Endarterectomy achieves lower stroke and death rates compared with stenting in patients with asymptomatic carotid stenosis.
It is currently unclear if carotid artery stenting (CAS) is as safe as carotid endarterectomy (CEA) for patients with significant asymptomatic stenosis. The aim of our study was to perform a systematic review and meta-analysis of trials comparing CAS with CEA. On March 17, 2017, a search for randomized controlled trials was performed in MEDLINE and Scopus databases with no time limits. We performed meta-analyses with Peto odds ratios (ORs) and 95% confidence intervals (CIs). Quality of evidence was assessed with the Grading of Recommendations Assessment, Development, and Evaluation method. The primary safety and efficacy outcome measures were stroke or death rate at 30 days and ipsilateral stroke at 1 year (including ipsilateral stroke and death rate at 30 days), respectively. Perioperative stroke, ipsilateral stroke, myocardial infarction (MI), and cranial nerve injury (CNI) were all secondary outcome measures. The systematic review of the literature identified nine randomized controlled trials reporting on 3709 patients allocated into CEA (n = 1479) or CAS (n = 2230). Stroke or death rate at 30 days was significantly higher for CAS (64/2176 [2.94%]) compared with CEA (27/1431 [1.89%]; OR, 1.57; 95% CI, 1.01-2.44; P = .044), with low level of heterogeneity beyond chance (I2 = 0%). Also, stroke rate at 30 days was significantly higher for CAS (63/2176 [2.90%]) than for CEA (26/1431 [1.82%]; OR, 1.63; 95% CI, 1.04-2.54; P = .032; I2 = 0%). MI at 30 days was nonsignificantly lower for CAS (12/1815 [0.66%]) compared with CEA (16/1070 [1.50%]; OR, 0.53; 95% CI, 0.24-1.14; P = .105; I2 = 0%); however, CNI at 30 days was significantly lower for CAS (2/1794 [0.11%]) than for CEA (33/1061 [3.21%]; OR, 0.13; 95% CI, 0.07-0.26; P < .00001; I2 = 0%). Regarding the long-term outcome of stroke or death rate at 30 days plus ipsilateral stroke during follow-up, this was significantly higher for CAS (79/2173 [3.64%]) than for CEA (35/1430 [2.45%]; OR, 1.51; 95% CI, 1.02-2.24; P = .04; I2 = 0%). Quality of evidence for all stroke outcomes was graded moderate. Among patients with asymptomatic stenosis undergoing carotid intervention, there is moderate-quality evidence to suggest that CEA had significantly lower 30-day stroke and also stroke or death rates compared with CAS at the cost of higher CNI and nonsignificantly higher MI rates. The long-term efficacy of CEA in ipsilateral stroke prevention, taking into account perioperative stroke and death, was preserved during follow-up. There is an urgent need for high-quality research before a firm recommendation is made that CAS is inferior or not to CEA.


Synthesis and electrochemical performance of graphene-like WS2.
Graphene-like and platelike WS2 were obtained by solid-state reactions. High-resolution (HR) TEM, BET, and Raman scattering studies show that the graphene-like WS2 is a few-layer-structured material. It exhibits better electrochemical performances than the platelike WS2. Structural characterization indicates that metallic W and Li2S are the end products of discharge (0.01 V versus Li(+)/Li), whereas metallic W and S are the recharge (3.00 V) products. In addition, X-ray absorption near-edge structure (XANES) characterization shows that the d electrons of W deviate towards the Li (or S) atom during the discharge/charge process, thus forming a weak bond between W and Li2S (or S).


Routine kidney variables, glomerular filtration rate and urinary cystatin C in cats with diabetes mellitus, cats with chronic kidney disease and healthy cats.
Diabetic kidney disease (DKD) is a frequent and serious complication in human diabetic patients, but data are limited in cats. This study was undertaken to assess whether diabetic cats are susceptible to DKD. Kidney function was compared between 36 cats with diabetes mellitus (DM), 10 cats with chronic kidney disease (CKD) and 10 age-matched healthy cats by measuring routine kidney variables (serum creatinine [sCreat], serum urea [sUrea], urine specific gravity [USG], urinary protein:creatinine ratio [UPC]), urinary cystatin C:creatinine ratio and glomerular filtration rate (GFR). Urinary cystatin C (uCysC) was measured with a human particle-enhanced nephelometric immunoassay, validated to measure feline cystatin C, in all but two diabetic cats. GFR was evaluated by exo-iohexol clearance in 17 diabetic cats, all cats with CKD and all healthy cats. Diabetic cats had significantly (mean ± SD) lower sCreat (123 ± 38 vs 243 ± 80 µmol/l), sUrea (11 ± 3 vs 18 ± 7 mmol/l) and urinary cystatin C:creatinine ratio (6 ± 31 vs 173 ± 242 mg/mol), and a significantly higher USG (1.033 ± 0.012 vs 1.018 ± 0.006) and GFR (2.0 ± 0.7 vs 0.8 ± 0.3 ml/min/kg) compared with cats with CKD. Compared with healthy cats, diabetic cats only had significantly lower USG (1.033 ± 0.012 vs 1.046 ± 0.008). Proteinuria (UPC >0.4) was present in 39% of diabetic cats, in 30% of cats with CKD and in none of the healthy cats. However, the UPC did not differ statistically between the three groups. Based on evaluation of routine kidney variables, GFR and uCysC as a tubular marker at a single time point, a major impact of feline DM on kidney function could not be demonstrated.


Recurrent glandular odontogenic cyst treatment.
The glandular odontogenic cyst (GOC) is a rare odontogenic cyst. Although none of the clinical or radiographic features of GOC are unique or pathognomonic, the lesion has a potentially aggressive behavior. Treatment of GOC includes curettage and enucleation or excision and cryotherapy; however marginal resection is usually considered a more reliable approach due to the low incidence of recurrence. In this article, we present a case with GOC which recurred five years after the initial surgical treatment.


Recurrence and relapse in geriatric depression: a review of risk factors and prophylactic treatment strategies.
An emerging body of epidemiologic data has substantiated that in younger and middle-aged populations, major depression may be characterized by early relapse, recurrence, and chronicity. Information regarding the prognosis of geriatric depression is less extensive. This article reviews the literature on the longitudinal outcome of major depression in older adults, with particular emphasis on the limited data on strategies for the pharmacologic and electroconvulsive prophylaxis of recurrent unipolar geriatric depression. Possible biological markers for relapse risk, derived from sleep electroencephalography, neuroendocrine tests, and neuroradiographic findings, are also discussed. Recommendations for the treatment and long-term follow-up of geriatric depression are presented.


Experimental animal models of acute pancreatitis.
Experimental animal models have been employed to study pancreatitis for more than a century. Although not always related to the disease in humans, they have contributed greatly to our current understanding of the pathophysiology and cell biology of this disease. They have also become a standard tool for testing new and promising treatments against pancreatitis. The following article will review the most commonly used experimental models of pancreatitis and some of the lessons we have learned from them.


Synthesis of Air-Stable Cyclopentadienyl Fe(CO)2 (Fp) Polymers by a Host-Guest Interaction of Cyclodextrin with Air-Sensitive Fp Pendant Groups.
Host-guest chemistry is used to address the challenge of the synthesis of air-stable polymers containing air-sensitive metal complexes. The complexation of the CpFe(CO)2 (Fp) pendent group with cyclodextrin (CD) molecules created air-stable poly(Fp-methylstyrene) P(CD/FpMSt). This CD complexation resulted in dimerization of the adjacent Fp groups, which was characterized by NMR, FTIR, and cyclic voltammetry (CV) analyses. P(CD/FpMSt) was soluble in DMSO and remained stable even the solution was exposed to air for months. The host-guest chemistry accounted for the improved stability, because the Fp groups decomposed upon removal of the CD molecules using competing guest molecules. The CD-complexed polymer showed light-trigged properties, including CO release and antimicrobial activity. Host-guest chemistry of air-sensitive organometallic complexes is therefore a promising technique that can be used to broaden the scope of metal-containing polymers (MCPs) with processable novel functions.


Pattern formation and nonlocal logistic growth.
Logistic growth process with nonlocal interactions is considered in one dimension. Spontaneous breakdown of translational invariance is shown to take place at some parameter region, and the bifurcation regime is identified for short and long-range interactions. Domain walls between regions of different order parameter are expressed as soliton solutions of the reduced dynamics for nearest-neighbor interactions. The analytic results are confirmed by numerical simulations.


Evaluation of ovarian toxicity of mono-(2-ethylhexyl) phthalate (MEHP) using cultured rat ovarian follicles.
Mono-(2-ethylhexyl) phthalate (MEHP) is the most toxic metabolite of di-(2-ethylhexyl) phthalate (DEHP). It has been reported that DEHP causes abnormal reproductive development in women, and suppresses estradiol synthesis and ovulation in female rats with diminished size of preovulatory follicles. The present study was conducted to evaluate the ovarian toxicity of MEHP using cultured rat ovarian follicles. Secondary follicles were isolated from the ovaries of 14-day-old female rats and cultured for 48 hr with MEHP (0, 10, 30, and 100 µg/ml). At 0, 24, and 48 hr of MEHP treatment, follicular diameters were measured. After the culture, viability and apoptosis of follicles were assessed, and progesterone, androstenedione, testosterone, and estradiol levels in culture media were measured. At 100 µg/ml, suppression of follicular development was observed, which is associated with decreased viability of follicles and apoptosis of granulosa cells. At this concentration, progesterone level increased markedly, whereas androstenedione, testosterone, and estradiol levels decreased. At 10 and 30 µg/ml, follicular development was not suppressed, no apoptotic change was observed, and the levels of all measured steroid hormones tended to increase. The combined levels of all steroid hormones increased at all concentrations of MEHP, and the increase implies that MEHP activates the synthetic pathway from cholesterol to estradiol including de novo synthesis of cholesterol. However, the progesterone/androstenedione ratio increased extremely at 100 µg/ml, and the increase implies that MEHP inhibits the conversion of progesterone to androstenedione. In conclusion, MEHP induces ovarian toxicity via suppression of follicular development and abnormal steroid hormone synthesis in cultured rat ovarian follicles.


