Diagnostic Accuracy of 4 Commercially Available Semiautomatic Packages for Carotid Artery Stenosis Measurement on CTA.
Semiautomatic measurement of ICA stenosis potentially increases observer reproducibility. In this study, we assessed the diagnostic accuracy and interobserver reproducibility of a commercially available semiautomatic ICA stenosis measurement on CTA and estimated the agreement among different software packages. We analyzed 141 arteries from 90 patients with TIA or ischemic stroke. Manual stenosis measurements were performed by 2 neuroradiologists. Semiautomatic measurements by using 4 methods (3mensio and comparable software from Philips, TeraRecon, and Siemens) were performed by 2 observers. Diagnostic accuracy was estimated by comparing semiautomatic with manual measurements. Interobserver reproducibility and agreement between different packages was assessed by calculation of the intraclass correlation coefficient and Bland-Altman 95% limits of agreement. False-negative classifications were retrospectively inspected by a neuroradiologist. There was no significant difference in the diagnostic performance of the 4 semiautomatic methods. The sensitivity for detecting ≥50% and ≥70% degree of stenosis was between 76% and 82% and 46% and 62%, respectively. Specificity and overall diagnostic accuracy were between 92% and 97% and 85% and 90%, respectively. The interobserver intraclass correlation coefficient was between 0.83 and 0.96 for semiautomatic measurements and 0.81 for manual measurement. The limits of agreement between each pair of semiautomatic packages ranged from -18%-24% to -33%-31%. False-negative classifications were caused by ulcerative plaques and observer variation in stenosis and reference measurements. Semiautomatic methods have a low-to-good sensitivity and a good specificity and overall diagnostic accuracy. The high interobserver reproducibility makes semiautomatic stenosis measurement valuable for clinical practice, but semiautomatic measurements should be checked by an experienced radiologist.


The Efficacy of Plant-Based Ionizers in Removing Aerosol for COVID-19 Mitigation.
Small-sized droplets/aerosol transmission is one of the factors responsible for the spread of COVID-19, in addition to large droplets and surface contamination (fomites). While large droplets and surface contamination can be relatively easier to deal with (i.e., using mask and proper hygiene measures), aerosol presents a different challenge due to their ability to remain airborne for a long time. This calls for mitigation solutions that can rapidly eliminate the airborne aerosol. Pre-COVID-19, air ionizers have been touted as effective tools to eliminate small particulates. In this work, we sought to evaluate the efficacy of a novel plant-based ionizer in eliminating aerosol. It was found that factors such as the ion concentration, humidity, and ventilation can drastically affect the efficacy of aerosol removal. The aerosol removal rate was quantified in terms of ACH (air changes per hour) and CADR- (clean air delivery rate-) equivalent unit, with ACH as high as 12 and CADR as high as 141 ft3/minute being achieved by a plant-based ionizer in a small isolated room. This work provides an important and timely guidance on the effective deployment of ionizers in minimizing the risk of COVID-19 spread via airborne aerosol, especially in a poorly-ventilated environment.


Bilateral intrarenal hematomas from anticoagulants.
A case is reported in which anticoagulant therapy for thrombophlebitis and pulmonary embolism produced bilateral massive intrarenal hematomas (pseudotumors). The role of radiologic investigation (nephrotomography, renal scan and selective high dose arteriography) was found to identify and localize the intrarenal hematomata and exclude underlying renal pathology. Although an abnormal kidney is more likely to bleed, this case presentation demonstrates that even carefully monitored anticoagulation within the therapeutic range can induce massive intrarenal hemorrhage in previously normal kidneys. The renal architecture returned to normal on late follow-up examination on simple conservative management.


How Do Taxonomic and Functional Diversity Metrics Change Along an Aridity Gradient in a Tropical Dry Forest?
Ecological indicators based on biodiversity metrics are valuable and cost-effective tools to quantify, track and understand the effects of climate change on ecosystems. Studying changes in these indicators along climatic gradients in space is a common approach to infer about potential impacts of climate change over time, overcoming the limitations of lack of sufficiently long time-series data. Here, we studied the response of complementary biodiversity metrics in plants: taxonomic diversity (species richness and Simpson index) and functional diversity (diversity and redundancy) in 113 sampling sites along a spatial aridity gradient (from 0.27 to 0.69 of aridity index-AI) of 700 km in a Tropical dry forest. We found different responses of taxonomic and functional diversity metrics to aridity. Species diversity showed a hump-shaped curve peaking at intermediate levels of aridity between 0.38 and 0.52 AI as an ecotone, probably because it is where most species, from both drier and more mesic environments, still find conditions to co-exist. Functional diversity showed a positive linear relation with increasing aridity, suggesting higher aridity favors drought-adapted species with diverse functional traits. In contrast, redundancy showed a negative linear relation with increasing aridity, indicating that drier sites have few species sharing the same functional traits and resource acquisition strategies. Thus, despite the increase in functional diversity toward drier sites, these communities are less resilient since they are composed of a small number of plant species with unique functions, increasing the chances that the loss of one of such "key species" could lead to the loss of key ecosystem functions. These findings show that the integration of complementary taxonomic and functional diversity metrics, beyond the individual response of each one, is essential for reliably tracking the impacts of climate change on ecosystems. This work also provides support to the use of these biodiversity metrics as ecological indicators of the potential impact of climate change on drylands over time.


Persuading US White evangelicals to vaccinate for COVID-19: Testing message effectiveness in fall 2020 and spring 2021.
The development of COVID-19 vaccines was an important breakthrough for ending the pandemic. However, people refusing to get vaccinated diminish the level of community protection afforded to others. In the United States, White evangelicals have proven to be a particularly difficult group to convince to get vaccinated. Here we investigate whether this group can be persuaded to get vaccinated. To do this, we leverage data from two survey experiments, one fielded prior to approval of COVID-19 vaccines (study 1) and one fielded after approval (study 2). In both experiments, respondents were randomly assigned to treatment messages to promote COVID-19 vaccination. In study 1, we find that a message that emphasizes community interest and reciprocity with an invocation of embarrassment for choosing not to vaccinate is the most effective at increasing uptake intentions, while values-consistent messaging appears to be ineffective. In contrast, in study 2 we observe that this message is no longer effective and that most messages produce little change in vaccine intent. This inconsistency may be explained by the characteristics of White evangelicals who remain unvaccinated vis à vis those who got vaccinated. These results demonstrate the importance of retesting messages over time, the apparent limitations of values-targeted messaging, and document the need to consider heterogeneity even within well-defined populations. This work also cautions against drawing broad conclusions from studies carried out at a single point in time during the COVID-19 pandemic.


Intraoperative cell salvage with autologous transfusion in liver transplantation.
Liver transplant (LT) is the primary treatment for patients with end-stage liver disease. About 25000 LTs are performed annually in the world. The potential for intraoperative bleeding is quite variable. However, massive bleeding is common and requires blood transfusion. Allogeneic blood transfusion has an immunosuppressive effect and an impact on recipient survival, in addition to the risk of transmission of viral infections and transfusion errors, among others. Techniques to prevent excessive bleeding or to use autologous blood have been proposed to minimize the negative effects of allogeneic blood transfusion. Intraoperative reinfusion of autologous blood is possible through previous self-donation or blood collected during the operation. However, LT does not normally allow autologous transfusion by prior self-donation. Hence, using autologous blood collected intraoperatively is the most feasible option. The use of intraoperative blood salvage autotransfusion (IBSA) minimizes the perioperative use of allogeneic blood, preventing negative transfusion effects without negatively impacting other clinical outcomes. The use of IBSA in patients with cancer is still a matter of debate due to the theoretical risk of reinfusion of tumor cells. However, studies have demonstrated the safety of IBSA in several surgical procedures, including LT for hepatocellular carcinoma. Considering the literature available to date, we can state that IBSA should be routinely used in LT, both in patients with cancer and in patients with benign diseases.


S-100ao protein in blood and urine during open-heart surgery.
Concentrations of S100a0 protein and CK-MB were measured by enzyme immunoassay in serial samples of arterial and coronary-sinus blood and urine taken from 26 patients who were undergoing mitral valve surgery. The mean concentration of arterial S100a0 in plasma was 0.32 (SD 0.28) ng/mL at the beginning of anesthesia, increased sharply after reperfusion, peaking [14.4 (SD 6.63) ng/mL] after 45 min of reperfusion, then decreased rapidly. The concentration of creatine kinase (CK) isoenzyme MB in arterial blood plasma was greatest 3 h after reperfusion [107 (SD 54.5) ng/mL]. S100a0 concentrations in urine increased dramatically after reperfusion [16,300 (SD 12,000) ng/h vs 44 (SD 32) ng/h], while CK-MB increased slightly [135 (SD 75) ng/h vs 19 (SD 12) ng/h]. These results suggest that S100a0 in cardiac muscle is released into the bloodstream during open-heart surgery and is discharged into the urine more rapidly than is CK-MB. Determination of S100a0 in plasma or urine thus may be useful for estimating damage to heart muscle during open-heart surgery.


