The Characteristics and Mortality of Osteoporosis, Osteomyelitis, or Rheumatoid Arthritis in the Diabetes Population: A Retrospective Study.
Patients with diabetes mellitus are prone to develop osteoporosis, osteomyelitis, or rheumatoid arthritis (RA). Furthermore, the presence of these complications in those with diabetes may lead to higher mortality. The aim of our study was to assess characteristics and mortality of osteoporosis, osteomyelitis, or rheumatoid arthritis in individuals with diabetes. We analyzed osteoporosis, osteomyelitis, and RA deaths associated with diabetes from 1999-2017 using the CDC WONDER system (CDC WONDER; https://wonder.cdc.gov). We used ICD-10 codes to categorize the underlying and contributing causes of death. Crude mortality rates (CMR) and age-adjusted mortality rates (AAMR) per 1,000,000 person-years were calculated. The AAMR for osteoporosis in the population with diabetes was significantly higher in females (AAMR: 4.17, 95% CI: 4.10-4.24) than in males (AAMR: 1.12, 95% CI: 1.07-1.16). Deaths due to osteoporosis increased gradually from 1999, peaked in 2003 (AAMR: 3.78, 95% CI: 3.55-4.00), and reached a nadir in 2016 (AAMR: 2.32, 95% CI: 2.15-2.48). The AAMR for RA associated with diabetes was slightly higher in females (AAMR: 4.04, 95% CI: 3.98-4.11) than in males (AAMR: 2.45, 95% CI: 2.39-2.51). The mortality rate due to RA increased slightly from 1999 (AAMR: 3.18, 95% CI: 2.97-3.39) to 2017 (AAMR: 3.20, 95% CI: 3.02-3.38). The AAMR for osteomyelitis associated with diabetes was higher in males (AAMR: 4.36, 95% CI: 4.28-4.44) than in females (AAMR: 2.31, 95% CI: 2.26-2.36). From 1999 to 2017, the AAMR from osteomyelitis in this population was 2.63 (95% CI: 2.44-2.82) per 1,000,000 person-years in 1999 and 4.25 (95% CI: 4.05-4.46) per 1,000,000 person-years in 2017. We found an increase in the age-adjusted mortality rates of RA and osteomyelitis and a decrease of osteoporosis associated with diabetes from 1999 to 2017. We suggest that increased attention should therefore be given to these diseases in the population with diabetes, especially in efforts to develop preventative and treatment strategies.


Effect of source-classified and mixed collection from residential household waste bins on the emission characteristics of volatile organic compounds.
The implementation of domestic waste classification following the principles of reduction, recycling, and harmlessness is an effective method to improve the urban and rural environments and to promote resource recycling. However, in many developing countries, the community residents lack awareness of the benefits of classified collection, which leads to a lack of initiative to classify MSW. To make the people realize the importance of MSW classification and increase the classification dynamics, Suzhou, China was taken as an example in this study, and residential areas were selected as sampling sites for classified and mixed collection of domestic waste. The main components of the odorous volatile organic compounds (VOCs) emitted from the dustbins via different disposal modes were determined by sampling in spring, summer, autumn, and winter. In addition, the ozone formation potential (OFP) and human health risk assessment of the VOCs were analyzed. Halogenated compounds were the major pollutants from the household waste dustbins of the residential areas. However, aromatic compounds contributed the most to the OFP of the VOCs. The OFP of VOCs reached the highest peak in summer, which was 1.02 × 103 μg/m3. Furthermore, more attention needs to be paid in classifying waste to reduce the concentration of OFP. Although there was a carcinogenic risk in spring and summer, it declined after waste classification. Compared with mixed collection, the source-classified collection of garbage had advantages in terms of controlling the emission of VOCs, ozone formation potential, and human health risk. These results could provide the evidence demonstrating the advantages of waste classification and attract people's attention. Furthermore, the results can also provide impetus to those countries, where separate collection of waste has not yet been implemented, to improve the enthusiasm for classification and the integrity of waste classification system. Residents should be encouraged to classify household waste in residential areas.


Experimental determination of mechanical shear stress about an anastomotic junction.
The present study is undertaken to determine whether the elastic tube model originally developed by Kuchar and Ostrach (Biomedical Fluid Mechanics Symposium, pp. 45-69, 1966) accurately provides a first approximation of the biomechanics of the anastomotic junction. The experimental protocol involves the use of canine carotid arteries as the host vessel and several graft materials including autogenous and prosthetic substitutes. The host artery-graft combinations are perfused in vitro in a pulsatile perfusion apparatus which simulates the natural hemodynamic environment. This apparatus provides accurate dynamic measurements of radial wall motion (measured at various longitudinal increments), associated pressures and rates of fluid flow. These data are then applied to the theoretical model for calculation of anastomotic induced bending stresses. The results indicate that the predictions derived from the elastic model consistently overestimate the measured radial change adjacent to the anastomotic junction. As a result shear stresses based on elastic theory deviate from values derived from a numerical curve fit to the experimental data.


Kwame Nkrumah University of Science and Technology School of Veterinary Medicine (KNUST SVM) A Model of "One-Health Concept" Application to Veterinary Education in West Africa.
Veterinary education in West Africa had been skewed over decades with Nigeria and Senegal leading in the training of veterinarians in the subregion. Most nationals from Ghana, Sierra Leone, Gambia as well as francophone countries within the subregion were trained in East Africa, Europe and South America. The aim of this paper is to provide an insight into the need for veterinary education in other West African countries including Ghana Information was sourced from individuals, literatures and other relevant archives on the history, current state and future approaches to veterinary education in Ghana. The advantages, challenges and coping strategies for application of the Principles of "The One World One Health concept" to veterinary education with the use of the medical professionals in the delivery were presented. This approach to veterinary education by Kwame Nkrumah University of Science and Technology School of Veterinary Medicine showcases a means to meet the health challenges of the twenty first century which demand pragmatic innovation to solve disease challenges.


The microtubule-dependent formation of a tubulovesicular network with characteristics of the ER from cultured cell extracts.
The formation of a dynamic tubulovesicular membrane network that resembles the endoplasmic reticulum (ER) has been observed in extracts of cultured chick embryo fibroblasts (CEF cells) using video-enhanced differential interference contrast microscopy. Initially, membranes in the CEF extracts appeared amorphous and aggregated, but with time, membrane tubules moved out along stationary microtubules. The membrane tubules formed new branches on intersecting microtubules and fused with other branches to form a network of interconnected polygons. The tubulovesicular network was solubilized by detergent and took on a beaded morphology in a hypotonic buffer. Formation of the tubulovesicular network required ATP and microtubules. The network did not contain elements of the plasma membrane, Golgi apparatus, or mitochondria but could be labeled with ER markers. We suggest that the tubulovesicular network contains components from the ER and is formed by membrane associated motors moving upon microtubules in a process we call microtubule-dependent tethering.


Medullary projections of rabbit carotid sinus nerve.
In New Zealand white rabbits, cholera-toxin HRP was injected into the carotid sinus nerve just proximal to the carotid sinus. After survival periods of 3-5 days the rabbits were anesthetized and the brain fixed with aldehyde solution. Transverse sections were cut on a sledge microtome and the sections reacted with the tetramethylbenzidine procedure. HRP-positive fibers entered the ipsilateral dorsolateral medulla at the level of the acoustic tubercle, joining the tractus solitarius. Positive fibres were found principally ipsilaterally in four regions of the medulla: in the caudal two thirds of the nucleus tractus solitarius, in its dorsolateral regions and, more caudally, in its commissural subdivision; in the dorsolateral aspect of the spinal nucleus of the trigeminal nerve; in the region ventral and ventrolateral to the tractus solitarius (extending beyond the nucleus tractus solitarius); and in the ventrolateral medulla oblongata.


Increased interhemispheric resting-state functional connectivity after sleep deprivation: a resting-state fMRI study.
Several functional imaging studies have investigated the regional effects of sleep deprivation (SD) on impaired brain function; however, potential changes in the functional interactions between the cerebral hemispheres after SD are not well understood. In this study, we used a recently validated approach, voxel-mirrored homotopic connectivity (VMHC), to directly examine the changes in interhemispheric homotopic resting-state functional connectivity (RSFC) after SD. Resting-state functional MRI (fMRI) was performed in 28 participants both after rest wakefulness (RW) and a total night of SD. An interhemispheric RSFC map was obtained by calculating the Pearson correlation (Fisher Z transformed) between each pair of homotopic voxel time series for each subject in each condition. The between-condition differences in interhemispheric RSFC were then examined at global and voxelwise levels separately. Significantly increased global VMHC was found after sleep deprivation; specifically, a significant increase in VMHC was found in specific brain regions, including the thalamus, paracentral lobule, supplementary motor area, postcentral gyrus and lingual gyrus. No regions showed significantly reduced VMHC after sleep deprivation. Further analysis indicates that these findings did not depend on the various sizes of smoothing kernels that were adopted in the preprocessing steps and that the differences in these regions were still significant with or without global signal regression. Our data suggest that the increased VMHC might reflect the compensatory involvement of bilateral brain areas, especially the bilateral thalamus, to prevent cognitive performance deterioration when sleep pressure is elevated after sleep deprivation. Our findings provide preliminary evidence of interhemispheric correlation changes after SD and contribute to a better understanding of the neural mechanisms of SD.


Protein kinase C is not involved in the homologous desensitization of bombesin responses in small cell lung cancer cells.
Homologous desensitization of responses to bombesin in small cell lung cancer cells can be mimicked by protein kinase C-activating phorbol esters. We show that phorbol ester-induced desensitization can be blocked by prior treatment with the protein kinase C inhibitor staurosporine or prolonged pretreatment with phorbol esters. However, under these conditions, homologous desensitization to bombesin persists. These data indicate that phorbol ester-induced desensitization is distinguishable from bombesin-induced homologous desensitization. Protein kinase C is not a dominant component in the homologous desensitization to bombesin in small cell lung cancer cells.


A bug's life: change and transformation in early modern China.
Chanting wasps and shape-shifting worms were all in a day's work for sixteenth-century Chinese naturalists such as Li Shizhen (1518-1593). In an effort to understand the metamorphoses of both nature and the human body, he and other early modern Chinese scholars looked towards tiny creatures like roundworms, lice and demon bugs. For them, such animals could reveal the most intimate secrets of the universe.


