Tracking between cardiovascular-related measures at 4 and 8 years of age in the INMA-Asturias cohort.
Identifying cardiovascular-related measures that track from early childhood into later ages may help inform early prevention targets for cardiovascular disease. In this study, the tracking of triglycerides (TG), high-density cholesterol (HDL-c), atherogenic coefficient (AC), waist circumference to height ratio (WC/Height), mean arterial pressure (MAP), and homeostatic model assessment of insulin resistance (HOMA-IR) was examined in the INMA-Asturias cohort between 4 and 8 years of age. The analysis was conducted in 307 children who participated in the INMA-Asturias cohort (Spain) at 4 and at 8 years of age. Quantile regression models were used to evaluate tracking between measures at both ages, with each measure at 8 years as the dependent variable and the rank transformation of the same measure at 4 years as the independent variable. We found a positive association between HDL-c rank at 4 years and higher quantiles of the HDL-c distribution at 8 years, with an increase of 2.93 mg/dL (95% CI: 1.98, 3.87) per decile in the 0.9 quantile. A positive association was also found for WC/Height, with an increase of 0.008 (95% CI: 0.004, 0.012) per decile in the 0.9 quantile. We observed that tracking for AC increased in the higher quantiles of the distribution at 8 years, with an increase of 0.11 (95% CI: 0.09, 0.14) in the 0.6 quantile compared to an effect of 0.15 (95% CI: 0.09, 0.21) in the 0.9 quantile. Conclusions: Adult markers of dyslipidemia and central obesity tracked between ages 4 and 8 years. For AC, tracking increased in the higher quantiles of the distribution. What is Known: • Atherosclerosis begins in early life, so preventive efforts that start in childhood may delay progression to clinical disease. Determine what cardiovascular risk factors track into time since childhood bring the opportunity to identified those subjects at risk for later cardiovascular disease. • The study of risk factors in health populations and, particularly in children, copes with not clear and/or controversial thresholds definition. This makes it challenging to study tracking in pediatric ages. What is New: • Quantile regression is a useful tool for assessing the tracking of risk factors for which there are no clinically meaningful thresholds. The increasing trend observed in the tracking of dyslipidemia suggests the possible difficulty that children with abnormal values at 4 years of age might have in normalizing them in future years. • The findings of this article may help to determine which cardiovascular-related measures could be screened and followed-up in children.


Determination of the growth rate of human prostatic cells in primary culture by a morphometric technique.
A morphometric technique, based on the measurement of the area of individual cell colonies and of its increase in time, was applied to study the rate of proliferation of human prostatic cells in vitro. The reliability of the method was checked by determination of the growth rate of cultures of the continuous cell line PC93 by the morphometrical technique as well as by counting of the cell number. No significant difference was found in the population doubling times measured by either of these methods. It was therefore concluded that the morphometrical technique could be applied also to study the growth rate of primary cultures of prostatic epithelial cells, in which counting of the cell number is generally impossible. The results showed that, with primary cultures derived from hyperplastic prostates and prostatic carcinomas as well as from the prostatic tumor line PC82, rapid growth occurred during the first two or three days of culture; measurements performed at a later time appeared to be less reliable. It was demonstrated by the effect of serum deprivation on the growth of PC82 cells that the technique described here is, in principle, suitable to monitor the effect of various agents on the growth of cells in primary culture. The method is non-destructive and requires minimal amounts of tissue; it may be applied especially to cultures that cannot be dispersed easily into single cell suspensions.


Two CML patients who subsequently developed features of essential thrombocythemia with JAK2-V617F mutation while in complete cytogenetic remission after treatment with imatinib mesylate.
The present report describes two chronic myelogenous leukemia (CML) patients with the JAK2-V617F mutation who were in complete hematologic and cytogenetic remission and subsequently developed clinical features of essential thrombocythemia under treatment with tyrosine kinase inhibitors. In light of the findings from previous reports, screening for the JAK2-V617F mutation should be considered for any Ph(+) CML patients with thrombocytosis, leukocytosis, or erythrocytosis at diagnosis and for patients who subsequently develop thrombocytosis, leukocytosis, or erythrocytosis during follow-up, even for CML patients in complete cytogenetic response and major molecular response.


A novel 3-dimensional EUS technique for real-time visualization of the volume data reconstruction process.
Three-dimensional EUS (3D-EUS) technology has facilitated spatial interpretation of US images. However, acquisition of consecutive US scans is time consuming and difficult. A new 3D-EUS system was developed that negates this problem by allowing rapid image renewal and the efficient production of consecutive US scans. Three-dimensional images were reconstructed from a series of 2-dimensional images corresponding to the rotation angle of the echoendoscope as measured with an electromagnetic tracking system. To evaluate the technical feasibility of the system, 3-dimensional images of splenic veins in 2 patients and an esophageal submucosal tumor in a third patient were generated. The 3D-EUS system acquired image data at a rate of 30 frames per second and allowed visualization of these data in real-time. The area of interest was clearly and rapidly portrayed in all 3 patients. This study demonstrates the efficiency of the new 3D-EUS system described in this report. Further development of this novel 3D-EUS system may lead to new applications of this technology.


Expression and prognostic impact of the protein tyrosine phosphatases PRL-1, PRL-2, and PRL-3 in breast cancer.
The aim of this study was to investigate the expression of the protein tyrosine phosphatases (PTP) PRL-1, PRL-2, and PRL-3 in human breast cancer and to evaluate its clinical and prognostic significance. PRL-PTP mRNA expression was examined in malignant (n = 7) and nonmalignant (n = 7) cryoconserved breast tissue samples as well as in eight breast cancer cell lines by RT-PCR. Furthermore, protein expression of PRL-3 was analysed semiquantitatively by immunohistochemistry in ductal breast carcinoma in situ (n = 135) and invasive breast cancer (n = 147) by use of tissue microarray technology (TMA). In 24 lymph node-positive patients we selected the corresponding lymph node metastases for analysis of PRL-3 expression, and a validation set (n = 99) of invasive breast cancer samples was examined. Staining results were correlated with clinicopathological parameters and long-term follow-up. PRL-3 mRNA expression was significantly higher in malignant compared to benign breast tissue. For PRL-1 and PRL-2 expression no significant differences were observed. Staining of TMAs showed PRL-3 expression in 85.9% ductal carcinoma in situ and 75.5% invasive breast carcinomas. Analysis of survival parameters revealed a shorter disease-free survival (DFS) in patients with PRL-3-positive carcinomas, and in particular a significantly shorter DFS in nodal-positive patients with PRL-3 overexpressing tumours as compared to PRL-3-negative breast carcinomas (66+/-7 months (95% CI, 52-80) vs 97+/-9 months (95% CI, 79-115); P = 0.032). Moreover, we found a more frequent expression of PRL-3 in lymph node metastases as compared to the primary tumours (91.7 vs 66.7%; P = 0.033). Our results suggest that PRL-3 might serve as a novel prognostic factor in breast cancer, which may help to predict an adverse disease outcome.


[Antifungal effects in vitro of jasmon and some similar compounds. Structure-activity relationship].
The antimycotic activity in vitro of jasmon and 6 closely related substances has been tested against four different dermatophytes, Candida albicans, Pityrosporum ovale and Aspergillus fumigatus. Jasmon had the highest activity. Among the other substances tested only thiazolidines with a carbonyl function developed antifungal properties against dermatophytes. 2,4 thiazolidinedione at 450 ppm inhibits the growth of Trichophyton rubrum.


Did augmenting the VERB campaign advertising in select communities have an effect on awareness, attitudes, and physical activity?
Although VERB was designed as a national media campaign, funding and donated media time enabled more-intensive advertising and marketing in certain communities. To investigate the effect of increased advertising on physical activity outcomes, six "high-dose" communities were selected to receive more hours of advertising and additional promotional activities. Longitudinal quasi-experimental design comparing outcomes in six communities that received additional VERB marketing activities with outcomes in a comparison group that received only the national dose of advertising. Two cohorts of dyads of youth aged 9-13 years (tweens) and one parent at baseline (2002), followed for 2 years. During the first year of the VERB campaign, each of the six high-dose communities received 50% more advertising and conducted special campaign activities. During the second year, only four of the six communities received the larger dose of advertising and additional promotional activities because of reduced funding. Awareness and understanding of VERB messages; attitudes about physical activity (self-efficacy, social influences, and outcome expectations); and physical activity behaviors. After 1 year, tweens in the high-dose communities reported higher levels of awareness and understanding of VERB and scored higher on the social influences scale than did tweens in a comparison group in areas that received only the national dose of advertising. After 2 years, tweens in the high-dose communities reported higher awareness and understanding of VERB, greater self-efficacy, more sessions of free-time physical activity per week, and were more active on the day before being surveyed than tweens in the comparison group who received the average national dose. Providing communities with a higher dose of marketing activities and sustaining those activities over time yields more positive outcomes.


Resilience and recovery of overexploited marine populations.
Recovery of overexploited marine populations has been slow, and most remain below target biomass levels. A key question is whether this is due to insufficient reductions in harvest rates or the erosion of population resilience. Using a global meta-analysis of overfished stocks, we find that resilience of those stocks subjected to moderate levels of overfishing is enhanced, not compromised, offering the possibility of swift recovery. However, prolonged intense overexploitation, especially for collapsed stocks, not only delays rebuilding but also substantially increases the uncertainty in recovery times, despite predictable influences of fishing and life history. Timely and decisive reductions in harvest rates could mitigate this uncertainty. Instead, current harvest and low biomass levels render recovery improbable for the majority of the world's depleted stocks.


Bacterial sepsis after living donor liver transplantation: the impact of early enteral nutrition.
Bacterial sepsis is a significant problem that must be addressed after living donor liver transplantation (LDLT). A retrospective analysis of 346 adult-to-adult LDLT patients was performed. Forty-six patients (13.3%) experienced bacterial sepsis, with primary and secondary origins in 23.9% and 76.1%, respectively. Gram-negative bacteria accounted for 71.7% of the bacteria isolated. The 2-year cumulative graft survival rate in patients with bacterial sepsis was 45.7%. Patients with bacterial sepsis secondary to pneumonia (n = 12) had poorer 2-year graft survival rates (16.7%) than did those with primary or other types of secondary sepsis (p = 0.004). Multivariate analysis showed that intraoperative massive blood loss >10L (p < 0.001) and no enteral feeding started within 48 hours after transplantation (p = 0.005) were significant risk factors for bacterial sepsis. Among patients who received enteral nutrition, the incidences of bacterial sepsis in patients who received enteral nutrition within 48 hours (n = 135) or later than 48 hours (n = 57) were 5.9% and 21.0%, respectively (p = 0.002). The incidence of early graft loss was 8-fold higher in recipients with massive intraoperative blood loss without early enteral nutrition (p < 0.001). Early enteral nutrition was associated with significantly reduced risk of developing bacterial sepsis after LDLT.


