Parental morphine exposure affects repetitive grooming actions and marble burying behavior in the offspring: Potential relevance for obsessive-compulsive like behavior.
Family, adoption and twin studies have highlighted the significant role of heritable influences on individual differences in opioid addiction. Meanwhile, obsessive-compulsive disorder (OCD) is a disorder wherein the individual experiences recurring thoughts that cause irrational fears and anxiety. In the present study, adult male and female rats received morphine solution for 21 days and were drug-free for 10 days. Offspring were used in 4 distinct groups; (1) paternal morphine-exposed, (2) maternal morphine-exposed, (3) maternal and paternal morphine-exposed, and (4) drug-naïve subjects. We assessed the grooming behavior and marble burying test as an indicator of obsessive-compulsive behavior. To clarify the mechanisms underlying these changes, the mRNA level of BDNF, the phosphorylation level of CREB and the protein level of D2 dopamine receptor (DR) were evaluated in the nucleus accumbens (NAc). The grooming behavior in male offspring with one or two morphine-abstinent parent(s) increased compared with the offspring of drug naïve rats. In addition, the offspring of morphine-exposed parents buried more marbles when compared with the offspring of drug-naïve parents. Also, the BDNF mRNA was down-regulated in the NAC. However, the levels of phospho-CREB and D2 DR were elevated. Previous studies indicated that exposure to morphine in adulthood enhances the risk of psychiatric disorders in offspring. OCD is one the comorbid disorders with addiction and increases the risk of substance abuse disorder in patients. In this survey, we found that morphine exposure in parents before gestation can encourage obsessive-compulsive behavior in offspring.


Cotransporters as molecular water pumps.
Molecular water pumps are membrane proteins of the cotransport type in which a flux of water is coupled to substrate fluxes by a mechanism within the protein. Free energy can be exchanged between the fluxes. Accordingly, the flux of water may be relatively independent of the external water chemical potential and can even proceed uphill. In short, water is being cotransported. The evidence for water cotransport is reviewed with particular emphasis on electrogenic cotransporters expressed in Xenopus oocytes under voltage clamped conditions. Phenomena such as uphill water transport, tight coupling between water transport and clamp current, cotransport of small hydrophilic molecules, and shifts in reversal potentials with osmolarity are discussed with examples from the Na+/glutamate and Na+/glucose cotransporters. Unstirred layers and electrode artifacts as alternative explanations for such cotransport can be ruled out for both experimental and theoretical reasons. Indeed, substrate fluxes mediated by channels or ionophores generate much smaller water fluxes than those observed with cotransporters. Theoretical models, using reasonable values for the intracellular diffusion coefficient, indicate the presence of only small unstirred layers in the membranes studied.


Molecular and pathogenicity characterization of Gallid herpesvirus 2 newly isolated in China from 2009 to 2013.
During the course of our continuous surveillance of Gallid herpesvirus 2 (GaHV-2), 44 isolates were obtained from GaHV-2-positive chickens of different flocks in China from 2009 to 2013. The meq gene, considered as a major GaHV-2 oncogene, was sequenced and was found to contain an open reading frame of 1020 nucleotides encoding a 339 amino acid (aa) polypeptide in all isolates. Compared with the GaHV-2 GA strain, the meq genes in 15.9 % (7/44) of the isolates analyzed in this study contained an aa substitution mutation at position 88 (A to T) of which is the first report. The main characteristics of Chinese GaHV-2 isolates meq genes included the substitutions K77E, D80Y, V115A, T139A, P176R, and P217A, and the aa substitution frequency at positions 139 and 176 showed an increase. To test the pathogenicity of the isolates, a pathogenicity study and a vaccination-challenge test were performed on three selected isolates (ZY/1203, WC/1203, and WC/1110) and reference strain GA. The results showed that the three isolates induced gross Marek's disease (MD) lesions in 95.0-100 % cases, which was a higher rate than that obtained for strain GA (82.4 %). Three isolates induced mortality in 10-21.1 % of specific-pathogen-free chickens, which was similar to results with strain GA (23.5 %). The commercially available CVI988 vaccine induced lower protective indices (PIs) against ZY/1203 (82.4) and WC/1110 (83.3) as compared to those against WC/1203 (100) and GA (100). These results showed an evolving trend in the meq genes of the isolates; three isolates exhibited higher morbidity as compared to the reference strain and the vaccine induced lower PIs against two isolates as compared to that against the reference strain.


New risk prediction model of coronary heart disease in participants with and without diabetes: Assessments of the Framingham risk and Suita scores in 3-year longitudinal database in a Japanese population.
The Framingham Risk Score (FRS) has been reported to predict coronary heart disease (CHD), but its assessment has been unsuccessful in Asian population. We aimed to assess FRS and Suita score (a Japanese CHD prediction model) in a Japanese nation-wide annual health check program, participants aged 40-79 years were followed up longitudinally from 2008 to 2011. Of 35,379 participants analyzed, 1,234 had new-onset CHD. New-onset CHD was observed in diabetic men [6.00%], non-diabetic men [3.96%], diabetic women [5.51%], and non-diabetic women [2.86%], respectively. Area under the curve (AUC) of receiver operating characteristic (ROC) curve for CHD prediction were consistently low in Suita score (TC), FRS (TC) and NCEP-ATPIII FRS (TC), suggesting that these scores have only a limited power. ROC, net reclassification improvement (NRI), integrated discrimination improvement (IDI), and decision curve analysis (DCA) and Hosmer-Lemeshow goodness-of-fit test did not show clear differences between Suita score (TC) and FRS (TC). New models combining waist circumference ≥85 cm in men or proteinuria ≥1+ in women to Suita score (TC) was superior in diabetic men and women. New models could be useful to predict 3-year risk of CHD at least in Japanese population especially in diabetic population.


Rotated prism-wear disrupts emmetropization but does not reliably induce hyperopia in the New World monkey.
To determine whether a disruption of binocular vision that has been previously shown to be amblyogenic disturbs visually guided growth, and in particular to follow-up the observation by Kiorpes and Wallman [Kiorpes, L., & Wallman, J. (1995). Does experimentally-induced amblyopia cause hyperopia in monkeys? Vision Research, 35(9), 1289-1297] that monkeys in whom strabismus had been induced some years earlier were hyperopic in eyes that had become amblyopic, we induced unilateral fixation in five infant New World monkeys (marmosets) through the wearing of a Fresnel prism (of 15 or 30 prism dioptres power) in front of one eye for four weeks. The prism was rotated every three hours during the prism-wear period to encourage a preference for fixating with the contralateral eye. Refractive error and intraocular axial dimensions were measured before, and at intervals after the prism-wearing period. Fixation preference was measured behaviourally, during and after the prism-wear period. Cortical visual function was subsequently assessed through recording of pattern-reversal VEPs in each marmoset between 11 and 14 months of age to assess whether amblyopia had developed in the non-fixing eye. All marmosets used the untreated eye almost exclusively for a monocular visual task by the end of the prism-rearing period. This preference was still present up to at least 7 months after prism-wear had ceased. VEP measures showed a loss of sensitivity at low spatial frequencies (the only ones we were able to test), compatible with amblyopia having developed in the non-fixating eyes of the prism-reared marmosets. Eyes that wore prisms were not significantly different from their fellow eyes in mean refractive error or mean vitreous chamber depth (repeated measures ANOVA; P>0.05) before or at any time after prism-wear had ceased. Two marmosets developed 2-3D of anisometropia (one hyperopic and one myopic) at the end of prism-wear, that was attributable to interocular differences in vitreous chamber depth, and which decreased towards isometropia in the period following prism-wear removal. Disruption of binocular vision with rotating prisms can influence emmetropization and ocular growth, although it does not appear to do so in a consistent way.


Loop flow analysis of dissolved reactive phosphorus in aqueous samples.
The current flow based method for the determination of dissolved reactive phosphorus (DRP) suffers interference from salinity (e.g. index refractive difference) and the incidentally formed bubbles, which can be a problem for optical detection. Here we reported a simple and robust loop flow analysis (LFA) method for accurate measurement of DRP in different aqueous samples. The chemistry is based on the classic phosphomolybdenum blue (PMB) reaction and the PMB formed in a novel cross-shaped flow cell was detected at 700 nm using a miniature spectrophotometer. The effects of reagents on the kinetic formation of PMB were evaluated. The detection limit was 32 nM with an optical pathlength of 1cm and the relative standard deviations for repetitive determinations of 1, 2 and 8 µM phosphate solutions were 1.8% (n=113, without any stoppage during repeating analysis for >7h), 1.0% (n=49) and 0.39% (n=9), respectively. The analysis time was 4 min sample(-1). The effects of salinity and interfering ions (silicate and arsenate) were evaluated and showed no interference under the proposed protocol for DRP analysis. Using the LFA method, different aqueous samples with a salinity range of 0-34 were analyzed and the results showed excellent agreement with the reference method (slope 0.9982±0.0063, R(2)=0.9987, n=34). Recoveries for spiked samples varied from 95.4% to 103.7%. The proposed method showed insignificant interference from salinity, silicate and arsenate, higher reproducibility, easier operation and was free of the bubble problem.


Microbial production of 2-pyrone-4,6-dicarboxylic acid from lignin derivatives in an engineered Pseudomonas putida and its application for the synthesis of bio-based polyester.
Lignin valorization depends on microbial upcycling of various aromatic compounds in the form of a complex mixture, including p-coumaric acid and ferulic acid. In this study, an engineered Pseudomonas putida strain utilizing lignin-derived monomeric compounds via biological funneling was developed to produce 2-pyrone-4,6-dicarboxylic acid (PDC), which has been considered a promising building block for bioplastics. The biosynthetic pathway for PDC production was established by introducing the heterologous ligABC genes under the promoter Ptac in a strain lacking pcaGH genes to accumulate a precursor of PDC, i.e., protocatechuic acid. Based on the culture optimization, fed-batch fermentation of the final strain resulted in 22.7 g/L PDC with a molar yield of 1.0 mol/mol and productivity of 0.21 g/L/h. Subsequent purification of PDC at high purity was successfully implemented, which was consequently applied for the novel polyester.