Alloreactivity as therapeutic principle in the treatment of hematologic malignancies. Studies of clinical and immunologic aspects of allogeneic hematopoietic cell transplantation with nonmyeloablative conditioning.
Allogeneic hematopoietic cell transplantation (HCT) represents a potentially curative treatment modality in a range of hematologic malignancies. High-dose myeloablative radio-chemotherapy has conventionally been used as part of the preparative regimen before HCT for two reasons: it has a profound immunosuppressive effect on the host, limiting the ability to reject the graft and it has substantial anti-tumor efficacy. Graft rejection is an example of alloreactivity as alloreactivity denotes the immunologic reactions that occur when tissues are transplanted between two individuals within the same species. If the immune system of the host is suppressed to a degree where rejection does not occur, the possibility arises that immunocompetent donor cells can attack the recipient tissues. This phenomenon is termed Graft-versus-Host disease (GVHD) if healthy tissues of the host are attacked and the Graft-versus-Tumor (GVT) effect if the malignant cells are the targets of the reaction. Clinical studies have shown that patients who develop GVHD have a lower risk of relapse of the malignant disease and that donor lymphocyte infusion can induce durable remissions in patients with relapsed disease following the transplant. These observations indicate that a GVT effect can be present following allogeneic HCT and that this effect, like GVHD, is an alloreactive response. The toxicity of HCT with myeloablative conditioning is considerable and this limits the use of this procedure to patients below 50-60 years of age. A large proportion of the patients with hematologic malignancies are older than 60 years at diagnosis and they are therefore not eligible for this treatment. During the last decade, conditioning regimens that are nonmyeloablative or have reduced intensity have been developed. The purpose of this development has been to extend the use of allogeneic HCT to older patients and to patients who due to the malignant disease or to comorbidities are unable to tolerate myeloablative conditioning. In allogeneic HCT with nonmyeloablative conditioning the curative potential relies entirely on the ability of the donor cells to elicit a GVT effect. Allogeneic HCT with nonmyeloablative conditioning was introduced at Department of Hematology at Rigshospitalet in March 2000. The results of this treatment modality have been promising and we and others have shown that durable remissions can be obtained in patients who are heavily pretreated. One of the goals of allogeneic HCT with nonmyeloablative conditioning was to perform both the actual transplant procedure and the clinical follow up in the outpatient setting. In the first 30 patients transplanted at Rigshospitalet, we observed that the transplant itself and the first weeks post transplant could be performed as an outpatient procedure in a number of patients. However, all the patients were admitted and the median duration of hospitalization was 44 days during the first year post transplant. Complications such as infections and GVHD were common causes of hospitalization and studies from other centers have shown that infections, GVHD and relapse of the malignancy are the major obstacles to a good result of allogeneic HCT with nonmyeloablative conditioning. One way to improve the results of this treatment would therefore be to reduce the incidence of GVHD without compromising the GVT effect. In HCT with nonmyeloablative conditioning the relatively well-defined antineoplastic effect of high-dose myeloablative radio-chemotherapy is substituted with the alloreactive effect of the donor cells. Because the level of alloreactivity varies widely between different donor-recipient pairs, the ability to monitor the level of alloreactivity following the transplant would therefore be desirable. To this end we have investigated the ability of different immunologic and molecular methods to quantify the level of ongoing alloreactivity following the transplant. By simultaneous determination of the fraction of T cells of donor origin (donor T-cell chimerism) and the total number of T cells in the peripheral blood, we observed that patients with a high number of donor CD8 + T cells on day +14 had a high risk of acute GVHD. Other studies have shown that the level of donor T-cell chimerism early after transplant predicts the development of acute GVHD. One way to exploit this knowledge could be to individualize the pharmacologic immunosuppression given post transplant. This immunosuppression is given primarily to prevent the development of GVHD but may also inhibit the GVT effect. In patients with a low risk of GVHD early tapering of the immunosuppression could be done, while the period of immunosuppression could be extended in patients with a high risk of GVHD. In this way the GVT effect could theoretically be optimized in each patient and the results of the treatment improved. In another study we used limiting dilution analysis to monitor the frequencies of interleukin (IL)-2 producing helper T cells responding to recipient or donor antigens following the transplant. The conclusion from this study was that both the technical performance and the data analysis were to complex for this method to be used as a routine clinical tool. However, the study showed that immune responses following HCT are subject to a tight regulation and suggested that this regulation could be due to regulatory cell populations. Such regulatory cell populations have been used successfully in animal models to treat acute GVHD. The secretion of cytokines is an important aspect of immune responses. We analyzed cytokine gene expression in mononuclear cells obtained from patients and donors before and after HCT. Patients with acute GVHD had lower levels of IL-10 mRNA on day +14 than patients who did not develop acute GVHD. Patients who experienced progression or relapse of the malignant disease were characterized by higher levels of IL-10 mRNA before the transplant than patients who remained in remission. The conclusion of this study was that IL-10 might be an inhibitor of alloreactivity following allogeneic HCT with nonmyeloablative conditioning. Allogeneic HCT with nonmyeloablative conditioning represents a major step forward in the treatment of patients with hematologic malignancies. However, many issues such as whom to transplant and when the transplant should be performed remain to be clarified. Large prospective studies, involving collaboration between centers, are needed to define the role of HCT with nonmyeloablative conditioning along with other treatment modalities. In addition, it is important to continue to elucidate the immunologic mechanisms that are responsible for GVHD and the GVT effect.


Investigating the autonomic nervous system and cognitive functions as potential mediators of an association between cardiovascular disease and driving performance.
Cardiovascular disease (CVD) impacts the autonomic nervous system and cognitive functions related to activities of daily living, including driving an automobile. Although CVD has been linked to unsafe driving, mechanisms underlying this relationship remain elusive. The aim of this study was to examine the role of cognitive functions and the autonomic nervous system as potential mediators of driving performance. Nineteen individuals having recently suffered a cardiac event and 16 individuals with no history of CVD completed a simulated drive using a STISIM simulator to assess driving performance. Heart rate was recorded throughout testing using a Polar RS800CX heart rate monitor, and measures of executive, orienting, and alerting functions were obtained through the Attention Network Test. We used the Baron and Kenny analysis method to assess potential mediating effects of the relationship between CVD and driving performance. Executive function was the only potential mediator investigated to be associated with driving (p < 0.01) and CVD (p < 0.05); however, it did not appear to play a mediating role (p = 0.28). These results suggest that individuals with CVD exhibit decrements in complex cognitive tasks such as driving and that further research is needed to better understand the mechanisms underlying this relationship.


A comparison of seven antiarrhythmic drugs in patients with ventricular tachyarrhythmias. Electrophysiologic Study versus Electrocardiographic Monitoring Investigators.
The relative efficacies of various antiarrhythmic drugs in the treatment of ventricular tachyarrhythmias are not well known. This study examined the effectiveness of imipramine, mexiletine, pirmenol, procainamide, propafenone, quinidine, and sotalol in patients with ventricular tachyarrhythmias who were enrolled in the Electrophysiologic Study versus Electrocardiographic Monitoring trial. Patients were randomly assigned to undergo serial testing of the efficacy of the seven antiarrhythmic drugs by one of two strategies: electrophysiologic study or Holter monitoring together with exercise testing. The seven drugs were then tested for efficacy in random order in patients who were eligible to receive them. The frequencies of predictions of drug efficacy and of adverse drug effects during the initial drug titration were tabulated for all 486 randomized subjects. Patients received long-term treatment with the first antiarrhythmic drug that was predicted to be effective on the basis of drug testing. Recurrences of arrhythmia, deaths, and adverse drug effects during long-term follow-up were recorded for the 296 patients in whom an antiarrhythmic drug was predicted to be effective. In the electrophysiologic-study group, the percentage of patients who had predictions of drug efficacy was higher with sotalol (35 percent) than with the other drugs (16 percent, P < 0.001). There was no significant difference among the drugs in the Holter-monitoring group. The percentage of patients with adverse drug effects was lowest among those receiving sotalol. The actuarial probability of a recurrence of arrhythmia after a prediction of drug efficacy by either strategy was significantly lower for patients treated with sotalol than for patients treated with the other drugs (risk ratio, 0.43; 95 percent confidence interval, 0.29 to 0.62; P < 0.001). With sotalol, as compared with the other drugs combined, there were lower risks of death from any cause (risk ratio, 0.50; 95 percent confidence interval, 0.30 to 0.80; P = 0.004), death from cardiac causes, (0.50; P = 0.02), and death from arrhythmia (0.50; P = 0.04). The cumulative percentage of patients in whom a drug was predicted to be effective and in whom it remained effective and tolerated was higher for sotalol than for the other drugs (P < 0.001). Sotalol was more effective than the other six antiarrhythmic drugs in preventing death and recurrences of arrhythmia. In patients similar to those in this study, if antiarrhythmic-drug therapy is to be used to prevent recurrences of ventricular tachyarrhythmias, treatment with sotalol and assessment of its potential efficacy by Holter monitoring are a reasonable initial strategy.


Utility of pulse oximetry screening for hepatopulmonary syndrome.
Hepatopulmonary syndrome is characterized by oxygenation abnormalities caused by intrapulmonary vasodilatation in the setting of liver disease and/or portal hypertension. This syndrome occurs in approximately 15%-30% of cirrhotic patients and influences mortality and transplant candidacy. However, no specific screening guidelines are established. We evaluated pulse oximetry with contrast echocardiography in detecting hepatopulmonary syndrome in a cohort of patients undergoing evaluation for liver transplantation. One hundred twenty-seven consecutive patients referred for liver transplantation evaluation were prospectively enrolled and underwent pulse oximetry, contrast echocardiography, and arterial blood gas measurements on room air. Demographic, clinical, and laboratory data were recorded and analyzed. Forty-one (32%) patients were found to have hepatopulmonary syndrome. There were no significant differences in demographic or clinical features compared with patients without hepatopulmonary syndrome, with the exception of pulse oximetry and oxygenation abnormalities. With a threshold value of <96%, pulse oximetry had a sensitivity and specificity of 100% and 88%, respectively, for detecting patients with a partial pressure of oxygen <60 mm Hg. Receiver operator characteristic analysis revealed that a pulse oximetry value of < or =94% detected all patients with a partial pressure of oxygen <60 mm Hg with an increased specificity of 93%. In addition, higher pulse oximetry thresholds reliably identified HPS patients with less severe hypoxemia, albeit with lower specificity. Pulse oximetry is a simple, low cost, and widely available technique that reliably predicts the presence and severity of hypoxemia in patients with hepatopulmonary syndrome. Institution of pulse oximetry screening might enhance detection and improve management of hepatopulmonary syndrome in cirrhosis.


[Nursing science in oncologic nursing].
The nursing care of cancer patients has increased in complexity over the past 20 years. Cancer nurses are offering highly specialized care that is frequently delivered in teamwork in hospitals as well as in the community. Cancer nursing uses the development of nursing science and research. Nurses could not be accountable for their practice if this expert knowledge was not made accessible to them. This article focuses on nursing science as a new development in clinical nursing practice in Germany, it identifies why cancer nursing is so demanding on part of the patients, their families (significant others) and professional nurses. Research studies are discussed to demonstrate how scientific knowledge can support the nursing expert in the development of cancer nursing care, a well developed domain of nursing science.


