Decreased expression levels of Ifi genes is associated to the increased resistance to spontaneous arthritis disease in mice deficiency of IL-1RA.
The mouse strain BALB/c deficient in IL-1 receptor antagonist protein (Il-1ra) develops spontaneous arthritis disease (SAD) while the strain DBA/1 IL1rn (-/-) with the same deficiency does not. Previously, we mapped a QTL on chromosome 1 for SAD and then developed a congenic mouse strain BALB.D1-1(-/-) that contains the QTL genomic fragment associated with resistance from DBA/1(-/-) on a BALB/c(-/-) background. The congenic strain was relatively resistant to spontaneous arthritis and had delayed onset and reduced severity of disease. We obtained whole genome expression profiles from the spleen of the congenic strain BALB.D1-1(-/-) and four other strains, the wild type BALB/c, DBA/1 and the deficient DBA/1 IL1rn (-/-) and the BALB/c IL1rn (-/-). We then compared the similarities and differences between the congenic strain and the four parental strains. Here we report the selected potential causal genes based on differential expression levels as well as function of genes. There is a considerable number of genes that are differentially expressed between the congenic strain and the three parental strains, BALB/c, DBA/1, and DBA/1(-/-). However there only a few differentially expressed genes were identified by comparing the congenic strain and the BALB/c(-/-)strain. These differentially expressed genes are mainly from T-cell receptor beta chain (Tcrb) and interferon-activatable protein (Ifi) genes. These genes are also differentially expressed between congenic strain and BALB/c strains. However, their expression levels in the congenic strain are similar to that in DBA/1 and DBA/1(-/-). The expression level of Tcrb-j gene is positively associated with two genes of Ifi gene 200 cluster. Decreased expression levels of Ifi genes is associated to the increased resistance to spontaneous arthritis disease and with down regulation of expressions of Tcrb genes in the mouse congenic strain. Ifi genes may play an important role in the susceptibility to SAD in mice.


Assessment of palmitoyl and sulphate conjugated glycol chitosan for development of polymeric micelles.
Amphiphilic copolymers are capable of forming core shell-like structures at the critical micellar concentration (CMC); hence, they can serve as drug carriers. Thus, in the present work, polymeric micelles based on novel chitosan derivative were synthesized. Block copolymer of palmitoyl glycol chitosan sulfate (PGCS) was prepared by grafting palmitoyl and sulfate groups serving as hydrophobic and hydrophilic fractions, respectively. Then, fourier transform infrared spectra (FTIR) and spectral changes in iodine/iodide mixture were carried out. FTIR studies confirmed the formation of palmitoyl glycol chitosan sulfate (PGCS) and spectral changes in iodine/iodide mixture indicated CMC which lies in the range of 0.003-0.2 mg/ml. Therefore, our study indicated that polymeric micelles based on palmitoyl glycol chitosan sulphate could be used as a prospective carrier for water insoluble drugs.


Motion State Estimation of Target Vehicle under Unknown Time-Varying Noises Based on Improved Square-Root Cubature Kalman Filter.
In the advanced driver assistance system (ADAS), millimeter-wave radar is an important sensor to estimate the motion state of the target-vehicle. In this paper, the estimation of target-vehicle motion state includes two parts: the tracking of the target-vehicle and the identification of the target-vehicle motion state. In the unknown time-varying noise, non-linear target-vehicle tracking faces the problem of low precision. Based on the square-root cubature Kalman filter (SRCKF), the Sage-Husa noise statistic estimator and the fading memory exponential weighting method are combined to derive a time-varying noise statistic estimator for non-linear systems. A method of classifying the motion state of the target vehicle based on the time window is proposed by analyzing the transfer mechanism of the motion state of the target vehicle. The results of the vehicle test show that: (1) Compared with the Sage-Husa extended Kalman filtering (SH-EKF) and SRCKF algorithms, the maximum increase in filtering accuracy of longitudinal distance using the improved square-root cubature Kalman filter (ISRCKF) algorithm is 45.53% and 59.15%, respectively, and the maximum increase in filtering the accuracy of longitudinal speed using the ISRCKF algorithm is 23.53% and 29.09%, respectively. (2) The classification and recognition results of the target-vehicle motion state are consistent with the target-vehicle motion state.


Cost-effectiveness of an insertable cardiac monitor in a high-risk population in the UK.
To evaluate the cost-effectiveness of insertable cardiac monitors (ICMs) compared with standard of care (SoC) for detecting atrial fibrillation (AF) in patients at high risk of stroke (CHADS2 >2), using a UK National Health Service (NHS) perspective. Using patient characteristics and clinical data from the REVEAL AF trial, a Markov model assessed the cost-effectiveness of detecting AF with an ICM compared with SoC. Costs and benefits were extrapolated across modelled patient lifetime. Ischaemic and haemorrhagic strokes, intracranial and extracranial haemorrhages and minor bleeds were modelled. Diagnostic and device costs were included, plus costs of treating stroke and bleeding events and costs of oral anticoagulants (OACs). Costs and health outcomes, measured as quality-adjusted life years (QALYs), were discounted at 3.5% per annum. One-way deterministic and probabilistic sensitivity analyses (PSA) were undertaken. The total per-patient cost for ICM was £13 360 versus £11 936 for SoC (namely, annual 24 hours Holter monitoring). ICMs generated a total of 6.50 QALYs versus 6.30 for SoC. The incremental cost-effectiveness ratio (ICER) was £7140/QALY gained, below the £20 000/QALY acceptability threshold. ICMs were cost-effective in 77.4% of PSA simulations. The number of ICMs needed to prevent one stroke was 21 and to cause a major bleed was 37. ICERs were sensitive to assumed proportions of patients initiating or discontinuing OAC after AF diagnosis, type of OAC used and how intense the traditional monitoring was assumed to be under SoC. The use of ICMs to identify AF in a high-risk population is cost-effective for the UK NHS.


Diagnostic schemes for fine needle aspirates of breast masses.
A comparison was made of four statistically based schemes for classifying epithelial cells from 243 fine needle aspirates of breast masses as benign or malignant. Two schemes were computer-generated decision trees and two were user generated. Eleven cytologic characteristics described in the literature as being useful in distinguishing benign from malignant breast aspirates were assessed on a scale of 1 to 10, with 1 being closest to that described as benign and 10 to that described as malignant. The original computer-generated dichotomous decision tree gave 6 false negatives and 12 false positives on the data set; another tree generated from the current data improved performance slightly, with 5 false negatives and 10 false positives. Maximum diagnostic overlap occurred at the cut-point of the original dichotomous tree. The insertion of a third node evaluating additional parameters resulted in one false negative and seven false positives. This performance was matched by summing the scores of the eight characteristics that individually were most effective in separating benign from malignant. We conclude that, while statistically designed, computer-generated dichotomous decision trees identify a starting sequence for applying cytologic characteristics to distinguish between benign and malignant breast aspirates, modifications based on human expert knowledge may result in schemes that improve diagnostic performance.


The Axial Alignment of Titin on the Muscle Thick Filament Supports Its Role as a Molecular Ruler.
The giant protein titin is expressed in vertebrate striated muscle where it spans half a sarcomere from the Z-disc to the M-band and is essential for muscle organisation, activity and health. The C-terminal portion of titin is closely associated with the thick, myosin-containing filament and exhibits a complex pattern of immunoglobulin and fibronectin domains. This pattern reflects features of the filament organisation suggesting that it acts as a molecular ruler and template, but the exact axial disposition of the molecule has not been determined. Here, we present data that allow us to precisely locate titin domains axially along the thick filament from its tip to the edge of the bare zone. We find that the domains are regularly distributed along the filament at 4-nm intervals and we can determine the domains that associate with features of the filament, such as the 11 stripes of accessory proteins. We confirm that the nine stripes ascribed to myosin binding protein-C are not related to the titin sequence previously assumed; rather, they relate to positions approximately 18 domains further towards the C terminus along titin. This disposition also allows a subgroup of titin domains comprising two or three fibronectin domains to associate with each of the 49 levels of myosin heads in each half filament. The results strongly support the role of titin as a blueprint for the thick filament and the arrangement of the myosin motor domains.


Synthetic Pattern Formation.
A fundamental question in biology is how biological patterns emerge. Because of the presence of numerous confounding factors, it is tremendously challenging to elucidate the mechanisms underlying pattern formation solely on the basis of studies of natural biological systems. Synthetic biology provides a complementary approach to investigating pattern formation by creating systems that are simpler and more controllable than their natural counterparts. In this Perspective, we summarize recent work on synthetic systems that generate spatial patterns, review the tools for building synthetic patterns, and discuss future directions of studying pattern formation with synthetic biology.


Nuclei-specific deposits of iron and calcium in the rat thalamus after status epilepticus revealed with quantitative susceptibility mapping (QSM).
To investigate pathological changes in the rat brain after pilocarpine-induced status epilepticus using quantitative susceptibility mapping (QSM). 3D multiecho gradient-echo (GRE) data were acquired from ex vivo brains of pilocarpine-injected and age-matched control rats at 11.7T. Maps of R2* and quantitative susceptibility were calculated from the acquired 3D GRE magnitude and phase data, respectively. QSM and R2* maps were compared with Perls' (iron) and Alizarin-red-S (calcium) stainings in the same brains to investigate the pathophysiological basis of susceptibility contrast. Bilaterally symmetric lesions were detected in reproducible thalamic regions of pilocarpine-treated rats, characterized by hyperintensity in R2* maps. In comparison, quantitative susceptibility maps demonstrated heterogeneous contrast within the lesions, with distinct hyperintense (paramagnetic) and hypointense (diamagnetic) areas. Comparison with histological assessment revealed localized deposits of iron- and calcium-positive granules in thalamic nuclei corresponding to paramagnetic and diamagnetic areas delineated in the susceptibility maps, respectively. Pronounced differences were observed in the lesions between background-corrected phase images and reconstructed susceptibility maps, indicating unreliable differentiation of iron and calcium deposits in phase maps. Multiple linear regression showed a significant association between susceptibility values and measured optical densities (ODs) of iron and calcium in the lesions (R2 = 0.42, P < 0.001), with a positive dependence on OD of iron and negative dependence on OD of calcium. QSM can detect and differentiate pathological iron and calcium deposits with high sensitivity and improved spatial accuracy compared to R2* or GRE phase images, rendering it a promising technique for diagnosing thalamic lesions after status epilepticus. 1 Technical Efficacy: Stage 1 J. Magn. Reson. Imaging 2018;47:554-564.