Molecular analysis of a laccase gene from the white rot fungus Pycnoporus cinnabarinus.
It was recently shown that the white rot basidiomycete Pycnoporus cinnabarinus secretes an unusual set of phenoloxidases when it is grown under conditions that stimulate ligninolysis (C. Eggert, U. Temp, and K.-E. L. Eriksson, Appl. Environ. Microbiol. 62:1151-1158, 1996). In this report we describe the results of a cloning and structural analysis of the laccase-encoding gene (lcc3-1) expressed by P. cinnabarinus during growth under xylidine-induced conditions. The coding region of the genomic laccase sequence, which is preceded by the eukaryotic promoter elements TATA and CAATA, spans more than 2,390 bp. The corresponding laccase cDNA was identical to the genomic sequence except for 10 introns that were 50 to 60 bp long. A sequence analysis indicated that the P. cinnabarinus lcc3-1 product has a Phe residue at a position likely to influence the reduction-oxidation potential of the enzyme's type 1 copper center. The P. cinnabarinus lcc3-1 sequence was most similar to the sequence encoding a laccase from Coriolus hirsutus (level of similarity, 84%).


Natural History of Small Pancreatic Lesions Suspected to Be Nonfunctioning Pancreatic Neuroendocrine Tumors.
Nonfunctioning pancreatic neuroendocrine tumors (NF-PNETs) are a rare disease but have been diagnosed more frequently than before. The aim of this study was to evaluate the natural course of small NF-PNETs. We performed a retrospective analysis of patients with incidentally found small NF-PNETs (<20 mm) from 1999 to 2015. The patients who were recommended surveillance were included. There were 69 patients with small NF-PNETs with a mean size of 10.9 (standard deviation [SD], 3.1) mm. The average follow-up period was 52.2 (SD, 38.7) months. The changes in tumor size were as follows: increased (13.0%), sustained (84.1%), and decreased (2.9%). Eighteen were evaluated with grade 1 NF-PNETs and 1 with grade 2 among the obtained tissues. Thirteen patients underwent surgery after an average 32.9 (SD, 42.6) months later. There were 7 patients of Ia, 1 of Ib, 2 of IIa, and 1 of IIb according to the pathologic stages. Two patients received reoperation for recurrent tumors, and 2 patients showed distant metastasis after surgery, but no disease-related death occurred. Most of the small NF-PNETs did not increase in size and seldom showed metastasis. The wait-and-see strategy can be used for NF-PNETs less than 2 cm.


In vivo transepidermal water loss and epidermal occlusive hydration in newborn infants: anatomical region variation.
Transepidermal water loss (TEWL) was measured from the abdomen, buttock, and central forearm in 13 term infants by employing an electrolytic water analyzer (Meeco). The hydration level (HL) at these sites following one hour of occlusion and the resulting post-occlusion TEWL were measured. No apparent difference in TEWL was found between regional sites. The forearm and buttock HL appeared similar, while the abdomen values tended to differ considerably from both. Post-occlusion TEWL appeared significantly higher than normal TEWL. Since the buttock and forearm TEWL reflected similarly structured stratum corneum, future studies on the more accessible forarm may be extended by application to the buttock.


Lifesaving citrate anticoagulation to bridge ineffective danaparoid [correction of to bridge to danaparoid] treatment.
A case of successful regional anticoagulation with trisodium citrate in a patient who developed heparin-induced thrombocytopenia while on continuous hemofiltration is described. Immediate citrate anticoagulation allowed for maintenance of extracorporeal circulation until effective danaparoid therapy could be established. Recommended plasma antifactor Xa levels for hemodialysis may be inadequate in some cases. Values similar to those in use during cardiopulmonary bypass could be required.


The Metabolic Role of Gut Microbiota in the Development of Nonalcoholic Fatty Liver Disease and Cardiovascular Disease.
The prevalence of metabolic disorders, such as type 2 diabetes (T2D), obesity, and non-alcoholic fatty liver disease (NAFLD), which are common risk factors for cardiovascular disease (CVD), has dramatically increased worldwide over the last decades. Although dietary habit is the main etiologic factor, there is an imperfect correlation between dietary habits and the development of metabolic disease. Recently, research has focused on the role of the microbiome in the development of these disorders. Indeed, gut microbiota is implicated in many metabolic functions and an altered gut microbiota is reported in metabolic disorders. Here we provide evidence linking gut microbiota and metabolic diseases, focusing on the pathogenetic mechanisms underlying this association.


Functional expression of mutations in the human NaCl cotransporter: evidence for impaired routing mechanisms in Gitelman's syndrome.
Gitelman's syndrome is an autosomal recessive renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. This disorder results from mutations in the thiazide-sensitive NaCl cotransporter (NCC). To elucidate the functional implications of mutations associated with this disorder, metolazone-sensitive (22)Na(+) uptake, subcellular localization, and glycosidase-sensitive glycosylation of human NCC (hNCC) were determined in Xenopus laevis oocytes expressing FLAG-tagged wild-type or mutant hNCC. Injection of 10 ng of FLAG-tagged hNCC cRNA resulted in metolazone-sensitive (22)Na(+) uptake of 3.4 +/- 0.2 nmol Na(+)/oocyte per 2 h. Immunocytochemical analysis revealed sharp immunopositive staining at the plasma membrane. In agreement with this finding, a broad endoglycosidase H-insensitive band of 130 to 140 kD was present in Western blots of total membranes. The plasma membrane localization of this complex-glycosylated protein was confirmed by immunoblotting of purified plasma membranes. The mutants could be divided into two distinct classes. Class I mutants (G439S, T649R, and G741R) exhibited no significant metolazone-sensitive (22)Na(+) uptake. Immunopositive staining was present in a diffuse band just below the plasma membrane. This endoplasmic reticulum and/or pre-Golgi complex localization was further suggested by the complete absence of the endoglycosidase H-insensitive band. Class II mutants (L215P, F536L, R955Q, G980R, and C985Y) demonstrated significant metolazone-sensitive (22)Na(+) uptake, although uptake was significantly lower than that obtained with wild-type hNCC. The latter mutants could be detected at and below the oocyte plasma membrane, and immunoblotting revealed the characteristic complex-glycosylated bands. In conclusion, this study substantiates NCC processing defects as the underlying pathogenic mechanism in Gitelman's syndrome.


Effects of (+)SKF 10047, a sigma-1 selective agonist, on isolation-induced aggression in male mice.
sigma-1 Receptors have been identified in numerous brain regions, including areas such as hypothalamus and amygdala, which have long been linked to the regulation of aggression. However, there is no clear information with respect to the possible effects of sigma-1 ligands on aggressive behavior in laboratory animals. Consequently, the present study examined the effects of (+)SKF 10047 (0.5-6 mg/kg, i.p.), a sigma-1 prototypical agonist, on isolation-induced aggression in male mice, using an ethopharmacological approach. Individually housed mice were exposed to anosmic "standard opponents" 30 min after drug administration. Ten minutes of diadic interactions were staged between a singly housed and an anosmic mouse in a neutral area. The encounters were videotaped, and the accumulated time allocated by subjects to 10 broad behavioral categories was estimated using an ethologically based analysis. Results showed that (+)SKF 10047 (6 mg/kg) produced a significant reduction of offensive behaviors, without affecting immobility. Social investigation behaviors were also slightly increased after drug treatment (2-6 mg/kg). These results suggest a role for sigma-1 receptors in aggression modulation in mice.


Destruction of Carbon and Glass Fibers during Chip Machining of Composite Systems.
Composite materials with carbon and glass fibers in an epoxy matrix are widely used systems due to their excellent mechanical parameters, and machining is a standard finishing operation in their manufacture. Previous studies focused exclusively on the characteristics of the fibers released into the air. This work aimed to analyze the nature of the material waste that remains on the work surface after machining. The dust on the work surface is made up of fibers and a polymer matrix, and due to its dimensions and chemical stability, it is a potentially dangerous inhalable material currently treated as regular waste. The smallest sizes of destroyed carbon fibers were generated during drilling and grinding (0.1 μm), and the smallest glass fiber particles were generated during milling (0.05 μm). Due to their nature, carbon fibers break by a tough fracture, and glass fibers by a brittle fracture. In both cases, the rupture of the fibers was perpendicular to or at an angle to the longitudinal axis of the fibers. The average lengths of destroyed carbon fibers from the tested processes ranged from 15 to 20 µm and 30 to 60 µm for glass fibers.


Direct effects of ethanol on the nervous system.
Neurophysiological, neurochemical and behavioral studies of the effects of ethanol on the nervous system have so far failed to identify specific, direct, primary mechnisms of action that may account for the typical pattern of alcohol intoxication in vivo. Electroencephalogram and evoked response studies indicate biphasic effects in the intact subject, which may correlate better with the level of arousal than with a specific drug action. Effects on spinal reflexes are also biphasic, probably representing the net result of direct influence on resting membrane potential, primary afferent depolarization, and neurotransmitter release. With the exception of its inhibitory effect on release of oxytocin, vasopressin and possibly other hypothalamic peptides, ethanol does not appear notably different in its spectrum of effects from a wide range of other hypnotics, anesthetics and minor tranquilizers. Interpretation of the findings is complicated by the fact that functional alteration of any given neuronal system by ethanol in vivo may reflect a) direct local action of ethanol on the cells under study, b) change in the input to those cells because of an action elsewhere in the nervous system, c) effects of ethanol metabolites, or d) indirect consequences of decreased blood flow, oxygen or metabolite supply, hormonal action, or hypothermia, due to disturbances of homeostasis in the whole body as a result of deep intoxication. To date, attempts to circmvent b, c and d by the study of brain tissue in vitro have shown consistent effects of ethanol only at concentrations well above those that are meaningful in vivo. Relatively specific patterns of action of different drugs in vivo may prove to be largely dependent on their customary rates and routes of administration, and on summation of minor differences in the dose-response curves with different types of neuron, even though the basic types of molecular action may be essentially similar.


Endocrine disrupters--potential modulators of the immune system and allergic response.
Endocrine disrupters (EDs) are environmental pollutants of industrial or agricultural origin (e.g. herbicides, fungicides, insecticides, industrial chemicals) that may influence health of wildlife and human. Endocrine-disrupting effect is obtained by mimicking the action of the steroid hormones and has been associated with several reproductive disorders as well as cancerogenesis both in animals and humans. EDs can also influence synthesis of cytokines, immunoglobulins, and cell mediators as well as immune cell activation and survival. Modulation by EDs of interleukin-4 production, Th1/Th2 balance and IgE production suggest their potential effect on allergic immune responses. The aim of this review was to summarize data indicating a potential effect of EDs exposure on the immune system and allergic responses.


