Potential pro-oxidative effects of single dose of mephedrone in vital organs of mice.
Mephedrone is a recreationally used synthetic cathinone, relatively new abusive substances with molecular structure similar to amphetamine. As there is still lack of scientific data regarding mechanisms of action as well as metabolism of mephedrone, especially in aspects other than neurotoxicity, addiction or behavioral changes, therefore we aimed, for the first time, to investigate potential pro-oxidative actions of a single dose of mephedrone in organs other than brain and its structures, i.e. in liver, kidneys, heart and spleen of Swiss mice. The following biomarkers of oxidative stress were measured: concentration of ascorbic acid (AA) and malondialdehyde (MDA) as well as total antioxidant capacity (TAC) of the tissues homogenates. Our study revealed that mephedrone intoxication induces oxidative stress by reducing concentration of AA and TAC and increasing concentration of MDA in these organs. Such occurred state of antioxidant-oxidant imbalance may be etiopathological factor of a number of severe diseases within cardiovascular, digestive as well as immunological systems.


Targeting senescent retinal pigment epithelial cells facilitates retinal regeneration in mouse models of age-related macular degeneration.
Although age-related macular degeneration (AMD) is a multifactorial disorder with angiogenic, immune, and inflammatory components, the most common clinical treatment strategies are antiangiogenic therapies. However, these strategies are only applicable to neovascular AMD, which accounts for less than 20% of all AMD cases, and there are no FDA-approved drugs for the treatment of dry AMD, which accounts for ~ 80% of AMD cases. Here, we report that the elimination of senescent cells is a potential novel therapeutic approach for the treatment of all types of AMD. We identified senescent retinal pigment epithelium (RPE) cells in animal models of AMD and determined their contributions to retinal degeneration. We further confirmed that the clearance of senescent RPE cells with the MDM2-p53 inhibitor Nutlin-3a ameliorated retinal degeneration. These findings provide new insights into the use of senescent cells as a therapeutic target for the treatment of AMD.


Actinomycosis of the nasal cavity.
Actinomycosis of the nasal cavity is very rare. The purpose of this study was to investigate the clinical features, treatment methods, and treatment results of actinomycosis of the nasal cavity in our hospital. We retrospectively enrolled 11 patients with histopathologically identified actinomycosis of the nasal cavity from January 2010 to May 2020. This study included five males and six females. The most common symptom was purulent nasal discharge (36.4%). Nasal actinomycosis occurred in the maxillary sinus in 5 (45.5%) patients, the ethmoid sinus in two, the hard palate in two, the frontal sinus in one, and the nasal septum in one. After surgery, intravenous administration of antibiotics was performed on average for 7.4 days and oral antibiotics were prescribed for about 120.5 days. The clinical characteristics of the patients with nasal actinomycosis and the duration of antibiotic usage were not significantly different. Trauma was significantly associated with repeated nasal actinomycosis infections (p < 0.05). Actinomycosis of the nasal cavity should be suspected when a patient with chronic sinusitis does not respond to medical therapy and has a history of dental treatment, local surgery or radiation therapy. Nasal can be sufficiently treated with antibiotics and endoscopic surgery.


The effectiveness of side marker lamps: an experimental study.
The present experiment investigated the effect of small amber lamps mounted near the front and rear on each side of a passenger car-so called side marker lamps-on visual detection and recognition of passenger cars in complex nighttime environments. It was determined whether cars equipped with side marker lamps are detected and recognized earlier and more accurately than cars without side marker lamps. Subjects were presented with slides of natural nighttime scenes in which a car, either with or without side marker lamps, viewed from its side, approaching from a side street, was either present or not. Subjects determined as fast as possible whether a car was present or not. Reaction time measures (speed and accuracy) indicated that both under clear and fog visibility conditions, a car equipped with side marker lamps was detected and recognized earlier and more accurately than a car without side marker lamps. The results indicate that side marker lamps increase both lateral conspicuity and recognizability suggesting that side marker lamps may be effective in reducing the number of nighttime angle collisions.


In vitro biocompatibility of ammonia-free silver fluoride products on human dental pulp stem cells.
Silver fluoride (SF) is a preventive and therapeutic option for dental pathological processes involving structural alterations of the hard tissues, either during their formation or those caused by caries or other pathological reasons. This study aimed to compare the biological properties of two commercial SF products, one of them with ammonium (Riva Star; SDF) and the other ammonium-free (Riva Star Aqua; AgF), both with or without potassium iodide (KI), by the assessment of the cytotoxicity of the materials' eluates. Human dental pulp stem cells (hDPSCs) were obtained from healthy 18-23-year-old donors. Three dilutions were prepared for the tested materials (0.005%, 0.0005%, and 0.0001%). The following groups were assessed: (AgF, AgF+KI, SDF, SDF+KI, KI, negative control). A series of cytocompatibility assays were performed: MTT assay, IC50 assay, wound healing (migration) assay, cell cytoskeleton staining, analysis of cell apoptosis and necrosis, and reactive oxygen species production. The normality in the distribution of the data was previously confirmed via a Q-Q plot. Statistical significance was tested using one way ANOVA and Tukey's post hoc test. The incorporation of KI improved the cytocompatibility of both SF products in terms of viability, migration, morphology, apoptosis, and reactive oxygen species production. This difference was higher in the AgF group. The lowest dilutions of SF+KI and AgF+KI showed a similar cytocompatibility to that of the control group (MTT assay (p > 0.05 after 24, 48, and 72 h of culture); migration assay (p > 0.05 after 24, 48, and 72 h of culture); reactive oxygen species production (p > 0.05 after 72 h of culture). Riva Star Aqua shows lower cytotoxicity than Riva Star on hDPSCs. It can be considered as a good alternative in the conservative treatment of dental caries and in the preservation and remineralisation of viable dentine tissue.


Cervical osteomyelitis and soft tissue polymicrobial abscess in an immunocompetent 16-year-old patient.
A 16-year-old man was hospitalised with a painful space-occupying lesion in his posterior neck involving muscles, soft tissues, C1 cervical vertebra and vital cervical blood vessels. The true-cut biopsy showed inflammatory tissue. The microbiological analysis, which combined classical bacteriological and molecular methods, yielded at least four different anaerobic species. The patient was treated successfully with a prolonged course of ceftriaxone and metronidazole.


Achievements of true whole-body imaging using a faster acquisition of the lower extremities in variable-speed continuous bed motion.
Variable-speed continuous bed motion 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG-PET/CT), a reliable imaging technique, allows setting the bed motion speed for arbitrary sections of the body. The purpose of this study was to evaluate the relationship between the PET image quality and the bed speed following shortening of the scanning time for the lower extremities to achieve whole-body acquisition optimization of the examination time. Four sets of images were created by editing four-phase dynamic whole-body PET/CT images acquired at a bed speed of 6 and 14 mm/s in the trunk and lower extremities, respectively. The signal-to-noise ratio (SNR) was calculated using regions of interest in the liver, gluteus muscles, thigh, and lower legs, and the relationship between the bed speed and the SNR was assessed. The number of patients with findings in the lower extremities among 967 cases was evaluated. Based on this relationship between the SNR and bed motion speed, it is reasonable to increase the speed of the lower extremities by up to three times that of the trunk. The findings from whole-body FDG-PET imaging revealed that the number of patients with detected lesions in the lower extremities was 6.6% (64/967), bone metastases were found in 2.6%, soft lesions in 1.8%, and inflammation in 2.3%. Images of the lower extremities, which have a better SNR than the trunk, can be acquired at a faster bed speed using the variable-speed continuous bed motion PET.


Tiletamine/zolazepam and dexmedetomidine with tramadol provide effective general anesthesia in rats.
Tiletamine/zolazepam is a dissociative anesthetic combination commonly used in small animals but information is limited in rats. The alpha-2 agonist, dexmedetomidine, has gained popularity in laboratory animal anesthesia. Tramadol is a weak opioid mu agonist. The aim of this study was to assess whether the tiletamine/zolazepam/dexmedetomidine (ZD) combination effectively provides a surgical anesthesia plane comparable to tiletamine/zolazepam/dexmedetomidine with tramadol (ZDT) in a minor procedure in rats. Rats were induced with ZD or ZDT. After the loss of paw withdrawal, a small incision was made on the rats' left thighs as a surgical stimulus. Rats were maintained under a surgical anesthesia plane by assessing the loss of the paw withdrawal reflex for 45 minutes, then atipamezole was administered. Monitored anesthesia parameters included: (a) physiological parameters - pulse rate (PR), respiratory rate (RR), tissue oxygen saturation (%SpO2), and body temperature; (b) duration parameters - induction time, onset and duration of surgical anesthesia plane, onset of recovery, and recovery time. PR was significantly lower at 10 minutes in ZD and 5 minutes in ZDT groups. No difference was observed for RR, %SpO2, and body temperature. Likewise, there were no differences for duration parameters: induction time was less than 3 minutes; onset and duration of surgical anesthesia plane were approximately 5 and 45 minutes, respectively; onset of recovery (time to move) was 51 minutes; and recovery time was 52 minutes, respectively. These data suggest the ZD combination provides a surgical anesthesia plane comparable to ZDT in a rat incisional pain model.


Effect of increasing the organic loading rate on the co-digestion and mono-digestion of cattle slurry and maize.
Co-digestion of cattle slurry and maize has been shown to have benefits for both, improving the biogas yield of the slurry and stability of digestion of the maize. The effect of increasing the total loading rate from 3 to 6 g VS l(-1) day(-1) on the co-digestion of cattle slurry and maize, mixed at equal volatile solids volumes, was investigated in laboratory-scale continuously stirred digesters. These were compared with similar digesters evaluating the increase of 1.5 to 3 g VS l(-1) day(-1) loading rates of slurry and maize digested separately. Compared with mono-digestion of the substrates, where the digestion of maize failed at loading rates greater than 2.5 g VS l(-1) day(-1), the co-digestion of cattle slurry and maize was feasible at all the loading rates tested with an increase in the volumetric methane yield occurring with loading rate. Even at the lowest rate of loading, the addition of equal amounts of volatile solids of maize to slurry leads to an increase in volumetric methane yield of 219%.


