11% vs. 22.4% respectively, p = 0.008). A similar reduction was seen in terms of target vessel revascularization (15.9% vs. 24.1%, p = 0.03). The 8-month MLD was found to be significantly larger in the START 40 patients (1.85 mm vs. 1.47 mm, p < 0.0001). The difference seen in the clinical endpoint of TVF (19.3% vs. 25.9%) did not reach statistical significance (p = 0.1). Analysis of the procedural angiograms revealed mismatch between the length of vessel injured and the location of the 90% isodose in 46% of the treated cases. Angiographic analysis revealed that geographic miss was associated with a higher rate of binary restenosis (32% vs. 18% p = 0.04) in the analysis segment. This multicenter registry demonstrates the safety and efficacy of a 40-mm 90Strontium/90Yttrium source train in the management of patients with in-stent restenosis. Restenosis rates were lowered with the use of this longer source train when compared to the placebo arm of the START trial for lesions with a maximum vessel injury length of 20 mm. Angiographic analysis identified the importance of the accurate delineation of injury length and correct source positioning. These results support the continued use of beta radiation for the treatment of this disease process.


Enzymatic method for measuring the absolute value of oxygen concentration.
An enzymatic method for measuring the absolute concentration of oxygen in aqueous solutions, using 4-hydroxybenzoate 3-monooxygenase and glucose oxidase, is described. The monooxygenase is used for quantitative oxidation of 4-hydroxybenzoate and NADPH with oxygen into 3,4-dihydroxybenzoate and NADP+; the amount of oxygen can be measured as the amount of NADPH decreased by the reaction. The monooxygenase reaction is performed in a syringe, a closed system. After the completion of the monooxygenase reaction, glucose oxidase is added to the assay solution to consume the oxygen from the atmosphere; this enables us to measure the NADPH concentration in the solution spectrophotometrically in an open system and to check the anaerobicity of closed systems. The oxygen concentrations at 25 degrees C of oxygen-saturated and air-saturated water were 1.10 and 0.23 mM, respectively. The value for argon-bubbled water was zero within the experimental error; this justifies the assay system. Thus, it is shown that a sample containing 8 microM-1.1 mM oxygen can be measured by this method.


Study of anticoagulant mechanism of low molecular weight heparin.
The binding ability of low molecular weight heparin (FR-860), and conventional unfractionated heparin (UF-heparin) to factor Xa (F.Xa), thrombin and AT III was investigated using FR-860- and UF-heparin-Sepharoses. FR-860 could not bind directly to F.Xa. FR-860 bound to thrombin and AT III with stronger affinity to AT III than to thrombin. On the other hand, UF-heparin bound to F.Xa, thrombin and AT III with the strongest affinity to AT III followed by thrombin and F.Xa. AT III mediated the binding between F.Xa and FR-860 and accelerated the reaction between F.Xa and UF-heparin. On the other hand, AT III did not affect the binding between thrombin and FR-860 or UF-heparin. Diisopropyl fluorophosphate-treated thrombin inhibited the binding between AT III and FR-860, but not that between AT III and UF-heparin. These results suggest that the anti-F.Xa activity of FR-860 is mediated by AT III. Furthermore, the difference of antithrombin activity between FR-860 and UF-heparin depends on the capability to form ternary complex of FR-860 or UF-heparin, AT III and thrombin.


[The contribution of capsular distension to the treatment of primary adhesive capsulitis of the shoulder: a comparative study versus rehabilitation].
To describe the epidemiological and clinical features of patients with primitive adhesive capsulitis of the shoulder treated by capsular distension and then rehabilitation; to evaluate the short-, mid- and long-term efficiency of this therapeutic protocol and compare it with rehabilitation alone. This was a two-year prospective study. Sixty patients were included and divided into populations P1 (capsular distension and rehabilitation) and P2 (rehabilitation only). Assessment of the treatments' efficacy was based on the following parameters: pain on a visual analogue scale (VAS), joint motion in several axes, a simplified Constant score (functional ability) and the SF-36 quality of life score. Thirty patients (mean age: 56) underwent capsular distension. The Constant score was judged to be poor in over half of the patients. All the quality of life parameters were modified. When compared with P2, the P1 group showed a statistically significant improvement in terms of the pain score (p=0.005), anterior elevation (p=0.001), lateral elevation (p=0.005), external rotation (p=0.006) and the Constant score (p<0.001) one week after capsular distension. One year after capsular distension, this gain persisted in a statistically significant manner for all functional parameters and all SF-36 dimensions (p<0.001 for PF, RP, BP, SF and RE; p=0.01 for GH and VT and p=0.002 for MH). Our results show that capsular distension and subsequent intensive rehabilitation have a beneficial effect. This combination enables rapid, significant improvement from the first week onwards. The improvement phase lasts for one month and may hold steady for up to 12 months.


The secondary structure analysis of a potent Ser14Gly analog of antiAlzheimer peptide, Humanin, by circular dichroism.
The structure of a highly potent Ser14Gly analog of antiAlzheimer peptide, Humanin, was examined by circular dichroism (CD). The secondary structure is more disordered in water than in phosphate-buffered saline (PBS). The peptide structure in water is little dependent on both peptide concentration and temperature. On the contrary, the peptide structure was significantly different in PBS from the structure in water, which is more apparent at a higher peptide concentration and temperature. The observed different structure in PBS appears to be due to self-association of the peptide, which is enhanced by elevated temperature and, hence, via hydrophobic interactions. The wild-type Humanin also behaved similarly, i.e., it assumed a disordered structure in water but underwent conformational changes in PBS. Although high peptide concentrations for CD measurements are not encountered in vivo, the results suggest the tendency of the peptide to interact hydrophobically with other structures as well as with itself.


Longitudinal Aging Study Amsterdam COVID-19 exposure index: a cross-sectional analysis of the impact of the pandemic on daily functioning of older adults.
The aim of this study was to develop an index to measure older adults' exposure to the COVID-19 pandemic and to study its association with various domains of functioning. Cross-sectional study. The Longitudinal Aging Study Amsterdam (LASA), a cohort study in the Netherlands. Community-dwelling older adults aged 62-102 years (n=1089) who participated in the LASA COVID-19 study (June-September 2020), just after the first wave of the pandemic. A 35-item COVID-19 exposure index with a score ranging between 0 and 1 was developed, including items that assess the extent to which the COVID-19 situation affected daily lives of older adults. Descriptive characteristics of the index were studied, stratified by several sociodemographic factors. Logistic regression analyses were performed to study associations between the exposure index and several indicators of functioning (functional limitations, anxiety, depression and loneliness). The mean COVID-19 exposure index score was 0.20 (SD 0.10). Scores were relatively high among women and in the southern region of the Netherlands. In models adjusted for sociodemographic factors and prepandemic functioning (2018-2019), those with scores in the highest tertile of the exposure index were more likely to report functional limitations (OR: 2.24; 95% CI: 1.48 to 3.38), anxiety symptoms (OR: 3.14; 95% CI: 1.82 to 5.44), depressive symptoms (OR: 2.49; 95% CI: 1.55 to 4.00) and loneliness (OR: 2.97; 95% CI: 2.08 to 4.26) than those in the lowest tertile. Among older adults in the Netherlands, higher exposure to the COVID-19 pandemic was associated with worse functioning in the physical, mental and social domain. The newly developed exposure index may be used to identify persons for whom targeted interventions are needed to maintain or improve functioning during the pandemic or postpandemic.


"My Teacher Is Going to Think They're Crazy": Responses to LOPI Practices in U.S. First-Grade Classrooms.
This chapter explores how children and adults have been responding when they watch first graders in the United States using their agency in classrooms that value and permit children to Learn by Observing and Pitching In (LOPI). First, I explore how video-cued ethnography helped to capture on film practices in classrooms that support LOPI through the Agency and Young Children Project. Then, I detail what happened when I showed these films to first-grade (age 6-8) children of Latina/o immigrants, elementary school administrators, teachers, and parents as a means to elicit ideas, perspectives, and concerns about the early education of young Latina/o children of immigrants. Findings from the initial analysis indicate that deficit views of immigrant families in the United States may prevent teachers and administrators from supporting LOPI.


Risk of developing metabolic syndrome after gestational diabetes mellitus - a systematic review and meta-analysis.
A systematic review and meta-analysis were conducted to quantitatively synthesize the current evidence regarding the risk of developing metabolic syndrome (MetS) in women with a personal history of gestational diabetes mellitus (GDM), without pre-existing diabetes, compared with those without a history of GDM. Four electronic databases [MEDLINE (via PubMed), Scopus, Cochrane Library, PROSPERO] were searched for relevant literature until July 29th 2020. Cochran's Q test was applied for the assessment of heterogeneity. The random-effects model was applied by calculating the odds ratio (OR) and 95% confidence interval (CI) for each study. Publication bias was estimated with Egger's linear regression test. The results from 23 studies (10,230 pregnant women; 5169 cases, 5061 controls), indicated that women with a history of GDM had a higher risk of developing MetS compared with those without such a history (OR 3.45; 95% CI 2.80-4.25, p < 0.0001). This risk remained higher, independently of maternal age and ethnicity (although the risk was not as high in Asians; OR 2.11; 95% CI 1.27-3.52). The risk of developing MetS was even higher in studies where women with GDM had increased body mass index (BMI) compared with the controls (OR 4.14; 95% CI 3.18-5.38). The risk for developing MetS following delivery is higher in women with a history of GDM compared with women without such a history. Timely recognition and appropriate intervention are critical to halt progression to MetS and its associated morbidity.