Prevalence and Biological Characteristics of Listeria Species Isolated from Livestock and Poultry Meat in Gansu Province, China.
Listeria monocytogenes is a widespread foodborne pathogen contaminating foods during their production or processing stages. Fresh meat is susceptible to such contamination if it is not properly preserved. Our study was conducted to reveal the level of contamination and prevalence of Listeria spp. present in livestock and poultry meat from Gansu province. A total of 1,387 samples were collected from five cities in Gansu Province according to standard sampling procedures, of which 174 samples (12.5%) were positive for Listeria species. Among them, 14 isolates of L. monocytogenes (1.0%), 150 isolates of Listeria innocua (10.8%), and ten isolates of Listeria welshimeri (0.7%) were identified by conventional bacteriological and molecular identification methods. All isolates were subjected to serological assays, antimicrobial susceptibility tests, growth curve assays, determination of biofilm-forming capacity, and cluster analysis of the 16S rRNA gene sequences. Four predominant serotypes of L. monocytogenes were identified, including 1/2a (35.7%, 5/14), 1/2b (14.3%, 2/14), 1/2c (42.9%, 6/14), and 4b (7.1%, 1/14). All L. monocytogenes isolates were resistant to tetracycline and cefoxitin. Most L. innocua isolates (63.6%, 14/22) and L. welshimeri (40%, 4/10) were resistant to tetracycline. The high biofilm-forming ability was observed among 1/2c and 1/2a serotype isolates. The cluster analysis of the 16S rRNA gene sequences revealed a close genetic relationship between the three Listeria species. This study fills the gap in the knowledge of livestock and poultry meat that carry Listeria in slaughterhouses and markets in Gansu Province.


FDA safety actions for antidiabetic drugs marketed in the US, 1980-2015.
Concerns about safety and complexity of diabetes treatments have increased overtime. We assessed secular trends in the FDA approvals, market discontinuations, and safety actions of all antidiabetic drugs marketed in the US in the period 1980-2015. Regulatory and safety related information about FDA-approved pharmaceuticals for diabetes treatment was collected from the FDA databases, the Orange Book, and Drugs@FDA. Descriptive statistics were performed to describe trends in approvals, discontinuations, and safety actions. The number of insulins and analogue approvals declined after the 1980s; whereas, the approvals of non-insulin antidiabetic drugs increased after 1995. The number of antidiabetic drugs with FDA safety actions significantly increased overtime. Overall, 59.0% of insulins and analogues and 5.7% of non-insulin antidiabetic drugs were discontinued from the market. The FDA released at least one safety action for 7.7% of insulins and analogues and 88.7% of non-insulin antidiabetic drugs. Newly approved antidiabetic drugs have raised safety concerns and led to FDA safety regulatory actions including boxed warnings, risk evaluation and mitigation strategies, medication guides, and safety communications to health care providers. There is a need for systematic post-marketing studies assessing the long-term safety of antidiabetic drugs to improve patient safety and health outcomes.


Identifying risk factors for potentially avoidable complications following radical cystectomy.
Morbidity after radical cystectomy is common and associated with increased health care resource use. Accurate characterization of complications after cystectomy, associated patient specific risk factors, and perioperative processes of care are essential to directing changes in perioperative management that will reduce morbidity and improve the quality of patient care. The National Surgical Quality Improvement Program (NSQIP) is a prospective quality management initiative of 123 Veterans Affairs Medical Centers nationwide. The NSQIP collects clinical information, intraoperative data and outcomes on a wide variety of surgical procedures from multiple surgical disciplines. Since 1991, 2,538 radical cystectomy procedures have been captured by the NSQIP. Modeling using logistic regression was performed to identify patient specific risk factors and perioperative process measures associated with postoperative morbidity. Of the 2,538 subjects at least 1 postoperative complication developed in 774 (30.5%). The most frequent complication was ileus (10%). Several factors were associated with the development of a complication, including age, dependent functional status, preoperative dyspnea, preoperative acute renal failure, chronic steroid use, preoperative alcohol consumption, American Society of Anesthesiology score, use of general anesthetic, operative time, intraoperative blood requirement and surgeon level of training. Morbidity remains high after cystectomy with 30.5% of subjects experiencing at least 1 complication. Measurable patient specific risk factors and perioperative processes associated with postoperative morbidity following cystectomy are now delineated which allows for improved risk stratification, patient counseling, and the development of novel processes that may incrementally reduce risk and improve outcomes.


The (-765 G→C) promoter variant of the COX-2/PTGS2 gene is associated with a lower risk for end-stage hip and knee osteoarthritis.
Functional polymorphisms in genes of proinflammatory signalling cascades may contribute to the genetic risk of osteoarthritis (OA). To examine a possible association between end-stage OA of the hip and knee joint and a known single nucleotide polymorphism (SNP) of the COX-2 gene promoter. The SNP -765 G→C (rs20417) of the COX-2 gene promoter was genotyped by pyrosequencing in 531 (320 women/211 men) patients with OA from the Ulm Osteoarthritis Study and 400 (200 women/200 men) regional controls from the south-west of Germany. In the whole study population the C allele was associated with a lower risk (per allele OR 0.57; 95% CI 0.43 to 0.75, p<0.0001) and the G allele with a higher risk for end-stage OA. Analysis of subgroups confirmed this result for primary, bilateral, hip and knee OA. The promoter polymorphism rs20417 of the COX-2 gene contributes to the genetic risk for end-stage hip and knee OA.


Scientific Evidence of the Beneficial Effects of Tomato Products on Cardiovascular Disease and Platelet Aggregation.
Cardiovascular disease (CVD) includes a group of disorders of the heart and blood vessels that includes numerous problems, many of which are related to the process called atherosclerosis. The present work is aimed to analyze the most relevant studies examining the potentially beneficial effects of tomato products on both CVD prevention and antiplatelet aggregation as well as an European Food Safety Authority health claims evaluation on tomato and tomato products. To date, only one health claim has been approved for a concentrated extract of tomato soluble in water (WSTC) marketed under the patented name of Fruitflow® with two forms of presentation: WSTC I and II, with the following claim "helping to maintain normal platelet aggregation, which contributes to healthy blood flow." Other studies also demonstrate similar beneficial effects for fresh tomatoes, tomato products and tomato pomace extracts.


Quantitative evidence for organic peroxy radical photochemistry at 254 nm.
Quantitative evidence is presented for the importance of alkyl peroxy photochemistry in the formation of secondary organic aerosol at 254 nm. Particles were generated by extensively oxidizing dodecanoic acid with photolytically generated hydroxyl radicals in a flow cell. The resulting particles were collected and analyzed for composition, which shows a lower contribution from multiply substituted parent molecules and much more decomposition product than expected from typical low-NOx oxidation mechanisms. Studies were performed at two separate reaction times, and kinetics modeling calculations were done using theoretical work from the combustion literature to estimate the branching of the photoexcited products. Extrapolation of the ethyl peroxy radical absorption spectrum compared to actinic flux measurements also shows that the alkyl peroxy radical absorption at ∼310 nm leads to photochemical lifetimes under pristine tropospheric conditions that are comparable to predicted lifetimes from peroxy-peroxy recombination reactions, particularly at higher altitudes.


Galectins as self/non-self recognition receptors in innate and adaptive immunity: an unresolved paradox.
Galectins are characterized by their binding affinity for β-galactosides, a unique binding site sequence motif, and wide taxonomic distribution and structural conservation in vertebrates, invertebrates, protista, and fungi. Since their initial description, galectins were considered to bind endogenous ("self") glycans and mediate developmental processes and cancer. In the past few years, however, numerous studies have described the diverse effects of galectins on cells involved in both innate and adaptive immune responses, and the mechanistic aspects of their regulatory roles in immune homeostasis. More recently, however, evidence has accumulated to suggest that galectins also bind exogenous ("non-self") glycans on the surface of potentially pathogenic microbes, parasites, and fungi, suggesting that galectins can function as pattern recognition receptors (PRRs) in innate immunity. Thus, a perplexing paradox arises by the fact that galectins also recognize lactosamine-containing glycans on the host cell surface during developmental processes and regulation of immune responses. According to the currently accepted model for non-self recognition, PRRs recognize pathogens via highly conserved microbial surface molecules of wide distribution such as LPS or peptidoglycan (pathogen-associated molecular patterns; PAMPs), which are absent in the host. Hence, this would not apply to galectins, which apparently bind similar self/non-self molecular patterns on host and microbial cells. This paradox underscores first, an oversimplification in the use of the PRR/PAMP terminology. Second, and most importantly, it reveals significant gaps in our knowledge about the diversity of the host galectin repertoire, and the subcellular targeting, localization, and secretion. Furthermore, our knowledge about the structural and biophysical aspects of their interactions with the host and microbial carbohydrate moieties is fragmentary, and warrants further investigation.


Implementation of Harmonized Food Consumption Data Collection in the Balkan Region According to the EFSA EU Menu Methodology Standards.
Initiatives in the Capacity Development in Nutrition Research in the Balkan region in the last decade have been toward the creation of contemporary, harmonized Research Infrastructure (RI) compliant with European standards. This study describes the process of creation and implementation of the European Food Safety Authority (EFSA) EU Menu methodology in the Balkan region during the EFSA support projects for food consumption data collection in four countries (Serbia, Montenegro, Bosnia and Herzegovina, and North Macedonia). This process entailed the application and improvement of an innovative tool, the DIET ASSESS and PLAN (DAP), a platform for standardized food consumption data collection and dietary intake assessment. DAP comprises computerized food consumption, anthropometric measurements, and physical activity questionnaires, validated food picture book, and FoodEx2 exposure hierarchy with sets of facet descriptors of the interest. It hosts the Balkan food platform with a Serbian food composition database (FCDB) and Regional FCDB, compliant with European Food Information Resource (EuroFIR™) standards. The implementation of the DAP platform in national dietary surveys conducted with the support of the EFSA EU Menu project in Balkan countries enabled harmonized food consumption data compilation and reporting. Application of the methodology entailed the development of study protocol and extensive education and training of study personnel. The entire data collection process was managed by internal and external survey coordinators. A pilot study was conducted to test the entire data collection and control process and was afterward used to make necessary improvements and adjustments to meet EU Menu requirements. Data collected are internationally comparable with food consumption data in other European countries within the framework of the EU Menu program. The existence of such data in the Balkan region will catalyze research activities in emerging topics, such as identification of dietary patterns, the establishment of national nutrient reference values and food-based dietary guidelines (not only in Serbia, but in the whole Balkan region), dietary exposure assessments, the endorsement and evaluation of new food legislations, the environmental and other effects of diet on the food system. The developed and implemented methodology underpins evidence-based policy-making processes lacking in the field of public health nutrition in the region.