In the Rat Midbrain, SG2NA and DJ-1 have Common Interactome, Including Mitochondrial Electron Transporters that are Comodulated Under Oxidative Stress.
Scaffold proteins Striatin and SG2NA assemble kinases and phosphatases into the signalling complexes called STRIPAK. Dysfunctional STRIPAKs cause cancer, cerebral cavernous malformations, etc. DJ-1, a sensor for oxidative stress, has long been associated with the Parkinson's disease, cancer, and immune disorders. SG2NA interacts with DJ-1 and Akt providing neuroprotection under oxidative stress. To dissect the role of SG2NA and DJ-1 in neuronal pathobiology, rat midbrain extracts were immunoprecipitated with SG2NA and sixty-three interacting proteins were identified. BN-PAGE followed by the LC-MS/MS showed 1030 comigrating proteins as the potential constituents of the multimeric complexes formed by SG2NA. Forty-three proteins were common between those identified by co-immunoprecipitation and the BN-PAGE. Co-immunoprecipitation with DJ-1 identified 179 interacting partners, of which forty-one also interact with SG2NA. Among those forty-one proteins immunoprecipitated with both SG2NA and DJ-1, thirty-nine comigrated with SG2NA in the BN-PAGE, and thus are bonafide constituents of the supramolecular assemblies comprising both DJ-1 and SG2NA. Among those thirty-nine proteins, seven are involved in mitochondrial oxidative phosphorylation. In rotenone-treated rats having Parkinson's like symptoms, the levels of both SG2NA and DJ-1 increased in the mitochondria; and the association of SG2NA with the electron transport complexes enhanced. In the hemi-Parkinson's model, where the rats were injected with 6-OHDA into the midbrain, the occupancy of SG2NA and DJ-1 in the mitochondrial complexes also increased. Our study thus reveals a new family of potential STRIPAK assemblies involving both SG2NA and DJ-1, with key roles in protecting midbrain from the oxidative stress.


Sudden death in ischemic heart disease - 2017.
At this time, we find ourselves with an abundance of guidelines for management of patients with manifest ventricular tachyarrhythmias, or at risk for such arrhythmias, in patients with coronary heart disease (CHD). The guidelines are focused primarily on the "appropriate use" of the implantable cardioverter/defibrillator (ICD). Unfortunately, the bulk of the guidelines have very little basis in the underlying pathophysiology responsible for sudden cardiac death (SCD) in patients with CHD. Rather, they are based primarily on the results of randomized clinical trials that merely sought to take broad populations at elevated total mortality risk and determining whether the ICD can reduce overall mortality. The trials were not aimed at elucidating or exploiting the varying pathophysiology responsible for the ventricular arrhythmias responsible for most sudden deaths in this setting. The goal of the trials is appropriate - to improve the survival. The problem with promoting trials that solely determine whether a broad-based population (identified by one parameter such as ejection fraction that bears no direct relation to the pathogenesis of arrhythmias) derives a survival benefit from a therapy such as the ICD, is that many patients that could benefit from the ICD are missed (not covered by the guidelines), and many patients that will never benefit from the ICD are exposed to its risks and costs. How can we advance the use of potent, but expensive therapies that carry risk such as the ICD to improve survival of patients with CHD today? There are several avenues worth pursuing, both for short-term as well as long-term gain. First, there are several models shown to have the potential to identify patients currently covered by the guidelines for ICD use, that are highly unlikely to benefit, because of the existing co-morbidities. These models are likely to be valid because there is significant overlap in the parameters identified in each model, and they have been tested retrospectively in a variety of study populations. These models are not likely to be incorporated into use guidelines, until they have been tested prospectively in a randomized trial in a contemporary patient population. This can, and should be done. Use of such a model, based on noninvasive, readily available clinical markers offers the possibility of improving the efficiency with which ICDs are used to reduce the risk of SCD in CHD patients. Second, we need to recognize the fact that SCD in this population is a result of multiple potential mechanisms. And, the electrophysiologic substrates underlying these mechanisms are influenced by interactions with the autonomic nervous system and hemodynamic conditions. While most out-of-hospital cardiac arrests do not occur in persons with overt heart failure, the presence of heart failure clearly increases the risk for SCD, likely by a variety of mechanisms. There is increasing evidence that altered left ventricular geometry may not only reduce LV mechanical efficiency, but may also have direct effects on the electrophysiologic substrate. Although there is an abundance of evidence supporting the importance of autonomic interactions in the genesis of spontaneous arrhythmias, the utility of prospectively measuring autonomic indices to predict future arrhythmic events has to date not proven to be useful. Of course, that is not to discount the significant impact of beta-adrenergic blockade on survival and reducing arrhythmic events. Future works must focus more on both animal models of post-infarction arrhythmias, as well as integrating findings from such studies into human physiology, with subsequent testing in the form of randomized clinical trials.


Recent structural advances towards understanding of the bacterial type III secretion injectisome.
The bacterial injectisome is a structurally conserved, syringe-shaped nanomachine that spans the Gram-negative envelope and forms a continuous channel for type III secretion of protein effectors. The injectisome, and the host-modulating effectors it secretes, are essential for the pathogenesis of several Gram-negative bacterial species, and it is a key virulence factor associated with the progression of many clinical and community-based infectious diseases. The molecular structure of the injectisome has been the focus of intense research efforts over the past 30 years, and during this time significant progress has been made in determining the molecular structures of many components. In this review we present major advances in our structural and mechanistic understanding of the injectisome, as facilitated by cryoelectron microscopy approaches.


Facial selectivities in the nucleophilic additions of 2,3-unsaturated 3-arylsulfinyl pyranosides.
2,3-Unsaturated 3-arylsulfinyl pyranosides undergo nucleophilic additions at C-2, with facial selectivities depending on the nucleophile and the substituent on sulfinyl sulfur. The reactions of such sugar vinyl sulfoxides lead to the addition of nucleophile preferring an axial orientation at C-2, with concomitant formation of an allylic bond at C-3 to C-4. This trend in the addition pattern is observed for primary amine, carbon and sulfur nucleophiles, whereas secondary amines prefer an equatorial addition at C-2. The effect of p-tolylthio- versus (p-isopropylphenyl)thio vinyl sulfoxide is that the equatorial nucleophilic addition is preferred even more with the latter vinyl sulfoxide.


A stochastic repair--misrepair model for the effects of radiation on cells.
The purpose of this paper is to present a stochastic model for effects of radiation on cells. The model includes provisions for lethal effects and for transformation to malignant status. Empirical findings indicate the presence of some repair mechanism in the cells, and a way to incorporate this idea into the model is discussed. Comparisons of the derived survival and transformation probabilities with actual data are favorable. The interpretation of the estimated values leads to questions to be investigated by the experimenters.


In vitro calcification in human osteoblastic cell line derived from periosteum.
Human osteoblastic cell cultures were established from human periosteum, identified on the basis of high alkaline phosphatase activity in the confluent state. The cells in the growing state showed a fibroblastic morphology and grew to form multiple layers. The cells could spontaneously calcify, and the process was accelerated by alpha-glycerophosphate. Minerals deposited on the cells consisted exclusively of calcium and phosphorus, and matured into hydroxyapatite crystals. The calcification was stimulated by the treatment with 1 alpha,25-dihydroxy-vitamin D3. These results indicate that the osteoblastic cells have the capacity to differentiate into osteocytes and form calcified human bone tissue in vitro.


Cost-Effectiveness Analysis of Oral Direct-Acting Antivirals for Chinese Patients with Chronic Hepatitis C.
All oral direct-acting antivirals (DAAs) have shown excellent efficacy and safety in Chinese patients with chronic hepatitis C (CHC). However, the cost of DAAs used to be expensive; therefore, large numbers of patients had no access to DAAs in China. Recently, prices have been greatly reduced. The objective of this study was to evaluate the cost-effectiveness of ledipasvir/sofosbuvir (LDV/SOF), sofosbuvir/velpatasvir (SOF/VEL), elbasvir/grazoprevir (EBR/GZR) and glecaprevir/pibrentasvir (GLE/PIB) in Chinese CHC patients stratified by hepatitis C virus (HCV) genotype (GT), cirrhosis status, and treatment history. On the basis of a Chinese healthcare perspective, a Markov model was constructed to estimate the lifetime costs and health outcomes of patients treated with different DAA regimens. Chinese-specific clinical, cost, and utility inputs were obtained or calculated from published sources and expert opinions. Costs, life-years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were reported as primary outcomes. Base-case analysis and sensitivity analysis were conducted. At a willing-to-pay (WTP) threshold of US$30,081/QALY (calculated by three times the GDP per capita in China), SOF/VEL was cost-effective in patients with HCV GT 1, 3, and 6 infections, and the probabilities that SOF/VEL was cost-effective were 9.7-75.7%, 39.1-63.9%, and 35.6-88.0%, respectively. For GT2 patients, noncirrhotic patients, treatment-naïve patients, and treatment-experienced patients, LDV/SOF was the most cost-effective regimen, and the probabilities of cost-effectiveness for each of these groups was 92.1-99.8%, 89.9-99.0%, 61.6-91.2%, and 99.3-100.0%, respectively below the WTP threshold. The GLE/PIB regimen (12-week duration) was the most cost-effective in cirrhotic patients, whereas the probability of its cost-effectiveness varied with that of EBR/GZR (4.1-93.8% versus 6.2-93.3%) below the WTP threshold. Overall, SOF/VEL and LDV/SOF regimens are more likely to be cost-effective among various subgroups of Chinese patients with CHC.


Antitumour evaluation of di-(2-ethylhexyl) phthalate (DEHP) isolated from Calotropis gigantea L. flower.
The objective of the study is to explore the anticancer activity of di-(2-ethylhexyl) phthalate (DEHP) isolated from Calotropis gigantea flower against Ehrlich ascites carcinoma cells (EAC) in Swiss albino mice. The activity of DEHP was evaluated at doses of 10, 20 and 40 mg kg-1 body mass applied intraperitoneally. DEHP showed a significant decrease in viable cell count (p < 0.05), mass gain (due to tumour burden) and elevated the life span of EAC cell bearing mice. Altered hematological profiles such as RBC, hemoglobin, WBC and differential count were reverted to normal levels in DEHP-treated mice. DEHP also brought back altered biochemical parameters (glucose, cholesterol, triglycerides, blood urea, SALP and SGOT) to normal level. Results of this study indicate that DEHP show potent dose dependent antitumour activity against EAC in vivo.