Biotransformation of 2,4,6-tris(2,4,6-tribromophenoxy)-1,3,5-triazine (TTBP-TAZ) can contribute to high levels of 2,4,6-tribromophenol (2,4,6-TBP) in humans.
2,4,6-Tribromophenol (2,4,6-TBP) is a brominated flame retardant that accumulates in human tissues and is a potential toxicant. Previous studies found 2,4,6-TBP levels in human tissues were significantly higher than those of brominated flame retardants measured in the same samples. In contrast, the levels of 2,4,6-TBP in the environment and foodstuff are not elevated, suggesting a low potential for direct intake through environmental exposure or diet. Here, we hypothesized that high levels of 2,4,6-TBP in human tissues are partially from the indirect exposure sources, such as biotransformation of highly brominated substances. We conducted in vitro assays utilizing human and rat liver microsomes to compare the biotransformation rates of four highly brominated flame retardants, which could potentially transform to 2,4,6-TBP, including decabromodiphenyl ethane (DBDPE), 2,4,6-tris-(2,4,6-tribromophenoxy)-1,3,5-triazine (TTBP-TAZ), 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), and tetrabromobisphenol A (TBBPA). Our results show that TTBP-TAZ rapidly metabolizes in both human and rat liver microsomes with a half-life of 1.1 and 2.2 h, respectively, suggesting that TTBP-TAZ is a potential precursor of 2,4,6-TBP. In contrast, 2,4,6-TBP was not formed as a result of biotransformation of TBBPA, BTBPE, and DBDPE in both human and rat liver microsomes. We applied suspect and target screening to explore the metabolic pathways of TTBP-TAZ and identified 2,4,6-TBP as a major metabolite of TTBP-TAZ accounting for 87% of all formed metabolites. These in vitro results were further tested by an in vivo experiment in which 2,4,6-TBP was detected in the rat blood and liver at concentrations of 270 ± 110 and 50 ± 14 μg/g lipid weight, respectively, after being exposed to 250 mg/kg body weight/day of TTBP-TAZ for a week. The hepatic mRNA expression demonstrated that TTBP-TAZ significantly activates the aryl hydrocarbon receptor (AhR) and promotes fatty degeneration (18 and 28-fold change compared to control, respectively) in rats.


The first outbreak of Taenia ovis infection in China.
Infection of Taenia ovis metacestodes in sheep or goats causes great economic losses due to condemnation of carcasses. T. ovis infection is not formally recorded in China to date. In October, 2015, T. ovis infection occurred in Jingtai County, China, and 113 of 192 sheep from one farm were infected. Cysts resided in the cardiac and skeletal muscle, and evaginated metacestodes had four suckers and scolex armed with approximately 23 hooks. Using cox1 and nad1 as molecular markers, the sample was further identified and the results showed that the cox1 and nad1 nucleotide sequences of the sample shared 99% identity with that of T. ovis and 75%-91.3% with those of other Taenia species. Taken together, these results confirm the first occurrence of T. ovis in China.


Volatile profiling of Arabidopsis thaliana - putative olfactory compounds in plant communication.
Arabidopsis thaliana from the Brassicaceae family has arisen as the model organism in plant biology research. The plant's genome has been characterized and worldwide studies are conducted at the genetic, protein and metabolic level to unravell the function of genes involved in growth, reproduction, biosynthesis, and plant communication. As part of the multidisciplinary project BIOEMIT at NTNU, metabolomic studies of Arabidopsis T-DNA knock-out mutants and ecotypes have been carried out. Volatile profiles of autolyzed, intact plants and single plant organs were obtained by solid-phase microextraction coupled with gas chromatography-mass spectrometry. The studies were aimed at the diversity of defense-related compounds from the glucosinolate-myrosinase system - the isothiocyanates and nitriles. Metabolites from methionine, leucine and phenylalanine-derived glucosinolates were most abundant (4-methylthiobutyl, 4-methylpentyl, 2-phenylethyl). In addition, 24 monoterpenes, 26 sesquiterpenes and 12 aromatic structures, predominantly observed in inflorescenses, are described. Excluding the vast group of straight chain aliphatic structures, a total of 102 volatile compounds were detected, of which 59 are reported in Arabidopsis thaliana for the first time, thus emphasizing the sensitivity and applicability of solid-phase microextraction for volatile profiling of plant secondary metabolites.


Membranoproliferative glomerulonephritis with polyarteritis: a case report.
A case of membranoproliferative glomerulonephritis with polyarteritis is described. The patient was a 68 year old male who had the disease for about four months. A kidney biopsy specimen taken just before the patient died was studied by light, immunofluorescence, and electron microscopy. Splitting of the basement membrane, IgG, IgA, BlC, Clq, fibrinogen, and electron dense deposits were found in the glomeruli. It is considered that perhaps some cases of membranoproliferative glomerulonephritis are produced by circulating immune complexes.


[Enhanced recovery after surgery (ERAS®) in cardiac anesthesia].
Enhanced Recovery After Cardiac Surgery (ERACS) is a multidisciplinary and multiprofessional treatment approach in cardiac surgery. Recently, a transfer and adaptation of enhanced recovery after surgery (ERAS) protocols from other disciplines, such as colorectal surgery, to cardiac surgery has been performed in different settings. First, prehabilitation programs have been established and investigated to improve patients' physical, psychological and nutritional status including treatment of preoperative anemia. Second, intraoperative therapeutic steps are described, such as infection reduction bundles, rigid sternal closure and guidance of perioperative anesthesia. For this, the use of short-acting agents, goal-directed fluid management and multimodal anesthesia are among the important measures. Third, early recovery and restoration of patient autonomy are achieved with early extubation and mobilization, efficient postoperative analgesia and diagnosis and treatment of delirium.The introduction of an ERACS protocol is a team effort requiring a protocol adapted to the institutional conditions and a willingness to perform a shift of culture in perioperative care. So far, the successful establishment of ERACS protocols in minimally invasive cardiac surgery has been reported and encourages the development of protocols of specific patient groups, such as pediatric cardiac surgery or left ventricular assist device implantation.


[Use of flocculants for detection of viruses in fluids (author's transl)].
Hydroxide flocs of iron, aluminium, zinc, and tin were tested for their capabilities of virus enrichment in fluids (such as water and liquid foods). The virus used was polio type II att. The flocculation with tin yielded the best results because it gave the highest recovery rates (90%) and good reproducibility. A satisfactory enrichment was also obtained with the flocculation with aluminium- and iron salts. The losses were 31 and 33%. The lowest recovery rates were obtained with nickel- and zinc flocculation (losses: 70 and 77%). The difficulties in filtering the flocs and eluting the virus with 3% beefextract could be overcome by centrifugation and dissolution of aluminium and iron flocs with sodium-potassium-tartrate (average recovery rates 5 and 27%). In addition we tested the flocculation in lemonade as a model fluid loaded with a high content of organic material which usually interfere with the formation of flocs and in consequence the enrichment of viruses. An enrichment of viruses in lemonade was possible only with previously prepared and aged flocs of tin and iron. The loss was 18 and 12% respectively.


Functional characterization of the DNA mismatch binding protein MutS from Haemophilus influenzae.
This investigation demonstrates DNA mismatch repair activity in Haemophilus influenzae cell free extracts. The mutS gene as well as purified protein of H. influenzae restored repair activity in complementation assays performed with mutS deficient Escherichia coli strain. The difference in affinity for GT and AC mismatched bases by H. influenzae MutS was reflected in the efficiency with which these DNA heteroduplexes were repaired in vitro, with GT being repaired well and AC the least. Unlike E. coli MutS, the H. influenzae homolog failed to give protein-DNA complex with homoduplex DNA. Interestingly, MutS was found to bind single-stranded DNA but with lesser affinity as compared to heteroduplex DNA. Apart from the nucleotide- and DNA-mediated conformational transitions, as monitored by circular dichroism and limited proteolysis, our data suggest a functional role when H. influenzae MutS encounters single-stranded DNA during exonucleolytic step of DNA repair process. We propose that, conformational changes in H. influenzae MutS not only modulate mismatch recognition but also trigger some of the down stream processes involved in the DNA mismatch repair process.


Short-TE projection reconstruction MR microscopy in the evaluation of articular cartilage thickness.
The aim of this study was to assess the potential of projection-reconstruction (PR) MR microscopy in the accurate measurement of cartilage thickness. Short-TE PR microimages were acquired at 7.05 T on bone-cartilage cylindrical plugs excised from four regions of two disarticulated femoral heads (i. e. superior, inferior, posterior and anterior), using an NMR instrument equipped with a microimaging accessory. The PR microimages were then correlated with conventional spin-echo (SE) microimages and with histology. On PR microimages, acquired with an echo time of 3.2 ms, the cartilage signal was increased, allowing an accurate delineation of the cartilage from the tidemark/cortical bone region. As a consequence, by the PR method a more precise measurement of cartilage thickness compared with that performed by the conventional SE approach was feasible. An excellent correlation between PR microimages and histology was also obtained (r = 0.90). By the proposed method it is possible to accurately determine the cartilage thickness better than with the conventional SE sequences.


[Effect of the high molecular weight fraction of non-collagenous bone tissue protein on osteogenesis and hematopoiesis in experimental elongation of an extremity].
High molecular fraction of HCl-extract from mature homologous bone was parenterally administered, during the predistraction period, into 16 rabbits, crus of which was elongated by Ilizarov procedure. The treatment affected positively the adaptation process, hemopoiesis and the ossification of distraction regenerate. Administration of the high molecular protein fraction into mice with depressed hemopoiesis demonstrated that physiological effect of the fraction consisted in stimulating effect on proliferation of both bone tissue and red blood cells.


Mammalian species richness on islands on the Sunda Shelf, Southeast Asia.
A rich mammalian fauna is found on islands that lie on the Sunda Shelf, a continental shelf extending from Vietnam to Borneo and Java that was periodically exposed as dry land during the Pleistocene. The correlation between log of island area and number of species is high (r 2=0.94); the slope of the curve is moderate (z=0.235). Distance from small islands to "source areas" (=Borneo, Sumatra, and the Malay Peninsula) does not appear to affect species richness, nor does depth of water to source area (a measure of isolation time). A species-area curve for forest reserves of varying sizes on the Malay Peninsula has a low slope (z=0.104); comparison of the mainlaind and island curves indicates that decreasing island area is strongly correlated with increased extinction. Extinction has left reduced but ecologically balanced sets of species on all islands, except that carnivores are under-represented on all but the largest islands. Initial body size and rarity appear to play a significant role in determining the probability of extinction of individual species.