Cajal-Retzius and subplate neurons: their role in cortical development.
Cajal-Retzius (C-R) neurons and their processes form a synaptic network in the marginal zone of the early telencephalon prior to the arrival of the first wave of radial migration of neuroblasts from the subventricular zone. Their origin is not yet proved but may be either the medial ganglionic eminence or the mesencephalic neuromere. These bipolar or multipolar neurons populate the molecular layers of both the fetus and the adult, though sparse in the adult. Their thick axon emits collaterals that make synaptic contact with pyramidal neurons initially in layer 6 and later within all layers. C-R neurons produce GABA, possibly ACh, several calcium-binding proteins (e.g. calmodulin; parvalbumin; possibly calretinin), several neuropeptides and are rich in ribosomes. Subplate neurons, beneath the cortical plate, emit pioneer axons in the incipient formation of the internal capsule and also commissural fibres of the early hippocampus. C-R cells express products of the genes reelin, LIS1 and DS-CAM, that mediate radial neuroblast migration and lamination of the cortical plate and are important in the pathogenesis of lissencephaly. In addition to forming the first intrinsic synaptic circuits of the cortical plate and its first afferent and efferent connections with subcortical structures, they may play additional roles in the formation of ocular dominance columns, in regulating neuronogenesis and in cortical repair. They do not later disappear by apoptosis as we previously thought, but their functional role in the mature brain is unknown.


Amniotic Band Syndrome with Severe Facial Cleft: A Case Report.
Cases of severe bilateral Tessier 4 cleft with unilateral Tessier 3 cleft and additional involvement of the amniotic band syndrome are rarer. This case reports a very rare case of ABS with severe facial cleft. Postoperative progress was satisfactory and the patient achieved functional recovery. The patient underwent several miner reconstructive surgeries and appropriate surgical treatment is necessary to restore the patient's social life.


A 6-year antifungal stewardship programme in a teaching hospital.
To describe the antifungal stewardship programme in our hospital and to assess its impact on total antifungal prescriptions and their cost, and on the process of care measures regarding the diagnostic and therapeutic management of invasive aspergillosis and candidaemia. We conducted a prospective observational study describing the multifaceted antifungal stewardship programme in place at our French teaching tertiary-care hospital since 2005. Several actions were implemented successively, including the systematic evaluation of all costly antifungal prescriptions (echinocandins, lipid formulations of amphotericin B, posaconazole and voriconazole). A total of 636 antifungal prescriptions were discussed by the antifungal management team from 2005 to 2010 inclusive, mainly from the haematology department (72 %). In 344/636 cases (54 %), a piece of advice was fed back to the physician in charge of the patient, with an 88 % compliance rate. Optimal standard of care was achieved for galactomannan antigen testing, performance of chest computed tomography (CT) scan and voriconazole therapeutic drug monitoring for invasive aspergillosis, with no combination therapies used since 2008. Regarding candidaemia, optimal standard of care was achieved for the timing of antifungal therapy, recommended first-line therapy, duration of therapy and the removal of central venous catheters. Total antifungal prescriptions (in defined daily doses, DDD) and their cost were contained between 2003 and 2010. The implementation of an antifungal stewardship programme was feasible, sustainable and well accepted. We observed an improved quality of care for some process of care measures, and antifungal use and cost were contained in our hospital.


Far lateral approach for resection of lower pontine cavernous malformation.
In this 3D video we review the case of a lower pontine cavernous malformation in a 31-year-old man who presented with hemiparesis and an abducens palsy. The cavernous malformation was completely resected through a far lateral approach and a peritrigeminal brainstem entry zone, with a significant improvement in the patient's hemiparesis. The relevant anatomy is reviewed in detail through multiple anatomical brainstem dissection specimens, as well as high-definition fiber tractography images. The rationale for the approach is analyzed relative to other possible options, and a number of technical pearls are provided. The video can be found here: https://youtu.be/fH2Q7RjlBKQ.


Bipolar analog signal multiplexing for position-sensitive PET block detectors.
This paper describes a block detector multiplexing technique that simplifies the extension of axial length or ring radius without employing extra data acquisition channels. The proposed multiplexing circuit (bipolar multiplexing) multiplexes block detectors by encoding the position-related signal outputs with different combinations of polarity. Accordingly, it is possible to distinguish the detectors using a shared readout channel. This method was evaluated by assessing one to 16 block detectors using four data acquisition channels and one trigger input at different count rates. The experimental results showed that the multiplexing of block detectors did not significantly degrade timing, energy or spatial performance at low count rates, while reducing the required number of data acquisition channels and wire routing density. On the other hand, the degradation was seen as total count rates of all blocks increased.


Novel rearrangements of arthropod mitochondrial DNA detected with long-PCR: applications to arthropod phylogeny and evolution.
Rearrangements of mitochondrial DNA gene order have been suggested as a tool for defining the pattern of evolutionary divergence in arthropod taxa. We have employed a combination of highly conserved insect-based polymerase chain reaction (PCR) primers with long-PCR to survey 14 noninsect arthropods for mitochondrial gene rearrangements. The size of the amplified fragments was used to order the primer containing genes. Five chelicerates exhibit amplicons that are consistent with the presumptive ancestral arthropod mtDNA gene order. These five species comprise two soft ticks, two prostriate hard ticks, and an opilionid. Six other chelicerates, all metastriate hard ticks, have a different arrangement that was originally discovered by this procedure and has been previously detailed in a complete mtDNA sequence. Three new arthropod mtDNA gene arrangements are described here. They were discovered in a terrestrial crustacean (Isopoda) and two myriapods (Chilopoda, centipede; Diplopoda, millipede). These rearrangements include major realignments of some of the large coding regions and two possible new positions for the tRNA(Met) (M) gene in arthropods. The long-PCR approach affords an opportunity to quickly screen divergent taxa for major rearrangements. Taxa exhibiting rearrangements can be targeted for DNA sequencing of gene boundaries to establish the details of the mtDNA organization.


Helpers: effects of experimental removal on reproductive success.
Experimental removal of helpers from a communal bird population decreased the reproductive success of the reduced units. By controlling for variables that are potentially correlated with both reproductive success and unit size, this experiment establishes that helpers-contribute significantly to their indirect fitness.


Lysosomal enzyme cytochemistry in acute leukaemia.
A cytochemical study of the lysosomal enzyme beta-glucuronidase in 60 cases of acute leukaemia has shown a qualitative difference in the cytoplasmic distribution of the enzyme between blast cells of the lymphoid and myeloid cell series. This difference provides a useful additional method for cytochemical classification of cell type and is superior in this respect to the other lysosomal enzymes studied (aryl sulphatase and acid phosphatase). The beta-glucuronidase reaction is recommended in those cases of acute leukaemia in which the periodic acid-Schiff reaction is negative or equivocal.


Clinicopathological correlations in pituitary adenomas.
Pituitary adenomas are common neuroendocrine neoplasms arising from adenohypophysial cells. Recent progress in our understanding of pituitary tumorigenesis as well as pathways involved in molecular cytodifferentiation of the adenohypophysis has impacted on the classification of pituitary adenomas. The detailed comprehensive classification of pituitary adenomas is now well recognized to reflect specific clinical features and genetic changes that predict targeted treatments, as well as prognostic information for patients with pituitary adenomas. Therefore, the clinical responsibility of pathologists is not only limited to the distinction of pituitary adenomas from other sellar lesions, but also to provide a comprehensive subtype classification using appropriate ancillary tools. In this article, we highlight an approach to clinical diagnosis and pitfalls in the classification of these common neoplasms.


Test-retest repeatability in macular retinal oximetry.
Evaluation of retinal macular oxygen saturation in healthy controls can aid in understanding the pathological changes seen in similar locations of those with vascular diseases like diabetes. The aim of this study was to determine the test-retest repeatability of localised retinal oximetry measurements in the macula on the Zilia Oximeter within healthy subjects of different races, 18-40 years old. Oxygen saturation was measured between three time points within the same locations of the right eye. Twenty seven subjects were included (aged 26.3 ± 3.6 years). All were confirmed to have healthy retinas and at least 6/9 vision. Oximetry measurements were taken using the Zilia to acquire local oxygen saturation measurements (300 µm diameter) at four points 3.1 degrees from the fovea in the superior/temporal, superior/nasal, inferior/temporal, and inferior/nasal locations. Oximetry measurements were taken twice on the same day 20 minutes apart and then again 1-2 weeks later. Oximetry data was analysed with intraclass correlation between visits. To assess intrasubject repeatability, the Bland-Altman repeatability coefficient and coefficient of variation were calculated. Average Intraclass correlation for the three acquisition times of the right eye was 0.78. The averaged intrasubject repeatability coefficient for the three acquisition times was 8.4. The averaged coefficient of variation was 5.4%. The Zilia oximeter has good macular test-retest repeatability; however, multiple measurements may be needed to ensure accuracy.


"Real-world" pediatric endocrine practice; how much is it influenced by physician's gender and region of practice. Results of an international survey.
To determine whether hormonal treatments for frequent clinical cases (short stature, delayed and precocious puberty) are prescribed strictly according to clinical guidelines or based on personal tendencies, and whether the decisions correlate with physician's personal demographics (age, sex, and place of practice). Cross-sectional survey, with made-up clinical cases, distributed to pediatric endocrinologists using 2 web-based professional forums, Israeli and an international. The questionnaire included 8 clinical cases and 5 demographic questions regarding the physician. Differences in practice between Israeli and international endocrinologists were assessed, and correlation between the physician's gender and their decisions regarding treatment. One hundred fifty-five physicians responded, 28% Israeli and 72% international. In girls with early puberty, 60% of international and 26% of Israeli physicians chose not to treat with a gonadotropin-releasing hormone agonist. In girls with short stature, 79% of Israeli and 34% of international physicians offered growth hormone treatment. In girls with early puberty, both male and female physicians responded similarly in the international group, but in the Israeli group 47% of male and 15% of female doctors would not treat. In girls with constitutional growth delay, 67% of Israeli male doctors would not treat with growth hormone compared to 30% of Israeli female physicians. Our study demonstrated significant practice differences between Israeli and international pediatric endocrinologists. Within the Israeli group, significant practice differences were seen between male and female physicians. Given that Israeli physicians follow the same clinical guidelines it is clear that a large "grey zone" of clinical cases exist and much of the decisions on treatment are personal and influenced by personal beliefs or gender.


