Intraoperative Doppler spectrum analysis of blood flow in the internal mammary artery used for myocardial revascularization.
Intraoperative Doppler-derived measurements of blood flow velocity were used to characterize the hemodynamics in 6 internal mammary artery grafts before and after anastomosis to the left anterior descending artery. Pulsed Doppler spectrum analysis demonstrated a change from a systolic to a predominantly diastolic flow pattern. The presented technique is a valuable aid to differentiate intraoperatively between normal and low flow states in the internal mammary artery. In addition, this study serve as a pilot study to investigate the clinical applicability of Doppler spectrum analysis in the functional assessment of the internal mammary artery in the pre- and postoperative stages of myocardial revascularization.


[The technical aspects of liver resection surgery: the authors' experience].
Based on their personal experience in hepatic resective surgery the authors dwell upon details of surgical technique which, well combined and sustained by advanced technological supports (ultrasonic dissector, laser-argon clotter, intraoperative echography), allow to perform wide parenchymal resections sheltered from dangerous complications. The safety achieved in such a surgery--now routinely performed--derives not only from improved diagnostic techniques (US, CT, MNR, angiography) and advances in anaesthesia-reanimation but, above all, from precise knowledge of organon segmental anatomy and close vascular correlations between the two hepatic hemisystems.


Composition of a protein-like fluorophore of dissolved organic matter in coastal wetland and estuarine ecosystems.
This study demonstrates the compositional heterogeneity of a protein-like fluorescence emission signal (T-peak; excitation/emission maximum at 280/325 nm) of dissolved organic matter (DOM) samples collected from subtropical river and estuarine environments. Natural water samples were collected from the Florida Coastal Everglades ecosystem. The samples were ultrafiltered and excitation-emission fluorescence matrices were obtained. The T-peak intensity correlated positively with N concentration of the ultrafiltered DOM solution (UDON), although, the low correlation coefficient (r(2)=0.140, p<0.05) suggested the coexistence of proteins with other classes of compounds in the T-peak. As such, the T-peak was unbundled on size exclusion chromatography. The elution curves showed that the T-peak was composed of two compounds with distinct molecular weights (MW) with nominal MWs of about >5 x 10(4) (T(1)) and approximately 7.6 x 10(3) (T(2)) and with varying relative abundance among samples. The T(1)-peak intensity correlated strongly with [UDON] (r(2)=0.516, p<0.001), while T(2)-peak did not, which suggested that the T-peak is composed of a mixture of compounds with different chemical structures and ecological roles, namely proteinaceous materials and presumably phenolic moieties in humic-like substances. Natural source of the latter may include polyphenols leached from senescent plant materials, which are important precursors of humic substances. This idea is supported by the fact that polyphenols, such as gallic acid, an important constituent of hydrolysable tannins, and condensed tannins extracted from red mangrove (Rhizophora mangle) leaves exhibited the fluorescence peak in the close vicinity of the T-peak (260/346 and 275/313 nm, respectively). Based on this study the application of the T-peak as a proxy for [DON] in natural waters may have limitations in coastal zones with significant terrestrial DOM input.


Food-grade titanium dioxide decreases hematocrit and hemoglobin and increases compulsive-like behavior in male mice.
Food-grade titanium dioxide (E171) is widely used as a food additive, and it is known that after oral consumption, E171 is translocated into the bloodstream reaching the highest titanium level at 6 h. E171 is accumulated in some organs triggering toxicity, but the effects on the blood parameters after oral consumption have been less studied. Recently, evidence shows that oral exposure to E171 induces behavioral signs of anxiety and depression. The relation between blood alterations and psychiatric disorders has been previously demonstrated. However, the oral exposure to E171 effects on alterations in blood parameters and effects linked to alterations in animal behavior has not been explored. In this short communication, we aimed to investigate the effects of E171 on specific blood parameters (hematocrit, hemoglobin, number of erythrocytes, and leukocytes) and anxiety and compulsive-like behavior in males and females orally exposed to ~5 mg/kg for 4 weeks. The results showed that E171 decreased hematocrit and hemoglobin in male but not in female mice while leukocyte and erythrocyte count remained unaltered. Oral consumption of E171 decreased the levels of anxiety-like behavior in females but not in male mice, while compulsive-like behavior was increased in both male and female mice.


The use of technology to address patterns of risk among teenage drivers.
The crash risk of teens is high, with fatal crash rates of teen drivers higher than any other age group. New approaches to reduce teen traffic fatalities are clearly needed. A possible approach to reduce the incidence of teen driver crashes and fatalities is through the use of vehicle-based intelligent driver support systems. To be most effective, the system should address the behaviors associated with an overwhelming number of teen fatal crashes: speed, low seatbelt use, and alcohol impairment. In-vehicle technology also offers an opportunity to address the issue of inexperience through enforcement of certain Graduated Driver's License provisions. To fully understand the capability of such technologies, there should be a concerted effort to further their development, and human factors testing should take place to understand their effects on the driver. If successfully implemented, a Teen Driver Support System (TDSS), such as the one described here, could significantly decrease the number of teens killed in traffic crashes.


Understanding the experience of sleep disturbance in psoriasis: a qualitative exploration using the Common-Sense Model of Self-Regulation.
Psoriasis is associated with significant morbidity, which negatively impacts upon quality of life. Sleep disturbance is reported to be common in patients with psoriasis and is associated with physical and psychological variables, although there is little published work in this area. Understanding sleep and the factors involved in its disturbance in psoriasis is a potentially important clinical area given the role of sleep in health and disease processes. To explore the experience of sleep and sleep disturbance in psoriasis using the Common-Sense Model of Self-Regulation (CS-SRM). Semistructured interviews were conducted with adults diagnosed with psoriasis. Interview questions were informed by the CS-SRM and previous research. Framework analysis was applied, including coding data into the CS-SRM dimensions and allowing additional inductive themes to emerge. Seventeen people with psoriasis (nine women, eight men; aged 19-86 years) were interviewed about sleep and sleep disturbance. Seven themes emerged, with six accounted for by the CS-SRM: characteristics of sleep disturbance, change in sleep patterns, thoughts about and symptoms of disease disturbing sleep, impact of poor sleep on daily life, attempts to improve sleep, a daily battle for control and a seventh relating to metacognitive processes. A reciprocal relationship between sleep and psoriasis was evident across themes with interactions between key sleep-related thoughts, emotions and behaviours. This study showed that sleep disturbance is a persistent concern for people with psoriasis; it has a 24-h impact, and interacts with the psychological and physical aspects of psoriasis. The distress and frustration felt when managing sleep disturbance perpetuated problematic sleep. Addressing this with currently available sleep treatments may therefore confer sleep and psoriasis-related benefits for people living with this condition.


Efficacy of Improvised Topical Zinc (1%) Ora-Base on Oral Mucositis during Cancer Chemo-Radiation-A Randomized Study.
Oral mucositis refers to erythematous and ulcerative lesions of oral mucosa during chemo/radiotherapy. Treatment modalities were directed towards reduction in severity of oral mucositis. Zinc plays an important role to retard oxidative processes and is considered as the critical component in wound healing. To compare the efficacy of zinc alone with improvised zinc preparation in reducing the severity of oral mucositis. Improvised zinc was a combination of zinc oxide, amla, tulsi and curcumin at 1% therapeutic concentrations. Seventy-five subjects undergoing chemo/radiotherapy were randomly divided into three groups: Group A (25 subjects) had received topical 5% zinc oxide paste trice daily application after food for entire treatment period, initiated 2 d prior to radiotherapy. Group B (25) received improvised zinc preparations (1%) and instructed to apply same as group A. Group C (25) received standard treatment offered by cancer hospital. All the groups were assessed for oral mucositis using WHO grading system at 7th, 14th, 21st, 28th, 35th day by the oncologist and results were tabulated for statistical analysis. Severity of oral mucositis reduced in zinc and improvised zinc group (p=0.096) when compared with controls with significant p value (0.037). Comparison of improvised zinc preparation (1%) group with only zinc group revealed that severity of overall mucositis though was not significant, was less in improvised zinc group with p value (0.029, 0.013) at 28 and 35 d respectively. Improvised zinc administration during radiation therapy was beneficial in reduction of oral mucositis during cancer treatment.


New developments in peritoneal fibroblast biology: implications for inflammation and fibrosis in peritoneal dialysis.
Uraemia and long-term peritoneal dialysis (PD) can lead to fibrotic thickening of the peritoneal membrane, which may limit its dialytic function. Peritoneal fibrosis is associated with the appearance of myofibroblasts and expansion of extracellular matrix. The extent of contribution of resident peritoneal fibroblasts to these changes is a matter of debate. Recent studies point to a significant heterogeneity and complexity of the peritoneal fibroblast population. Here, we review recent developments in peritoneal fibroblast biology and summarize the current knowledge on the involvement of peritoneal fibroblasts in peritoneal inflammation and fibrosis.


Direct Analysis of Samples of Various Origin and Composition Using Specific Types of Mass Spectrometry.
One of the major sources of error that occur during chemical analysis utilizing the more conventional and established analytical techniques is the possibility of losing part of the analytes during the sample preparation stage. Unfortunately, this sample preparation stage is required to improve analytical sensitivity and precision. Direct techniques have helped to shorten or even bypass the sample preparation stage; and in this review, we comment of some of the new direct techniques that are mass-spectrometry based. The study presents information about the measurement techniques using mass spectrometry, which allow direct sample analysis, without sample preparation or limiting some pre-concentration steps. MALDI - MS, PTR - MS, SIFT - MS, DESI - MS techniques are discussed. These solutions have numerous applications in different fields of human activity due to their interesting properties. The advantages and disadvantages of these techniques are presented. The trends in development of direct analysis using the aforementioned techniques are also presented.


Allergic reactions to inhalant glucocorticosteroids: a hot topic for pneumologists and allergologists.
Allergic contact dermatitis to topical glucocorticosteroids (GCS) is a delayed type cell-mediated hypersensitivity reaction; it is frequently observed in dermatological and allergological practice, although its incidence is likely underestimated. By contrast, allergic contact sensitization to inhalant GCS is virtually unknown to most pneumologists. Here, we review some cases of adverse reactions to inhalant GCS in terms of pathogenetic mechanisms, risk factors, epidemiology, and allergic cross-sensitivity. In fact, this particular form of sensitization to drugs that have a wide spectrum of use in pneumological practice deserves more attention than in the past.