[Leishmaniasis in a splenectomized thalassodrepanocytic young adult].
We report a 23-year-old thalassodrepanocytic man who contracted leishmaniasis. The diagnostic difficulties related to some overlapping features between the two conditions are discussed. To the best of our knowledge, this is the first reported occurrence of leishmaniasis in a thalassodrepanocytic patient.


Antibodies against dietary antigens in rheumatoid arthritis patients treated with fasting and a one-year vegetarian diet.
To compare serum antibody activity against dietary antigens in patients with rheumatoid arthritis (RA) and healthy controls, and to examine whether anti-food antibody activity fluctuated with disease activity during a trial of fasting followed by a one-year vegetarian diet. Serum IgG, IgA and IgM antibody activity against several food antigens was measured by an enzyme immunoassay. Abnormally high antibody activity was defined as values above the 90th percentile of the measurements in 30 healthy controls. Serum IgE antibody activity was measured by a radioallergosorbent test. During the trial 10 of 27 patients suspected that certain food items aggravated their arthritis symptoms. Elevated antibody activity against one or more of the dietary antigens was found in all RA patients, but these measurements could not be used to predict which food would aggravate the symptoms. Elevated IgG and IgA antibody activity against alpha-lactalbumin was found in a significantly larger number of RA patients than in controls. With the exception of one patient, there was no concordance between the clinical course and antibody activity against the various dietary antigens. The results indicate that a systemic humoral immune response against food items is probably not involved in the pathogenesis of RA.


Inferred kinship patterns reveal low levels of extra-pair paternity in the endangered Neotropical Jabiru Stork (Jabiru mycteria, Aves: Ciconiiformes).
The present study inferred the genetic mating system in a natural breeding population of the Jabiru Stork (Jabiru mycteria), a Neotropical wading bird considered endangered in part of its distribution range. Based on data from eight microsatellite loci, maximum-likelihood kinship reconstruction techniques, parentage assignment analyses and effective population size (Ne) estimates were applied to samples collected in the Brazilian Pantanal wetland (N = 45 nestlings from 20 nests; N = 17 shed adult feathers from 11 nests). The relationship diagnosis was determined for most of the complete clutches (86.66 %): 92.31 % were full siblings and 7.69 % were half siblings. Shed feathers collected from the nests matched the genetic parents of the offspring in 80 % of cases. Feathers collected from the ground below the nests were compatible with the putative parents in 41.67 % of cases. A mean Ne of 35 reproductive individuals was inferred, corresponding to an Ne/Nc ratio of 0.09, which is similar to the ratio found in populations of a number of different wild animals. The higher proportion of full siblings identified in the broods suggests that genetic monogamy is the prevalent mating system in the Jabiru Stork, while the detection of half siblings suggests some degree of extra-pair paternity. The present findings are in agreement with previous ecological observations of social monogamy in this species, despite the isolated evidence of extra-pair copulation events. This study also demonstrates the usefulness of a noninvasive approach to sampling adults and performing parentage and relatedness analyses in an elusive, threatened species.


Reoperations after tricuspid valve repair.
The objective was to analyze the short- and long-term results of patients with previous tricuspid valve repair who had valve dysfunction and required cardiac reoperations. Between 1976 and 2002, 74 patients with a mean age of 53.8 +/- 12.2 years underwent valve reoperations for dysfunction of previous tricuspid valve repair. Mitral and tricuspid lesions were diagnosed in 40 patients (54%), triple valve disease (mitral, aortic, tricuspid) was diagnosed in 26 patients (35.1%), isolated tricuspid disease was diagnosed in 6 patients (8.1%), and aortic and tricuspid lesions were diagnosed in 2 patients (2.7%). Reoperations included tricuspid valve replacement in 43 patients (58.1%) and a new tricuspid valve repair procedure in the remaining 31 patients (41.9%). Hospital mortality (30-day or within first admission) was 35.1% (n = 26). In the multivariate analysis, risk factors for hospital mortality included body mass index less than 20 kg/m2 and greater than 24 kg/m2 , triple valve disease, use of intra-aortic balloon counterpulsation, and presence of postoperative complications. The follow-up was complete in 100% of patients, with a mean follow-up of 14.2 years (range 4 months to 26 years). The late mortality was 40.5% (n = 30). Predictors of late mortality were body mass index less than 20 kg/m2 , cardiac surgery before 1991, and development of dysfunction early after tricuspid valve repair. At the follow-up closing date, 19 patients are alive (25.7%). The actuarial survival was 11.8% +/- 4.9% at 26 years. Patients with failure of a tricuspid valve repair procedure requiring reoperation have a poor prognosis with a high mortality rate both in-hospital and in the long-term.


Nutrition for Infants with Congenital Heart Disease.
Perioperative malnutrition in infants with congenital heart disease can lead to significant postnatal growth failure and poor short- and long-term outcomes. A standardized approach to nutrition is needed for the neonatal congenital heart disease population, taking into consideration the type of cardiac lesion, the preoperative and postoperative period, and prematurity. Early enteral feeding is beneficial and should be paired with parenteral nutrition to meet the fluid and nutrient needs of the infant.


Erythropoietin Pretreatment Attenuates Seawater Aspiration-Induced Acute Lung Injury in Rats.
Seawater drowning-induced acute lung injury (ALI) is a serious clinical condition characterized by increased alveolar-capillary permeability, excessive inflammatory responses, and refractory hypoxemia. However, current therapeutic options are largely supportive; thus, it is of great interest to search for alternative agents to treat seawater aspiration-induced ALI. Erythropoietin (EPO) is a multifunctional agent with antiinflammatory, antioxidative, and antiapoptotic properties. However, the effects of EPO on seawater aspiration-induced ALI remain unclear. In the present study, male rats were randomly assigned to the naive group, normal saline group, seawater group, or seawater + EPO group. EPO was administered intraperitoneally at 48 and 24 h before seawater aspiration. Arterial blood gas analysis was performed with a gas analyzer at baseline, 30 min, 1 h, 4 h, and 24 h after seawater aspiration, respectively. Histological scores, computed tomography scan, nuclear factor kappa B p65, inducible nitric oxide synthase, caspase-3, tumor necrosis factor-alpha, interleukin (IL)-1β, IL-6, IL-10, wet-to-dry weight ratio, myeloperoxidase activity, malondialdehyde, and superoxide dismutase in the lung were determined 30 min after seawater aspiration. Our results showed that EPO pretreatment alleviated seawater aspiration-induced ALI, as indicated by increased arterial partial oxygen tension and decreased lung histological scores. Furthermore, EPO pretreatment attenuated seawater aspiration-induced increase in the expressions of pulmonary nuclear factor kappa B p65, inducible nitric oxide synthase, caspase-3, tumor necrosis factor-alpha, IL-1β, myeloperoxidase activity, and malondialdehyde when compared with the seawater group. Collectively, our study suggested that EPO pretreatment attenuates seawater aspiration-induced ALI by down-regulation of pulmonary pro-inflammatory cytokines, oxidative stress, and apoptosis.


Cloning, characterization and expression of escapin, a broadly antimicrobial FAD-containing L-amino acid oxidase from ink of the sea hare Aplysia californica.
A 60 kDa monomeric protein isolated from the defensive purple ink secretion of the sea hare Aplysia californica was cloned and sequenced, and is the first sea hare antimicrobial protein to be functionally expressed in E. coli. Sequence analysis suggested that this protein is a flavin-containing l-amino acid oxidase (LAAO), with one predicted potential glycosylation site, although the glycosylation could not be experimentally confirmed. This protein, which we call ;escapin', has high sequence similarity to several other gastropod proteins. Escapin was verified by NMR, mass spectroscopy and HPLC to have FAD as its flavin cofactor. Escapin's antimicrobial effects, bacteriostasis and bactericidal, were determined using a combination of two assays: (1) incubation of bacteria on solid media followed by assessment of inhibition by direct observation of zones of inhibition or by turbidity measurements; and (2) incubation of bacteria in liquid media followed by counting viable colonies after growing on agar plates. Native escapin inhibited the growth of Gram-positive and Gram-negative bacteria, including marine bacteria (Vibrio harveyii and Staphylococcus aureus) and pathogenic bacteria (Staphylococcus aureus, Streptococcus pyogenes and Pseudomonas aeruginosa). Escapin also inhibited the growth of yeast and fungi, with different efficacies. Escapin's antimicrobial activity was concentration dependent and did not decrease when stored for more than 5 months at room temperature. Escapin was bacteriostatic and not bactericidal in minimal media (e.g. salt media) with glucose, yeast extract, and a mixture of 20 amino acids each at 50 micromol l(-1), but was bactericidal in media enriched with Tryptone Peptone. Escapin was also strongly bactericidal in media with l-lysine at concentrations as low as 3 mmol l(-1) and slightly bactericidal in 50 mmol l(-1) l-arginine, but not in most other amino acids even at 50 mmol l(-1). Escapin had high oxidase activity (producing hydrogen peroxide) with either l-arginine or l-lysine as a substrate and little to no oxidase activity with other l-amino acids. Hydrogen peroxide alone (without escapin or amino acids) was strongly bacteriostatic but poorly bactericidal, similar in this respect to l-arginine but different from l-lysine in the presence of escapin. Together these results suggest that there are multiple mechanisms to escapin's antimicrobial effects, with bacteriostasis resulting largely or entirely from the effects of hydrogen peroxide produced by escapin's LAAO activity, but bactericidal effects resulting from lysine-dependent mechanisms not directly involving hydrogen peroxide. Recombinant escapin expressed in bacteria was also active against Gram-positive and Gram-negative bacteria, suggesting that glycosylation is not essential for antimicrobial activity.


Distribution of the isoprenaline-induced chloride current in rabbit heart.
Current density of the isoprenaline-induced chloride current (ICl) was measured in sino-atrial (SA) node cells and atrial and ventricular myocytes dissected enzymatically from the rabbit heart. In addition to the conventional voltage clamp method the whole-cell patch clamp method using nystatin was employed to avoid run-down of ICl in dialysed cells. Isoprenaline (0.3 microM) failed to induce ICl in the 20 atrial cells examined. The integrity of the beta-adrenergic system was established by recording the response of the Ca2+ current in the same cell. Both isoprenaline and acetylcholine failed to affect the background membrane conductance in the 20 SA node cells studied. Myocytes isolated from the epicardial region of the left ventricular wall showed relatively higher ICl density (24.9 +/- 12.1 microS/microF) than those from the endocardial side (12.3 +/- 8.5 microS/microF). We conclude that beta-receptor-operated ICl is insignificant in atrial and SA node cells.