The Promise and Pitfalls of Prophages.
Phages dominate every ecosystem on the planet. While virulent phages sculpt the microbiome by killing their bacterial hosts, temperate phages provide unique growth advantages to their hosts through lysogenic conversion. Many prophages benefit their host, and prophages are responsible for genotypic and phenotypic differences that separate individual microbial strains. However, the microbes also endure a cost to maintain those phages: additional DNA to replicate and proteins to transcribe and translate. We have never quantified those benefits and costs. Here, we analysed over two and a half million prophages from over half a million bacterial genome assemblies. Analysis of the whole dataset and a representative subset of taxonomically diverse bacterial genomes demonstrated that the normalised prophage density was uniform across all bacterial genomes above 2 Mbp. We identified a constant carrying capacity of phage DNA per bacterial DNA. We estimated that each prophage provides cellular services equivalent to approximately 2.4 % of the cell's energy or 0.9 ATP per bp per hour. We demonstrate analytical, taxonomic, geographic, and temporal disparities in identifying prophages in bacterial genomes that provide novel targets for identifying new phages. We anticipate that the benefits bacteria accrue from the presence of prophages balance the energetics involved in supporting prophages. Furthermore, our data will provide a new framework for identifying phages in environmental datasets, diverse bacterial phyla, and from different locations.


The Modern View of B Chromosomes Under the Impact of High Scale Omics Analyses.
Supernumerary B chromosomes (Bs) are extra karyotype units in addition to A chromosomes, and are found in some fungi and thousands of animals and plant species. Bs are uniquely characterized due to their non-Mendelian inheritance, and represent one of the best examples of genomic conflict. Over the last decades, their genetic composition, function and evolution have remained an unresolved query, although a few successful attempts have been made to address these phenomena. A classical concept based on cytogenetics and genetics is that Bs are selfish and abundant with DNA repeats and transposons, and in most cases, they do not carry any function. However, recently, the modern quantum development of high scale multi-omics techniques has shifted B research towards a new-born field that we call "B-omics". We review the recent literature and add novel perspectives to the B research, discussing the role of new technologies to understand the mechanistic perspectives of the molecular evolution and function of Bs. The modern view states that B chromosomes are enriched with genes for many significant biological functions, including but not limited to the interesting set of genes related to cell cycle and chromosome structure. Furthermore, the presence of B chromosomes could favor genomic rearrangements and influence the nuclear environment affecting the function of other chromatin regions. We hypothesize that B chromosomes might play a key function in driving their transmission and maintenance inside the cell, as well as offer an extra genomic compartment for evolution.


[Treatment of chronic Brucellosis with combined traditional Chinese medicine and Western medicine therapy].
66 patients of chronic Brucellosis were treated by two programs and their differences were analysed. 30 (control) were treated with Brucella phenol insoluble portion (PI), injected intramuscularly by increasing the doses gradually, 2 times a week, 20 times as a course. 36 treated with combined traditional Chinese and Western medicine (TCM-WM), besides using PI, they were treated with Modified Duhuo Jisheng Tang. Results were evaluated 70 days later. The basic cure rate between two groups were 86.11% and 53.17%, the effective rates were 99.22% and 86.66% respectively. The difference is significant (P < 0.01 and 0.05). Most symptoms disappeared or alleviated in both groups, but improved more quickly in TCM-WM group. The side effect in control group was more serious. The objective indexes, such as serological test, skin hypersensitivity reaction and WBC count, etc. were improved better in combined therapy group than that in control group (P < 0.05-0.01). Duhuo Jisheng Tang has the function of replenishing Liver and Kidney, nourishing the Blood and Qi, getting rid of rheumatism and relieving pain, if used with PI, it could strengthen immunity and inhibit the release of alergin.


Sympathetic Nerve Traffic Activation in Essential Hypertension and Its Correlates: Systematic Reviews and Meta-Analyses.
Muscle sympathetic nerve activity (MSNA) has shown that sympathetic activation may occur in essential hypertension (EHT). However, the small sample size of the studies, the heterogeneity of the patients examined, and the presence of confounders represented major weaknesses not allowing to draw definite conclusions. Among the 432 studies identified providing information in EHT on MSNA, 63 were eligible (1216 patients) and meta-analyzed grouping them on the basis of clinically relevant questions: (1) Is MSNA increased in hypertension of mild/moderate-to-severe degree? (2) Does sympathetic activation occur in borderline, white-coat, and masked EHT? (3) Is MSNA related to clinic and ambulatory blood pressure and target organ damage? (4) Are heart rate and venous plasma norepinephrine valuable surrogate markers of MSNA in clinical practice? The results show that MSNA was significantly greater (1.5×; P<0.001) in mild-to-moderate and severe EHT as compared with normotensive controls and that this was the case also in borderline, white-coat, and masked hypertension as well. Interestingly, MSNA was significantly greater in both untreated and treated hypertension (P<0.001 for both), related to clinic and ambulatory blood pressure (r=0.67 and r=0.83; P<0.001 for both), inversely related to heart rate (r=-0.38; P<0.001) and directly to venous plasma norepinephrine (r=0.28; P<0.001) and left ventricular mass index (r=0.27; P<0.001). Thus, EHT is a condition characterized by a sustained sympathetic overdrive, whose magnitude is proportional to its clinical severity. This is more clearly manifest when MSNA rather than indirect markers of adrenergic drive, such as heart rate and plasma norepinephrine, are used.


The chemohormonal therapy of metastatic melanoma: possible benefit of tamoxifen.
Metastatic melanoma is difficult to treat because of low response rates to most chemotherapy regimens and short remission durations. Recently, a new chemohormonal regimen containing BCNU, cisplatin, DTIC and tamoxifen (BCDT) has been reported to be more promising. We have treated eight patients with this regimen and five patients responded, including three with complete responses (CR). One of these patients remains in CR beyond two years. Others have also reported response rates of 50% with this regimen with a few long-term remissions also. Two of our patients developed deep venous thromboses (DVT). The increased incidence of DVT with BCDT is attributed to the tamoxifen, which nevertheless appears to be a necessary component of this regimen. In two of our patients, short courses of tamoxifen were used and they both obtained responses (one CR, one PR) without DVT. The possibility of using short-course tamoxifen to reduce the incidence of DVT in this regimen, without impairing its efficacy, should be investigated.


The utility metric: a novel method to assess the overall performance of discrete brain-computer interfaces.
A relevant issue in a brain-computer interface (BCI) is the capability to efficiently convert user intentions into correct actions, and how to properly measure this efficiency. Usually, the evaluation of a BCI system is approached through the quantification of the classifier performance, which is often measured by means of the information transfer rate (ITR). A shortcoming of this approach is that the control interface design is neglected, and hence a poor description of the overall performance is obtained for real systems. To overcome this limitation, we propose a novel metric based on the computation of BCI Utility. The new metric can accurately predict the overall performance of a BCI system, as it takes into account both the classifier and the control interface characteristics. It is therefore suitable for design purposes, where we have to select the best options among different components and different parameters setup. In the paper, we compute Utility in two scenarios, a P300 speller and a P300 speller with an error correction system (ECS), for different values of accuracy of the classifier and recall of the ECS. Monte Carlo simulations confirm that Utility predicts the performance of a BCI better than ITR.


The biopersistence and pathogenicity of man-made vitreous fibres after short- and long-term inhalation.
A summary is given of the biopersistence and pathology after inhalation by rats of two different Man-made Vitreous Fibres, MMVF21 (traditional stone wool) and MMVF34 (HT stone wool), and the results are discussed in relation to biopersistence measured after intra-tracheal instillation. The results are given from a short-term inhalation biopersistence study, a completed chronic inhalation study, and interim results from an on-going chronic inhalation study. In both the short-term and chronic studies, laboratory rats were exposed by nose-only inhalation to well-characterised fibre test atmospheres that had been selected to be largely rat respirable. The short-term inhalation study included groups exposed to aerosols targeted at 150 fibres longer than 20 microns per cm3. The exposure duration was 6 hours/day for 5 days, with subsequent post-exposure periods lasting up to 12 months. For lung burden analyses, interim sacrifices were performed at regular intervals. The ongoing chronic study comprises a group of rats exposed to the MMVF34 fibre at one exposure level of 30 mg/m3. The negative control group is filtered air. The exposure duration is 6 hours/day, 5 days/week for 2 years, with a subsequent post-exposure period lasting until approximately 20% survival in the test fibre group. Interim sacrifices are performed at months 3, 6, 12, 18 and 24 and biopersistence monitored for rats exposed for 3 and 12 months, with subsequent post-exposure periods lasting 6 months. Effectively the main protocol for the previously conducted chronic study was the same, except that there were 3 fibre exposure groups (3, 16 and 30 mg/m3) and no specific biopersistence satellite groups were included. For MMVF34, the inhalation tests of different duration show a similar biopersistence pattern, while the intra-tracheal test gives longer elimination half-times especially for long fibres. The MMVF34 fibre is considerably less biopersistent than the traditional MMVF21 fibre when comparing the calculated elimination half-times after short-term inhalation. When comparing the pathology after 3, 6, 12 and 18 months exposure, MMVF34 showed minor histopathological changes compared to MMVF21. The carcinogenicity and toxicity results of the chronic study with MMVF21 suggest that this fibre does not pose a significant health risk to humans and the current results with MMVF34 indicate that this fibre consequently should pose an even smaller risk, if any.


Correction on the Nomenclature of Human Plasmodium.
In the nomenclatorial and zoological confusion in the names for the human malaria parasites (Sabrosky and Usinger. Science, 1944, 100, 190-192; Beltran. Gaceta Med. Mexico, 1944, 74, 61-74), one further point has been discovered. It has usually been considered that there were only two different proposals involving malariae as a new specific name-Oscillaria malariae Laveran, 1881, and Haemamoeba malariae Feletti and Grassi, 1890. Actually it now appears that there were three!