Hypermanganesemia in an acute care setting.
Hypermanganesemia has recently been reported in long-term home parenteral nutrition patients receiving routine trace element supplementation. Because the regulation of manganese involves intestinal absorption and biliary excretion, patients receiving parenteral nutrition, especially those with hepatic dysfunction, may be at risk for manganese toxicity. This case study describes a patient in an acute care setting who had been receiving parenteral nutrition for 7 months. When neurologic symptoms developed, she was found to have a whole blood manganese level almost 3 times normal. Manganese was eliminated from the trace element solution, and a whole blood level was rechecked 3 months later, showing a significant decrease and a marked improvement in facial paralysis and headaches.


Differences between HbA1c and glucose-related variables in predicting weight loss and glycaemic changes in individuals with overweight and hyperglycaemia - The PREVIEW trial.
To examine the differences between HbA1c and glucose related variables in predicting weight loss and glycaemic changes following 8 weeks of low energy diet (LED) in individuals with overweight and hyperglycaemia. 2178 individuals with ADA-defined pre-diabetes - impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) - who started an 8 week LED weight loss diet, were included in this analysis. Participants were enrolled in the PREVIEW (PREVention of diabetes through lifestyle interventions and population studies In Europe and around the World) clinical trial. Multivariable linear mixed effects regression models and generalised additive mixed effect logistic models were used. Only 1 in 3 participants (33%) had HbA1c levels defined as pre-diabetes. Neither baseline HbA1c, IFG or IGT were associated with body weight change at 8 weeks. Higher baseline body weight, baseline fasting insulin and weight loss predicted normalisation of fasting plasma glucose (FPG), whilst higher baseline fasting insulin, C-reactive protein (hsCRP) and older age predicted normalisation of HbA1c. Additionally, male sex and higher baseline BMI, body fat and energy intake were positively associated with weight loss, whereas greater age and higher HDL-cholesterol predicted less weight loss. Whilst neither HbA1c nor fasting glucose predicts short-term weight loss success, both may impact the metabolic response to rapid weight loss. We propose a role of inflammation versus total body adiposity since these variables are independent predictors of the normalisation of HbA1c and fasting glucose, respectively.


Minimising potential side-effects of medication at different ages.
When prescribing and administering drugs, it is important to consider the patient's developmental stage. As individuals pass from fetus to a neonate, through infancy to childhood, adolescence, maturity and old age, major changes in anatomy and physiology occur that are reflected in different abilities to handle and respond to drugs.


Differential effect of inflammatory stimuli on murine plasma C4 and factor B concentrations.
The in vivo effects of a variety of inflammatory stimuli on complement C4 and factor B plasma levels have been examined. MRL/++ (H-2k) mice were given intraperitoneal injections of lipopolysaccharide, turpentine, Corynebacterium parvum pyridine extract residue or high doses of indomethacin. All of these treatments induced an increase in plasma factor B concentrations, which in the case of C. parvum was dose dependent and persisted for at least 7 days. Lipopolysaccharide, turpentine and indomethacin produced decreases in plasma complement C4. C. parvum, however, produced an increase in plasma complement C4 to approximately 240% of controls which was independent of gender. It was also independent of major histocompatibility complex haplotype, since the same effect was seen in C57B1/6J-bg/bg and C57B1/6J-bg/+ mice. The gross increment in complement C4 was, however, related to the major histocompatibility complex. H-2K mice ("low complement C4") had smaller increments than H-2b ("high complement C4"). Mycobacterium bovis (BCG) also produced a transient increase in C4 in the H-2b mice as well as a prolonged increase in factor B levels. These data (i) suggest that different inflammatory stimuli induce different mediators which may have differential effects on factor B and complement C4 synthesis, and (ii) emphasize the independent regulation of complement C4 and factor B. Qualitative variations in the mediators elaborated during chronic inflammatory diseases may help determine complement C4 fluctuations in systemic lupus erythematosus and the wide range of complement C4 concentrations seen in MRL/1 pr mice with active immune complex disease.


DNA methylation as mechanism of apoptotic resistance development in endometrial cancer patients.
DNA methylation is a significant epigenetic modification which plays a key role in regulation of gene expression and influences functional changes in endometrial tissue. Aberrant DNA methylation changes result in deregulation of important apoptotic proteins during endometrial carcinogenesis and apoptosis resistance development. Evading apoptosis is still a major problem in the successful treatment of endometrial cancer patients. The aim of our study was to examine the promoter DNA methylation changes in 22 apoptosis-associated genes in endometrioid endometrial cancer patients, precancerous lesions and healthy tissue from various normal menstrual cycle phases using a unique pre-designed methylation platform. We observed as the first a significant difference in promoter DNA methylation status in genes: BCL2L11 (p < 0.001), CIDEB (p < 0.03) and GADD45A (p < 0.05) during endometrial carcinogenesis and BIK gene (p < 0.03) in different phases of normal menstrual cycle. The results of our study indicate that deregulation of mitochondrial apoptotic pathway can considerably contributes to the apoptosis resistance development and may be helpful in identifying of new potent biomarkers in endometrial cancer.


[Congenital anomaly of serum pseudocholinesterase originating in neonatal respiratory distress].
Prolonged suxamethonium-induced apnoea was observed after obstetrical anaesthesia in a 30 year old woman with abnormal plasma cholinesterases (homozygous Ea1-Ea1). Flaccidity and apnoea in the child required controlled ventilation for 30 min. Possible mechanisms underlying prolonged apnoea after the use of suxamethonium for obstetrical anaesthesia are discussed. Atypical pseudocholinesterases were identified using quantitative dosage of enzymatic activity and inhibition of atypical pseudocholinesterases by dibucaine, fluoride, chloride, scoline and urea. This was carried out in the patient, her baby and family, thus identifying the genotype of the different family members.


Contribution of electron-atom collisions to the plasma conductivity of noble gases.
We present an approach which allows the consistent treatment of bound states in the context of dc conductivity in dense partially ionized noble gas plasmas. Besides electron-ion and electron-electron collisions, further collision mechanisms owing to neutral constituents are taken into account. Especially at low temperatures of 10^{4}to10^{5} K, electron-atom collisions give a substantial contribution to the relevant correlation functions. We suggest an optical potential for the description of the electron-atom scattering which is applicable for all noble gases. The electron-atom momentum-transfer cross section is in agreement with experimental scattering data. In addition, the influence of the medium is analyzed, the optical potential is advanced including screening effects. The position of the Ramsauer minimum is influenced by the plasma. Alternative approaches for the electron-atom potential are discussed. Good agreement of calculated conductivity with experimental data for noble gas plasmas is obtained.


Gene position within chromosome territories correlates with their involvement in distinct rearrangement types in thyroid cancer cells.
Chromosomal rearrangements in human cancers are of two types, interchromosomal, which are rearrangements that involve exchange between loci located on different chromosomes, and intrachromosomal, which are rearrangements that involve loci located on the same chromosome. The type of rearrangement that typically activates a specific oncogene may be influenced by its nuclear location and that of its partner. In interphase nuclei, each chromosome occupies a distinct three-dimensional (3D) territory that tends to not overlap the territories of other chromosomes. It is also known that after double strand breaks in the genome, mobility of free DNA ends is limited. These considerations suggest that loci located deep within a chromosomal territory might not participate in interchromosomal rearrangements as readily as in intrachromosomal rearrangements. To test this hypothesis, we used fluorescence in situ hybridization with 3D high-resolution confocal microscopy to analyze the positions of six oncogenes known to be activated by recombination in human cancer cells. We found that loci involved in interchromosomal rearrangements were located closer to the periphery of chromosome territories as compared with the loci that were involved in intrachromosomal inversions. The results of this study provide evidence suggesting that nuclear architecture and location of specific genetic loci within chromosome territories may influence their participation in intrachromosomal or interchromosomal rearrangements in human thyroid cells.


Clinicopathological and operative factors for prognosis of carcinoma of the ampulla of vater.
The prognostic factor(s) of carcinoma of the ampulla of Vater were analyzed retrospectively and the significance of lymphadenectomy around the superior mesenteric artery and para-aortic region on the clinical outcome was evaluated. From 1985 to 2008, 34 carcinomas of the ampulla of Vater patients who underwent pancreaticoduodenectomy with curative intent were analyzed with respect to tumor extent, operation method and prognosis. Overall 5-year survival was 52.6%. On multivariate analysis, lymph node metastasis, pancreatic invasion, venous invasion, perineural invasion and lymphadenectomy around the superior mesenteric artery were the significant prognostic factors. However, the dissection of para-aortic lymph nodes had no substantial survival benefit. Compared with the duodenal cancer, the prognosis for carcinoma of the ampulla of Vater was significantly worse although no differences in clinicopathological characteristics of patients were observed. Lymph node metastasis, pancreatic invasion, venous invasion, perineural invasion, and lymphadenectomy around the superior mesenteric artery are important prognostic factors. Pylorus-preserving pancreaticoduodenectomy, with lymphadenectomy around the superior mesenteric artery without dissection of para-aortic lymph nodes is recommended as optimal surgery. Though the treatment results were worse than that of duodenal cancer, curative operation should be performed, regardless of site of origin.


The IREM-1 (CD300f) inhibitory receptor associates with the p85alpha subunit of phosphoinositide 3-kinase.
The immune receptor expressed by myeloid cell 1 (IREM-1) (CD300f) inhibitory receptor displays five cytoplasmic tyrosine residues, two of them (Y205 and Y249) fit with ITIMs, whereas Y236 and Y263 constitute putative binding sites for PI3K. In the present study, immunoprecipitation analysis revealed that both the p85alpha subunit of PI3K and Src homology region 2 domain-containing phosphatase-1 could be recruited by IREM-1 in transfected cells as well as in the U937 monocytic leukemia cells, which constitutively express the receptor. By assaying the ability of different IREM-1 mutants to regulate the secretion of beta-hexosaminidase induced via FcRepsilonI in rat basophilic leukemia cells, both Y205 and Y249 appeared crucial for IREM-1-mediated inhibition. Remarkably, engagement of an IREM-1 mutant (Y(205,249,284)F), which did not recruit Src homology region 2 domain-containing phosphatase-1 and lost its inhibitory function, induced rat basophilic leukemia cell degranulation. This effect was dependent on the recruitment of PI3K, requiring the integrity of Y236 and Y263, and was blocked by PI3K inhibitors (i.e., wortmannin and LY-294002). Altogether, these data reveal a putative functional duality of the IREM-1 myeloid cell receptor.