Evaluation of the Use of Cancer Registry Data for Comparative Effectiveness Research.
Researchers often analyze cancer registry data to assess for differences in survival among cancer treatments. However, the retrospective, nonrandomized design of these analyses raises questions about study validity. To examine the extent to which comparative effectiveness analyses using observational cancer registry data produce results concordant with those of randomized clinical trials. In this comparative effectiveness study, a total of 141 randomized clinical trials referenced in the National Comprehensive Cancer Network Clinical Practice Guidelines for 8 common solid tumor types were identified. Data on participants within the National Cancer Database (NCDB) diagnosed between 2004 and 2014, matching the eligibility criteria of the randomized clinical trial, were obtained. The present study was conducted from August 1, 2017, to September 10, 2019. The trials included 85 118 patients, and the corresponding NCDB analyses included 1 344 536 patients. Three Cox proportional hazards regression models were used to determine hazard ratios (HRs) for overall survival, including univariable, multivariable, and propensity score-adjusted models. Multivariable and propensity score analyses controlled for potential confounders, including demographic, comorbidity, clinical, treatment, and tumor-related variables. The main outcome was concordance between the results of randomized clinical trials and observational cancer registry data. Hazard ratios with an NCDB analysis were considered concordant if the NDCB HR fell within the 95% CI of the randomized clinical trial HR. An NCDB analysis was considered concordant if both the NCDB and clinical trial P values for survival were nonsignificant (P ≥ .05) or if they were both significant (P < .05) with survival favoring the same treatment arm in the NCDB and in the randomized clinical trial. Analyses using the NCDB-produced HRs for survival were concordant with those of 141 randomized clinical trials in 79 univariable analyses (56%), 98 multivariable analyses (70%), and 90 propensity score models (64%). The NCDB analyses produced P values concordant with randomized clinical trials in 58 univariable analyses (41%), 65 multivariable analyses (46%), and 63 propensity score models (45%). No clinical trial characteristics were associated with concordance between NCDB analyses and randomized clinical trials, including disease site, type of clinical intervention, or severity of cancer. The findings of this study suggest that comparative effectiveness research using cancer registry data often produces survival outcomes discordant with those of randomized clinical trial data. These findings may help provide context for clinicians and policy makers interpreting observational comparative effectiveness research in oncology.


Roux-En-Y Gastric Bypass versus Sleeve Gastrectomy as Revisional Procedure after Adjustable Gastric Band: a Systematic Review and Meta-Analysis.
We aim to review the available literature on obese patients treated with laparoscopic Roux-en-Y gastric bypass (LRYGB) or laparoscopic sleeve gastrectomy (LSG) after failed laparoscopic adjustable gastric banding (LAGB), in order to compare the clinical outcomes of the two methods. A systematic literature search was performed in PubMed, CENTRAL, and Scopus databases, in accordance with the PRISMA guidelines. Eight studies met the inclusion criteria incorporating 635 patients. Both procedures are associated with comparable complications, conversions, mean hospital stay, and weight loss at 6 and 12 months. In the LRYGB group, % excess weight loss (%EWL) and BMI reduction after 24 months were increased. Well-designed, randomized controlled studies, comparing revisional LRYGB and LSG, are necessary to further assess their outcomes.


Hypoxia-induced alternative splicing in human diseases: the pledge, the turn, and the prestige.
Maintenance of oxygen homeostasis is an indispensable criterion for the existence of multicellular life-forms. Disruption of this homeostasis due to inadequate oxygenation of the respiring tissues leads to pathological hypoxia, which acts as a significant stressor in several pathophysiological conditions including cancer, cardiovascular defects, bacterial infections, and neurological disorders. Consequently, the hypoxic tissues develop necessary adaptations both at the tissue and cellular level. The cellular adaptations involve a dramatic alteration in gene expression, post-transcriptional and post-translational modification of gene products, bioenergetics, and metabolism. Among the key responses to oxygen-deprivation is the skewing of cellular alternative splicing program. Herein, we discuss the current concepts of oxygen tension-dependent alternative splicing relevant to various pathophysiological conditions. Following a brief description of cellular response to hypoxia and the pre-mRNA splicing mechanism, we outline the impressive number of hypoxia-elicited alternative splicing events associated with maladies like cancer, cardiovascular diseases, and neurological disorders. Furthermore, we discuss how manipulation of hypoxia-induced alternative splicing may pose promising strategies for novel translational diagnosis and therapeutic interventions.


Single nucleotide polymorphism (SNP) markers for genetic diversity and population structure study in Ethiopian barley (Hordeum vulgare L.) germplasm.
High-density single nucleotide polymorphisms (SNPs) are the most abundant and robust form of genetic variants and hence make highly favorable markers to determine the genetic diversity and relationship, enhancing the selection of breeding materials and the discovery of novel genes associated with economically important traits. In this study, a total of 105 barley genotypes were sampled from various agro-ecologies of Ethiopia and genotyped using 10 K single nucleotide polymorphism (SNP) markers. The refined dataset was used to assess genetic diversity and population structure. The average gene diversity was 0.253, polymorphism information content (PIC) of 0.216, and minor allelic frequency (MAF) of 0.118 this revealed a high genetic variation in barley genotypes. The genetic differentiation also showed the existence of variations, ranging from 0.019 to 0.117, indicating moderate genetic differentiation between barley populations. Analysis of molecular variance (AMOVA) revealed that 46.43% and 52.85% of the total genetic variation occurred within the accessions and populations, respectively. The heat map, principal components and population structure analysis further confirm the presence of four distinct clusters. This study confirmed that there is substantial genetic variation among the different barley genotypes. This information is useful in genomics, genetics and barley breeding.


Validation of self-reported help-seeking, and measurement of the patient interval, for cancer symptoms: an observational study to inform methodological challenges in symptomatic presentation research.
To improve earlier presentation with potential symptoms of cancer, accurate data are needed on how people respond to these symptoms. It is currently unclear how self-reported medical help-seeking for symptoms associated with cancer by people from the community correspond to what is recorded in their general practice records, or how well the patient interval (time from symptom onset to first presentation to a health-professional) can be estimated from patient records. Data from two studies that reviewed general practice electronic records of residents in Scotland, (i) the 'Useful Study': respondents to a general population survey who reported experiencing symptoms potentially associated with one of four common cancers (breast, colorectal, lung and upper gastro-intestinal) and (ii) the 'Detect Cancer Early' programme: cancer patients with one of the same four cancers. Survey respondents' self-reported help-seeking (yes/no) was corroborated; Cohen's Kappa assessed level of agreement. Combined data on the patient interval were evaluated using descriptive analysis. 'Useful Study' respondents' self-report of help-seeking showed exact correspondence with general practice electronic records in 72% of cases (n = 136, kappa 0.453, moderate agreement). Between both studies, 1269 patient records from 35 general practices were reviewed. The patient interval could not be determined in 44% (n = 809) of symptoms presented by these individuals. Patient self-report of help-seeking for symptoms potentially associated with cancer offer a reasonably accurate method to research responses to these symptoms. Incomplete patient interval data suggest routine general practice records are unreliable for measuring this important part of the patient's symptom journey.


Descriptive analysis of infant population younger than 1 year admitted for BRUE.
In 2016, the American Academy of Pediatrics defined the brief resolved unexplained event (BRUE) of high and low risk to characterize fainting in infants under 1 year of age. In the case of low-risk BRUE, it is recommended to perform no further systematic examination, but to monitor the child with a saturometer in the emergency room for 1-4 h. The objective of this study was to identify events corresponding to high- and low-risk BRUE criteria for infants admitted to the Angers University Hospital Center, and to analyze their medical care. We conducted an observational, retrospective, descriptive and single-center study of the population of infants younger than 1 year admitted for an unexplained event to the Pediatric Emergency Department of Angers University Hospital Center between 1 January 2017 and 31 December 2019. Two patient databases were crossed to identify patients. Among the 203 patients presenting for fainting, 54 patients met the criteria for BRUE, including 40 high-risk BRUE and 14 low-risk BRUE cases. All complementary examinations performed on low-risk BRUE children were normal. Two of these patients had a recurrence of non-severe fainting several months after the first episode. Identification of infants according to the BRUE criteria helps to harmonize practices and to limit the number of complementary examinations or hospitalizations for low-risk BRUE.


Novel HRPT2/CDC73 gene mutations and loss of expression of parafibromin in Chinese patients with clinically sporadic parathyroid carcinomas.
It is widely recognized that the diagnosis of parathyroid carcinoma (PC) is often difficult because of the overlap of characteristics between malignant and benign parathyroid tumors, especially at an early stage. Based on the identification of tumor suppressor gene HRPT2/CDC73 and its association with hereditary and sporadic PC, screening of gene mutations and detection of parafibromin immunoreactivity have been suggested as diagnostic instruments of PC in Whites. There is little information about HRPT2/CDC73 mutations and its corresponding protein expression in patients with sporadic PC in Chinese population, and the long-term follow-up data is scarce. Paraffin-embedded tissues were obtained from 13 patients with PC, 13 patients with parathyroid adenoma (PA) and 7 patients with parathyroid hyperplasia(PH), and 6 normal parathyroid (NP) tissues as controls. Peripheral blood from 11 patients with PC was collected. PCR products using Genomic DNA extracted from tumor tissues or blood as template was sequenced for HRPT2/CDC73 gene. Expression of parafibromin in tumor tissues was evaluated by immunohistochemical analysis. Six mutations in 6 of 13 patients with PC were identified, with three being novel. Four of them were germ-line mutations. Patients with mutations were susceptible to recurrence of the PC. Complete (8/13, 61.5%) or partial (5/13, 38.5%) loss of parafibromin expression was observed in PC tissues. All of tissue samples from normal parathyroid or benign parathyroid tumors displayed positive immunostaining of parafibromin except one adenoma. The present study supplies information on the mutations and protein expression of HRPT2/CDC73 gene and phenotypes of parathyroid carcinoma in Chinese population. And the expanded mutation database of this gene may benefit patients in the diagnosis and treatment of this disease.


Ventricular size, the dexamethasone suppression test and outcome of severe endogenous depression following psychosurgery.
To assess the possible significance of cerebral ventricular size and the dexamethasone suppression test (DST) in the outcome of severe endogenous depression, 28 patients were followed up and reviewed 1 year after stereotactic subcaudate tractotomy. Neither ventricular size nor the dexamethasone suppression test predicted either a good or poor outcome. There was no relationship between ventricular size and the DST results.