Prediction of the Disordered Regions of Intrinsically Disordered Proteins Based on the Molecular Functions.
Intrinsically disordered proteins lack a well-defined three dimensional structure under physiological conditions while possessing the essential biological functions. They take part in various physiological processes such as signal transduction, transcription and posttranslational modifications and etc. The disordered regions are the main functional sites for intrinsically disordered proteins. Therefore, the research of the disordered regions has become a hot issue. In this paper, our motivation is to analysis of the features of disordered regions with different molecular functions and predict of different disordered regions using valid features. In this article, according to the different molecular function, we firstly divided intrinsically disordered proteins into six classes in DisProt database. Then, we extracted four features using bioinformatics methods, namely, Amino Acid Index (AAIndex), codon frequency (Codon), three kinds of protein secondary structure compositions (3PSS) and Chemical Shifts (CSs), and used these features to predict the disordered regions of the different functions by Support Vector Machine (SVM). The best overall accuracy was 99.29% using the chemical shift (CSs) as feature. In feature fusion, the overall accuracy can reach 88.70% by using CSs+AAIndex as features. The overall accuracy was up to 86.09% by using CSs+AAIndex+Codon+3PSS as features. We predicted and analyzed the disordered regions based on the molecular functions. The results showed that the prediction performance can be improved by adding chemical shifts and AAIndex as features, especially chemical shifts. Moreover, the chemical shift was the most effective feature in the prediction. We hoped that our results will be constructive for the study of intrinsically disordered proteins.


Motivations and Experiences in a Physical Activity Program for Cancer Survivors: Findings from Key Informant Interviews.
LIVESTRONG at the YMCA is an evidence-based 12-week physical activity (PA) program for cancer survivors. The purpose of our study was to understand the factors that motivated cancer survivors to begin the program, how the program impacted their habits, and how their experience influenced their motivation to continue with the program. Key informant interviews. Phone interviews conducted between April 15 and June 1, 2020. 27 cancer survivors in Texas who previously participated in the LS program. Participants completed a 30- to 60-minute interview with one of four interviewers. All interviews were recorded, transcribed, and analyzed for themes. Most interviewees were motivated to begin the program because of a desire to feel better after treatment. The most cited motivator to continue in the program was the community of cancer survivors. During the program, interviewees enjoyed learning different exercises, the community of cancer survivors, and the supportive teachers. Nearly all interviewees adopted or changed a healthy habit as a result of the program. These results could be used by healthcare professionals to better understand what motivates cancer survivors to participate in a PA program. Results could also be used to plan or modify other PA programs for cancer survivors.


[Legal consequences in cases of child abuse].
Medical child protection includes besides interdisciplinary diagnostics and treatment of physical and psychological symptoms also a discussion that looks at the ensuing legal consequences.This study analyses 21 criminally investigated cases of suspected child abuse from a 2 year study period and compares severity of injury to legal outcome.7 of those 21 criminal proceedings were already dropped by the prosecution and never went to trial. 4 of the 8 cases that led to a trial ended with a conviction. In all of the 4 cases that resulted in an acquittal the judges had been convinced that the child had been abused but found themselves unable to exactly identify the perpetrator. Our study's cases did not show a positive correlation between severity of injury and legal outcome.Diagnosing and treating children and minors within the context of medical child protection should always also include the ques-tion of possible legal consequences. The judicial process in cases of serious child abuse requires high medical expertise. Such expertise particularly includes the ability to determine the time of injury as exactly as possible and to provide precise written documentation of any medical findings. However, our study also shows that medical assessment is only one of many aspects in the legal response to child abuse.


Characteristics of infantile cases of congenital dilatation of the bile duct.
This study was performed to clarify whether infants with congenital dilatation of the bile duct (CDBD) have any specific characteristics in comparison with older children. Of 153 cases with CDBD treated at our institution between 1959 and 1997, 34 (22.2%) were infants less than 1 year of age. The control group consisted of 46 children between 1 and 4 years of age. Symptoms, laboratory data, and histological findings were compared between these two groups. As the initial symptoms, abdominal pain was not present in infantile cases, with a significant difference from the older children, and a significantly higher incidence of abdominal mass and acholic stools was noted in infantile cases. Laboratory data of serum aspartate transaminase and amylase level and amylase concentration in the bile of the common bile duct were significantly lower in the infant group than in the older children. The ratio of morphological type of cystic to cylindrical dilatation was 33 to 1 in infants with a significant difference from the control group. Infantile cases of CDBD, which mostly have cystic type dilatation, in contrast to older children, are likely to present with abdominal mass. Pancreatitis with abdominal pain related to reflux of pancreatic juice into the biliary duct appears to be uncommon in infantile cases.


Food marketing to children in the United States: Can industry voluntarily do the right thing for children's health?
Food marketing is a major contributor to high rates of obesity and diet-related disease among children. Researchers, advocates, and policymakers have called for improvements in the nutrition quality of foods marketed to children to improve children's health. In the United States, for over 10 years, the food and beverage industry has responded with self-regulatory initiatives, touting the success of these efforts. However, public health researchers have documented very limited improvements. As a product of conference proceedings, we briefly summarize US self-regulation of food and beverage marketing to children, argue that reliance on industry self-regulation limits meaningful change, and explain why existing food companies cannot market truly healthy foods to children. After over a decade of self-regulation, industry continues to exploit loopholes and bombard children with marketing for foods that can negatively impact their health. Still, the political will to advocate for effective government regulation remains a challenge. Shifts in parents' attitudes toward supporting policies to protect children from food marketing and local government actions to improve the food environment are promising indicators of increasing demand for action. However, sustained and well-publicized research and advocacy are necessary to generate broader support to enact such policies at the state and federal level in order to effectively address this public health crisis.


DNA cytometry and cytology by quantitative fluorescence image analysis in symptomatic bladder cancer patients.
A semi-automated quantitative fluorescence image analysis (QFIA) technique was developed with the Leitz TAS-Plus to detect bladder cancer using hyperploidy in urinary cells. Absolute nuclear fluorescence intensity (ANFI) (emission at 540 nm with excitation at 436 nm) of individual acridine-orange-stained cells was quantitated using (1) QFIA and (2) simple filter microspectrofluorophotometry (SFM). Both methods employed an internal phosphor particle standard which, when once calibrated against the DNA content of normal cells, obviates the necessity of routinely calibrating against normal cells in each sample. Results of SFM and QFIA were compared with routine Papanicolaou (Pap) cytopathology, using histopathology as the diagnostic standard in 272 samples from 67 symptomatic patients. The sensitivities for detecting low-grade transitional-cell carcinoma were 86% for SFM, 76% for QFIA, and 33% for Pap cytology. QFIA and SFM were significantly more sensitive at detecting bladder cancer than was Pap (0.01 greater than p greater than 0.001). Comparison of sensitivity obtained with bladder washings and urine samples showed that noninvasively obtained urines can be used. ANFI also detected recurrent and precancerous bladder lesions and kidney, ureter, and prostate lesions. This approach may prove generally useful in quantifying biochemical and immunological probes and should be broadly applicable as a research tool for studying the relationship of biochemical markers in the pathogenesis of disease and as a test for cancer control.


PAF antagonistic activity of 2-hydroxy-3-methoxybenzoic acid glucose ester from Gentiana scabra.
In order to find out anti-platelet activating factor (PAF) from natural resources, Korean medicinal plants used for the treatments of peripheral circulation disorders were tested for their possible protective effects on PAF-induced anaphylactic shock. From the above screening, the methanol extract of Gentiana scabra showed a potent antagonistic activity against PAF. Water suspension of the extract was partitioned with CH2Cl2 and EtOAc, successively. The EtOAc fraction which showed the highest activity was chromatographed on silica gel to yield 6 fractions. From the fraction which showed higher PAF-antagonistic activity than the other fractions, compound 1 was isolated by recrystallization. On the basis of spectral data, compound 1 was identified as 2-hydroxy-3-methoxybenzoic acid glucose ester. The compound prevented the mice from the PAF-induced death at a dose of 300 micrograms/mouse.


Deficiency in homogentisic acid oxidase activity associated with the brown phenotype of Dictyostelium discoideum.
Mutations at the bwnA locus of Dictyostelium discoideum were found to result in drastically reduced levels of activity of the enzyme homogentisic acid oxidase. It is proposed that the brown phenotype associated with these mutations results from the accumulation of an intermediate in the tyrosine degradative pathway, homogentisic acid, and its subsequent spontaneous oxidation. This knowledge is used to devise improved screening procedures potentially useful in the parasexual genetics system of this organism.


A Comparative Evaluation of Low-Level Laser and Topical Steroid Therapies for the Treatment of Erosive-Atrophic Lichen Planus.
Oral lichen planus (OLP) is a chronic inflammatory disease that causes bilateral white striations, papules, or plaques on the buccal mucosa, tongue, and gingivae. Erythema, erosions, and blisters may or may not be present. Several empirical therapies have been used in the treatment of (OLP). To evaluate the effect of low level laser therapy (LLLT) versus topical steroids for the treatment of erosive-atrophic lichen planus. Twenty-four patients with erosive-atrophic (OLP) were categorized into two groups. In the first group patients were treated with 970 nm diode laser irradiation, while, in the second group patients used topical corticosteroids (0.1% triamcinolone acetonide orabase). The gender, medical history and pain score were recorded. The pain score was measured before and after treatment by visual analogue scale (VAS). Steroid-treated group (0.1% triamcinolone acetonide orabase) show reduced pain score than laser group. Topical steroids are more effective than LLLT. LLLT may be used as an alternative treatment for symptomatic OLP when steroids are contraindicated.


Dentin smear layer: an asset or a liability for bonding?
Despite concerns and claims that the smear layer on dentin is undesirable for bonding, supportive evidence is lacking. The clinical efficacy of various agents for smear layer removal and the effect of smear layer removal on the bond strengths of a glass-ionomer cement and three representative dentin bonding agents were examined. For all but one dentin bonding agent (Gluma), a 15-second treatment with 17% EDTA caused a reduction in bond strength. For Gluma, no significant bond was obtained without EDTA treatment. While Gluma probably bonds via dentinal collagen, the other materials interact primarily with dentinal calcium. Removal of the smear layer for adhesives reliant on the presence of calcium is therefore undesirable. The clinical effects of some agents proposed for smear layer removal were examined by SEM of replicas.