Management of aldose reductase mRNA abundance in rat lens undergoing reversal of galactose induced cataracts. A model for gene response to changes in the environment.
Aldose reductase (AR) mRNA concentration in rat lens was quantitated by hybridization of a RNA transcript from a previously described AR cDNA clone to mRNA found in epithelial and cortical cytosols. This was done on normal rat lens and on lens initially made cataractous by feeding of a diet of Purina Chow containing 50% galactose, followed by reversal of the cataracts due to the removal of the galactose from the diet. Recent data from this laboratory has shown that AR mRNA was increased in lens epithelial cells upon administration of galactose; while in the cortex it was reduced to insignificant levels when fiber cell damage became extensive by day 20 on galactose. Present data reveals that, upon removal of galactose from the diet, the lens epithelial AR mRNA was gradually reduced from the high levels found at day 20 of galactose feeding to low levels by day 30 of reversal. On the other hand, the cortex exhibited an initial sudden increase in AR mRNA at days 1 to 6 of reversal and by day 30 it was reduced to levels below those found in the untreated lens. DNA content in the epithelium also began to decrease to normal levels by day 16 following reversal of the cataracts. The data demonstrate that the concentration of AR mRNA in lens of reversed cataracts appears to faithfully reflect the loss of epithelial cellular need for AR mRNA in favor of enhanced differentiation of epithelial cells to secondary fiber cells.


Flavonoids from Abutilon theophrasti flowers.
Nine flavonoid compounds: kaempferol 3-0-beta-(6"-p-coumaroyl)-glucopyranoside, myricetin 3-O-beta-glucopyranoside, quercetin 3-0-beta-glucopyranoside, quercetin 3-0-alpha-rhamnopyranosyl (1-->6)-beta-glucopyranoside, kaempferol 3-0-beta-glucopyranoside, kaempferol 3-0-alpha-rhamnopyranosyl (1-->6)-beta-glucopyranoside, quercetin 7-0-beta-glucoside, quercetin 7-0-beta-diglucoside, kaempferol 7-0-beta-diglucoside were isolated and identified from the flowers of Abutilon theophrasti.


Doppler evaluation of homograft valved conduits in children.
To assess the flow characteristics of homograft valved conduits in the immediate postoperative period, 69 children with 71 homograft conduits underwent 2-dimensional and Doppler echocardiographic examination at 1 to 40 days (mean 8) after surgery. Of the 71 conduits studied, 19 were aortic and 52 were pulmonary homograft valved conduits. Two aortic homograft valved conduits were inserted in the aortic position, whereas all remaining homografts were placed in the pulmonary position. On the immediate postoperative echocardiogram, 25 (35%) of the conduit valves had no regurgitation and 44 (62%) had 1+ (mild) regurgitation. Two pulmonary valved conduits (3%) in the pulmonary position had 2+ (moderate) regurgitation and right ventricular dimensions greater than 95% for body surface area. The peak velocity across the homograft valve was normal (less than 1.3 m/s) in 58 valves (82%). In the remaining 13 valves, peak velocity ranged from 1.4 to 2.6 m/s. No homograft valve had a peak velocity greater than 2.6 m/s in the immediate postoperative period. To assess the fate of homograft valved conduits in the intermediate-term follow-up period, 38 children with 38 conduits had a repeat echocardiogram at 6 to 25 months (mean 15 +/- 6) after surgery. Of the 38 conduits examined, 10 (26%) had no regurgitation, 25 (66%) had 1+ regurgitation and 3 (8%) had 2+ regurgitation. Progression of the amount of regurgitation occurred in 11 (29%) patients. At the follow-up examination, peak velocity was less than or equal to 1.4 m/s across 34 conduit valves, between 1.4 and 2.6 m/s across 3 valves and greater than 2.6 m/s across 1 valve.(ABSTRACT TRUNCATED AT 250 WORDS)


Assessing predictors of students' academic performance in Ethiopian new medical schools: a concurrent mixed-method study.
Since 2012 the Ethiopian Federal Ministry of Health and Education implemented a new medical curriculum in 13 institutions. The new curriculum introduced some questions on its admission policy: students can join with different educational backgrounds. Students' performance on qualifying exams and grade point average are lower than desired. Therefore, the aim of the study was to investigate what factors predict the academic performance of students in the New Medical Education Initiative in Ethiopia. A concurrent mixed method of survey and qualitative was used; for the survey, a structured self-administered questionnaire was distributed to students of four randomly selected medical schools from December 2018 to January 2019. The questionnaire includes questions about socio-demographic and educational background of participants. Multiple linear regression analysis was used in order to identify the factors associated with academic performance. In-depth interviews were conducted with 15 key informants to explore qualitatively. In the multiple linear regressions, stress was associated with lower academic performance. Students with prior education in the field of health science outperformed students with other bachelors. The cumulative grade point average of the previous bachelor degree and the score on the entrance exam to join medicine also significantly predicted performance. Although some more variables are identified from the qualitative interviews, its findings supported the survey results. Of the number of predictor variables analyzed in the model, only stress, prior educational degree, performance in the prior degree and entrance exam score were significantly correlated with the performance of students in their preclinical medical engagement.


Determination of the in vivo loading of the lumbar spine with a new approach directly at the workplace--first results for nurses.
To determine the magnitude of workplace loading for nurses with and without a history of low back pain. A measurement system for the assessment of workplace loading as well as a model for the calculation of lumbo-sacral junction loading was designed and applied to a group of 12 nurses with and without a history of low back pain. Disagreement exists regarding the key factors in the aetiology of low back pain. Traditionally workplace loading is viewed as the dominant influence. Data for workplace loading in jobs with non-uniform tasks, however, do rarely exist. A three-dimensional inverse-dynamic and force distribution model as well as the respective data acquisition system was used to assess the workplace loading of 12 nurses from surgical departments of two hospitals. The nurses were assigned to two groups based on their history of low back pain (with/without). Workplace loading was measured continuously for 4 h. No differences in workplace loading between nurses with/without a history of low back pain were found. Maximum values of the compressive force at the lumbo-sacral junction were high and well above suggested workplace load limits. High values occurred only during short-time periods (about 0.4% of total shift duration). A system for the assessment of overall workplace loading has been developed. First results for nurses suggest that critical loadings do exist at the workplace, even so they might not be the decisive factor for the development of low back pain. Preventative measures for low back pain in nursing have to include prevention of critical workplace loading. This approach by itself, however, is probably not sufficient.


Assessing the results of thrust plate prosthesis: a comparison of four different rating systems.
To evaluate four rating systems designed to assess patients following provision of a thrust plate prosthesis. Sixty-one patients undergoing total hip replacement with thrust plate prosthesis. Patients were evaluated preoperatively and six months postoperatively by four different hip rating systems (Harris, Iowa, Charnley and Merle d'Aubigne), both on a categorical and on a numerical basis. Department of orthopaedics and traumatology in a university hospital. Patients were evaluated by four rating systems preoperatively and postoperatively either on a categorical or a numerical basis. All patients showed significant improvement after surgery in all rating systems. Although preoperative categorical evaluation revealed that the strongest correlation was between Charnley and Merle d'Aubigne scores (r = 0.876), numerical comparison of the rating systems showed strong correlation among all systems, both pre- and postoperatively. Responsiveness analysis revealed larger effect size for the Iowa and Harris hip scores. Our results suggest that hip rating systems should be compared numerically rather than by categorical evaluation and that the Iowa and Harris hip scores are more convenient in evaluating thrust plate prosthesis patients because they have larger effect sizes without floor and ceiling effects.


Thyroid hormone and "cardiac metamorphosis": potential therapeutic implications.
Recent research has revealed novel actions of thyroid hormone (TH) on the heart which may be of important physiological and therapeutic relevance. TH, apart from its "classical" actions on cardiac contractility and heart rhythm, appears to regulate various intracellular signaling pathways related to stress responses and cardiac remodelling. Accumulating experimental evidence suggests that changes in TH may constitute an important component in the pathophysiology of heart failure. In fact, TH seems to be a "switch" for the fetal cardiac phenotype. Changes in the TH-thyroid hormone receptor axis are also evident in patients with heart failure and associated with impaired cardiac function and increased mortality. More importantly, experimental and clinical studies demonstrate that TH can limit ischaemic injury, attenuate cardiac remodeling and improve cardiac hemodynamics. TH analogs have already been developed and may allow exploitation of the TH-thyroid hormone receptor in clinical practice. At present, the therapeutic potential and efficacy of TH in the treatment of cardiac diseases await evaluation in large clinical trials.


The Vaccine Adjuvant Chitosan Promotes Cellular Immunity via DNA Sensor cGAS-STING-Dependent Induction of Type I Interferons.
The cationic polysaccharide chitosan is an attractive candidate adjuvant capable of driving potent cell-mediated immunity, but the mechanism by which it acts is not clear. We show that chitosan promotes dendritic cell maturation by inducing type I interferons (IFNs) and enhances antigen-specific T helper 1 (Th1) responses in a type I IFN receptor-dependent manner. The induction of type I IFNs, IFN-stimulated genes and dendritic cell maturation by chitosan required the cytoplasmic DNA sensor cGAS and STING, implicating this pathway in dendritic cell activation. Additionally, this process was dependent on mitochondrial reactive oxygen species and the presence of cytoplasmic DNA. Chitosan-mediated enhancement of antigen specific Th1 and immunoglobulin G2c responses following vaccination was dependent on both cGAS and STING. These findings demonstrate that a cationic polymer can engage the STING-cGAS pathway to trigger innate and adaptive immune responses.


Reflections on the dynamics of bacterial and viral contamination of blood components and the levels of efficacy for pathogen inactivation processes.
Blood transfusion safety has been increasingly improving during the past two decades. However, threats from both known and emerging pathogens require continual improvement and re-assessment of blood safety measures. In this respect, we are currently witnessing the broader implementation of Pathogen reduction technology (PRT) for blood complements. These methods, combined with existing safety measures, have helped to reduce the pathogen risks of transfusion-transmitted infections. Currently multiple reviews have compared levels of inactivation between different commercialized PRTs. However, to analyze levels of pathogen inactivation, it is necessary to understand the dynamics of infectivity as well as the modes of disease transmission by blood transfusion for various pathogens. It is well known that contributing variables include donor characteristics through the processing of blood components to ultimately the recipient characteristics, which create enormous variability in overall outcomes relative to disease transmission. The aim of this paper is to discuss bacterial and viral contamination of blood components in order to determine adequate levels of efficacy and subsequent disease transmission safety of current pathogen inactivation protocols that are designed to reduce the risk of transfusion-transmitted infections. In such a conceptual analysis, however, it is important to understand several contributing factors including the measurement of pathogen load in blood products and the dynamics, infectivity and disease transmission of various pathogens via transfusion of blood components and products. In many cases, the log reduction values observed do not truly reflect the extent of reduction in the levels of infectivity that are observed clinically. Results from clinical trials and hemovigilance programs upon routine implementation of PRT methods provide a more direct insight into effectiveness with regard to clinical relevance of in vitro spiking studies. These issues are briefly addressed in this manuscript.