Cleaning and shaping the apical third of a root canal system.
The apical third of a root canal system is the most difficult section to clean and shape because of its ramifications and tortuosities. This article discusses the clinical anatomy of the root and lists the "10 commandments" of cleaning and shaping to achieve predictably successful endodontics.


Hydroelastic behaviour of a structure exposed to an underwater explosion.
The hydroelastic interaction between an underwater explosion and an elastic plate is investigated num- erically through a domain-decomposition strategy. The three-dimensional features of the problem require a large computational effort, which is reduced through a weak coupling between a one-dimensional radial blast solver, which resolves the blast evolution far from the boundaries, and a three-dimensional compressible flow solver used where the interactions between the compression wave and the boundaries take place and the flow becomes three-dimensional. The three-dimensional flow solver at the boundaries is directly coupled with a modal structural solver that models the response of the solid boundaries like elastic plates. This enables one to simulate the fluid-structure interaction as a strong coupling, in order to capture hydroelastic effects. The method has been applied to the experimental case of Hung et al. (2005 Int. J. Impact Eng. 31, 151-168 (doi:10.1016/j.ijimpeng.2003.10.039)) with explosion and structure sufficiently far from other boundaries and successfully validated in terms of the evolution of the acceleration induced on the plate. It was also used to investigate the interaction of an underwater explosion with the bottom of a close-by ship modelled as an orthotropic plate. In the application, the acoustic phase of the fluid-structure interaction is examined, highlighting the need of the fluid-structure coupling to capture correctly the possible inception of cavitation.


Facilitating Transfer of Skills and Strategies in Occupational Therapy Practice: Practical Application of Transfer Principles.
In Occupational Therapy (OT) practice, practitioners assume that the skills and strategies taught to clients during rehabilitation will transfer to performance and participation in everyday life. Despite transfer serving as a practice foundation, outcome studies conclude that this assumption of transfer is not occurring and it often results in decreased efficacy of rehabilitation. This paper investigated key aspects of transfer and found concepts in the psychology literature that can support transfer of skills and strategies in OT. Six key principles proposed from educational psychology can serve as a guide for practitioners to better train for transfer. In this paper, we discuss the six principles and apply concepts from psychology. Each principle is supported with examples of how they may be incorporated OT practice. If occupational therapists understand these principles and implement them in treatment, the efficacy of treatment may improve for many populations.


Release of inorganic phosphate from irradiated yeast: radiation biodosimetry and evaluation of radioprotective compounds.
When cells of bakers' yeast, Saccharomyces cerevisiae, were irradiated with ionizing radiation, inorganic phosphate, ninhydrin-reactive material, and substances absorbing at 260 mmu were released into the suspending medium. The amount of inorganic phosphate released depended on the radiation dose and on the temperature and pH during irradiation. The concentration of yeast cells did not affect the phosphate yield per milligram of yeast. It is suggested that the release of phosphate may serve as an index of the total radiation environment (i.e., as a biodosimeter) where radiation inactivation of microrganisms is of primary importance, e.g., in radiation preservation of foods. The somewhat limited range of the yeast biodosimeter (ca. 0.5 to 1.75 Mrad) may be extended by use of other more resistant microorganisms, such as bacterial spores. Compounds which have been reported as protecting microorganisms and mammals against the lethal effect of ionizing radiation also inhibited the radiation-induced release of inorganic phosphate from yeast. This phosphate release system is proposed as the basis for an economical, rapid supplement to screening procedures in the evaluation of radioprotective compounds.


Navigating Drug-Like Chemical Space of Anticancer Molecules Using Genetic Algorithms and Counterpropagation Artificial Neural Networks.
A total of 6289 drug-like anticancer molecules were collected from Binding database and were analyzed by using the classification techniques. The collected molecules were encoded to a diverse set of descriptors, spanning different physical and chemical properties of the molecules. A combination of genetic algorithms and counterpropagation artificial neural networks was used for navigating the generated drug-like chemical space and selecting the most relevant molecular descriptors. The proposed method was used for the classification of the molecules according to their therapeutic targets and activities. The selected molecular descriptors in this work define discrete areas in chemical space, which are mainly occupied by particular classes of anticancer molecules. The obtained structure-activity relationship (SAR) patterns and classification rules contain valuable information, which help to screen the large databases of compounds, more precisely. Such rules and patterns can be considered as virtual filters for mining the large databases of compounds and are useful in finding new anticancer candidates.


Epigenetic mechanisms to propagate histone acetylation by p300/CBP.
Histone acetylation is important for the activation of gene transcription but little is known about its direct read/write mechanisms. Here, we report cryogenic electron microscopy structures in which a p300/CREB-binding protein (CBP) multidomain monomer recognizes histone H4 N-terminal tail (NT) acetylation (ac) in a nucleosome and acetylates non-H4 histone NTs within the same nucleosome. p300/CBP not only recognized H4NTac via the bromodomain pocket responsible for reading, but also interacted with the DNA minor grooves via the outside of that pocket. This directed the catalytic center of p300/CBP to one of the non-H4 histone NTs. The primary target that p300 writes by reading H4NTac was H2BNT, and H2BNTac promoted H2A-H2B dissociation from the nucleosome. We propose a model in which p300/CBP replicates histone N-terminal tail acetylation within the H3-H4 tetramer to inherit epigenetic storage, and transcribes it from the H3-H4 tetramer to the H2B-H2A dimers to activate context-dependent gene transcription through local nucleosome destabilization.


Molecular xenomonitoring for post-validation surveillance of lymphatic filariasis in Togo: no evidence for active transmission.
Lymphatic filariasis (LF) is a mosquito-borne filarial disease targeted for elimination by the year 2020. The Republic of Togo undertook mass treatment of entire endemic communities from 2000 to 2009 to eliminate the transmission of the disease and is currently the first sub-Saharan African country to be validated by WHO for the elimination of LF as a public health problem. However, post-validation surveillance activities are required to ensure the gains achieved are sustained. This survey assessed the mosquito vectors of the disease and determined the presence of infection in these vectors, testing the hypothesis that transmission has already been interrupted in Togo. Mosquitoes were collected from 37 villages located in three districts in one of four evaluation units in the country. In each district, 30 villages were selected based on probability proportionate to size; eight villages (including one of the 30 villages already selected) where microfilaremia-positive cases had been identified during post-treatment surveillance activities were intentionally sampled. Mosquitoes were collected using pyrethrum spray collections (PSC) in households randomly selected in all villages for five months. In the purposefully selected communities, mosquitoes were also collected using human landing collections (HLC) and exit traps (ET). Collected mosquitoes were identified morphologically, and the identification of Wuchereria bancrofti DNA in the mosquitoes was based on the pool screening method, using the LAMP assay. A total of 15,539 mosquitoes were collected during the study. Anopheles gambiae (72.6%) was the predominant LF vector collected using PSC. Pool screen analysis of 9191 An. gambiae in 629 pools revealed no mosquitoes infected with W. bancrofti (0%; CI: 0-0.021). These results confirm the findings of epidemiological transmission assessment surveys conducted in 2012 and 2015, which demonstrated the absence of LF transmission in Togo. The challenges of implementing molecular xenomonitoring are further discussed.


Association of DTNBP1 With Schizophrenia: Findings From Two Independent Samples of Han Chinese Population.
Schizophrenia (SZ) is a complex psychiatric disorder that has a strong genetic basis. Dystrobrevin-binding protein 1 (DTNBP1) is one of the genes thought to be pivotal in regulating the glutamatergic system. Studies have suggested that variations in DTNBP1 confer susceptibility to SZ and clinical symptoms. Here, we performed a two-stage independent verification study to identify polymorphisms of the DTNBP1 gene that might be associated with SZ in the Han Chinese population. In stage 1, 14 single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 healthy controls (HCs) using the Illumina GoldenGate assays on a BeadStation 500G Genotyping System. In stage 2, ten SNPs were genotyped in an independent sample of 1,031 SZ patients and 621 HCs using the Illumina 660k Genotyping System. Clinical symptoms were assessed using the Positive and Negative Syndrome Scale. There was a significant association related to allele frequency, and a trend association in relation to genotype between SZ patients and HCs at rs4712253 (p = 0.03 and 0.05, respectively). These associations were not evident following Bonferroni correction (p > 0.05 for both). Haplotype association analysis revealed that only two haplotypes (GAG and GAA; rs16876575-rs9464793-rs4712253) were significantly different between SZ patients and HCs (χ2 = 4.24, 6.37, p = 0.04 and 0.01, respectively). In addition, in SZ patients there was a significant association in the rs4964793 genotype for positive symptoms, and in the rs1011313 genotype for excitement/hostility symptoms (p = 0.01 and 0.002, respectively). We found a significant association in the baseline symbol digital modalities test (SDMT), forward-digital span (DS), backward-DS, and semantic fluency between SZ patients and HCs (p < 0.05 for all). Finally, the SNP rs1011313 genotypes were associated with SDMT in SZ patients (p = 0.04). This study provides further evidence that SNP rs4712253 of DTNBP1 has a nominal association with SZ in the Han Chinese population. Such a genotype variation may play a role in psychopathology and cognitive function.


[Stomatitis and antimitotics (author's transl)].
The authors report a case of stomatitis, in a patient receiving antimitotic therapy, which was found to be due to an acute leukosis. They feel that patients on antimitotics who develop stomatitis should have a white cell count to exclude leukosis, which is not a very rare finding today.