Lactation during and after Breast Cancer.
Breastfeeding is an important aspect of mother-newborn relationship and is of great benefit for the baby. Unfortunately, many drugs taken by the mother may pass into her milk and exert an effect on the newborn. Very limited data is available and a cautionary approach is warranted especially when the woman receives anticancer treatment including chemotherapy , hormonal treatment and the recently introduced target agents as well as monoclonal antibodies. In all these conditions breastfeeding should be put on hold.More and more often physicians are faced with women that are pregnant years after the diagnosis of cancer: this has long been considered dangerous for the mother, but data show that prognosis is definitely not worse. If the woman is no longer being actively treated, breastfeeding is advisable every time it is possible, even if patients that received breast radiation may be unable to produce a sufficient amount of milk on that side.


Observations on an Eimeria sp. (Apicomplexa) from the green kingfisher Chloroceryle americana (Gmelin, 1788) (Coraciiformes) in Southeastern Brazil: an example of how the ecological aspects of the host can be essential for the identification of its coccidians.
Parasitism in kingfishers is very little reported and predominantly related to hemoparasites, helminths, and ectoparasites. The present study provided a morphological and genotypic study of an Eimeria sp. recovered from a green kingfisher Chloroceryle americana (Gmelin, 1788) captured in the Marambaia Island, on the coast of the state of Rio de Janeiro, Southeastern Brazil. The coccidial density, some morphological aspects of its oocysts, the molecular results, and, mainly, the ecological niche of C. americana in the mangrove of the Marambaia Island suggest that this coccidian species is a pseudoparasite.


The use of biomarkers as integrative tools for transitional water bodies monitoring in the Water Framework Directive context - A holistic approach in Minho river transitional waters.
The Water Framework Directive (WFD) provides an important legislative opportunity to promote and implement an integrated approach for the protection of inland surface waters, transitional waters, coastal waters and groundwaters. The transitional waters constitute a central piece as they are usually under high environmental pressure and by their inherent characteristics present monitoring challenges. Integrating water quality monitoring with biological monitoring can increase the cost-effectiveness of monitoring efforts. One way of doing this is with biomarkers, which effectively integrate physical-chemical status and biological quality elements, dealing holistically with adverse consequences on the health of water bodies. The new Marine Strategy Framework Directive (MSFD) already incorporates the biomarker approach. Given the recent activities of OSPAR and HELCOM to harmonize existing monitoring guidelines between MSFD and WFD the use of similar methodologies should be fostered. To illustrate the potential of the biomarker approach, juveniles of flounder (Platichthys flesus) were used to evaluate the quality of the Minho river-estuary water bodies. The use of juveniles instead of adults eliminates several confounding factors such changes on the biological responses associated with reproduction. Here, a panel of well-established biomarkers, EROD, AChE, SOD, CAT, GST, LPO, ENA and FACs (1-Hydroxyrene) were selected and measured along with a gradient of different physical conditions, and integrated with trace elements characterization on both biota and sediments. In general, a clear profile along the water bodies was found, with low seasonal and spatial variation, consistent with a low impacted area. Overall, the results support the use of both the battery of biomarkers and the use of juvenile flounders in the monitoring of the water quality status within the WFD.


Hemodynamic effects of intravenous bolus injection of iopromide 370 twice in abdominal contrast-enhanced CT and coronary CTA dual-site sequential examinations.
Little information is available about how intravenous bolus injection of iopromide 370 twice in a short time will affect hemodynamics and whether the changes reach clinically relevant levels. In the present study, 31 healthy adult volunteers received abdominal contrast-enhanced CT and coronary CTA sequential examinations. The same dose and rate of normal saline was injected 30 min in advance as self-control. Hemodynamic data were noninvasively collected at selected time points from 1 min prior to injection to 30 min post-injection. The results showed that after iopromide 370 injection, except for stroke volume, all other indicators changed immediately during the first injection, changed most significantly during the second injection (P < 0.05), and returned to baseline within 10 min. Heart rate and cardiac output exhibited the most pronounced changes, with an increasing rate of 33.5% and 33.8%, respectively. For indicators with a change range of > 15% during the second injection, except for mean arterial pressure and total peripheral resistance, the proportions of subjects for the other indicators between the two groups were statistically different (P < 0.05). In conclusion, intravenous bolus injection of iopromide 370 twice in dual-site sequential examinations induced dose-cumulative and time-dependent hemodynamic effects, which all fluctuated within the normal ranges.


Evaluation of flow scintillation analysis for the determination of Sr-90 in bioassay samples.
An automated procedure for the determination of (90)Sr was adapted from existing methods of flow scintillation analysis (FSA) for use on aqueous samples with low levels of activity (<1000 dpm per sample). This technique employs high-performance extraction chromatography (HPEC) and an on-line liquid scintillation counter to provide automated separation and subsequent detection of (90)Sr. The total analysis time is 30 min per sample. Dilute urine samples, spiked with (90)Sr, were also processed by this method to test the application of this technique for bioassay monitoring.


The influence of newborn screening for cystic fibrosis on pulmonary outcomes in new South Wales.
To determine whether early treatment of cystic fibrosis made possible by diagnosis after newborn screening results in improved pulmonary outcomes in adolescence. Both screening (SG) and non-screening groups (NSG) comprised a cohort of children from Australia previously studied at 1, 5, and 10 years of age. The groups were compared on measures of clinical status obtained during their comprehensive annual review conducted at or near the 15th birthday of the subjects. Data were collected on 48 of 57 original subjects in the NSG (7 had died; 2 were lost to follow-up) and 52 of 60 original subjects in the SG (4 had died; 2 transferred out of the country; 2 were lost to follow-up). Those dying in the SG were significantly older (by 48 months, P < .05) than those in the NSG. No statistically significant differences were found between the groups in nutritional status. However, subjects in the SG displayed statistically better total Shwachman-Kulczycki scores (7.0, P <or= .05), chest x-ray scores (2.3, P <or= .05) and lung function (forced expiratory volume in 1 second by 12.3%, P <or= .01; forced vital capacity by 12.6%, P <or= .01; and mean airflow by 23.3%, P <or= .01). The previously observed advantage conferred by cystic fibrosis newborn screening on clinical outcomes in infancy and childhood is still apparent in adolescence.


Socio-demographic determinants of childhood immunization incompletion in Koforidua, Ghana.
Immunization saves more than 3 million lives worldwide each year, and it saves millions from suffering illness and lifelong disability. The study sought to assess the socio-demographic factors that influence childhood immunization incompletion. A cross-sectional descriptive design was employed for the study conducted at the Child Welfare Clinic in the Regional Hospital, Koforidua. A total of 280 caregivers/mothers who have children aged between 0 and 59 months were included in this study. Data were entered and analyzed using SPSS. The study found that being divorced (p = 0.048) and working part-time (p = 0.049) has a significant and positive association with immunization incompletion. Women who were divorced [AOR (95% CI) 3.01 (1.59-58.2)] were 3 times less likely to complete immunization than those who were cohabiting, married and widowed taken into account the effect due to all the additional confounder variables included in the analysis. Women who were working part-time were 2.28 times less likely to complete immunization schedule than those working full-time; [AOR (95% CI) 2.28 (1.031-9.11)]. This study has documented socio-demographic factors influencing childhood immunization incompletion in the Regional Hospital, Koforidua. The Ministry of Health should, therefore, put in measures like public education to encourage mothers to complete each immunization schedule.


Plasticity in the synaptic number associated with neuropathic pain in the rat spinal dorsal horn: A stereological study.
This study aimed to determine whether neuropathic pain is associated with a plasticity change in the number of synapses in the spinal dorsal horn. 12 normal adult SD rats were randomly divided into two groups: 7 animals were subjected to unilateral loose ligation (to induce chronic constriction injury) of the sciatic nerve (CCI group) and 5 animals subjected to unilateral sham-operation (sham-operated group). 28 days after operation, the L4-L6 segment of the spinal cord was removed, and paraffin-embedded sections were prepared and stained with Nissl's method and synaptophysin immunohistochemistry. The numbers of neurons and synapses in the spinal dorsal horn were estimated using a contemporary stereological technique-the optical disector. An 86% increase in the number (per unit length of the spinal cord) of synapses or 98% increase in the ratio between the numbers of synapses and neurons in the spinal dorsal horn was found in the middle tissue block but not in both the rostral and caudal tissue blokes cut from L4-L6 segment of the spinal cord. The results suggest that neuropathic pain, as established by the CCI model, is associated with a plasticity change in the spinal dorsal horn: increase in the number of synapses.


Mechanical properties and biocompatibility of plasma-nitrided laser-cut 316L cardiovascular stents.
The effect of surface modification of laser-cut 316L cardiovascular stents by low-T plasma nitriding was evaluated in terms of mechanical properties and biocompatibility of the stents. The plasma nitriding was performed at 400, 450 or 500 degrees C using various ratios of nitrogen-hydrogen gas mixtures. The flexibility and radial strength were measured in crimped and expanded state of the stents, respectively. The mechanical properties could be adjusted and improved by plasma nitriding conducted at temperatures lower than 450 degrees C and/or nitrogen content less than 10% in the treatment gas. An osteoblast cell culture model system was utilized to investigate the effect of plasma nitriding of the stents on the biological response towards the stents, using biological criteria such as cell viability, alkaline phosphatase and nitric oxide production. In terms of cell viability and alkaline phosphatase production, the plasma nitriding procedure did not appear to negatively affect the biocompatibility of the 316L steel stents. However, in terms of nitric oxide production that was slightly increased in the presence of the plasma-nitrided stents, an indirect improvement in the biocompatibility could possibly be expected.


Retrospective Analysis of Axial Length Changes in Overnight Orthokeratology in an Academic Myopia Control Clinic.
Although the myopia control efficacy of orthokeratology lenses has been established with clinical trials, reports of axial length change in non-study-based patient care are scarce. This study investigates the use of orthokeratology lenses for myopia control in a clinical population and compares axial elongation against those published in recent clinical investigations. This study aimed to investigate factors affecting axial elongation during use of orthokeratology lenses for myopia control in an academic clinical setting. This study was a retrospective consecutive case series from the Myopia Control Clinic at the Herbert Wertheim School of Optometry at the University of California, Berkeley (Berkeley, CA). Patients ranging from 5 to 18 years old using orthokeratology for at least 1 year were included in the study. Data from 102 patients' eyes were analyzed at baseline (before the initiation of treatment) and after 1 year of wear (12 ± 3 months). Multivariate analysis was undertaken to identify factors significantly associated with axial elongation over this period. Mean (±standard deviation) spherical equivalent refraction and axial length at baseline were -2.54 (±1.21) D and 24.53 (±0.82) mm, respectively. By the 1-year follow-up, eyes had shown significant axial elongation (0.18 ± 0.24 mm; P < .001), which was found to be inversely correlated with age ( P < .001). Race, sex, baseline axial length, and baseline refraction were not significantly associated with axial elongation. Factors influencing axial length and the magnitude of axial elongation in our orthokeratology patient population are consistent with orthokeratology treatment groups from published randomized clinical trials and support the use of these lenses for myopia control in a clinical practice setting.