Indicators for the Data Usage Index (DUI): an incentive for publishing primary biodiversity data through global information infrastructure.
A professional recognition mechanism is required to encourage expedited publishing of an adequate volume of 'fit-for-use' biodiversity data. As a component of such a recognition mechanism, we propose the development of the Data Usage Index (DUI) to demonstrate to data publishers that their efforts of creating biodiversity datasets have impact by being accessed and used by a wide spectrum of user communities. We propose and give examples of a range of 14 absolute and normalized biodiversity dataset usage indicators for the development of a DUI based on search events and dataset download instances. The DUI is proposed to include relative as well as species profile weighted comparative indicators. We believe that in addition to the recognition to the data publisher and all players involved in the data life cycle, a DUI will also provide much needed yet novel insight into how users use primary biodiversity data. A DUI consisting of a range of usage indicators obtained from the GBIF network and other relevant access points is within reach. The usage of biodiversity datasets leads to the development of a family of indicators in line with well known citation-based measurements of recognition.


Sleep and adverse environmental factors in sedated mechanically ventilated pediatric intensive care patients.
To document the quantity and architecture of sleep using objective electrophysiologic assessment in sedated mechanically ventilated pediatric intensive care unit patients over a 24-hr period and to investigate the effect of noise and staff interventions on sleep pattern in these subjects. Prospective observational study. Pediatric intensive care unit at a university hospital. A total of 11 patients studied between September 2000 and June 2001, with ages ranging from 3 to 21 months. All patients were intubated, mechanically ventilated, and sedated with morphine and midazolam infusions. Limited sleep polysomnograph, staff interventions, and noise levels were continuously monitored during a 24-hr period. Noise levels were consistently >48 dB(A); the highest night peak reached 103 dB(A). Staff interventions lasted for a mean of 240 (SD 90) mins in a 24-hr period. There was no significant difference in the number of interventions between day and night. Severe alterations to sleep architecture were found throughout the 24 hrs, with no diurnal variations. Active sleep was severely reduced to a mean of 3% (SD 4%; range, 0-11%) of total sleep time. There was severe sleep fragmentation as reflected by the high number (mean, 40 [SD 20]) of wake episodes. The above findings suggest a significant electrophysiologic abnormality of sleep in the pediatric intensive care unit patients. Our pediatric intensive care unit environment is characterized by both, high noise levels and frequent staff interventions. This study has several limitations and future studies are needed, with larger sample size and an attempt to manipulate the environmental factors to minimize their negative effects on sleep.


Evaluating the quality of health technology assessment reports in a developing country.
No single method of health technology assessment (HTA) can meet all the policy- and decision-making needs in a country. However, there should be minimum criteria for performing HTA worldwide, and many HTA agencies have reached a consensus on this. This study aimed to assess the quality of HTA reports in the Islamic Republic of Iran. We examined all the HTA research reports published by the Iranian HTA office up to 2020, using the International Network of Agencies for Health Technology Assessment checklist for quality assessment. A total of 97 reports were examined, of which only 10.0% provided complete and appropriate contact details for further information and 5.6% clearly stated a conflict of interest. In 87.78% of the reports, the scope of assessment was clearly determined. The quality of the reports was relatively appropriate as well as details of the sources of information and text search strategies. Some 7.8%, 74.4%, 11.1%, 8.9%, and 4.4%, respectively, of the reports considered legal aspects, economic analysis, ethical implications, social implications, and other stakeholder perspectives. We recommend that minimum standards be established for the HTA process so that healthcare policy- and decision-makers can make reliable decisions on the basis of the HTA reports.


Effects of single-lung inflation on inspiratory muscle function in dogs.
After single-lung transplantation (SLT) for emphysema, a hyperinflated (native) lung operates in parallel with a normal (transplanted) lung. The interpulmonary distribution of the changes in pleural pressure (DeltaP(pl)) during breathing, however, is unknown. To approach the problem, two endotracheal tubes were inserted in the right and left main stem bronchi of anaesthetized dogs, one lung was passively inflated, and the values of inspiratory DeltaP(pl) over the two lungs were assessed by measuring the changes in airway opening pressure (DeltaP(ao)) in the two tubes during occluded breaths. With single-lung inflation, DeltaP(ao) decreased in both lungs, but the decrease in the inflated lung was invariably larger than in the non-inflated lung; when transrespiratory pressure in the inflated lung was set at 30 cmH(2)O, DeltaP(ao) in this lung was 27.7 +/- 2.0% of the value of functional residual capacity (FRC), whereas DeltaP(ao) in the non-inflated lung was 74.4 +/- 4.5% (P < 0.001). This difference was abolished after the ventral mediastinal pleura was severed. The ribs in both hemithoraces were displaced cranially with inflation, such that the displacement in the contralateral hemithorax was 75% of that in the ipsilateral hemithorax, and parasternal intercostal activity remained unchanged. These observations suggest that in patients with SLT for emphysema (1) the inspiratory DeltaP(pl) over the transplanted lung are greater than those over the native lung and (2) this difference results primarily from the greater pressure-generating ability of the inspiratory muscles, in particular the diaphragm, on the transplanted side.


Applications of Resting State Functional MR Imaging to Neuropsychiatric Diseases.
Resting state studies in neuropsychiatric disorders have already provided much useful information, but the field is regarded as being at a relatively preliminary stage and subject to several design issues that set limits on the overall utility.


Smoothing splines approximation using Hilbert curve basis selection.
Smoothing splines have been used pervasively in nonparametric regressions. However, the computational burden of smoothing splines is significant when the sample size n is large. When the number of predictors d ≥ 2 , the computational cost for smoothing splines is at the order of O(n 3) using the standard approach. Many methods have been developed to approximate smoothing spline estimators by using q basis functions instead of n ones, resulting in a computational cost of the order O(nq 2). These methods are called the basis selection methods. Despite algorithmic benefits, most of the basis selection methods require the assumption that the sample is uniformly-distributed on a hyper-cube. These methods may have deteriorating performance when such an assumption is not met. To overcome the obstacle, we develop an efficient algorithm that is adaptive to the unknown probability density function of the predictors. Theoretically, we show the proposed estimator has the same convergence rate as the full-basis estimator when q is roughly at the order of O[n 2d/{(pr+1)(d +2)}] , where p ∈[1, 2] and r ≈ 4 are some constants depend on the type of the spline. Numerical studies on various synthetic datasets demonstrate the superior performance of the proposed estimator in comparison with mainstream competitors.


The cultural transmission of acquired variation: effects on genetic fitness.
In a cultural species individuals acquire some aspects of their phenotypes by imitating conspecifics. Presumably, cultural transmission has some adaptive function in such species. Some authors have suggested that one such function may be the ability to transmit phenotypes that have been modified by learning or some other form of phenotypic plasticity. To examine this hypothesis we have compared the genetic fitness of cultural and noncultural individuals in three different models. In each model the environment is assumed to be variable, either in space or time, and learning modifies each individual's phenotype so as to increase the individual's fitness in the local environment. Cultural individuals transmit the modified phenotype to their offspring, while noncultural individuals do not. The models are different in the following ways: two models assume a dichotomous phenotype, one in a temporally varying environment and one in a spatially varying environment; the third model assumes a quantitative phenotype in a temporally variable environment. The two models which assume a temporally varying environment yield similar results. Genetic transmission is favored in highly autocorrelated environments while cultural transmission in environments with intermediate autocorrelation. In the spatially varying model cultural transmission is always favored.


Endophytic fungi alter foraging and dispersal by desert seed-harvesting ants.
Endophytic fungi are thought to interact mutualistically with host plants by producing alkaloid metabolites that deter herbivory. Since such fungi are transmitted via seed in some grasses, the presence of endophytes may also protect plants from seed predators. We conducted seed choice experiments for two dominant seed harvesting ants, Pogonomyrmex rugosus in the Sonoran desert and Pogonomyrmex occidentalis at a higher elevation, riparian zone in Arizona, USA. Non-infected fescue (Festuca arundinacea) seeds and seeds infected with the endophytic fungus, Acremonium coenophialum, were presented to ant colonies in three different populations. Infected seeds were harvested less frequently than non-infected seed for the two populations of Pogonomyrmex rugosus but not for the population of Pogonomyrmex occidentalis. We also a conducted seed dispersal experiment for one population of Pogonomyrmex rugosus. Of the seeds that were harvested, most of the colonies discarded more infected seeds into refuse piles than expected by chance. Seeds discarded into refuse piles have greater germination success than surrounding areas. The most important interaction of endophytes and grasses may be deterrence of seed predation and enhancing the probability of germinating in favorable sites, since these processes directly increase plant fitness.