Gender Differences in the Association Between Alcohol Use and Sedentary Behavior Among Adults.
We examined differences in the association between alcohol use and sedentary behavior by gender among adults. Cross-sectional study that employs a complex, multistage stratified probability cluster sample design. National Health and Nutrition Examination Survey (NHANES) 2007 to 2014. NHANES participants aged ≥20 years and identifying as Hispanic, white, or black (N = 18 441). Demographic characteristics, sedentary behavior, and alcohol consumption. Sedentary behavior was measured based on the number of minutes of sedentary activity per week. Alcohol consumption in the last year was measured based on responses to items assessing whether the participant consumes alcoholic beverages and the number of alcoholic beverages consumed on average. Multinomial logistic regression analysis was used to estimate associations of alcohol use with categories of sedentary behavior by gender. Compared to women who reported not consuming alcohol, women who were heavy drinkers were significantly more likely to engage in high sedentary activity (odds ratio [OR]: 1.47; 95% confidence interval [CI]: 1.16-1.87), relative to low levels of sedentary activity. Similarly, women who were binge drinkers were more likely to engage in moderate levels of sedentary activity (OR: 1.39; 95% CI: 1.05-1.85). There were no significant associations between alcohol use and sedentary activity among men. Findings suggest that alcohol consumption should be considered in health promotion efforts targeting sedentary behavior among women.


Role of N-linked glycans on bunyamwera virus glycoproteins in intracellular trafficking, protein folding, and virus infectivity.
The membrane glycoproteins (Gn and Gc) of Bunyamwera virus (BUN, family Bunyaviridae) contain three potential sites for the attachment of N-linked glycans: one site (N60) on Gn and two (N624 and N1169) on Gc. We determined that all three sites are glycosylated. Digestion of the glycoproteins with endo-beta-N-acetylglucosaminidase H (endo H) or peptide:N-glycosidase F revealed that Gn and Gc differ significantly in their glycan status and that late in infection Gc glycans remain endo H sensitive. The roles of the N-glycans in intracellular trafficking of the glycoproteins to the Golgi, protein folding, and virus replication were investigated by mutational analysis and confocal immunofluorescence. Elimination of the glycan on Gn, by changing N60 to a Q residue, resulted in the protein misfolding and failure of both Gn and Gc proteins to traffic to the Golgi complex. We were unable to rescue a viable virus by reverse genetics from a cDNA containing the N60Q mutation. In contrast, mutant Gc proteins lacking glycans on either N624 or N1169, or both sites, were able to target to the Golgi. Gc proteins containing mutations N624Q and N1169Q acquired endo H resistance. Three viable N glycosylation-site-deficient viruses, lacking glycans on one site or both sites on Gc, were created by reverse genetics. The viability of these recombinant viruses and analysis of growth kinetics indicates that the glycans on Gc are not essential for BUN replication, but they do contribute to the efficiency of virus infection.


Professional quality of life of adult protective service workers.
Adult Protective Services (APS) workers are exposed to substantial occupational hazards and job stress, but these stressors are underdocumented. Therefore, we sought to describe APS workers' work environments and responses to occupational hazards and stressors, including compassion fatigue, burnout, and secondary traumatic stress. Survey data were gathered with closed-ended questionnaires administered to APS workers in an urban setting. Virtually all workers (97%) reported exposure to one or more environmental hazards in their work, and 80% reported hazard exposure in the past month. Workers also reported mixed responses to their work environment and to experiences with supervision. A sizable minority (22.7%) was at high risk for burnout, 24.6% were at risk for secondary traumatic stress, and 19.9% reported low compassion satisfaction. The results document multiple stressors in APS work. The APS partner is committed to ongoing efforts to better support its staff, and these findings can inform future efforts to enhance supervisor support and worker self-care, to minimize burnout and secondary traumatic stress.


In vitro biocompatibility of novel biphasic calcium phosphate-mullite composites.
In designing new calcium phosphate (CaP)-based composites, the improvement in physical properties (strength, toughness) without compromising the biocompatibility aspect is essential. In a recent study, it has been demonstrated that significant improvement in compressive strength as well as modest enhancement in toughness is achievable in biphasic calcium phosphate (BCP)-based composites with mullite addition (up to 30 wt%). Herein, we report the results of the in vitro cell adhesion, cell proliferation, alkaline phosphatase (ALP) activity, and osteocalcin (OC) production for a series of BCP-mullite (up to 30 wt%) composites. Mouse fibroblast (L929) cell lines were used to examine in vitro cell adhesion and cell proliferation; while osteoblast-like (osteosarcoma, MG63) cells were used for in vitro osteoblastic function study by ALP and OC expression. Much emphasis has been provided to discuss the cell viability and proliferation as well as osteoblastic differentiation marker on the investigated biocomposites in relation to the characteristics of the phase assemblage. On the basis of various observations using multiple biochemical assays, it has been suggested that BCP-mullite composites would be a candidate material for orthopedic applications.


Bile Acid Administration Elicits an Intestinal Antimicrobial Program and Reduces the Bacterial Burden in Two Mouse Models of Enteric Infection.
In addition to their chemical antimicrobial nature, bile acids are thought to have other functions in the homeostatic control of gastrointestinal immunity. However, those functions have remained largely undefined. In this work, we used ileal explants and mouse models of bile acid administration to investigate the role of bile acids in the regulation of the intestinal antimicrobial response. Mice fed on a diet supplemented with 0.1% chenodeoxycholic acid (CDCA) showed an upregulated expression of Paneth cell α-defensins as well as an increased synthesis of the type-C lectins Reg3b and Reg3g by the ileal epithelium. CDCA acted on several epithelial cell types, by a mechanism independent from farnesoid X receptor (FXR) and not involving STAT3 or β-catenin activation. CDCA feeding did not change the relative abundance of major commensal bacterial groups of the ileum, as shown by 16S analyses. However, administration of CDCA increased the expression of ileal Muc2 and induced a change in the composition of the mucosal immune cell repertoire, decreasing the proportion of Ly6G+ and CD68+ cells, while increasing the relative amount of IgGκ+ B cells. Oral administration of CDCA to mice attenuated infections with the bile-resistant pathogens Salmonella enterica serovar Typhimurium and Citrobacter rodentium, promoting lower systemic colonization and faster bacteria clearance, respectively. Our results demonstrate that bile acid signaling in the ileum triggers an antimicrobial program that can be potentially used as a therapeutic option against intestinal bacterial infections.


Seasonal and racial incidence of infantile gastroenteritis in South Africa.
The etiology of summer diarrhea, which formerly caused extensive mortality in children living in industrialized countries, was never discovered. This condition no longer occurs in developed countries, having been replaced by winter diarrhea, which is associated with a low mortality. Summer epidemics of diarrhea still take place in black South African infants, whereas, in white South African children, the pattern of diarrhea is similar to that seen in children in industrialized countries today. In 1977-1980, the author studied the records of patients less than two years of age admitted for treatment of dehydrating diarrhea to two teaching hospitals in Johannesburg, the Johannesburg General and Baragwanath Hospitals, which serve the needs of white and black patients, respectively. The incidence of severe diarrhea (i.e., diarrhea necessitating hospitalization) showed highly significant seasonality (p less than 0.001) and distinctive patterns by race. Dehydrating diarrhea in black children was strongly associated with warm weather, while diarrhea in white children occurred more regularly throughout the year, with a peak incidence in late fall. Laboratory studies have shown that bacteria, in particular "classical" enteropathogenic Escherichia coli, are the leading cause of diarrhea in black South African children, and that diarrhea in white children is largely attributable to rotaviruses. The association of enteropathogenic E. coli with diarrhea in black children suggests that these bacteria were responsible for earlier outbreaks of summer diarrhea. The finding that the etiology of diarrhea varies according to socioeconomic class has important implications for diarrhea control programs.


Dissimilar allergic disease in identical twins; a study of psychosomatic aspects.
Identical twins with bronchial asthma were studied. One had the first attack of the disease in late adolescence, the other not until he was adult. Both were demonstrated by immunologic means to be sensitive to house dust and certain foods. Yet, of itself, the factor of exposure to a known allergen seemed not enough to precipitate clinical allergic reaction in either of them. It is believed that emotional stress is accompanied by physiologic changes which facilitate increased reactions to antigenic agents that in normal circumstances would not cause clinical disease.The twins were widely different with regard to emotional development and in their reaction to situations of stress. In both of them allergic manifestations were associated with periods of emotional conflict.The dissimilar clinical manifestations of allergy in these identical twins may be explained by differences in personality and therefore in reactions to stress situations.


Child consent and the law: an insight and discussion into the law relating to consent and competence.
The law governing consent for children is not very clear. A child can consent to treatment but usually in practice is unable to refuse it. Even if both the child and parents refuse treatment, courts are reluctant to accept this, particularly if it is in the best interest of the child. In order to consent to treatment, a child must be competent enough to do so, and this competence is judged usually by a doctor. Children can even consent to contraceptives and abortion if 'competent' to do so. This concept perfectly lacks moral, ethical and emotional competence, and judgement of competence is carried out usually purely scientifically by pure science-orientated objective professionals like doctors. A broad discussion about the issues of children refusing treatment is conducted from the legal, ethical and philosophical point of view. Life-saving treatment and various other cases are also discussed. There is no right answer to the question. A more holistic approach is needed, and not only doctors but also sociologists, care specialists and even clergymen should be asked to judge competence in a multidisciplinary environment, particularly for contraceptives and abortion. This multidisciplinary working can be extended to other areas in medical law as well particularly in light of changes in medicine. Experience in life should be valued in a decision-making environment for judging competence. The law in relation to child consent is unclear and requires changes in order to clarify what is perceived as the child's best interest.


A40926 aglycone and pseudoaglycones: preparation and biological activity.
A40926 antibiotics are new glycopeptides which are much more active than other members of this class against Neisseria gonorrhoeae. Their activity against Gram-positive bacteria, including coagulase-negative Staphylococci, is similar to that of other glycopeptides. An A40926 preparation containing factors A and B ("A40926 A + B complex") was hydrolyzed to the aglycone and to the mannosyl and N-acylaminoglucuronyl aglycones. The mannosyl aglycone and the aglycone were less active than A40926 A + B complex against Streptococci and Gram-positive anaerobes and lost the anti-gonorrheal activity. In contrast, the N-acylaminoglucuronyl aglycones were as active as the parent complex against these Gram-positive bacteria and were moderately active against N. gonorrhoeae. The aglycone and, even more so, the N-acylaminoglucuronyl aglycones, had better activity than the parent complex against coagulase-negative Staphylococci. In experimental septicemia in the mouse, A40926 A + B complex and its derivatives had activity proportional to their MIC for the test organism.