Prevalence of Left Atrial Appendage Thrombus in Patients Anticoagulated With Direct Oral Anticoagulants: Systematic Review and Meta-analysis.
Multiple studies have examined the prevalence of left atrial appendage thrombus (LAAT) in patients anticoagulated with direct oral anticoagulants (DOACs) and have reported conflicting results. Studies reporting the prevalence of LAAT on transesophageal echocardiography (TEE) after 3 or more weeks of DOAC therapy were identified. The proportions of anticoagulated patients diagnosed with LAAT were pooled using random-effects models. Prespecified subgroup analyses by the indication of TEE (pre-atrial fibrillation [AF] ablation vs cardioversion) and TEE strategy (routine use vs selective) were conducted via stratification. Forty studies were identified: 22 full manuscripts and 18 abstracts. Only 11 studies performed TEE routinely. Most studies included patients with paroxysmal AF and low thromboembolic risk. The pooled prevalence of LAAT was 2.5% (95% confidence interval [1.6%-3.4%]). The prevalence of LAAT is lower in the pre-AF ablation group compared with pre-cardioversion (1.1% vs 4.0%, P = 0.033). Routine TEE strategy yielded a lower LAAT prevalence in both groups (0.1% vs 2.3%, P = 0.002 and 3.2% vs 5.8%, P = 0.432, respectively). The reported prevalence of LAAT on TEE in patients treated with DOACs is highly variable. Factors associated with a high LAAT prevalence were pre-cardioversion indication and selective TEE strategy. Routine use of TEE before AF ablation may not be warranted.


Optimal temperature in short-term hypothermic preservation of rat pancreas.
Rat pancreases were hypothermically preserved for 24 hr in University of Wisconsin preservation solution at specific temperatures (4, 7, 10, and 15 degrees C) to evaluate the effect of preservation temperature on islet yield and islet function. Following hypothermic storage, the loss of recoverable islets was highest in the 15 degrees C-preservation group, followed by that of the 4 degrees C group and significantly less in the 7 and 10 degrees C groups (p less than 0.05). Islet function, as measured by insulin output following glucose challenge in perifusion, was reduced (p less than 0.0001) in all preservation groups. The mean insulin secretion rate was lowest in the 4 degrees C group, highest in the 7 degrees C group, and intermediate in the 10 degrees C group. The islet preservation index, a parameter taking into consideration both islet yield and islet function after preservation, was more than double in the 7 and 10 degrees C preservation groups as compared to the 4 degrees C group (p less than 0.0001). This study shows that significant improvement in islet yield and function occurs when the rat pancreas was preserved at 7-10 degrees C rather than at 4 degrees C.


Combined ultrasonic thermal ablation with interleaved ARFI image monitoring using a single diagnostic curvilinear array: a feasibility study.
The goal of this work is to demonstrate the feasibility of using a diagnostic ultrasound system (Siemens Antares and CH6-2 curvilinear array) to ablate ex vivo liver with a custom M-mode sequence and monitor the resulting tissue stiffening with 2-D Acoustic Radiation Force Impulse (ARFI) imaging. Images were taken before and after ablation, as well as in 5- s intervals during the ablation sequence in order to monitor the ablation lesion formation temporally. Ablation lesions were generated at depths up to 1.5 cm from the surface of the liver and were not visible in B-mode. ARFI images showed liver stiffening with heating that corresponded to discolored regions in gross pathology. As expected, the contrast of ablation lesions in ARFI images is observed to increase with ablation lesion size. This study demonstrated the ability of a diagnostic system using custom beam sequences to localize an ablation site, heat the site to the point of irreversible damage and monitor the formation of the ablation lesion with ARFI imaging.


MIRO-1 Determines Mitochondrial Shape Transition upon GPCR Activation and Ca2+ Stress.
Mitochondria shape cytosolic calcium ([Ca2+]c) transients and utilize the mitochondrial Ca2+ ([Ca2+]m) in exchange for bioenergetics output. Conversely, dysregulated [Ca2+]c causes [Ca2+]m overload and induces permeability transition pore and cell death. Ablation of MCU-mediated Ca2+ uptake exhibited elevated [Ca2+]c and failed to prevent stress-induced cell death. The mechanisms for these effects remain elusive. Here, we report that mitochondria undergo a cytosolic Ca2+-induced shape change that is distinct from mitochondrial fission and swelling. [Ca2+]c elevation, but not MCU-mediated Ca2+ uptake, appears to be essential for the process we term mitochondrial shape transition (MiST). MiST is mediated by the mitochondrial protein Miro1 through its EF-hand domain 1 in multiple cell types. Moreover, Ca2+-dependent disruption of Miro1/KIF5B/tubulin complex is determined by Miro1 EF1 domain. Functionally, Miro1-dependent MiST is essential for autophagy/mitophagy that is attenuated in Miro1 EF1 mutants. Thus, Miro1 is a cytosolic Ca2+ sensor that decodes metazoan Ca2+ signals as MiST.


Evolution from small molecule to nano-drug delivery systems: An emerging approach for cancer therapy of ursolic acid.
Ursolic acid (UA), a natural pentacyclic triterpenoid, possesses widespread biological and pharmacological activities. However, drawbacks such as low bioavailability, poor targeting and rapid metabolism greatly hinder its further clinical application. Recently, with the development of nanotechnology, various UA nanosystems have emerged as promising strategies for effective cancer therapy. This article reviews various types of UA-based nano-delivery systems, primarily with emphasis placed on novel UA-based carrier-free nano-drugs, which are considered to be innovative methods for cancer therapy. Moreover, this review presents carrier-free nano-drugs that co-assembled of UA and photosensitizers that displayed synergistic antitumor performance. Finally, the article also describes the development and challenges of UA nanosystems for future research in this field. Overall, the information presented in this review will provide new insight into the rational utilization of nano-drugs in cancer therapy.


Effects of green infrastructure on the dispersion of PM2.5 and human exposure on urban roads.
Urban green infrastructure (GI) has been widely demonstrated to effectively improve air quality in the built environment. However, due to the lack of comparative studies of the effects of different GI forms on PM2.5 dispersion, optimal GI designs suitable for different urban road types currently remain unclear. In this study, we adopted different roadside GI types in Hangzhou city as case studies and used the ENVI-met model to compare the effects of the different GI forms on PM2.5 dispersion and human exposure to PM2.5. The results indicated that 1) In open roads, the concave-shaped GI type could effectively reduce PM2.5 aggregation and human exposure on motorways, and the all-tree GI type performed the best in terms of sidewalk PM2.5 purification. 2) In street canyons, green roof and green screen were highly conducive to PM2.5 concentration reduction under commuter exposure compared with traditional green solutions. 3) There were trade-offs in the GI-PM2.5 interaction. GI types which can reduce pedestrian exposure tend to increase exposure in motorways. The same GI type deployed along the two different road types could yield completely opposite dispersion effects. Novel GI types had better environmental performance and relatively high economic cost. All decision-making should be based on the trade-offs between the advantages and disadvantages of GI. Our study also highlights the importance of comprehensive consideration of GI and road types and local wind conditions in future urban road planning and GI applications.


Cardiovascular consequences of obstructive sleep apnea.
Sleep apnea is associated with several cardiovascular disease conditions. A causal relationship between sleep apnea and each of these diseases is likely, but remains to be proven. The clearest evidence implicating OSA in the development of new cardiovascular disease involves data that show an increased prevalence of new hypertension in patients with OSA followed over 4 years [3]. Circumstantial evidence and data from small study samples suggest that OSA, in the setting of existing cardiovascular disease, may exacerbate symptoms and accelerate disease progression. The diagnosis of OSA always should be considered in patients with refractory heart failure, resistant hypertension, nocturnal cardiac ischemia, and nocturnal arrhythmias, especially in individuals with risk factors for sleep apnea (e.g., central obesity, age, and male gender). Treating sleep apnea may help to achieve better clinical control in these diseases and may improve long-term cardiovascular prognosis.


Biomechanical analysis of human chorioamniotic membranes.
The biomechanical properties of human fetal membranes were analyzed by means of a materials testing machine. Special attention was paid to the biomechanical properties of the intact chorioamniotic membrane and the amniotic and chorionic components, separately, and thickness and storage of membrane samples. The load-strain and stress-strain relationships, and parameters calculated from the curves: extensibility, strength, elastic stiffness and failure energy, express the visco-elastic behavior of these membranes. The mechanical properties of the chorioamniotic membranes are determined by the interaction between the amniotic and chorionic components of the membrane. The strength of the intact chorioamniotic membrane, however, is primarily determined by the amniotic component, because the amniotic component is much less extensible. Thus, the chorionic component only contributes 10-15% of the strength when the amniotic component breaks. The chorionic component is twice as extensible as the amniotic component. Samples of fetal membranes can be stored at -70 degrees C, with no significant changes in the biomechanical properties. No significant differences were found between specimens, which were oriented in parallel with and at right angles to the placental edge. Small samples can be analysed and the localization of samples in relation to the placental edge and rupture site of the membranes can be standardized. The method is well suited for studies of premature rupture of fetal membranes.


Obstetric ultrasound aids prompt referral of gestational trophoblastic disease in marginalized populations on the Thailand-Myanmar border.
The use of obstetric ultrasound in the diagnosis of gestational trophoblastic disease (GTD) in high-income settings is well established, leading to prompt management and high survival rates. Evidence from low-income settings suggests ultrasound is essential in identifying complicated pregnancies, but with limited studies reviewing specific conditions including GTD. The aim of this study is to review the role of ultrasound in diagnosis and management of GTD in a marginalized population on the Thailand-Myanmar border. Antenatal ultrasound became available in this rural setting in 2001 and care for women with GTD has been provided by Thailand public hospitals for 20 years. Retrospective record review. The incidence of GTD was 103 of 57,004 pregnancies in Karen and Burmese women on the Thailand-Myanmar border from 1993-2013. This equates to a rate of 1.8 (95% CI 1.5-2.2) per 1000 or 1 in 553 pregnancies. Of the 102 women with known outcomes, one (1.0%) died of haemorrhage at home. The median number of days between first antenatal clinic attendance and referral to hospital was reduced from 20 (IQR 5-35; range 1-155) to 2 (IQR 2-6; range 1-179) days (p = 0.002) after the introduction of ultrasound. The proportion of severe outcomes (death and total abdominal hysterectomy) was 25% (3/12) before ultrasound compared to 8.9% (8/90) with ultrasound (p = 0.119). A recurrence rate of 2.5% (2/80) was observed in the assessable population. The presence of malaria parasites in maternal blood was not associated with GTD. The rate of GTD in pregnancy in this population is comparable to rates previously reported within South-East Asia. Referral time for uterine evacuation was significantly shorter for those women who had an ultrasound. Ultrasound is an effective method to improve diagnosis of GTD in low-income settings and an effort to increase availability in marginalized populations is required.