Correlating Molar Mass, π-Conjugation, and Optical Properties of Narrowly Distributed Anionic Polythiophenes in Aqueous Solutions.
Polythiophene-based conjugated polyelectrolytes (CPE) are attracting increasing attention as sensor or interface materials in chemistry and biology. While cationic polythiophenes are better understood, limited structural information is available on their anionic counterparts. Limited access to well-defined polymers has made the study of structure-property relationships difficult and clear correlations have remained elusive. By combining controlled Kumada catalyst transfer polymerization with a polymer-analog substitution, regioregular and narrowly distributed poly(6-(thiophen-3-yl)hexane-1-sulfonate)s (PTHS) with tailored chain length are prepared. Analysis of their aqueous solution structures by small-angle neutron scattering (SANS) revealed a cylindrical conformation for all polymers tested, with a length close to the contour length of the polymer chains, while the estimated radii remain too small (<1.5 nm) for extensive π-stacking of the chains. The latter is particularly interesting as the longest polymer exhibits a concentration-independent structured absorption typical of crystalline polythiophenes. Increasing the ionic strength of the solution diminishes these features as the Coulomb repulsion between the charged repeat units is shielded, allowing the polymer to adopt a more coiled conformation. The extended π-conjugation, therefore, appears to be a key parameter for these unique optical features, which are not present in the corresponding cationic polythiophenes.


[The application of the Minimum Data Set (MDS) in the surveillance of nosocomial infections].
Analysis of the application of the Minimum Data Set in the vigilance of nosocomial infection. Study of the risk of nosocomial infection according to the Deyo-Charlson Comorbidity Index. The database of the Minimum Data Set of the hospital was related with the database containing the infections collected by the Infectious Diseases Surveillance Unit of the Preventive Medicine Service for the year 1997. Surgical procedures were classified by the North American system of vigilance of nosocomial infections. The diagnoses appearing in the Deyo-Charlson Index were localised. The rates of nosocomial infection were calculated in relation to the presence of comorbidities and procedures. Not all discharges were codified (6.2%). Mortality and the rate of nosocomial infection were lower in codified discharges than in non-codified (4 and 1.5 respectively, p<0.01). Amongst the codified discharges, the rates of nosocomial infection and the surgical site are higher amongst surgery patients than in non-surgery cases according to the North American vigilance system of nosocomial infections. Nosocomial infection is associated with a higher hospital mortality. As scoring increases on the Deyo-Charlson Index, there is a rise in the rate of nosocomial infection (1.8% to 9.9%), average stay (average 14-22 days) and hospital mortality (0.2% to 17.8%). The validity of these results depends on the validity of the data gathered in the Minimum Data Set, which is in its turn determined, amongst other factors, by the quality of the Discharge Report with respect to its inclusion of diagnoses and principal and secondary procedures, and by exhaustiveness in the codification of hospital discharges.


Bortezomib-mediated proteasome inhibition as a potential strategy for the treatment of rhabdomyosarcoma.
Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood, divided into two major histological subtypes, embryonal (ERMS) and alveolar (ARMS). To explore the possibility that the proteasome could be a target of therapeutic value in rhabdomyosarcoma, we treated several RMS cell lines with the proteasome inhibitor bortezomib (Velcade or PS-341) at a concentration of 13-26 nM. RMS cells showed high sensitivity to the drug, whereas no toxic effect was observed in primary human myoblasts. In both ERMS and ARMS cells bortezomib promoted apoptosis, activation of caspase 3 and 7 and induced a dose-dependent reduction of anchorage-independent growth. Furthermore, bortezomib induced activation of the stress response, cell cycle arrest and the reduction of NF-kappaB transcriptional activity. Finally, bortezomib decreased tumour growth and impaired cells viability, proliferation and angiogenesis in a xenograft model of RMS. In conclusion, our data indicate that bortezomib could represent a novel drug against RMS tumours.


The serine protease autotransporter Tsh contributes to the virulence of Edwardsiella tarda.
The temperature-sensitive hemagglutinin (Tsh), identified as serine protease autotransporters of the Enterobacteriaceae (SPATEs) proteins, is an important virulence factor for avian-pathogenic Escherichia coli (APEC) and uropathogenic E. coli. However, little is known about the role of Tsh as a virulence factor in Edwardsiella tarda, a severe fish pathogen. In this study, we characterized the Tsh of E. tarda (named TshEt) and examined its function and vaccine potential. TshEt is composed of 1224 residues and has three functional domains typical for autotransporters. Quantitative real-time reverse transcriptase-PCR analysis showed that expression of tshEt was upregulated under conditions of high temperature, increased cell density, high pH, and iron starvation and during the infection of host cells. A markerless tsh in-frame mutant strain, TX01Δtsh, was constructed to determine whether TshEt participates in the pathogenicity of E. tarda, Compared to the wild type TX01, TX01Δtsh exhibited (i) retarded biofilm growth, (ii) decreased resistance against serum killing, (iii) impaired ability to block the host immune response, (iv) attenuated tissue and cellular infectivity. Introduction of a trans-expressed tsh gene restored the lost virulence of TX01Δtsh. The passenger domain of TshEt contains a putative serine protease (PepS) that exhibits apparent proteolytic activity when expressed in and purified from E. coli as a recombinant protein (rPepS). When used as a subunit vaccine to immunize Japanese flounder, rPepS was able to induce effective immune protection. This is the first study of Tsh in a fish pathogen, and the results suggest that TshEt exerts pleiotropic effects on the pathogenesis of E. tarda.


Negative regulation of natural killer cell in tumor tissue and peripheral blood of oral squamous cell carcinoma.
Natural killer (NK) cells are the key lymphocytes in solid tumors. Its activity is regulated by both germline encoded receptors and cytokine microenvironment. We conducted a case-control study to investigate the activation status of NK cell in oral squamous cell carcinoma (OSCC). NK cell activation was assessed in context of NK cell cytotoxicity and transcript expression of NK cell receptors (NKp46 and KIRs) and NK cell associated cytokines (IL-1β, IL-2, IL-10, IL-12β, IL-15, IL-18, IL-21, IFN-γ, TNF-α and TGF-β). The results revealed possible mechanisms involved in reduced NK cell activation in peripheral circulation: quantitative deficiency of NK cell number and lowered cytotoxicity together with qualitative NK impairments caused by--(1) decreased expression of NK activating receptor NKp46, (2) increased expression of NK suppressive cytokines--IL-10 and TGF-β and (3) induction of FOXP3(+)CTLA4(+) suppressor cells. On the other hand, in the tumor tissue, escape of NK immune surveillance appeared to be modulated by upregulation of TGF-β and IL-10 together with downregulation of NK cell activating cytokines (IL-2, IL-12β, IL-15, IL-18, IL-21 and IFN-γ) and NK receptors (NKp46 and KIRs). In addition, our study supported the earlier contention that TNF-α and IL-1β expression levels may be used as markers of malignant transformation in oral leukoplakia. In conclusion, the study provided an insight into the negative regulation of NK cell in tumor tissue and peripheral blood of OSCC patients, which can be exploited to boost the current NK cell and cytokine based immunotherapy for the treatment of oral cancer.


Effect of the R92H and A379V genotypes of platelet-activating factor acetylhydrolase on its enzyme activity, oxidative stress and metabolic profile in Chinese women with polycystic ovary syndrome.
The G994T polymorphism in platelet-activating factor acetylhydrolase (PAF-AH) gene is associated with the risk of polycystic ovary syndrome (PCOS). The aim of this study was to investigate the relationship between R92H and A379V variants of the PAF-AH gene and the risk of PCOS and to evaluate the effects of the genotypes on PAF-AH activities and clinical, metabolic and oxidative stress indexes in Chinese women. A total of 862 patients with PCOS based on the Rotterdam consensus criteria and 750 control women from a population of Chinese Han nationality in the Chengdu area were studied from 2006-2015. PAF-AH genotypes were determined by PCR and restriction fragment length polymorphism analysis. Plasma PAF-AH, high-density lipoprotein (HDL)-associated PAF-AH (H-PAF-AH) and apolipoprotein (apo) B-containing lipoprotein-associated PAF-AH (apoB-PAF-AH) activities were measured using the trichloroacetic acid precipitation procedure with PAF C-16 as a substrate. Circulating markers of oxidative stress, including serum total oxidant status, total antioxidant capacity, oxidative stress index and malondialdehyde levels, and clinical and metabolic parameters were also analyzed. No significant differences were observed in the frequencies of R92H and A379V genotypes and alleles of the PAF-AH gene between PCOS and control groups (P > 0.05). Compared with patients with the 92RR genotype, patients with H allele of R92H (RH + HH genotype) had significantly higher plasma PAF-AH and apoB-PAF-AH activities (P < 0.05) and tended to exhibit increased H-PAF-AH activity (P = 0.063) after adjusted for age and BMI. However, when serum LDL-C, HDL-C, TG and HOMA index were added as covariates, the comparisons no longer remained statistical significance (P > 0.05). There were no significant differences in clinical, hormonal, metabolic and circulating oxidative stress parameters and the frequencies of PAF-AH G449T genotype according to PAF-AH R92H or A379V genotyping in patients with PCOS and control women. There were no significant associations between R92H and A379V variants of PAF-AH gene and risk of PCOS in Chinese women. The increased plasma PAF-AH and apoB-PAF-AH activities in patients with H allele of R92H are related to the R92 → H variation, changes in plasma lipoprotein levels, insulin resistance, aging, and gaining weight and thus may be involved in the pathogenesis of PCOS and the increased risks of future cardiovascular diseases.