Post-Discharge Worsening Renal Function in Patients with Type 2 Diabetes and Recent Acute Coronary Syndrome.
Worsening renal function during hospitalization for an acute coronary syndrome is strongly predictive of in-hospital and long-term outcome. However, the role of post-discharge worsening renal function has never been investigated in this setting. We considered the placebo cohort of the AleCardio trial comparing aleglitazar with standard medical therapy among patients with type 2 diabetes mellitus and a recent acute coronary syndrome. Patients who had died or had been admitted to hospital for heart failure before the 6-month follow-up, as well as patients without complete renal function data, were excluded, leaving 2776 patients for the analysis. Worsening renal function was defined as a >20% reduction in estimated glomerular filtration rate from discharge to 6 months, or progression to macroalbuminuria. The Cox regression analysis was used to determine the prognostic impact of 6-month renal deterioration on the composite of all-cause death and hospitalization for heart failure. Worsening renal function occurred in 204 patients (7.34%). At a median follow-up of 2 years the estimated rates of death and hospitalization for heart failure per 100 person-years were 3.45 (95% confidence interval [CI], 2.46-6.36) for those with worsening renal function, versus 1.43 (95% CI, 1.14-1.79) for patients with stable renal function. At the adjusted analysis worsening renal function was associated with the composite endpoint (hazard ratio 2.65; 95% CI, 1.57-4.49; P <.001). Post-discharge worsening renal function is not infrequent among patients with type 2 diabetes and acute coronary syndromes with normal or mildly depressed renal function, and is a strong predictor of adverse cardiovascular events.


Apparent continuity between the messenger transport organizer and late RNA localization pathways during oogenesis in Xenopus.
The localization of RNAs at the vegetal cortex in Xenopus oocytes is a complex process, involving at least two different pathways. The early, or messenger transport organizer (METRO), pathway, localizes RNAs such as Xlsirts, Xcat2 and Xwnt11 during stages 1 and 2 of oogenesis, while the late pathway localizes RNAs such as Vg1 during stages 2-4. We demonstrate that the onset of Vg1 localization is characterized by its microtubule-independent binding to a subdomain of the endoplasmic reticulum (ER). The formation of this unique ER structure is intimately associated with the movement of the mitochondrial cloud toward the vegetal cortex. In addition, we demonstrate that the mitochondrial cloud contains a gamma-tubulin-positive structure that may function as a microtubule organizing center for establishing microtubule tracks for Vg1 localization. These data, support, although they do not prove, a model in which the development of the late pathway machinery relies upon the prior functioning of the early pathway.


Microhabitat partitioning between sympatric intertidal fish species highlights the importance of sediment composition in gravel beach conservation.
Gravel beaches in the Mediterranean ecoregion represent an economically important and unique habitat type. Yet, burgeoning tourism, intensive coastal development and artificial nourishment of beaches may jeopardize their ecological communities. To date, species that reside on gravel beaches and the consequences of beach alterations are poorly understood, which hampers the development of a sustainable coastal tourism industry along the region's shorelines. Using a simple collection method based on dredging buckets through the intertidal section of beaches, we quantified the microhabitat association of two sympatric clingfish species in the genus Gouania at seven natural and an artificial gravel beach based on sediment characteristics. We hypothesized that slender (G. pigra) and stout (G. adriatica) morphotypes would partition interstitial niche space based on sediment size, which may affect the vulnerability of the species to changes in gravel beach composition due to coastal development. We detected substantial differences in gravel composition within and among the sampled beaches which suggests scope for microhabitat partitioning in Gouania. Indeed, we found significant relationships between species identity and the presence/absence and abundance of individuals in hauls based on their positioning on PC1. Our results suggest that modifications of gravel beaches through coastal development, including beach nourishment, intensifying coastal erosion, or artificial beach creation, may have detrimental consequences for the two species if sediment types or sizes are altered. We posit that, given the simplicity and efficacy of our sampling method and the sensitivity of Gouania species to prevailing gravel composition, the genus could serve as an important indicator for gravel beach management in the Mediterranean ecoregion.


Antacid maintenance therapy in the prevention of duodenal ulcer relapse.
The effectiveness of antacid maintenance therapy in preventing duodenal ulcer (DU) relapse was investigated. Two hundred and fifty one asymptomatic patients with healed DU were stratified into smokers and non-smokers and randomised to receive for one year either placebo, or Maalox TC three tablets (81 mmol) at bedtime (hs), or Maalox TC three tablets in the morning plus three tablets at bedtime (bd) (162 mmol), or cimetidine 400 mg at bedtime. A double dummy technique was used to render the study double blind. In 176 patients evaluable for efficacy, the cumulative relapse at one year was: placebo 57%; Maalox TC hs 39%; Maalox TC bd 23%; cimetidine 25%. Maalox TC bd and cimetidine were equally effective and superior to placebo (p less than 0.01) and bedtime Maalox TC (p less than 0.04). The benefit of treatment was significant for the overall sample and for the subgroup of smokers. The results for the non-smokers also supported efficacy for these two treatments but, perhaps because of small sample sizes, these comparisons were not significant. All 251 patients were assessed for safety. Approximately half the patients in each treatment group had adverse events, leading to withdrawal in three, seven, 12, and four patients on placebo, Maalox hs, Maalox bd, and cimetidine respectively. Diarrhoea occurred in 12 patients in Maalox TC bd and eight in each other group. Serum magnesium concentrations were unchanged; aluminium concentrations were higher than baseline at six and 12 months in both antacid groups and at 12 months in the cimetidine group but the differences were not significant. Maalox TC three tablets bd are as effective as cimetidine 400 mg at bedtime in reducing DU relapse and both are superior to placebo.


Laser-direct-drive fusion target design with a high-Z gradient-density pusher shell.
Laser-direct-drive fusion target designs with solid deuterium-tritium (DT) fuel, a high-Z gradient-density pusher shell (GDPS), and a Au-coated foam layer have been investigated through both 1D and 2D radiation-hydrodynamic simulations. Compared with conventional low-Z ablators and DT-push-on-DT targets, these GDPS targets possess certain advantages of being instability-resistant implosions that can be high adiabat (α≥8) and low hot-spot and pusher-shell convergence (CR_{hs}≈22 and CR_{PS}≈17), and have a low implosion velocity (v_{imp}<3×10^{7}cm/s). Using symmetric drive with laser energies of 1.9 to 2.5MJ, 1D lilac simulations of these GDPS implosions can result in neutron yields corresponding to ≳50-MJ energy, even with reduced laser absorption due to the cross-beam energy transfer (CBET) effect. Two-dimensional draco simulations show that these GDPS targets can still ignite and deliver neutron yields from 4 to ∼10MJ even if CBET is present, while traditional DT-push-on-DT targets normally fail due to the CBET-induced reduction of ablation pressure. If CBET is mitigated, these GDPS targets are expected to produce neutron yields of >20MJ at a driven laser energy of ∼2MJ. The key factors behind the robust ignition and moderate energy gain of such GDPS implosions are as follows: (1) The high initial density of the high-Z pusher shell can be placed at a very high adiabat while the DT fuel is maintained at a relatively low-entropy state; therefore, such implosions can still provide enough compression ρR>1g/cm^{2} for sufficient confinement; (2) the high-Z layer significantly reduces heat-conduction loss from the hot spot since thermal conductivity scales as ∼1/Z; and (3) possible radiation trapping may offer an additional advantage for reducing energy loss from such high-Z targets.


[Serial changes in mitral regurgitation after mitral valve repair with artificial chordae tendineae: assessment by transesophageal echocardiography].
Serial changes in mitral regurgitation after anterior mitral valve repair were examined by transesophageal echocardiography (TEE) in 34 of 86 consecutive patients with pure mitral regurgitation who underwent anterior mitral valve repair from 1987 to 1996. The patients were divided into two groups: 15 patients undergoing mitral repair with polytetrafluoroethylene (PTFE; PTFE group) and 19 undergoing conventional mitral repair without PTFE (non-PTFE group). The PTFE group included 11 men and 4 women with a mean age of 52.1 years. They were followed for mean 22.8 +/- 12.0 months. The non-PTFE group included 12 men and 7 women with a mean age of 53.9 years. They were followed for mean 33.9 +/- 20.4 months. Mitral regurgitation jet areas were observed at the time of operation, 1 month after mitral valve repair, and in the late follow-up period. Regurgitation jet areas were 0.7 +/- 0.7, 1.1 +/- 0.9 and 2.5 +/- 2.1 cm2 in the PTFE group, and 1.1 +/- 1.3, 2.4 +/- 1.7, 4.7 +/- 2.9 cm2 in the non-PTFE group. The jet area was significantly smaller in the PTFE group than in the non-PTFE group at 1 month after operation and in the late follow-up period. Moderate to severe regurgitation was observed in two patients (13.3%) in the PTFE group, and eight patients (42.1%) in the non-PTFE group. Mitral valve repair with PTFE showed better results than conventional mitral valve repair without PTFE during the mean follow-up period of 23 months.


The role of extracellular matrix in human astrocytoma migration and proliferation studied in a microliter scale assay.
Ligands in the extracellular matrix (ECM) are known to mediate migration of normal as well as tumor cells via adhesion molecules such as the integrin receptor family. We develop a microliter scale (15-20 microliters total volume) monolayer migration assay to investigate the ability of astrocytoma cells to disperse on surfaces coated with purified human ECM protein ligands. In this system the rate of radial migration of the cell population was constant over time. For human astrocytoma cell lines U-251 and SF-767, laminin and collagen type IV supported a migratory phenotype; fibronectin and vitronectin only minimally supported migration. The different ECM proteins also influenced growth rate: cells on laminin and collagen had a protracted lag phase. Furthermore, migrating cells seeded on laminin or collagen showed a lower labeling index than did stationary cells in the central, crowded region on the same substrate. This micro-scale migration assay should enable detailed molecular and biochemical studies of the determinants of migration.