Behavioral recovery patterns in rats receiving the NMDA receptor antagonist MDL 100,453 immediately post-stroke.
Rats were given MDL 100,453 ((R)-4-Oxo-5-phosphononorvaline) in a pre-determined neuroprotective dose consisting of a bolus of 24.8 mg/kg followed by an infusion of 1.05 mg/kg*h for 24 h (MDL group; n = 8) or saline of the same volume (SALINE group; n = 8) 30 min. after the onset of a 90 min. period of middle cerebral artery occlusion. Eight animals underwent SHAM surgery. Rats were evaluated post-operatively for 14 days using seven neurological tests, including water maze. SALINE animals exhibited a pattern of neurological impairment compared to SHAMs (poor performance in five of the six motor/reflex tests) peaking five days post-injury. Relative to the SALINE group, the MDL group exhibited significantly improved outcome on two of the tests and a pattern of improved behavior on the remainder of the battery. By day 14 post-ischemia, all groups exhibited recovery on the motor/reflex tests. Learning ability was disrupted in the SALINE group on days 17 and 18, whereas the MDL group's performance was not distinguishable from the SHAM group in the water maze. Thus, a neuroprotective dose of MDL 100,453 produced a pattern of behavioral sparing in the immediate post-ischemic days that was uniquely different than saline. The addition of behavioral outcome measures to histological neuroprotection data adds significantly to the ability to better evaluate a putative neuroprotective compound.


Magnetoresponsive nanozyme: magnetic stimulation on the nanozyme activity of iron oxide nanoparticles.
The iron oxide nanoparticles (IONPs) that combine the nanozyme activity and magnetothermal properties have attracted significant interest for various biomedical applications. However, the effect of magnetic stimulation in fine-tuning the nanozyme activities remains unclear. Here, we have constructed a series of IONPs with different magneto-thermal conversion abilities, and systematically study the effect of magnetic field stimulation on the peroxidase (POD) activity of IONPs. The results show that POD activity is effectively amplified via an in situ alternating magnetic field (AMF) stimulation with no solution temperature rise, and the degree of activity enhancement is closely related to the magnetic heating ability of the IONPs, confirming the origin of activity enhancement arises from the local magnetothermal effect. As the first report to prove magnetothermal regulation on nanozyme activity and to shed lights on the underlying correlation between activity enhancement and the intrinsic specific absorption rate (SAR), this work is expected to provide important support for future design of new magnetoresponsive nanozymes in various practical applications.


Micromolar sodium fluoride promotes osteo/odontogenic differentiation in dental pulp stem cells by inhibiting PI3K/AKT pathway.
Sodium fluoride (NaF) plays an important role in preventing dental caries. However, the regulatory effect of NaF on the committed differentiation of DPSCs is not fully understood. In this study, we characterized the impact of micromolar levels of NaF on the osteo/odontogenic differentiation of DPSCs. DPSCs were isolated from healthy human third molars and were cultured in conditioned media with different concentrations of NaF. RNA sequencing (RNA-seq) combined with Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis was used to assess the pathways regulated by NaF. Alkaline phosphatase activity, Alizarin red staining, Western blotting, and real-time qRT-PCR were used to determine the osteo/odontogenic differentiation in DPSCs treated with NaF. NaF significantly promoted the osteo/odontogenic differentiation of DPSCs at micromolar levels. Furthermore, RNA-seq and KEGG pathway enrichment analysis indicated that the PI3K/AKT pathway was involved in the pro-osteoclastogenesis effect of NaF. Western blotting analysis exhibited that the phosphorylation of AKT was decreased in NaF-treated DPSCs. Chemical inhibition of the PI3K/AKT pathway abrogated the NaF-promoted DPSCs osteo/odontogenic differentiation. Micromolar NaF can promote the osteo/odontogenic differentiation of DPSCs by inhibiting the PI3K/AKT pathway. The data used to support the findings of this study are available from the corresponding author upon request.


Reactionary responses to the Bad Lot Objection.
As it is standardly conceived, Inference to the Best Explanation (IBE) is a form of ampliative inference in which one infers a hypothesis because it provides a better potential explanation of one's evidence than any other available, competing explanatory hypothesis. Bas van Fraassen famously objected to IBE thus formulated that we may have no reason to think that any of the available, competing explanatory hypotheses are true. While revisionary responses to the Bad Lot Objection concede that IBE needs to be reformulated in light of this problem, reactionary responses argue that the Bad Lot Objection is fallacious, incoherent, or misguided. This paper shows that the most influential reactionary responses to the Bad Lot Objection do nothing to undermine the original objection. This strongly suggests that proponents of IBE should focus their efforts on revisionary responses, i.e. on finding a more sophisticated characterization of IBE for which the Bad Lot Objection loses its bite.


Effects of microplastics on head kidney gene expression and enzymatic biomarkers in adult zebrafish.
Due to massive production, improper use, and disposal of plastics, microplastics have become global environmental pollutants affecting both freshwater and marine ecosystems. Several studies have documented the uptake of microplastics in wild species and the correlated biological effects, such as epithelial damage, inflammation, metabolic alterations, and neurotoxicity. However, the effects of microplastics are not fully understood yet. In this study, adult zebrafish have been exposed for twenty days to two concentrations of a mix of polystyrene and high-density polyethylene microplastics. The biological effects were investigated through the expression levels of a set of selected genes in head kidney samples and two enzymatic biomarkers, acetylcholinesterase and lactate dehydrogenase, in head and body homogenates respectively. The lowest microplastic concentration up-regulated genes involved in xenobiotics catabolic processes (cyp2p8), and adaptive immunity (tcra). Acetylcholinesterase activity was inhibited by the highest microplastics exposure, while a weaker and no significant inhibition was induced by the lowest concentration. No significant effects on lactate dehydrogenase activity were observed. The results presented in this study support the hypothesis that MPs exposure could induce the activation of an immune response and the xenobiotic metabolism, suggesting also that the cytochrome P450 enzyme cyp2p8 and acetylcholinesterase may be sensitive to MPs contamination.


Conservative management of vesicouterine fistula after uterine rupture.
We report the closure of a vesicouterine fistula with conservative management utilizing an indwelling transurethral Foley catheter. Uterine rupture occurred during a trial of vaginal birth after cesarean section, necessitating an emergency cesarean section. Upon entry into the abdomen, the base of the bladder was noted to be involved in the uterine rupture. The bladder trigone and ureteral orifices appeared normal. A primary, two-layer bladder repair was performed. A cystogram on postoperative day 14 demonstrated a vesicouterine fistula. Conservative management involving bladder drainage for 21 days with a transurethral Foley catheter was successful in closure of the fistula. Vesicouterine fistula, a documented complication of uterine rupture due to attempted vaginal birth after previous cesarean section, can spontaneously resolve with conservative management alone.


Trypanosoma cruzi: experimental parasitism of bone and cartilage.
Trypanosoma cruzi causes Chagas' disease, a systemic infection that affects cells of meso-, endo-, and ectodermic origin. However, as far as we know, the presence of T. cruzi stages in bone has not been reported previously, and it has scarcely been investigated in cartilage. We inoculated 7- and 20-day-old (8 and 15 g) NMRI albino mice i.p. with metacyclic trypomastigotes from Rhodnius prolixus used for xenodiagnosis of mice previously infected with mammalian, human, and triatomines isolates, characterized by randomly amplified polymorphic DNA as zymodeme 1 (equivalent to T. cruzi I). Tissular parasitism (quantified according to the number of pseudocysts/50 fields 400x) showed amastigotes, intermediate forms, or trypomastigotes in sternum chondroblasts, osteoblasts, macrophages, and fibroblasts; chondrocyte and osteocyte invasion was rare. All isolates parasitized bone marrow macrophages, with few amastigotes. We observed marked associated myotropism, with or without inflammatory infiltration; there were small numbers of intensely parasitized mononuclear cells in perichondrium and periosteum. We discuss the results in relation to the marked differences of the T. cruzi tropism toward the different types of sternum cells, and, additionally, we outline the possibility of transmitting parasitized bone marrow through transplants. The fact of finding parasite stages in sternum bone and cartilage may be considered important due to the studies on Chagas' disease paleoparasitology that are based on histological and molecular analysis.


Disparity in access for people with disabilities to outpatient dental care services: a retrospective cohort study.
People with disabilities face difficulties in oral health management and gaining access to dental care. The availability of a regular source of dental care (RSDC) is an important factor that influences the access to health services and care management. The purpose of this study was to determine the effect of the availability of RSDC on the number of annual dental visits and dental expenses per visit among people with disabilities. Data of 7,896,251 patients with dental problems in South Korea were analyzed using the 2002-2018 National Health Insurance claims data. A generalized estimating equation was applied to analyze the repeated-measurement data, and the interaction effect between RSDC and the disability severity was evaluated. The number of annual dental visits was higher among people with (2.62) than among those without (2.23) disabilities. Despite their increased dental needs, both annual dental visits and dental expenses per visit were low among older individuals (p < 0.001). The proportion and frequency of annual dental visits was lower among women than among men with disabilities. RSDC had differential effects on the severity of disability. Compared to people without disabilities, RSDC increased the number of annual dental visits (p = 0.067) and the dental expenses per visit (p < 0.05) among those with severe disabilities, but the effect on the number of annual dental visits was not significant among those with mild disabilities (p = 0.698). Our results suggest a need for a special dental care system for people with disabilities, to ensure an RSDC, particularly for women and for older people with disabilities.


The influence of travel time on breast cancer characteristics, receipt of primary therapy, and surveillance mammography.
Travel time has been shown to influence some aspects of cancer characteristics at diagnosis and care for women with breast cancer, but important gaps remain in our understanding of its impact. We examined the influence of travel time to the nearest radiology facility on breast cancer characteristics, treatment, and surveillance for women with early-stage invasive breast cancer. We included 1,012 women with invasive breast cancer (stages I and II) who had access to care within an integrated health care delivery system in western Washington State. The travel times to the nearest radiology facility were calculated for all the U.S. Census blocks within the study area and assigned to women based on residence at diagnosis. We collected cancer characteristics, primary and adjuvant therapies, and surveillance mammography for at least 2.5 years post diagnosis and used multivariable analyses to test the associations of travel time. The majority of women (68.6%) lived within 20 min of the nearest radiology facility, had stage I disease (72.7%), received breast conserving therapy (68.7%), and had annual surveillance mammography the first 2 years after treatment (73.7%). The travel time was not significantly associated with the stage or surveillance mammography after adjusting for covariates. Primary therapy was significantly related to travel time, with greater travel time (>30 min vs. ≤ 10 min) associated with a higher likelihood of mastectomy compared to breast conserving surgery (RR = 1.53; 95% CI, 1.16-2.01). The travel time was not associated with the stage at diagnosis or surveillance mammography receipt. The travel time does seem to influence the type of primary therapy among women with breast cancer, suggesting that women may prefer low frequency services, such as mastectomy, if geographic access to a radiology facility is limited.