Should usual criteria for intervention in abdominal aortic aneurysms be "downsized," considering reported risk reduction with endovascular repair?
Two randomized trials have demonstrated the safety of waiting until abdominal aortic aneurysm (AAA) diameter reaches 5.5 cm for repair in most patients. Other recent randomized trials have demonstrated lower perioperative mortality and morbidity with endovascular aneurysm repair (EVAR) compared to open surgery. Therefore, it is logical to assume that endovascular repair may change the appropriate threshold for intervention. However, endovascular repair is not as durable as open surgery and is associated with ongoing risks of rupture and reintervention. Decision analysis based on data available in 1998 showed that endovascular repair should not change the threshold for intervention. Since that time retrospective data have emerged to suggest that outcomes with endovascular repair are improved in smaller AAAs, although this may simply represent selection bias and the natural history of small AAAs. Randomized trials are appropriate to determine whether improved endovascular outcomes in small AAAs reduce late rupture and reintervention enough to justify early intervention in patients with appropriate anatomy. In the absence of data from these trials, the threshold for intervention should not be changed.


Reliability of sibling reports on parental drinking behaviors.
Questionnaire data from the Colorado Alcohol Research on Twins and Adoptees (CARTA) were analyzed to explore the reliability of sibling responses to items from the CARTA Family Alcoholism History Questionnaire (FHQ) concerning parental drinking behaviors. Subjects included 142 pairs of male and female, twin and nontwin siblings who reported on paternal and maternal problem drinking. FHQ items were summed to produce drinking-problem scales for fathers and mothers. There was generally good concordance across sibling reports of parental problem-drinking symptoms. There was a significant gender difference in that male offspring were more in agreement about their mothers' drinking behavior, while female offspring were more in agreement about their fathers' drinking behavior. For the most part, objective items, such as having two or more drunk-driving arrests, were more reliable (paternal kappa total = .56, maternal = .66) than subjective items, such as being happy only when drinking (paternal = .24, maternal = -.03). This evidence for reliability of sibling reports about parental drinking does seem to validate the use of such questionnaire data in alcohol studies.


Interoceptive training to target anxiety in autistic adults (ADIE): A single-center, superiority randomized controlled trial.
This trial tested if a novel therapy, Aligning Dimensions of Interoceptive Experience (ADIE), reduces anxiety in autistic adults. ADIE targets the association of anxiety with mismatch between subjective and behavioral measures of an individual's interoceptive sensitivity to bodily signals, including heartbeats. In this superiority randomized controlled trial, autistic adults (18-65 years) from clinical and community settings in Southern England were randomly assigned (1:1) to receive six sessions of ADIE or an active 'exteroceptive' control therapy (emotional prosody identification). Researchers conducting outcome assessments were blind to allocation. ADIE combines two modified heartbeat detection tasks with performance feedback and physical activity manipulation that transiently increases cardiac arousal. Participants were followed-up one-week (T1) and 3-months post-intervention (T2). The primary outcome was Spielberger Trait Anxiety Score (STAI-T) at T2. Outcomes were assessed on an intention-to-treat basis using multiple imputation for dealing with missing values. This trial was registered at International Standard Randomized Controlled Trial Registry, ISRCTN14848787. Between July 01, 2017, and December 31, 2019, 121 participants were randomly allocated to ADIE (n = 61) or prosody (n = 60) intervention groups. Data at T1 was provided by 85 (70%) participants (46 [75%] ADIE; 39 [65%] prosody). Data at T2 was provided by 61 (50%) participants (36 [59%] ADIE; 25 [42%] prosody). One adverse event (cardiac anxiety following ADIE) was recorded. A statistically significant group effect of ADIE on trait anxiety continued at T2 (estimated mean difference 3•23 [95% CI 1•13 to 5•29]; d = 0•30 [95% CI 0•09 to 0•51]; p = 0•005) with 31% of ADIE group participants meeting trial criteria for recovery (compared to 16% in the control group). ADIE can reduce anxiety in autistic adults, putatively improving regulatory control over internal stimuli. With little reliance on language and emotional insight, ADIE may constitute an inclusive intervention. Transforming Mental Health PsyImpact Grant.


The moderating role of colour in modelling the effectiveness of COVID-19 YouTube animated cartoons on the health behaviour of social media users in Nigeria.
Previous studies on the effect of cartoon hardly consider the moderating role of colour. Additionally, studies on the use of social media for health promotion pay less attention to sustainability of health behaviour. In this study, we examined the moderating role of colour on the effectiveness of COVID-19 YouTube animated cartoons on health behaviour of social media users in Nigeria. We survey a total of 470 social media users in Nigeria who reported exposure to YouTube COVID-19 animated cartoons. It was found that colour significantly predict recall of YouTube animated cartoons on COVID-19. In addition, the result of the study revealed that colour significantly moderate impact ofCOVID-19 YouTube animated cartoons on health behaviour of social media users. The result further showed that exposure to COVID-19 YouTube animated cartoons will significantly predict knowledge of the virus. The result also showed that recall of messages theme in COVID-19 YouTube animated cartoons significantly predicts health behaviour of social media users. Finally, the result of the study showed that self-efficacy, task self-efficacy, coping self-efficacy, and outcome expectancy significantly predict health behaviour sustainability among social media users who are exposed to COVID-19 YouTube animated cartoon. We highlighted the implications of these results on health promotions.


Molecular characterization of bromeliads from northeast Brazil.
Bromeliaceae is an important botany family that includes many species with economic value; demand for members of this family is increasing. However, illegal collection frequently occurs, drastically reducing the species populations; thus, it is necessary to collect and store Bromeliaceae genetic material. In this study, we identified and quantified genetic variability of the Bromeliad family using dominant markers to create the first Germplasm Bank in the northeast region of Brazil. Molecular tools were used to characterize the collected accessions. The combination of 11 inter-simple sequence repeats and 13 random amplified polymorphic DNA markers were used to detect the genetic variability of wild bromeliad accessions.


Association of human cholesteryl ester transfer protein-TaqI polymorphisms with serum HDL cholesterol levels in a normolipemic Japanese rural population.
We examined allele frequencies for the common cholesteryl ester transfer protein (CETP) TaqI polymorphisms and the associations of CETP-TaqI polymorphisms with serum lipid and lipoprotein levels taking into account for selected lifestyle factors in a well-characterized random sample of 527 healthy subjects living a rural community in Japan (256 men and 271 women aged 40-69 years). B2 allele frequency was 0.39 in men and 0.41 in women, and its presence was significantly associated with increased levels of HDL cholesterol (HDL-C) in men (P=0.003 for linear trend). A similar tendency in women was observed, although P value for trend did not reach 0.05. There were not significant interactions between TaqIB genotype and smoking and alcohol drinking or daily physical activity in HDL-C. There were no statistically significant differences among TaqIA genotype in lipid and lipoprotein levels. Multiple linear regression analysis showed that B1B2 and B2B2 explained 1.7% and 2.2%, and 0.6% and 1.0% of variation in men and in women in HDL-C, respectively. We conclude that the CETP-TaqIB polymorphism has a quantitative influence, but appears to be stronger one in men, on HDL-C levels even after adjustment for important lifestyle factors (smoking, alcohol drinking, and daily physical activity).


Front-end XY-slits assembly for the SPring-8 undulator beamlines.
A front-end XY-slits assembly has been designed for the SPring-8 undulator beamlines. This assembly can handle the high heat flux from the undulator, its grazing-incidence L-shaped configuration employing an enhanced heat-transfer technology.


Recurrence of Cushing's disease 10 years after transsphenoidal adenomectomy: report of a case.
To report a case of recurrent Cushing's disease after an apparent cure and long-term surveillance. We describe in detail the follow-up course of a woman who underwent transsphenoidal resection of a corticotropin-secreting pituitary microadenoma in 1981. For 2 years postoperatively, the patient exhibited adrenocortical insufficiency. In 1983, the pituitary-adrenal axis was normal. She remained eucorticoid until May 1992, when features of Cushing's syndrome redeveloped. Plasma and urine cortisol and plasma corticotropin levels were once again increased in conjunction with a loss of diurnal variation and abnormal responses to dexamethasone suppression. A magnetic resonance imaging scan of the pituitary gland was consistent with a small lesion on the left side, and petrosal sinus sampling after ovine corticotropin-releasing hormone stimulation was consistent with increased activity on the right side. This 10-year interval between apparent cure and recurrence appears to be the longest thus far reported for a patient with Cushing's disease. These observations reinforce the impression that permanent cure of this disorder is uncertain and indicate the need for indefinite follow-up.


Associations of Clinical Risk Factors and Novel Biomarkers with Age at Onset of Type 2 Diabetes.
To prospectively assess risk profiles for incident T2D stratified by age at onset. A total of 471,269 participants free of T2D at baseline were included from the UK Biobank. Approximately 70 clinical, lipid, lipoprotein, inflammatory and metabolic markers, and genetic risk scores were analyzed. Stratified Cox proportional hazards regression models were used to estimate hazard ratios (HRs) for T2D with age of diagnosis divided into four groups (≤50.0, 50.1 to 60.0, 60.1 to 70.0, and >70.0 years). During 11 years of follow-up, 15,805 incident T2D were identified. Among clinical risk factors, obesity had the highest HR at any age, ranging from 13.16 (95% CI, 9.67-17.91) for ≤50.0 years to 4.13 (3.78-4.51) for >70.0 years. Other risks associated with T2D onset at ≤50.0 years included dyslipidemia (3.50, 2.91-4.20), hypertension (3.21, 2.71-3.80), cardiovascular disease (2.87, 2.13-3.87), parental history of diabetes (2.42, 2.04-2.86), education lower than college (1.89, 1.57-2.27), physical inactivity (1.73, 1.43-2.10), smoking (1.38, 1.13-1.68), several lipoprotein particles, inflammatory markers, liver enzymes, fatty acids, amino acids, as well as genetic score. Associations of most risk factors and biomarkers were markedly attenuated with increasing age at onset (P interaction <0.05), and some were not significant for onset at age >70.0 years, such as smoking, systolic blood pressure, and apolipoprotein B. Most risk factors or biomarkers had stronger relative risks for T2D at younger ages, which emphasized the necessity to promote primary prevention among younger individuals. Moreover, obesity should be prioritized.