Detection of integrated type-C viral DNA fragments in two primates (human and gibbon) by the restriction enzyme blotting technique.
We have shown that 1. partial provirus integration can be a possible result of a natural infection, and may serve as a model in animal systems where a viral etiology is implicated but detection of a major fraction of the virus genome is rare; 2. All human DNA contains some sequences that hybridize specifically with genomes of SiSV-SiSAV, suggesting that viruses of this group have infected humans in the past and recombined with human cellular DNA. 3. Finally, DNA from uncultured leukocytes of two leukemic patients, one being HL23, which yielded the virus HL23V in culture, was shown to have virus specific fragments related to BaEV. Another human DNA sample revealed virus specific fragments related to SiSV(SiSAV). These fragments are probably acquired by infection.


Identification of hepatitis C virus RNA in peritoneal dialysis fluid of patients with viremia.
The potential risk for transmission of hepatitis C virus (HCV) by peritoneal dialysis (PD) has been studied previously, with conflicting results. To assess whether HCV crosses the peritoneal membrane, the following determinations were performed in 16 patients (7 males, 9 females; mean age 41.8 years; mean time on PD 14 +/- 15 months) undergoing PD: serum anti-HCV using second-generation enzyme-linked immunosorbent assay (ELISA), serum and PD fluid HCV RNA by nested polymerase chain reaction, HCV genotyping by restriction fragment length polymorphism, and serum HCV load by branched DNA assay. Anti-HCV was positive in 10 patients. Serum HCV RNA was positive in 7 anti-HCV-positive patients and negative in all anti-HCV-negative patients. Fluid HCV RNA was detected in 5 (71.4%) patients testing positive for serum HCV RNA and in none testing negative for serum HCV RNA. Serum HCV genotype was 1a in 3 patients and 1b in 4; PD fluid HCV genotype was 1a in 1 patient and 1b in 4. Genotypes in serum and fluid were concordant when both were positive. Serum viral load ranged from nondetectable by the quantitative method to 5.1 MEq genome/mL in patients with fluid infection, and 1.05 MEq and 29 MEq genome/mL in the remaining 2 patients without detectable HCV in PD fLuid. HCV crosses the peritoneal membrane and may be detected in the dialysate of PD patients with proven viremia. Although our study population was small for firm conclusions to be drawn, this passage does not seem to depend upon the serum viral load. Our data support the notion that PD fluid needs careful handling and local disinfection to prevent possible spreading of viruses, in the institutional and the domestic environments.


Behavioral effects of the novel potent cannabinoid CB1 agonist AM 4054.
Due to the ubiquity of the CB1 cannabinoid receptor throughout the nervous system, as well as the many potential therapeutic uses of CB1 agonist-based interventions, it is desirable to synthesize novel probes of the CB1 receptor. Here, the acute behavioral effects of systemic (i.p.) administration of the putative novel CB1 full agonist AM 4054 were tested in rats. In Experiment 1, a dose range (0.15625-1.25 mg/kg) of AM 4054 produced effects consistent with CB1 agonism in the cannabinoid tetrad of tasks in rats, including induction of analgesia, catalepsy, hypothermia, and locomotor suppression. These effects were reversed with the CB1-selective inverse agonist AM 251 in Experiment 2, indicating that AM 4054 produced CB1 receptor-mediated effects. Analysis of open-field activity indicated that the reduction in locomotion is more consistent with general motor slowing than anxiogenesis. AM 4054 (0.0625-0.5 mg/kg) also dose-dependently reduced fixed-ratio 5 (FR5) operant responding for food in Experiment 3, and microanalysis of the timing and rate of lever pressing indicated a pattern of suppression similar to other CB1 agonists. Minimum doses of AM 4054 (0.125-0.3125 mg/kg) required to produce significant effects in these behavioral assays were lower than those of many CB1 agonists. It is likely that AM 4054 is a potent pharmacological tool for assessment of cannabinoid receptor function.


Early diagnosis of chemotherapy-induced cardiomyopathy: a prospective tissue Doppler imaging study.
The aim of our study was to compare the applicability of the conventional echocardiography and a novel method, tissue Doppler imaging (TDI) in detection of late or subclinical cardiotoxicity following anthracycline chemotherapy in long-term follow up. Forty women (31 to 65 years) were enrolled, who had not received anthracyclines previously and had normal cardiac function. The control group consisted of 20 healthy persons of similar age range. In addition to standard echocardiographic measurements, each patient underwent specific measurements (E-septum separation, pulmonary venous flow) as well. Furthermore, the myocardial velocity of numerous segments of the mitral anulus obtained with pulsed wave TDI was also detected over a two-year-long period. Systolic left ventricular function did not change significantly either in the study or in the control group. After one year, diastolic left ventricular function was impaired in 39 patients (97.5%), and 29 (72.5%) of these showed clear changes by means of the traditional E/A ratio and TDI. However, in ten patients (25%) the diastolic dysfunction could only be detected with TDI. At the end of the study diastolic dysfunction was detected in each patient, but in 13 patients (32.5%) the relaxation disorder could be revealed only with TDI. Detectable myocardial damage occurred in the study group as a result of anthracycline therapy. Our results confirmed our assumptions that TDI is a more precise and useful examination method than the traditional ones (E/A ratio or deceleration time) to demonstrate isolated diastolic dysfunction. TDI may become a regularly and more widely used noninvasive method to detect subclinical cardiotoxicity emerging after chemotherapy.


Timely detection of influenza outbreaks in Iran: Evaluating the performance of the exponentially weighted moving average.
Real time detection of influenza outbreaks is necessary by public health authorities. The aim of this study was to determine the performance of the Exponentially Weighted Moving Average (EWMA) in detection of influenza outbreaks in Iran from January 2010 to December 2015. The EWMA algorithms were applied to weekly counts of suspected cases of influenza (influenza-like illnesses) to detect real outbreaks which have occurred in Iran from January 2010 to December 2015. The performance of EWMA algorithms was measured using sensitivity, specificity, false alarm rate, likelihood ratios and area under the receiver operating characteristics (ROC) curve. Sensitivity of the EWMA for all of occurred outbreaks from 2010 to 2015 was 40% (95% CI: 29%, 50%). The corresponding value of detection of occurred outbreaks in 2010, 2011, 2013, 2014 and 2015 were 50%, 100%, 76%, 64% and 100% respectively. Among different algorithms, EWMA with λ=0.5 had the best performance (area under the Curve=100%) for the detection of occurred outbreaks in 2011. Our findings revealed that the performance of the EWMA in the real time detection influenza outbreak in Iran is appropriate. However, public health surveillance systems need to use different outbreak detection methods for detecting aberrations in influenza-like illnesses activity.


Understanding the physiology of the asymptomatic diaphragm of the M1592V hyperkalemic periodic paralysis mouse.
The diaphragm muscle of hyperkalemic periodic paralysis (HyperKPP) patients and of the M1592V HyperKPP mouse model rarely suffers from the myotonic and paralytic symptoms that occur in limb muscles. Enigmatically, HyperKPP diaphragm expresses the mutant NaV1.4 channel and, more importantly, has an abnormally high Na(+) influx similar to that in extensor digitorum longus (EDL) and soleus, two hindlimb muscles suffering from the robust HyperKPP abnormalities. The objective was to uncover the physiological mechanisms that render HyperKPP diaphragm asymptomatic. A first mechanism involves efficient maintenance of resting membrane polarization in HyperKPP diaphragm at various extracellular K(+) concentrations compared with larger membrane depolarizations in HyperKPP EDL and soleus. The improved resting membrane potential (EM) results from significantly increased Na(+) K(+) pump electrogenic activity, and not from an increased protein content. Action potential amplitude was greater in HyperKPP diaphragm than in HyperKPP soleus and EDL, providing a second mechanism for the asymptomatic behavior of the HyperKPP diaphragm. One suggested mechanism for the greater action potential amplitude is lower intracellular Na(+) concentration because of greater Na(+) K(+) pump activity, allowing better Na(+) current during the action potential depolarization phase. Finally, HyperKPP diaphragm had a greater capacity to generate force at depolarized EM compared with wild-type diaphragm. Action potential amplitude was not different between wild-type and HyperKPP diaphragm. There was also no evidence for an increased activity of the Na(+)-Ca(2+) exchanger working in the reverse mode in the HyperKPP diaphragm compared with the wild-type diaphragm. So, a third mechanism remains to be elucidated to fully understand how HyperKPP diaphragm generates more force compared with wild type. Although the mechanism for the greater force at depolarized resting EM remains to be determined, this study provides support for the modulation of the Na(+) K(+) pump as a component of therapy to alleviate weakness in HyperKPP.


Human cytomegalovirus induced changes in rabbit cells. Brief report.
After infection with human cytomegalovirus, rabbit lung fibroblasts showed, during the four week period of the experiment, cytopathic changes and virus-specific antigens demonstrable by fluorescent antibody. Infectious virus could be recovered from the infected cells by co-cultivation with human lung fibroblasts.


An optimum strategy for substrate mixture and pretreatment in biogas plants: Potential application for high-pH waste management.
Optimization of anaerobic digestion poses many practical constraints. Therefore, a new approach was developed by integrating mathematical modeling and desirability analysis to determine optimum amounts of input factors. For this purpose, different proportions of co-digestion (grapefruit waste:cow manure) and pretreatments (NaOH and H2O2) were tested on the basis of a combined D-optimal experimental design. Different models were developed for certain slurry properties and CH4 production (responses) depending on the input factors. To improve the models, Box-Cox transformation was used to transform the models into more accurate formats. The improved models were then used in desirability analysis, and optimum ranges were determined instead of optimum absolute values in three cases of given constraints, (i) constraints of the slurry properties, (ii) increase in CH4 production, and (iii) constraints on all the responses (more important for plant efficiency). The optimum ranges were extracted for the desirability levels with values greater than 0.9 × (maximum desirability value). For the constraints given in all the responses, the optimum range of grapefruit waste:cow manure proportion was 2.5%:97.5% to 25%:75%, the optimum range of NaOH pretreatment was 0.3-2.64%, and the optimum range of H2O2 was range experimented except for 1.32-1.68%. Similar trends were determined for the other cases of constraints. To clarify the method of desirability analysis, the overlaying method was used to determine regions of interest according to some predefined constraints. Simultaneous consideration of range optimization and region of interest showed that (i) an amount greater than 25% grapefruit waste in the digestion decreased the CH4 production significantly, and (ii) plant efficiency was improved with all amounts of H2O2 except 1.32-1.68%, and with amounts of 0.3-1.2% and 1.8-2.64% of NaOH. As shown the optimum ranges are more common for practical use in plants.