Genetic diversity and molecular characterization of Cucumber mosaic cucumovirus (CMV) subgroup II infecting Spinach (Spinacia oleracea) and Pea (Pisum sativum) in Pothwar region of Pakistan.
Cucumber mosaic virus (CMV) is a tremendous threat to vegetables across the globe, including in Pakistan. The present work was conducted to investigate the genetic variability of CMV isolates infecting pea and spinach vegetables in the Pothwar region of Pakistan. Serological-based surveys during 2016-2017 revealed 31.70% overall CMV disease incidence from pea and spinach crops. Triple-antibody sandwich enzyme-linked immunosorbent assay (TAS-ELISA) revealed that all the positive isolates belong to CMV subgroup II. Two selected cDNA from ELISA-positive samples representing each pea and spinach crops were PCR-amplified (ca.1100 bp) and sequenced corresponding to the CMV CP gene which shared 93.7% nucleotide identity with each other. Both the sequences of CMV pea (AAHAP) and spinach (AARS) isolates from Pakistan were submitted to GenBank as accession nos. MH119071 and MH119073, respectively. BLAST analysis revealed 93.4% sequence identity of AAHAP isolate with SpK (KC763473) from Iran while AARS isolate shared maximum identity (94.5%) with the strain 241 (AJ585519) from Australia and clustered with some reference isolates of CMV subgroup II from UK (Z12818) and USA (AF127976) in a Neighbour-joining phylogenetic reconstruction. A total of 59 polymorphic (segregating) sites (S) with nucleotide diversity (π) of 0.06218 was evident while no INDEL event was observed in Pakistani isolates. The evolutionary distance of Pakistani CMV isolates was recorded as 0.0657 with each other and 0.0574-0.2964 with other CMV isolates reported elsewhere in the world. A frequent gene flow (Fst = 0.30478 <0.33) was observed between Pakistani and earlier reported CMV isolates. In genetic differentiation analysis, the value of three permutation-based statistical tests viz; Z (84.3011), Snn (0.82456), and Ks* (4.04042) were non-significant. The statistical analysis revealed the values 2.02535, 0.01468, and 0.71862 of Tajima's D, Fu, & Li's F* and D* respectively, demonstrating that the CMV population is under balancing selection.


Rare human infection with the trematode Echinochasmus japonicus in Lao PDR.
Food-borne trematodiases are often neglected although millions of people are affected and these zoonotic diseases are emerging in some parts of the world. Humans acquire an infection through consumption of the second intermediate hosts (e.g. freshwater fish) that harbour the metacercariae of the parasite. Here, we report the first three cases of Echinochasmus japonicus infection in Lao PDR. Adult E. japonicus flukes were recovered from a woman (age: 37 years) and two men (age: 42 and 75 years) following treatment with praziquantel (single oral dose of 40 mg/kg) and purgation (45 ml monosodium sulphate). All three individuals were infected with two other species of trematodes concurrently, namely Opisthorchis viverrini and Haplorchis taichui. The two male patients moreover harboured Prosthodendrium molenkampi and Phaneropsolus bonnei trematodes. All three cases suffered from diarrhoeal episodes and other gastro-intestinal discomforts in the month preceding praziquantel administration and purgation. The frequent consumption of raw or insufficiently cooked freshwater fish and other aquatic products is the root cause of acquiring rare zoonotic infections such as E. japonicus.


Gatorbulin-1, a distinct cyclodepsipeptide chemotype, targets a seventh tubulin pharmacological site.
Tubulin-targeted chemotherapy has proven to be a successful and wide spectrum strategy against solid and liquid malignancies. Therefore, new ways to modulate this essential protein could lead to new antitumoral pharmacological approaches. Currently known tubulin agents bind to six distinct sites at α/β-tubulin either promoting microtubule stabilization or depolymerization. We have discovered a seventh binding site at the tubulin intradimer interface where a novel microtubule-destabilizing cyclodepsipeptide, termed gatorbulin-1 (GB1), binds. GB1 has a unique chemotype produced by a marine cyanobacterium. We have elucidated this dual, chemical and mechanistic, novelty through multidimensional characterization, starting with bioactivity-guided natural product isolation and multinuclei NMR-based structure determination, revealing the modified pentapeptide with a functionally critical hydroxamate group; and validation by total synthesis. We have investigated the pharmacology using isogenic cancer cell screening, cellular profiling, and complementary phenotypic assays, and unveiled the underlying molecular mechanism by in vitro biochemical studies and high-resolution structural determination of the α/β-tubulin-GB1 complex.


Attitudes towards cross-border reproductive care among infertile Japanese patients.
The attitudes towards cross-border reproductive care (CBRC) held by infertile Japanese patients have not been explored. The objective of the present study was to examine interest levels, preferred destinations, motivations, and sources of information related to CBRC. Our findings provide a general outline of CBRC and the future of reproduction and assisted reproductive technology (ART) in Japan. The study used a cross-sectional design. Data were collected from 2,007 infertile Japanese patients from 65 accredited ART clinics in Japan (response rate, 27.4 %) via anonymous questionnaires. Most of the infertile Japanese patients who responded denied using CBRC. However, by group, 171 (8.5 %) patients in non-donor in vitro fertilization, 150 (7.5 %) in egg donation, 145 (7.2 %) in pre-implantation genetic diagnosis, and 129 (6.4 %) in surrogacy said that, depending on the situation, they might travel abroad in the future. Older respondents were more likely to express an intention to travel overseas for egg donation in the future. The most popular destination for CBRC was the United States. Popular reasons for interest in CBRC among those considering or planning using this approach to third-party reproduction were that egg donation or surrogacy was unavailable or that obtaining ethical approval takes too long in Japan, whereas these processes are legal and affordable overseas. However, high cost was the most common reason for hesitancy regarding CBRC. Among the participants who were considering or planning to travel abroad for this purpose, TV, medical agencies, print media, and message boards on websites were popular sources of information, whereas doctors, friends, and patient self-help groups were not. Although CBRC among infertile Japanese patients is not at present common, the demand for and use of this approach may increase in the future in the context of the increasingly aging population. Lack of regulation and unavailability of third-party reproduction is a major cause of CBRC among Japanese patients. Health care provider faces an urgent need for giving useful information for patients regarding CBRC.


Altered localization of Cav1.2 (L-type) calcium channels in nerve fibers, Schwann cells, odontoblasts, and fibroblasts of tooth pulp after tooth injury.
We have determined the localization of Cav1.2 (L-Type) Ca2+ channels in the cells and nerve fibers in molars of normal or injured rats. We observed high levels of immunostaining of L-type Ca2+ channels in odontoblast cell bodies and their processes, in fibroblast cell bodies and in Schwann cells. Many Cav1.2-containing unmyelinated and myelinated axons were also present in root nerves and proximal branches in coronal pulp, but were usually missing from nerve fibers in dentin. Labeling in the larger fibers was present along the axonal membrane, localized in axonal vesicles, and in nodal regions. After focal tooth injury, there is a marked loss of Cav1.2 channels in injured teeth. Immunostaining of Cav1.2 channels was lost selectively in nerve fibers and local cells of the tooth pulp within 10 min of the lesion, without loss of other Cav channel or pulpal labels. By 60 min, Cav1.2 channels in odontoblasts were detected again but at levels below controls, whereas fibroblasts were labeled well above control levels, similar to upregulation of Cav1.2 channels in astrocytes after injury. By 3 days after the injury, Cav1.2 channels were again detected in nerve fibers and immunostaining of fibroblasts and odontoblasts had returned to control levels. These findings provide new insight into the localization of Cav1.2 channels in dental pulp and sensory fibers, and demonstrate unexpected plasticity of channel distribution in response to nerve injury.


Cognitive Training Deep Dive: The Impact of Child, Training Behavior and Environmental Factors within a Controlled Trial of Cogmed for Fragile X Syndrome.
Children with fragile X syndrome (FXS) exhibit deficits in a variety of cognitive processes within the executive function domain. As working memory (WM) is known to support a wide range of cognitive, learning and adaptive functions, WM computer-based training programs have the potential to benefit people with FXS and other forms of intellectual and developmental disability (IDD). However, research on the effectiveness of WM training has been mixed. The current study is a follow-up "deep dive" into the data collected during a randomized controlled trial of Cogmed (Stockholm, Sweden) WM training in children with FXS. Analyses characterized the training data, identified training quality metrics, and identified subgroups of participants with similar training patterns. Child, parent, home environment and training quality metrics were explored in relation to the clinical outcomes during the WM training intervention. Baseline cognitive level and training behavior metrics were linked to gains in WM performance-based assessments and also to reductions in inattention and other behaviors related to executive functioning during the intervention. The results also support a recommendation that future cognitive intervention trials with individuals with IDD such as FXS include additional screening of participants to determine not only baseline feasibility, but also capacity for training progress over a short period prior to inclusion and randomization. This practice may also better identify individuals with IDD who are more likely to benefit from cognitive training in clinical and educational settings.


Ureteroscopic endopyelotomy in an ectopic kidney.
A patient with an ectopic, pelvic kidney with congenital ureteropelvic junction obstruction was treated by retrograde, ureteroscopic endopyelotomy without percutaneous access. Preoperative ureteral stent placement and angiography facilitated the procedure. The patient had an uneventful recovery with improved drainage from the involved collecting system demonstrated by renal scintigraphy 6 months postoperatively. Ureteroscopic endopyelotomy avoids the need for percutaneous access, which may be difficult in patients with ectopic, malrotated kidneys and appears particularly well suited to the treatment of ureteropelvic junction obstruction in such cases.


The Impact of Age on Statin-Related Glycemia: A Propensity Score-Matched Cohort Study in Korea.
The aim of this study was to investigate the influence of statin on glycemic control in different age groups. Patients admitted for suspected or confirmed coronary artery disease between January 2005 and December 2013 in Seoul, Korea were initially enrolled. After propensity score matching, 2654 patients (1:1 statin users and non-users) were selected out of total 5041 patients, including 1477 "young" patients (≤60 y) and 1177 elderly patients (>60 y). HbA1c was decreased by 0.04% (±0.86%) in statin non-users. On the contrary, a slight increment of 0.05% (±0.71%) was found in statin users (p < 0.001). The change patterns of HbA1c were constant in both young and elderly patient groups. Furthermore, elderly statin users demonstrated significantly worse glycemic control in serum insulin and homeostatic model assessment—insulin resistance (HOMA-IR) index. In elderly patients, statin users were found to have a 2.61 ± 8.34 μU/mL increment in serum insulin, whereas it was 2.35 ± 6.72 μU/mL for non-users (p = 0.012). Statin users had a 0.78 ± 3.28 increment in HOMA-IR, in contrast to the 0.67 ± 2.51 increment in statin non-users (p = 0.008). In conclusion, statin treatment was associated with adverse glycemic control in the elderly population.