Medicaid: a comparison of Oklahoma and surrounding states, 1990-1994.
Medicaid has been the "safety net" for certain low-income people. In recent years, many states, including Oklahoma, have determined to enroll beneficiaries in managed care plans in an attempt to hold down the costs. Oklahoma began enrolling people in 1995, and the issue will be: was the managed care approach successful at least in controlling costs? To prepare, expenditures for the four years prior to the managed care approach have been analyzed. Comparison with surrounding states indicates that Oklahoma was already successful with negative average annual growth rates for the period 1992-1994, and that Oklahoma was more successful than surrounding states.


Substance use disorder and the early course of illness in schizophrenia and affective psychosis.
The relationship between a history of substance use disorder and the early course of psychotic illness was examined in 96 subjects with schizophrenia and 106 subjects with affective psychosis followed in the Suffolk County Mental Health Project, a longitudinal study of first-admission psychosis. Subjects received a structured diagnostic interview and clinical ratings at baseline assessment and again 6 months later. The 6-month assessment included information about treatment received during the interval. A lifetime history of substance use disorder was associated with worse clinical functioning at 6 months for schizophrenia subjects, but not for those with affective psychosis. There were no significant associations of substance use disorder with type of treatment during the interval or with self-reported compliance with medication. Schizophrenia subjects were more likely than subjects with affective psychosis to report cannabis use during the interval and to meet criteria for cannabis use disorder.


The holism of aesthetic knowing in nursing.
In 1978, Carper identified 'four fundamental patterns of knowing' that became largely foundational to subsequent epistemological discourse within the nursing discipline. These patterns of empirical, personal, aesthetic, and ethical knowing were presented as conceptually distinct yet related patterns of knowing. In order to provide an alternative conceptualization of aesthetics in nursing, the main tenants of Carper's discussion of aesthetic knowing will be revisited, and the foundations for her arguments will be examined. Specifically, Dewey's Art as Experience will be examined in relation to the 'holism' of nursing, and an alternative position on pragmatic aesthetics in nursing will be offered. A preliminary reintegration of the four patterns of knowing will then be presented as will an example of a potential cultivation of aesthetics in nursing, through an example of Rodin's 19th century sculpture, the Burghers of Calais.


Predicting the impact of climate change on the re-emergence of malaria cases in China using LSTMSeq2Seq deep learning model: a modelling and prediction analysis study.
Malaria is a vector-borne disease that remains a serious public health problem due to its climatic sensitivity. Accurate prediction of malaria re-emergence is very important in taking corresponding effective measures. This study aims to investigate the impact of climatic factors on the re-emergence of malaria in mainland China. A modelling study. Monthly malaria cases for four Plasmodium species (P. falciparum, P. malariae, P. vivax and other Plasmodium) and monthly climate data were collected for 31 provinces; malaria cases from 2004 to 2016 were obtained from the Chinese centre for disease control and prevention and climate parameters from China meteorological data service centre. We conducted analyses at the aggregate level, and there was no involvement of confidential information. The long short-term memory sequence-to-sequence (LSTMSeq2Seq) deep neural network model was used to predict the re-emergence of malaria cases from 2004 to 2016, based on the influence of climatic factors. We trained and tested the extreme gradient boosting (XGBoost), gated recurrent unit, LSTM, LSTMSeq2Seq models using monthly malaria cases and corresponding meteorological data in 31 provinces of China. Then we compared the predictive performance of models using root mean squared error (RMSE) and mean absolute error evaluation measures. The proposed LSTMSeq2Seq model reduced the mean RMSE of the predictions by 19.05% to 33.93%, 18.4% to 33.59%, 17.6% to 26.67% and 13.28% to 21.34%, for P. falciparum, P. vivax, P. malariae, and other plasmodia, respectively, as compared with other candidate models. The LSTMSeq2Seq model achieved an average prediction accuracy of 87.3%. The LSTMSeq2Seq model significantly improved the prediction of malaria re-emergence based on the influence of climatic factors. Therefore, the LSTMSeq2Seq model can be effectively applied in the malaria re-emergence prediction.


Transient appearance of EDTA-dependent pseudothrombocytopenia in a postoperative patient with sepsis: A case report.
Ethylenediaminetetraacetic acid-dependent pseudothrombocytopenia (EDTA-PTCP) is a rare phenomenon characterized by spuriously low platelet counts when EDTA reacts with harvested blood. However, to the best of our knowledge, only two cases involving EDTA-PTCP in postoperative patients with sepsis have been reported. Here, we describe a case of EDTA-PTCP that appeared transiently in a postoperative patient with sepsis. A 68-year-old female patient underwent laparoscopic tension-free hernioplasty for incisional hernia. Postoperatively, the patient developed very low platelet counts. The number of platelets in this patient had not improved following treatment with fresh-frozen plasma and platelet transfusions. The diagnosis of EDTA-PTCP was confirmed from the discovery of platelet aggregation in peripheral blood smears. We used sodium citrate-anticoagulated blood samples for platelet counting. The patient's platelet counts returned to normal with the use of sodium citrate-anticoagulated blood samples. Furthermore, the phenomenon of EDTA-PTCP disappeared when the patient was cured. The phenomenon of low platelet counts in postoperative patients with sepsis should be considered as possible EDTA-PTCP. In addition, peripheral blood smears and the use of sodium citrate anticoagulant are effective and valuable methods that can help identify EDTA-PTCP.


Resilience Protected against Suicidal Behavior for Men But Not Women in a Community Sample of Older Adults in Korea.
Suicide prevention efforts in reducing risk factors have been found to be more beneficial to older women than men, suggesting potential gender differences in effective prevention. The study aimed to examine gender difference in resilience for suicidal behavior in a community sample of older adults in Korea. A community-based survey was conducted to investigate resilience and risk factors of suicidal behavior using the Suicidal Behaviors Questionnaire-Revised, Connor-Davidson Resilience Scale, Center for Epidemiologic Studies Depression Scale (CES-D), as well as questions regarding physical illness and depression history. After accounting for well-known risk factors, resilience was inversely associated with suicidal behavior, but this protective role of resilience was applicable to men only. The findings of this study indicated gender difference in resilience against suicidal behavior in the elderly population. Gender-specific preventive intervention strategies need to be developed for community-based suicide prevention for older adults.


[A study on PARKIN gene in three pedigrees with autosomal recessive early-onset Parkinson's disease].
To detect the possible relationship between PARKIN gene and the Chinese pedigree with autosomal recessive early-onset Parkinson's disease(AREP). Clinical examination was carried out in 6 patients from 3 Chinese pedigrees with AREP and their 23 family members. PCR amplification of all exons of PARKIN gene was performed. The PCR products were analyzed by denaturing high-performance liquid chromatography(DHPLC) to screen for point mutation and polymorphism. And in the samples with abnormal DHPLC result, further sequencing was conducted to confirm the type of mutation and polymorphism. All exons of PARKIN gene from the research subjects were successfully amplified. A heterozygous point mutation (Gly284Arg) in exon 7 was found in one pedigree. A polymorphism (Ser167Asn) in exon 4 was found in another pedigree. All the patients had the past history of exposure to environmental poison. When acting together with risky environmental factors, the heterozygous mutation Gly284Arg in PARKIN gene may cause AREP. The polymorphism Ser167Asn in PARKIN gene increases the risk of developing Parkinson's disease and may cause AREP when acting together with hydrargyrism.


Secondary antifungal prophylaxis in pediatric hematopoietic stem cell transplants.
Invasive fungal infections (IFIs) constitute a leading cause of morbidity and infection-related mortality among hematopoietic stem cell transplant (HSCT) recipients. With the use of secondary prophylaxis, a history of IFI is not an absolute contraindication to allo-HSCT. However, still, IFI recurrence remains a risk factor for transplant-related mortality. In this study, of the 105 children undergoing HSCT between April 2010 and February 2013, 10 patients who had IFI history before transplantation and had undergone allo-HSCT were evaluated retrospectively to investigate results of secondary prophylaxis. In conclusion, our study shows that amphotericin B and caspofungin was successful as secondary antifungal prophylaxis agents with no relapse of IFI. In addition, after engraftment, secondary prophylaxis was continued with voriconazole orally in 4 patients that yielded good results.


A case of cervical myelopathy with developmental canal stenosis at the level of the atlas. A case report.
The craniocervical junction is one of the most common sites of malformations. Only three cases of myelopathy due to hypoplasia of atlas have been reported previously. Among these malformations, the hypoplasia of atlas was first described by Wackenheim in 1974. Although developmental canal stenosis due to the hypoplasia of atlas seems to have a tendency of causing the cervical myelopathy, only three cases of cervical myelopathy due to this condition have been reported previously. A 77-year-old man with severe canal stenosis at the level of the atlas is reported. The clinical manifestations were 20-year history of progressive gait disturbance and paresis of both upper and lower extremities. The spinal cord was markedly compressed at the level of the atlas. The clinical manifestations improved after a resection of posterior arch of the atlas.


Use of mix of clay/solid waste from steel works for civil construction materials.
The present study focuses on the use of solid waste generated by the steel works in Brazil for manufacturing clay-based structural products. The waste sample was characterized regarding chemical composition, X-ray diffraction, particle size, morphology, specific surface and plastic properties. The waste was added in gradual proportions to a kaolinitic clay from zero up to 3 wt.%. Ceramic bodies were formed by vacuum extrusion and fired at 950 degrees C. The physical-mechanical properties (linear shrinkage, water absorption, apparent density and flexural strength) of the resulting clay/solid waste mixtures were determined. In addition, leaching tests were performed according Brazilian Standards as well as a preliminary analysis of gases evolved during the thermal process. It was found that the solid waste is formed by irregular particles, ranging in size from 1 to 500 microm. The test results indicate that solid wastes generated by steel works can be used as filler in construction materials, thereby increasing reuse in an environmentally safe manner.


