Heat-induced endoplasmic reticulum stress in soleus and gastrocnemius muscles and differential response to UPR pathway in rats.
The present study aimed to investigate the differential response of oxidative (soleus) and glycolytic (gastrocnemius) muscles to heat-induced endoplasmic reticulum (ER) stress. It was hypothesized that due to compositional and functional differences, both muscles respond differently to acute heat stress. To address this, male Sprague Dawley rats (12/group) were subjected to thermoneutral (25 °C) or heat stress (42 °C) conditions for 1 h. Soleus and gastrocnemius muscles were removed for analysis post-exposure. A significant increase in body temperature and free radical generation was observed in both the muscles following heat exposure. This further caused a significant increase in protein carbonyl content, AOPP, and lipid peroxidation in heat-stressed muscles. These changes were more pronounced in heat-stressed soleus compared to the gastrocnemius muscle. Accumulation of unfolded, denatured proteins results in ER stress, causing activation of unfolded protein response (UPR) pathway. The expressions of UPR transducers were significantly higher in soleus as compared to the gastrocnemius muscle. A significant elevation in resting intracellular calcium ion was also observed in heat-stressed soleus muscle. Overloading of cells with misfolded proteins in soleus muscle activated ER-induced apoptosis as indicated by significant upregulation of C/EBP homologous protein and Caspase12. The study provides a detailed mechanistic representation of the differential response of muscles toward UPR under heat stress. Data suggests that soleus majorly being an oxidative muscle is more prone to heat stress-induced insult indicated by enhanced apoptosis. This study may aid in devising mitigation strategies to improve muscle performance under heat stress.


[Changes in the immunity indices of children suffering from inflammatory lung diseases undergoing cold exposures].
Cooling and heating the feet in children with pulmonary inflammatory diseases in remission improved immunity. Air baths in addition to stimulating immunity enhanced bactericidal potential of blood neutrophils. Cool and warm showers decreased this potential.


Machine Learning Prediction Models for Diagnosing Hepatocellular Carcinoma with HCV-related Chronic Liver Disease.
Considered as one of the most recurrent types of liver malignancy, Hepatocellular Carcinoma (HCC) needs to be assessed in a non-invasive way. The objective of the current study is to develop prediction models for Chronic Hepatitis C (CHC)-related HCC using machine learning techniques. A dataset, for 4423 CHC patients, was investigated to identify the significant parameters for predicting HCC presence. In this study, several machine learning techniques (Classification and regression tree, alternating decision tree, reduce pruning error tree and linear regression algorithm) were used to build HCC classification models for prediction of HCC presence. Age, alpha-fetoprotein (AFP), alkaline phosphate (ALP), albumin, and total bilirubin attributes were statistically found to be associated with HCC presence. Several HCC classification models were constructed using several machine learning algorithms. The proposed HCC classification models provide adequate area under the receiver operating characteristic curve (AUROC) and high accuracy of HCC diagnosis. AUROC ranges between 95.5% and 99%, plus overall accuracy between 93.2% and 95.6%. Models with simplistic factors have the power to predict the existence of HCC with outstanding performance.


Polar cod in jeopardy under the retreating Arctic sea ice.
The Arctic amplification of global warming is causing the Arctic-Atlantic ice edge to retreat at unprecedented rates. Here we show how variability and change in sea ice cover in the Barents Sea, the largest shelf sea of the Arctic, affect the population dynamics of a keystone species of the ice-associated food web, the polar cod (Boreogadus saida). The data-driven biophysical model of polar cod early life stages assembled here predicts a strong mechanistic link between survival and variation in ice cover and temperature, suggesting imminent recruitment collapse should the observed ice-reduction and heating continue. Backtracking of drifting eggs and larvae from observations also demonstrates a northward retreat of one of two clearly defined spawning assemblages, possibly in response to warming. With annual to decadal ice-predictions under development the mechanistic physical-biological links presented here represent a powerful tool for making long-term predictions for the propagation of polar cod stocks.


Decoding the infrastructure of the cerebellum.
High-end technical approaches help to untangle the substructure and projection patterns of the cerebellum.