Social media, parenting, and well-being.
One of the key challenges faced by many parents is to manage the pervasiveness of social media in adolescents' lives and its effects on adolescents' well-being (e.g., life satisfaction) and ill-being (e.g., depressive symptoms). Parents may manage adolescents' social media use and social media-induced well-being and ill-being through media-specific parenting: parental actions to restrict, regulate, and discuss adolescents' social media use. Recent evidence suggests that media-specific parenting may reduce adolescents' anxiety and depressive symptoms and minimize the effects of cyberbullying on adolescents' depressive symptoms. However, more robust evidence regarding the moderating role of media-specific parenting and the direction of effects has to be established to understand how parents may shape the effects of social media on adolescents' well-being and ill-being.


Repressing distress in childhood: a defense against health-related stress.
This paper is a review of empirical investigations of the repressive adaptive style in youth. Studies were selected on the basis of their adherence to Weinberger et al.'s (J Abnorm Psychol 88: 369-380, 1979) paradigm, consisting of the interaction between a measure of distress and a measure of defensiveness to categorize repressors. The presence of a repressive style of adaptation was identified in adolescence, especially among pediatric populations. Adolescent repressors were found to exhibit characteristics similar to those identified among adult samples (i.e., self-deception, biased self-reports, and inhibition of signals of distress). Only one study focused on young repressors' autonomic reactivity, which is another main characteristic of a repressive adaptive style in adulthood. Methodological inconsistencies between child studies are highlighted and weaknesses in the psychometric properties of defensiveness measures in childhood are discussed. Future investigations should examine the impact of a repressive adaptive style on health outcomes and behaviors to see if adult health data associated with a repressive style of adaptation are replicable in childhood.


Psychosocial assessment of adolescents and young adults in paediatric hospital settings: patient and staff perspectives on implementation of the e-HEEADSSS.
The main causes of morbidity and mortality for adolescents and young adults are preventable and stem from psychosocial and behavioural concerns. Psychosocial assessments can help clinicians to identify and respond holistically to risks and strengths that may impact upon a young person's physical and mental health. Despite broad support at a policy level, the implementation of routine psychosocial screening for young people remains varied in Australian health settings. The current study focused on the pilot implementation of a digital patient-completed psychosocial assessment (the e-HEEADSSS) at the Sydney Children's Hospital Network. The aim of this research was to evaluate patient and staff barriers and facilitators to local implementation. The research used a qualitative descriptive research design. Semi-structured interviews were conducted online with 8 young patients and 8 staff members who had completed or actioned an e-HEEADSSS assessment within the prior 5 weeks. Qualitative coding of interview transcripts was carried out in NVivo 12. The Consolidated Framework for Implementation Research guided the interview framework and qualitative analyses. Results demonstrated strong support for the e-HEEADSSS from patients and staff. Key reported facilitators included strong design and functionality, reduced time requirements, greater convenience, improved disclosure, adaptability across settings, greater perceived privacy, improved fidelity, and reduced stigma for young people. The key barriers were related to concerns over available resources, the sustainability and continuity of staff training, perceived availability of clinical pathways for follow-up and referrals, and risks related to off-site completions. Clinicians need to adequately explain the e-HEEADSSS assessment to patients, educate them about it, and make sure that they receive timely feedback on the results. Greater reassurance and education regarding the rigour of confidentiality and data handling procedures is required for patients and staff. Our findings indicate that continued work is required to support the integration and sustainability of digital psychosocial assessments for young people at the Sydney Children's Hospital Network. The e-HEEADSSS shows promise as an implementable intervention to achieve this goal. Further research is required to determine the scalability of this intervention across the broader health system.


The "human"-like morphology of the swine papilla ilealis.
The morphology of the ileocecocolic transition, between the small and large intestine was studied in 33 male, adult pigs of unknown breed. The results were analyzed by the Wilcoxon Test (alpha < or = 0.05). The ileum opened into the large intestine, in all of the cases, at the level of the cecocolic junction in the form of a conical papilla (ileal papilla) turned towards the large intestine, with an oblique caudal and lateral direction, pointing to the cecal lumen. The cranial contour is higher than the caudal one, with average values of 3.0 cm, and 1.5 cm in the fresh specimens and 2.8 cm and 1.4 cm after fixation of the specimens. The average diameter of the papilla apex was 1.5 cm, both in the fresh specimens and in the fixed ones. In 100% of the cases the ileal papilla appeared with a star-shaped orifice in its apex in both the fresh and in the fixed specimens. Our studies showed that the transition between the small and large intestine of the swine is ileocecocolic, thus similar to humans and different from the ileocecal (Perissodactyla, Rodentia, Lagomorpha) and, according to most descriptions, ileocolic (dog) transitions found in other animals.


Monitoring of Staphylococcus xylosus DSM 20266 added as starter during fermentation and ripening of soppressata molisana, a typical Italian sausage.
"Soppressata molisana", a fermented sausage produced in southern Italy, is commonly obtained without starter addition. However, the use of starter cultures is more and more recommended in meat fermentation processes in order to guarantee stable production performance. In this study, the survival of the Staphylococcus xylosus DSM 20266 was evaluated during the ripening of "soppressata molisana" fermented sausage. The fastest method of RAPD-PCR was employed for discrimination of the added strain from those naturally present during the ripening of the "soppressata molisana". The results obtained were confirmed by analysis of the DNA macrorestriction profile by PFGE. The electrophoretic pattern of bacterial total proteins was also studied, but clear differences between the different strains could not be detected. The RAPD technique was a valid tool for monitoring Staph. xylosus DSM 20266 in "sopressata molisana". This study highlights the possibility of monitoring the presence of Staph. xylosus strains during the ripening of fermented sausages by a reliable and repeatable technique such as RAPD.


Evidence for a dual-factor concept of psychopathological emotional deficit: anhedonia and sensation-seeking.
Correlations between measures of anhedonia and sensation-seeking were calculated in two psychiatric samples. The correlations indicated that, despite their conceptual similarity, the two represent different motivational deficits. Ther correlates appeared to indicate that sensation-seeking represents neurotic inhibition, while anhedonia reflects a separate motivational deficit apparently characteristic of process schizophrenics.


Is there an interrelationship between the effects of antipsychotics on psychopathology and on metabolism?
Increased body weight and hyperlipidemia caused by antipsychotics may be associated with improved antipsychotic efficacy in schizophrenia. If this association has a causal interrelationship via a genuine pathophysiological mechanism, then body weight loss in antipsychotic-treated patients would be accompanied by worsened psychopathology. This could have clinical implications. To explore whether the decreased body weight in these patients is associated with a worsened psychopathology. In our previously published study, a 16 week treatment period with add-on orlistat (but not placebo) resulted in body weight loss in male (but not female) clozapine- or olanzapine-treated overweight or obese patients. In the current study, we investigated whether body weight loss in those male patients could worsen psychosis. Changes in the Positive and Negative Syndrome Scale (PANSS) scores within groups and body weight changes and lipid profiles over the treatment period were analysed by the paired samples t-test. Between-group comparisons were analysed by the independent samples t-test. Over the treatment period body weight decreased by 2.56 ± 3.25 kg from initial 106.02 ± 12.61 kg (p = 0.04) for the orlistat group, with no statistically significant changes for the placebo group. Lipid levels did not change in either group. The orlistat-induced weight decrease was not associated with worsening in the PANSS scores. Weight loss was not associated with a worsening of psychosis. The interrelationship between the antipsychotic-induced weigh gain and improved schizophrenia psychopathology observed in earlier studies appears to be indirect. Orlistat treatment in our study did not worsen psychopathology in this population.


Three antigenic variant groups in human respiratory syncytial virus subgroup B isolated in Japan.
Nineteen hybridomas producing monoclonal antibodies (MAbs) against the structural proteins of strain 58-17, a subgroup B field strain of respiratory syncytial virus (RSV) isolated in Japan, were obtained by fusion of X63 myeloma cells with spleen cells from BALB/c mice immunized with the virus-infected HEp-2 cells. Seven clones were found to produce antibodies against the fusion protein (F), five against the large glycoprotein (G), five against the nucleoprotein (NP) and two against the 22k protein by radioimmunoprecipitation assay. By competitive binding assay with the MAbs, at least seven, two, three and one epitopes were defined on the F, G, NP and 22k protein components of subgroup B strain, respectively. Of these epitopes, three, two and one epitopes on the F, G and NP components were different from subgroup A strain, respectively. Fifty-three other field strains of subgroup B isolated in Sapporo, Japan, during nine epidemic years from 1980 to 1989, were examined for reactivity with the MAbs by ELISA. Different reactivity to one anti-NP antibody suggested that the 53 strains can be divided into three groups (B-a: 26 strains, B-b: 26 strains, and one other strain). The dominant strain prevailing during the 1984 to 1988 epidemic years had changed from B-a to B-b. All of the 53 subgroup B strains reacted similarly with the other 18 MAbs.


Right ventricular involvement and the extent of left ventricular enhancement with magnetic resonance predict adverse outcome in pulmonary sarcoidosis.
Cardiac involvement is the main determinant of poor outcomes in sarcoidosis. Right ventricular (RV) dysfunction and left ventricular (LV) late gadolinium enhancement (LGE) have been reported to be predictive of adverse outcome in non-ischaemic cardiomyopathies. The aim of our study was to determine whether delayed RV LGE with cardiovascular magnetic resonance would be predictive of adverse events in addition to LV LGE during the long-term follow-up of pulmonary sarcoidosis patients. Eighty-four consecutive biopsy-proven pulmonary sarcoidosis patients were followed for a median of 56 months [38-74] after baseline delayed contrast-enhanced cardiac magnetic resonance. The composite primary endpoint consisted of admission for congestive heart failure, sustained ventricular tachycardia, appropriate implantable cardioverter defibrillator therapy, pacemaker implantation for high degree atrio-ventricular block, or cardiac death. The composite secondary endpoint included all-cause mortality in addition to the primary endpoint. RV and LV LGE were demonstrated in respectively 12 and 27 patients. Five of 10 events included in the primary endpoint occurred in the group with RV LGE. RV LGE, LV, or biventricular LGE yielded Cox hazard ratios of 8.71 [95% confidence interval (CI) 1.90-23.81], 9.22 (95% CI 1.96-43.45), and 12.09 (95% CI 3.43-42.68) for the composite primary endpoint. In a multivariate model, the predictive value of biventricular LGE for the composite primary and secondary endpoints was strongest. Kaplan-Meier event-free survival curves were most significant for RV LGE and biventricular LGE (log rank with P < 0.001). Biventricular LGE at presentation is the strongest, independent predictor of adverse outcome during long-term follow-up. Asymptomatic myocardial scar <8% of LV mass carried a favourable long-term outcome.