Prophylactic and therapeutic potential of selected immunomodulatory agents from Ayurveda against coronaviruses amidst the current formidable scenario: an in silico analysis.
There is currently a dearth of specific therapies to treat respiratory infections caused by the three related species of coronaviruses viz. SARS-CoV-2, SARS-CoV and MERS-CoV. Prevention from disease is currently the safest and most convenient alternative available. The present study aimed to evaluate the preventive and therapeutic effect of fifteen phytoconstituents from medicinal plants of Ayurveda against coronaviruses by in silico screening. All the phytoconstituents exhibited rapid GI absorption and bioavailability and most of them had no toxicity versus reference drug chloroquine. BAS analyses revealed that most of the phytocomponents had favorable bioactivity scores towards biological target proteins. Principal component analysis revealed that most of the phytoconstituents fell close to chloroquine in 3D projection of chemical space. Affinity of phytoconstituents towards SARS-CoV-2 spike protein-human ACE2 complex decreased as isomeldenin > tinosporaside > EGCG whereas in case of unbound ACE2, the strength of binding followed the order isomeldenin > tinosporaside > ellagic acid. Towards SARS-CoV-2 main and papain-like proteases, the affinity decreased as isomeldenin > EGCG > tinosporaside and EGCG > tinosporaside > isomeldenin, respectively. Most phytoconstituents displayed significant binding kinetics to the selected protein targets than chloroquine. SAR analysis revealed that isomeldenin, tinosporaside, EGCG and ellagic acid bind to viral spike glycoproteins via H-bond, Pi-Pi, Pi-sigma and Pi-alkyl type interactions. Molecular dynamics simulation of isomeldenin and EGCG with SARS-CoV and SARS-CoV-2 spike glycoproteins exhibited low deviations throughout the 100 ns simulation indicating good stability and compactness of the protein-ligand complexes. Thus, the above four phytoconstituents have the potential to emerge as prophylactic and therapeutic agents against coronaviruses if investigated further in vitro and in vivo.


Inferring causal pathways among three or more variables from steady-state correlations in a homeostatic system.
Cross-sectional correlations between two variables have limited implications for causality. We examine here whether it is possible to make causal inferences from steady-state data in a homeostatic system with three or more inter-correlated variables. Every putative pathway between three variables makes a set of differential predictions that can be tested with steady state data. For example, among 3 variables, A, B and C, the coefficient of determination, [Formula: see text] is predicted by the product of [Formula: see text] and [Formula: see text] for some pathways, but not for others. Residuals from a regression line are independent of residuals from another regression for some pathways, but positively or negatively correlated for certain other pathways. Different pathways therefore have different prediction signatures, which can be used to accept or reject plausible pathways using appropriate null hypotheses. The type 2 error reduces with sample size but the nature of this relationship is different for different predictions. We apply these principles to test the classical pathway leading to a hyperinsulinemic normoglycemic insulin-resistant, or pre-diabetic, state using four different sets of epidemiological data. Currently, a set of indices called HOMA-IR and HOMA-β are used to represent insulin resistance and glucose-stimulated insulin response by β cells respectively. Our analysis shows that if we assume the HOMA indices to be faithful indicators, the classical pathway must in turn be rejected. In effect, among the populations sampled, the classical pathway and faithfulness of the HOMA indices cannot be simultaneously true. The principles and example shows that it is possible to infer causal pathways from cross sectional correlational data on three or more correlated variables.


Seasonal variation in blood pressure: what is still missing?
Seasonal variation of blood pressure (BP) is a topic in cardiology that has gained more attention throughout the years. Although it is extensively documented that BP increases in seasons coupled with lower temperatures, there are still many gaps in this knowledge field that need to be explored. Notably, seasonal variation of BP phenotypes, such as masked and white coat hypertension, and the impact of air pollution, latitude, and altitude on seasonal variation of BP are still poorly described in the literature, and the levels of the existing evidence are low. Therefore, further investigations on these topics are needed to provide robust evidence that can be used in clinical practice.


[Dacryoendoscopic Surgery-Factors Influencing Postoperative Results].
Dacryoendoscopy (DE) is an established method in lacrimal surgery. Long-term follow-up-analyses of this surgery are of great interest. Here, factors influencing postoperative success rates should be considered to elect suitable patients. In this retrospective study, patients having had dacryoendoscopic surgery were included. Using a questionnaire, a prospective follow-up analysis was made. Pre- and intraoperative factors were correlated with treatment success, which was defined as improved epiphora, absence of a second lacrimal surgery and no signs of chronic dacryocystitis (secretion, pain at the lacrimal sac). Additionally, we asked for patient's satisfaction with the postoperative result (categorized in "very good", "good", "poor", and "bad"). Overall, 215 DE of 182 patients (130 women, 52 men) were studied. Mean patient age was 58 ± 17 years (range: 18 to 91 years). Follow-up was 31 to 77 months (median: 55 months). Treatment success after this time was 59.1%, in which neither patient's age nor sex showed significant influences. In comparison to complete stenosis, incomplete obstruction could be treated successfully twice as often (p = 0.02). Patients suffering from ectatic lacrimal sacs had a risk of 1.9 for failing therapy (p = 0.01). A trend concerning worse cure rates could be observed in patients with postsaccal localization of stenosis (p = 0.2) and an age of older than 49 years (p = 0.1). Surgical results evaluated by the patients were "very good" in 32.1% and "good" in 30.2%. Dacryoendoscopy with its minimally invasive approach is suitable as a first-step procedure in lacrimal surgery. The absence of a scar and the quick recovery are vitally important for the patients. Medically important is that the topographic anatomy is preserved by using dacryoendoscopy, so other surgical techniques can be performed later without limitations, if necessary. Patients with incomplete obstructions and a localization of stenosis, being pre- to intrasaccal, profit from this treatment method in particular.


Lamb Dip of a Quadrupole Transition in H_{2}.
The saturated absorption spectrum of the hyperfineless S(0) quadrupole line in the (2-0) band of H_{2} is measured at λ=1189 nm, using the NICE-OHMS technique under cryogenic conditions (72 K). It is the first time that a Lamb dip of a molecular quadrupole transition has been recorded. At low (150-200 W) saturation powers a single narrow Lamb dip is observed, ruling out an underlying recoil doublet of 140 kHz. Studies of Doppler-detuned resonances show that the redshifted recoil component can be made visible for low pressures and powers, and prove that the narrow Lamb dip must be interpreted as the blue recoil component. A transition frequency of 252 016 361 164 (8) kHz is extracted, which is off by -2.6 (1.6) MHz from molecular quantum electrodynamical calculations therewith providing a challenge to theory.


Land use affects the relationship between species diversity and productivity at the local scale in a semi-arid steppe ecosystem.
1The accelerating extinction rate of plant species and its effect on ecosystem functioning is a hotly debated topic in ecological research. Most research projects concerning the relationship between species diversity and productivity have been conducted in artificial plant communities, with only a few in natural ecosystems. In this study we examined the relationship between species diversity and above-ground net primary productivity (ANPP) over two consecutive growth seasons (2004 and 2005) in a semi-arid steppe ecosystem of northern China, that were subjected to different land uses.2Land use affected the relationship between species diversity and ANPP in this semi-arid steppe ecosystem. Exclusion of grazing without or with biomass removal by mowing increased ANPP, species richness and species diversity compared with free grazing; the effect was reflected mainly as enhanced importance of the perennial forbs functional group in terms of their relative contributions to ANPP, plant cover and plant abundance.3Many mechanisms regulate the relationship between species diversity and productivity. Differential effects of anthropogenic activities on biodiversity and ecosystem functioning greatly complicate the analysis of such relationships. On grazing-exclusion sites the relationship between ANPP and species richness can be best described as an exponential growth function (R 2 = 0·99, P < 0·001, n = 24); whereas on the free-grazing site the relationship takes the form of exponential decay (R 2 = 0·96, P < 0·001, n = 24). Our study concludes that the mode and severity of disturbance are important factors for interpreting the relationship between species diversity and productivity in semi-arid steppe ecosystems.


THE SYMMETRY OF CORRELATED SELECTION RESPONSES IN ADAPTIVE EVOLUTION: AN EXPERIMENTAL STUDY USING DROSOPHILA.
The relationship between the processes of density-dependent and age-specific selection has been investigated by examining a common phenotype, urea resistance, which has apparently evolved in response to each of these selection mechanisms. Twenty populations that have experienced differing levels of age-specific selection show differences in egg-to-adult viability in environments with high levels of urea. Among this group of populations, it appears that resistance to urea is correlated with longevity, but not development time. Ten populations kept at extreme larval densities for many generations also show responses to urea: those kept at high larval densities appear to be most resistant to urea. However, these populations show no differences in adult longevity. An additional five populations were selected directly for urea resistance by adding this compound to the larval food environment. Again, there was a strong response to this artificial selection, with urea resistance increasing dramatically, but these populations showed no response in adult longevity or resistance to crowding when compared to five control populations. There is clearly no simple relationship between longevity and larval urea resistance. It may be that age-specific and density-dependent selection induce similar changes in this phenotype, but do so through different genetic and physiological pathways. We suggest that these data are not consistent with the view of constant and symmetric genetic variance-covariance matrices. These data support a more prominent role for observations of evolutionary trajectories rather than static measurements of genetic components of variance.


To Transfer or Not to Transfer? Development of a Dinitrosyl Iron Complex as a Nitroxyl Donor for the Nitroxylation of an Fe(III) -Porphyrin Center.
A positive myocardial inotropic effect achieved using HNO/NO(-) , compared with NO⋅, triggered attempts to explore novel nitroxyl donors for use in clinical applications in vascular and myocardial pharmacology. To develop M-NO complexes for nitroxyl chemistry and biology, modulation of direct nitroxyl-transfer reactivity of dinitrosyl iron complexes (DNICs) is investigated in this study using a Fe(III) -porphyrin complex and proteins as a specific probe. Stable dinuclear {Fe(NO)2 }(9) DNIC [Fe(μ-(Me) Pyr)(NO)2 ]2 was discovered as a potent nitroxyl donor for nitroxylation of Fe(III) -heme centers through an associative mechanism. Beyond the efficient nitroxyl transfer, transformation of DNICs into a chemical biology probe for nitroxyl and for pharmaceutical applications demands further efforts using in vitro/in vivo studies.


Learning curve in tracheal allotransplantation.
The first vascularized tracheal allotransplantation was performed in 2008. Immunosuppression was stopped after forearm implantation and grafting of the recipient mucosa to the internal site of the transplant. Nine months after forearm implantation, the allograft was transplanted to the tracheal defect on the radial blood vessels. Since then, four additional patients have undergone tracheal allotransplantation, three (patients 2-4) for long-segment stenosis and one (patient 5) for a low-grade chondrosarcoma. Our goal was to reduce the time between forearm implantation and orthotopic transplantation and to determine a protocol for safe withdrawal of immunosuppressive therapy. Following forearm implantation, all transplants became fully revascularized over 2 months. Withdrawal of immunosuppression began 4 months after graft implantation and was completed within 6 weeks in cases 2-4. Repopulation of the mucosal lining by recipient cells, to compensate for the necrosis of the donor mucosa, was not complete. This resulted in partial loss of the allotransplant in patients 2-4. In patient 5, additional measures promoting recipient cell repopulation were made. The trachea may be used as a composite tissue allotransplant after heterotopic revascularization in the forearm. Measures to maximize recipient cell repopulation may be important in maintaining the viability of the transplant after cessation of immunosuppression.