Non-cultural detection and molecular genotyping of Neisseria gonorrhoeae from a piece of clothing.
Isolation of Neisseria gonorrhoeae is currently the gold standard for the definitive diagnosis of gonorrhoea and for use in medico-legal cases in the UK. Molecular detection methods are used increasingly but are untested as evidence of infection in a court of law. An isolate of N. gonorrhoeae was obtained from a child and an article of clothing from an adult male who was suspected of sexual abuse of the child. Biochemical and immunological tests were used to confirm the isolate as N. gonorrhoeae. Amplification by PCR using two targets, cppB and ompIII, was used both as further confirmation of the isolate and to detect the presence of gonococcal-specific DNA from the clothing. The relationship of the gonococcal DNA from the child and the adult was investigated using genotyping (N. gonorrhoeae multi-antigen sequence typing; NG-MAST), including a nested PCR for the por gene. Both samples were indistinguishable by NG-MAST and shared the same sequence type, 403. This is the first report of molecular detection and genotyping of N. gonorrhoeae on an article of clothing, which resulted in conviction of the man for sexual assault.


The intravenous catheter at McBurney's point.
The manipulation of the inflamed appendix during laparoscopic surgery and avoiding its disintegration or leakage can be challenging even to experts. A suture loop form through an intravenous catheter may offer the least traumatic handling of the appendix, and it serves the extra benefit of leaving no scar. Furthermore, multiple loops can be formed conveniently and economically by a single long suture material. It can also ensure snaring at the very base of the appendix. We attempted this technique in 15 patients with 14 successful operations; there was great patient satisfaction and there were no surgical complications. Difficulty was encountered only when the surgeon tried to loop the buried appendix tip that cannot be delivered by one-hand manipulation.


Homogeneous fluorescence detection method for human leukocyte antigen-DR typing following polymerase chain reaction amplification with sequence-specific primer.
A fluorescent homogeneous method for the detection of sequence-specific amplification of human leukocyte antigen (HLA) alleles has been developed. In this approach, polymerase chain reaction sequence-specific primers (PCR-SSP) are used to amplify DRB1, DRB3, and DRB4 alleles. Lambda exonuclease and Exonuclease I are added to reduce background by digesting template DNA, partial primer dimer, and primer. PCR amplicons are then detected following the addition of a fluorescent dye (thiazole yellow dimer) which binds to double-stranded DNA. No transfer or wash steps are required. Thus, the risk of sample contamination, which is a major source of inaccuracy for DNA amplification methods, is greatly reduced. This approach is also faster and more easily automated than the standard approach using gel electrophoresis and ethidium bromide staining. Speed and automation are important considerations for HLA typing since the number of possible alleles for each HLA type is substantial. A homogeneous HLA-SSP typing method may be especially useful for clinical labs doing large numbers of samples and for the eventual automation of HLA DNA typing.


Profile of doxazosin in the hypertensive man with benign prostatic hyperplasia.
A number of studies have confirmed the beneficial effects of selective alpha 1-adrenoceptor inhibitors in patients with benign prostatic hyperplasia (BPH). Most produce clinically significant improvements in symptom scores and uroflow, although some of the shorter-acting agents often do so at the expense of adverse events. Doxazosin has a slower onset of action and longer plasma half-life than any other available selective alpha 1-adrenoceptor inhibitor, which may confer advantages in terms of tolerability over the more rapidly absorbed and eliminated selective alpha 1-adrenoceptor inhibitors. Doxazosin produces statistically significant increases in mean and maximum uroflow, as well as small but significant reductions in maximum voiding pressures and statistically significant improvements in symptoms of frequency, urgency, nocturia, reduced uroflow and sensation of incomplete emptying. Changes in uroflow and symptoms are similar in normotensive and hypertensive patients with BPH, and are accompanied in hypertensive patients by a statistically significant fall in blood pressure. Treatment is well tolerated in both normotensive and hypertensive patients. Doxazosin, by virtue of its unique pharmacological profile, is a valuable new treatment option for the many patients with mild to moderate bladder outflow obstruction due to BPH. It may be especially appropriate therapy for those considerable numbers of elderly men who have both hypertension and bladder outflow obstruction due to prostatic enlargement.


Fine mapping and positional candidate studies identify HLA-G as an asthma susceptibility gene on chromosome 6p21.
Asthma affects nearly 14 million people worldwide and has been steadily increasing in frequency for the past 50 years. Although environmental factors clearly influence the onset, progression, and severity of this disease, family and twin studies indicate that genetic variation also influences susceptibility. Linkage of asthma and related phenotypes to chromosome 6p21 has been reported in seven genome screens, making it the most replicated region of the genome. However, because many genes with individually small effects are likely to contribute to risk, identification of asthma susceptibility loci has been challenging. In this study, we present evidence from four independent samples in support of HLA-G as a novel asthma and bronchial hyperresponsiveness susceptibility gene in the human leukocyte antigen region on chromosome 6p21, and we speculate that this gene might contribute to risk for other inflammatory diseases that show linkage to this region.


Effects of subcutaneous methylnaltrexone on morphine-induced peripherally mediated side effects: a double-blind randomized placebo-controlled trial.
Methylnaltrexone, the first peripheral opioid receptor antagonist, has the potential to prevent or reverse opioid-induced peripherally mediated side effects without affecting analgesia. In previous human trials, we demonstrated that intravenous methylnaltrexone prevented morphine-induced delay in gastrointestinal transit time. We also observed that the compound decreased some of the morphine-induced troublesome subjective effects. However, the effects of subcutaneous methylnaltrexone, a more convenient route of administration, have not been evaluated. In this controlled trial, we evaluated the efficacy of subcutanous methylnaltrexone in antagonizing morphine-induced delay in oral-cecal transit time. In addition, opioid-induced unpleasant subjective effects and pharmacokinetics were studied. We observed that in the first group (n = 6) morphine (0.05 mg/kg intravenously) increased the transit time from a baseline level of 85 +/- 20.5 min to 155 +/- 27.9 min (mean +/- S.D., P < 0.01). After 0.1 mg/kg subcutaneous methylnaltrexone plus morphine, the transit time reduced to 110 +/- 41.0 min. In the second group (n = 6), morphine increased the transit time from a baseline level of 98 +/- 49.1 min to 140 +/- 58.2 min (P < 0.01). After 0.3 mg/kg subcutaneous methylnaltrexone plus morphine, the transit time reduced to 108 +/- 59.6 min (P < 0.05 compared with placebo plus morphine). In addition, subcutaneous methylnaltrexone significantly decreased morphine-induced subjective rating changes. Pharmacokinetic data after subcutaneous drug injection were compared to the data obtained from previous intravenous and oral administrations. Our results suggest that subcutaneous methylnaltrexone may have clinical utility in treating opioid-induced constipation and reducing opioid-induced unpleasant subjective symptoms.


An integrated approach to child psychotherapy with co-parental support: a longitudinal outcome study.
Studies about the effectiveness of psychodynamic psychotherapy interventions with children and adolescents suggest potential adverse effects of this treatment when not supported by a parallel work with parents: it seems that it could damage family functioning and affect family balances. This research aims to assess psychopathological outcomes after two years of psychodynamic psychotherapy by comparing two groups (G) of children and adolescents, related to a Childhood Adolescence Family Service: G1 - individual therapy for child/adolescent only; G2 - therapy for child/adolescent and a separate session of co-parenting support. 21 families with children aged between 6 and 17 years completed the entire treatment. The research protocol involves: Lausanne Trilogue Play, Children Behavior Check List and Family Empowerment Scale. Results show a positive effect of the treatment on the child/adolescent psychopathological profile with a significant improvement concerning the reduction of both internalizing and externalizing problems. Results show the effectiveness of the integrated intervention in the improvement of parents' abilities to validate the children emotional state. Our results suggesting that parenting support increase parental sensitivity, helping the parents to become more able to recognize the children's emotional state and to validate it.


Bronchoalveolar lavage procollagen-III-peptide in recent onset hypersensitivity pneumonitis: correlation with extracellular matrix components.
Hypersensitivity pneumonitis (HP) is characterized by the accumulation of inflammatory cells in the lung parenchyma, and may progress to fibrosis. The content of the fibroblast derived collagen metabolite procollagen-III-peptide (PCP-III) in bronchoalveolar lavage (BAL) fluid of HP patients has been found to be increased. Previous studies have shown elevation of the fibroblast adhesion molecules, vitronectin and fibronectin in the BAL fluid of recent onset HP. In view of these observations, it was hypothesized that increases in PCP-III would be associated with increases in vitronectin and fibronectin in the BAL fluid of subjects with untreated recent onset HP. BAL was performed in 14 patients with HP and nine normal controls. The aminoterminal domain of PCP-III was measured by radioimmunoassay, and vitronectin and fibronectin by enzyme-linked immunosorbent assay. Detectable amounts of BAL PCP-III were seen in all HP patients but not in the normal controls (mean +/- SEM 5.1 +/- 1.2 versus < 0.2 ng.ml-1; i.e. below the limit of detection of the PCP-III assay). The BAL fluid concentration of PCP-III correlated well with the amount of vitronectin (r = 0.638) and fibronectin (r = 0.710). Except for PCP-III and mast cells, no significant correlations were found between PCP-III, vitronectin, fibronectin and the cellular parameters. The findings suggest that an increased turnover of collagens and proteoglycans is present in the lower respiratory tract of patients with recent onset HP, possibly reflecting remodelling of the extracellular matrix.


Enhancing the yield of calcium carbonate precipitation by obstacles in laminar flow in a confined geometry.
Flow-driven precipitation experiments are performed in model porous media shaped within the confinement of a Hele-Shaw cell. Precipitation pattern formation and the yield of the reaction are investigated when borosilicate glass beads of different sizes are used in a mono-layer arrangement. The trend of the amount of precipitate produced in various porous media is estimated via visual observation. In addition, a new method is elaborated to complement such image analysis based results by titration experiments performed on gel-embedded precipitate patterns. The yield of confined porous systems is compared to experiments carried out in unsegmented reactors. It is found that the obstacles increase the amount of product and preserve its radial spatial distribution. The precipitate pattern is successfully conserved in a slightly cross-linked hydrogel matrix and its microstructure is examined using SEM. The spatial distribution of the precipitate across the cell gap is revealed using X-ray microtomography.