Rigid spine syndrome caused by a novel mutation in four-and-a-half LIM domain 1 gene (FHL1).
Four-and-a-half LIM domain 1 gene (FHL1) has recently been identified as the causative gene for reducing body myopathy (RBM), X-linked scapuloperoneal myopathy (SPM) and X-linked myopathy with postural muscle atrophy (XMPMA). Rigid spine is a common clinical feature of the three diseases. We searched for FHL1 mutations in eighteen patients clinically diagnosed as rigid spine syndrome (RSS). We identified one RSS patient with FHL1 mutation. Reducing bodies were observed in few fibers of the patient's muscle sample. Amount of FHL1 protein was decreased on immunoblotting. In conclusion, FHL1 can be one of the causative genes for RSS.


Development of a fast-dissolving tablet formulation of a live attenuated enterotoxigenic E. coli vaccine candidate.
Vaccination is considered the most cost-effective approach to preventing infectious diseases, yet better formulations and delivery methods for efficient distribution and administration of vaccines are needed, especially for low-resource settings. A fast-dissolving tablet (FDT) that could be packaged in a compact stackable blister sheet is a potentially attractive option for formulating oral vaccines, since it would minimally impact the cold chain and could potentially be administered directly to patients without reconstitution. This study focused on using one component of a live attenuated trivalent vaccine under development to produce a FDT for the prevention of diarrhea induced by enterotoxigenic Escherichia coli (ETEC). Ten formulations were prepared and freeze dried to produce FDTs. Three freezing conditions were explored, along with different drying and package sealing methods. Physical properties examined included structural integrity, dissolution time, moisture content, and glass transition temperature. Bacterial viability was tested by assaying for colony-forming units. The formulation compositions and freeze-drying parameters were adjusted in an iterative process to arrive at a promising formulation for the ETEC vaccine tablet. This formulation included sucrose and trehalose as cryoprotectants; phosphate and glutamate salts as buffers and stabilizers; and Natrosol(®), polyvinylpyrrolidone, and mannitol as binders. The process loss in viability during freeze drying was less than 0.3 log 10 (50% recovery) for the optimized vaccine tablet formulation. The final tablets were robust, disintegrated in less than 10s, and preserved the bacteria at 2-8°C for at least 12 months with less than 0.4 log 10 loss (40% recovery) in viability during storage. This study indicates that the FDT produced by freeze drying directly in a blister sheet could be a practical option for formulating ETEC vaccines for oral immunization and help to facilitate delivery of lifesaving vaccines, particularly in low-resource settings.


Long-term results after transscleral diode laser cyclophotocoagulation in refractory posttraumatic glaucoma and glaucoma in aphakia.
To evaluate the long-term effect and safety of transscleral diode laser cyclophotocoagulation (TDLC) in eyes with advanced glaucoma in aphakia and posttraumatic glaucoma. Twenty-one eyes of 21 patients with glaucoma in aphakia and 25 eyes of 25 patients with posttraumatic glaucoma were treated with TDLC between 1996 and 2004. If the intraocular pressure (IOP) remained above 21 mmHg despite medication for more than 4 weeks after TDLC, the procedure was repeated. The IOP, number of medications, visual acuity, complications and need of further surgical intervention were all recorded during the follow-up period. Follow-up ranged from 12 to 93 months (mean 42.0 +/- 29.2) in glaucoma in aphakia and from 12 to 73 months (mean 33.3 +/- 17.4) in posttraumatic glaucoma. TDLC was successful in 48% of aphakic eyes with glaucoma and 40% of eyes with posttraumatic glaucoma. More than one TDLC was performed in 85% of cases of glaucoma in aphakia and 76% of cases of posttraumatic glaucoma). In both groups, TDLC was more effective in older patients than younger patients. Further glaucoma surgeries other than TDLC were performed in 43% of glaucoma in aphakic cases, and 44% of posttraumatic glaucoma cases, within the follow-up period. Loss of any light perception was recorded in two aphakic eyes with glaucoma (9.5%) and three eyes with posttraumatic glaucoma (12%). No hypotonia and no phthisis occurred. TDLC is moderately effective in advanced posttraumatic glaucoma and glaucoma in aphakia, more effective in older than younger patients, not influenced by prior other glaucoma surgery, and despite a high re-treatment rate very safe in both groups of glaucoma. For younger patients with severe secondary glaucoma in particular, new treatment strategies are needed.