Pressure reversal of the depressant effect of ethanol on spontaneous behavior in rats.
This study deals with the interaction between high pressure and a sub-hypnotic dose of ethanol in rats. Male Sprague-Dawley rats were given either ethanol 1.5 g/kg or saline IP and subsequently exposed to 1 atmosphere absolute pressure (ATA) air or to 1, 12, 24 or 48 ATA of helium-oxygen (heliox). The gas temperature was adjusted to offset ethanol and helium-induced hypothermia. Ethanol induced a characteristic unsteady pattern of locomotion which was completely reversed at 48 ATA, partially reversed at 24 ATA, but not affected at 12 ATA. Other behavioral effects of ethanol such as depression of total motor activity and rearing were similarly affected. Blood and brain concentrations of ethanol in the pressure groups did not differ significantly from concentrations measured in the 1 ATA groups. A similar pattern of reversal was observed whether the compression was initiated 4, 10 or 16 min after injection. These results show that hyperbaric exposure antagonizes the depressant effect of ethanol on spontaneous behavior in rats. This antagonism does not appear to be due to changes in ethanol distribution or elimination.


Intrinsic proteins of the intestinal microvillus membrane. Iodonaphthylazide labeling studies.
Isolated brush border membranes of the intestinal epithelial cell were labeled with a hydrophobic photoactive compound [125U]iodonaphthylazide. High incorporation of the radioactive naphthylazide was noted for molecular weight bands of 99 000, 86 000, 65 000, 54 000 and 30 000. Minimal labeling occurred in the higher bands of 300 000, 135 000, 125 000 and 17 000. The iodonaphthylazide label was not removed by extensive papain digestion whereas chloramine T iodinated membranes released radioactivity under the same conditions. Neither enzymatic nor transport activities were inhibited by the presence of iodonaphthylazide or the irradiation process. On the basis of the presented data it is concluded that the iodonaphthylazide unspecifically labels those portions of membrane proteins which are inserted into the lipid bilayer matrix.


Utilization of follow-up specimens from viremic blood donors to assess the value of west nile virus immunoglobulin G avidity as an indicator of recent infection.
The value of West Nile virus immunoglobulin G avidity for distinguishing recent from past infection was investigated using 348 follow-up specimens from 170 viremic blood donors. Low avidity accurately indicated infection within the previous 4 months. However, due to rapid avidity maturation in some individuals, high avidity did not accurately indicate past infection.


Hypoxia promotes the tolerogenic phenotype of plasmacytoid dendritic cells in head and neck squamous cell carcinoma.
We aim to review the roles of plasmacytoid dendritic cells (pDCs) in head and neck squamous cell carcinoma (HNSCC) and explore the effects of hypoxia on the tolerogenic transformation of pDCs. pDCs, best known as professional type I interferon-secreting cells, play key roles in immune surveillance and antitumor immunity. Recently, pDCs have been shown to be tolerogenic and correlate with poor prognosis in a variety of cancers, including HNSCC. However, it remains unclear what drives the tolerogenic transformation of pDCs in the HNSCC microenvironment. Hypoxia, a prominent hallmark of the tumor microenvironment (TME) of HNSCC, can interfere with multiple immune cells and establish an immunosuppressive TME. In this review, we summarize the antitumor and protumor functions of pDCs, explore the effects of hypoxia on the migration and maturation of pDCs, and discuss related mechanisms in HNSCC. pDCs mainly display protumor functions in HNSCC. The hypoxic TME in HNSCC can enhance the migration of pDCs and inhibit the differentiation and maturation of pDCs, promoting the tolerogenic phenotype of pDCs.


Electroacupuncture preconditioning reduces ROS generation with NOX4 down-regulation and ameliorates blood-brain barrier disruption after ischemic stroke.
Electroacupuncture (EA) is a modern application based on combination of traditional manual acupuncture and electrotherapy that is frequently recommended as an adjuvant treatment for ischemic stroke. EA preconditioning can ameliorate blood-brain barrier (BBB) dysfunction and brain edema in ischemia-reperfusion injury; however, its mechanism remains unclear. This study investigated the preventive effects of EA preconditioning, particularly on BBB injury, followed by a transient middle cerebral artery occlusion (MCAO) model in mice. Mice were treated with EA (20 min) at Baihui (GV20) and Dazhui (GV14) acupoints once a day for 3 days before ischemic injury. Infarct volume, neurological deficits, oxidative stress, Evans blue leakage and brain edema were evaluated at 24 h after ischemia-reperfusion injury. EA preconditioning significantly decreased infarct volume and improved neurological function even after ischemic injury. In addition, both Evans blue leakage and water content were significantly reduced in EA preconditioned mice. Whereas the expression of tight junction proteins, ZO-1 and claudin-5, were remarkably increased by EA preconditioning. Mice with EA preconditioning showed the reduction of astrocytic aquaporin 4, which is involved in BBB permeabilization. In addition, we found that EA preconditioning decreased reactive oxygen species (ROS) in brain tissues after ischemic injury. The expression of NADPH oxidase 4 (NOX4), not NOX2, was significantly suppressed in EA preconditioned mice. These results suggest that EA preconditioning improve neural function after ischemic injury through diminishing BBB disruption and brain edema. And, the reduction of ROS generation and NOX4 expression by EA preconditioning might be involved in BBB recovery. Therefore, EA may serve as a potential preventive strategy for patients at high risk of ischemic stroke.


The performance of hybrid DFT for mechanisms involving transition metal complexes in enzymes.
The accuracy of density functional theory with the B3LYP functional is reviewed for systems of relevance to transition-metal-containing enzymes. Calculated energies are commonly within 3-5 kcal/mol of the correct values; however, some exceptions have appeared in the literature and are discussed here. For example, the binding of NO and that of O(2) to metal centers have for some time been known to be underestimated. Most barriers for chemical reactions are overestimated except those involving hydrogen (or proton) transfer, which instead tend to be underestimated. A minor general improvement of the accuracy can probably be obtained by slightly reducing the amount of exact exchange in the B3LYP functional.


Synthesis, anticonvulsant and neurotoxicity evaluation of some new pyrimidine-5-carbonitrile derivatives.
A series of 2-[2-(substituted benzylidene) hydrazinyl]-4-(4-methoxyphenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile (3-16) were synthesized by refluxing 2-hydrazino-4-(4-methoxy-phenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile (2) with different substituted aromatic aldehydes in glacial acetic acid and absolute alcohol mixture (8:2). The compounds were evaluated for their anticonvulsant and neurotoxicity effect. In MES test compounds 2-[2-(4-bromo-benzylidene)-hydrazinyl]-4-(4-methoxyphenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile (5), 2-[2-(4-hydroxy-benzylidene)-hydrazinyl]-4-(4-methoxyphenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile (9), and 2-[2-(3-fluoro-benzylidene)-hydrazinyl]-4-(4-methoxyphenyl)-6-oxo-1,6-dihydro-pyrimidine-5-carbonitrile (16) were found to be highly active at a dose level of 30 mgkg(-1) at 0.5 h time interval, indicating their ability to prevent seizure spread at a relatively low dose.


Ruthenium dioxide nanoparticles as a high-capacity transducer in solid-contact polymer membrane-based pH-selective electrodes.
A new approach is presented for the design of ion selective electrodes. Ruthenium dioxide nanoparticles were incorporated into solid-contact electrodes, and their properties were studied for the case of pH-selective electrodes. The use of the RuO2 is shown to significantly improve the potentiometric response, while no redox response is observed. The use of RuO2 results in a Nernstian slope (59 mV/decade) towards hydrogen ions over a wide linear range (pH 2 to 12). The results obtained by chronopotentiometry reveal small resistance, and the capacitance is as high as 1.12 mF. This results in a good stability of the response and in a low potential drift (0.89 μV∙s-1). The electrodes exhibit properties nearly as excellent as those of a glass electrode, but they are much smaller, less fragile, and easy to use. Graphical abstractSchematic representation of the construction of the new kind of electrodes along with calibration and chronopotentiometric plots compared to non-modified GCD/H+-ISM and modified GCD/RuO2/H+-ISM electrodes, respectively. The use of ruthenium dioxide results in a wide analytical pH range (2-12) and in high electrical capacitance (1.12 mF).