Multiple metastatic leiomyosarcoma of the pancreas: a first case report and review of the literature.
A 60-year-old woman was referred to our hospital with swelling of the right leg. After surgery, leiomyosarcoma of the right leg was diagnosed. Computed tomography showed two hypovascular masses in the pancreatic body and tail that were heterogeneously enhanced compared with the pancreatic parenchyma. On endoscopic ultrasonography, the tumors in the pancreatic body and tail both exhibited regular margins and were visualized as well-circumscribed masses with uneven interiors. Distal pancreatectomy was performed under a presumptive diagnosis of metastatic pancreatic leiomyosarcoma diagnosed based on the findings of EUS-FNA. On laparotomy, peritoneal washing cytology yielded negative results, and no dissemination was observed. Ultimately, metastatic pancreatic leiomyosarcoma was histologically diagnosed.


Occipital condyle fractures: a hidden nosologic entity. An experience with 10 cases.
To report the incidence, treatment and outcome of occipital condyle fractures (OCFs) based on the experience of a single neurosurgical department over a period of two years. From April 1999 to April 2001, ten cases of OCFs were identified in 110 cervical traumas observed over a period of two years. Patients were studied by cervical x-rays, high-resolution CT scan with a 1-2 mm slice of the cranio-cervical junction (CCJ) and MRI in selected cases to evaluate the integrity of supporting ligaments. According to the Anderson and Montesano classification, 5 cases of type III, 3 cases of type II and 2 cases of type I fractures were found. Dysfunction of lower cranial nerves was observed in 8 cases. Treatment was conservative in all cases. At follow-up, ranging from 18 months to 2 years, fusion was obtained in all cases; 8 patients were neurologically intact, one patient presented a mild persistent dysphonia and another mild trapezius weakness. OCFs are actually not rare, rather they are often overlooked. In cases of high-energy trauma of the cervical spine, the diagnostic suspicion should be kept in mind.High-resolution CT scan with slice at 1-2 mm of the CCJ is the key radiological examination in the diagnosis of this lesion. Conservative treatment using a hard collar is sufficient to obtain sound fusion.


Statin use and fracture risk: can we quantify the healthy-user effect?
Numerous observational studies show that statin use is associated with lower risk of osteoporotic fractures. However, a causal relationship is not supported by data from randomized trials. Unmeasured confounding is implicated as a likely culprit for the controversy because of failure to measure and adjust for patient-level tendencies to engage in healthy behaviors. However, an alternative explanation is selection bias because of the inclusion of prevalent users of statins in the analysis. The relative importance of either bias has not been investigated in a quantitative sensitivity analysis. We conducted a systematic review to summarize the pattern of association between statin use and fracture risk in observational studies. Our objective was to quantify the magnitude of unmeasured confounding and selection bias in a sensitivity analysis. In 17 published studies, the pooled relative risk for the association between current use of statins and fracture risk was 0.75 (95% confidence interval = 0.66-0.85). Upon adjustment for individual-level use of preventative health services, the pooled relative risk shifted by less than 5% on the log scale. However, a sensitivity analysis for selection bias revealed that moderate levels of bias could eliminate the association between statins and fracture risk. It appears that confounding from unmeasured variables cannot explain the protective association between statins and fractures that has been observed in the literature.


Dental treatment for high-risk patients with refractory heart failure: a retrospective observational comparison study.
Heart failure affects large population groups. The understanding of the etiology, pathophysiology, and treatment of heart failure has changed considerably within the last few years. The changes have significant implications for the medical management of the disease, as well as on the ability to provide proper dental treatment for these patients. A retrospective observational study of the outcome following dental treatment of 54 patients was performed: 32 with refractory heart failure stage D (study group) and 22 patients at risk for heart failure stages A to C (control group). Dental management of these patients concentrated on the prevention of iatrogenic, dental setting- induced, and precipitating factors of heart failure. To prevent deterioration of patients' medical condition, a comprehensive, tailored treatment including adequate anxiolysis, close monitoring, profound dental anesthesia, and close follow-up was used. A previously described three-step gradual level protocol (at home, waiting room, and dental chair) was adopted. All the planned dental procedures were successfully completed. Six patients experienced respiratory distress during treatment, and five patients demonstrated arrhythmias during dental treatment. Only minute differences were found between the groups regarding blood pressure and heart rate. Use of the suggested protocol facilitated the completion of planned dental treatments for all patients. Thus, providing essential dental treatment for severe heart failure patients with special attention to their medical problems and the use of medications and supporting means to prevent health-compromising situations is recommended.


Roles of bound quinone in the single subunit NADH-quinone oxidoreductase (Ndi1) from Saccharomyces cerevisiae.
To understand the biochemical basis for the function of the rotenone-insensitive internal NADH-quinone (Q) oxidoreductase (Ndi1), we have overexpressed mature Ndi1 in Escherichia coli membranes. The Ndi1 purified from the membranes contained one FAD and showed enzymatic activities comparable with the original Ndi1 isolated from Saccharomyces cerevisiae. When extracted with Triton X-100, the isolated Ndi1 did not contain Q. The Q-bound form was easily reconstituted by incubation of the Q-free Ndi1 enzyme with ubiquinone-6. We compared the properties of Q-bound Ndi1 enzyme with those of Q-free Ndi1 enzyme, with higher activity found in the Q-bound enzyme. Although both are inhibited by low concentrations of AC0-11 (IC(50) = 0.2 microm), the inhibitory mode of AC0-11 on Q-bound Ndi1 was distinct from that of Q-free Ndi1. The bound Q was slowly released from Ndi1 by treatment with NADH or dithionite under anaerobic conditions. This release of Q was prevented when Ndi1 was kept in the reduced state by NADH. When Ndi1 was incorporated into bovine heart submitochondrial particles, the Q-bound form, but not the Q-free form, established the NADH-linked respiratory activity, which was insensitive to piericidin A but inhibited by KCN. Furthermore, Ndi1 produces H(2)O(2) as isolated regardless of the presence of bound Q, and this H(2)O(2) was eliminated when the Q-bound Ndi1, but not the Q-free Ndi1, was incorporated into submitochondrial particles. The data suggest that Ndi1 bears at least two distinct Q sites: one for bound Q and the other for catalytic Q.


The social phenotype of Williams syndrome.
Williams syndrome (WS) offers an exciting model for social neuroscience because its genetic basis is well-defined, and the unique phenotype reflects dimensions of prosocial behaviors. WS is associated with a strong drive to approach strangers, a gregarious personality, heightened social engagement yet difficult peer interactions, high nonsocial anxiety, unusual bias toward positive affect, and diminished sensitivity to fear. New neurobiological evidence points toward alterations in structure, function, and connectivity of the social brain (amygdala, fusiform face area, orbital-frontal regions). Recent genetic studies implicate gene networks in the WS region with the dysregulation of prosocial neuropeptides. The study of WS has implications for understanding human social development, and may provide insight for translating genetic and neuroendocrine evidence into treatments for disorders of social behavior.


Architecture for multi-technology real-time location systems.
The rising popularity of location-based services has prompted considerable research in the field of indoor location systems. Since there is no single technology to support these systems, it is necessary to consider the fusion of the information coming from heterogeneous sensors. This paper presents a software architecture designed for a hybrid location system where we can merge information from multiple sensor technologies. The architecture was designed to be used by different kinds of actors independently and with mutual transparency: hardware administrators, algorithm developers and user applications. The paper presents the architecture design, work-flow, case study examples and some results to show how different technologies can be exploited to obtain a good estimation of a target position.


Functional mapping and single chain construction of the anti-cytokeratin 8 monoclonal antibody TS1.
The anti-cytokeratin (CK) 8 monoclonal antibody (mab) TS1 has been shown to efficiently bind to CK8 expressed in carcinomas in vivo. The anti-idiotypic antibody of TS1, alphaTS1, can be used to regulate the tumor:non-tumor ratio of TS1 by clearing non-tumor binding TS1 from the circulation. If the interaction of TS1 to CK8 and alphaTS1 is fully understood, mutations can be used to improve the tumor:non-tumor ratio. A scFv was made of the mab TS1 and residues earlier identified by Erlandsson et al. as important for the interaction with both its antigen CK8 and its anti-idiotype alphaTS1, were mutated to alanine or amides and expressed in E. coli. The effects of the mutations were studied by ELISA and residues important for the interactions to both CK8 and alphaTS1 were identified as mainly tyrosines, charged residues, a serine and a tryptophan. Altogether, nine amino acid residues in TS1 were found to be important in the interaction to alphaTS1 and six residues for the interaction to CK8. Important residues, clustered together in the modelled protein, were identified as residues from CDR 3 of the heavy chain and the unexpected participation of a residue in CDR 2 of the light chain. Some of the important residues are likely to be hotspots. Hotspots constitute a few residues in an interaction that contribute most to the binding, energetically. Amino acid residues in hotspots often cluster together in the center of the interaction interface, but can also be spread out to the periphery. The hotspots are often surrounded by hydrophobic patches, which are seen in the modelled TS1 protein used in this study. Amino acid residues that increased the affinity when mutated were also identified for both interactions. These residues are likely to be located outside the interacting interface. It can from this study be concluded that it is wise to precede the mutational procedure with experiments that can give guidelines for the selection of which amino acid residues to mutate. If the guidelines from the chemical modifications from Erlandsson et al. not had been used, this study would have left some residues unmutated and thereby missed important information.