Macular ganglion cell-inner plexiform layer thinning as a biomarker of disability progression in relapsing multiple sclerosis.
Macular ganglion cell-inner plexiform layer (mGCIPL) is an emerging biomarker of neuroaxonal degeneration in multiple sclerosis (MS). We aimed to determine cut-off values of mGCIPL thinning for discriminating between progressing and stable patients in relapsing multiple sclerosis (RMS). This is a 3-year prospective longitudinal study on 183 RMS patients with annual optical coherence tomography. Best possible cut-off values of baseline mGCIPL and annual loss of macular ganglion cell-inner plexiform layer (aLmGCIPL) for discriminating clinically progressing (physical progression or cognitive decline) from stable patients were defined by receiver operating characteristics analysis and tested using multivariate regression models. Baseline mGCIPL thickness <77 µm was associated with an increased risk (hazard ratio: 2.7, 95% confidence interval (CI): 1.5-4.7, p < 0.001) of disability progression. An aLmGCIPL cut-off ⩾1 µm accurately identified clinically progressing patients (87% sensitivity at 90% specificity) and was a strong predictor of clinical progression (odds ratio: 18.3, 95% CI: 8.8-50.3). We present evidence that cross-sectionally measured mGCIPL thickness and annualized thinning rates of mGCIPL are able to identify clinically progressing RMS with high accuracy.


International Differences in the Frequency of Chronic Obstructive Pulmonary Disease Exacerbations Reported in Three Clinical Trials.
Rationale: Exacerbations of chronic obstructive pulmonary disease (COPD) are an important endpoint in multinational clinical treatment trials, but the observed event rate is often lower than anticipated and appears to vary between countries. Objectives: We investigated whether systematic differences in national exacerbation rates might explain this observed variation. Methods: We reviewed data from three large multicenter international randomized trials conducted over an 18-year period with different designs and clinical severities of COPD, comparing bronchodilator and/or inhaled corticosteroids with bronchodilators alone and/or placebo. Exacerbations were defined by antibiotic and/or oral corticosteroid use (moderate) or need for hospitalization (severe). We calculated crude exacerbation rates in the 30 countries contributing 30 or more patients to at least two trials. We grouped data by exacerbation rate based on their first study contribution. Measurements and Main Results: For the 29,756 patients in 41 countries analyzed, the mean exacerbation rate was two- to threefold different between the highest and lowest tertiles of the recruiting nations. These differences were not explained by demographic features, study protocol, or reported exacerbation history at enrollment. Of the 18 countries contributing to all trials, half of those in the highest and half in the lowest tertiles of exacerbation history remained in these groups across trials. Severe exacerbations showed a different rank order internationally. Conclusions: Countries contributing to COPD trials differ consistently in their reporting of healthcare-defined exacerbations. These differences help explain why large studies have been needed to show differences between treatments that decrease exacerbation risk.


Acute tracheal compression in a large breed dog due to a dorsal tracheal membrane abscess.
To describe a case of acute tracheal compression due to a dorsal tracheal membrane abscess in a dog. A 3-year-old intact male Bluetick Coonhound presented for evaluation of 36 hours of marked inspiratory dyspnea and stridor. A radiographic diagnosis of tracheal collapse was made on thoracic radiographs, which was confirmed to be static compression by tracheoscopy. Dorsal extraluminal tracheal compression from a fluid filled structure adjacent to the trachea was suspected based on ultrasonography. Endoscopic-guided transtracheal fine needle aspiration yielded septic suppurative inflammation. At surgery an abscess in the dorsal tracheal membrane was identified, lanced, and lavaged, which resulted in restoration of normal tracheal diameter. The dog developed bilateral pneumothorax, which was treated medically by thoracostomy tube placement and manual evacuation of the accumulated air. Postoperative radiographs also revealed evidence of pneumomediastinum. Pneumothorax and pneumomediastinum likely occurred secondary to the surgical approach, worsened by positive pressure ventilation. Cultures of the abscess isolated a nonhemolytic Streptococcus species but with no evidence of anaerobic bacteria. The dog made a full functional recovery. Tracheal compression is a rare diagnosis in dogs. To the authors' knowledge, this represents the first report of an abscess in the dorsal tracheal membrane, diagnosed by endoscopic-guided transtracheal fine needle aspiration, causing clinically relevant acute tracheal obstruction.


Sources of social support as predictors of health, psychological well-being and life satisfaction among Dutch male and female dual-earners.
We examined whether gender differences in health, psychological well-being, and life satisfaction, can be explained by effects of work-related and nonwork-related sources of social support. The sample consisted of 459 men and women from dual earner families. Men report better health and psychological well-being than women, whereas women report higher life satisfaction than men. Contrary to our expectations, women receive more social support from colleagues than men, while men and women equally receive support from their supervisor. As for the nonwork-related sources of social support, men receive more social support from their spouse, while women receive more social support from relatives and friends. No gender differences exist in the effects of social support. Although men and women differ with respect to the social support they receive from different sources, these differences cannot explain gender differences in health, psychological well-being and life satisfaction.


Proinflammatory polarization of monocytes by particulate air pollutants is mediated by induction of trained immunity in pediatric asthma.
The impact of exposure to air pollutants, such as fine particulate matter (PM), on the immune system and its consequences on pediatric asthma, are not well understood. We investigated whether ambient levels of fine PM with aerodynamic diameter ≤2.5 microns (PM2.5 ) are associated with alterations in circulating monocytes in children with or without asthma. Monocyte phenotyping was performed by cytometry time-of-flight (CyTOF). Cytokines were measured using cytometric bead array and Luminex assay. ChIP-Seq was utilized to address histone modifications in monocytes. Increased exposure to ambient PM2.5 was linked to specific monocyte subtypes, particularly in children with asthma. Mechanistically, we hypothesized that innate trained immunity is evoked by a primary exposure to fine PM and accounts for an enhanced inflammatory response after secondary stimulation in vitro. We determined that the trained immunity was induced in circulating monocytes by fine particulate pollutants, and it was characterized by the upregulation of proinflammatory mediators, such as TNF, IL-6, and IL-8, upon stimulation with house dust mite or lipopolysaccharide. This phenotype was epigenetically controlled by enhanced H3K27ac marks in circulating monocytes. The specific alterations of monocytes after ambient pollution exposure suggest a possible prognostic immune signature for pediatric asthma, and pollution-induced trained immunity may provide a potential therapeutic target for asthmatic children living in areas with increased air pollution.


Fibre types in skeletal muscle: a personal account.
Muscle performance is in part dictated by muscle fibre composition and a precise understanding of the genetic and acquired factors that determine the fibre type profile is important in sport science, but is also relevant to neuromuscular diseases and to metabolic diseases, such as type 2 diabetes. The dissection of the signalling pathways that determine or modulate the muscle fibre phenotype has thus potential clinical significance. In this brief review, I examine the evolution of the notion of muscle fibre types, discuss some aspects related to species differences, point at problems in the interpretation of transgenic and knockout models and show how in vivo transfection can be used to identify regulatory factors involved in fibre type diversification, focusing on the calcineurin-nuclear factor of activated T cells (NFAT) pathway.


Air-directed attachment of coccoid bacteria to the surface of superhydrophobic lotus-like titanium.
Superhydrophobic titanium surfaces fabricated by femtosecond laser ablation to mimic the structure of lotus leaves were assessed for their ability to retain coccoid bacteria. Staphylococcus aureus CIP 65.8T, S. aureus ATCC 25923, S. epidermidis ATCC 14990T and Planococcus maritimus KMM 3738 were retained by the surface, to varying degrees. However, each strain was found to preferentially attach to the crevices located between the microscale surface features. The upper regions of the microscale features remained essentially cell-free. It was hypothesised that air entrapped by the topographical features inhibited contact between the cells and the titanium substratum. Synchrotron SAXS revealed that even after immersion for 50 min, nano-sized air bubbles covered 45% of the titanium surface. After 1 h the number of cells of S. aureus CIP 65.8T attached to the lotus-like titanium increased to 1.27×10(5) mm(-2), coinciding with the replacement of trapped air by the incubation medium.


Idiopathic pulmonary artery aneurysm.
Pulmonary artery aneurysm (PAA) is an uncommon lesion, which may be associated with different etiologies including congenital cardiovascular diseases, systemic vasculitis, connective tissue diseases, infections, and trauma. Idiopathic PAA is sporadically diagnosed by exclusion of concomitant major pathology. We report a case of a 56-year-old female with an idiopathic pulmonary artery dilatation identified fortuitously by echocardiography and confirmed by contrast-enhanced computed tomography. Neither significant pulmonary valve dysfunction nor pulmonary hypertension and other cardiac abnormalities which might contribute to the PAA development were found. Here, we describe echocardiographic and computed tomography findings and review the literature on PAA management.


Functional activation of Nedd2/ICH-1 (caspase-2) is an early process in apoptosis.
The ICE/CED-3 family of proteases (caspases) play a central role in the execution phase of apoptosis. These proteases are synthesised as precursor molecules that require processing at specific aspartate residues to produce the two subunits that comprise the active enzyme. The activation of some of these proteases has been shown to occur during apoptosis. Here we show that Nedd2/ICH-1 (caspase-2) is activated during apoptosis induced by a variety of apoptotic stimuli. This activation occurs very early upon treatment of cells with apoptotic agents and appears to precede the activation of CPP32 (caspase-3). The activation of Nedd2 was not seen in cells that are resistant to apoptosis. These observations suggest that Nedd2 is an early effector in the pathway leading to cell death. Our observations also lend weight to the hypothesis that a group of caspases containing long prodomains are the first to be activated in response to apoptotic signals and that they lie upstream of a second class of caspases such as CPP32 containing short or no prodomains.


Opposing actions of hippocampus TNFα receptors on limbic seizure susceptibility.
Resected epileptic tissues exhibit elements of chronic neuroinflammation that include elevated TNFα and increased TNFα receptor activation, but the seizure related consequences of chronic TNFα expression remain unknown. Twenty four hours after acute limbic seizures the rat hippocampus exhibited a rapid upregulation of TNFR1, but a simultaneous downregulation of TNFR2. These limbic seizures also evoked significant increases in measures of neuroinflammation and caused significant neuronal cell death in both the hilus and CA3 of the hippocampus. In order to mimic a state of chronic TNFα exposure, adeno-associated viral vectors were packaged with a TNF receptor 1 (TNFR1) specific agonist, human TNFα, or a TNF receptor 1/2 agonist, rat TNFα. Subsequently, chronic hippocampal overexpression of either TNFR ligand caused microglial activation and blood-brain barrier compromise, a pattern similar to limbic seizure-induced neuroinflammation. However, no evidence was found for neuronal cell death or spontaneous seizure activity. Thus, chronic, in vivo TNFα expression and the subsequent neuroinflammation alone did not cause cell death or elicit seizure activity. In contrast, chronic hippocampal activation of TNFR1 alone significantly increased limbic seizure sensitivity in both amygdala kainic acid and electrical amygdala kindling models, while chronic activation of both TNFR1 and TNFR2 significantly attenuated the amygdala kindling rate. With regard to endogenous TNFα, chronic hippocampal expression of a TNFα decoy receptor significantly reduced seizure-induced cell death in the hippocampus, but did not alter seizure susceptibility. These findings suggest that blockade of endogenous TNFα could attenuate seizure related neuropathology, while selective activation of TNFR2 could exert beneficial therapeutic effects on in vivo seizure sensitivity.