"Medullary ray glomerular counting" as a method of assessment of human nephrogenesis.
Renal weight (left-right combined), as a parameter of renal development, is required to be less than half the normal value for age for a statistically confident diagnosis of hypoplasia. "Medullary ray glomerular counting" (MRGC), counting cortical glomerular generations, has been proposed as a simple technique of possibly greater sensitivity. Recent development of the Disector method for the unbiased stereological estimation of total glomerular number has provided a, hitherto unavailable, "golden standard" with which to determine the diagnostic potential of MRCG. Both "true" (actual number of generations seen) and "assumed" (a subjective "guess" of the total number of generations) MRGC counts were determined in 11 pairs of kidneys from spontaneously aborted, normally developed, non-malformed fetuses (gestational age: 15-40 weeks). Each kidney was randomly analysed blind and on two separate occasions by two paediatric pathologists using a written protocol. Results were compared with unbiased stereological estimates of glomerular number. Intra- and inter-observer and intra- and inter-(left-right)renal reproducibility were analysed. In conclusion, MRGC, using "real" counts, is a highly reproducible parameter of renal development from 15-36 weeks' gestation. Sensitivity for detection of both hypoplasia and maturation delay increase with gestational age and generally exceeds that of renal weight.


A feasibility study of carboplatin and weekly paclitaxel combination chemotherapy in endometrial cancer: a Kansai Clinical Oncology Group study (KCOG0015 trial).
The optimal chemotherapy regimen for women with endometrial cancer has not been established. We assessed the feasibility, toxicity and clinical efficacy of combination triweekly carboplatin and weekly paclitaxel in women with endometrial cancer. Eligible patients had histologically confirmed primary advanced or recurrent endometrial cancer (Group A), or had localized high-risk features (Group B). All were treated with paclitaxel 80 mg/m(2) (days 1, 8 and 15) and carboplatin AUC 5 (day 1) each 21-day cycle. A minimum of 3 cycles was planned; if 75% or more of patients were able to receive at least 3 cycles with acceptable toxicity, the regimen was declared "feasible." Forty patients were enrolled and administered 163 cycles of therapy; 38 (95%) were chemo-naive. No patients received radiation previously. Group A (measurable disease) contained 15 patients (5 with recurrent disease, 7 receiving neo-adjuvant chemotherapy, and 3 treated adjuvantly following suboptimal cytoreduction). Group B (non-measurable disease) contained 25 patients (primary stage I:10, II:5, III:8, IV:1 and relapse 1). Hematological toxicities(G3/G4) were neutropenia (31%/33%) and thrombocytopenia (6%/0%). Reversible G3 hypersensitivity (5%) and G2 cardiotoxicity (3%) was uncommon. Thirty-one patients (78%) completed ≥3 cycles (median 4, range: 1-9). Thirteen of 15 (87%) measurable patients responded (3CR, 10PR). Eighty-seven percent of measurable patients were not progressive at 6 months. In Group A, QOL scores were significantly improved after 3 cycles of chemotherapy (p=0.037), and at the completion of chemotherapy (p=0.045). QOL scores in Group B did not change during therapy. This combination chemotherapy is feasible and effective for endometrial cancer patients.


uPA receptor expression in benign and malignant thyroid tumors.
Urokinase type plasminogen activator receptor (uPAR) plays an important role in cancer invasion and metastasis. However, the uPAR expression has been rarely investigated in thyroid carcinomas. The aim of this study was to evaluate the clinical relevance of uPAR in thyroid tumors. Samples included 53 benign tumors (follicular adenoma 34, Graves' disease 8, adenomatous goiter 7 and others 4) and 62 cancers (papillary thyroid cancer (PTC) 47, follicular TC (FTC) 5, medullary TC (MTC) 5 and anaplastic TC (ATC) 5). uPAR expression was prospectively investigated with a labeled streptavidin-biotin method using an anti-uPAR monoclonal antibody. Patients were classified into a low- and high-staining group according to the percentage of positive cells (cut-off value=10%). uPAR was more strongly expressed in thyroid cancers (35.5%) than benign tumors (7.5%). FTC had a significantly higher uPAR expression compared to follicular adenoma (p<0.01). The positivity of uPAR was as follows: PTC 36.2%, FTC 60%, MTC 0% and ATC 40%. In PTC, high uPAR expression was associated with poorly-differentiated PTC (p<0.01) while had a trend to develop more distant metastases than those with low uPAR expression (p=0.17, by the Kaplan-Meier method). This study has shown that uPAR expression might be useful for the discrimination between FTC and follicular adenoma and could possibly be used as a prognostic factor in PTC.


Electrode recovery potential.
In some instances the same electrodes are used for stimulation and then for recording a bioelectric event immediately after the stimulus. However, after the current pulse there remains an electrode potential that decays quasiexponentially. We have designated this falling potential the electrode-recovery potential. This study investigated the recovery potentials of single electrodes of rhodium, stainless steel, platinum and platinum-iridium in contact with 0.9% saline at room temperature (25 degrees C) over a current density ranging from 0.1 to 100 mA/cm2 using a constant-current pulse. In all cases, with increasing current density, there was a decrease in the time for the electrode potential to fall to one half of the immediate post-stimulus value. Above about 20 mA/cm2 the decrease in recovery time was smooth with increasing current density. Below 20 mA/cm2, the recovery time was slightly irregular. The shortest recovery times were for platinum and platinum-iridium. The largest decrease in recovery time with increasing current density was for stainless steel, which decreased 10 fold from 0.1 to 100 mA/cm2. The recovery time for rhodium decreased about three-and-one half fold over the same current density range. It was found that the waveform of the recovery potential is not a simple exponential because the Warburg and Faradic components of the electrode-electrolyte interface are current-density dependent. In general, for all current densities studied (0.1-100 mA/cm2), there was a sudden initial fall in electrode potential with cessation of current flow, followed by a very gradual nonexponential decrease in potential.


Psychoneuroendocrinological effects of music therapy versus mindfulness in palliative care: results from the 'Song of Life' randomized controlled trial.
Although research on psychosocial interventions in palliative care provided evidence for their effectiveness regarding patient-reported outcomes, few studies have examined their psychobiological effects yet. Therefore, the purpose of the present work as part of an overarching study was to investigate differential effects of music therapy versus mindfulness on subjective distress and both neuroendocrine and autonomic stress biomarkers. A total of 104 patients from two palliative care units were randomly assigned to three sessions of either music therapy or mindfulness. Before and after the second session (completed by 89 patients), participants rated their momentary distress and provided three saliva samples for cortisol and α-amylase analysis. Furthermore, photoplethysmography recordings were continuously assessed to calculate mean heart rate and heart rate variability. Data were analyzed using multilevel modeling of all available data and sensitivity analysis with multiply imputed data. Between 67 and 75% of the maximally available data points were included in the primary analyses of psychobiological outcomes. Results showed a significant time*treatment effect on distress (b = - 0.83, p = .02) indicating a greater reduction in the music therapy group. No interaction effects were found in psychobiological outcomes (all p > .05), but multilevel models revealed a significant reduction in cortisol (b = - 0.06, p = .01) and mean heart rate (b = - 7.89, p = .05) over time following either intervention. Findings suggest a beneficial effect music therapy on distress while no differential psychobiological treatment effects were found. Future studies should continue to investigate optimal stress biomarkers for psychosocial palliative care research. German Clinical Trials Register (DRKS)-DRKS00015308 (date of registration: September 7, 2018).


Effects of activation sequence on ventricular refractory periods of ischemic canine myocardium.
Refractory periods were measured in pentobarbital-anesthetized dogs during control periods and one to one and a half hours after distal left anterior descending coronary artery occlusion. The refractory period test site was on the anterior surface of the left ventricle in the distribution of the artery to be occluded. Measurements were made during drive of the refractory period test site, drive of a distant site on the pulmonary conus and during fusion drive in which drive of the test site was delayed with respect to drive of the pulmonary conus. Refractory periods were longer during test site drive than during pulmonary conus or fusion drives in both the control periods and following coronary occlusion. However, the effects of driving mode on refractory periods were greater following coronary occlusion than in the control periods. The findings are likely secondary to different magnitudes of change in electrotonic interactions associated with changes in activation sequence in ischemic and nonischemic myocardium. The greater dependence of repolarization properties in ischemic than nonischemic tissue suggests that inhomogeneity of these properties could be modified considerably by the site of origin of ectopic ventricular complexes.


Cutaneous HPV and skin cancer.
Papillomaviruses (HPVs) are small non-enveloped icosahedral viruses that infect the keratinocytes of skin and mucosa. The cutaneous HPV types are represented mainly by the beta and gamma genera, which are widely present in the skin of normal individuals. More than 40 beta-HPV types and 50 gamma-HPV types have been isolated, and these numbers are continuously growing. The main cause of non-melanoma skin cancer is exposure to ultraviolet radiation (UVR). However, cutaneous HPVs that belong to the beta genus may act as a co-carcinogen with UVR. The association between beta-HPVs and skin cancer was first reported in patients with epidermodysplasia verruciformis (EV), who frequently develop cutaneous squamous cell carcinoma (SCC) on sun-exposed areas. Isolation of HPVs from the lesions suggested that HPVs might act as a co-carcinogen with UVR in EV patients. Beta-HPVs may also play a role in cutaneous SCC in immunocompromised non-EV and in immunocompetent individuals. Several studies have reported an association of viral DNA and/or antibodies to beta HPV types with SCC. Interestingly, HPV prevalence and viral load decrease during skin carcinogenesis, being significantly higher in actinic keratosis than in SCC, suggesting that the virus may play a role in the early stages of tumour development (the "hit-and-run" hypothesis). Concordantly, in vivo and in vitro studies have shown that E6 and E7 from certain cutaneous HPV types display transforming activities, further confirming their potential role in carcinogenesis.