Diagnosing psychiatric disorders in adolescent females with abdominal pain.
Psychiatric diseases, recently renamed psychiatric disorders by the American Psychiatric Association, are commonly associated with abdominal pain in adolescents but may be difficult to diagnose. In a prospective study, we evaluated four psychiatric scales, including the Childhood Depression Inventory (CDI) and the Speilberger State-Trait Anxiety Inventory (STAI) as aids in the diagnosis of psychiatric disorders in 40 adolescent females with abdominal pain. Final diagnosis of organic-dysfunctional disease was made in 32 patients, and a psychiatric disorder was found in eight. Only the CDI (p = 0.001) and the State (p = 0.006) and Trait (p = 0.022) scales of the STAI had significantly different mean values between subjects with organic-dysfunctional disease and a psychiatric disorder. Almost all subjects with a psychiatric disorder had abnormally high scores, whereas the subjects with organic-dysfunctional disease did not. We conclude that three brief, self-administered psychiatric scales may be useful in differentiating between organic-dysfunctional disease and a psychiatric disorder in adolescent patients with abdominal pain.


Mutation analysis of the TSC1 and TSC2 genes in Japanese patients with pulmonary lymphangioleiomyomatosis.
Pulmonary lymphangioleiomyomatosis (LAM) is a destructive lung disease characterized by a diffuse hamartomatous proliferation of smooth muscle cells (LAM cells) in the lungs. Pulmonary LAM can occur as an isolated form (sporadic LAM) or in association with tuberous sclerosis complex (TSC) (TSC-LAM), a genetic disorder with autosomal dominant inheritance with various expressivity resulting from mutations of either the TSC1 or TSC2 gene. We examined mutations of both TSC genes in 6 Japanese patients with TSC-LAM and 22 patients with sporadic LAM and identified six unique and novel mutations. TSC2 germline mutations were detected in 2 (33.3%) of 6 patients with TSC-LAM and TSC1 germline mutation in 1 (4.5%) of 22 sporadic LAM patients. In accordance with the tumor-suppressor model, loss of heterozygosity (LOH) was detected in LAM cells from 3 of 4 patients with TSC-LAM and from 4 of 8 patients with sporadic LAM. Furthermore, an identical LOH or two identical somatic mutations were demonstrated in LAM cells microdissected from several tissues, suggesting LAM cells can spread from one lesion to another. Our results from Japanese patients with LAM confirmed the current concept of pathogenesis of LAM: TSC-LAM has a germline mutation but sporadic LAM does not; sporadic LAM is a TSC2 disease with two somatic mutations; and a variety of TSC mutations causes LAM. However, our study indicates that a fraction of sporadic LAM can be a TSC1 disease; therefore, both TSC genes should be examined, even for patients with sporadic LAM.


Checking for optimal solutions in some NP-complete problems.
For some weighted NP-complete problems, checking whether a proposed solution is optimal is a nontrivial task. Such is the case for the traveling salesman problem, or the spin-glass problem in three dimensions. In this Letter, we consider the weighted tripartite matching problem, a well known NP-complete problem. We write mean-field finite temperature equations for this model and derive their zero temperature limit. We show that any solution of the zero temperature equations provides an exact absolute ground state of the system. As a consequence, we propose a criterion which can be checked in polynomial time, and such that given a putative optimal solution, if the criterion is satisfied, then the solution is indeed optimal. This criterion is generalized to a class of variants of the multiple traveling salesmen problems.


Efficacy of cancer-specific anti-podoplanin CAR-T cells and oncolytic herpes virus G47Δ combination therapy against glioblastoma.
Glioblastoma is a devastating malignant brain tumor with a poor prognosis despite standard therapy. Podoplanin (PDPN), a type I transmembrane mucin-like glycoprotein that is overexpressed in various cancers, is a potential therapeutic target for the treatment of glioblastoma. We previously reported the efficacy of chimeric antigen receptor (CAR)-T cells using an anti-pan-PDPN monoclonal antibody (mAb; NZ-1)-based third-generation CAR in a xenograft mouse model. However, NZ-1 also reacted with PDPN-expressing normal cells, such as lymphatic endothelial cells, pulmonary alveolar type I cells, and podocytes. To overcome possible on-target-off-tumor effects, we produced a cancer-specific mAb (CasMab, LpMab-2)-based CAR. LpMab-2 (Lp2) reacted with PDPN-expressing cancer cells but not with normal cells. In this study, Lp2-CAR-transduced T cells (Lp2-CAR-T) specifically targeted PDPN-expressing glioma cells while sparing the PDPN-expressing normal cells. Lp2-CAR-T also killed patient-derived glioma stem cells, demonstrating its clinical potential against glioblastoma. Systemic injection of Lp2-CAR-T cells inhibited the growth of a subcutaneous glioma xenograft model in immunodeficient mice. Combination therapy with Lp2-CAR-T and oncolytic virus G47Δ, a third-generation recombinant herpes simplex virus (HSV)-1, further inhibited the tumor growth and improved survival. These findings indicate that the combination therapy of Lp2-CAR-T cells and G47Δ may be a promising approach to treat glioblastoma.


Human Dirofilariasis Caused by Dirofilaria repens in Sri Lanka from 1962 to 2020.
Sri Lanka has reported the highest prevalence of human dirofilariasis cases in Asia. Thus far, Dirofilaria repens is the only reported Dirofilaria species that affect humans, dogs, and cats in Sri Lanka. Therefore, this systematic review was carried out to analyse the studies performed on dirofilariasis in Sri Lanka. Peer-reviewed articles were searched on dirofilariasis published on Google Scholar, PubMed, Cochrane, and ResearchGate from January to March 2021. Articles were selected using inclusion and exclusion criteria. Three reviewers assessed the studies and extracted data independently to minimize the risk of bias. Extracted data were compiled, and then the results were compared and discussed in this systematic review. Twenty-five studies performed in Sri Lanka were analysed, and high prevalence areas, frequent clinical presentations, diagnostic methods, reservoir hosts, and treatment were identified. More than 173 cases of human dirofilariasis caused by D. repens were reported from 1962 to 2020 in 20 districts among 25 investigated. The highest number of cases (n = 80) was recorded during 2010-2012 period. Canine and feline dirofilariasis are reported countrywide, and a large number of potential mosquito breeding sites could be seen in Sri Lanka. The number of reported cases of human dirofilariasis has been varied from 1962 to 2020. The highest number of cases has reported in 2010-2012, and then the number of cases has dropped. This may be due to underreporting. Thus, awareness of Dirofilaria repens infection in humans, control measures in endemic areas and further research on dirofilariasis in other districts of Sri Lanka are crucial.


Evaluation of the fit and strength of an all-ceramic fixed partial denture.
A laboratory investigation of the fit and strength of three-unit all-ceramic FPDs was performed with a metal-ceramic FPD control. The conclusions were: 1. No difference was found between the marginal seal of the metal-ceramic and all-ceramic FPDs. 2. The all-ceramic FPDs had a more uniform cement space and their occlusal seat was significantly (99.9%) better than the metal-ceramic restorations. 3. The metal-ceramic FPDs were significantly stronger than the all-ceramic FPDs. 4. Load calculations suggest that short-span all-ceramic FPDs may be strong enough to resist normal masticatory forces for selected patients. However, generalized usage will probably result in an unacceptable failure rate.


Standardizing 25-hydroxyvitamin D data from the HunMen cohort.
Standardization of 25-hydroxyvitamin D (25OHD) values is still a challenge. We propose standardization by correction of the measured 25OHD values using the linear regression bias from the National Institute of Standards and Technology (NIST) 'total' target values reported by Vitamin D External Quality Assessment Scheme (DEQAS). Our approach could perhaps be a practical solution to the anomaly surrounding non-standardized 25OHD values. Standardization of 25OHD values is still a challenge. We propose standardization by correction of the measured 25OHD values using the linear regression equation derived from the analysis of relationship between total 25OHD values measured by the methodology used by the laboratory and the NIST total target values (TV) reported by the DEQAS for all 5 of the DEQAS samples in a given survey. We applied our approach to standardize total 25OHD values of the HunMen cohort. All 206 samples for the HunMen cohort were evaluated using the automated Liaison DiaSorin total 25OHD chemiluminescence immunoassay (CLIA). The timing of these measurements coincided with that of the October 2015 DEQAS survey using samples 481 to 485. Following standardization, the mean total 25OHD changed from 53 to 62 nmol/L and the prevalence of hypovitaminosis D (<75 nmol/L) decreased significantly from 84 to 72%. A simple approach readily applicable at the routine diagnostic laboratory could perhaps be a practical solution to the anomaly surrounding non-standardized 25OHD values.


Design, synthesis and biological evaluation of hesperetin derivatives as potent anti-inflammatory agent.
A flavonoid hesperetin is reported to have a variety of biological activities, including anticancer, antiviral, antioxidant, neuroprotective and anti-inflammatory properties. Thirty-one novel hesperetin derivatives were designed, synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells and CCl4-induced acute liver injury model. Among these compounds, 5b displayed the excellent anti-inflammatory activity on decreasing NO, IL-6 and TNF-α both in vitro and vivo. In addition, 5b could also reduce the release of NO, IL-6 and TNF-α production by LPS stimulated RAW 264.7 cell through MAPK and NF-κB signaling pathway in a concentration dependent manner. From in vivo study, it was also observed that 5b attenuated liver histopathologic changes in mouse models.


Publication biases and phase II trials investigating anticancer targeted therapies.
The aim of this study was to determine which parameter may affect impact factor (IF) of journals publishing reports of phase II trial (P2T) investigating molecular targeted therapies (MTT). We reviewed 74 reports of P2Ts investigating MTT (imatinib, n = 55; sorafenib, n = 11; sunitinib, n = 5; dasatinib, n = 3) issued between 1/2002 and 6/2008. As a result, we found that the final result of the trial itself was the most important parameter that was related to IF, as the median-IF was significantly lower for negative trials than for positive trials (2.71 vs 6.14, p = 0.004).