Incidence of postoperative residual paralysis in a nigerian teaching hospital.
Postoperative residual paralysis (PORP) is a known risk factor after general anesthesia (GA) for critical respiratory events and increased postoperative morbidity. PORP is defined as a train-of-four ratio (TOFR) of <0.9 using acceleromyography (AMG). TOFR <0.9 has been associated with increased risk of aspiration, obstruction of the upper airway and an impaired hypoxic ventilatory response. The aim of this study was to determine the incidence of PORP, associated factors related with its occurrence and critical respiratory events in the postanesthesia recovery room (PAR) at our institution. Forty-one adult patients were scheduled for elective surgeries requiring GA with the use of at least 1 dose of a nondepolarizing neuromuscular blocking drug (NMBD). An independent anesthetist quantitatively measured TOFR of recruited patients postoperatively in the recovery room using the TOF-watch SX acceleromyograph (Organon Teknika) 5 min after arrival. The incidence of PORP was 75.6% (n = 31), with severe PORP (TOFR <0.7) seen in 41.5% (n = 17) of patients. Median time to full recovery in the PAR was 33 min (range 5-164 min). There was no statistical difference in the incidence of PORP related to the choice of NMBD (P = 0.186) or duration of surgery (P = 0.175). No respiratory complications or events were observed in patients with residual blockade. The incidence of PORP is quite high and undetected in our environment. Quantitative monitoring for residual paralysis is advocated as part of routine monitoring with the use of NMBDs for improved patient safety.


Diffuse-type tenosynovial giant cell tumour: Current treatment concepts and future perspectives.
At present, the optimal treatment strategy in patients with diffuse-type tenosynovial giant cell tumour (D-TGCT) is unclear. The purpose of this review was to describe current treatment options, and to highlight recent developments in the knowledge of the molecular pathogenesis of D-TGCT as well as related therapeutic implications. Epidemiology, clinical features, and the pathogenesis of D-TGCT and the most widely used treatment modalities are described. D-TGCT is a benign clonal neoplastic proliferation arising from the synovium. Patients are often symptomatic and require multiple surgical procedures during their lifetime. Currently, surgery is the main treatment for patients with D-TGCT, with relapse rates ranging from 14% to 55%. Radiosynovectomy and external beam radiotherapy have been used in combination with surgical excision or as single modalities. The finding that D-TGCT cells overexpress colony-stimulating factor 1 (CSF1), resulting in recruitment of CSF1 receptor (CSF1R)-bearing macrophages that are polyclonal and make up the bulk of the tumour, has led to clinical trials with CSF1R inhibitors. These inhibitors include small molecules such as imatinib, nilotinib, PLX3397, and the monoclonal antibody RG7155. In conclusion, D-TGCT impairs patients' quality of life significantly. The evidence that the pathogenetic loop of D-TGCT can be inhibited could potentially change the therapeutic armamentarium for this condition. Clinical trials of agents that target D-TGCT are currently ongoing. In the meantime, international registries should be activated in order to provide useful information on this relatively rare tumour.


Input reconstruction of chaos sensors.
Although the sensitivity of sensors can be significantly enhanced using chaotic dynamics due to its extremely sensitive dependence on initial conditions and parameters, how to reconstruct the measured signal from the distorted sensor response becomes challenging. In this paper we suggest an effective method to reconstruct the measured signal from the distorted (chaotic) response of chaos sensors. This measurement signal reconstruction method applies the neural network techniques for system structure identification and therefore does not require the precise information of the sensor's dynamics. We discuss also how to improve the robustness of reconstruction. Some examples are presented to illustrate the measurement signal reconstruction method suggested.


Incidence of in-hospital mortality or nonfatal myocardial infarction or nonfatal stroke in 216 diabetics and 552 nondiabetics undergoing percutaneous coronary intervention with stenting.
We investigated the incidence of in-hospital mortality or nonfatal myocardial infarction or nonfatal stroke in 216 patients with diabetes mellitus and in 552 patients without diabetes mellitus (68% men and 32% women, mean age 66 +/- 14 y) who underwent percutaneous coronary intervention with stenting. Symptomatic chest pain was present in 95% of diabetics and in 95% of nondiabetics. Unstable symptoms were present in 67% of diabetics and in 68% of nondiabetics. Aspirin was used in 99% of diabetics and nondiabetics. Clopidogrel was used in 98% of diabetics and nondiabetics. Beta blockers were used in 85% of diabetics and nondiabetics. Lipid-lowering drugs were used in 96% of diabetics and in 95% of nondiabetics. In-hospital mortality occurred in 2 of 216 diabetics (0.9%) and in 2 of 552 nondiabetics (0.4%), P not significant. In-hospital mortality or nonfatal myocardial infarction or nonfatal stroke occurred in 3 of 216 diabetics (1.4%) and in 6 of 552 nondiabetics (1.1%), P not significant.


Radiotherapy for palliation of locally advanced prostatic carcinoma.
Some patients present with distressing symptoms due to locally advanced prostatic carcinoma which may be refractory to hormonal manipulation and/or surgical treatment. Over an 8-year period 26 patients received local palliative radiotherapy for recurrent bleeding and lower urinary outflow tract obstruction. All were treated with conventional external beam radiotherapy and all but 2 obtained useful palliation of symptoms, especially those with recurrent bleeding. We also found that radiotherapy could be given to the majority of patients on an out-patient basis in 2 or 3 fractions. This was well tolerated and there were few side effects.


In situ detection of salicylate in Ocimum basilicum plant leaves via reverse iontophoresis.
The quantitative analysis of salicylate provides useful information for the evaluation of metabolic processes in plants. We report a simple, noninvasive method to measure salicylate in situ in Ocimum basilicum leaves using reverse iontophoresis in combination with cyclic voltammetry at disposable screen-printed electrodes and the concentration of salicylate in basil leaves was found to be 3 mM.


Phylogeographic structure, outbreeding depression, and reluctant virgin oviposition in the bean thrips, Caliothrips fasciatus (Pergande) (Thysanoptera: Thripidae), in California.
Bean thrips, Caliothrips fasciatus, is native to western North America. Once considered a pest of several crops in its native area, its pest status has waned over recent decades. However, due to its habit of aggregating in the navel of navel oranges, bean thrips remains economically important because some countries importing oranges from California have designated it a quarantine pest. Despite continued propagule pressure, bean thrips has never established outside North America. We examined genetic variation in mitochondrial DNA among Californian populations of C. fasciatus and found that potentially two cryptic species are present (supported by Kimura 2-P distances): a common widespread form B and a rarer form A with a very limited distribution. Form B showed strong phylogeographic structure, with many haplotypes having a limited geographic distribution. Inter-population crossing experiments between three geographically isolated populations of form B resulted in the production of some female offspring, indicating a degree of compatibility between these populations of this haplodiploid species. However, substantial outbreeding depression was also detected. A low frequency of offspring production by hetero-population pairs was evidence of pre-mating isolation, while post-mating isolation was also evident in the elevated mortality of fertilized eggs in successful hetero-population crosses. One surprising finding was the total lack of offspring production by virgin females when isolated individually. However, virgin females did produce sons in the presence of other virgin females. A test for the presence of Wolbachia showed that form B was not infected, but that some populations of the rarer form A were.


COVTree: Coevolution in OVerlapped sequences by Tree analysis server.
Overlapping genes are commonplace in viruses and play an important role in their function and evolution. For these genes, molecular coevolution may be seen as a mechanism to decrease the evolutionary constraints of amino acid positions in the overlapping regions and to tolerate or compensate unfavorable mutations. Tracing these mutational sites, could help to gain insight on the direct or indirect effect of the mutations in the corresponding overlapping proteins. In the past, coevolution analysis has been used to identify residue pairs and coevolutionary signatures within or between proteins that served as markers of physical interactions and/or functional relationships. Coevolution in OVerlapped sequences by Tree analysis (COVTree) is a web server providing the online analysis of coevolving amino-acid pairs in overlapping genes, where residues might be located inside or outside the overlapping region. COVTree is designed to handle protein families with various characteristics, among which those that typically display a small number of highly conserved sequences. It is based on BIS2, a fast version of the coevolution analysis tool Blocks in Sequences (BIS). COVTree provides a rich and interactive graphical interface to ease biological interpretation of the results and it is openly accessible at http://www.lcqb.upmc.fr/COVTree/.


Tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic soft tissue: new entities and new variants of old entities recorded during the last 25 years. Part XII: appendix.
In an eleven part series published in Pathologica, we have presented various tumoral, quasitumoral and pseudotumoral lesions of the superficial and somatic soft tissue (ST), which emerged as new entities or as variants of established entities during the last quarter of a century. Detailed clinicomorphological and differential diagnostic features of approximately sixty entities were chosen on the basis of their clinical significance and morphologic distinctiveness. The series included fibrous and myofibroblastic tumors (e.g. solitary fibrous tumor, high grade classic and pigmented dermatofibrosarcoma protuberans, inflammatory myofibroblastic tumor and myofibrosarcomas), fibromyxoid and fibrohistiocytic neoplasms (e.g., Evans' tumor, phosphaturic mesenchymal tumor, inflammatory myxohyaline tumor), special adipocytic/vascular/and smooth muscle lesions (e.g., chondroid lipoma, Dabska's tumor, ST hemangioblastoma, lipoleiomyosarcoma), epithelioid mesenchymal malignancies of diverse lineages (e.g., epithelioid liposarcoma, proximal-type epithelioid sarcoma, neuroendocrine extraskeletal chondromyxoid sarcoma), ST Ewing's tumor and peripheral nerve sheath tumors (perineuriomas and pigmented and rosetting tumors of the schwannoma/neurofibroma group), extranodal dendritic or histiocytic proliferative processes (follicular dendritic cell sarcoma, Rosai-Dorfman disease, Castleman's disease, and plexiform xanthomatous tumor), and tumors with myoepithelial differentiation. The section devoted to selected pseudotumoral entities considered representatives of the hamartoma group (neural fibrolipomatous hamartoma, ectopic hamartomatous thymoma, rudimentary meningocele), metabolic diseases (amyloid tumor, nephrogenic fibrosing dermopathy, tophaceous pseudogout, pseudoinfiltrative parathyromatosis), stromal tissue reactions to trauma (fibroosseous pseudotumors of digits) and infections (bacillary angiomatosis), and normal organs (glomus coccygeum). To conclude the descriptive phase, supplementary material has now been collected and appended in an attempt to provide a quick digest of essential knowledge both for comparison and differential diagnosis. The data have been tailored to synthesize diverse sources, integrating clinical elements and references to articles that previously appeared in Part I ("Introduction"), Part II ("The List and Review of New Entities") and Parts III to XI ("Excerpta"). At the very least we hope this final part ("Appendix") will provide the reader with a useful tabular organization of ST lesions and a reference resource.