Myostatin induces p300 degradation to silence cyclin D1 expression through the PI3K/PTEN/Akt pathway.
Myostatin is a negative regulator of skeletal muscle growth and affects numerous genes expression involved in cell proliferation, differentiation and metabolism. However, the molecular mechanisms underlying myostatin-regulated genes expression remain to be elucidated. In this study, we showed that myostatin blocked the recruitment of p300 to the cyclin D1 promoter, resulting in the silence of cyclin D1 expression. Our data further demonstrated that myostatin decreased the protein level of p300 by inducing p300 degradation via the ubiquitin-proteasome system. In addition, we provided experimental evidence to show that myostatin-induced p300 degradation was mediated by the phosphatidylinositol 3-kinase/PTEN/Akt signaling pathway and this could be antagonized by IGF-1 or insulin. Results presented in this study uncovered an epigenetic control of genes expression in response to myostatin.


Classification of Recombinant Biologics in the EU: Divergence Between National Pharmacovigilance Centers.
Biological medicinal products (biologics) are subject to specific pharmacovigilance requirements to ensure that biologics are identifiable by brand name and batch number in adverse drug reaction (ADR) reports. Since Member States collect ADR data at the national level before the data is aggregated at the European Union (EU) level, it is important that an unambiguous understanding of which medicinal products belong to the biological product category exists. This study aimed to identify the level of consistency between Member States regarding the classification of biologics by national authorities responsible for ADR reporting. A sample list of recombinant biologics from the European Medicines Agency database of European Public Assessment Reports was created to analyze five Member States (Belgium, the Netherlands, Spain, Sweden, and the UK) according to which products were classified as biologics by each Member State. We calculated the Fleiss kappa value to analyze interrater reliability. A considerable divergence was identified regarding the classification of the 146 recombinant biologics from the sample list: one Member State classified 100 % of the recombinant biologics from the sample list as biologics, whereas the classification rates in the remaining four Member States ranged between 70 and 88 % for products available on the national market. The interrater reliability for 87 products available on the market in all five Member States was considered poor. Discrepancies exist between Member States in the classification of biologics; less divergence exists for common well-known biologics. These findings highlight the need to think about the best approaches to translate EU legislation into national practices. Additionally, we recommend a publicly available and frequently updated list of centrally authorized biologics.


Rapidly progressive growth of Renal Clear Cell Carcinoma and Gastrointestinal Stromal Tumor during the 3rd trimester of pregnancy: A clinical and diagnostic dilemma.
The incidence of cancer among pregnancy, albeit rare, presents as a significant diagnostic challenge for clinicians especially with considerations for materno-fetal well-being. The double-edged sword of Renal Clear Cell Carcinoma and Gastrointestinal Stromal Tumor in near-term pregnant woman was encountered in our case and skillfully maneuvered via combination of advanced diagnostic techniques involving CT, MRI and endoscopy. A discussion board comprising of experts was set up and after extended consultation involving patient's relatives, elective cesarean was performed at 34 weeks after which surgical excision resulted in successful extraction of both the tumors, ensuring the survival of both mother and child.


Treacher Collins syndrome: present concepts of the disorder and their surgical correction.
Treacher Collins Syndrome is a rare bilateral congenital deformity occurring in 1 in 10,000 births. It is also known, in the European literature, as Franceschetti Syndrome, and is additionally known as mandibulofacial dysostosis. It is a syndrome with a very wide spectrum of manifestations characterized by distortions of the orbit secondary to hypoplasia of the maxilla, mandible, and, most markedly, of the zygoma. Soft tissue deformities include lower lid colobomas, laxity and dystopia of the lateral canthus, microtia, and a paucity of the muscular aponeurosis of the midface. The syndrome is frequently accompanied by significant hearing loss, early failure to thrive, chronic respiratory insufficiency, and sleep apnea. Intelligence is usually within normal limits although learning disabilities are common in early life. These major anatomical and physiological abnormalities, as well as the psychological and social stigma associated with severe facial deformity, make this syndrome one of the most challenging reconstructive problems presented to the craniofacial surgeon.