Lower esophageal sphincter relaxation characteristics using a sleeve sensor in clinical manometry.
We undertook this study to determine the characteristics of swallow-induced lower esophageal sphincter (LES) relaxation in the setting of clinical manometry using a standardized methodology. We reviewed 170 manometric recordings performed using a perfused manometric assembly with a sleeve sensor and a computer polygraph. Patients were categorized as patient controls, gastroesophageal reflux disease (GERD), diffuse esophageal spasm (DES), or achalasia. Tracing were semiautomatically analyzed for basal LES pressure, LES pressure during deglutitive relaxation (relaxation LES pressure), duration of LES relaxation, timing of LES relaxation, and the success rate of primary peristalsis. Forty-six patient controls, 93 with GERD, five with DES, and 26 with achalasia were identified. GERD and achalasia patients had lower or higher basal LES pressures than patient controls, respectively. Compared with patient controls, achalasia patients had higher relaxation LES pressures, lower percent LES relaxation, and shorter durations of LES relaxation. The best single measure for distinguishing achalasia was the relaxation LES pressure; using the 95th percentile value of patient controls (12 mm Hg) as the upper limit of normal, its sensitivity and positive predictive value for the diagnosis of achalasia were 92% and 88%, respectively. Coupled with the finding of aperistalsis, a relaxation LES pressure > or = 10 mm Hg achieved 100% sensitivity and positive predictive value among these patients. Sleeve sensor recording is a practical method for clinical manometry that reliably records LES relaxation characteristics and is amenable to both a standardized manometry protocol and a semiautomated analysis routine. Relaxation LES pressure has a high diagnostic value for achalasia.


High expression of MCL1 gene related to vascular endothelial growth factor is associated with poor outcome in non-Hodgkin's lymphoma.
We evaluated the level of MCL1 gene expression using quantitative reverse transcription polymerase chain reaction in lymph nodes of patients with non-Hodgkin lymphoma (NHL). MCL1 expression in patients in complete remission (CR) was significantly lower than in patients with progressive disease (PD, P = 0.0043). The disease-free survival rate was significantly higher in patients with MCL1 levels below the median level (P = 0.007). We also found that the level of expression of MCL1 mRNA was related to that of vascular endothelial growth factor mRNA in NHL lymph nodes. Our data suggest that the MCL1 expression level could be considered a prognostic factor in NHL.


Setting up a 2D-LC/MS/MS method for the rapid quantitation of the prostanoid metabolites 6-oxo-PGF(1alpha) and TXB2 as markers for hemostasis assessment.
6-oxo-PGF(1alpha) and TXB(2) are the metabolites of the prostanglandin PGI(2) and of the thromboxane TXA(2), respectively. PGI(2) and TXA(2) are arachidonic acid-derived compounds which regulate the blood hemostasis. Their quick metabolism leads to the 6-oxo-PGF(1alpha) and TXB(2) metabolites in plasma. In order to study on a large base the external factors influencing the hemostatic conditions, there is a need for a fast and reliable assay for quantitating these metabolites. Some methods have been published for the analysis of the arachidonic acid-derived compounds and some are dealing with mass spectrometry but nonspecifically centered on these specific compounds with a fast and cheap protocol, amenable for large-scale studies. Here we describe an analytical strategy that incorporates a two-dimensional chromatography running coupled to tandem mass spectrometry that minimizes the sample preparation and addresses the presence of the TXB(2) anomers for a robust quantitation measurement. After a protein precipitation, 100 microl of the supernatant (corresponding to 50 microl of the original plasma) was injected in a two-dimensional chromatographic system which operates an on-line clean-up and a subsequent chromatographic separation of the targeted analytes with a limit of quantitation (LOQ) of 22 pg/ml for 6-oxo-PGF(1alpha), and and a LOQ of 25 pg/ml for TXB(2).


Unravelling the genetic components involved in the immune response of pigs vaccinated against influenza virus.
A genome-wide association study for immune response to influenza vaccination in a crossbred swine population was conducted. Swine influenza is caused by influenza A virus (FLUAV) which is considered one of the most prevalent respiratory pathogens in swine worldwide. The main strategy used to control influenza in swine herds is through vaccination. However, the currently circulating FLUAV subtypes in swine are genetically and antigenically diverse and their interaction with the host genetics poses a challenge for the production of efficacious and cross-protective vaccines. In this study, 103 pigs vaccinated with an inactivated H1N1 pandemic virus were genotyped with the Illumina PorcineSNP60V2 BeadChip for the identification of genetic markers associated with immune response efficacy to influenza A virus vaccination. Immune response was measured based on the presence or absence of HA (hemagglutinin) and NP (nucleoprotein) antibodies induced by vaccination and detected in swine sera by the hemagglutination inhibition (HI) and ELISA assays, respectively. The ELISA test was also used as a measurement of antibody levels produced following the FLUAV vaccination. Associations were tested with x(2) test for a case and control data and using maximum likelihood method for the quantitative data, where a moderate association was considered if p<5×10(-5). When testing the association using the HI results, three markers with unknown location and three located on chromosomes SSCX, SSC14 and SSC18 were identified as associated with the immune response. Using the response to vaccination measured by ELISA as a qualitative and quantitative phenotype, four genomic regions were associated with immune response: one on SSC12 and three on chromosomes SSC1, SSC7, and SSC15, respectively. Those regions harbor important functional candidate genes possibly involved with the degree of immune response to vaccination. These results show an important role of host genetics in the immune response to influenza vaccination. Genetic selection for pigs with better response to FLUAV vaccination might be an alternative to reduce the impact of influenza virus infection in the swine industry. However, these results should to be validated in additional populations before its use.


Participation of two N-terminal residues in LPS-neutralizing activity of sarcotoxin IA.
Sarcotoxin IA is a cecropin-type antibacterial peptide of flesh fly. Using a mutant sarcotoxin IA lacking two N-terminal residues, we demonstrated that these residues are indispensable for its antibacterial activity against Escherichia coli and LPS-binding. Contrary to the native sarcotoxin IA, the mutant sarcotoxin IA could not neutralize various biological activities of LPS. It was suggested that sarcotoxin IA firmly binds to the lipid A core of LPS via these two N-terminal residues and forms a stable binding complex that exhibits no appreciable biological activity like native LPS.


Daratumumab, bortezomib, and dexamethasone in relapsed or refractory multiple myeloma: subgroup analysis of CASTOR based on cytogenetic risk.
Multiple myeloma (MM) patients with high cytogenetic risk have poor outcomes. In CASTOR, daratumumab plus bortezomib/dexamethasone (D-Vd) prolonged progression-free survival (PFS) versus bortezomib/dexamethasone (Vd) alone and exhibited tolerability in patients with relapsed or refractory MM (RRMM). This subgroup analysis evaluated D-Vd versus Vd in CASTOR based on cytogenetic risk, determined using fluorescence in situ hybridization and/or karyotype testing performed locally. High-risk patients had t(4;14), t(14;16), and/or del17p abnormalities. Minimal residual disease (MRD; 10-5 sensitivity threshold) was assessed via the clonoSEQ® assay V2.0. Of the 498 patients randomized, 40 (16%) in the D-Vd group and 35 (14%) in the Vd group were categorized as high risk. After a median follow-up of 40.0 months, D-Vd prolonged median PFS versus Vd in patients with standard (16.6 vs 6.6 months; HR, 0.26; 95% CI, 0.19-0.37; P < 0.0001) and high (12.6 vs 6.2 months; HR, 0.41; 95% CI, 0.21-0.83; P = 0.0106) cytogenetic risk. D-Vd achieved deep responses, including higher rates of MRD negativity and sustained MRD negativity versus Vd, regardless of cytogenetic risk. The safety profile was consistent with the overall population of CASTOR. These updated data reinforce the effectiveness and tolerability of daratumumab-based regimens for RRMM, regardless of cytogenetic risk status. ClinicalTrials.gov, NCT02136134 . Registered 12 May 2014.


Hair follicle-MSC-derived small extracellular vesicles as a novel remedy for acute pancreatitis.
Hair follicle-derived mesenchymal stem cell (HF-MSC)-based therapies protect against acute pancreatitis (AP). However, accumulating evidence suggests that MSC-based therapy mainly involves the secretion of MSC-derived small extracellular vesicles (MSC-sEVs) through paracrine effects. Thus, the present research investigated the therapeutic effect of HF-MSC-sEVs in AP and the underlying mechanisms. SEVs were purified from cultured HF-MSC supernatant. The effects of sEVs in vitro were analyzed on caerulein-simulated pancreatic acinar cells (PACs). The therapeutic potential of sEVs in vivo was examined in a caerulein-induced AP model. The organ distribution of sEVs in mice was determined by near-infrared fluorescence (NIRF) imaging. Serum specimens and pancreatic tissues were collected to analyze the inhibition of inflammation and pyroptosis in vivo, as well as the appropriate infusion route: intraperitoneal (i.p.) or intravenous (i.v.) injection. HF-MSC-sEVs were taken up by PACs and improved cell viability in vitro. In vivo, sEVs were abundant in the pancreas, and the indicators of pancreatitis, including amylase, lipase, the inflammatory response, myeloperoxidase (MPO) expression and histopathology scores, in sEV-treated mice were markedly improved compared with those in the AP group, especially via tail vein injection. Furthermore, we revealed that sEVs observably downregulated the levels of crucial pyroptosis proteins in both PACs and AP tissue. We innovatively demonstrated that HF-MSC-sEVs could alleviate inflammation and pyroptosis in PACs in AP, suggesting a refreshing cell-free remedy for AP.


Effects of membrane orientation on fouling characteristics of forward osmosis membrane in concentration of microalgae culture.
Application of forward osmosis (FO) membrane to microalgae cultivation processes enables concentration of microalgae and nutrients with low energy consumption. To understand fouling characteristics of FO membrane in concentration of microalgae culture, we studied flux decline, flux recovery by cleaning, and foulants characteristics, in different membrane orientation of active-layer-facing-feed-solution (AL-FS) and active-layer-facing-draw-solution (AL-DS) modes. Batch concentration of Chlorella vulgaris was conducted with a cellulose-triacetate FO membrane. Rapid flux decline and lower flux recovery was observed in AL-DS mode because of inner-membrane fouling including internal pore clogging, adsorption and internal concentration polarization in the support layer. A proportion of polysaccharides in extracellular polymeric substances to soluble microbial products were larger in chemical cleaning effluent than physical one in AL-DS mode, although those were not significantly different in AL-FS mode. Excitation-emission matrix analysis revealed that proteins and humic-like substances were also possible irreversible foulants both in AL-DS and AL-FS modes.


Bringing Health Care Equity to Diverse and Underserved Populations in Sleep Medicine and Research Through a Digital Health Equity Framework.
Individuals from minoritized groups are less likely to receive sleep medicine care and be the focus of sleep research. Several barriers may explain under-representation and low participation. The coronavirus disease 2019 (COVID-19) pandemic highlighted a digital divide that exacerbated disproportionate sleep health outcomes and access to sleep medicine and research opportunities among minoritized groups. The authors' team developed a digital health equity and inclusion model and revamped its culturally-tailored community outreach program to advance sleep health equity among minoritized groups. This article describes how the authors implemented their digital sleep health equity and inclusion model during the COVID-19 pandemic.