The mechanism of aquatic photodegradation of organophosphorus sensitized by humic acid-Fe3+ complexes.
Organic phosphorus is an important source of eutrophication. In this study, to understand the mechanism of organophosphorus photodegradation, humic acid-Fe3+ (HA-Fe3+) complexes were prepared as a sensitizer, and glyphosate (GP) was used as a substrate for photodegradation. The effects of the initial GP concentration, HA concentration, Fe3+ concentration and microbial factors on photodegradation were investigated. The initial concentrations of GP, HA and Fe3+ could significantly affect the degradation rate of GP. Phosphate is the main product of GP photodegradation. Based on the identification of the active species in the reaction process, t-butanol was found to have the most significant inhibitory effect on the degradation. The reaction rate after t-butanol treatment was reduced from 0.017 to 0.003. This confirmed that OH was the main oxidant in the system, which was also demonstrated by EPR spectroscopy. A possible mechanism of GP photodegradation sensitized by HA-Fe3+ complexes was revealed for the first time. The HA-Fe3+ complexes in the reaction system were photodegraded and oxidized to finally produce OH, which promotes GP photodegradation. This study facilitates understanding the phosphorus cycle in a water environment and provides a scientific basis for the restoration of eutrophic lakes.


Failure to complete apoptosis following neonatal hypoxia-ischemia manifests as "continuum" phenotype of cell death and occurs with multiple manifestations of mitochondrial dysfunction in rodent forebrain.
Controversy surrounds proper classification of neurodegeneration occurring acutely following neonatal hypoxia-ischemia (HI). By ultrastructural classification, in the first 24 h after neonatal hypoxia-ischemia in the 7-day-old (p7) rat, the majority of striatal cells die having both apoptotic and necrotic features. There is formation of a functional apoptosome, and activation of caspases-9 and -3 occurring simultaneously with loss of structurally intact mitochondria to 34.7+/-25% and loss of mitochondrial cytochrome c oxidase activity to 34.7+/-12.7% of control levels by 3 h after hypoxia-ischemia. There is also loss of the mitochondrial motor protein, kinesin. This combination of activation of apoptosis pathways simultaneous with significant mitochondrial dysfunction may cause incomplete packaging of nuclear and cytoplasmic contents and a hybrid of necrotic and apoptotic features. Evidence for an intermediate biochemistry of cell death including expression of the 17 kDa isoform of caspase-3 in dying neurons lacking a classic apoptotic morphology and degradation of the neuronal cytoskeletal protein spectrin by caspase-3 and calcium-activated calpains yielding 120 kDa and 145/150 kDa fragments, respectively, is also found. In summary, neonatal hypoxia-ischemia triggers apoptotic cascades, and simultaneously causes mitochondrial structural and functional failure. The presence of a "continuum" phenotype of cell death that varies on a cell-by-cell basis suggests that the phenotype of cell death is dependent on the energy available to drive the apoptotic pathways to completion.


Effects of acetate and bicarbonate dialysate on left ventricular performance.
Whether bicarbonate dialysis (BiHD) improves left ventricular (LV) function more than acetate dialysis (AcHD) and whether AcHD exerts a negative inotropic effect remains controversial. To address this question, the LV contractile responses to both dialysate buffers were tested in six stable chronic dialysis patients not taking any cardiac or antihypertensive medicines. The patients were studied with echocardiography before and after an isovolemic dialysis (no weight change) with either buffer, and neither heart rate nor blood pressure were significantly altered during either procedure. The patients were studied at three different filling volumes so that LV function curves could be constructed. Both dialysates were associated with comparable and significant changes in LV end systolic volume (AcHD, 55 +/- 5 to 49 +/- 5 mL, P less than .001; BiHD, 56 +/- 5 to 49.5 +/- 5 mL, P less than .001), stroke volume (AcHD, 88 +/- 7 to 97 +/- 5 mL, P less than .01; BiHD, 89 +/- 7 to 97 +/- mL, P less than .05), and LV ejection fraction (AcHD, 60 +/- 7% to 65 +/- 8%, P less than .05; BiHD, 60 +/- 3 to 67 +/- 2%, P less than .001). In addition, the mean velocity of circumferential fiber shortening (VCF), an index of ventricular contractility, also increased significantly after dialysis with both dialysates (AcHD, .96 +/- .08 to 1.20 +/- .15, P less than .001; BiHD, .93 +/- .09 to 1.29 +/- .11, P less than .001). Finally, both dialysates were associated with upward shifts in the LV function curve of a similar magnitude.(ABSTRACT TRUNCATED AT 250 WORDS)


Perinatal metabolic inflammation in the hypothalamus impairs the development of homeostatic feeding circuitry.
Over the past few decades, there has been a global increase in childhood obesity. This rise in childhood obesity contributes to the susceptibility of impaired metabolism during both childhood and adulthood. The hypothalamus, specifically the arcuate nucleus (ARC), houses crucial neurons involved in regulating homeostatic feeding. These neurons include proopiomelanocortin (POMC) and agouti-related peptide (AGRP) secreting neurons. They play a vital role in sensing nutrients and metabolic hormones like insulin, leptin, and ghrelin. The neurogenesis of AGRP and POMC neurons completes at birth; however, axon development and synapse formation occur during the postnatal stages in rodents. Insulin, leptin, and ghrelin are the essential regulators of POMC and AGRP neurons. Maternal obesity and postnatal overfeeding or a high-fat diet (HFD) feeding cause metabolic inflammation, disrupted signaling of metabolic hormones, netrin-1, and neurogenic factors, neonatal obesity, and defective neuronal development in animal models; however, the mechanism is unclear. Within the hypothalamus and other brain areas, there exists a wide range of interconnected neuronal populations that regulate various aspects of feeding. However, this review aims to discuss how perinatal metabolic inflammation influences the development of POMC and AGRP neurons within the hypothalamus.


Influence of temperature and pretreatments on the anaerobic digestion of wastewater grown microalgae in a laboratory-scale accumulating-volume reactor.
This laboratory-scale study investigated the performance of a low-cost anaerobic digester for microalgae. Low (∼2%) solids content wastewater-grown microalgal biomass (MB) was digested in an unmixed, accumulating-volume reactor (AVR) with solid and liquid separation that enabled a long solids retention time. AVRs (2 or 20 L) were operated at 20 °C, 37 °C or ambient temperature (8-21 °C), and the influence of two pretreatments - low-temperature thermal (50-57 °C) and freeze-thaw - on algal digestion were studied. The highest methane yield from untreated MB was in the 37 °C AVR with 225 L CH4 kg volatile solids (VS)(-1), compared with 180 L CH4 kg VS(-1)added in a conventional, 37 °C completely stirred tank reactor (CSTR), and 101 L CH4 kg VS(-1)added in the 20 °C AVR. Freeze-thaw and low-temperature thermal pretreatments promoted protein hydrolysis and increased methane yields by 32-50% at 20 °C, compared with untreated MB. Pretreatments also increased the mineralisation of nitrogen (41-57%) and phosphorus (76-84%) during digestion. MB digestion at ambient temperature was comparable with digestion at 20 °C, until temperature dropped below 16 °C.


The temporal component of the auditory evoked potential: a reinterpretation.
The auditory evoked potentials in man cannot be explained by a single source even though a strong influence of the primary areas in the supra-temporal plane has been pointed out in different works. In 26 normal adults we mathematically extracted the greater part of the experimental AEPs explicable by such an origin. The residual part obtained by subtracting this first component from the experimental data is in agreement with an origin in the precentral motor cortex.


Influence of maternal preeclampsia on recombinant human granulocyte colony-stimulating factor effect in neutropenic neonates with suspected sepsis.
To evaluate the effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in preterm neonates with suspected sepsis and severe neutropenia (<1500 mm(3)), and to define the influence of maternal preeclampsia on rhG-CSF activity. Twenty neonates of normotensive mothers (NNMs) (GA 29.2+/-0.5 weeks and BW 1.024+/-81 g) and 20 born to preeclamptic mothers (NPMs) (GA 29+/-0.4 weeks and BW 946+/-55 g) were treated with rhG-CSF, 10 microg/kg per day for 3 days. Complete blood counts were obtained at day 0 (before rhG-CSF administration) and 1-4, 6, 9, 20 and 30 days later. Absolute neutrophil count (ANC) increased rapidly (three-fold within 24h), and significantly (maximum approximately 20-25 times starting values) and remained within normal range in both groups. However, in NNMs a two-phase increase occurred with an early peak on day 2 and a further peak on day 6 giving significantly higher ANC (P<0.001) than for NPMs at days 2-4 and 6. NPMs showed a gradual ANC increase with a single late peak occurring 3 days later than NNMs (day 9). The highest peak values for ANC were similar (15,900+/-1395 mm(-3) for NNMs and 13,880+/-1097 mm(-3) for NPMs). Neutropenia was completely resolved within 2 days in NNMs and within 4 days in NPMs. Preeclampsia seemed to influence the course of the ANC in spite of rhG-CSF administration, and a higher daily-dose for NPMs with neutropenic sepsis may more rapidly resolve neutropenia by overcoming the preeclampsia-associated inhibitor of rhG-CSF through a dose-dependent mechanism.


Delirium and Its Association with Short- and Long-Term Health Outcomes in Medically Admitted Patients: A Prospective Study.
Delirium is highly prevalent among elderly hospitalized patients in various healthcare settings. This study aimed to assess the impact of delirium on short- and long-term health outcomes. A prospective cohort included medically ill patients (≥65 years) admitted to a tertiary healthcare facility. Delirium was screened using the 3-Minute Diagnostic confusion assessment method (3D-CAM). During hospitalization, 53.8% (n = 153/284) had delirium. Patients with delirium had a longer length of hospital stay (LOS) (7 vs. 5 days; p < 0.01) compared to patients without delirium. Delirium caused a higher frequency of high-dependency unit (HDU) or intensive care unit (ICU) admission (p < 0.01) and an increased incidence of hospital-acquired complications, including infections (p = 0.03), pressure injuries (p = 0.01), and upper gastrointestinal bleeding (p < 0.01). Inpatient all-cause mortality was higher in patients with delirium than those without delirium (16.3% vs. 1.5%; p < 0.01). Patients with delirium had higher rates of 90-day all-cause mortality (25.4% vs. 8.4%; p < 0.01) and 1-year all-cause mortality (35.9% vs. 16%; p < 0.01) compared to patients without delirium. Patients with delirium exhibited shorter survival periods at 90 days and 1 year compared to patients without delirium with a hazard ratio (HR) = 3.41, 95% CI: 1.75-6.66, p < 0.01 and HR = 2.64, 95% CI: 1.59-4.37, p < 0.01, respectively. Delirium is associated with serious short-term and long-term clinical consequences. Early recognition, prevention, and targeted interventions addressing reversible risk factors are crucial. Further research is warranted to explore effective strategies for delirium management in general medical wards.