The Impact of a Biopsy Based 17-Gene Genomic Prostate Score on Treatment Recommendations in Men with Newly Diagnosed Clinically Prostate Cancer Who are Candidates for Active Surveillance.
The biopsy based 17-gene GPS was clinically validated to predict the likelihood of adverse surgical pathology in men with NCCN® very low, low or low-intermediate risk prostate cancer. We performed a prospective study to assess the impact of incorporating GPS into treatment recommendations in 3 high volume urology practices. Men with newly diagnosed prostate cancer meeting specific NCCN criteria were prospectively enrolled in the trial. Biopsy tissue was analyzed. Urologists indicated treatment recommendations on questionnaires administered before and after GPS. The primary study objectives were to assess all changes in treatment modality and/or treatment intensity after GPS. A total of 158 men were included in analysis, including 35, 71 and 52 at NCCN very low, low and low-intermediate risk. Biological risk predicted by GPS differed from NCCN clinical risk alone in 61 men (39%). Overall 18% of recommendations between active surveillance and immediate treatment changed after GPS. The relative increase in recommendations for active surveillance was 24% (absolute change 41% to 51%). In 41 of 158 men (26%) modality and/or intensity recommendations changed after GPS, including 25, 14 and 2 in whom recommendation intensity decreased, increased and were equivocal, respectively. All changes were directionally consistent with GPS. The NCCN low risk group showed the greatest absolute recommendation change after GPS (37%). In 17 of 57 men (30%) the initial recommendation of radical prostatectomy was changed to active surveillance after GPS. Urologists indicated greater confidence and found that incorporating GPS was useful in 85% and 79% of cases, respectively, including when biological risk confirmed the clinical risk category. This study demonstrates that the 17-gene GPS influenced treatment recommendations among urologists and provided increased confidence in these recommendations in patients at NCCN very low to low-intermediate risk.


Validated Assessment Scales for Décolleté Wrinkling and Pigmentation.
Décolleté aging includes skin dyspigmentation, laxity, and visible wrinkling. The development of globally accepted scales for the assessment of décolleté aging is essential for aesthetic research and patient evaluation. To develop a set of grading scales for the objective assessment of décolleté aging criteria and establish the reliability and validity of these scales. To describe age-related changes to the décolleté, 3 photonumeric grading scales were created and validated: décolleté wrinkles-at rest, décolleté wrinkles-dynamic, and décolleté pigmentation-at rest. Thirteen aesthetic experts rated photographs of the décolleté of 50 women at rest and at dynamic "hand-to-elbow" positions in 2 validation sessions. Responses were analyzed to assess interrater and intrarater reliability. Interrater and intrarater reliability were both "almost perfect" (≥0.81, intraclass correlation coefficient and weighted kappa) for décolleté wrinkles-dynamic, summary score for décolleté, and estimated age. Reliability was "substantial" (0.61-0.80) for all other décolleté assessments. There was high correlation between all décolleté scales, estimated age, and estimated aesthetic treatment effort. Consistent outcomes between raters and by individual raters at different time points confirm the reliability of the décolleté grading scales, indicating that they will be a valuable tool for use in clinical research and practice.


Polymorphic differences within HLA-C alleles contribute to alternatively spliced transcripts lacking exon 5.
The HLA genes are amongst the most polymorphic in the human genome. Alternative splicing could add an extra layer of complexity, but has not been studied extensively. Here, we applied an RNA based approach to study the influence of allele polymorphism on alternative splicing of HLA-C in peripheral blood. RNA was isolated from these peripheral cells, converted into cDNA and amplified specifically for 12 common HLA-C allele groups. Through subsequent sequencing of HLA-C, we observed alternative splicing variants of HLA-C*04 and *16 that resulted in exon 5 skipping and were co-expressed with the mature transcript. Investigation of intron 4 sequences of HLA-C*04 and *16 compared with other HLA-C alleles demonstrated no effect on predicted splice sites and branch point. To further investigate if the unique polymorphic positions in exon 5 of HLA-C*04 or *16 may facilitate alternative splicing by acting on splicing regulatory elements (SRE), in-silico splicing analysis was performed. While the HLA-C*04 specific SNP in exon 5 had no effect on predicted exonic SRE, the HLA-C*16 specific exon 5 SNP did alter exonic SRE. Our findings provide experimental and theoretical support for the concept that polymorphisms within the HLA-C alleles influence the alternative splicing of HLA-C.


Aboriginal versus non-aboriginal alcoholics in an alcohol withdrawal unit.
Fifty-five Aboriginal alcoholic males were compared with ninety non-Aboriginal alcoholic males, presenting voluntarily for treatment at an alcohol withdrawal unit. Although the chronological development of excessive drinking habits was similar, significant differences in drinking patterns and social backgrounds were found. Aboriginal patients consumed more alcohol, had lower levels of education and vocational achievement and were more often homeless. However, physical condition was similar in both groups. It was suggested that treatment of both groups should be similar in the acute withdrawal phase and that there was need for more rehabilitation and after-care facilities for Aboriginal alcoholics rather than for more medical units.


MiR-497 promotes metastasis of colorectal cancer cells through Nrdp1 inhibition.
We have recently shown that Nrdp1 inhibits phosphorylation of ErB3 in colorectal cancer (CRC) cells, to suppress epidermal growth factor receptor (EGFR) signaling-stimulated MMP7 activation for CRC metastasis. In this study, we examined the control of Nrdp1 in CRC cells. We detected significant increases in miR-497 in CRC specimen, compared to paired normal colorectal tissue. Moreover, we detected a strong positive correlation between miR-497 levels and Nrdp1 levels, and a strong inverse correlation between miR-497 levels and MMP7 levels. In vitro, overexpression of miR-497 in human CRC cells significantly decreased Nrdp1 transcripts and protein, and vice versa. Moreover, overexpression of miR-497 in human CRC cells also significantly increased MMP7 transcripts, cellular protein, and secreted protein, resulting in increases in cell invasiveness in a transwell cell migration assay. Furthermore, we found that MiR-497 directly targeted 3'-UTR of Nrdp1 mRNA to inhibit its translation. Together, our data suggest that the regulation of MMP7 by Nrdp1 in CRC cells could be inhibited by miR-497 through suppressing Nrdp1 translation. Our work thus highlights a novel molecular regulatory machinery that regulates metastasis of CRC.


[Anatomy of the glenoid labrum].
Most instabilities or pain syndromes are associated with injuries or morphologic changes in the glenoid labrum complex or long head of the biceps tendon origin. The first anatomic descriptions go back to Fick in 1910 and since then many authors have described the anatomy of these structures. It was Snyder who introduced the term SLAP lesions, classifying superior, anterior, posterior labrum changes into four grades. It is still unclear whether all of the described and arthroscopically observed changes are due to a post-traumatic, acquired lesion or whether anatomic variations can be present as well. In order to elucidate this problem, 36 cadaver shoulder joints were inspected macroscopically and sectioned for microscopic evaluation. Here the glenoid could be divided into an superior and an anterior- superior area demonstrating a wide variety of morphologic labral glenoid changes, while the dorsal and inferior sectors of the glenoid showed a relatively uniform anatomy of a firm labrum-glenoid bond. Four types of biceps tendon attachments could be identified similar to the description given by Vangsness. In addition, a variety of anterior-superior changes could be found. The sublabral hole as described by Esch in the clinical setting was found to be a physiologic variant. Precise knowledge of the anatomic morphology of the normal glenoid in its variations seems to be necessary to understand variants and allow for distinguishing between physiologic anatomic variants and pathoanatomic changes in imaging and the clinical setting.


Management of non-small-cell lung cancer: recent developments.
Non-small-cell lung cancer is one of the leading causes of deaths from cancer worldwide. Therefore, improvements in diagnostics and treatments are urgently needed. In this review, we will discuss the evolution of lung cancer staging towards more non-invasive, endoscopy-based, and image-based methods, and the development of stage-adapted treatment. A special focus will be placed on the role of novel surgical approaches and modern radiotherapy strategies for early stages of disease, the effect of multimodal treatment in locally advanced disease, and ongoing developments in the treatment of patients with metastatic disease. In particular, we will include an emphasis on targeted therapies, which are based on the assumption that a treatable driver mutation or gene rearrangement is present within the tumour. Finally, the position of lung cancer treatment on the pathway to personalised therapy will be discussed.


Morbidity of patients with analgesic-associated nephropathy on regular dialysis treatment and after renal transplantation.
In a retrospective study, patients with end-stage renal failure from analgesic-associated nephropathy - 55 on regular dialysis treatment and 12 after renal transplantation - were under observation for 57 and 33 months, respectively. Of these 34 patients on chronic hemodialysis had suffered from different cardiovascular diseases. Hypertriglyceridemia was diagnosed in 62% of the patients, arterial hypertension requiring antihypertensive therapy in 44%. In three patients (5%) carcinoma of the urinary bladder were diagnosed. The leading causes of death in 21 patients included cardiovascular diseases (29%), hyperkalemia (19%), sepsis, and malignant tumors (14% each). Rejection occurred in 3 out of 12 patients after renal transplantation. Again, cardiovascular morbidity was high (58%) with coronary heart disease being present in 33% of the patients. Hypertriglyceridemia was observed in 5 out of 6 patients, antihypertensive therapy was needed in 50%. One patient died from primary pulmonary hypertension.