The association between patients' frailty status, multimorbidity, and demographic characteristics and changes in primary care for chronic conditions during the COVID-19 pandemic: a pre-post study.
The purpose of this study was to assess the impact of SARS-COV-2 (Severe acute respiratory syndrome coronavirus 2) pandemic on primary care management (frequency of monitoring activities, regular prescriptions, and test results) of older adults with common chronic conditions (diabetes, hypertension, and chronic kidney disease) and to examine whether any changes were associated with age, sex, neighbourhood income, multimorbidity, and frailty. A research database from a sub-set of McMaster University Sentinel and Information Collaboration family practices was used to identify patients ≥65 years of age with a frailty assessment and 1 or more of the conditions. Patient demographics, chronic conditions, and chronic disease management information were retrieved. Changes from 14 months pre to 14 months since the pandemic were described and associations between patient characteristics and changes in monitoring, prescriptions, and test results were analysed using regression models. The mean age of the 658 patients was 75 years. While the frequency of monitoring activities and prescriptions related to chronic conditions decreased overall, there were no clear trends across sub-groups of age, sex, frailty level, neighbourhood income, or number of conditions. The mean values of disease monitoring parameters (e.g. blood pressure) did not considerably change. The only significant regression model demonstrated that when controlling for all other variables, patients with 2 chronic conditions and those with 4 or more conditions were twice as likely to have reduced numbers of eGFR (Estimated glomerular filtration rate) measures compared to those with only 1 condition ((OR (odds ratio) = 2.40, 95% CI [1.19, 4.87]); (OR = 2.19, 95% CI [1.12, 4.25]), respectively). In the first 14 months of the pandemic, the frequency of common elements of chronic condition care did not notably change overall or among higher-risk patients.


Natural history of nonenhancing lesions incidentally detected during the diagnosis of hepatocellular carcinoma.
Incidental detection of nonenhancing tumors during imaging studies for patients with classical hepatocellular carcinoma is not unusual. These tumors are considered to have a high potential of malignant transformation. The aim of this study was to clarify the natural history of such tumors. In 93 patients who underwent liver resection for hepatocellular carcinoma, 138 nonenhancing or enhancing nodules without washout were detected during dynamic computed tomography and observed without further treatments. We subsequently compared the cumulative occurrence of new hepatocellular carcinomas to that of the malignant transformation of these lesions. We additionally compared the appearance of new hepatocellular carcinomas between the patients with (n = 93) and without (n = 782) nonenhancing lesions or enhancing lesions without washout. After a median follow-up period of 0.7 years (range, 0.2-6.8), the median intervals from resection to the appearance of new classical hepatocellular carcinoma and malignant transformation of nonenhancing lesions or enhancing lesions without washout were 1.6 years (95% confidence interval, 1.2-1.9) and 2.3 years (1.9-6.8 years; P = .002), respectively. On the other hand, the median intervals from resection to the appearance of new lesions in patients with and without nonenhancing lesions or enhancing lesions without washout were 1.6 years (95% confidence interval, 1.2-1.9) and 2.1 years (1.9-2.1 years; P = .031), respectively. During the natural history of nonenhancing lesions and enhancing lesions without washout that coexist with hepatocellular carcinoma, new lesions often develop prior to the malignant transformation of these lesions. This should be considered a risk factor for the appearance of new hepatocellular carcinoma.


Hydrolytic activity of new bioinspired MnIIIMnII and FeIIIMnII complexes as mimetics of PAPs: Biological and environmental interest.
Coordination compounds that mimic Purple Acid Phosphatases (PAPs) have drawn attention in the bioinorganic field due to their capacity to cleave phosphodiester bonds. However, their catalytic activity upon phosphate triesters is still unexplored. Thus, we report the synthesis and characterization of two binuclear complexes, [MnIIMnIII(L1)(OAc)2]BF4 (1) and [MnIIFeIII(L1)(OAc)2]BF4 (2) (H2L1 = 2-[N,N-bis-(2- pyridilmethyl)aminomethyl]-4-methyl-6-[N-(2-hydroxy-3-formyl-5-methylbenzyl)-N-(2-pyridylmethyl)aminomethyl]phenol), their hydrolytic activity and antioxidant potential. The complexes were fully characterized, including the X-Ray diffraction (XRD) of 1. Density functional theory (DFT) calculations were performed to better understand their electronic and structural properties and phosphate conjugates. The catalytic activity was analyzed for two model substrates, a diester (BDNPP) and a triester phosphate (DEDNPP). The results suggest enhancement of the hydrolysis reaction by 170 to 1500 times, depending on the substrate and complex. It was possible to accompany the catalytic reaction of DEDNPP hydrolysis by phosphorus nuclear magnetic resonance (31P NMR), showing that both 1 and 2 are efficient catalysts. Moreover, we also addressed that 1 and 2 present a relevant antioxidant potential, protecting the yeast Saccharomyces cerevisiae, used as eukaryotic model of study, against the exposure of cells to acute oxidative stress.


In Vitro Anti-arthritic Activity.
Formaldehyde-induced arthritis and complete Freund's adjuvant (CFA)-induced arthritis in rats are well-known models to determine the anti-arthritic activity. Arthritis is a symptom of chronic inflammation. It is a chronic progressive disorder, developing over months or years and involving essentially the synovial joints of the body. Hence, these two models become the basis of this chapter to analyse the anti-arthritic activity.