5-Hydroxytryptamine promotes hepatocellular carcinoma proliferation by influencing β-catenin.
5-Hydroxytryptamine (5-HT), a neurotransmitter and vasoactive factor, has been reported to promote proliferation of serum-deprived hepatocellular carcinoma (HCC) cells but the detailed intracellular mechanism is unknown. As Wnt/β-catenin signalling is highly dysregulated in a majority of HCC, this study explored the regulation of Wnt/β-catenin signalling by 5-HT. The expression of various 5-HT receptors was studied by quantitative real-time polymerase chain reaction (qPCR) in HCC cell lines as well as in 33 pairs of HCC tumours and corresponding adjacent non-tumour tissues. Receptors 5-HT1D (21/33, 63.6%), 5-HT2B (12/33, 36.4%) and 5-HT7 (15/33, 45.4%) were overexpressed whereas receptors 5-HT2A (17/33, 51.5%) and 5-HT5 (30/33, 90.1%) were reduced in HCC tumour tissues. In vitro data suggests 5-HT increased total β-catenin, active β-catenin and decreased phosphorylated β-catenin protein levels in serum deprived HuH-7 and HepG2 cells compared to control cells under serum free medium without 5-HT. Activation of Wnt/β-catenin signalling was evidenced by increased expression of β-catenin downstream target genes, Axin2, cyclin D1, dickoppf-1 (DKK1) and glutamine synthetase (GS) by qPCR in serum-deprived HCC cell lines treated with 5-HT. Additionally, biochemical analysis revealed 5-HT disrupted Axin1/β-catenin interaction, a critical step in β-catenin phosphorylation. Increased Wnt/β-catenin activity was attenuated by antagonist of receptor 5-HT7 (SB-258719) in HCC cell lines and patient-derived primary tumour tissues in the presence of 5-HT. SB-258719 also reduced tumour growth in vivo. This study provides evidence of Wnt/β-catenin signalling activation by 5-HT and may represent a potential therapeutic target for hepatocarcinogenesis.


No association between the use of cellular or cordless telephones and salivary gland tumours.
To investigate the association between the use of cellular or cordless telephones and the risk for salivary gland tumours. Cases were assessed from the six regional cancer registries in Sweden. Four controls matched for sex and age in five year age groups were selected for each case. A total of 293 living cases and 1172 controls were included. There were 267 (91%) participating cases and 1053 (90%) controls. Overall no significantly increased risk was found. Odds ratios were 0.92 (95% CI 0.58 to 1.44) for use of analogue phones, 1.01 (95% CI 0.68 to 1.50) for use of digital phones, and 0.99 (95% CI 0.68 to 1.43) for use of cordless phones. Similar results were found for different salivary gland localisations. No effect of tumour induction period or latency was seen, although few subjects reported use for more than 10 years. No association between the use of cellular or cordless phones and salivary gland tumours was found, although this study does not permit conclusions for long term heavy use.


Visual function assessment, ocular examination, and intervention in children with developmental delay: A systematic approach. Part 1.
Children with special needs form a unique subset with regards to visual function and examination techniques needed to assess them. With more awareness among the general public, neurologists, and pediatricians, these children are referred for assessment to the ophthalmologist or optometrist and sometimes even to the rehabilitation professional at an early age. This clinical practice guideline and review gives a systematic approach for examining the visual functions of a child with special needs. It outlines the procedures to be followed with equipment needed in clinical practice. Functional vision assessment guidelines are also included. This is the first part in a two-part series, with the first part presenting clinical examination guidelines and the second presenting intervention and vision enhancement techniques.


Self-limiting diarrhea in an infant exposed to sertraline in breast milk.
Sertraline is widely used to treat postpartum depression. Though studies found detectable levels of sertraline in infant blood, very few adverse effects are reported. Reporting hereby is a case of an infant who developed self-limiting diarrhea, probably due to exposure to sertraline in breast milk.


Upregulation of pentose phosphate pathway and preservation of tricarboxylic acid cycle flux after experimental brain injury.
The metabolic fate of [1,2 13C]-labeled glucose was determined in male control and unilateral controlled cortical impact (CCI) injured rats at 3.5 and 24 h after surgery. The concentration of 13C-labeled glucose, lactate, glutamate and glutamine were measured in the injured and contralateral cortex. CCI animals showed a 145% increase in 13C lactate in the injured cortex at 3.5 h, but not at 24 h after injury, indicating increased glycolysis in neurons and/or astrocytes ipsilateral to CCI. Total levels of 13C glutamate in cortical tissue extracts did not differ between groups. However, 13C glutamine increased by 40% in the left and 98% in the right cortex at 3.5 h after injury, most likely resulting from an increase in astrocytic metabolism of glutamate. Levels of 13C incorporation into the glutamine isotopomers had returned to control levels by 24 h after CCI. The singlet to doublet ratio of the lactate C3 resonances was calculated to estimate the flux of glucose through the pentose phosphate pathway (PPP). CCI resulted in bilateral increases (9-12%) in the oxidation of glucose via the PPP, with the largest increase occurring at 24 h. Since an increase in PPP activity is associated with NADPH generation, the data suggest that there was an increasing need for reducing equivalents after CCI. Furthermore, 13C was incorporated into glutamate and glutamine isotopomers associated with multiple turns of the tricarboxylic acid (TCA) cycle, indicating that oxidative phosphorylation of glucose was maintained in the injured cortex at 3.5 and 24 h after a moderate to severe CCI injury.


Molecular cloning and characterisation of three new ATP-binding cassette transporter genes from the wheat pathogen Mycosphaerella graminicola.
Three single copy ATP-binding cassette (ABC) transporter encoding genes, designated MgAtr3, MgAtr4, and MgAtr5, were cloned and sequenced from the plant pathogenic fungus Mycosphaerella graminicola. The encoded ABC proteins all exhibit the [NBD-TMS(6)](2) configuration and can be classified as novel members of the pleiotropic drug resistance (PDR) class of ABC transporters. The three proteins are highly homologous to other fungal and yeast, ABC proteins involved in multidrug resistance or plant pathogenesis. MgAtr4 and MgAtr5 possess a conserved ABC motif at both the N- and C-terminal domain of the protein. In contrast, the Walker A motif in the N-terminal and the ABC signature in the C-terminal domain of MgAtr3, deviate significantly from the consensus sequence found in other members of the PDR class of ABC transporters. Expression of MgAtr3 could not be detected under any of the conditions tested. However, MgAtr4 and MgAtr5 displayed distinct expression profiles when treated with a range of compounds known to be either substrates or inducers of ABC transporters. These included synthetic fungitoxic compounds, such as imazalil and cyproconazole, natural toxic compounds, such as the plant defence compounds eugenol and psoralen, and the antibiotics cycloheximide and neomycin. The expression pattern of the genes was also dependent on the morphological state of the fungus. The findings suggest a role for MgAtr4 and MgAtr5 during plant pathogenesis and in protection against toxic compounds.


Roles of clinical and subclinical reactivated herpes simplex virus type 2 infection and human immunodeficiency virus type 1 (HIV-1)-induced immunosuppression on genital and plasma HIV-1 levels.
Few longitudinal studies have described the interactions between reactivation of herpes simplex virus type 2 (HSV-2) infection (hereafter, "HSV-2 reactivation") and genital and systemic replication of human immunodeficiency virus type 1 (HIV-1). Women in Burkina Faso who were seropositive for both HIV-1 and HSV-2 were enrolled in a randomized placebo-controlled trial of therapy to suppress reactivation of HSV-2 infection (hereafter, "HSV suppressive therapy"). During the baseline phase, 6 enriched cervicovaginal lavage specimens were obtained over 12 weeks to detect and quantify the HIV-1 RNA and HSV-2 DNA loads. Women with genital ulcer disease (GUD) detected at least once were more likely than women in whom GUD was not detected (risk ratio [RR], 1.23; 95% confidence interval [CI], 1.09-1.37) to have genital HIV-1 RNA detected during >or=1 visit. Similarly, women with genital HSV-2 DNA detected during >or=1 clinic visit were more likely than women in whom genital HSV-2 DNA was not detected (RR, 1.17; 95% CI, 1.01-1.34) to have genital HIV-1 RNA detected at least once. In addition, the mean genital HIV-1 RNA loads for women with GUD detected during >or=1 visit and women with HSV-2 genital shedding detected during >or=1 visit were greater than that for women in whom genital HSV-2 DNA or GUD was never detected. The plasma HIV-1 RNA load was increased among women for whom >or=1 visit revealed GUD (+0.25 log(10) copies/mL; 95% CI, -0.05-0.55) or genital HSV-2 DNA (+0.40 log(10) copies/mL; 95% CI, 0.15-0.66), compared with women who did not experience GUD or HSV-2 genital shedding, respectively. The association of HSV-2 reactivations on HIV-1 replication tended to be stronger in patients with a higher CD4(+) cell count (i.e., >500 cells/microL). The contribution of HSV-2 to HIV-1 replication among women with CD4(+) cell count of <or=500 cells/microL was reduced because almost all experienced HIV-1 genital shedding. Both clinical and subclinical HSV-2 reactivations play a role in increasing the rate of HIV-1 replication. HSV suppressive therapy is a promising tool for HIV control. Initiation of such therapy when the CD4(+) cell count is >500 cells/microL deserves further investigation. The ANRS 1285 Study is registered with the National Institutes of Health (registration number NCT00158509).


What health sciences programs want from biomedical communications.
A survey of all active U.S. members (1979) of the Association of Biomedical Communications Directors asked each of them to rank the importance of eight types of service to each professional program that his unit supports. Service priorities are reported for the programs characteristic of medicine, allied health, dentistry, nursing, and pharmacy. The services' orders of importance are program-related, which suggests that there is no single model of a biomedical communications unit and that each unit should be shaped by the particular program or programs that it supports.


Case Report: Paraneoplastic psoriasis in thymic carcinoma.
Thymic carcinomas are exceedingly rare and very aggressive malignancies of the anterior mediastinum. While thymomas exhibit a high association with paraneoplastic syndromes, these phenomena are a rarity in thymic carcinomas. In general, acanthotic syndromes such as acroceratosis neoplastica and acanthosis nigricans maligna are commonly observed as paraneoplastic phenomena in patients with carcinomas. In contrast, psoriasis vulgaris, another acanthotic disease, rarely occurs as a paraneoplasia. We report the case of a 36-year-old patient with progressive thymic carcinoma (undifferentiated carcinoma, T3N2M1a) and paraneoplastic psoriasis occurring ten months before the initial diagnosis of the carcinoma. Over the course of the disease, new psoriatic flares heralded relapse or progression of the carcinoma. To our knowledge, this is the first reported case of paraneoplastic psoriasis in thymic carcinoma.