Rapid efficacy of highly active antiretroviral therapy in a case of HIV myelitis.
An HIV-seropositive patient with severe immunodepression was diagnosed as having HIV myelitis. Plasma and cerebrospinal fluid (CSF) HIV-RNA PCR were, respectively, 4.11 and 5.19log(10). After 1 month of treatment with highly active antiretroviral therapy (HAART), there was clinical recovery and both plasma and CSF HIV viral load had decreased considerably. This dramatic improvement was associated with a high concentration of antiviral drugs in the CSF, suggestive of the direct efficacy of HAART on HIV myelitis.


Physician Assistants--a solution to wait times in Canada?
Access to medical care is limited in most of Canada, and the population often endures lengthy waiting times to see a physician. The use of new and varied health care providers has been suggested as a means to alleviate the shortage of physicians. This paper reviews the history and role of the Physician Assistant (PA), both in Canada and internationally, and outlines the clinical competencies currently held by this provider to fill the role of a physician extender in our country. PAs' experiences are reported in the Canadian Forces (CF), where they have been employed for many years, and in Manitoba, where they are used as surgical assistants. The potential for the PA to be incorporated into our provincial health care systems will be considered in light of common barriers to Health Human Resources (HHR) strategic implementation.


Efficacy of Interpretation Bias Modification in Patients With Chronic Pain.
Patients with chronic pain demonstrate interpretational bias to pain, and models of pain suggest interpretational bias affects subsequent pain experience. This study developed an interpretation bias modification for pain (IBM-P) and examined its efficacy. A total of 48 patients with chronic pain were recruited and randomly assigned to either the training group (n = 24) or the control group (n = 24). Interpretational bias, negative emotions, and attentional bias to pain-related stimuli were assessed before and after conducting IBM-P. The main results indicated that the training group showed less interpretational bias and negative emotions after IBM-P than the control group. The training group also gazed at neutral words longer than at "new" affective pain words after IBM-P than they did prior to the intervention. Furthermore, significant mediating effects of postinterpretational bias were found in the relationship between the group type and postnegative emotions and postdwell time bias. These results suggest that IBM-P can modify interpretational bias which leads to changes in negative emotions and attentional bias. Future research is needed to confirm the effect of modifying interpretational bias and its clinical utility in the field of pain management. PERSPECTIVE: This article investigated the efficacy of IBM-P and suggested that modifying interpretational bias is followed by changes in negative emotions and attentional bias. These findings may help health professionals understand the role of interpretational bias in chronic pain and encourage the potential use of IBM in pain management.


Effects and permanency of the training program "communication with cancer patients" on the opinions of students.
Learning to develop the doctor-patient relationship is very important in the treatment of patients with cancer. We aim to train our students in the early years of study about this subject with a course on the patient-doctor communication, prepared for third year students. One hundred fifty-four third year students participated in our study during the 2006-2007 academic years. The same questionnaire was given to the students in the 2009-2010 academic year; their sixth year of study. The rate of return for the questionnaire is 88.7%. Based on this study, we have the opinion that the training given in the third year is beneficial; however, the efficacy of the training diminishes with the advancing years, and therefore, the length of this training should be increased in the upper classes and additional hours should be added.


Percutaneous Cardiac Chambers and Pulmonary Artery Aspiration.
The clinical guidelines and current practice in the field of removable cardiovascular pathologies are not aligned and are in fluctuation. The purpose of this review manuscript is to propose adjustments and forecast changes in clinical practice in this field ahead of irrefutable evidence. Percutaneous aspiration devices may be used in case of pulmonary embolism, endocarditis, cardiac thrombi, and tumors. The rationale of treatment includes prevention of emboli, endocarditis debulking and modification, sampling of tissue, and salvage therapy. We are describing the contemporary treatments that are occurring in practice outside and above guidelines. The current standard therapy for the above-mentioned entities is not supported by robust data. Moreover, evidence suggesting priority for the use of percutaneous aspiration devices as first-line therapy-before turning to or in lieu of surgery or thrombolysis-continues to accumulate. However, guidelines still mention percutaneous aspiration only as an alternative to standard treatment. In the current review, we discuss the pathophysiology that supports percutaneous cardiac and pulmonary artery aspiration, the commonly used devices for that purpose, their clinical evidence, and accordingly propose a modified approach to patient management. In addition, this review highlights fluid dynamic principles important in matter extraction in order to better define the utility of catheter-based technologies in different cardiovascular territories. The target diseases encompassed in this review are pulmonary embolism, cardiac masses, and vegetations.


Predisposing factors in diabetic emergencies.
Diabetes mellitus is a lifelong condition which requires acceptance, understanding and some degree of lifestyle discipline in order to maintain glycaemic equilibrium. The situation is complicated by the fact that poor glycaemic control is not necessarily symptomatic. Routines recommended by health professionals may not always be acceptable to the recipients or may be difficult to translate into the individual's framework of daily living. Dramatic emergencies may arise from a complex interrelated multiplicity of actions or omissions, or for reasons outside the control of the patient. Most emergencies are technically preventable. An attempt should be made by Accident and Emergency (A & E) staff to determine the cause. Referral to the diabetes specialist team is usually indicated.


Computed tomography of the aortopulmonary window: normal anatomy and pathology.
There can be many diagnostic pitfalls in the evaluation of the aortopulmonary window by chest radiography alone. Large masses that are easily identified on computed tomography may be essentially undetectable; also the appearances of aortopulmonary window lesions on conventional radiographs are frequently nonspecific, or may even be misleading. Careful evaluation of this region of the mediastinum is important because the aortopulmonary window is commonly the site of adenopathy secondary to neoplastic and inflammatory diseases, as well as vascular pathology. After review of the normal anatomy of the aortopulmonary window, seven selected cases are presented that demonstrate the importance of computed tomography in arriving at the correct diagnosis when conventional chest radiographs are nonspecific or equivocal.


Effects of a nonpeptide vasopressin antagonist (OPC-21268) on cytosolic Ca2+ concentration in vascular and cardiac myocytes.
A selective V1 antagonist, 1-(1-[4(3-acetylaminopropoxy)benzoyl]-4-piperidyl)-3,4-dihydro-2(1 H)- quinolinone (OPC-21268), which is nonpeptide and orally effective, has been recently synthesized. We studied the effects of vasopressin and OPC-21268 on cell contraction with a video motion detector and cytosolic Ca2+ concentration ([Ca2+]i) by using indo-1 in cultured rat vascular smooth muscle cells and cultured chick embryo ventricular myocytes. Exposure of cultured vascular smooth muscle cells to vasopressin (1-100 nM) dose-dependently produced an initial transient increase (from control level [Ca2+]i of 133.6 +/- 10.9 nM to peak [Ca2+]i of 842.7 +/- 172.8 nM at 100 nM vasopressin, p less than 0.01) and then a small sustained increase in [Ca2+]i. After pretreatment of vascular smooth muscle cells with 1 microM OPC-21268, the effects of 100 nM vasopressin on [Ca2+]i were abolished. Exposure of ventricular myocytes to 100 nM vasopressin slightly but significantly decreased peak systolic cell position (-8.7 +/- 3.7%, p less than 0.05) and also produced reductions in peak systolic [Ca2+]i (from 962.2 +/- 76.4 to 751.2 +/- 70.5 nM, p less than 0.01) within 30 seconds. Pretreatment of ventricular myocytes with OPC-21268 (1 microM) completely suppressed vasopressin-induced changes in peak systolic cell position and [Ca2+]i. These results suggest that vasopressin may increase vascular tone and may also cause a direct negative inotropic effect via V1 receptors and that this orally active V1 antagonist (OPC-21268) may have potential clinical usefulness.


Why leading is (almost) as important as winning.
Competitions in sports, business, or politics often provide perceivers with cumulative standings over time. Recent research suggests that people fail to accurately update their impressions from cumulative observations as they are influenced by previous standings. This cumulative redundancy bias (CRB) implies that competitors that are leading during a competition will receive more favorable evaluations, over and beyond their eventual success or failure. While the CRB has far-reaching implications, its underlying mechanisms are not fully understood. We present data from four experiments in which we modified the standard CRB task by adding a step-by-step procedure to track the dynamics of perceivers' impressions during the competition. We also manipulated the length of the competition and tested different possible explanations for the CRB. Results suggest that the CRB is a robust phenomenon that constitutes an actual bias and that is best explained by an additive effect of cumulative redundancy.