Extrasolar planets: constraints for planet formation models.
Since 1995, more than 150 extrasolar planets have been discovered, most of them in orbits quite different from those of the giant planets in our own solar system. The number of discovered extrasolar planets demonstrates that planetary systems are common but also that they may possess a large variety of properties. As the number of detections grows, statistical studies of the properties of exoplanets and their host stars can be conducted to unravel some of the key physical and chemical processes leading to the formation of planetary systems.


The effect of perioperative blood transfusion on kidney functions in total knee Arthroplasty.
Various studies have examined the effects of perioperative blood transfusion on kidney functions. In this study, we investigated the effects of blood transfusion on the kidney functions of patients undergoing total knee arthroplasty. : This retrospective study was carried out on 216 patients who had undergone total knee arthroplasty between January 2016 and January 2017. The patients were divided into two groups according to the level of blood transfusion used during surgery. Group-1 comprised 157 patients (72.7%) needing a blood transfusion of less than three units, while the 59 (27.3) patients in Group-2 required three or more than three units. No statistical difference was found between the two groups regarding hypertension before surgery, diabetes mellitus, chronic kidney failure, smoking habits or lung disease (p> 0.05). Likewise, there was no significant difference related to pulmonary and other complications or mortality (p> 0.05). When the groups were compared according to their blood parameters, no statistical differences in postoperative renal or other system functions were found (p> 0.05). Blood transfusion does not have a negative effect on postoperative blood urea nitrogen (BUN) and creatinine levels, or glomerular filtration rate in total knee arthroplasty.


[Correlation of adipocytokines and insulin resistance in normal pregnancy].
To explore the dynamic changes of adipocytokines and its correlation with insulin resistance during different stages of normal pregnancy. Sixty-seven healthy pregnant women (18 first, 19 second and 30 third trimester) as experimental groups and 46 healthy age-matched non-pregnant women as a control group were investigated in a case-control cross-sectional study. Serum soluble tumor necrosis factor receptor (sTNFR) was determined by enzyme linked immunoadsorbent assay (ELISA). Maternal serum leptin and adiponectin were detected by radial immunodiffusion. TNF-alphaR in placenta and fat tissue was examined by streptavidin/peroxidase. The sTNFR-I level was higher in pregnant women than that in the control group (729 +/- 167) ng/L, being significantly higher in second (1003 +/- 241) ng/L and third trimesters (1278 +/- 306) ng/L (P < 0.001). sTNFR-II level of first, second and third trimester groups (1383 +/- 305) ng/L, (1772 +/- 293) ng/L, (1933 +/- 498) ng/L was higher than that in the control group (1002 +/- 221) ng/L (P < 0.001) and was increased with the progress of gestation. Leptin level in late trimester (89 +/- 57) microg/L was significantly higher than that in control group (61 +/- 37) microg/L (P < 0.05). Adiponectin level in second (9 +/- 5) mg/L and third trimesters (10 +/- 4) mg/L was significantly lower than that in control group (14 +/- 7) mg/L (P < 0.05). The sTNFR-I and sTNFR-II were expressed in placenta and fat tissue. The dynamic changes of adipocytokines contribute to occurrence of insulin resistance.


OFF-State-Specific Inhibition of the Proprotein Convertase Furin.
The pro-protein convertase furin is a highly specific serine protease involved in the proteolytic maturation of many proteins in the secretory pathway. It also activates surface proteins of many viruses including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Furin inhibitors effectively suppress viral replication and thus are promising antiviral therapeutics with broad application potential. Polybasic substrate-like ligands typically trigger conformational changes shifting furin's active site cleft from the OFF-state to the ON-state. Here, we solved the X-ray structures of furin in complex with four different arginine mimetic compounds with reduced basicity. These guanylhydrazone-based inhibitor complexes showed for the first time an active site-directed binding mode to furin's OFF-state conformation. The compounds undergo unique interactions within the S1 pocket, largely different compared to substrate-like ligands. A second binding site was identified at the S4/S5 pocket of furin. Crystallography-based titration experiments confirmed the S1 site as the primary binding pocket. We also tested the proprotein convertases PC5/6 and PC7 for inhibition by guanylhydrazones and found an up to 7-fold lower potency for PC7. Interestingly, the observed differences in the Ki values correlated with the sequence conservation of the PCs at the allosteric sodium binding site. Therefore, OFF-state-specific targeting of furin can serve as a valuable strategy for structure-based development of PC-selective small-molecule inhibitors.


New neurons in adult brain: distribution, molecular mechanisms and therapies.
"Are new neurons added in the adult mammalian brain?" "Do neural stem cells activate following CNS diseases?" "How can we modulate their activation to promote recovery?" Recent findings in the field provide novel insights for addressing these questions from a new perspective. In this review, we will summarize the current knowledge about adult neurogenesis and neural stem cell niches in healthy and pathological conditions. We will first overview the milestones that have led to the discovery of the classical ventricular and hippocampal neural stem cell niches. In adult brain, new neurons originate from proliferating neural precursors located in the subventricular zone of the lateral ventricles and in the subgranular zone of the hippocampus. However, recent findings suggest that new neuronal cells can be added to the adult brain by direct differentiation (e.g., without cell proliferation) from either quiescent neural precursors or non-neuronal cells undergoing conversion or reprogramming to neuronal fate. Accordingly, in this review we will also address critical aspects of the newly described mechanisms of quiescence and direct conversion as well as the more canonical activation of the neurogenic niches and neuroblast reservoirs in pathological conditions. Finally, we will outline the critical elements involved in neural progenitor proliferation, neuroblast migration and differentiation and discuss their potential as targets for the development of novel therapeutic drugs for neurodegenerative diseases.


N,N-Dibenzoyl-ferrocenecarboxamide.
In the title compound, [Fe(C(5)H(5))(C(20)H(14)NO(3))], the cyclo-penta-dienyl rings deviate by 9.3 (2)° from an eclipsed conformation, defined by C-Cg(1)-Cg(2)-C pseudo-torsion angles ranging from 8.8 (1) to 9.85 (1)°. The coordination at the N atom is slightly pyramidal, as indicated by the angular sum around it of 352.6°. The amide group is inclined at 17.86 (9) and 27.27 (11)° with respect to the aromatic rings. In the crystal, mol-ecules are linked by one C-H⋯O hydrogen bond and one C-H⋯π inter-action into a two-dimensional framework parallel to the b axis.


Development of performance indicators for municipal solid waste management (PIMS): A review.
The aim of this paper is to review papers on municipal solid waste management (SWM) systems, especially on performance indicators (PIs), and suggest practical methods to manage the same by administrators. Worldwide, about 4 billion metric tons of solid waste (SW) is generated annually; the management of SW across cities is increasingly getting more complex and the funds available for providing service to citizens are shrinking. Analysis of the non-technical research papers shows that focus areas on SW can be grouped into 18 types, one being PIs. Historically, PIs for municipal SWM (PIMS) commenced with the publication of guidelines by various government agencies, starting in 1969. This was followed by a few benchmarking studies, commencing in 1998, by various international institutions. Many published comparative studies also disseminated good practices across the cities. From the 1990s onwards, research work started defining PIMS. These initiatives by various researchers took multiple dimensions and are reviewed in this paper. In almost all studies, the PIMS is measured in terms of investment decisions, public acceptance levels, social participation and environmental needs. The multiple indicators are complex, however, and managers of cities need simple tools to use. To make it simple, five-factor PIs are arrived at, considering simplicity and covering all the factors. A research agenda is outlined for future directions in the areas of cost reduction, citizens' services, citizen involvement and environmental impact.


Non-adrenergic non-cholinergic (NANC) excitatory response of the channel catfish intestine.
1. Optimal parameters for electrical field stimulation (EFS) of catfish pyloric and middle intestinal segments were determined (15 Hz, 60 V) from a range of frequencies (5-45 Hz) and voltages (40-120 V) using a modified Magnus' method. Contractile responses were produced by EFS which were reproducible and showed no significant difference between the tissues. 2. The contractile cholinergic responses of the tissues to carbachol and acetylcholine (ACh) were blocked by atropine on an equimolar concentration, whereas, these responses were enhanced in the presence of neostigmine, and acetylcholinesterase inhibitor. 3. Adrenergic responses were examined with noradrenaline (NA). NA produced contraction of the segments only, at a concentration of 10(-4) M. Among the various adrenoceptors, beta-adrenoceptor stimulation produced a weak relaxation whereas, both alpha 1- and alpha 2-adrenoceptor stimulation produced contractions, of which alpha 2-induced contraction was of greater magnitude. The beta, alpha 1 and alpha 2 responses were blocked by their respective blocking agents propranolol, prazosin and yohimbine. 4. The autonomic components of the response to EFS were determined by using selected cholinergic and adrenergic antagonists separately or collectively. Cholinergic blockade with atropine did not produce a significant blockade of the EFS-induced response. Similarly, blockade of beta-adrenoceptors with propranolol did not modulate the contractile response to EFS to any significant level. Blockade by prazosin or yohimbine did not significantly change the contractile response to EFS. After a complete blockade of the adrenergic and cholinergic divisions, the intestinal segments still showed a contractile response to EFS which was not significantly different from the control response. This indicated the presence of a non-adrenergic non-cholinergic (NANC) response. 5. Tetrodotoxin, at 10(-6) M, significantly blocked the EFS-induced NANC response suggesting a neurogenic origin for the response. 6. The present study indicated that the EFS-induced response of the catfish intestinal segments is predominantly NANC-e in nature suggesting an important role for it in the regulation of intestinal motility.


Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer.
In breast cancer, estrogen receptor alpha (ERα) positive cancer accounts for approximately 74% of all diagnoses, and in these settings, it is a primary driver of cell proliferation. Treatment of ERα positive breast cancer has long relied on endocrine therapies such as selective estrogen receptor modulators, aromatase inhibitors, and selective estrogen receptor degraders (SERDs). The steroid-based anti-estrogen fulvestrant (5), the only approved SERD, is effective in patients who have not previously been treated with endocrine therapy as well as in patients who have progressed after receiving other endocrine therapies. Its efficacy, however, may be limited due to its poor physicochemical properties. We describe the design and synthesis of a series of potent benzothiophene-containing compounds that exhibit oral bioavailability and preclinical activity as SERDs. This article culminates in the identification of LSZ102 (10), a compound in clinical development for the treatment of ERα positive breast cancer.


Upregulation of miR-183 represses neuropathic pain through inhibiton of MAP3K4 in CCI rat models.
Many studies have verified that microRNAs contribute a lot to neuropathic pain progression. Furthermore, nerve-related inflammatory cytokines play vital roles in neuropathic pain progression. miR-183 has been identified to have a common relationship with multiple pathological diseases. However, the potential effects of miR-183 in the process of neuropathic pain remain undetermined. Therefore, we performed the current study with the purpose of finding the functions of miR-183 in neuropathic pain progression using a chronic sciatic nerve injury (CCI) rat model. We demonstrated that miR-183 expression levels were evidently reduced in CCI rats in contrast with the control group. Overexpression of miR-183 produced significant relief of mechanical hyperalgesia, as well as thermal hyperalgesia in CCI rats. Furthermore, neuropathic pain-correlated inflammatory cytokine expression levels containing interleukin-6 (IL-6) and interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2) were obviously inhibited by upregulation of miR-183. Meanwhile, dual-luciferase reporter assays showed MAP3K4 was a direct downstream gene of miR-183. The expression levels of MAP3K4 were modulated by the increased miR-183 negatively, which lead to the downregulation of IL-6, IL-1β, and COX-2, and then reduced neuropathic pain progression, respectively. Overall, our study pointed out that miR-183 was a part of the negative regulator which could relieve neuropathic pain by targeting MAP3K4. Thus it may provide a new clinical treatment for neuropathic pain patients clinical therapy.


Pharmacodynamics of moxifloxacin against Streptococcus pyogenes in an in vitro kinetic model.
The aim of the present study was to investigate the pharmacodynamics of moxifloxacin against strains of Streptococcus pyogenes with different susceptibilities to erythromycin by using an in vitro kinetic model simulating human pharmacokinetics of moxifloxacin at oral doses of 400 and 200 mg, respectively. When the different strains of S. pyogenes were exposed to the higher dose, the number of bacteria was reduced below the detection limit after 12 h and no regrowth was noted during the following 12 h. At the lower dose there was regrowth of the strains with constitutive and inducible erythromycin resistance of the MLS(B) phenotype. Replication assays of the regrowing bacteria indicated that the failure of moxifloxacin to kill the MLS(B) strains at the lower dose was likely caused by the emergence of preexisting resistant subpopulations. Thus, the present study indicates that the presently used 400-mg dose seems to have an advantage over the lower dose in that the risk for selection of resistant subpopulations is minimized.


Social Cognition Deficits: Current Position and Future Directions for Neuropsychological Interventions in Cerebrovascular Disease.
Neuropsychological assessments of cognitive dysfunction in cerebrovascular illness commonly target basic cognitive functions involving aspects of memory, attention, language, praxis, and number processing. Here, I highlight the clinical importance of often-neglected social cognition functions. These functions recruit a widely distributed neural network, making them vulnerable in most cerebrovascular diseases. Sociocognitive deficits underlie most of the problematic social conduct observed in patients and are associated with more negative clinical outcomes (compared to nonsocial cognitive deficits). In clinical settings, social cognition deficits are normally gleaned from collateral information from caregivers or from indirect inferences made from patients' performance on standard nonsocial cognitive tests. Information from these sources is however inadequate. I discuss key social cognition functions, focusing initially on deficits in emotion perception and theory of mind, two areas that have gained sizeable attention in neuroscientific research, and then extend the discussion into relatively new, less covered but crucial functions involving empathic behaviour, social awareness, social judgements, and social decision making. These functions are frequently impaired following neurological change. At present, a wide range of psychometrically robust social cognition tests is available, and this review also makes the case for their inclusion in neuropsychological assessments.


An approach to the development of decision support for diagnosing pathology from radiographs.
Large inter-observer variation has been reported in oral radiology. Providing observers with a checklist prompting them to focus on specific radiographically visible features with known relevance to the diagnosis has been shown to improve diagnostic accuracy. We intended to investigate whether diagnostic accuracy for bony pathology could be improved by a computerized decision aid. The decision support provided the user with radiographic reference images for the degree of presence of a radiographic feature (such as radiopacity) and structured the use of diagnostic knowledge. Twenty-seven general dental practitioners participated in the study. They diagnosed seven radiographic cases of bony pathology using a prototype decision aid and seven other cases unaided. For each radiograph the dentists assessed the degree of presence of five radiographically visible features which had been selected from the literature oral radiology because of their use in describing, radiographically visible bony pathology. The dentists' assessments of degree of feature presence, and their diagnoses, were recorded. Histopathology was used as a diagnostic 'gold standard'. The degree of presence of the features in the radiographic images was also assessed by an independently selected panel of expert oral radiologists in a Delphi consensus procedure. Determination of the degree of presence of three radiographically visible features assessed by the dentists using the prototype decision aid was significantly improved (by up to 12%) compared to the results of their unaided assessments. The diagnostic accuracy of one-third of the dentists was also improved. The use of reference images can improve dentists' assessments of the degree of feature presence.


Is C-reactive protein useful in the management of children with suspected bacterial meningitis?
C-reactive protein (CRP) was evaluated in both serum and cerebrospinal fluid in 119 patients to determine if either or both measurements were of clinical value in the diagnosis of bacterial meningitis. CSF C-reactive protein is too insensitive (sensitivity = 66%) to be useful, while serum CRP is too nonspecific for routine application. Serum CRP may have a role if used selectively in those patients with a low-grade CSF pleocytosis and a negative Gram's stain.


The use of lyophilized Schistosoma mansoni eggs as antigenic particles in a radioimmunoassay.
Lyophilized eggs of Schistosoma mansoni, when incubated briefly with serum from infected mice, bind antibodies, as made evident by subsequent binding of fluorescein labelled anti-IgG or 125I-labelled Protein A. On the basis of these findings, a radioimmunoassay was devised which employs whole lyophilized eggs (500 or 250 eggs/serum sample) as antigenic particles and 125I-labelled Protein A as a probe for antibody binding. Only 10 microliters of serum are required to obtain 90% of the maximal binding. Kinetic studies indicated that 70% of the maximal seropositivity develops in mice between five and six weeks after a light infection, reaches a maximum at eight weeks and fluctuates around a high plateau thereafter. Pre-incubation of the test serum with soluble egg antigen (SEA) considerably inhibits antibody binding to the eggs, suggesting that SEA-like antigens participate in the reaction.


Quantitative electron-microscopic analysis of the in vivo effects of tetrahydrocannabinol on rat preovulatory follicles.
The ultrastructural composition of 4 regions of rat preovulatory follicles was examined using stereological techniques following an intraperitoneal injection of tetrahydrocannabinol (THC), once each day, for 3 days prior to sacrifice on proestrus. Control rats were injected with solvent alone. Changes in nuclear, mitochondrial, lipid droplet and dense-body volume density were measured. No differences in volume density were noted in the theca or antral region of the membrana granulosa. Compared to controls, the mitochondrial volume density decreased in the peripheral region and the corona radiata. The volume density of lipid droplets decreased in the peripheral region. These changes, and their relationship to the roles of these regions in follicular steroidogenesis, are discussed.


Injuries in Patients with Epilepsy and Some Factors Associated with Injury.
The aim of the study was to evaluate injuries in patients with epilepsy and some factors associated with injury. This study included 126 epileptic patients who attended a neurology outpatient clinic of a hospital between March 2009 and March 2010. Data were collected using a patient information form and an injury evaluation form. The data were evaluated using percentage, mean and the Chi square test. 82.5% of patients have sustained injury due to an epileptic seizure. Soft tissue injuries were the most common (70.2%), followed by head injury (61.5%), dental and tongue injury (%58.6), burns (24%), and orthopaedic injury (21.2%). The most common site of burns were the upper extremities and the face (36% and 24%, respectively). Burns occurred during cooking in 32% of cases. Five patients had upper extremity fractures. Four patients faced the risk of bathtub drowning. The injuries usually occurred at home. The significant risk factors for injury were generalized tonic-clonic seizures and high frequency of seizures. Twenty-six patients were taken to the emergency unit due to an injury. Injury is a common problem in patients with epilepsy. Dental and tongue injury was the most common seizure-related injury. The risk factors were generalized tonic-clonic seizures, and high frequency of seizures. Patients with epilepsy can lead normal lives but certain precautions are needed to prevent seizure-related injuries.


Is cell block technique useful to predict histological type in patients with ovarian mass and/or body cavity fluids?
The cell block (CB) technique is a generalized method utilized for the diagnostic evaluation of body cavity fluids. Ascites cytology is one of the most important diagnostic processes for epithelial ovarian cancer. However, in clinical practice, the usefulness of the CB method to diagnose this tumor remains unelucidated. Between 2008 and 2017, 15 peritoneal or pleural fluid samples obtained from patients with ovarian or peritoneal carcinoma or other gastrointestinal malignancies were preoperatively subjected to a diagnostic evaluation to predict the histological type and original organ. The CBs were made from 10% formalin neutral buffer solution fixed sediments of fluid samples after cytological smears were made by conventional method. Four-μm thickness sections were prepared from the cell blocks and stained with immunohistochemical method, using 16 kinds of antibodies and hematoxylin eosin staining method. The cellularity, architectural patterns, and morphological details were also studied. The median (range) age of patients was 73 (35-87) years. The clinical features were identified as follows: pleural effusion in 4, ovarian mass in 7, peritoneal dissemination in 12, para-aortic nodal swelling in one, and liver tumor in one (some overlapping). Five patients had a history of prior malignancy. Finally, we could accurately diagnose the histological type in 9 patients based on subsequent biopsy, surgery, and autopsy. In all 9 women, the clinical diagnosis, CB diagnosis and final pathological diagnosis were consistent. The CB technique may be a helpful modality for evaluating fluid cytology to obtain a final histopathologic diagnosis.