Genome-wide association and targeted transcriptomic analyses reveal loci and candidate genes regulating preharvest sprouting in barley.
Genome-wide association study of diverse barley genotypes identified loci, single nucleotide polymorphisms and candidate genes that control seed dormancy and therefore enhance resistance to preharvest sprouting. Preharvest sprouting (PHS) causes significant yield and quality loss in barley and it is strongly associated with the level of seed dormancy. This study performed genome-wide association study using a collection of 255 diverse barley genotypes grown over four environments to identify loci controlling dormancy/PHS. Our phenotypic analysis revealed substantial variation in germination index/dormancy levels among the barley genotypes. Marker-trait association and linkage disequilibrium (LD) decay analyses identified 16 single nucleotide polymorphisms (SNPs) and two QTLs associated with dormancy/PHS, respectively, on chromosome 3H and 5H explaining 6.9% to 11.1% of the phenotypic variation. QTL.5H consist of 14 SNPs of which 12 SNPs satisfy the FDR threshold of α = 0.05, and it may represent the SD2 locus. The QTL on 3H consists of one SNP that doesn't satisfy FDR (α = 0.05). Genes harbouring the significant SNPs were analyzed for their expression pattern in the seeds of selected dormant and non-dormant genotypes. Of these genes, HvRCD1, HvPSRP1 and HvF3H exhibited differential expression between the dormant and non-dormant seed samples, suggesting their role in controlling seed dormancy/PHS. Three SNPs located within the differentially expressed genes residing in QTL.5H explained considerable phenotypic variation (≥ 8.6%), suggesting their importance in regulating PHS resistance. Analysis of the SNP marker data in QTL.5H identified a haplotype for PHS resistance. Overall, the study identified loci, SNPs and candidate genes that control dormancy and therefore play important roles in enhancing PHS resistance in barley through marker-assisted breeding.


Pulmonary hypertension from prominent vascular involvement in diffuse amyloidosis.
Pulmonary arterial hypertension was found in a patient with myeloma who had a diffuse lung lesion. Echocardiographic and hemodynamic data from pulmonary arterial catheterization demonstrated relatively well-preserved left ventricular function. The diagnosis of diffuse pulmonary amyloidosis was established by open lung biopsy, which revealed severe diffuse vascular deposition of amyloid with mild involvement of the alveolar septa. Pulmonary arterial hypertension secondary to vascular deposition of amyloid in the lungs is rare. This case corroborates the clinicopathologic relationship.


Theoretical study of chlordecone and surface groups interaction in an activated carbon model under acidic and neutral conditions.
Activated carbons (ACs) are widely used in the purification of drinking water without almost any knowledge about the adsorption mechanisms of the persistent organic pollutants. Chlordecone (CLD, Kepone) is an organochlorinated synthetic compound that has been used mainly as agricultural insecticide. CLD has been identified and listed as a persistent organic pollutant by the Stockholm Convention. The selection of the best suited AC for this type of contaminants is mainly an empirical and costly process. A theoretical study of the influence of AC surface groups (SGs) on CLD adsorption is done in order to help understanding the process. This may provide a first selection criteria for the preparation of AC with suitable surface properties. A model of AC consisting of a seven membered ring graphene sheet (coronene) with a functional group on the edge was used to evaluate the influence of the SGs over the adsorption. Multiple Minima Hypersurface methodology (MMH) coupled with PM7 semiempirical Hamiltonian was employed in order to study the interactions of the chlordecone with SGs (hydroxyl and carboxyl) at acidic and neutral pH and different hydration conditions. Selected structures were re-optimized using CAM-B3LYP to achieve a well-defined electron density to characterize the interactions by the Quantum Theory of Atoms in Molecules approach. The deprotonated form of surface carboxyl and hydroxyl groups of AC models show the strongest interactions, suggesting a chemical adsorption. An increase in carboxylic SGs content is proposed to enhance CLD adsorption onto AC at neutral pH conditions.


Gelatinized sweet potato starches obtained at different preheating temperatures in a spray dryer.
Native sweet potato starch was gelatinized at temperatures between 57 and 69 °C and then spray dried, to verify the changes caused by this process. The spray dried starch granules initially swelled with the increase in preheating temperature, displaying a larger diameter, but shrank upon colling. There was an increase in the gelatinization temperature and a decrease in the enthalpy change of the spray dried starches relative to those of native starch. Spray dried starch preheating at 69 °C showed highly reduced enthalpy change (80%) and relative crystallinity. Based on the parameters studied, the best preheating temperature was 67 °C. Under this condition, the starch can be applied in more viscous products that require a greater thickness, and with great process yield (65%). This study showed the feasibility of the application of this process to produce sweet potato starches with specific properties for different purposes in the food and non-food industries.


Autism-Spectrum Quotient-Japanese version and its short forms for screening normally intelligent persons with pervasive developmental disorders.
A Japanese version of the Autism Spectrum Quotient (AQ), AQ-J was administered to 25 normally intelligent high-functioning pervasive developmental disorder (HPDD) patients (mean age, 24.2 years; 24 male, one female) and 215 controls (mean age, 30.4 years; 86 male, 129 female) randomly selected from the general population. The AQ-J had satisfactory internal consistency reliability (Cronbach's alpha > 0.70 in the two groups), test-retest reliability, and discriminant validity [i.e. the AQ-J score was significantly higher in the HPDD (mean, 29.6) than controls (mean, 22.2)]. At a cut-off of 26, the AQ-J had satisfactory sensitivity, specificity, and negative predictive value, but it had low positive predictive value (0.24) possibly due to the facts that the 25 mild HPDD patients scored lower and the controls scored higher on the AQ-J than British counterparts on the AQ. The AQ-J-21 (consisting of 21 items significantly associated with HPDD diagnosis) and the AQ-J-10 (consisting of 10 of the 21 items with an effect size > 0.17) had higher, although not satisfactory, positive predictive values of 0.35 and 0.46 at cut-offs of 12 and 7, respectively, than the AQ-J. The AQ-J and two short forms are useful not to predict but to rule out mild HPDD, the most difficult part of HPDD to be distinguished from non-PDD conditions, in persons scoring under the cut-offs and to consider professionals' examination of HPDD in persons scoring over them, because their negative predictive values were satisfactory.


Insulin-like growth factor binding protein-2 as a novel biomarker for disease activity and renal pathology changes in lupus nephritis.
Lupus nephritis (LN) is one of the most serious manifestations of systemic lupus erythematosus. Invasive renal biopsy remains the gold standard for the diagnosis and management of LN. The objective of this study is to validate serum insulin-like growth factor binding protein-2 (IGFBP-2) as a novel biomarker for clinical disease and renal pathology in LN. Eighty-five biopsy-proven lupus nephritis patients, 18 chronic kidney disease (CKD) patients and 20 healthy controls were recruited for enzyme-linked immunosorbent assay (ELISA) testing of serum IGFBP-2 levels. Compared to CKD patients of origins other than lupus or healthy controls, serum IGFBP-2 levels were elevated significantly in LN patients. Serum IGFBP-2 was able to discriminate LN patients from the other two groups of patients [area under the curve (AUC) = 0·65, 95% confidence interval (CI) = 0·52-0·78; P = 0·043 for LN versus CKD; 0·97, 95% CI = 0·93-1·00; P < 0·0001 for LN versus healthy controls]. Serum IGFBP-2 was a potential indicator of both global disease activity and renal disease activity in LN patients, correlated with serum creatinine levels (r = 0·658, P < 0·001, n = 85) and urine protein-to-creatinine levels (r = 0·397, P < 0·001, n = 85). More importantly, in 19 concurrent patient samples, serum IGFBP-2 correlated with the chronicity index of renal pathology (r = 0·576, P = 0·01, n = 19) but not renal pathological classification. In conclusion, serum IGFBP-2 is a promising biomarker for lupus nephritis, reflective of disease activity and chronicity changes in renal pathology.


Identification of plant tissues from the gut of Phlebotomus papatasi by DNA analysis.
Sugar and cellulose assays can determine if an insect has fed on sugar and plant tissue but they cannot identify the species of source plant. In this study, we used DNA analysis together with traditional cellulose and sugar assays to examine the plant feeding habits of wild Phlebotomus papatasi during the dry season in the Lower Jordan Valley, Israel. About 37% of the sand flies were positive for sugar, 45% were positive for cellulose in the gut, and 41% contained amplifiable plant DNA. All of the plant DNA fragments sequenced from both males and females were identified as Suaeda asphaltica.


Patient empowerment and hand hygiene, 1997-2012.
Multi-modal hand hygiene programmes that include patient empowerment are promoted as a necessary component of hand hygiene compliance. However, the question still remains, do we have enough information to determine if, and under what conditions, patients will be able to play an immediate role in healthcare workers' hand hygiene behaviour? To review the current literature on patient willingness to be empowered, barriers to empowerment, and hand hygiene programmes that include patient empowerment and hand hygiene improvement. A Medline (Ovid) search of all English-language papers for 1997-2007 and 2008-2012 was conducted using the following keywords alone and in various combinations: 'patient participation', 'involvement', 'empowerment', 'education', 'decision-making', 'professional-patient relations', 'behavioural change', 'culture of safety', 'social marketing', 'consumer awareness', 'leadership', 'institutional climate', 'hand hygiene' and 'patient reminders'. The 1997-2007 review was conducted as part of the World Health Organization's Guidelines on Hand Hygiene in Health Care, and updated with the 2008-2012 review. Several studies show that, in principle, patients are willing to be empowered. However, there is variation in the actual number of patients that practice empowerment for hand hygiene, ranging from 5% to 80%. The actual performance of patient empowerment can be increased when a patient is given explicit permission by a healthcare worker. There is ongoing support from patients that they are willing to be empowered. There is a need to develop programmes that empower both healthcare workers and patients so that they become more comfortable in their roles.