Decreased admissions and change in arrival mode in patients with cerebrovascular events during the first surge of the COVID-19 pandemic.
Investigating clinical characteristics of patients presenting with cerebrovascular events during the pandemic may provide valuable insight into further understanding the phenomenon of decreased stroke admissions during the COVID-19 pandemic. Data of patients presenting with a cerebrovascular event to the emergency department during weeks 12-17/2020 were compared to data from the respective weeks in 2019. A significant reduction in the number of admissions by 35.9% (p = 0.005) was observed during the COVID-19 epoch. In addition, significantly more patients arrived by ambulance during the COVID-19 epoch (2019: 75.7%, 2020: 94.2%; p = 0.001). Our data may have implications as to how campaigns raising awareness for serious medical conditions in the context of the pandemic should be framed.


Corrigendum: Yield of the electrophysiological study in patients with new-onset left bundle branch block after transcathether aortic valve replacement: The PR interval matters.
[This corrects the article DOI: 10.3389/fcvm.2022.910693.].


Hospital budget and rate regulation: why Colorado failed.
A state legislature created an agency to develop a system for regulating hospital budgets and rates, then terminated it two years later. The agency's chairman analyzes the Colorado experience and what can be learned from it.


The menstrual cycle and blood loss during laparoscopic myomectomy.
Operative morbidity of laparoscopic myomectomy largely relates to the potential for intraoperative blood loss. We sought to determine whether blood loss varies according to the menstrual cycle. A retrospective study of 268 women who underwent a laparoscopic myomectomy from 2007 to 2012. Patients were categorized into five menstrual groups: follicular phase, luteal phase, oligomenorrheic or amenorrheic on hormonal therapy, postmenopausal or other. Patient and procedure characteristics were compared for the follicular phase group, luteal phase group, and hormonal therapy group. The estimated blood loss was compared across the five groups using a regression model. A total of 268 women underwent a laparoscopic myomectomy: 108 (40.3%) were in the follicular phase, 92 (34.3%) were in the luteal phase, 44 (16.4%) were on hormonal therapy, nine (3.4%) were postmenopausal, and 15 (5.6%) could not be classified. Baseline patient characteristics were similar between the groups with the exception of endometriosis. Geometric mean estimated blood loss was 91.9 mL in the follicular phase group, 108.7 mL in the luteal phase group, 114.1 mL in the hormonal therapy group, and 39.8 mL in the postmenopausal group. There was no significant difference in the geometric mean estimated blood loss when comparing the follilcuar phase, luteal phase, and hormonal phase groups (p = 0.41). Upon adjusted multivariable analysis of all five menstrual groups, there was also no difference in estimated blood loss. Intraoperative blood loss during laparoscopic myomectomy does not vary significantly with the phase of the menstrual cycle.


Genetic diversity and natural selection of Plasmodium vivax reticulocyte invasion genes in Ecuador.
Knowledge of the diversity of invasion ligands in malaria parasites in endemic regions is essential to understand how natural selection influences genetic diversity of these ligands and their feasibility as possible targets for future vaccine development. In this study the diversity of four genes for merozoite invasion ligands was studied in Ecuadorian isolates of Plasmodium vivax. Eighty-eight samples from P. vivax infected individuals from the Coast and Amazon region of Ecuador were obtained between 2012 and 2015. The merozoite invasion genes pvmsp-1-19, pvdbpII, pvrbp1a-2 and pvama1 were amplified, sequenced, and compared to the Sal-1 strain. Polymorphisms were mapped and genetic relationships between haplotypes were determined. Only one nonsynonymous polymorphism was detected in pvmsp-1-19, while 44 nonsynonymous polymorphisms were detected in pvdbpII, 56 in pvrbp1a-2 and 33 in pvama1. While haplotypes appeared to be more related within each area of study and there was less relationship between parasites of the coastal and Amazon regions of the country, diversification processes were observed in the two Amazon regions. The highest haplotypic diversity for most genes occurred in the East Amazon of the country. The high diversity observed in Ecuadorian samples is closer to Brazilian and Venezuelan isolates, but lower than reported in other endemic regions. In addition, departure from neutrality was observed in Ecuadorian pvama1. Polymorphisms for pvdbpII and pvama1 were associated to B-cell epitopes. pvdbpII and pvama1 genetic diversity found in Ecuadorian P. vivax was very similar to that encountered in other malaria endemic countries with varying transmission levels and segregated by geographic region. The highest diversity of P. vivax invasion genes in Ecuador was found in the Amazonian region. Although selection appeared to have small effect on pvdbpII and pvrbp1a-2, pvama1 was influenced by significant balancing selection.


Two new species of Anaglyptus Mulsant from China (Coleoptera: Cerambycidae: Cerambycinae: Anaglyptini).
Two new Anaglyptus species, Anaglyptus mucheni sp. nov. and Anaglyptus zhangjunqii sp. nov., are described and illustrated from China.


Peri- and Postoperative Outcomes for Obstructive Sleep Apnoea Patients after Bariatric Surgery-a Systematic Review and Meta-analysis.
Obstructive sleep apnoea (OSA) is prevalent among patients undergoing bariatric surgery. Previous studies have reported a higher risk of complications, ICU admission and longer length of stay in patients with OSA following surgery. However, clinical outcomes following bariatric surgery are unclear. The hypothesis is that patients with OSA will have an increased risk of these outcome measures after bariatric surgery. A systematic review and meta-analysis were performed to answer the research question. Searches for bariatric surgery and obstructive sleep apnoea were performed using PubMed and Ovid Medline. Studies which compared OSA and non-OSA patients undergoing bariatric surgery and used outcome measures that included length of stay, risk of complications, 30-day readmission and need for ICU admission were selected for the systematic review. Comparable datasets from these studies were used for the meta-analysis. Patients with OSA are at greater risk of complications after bariatric surgery (RR = 1.23 [CI: 1.01, 1.5], P = 0.04), driven mostly by an increased risk of cardiac complications (RR = 2.44 [CI: 1.26, 4.76], P = 0.009). There were no significant differences between the OSA and non-OSA cohorts in the other outcome variables (respiratory complications, length of stay, 30-day readmission and need for ICU admission). Following bariatric surgery, patients with OSA must be managed carefully due to the increased risk of cardiac complications. However, patients with OSA are not more likely to require a longer length of stay or readmission.


Carnitine deficiency and L-carnitine supplementation in lysinuric protein intolerance.
The aim of the study was to investigate the prevalence and mechanisms of development of carnitine deficiency in patients with lysinuric protein intolerance (LPI). In our cohort of 37 Finnish patients with LPI, 8 (8-52 years of age) have been diagnosed with hypocarnitinemia. Their free and total serum carnitine levels, acyl carnitine profiles, renal function, diet, and medication were compared with the data from 8 age- and sex-matched patients with LPI not treated with carnitine supplementation. In patients with LPI, hypocarnitinemia was strongly associated with female sex, renal insufficiency, and the use of ammonia-scavenging drugs. Of the 8 hypocarnitinemic patients, 3 complained of muscle weakness, and their symptoms disappeared during carnitine supplementation. Oral lysine supplementation did not correct hypocarnitinemia in our patients. The patients with LPI are at considerable risk for carnitine deficiency. Supplementation of hypocarnitinemic LPI patients with oral L-carnitine improved serum total carnitine values, but the ratio of free and total carnitine remained subnormal in all supplemented patients except one. Furthermore, decreased ratio of free and total serum carnitine was common even in LPI patients with normal total serum carnitine concentration.


Versatile isocratic high-performance liquid chromatographic assay for propranolol and its basic, neutral and acidic metabolites in biological fluids.
A comprehensive high-performance liquid chromatographic method was developed for quantitating propranolol and its known metabolites in serum, bile and urine. Analysis was performed before and after incubation of the samples with beta-glucuronidase-arylsulfatase to quantitate both free and conjugate forms of the oxidative metabolites. Fractionation of the basic, neutral and acidic metabolites was achieved by differential pH solvent extraction. The basic and neutral metabolites were extracted from the biological samples at pH 10.5 with 2% n-butanol in dichloromethane. Additional clean-up of the basic fraction by back-extraction into dilute acid was needed for those samples that were subjected to enzymatic hydrolysis. The original aqueous sample was titrated with acid to pH 1, followed by extraction of the remaining acidic metabolites into either n-butanol-dichloromethane (with unhydrolyzed serum) or carbon tetrachloride (with all other samples). Chromatographic separation of the metabolites in the different extracts was achieved on a reversed-phase C18 column, using a single isocratic mobile phase consisting of 0.044 M pH 2.7 phosphate buffer, tetrahydrofuran, methanol and acetonitrile, with the addition of n-butylamine as a competing base to control retention volume and peak shape. Detection and quantitation of propranolol and its metabolites in the low nanogram to sub-nanogram range was afforded by fluorescence at a low UV excitation wavelength. The coefficients of variation for replicate assay of spiked samples were uniformly less than 6% for all the analytes.