Hydrogen sulphide reduces insulin secretion from HIT-T15 cells by a KATP channel-dependent pathway.
Hydrogen sulphide (H(2)S), a naturally occurring gas exerts physiological effects by opening K(ATP) channels. Anti-diabetic drugs (e.g. glibenclamide) block K(ATP) channels and abrogate H(2)S-mediated physiological responses which suggest that H(2)S may also regulate insulin secretion by pancreatic beta-cells. To investigate this hypothesis, insulin-secreting (HIT-T15) cells were exposed to NaHS (100 microM) and the K(ATP) channel-driven pathway of insulin secretion was tracked with various fluorescent probes. The concentration of insulin released from HIT-T15 cells decreased significantly after NaHS exposure and this effect was reversed by the addition of glibenclamide (10 microM). Cell viability and intracellular ATP and glutathione (GSH) levels remained unchanged, suggesting that changes in insulin secretion were not ATP linked or redox dependent. Through fluorescence imaging studies, it was found that K(+) efflux occurs in cells exposed to NaHS. The hyperpolarised cell membrane, a result of K(+) leaving the cell, prevents the opening of voltage-gated Ca(2+) channels. This subsequently prevents Ca(2+) influx and the release of insulin from HIT-T15 cells. This data suggest that H(2)S reduces insulin secretion by a K(ATP) channel-dependent pathway in HIT-T15 cells. This study reports the molecular mechanism by which H(2)S reduces insulin secretion and provides further insight into a recent observation of increased pancreatic H(2)S production in streptozotocin-diabetic rats.


Primary structure of murine major histocompatibility complex alloantigens: isolation, biochemical characterization, and preliminary alignment of CNBr fragments from the H-2Ib glycoprotein.
Radiochemical methodology has been applied in studies directed toward the determination of the amino acid sequence of the murine H-2Kb gene product. Five major CNBr fragments, which comprise the NH2-terminal 80% of the intact glycoprotein and include the H-2Kb fragment isolated by papain cleavage, were isolated and characterized. By means of amino-terminal sequence analysis, homology to other products of the major histocompatibility complex, identification of partial CNBr cleavage products, and localization of the site of papain cleavage, it was possible to align the fragments obtained from the molecule in the following order: the NH2-terminal fragment, designated IIIn, contains 23 residues and is followed by fragment IIIa, which contains 29 residues. Two peptides Ib (Mr 11,500) and Ia (Mr 12,000), each of which contains a carbohydrate moiety, are followed by fragment Ic (Mr 5800), which includes the site of papain cleavage. The data indicate the presence of disulfide bonds between fragments Ib and Ia and between Ia and Ic.


Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio are prolonged in patients with moderate and severe obstructive sleep apnea.
Prolongation of the peak and the end of T wave (Tp-e) has been reported to be associated with ventricular arrhythmias. Tp-e/QT ratio and Tp-e/QTc ratio are used as an index of ventricular arrhythmogenesis. An increased incidence of ventricular arrhythmias has been reported in patients with obstructive sleep apnea (OSA). The aim of this study was to assess ventricular repolarization in patients with OSA by using Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio. We have studied 72 patients who underwent overnight polysomnography (PSG) between the years 2010-2011 at our institution. Patients with moderate and severe OSA (23 patients; mean age: 45±10), according to the apnea-hypopnea index, constituted the study group. Patients with normal PSG (23 patients; mean age: 42±11) were used as the control group. In all patients, Tp-e interval, Tp-e/QT ratio, Tp-e/QTc ratio, as well as some other electrocardiogram intervals were measured. Independent samples t-tests were used for comparison of continuous and categorical variables and correlations were calculated by Spearman rank correlation. Although QT and QTc intervals were not different between the groups, mean Tp-e interval (81.6±11.1 msn; 63.9±7.3 msn; respectively; P < 0.001), Tp-e/QT ratio (0.21±0.03; 0.17±0.02; respectively; P < 0.001), and Tp-e/QTc ratio (0.20±0.03; 0.16±0.02; respectively; P < 0.001) were prolonged in the study group compared to the control group. Correlation analysis showed a significant positive correlation between the presence of moderate and severe OSA and Tp-e interval (r = 0.72; P < 0.001), Tpe/QT ratio (r = 0.70; P < 0.001), and Tp-e/QTc ratio (r = 0.70; P < 0.001). Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio are prolonged in patients with moderate and severe OSA patients. There is a positive correlation between the presence of OSA and Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio.


A retrospective exploratory study of fetal genetic invasive procedures at a University Hospital.
This is a retrospective analysis of the patient demographics and cytogenetic results of patients who underwent prenatal invasive testing for genetic analysis at the Foetal Medicine Division of the Department of Obstetrics and Gynecology, Sri Ramachandra Medical College and Research Institute. The main objective of this study was to characterise the changing trends in indications of pregnant women for foetal karyotyping in a 7-year period. A total of 257 procedures were performed in this period, and there was a significant change in the trend of indications for invasive prenatal diagnosis from an advanced maternal age in 2009 to a positive screen test by 2014. Chromosome abnormalities were observed in 9.8% of the cases, with trisomy 21 being the most frequent finding. The findings demonstrate the changing trends in screening and diagnostic testing in the tertiary care centre, with an acceptance of the first and second trimester maternal serum screening tests as a determinant for high-risk pregnancies. Impact statement What is already known on this subject? Despite the fact that India has one of the world's highest birth rates, there is still no public health care policy for the application of cytogenetic prenatal diagnosis. Nevertheless, we have been offering this test in our university teaching hospital since 2008, allowing us to characterise the changing trends in indications of pregnant women who sought invasive diagnostic procedures for foetal genetic studies. What do the results of this study add? The results of our study show that there were major changes in the common indications for prenatal diagnosis during the study period. In 2009, the main indication was an advanced maternal age, referred to in 31% of the cases, which declined steadily to 5% by 2014. In 2014, 51% of cases opted for a prenatal diagnosis because of a first trimester screen positive result, increasing from 12% in 2009. What are the implications of these findings for clinical practice and/or further research? This data is relevant as it would encourage other tertiary hospitals in developing countries like India to consider extending first trimester screening for all women, regardless of age and educate them on the options of prenatal genetic diagnosis for reassurance.


Management of overactive bladder in a difficult-to-treat patient with a transdermal formulation of oxybutynin.
Antimuscarinic agents, effective in relieving symptoms of overactive bladder, are associated with anticholinergic-mediated adverse events, particularly at high dosages. The outcome of a difficult-to-treat patient requiring high doses of anticholinergic therapy who was successfully treated with transdermal oxybutynin after failing oral therapies is reported.


A randomized clinical trial investigating the performance of two commercially available posterior pediatric preveneered stainless steel crowns: a continuation study.
This study aimed to compare the clinical and radiographic success of preveneered posterior NuSmile® and Kinder Krowns® over one year and to assess the level of parental satisfaction with their esthetics. Three trained operators placed 120 crowns in a split-mouth design with a random allocation for 36 participants (mean age: 5.8 years) who received two, four, six, or eight crowns. Blind assessment of the clinical and radiographic performance of the restorations was performed by four calibrated examiners after one year. Results were analyzed by Fisher's exact test and McNemar test. Examiner reliability was determined by Cohen's kappa score. Visual analogue scale (VAS) was used to assess the level of parental satisfaction. All crowns but one were retained, and the majority (83 percent) had no facing fractures. Parental satisfaction was high (9.4/10 on the VAS). Primary maxillary first molar crowns had more occlusal facing fractures than their mandibular counterparts (P=.02). Primary mandibular second molar crowns showed more facing fractures than their maxillary counterparts (P=.008). Both types showed no statistical difference in most categories, but Kinder Krowns had more facing fractures (P<.02). Posterior preveneered crowns have predictable durability at 12 months while offering natural appearance to restored teeth.


Detection of G-Quadruplex Structures Formed by G-Rich Sequences from Rice Genome and Transcriptome Using Combined Probes.
Putative G-quadruplex (G4) forming sequences (PQS) are highly prevalent in the genome and transcriptome of various organisms and are considered as potential regulation elements in many biological processes by forming G4 structures. The formation of G4 structures highly depends on the sequences and the environment. In most cases, it is difficult to predict G4 formation by PQS, especially PQS containing G2 tracts. Therefore, the experimental identification of G4 formation is essential in the study of G4-related biological functions. Herein, we report a rapid and simple method for the detection of G4 structures by using a pair of complementary reporters, hemin and BMSP. This method was applied to detect G4 structures formed by PQS (DNA and RNA) searched in the genome and transcriptome of Oryza sativa. Unlike most of the reported G4 probes that only recognize part of G4 structures, the proposed method based on combined probes positively responded to almost all G4 conformations, including parallel, antiparallel, and mixed/hybrid G4, but did not respond to non-G4 sequences. This method shows potential for high-throughput identification of G4 structures in genome and transcriptome. Furthermore, BMSP was observed to drive some PQS to form more stable G4 structures or induce the G4 formation of some PQS that cannot form G4 in normal physiological conditions, which may provide a powerful molecular tool for gene regulation.