Bitter Taste Perception and Dental Biofilm Cariogenicity in Orthodontics.
Bitter taste perception and sweetness preference have been associated with dental caries. Propylthiouracil (PROP) has been used to determine the genetic sensitivity to bitter taste in early childhood caries. However, the role of the bitter threshold in dental biofilm cariogenicity has not been reported. The purpose of this study was to investigate the role of individual taste sensitivity using PROP in dental biofilm cariogenicity in orthodontic patients. Forty orthodontic patients (12-42 years old) undergoing fixed appliance orthodontic treatment participated in this cross-sectional study. Their demographic, oral hygiene practice, and dietary habits data were obtained using a questionnaire. The patients' bitter taste threshold was measured using a PROP assay. The patients were subsequently classified as super-tasters (STs), medium-tasters (MTs), and non-tasters (NTs). Dental biofilm cariogenicity was determined using a 3-tone disclosing gel that becomes pink (new dental biofilm), purple (mature dental biofilm), and light blue (cariogenic dental biofilm) based on dental biofilm maturity. The NT, MT, and ST groups comprised 10%, 27.5%, and 62.5% of the patients, respectively. Most of the STs (56%) and MTs (63.6%) were female, whereas no females were NTs. The dental biofilm cariogenicity was significantly different between the PROP bitterness groups (P < .05). The highest percentage of mature biofilm, followed by cariogenic and new biofilm, was found in the MT and ST groups. However, the cariogenic biofilm percentage was significantly higher compared with mature biofilm (P < .05) in the NT group. A low frequency (<1 time/d) of sugary and acidic food intake between meals was observed in the ST, MT, and NT groups with no significant difference amongst the groups (P > .05). Cariogenic dental biofilm was highly present in orthodontic patients with the NT phenotype.


Low titers of SARS-CoV-2 neutralizing antibodies after first vaccination dose in cancer patients receiving checkpoint inhibitors.
Vaccination for SARS-CoV-2 provides significant protection against the infection in the general population. However, only limited data exist for patients with cancer under systemic therapy. Based on this, our site has initiated a study evaluating safety and efficacy of SARS-CoV-2 vaccination in patients with solid and hematological malignancies under several systemic therapies. The initial results of the cohort of 59 patients receiving Immune Checkpoint Inhibitors are presented here. Despite no new safety issues have been noticed, the levels of SARS-CoV-2 neutralizing antibodies are significantly lower in comparison to matched healthy volunteers up to day 22 post the first dose. These results should be taken into consideration for the patients under treatment.


What does engagement mean to participants in longitudinal cohort studies? A qualitative study.
Engagement is important within cohort studies for a number of reasons. It is argued that engaging participants within the studies they are involved in may promote their recruitment and retention within the studies. Participant input can also improve study designs, make them more acceptable for uptake by participants and aid in contextualising research communication to participants. Ultimately it is also argued that engagement needs to provide an avenue for participants to feedback to the cohort study and that this is an ethical imperative. This study sought to explore the participants' experiences and thoughts of their engagement with their birth cohort study. Participants were recruited from the Children of the 90s (CO90s) study. Qualitative semi-structured interviews were conducted with 42 participants. The interviews were transcribed verbatim, and uploaded onto Nvivo software. They were then analysed via thematic analysis with a constant comparison technique. Participants' experiences of their engagement with CO90s were broadly based on three aspects: communication they received from CO90s, experiences of ethical conduct from CO90s and receiving rewards from CO90s. The communication received from CO90s, ranged from newsletters explaining study findings and future studies, to more personal forms like annual greeting cards posted to each participant. Ethical conduct from CO90s mainly involved participants understanding that CO90s would keep their information confidential, that it was only involved in 'good' ethical research and their expectation that CO90s would always prioritise participant welfare. Some of the gifts participants said they received at CO90s included toys, shopping vouchers, results from clinical tests, and time off from school to attend data collection (Focus) days. Participants also described a temporality in their engagement with CO90s and the subsequent trust they had developed for the cohort study. The experiences of engagement described by participants were theorized as being based on reciprocity which was sometimes overt and other times more nuanced. We further provide empirical evidence of participants' expectation for a reciprocal interaction with their cohort study while highlighting the trust that such an interaction fosters. Our study therefore provides key insights for other cohort studies on what participants value in their interactions with their cohort studies.


Toward a microscopic model of light absorbing dissolved organic compounds in aqueous environments: theoretical and experimental study.
Water systems often contain complex macromolecular systems that absorb light. In marine environments, these light absorbing components are often at the air-water interface and can participate in the chemistry of the atmosphere in ways that are poorly understood. Understanding the photochemistry and photophysics of these systems represents a major challenge since their composition and structures are not unique. In this study, we present a successful microscopic model of this light absorbing macromolecular species termed "marine derived chromophoric dissolved organic matter" or "m-CDOM" in water. The approach taken involves molecular dynamics simulations in the ground state using on the fly Density Functional Tight-Binding (DFTB) electronic structure theory; Time Dependent DFTB (TD-DFTB) calculations of excited states, and experimental measurements of the optical absorption spectra in aqueous solution. The theoretical hydrated model shows key features seen in the experimental data for a collected m-CDOM sample. As will be discussed, insights from the model are: (i) the low-energy A-band (at 410 nm) is due to the carbon chains combined with the diol- and the oxy-groups present in the structure; (ii) the weak B-band (at 320-360 nm) appears due to the contribution of the ionized speciated form of m-CDOM; and (iii) the higher-energy C-band (at 280 nm) is due to the two fused ring system. Thus, this is a two-speciated formed model. Although a relatively simple system, these calculations represent an important step in understanding light absorbing compounds found in nature and the search for other microscopic models of related materials remains of major interest.


Novel 2-(4-methylsulfonylphenyl)pyrimidine derivatives as highly potent and specific COX-2 inhibitors.
New series of 2-(4-methylsulfonylphenyl) and 2-(4-sulfamoylphenyl)pyrimidines were synthesized and evaluated for their ability to inhibit cyclooxygenase-2 (COX-2). COX-1 and COX-2 inhibitory activity of these compounds was determined using purified enzyme (PE) and human whole blood (HWB) assays. Extensive structure-activity relationship (SAR) work was carried out within these series, and a wide number of potent and specific COX-2 inhibitors were identified (HWB COX-2 IC(50)=2.4-0.3nM and 80- to 780-fold more selective than rofecoxib).


Hepatoprotective effects of geniposide in a rat model of nonalcoholic steatohepatitis.
Nonalcoholic steatohepatitis (NASH), a metabolic disorder of the liver, may gradually evolve into fibrosis or cirrhosis. Recent studies have suggested that geniposide can effectively inhibit experimental liver fibrosis. Therefore, the aim of this study was to determine whether geniposide can influence the early phase of fibrogenesis in an animal model of NASH. Male Sprague-Dawley rats were given a high fat diet alone or the same diet combined with geniposide at doses of 25, 50 or 100 mg/kg for six weeks. Ten rats received corresponding solvent as a normal control. Treatment with geniposide could improve liver histology through reducing the elevated liver index (liver weight/body weight), serum alanine aminotransferase and aspartate aminotransferase. Total cholesterol, triglycerides and free fatty acids in serum and liver decreased in geniposide-treated rats. Furthermore, geniposide increased serum insulin levels but reduced serum tumour necrosis factor-α level in high-fat diet rats. In addition, geniposide suppressed expression of CYP2E1 and increased peroxisome proliferator-activated receptor-α (PPARα) expression. These benefits may be associated with increased superoxide dismutase and decreased malondialdehyde in liver. Geniposide exerts protective effects against hepatic steatosis in rats fed with a high fat diet; the underlying mechanism may be associated with its antioxidant actions or regulation of adipocytokine release and expression of PPARα.


The role of carbonic anhydrase in gastric mucosal protection with special reference to H+ back diffusion and concomitant metabolic acidosis induced by acetazolamide.
It is suggested that carbonic anhydrase is implicated not only in gastric acid secretion, but in mucosal protection. It was reported that acetazolamide induced gastric mucosal lesions. But acetazolamide also caused concomitant metabolic acidosis by inhibiting H+ secretion from renal tubules. We investigated whether concomitant metabolic acidosis is implicated in gastric mucosal lesions induced by acetazolamide in vivo. We also evaluated the effect of acetazolamide on gastric H+ back diffusion in vivo. Correction of metabolic acidosis with sodium bicarbonate had no effect on the degree of the gastric mucosal lesions. Acetazolamide caused no change in gastric H+ and Na+ flux. These results suggest that metabolic acidosis induced by acetazolamide is not implicated in gastric mucosal lesions. Carbonic anhydrase has no effect on H+ back diffusion but may be implicated in mucosal protection by the disposition of back diffused H+ into the gastric mucosa.


Teaching on the spiritual dimension in care to undergraduate nursing students: the content and teaching methods.
The study unit on 'The spiritual dimension in care'had a Judeo-Christian orientation. It was introduced to the Diploma nursing curriculum at the University of Malta in the academic year 2002-2003. The aim was to increase students' awareness about the essence of spirituality in care so as to enable them to implement holistic care. Spirituality may or may not incorporate religiosity. Thus, believers may have spiritual needs which may include religious needs whilst the atheists and agnostics may still have spiritual needs. While considering secularisation, the Christian culture of Malta was addressed in this study unit. This article describes the content structure of the study unit based on the ASSET model (Narayanasamy, A., 1999. ASSET: a model for actioning spirituality and spiritual care education and training in nursing. Nurse Education Today 19, 274-285) and outlines the various teaching methods used. Following feedback from the first and second cohort groups in 2003 and 2004, respectively, the reviewed study unit was delivered to the third cohort group of students (n=65) in Semester 2 in the academic year 2004-2005. Apart from the use of traditional teaching methods, such as lessons and a seminar, other methods were used constantly throughout the study unit, for example, self-reflection exercises, case-studies and small group discussions to enhance learning. Recommendations are proposed to review the content of this study unit and to introduce other teaching methods for effective learning.