Transforming growth factor-beta1 blocks the enhancement of tumor necrosis factor cytotoxicity by hyaluronidase Hyal-2 in L929 fibroblasts.
Functional antagonism between transforming growth factor beta (TGF-beta) and hyaluronidase has been demonstrated. For example, testicular hyaluronidase PH-20 counteracts TGF-beta1-mediated growth inhibition of epithelial cells. PH-20 sensitizes various cancer cells to tumor necrosis factor (TNF) cytotoxicity by upregulating proapoptotic p53 and WW domain-containing oxidoreductase (WOX1). TGF-beta1 blocks PH-20-increased TNF cytotoxicity. In the present study, the functional antagonism between TGF-beta1 and lysosomal hyaluronidases Hyal-1 and Hyal-2 was examined. Murine L929 fibroblasts were engineered to stably express green-fluorescent protein (GFP)-tagged hyaluronidase (GFP-Hyal-1 or GFP-Hyal-2) or GFP alone. Compared to control cells, Hyal-2-expressing cells had a significantly increased sensitivity to TNF cytotoxicity (approximately 60-110% increase), while Hyal-1-expressing cells were less sensitive to TNF (approximately 20-90% increase). TNF activated NF-kappaB, along with IkappaBalpha degradation, occurred at 20 to 60 min in Hyal-2 cells post stimulation, but at the 20 min time point in both control and Hyal-1 cells. Hyal-2 cells, but not Hyal-1 and control cells, constitutively expressed WOX1, and transiently expressed Hyal-2 enhanced WOX1-mediated cell death. Unlike PH-20, Hyal-1 and Hyal-2 did not induce p53 expression. Hyal-2 translocated from the lysosome to the mitochondria during staurosporine-mediated apoptosis, suggesting that Hyal-2 may damage mitochondria. Finally, Hyal-1 and Hyal-2 blocked TGF-beta1-enhanced L929 cell growth. In contrast, TGF-beta1 inhibited Hyal-1- and Hyal-2-increased TNF cytotoxicity in L929 cells by 30-50%. TGF-beta1 limits the ability of Hyal-2 to induce TNF cytotoxicity in L929 cells. Hyal-2-increased TNF cytotoxicity in L929 cells appears to be correlated with upregulation of WOX1, a prolonged NF-kappaB activation, and Hyal-2 translocation to the mitochondria during apoptosis.


The relationship between patients' concerns and psychological distress in a hospice setting.
A total of 87 patients admitted to two hospices during a 9 month period were assessed by trained nurses to determine their current concerns. These assessment interviews were tape recorded. A trained researcher then administered a semi structured concerns interview using the Concerns Checklist, the Hospital Anxiety and Depression Scale and the Spielberger State Anxiety Inventory. Patients reported an average of 6.5 concerns. Concerns about loss of independence and the family were most common. Although a third of the patient sample died within a short time after the interview, concerns about cancer, the future and dying were infrequent. Using a threshold score on the Hospital Anxiety and Depression Scale of > 19 to allow for the effect of disease, 17% of the sample were judged to be probable cases of clinical anxiety and/or depression. There was a strong association between the number of concerns patients experienced and psychological distress (p < 0.001). Concerns about pain and treatment were particularly associated with anxiety whereas concerns about disability were linked with depressed mood. Concerns about cancer were linked with both anxious and depressive changes in mood (p < 0.001). The study highlights the diverse nature of hospice patients' concerns and shows a clear link between psychological distress and number of concerns expressed by patients.


Risk factors for heroin use following release from jail or prison in adults in a Central Appalachian state between 2012-2017.
Corrections-involved adults with a history of opioid use disorder are at elevated risk of opioid overdose following release from correctional settings. Increased opioid prescribing restrictions and monitoring during a time when heroin is becoming cheaper and ubiquitous means that adults who misused prescription opioids prior to incarceration may be reentering communities at greater risk for heroin exposure and use. Determine risk factors of post-release heroin use among a sample of adults who participated in corrections-based drug treatment in Kentucky released between 2012 and 2017. Survey data obtained as part of an ongoing evaluation of corrections-based drug treatment were examined. The final sample (N = 1,563) was majority male (80.9%). Nearly 11.0% reported past-year heroin use following their release. Depressive symptoms, polydrug use, and urban proximity were more common among participants reporting post-release heroin use. Heroin use 30 days prior to incarceration was associated with a 432.1% increase in odds of heroin use subsequent to incarceration. Post-release suicidal ideation increased odds of heroin use by 154.2%, whereas reporting satisfaction from social interactions decreased odds of use by nearly 60%. Post-release use of cocaine and diverted buprenorphine were associated with increased likelihood of heroin use during this time period, increasing odds by 469.1% and 265.9%, respectively. Residing in Central Appalachia subsequent to incarceration was associated with decreased likelihood of use. In this sample, post-release heroin use was associated with concerning features, such as polydrug use, lack of social satisfaction, and suicidal ideation. These features can serve as clear targets for clinical intervention.


Deletion of Y chromosome sequences located outside the testis determining region can cause XY female sex reversal.
An approach designed to map and generate mutations in the region of the short arm of the mouse Y chromosome, known to be involved in sex determination and spermatogenesis, is described. This relies on homologous Yp-Sxra pairing and asymmetrical exchange which can occur at meiosis in XY males carrying Sxra on their X chromosome. Such exchange potentially generates deficiencies and duplications of Yp or Sxra. Three fertile XY females were found out of about 450 XY offspring from XSxra/Y x XX crosses. In all three, despite evidence for deletion of Y chromosomal material, the Sry locus was intact. Each deletion involved a repeat sequence, Sx1, located at a distance from Sry. Since expression of Sry was affected these results suggest that long range position effects have disrupted Sry action.


Translational models of workplace violence in health care.
Decision makers have little time to study literature on the prevention and management of workplace violence (WPV). In a health care workplace setting, identifying the person, stimulus, and environmental interactions that can lead to violence is a complicated process. Those in positions of leadership make decisions that affect many individuals, agencies, and communities. Often, they come from different professional backgrounds yet need ways of rapidly understanding concepts of violence that transcend their profession, training, or experience. Translational models (TMs) in WPV visually summarize and interprofessionally facilitate this understanding of concepts, enhancing the chances of more effective collaborative solutions to WPV. The purpose of this article is to demonstrate how TM can be used in interprofessional settings to find effective solutions to reduce WPV.


Current concepts in management of meningiomas and schwannomas.
Meningiomas and schwannomas are the two most common extra-axial intracranial tumors in adults. Since their initial discovery, these often-benign lesions have shared a parallel metamorphosis in their management. The goal of this article is to provide a review of the current literature surrounding the mainstays of therapy for these lesions.


Lead(II) resistance in Cupriavidus metallidurans CH34: interplay between plasmid and chromosomally-located functions.
Proteome and transcriptome analysis, combined with mutagenesis, were used to better understand the response of Cupriavidus metallidurans CH34 against lead(II). Structural Pb(II)-resistance genes of the pMOL30-encoded pbrUTRABCD operon formed the major line of defense against Pb(II). However, several general stress response mechanisms under the control of alternative sigma factors such as sigma24/rpoK, sigma32/rpoH and sigma28/fliA were also induced. In addition, the expression of the pbrR(2) cadA pbrC(2) operon of the CMGI-1 region and the chromosomally encoded zntA were clearly induced in the presence of Pb(II), although their respective gene products were not detected via proteomics. After inactivation of the pbrA, pbrB or pbrD genes, the expression of the pbrR(2) cadA pbrC(2) operon went up considerably. This points towards synergistic interactions between pbrUTRABCD and pbrR(2) cadA pbrC(2) to maintain a low intracellular Pb(II) concentration, where pbrR(2) cadA pbrC(2) gene functions can complement and compensate for the mutations in the pbrA and pbrD genes. This role of zntA and cadA to complement for the loss of pbrA was further confirmed by mutation analysis. The pbrB:: colonsTn(Km2) mutation resulted in the most significant decrease of Pb(II) resistance, indicating that Pb(II) sequestration, avoiding re-entry of this toxic metal ion, forms a critical step in the pbr-encoded Pb(II) resistance mechanism.


Intranuclear and cytoplasmic hemoglobin in human erythroblasts during maturation. Electron microscopic immunocytochemistry.
Changes in the hemoglobin level in human bone marrow erythroblasts associated with cell maturation were studied by the electron microscopic immunocytochemical technique using protein A-gold. Intense reaction of gold to hemoglobin was observed diffusely in the cytoplasm, but the reaction was weak in the Golgi zone. No reaction was observed in mitochondria or granules. Cytoplasmic hemoglobin was noted in basophilic erythroblasts and increased with maturation. Hemoglobin was also noted in the nucleus, especially in the euchromatin, though in smaller amounts than in the cytoplasm. Since intranuclear hemoglobin tended to increase in the euchromatin but to decrease in the heterochromatin with erythroblast maturation, the ratio of the amount of hemoglobin in the euchromatin to that in the heterochromatin increased with maturation.


Visible-Light-Mediated Synthesis of α-Ketoamides via Oxidative Amination of 2-Bromoacetophenones Using Eosin Y as a Photoredox Catalyst.
An oxidative amination of 2-bromoacetophenones has been accomplished to provide α-ketoamides by using photoredox catalysis with air as oxidant. The reactants are readily accessible, and the method is endowed with broad substrate scope and good functional group tolerance. The practicality of the approach is also shown by a gram-scale reaction.


Cyclic AMP-receptor protein activates aerobactin receptor IutA expression in Vibrio vulnificus.
The ferrophilic bacterium Vibrio vulnificus can utilize the siderophore aerobactin of Escherichia coli for iron acquisition via its specific receptor IutA. This siderophore piracy by V. vulnificus may contribute to its survival and proliferation, especially in mixed bacterial environments. In this study, we examined the effects of glucose, cyclic AMP (cAMP), and cAMP-receptor protein (Crp) on iutA expression in V. vulnificus. Glucose dose-dependently repressed iutA expression. A mutation in cya encoding adenylate cyclase required for cAMP synthesis severely repressed iutA expression, and this change was recovered by in trans complementing cya or the addition of exogenous cAMP. Furthermore, a mutation in crp encoding Crp severely repressed iutA expression, and this change was recovered by complementing crp. Accordingly, glucose deprivation under iron-limited conditions is an environmental signal for iutA expression, and Crp functions as an activator that regulates iutA expression in response to glucose availability.