Actual and theoretical risks for visual loss following use of the implantable contact lens for moderate to high myopia.
To estimate the actual and theoretical risks for visual loss associated with use of the implantable contact lens (ICL). Multicenter clinical trial data. An established model for estimating the risk for visual loss associated with retinal detachment (RD) following clear lens extraction (CLE) was modified to be applicable to the ICL. The risk for developing RD and the outcomes of RD surgery based on current lens extraction and RD repair techniques were updated. Non-RD-related risks for pseudophakia based on United States Food and Drug Administration (FDA) guidelines, actual visual loss data from the FDA ICL study, and calculated risks assuming a large future risk (10 times the current risk) of cataract development were also added. The additional risk for visual loss due to cataract surgery is estimated at 0.19% and for subsequent RD assuming 10 times the current rate of cataract is 0.37%. Using an ultraconservative (high) model and adding the actual loss observed with the ICL, the total risk is 1.39%. The risk increases by 0.5% to 0.6% with each 10% increase in cataract incidence (eg, 10% to 20%, 20% to 30%). The risk for visual loss with CLE and/or laser in situ keratomileusis/photorefractive keratectomy in the same range of myopia is possibly 3.0% to 6.5%. The ICL represents a viable alternative to currently available refractive procedures based on an analysis of the risk for visual loss.


Experimental study on freeze-thaw damage characteristics of coal samples of different moisture contents in liquid nitrogen.
In this study, the surface crack-propagation law and pore damage characteristics of coal samples of different water contents after they undergo leaching in liquid nitrogen are investigated using a 4 K scientific-research camera, HC-U7 non-metal ultrasonic detector, nuclear magnetic resonance testing technology, and self-made multi-functional three axial fluid-solid coupling test system. Experimental investigations are conducted on coal samples of different water contents before and after they undergo liquid-nitrogen freezing and thawing in order to determine the propagation law of surface fissures, the development law of internal micro-fissures, the development process of internal pores, the change law of the pore-size distribution, and the law of coal-sample deformation and gas seepage during the stress process. The test results show that, with the increase in water content in the liquid-nitrogen leaching process, the frost heave force on the coal surface increases, and the greater the increase ratio of the coal porosity, the faster is the development of micro-cracks and pores. Under the action of liquid nitrogen, the number of micro-pores, meso-pores, and macro-pores in the coal sample increased, and with the formation of new cracks and the connection of the original cracks, liquid-nitrogen freezing and thawing can promote the development of the pore structure in the coal body. The permeability changes of coal samples of different water contents during unloading failure exhibit obvious stage characteristics. The above results demonstrate that the moisture content of coal has a significant effect on the development of surface cracks and pore-damage characteristics of coal after liquid-nitrogen freezing and thawing, and there is a positive correlation between the surface crack expansion and internal damage of the coal samples of different moisture contents leached in liquid nitrogen.


A HIF independent oxygen-sensitive pathway for controlling cholesterol synthesis.
Cholesterol biosynthesis is a highly regulated, oxygen-dependent pathway, vital for cell membrane integrity and growth. In fungi, the dependency on oxygen for sterol production has resulted in a shared transcriptional response, resembling prolyl hydroxylation of Hypoxia Inducible Factors (HIFs) in metazoans. Whether an analogous metazoan pathway exists is unknown. Here, we identify Sterol Regulatory Element Binding Protein 2 (SREBP2), the key transcription factor driving sterol production in mammals, as an oxygen-sensitive regulator of cholesterol synthesis. SREBP2 degradation in hypoxia overrides the normal sterol-sensing response, and is HIF independent. We identify MARCHF6, through its NADPH-mediated activation in hypoxia, as the main ubiquitin ligase controlling SREBP2 stability. Hypoxia-mediated degradation of SREBP2 protects cells from statin-induced cell death by forcing cells to rely on exogenous cholesterol uptake, explaining why many solid organ tumours become auxotrophic for cholesterol. Our findings therefore uncover an oxygen-sensitive pathway for governing cholesterol synthesis through regulated SREBP2-dependent protein degradation.


Differential projections of B and C sympathetic axons in peripheral nerves of the bullfrog.
Accumulating evidence indicates that electrophysiologically distinct subsets of sympathetic neurons selectively innervate different classes of targets. The organization of this system may therefore be reflected in the sympathetic fiber contents of peripheral nerves. To test this possibility, we have mapped the pathways followed by three groups of postganglionic sympathetic axons in the bullfrog by recording compound action potentials and by retrograde tracing with horseradish peroxidase (HRP). The axons that were studied arise from fast B, slow B, and C-type neurons in ganglia 9 and 10 at the lumbar end of the paravertebral sympathetic chain. They project to peripheral targets primarily by way of the sciatic nerve and can be distinguished by the velocities with which they conduct action potentials. Action potentials were recorded with suction electrodes from isolated preparations composed of paravertebral chain ganglia 7-10, the sciatic nerve, and branches of the sciatic nerve that supply striated muscles, skin, and the bladder. Preganglionic B fibers were selectively activated by stimulating the paravertebral chain rostral to ganglion 7, and preganglionic C fibers were selectively activated by stimulating spinal nerves 7 and 8 at points central to their rami communicantes. Compound action potentials recorded from the sciatic, peroneal, tibial, and sural nerves and from the primary trunk of the pelvic nerve were each found to contain three components produced, respectively, by fast B, slow B, and C-type sympathetic axons. Similarly, action potentials recorded from cutaneous branches of the sciatic tree were found to contain three sympathetic components. By contrast, when compound action potentials were recorded from branches of the sciatic tree that directly enter and innervate striated muscles and also the bladder, the sympathetic responses were found to arise solely from C-type axons. HRP was used to label the sympathetic neurons that project to the sartorius muscle and into the cutaneous lateral crural nerve. Retrograde transport of HRP from the sartorius muscle labeled 17 +/- 4 (mean +/- s.d.) sympathetic neurons and 27 +/- 3 spinal motoneurons while transport from the lateral crural nerve labeled 68 +/- 47 sympathetic neurons but no spinal neurons. The average somatic diameter of ganglion cells projecting to the sartorius muscle was significantly smaller than that of cells projecting to the lateral crural nerve. The electrophysiological results indicate that fast B and slow B sympathetic axons in the sciatic trunk and its primary branches project selectively into cutaneous nerves while sympathetic C axons project into all peripheral nerves.(ABSTRACT TRUNCATED AT 400 WORDS)


Itaconate prevents abdominal aortic aneurysm formation through inhibiting inflammation via activation of Nrf2.
Identifying effective drugs to suppress vascular inflammation is a promising strategy to delay the progression of abdominal aortic aneurysm (AAA). Itaconate has a vital role in regulating inflammatory activation in various inflammatory diseases. However, the role of itaconate in the progression of AAA is unknown. In this study, we explored the inhibitory effect of itaconate on AAA formation and its underlying mechanisms. Quantitative PCR, western blotting and immunohistochemistry were used to determine Irg1 and downstream Nrf2 expression in human and mouse AAA samples. Liquid chromatograph-mass spectrometry (LC-MS) analysis was performed to measure the abundance of itaconate. OI treatment and Irg1 knockdown were performed to study the role of OI in AAA formation. Nrf2 intervention in vivo was performed to detect the critical role of Nrf2 in the beneficial effect of OI on AAA. We found that itaconate suppressed the formation of angiotensin II (Ang II)-induced AAA in apolipoprotein E-deficient (Apoe-/-) mice, while Irg1 deficiency exerted the opposite effect. Mechanistically, itaconate inhibited vascular inflammation by enabling Nrf2 to function as a transcriptional repressor of downstream inflammatory genes via alkylation of Keap1. Moreover, Nrf2 deficiency significantly aggravated inflammatory factor expression and promoted AAA formation. In addition, Keap1 overexpression significantly promoted Ang II-induced AAA formation, which was inhibited by itaconate. Itaconate inhibited AAA formation by suppressing vascular inflammation, and therapeutic approaches to increase itaconate are potentially beneficial for preventing AAA formation. National Natural Science Foundations of China and Guangzhou regenerative medicine and Health Laboratory of Guangdong.


The effect of substrate modification on binding of porcine pancreatic alpha amylase: hydrolysis of modified amylose containing D-allose residues.
A modified amylose containing 10% of tritiated D-allose residues has been hydrolyzed by porcine pancreatic alpha amylase (PPA). This reaction produced a number of radioactive oligosaccharides of low molecular weight, including modified mono-, di-, and tri-saccharides, as well as larger products. Analysis of these products by chemical and enzymic methods identified D-allose, two isomers of modified maltose, and isomers of modified maltotriose. These results may be interpreted in terms of current PPA models to indicate that D-allose residues may be productively bound at all five subsites of the active site of the enzyme. The distribution of modified residues in these products, however, further suggests that productive binding of D-allose at the subsite where catalytic attack occurs (subsite 3) is less favorable than binding of D-glucose. These results are compared with results of a series of PPA substrates having modifications at C-3 and at other positions. Trends observed in enzyme hydrolysis of these modified substrates reflect factors that contribute to PPA catalysis, with respect to steric, electronic, and hydrogen-bonding interactions between enzyme and substrate.


Judgement aggregation in scientific collaborations: The case for waiving expertise.
The fragmentation of academic disciplines forces individuals to specialise. In doing so, they become experts over their narrow area of research. However, ambitious scientific projects, such as the search for gravitational waves, require them to come together and collaborate across disciplinary borders. How should scientists with expertise in different disciplines treat each others' expert claims? An intuitive answer is that the collaboration should defer to the opinions of experts. In this paper we show that under certain seemingly innocuous assumptions, this intuitive answer gives rise to an impossibility result when it comes to aggregating the beliefs of experts to deliver the beliefs of a collaboration as a whole. We then argue that when experts' beliefs come into conflict, they should waive their expert status.


Facile preparation of amine and amino acid adducts of [60]fullerene using chlorofullerene C60Cl6 as a precursor.
We report a general synthetic approach to the preparation of highly functionalized amine and amino acid derivatives of [60]fullerene starting from readily available chlorofullerene C(60)Cl(6). The synthesized water-soluble amino acid derivative of C(60) demonstrated pronounced antiviral activity, while the cationic amine-based compound showed strong antibacterial action in vitro.


Neonatal tolerance increases efficacy of antisera production.
In this investigation we demonstrate that neonatal tolerance can be used to increase the specificity of antisera. We have shown that if mice are immunized with a human B cell line then the antisera they produce also reacts strongly with human T cells. However, if the mice are first neonatally tolerized to a human T cell line and then immunized with the B cell line the antisera becomes much more specific for the B cell line. In theory this approach, of initially tolerizing the animal to uninteresting antigens, may also make it possible to produce monoclonal antibodies to rare cellular determinants more efficiently.