Chest Physiotherapy Interventions for Children During SARS-COV-2 Pandemic.
Since the first case of Severe Acute Respiratory Syndrome Coronavirus-2/Coronavirus Disease 2019 (SARS-COV-2/COVID-19) was discovered in Wuhan, China, it spread to vast limits globally and became a public health disaster, affecting nearly all countries around the globe. Along with mainstream medical treatment, alternative medicine desperately was the need of the hour for youngsters to manage their symptoms while being self-quarantined and ultimately to improve their chances of survival and recovery from COVID-19. Since the beginning of SARS-COV-2, few studies address the clinical-functional presentation of viral infection and management with physiotherapy for children. Major online electronic databases PubMed, PEDro, and Google Scholar were researched to identify, organize and commission the current review. To create a search strategy, Medical Subject Headings and Descriptors of Science and Health were utilized. The authors looked for other studies by screening the references list of the potentially pertinent papers. These computerized searches turned up studies and those studies' bibliographies with pertinent citations were examined. Personal protective equipment was a crucial component for protection and contact precaution. Following hypoxia, effective oxygen therapy is administered right away. When necessary, under the right circumstances, nasal high-flow oxygen therapy, non-invasive ventilation, lung-protective breathing methods, and prone positioning can be used. Children with SARS-CoV-2/COVID-19 may benefit from physiotherapy interventions with a focus on ventilatory management, airway clearance procedures, early activities, and mobilization.


Enhancement of cisplatin cytotoxicity by benzyl isothiocyanate in HL-60 cells.
Cis-diamminedichloroplatinum (II) (cisplatin) is one of the most widely used chemotherapeutic drugs, but its effectiveness is limited by tumor cell resistance and the severe side effects it causes. One strategy for overcoming this problem is the concomitant use of natural dietary compounds as therapeutic agents. Benzyl isothiocyanate (BITC) is a promising chemopreventive agent found in cruciferous vegetables and papaya fruits. The aim of this study was to investigate the effects of BITC on cisplatin-induced cytotoxicity in human promyelocytic leukemia cells and normal human lymphocytes. The combined treatment of HL-60 cells with BITC followed by cisplatin (BITC/cisplatin) caused a significant decrease in cell viability. BITC also increased apoptotic cell death compared to cisplatin treatment alone. In normal human lymphocytes, BITC did not enhance the cytotoxic effects of cisplatin. Cellular exposure to BITC/cisplatin increased reactive oxygen species (ROS) generation but decreased the total glutathione (GSH) level in HL-60 cells. Pretreatment of HL-60 cells with N-acetylcysteine or glutathione monoethyl ester effectively decreased BITC/cisplatin-induced cell death. The addition of the extracellular signal-regulated kinase (ERK) inhibitor PD98059 abolished BITC/cisplatin-induced apoptosis. Taken together, our results suggest that BITC enhances cisplatin-induced cytotoxicity through the generation of ROS, depletion of GSH, and ERK signaling in HL-60 cells.


Phenotyping Tomato Root Developmental Plasticity in Response to Salinity in Soil Rhizotrons.
Plants have developed multiple strategies to respond to salt stress. In order to identify new traits related to salt tolerance, with potential breeding application, the research focus has recently been shifted to include root system architecture (RSA) and root plasticity. Using a simple but effective root phenotyping system containing soil (rhizotrons), RSA of several tomato cultivars and their response to salinity was investigated. We observed a high level of root plasticity of tomato seedlings under salt stress. The general root architecture was substantially modified in response to salt, especially with respect to position of the lateral roots in the soil. At the soil surface, where salt accumulates, lateral root emergence was most strongly inhibited. Within the set of tomato cultivars, H1015 was the most tolerant to salinity in both developmental stages studied. A significant correlation between several root traits and aboveground growth parameters was observed, highlighting a possible role for regulation of both ion content and root architecture in salt stress resilience.


The cost of believing emotions are uncontrollable: Youths' beliefs about emotion predict emotion regulation and depressive symptoms.
As humans, we have a unique capacity to reflect on our experiences, including emotions. Over time, we develop beliefs about the nature of emotions, and these beliefs are consequential, guiding how we respond to emotions and how we feel as a consequence. One fundamental belief concerns the controllability of emotions: Believing emotions are uncontrollable (entity beliefs) should reduce the likelihood of trying to control emotional experiences using effective regulation strategies like reappraisal; this, in turn, could negatively affect core indices of psychological health, including depressive symptoms. This model holds particular relevance during youth, when emotion-related beliefs first develop and stabilize and when maladaptive beliefs could contribute to emerging risk for depression. In the present investigation, a pilot diary study (N = 223, aged 21-60) demonstrated that entity beliefs were associated with using reappraisal less in everyday life, even when controlling for possible confounds (i.e., self-efficacy, pessimism, stress exposure, stress reactivity). Then, two studies examined whether entity beliefs and associated impairments in reappraisal may set youths on a maladaptive trajectory: In a cross-sectional study (N = 136, aged 14-18), youths with stronger entity beliefs experienced greater depressive symptoms, and this link was mediated by lower reappraisal. This pattern was replicated and extended in a longitudinal study (N = 227, aged 10-18), wherein youth- and parent-reported depressive symptoms were assessed 18 months after assessing beliefs. These results suggest that entity beliefs about emotion constitute a risk factor for depression that acts via reappraisal, adding to the growing literature on emotion beliefs and their consequences for self-regulation and health. (PsycINFO Database Record


Smoking and colorectal cancer in a non-Western population: a prospective cohort study in Japan.
The risk of colorectal cancer in relation to smoking habits has been examined mostly in Caucasians, and evidence for other ethnic groups is still scarce. Our data came from the Japan Collaborative Cohort (JACC) Study. From 1988 through 1990, 25,260 men and 34,619 women aged 40-79 years completed a questionnaire on cigarette smoking and other lifestyle factors. Hazard ratios (HR) were estimated by fitting proportional hazards models. During the mean follow-up of 7.6 years through December 1997, we documented 408 incident colon cancers and 204 rectal cancers. We found a non-significant increase in colon cancer risk in male current smokers compared with never smokers. The multivariate-adjusted hazard ratios were 1.07 (95% confidence interval [CI]: 0.72-1.59) for ex-smokers and 1.23 (95% CI: 0.85-1.78) for current smokers. We however failed to observe a clear dose-response relationship between smoking intensity or duration and colon cancer risk. The adjusted hazard ratio was 1.07 (95% CI: 0.71-1.61) even for 40+ years of smoking. Almost no increase in colon cancer risk was detected for female smokers, and male smokers were not at an enhanced risk of rectal cancer. Cigarette smoking was not a strong risk factor for colorectal cancer even after a long-term exposure, although a weak association remains open to discussion.


Laparoscopic colorectal surgery and cancer.
Laparoscopy has become a part of the surgeon's armamentarium in benign colorectal diseases. Expected advantages include better cosmesis, shorter hospital stay and earlier return to preoperative status than similar open surgery. The advisability of performing laparoscopy for cure of colorectal malignancy has been challenged because the recurrence rates and overall cure rates remain unknown. Therefore, laparoscopy for colorectal cancer should be offered within the confines of a prospective randomized trial in order to resolve these issues.


Current status and perspective of antiangiogenic therapy for cancer: urinary cancer.
Angiogenesis is considered a prerequisite for solid tumor growth. Antiangiogenic therapy reduces tumor size and extends host survival in a number of preclinical animal models. However, in humans antiangiogenic therapy is a poor promoter of tumor regression and has shown minimal effect on patient survival. In urinary cancers, such as renal cell cancer, prostate cancer, and bladder cancer, advanced refractory disease is a good candidate for antiangiogenic therapy because of its resistance to ordinary chemotherapy, radiotherapy, and hormonal therapy. Unique characteristics of molecular mechanisms underlie the induction of angiogenesis in urinary cancers. In this review, we summarize these unique mechanisms and review the results of clinical trials of antiangiogenic therapy for these cancers, discussing prospects and problems relating to antiangiogenic therapy.


Limited heat transfer between thermal compartments during rewarming in vasoconstricted patients.
Thermoregulatory vasoconstriction may serve to separate and limit heat transfer between peripheral and central thermal compartments, in effect providing a thermal buffer for central temperature. We hypothesized that thermoregulatory vasoconstriction would limit heat transfer to the central compartment in patients warmed cutaneously. Hypothermic patients (central temperatures < 35 degrees C) recovering from surgery were randomly assigned to receive forced-air warming (n = 6) or warmed cotton blankets (n = 6). The forced-air warmer delivers approximately 50 W of heat, compared to a heat loss of approximately 50 W with warmed cotton blankets. Despite a significantly greater increase in mean skin-surface temperature with forced-air warming, central temperature in the two groups did not significantly differ. All patients vasoconstricted and there was no difference in oxygen consumption between groups. These data confirm that thermoregulatory vasoconstriction limits heat transfer from peripheral to central thermal compartments and impedes skin surface warming of the body core.


Functional characteristics of the oxyanion hole in human acetylcholinesterase.
The contribution of the oxyanion hole to the functional architecture and to the hydrolytic efficiency of human acetylcholinesterase (HuAChE) was investigated through single replacements of its elements, residues Gly-121, Gly-122 and the adjacent residue Gly-120, by alanine. All three substitutions resulted in about 100-fold decrease of the bimolecular rate constants for hydrolysis of acetylthiocholine; however, whereas replacements of Gly-120 and Gly-121 affected only the turnover number, mutation of residue Gly-122 had an effect also on the Michaelis constant. The differential behavior of the G121A and G122A enzymes was manifested also toward the transition state analog m-(N,N, N-trimethylammonio)trifluoroacetophenone (TMTFA), organophosphorous inhibitors, carbamates, and toward selected noncovalent active center ligands. Reactivity of both mutants toward TMTFA was 2000-11, 000-fold lower than that of the wild type HuAChE; however, the G121A enzyme exhibited a rapid inhibition pattern, as opposed to the slow binding kinetics shown by the G122A enzyme. For both phosphates (diethyl phosphorofluoridate, diisopropyl phosphorofluoridate, and paraoxon) and phosphonates (sarin and soman), the decrease in inhibitory activity toward the G121A enzyme was very substantial (2000-6700-fold), irrespective of size of the alkoxy substituents on the phosphorus atom. On the other hand, for the G122A HuAChE the relative decline in reactivity toward phosphonates (500-460-fold) differed from that toward the phosphates (12-95-fold). Although formation of Michaelis complexes with substrates does not seem to involve significant interaction with the oxyanion hole, interactions with this motif are a major stabilizing element in accommodation of covalent inhibitors like organophosphates or carbamates. These observations and molecular modeling suggest that replacements of residues Gly-120 or Gly-121 by alanine alter the structure of the oxyanion hole motif, abolishing the H-bonding capacity of residue at position 121. These mutations weaken the interaction between HuAChE and the various ligands by 2.7-5.0 kcal/mol. In contrast, variations in reactivity due to replacement of residue Gly-122 seem to result from steric hindrance at the active center acyl pocket.