Declined Offers for Deceased Donor Kidneys Are Not an Independent Reflection of Organ Quality.
Deceased donor kidney offers are frequently declined multiple times before acceptance for transplantation, despite significant organ shortage and long waiting times. Whether the number of times a kidney has been declined, reflecting cumulative judgments of clinicians, is associated with long-term transplant outcomes remains unclear. In this national, retrospective cohort study of deceased donor kidney transplants in the United States from 2008 to 2015 (n=78,940), we compared donor and recipient characteristics and short- and long-term graft and patient survival outcomes grouping by the sequence number at which the kidney was accepted for transplantation. We compared outcomes for kidneys accepted within the first seven offers in the match-run, after 8-100 offers, and for hard-to-place kidneys distinguishing those requiring >100 and >1000 offers before acceptance. Harder-to-place kidneys had lower donor quality and higher rates of delayed graft function (46% among kidneys requiring >1000 offers before acceptance versus 23% among kidneys with ≤7 offers). In unadjusted models, later sequence groups had higher hazard of all-cause graft failure, death-censored graft failure, and patient mortality; however, these associations were attenuated after adjusting for Kidney Donor Risk Index (KDRI). After adjusting for donor factors already taken into consideration during allocation, and recipient factors associated with long-term outcomes, graft, and patient survival outcomes were not significantly different for the hardest-to-place kidneys compared with the easiest-to-place kidneys, with the exception of death-censored graft failure (adjusted hazard ratio, 1.16, 95% CI, 1.05 to 1.28). Late sequence offers may represent missed opportunities for earlier successful transplant for the higher-priority waitlisted candidates for whom the offers were declined.


Choosing the right level of analysis: Stereotypes shape social reality via collective action.
In his 2012 book Jussim argues that the self-fulfilling prophecy and expectancy effects of descriptive stereotypes are not potent shapers of social reality. However, his conclusion that descriptive stereotypes per se do not shape social reality is premature and overly reductionist. We review evidence that suggests descriptive stereotypes do have a substantial influence on social reality, by virtue of their influence on collective action.


Key peptide processing enzymes are expressed by a variant form of small-cell carcinoma of the lung.
Small-cell carcinoma of the lung (SCCL) is a neuroendocrine tumor characterized by having the capacity to produce and secrete a number of small neuropeptides. These peptides serve the tumor as autocrine growth factors. SCCL is known to undergo a process of dedifferentiation to a variant (drug-resistant) form, and this process is associated with loss of marker enzymes such as neuron-specific enolase (NSE) and dopa decarboxylase (DDC). The current study was designed to discover if variant SCCL, represented by cell line NCI H82, retains some capacity to generate active neuropeptides (like vasopressin) from their precursors by continuing to express the three key classes of enzymes necessary for such conversions, namely prohormone convertases (PCs), carboxypeptidases (CPs), and peptidylglycine a-amidating monooxygenase (PAM). RT-PCR for mRNAs representing PC1, PC2, CPE, and PAM was performed on total RNA extracted from NCI H82. The primers selected for PCR and partial sequencing were synthetic 20, 21, 22, and 24 oligomers designed to yield products of 533, 880, 405, and 560 base pairs (bp) for PC1, PC2, CPE, and PAM, respectively. For the conditions used, we were able to demonstrate products for all four enzymes. Each of the four products generated were of the expected size. Cloning and sequencing of these products revealed that each had a structure identical to that published for the human form of the respective enzyme. Western analysis with antibodies against PC1, PC2, CPE, and PAM, provided evidence that mRNAs for the four enzymes are translated into proteins that could represent functional forms. Our findings therefore demonstrate that key enzymes involved in the generation of active neuropeptides, unlike the marker enzymes NSE and DDC, continue to be expressed by variant SCCL.


Synthesis of Magnetic Fe3O4-Chitosan Nanoparticles by Ionic Gelation and Their Dye Removal Ability.
The aim of this study was to synthesize magnetic Fe3O4 chitosan nanoparticles (m-Fe3O4-CNs) by ionic gelation method and use them as adsorbent for the removal of Bromothymol Blue (BB) from aqueous solutions. Also, the effect of various parameters on the preparation of m-Fe3O4-CNs was investigated in this study. The nanoparticles were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), dynamic light scattering (DLS), Fourier transform infrared (FTIR) spectroscopy and vibrating sample magnetometry (VSM). Adsorption of BB on m-Fe3O4-CNs was studied in a batch reactor at different experimental conditions such as adsorbent dosage, pH, contact time, initial BB concentration and temperature. Kinetic behaviors, equilibrium isotherms and thermodynamics of the adsorption process were investigated in detail. The Langmuir adsorption isotherm model and pseudo-second-order kinetic model well fitted the adsorption experimental results. The thermodynamic parameters showed that the adsorption was a spontaneous, favorable and exothermic process in nature.


Temperature prediction and the timing of sex in aphids.
The aphid life cycle contains a series of parthenogenetic, viviparous generations, followed usually by a sexual generation that produces resistant overwintering eggs. Since the decision to produce sexually-reproducing offspring ends the period of rapid growth of the clone, it should be postponed as late as is compatible with successful oviposition. The time of leaf fall determines the latest possible time of oviposition, and is itself determined mainly by daylength. The time required for the development of the final generations of aphid depends on temperature. The decision to end the sequence of parthenogenetic generations should thus depend on temperature and photoperiod. This paper calculates the optimal combination of daylength and temperature for the cueing of this decision in Rhopalosiphum padi. It is shown that the experimental data of Dixon and Glen (1971) are in agreement with the predictions, and that, in the field, the time of production of male R. padi does vary adaptively with July temperature.


Dermatopathia pigmentosa reticularis.
Dermatopathia pigmentosa reticularis is a rare inherited pigmentary disorder of the skin characterized by generalized reticulate hyperpigmentation, nonscarring alopecia and onychodystrophy. The reticulate pigmentation occurs at birth or during early childhood. We hereby report a 12-year-old Indian patient with this disorder.


Self-administered nicotine activates the mesolimbic dopamine system through the ventral tegmental area.
Microinfusions of the nicotinic antagonist dihydro-beta-erythroidine (DH beta E) were used to examine the role of the mesolimbic dopamine system in nicotine reinforcement in rats. Infusions of DH beta E into the ventral tegmental area (VTA) prior to the start of i.v. nicotine self-administration sessions resulted in a significant decrease in the number of nicotine infusions voluntarily obtained. In contrast, the same doses of DH beta E infused into the nucleus accumbens were without effect on nicotine self-administration. The reductions caused by DH beta E were specific to nicotine reinforcement; neither operant responding maintained by food, cocaine self-administration, or spontaneous locomotor activity were altered by local applications of DH beta E within the VTA. The reduction in nicotine self-administration following treatment in the VTA was also specific to the nicotinic antagonist, and was not duplicated by infusions of the muscarinic antagonist atropine. Partial lesions of the pedunculopontine tegmental nucleus, the likely origin of cholinergic fibers to the VTA, were without effect on nicotine self-administration, suggesting that the effects of DH beta E were not due to disruption of a tonically active cholinergic input to the VTA from this source. These data show that nicotine acts within the VTA region to initiate processes which are critical to the reinforcing properties of the drug.


Evaluation of a school-based teen obesity prevention minimal intervention.
A school-based nutrition education minimal intervention (MI) was evaluated. The design was experimental, with random assignment at the school level. Seven schools were randomly assigned as experimental, and 7 as delayed-treatment. The experimental group included 551 teens, and the delayed treatment group included 329 teens. The minimal intervention was Present and Prevent, a commercially available PowerPoint program presented in two 30-minute time slots over 1 week. The dependent variables were nutrition knowledge, attitudes, peer and family influences, behavioral intentions, and program satisfaction. The independent variable was group assignment. A matched-pairs and 2-sample t test were used respectively to assess within-group and between-group changes. Significant experimental posttest improvements occurred in the following: knowledge (P < .001); intention to maintain a healthy body weight because of importance to friends (P < .001); and intention to eat fewer fried foods, eat fewer sweets, look more at food labels, and limit TV watching (all P < .001). Program satisfaction measures were significantly associated with each of the healthy weight maintenance behavioral intentions. The MI teen obesity prevention program made an impact on nutrition knowledge and positive behavioral intentions in only 2 classroom sessions and was well received by participants.


Endotoxin down-modulates P-selectin glycoprotein ligand-1 (PSGL-1, CD162) on neutrophils in humans.
P-selectin glycoprotein ligand-1 (PSGL-1, CD162), the counter-receptor for P-selectin and possibly E- and L-selectin, mediates rolling of leukocytes during inflammation and, thus, plays a pivotal role in hemostasis and inflammation. PSGL-1 is constitutively expressed on circulating leukocytes. Until recently, PSGL-1 has been considered not to be regulated upon cell activation. As modulation of PSGL-1 has only recently been reported for three proinflammatory substances, PSGL-1 regulation was examined during systemic inflammation in humans. Nine healthy human volunteers received a bolus of 2 ng/kg LPS i.v. Endotoxin infusion down-modulated PSGL-1 expression on neutrophils, with a maximum at 6-8 hr (-22%; P =0.001 vs. baseline and placebo), which correlated with peak neutrophilia. Similar PSGL-1 down-regulation was observed on monocytes. sPSGL-1 plasma levels increased trendwise after LPS infusion (+12% at 6 hr; P =0.10). In vitro LPS stimulation of whole blood significantly down-regulated PSGL-1 on neutrophils (-43%) and monocytes (-35%) as early as 2 hr ( P <0.05; n =5) in both EDTA and lepirudin anticoagulated samples. In summary, PSGL-1 is down-modulated on neutrophils and monocytes during endotoxemia in humans. PSGL-1 down-regulation could potentially facilitate the development of neutrophilia.


Effect of hypovolemia on traumatic spinal cord injury.
Experimentally evaluate the effect of hypovolemia in acute traumatic spinal cord injury. Twenty adult male Wistar rats were submitted to traumatic spinal cord injury through spinal cord contusion by direct impact. Ten animals were subjected to bleeding of 20% of their estimated blood to simulate a hypovolemic condition after spinal cord contusion and 10 animals were used as control. The animals were evaluated before, 1, 3, 7 and 14 days after the production of the spinal cord injury through behavioral tests (inclined plane test and motor assessment). The spinal cord contusion associated with hypovolemia had a negative influence on functional outcomes of the spinal cord injury. The animals submitted to hypovolemia after spinal cord contusion had lower scores in behavioral tests (inclined plane test and motor assessment), presenting a slower recovery of the motor function. In the experimental model used, the group of animals with hypovolemia after traumatic spinal cord injury had slower recovery and lower intensity in behavioral tests.