Social Media Addiction Among Individuals Who Underwent Rhinoplasty: Myth or Reality?
Background: Social media addiction is currently a common problem worldwide. Studies have suggested that individuals who underwent rhinoplasty are susceptible to the aforementioned condition, but no evidence-based research has been conducted to derive a definitive conclusion to this issue. Objective: This study was aimed at comparing the self-esteem, body perception, and social media use of individuals with and without a history of rhinoplasty. Design, Setting, and Participants: The study was conducted at two treatment centers. Rhinoplasty patients were selected from those who sought treatment in the private clinic of one of the researchers, whereas the control cohort participants were chosen from among employees of a university hospital. After the implementation of inclusion and exclusion criteria, 100 patients and 102 healthy unmatched control subjects were enrolled in the research. Main Measures and Outcomes: The collected sociodemographic data covered age, gender, years of education, and type of social media use. Social media addiction was measured using the social media addiction scale, self-esteem was ascertained with the Rosenberg self-esteem scale, and body perception was assessed using the body perception scale. The independent samples t-test was conducted twice to compare the mean scores of the participants, and mediation analysis was carried out to determine the effects of body image and self-esteem scores on social media addiction scores. Two-sided p-values were calculated, and differences were considered significant at the 0.1, 0.05, and 0.001 levels. Results: The groups obtained similar body image and self-esteem scores, but the difference in the social media addiction scores of the rhinoplasty patients and control participants was statistically significant at the 0.05 level, with the former having higher addiction scores. On the basis of the cutoff for social media addiction, 8 and 10 participants from the rhinoplasty and control groups, respectively, exhibited signs of dependency on Web-based social networks and similar innovations. The self-esteem scores (X) and body image scores (M) predicted the social media addiction scores (Y). The coefficient of the body image scores was statistically significant, but that of the self-esteem scores was not. The X + M → Y model indicated statistically significant effects. Conclusion and Relevance: We compared the social media usage of rhinoplasty patients and control participants. Our findings indicated no evidentiary support for the view of rhinoplasty patients as social media addicts and suggested that such a perception is a form of stigmatization.


Exploration and decompression of the spinal canal using split laminotomy and its modification, the "archbone" technique.
To develop a novel minimally invasive approach suitable for exploring different pathologies located in the spinal canal, allowing moderate enlargement of the canal with preservation of the majority of posterior structures so muscle attachments remain intact and postoperative complications are reduced. The authors developed a multilevel spinous process splitting and distracting laminotomy technique with or without complementary corticocancellous iliac crest "archbone" autografting. Technical details are discussed. The multilevel spinous process splitting and distracting laminotomy technique with or without complementary iliac bone grafting was used in 19 patients with different pathologies of the spinal canal. Satisfactory surgery of the lesions located within the spinal canal, especially intramedullary, was achieved in all patients using this new approach. The affected area of the spine was cervical in seven patients, cervicothoracic in four patients, thoracic in five patients, and thoracolumbar in three patients. The average number of split laminae was three (range, 2-6). Histological results were as follows: seven intramedullary astrocytomas, eight ependymomas, two cavernous hemangiomas, one dural arteriovenous malformation, and one hemangioblastoma. Of the eight ependymomas, 75% were removed completely and 25% were partially removed. Of the seven astrocytomas, 28.7% were removed completely, 14.3% were removed subtotally, and 57% were partially removed. The cavernous hemangiomas and the hemangioblastoma were completely removed. The approach used did not affect the extent of resection or neurological outcome. The spinous processes were closed directly in 13; in six cases, a tricortical iliac bone graft was placed between the facing bony parts of the spinous processes. The mean duration of splitting and distracting the spinous process was 16 minutes (range, 11-28 min) for the first process and 8 minutes (range, 5-14 min) for each additional spinous process. The mean duration of the whole surgical procedure, including intraspinal surgery, was 159 minutes (range, 90-290 min). The mean blood loss was 158 ml (range, 48-442 ml). The average length of hospital stay was 7.2 days. The average follow-up period was 15.4 months. Fifty-one of the 57 (89.5%) spinous process computed tomographic scans demonstrated bony healing with or without a graft between the osteotomized faces. Of the 57 spinous process computed tomographic scans, fracture of the spinous process was seen in nine (15.8%) and traumatic bony changes of the body of the vertebra in the midline in three (5.2%); these were without clinical significance and they later showed complete healing. This surgical approach fulfills the requirements of other laminotomy techniques and helps prevent damage to the crucial posterior stabilizers of the spine. In contrast to conventional spinal canal approaches, preservation of the majority of posterior structures leaves muscle attachments on the spinous processes and laminae completely intact. Furthermore, the technique for exposure and decompression of the spinal canal is a suitable method for all spinal segments, the cervical, thoracic, and the lumbar spine in all age groups.


Chronic Exertional Compartment Syndrome in the Forearm of a Collegiate Softball Pitcher.
Chronic exertional compartment syndrome (CECS) is a recognized condition in the lower limb, with many reports in the literature. However, very few instances include CECS of the upper limb. This article presents the case of a collegiate softball pitcher presenting with CECS in her right forearm. To our knowledge, this is the first case report of a softball player with CECS, with only one similar incident in a major league baseball player. The rarity of this condition normally places it low on the differential diagnosis. However, we hope that the presentation of this case and the review of the literature will aid in making swift and accurate diagnoses of CECS in future patients. We discuss the importance of three specific modalities in the diagnosis of this patient, what diagnostic criteria proved less conclusive, and the paradoxical course the syndrome presented with. Case Review RESULTS: Over a six-month period, the patient presented with peculiar presentations and exam results. A broad list of differential diagnoses had to be narrowed down through the presence or absence of relevant findings. These included cessation of exercise for 1 month, physical therapy, anti-inflammatory medicines, an electromyography/electromyogram (EMG), nerve conduction study (NCS), non-exercise magnetic resonance imaging (MRI) of the forearm, cervical MRI, and cervical computed tomography (CT) angiogram. After the above interventions were attempted and the relative findings of three important modalities were summarized, a fasciotomy and release of the dorsal, volar, and mobile wad compartments was performed. The patient's symptoms were relieved, and she eventually returned to full play in softball at the university. The three diagnostic criteria we believed to be most helpful in this case, and for future cases of CECS in the forearm, include the clinical presentation, pre- and post-exercise MRI, and pre- and post-exercise compartment pressure measurements. Chronic exertional compartment syndrome of the forearm is extremely rare, especially in the female athlete. This case report and review of the literature may be helpful to the clinician facing similar cases. It describes which clinical tests are most helpful for diagnosis and which findings may be distracting.


Delayed onset filler complication: Two case reports and literature review.
Soft tissue augmentation by fillers has become a popular cosmetic tool to offer rejuvenation and aesthetic improvement. Its results are comparable to those previously achieved only by plastic surgery. However, marked increase of filler procedures is associated with a great number of complications. Complications associated with filler injection might have early onset (within days) or late onset (after weeks to years). Delayed complications include infections, foreign body granulomatous reaction, migration of filler material, persistent discoloration, and scarring. Here we report two cases of delayed complications: one case of foreign body granuloma with migration and one case of acute inflammation involving a quiescent granuloma.


3111T/C clock gene polymorphism is not associated with sleep disturbances in untreated depressed patients.
Sleep patterns, frequently altered in depression, have been hypothesized to be under genetic control. The circadian locomotor output cycles kaput (CLOCK) T3111C variant has been studied in association with sleep disturbances in depressed patients. The aim of this study was to investigate possible effects of T3111C CLOCK on insomnia, daytime sleepiness, sleep quality, and depression severity in a sample of 100 major depressive disorder patients. Inclusion criteria were: major depressive disorder, drug-free for any antidepressant and/or benzodiazepines for at least four weeks previously to the study, and a minimum score of >17 on the Hamilton Rating Scale for Depression. The Morningness-Eveningness Questionnaire, Epworth Sleepiness Scale, Athens Insomnia Scale, and Pittsburgh Sleep Quality Index were applied. No significant difference was found concerning genotype or allele groups and Hamilton Rating Scale for Depression items or clusters. No difference was found between genotypes and comorbidity, chronotype distribution, Epworth Sleepiness Scale, Athens Insomnia Scale, or Pittsburgh Sleep Quality Index total scores. Overall, the present findings did not support the hypothesis of an effect of the T3111C CLOCK variant on sleep disturbances in major depressive disorder. Further analysis of clock machinery will clarify the contribution of clock genes to the maintenance of mental health.


Novel device for quantitatively collecting small volumes of urine from laboratory rats.
A reusable urinary collection device suitable for quantitative collection of uncontaminated urinary samples from rats without using a metabolism cage has been designed. The device can be attached to the pelvic skin within 5 min with minimum handling and discomfort to the unanesthetized rat using an adhesive. The suitability of this device was investigated by collecting and analyzing urine over a 48-h period following the intraperitoneal injection of [14C]inulin. A two-way crossover study was done with samples from one of the two experiments being collected while the animal was housed in a commercially available metabolism cage equipped to separate urine and feces. The percent of the dose excreted, food and water consumption, and the urinary output were not statistically different for rats housed in the metabolism cages or with the collection device attached. Histopathological examination of the rats revealed no pathology after a 24-h period except minor skin inflammation which occurred both in controls and animals to which the device was attached. These studies demonstrate the comparability of the new urine collection device to a commercially available metabolism cage in the quantitative collection of small (0-7 mL) urine samples with less contamination of the samples from the environment.


Recessive transmission of a multiple endocrine neoplasia syndrome in the rat.
We describe a novel hereditary cancer syndrome in the rat that is transmitted by a recessive gene mutation. Animals exhibiting the mutant phenotype develop multiple neuroendocrine malignancies within the first year of life. The endocrine neoplasia is characterized by bilateral adrenal pheochromocytoma, multiple extra-adrenal pheochromocytoma, bilateral medullary thyroid cell neoplasia, bilateral parathyroid hyperplasia, and pituitary adenoma. The appearance of neoplastic disease is preceded by the development of bilateral juvenile cataracts. Although the spectrum of affected tissues is reminiscent of human forms of multiple endocrine neoplasia (MEN), no germ-line mutations were detected in the Ret or Menin genes that are responsible for the dominantly inherited MEN syndromes in humans. Segregation studies in F1 and F2 crosses yielded frequencies of affected animals entirely consistent with a recessive autosomal mode of inheritance. The lack of the phenotype in F1 animals effectively excludes a germ-line tumor suppressor gene mutation as the causal event. The absence of mutation of known MEN genes and the unique constellation of affected tissues, plus the recessive mode of inheritance, lead us to conclude that the mutation of an as yet unknown gene is responsible for this syndrome of inherited neuroendocrine cancer.