Behavioural and neuropsychiatric disturbance in three clinical subtypes of frontotemporal dementia: A Clinical Research Center for Dementia of South Korea-FTD Study.
To characterise the behavioural and neuropsychiatric disturbances of patients with three clinical subtypes of frontotemporal dementia (FTD): behavioural variant FTD (bvFTD), semantic dementia (SD) and progressive non-fluent aphasia (PNFA). Consecutive series of 66 patients with bvFTD, 58 patients with SD and 21 patients with PNFA were compared using the Frontal Behavioural Inventory (FBI) and the Neuropsychiatric Inventory (NPI). Patients with bvFTD had more behavioural and neuropsychiatric disturbances than patients with PNFA based on the total scores of FBI and NPI. When comparing subtotal and item scores of FBI and NPI, there were some significant differences among three clinical subtypes of FTD. There are some distinct patterns of behavioural and neuropsychiatric disturbance among three clinical subtypes of FTD.


Effect of sera from hyperlipidemic subjects and high-density lipoproteinemic runners on the synthesis of DNA and glycosaminoglycans by cultured human aortic smooth muscle cells.
Effects of hyperlipidemic, normolipidemic and high-density-lipoproteinemic (HD lipoproteinemic) sera from active runners were studied on cultured human aortic smooth muscle cells. The synthesis of DNA, hyaluronic acid and sulphated glycosaminoglycans (GAGs) in the presence of the various sera was measured by the incorporation of [3H]-thymidine and [3H]-glucosamine. The HD lipoproteinemic sera from runners stimulated the synthesis of DNA and sulphated GAGs less than normolipidemic and hyperlipidemic sera. The hyperlipidemic sera stimulated the synthesis of DNA slightly more than the other sera, but only after a 24 h preincubation. Accordingly, the concentration of HDL-cholesterol in serum was negatively correlated with the synthesis of DNA (r = -0.77, P less than 0.01) and sulphated glycosaminoglycans (r = -0.81, P less than 0.01). The sulphated GAGs/hyaluronate ratio was smaller in the presence of HD lipoproteinemic serum as compared with the other sera. The proliferation of aortic smooth muscle cells and the rate at which they synthesize sulphated GAGs have been considered important during the initiation of atherosclerosis in vivo. The present results suggest that sera having differences in the relative amounts of various lipoprotein fractions differ significantly in their influence on both of these arterial smooth muscle cell functions in vitro.


Surgical closure of left coronary artery-left ventricular fistula: the second case reported in the literature and a review of the five previously reported cases of coronary artery fistula terminating in the left ventricle.
Surgical closure of a left coronary artery-left ventricular fistula in a 44-year-old black man is reported. The fistula was discovered by coronary arteriography after the patient was admitted to the hospital complaining of recurrent chest pain. The fistula was closed with cardiopulmonary bypass, ischemic arrest, and hypothermia, and there was an uneventful postoperative recovery. The previously reported five cases of fistulas terminating in the left ventricle that were closed surgically are reviewed. Four of these cases originated in the right coronary artery and one in the left coronary artery. Three of the six patients were symptomatic at the time of discovery of the lesion. Cardiopulmonary bypass was necessary in five of the six cases. One patient died in the postoperative period from intractable hemorrhage. It is recommended that coronary artery fistulas by closed upon establishment of the diagnosis because of the sequelae if they are allowed to remain open; these include premature atherosclerosis, aneurysmal dilatation of the coronary artery, and congestive heart failure.


Prognostic factors of early gastric cancer--results of long-term follow-up and analysis of recurrent cases.
The prognosis of early gastric cancer (EGC) is generally excellent, however, EGC is not an exception to recurrence. In order to know what type of EGC is liable to recur, long-term results were studied in 304 cases of resection. The cumulative 10-year survival rate was poorer in patients with positive lymph nodes than in those with negative nodes (52.8 +/- 15.8 per cent vs 94.1 +/- 2.4 per cent; p less than 0.05). It was also less favorable when the EGC was greater than 5 cm in diameter (61.5 +/- 13.2 per cent vs 92.9 +/- 2.4 per cent; p less than 0.05). Among 50 cases which died postoperatively, six deaths were due to recurrence. A predominant mode of recurrence was hematogenous metastasis (4/6). The characteristics of EGC which recurred later included large cancer (greater than or equal to 5 cm) (6/6), macroscopically combined-type cancer (5/6), cancer of depth invasion to the submucosa (4/6) and histologically differentiated cancer (6/6). Lymph node dissection was not carried out in two of these patients at their primary operation. Adjuvant therapy should be added in the EGC bearing risk factors depicted above. Primary cancer in other organs, either metachronous or synchronous, was found in 13 cases (4.3 per cent). Colonic cancer, in particular, was seen in three, and it was 4.8 times as frequent as the expected number of the general population, calculated using the person-year method.


Probing the overlap of chorismate mutase and prephenate dehydrogenase sites in the escherichia coli T-protein: a dehydrogenase-selective inhibitor.
An inhibitor of prephenate dehydrogenase has been identified that has no effect on the chorismate mutase activity in the Escherichia coli T-protein, thus supporting the idea of two separate active sites.


Bacterial resistance to ultrasonic waves under pressure at nonlethal (manosonication) and lethal (manothermosonication) temperatures.
The decimal reduction times of Streptococcus faecium, Listeria monocytogenes, Salmonella enteritidis, and Aeromonas hydrophila corresponding to heat treatment at 62 degrees C were 7.1, 0.34, 0.024, and 0.0096 min, and those corresponding to manosonication treatment (40 degrees C, 200 kPa, 117 microm) were 4.0, 1.5, 0.86, and 0.90 min, respectively. The manosonication decimal reduction times of the four species investigated decreased sixfold when the amplitude was increased from 62 to 150 microm and fivefold when the relative pressure was raised from 0 to 400 kPa. In L. monocytogenes, S. enteritidis, and A. hydrophila, the lethal effect of manothermosonication was the result of the addition of the lethal effects of heat and manosonication, whereas in S. faecium it was a synergistic effect.


Elaboration and validation of a booklet on diabetes for Community Health Workers.
to develop and validate a diabetes booklet for Community Health Workers. methodological study developed in seven steps: Bibliographic review; Development of the booklet; Calculation of readability and comprehensibility scores; Validation of the booklet by the committee of judges; Discussion between experts; Validation of the booklet by the target audience; and Final discussion between experts. Validation was performed by 10 judges via e-Surv and on a face-to-face test with 5 Community Health Workers, considering the minimum Content Validity Coefficient of 0.80. the booklet had a mean Content Validity Coefficient of 0.97 in the validation by the committee of judges, and the images had 96.67% approval. In the face-to-face test, the Community Health Workers considered the material clear and appropriate to the function. the booklet was developed and validated on its content and relevance, and it can be used by Community Health Workers for diabetes education.


Metal artifact reduction (MAR) based on two-compartment physical modeling: evaluation in patients with hip implants.
Artifacts from metallic implants can hinder image interpretation in computed tomography (CT). Image quality can be improved using metal artifact reduction (MAR) techniques. To evaluate the impact of a MAR algorithm on image quality of CT examinations in comparison to filtered back projection (FBP) in patients with hip prostheses. Twenty-two patients with 25 hip prostheses who underwent clinical abdominopelvic CT on a 64-row CT were included in this retrospective study. Axial images were reconstructed with FBP and five increasing MAR levels (M30-34). Objective artifact strength (OAS) (SIart-SInorm) was assessed by region of interest (ROI) measurements in position of the strongest artifact (SIart) and in an osseous structure without artifact (SInorm) (in Hounsfield units [HU]). Two independent readers evaluated subjective image quality regarding metallic hardware, delineation of bone, adjacent muscle, and pelvic organs on a 5-point scale (1, non-diagnostic; 5, excellent image quality). Artifacts in the near field, far field, and newly induced artifacts due to the MAR technique were analyzed. OAS values were: M34: 243.8 ± 155.4 HU; M33: 294.3 ± 197.8 HU; M32: 340.5 ± 210.1 HU; M31: 393.6 ± 225.2 HU; M30: 446.8 ± 224.2 HU and FBP: 528.9 ± 227.7 HU. OAS values were significantly lower for M32-34 compared to FBP (P < 0.01). For overall subjective image quality, results were: FBP, 2.0 ± 0.2; M30, 2.3 ± 0.8; M31, 2.6 ± 0.5; M32, 3.0 ± 0.6; M33, 3.5 ± 0.6; and M34, 3.8 ± 0.4 (P < 0.001 for M30-M34 vs. FBP, respectively). Increasing MAR levels resulted in new artifacts in 17% of reconstructions. The investigated MAR algorithm led to a significant reduction of artifacts from metallic hip implants. The highest MAR level provided the least severe artifacts and the best overall image quality.


Acceptability of BCG vaccination.
The acceptability of BCG vaccination varies a great deal according to the country and to the period when the vaccine is given. The incidence of complications has not always a direct influence on this acceptability, which depends, for a very large part, on the risk of tuberculosis in a given country at a given time.


The prospective randomized trial of the optimal evaluation of cardiac symptoms and revascularization: Rationale and design of the PRECISE trial.
Clinicians vary widely in their preferred diagnostic approach to patients with non-acute chest pain. Such variation exposes patients to potentially avoidable risks, as well as inefficient care with increased costs and unresolved patient concerns. The Prospective Randomized Trial of the Optimal Evaluation of Cardiac Symptoms and Revascularization (PRECISE) trial (NCT03702244) compares an investigational "precision" diagnostic strategy to a usual care diagnostic strategy in participants with stable chest pain and suspected coronary artery disease (CAD). PRECISE randomized 2103 participants with stable chest pain and a clinical recommendation for testing for suspected CAD at 68 outpatient international sites. The investigational precision evaluation strategy started with a pre-test risk assessment using the PROMISE Minimal Risk Tool. Those at lowest risk were assigned to deferred testing (no immediate testing), and the remainder received coronary computed tomographic angiography (cCTA) with selective fractional flow reserve (FFRCT) for any stenosis meeting a threshold of ≥30% and <90%. For participants randomized to usual care, the clinical care team selected the initial noninvasive or invasive test (diagnostic angiography) according to customary practice. The use of cCTA as the initial diagnostic strategy was proscribed by protocol for the usual care strategy. The primary endpoint is time to a composite of major adverse cardiac events (MACE: all-cause death or non-fatal myocardial infarction) or invasive cardiac catheterization without obstructive CAD at 1 year. Secondary endpoints include health care costs and quality of life. PRECISE will determine whether a precision approach comprising a strategically deployed combination of risk-based deferred testing and cCTA with selective FFRCT improves the clinical outcomes and efficiency of the diagnostic evaluation of stable chest pain over usual care.