Proteomic analysis of interstitial aortic valve cells acquiring a pro-calcific profile.
Cell-driven processes are now considered of relevance for the pathogenesis of aortic stenosis. In particular, during calcific valve degeneration, interstitial valve cells (VIC) resident in the leaflet can acquire an osteogenic/pro-calcific profile and actively contribute to matrix mineralization. The proteomic study described in this chapter is undertaken to investigate modifications in the proteome of bovine aortic VIC acquiring a calcifying phenotype. This approach can be useful to clarify cellular pathways involved in VIC pro-calcific differentiation and identify innovative therapeutic targets.


Neuroprotective action of MPEP, a selective mGluR5 antagonist, in methamphetamine-induced dopaminergic neurotoxicity is associated with a decrease in dopamine outflow and inhibition of hyperthermia in rats.
The aim of this study was to examine the role of metabotropic glutamate receptor 5 (mGluR5) in the toxic action of methamphetamine on dopaminergic neurones in rats. Methamphetamine (10 mg/kg sc), administered five times, reduced the levels of dopamine and its metabolites in striatal tissue when measured 72 h after the last injection. A selective antagonist of mGluR5, 2-methyl-6-(phenylethynyl)pyridine (MPEP; 5 mg/kg ip), when administered five times immediately before each methamphetamine injection reversed the above-mentioned methamphetamine effects. A single MPEP (5 mg/kg ip) injection reduced the basal extracellular dopamine level in the striatum, as well as dopamine release stimulated either by methamphetamine (10 mg/kg sc) or by intrastriatally administered veratridine (100 microM). Moreover, it transiently diminished the methamphetamine (10 mg/kg sc)-induced hyperthermia and reduced basal body temperature. MPEP administered into the striatum at high concentrations (500 microM) increased extracellular dopamine levels, while lower concentrations (50-100 microM) were devoid of any effect. The results of this study suggest that the blockade of mGluR5 by MPEP may protect dopaminergic neurones against methamphetamine-induced toxicity. Neuroprotection rendered by MPEP may be associated with the reduction of the methamphetamine-induced dopamine efflux in the striatum due to the blockade of extrastriatal mGluR5, and with a decrease in hyperthermia.


"Hunting Otherwise" : Women's Hunting in Two Contemporary Forager-Horticulturalist Societies.
Although subsistence hunting is cross-culturally an activity led and practiced mostly by men, a rich body of literature shows that in many small-scale societies women also engage in hunting in varied and often inconspicuous ways. Using data collected among two contemporary forager-horticulturalist societies facing rapid change (the Tsimane' of Bolivia and the Baka of Cameroon), we compare the technological and social characteristics of hunting trips led by women and men and analyze the specific socioeconomic characteristics that facilitate or constrain women's engagement in hunting. Results from interviews on daily activities with 121 Tsimane' (63 women and 58 men) and 159 Baka (83 women and 76 men) show that Tsimane' and Baka women participate in subsistence hunting, albeit using different techniques and in different social contexts than men. We also found differences in the individual and household socioeconomic profiles of Tsimane' and Baka women who hunt and those who do not hunt. Moreover, the characteristics that differentiate hunter and non-hunter women vary from one society to the other, suggesting that gender roles in relation to hunting are fluid and likely to change, not only across societies, but also as societies change.


Molecular mechanisms of CRISPR-mediated microbial immunity.
Bacteriophages (phages) infect bacteria in order to replicate and burst out of the host, killing the cell, when reproduction is completed. Thus, from a bacterial perspective, phages pose a persistent lethal threat to bacterial populations. Not surprisingly, bacteria evolved multiple defense barriers to interfere with nearly every step of phage life cycles. Phages respond to this selection pressure by counter-evolving their genomes to evade bacterial resistance. The antagonistic interaction between bacteria and rapidly diversifying viruses promotes the evolution and dissemination of bacteriophage-resistance mechanisms in bacteria. Recently, an adaptive microbial immune system, named clustered regularly interspaced short palindromic repeats (CRISPR) and which provides acquired immunity against viruses and plasmids, has been identified. Unlike the restriction–modification anti-phage barrier that subjects to cleavage any foreign DNA lacking a protective methyl-tag in the target site, the CRISPR–Cas systems are invader-specific, adaptive, and heritable. In this review, we focus on the molecular mechanisms of interference/immunity provided by different CRISPR–Cas systems.


Incidence of reentry with an excitable gap in ventricular tachycardia: a prospective evaluation utilizing transient entrainment.
The demonstration of transient entrainment has been proposed as evidence of reentry, with an excitable gap as the probable mechanism of tachycardia. A prospective series of 27 consecutive patients with sustained ventricular tachycardia induced by programmed electrical stimulation was studied to determine the frequency with which transient entrainment can be demonstrated and to define the optimal location of pacing and recording electrodes. In all patients, electrodes for pacing and recording were placed in both the left and right ventricles during electrophysiologic study. Among the 19 patients in whom the response to rapid pacing could be evaluated (25 episodes of ventricular tachycardia), transient entrainment was demonstrated in 79% (76% of episodes). Ten of 12 episodes of ventricular tachycardia with a left bundle branch block QRS configuration in lead V1 and 9 of 13 episodes with a right bundle branch block QRS configuration could be transiently entrained (p = NS). Transient entrainment was demonstrated for 8 of 11 episodes of ventricular tachycardia with a left bundle branch block configuration during pacing from the left ventricle, but for only 2 of 10 episodes during pacing from the right ventricular apex (p less than 0.05). Conversely, 9 of 13 episodes of ventricular tachycardia with a right bundle branch block configuration were transiently entrained during pacing from the right ventricular apex, but 0 of 10 episodes were transiently entrained by left ventricular pacing (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


[A case of returning radial nerve function after the excision of a neuro-sarcoma type tumor].
A case of 68 years old patient with neurosarcoma of the radial nerve is presented. After total resection of the tumour and the suture of the sheath of the nerve its function has returned. Eight years later the recurrence took place and 2 years later the limb has been amputated.


Aortic dissection presenting with pancreatitis.
Aortic dissections can be challenging to diagnose in the emergency department (ED) because patients can present with a variety of complaints. We present a case involving a woman with multiple comorbidities, who had experienced intermittent abdominal pain for several months, which worsened in the days leading up to her ED visit. She was diagnosed with pancreatitis based on her history and blood work but, incidentally, on computed tomographic scan, also was found to have a Stanford type B aortic dissection. Her dissection and pancreatitis were managed medically with tight blood pressure control without the need for surgical intervention. Several case studies associating acute aortic dissection with acute pancreatitis have been published, but it remains unclear whether these 2 conditions have a causal relationship.


Photoluminescence enhancement in quantum-dot-polymer films with CO2 micropores through KHCO3 decomposition.
Quantum-dot (QDs) polymer composite films, which are key components in recent display applications, require improved photoluminescence (PL) intensity and color conversion efficiency for better display quality and low power consumption. In this study, we developed a novel approach to improve the photoluminescence (PL) of quantum dot (QDs)-polymer nanocomposite films. This was achieved by incorporating CO2 micropores and scattering particles into QD-embedded photopolymerizable polymer films. CO2 micropores were generated by the decomposition of KHCO3 in the film. The CO2 micropores, along with the partially decomposed KHCO3 microparticles, act as a scattering medium that increases the photon absorbance and improves the PL intensity. The effect of KHCO3 annealing temperature on various optical properties is investigated, and it is found that a large number of uniform micropores are created in the film at an optimal temperature, 110 ℃. Compared to an ordinary QD-polymer film, the PL of the QD-hybrid-foamed polymer film increases by 4.2 times. This method is fast and economically efficient, and provides insights into the design of high-performance optoelectronic devices.


Vessel density changes in choroid, chorio-capillaries, deep and superficial retinal plexues on OCTA in normal ageing and various stages of age-related macular degeneration.
To study vessel density (VD) on optical coherence tomography angiography at choroid, chorio-capillaries (CC) and various retinal levels in normal population and various stages of dry AMD and how these changes progress with increase in severity of the disease. Prospective, observational, cross-sectional study was done on 252 eyes of 132 patients (males: 61, females: 71) presenting to tertiary-care centre in Central India between February 2021 and January 2022. For study purpose, eyes were divided into five groups according to the size and number of the drusen, viz, Group 1: No AMD (< 50 years), Group 2: No AMD (> 50 years), Group 3: Early AMD, Group 4: Intermediate AMD and Group 5: Advanced AMD. In all eyes, VD was measured at choroid, CC, deep capillary plexus (DCP) of retina and superficial capillary plexus (SCP) of retina. The mean age in case cohort is 61.90 ± 7.97 years. The mean vascular density differed significantly across diagnosis types in all the quadrants (p < 0.05) at choroid, CC and DCP level. At SCP level, the differences were significant across the groups except at the central quadrant. Vessel density was found to be more in early AMD cohort when compared to No AMD (> 50 years) cohort at SCP and DCP level, while it showed continuous reduction later in intermediate and advanced AMD cohort. With increase in the severity of disease, significant reduction in VD is also seen in retinal plexuses, along with the changes in choroid and CC. These VD maps may play a role as non-invasive biomarkers for healthy and diseased ageing.