Evaluation of superficial papillary ablation by endoscopic lasers in an ex vivo kidney model.
Endoscopic examinations of stone-forming kidneys show a coincidence of plaques and microliths on the surface of and within papillary epithelial tissue. These calcifications are thought to be precursors of calcium oxalate urolithiasis. We hypothesized that minimally invasive endoscopic laser ablation of microliths and necrotic cell layers enables epithelial regeneration and prevents recurrent urolithiasis. The aim of this study was to determine the most suitable laser type and dose intensity for selective superficial cell ablation. Conventional Nd:YAG (1-40 W) or Ho:YAG (0.5-3 J/single impulse) lasers were used endoscopically on an ex vivo blood-perfused porcine kidney model. Defined doses were applied to the papillary surface in the contact and noncontact modes for 10 to 30 seconds. Papillae were excised after treatment and histopathologically analyzed in continuous sections. Lesions were microscopically assessed with the aid of a Leica Quantimed computer program. Depending on the time and dose, vaporization by the Nd:YAG laser caused large tissue defects and coagulation necrosis at energy levels over 5 W (contact and noncontact mode). Lower energy levels with tissue contact produced only superficial cell defects (<20 cell layers) but more extensive coagulation necrosis, whereas no histologic effects were observed at the same energy level without contact. In contrast, independent of delivered energy but dependent on time, Ho:YAG laser application caused pure tissue loss without relevant coagulation necrosis. The generation of small lesions (6-10 cell layers) without tissue contact was possible at energy levels under 2 J. Selective superficial papillary cell ablation is possible. Low-energy Nd:YAG treatment in the contact mode and Ho:YAG treatment in the noncontact mode led to superficial vaporization with no (Ho:YAG) or minimum (Nd:YAG) coagulation defects.


The capacity of rat hepatoma cell lines for O6-methylguanine-DNA repair correlates with their status of differentiation.
O6-Methylguanine-DNA methyltransferase activity, i.e., the capacity of cells to transfer the methyl group from O6-methylguanine in DNA to protein, was determined in 10 hepatoma cell lines, all derived from Reuber H35 hepatoma but differing in their status of differentiation. Methyltransferase activity of the six differentiated lines tested was at least 4-5 times higher than that of two dedifferentiated lines. The activity of the two poorly differentiated lines examined was low to intermediate. Some of the differentiated lines possessed methyltransferase activities comparable to those in hepatocytes freshly isolated from adult rat. The results suggest that certain differentiated hepatoma lines are capable of mimicking liver in the capacity for repair of O6-methylguanine lesions and in this respect may be useful as model systems for studying liver-specific effects of monofunctional alkylating agents.


Profitability of Chemically Cross-Linked Collagen Scaffold Production Using Bovine Pericardium: Revaluing Waste from the Meat Industry for Biomedical Applications.
The meat industry generates a large amount of waste that can be used to create useful products such as bio-implants, which are usually expensive. In this report, we present an economic analysis of a continuous process for large-scale chemically cross-linked collagen scaffold (CCLCS) production in a Mexican context. For this purpose, three production capacities were simulated using SuperPro Designer® v 12.0: 5, 15, and 25 × 103 bovine pericardium units (BPU) per month as process feedstock. Data indicated that these capacities produced 2.5, 7.5, and 12.5 kg of biomesh per batch (per day), respectively. In addition, Net Unit Production Costs (NUPC) of 784.57, 458.94, and 388.26 $USD.kg-1 were obtained, correspondingly, with selling prices of 0.16 ± 0.078 USD.cm-2, 0.086 ± 0.043 USD.cm-2, and 0.069 ± 0.035 USD.cm-2, in the same order. We found that these selling prices were significantly lower than those in the current market in Mexico. Finally, distribution of costs associated with the process followed the order: raw materials > facility-dependent > labor > royalties > quality analysis/quality control (QA/QC) > utilities. The present study showed the feasibility of producing low-cost and highly profitable CCLCS with a relatively small investment. As a result, the circular bioeconomy may be stimulated.


Value of Personalized Dementia-Specific Quality of Life Scales: An Explorative Study in 3 European Countries.
Measuring Quality of Life (QOL) can be difficult due to its individual character. To explore the value of personalized QOL measurement for people with dementia, personalized versions of two dementia-specific QOL scales (Dementia quality of Life (DQoL) and Quaility of Life in Alzheimer's Disease (QoL-AD)) were constructed. This study investigated whether the personalized measures are more valid to detect variations in QOL than their standard versions for people with mild to moderate dementia, with sufficient internal consistency. Moreover, the relationship between the personalized QOL measures and severity of dementia was investigated. Finally, the study explored the differences between countries regarding the personalized overall QOL and differences in the importance of QOL domains. This explorative one-group design study used baseline data from the MEETINGDEM study into the implementation of the Meeting Centres Support Programme in Italy, Poland and the UK. The personalized versions of the DQoL and QoL-AD were reliable, but not more valid than their standard versions. No relationship between severity of dementia and personalized QOL was found. While no differences were found between countries for the overall QOL score, some QOL domains were valued differently: people with dementia from the UK rated self-esteem, mood, physical health, energy level and the ability to do chores around the house significantly less important than people from Italy and Poland. The personalized versions of the DQoL and QoL-AD may offer dementia care practice important insights into what domains contribute most to an individual's QOL.


Comparative Analysis of Uncoupled Mode Approximations for Molecular Thermochemistry and Kinetics.
The accurate prediction of thermochemistry and kinetic parameters is an important task for reaction modeling. Unfortunately, the commonly used harmonic oscillator model is often not accurate enough due to the absence of anharmonic effects. In this work, we improve the representation of an anharmonic potential energy surface (PES) using uncoupled mode (UM) approximations, which model the full-dimensional PES as a sum of one-dimensional potentials of each mode. We systematically analyze different PES sampling schemes and coordinate systems for constructing the one-dimensional potentials, and benchmark the performance of UM methods on data sets of molecular thermochemistry and kinetic properties. The results show that the accuracy of the UM approach strongly depends on how the one-dimensional potentials are defined. If one-dimensional potentials are constructed by sampling along normal mode directions (UM-N) or along the directions that minimize intermode coupling (E- and E'-optimized), the accuracies of the predicted properties are not significantly improved compared to the harmonic oscillator model. However, significant improvements can be achieved by sampling the torsional modes separately from the vibrational modes (UM-T and UM-VT). In this work, three types of coordinate systems are examined, including redundant internal coordinates (RIC), hybrid internal coordinates (HIC), and translation-rotation-internal coordinates (TRIC). The HIC and TRIC coordinate systems can outperform RIC since transition state species may contain large-amplitude interfragmentary motions that regular internal coordinates can not describe adequately. Among all the methods we examined, the activation energies and pre-exponential factors calculated using UM-VT with either TRIC or HIC best agree with the reference values. Since UM-VT requires only a number of additional single point energy calculations for each independent mode, the scaling of computational costs of UM-VT is the same as that of the standard harmonic oscillator model, making UM-VT an appealing way of calculating the thermochemistry and kinetic properties for large-size systems.


Toxicity of Balb-c mice exposed to recently identified 1,1,2,2-tetrafluoro-2-[1,1,1,2,3,3-hexafluoro-3-(1,1,2,2-tetrafluoroethoxy)propan-2-yl]oxyethane-1-sulfonic acid (PFESA-BP2).
1,1,2,2-tetrafluoro-2-[1,1,1,2,3,3-hexafluoro-3-(1,1,2,2-tetrafluoroethoxy)propan-2-yl]oxyethane-1-sulfonic acid (PFESA-BP2) was first detected in 2012 in the Cape Fear River downstream of an industrial manufacturing facility. It was later detected in the finished drinking water of municipalities using the Cape Fear River for their water supply. No toxicology data exist for this contaminant despite known human exposure. To address this data gap, mice were dosed with PFESA-BP2 at 0, 0.04, 0.4, 3, and 6 mg/kg-day for 7 days by oral gavage. As an investigative study, the final dose groups evolved from an original dose of 3 mg/kg which produced liver enlargement and elevated liver enzymes. The dose range was extended to explore a no effect level. PFESA-BP2 was detected in the sera and liver of all treated mice. Treatment with PFESA-BP2 significantly increased the size of the liver for all mice at 3 and 6 mg/kg-day. At the 6 mg/kg-day dose, the liver more than doubled in size compared to the control group. Male mice treated with 3 and 6 mg/kg-day and females treated with 6 mg/kg-day demonstrated significantly elevated serum markers of liver injury including alanine aminotransferase (ALT), glutamate dehydrogenase (GLDH), and liver/body weight percent. The percent of PFESA-BP2 in serum relative to the amount administered was similar in male and female mice, ranged from 9 to 13 %, and was not related to dose. The percent accumulation in the liver of the mice varied by sex (higher in males), ranged from 30 to 65 %, and correlated positively with increasing dose level.


Higher Prevalence of Extended Spectrum β-Lactamase Producing Uropathogenic Escherichia coli Among Patients with Diabetes from a Tertiary Care Hospital of Kathmandu, Nepal.
This study aimed to determine the occurrence of antibiotic resistance genes for β-lactamases; blaTEM and blaCTX-M in uropathogenic Escherichia coli isolates from urinary tract infection (UTI) suspected diabetic and nondiabetic patients. A hospital-based cross-sectional study was conducted in Kathmandu Model Hospital, Kathmandu, in association with the Department of Microbiology, GoldenGate International College, Kathmandu, Nepal, from June to December 2018. A total of 1,267 nonduplicate midstream urine specimens were obtained and processed immediately for isolation of uropathogens. The isolates were subjected to antibiotic susceptibility testing and extended spectrum β-lactamase (ESBL) confirmation. In addition, blaTEM and blaCTX-M genes were detected using specific primers. The overall prevalence of UTI was 17.2% (218/1,267), of which patients with diabetes were significantly more infected; 32.3% (31/96) as compared with nonpatients with diabetes, 15.9% (187/1,171). A total of 221 bacterial isolates were obtained from 218 culture-positive specimens in which E. coli was the most predominant; 67.9% (150/221). Forty-four percent (66/150) of the total E. coli was multidrug resistant and 37.3% (56/150) were ESBL producers. Among 56 isolates, 92.3% (12/13) were from patients with diabetes, and 83.0% (44/53) were from nondiabetics. Furthermore, 84.9% of the screened ESBL producers were confirmed to possess either single or both of blaTEM and blaCTX-M genes. The blaTEM and blaCTX-M genes were detected in 53.6% and 87.5% of the phenotypically ESBL confirmed E. coli, respectively. Higher rates of ESBL producing uropathogenic E. coli are associated among patients with diabetes causing an alarming situation for disease management. However, second-line drugs with broad antimicrobial properties are still found to be effective drugs for multidrug resistance strains.