Use of rapid diagnostic tests for the detection of ancient malaria infections in dental pulp from the sixth century in Versailles, France.
Paleomicrobiological data have clarified that Plasmodium spp. was circulating in the past in southern European populations, which are now devoid of malaria. The aim of this study was to evaluate the efficacy of immunodetection and, more particularly, rapid diagnostic tests (RDT), in order to further assess Plasmodium infections in ancient northern European populations. A commercially available RDT, PALUTOP® + 4 OPTIMA, which is routinely used to detect malaria, was used to detect Plasmodium antigens from proteins recovered from ancient specimens extracted from 39 dental pulp samples. These samples were collected from 39 individuals who were buried in the sixth century, near the site of the current Palace of Versailles in France. Positive and negative controls were also used. Antigens detected were quantified using chemiluminescence imaging system analysis. Plasmodium antigens were detected in 14/39 (35.9%) individuals, including Plasmodium vivax antigens in 11 individuals and Plasmodium falciparum antigens co-detected in two individuals, while Pan-Plasmodium antigens were detected in three individuals. Controls all yielded expected results. The data reported here showed that RDTs are a suitable tool for detecting Plasmodium spp. antigens in ancient dental pulp samples, and demonstrated the existence of malaria in Versailles, France, in the sixth century. Plasmodium vivax, which is regarded as being responsible for an attenuated form of malaria and less deadly forms, was the most prevalent species. This illustrates, for the first time in ancient populations, co-infection with P. falciparum, bringing into question the climate-driven ecosystems prevailing at that time in the Versailles area.


Sialic acid diversity in the human gut: Molecular impacts and tools for future discovery.
Sialic acids are a family of structurally related sugars that are prevalent in mucosal surfaces, including the human intestine. In the gut, sialic acids have diverse biological roles at the interface of the host epithelium and the microbiota. N-acetylneuraminic acid (Neu5Ac), the best studied sialic acid, is a nutrient source for bacteria and, when displayed on the cell surface, a binding site for host immune factors, viruses, and bacterial toxins. Neu5Ac is extensively modified by host and microbial enzymes, and the impacts of Neu5Ac derivatives on host-microbe interactions, and generally on human and microbial biology, remain underexplored. In this mini-review, we highlight recent reports describing how host and microbial proteins differentiate Neu5Ac and its derivatives, draw attention to gaps in knowledge related to sialic acid biology, and suggest cutting-edge methodologies that may expand our appreciation and understanding of Neu5Ac in health and disease.


Microdroplet-guided intercalation and deterministic delamination towards intelligent rolling origami.
Three-dimensional microstructures fabricated by origami, including folding, rolling and buckling, gain great interests in mechanics, optics and electronics. We propose a general strategy on on-demand and spontaneous rolling origami for artificial microstructures aiming at massive and intelligent production. Deposited nanomembranes are rolled-up in great amount triggered by the intercalation of tiny droplet, taking advantage of a creative design of van der Waals interaction with substrate. The rolling of nanomembranes delaminated by liquid permits a wide choice in materials as well as precise manipulation in rolling direction by controlling the motion of microdroplet, resulting in intelligent construction of rolling microstructures with designable geometries. Moreover, this liquid-triggered delamination phenomenon and constructed microstructures are demonstrated in the applications among vapor sensing, microresonators, micromotors, and microactuators. This investigation offers a simple, massive, low-cost, versatile and designable construction of rolling microstructures for fundamental research and practical applications.


Synthetic chalcones as efficient inhibitors of Mycobacterium tuberculosis protein tyrosine phosphatase PtpA.
In the search for lead compounds for new drugs for tuberculosis, the activity of 38 synthetic chalcones were assayed for their potential inhibitory action towards a protein tyrosine phosphatase from Mycobacterium tuberculosis--PtpA. The compounds were obtained by aldolic condensation between aldehydes and acetophenones, under basic conditions. Five compounds presented moderate or good activity. The structure-activity analysis reveals that the predominant factor for the activity is the molecule planarity/hydrophobicity and the nature of the substituents.


Posterior Shoulder Instability in Overhead Athletes.
Posterior shoulder instability in overhead athletes presents a unique and difficult challenge. Often, this group has an inherent capsular laxity and/or humeral retroversion to accommodate the range of motion necessary to throw. This adaptation makes the diagnosis of posterior capsulolabral pathology challenging, as the examiner must differentiate between adaptive capsular laxity and pathologic instability. Further complicating matters, the intraoperative surgeon must find the delicate balance of achieving stability while still allowing the necessary range of motion.


Bi-directional interaction between hypoglycaemia and cognitive impairment in elderly patients treated with glucose-lowering agents: a systematic review and meta-analysis.
To examine the bi-directional relationship, whereby hypoglycaemia is a risk factor for dementia, and where dementia increases risk of hypoglycaemia in older patients with diabetes mellitus treated with glucose-lowering agents. We searched MEDLINE and EMBASE over a 10-year span from 2005 to 2015 (with automated PubMed updates to August 2015) for observational studies of the association between hypoglycaemia and cognitive impairment or dementia in participants aged >55 years. Assessment of study validity was based on ascertainment of hypoglycaemia, dementia and risk of confounding. We conducted random effects inverse variance meta-analyses, and assessed heterogeneity using the I(2) statistic. We screened 1177 citations, and selected 12 studies, of which nine were suitable for meta-analysis. There were a total of 1,439,818 participants, with a mean age of 75 years. Meta-analysis of five studies showed a significantly increased risk of dementia in patients who had hypoglycaemic episodes: pooled odds ratio 1.68 [95% confidence interval (CI) 1.45, 1.95]. We also found a significantly increased risk of hypoglycaemia in patients with dementia: pooled odds ratio from five studies 1.61 (95% CI 1.25, 2.06). Limitations of the study were heterogeneity in the meta-analysis, and uncertain ascertainment of dementia and hypoglycaemic outcomes and temporal relationships. Publication bias may have favoured the reporting of more significant findings. Our meta-analysis shows a bi-directional relationship between cognitive impairment and hypoglycaemia in older patients. Glucose-lowering therapy should be carefully tailored and monitored in older patients who are susceptible to cognitive decline.


Epstein-Barr virus DNA detection in gingival tissues of patients undergoing surgical extractions.
The main oral manifestation of Epstein-Barr virus (EBV) infection is hairy leukoplakia, a lesion associated with the acquired immunodeficiency syndrome (AIDS) and occasionally in other immunocompromised patients. However, the recent literature describes the presence of viral genome in clinically normal oral tissues. The purpose of this work was to investigate these occult EBV infections in gingival epithelium. The Southern blot method with 32P-radiolabelled DNA probes under stringent conditions was applied to 20 interproximal gingival papillae specimens and revealed homologous EBV sequences in 4 of 10 AIDS patients as well as in 4 of 10 HIV negative patients. In order to determine whether EBV has a predilection for the gingival tissues, samples of nasal, laryngeal and oral mucosa, other than gingival mucosa, were collected from 10 HIV-negative patients undergoing surgical treatment for a variety of clinical conditions. None of these extra-periodontal mucosal specimens contained homologous EBV DNAs, except an edentulous palatal gingival specimen. With the present detection of EBV DNAs in the gingival tissues of patients undergoing surgical extractions, it would be of interest to investigate more systematically these subclinical infections in order to determine their exact implications in oral disease.


Renal uric acid clearance in human neonates.
Renal clearance of uric acid was examined in 40 premature and term infants during the first 24 hours of life. Creatinine clearance and uric acid clearance increased with increasing gestational age. Serum uric acid concentration (r = -0.31, P less than 0.05) and fractional excretion of uric acid (r = -0.50, P less than 0.01) were inversely related to gestational age; FEUA was nearly 70% at 29 to 31 weeks gestational age, and decreased to a mean value of 39 +/- 14% (+/- SD) at 38 to 40 weeks gestational age. The decline in FEUA with advancing gestational age appears to represent alterations in net renal tubular transport of uric acid, because the filtered load of uric acid increased with gestational age. Postnatal clearance studies were performed in 18 premature infants of 29 to 35 weeks gestational age; FEUA also declined during early postnatal development (r = -0.44, P less than 0.01). In all studies, a relationship between FEUA and fractional excretion of sodium was observed. The high basal excretion of uric acid in infants may increase the risk of acute uric acid nephropathy when excretion demands are increased.


Kinetics of continuous cultivation of the oleaginous yeast Rhodosporidium toruloides.
Microbial lipids are potential alternative feedstock for biofuel and oleochemical industries. The oleaginous yeast Rhodosporidium toruloides AS 2.1389 is an excellent lipid producer. To attain parameters for the understanding of the lipid production process, we performed continuous cultivation experiments under either carbon or nitrogen limitation. The maintenance coefficient and maximum cell mass yield for this yeast were determined as 5.7 mg glucose/g cell/h and 0.42 g cell/g glucose, respectively, under carbon limitation. Under nitrogen limitation, the highest lipid yield of 0.19 g/g was observed at the dilution rate of 0.02 h(-1) while the highest specific lipid formation rate of 0.058 g/g cell/h at the dilution rate of 0.08 h(-1). A kinetic model of lipid formation under steady state conditions was developed, parameters estimated, and optimal continuous cultivation conditions forecasted. These data should be very helpful to develop and design more efficient bioprocesses for microbial lipid production.


Hyperinsulinemia shifted energy supply from glucose to ketone bodies in early nonalcoholic steatohepatitis from high-fat high-sucrose diet induced Bama minipigs.
The minipig can serve as a good pharmacological model for human subjects. However, the long-term pathogenesis of high-calorie diet-induced metabolic syndromes, including NASH, has not been well described in minipigs. We examined the development of metabolic syndromes in Bama minipigs that were fed a high-fat, high-sucrose diet (HFHSD) for 23 months, by using histology and serum biochemistry and by profiling the gene expression patterns in the livers of HFHSD pigs compared to controls. The pathology findings revealed microvesicular steatosis, iron overload, arachidonic acid synthesis, lipid peroxidation, reduced antioxidant capacity, increased cellular damage, and inflammation in the liver. RNA-seq analysis revealed that 164 genes were differentially expressed between the livers of the HFHSD and control groups. The pathogenesis of early-stage NASH was characterized by hyperinsulinemia and by de novo synthesis of fatty acids and nascent triglycerides, which were deposited as lipid droplets in hepatocytes. Hyperinsulinemia shifted the energy supply from glucose to ketone bodies, and the high ketone body concentration induced the overexpression of cytochrome P450 2E1 (CYP2E1). The iron overload, CYP2E1 and alcohol dehydrogenase 4 overexpression promoted reactive oxygen species (ROS) production, which resulted in arachidonic and linoleic acid peroxidation and, in turn, led to malondialdehyde production and a cellular response to ROS-mediated DNA damage.