Extrapulmonary tuberculosis in colombian children: Epidemiological and clinical data in a reference hospital.
The pediatric population is at increased risk of disseminated and extrapulmonary tuberculosis (TB). There is little information on children affected by this entity. The demographic, clinical, and outcome characteristics of the treatment of children with extrapulmonary TB, treated at a national reference institution between January 1, 2008, and December 31, 2016, are described and analyzed in this work. This was a retrospective observational study. Cases of extrapulmonary TB were identified, and variables were collected based on each criterion used for diagnosis and treatment outcomes. A descriptive analysis of the variables collected was performed. Ninety-three cases were identified, of which 32 (34.4%) met the criteria for extrapulmonary TB. The mean age was 10.2 years (range 0.8-17 years), and the most frequent site of extrapulmonary TB was lymph node 40.6%, meningeal 21.9%, and ocular 18.8%. Bacteriological confirmation was obtained in 8 cases (25%) while the remaining 24 cases (75%) were classified as cases of clinically diagnosed TB. Two patients (6.2%) died during treatment although their decease was not attributable to TB. The clinical criterion was fundamental to establish the diagnosis. The microbiological isolation rate was low. Molecular biology tools increase bacteriological performance although their extended use is limited by cost. Regional multicenter studies are required to identify the target population and the tools necessary for timely management and treatment.


AIDS vaccines that allow HIV-1 to infect and escape immunologic control: a mathematic analysis of mass vaccination.
Cytotoxic T lymphocyte (CTL)-based HIV vaccine concepts shown to reduce viremia and postpone disease but not to prevent infection in monkeys are currently in human phase 1 trials. To evaluate the potential efficacy of vaccines that cannot prevent HIV-1 to infect and escape immunologic control, we designed a mathematic model that correlates the level of viremia to both infectiousness and disease progression. We speculate that vaccinees will have a virologic set point and disease progression rates comparable to untreated HIV-1-infected individuals with the best prognosis. Our model (illustrated with R0 = 3) shows that a sexually active population can ultimately be reduced to 26% of its initial size as a result of AIDS-related mortality in the absence of treatment or vaccination. Start of vaccination when HIV-1 prevalence is still low might postpone the peak incidence of infection and the dramatic decline in population size by up to 22 years. In conclusion, CTL-based vaccines that do not prevent HIV-1 infection but do postpone the time to onset of AIDS have considerable potential to curb the spread of HIV-1 and to postpone high AIDS-related mortality on a population level. The number of long-term survivors is substantially increased only when vaccination is initiated early in an AIDS epidemic, however.


The importance of nuclear quantum effects in spectral line broadening of optical spectra and electrostatic properties in aromatic chromophores.
In this work, we examine the importance of nuclear quantum effects on capturing the line broadening and vibronic structure of optical spectra. We determine the absorption spectra of three aromatic molecules indole, pyridine, and benzene using time dependent density functional theory with several molecular dynamics sampling protocols: force-field based empirical potentials, ab initio simulations, and finally path-integrals for the inclusion of nuclear quantum effects. We show that the absorption spectrum for all these chromophores are similarly broadened in the presence of nuclear quantum effects regardless of the presence of hydrogen bond donor or acceptor groups. We also show that simulations incorporating nuclear quantum effects are able to reproduce the heterogeneous broadening of the absorption spectra even with empirical force fields. The spectral broadening associated with nuclear quantum effects can be accounted for by the broadened distribution of chromophore size as revealed by a particle in the box model. We also highlight the role that nuclear quantum effects have on the underlying electronic structure of aromatic molecules as probed by various electrostatic properties.


Longitudinal elastic properties and porosity of cortical bone tissue vary with age in human proximal femur.
Tissue level structural and mechanical properties are important determinants of bone strength. As an individual ages, microstructural changes occur in bone, e.g., trabeculae and cortex become thinner and porosity increases. However, it is not known how the elastic properties of bone change during aging. Bone tissue may lose its elasticity and become more brittle and prone to fractures as it ages. In the present study the age-dependent variation in the spatial distributions of microstructural and microelastic properties of the human femoral neck and shaft were evaluated by using acoustic microscopy. Although these properties may not be directly measured in vivo, there is a major interest to investigate their relationships with the linear elastic measurements obtained by diagnostic ultrasound at the most severe fracture sites, e.g., the femoral neck. However, before the validity of novel in vivo techniques can be established, it is essential to understand the age-dependent variation in tissue elastic properties and porosity at different skeletal sites. A total of 42 transverse cross-sectional bone samples were obtained from the femoral neck (Fn) and proximal femoral shaft (Ps) of 21 men (mean±SD age 47.1±17.8, range 17-82years). Samples were quantitatively imaged using a scanning acoustic microscope (SAM) equipped with a 50MHz ultrasound transducer. Distributions of the elastic coefficient (c33) of cortical (Ct) and trabecular (Tr) tissues and microstructure of cortex (cortical thickness Ct.Th and porosity Ct.Po) were determined. Variations in c33 were observed with respect to tissue type (c33Tr<c33Ct), location (c33(Ct.Ps)=37.7GPa>c33(Ct.Fn)=35.3GPa>c33(Tr.Ps)=33.8GPa>c33(Tr.Fn)=31.9GPa), and cadaver age (R(2)=0.28-0.46, p<0.05). Regional variations in porosity were found in the neck (superior 13.1%; inferior 6.1%; anterior 10.1%; posterior 8.6%) and in the shaft (medial 9.5%; lateral 7.7%; anterior 8.6%; posterior 12.0%). In conclusion, significant variations in elastic coefficients were detected between femoral neck and shaft as well as between the quadrants of the cross-sections of neck and shaft. Moreover, an age-related increase in cortical porosity and a stiffening of the bone tissue were observed. These findings may explain in part the increase in susceptibility to suffer low energy fractures during aging and highlight the potential of ultrasound in clinical osteoporosis diagnostics.


Biocompatibility assessment of a long-term wearable artificial pump-lung in sheep.
The purpose of this study was to assess the biocompatibility of a newly developed long-term wearable artificial pump-lung (APL) in a clinically relevant ovine animal model. The wearable APL device was implanted in five sheep through left thoracotomy. The device was connected between the right atrium and pulmonary artery and evaluated for 30 days. Three sheep were used as the sham control. Platelet activation was assessed by measuring platelet surface P-selectin (CD62P) expression with flow cytometry and plasma soluble P-selectin with an enzyme-linked immunosorbent assay. Thrombotic deposition on the device components and hollow fiber membranes were analyzed with digital imaging and scanning electron microscopy. Surface P-selectin of the APL and sham groups changed significantly over the study period, but without significant differences between the two groups. Soluble P-selectin for the two groups peaked in the first 24 h after the surgery. Soluble P-selectin of the APL group remained slightly elevated over the study period compared to the presurgical baseline value and was slightly higher compared to that of the sham group. Plasma free hemoglobin remained in the normal ranges in all the animals. In spite of the surgery-related alteration in laboratory tests and elevation of platelet activation status, the APL devices in all the animals functioned normally (oxygen transfer and blood pumping) during the 30-day study period. The device flow path and membrane surface were free of gross thrombus. Electron microscopy images showed only scattered thrombi on the fibers (membrane surface and weft). In summary, the APL exhibited excellent biocompatibility. Two forms of platelet activation, surgery-related and device-induced, in the animals implanted with the wearable APL were observed. The limited device-induced platelet activation did not cause gross thrombosis and impair the long-term device performance.


Sexual activity in patients after proctocolectomy with ileal pouch-anal anastomosis.
Introduction: Proctocolectomy with ileal pouch-anal anastomosis is the gold standard in the surgical treatment of patients with ulcerative colitis, familial adenomatous polyposis and other colorectal diseases requiring colectomy. The treatment consists in removing the large intestine and creating an intestinal reservoir from the last ileum loop and then anastomosing the intestinal reservoir with the anal canal. Like any surgical procedure, RPC-IPAA also carries the risk of complications, both early and late. Late postoperative complications include sexual dysfunction.
Aim: The main goal of the following work is to assess the quality of life and sexual activity in patients having undergone the RPC-IPAA procedure at the General and Colorectal Surgery Clinic.
Material and methods: The study group consisted of patients aged 19-79 who had been subjected to RPC-IPAA procedures at the General and Colorectal Surgery Clinic in years 2010-2019. The study was conducted on the basis of a survey consisting of 50 questions about the social and mental condition, medical history and previous treatment as well as the quality of sexual life before and after surgery. The scale used for the assessment of the quality of sex life consisted of 5 grades: very low, low, medium, high, very high. Thirty subjects (21 men and 9 women) took part in the survey. Ulcerative colitis (86.6%) was the most common reason for qualification for restorative proctectomy among the examined patients; less common reasons included familial adenomatous polyposis (13.3%) and synchronous colorectal cancer (3.3%). A vast majority of the surgeries had been performed after 10 years' duration of ulcerative colitis, and the intestinal reservoir had been functioning for over a year at the time of the examination. In addition, the effect of taking steroids and the impact of early postoperative complications on the quality of sex life of patients was assessed.
Results: High or very high sexual activity before surgery was reported by 46% of patients whereas low or very low quality was reported by 13%. The rest of the responders assessed their pre-operative sexual activity as average. After surgery, 23% of patients rated their sexual activity as high or very high while 36.6% of patients rated it as low or very low (P = 0.07). It was also noted that taking corticosteroids before surgery decreased the quality of sex life after surgery (P = 0.07 for activity, P = 0.04 for quality). None of the women surveyed used artificial moisturizing of intimate places during sex. Only 1 person stated that they started using artificial moisturization of intimate places after the procedure (P = 0.5). None of the men surveyed had used pharmacological agents to help them obtain an erection before surgery while as many as 33% of responders reported the need for their use after surgery (P = 0.008). Other postoperative sexual dysfunctions were also registered, such as dyspareunia (13.3%), sensory disorder within the intimate region, fecal incontinence, and urinary incontinence.
Conclusions: To sum up, sexual activity and quality of sexual life deteriorated after RPC-IPAA in our patients.