School attendance during a pandemic.
When officials relax school attendance requirements as a prophylactic measure against a pandemic, students of higher prior performance take more absences, while students of lower prior performance keep going to school. Prior performance is positively associated with neighborhood income.


A decade of Ecuador´s efforts to raise its health research output: a bibliometric analysis.
Background: Over the past decade, the political movement called 'Revolución Ciudadana' implemented a variety of policies and interventions (P&I) in Ecuador to improve higher education and strengthen local research capacity. We refer specifically to the 'Mandato 14' and the Higher Education Law (LOES, Spanish acronym) launched in 2008 and 2010, respectively. Objective: To assess the impact of these P&I (Mandato 14/LOES) on the production of health sciences-related articles (HSRA), and the relationship of these HSRA with the country's health priorities. Methods: A Scopus search was performed to retrieve HSRA published from 1999 to 2017. Bivariate analysis was used to assess variation between the period I (1999-2008) and period II (2009-2017). Further, we examined the association between the top 10 causes of mortality and the total HSRA output. Results: The final study sample consisted of 2784 articles. After 2008, Ecuadorian production of HSRA increased steadily from 671 to 2133 publications (p<.001). Overall (1999-2017), the most common study design was cross-sectional (32.3%), the primary research focus was in the clinical-surgical area (49.3%), and the academic institutions were the primary drivers of scientific production during period II (56.9% vs. 29.5%, p<.001). Further, we found a decrease in the production of randomized controlled trials (6.7% vs. 1.8%, p<.001). Only 9% of research production involved the primary causes of mortality, and the proportion has remained unchanged over time (8.2% vs. 9.3%, p>.05). Conclusions: Ecuadorian HSRA output increased significantly after 2008. This larger volume of scientific output could be the result to the Mandato 14/LOES implemented in the last decade. However, a low percentage of HSRA are dedicated to addressing the country's health priorities. Proper planning, execution and monitoring of national health research agendas would reduce the mismatch between health burden and the HSRA output in Ecuador and other low-and middle-income countries.


Protein binding of cortisol by means of competitive adsorption: application to cortisol binding by serum of sixteen eutherian mammals.
1. Binding of 3H-cortisol by serum proteins by means of competitive adsorption was relatively high by serum of the gerbil, human, rabbit, sheep, tree shrew, hamster, rhesus monkey and horse. 2. A somewhat lower binding was observed by serum proteins of the baboon, cattle, dog, rat and cat. 3. Serum taken from either the mouse, guinea pig or pig gave very flat binding curves, specific binding not exceeding 5% of added 3H-cortisol. 4. It is concluded that the measurement of protein-binding of 3H-cortisol by means of competitive adsorption is a reliable method for serum of most eutherian species but is unsuited if serum of the mouse, guinea pig or pig is used.


Evaluation of image features and search strategies for segmentation of bone structures in radiographs using Active Shape Models.
In this paper, we evaluate various image features and different search strategies for fitting Active Shape Models (ASM) to bone object boundaries in digitized radiographs. The original ASM method iteratively refines the pose and shape parameters of the point distribution model driving the ASM by a least squares fit of the shape to update the target points at the estimated object boundary position, as determined by a suitable object boundary criterion. We propose an improved search procedure that is more robust against outlier configurations in the boundary target points by requiring subsequent shape changes to be smooth, which is imposed by a smoothness constraint on the displacement of neighbouring target points at each iteration and implemented by a minimal cost path approach. We compare the original ASM search method and our improved search algorithm with a third method that does not rely on iteratively refined target point positions, but instead optimizes a global Bayesian objective function derived from statistical a priori contour shape and image models. Extensive validation of these methods on a database containing more than 400 images of the femur, humerus and calcaneus using the manual expert segmentation as ground truth shows that our minimal cost path method is the most robust. We also evaluate various measures for capturing local image appearance around each boundary point and conclude that the Mahalanobis distance applied to normalized image intensity profiles extracted normal to the shape is the most suitable criterion among the tested ones for guiding the ASM optimization.


Explainable multi-module semantic guided attention based network for medical image segmentation.
Automated segmentation of medical images is crucial for disease diagnosis and treatment planning. Medical image segmentation has been improved based on the convolutional neural networks (CNNs) models. Unfortunately, they are still limited by scenarios in which the segmentation objective has large variations in size, boundary, position, and shape. Moreover, current CNNs have low explainability, restricting their use in clinical decisions. In this paper, we involve substantial use of various attentions in a CNN model and present an explainable multi-module semantic guided attention based network (MSGA-Net) for explainable and highly accurate medical image segmentation, which involves considering the most significant spatial regions, boundaries, scales, and channels. Specifically, we present a multi-scale attention module (MSA) to extract the most salient features at various scales from medical images. Then, we propose a semantic region-guided attention mechanism (SRGA) including location attention (LAM), channel-wise attention (CWA), and edge attention (EA) modules to extract the most important spatial, channel-wise, boundary-related features for interested regions. Moreover, we present a sequence of fine-tuning steps with the SRGA module to gradually weight the significance of interesting regions while simultaneously reducing the noise. In this work, we experimented with three different types of medical images such as dermoscopic images (HAM10000 dataset), multi-organ CT images (CHAOS 2019 dataset), and Brain tumor MRI images (BraTS 2020 dataset). Extensive experiments on all types of medical images revealed that our proposed MSGA-Net substantially increased the overall performance of all metrics over the existing models. Moreover, displaying the attention feature maps has more explainability than state-of-the-art models.


Characterization of an intraocular retinoblastoma-like tumour.
A transplantable intraocular retinoblastoma-like tumour growing in F 344 rat eyes and tissue cultures suitable for therapeutic experiments is characterized. The tumours grew in the vitreous and infiltrated the internal layers of the retina. Feeder vessels from the retina supplied the tumours. Few and often incomplete rosettes were seen, and calcification was sparse in areas of necrosis. Stainings for glial fibrillary acidic protein, S-100 protein, neuron-specific enolase and desmin were negative. Ultrastructural analysis brought out a close correspondence between the tumour cell and the human retinoblastoma and other virus-induced retinoblastoma-like tumours. The experimental tumour cells lacked cilia, but had neurosecretory granules. Chromosome analysis showed a modal chromosome number in the triploid range, and 6 marker chromosomes were demonstrated. Flow-cytometric analysis showed a S-phase cell fraction of 42%, and chromosome stability was suggested by a tumour-cell DNA index which remained stable for more than 3 months.


Epiglottitis presenting as acute pulmonary edema.
Presented is the case of a 2 1/2-year-old with acute pulmonary edema associated with epiglottitis prior to intubation. The patient complained only of odynophagia and had one brief episode of apnea and flaccid posturing. Chest radiograph demonstrated pulmonary edema. A soft tissue radiograph of the neck confirmed the diagnosis of epiglottitis. The patient was managed successfully with prompt intubation, PEEP, and antibiotics. Pulmonary edema associated with epiglottitis may be more common than previously recognized. It may occur prior to or after intubation. When pulmonary edema is clinically evident, PEEP should be administered early.


Bionic natural small molecule co-assemblies towards targeted and synergistic Chemo/PDT/CDT.
Multi-component nano-delivery systems based on chemotherapy (chemo)- photodynamic therapy (PDT)- chemodynamic therapy (CDT) have gained increased attention as a promising strategy to improve clinical outcomes in cancer treatment. However, there remains a challenge in developing biodegradable, biocompatible, less toxic, yet highly efficient multicomponent nanobased drug delivery systems (DDS). Here, our study presents the screening and development of a novel DDS based on co-assemblies natural small molecule (NSMs). These molecules (oleanolic acid, and betulinic acid) are combined with photosensitizers Chlorine6 (Ce6) and Cu2+ that are encapsulated by tumor cell membranes. This nanocarrier encapsulated in tumor cell membranes achieved good tumor targeting and a significant improvement in tumor accumulation. A reprecipitation method was used to prepare the co-assembled nanocarrier, followed by the introduction of Cu2 + into the DDS (OABACe6 NPs). Then, by wrapping the surface of NPs with the cell membranes of 4T1 which is a kind of mouse breast cancer cells (CM@OABACe6/Cu NPs). and analysis of its structure and size distribution with UV-Vis, XPS, FT-IR, SEM, TEM, and DLS. The synergistic effects of in vitro chemotherapy, CDT and PDT and targeting were also validated by cellular and animal studies. It was shown that CM@OABACe6/Cu NPs achieved good tumor targeting and a significant improvement in tumor accumulation. In the composite nano-assembly, the NSMs work together with the Ce6 to provide effective and safe chemo and PDT. Moreover, the effect of reduced PDT due to the depletion of reactive oxygen species (ROS) by excess glutathione (GSH) in the tumor can be counteracted when Cu2 + is introduced. More importantly, it also confers CDT through a Fenton-like catalytic reaction with H2O overexpressed at the tumor site. By constructing CM@OABACe6/Cu NPs with homologous targeting, we create a triple synergistic platform for cancer therapy using PDT, chemo, and CDT. We propose here a novel combinatorial strategy for designing more naturally co-assembled small molecules, especially for the development of multifunctional synergistic therapies that utilize NSMs.


Template-Enabled Biofabrication of Thick 3D Tissues with Patterned Perfusable Macrochannels.
Interconnected pathways in 3D bioartificial organs are essential to retaining cell activity in thick functional 3D tissues. 3D bioprinting methods have been widely explored in biofabrication of functionally patterned tissues; however, these methods are costly and confined to thin tissue layers due to poor control of low-viscosity bioinks. Here, cell-laden hydrogels that could be precisely patterned via water-soluble gelatin templates are constructed by economical extrusion 3D printed plastic templates. Tortuous co-continuous plastic networks, designed based on triply periodic minimal surfaces (TPMS), serve as a sacrificial pattern to shape the secondary sacrificial gelatin templates. These templates are eventually used to form cell-encapsulated gelatin methacryloyl (GelMA) hydrogel scaffolds patterned with the complex interconnected pathways. The proposed fabrication process is compatible with photo-crosslinkable hydrogels wherein prepolymer casting enables incorporation of high cell populations with high viability. The cell-laden hydrogel constructs are characterized by robust mechanical behavior. In vivo studies demonstrate a superior cell ingrowth into the highly permeable constructs compared to the bulk hydrogels. Perfusable complex interconnected networks within cell-encapsulated hydrogels may assist in engineering thick and functional tissue constructs through the permeable internal channels for efficient cellular activities in vivo.