The efficacy of chlordimeform for the control of the northern fowl mite, Ornithonyssus sylvarium (Canestrini and Fanzago) (Acarina, Dermanyssidae).
Chlordimeform applied as a 0.06% low pressure spray controlled the northern fowl mite (NFM) for at least 90 days. Tetrachlorvinphos applied as a 0.5% low pressure spray was equally effective. Chi square analysis of NFM population estimates indicated that NFM populations on the untreated control birds stayed essentially the same throughout the test, whereas, the NFM populations on both acaricide-treated groups were significantly lowered by the seventh day of the test (P less than .01). Chlordimeform seemed to work more slowly than tetrachlorvinphos in controlling NFM.


Electrode and brain modeling in stereo-EEG.
To quantify the perturbation due to the presence of a measuring depth electrode on the intracranial electric potential distribution, and to study the effect of the heterogeneity and anisotropy of the brain tissues' electric conductivity. The governing differential equations are solved with the Boundary Elements Method to compute the perturbation on the electric potential distribution caused by the presence of the measuring electrode, and with the Finite Elements Method to simulate measurements in an heterogeneous anisotropic brain model. The perturbation on the measured electric potential is negligible if the source of electric activity is located more than approximately 1mm away from the electrode. The error induced by this perturbation in the estimation of the source position is below 1mm in all tested situations. The results hold for different sizes of the electrode's contacts. The effect of the brain's heterogeneity and anisotropy is more important. In a particular example simulated dipolar sources in the gray matter show localization differences of up to 5mm between homogeneous isotropic and heterogeneous anisotropic brain models. It is not necessary to include detailed electrode models in order to solve the stereo-EEG (sEEG) forward and inverse problems. The heterogeneity and anisotropy of the brain electric conductivity should be modeled if possible. The effect of using an homogeneous isotropic brain model approximation should be studied in a case by case basis, since it depends on the electrode positions, the subject's electric conductivity map, and the source configuration. This simulation study is helpful for interpreting the sEEG measurements, and for choosing appropriate electrode and brain models; a necessary first step in any attempt to solve the sEEG inverse problem.


Mammalian aquaglyceroporin function in metabolism.
Aquaglyceroporins are integral membrane proteins that are permeable to glycerol as well as water. The movement of glycerol from a tissue/organ to the plasma and vice versa requires the presence of different aquaglyceroporins that can regulate the entrance or the exit of glycerol across the plasma membrane. Actually, different aquaglyceroporins have been discovered in the adipose tissue, small intestine, liver, kidney, heart, skeletal muscle, endocrine pancreas and capillary endothelium, and their differential expression could be related to obesity and the type 2 diabetes. Here we describe the expression and function of different aquaglyceroporins in physiological condition and in obesity and type 2 diabetes, suggesting they are potential therapeutic targets for metabolic disorders.


Identification of novel allele on the locus 47z (DXYS5) in the Korean population.
Two homogenous sequences of 47z (DXYS5) are located on the X (DXYS5X) and Y (DXYS5Y) chromosomes, and these are known to be useful polymorphic markers for tracing male-specific gene flow such as the migration routes of human populations. Using the 47z/StuI PCR-RFLP system, we found a novel allele which showed two bands, in contrast to the previous two allele types, one band (Y1) and three bands (Y2). This means that copies of PCR products derived from both the DXYS5X and DXYS5Y loci were clearly cut by the StuI enzyme, implying that the DXYS5X locus of the X chromosome is polymorphic. Allelic frequencies examined in 267 male Korean individuals showed that 95.8% had Y1, 3.4% Y2, and 0.8% had the novel allele. Our findings should contribute to a better understanding of genetic polymorphism on X and Y chromosomes, the molecular evolution mechanism of sex chromosomes, and how the migration route of Koreans is related to those of other East Asian populations.


New Concepts in Therapeutic Manipulation of HIV-1 Transcription and Latency: Latency Reversal versus Latency Prevention.
Antiretroviral therapy (ART) has dramatically improved the prognosis for people living with HIV-1, but a cure remains elusive. The largest barrier to a cure is the presence of a long-lived latent reservoir that persists within a heterogenous mix of cell types and anatomical compartments. Efforts to eradicate the latent reservoir have primarily focused on latency reversal strategies. However, new work has demonstrated that the majority of the long-lived latent reservoir is established near the time of ART initiation, suggesting that it may be possible to pair an intervention with ART initiation to prevent the formation of a sizable fraction of the latent reservoir. Subsequent treatment with latency reversal agents, in combination with immune clearance agents, may then be a more tractable strategy for fully clearing the latent reservoir in people newly initiating ART. Here, we summarize molecular mechanisms of latency establishment and maintenance, ongoing efforts to develop effective latency reversal agents, and newer efforts to design latency prevention agents. An improved understanding of the molecular mechanisms involved in both the establishment and maintenance of latency will aid in the development of new latency prevention and reversal approaches to ultimately eradicate the latent reservoir.


Spontaneous rupture of trachea treated conservatively: A case report.
Spontaneous rupture of the trachea is a rare, life-threatening condition. Spontaneous rupture associated with corticosteroid use has been rarely reported in the literature. We report a case of a 17-year-old male, a known case of nephrotic syndrome managed by corticosteroid treatment, who presented with diffuse neck and chest swelling after forceful coughing resulting in a spontaneous rupture of the trachea. The diagnosis was established using radiological imaging. The patient was managed conservatively with significant improvement and was discharged shortly. Prolonged use of corticosteroids may lead to spontaneous rupture of the trachea due to tracheal wall weakness. Radiological imaging followed by bronchoscopy can be used to confirm the diagnosis. Management can either be conservative or surgical, depending on the case. Conservative treatment by pain relief, intravenous fluids, and antibiotics should be considered an alternative to surgery in selected patients.


Distress and the religious and spiritual coping of Brazilians living with cancer: A cross-sectional study.
To analyze the relationship between the subjective experience of distress and the use of religious and/or spiritual coping by adult chemotherapy patients. A cross-sectional study conducted in 2018, with 100 patients undergoing chemotherapy. The data were collected through three tools: a characterization form, the Inventory of Subjective Distress Experiences in Illness, and the Brief Religious/Spiritual Coping Scale. The analysis was based on descriptive and inferential statistics, using the Spearman correlation test (p < 0.05), ANOVA, the Kruskall-Wallis test, and negative binomial regression. A low level of overall, physical, existential, psychological and sociorelational distress was observed. The dimension of positive distress experiences, however, was above the intermediate level in the scale. With respect to coping, use of positive and negative facets was moderate and low, respectively. Very weak positive correlations were noted between negative coping and physical, existential, and overall distress. The regression analysis indicated a higher risk of distress with increasing age and greater negative religious coping. In this sample, higher means were found in the dimension of positive distress experiences; negative coping, although utilized less, had greater potential to exacerbate distress after adjustment for age, in contrast to that expected for positive coping, which did not manifest significant effects in alleviating it.


Improving weight maintenance using virtual reality (Second Life).
Compare weight loss and maintenance between a face-to-face (FTF) weight management clinic and a clinic delivered via virtual reality (VR). Participants were randomized to 3 months of weight loss with a weekly clinic delivered via FTF or VR and then 6 months' weight maintenance delivered with VR. Data were collected at baseline and 3 and 6 months for weight and process variables. Twenty overweight and obese individuals (31.1 ± 3.6 years of age; body mass index, 32.8 ± 5.1; 85% females; 20% minorities) responded to advertisement and met inclusion criteria. Diets (1,200-1,800 kcal/d) used prepackaged meals, fruits and vegetables, and physical activity (300 min/wk). Weight loss was significantly greater for FTF at 10.8% compared with 7.6% for VR (P < .05). However, weight maintenance was significantly greater for VR at 14.0% compared with 9.5% for FTF (P < .05). Virtual reality compares favorably with FTF for weight loss and may facilitate greater weight maintenance.


Outcomes of endovascular treatment in acute ischemic stroke patients with current malignancy.
The role of endovascular recanalization in the treatment of cancer patients with acute stroke remains elusive. Our study aimed to investigate the clinical and imaging outcomes of endovascular recanalization treatment in patients with acute large vessel occlusion stroke who had active cancer. We retrospectively reviewed the data from our stroke registry from January 2011 to September 2016 which was collected prospectively. Acute stroke patients with large artery occlusion in the anterior circulation who had active cancer were identified. Baseline clinical characteristics and postprocedural and long-term clinicoradiological outcomes were evaluated. A good outcome was defined as a 90-day modified Rankin Scale score of 0 to 2. Outcomes were also compared with those of non-malignancy patients who had received endovascular therapy during the same period. A total of 378 ischemic stroke patients received endovascular treatment, of whom 27 (7.14 %) had current malignancy. In patients with current malignancy, a low baseline NIHSS score and male sex were associated with functional independency at 90 days. When comparing with non-malignancy patients, no significant differences in the proportions of patients with symptomatic intracranial hemorrhage (11.1% vs 16.2%, p = 0.60) and good functional outcome (37.0% vs 39.6%, p = 0.84) were found in the malignancy patients. Endovascular treatment might be a feasible therapeutic option for acute ischemic stroke patients with current malignancy when candidates are selected carefully because the outcomes were not differed. Future large-scale prospective studies are necessary.