Incidence of stomach cancer and its relation to dietary habits and nutrition in Japan between 1900 and 1975.
The diet of the Japanese people may be an important factor contributing to the high morbidity and morality rates of stomach cancer in Japan. Heavy rice consumption plus many salty foods in the diet are characteristic of the traditional eating habits in Japan. Fat intake and use of alcohol and tobacco are also considered possible factors. As the diet of the Japanese people changes to a more Western diet, there may be a concomitant change in the incidence of stomach cancer.


Effect of closure and packaging type on 3-alkyl-2-methoxypyrazines and other impact odorants of Riesling and Cabernet Franc wines.
3-Alkyl-2-methoxypyrazines (MPs) represent an important and potent class of grape- and insect-derived odor-active compounds associated with wine quality. Thirty nanograms per liter each of 3-isobutyl-2-methoxypyrazine (IBMP), 3-isopropyl-2-methoxypyrazine (IPMP), and 3-sec-butyl-2-methoxypyrazine (SBMP) was added to Riesling and Cabernet Franc wines and monitored with headspace solid-phase microextraction and gas chromatography-mass spectrometry over 18 months to investigate the effects of various closure and packaging options on MPs. Changes in MP concentrations during bottle aging varied with closure/packaging option, with the greatest decrease evident in Tetrapak cartons. After 18 months, IBMP, IPMP, and SBMP in both Tetrapak-stored wines decreased by approximately 45, 32, and 26%, respectively. Similar changes were observed in other impact odorants to previous studies, including a greater decrease in odorant concentrations in wines closed with synthetic corks compared to natural corks and screw caps. These differences are thought to be due to the differential sorptive capacities of the various closure types. Overall, the data suggest that differences in gas permeability/contribution from the different closure and packaging options strongly associate with changes in wine composition during aging.


[Interaction of 8-substituted derivatives and adenosine-3',5'-cyclophosphate esters with protein kinase from pig brain].
A synthesis of previously unknown 8-substituted derivatives and alkyl esters of cyclic adenosine-3',5'-monophosphate, containing reactive groups, was carried out. The interaction of the compounds obtained with a homogeneous preparation of protein kinase from pig brain was studied. It was found that all compounds, with the exception of neutral esters of 3',5'-AMP, activate the enzyme and competitively inhibit 3H-labelled 3',5'-cAMP binding by the regulatory subunit of protein kinase. The activating effect and affinity of 8-(beta-aminoethylamino)-3',5'-cAMP for protein kinase was 10 times lower than that for 3',5'-cAMP and other 8-substituted derivatives of the cyclic nucleotide. It was found that 8-(N-chloroacetylaminoethylamino)-3',5'-cAMP interaction with the enzyme is of irreversible type, which suggest covalent blocking of the nucleophilic group of the 3',5'-cAMP binding site of protein kinase. The data obtained indicate that the 3',5'-cAMP molecule is bound to the regulatory site of protein kinase in the syn-conformation. The previously made assumption on the crucial importance of the negative charge in the 3',5'-cyclophosphate system for the interaction of cyclic AMP with the regulatory subunit of protein kinase has been thus confirmed.


Pressurized Hot Liquid Extraction with 15% v/v Glycerol-Water as An Effective Environment-Friendly Process to Obtain Durvillaea incurvata and Lessonia spicata Phlorotannin Extracts with Antioxidant and Antihyperglycemic Potential.
Brown seaweed phlorotannins have shown the potential to promote several health benefits. Durvillaea incurvata and Lessonia spicata-species that are widely distributed in central and southern Chile-were investigated to obtain phlorotannin extracts with antioxidant and antihyperglycemic potential. The use of an environmentally friendly and food-grade glycerol-based pressurized hot liquid extraction (PHLE) process (15% v/v glycerol water) was assessed for the first time to obtain phlorotannins. Multiple effects were analyzed, including the effect of the species, harvesting area (Las Cruces and Niebla), and anatomical part (holdfast, stipe, and frond) on the extracts' polyphenol content (TPC), antioxidant capacity (AC), and carbohydrate-hydrolyzing enzyme-α-glucosidase and α-amylase-inhibitory activity. Contaminants, such as mannitol, heavy metals (As, Cd, Pb, Hg, and Sn), and 5-hydroxymethylfurfural (HMF), were also determined. The anatomical part used demonstrated a significant impact on the extracts' TPC and AC, with holdfasts showing the highest values (TPC: 95 ± 24 mg phloroglucinol equivalents/g dry extract; DPPH: 400 ± 140 μmol Trolox equivalents/g dry extract; ORAC: 560 ± 130 μmol TE/g dry extract). Accordingly, holdfast extracts presented the most potent α-glucosidase inhibition, with D. incurvata from Niebla showing an activity equivalent to fifteen times that of acarbose. Only one frond and stipe extract showed significant α-glucosidase inhibitory capacity. No α-amylase inhibition was found in any extract. Although no HMF was detected, potentially hazardous cadmium levels (over the French limit) and substantial mannitol concentrations-reaching up to 50% of the extract dry weight-were found in most seaweed samples and extracts. Therefore, further purification steps are suggested if food or pharmaceutical applications are intended for the seaweed PHLE extracts obtained in this study.


HBVPathDB: a database of HBV infection-related molecular interaction network.
To describe molecules or genes interaction between hepatitis B viruses (HBV) and host, for understanding how virus' and host's genes and molecules are networked to form a biological system and for perceiving mechanism of HBV infection. The knowledge of HBV infection-related reactions was organized into various kinds of pathways with carefully drawn graphs in HBVPathDB. Pathway information is stored with relational database management system (DBMS), which is currently the most efficient way to manage large amounts of data and query is implemented with powerful Structured Query Language (SQL). The search engine is written using Personal Home Page (PHP) with SQL embedded and web retrieval interface is developed for searching with Hypertext Markup Language (HTML). We present the first version of HBVPathDB, which is a HBV infection-related molecular interaction network database composed of 306 pathways with 1 050 molecules involved. With carefully drawn graphs, pathway information stored in HBVPathDB can be browsed in an intuitive way. We develop an easy-to-use interface for flexible accesses to the details of database. Convenient software is implemented to query and browse the pathway information of HBVPathDB. Four search page layout options-category search, gene search, description search, unitized search-are supported by the search engine of the database. The database is freely available at http://www.bio-inf.net/HBVPathDB/HBV/. The conventional perspective HBVPathDB have already contained a considerable amount of pathway information with HBV infection related, which is suitable for in-depth analysis of molecular interaction network of virus and host. HBVPathDB integrates pathway data-sets with convenient software for query, browsing, visualization, that provides users more opportunity to identify regulatory key molecules as potential drug targets and to explore the possible mechanism of HBV infection based on gene expression datasets.


[The blocking effect of topically subepithelial injection of thioproline and vitamin A acid in experimental oral premalignant].
The purpose of this paper is to observe the blocking effect of topically subepithelial injected drug and Vit A acid painting on chemically induced oral precancerous lesion and to prove, on a certain extent, the hypothesis that subepithelial connective tissue could exert great influence on the differentiation of the epithelium. A total of 49 syrian hamster was used as experimental animal. Both buccal pouches of all animals were painted thrice weekly with 0.5% DMBA in acetone for 6 weeks. Then, they were divided into two groups: Control group and Experimental group. In the latter group, 70.8% precancerous lesions turned into normal epithelial tissue, whereas those untreated animals developed carcinoma by 62%.


Characterization of three types of human alpha s1-casein mRNA transcripts.
Here we report the molecular cloning and sequencing of three types of human alpha s1-casein transcripts and present evidence indicating that exon skipping is responsible for deleted mRNA transcripts. The largest transcript comprised 981 bp encoding a signal peptide of 15 amino acids followed by the mature alpha s1-casein sequence of 170 amino acids. Human alpha s1-casein has been reported to exist naturally as a multimer in complex with kappa-casein in mature human milk, thereby being unique among alpha s1-caseins [Rasmussen, Due and Petersen (1995) Comp. Biochem. Physiol., in the press]. The present demonstration of three cysteines in the mature protein provides a molecular explanation of the interactions in this complex. Tissue-specific expression of human alpha s1-casein was indicated by Northern-blot analysis. In addition, two cryptic exons were localized in the bovine alpha s1-casein gene.


Discriminating among ADHD alone, ADHD with a comorbid psychological disorder, and feigned ADHD in a college sample.
Since the early 2000s concern has increased that college students might feign ADHD in pursuit of academic accommodations and stimulant medication. In response, several studies have validated tests for use in differentiating feigned from genuine ADHD. Although results have generally been positive, relatively few publications have addressed the possible impact of the presence of psychological disorders comorbid with ADHD. Because ADHD is thought to have accompanying conditions at rates of 50% and higher, it is important to determine if the additional psychological disorders might compromise the accuracy of feigning detection measures. The present study extended the findings of Jasinski et al. (2011) to examine the efficacy of various measures in the context of feigned versus genuine ADHD with comorbid psychological disorders in undergraduate students. Two clinical groups (ADHD only and ADHD + comorbid psychological disorder) were contrasted with two non-clinical groups (normal controls answering honestly and normal participants feigning ADHD). Extending previous research to individuals with ADHD and either an anxiety or learning disorder, performance validity tests such as the Test of Memory Malingering (TOMM), the Letter Memory Test (LMT), and the Nonverbal Medical Symptom Validity Test (NV-MSVT) were effective in differentiating both ADHD groups from normal participants feigning ADHD. However, the Digit Memory Test (DMT) underperformed in this study, as did embedded validity indices from the Wechsler Adult Intelligence Scale-IV (WAIS-IV) and Woodcock Johnson Tests of Achievement-III (WJ-III).


Contextual constraints in situation model construction: an investigation of age and reading span.
This study examined the effects of age and reading span on the ability to use contextual constraints during language comprehension. Older and younger participants listened to sentences over headphones and named pictures that appeared subsequently. Older adults named pictures faster when the preceding sentence context matched rather than mismatched the shape of the depicted object, but younger adults showed less of a match advantage. This effect of contextual match was especially pronounced in older high-span participants, consistent with models of cognitive aging in which surface level processing declines in older adulthood whereas processing at the situation model level remains intact. Results suggest that the practiced ability to immediately construe word meanings and activate the appropriate stored representations is preserved, if not strengthened throughout the lifespan.