Contactless conductivity detection for capillary electrophoresis. Hardware improvements and optimization of the input-signal amplitude and frequency.
A new prototype of contactless conductivity detector, smaller and easier to operate than the former version, is described. For a fused-silica capillary with 142-microm wall thickness and voltages up to 25 kV, it can be placed at the low- or high-voltage end of the column. This feature allowed implementation of an apparatus with sample introduction at the grounded end of the column. The input signal is an important parameter for determining the signal-to-noise ratio (S/N) of the detection system. An optimization procedure of its amplitude and frequency is proposed. Although the SIN must be determined by introduction of actual samples, the operating conditions can be optimized merely by changing the signal parameters and by using a mathematical procedure. Thus, an easy and fast optimization routine can be carried out. Mathematical and instrumental backgrounds are discussed, and experimental support of the technique's effectiveness is presented.


Effect of transcutaneous auricular vagus nerve stimulation on post-stroke dysphagia.
It has been proved that electrical vagus nerve stimulation can promote the recovery of motor function after stroke. There were no trials on the use of transcutaneous auricular electrical vagus nerve stimulation (ta-VNS) in patients with dysphagia after acute stroke. Our aim was to confirm whether ta-VNS can promote the recovery of swallowing function in these acute stroke patients with dysphagia. We conducted a sham-controlled, double-blinded, parallel pilot study in 40 acute stroke patients randomly assigned to receive ta-VNS or sham ta-VNS combined with conventional rehabilitation training. The intensity of ta-VNS treatment was adjusted according to the patient's tolerance, 30 min each time, twice a day, five times a week, with a total course of 3 weeks. In the sham group, the parameters were the same except energy output. Swallowing function was assessed with Modified Mann assessment of swallowing ability (MASA), functional communication measure swallowing test (FCM), and the Rosenbek leakage/aspiration scale (RAS) according to swallowing video fluoroscopic (SVF) before the intervention (baseline, T0), immediately after the intervention (T1) and 4 weeks after the intervention (T2). After treatment, ta-VNS group statistically and clinically had larger change of MASA, FCM, and RAS scores compared with control group (P < 0.05) and this improvement continued at least 4 weeks after the end of treatment. There were no serious adverse events occurred during the whole intervention. The transcutaneous auricular electrical vagus nerve stimulation is effective as a novel and noninvasive treatment strategy for patients with dysphagia after acute stroke. No: kelunshen No. 63 in 2020.


Nuclear magnetic resonance imaging in detecting and staging prostatic cancer.
Thirteen patients were examined for grade, stage, and extent of their prostatic cancer, utilizing nuclear magnetic resonance imaging (MRI) and clinical workup for metastases. Of these 13 patients, 12 had known prostatic cancer proved by needle biopsy or by pathologic examination of transurethral prostatectomy tissue. Five of these patients underwent radical surgery allowing further correlation of clinical findings and MRI data with the surgical pathologic findings. MRI of the prostate was found to be a sensitive modality in detecting prostatic carcinoma and showing extension of disease in some cases. Also, in some cases it was not always possible to differentiate between prostatic carcinoma and benign prostatic hyperplasia with MRI.


[Carcinoma of the stomach in the light of epidemiologic, clinical and pathologic research (definition of etiologic and pathogenic phenomena in our data and the literature)].
The malignant diseases are ever more frequent; the carcinoma of the stomach occupies a significant position here with approximately 20% of all cases of malignant diseases and therefore represents a fairly serious health problem, even more so since the only, somewhat successful, therapy is surgical treatment. Yet, even when it is performed on time (partial resection) the results are not particularly good, similarly to the unperspective life following a total amputation of the stomach. Only the disease which we recognize well in etiologic, epidemiologic, and pathogenetic terms can successfully be treated. This paper is concerned with these three elements, that are described in regards to our epidemiological, etiological and clinical research. Presently, in sciences three phenomena are thought of as being important in malignant diseases: the immunologic condition of the organism, the role of the virus as an etiologic factor, and the intracellular derangements. These first two problems have been considered in a somewhat original manner, while the third problem has been considered through the literature and our experience, which compromise the theoretical basis of our paper.


Coping styles mediating the relationship between perceived chronic stress and conspiracy beliefs about COVID-19.
As a global health crisis, COVID-19 has led to a rise in overall stress levels. Concurrently, conspiracy beliefs regarding the origin and spread of the disease have become widespread. Engaging in such beliefs can be explained as a form of coping in order to deal with elevated levels of stress. The present study investigated the indirect effects of coping strategies in the association between perceived chronic stress and COVID-related conspiracy beliefs. We report data from an online survey (N = 1,354 individuals: 807 female; 508 male; 8 diverse; 6 not specified; mean age 39.14 years) in German-speaking countries collected between January and March 2021. Our results indicate that people who felt more stressed were more prone to conspiracy beliefs. Coping via acceptance and self-blame was associated with decreased tendencies towards COVID-related conspiracy beliefs, while people who used denial as a strategy were more prone to these beliefs. These findings emphasize the need for stress management interventions and effective coping strategies during times of crisis in order to reduce chronic perceived stress, promote adaptive coping, and ultimately reduce conspiracy beliefs.


Progesterone receptors in the foetal uterus of guinea-pig: its stimulation after oestradiol treatment.
This paper shows for the first time the presence of progesterone receptors in the foetal guinea-pig uterus, as well as the stimulation of progesterone receptors in foetal uterus in animals treated with oestradiol.


Inhibition of connexin hemichannels alleviates neuroinflammation and hyperexcitability in temporal lobe epilepsy.
Temporal lobe epilepsy (TLE) is one of the most common types of epilepsy, yet approximately one-third of patients are refractory to current anticonvulsive drugs, which target neurons and synapses. Astrocytic and microglial dysfunction is commonly found in epileptic foci and has been shown to contribute to neuroinflammation and hyperexcitability in chronic epilepsy. Accumulating evidence points to a key role for glial hemichannels in epilepsy, but inhibiting both connexin (Cx) gap junctions and hemichannels can lead to undesirable side effects because the former coordinate physiological functions of cell assemblies. It would be a great benefit to use an orally available small molecule to block hemichannels to alleviate epileptic symptoms. Here, we explored the effect of D4, a newly developed compound that inhibits the Cx hemichannels but not Cx gap junctions using the pilocarpine mouse model of TLE. In vitro application of D4 caused a near-complete reduction in the pilocarpine-induced cell membrane permeability associated with increased Cx hemichannel activity. Moreover, preadministration of D4 in vivo effectively reduced neuroinflammation and altered synaptic inhibition, which then enhanced the animal survival rate. Posttreatment with a single dose of D4 in vivo has prolonged effects on suppressing the activation of astrocytes and microglia and rescued the changes in neuroinflammatory and synaptic gene expression induced by pilocarpine. Collectively, these results indicate that targeting Cx hemichannels by D4 is an effective and promising strategy for treating epilepsy in which neuroinflammation plays a critical role.


Pleiotropic effects of dronedarone on ischemia/reperfusion injury in heart and brain.
In the present manuscript we critically review the available evidence for pleiotropic effects of dronedarone in settings of myocardial and cerebral ischemia/reperfusion, both from experimental and clinical data.


Interexaminer reliability of lumbar segmental mobility tests.
The purpose of this study was to investigate the interexaminer reliability of segmental mobility tests for the lumbar flexion and extension movement. Available reliability studies are rare and investigate total segmental mobility through several tests, making the understanding of the effect of each test more difficult. There is also a risk of creating a test situation that has less resemblance to the work situation of physiotherapists if two physiotherapists who have trained and coordinated their manual techniques together in advance are studied. Three physiotherapists with step 2 of the Swedish orthopaedic manual therapy education (OMT) performed one segmental mobility test for lumbar flexion and one for lumbar extension on twenty subjects. They were not permitted to obtain additional information, apart from a standing inspection without movements. The physiotherapists had not worked together, nor did they have a chance to coordinate their manual techniques prior to the examinations. The results showed no interexaminer reliability and suggest that future research is essential if a conclusion about lumbar intersegmental mobility tests is to be reached.


[Importance of protein-protein interactions for the structural integrity of membrane framents from Torpedo marmorata electric organ].
Electron spin resonance and electron microscopy were used to show that alkaline extraction of a 43,000 dalton protein from torpedo membrane induces structural destabilization of the membrane and rotational diffusion of the cholinergic receptor protein.


Inhibition of p53, p21 and Bax by pifithrin-alpha does not affect UV induced apoptotic response in CS-B cells.
Cockayne syndrome (CS) is a human autosomal recessive disorder characterized by many neurological and developmental abnormalities. CS cells are defective in transcription coupled repair (TCR) pathway that removes DNA damage from the transcribed strand of active genes. In spite of a TCR deficiency at the cellular level, CS patients do not develop cancer. The lack of cancer incidence in CS patients may be due to the selective elimination of cells by an apoptotic pathway. In order to verify the role of p53-associated pathway in ultraviolet (UV) induced apoptosis in human CS-B cells, the expression of p53 and p53 responsive genes was analysed in UV irradiated human cells after treatment with pifithrin-alpha (PFTalpha). PTFalpha effectively inhibited the induction of p53, p21 and Bax after UV treatment without affecting the apoptotic response in CS-B cells. Our results indicate that the p53-associated pathway involving p21 and Bax does not largely contribute to UV induced apoptosis in TCR defective human CS-B cells.


Assessment of other-cause mortality in localized renal cell carcinoma patients within 15 years: A population-based analysis.
Five-year other cause mortality (OCM) after nephrectomy for non-metastatic renal cell carcinoma (RCC) should be marginal in properly selected surgical candidates. We examined 5-year OCM rates as a quality of care indicator for patient selection. Within the Surveillance, Epidemiology, and End Results database (1997-2011), we identified 59267 RCC patients treated with either radical (n = 27 804, 46.9%) or partial nephrectomy (n = 31 463, 53.1%). Temporal trends and multivariable Cox regression analyses assessed 5-year OCM. Data were stratified according to age group, year of diagnosis, race, marital status, gender, and socio-economic status. The overall OCM rates for the entire cohort at 5 years of follow-up was 4.7% and decreased from 9.4% to 5.6% over the study span (-3.8%, P < .001). The greatest decrease in 5-year OCM rates over time was recorded in patients >70 years (17.0%-9.6%, slope, -0.6%/y), as well as in African-Americans (12.0-6.2%; slope, -0.3%/y) and in males (8.9%-4.7%; slope, -0.3%, all P < .001). An important OCM decrease was recorded over the study span. Nonetheless, further improvement may be accomplished, especially in African-Americans, unmarried and older individuals, who exhibited higher OCM rates than others. These three groups may represent ideal targets for better patient selection based on OCM considerations.