Modulation of endothelial cell proliferation and capillary network formation by the ox-LDL component: 1-palmitoyl-2-archidonoyl-sn-glycero-3-phosphocholine (ox-PAPC).
Atherosclerotic plaque formation is often associated with pathological angiogenesis. Modified phospholipids, including oxidized lipoproteins such as LDL, are found to induce adhesion of the monocytes to the endothelial cells and to stimulate their chemotaxis. Effects of oxidized 1-palmitoyl-2-archidonoyl-sn-glycero-3-phosphocholine (ox-PAPC) mimic actions of minimally modified LDL in vivo. Interleukin-8 (IL-8) and interleukin-15 (IL-15) are known to induce both inflammation and angiogenesis. The goal of our study was to analyze a potential synergism between ox-PAPC and IL-15 in the in vitro model of angiogenesis carried out in the human endothelial cells (HUVECs). Increasing IL-15 concentrations led to formation of the tube-like structures in the matrigel 3D-model of angiogenesis (P < 0.05), in contrast to ox-PAPC that inhibited this process. HUVECs incubation with ox-PAPC led to reduced IL-15 gene basal expression (P = 0.033) along with parallel increase, however statistically insignificant, of basal gene expression of IL-8 (P = 0.086). Our findings point to the ox-PAPC opposite effects on the IL-8- and IL-15-mediated angiogenic responses that contribute to pathological angiogenesis induced by ox-LDL.


"Redo" fundoplications: satisfactory symptomatic outcomes with higher cost of care.
With ever greater numbers of fundoplications being undertaken, inevitably there will be an increase in the number of failed fundoplications, which will be considered for operative revision. This study was undertaken to compare the hospital costs of and outcomes after "redo" fundoplications to those of "first time" fundoplications. Patients undergoing anti-reflux surgery were prospectively followed. From 2000 to 2006, costs of and outcomes after 76 "redo" fundoplications were compared with 76 concurrent "first time" fundoplications. Prior to and after fundoplication, patients scored the frequency and severity of many symptoms, including dysphagia, chest pain, regurgitation, choking, and heartburn, using a Likert scale (0 = none/never, 10 = severe/always). The cost of care, including medical equipment, operating room expenses, and anesthesia was determined with standardization to 2006 cost and dollars. Data are presented as median (mean +/- standard deviation) where appropriate. Prior to "redo" fundoplications, patients reported significantly greater dysphagia frequency and severity scores and significantly greater chest pain severity. DeMeester scores for patients undergoing "redo" fundoplications versus "first time" fundoplications were similar (45 (62 +/- 55.6) versus 39 (44 +/- 27.7)). After fundoplication, dysphagia frequency and severity significantly improved for all patients. Length of stay was significantly longer for patients requiring "redo" fundoplications [3 d (6 +/- 8.5) versus 1 d (3 +/- 7.6)]. Hospital costs for patients undergoing "redo" fundoplications were significantly greater. Patients requiring re-operative fundoplications report more frequent and severe symptoms, especially of dysphagia, when compared with patients undergoing "first-time" fundoplications. Laparoscopic "redo" fundoplications are technically challenging, more expensive, and more morbid (e.g., longer hospital stays). However, symptoms of reflux and dysphagia are ameliorated with "redo" fundoplications and application of "redo" fundoplication is warranted.


Relationship between lead-induced biochemical and behavioral changes with trace element concentrations in rat brain.
Lead has an obvious potential to disturb learning ability, adaptive responses, and other aspects of behavior and even personality in those who may appear healthy according to conventional medical criteria. These disturbances are shown to be associated with alterations in ionic, cholinergic, and dopaminergic neurotransmission in the central nervous system (CNS). The present experiment was designed to study the neurotoxic consequences of lead exposure on neurotransmitters like dopamine, serotonin, norepinephrine, and activity of acetylcholinestrase, as well as some ions like zinc, calcium, sodium, and potassium. The locomotory functions along with cognitive functions and memory loss were also studied at various dose levels. Lead was administrated orally in doses of 10 mg/kg, 50 mg/kg, and 200 mg/kg for a period of 12 wk and the study was done at the end of exposure. A dose-dependent decrease in the concentration of sodium, potassium, and zinc was observed; there was increase in the concentrations of lead and calcium. The most significant change noted was the decrease in activity of the acetylcholinestrase and other neurotransmitters. Lead exposure affected the locomotor and cognitive functions. Short-term memory remained unchanged at all lead exposure doses.


Study on the interaction of nucleic acids with silver nanoparticles--Al(III) by resonance light scattering technique and its analytical application.
It is found that Al(III) can further enhance the intensity of resonance light scattering (RLS) of the silver nanoparticles (AgNPs) and nucleic acids system. Based on this, a novel method of determination of nucleic acids is proposed in this paper. Under optimum conditions, there are linear relationships between the enhancing extent of RLS and the concentration of nucleic acids in the range of 1.0 x 10(-9)-1.0 x 10(-7) g mL(-1), 1.0 x 10(-7)-2.0 x 10(-6)g mL(-1) for fish sperm DNA (fsDNA), 1.0 x 10(-9)-7.0 x 10(-8)g mL(-1) for calf thymus DNA (ctDNA) and 1.0 x 10(-9)-1.0 x 10(-7)g mL(-1) for yeast RNA (yRNA). The detection limits (S/N=3) of fsDNA, ctDNA and yRNA are 4.1 x 10(-10)g mL(-1), 4.0 x 10(-10)gmL(-1) and 4.5 x 10(-10)g mL(-1), respectively. The studies indicate that the RLS enhancement effect should be ascribed to the formation of AgNPs-Al(III)-DNA aggregations through electrostatic attraction and adsorption bridging action of Al(III). And the sensitivity and stability of the AgNPs-fsDNA system could be enhanced by Al(III).


Optimising diffusion weighted MRI for imaging metastatic and myeloma bone disease and assessing reproducibility.
To establish normal bone marrow values of apparent diffusion coefficient (ADC) over an age range, compare them with metastatic and myelomatous involvement, to establish reproducibility and to optimise b values. The ADCs of bone marrow in 7 volunteers (mean age 29.7 years), 34 volunteers (mean age 63.3 years) and 43 patients with metastatic and myelomatous involvement (mean age 65.5 years) were measured. In 9 volunteers diffusion weighted MRI was repeated within 7 days. b values were derived to optimise contrast between normal and pathological marrow. The mean ADC of bone marrow in younger volunteers was significantly higher than that of older volunteers. The coefficient of reproducibility was 14.8%. The ADC mean of metastatic and myeloma bone disease was 1054 + / -456 x 10⁻⁶mm²s⁻¹. An ADC threshold of 655 × 10(-6) mm(2)s(-1) separated normal and abnormal marrow with a sensitivity and specificity of 90% and 93% respectively. Contrast between normal and abnormal marrow was optimal at b = 1389 smm(-2). The reproducibility of ADC measurements in bone is equivalent to published data for soft tissue with a high sensitivity and specificity for separating abnormal from age matched normal bone marrow. A b value of around 1,400 smm(-2) is optimal for imaging bone marrow.


The proliferation rule of Microcystis aeruginosa under different initial pH conditions and its influence on the pH value of the environment.
This study investigated the characteristics of the proliferation process of Microcystis aeruginosa and its changes to environmental pH values under different initial pH values and different initial inoculation densities. The results showed that although the initial pH value or the initial inoculation density was different, the pH values of the culture systems fluctuated up and down throughout the proliferation of M. aeruginosa, both on a daily and hourly time scale, and then tended to stabilize around the same value of 10.0 at the end of proliferation. The optimal pH value for the proliferation of M. aeruginosa was 9.55. This study creatively proposes that the period when the environmental pH value starts to rise rapidly toward 9.0 could be selected as an early warning period for a cyanobacterial outbreak, and the environmental pH value could be adjusted to below 8.0 to delay the outbreak. These results provide a scientific basis for further understanding the mechanism of cyanobacterial blooms and formulating pH-based control strategies.


Molecular phylogeny and evolution of Caricaceae based on rDNA internal transcribed spacers and chloroplast sequence data.
This study focused on clarifying phylogenetic relationships and evolution within Caricaceae. Our phylogenetic analysis based on nucleotide sequences from the ITS of the ribosomal DNA and three chloroplast fragments (matK, trnL-trnF, and psbA-trnH) included 29 taxa belonging to five genera: the neotropical genera Carica, Vasconcellea, Jarilla, and Jacaratia and the equatorial African genus Cylicomorpha. Having a relatively low mutation rate, matK, and trnL-trnF were used for estimating relationships at the generic level, while intrageneric evolution within Vasconcellea was studied with the more variable ITS and psbA-trnH sequences. Gaps, coded as binary characters, were added to the sequence alignments before performing Maximum Parsimony and Maximum Likelihood analyses. Monophyly of Caricaceae as well as phylogenetic distance between Carica and Vasconcellea species, previously belonging to the same genus, and monophyly of the resurrected genus Vasconcellea were emphasized. Within Vasconcellea, the largest genus of this family, two well-confirmed evolutionary lineages could be discerned: (1) V.xheilbornii, V. weberbaueri, V. stipulata, and V. parviflora and (2) a clade holding all other taxa of the genus. Incongruence between nuclear ITS and chloroplast psbA-trnH datasets, shown to be significantly caused by some taxa of the genus Vasconcellea, indicated that reticulate events in this genus might be more frequent than previously suspected. Moreover, intra-individual ITS sequence heterogeneity provided further evidence for the hybrid or introgressed origin of different taxa and one presumed hybrid belonging to this genus.


Superinfective Hepatitis E Virus Infection Aggravates Hepatocytes Injury in Chronic Hepatitis B.
Hepatitis E virus (HEV) infection is a major cause of morbidity in endemic areas. Its consequences among chronic hepatitis B (CHB) patients have been under-reported. The aim of this study was to assess the impact of superinfective HEV infection (acute and past) on virological and clinical features of patients with CHB infection. Clinical, biochemical, virological and immunological data of 153 CHB patients including 98 with hepatitis B virus (HBV) monoinfection and 55 with HBV-HEV superinfection with both HEV and HBV infection was retrospectively investigated and analyzed in this study conducted in Wuhan, China. An overall anti-HEV IgG seroprevalence was found to be 35.9% in CHB patients. HBV-HEV superinfection patients showed significantly higher rate of complications (ascites, hepato-renal syndrome & encephalopathy) (all with P=0.04), cirrhosis (P<0.001) and acute-on-chronic liver failure (P<0.001) than HBV monoinfection patients. They also displayed elevated ALTs (P<0.001) and total serum bilirubin (P<0.001) with diminished albumin (P<0.001) and HBV viral load (P<0.001). Cytokines assay revealed increased expression of IL-6 (P=0.02), IL-10 (P=0.009) and TNF-α (P=0.003) in HBV-HEV superinfection patients compared to HBV monoinfection patients. Our study demonstrated that HEV superinfection in CHB patients was associated with progressive clinical manifestation, which is likely due to the enhanced expression of cytokines related with hepatocytes necrosis. HEV was also associated with repressed HBV replication, but the underlying mechanism requires further investigation.