[Study of the resistance of Mycobacterium tuberculosis to the principal tuberculostatics (Hospital of Navarra 1996-2003)].
The aim of this study was to evaluate the sensitivity to the principal tuberculostatics of the M. tuberculosis stocks isolated in our laboratory and to study the factors related to resistance. Study of 475 stocks of M. tuberculosis corresponding to all cases diagnosed in the eight year period between 1996 and 2003. We employed the BACTEC 460TB system, together with Lowenstein solid medium, in the cultivation of the samples. The sensitivity studies were carried out using the BACTEC 460TB system. Both the incidence and the number of cases of resistant tuberculosis showed oscillations over the eight years of the study. The fact that there is no homogeneous tendency makes it necessary to maintain active surveillance of this process. Global resistance to isoniacide was 8%, making it is convenient to carry out sensitivity studies in all the diagnosed cases. The cases of multiresistant tuberculosis (resistant to at least isoniacide and rifampicin), did not exceed 3%. The prognosis of the patients with resistant tuberculosis was bleak in cases of coinfection with HIV; however, when the immunological defences were conserved, and guidelines for treatment with active drugs were provided, the recovery of the majority of the patients was achieved. At present, sensitive and rapid procedures are available to us, making it recommendable to study the sensitivity of all the stocks of M. tuberculosis that are isolated; this is essential in the case of HIV positive or immigrant patients.


Mechanical Stimulation of the Retina: Therapeutic Feasibility and Cellular Mechanism.
Retinal prostheses that seek to restore vision by artificially stimulating retinal neurons with electrical current are an emerging treatment for photoreceptor degenerative diseases but face difficulties achieving naturalistic vision with high spatial resolution. Here, we report the unexpected discovery of a technique for mechanically stimulating retinal neurons with the potential to bypass the limitations of electrical stimulation. We found that pulsatile injections of standard Ames medium solution into explanted retinas of wild type rats under certain injection conditions (pulse-width > 50ms at 0.69 kPa pressure) elicit spatially localized retinal responses similar to light-evoked responses. The same injections made into photoreceptor degenerated retinas of transgenic S334ter-3 rats also elicit robust neural responses. We investigated the cellular mechanism causing these responses, by repeating the injections after treating the retinas with a pharmacological blocker of the transient receptor potential vanilloid (TRPV) channel group, a common mechanoreceptor found on retinal neurons, and observed a significant reduction in retinal ganglion cell spike rate response amplitudes. Together, these data reveal that therapeutic mechanical stimulation of the retina, occurring in part through TRPV channel activation, is feasible and this little explored neurostimulation paradigm could be useful in stimulating photoreceptor degenerated retinas for vision restoration.


[Poor self-rated mastication and associated factors in Brazilian adults].
This study estimated the prevalence of bad/very bad self-rated mastication and investigated associated factors among Brazilian adults. The sample included 13,431 adults examined and interviewed in the SBBrazil project. Self-rated mastication was combined in three categories: good/ very good (the reference), fair, and bad/very bad. Multinomial logistic regression was performed to measure the association between fair and bad/very bad self-rated mastication and all independent variables included in the analysis, with significance set at p < 0.05. 55.6% of participants rated their mastication as good/very good, 24.9% as fair, and 19.5% as bad/very bad. In the final multivariate analysis, factors associated with bad or fair self-rated mastication were: receiving no information on how to avoid oral problems; presenting fewer than 23 remaining teeth; requiring total or partial prosthesis; bad/very bad self-rated oral health; gingival pain and/or toothache in the previous year; and need of dental treatment. In conclusion, various factors were associated with self-rated mastication, especially subjective conditions, thus emphasizing its importance as an oral health indicator.


DNA length tunes the fluidity of DNA-based condensates.
Living organisms typically store their genomic DNA in a condensed form. Mechanistically, DNA condensation can be driven by macromolecular crowding, multivalent cations, or positively charged proteins. At low DNA concentration, condensation triggers the conformational change of individual DNA molecules into a compacted state, with distinct morphologies. Above a critical DNA concentration, condensation goes along with phase separation into a DNA-dilute and a DNA-dense phase. The latter DNA-dense phase can have different material properties and has been reported to be rather liquid-like or solid-like depending on the characteristics of the DNA and the solvent composition. Here, we systematically assess the influence of DNA length on the properties of the resulting condensates. We show that short DNA molecules with sizes below 1 kb can form dynamic liquid-like assemblies when condensation is triggered by polyethylene glycol and magnesium ions, binding of linker histone H1, or nucleosome reconstitution in combination with linker histone H1. With increasing DNA length, molecules preferentially condense into less dynamic more solid-like assemblies, with phage λ-DNA with 48.5 kb forming mostly solid-like assemblies under the conditions assessed here. The transition from liquid-like to solid-like condensates appears to be gradual, with DNA molecules of roughly 1-10 kb forming condensates with intermediate properties. Titration experiments with linker histone H1 suggest that the fluidity of condensates depends on the net number of attractive interactions established by each DNA molecule. We conclude that DNA molecules that are much shorter than a typical human gene are able to undergo liquid-liquid phase separation, whereas longer DNA molecules phase separate by default into rather solid-like condensates. We speculate that the local distribution of condensing factors can modulate the effective length of chromosomal domains in the cell. We anticipate that the link between DNA length and fluidity established here will improve our understanding of biomolecular condensates involving DNA.


Identifying an efficient set of items sensitive to clinical-range externalizing problems in children.
The present study applied item response theory to identify an efficient set of items of the Achenbach Externalizing scale from the Child Behavior Checklist (CBCL; 33 items) and Teacher's Report Form (TRF; 35 items) that were sensitive to clinical-range scores. Mothers and teachers rated children's externalizing problems annually from ages 5 to 13 years in 2 independent samples (Ns = 585 and 1,199). Item properties for each rater across ages 5-8 and 9-13 were examined with item response theory. We identified 10 mother- and teacher-reported items from both samples based on the items' measurement precision for subclinical and clinical levels of externalizing problems: externalizing problems that involve meanness to others, destroying others' things, fighting, lying and cheating, attacking people, screaming, swearing/obscene language, temper tantrums, threatening people, and being loud. Scores on the scales using these items had strong reliability and psychometric properties, capturing nearly as much information as the full Externalizing scale for classifying clinical levels of externalizing problems. Scores on the scale with the 10 CBCL items had moderate accuracy, equivalent to the full Externalizing scale, in classifying diagnoses of conduct disorder based on a research diagnostic interview. Of course, comprehensive clinical assessment would consider additional items, dimensions of behavior, and sources of information, too, but it appears that the behaviors tapped by this select set of items may be core to externalizing psychopathology in children. (PsycINFO Database Record


GAB2 regulates type 2 T helper cell differentiation in humans.
Th2 cell differentiation involves complex changes in expression of multiple genes, many of which have poorly characterized roles. In a gene expression microarray analysis of human primary CD4+ effector T subsets, we identified that an adaptor protein, GAB2, was preferentially expressed in human Th2 cells. The role of GAB2 in human Th2 cells is unknown. Through analysis of primary and in vitro differentiated human T effector subsets, we confirmed that human Th2 cells preferentially expressed GAB2. Further analysis of public gene expression microarray data of STAT6-knockdowned Th2 cells indicated that GAB2 expression was regulated by IL-4 and STAT6. Both siRNA knockdown and ectopic expression of GAB2 in activated T cells showed that GAB2 positively regulated IL-4 and IL-13 expression in human Th2 cells. We hence identified the adaptor protein, GAB2, as an important novel regulator of the human Th2 immune response.


Dissecting the bacterial type VI secretion system by a genome wide in silico analysis: what can be learned from available microbial genomic resources?
The availability of hundreds of bacterial genomes allowed a comparative genomic study of the Type VI Secretion System (T6SS), recently discovered as being involved in pathogenesis. By combining comparative and phylogenetic approaches using more than 500 prokaryotic genomes, we characterized the global T6SS genetic structure in terms of conservation, evolution and genomic organization. This genome wide analysis allowed the identification of a set of 13 proteins constituting the T6SS protein core and a set of conserved accessory proteins. 176 T6SS loci (encompassing 92 different bacteria) were identified and their comparison revealed that T6SS-encoded genes have a specific conserved genetic organization. Phylogenetic reconstruction based on the core genes showed that lateral transfer of the T6SS is probably its major way of dissemination among pathogenic and non-pathogenic bacteria. Furthermore, the sequence analysis of the VgrG proteins, proposed to be exported in a T6SS-dependent way, confirmed that some C-terminal regions possess domains showing similarities with adhesins or proteins with enzymatic functions. The core of T6SS is composed of 13 proteins, conserved in both pathogenic and non-pathogenic bacteria. Subclasses of T6SS differ in regulatory and accessory protein content suggesting that T6SS has evolved to adapt to various microenvironments and specialized functions. Based on these results, new functional hypotheses concerning the assembly and function of T6SS proteins are proposed.


Effectiveness of exercise intervention and health promotion on cardiovascular risk factors in middle-aged men: a protocol of a randomized controlled trial.
Although cardiovascular disease has decreased, there is still potential for prevention as obesity and diabetes increase. Exercise has a positive effect on many cardiovascular risk factors, and it can significantly reduce the components of metabolic syndrome. The main challenge with exercise in primary care is how to succeed in motivating the patients at risk to change and increase their exercise habits. The objective of this study is to modify the cardiovascular risk in middle-aged men, either through a health promotion intervention alone or combined with an exercise intervention. During a two-year period we recruit 300 men aged from 35 to 45 years with elevated cardiovascular risk (> two traditional risk factors). The men are randomized into three arms: 1) a health promotion intervention alone, 2) both health promotion and exercise intervention, or 3) control with usual community care and delayed health promotion (these men receive the intervention after one year). The main outcome measures will be the existence of metabolic syndrome and physical activity frequency (times per week). The participants are assessed at baseline, and at 3, 6, and 12 months. The follow-up of the study will last 12 months. This pragmatic trial in primary health care aimed to assess the effect of a health promotion programme with or without exercise intervention on cardiovascular risk and physical activity in middle-aged men. The results of this study may help to plan the primary care interventions to further reduce cardiovascular mortality.The study was registered at the Controlled Trials ( http://www.controlled-trials.com). ISRCTN80672011. The study received ethics approval from the Coordinating Ethics Committee at Helsinki University Hospital on 8 June 2009 (ref: 4/13/03/00/09).