A new type of Hypersensitivity Pneumonitis: salami brusher's disease.
We observed five consecutive cases of Hypersensitivity Pneumonitis in subjects working in a salami factory. The workers had to clean the white mould growing on salami surface using a manual wire brush. The five patients (four female) had a mean age of 39 +/- 15 years; two were smokers. Three patients had an acute clinical presentation with fever, dyspnoea, dry cough, oxygen desaturation, and presented at the emergency department with suspected diagnosis of community acquired pneumonia. The mean latency for developing respiratory symptoms was 11.6 days. Pulmonary function test demonstrated a reduction in diffusing capacity (DLCO) in all 5 patients (60 +/- 15% of predicted value). Skin prick test was positive for Penicillium spp in 3 cases and for Cladosporium and Aspergillus spp in 2 others. Specific IgG antibodies against Penicillium spp were positive in 3 subjects; 2 were positive for Aspergillus Fumigatus. The prevailing radiological pattern was a ground glass appearance in the three patients with acute clinical onset and a centrilobular one in patients with subacute onset. All patients were advised to avoid exposure to the antigens. Follow-up visits including pulmonary function testing, and DLCO measurement were conducted at one, three and six months. HRCT was performed at six month. Four subjects had a complete radiological and clinical resolution after changing work. Only one patient was treated with oral steroids for severe dyspnoea and progressive reduction of DLCO, gaining a complete radiological and clinical stability at six months.


Thermal Pretreatment of Harvest Residues and Their Use in Anaerobic Co-digestion with Dairy Cow Manure.
Several batch experiments were conducted on the anaerobic co-digestion of dairy cow manure (DCM) with three harvest residues (HR) (soybean straw, sunflower stalks, and corn stover). The influence of thermal pretreatment of HR on biogas production was investigated, where the HR were thermally pretreated at two different temperatures: T = 121 °C and T = 175 °C, during t = 30 and t = 90 min, respectively. All anaerobic co-digestion batch experiments were performed simultaneously under thermophilic regime, at T = 55 °C. Biogas and methane yields were significantly improved in experiments performed with corn stover thermally pretreated at 175 °C for 30 min (491.37 cm3/g VS and 306.96 cm3/g VS, respectively), if compared to experiments performed with untreated corn stover. The highest VS and COD removal rates were also observed in the same group of experiments and were 34.5 and 50.1%, respectively. The highest biogas and methane yields with soybean straw (418.93 cm3/g VS and 261.44 cm3/g VS, respectively) were obtained when soybean straw pretreated at 121 °C during 90 min. The highest biogas and methane yields with sunflower stalk (393.28 cm3/g VS and 245.02 cm3/g VS, respectively) were obtained when sunflower stalk was pretreated at 121 °C during 90 min.


Common and divergent immune response signaling pathways discovered in peripheral blood mononuclear cell gene expression patterns in presymptomatic and clinically apparent malaria.
Using genome-wide expression profiles from persons either experimentally challenged with malaria-infected mosquitoes or naturally infected with Plasmodium falciparum malaria, we present details of the transcriptional changes that occur with infection and that either are commonly shared between subjects with presymptomatic and clinically apparent malaria or distinguish these two groups. Toll-like receptor signaling through NF-kappaB pathways was significantly upregulated in both groups, as were downstream genes that function in phagocytosis and inflammation, including the cytokines tumor necrosis factor alpha, gamma interferon (IFN-gamma), and interleukin-1beta (IL-1beta). The molecular program derived from these signatures illuminates the closely orchestrated interactions that regulate gene expression by transcription factors such as IRF-1 in the IFN-gamma signal transduction pathway. Modulation of transcripts in heat shock and glycolytic enzyme genes paralleled the intensity of infection. Major histocompatibility complex class I molecules and genes involved in class II antigen presentation are significantly induced in 90% of malaria-infected persons regardless of group. Differences between early presymptomatic infection and natural infection involved genes that regulate the induction of apoptosis through mitogen-activated protein (MAP) kinases and signaling pathways through the endogenous pyrogen IL-1beta, a major inducer of fever. The induction of apoptosis in peripheral blood mononuclear cells from patients with naturally acquired infection impacted the mitochondrial control of apoptosis and the activation of MAP kinase pathways centered around MAPK14 (p38alpha and p38beta). Our findings confirm and extend findings regarding aspects of the earliest responses to malaria infection at the molecular level, which may be informative in elucidating how innate and adaptive immune responses may be modulated in different stages of infection.


Porcine epidemic diarrhea virus (PEDV) detection and antibody response in commercial growing pigs.
Longitudinal samples from two production sites were used to (1) describe the pattern of PEDV shedding (rRT-PCR) in individual rectal swabs, pen fecal samples, and pen oral fluids (OF); (2) describe the kinetics of PEDV antibody by ELISA (IgA, IgG) testing of pig serum and pen oral fluid samples; and (3) establish cutoffs and performance estimates for PEDV WV ELISAs (IgA, IgG). Site One was PEDV positive; Site Two was PEDV negative. On Site One, pen samples (feces and oral fluids) and pig samples (rectal swabs and sera) were collected both before and after the population was exposed to PEDV. On Site Two, pen oral fluid samples and individual pig serum samples were negative for both PEDV antibody and nucleic acid. On Site One, PEDV was detected by rRT-PCR at 6 days post exposure (DPE) in all sample types. The last rRT-PCR positives were detected in rectal swabs and oral fluids on 69 DPE. IgG and IgA were detected in oral fluids and serum samples by 13 DPE. Analysis of the PEDV serum IgG WV ELISA data showed that a sample-to-positive (S/P) cutoff of ≥ 0.80 provided a diagnostic sensitivity of 0.87 (95% CI: 0.82, 0.91) and specificity of 0.99 (95% CI: 0.98, 1.00). Serum IgG results declined slowly over the monitoring period, with 60% of serum samples positive (S/P ≥ 0.80) at the final sampling on 111 DPE. Analysis of the PEDV oral fluid IgA WV ELISA found that a cutoff of S/P ≥ 0.80 provided a diagnostic sensitivity of 1.00 (95% CI: 0.92, 1.00) and a diagnostic specificity of 1.00 (95% CI: 0.99, 1.00). The oral fluid IgA response increased through 96 DPE and began to decline at the last sampling on 111 DPE. This study showed that oral fluid-based testing could provide an easy and "animal-friendly" approach to sample collection for nucleic acid and/or antibody-based surveillance of PEDV in swine populations.


Zwitterionic (E)-1-[(4-nitro-phen-yl)iminio-meth-yl]naphthalen-2-olate.
The title compound, C(17)H(12)N(2)O(3), was synthesized by the reaction of 2-hy-droxy-1-naphthaldehyde with 4-nitro-benzenamine. These condense to form the Schiff base, which crystallizes in the zwitterionic form. In the structure, the keto-amino tautomer has a fairly short intra-molecular N-H⋯O hydrogen bond between the 2-naphthalenone and amino groups, with electron delocalization. The mol-ecule is essentially planar, with a dihedral angle of 1.96 (3)° between the ring systems. In the crystal, the mol-ecules are linked via inter-molecular C-H⋯O hydrogen bonds, forming a layer parallel to (101).


Learning to provide end-of-life care: postgraduate medical training programs in Michigan.
A statewide survey of postgraduate medical training programs was conducted to determine the current status of training related to end-of-life (EOL) care and hospice care training. A mail survey of 275 program directors was conducted with a response rate of 70%. The questionnaire focused on information about training in EOL care and hospice care: specific content, required and elective experiences, teaching formats, and program directors' ratings of the perceived adequacy of training. This study received Institutional Review Board (IRB) approval. Less than half (46%) of the residency programs reported any formal training in EOL care, and less than one third (31%) reported training in hospice care. A majority of programs with EOL and/or hospice training required it for all residents. Of the programs with required hospice training, only half included a clinical component; fewer programs with EOL training reported a clinical component. Most program directors rated their programs as adequate or excellent in terms of EOL and hospice care, whether they had formal training or not. The results of the survey demonstrate considerable variability in training with respect to hospice and EOL care. Training through direct clinical experience was infrequently reported. There has been little formal adoption of published curricula in this area. The high level of adequacy in the rating of training by program directors contrasts with relative lack of reported curriculum content and implementation, suggesting that improvements in EOL care training will be slow to come if left in the hands of program directors.


Unusual complication of late presentation deceleration aortic injury.
A 50-year-old patient presented with a stroke. An ascending aortic mass noted by computed tomography was attached to the aortic wall and was found to be thrombus at surgery. Pathologic examination revealed an intraluminal thrombus attached to a focal segment of intimal fragmentation. Sectioning of the aortic wall revealed what were findings consistent with what would be noted with a previously unrecognized traumatic ascending aortic deceleration injury. To our knowledge, this is the first case of a late presentation of deceleration aortic injury, presenting with a thrombus within the ascending aorta.


[Outcomes of reconstructive operations in lesions of the nerves of the hand and the distal third of the forearm].
269 cases of the hand and distal third of the forearm peripheral nerves injuries have been treated in the Regional Clinical Surgical-Orthopedic Hospital for 10 years. Primary suture was carried out on 154 cases, early delayed suture-on 38, late delayed suture-on 22 repeated operations were performed upon 31 patients. The long-term results proved that the operations on the peripheral nerves should be performed after trauma as early as possible.


Tryptophan Metabolism, Regulatory T Cells, and Inflammatory Bowel Disease: A Mini Review.
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract resulting from the homeostasis imbalance of intestinal microenvironment, immune dysfunction, environmental and genetic factors, and so on. This disease is associated with multiple immune cells including regulatory T cells (Tregs). Tregs are a subset of T cells regulating the function of various immune cells to induce immune tolerance and maintain intestinal immune homeostasis. Tregs are correlated with the initiation and progression of IBD; therefore, strategies that affect the differentiation and function of Tregs may be promising for the prevention of IBD-associated pathology. It is worth noting that tryptophan (Trp) metabolism is effective in inducing the differentiation of Tregs through microbiota-mediated degradation and kynurenine pathway (KP), which is important for maintaining the function of Tregs. Interestingly, patients with IBD show Trp metabolism disorder in the pathological process, including changes in the concentrations of Trp and its metabolites and alteration in the activities of related catalytic enzymes. Thus, manipulation of Treg differentiation through Trp metabolism may provide a potential target for prevention of IBD. The purpose of this review is to highlight the relationship between Trp metabolism and Treg differentiation and the role of this interaction in the pathogenesis of IBD.


Examining the Causes of Autism.
Autism is a broad, complex, and increasingly important brain disorder. New data from the Center for Disease Control and Prevention indicate that one in sixty-eight children is born with some degree of autism. Autism is also more common in males by a four to one ratio. Making it especially difficult to discuss in finite, conclusive terms is the fact that there is no biological test for autism; diagnosis is based on behavior, and the only verified treatment is intensive behavior therapy. Our author, one of the nation's foremost researchers on autism, examines the prenatal factors that contribute to the disorder.