Non-protein amino acids in plant defense against insect herbivores: representative cases and opportunities for further functional analysis.
Chemical defense against herbivores is of utmost importance for plants. Primary and secondary metabolites, including non-protein amino acids, have been implicated in plant defense against insect pests. High levels of non-protein amino acids have been identified in certain plant families, including legumes and grasses, where they have been associated with resistance to insect herbivory. Non-protein amino acids can have direct toxic effects via several mechanisms, including misincorporation into proteins, obstruction of primary metabolism, and mimicking and interfering with insect neurological processes. Additionally, certain non-protein amino acids allow nitrogen to be stored in a form that is metabolically inaccessible to herbivores and, in some cases, may act as signals for further plant defense responses. Specialized insect herbivores often possess specific mechanisms to avoid or detoxify non-protein amino acids from their host plants. Although hundreds of non-protein amino acids have been found in nature, biosynthetic pathways and defensive functions have been elucidated in only a few cases. Next-generation sequencing technologies and the development of additional plant and insect model species will facilitate further research on the production of non-protein amino acids, a widespread but relatively uninvestigated plant defense mechanism.


[Psoriasis-associated keratitis: case report].
Psoriasis is a common skin disease, which is associated with multiple extracutaneous manifestations. This article presents a case report of a rare ocular manifestation of psoriasis; psoriasis-associated keratitis. In a 37-year-old man we could show that systemic immunomodulatory therapy led to a rapid improvement of the ocular symptoms.


Chemically-induced cation permeability in red cell membrane vesicles. The sidedness of the response and the proteins involved.
Cation fluxes were measured in right-side-out and inside-out vesicles obtained from human red cells. Rubidium, which is spontaneously released at very slow rates, can be rapidly released from both types of vesicle by addition of valinomycin. P-Chloromercuriphenyl sulfonic acid (PCMBS) also increases the cation permeability of the vesicles with reversal to normal after addition of dithiothreitol. The effect of PCMBS is considerably larger and appears faster in the inside-out vesicles as compared to the right-side-out vesicles, the difference being greater at low temperatures. These data indicate that the SH groups responsible for the changes in cation permeability are more accessible from the inside face of the membrane. The response to PCMBS was not diminished after selective removal of extrinsic proteins by alkaline extraction, and/or after the membranes were exposed to proteolytic enzymes. The major polypeptide component remaining in vesicles after both treatments was a 17 000-dalton transmembrane fragment derived from band 3 which might, therefore, be responsible for the permeability response. Addition of Ca2+ to either right-side-out or inside-out vesicles, in the presence or absence of ionophore A23187, was without effect on monovalent cation permeability, indicating that the mechanism of Ca2+-induced K+ permeation was lost or inactivated during the preparation of the vesicles.


Cavitating lung lesion as a manifestation of inflammatory tumor (pseudotumor) of the lung: A case report and literature review.
Female, 60 FINAL DIAGNOSIS: Inflammatory pseudotumor of the lung Symptoms: Cough dry • fever - Clinical Procedure: - Specialty: - Rare disease. Inflammatory pseudotumor of the lung involves a benign, non-neoplastic lung lesion of unknown etiology. We present a case of a 60-year-old female smoker who had been under intermittent immunosuppressive medication for discoid lupus, who was admitted to hospital with fever of 39.5°C of 10-day duration, not responding to an oral cephalosporin. Chest CT examination showed a cavitating opacity in the upper zone of the left lung. It was not feasible to establish a diagnosis based on clinical and laboratory testing nor based on CT scanning and bronchoscopy. Thus, the patient underwent left thoracotomy and sphenoid resection of the lesion, which was sent for biopsy. The histopathologic features aided by immunohistochemical staining proved the lesion to be an inflammatory pseudotumor of the lung. The case is reported because of the extremely rare radiologic presentation of the development of a lung pseudotumor emerging as a cavitated lesion, which relapsed during the follow-up period while the patient was still under immunosuppressive medication.


Vitamin C depletion and pressure sores in elderly patients with femoral neck fracture.
To evaluate the contribution of specific nutritional deficiencies (as indicated by zinc; vitamin A, C, and E; albumin; and haemoglobin concentrations) to the risk of pressure sores. Observational cohort study. St James's University Hospital, Leeds. 21 elderly patients presenting consecutively to the orthopaedic unit with femoral neck fracture. Full thickness epidermal break over a pressure bearing surface. 10 patients (48%) developed a pressure sore during their hospital stay. Indices of zinc status and concentrations of albumin, haemoglobin, and vitamins A and E were similar in patients who developed a pressure sore and those who did not. Mean leucocyte vitamin C concentration, however, was 6.3 (SD 2.2) micrograms/10(8) cells in patients who developed a pressure sore as compared with 12.8 (4.6) micrograms/10(8) cells in patients who did not. Low concentrations of leucocyte vitamin C appear to be associated with subsequent development of pressure sores in elderly patients with femoral neck fractures.


Tentative immunohistochemical demonstration of melatonin in the rat pineal gland.
In the present study an attempt was made to demonstrate melatonin in the rat pineal gland by means of immunohistochemistry. The anitbody used was raised against 5-methoxy-N-acetyltryptophan which is chemically similar to melatonin. Specific fluorescence was demonstrable only in pineals from rats killed during the night, when melatonin formation is high. It was restricted to parenchymal cells lying in a marginal zone of the organ. These results are discussed in relation to a subdivision of the pineal parenchyma into cortical and medullary areas.


Adrenal cortical adenoma: current update, imaging features, atypical findings, and mimics.
Adrenal adenoma is the most common adrenal lesion. Due to its wide prevalence, adrenal adenomas may demonstrate various imaging features. Thus, it is important to identify typical and atypical imaging features of adrenal adenomas and to be able to differentiate atypical adrenal adenomas from potentially malignant lesions. In this article, we will discuss the diagnostic approach, typical and atypical imaging features of adrenal adenomas, as well as other lesions that mimic adrenal adenomas.


Inhibitory activity of quercetin and its metabolite on lipopolysaccharide-induced activation of macrophage U937 cells.
The potential of quercetin and its metabolite 3-O-methyl quercetin in inhibiting lipopolysaccharide (LPS)-mediated activation of macrophage U937 cells was investigated. Cells were pre-incubated for different periods with 100 ng/mL phorbol myristate acetate (PMA), and later with LPS and quercetin or 3-O-methyl quercetin (30 microM). Later, the supernatant of each cell culture was assessed for catalase activity, nitric oxide, and the production of tumour necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and interleukin 1 (IL-1). The results showed that when the cells were incubated with LPS, there were elevations in the levels of all the markers over the cells not incubated with LPS (P < 0.05). For the cells that were incubated with LPS, there were significant differences between the various cells when they were pre-incubated with PMA for various periods (P < 0.05). However, greatest production of the markers was attained when the cells were pre-treated with PMA for 48 h. Both quercetin and 3-O-methyl quercetin (at 30 mM) reduced the levels of all the markers with 3-O-methyl quercetin possessing more inhibitory potential (P < 0.05). This suggests that the flavonoids possessed significant immunomodulatory activities which depend on methylation especially at position 3.


Using a neural network to identify potential HLA-DR1 binding sites within proteins.
The presentation by antigen-presenting cells of immunodominant peptide segments in association with major histocompatibility complex (MHC) encoded proteins is fundamental to the efficacy of a specific immune response. One approach used to identify immunodominant segments within proteins has involved the development of predictive algorithms which utilize amino acid sequence data to identify structural characteristics or motifs associated with in vivo antigenicity. The parallel-computing technique termed 'neural networking' has recently been shown to be remarkably efficient at addressing the problem of pattern recognition and can be applied to predict protein secondary structure attributes directly from amino acid sequence data. In order to examine the potential of a neural network to generalize peptide structural features related to binding within class II MHC-encoded proteins, we have trained a neural network to determine whether or not any given amino acid of a protein is part of a peptide segment capable of binding to HLA-DR1. We report that a neural network trained on a data base consisting of peptide segments known to bind to HLA-DR1 is able to generalize features relating to HLA-DR1-binding capacity (r = 0.17 and p = 0.0001).


Current Role of Blood and Urine Biomarkers in the Clinical Care of Adults with Congenital Heart Disease.
There is an increasing number of adult patients with congenital heart disease (CHD). While several biomarkers have been validated and integrated into general cardiology clinical practice, these tests are often applied to adults with CHD in the absence of disease-specific validation. Although these patients are often grouped into a single population, there is heterogeneous pathophysiology, variable disease chronicity, extensive multisystem involvement, and a low event rate relative to acquired heart disease. These stand as challenges to systematic investigation and clinical application of biomarkers for adults with CHD. This paper reviews recent studies investigating the use of biomarkers in this population, with emphasis on biomarkers applied in clinical adult CHD care. A handful of biomarkers have been integrated into adult CHD practice, such as iron studies in cyanotic heart disease and stool alpha-1 antitrypsin for diagnosis of protein losing enteropathy in the Fontan circulation. Use of kidney and liver tests has been studied in prognostication of adult CHD patients. A few other biomarkers like natriuretic peptides and troponins seem likely to provide useful information in other ACHD situations based on limited disease-specific data and extrapolation from acquired heart disease. More research is needed to support the robust validity of most existing clinical biomarkers in adult congenital cardiology practice. Until data from larger, prospectively enrolled cohorts are available, clinical use of biomarkers in these patients will require careful interpretation with attention to underlying pathophysiology, as well as detailed understanding of potential pitfalls of specific assays and clinical contexts.


Transdermal fentanyl as treatment for chronic low back pain.
Management of chronic low back pain often includes oral opioid use. The effectiveness of therapy is dependent upon compliance, which in turn is dependent upon response, side effects, access, and convenience. Our hypothesis was that a transdermal fentanyl system would provide more effective pain management than oral opioids. Fifty patients with chronic low back pain were examined. After litration to levels corresponding to current oral opioid use, each patient was maintained on transdermal fentanyl for one month. Oral opioid therapy was then resumed. Their experience was assessed with the a visual analogue scale for pain intensity, a numerical pain score, the Oswestry disability questionnaire, the pain disability index, and the Verran Snyder-Halpern sleep scale. Significant improvement in pain relief and disability was found with transdermal fentanyl compared with oral opioids. Mild opioid side effects were common, but easily controlled. Use of transdermal fentanyl is an effective alternative to oral opioids for managing chronic low back pain.