Dose distributions around selectron applicators.
Measured and calculated dose distributions around selectron applicators, loaded with 60Co high dose rate pellets, are presented. The effect of the stopping screw, spacers, pellets themselves and the applicator wall on the dose distribution is discussed. The measured dose distribution is in almost perfect agreement with the calculated distribution in planes perpendicular to the applicator axis and containing a source. On the applicator axis directly below the applicator the measured dose amounts to about 75% of the calculated value, when only the stopping screw attenuates the beam from a pellet. When the beam is attenuated by spacers in addition to the stopping screw, the discrepancy between the calculated and measured dose may exceed 50%. Clinically relevant source geometries are also discussed. It is shown that for most regions around the applicator the method of a simple addition of dose contributions from individual point sources is an acceptable approximation for the calculation of dose distributions around the selectron applicators.


Pediatric delirium is associated with increased brain injury marker levels in cardiac surgery patients.
Despite global consensus on the importance of screening pediatric delirium, correlations between pediatric delirium during acute brain injury and adult delirium are unclear. Therefore, we hypothesized that similar pediatric biomarkers reflect acute brain injury as in adult delirium. We observed pediatric cardiac surgery patients from neonatal age to 18 years, who were admitted to our pediatric intensive care unit after cardiovascular operations between October 2019 to June 2020, up to post-operative day 3 (4 days total). We recorded age, sex, risk score (Risk Adjustment in Congenital Heart Surgery [RACHS-1]), midazolam/dexmedetomidine/fentanyl dosage, and pediatric Sequential Organ Failure Assessment (pSOFA). Richmond Agitation-Sedation Scale (RASS), Cornell Assessment of Pediatric Delirium (CAPD), Face, Leg, Activity, Consolability (FLACC) behavioral scale, and Withdrawal Assessment Tool (WAT-1) scales were used and serum sampling for neuron specific enolase (NSE) was conducted. Consciousness status was considered hierarchical (coma > delirium > normal) and associations between conscious status and NSE were conducted by hierarchical Bayesian modeling. We analyzed 134 data points from 40 patients (median age 12 months). In the multi-regression model, NSE was positively associated with coma [posterior odds ratio (OR) = 1.1, 95% credible interval (CrI) 1.01-1.19] while pSOFA [posterior OR = 1.63, 95% CrI 1.17-2.5], midazolam [posterior OR = 1.02, 95% CrI 1.01-1.04], and dexmedetomidine [posterior OR = 9.52, 95% CrI 1.02-108.85] were also associated. We also evaluated consciousness state probability at each NSE concentration and confirmed both that consciousness was hierarchically sorted and CAPD scores were also associated with NSE [posterior OR = 1.32, 95% CrI 1.09-1.58]. "Eye contact" (r = 0.55) was the most correlated component with NSE within the pain, withdrawal syndrome, and PD items. PD within the hierarchy of consciousness (coma, delirium, normal) and CAPD scores are associated with brain injury marker levels. Using pediatric delirium assessment tools for monitoring brain injury, especially eye contact, is a reliable method for observing PD.


Selective, stability-indicating assay of the major ipecacuanha alkaloids, emetine and cephaeline, in pharmaceutical preparations by high-performance liquid chromatography using spectrofluorimetric detection.
A selective high-performance liquid chromatographic procedure has been developed for the determination of the major Ipecacuanha alkaloids, emetine and cephaeline, in a number of linctus and pastille preparations. The reversed-phase chromatographic procedure uses an octadecyl-bonded column with a mobile phase of aqueous methanol containing an ion-pairing reagent. A spectrofluorimetric detector is used for increased sensitivity and selectivity. Sample preparation is simple, involving either straight dilution for linctus formulations or simple dissolutions for pastilles. The procedure has been shown to be stability-indicating. Validation studies, to show that the method is precise, accurate and rectilinear, have been carried out on four linctus formulations and two pastille formulations. The method has been used to determine both emetine and cephaeline at levels as low as 5 micrograms/g in formulations.


An advantageous method utilizing new homogenizing device BioMasher and a sensitive ELISA to detect bovine spongiform encephalopathy accurately in brain tissue.
A new screening method was developed to detect bovine spongiform encephalopathy (BSE). This method is advantageous because it has a simpler and safer protocol than commercial kits. A new device was developed for this method; it was named the BioMasher, to homogenize brain tissue by passing it through a porous rigid polypropylene filter. In this system, a purification step was eliminated in the sample preparation. Thus, the time needed for sample pretreatment is substantially shortened, and the risk of infection during sample processing is effectively reduced. Monoclonal antibodies to prion protein were created and used to construct a sensitive sandwich enzyme-linked immunosorbent assay system. The sensitivity of this assay kit using frozen BSE-positive brain is comparable or more sensitive than commercial kits. Moreover, the detection sensitivity for deteriorated samples, which were kept at 37 degrees C for 1 day, is 10- to 30-fold more sensitive than a commercial kit.


Mechanical Shock During Shipping of Medications: The Roles of Packaging and Transportation Vendors.
Protein-based medications are expensive and susceptible to damage from mechanical shock, which may occur during shipping to patients from pharmacies. Our objectives were to evaluate the performance of 2 packaging systems and to describe the mechanical shock that occurs during shipments. The packaging systems evaluated were boxes containing expanded polystyrene (EPS) or soft lint-like foam, prepared with and without polymer cooling packs. In laboratory-based studies, accelerometers measured g forces in boxes dropped from varying heights. Transportation studies evaluated the EPS cooler when sent to locations via 2 vendors. The relationship between drop height and maximum force vector was approximately linear for drop heights of 7.5″ through 30″, with lower magnitude forces at 45″ and 60″. Soft foam reduced force by 9.8 g on average compared to EPS (p < 0.009). The presence of polymer packs mitigated forces; frozen packs reduced forces by 28 g versus thawed packs (p < 0.001). Transportation experiments demonstrated most impacts were in the low (10-24 g) and low-medium (25-49 g) range (95% of all impacts). There was no difference between impacts during shipments with the vendors, and there was no correlation between distance traveled and number of impacts. Overall, mechanical shock during shipping is both prevalent and contingent upon the packing materials used.


Navigating Voice, Vocabulary and Silence: Developing Critical Consciousness in a Photovoice Project with (Un)Paid Care Workers in Long-Term Care.
Photovoice is a widely used approach for community participation in health promotion and health promotion research. However, its popularity has a flip-side. Scholars raise concerns that photovoice drifts away from its emancipatory roots, neglecting photovoice's aim to develop critical consciousness together with communities. Our four-year photovoice project aimed to unravel how the health of (un)paid care workers was shaped at the intersection of gender, class and race. This article springs from first, second and third-person inquiry within our research team of (un)paid care workers, academic researchers and a photographer. We observed that critical consciousness emerged from an iterative process between silence, voice and vocabulary. We learned that photovoice scholars need to be sensitive to silence in photovoice projects, as silence can be the starting point for finding voice, but also a result of silencing acts. Social movements and critical theories, such as intersectionality, provide a vocabulary for participants to voice their critical perspectives to change agents and to support collective action. We discuss our experiences using Frickers' concept of 'epistemic justice', arguing that critical consciousness not only requires that communities are acknowledged as reliable knowers, but that they need access to interpretative tropes to voice their personal experiences as structural.


Low CD10 mRNA expression identifies high-risk ductal carcinoma in situ (DCIS).
Optimal management of breast ductal carcinoma in situ (DCIS) is controversial, and many patients are still overtreated. The local death of myoepithelial cells (MECs) is believed to be a pre-requisite to tumor invasion. We thus hypothesized that loss of CD10 expression, a MEC surface peptidase, would signify basement membrane disruption and confer increased risk of relapse in DCIS. The aim of our study was to retrospectively evaluate the prognostic value of CD10 in DCIS. CD10 expression was evaluated by quantitative RT-PCR and immunohistochemistry using paraffin-embedded samples of normal breast tissue (n = 11); of morphologically normal ducts associated with DCIS (n = 10); and of DCIS without an invasive component (n = 154). CD10 immunostaining was only observed in MECs in normal tissue and in DCIS. Normal tissue showed high mRNA expression levels of CD10, whereas DCIS showed a variable range. After a median follow-up of 6 years, DCIS with CD10 expression below the levels observed in normal tissue (71%) demonstrated a higher risk of local relapse (HR = 1.88; [95CI:1.30-2.70], p = 0.001) in univariate analysis. No relapse was observed in patients expressing high CD10 mRNA levels (29%) similar to the ones observed in normal tissue. In multivariate analysis including known prognostic factors, low CD10 mRNA expression remained significant (HR = 2.25; [95%CI:1.24-4.09], p = 0.008), as did the recently revised Van Nuys Prognostic Index (VNPI) score (HR = 2.03; [95%CI:1.23-3.35], p = 0.006). The decrease of CD10 expression in MECs is associated with a higher risk of relapse in DCIS; this knowledge has the potential to improve DCIS management.


The Potential of Artemisinins as Novel Treatment for Thyroid Eye Disease by Inhibiting Adipogenesis in Orbital Fibroblasts.
Thyroid eye disease (TED) causes cosmetic defect and even threatens eyesight due to tissue remodeling in which orbital fibroblast (OF) plays a central role mainly by differentiating into adipocytes. Repurposing old drugs to novel applications is of particular interest. Here, we aimed to evaluate the effects of the antimalarials artemisinin (ARS) and the derivatives on the OFs isolated from patients with TED and their counterparts. OFs isolated from patients with TED or their counterparts were cultured and passaged in proliferation medium (PM) and stimulated by differentiation medium (DM) for adipogenesis. OFs were treated with or without ARS, dihydroartemisinin (DHA), and artesunate (ART) at different concentrations, before being examined in vitro. CCK-8 were used to assess cellular viability. Cell proliferation was determined by EdU incorporation and flow cytometry. Lipid accumulation within the cells was evaluated by Oil Red O staining. Hyaluronan production was determined by ELISA. RNAseq, qPCR, and Western blot analysis were performed to illustrate the underlying mechanisms. ARSs dose-dependently interfered with lipid accumulation of TED-OFs, rather than non-TED-OFs. Meanwhile, the expression of key adipogenic markers, such as PLIN1, PPARG, FABP4, and CEBPA, was suppressed. During adipogenesis as being cultivated in DM, instead of PM, ARSs also inhibited cell cycle, hyaluronan production and the expression of hyaluronan synthase 2 (HAS2) in a concentration-dependent manner. Mechanically, the favorable effects were potentially mediated by the repression of IGF1R-PI3K-AKT signaling by dampening IGF1R expression. Collectedly, our data evidenced that the conventional antimalarials ARSs were potentially therapeutic for TED.