Three-Dimensional vs Two-Dimensional Completely Minimally Invasive 2-Stage Esophagectomy With Intrathoracic Hand-Sewn Anastomosis for Esophageal Cancer: Comparison of Intra-and Postoperative Outcomes.
Background. Completely minimally invasive esophagectomy (CMIE) has been associated with reduced morbidity compared to open esophagectomy in the treatment of esophageal cancer. Three-dimensional (3D) vision can enhance depth perception during minimally invasive surgery when compared to two-dimensional (2D) vision. We aimed to compare outcomes from 2-stage CMIEs when performed in 2D vs 3D. Method. All consecutive 2-stage CMIEs performed for esophageal or gastroesophageal junctional cancer at a single-centre between 2016 and 2018 were identified from a prospectively maintained database. All operations were completed in either 2D or 3D. All esophagogastric anastomoses were hand-sewn thoracoscopically. Intraoperative and postoperative clinical parameters were compared between 2D and 3D CMIE. Results. Overall, 98 patients underwent a 2-stage CMIE, of which 59 (60.2%) were in 2D and 39 (39.8%) in 3D. Median operative blood loss was less in the 3D group compared to the 2D group (283 mls vs 409 mls, P = .016). A higher number of lymph nodes were retrieved from 3D CMIE (30 vs 25, P = .010). The median duration of surgery was 407 minutes (interquartile ranges (IQR): 358-472 minutes) and 426 minutes (IQR: 369-509 minutes) when performed in 2D and 3D, respectively (P = .162). There were no significant intergroup differences in 30-day postoperative complications, short-term mortality, and hospital stay. Conclusion. We report reduced blood loss and higher lymph node yield when performing 3D CMIE than 2D CMIE. Other intraoperative and postoperative clinical outcomes were similar in both groups. A randomized controlled trial is needed to validate these findings of superior outcomes from CMIE performed in 3D over 2D.


A semi-immobilizing system associated with microspectrofluorimetric and videoimaging analysis for intracytoplasmic calcium measurement in individual viable spermatozoa.
We describe a fast and simple method to monitor variations of intracytoplasmic calcium concentrations in very small and motile cells such as mammalian spermatozoa during measurement time. The method combines a procedure of sperm cells semi-immobilization with microspectrofluorimetric measurement of intracytoplasmic calcium concentrations supported by videoimaging that allows also a constant monitoring of viability during the time of calcium recording. In this paper we show that a semi-immobilization of individual viable spermatozoa can be obtained preparing the agar matrix in a two step procedure. The cell immobilizing system proposed, associated with the microspectrofluorimetric analysis supported by videoimaging, is a simple, rapid and useful tool for those studies having the goal of correlating the presence and cellular distribution of ion channels with their functional status and their response to physiologic and/or pharmacological molecules.


Residents as Medical Student Mentors During an Obstetrics and Gynecology Clerkship.
Resident physicians provide much of the clinical teaching for medical students during their clerkship rotations, but often receive no formal preparation or structure for teaching and mentoring students. We sought to evaluate a medical student mentoring program (MSMP) for students during their obstetrics and gynecology clerkship at a midwestern teaching hospital during the 2013-2014 academic year. A senior resident physician was assigned 1 to 2 medical students for a 6-week rotation. Students were provided MSMP information during clerkship orientation; residents were given information on MSMP requirements and were randomly assigned to students. We surveyed students and residents about their experience with the MSMP. Of 49 eligible medical students, 43 (88%) completed postsurveys. All students reported not having a mentoring program on other clerkships. Postclerkship, students indicated that they would participate in the MSMP again (32 of 38, 84%), and felt that having a mentor on other clerkships (30 of 36, 83%) would be beneficial. Students reported receiving educational (20 of 41, 49%) and procedural (33 of 41, 80%) instruction, personal development feedback (23 of 41, 56%), and career advice (14 of 41, 34%) from resident mentors. Out of a total of 45 possible surveys by residents, 17 (38%) were completed. Residents did not feel burdened by students (14 of 17, 82%), and all responded that they would participate in the MSMP again. Feedback from medical students suggests that a mentoring program during clerkships may provide potential benefits for their careers and in 1-on-1 instruction.


[Differentiation of new bone formation at the site of limb lengthening procedures in ultrasonographic examination].
Three different types of newly produced bone were found in 2500 ultrasound appearances of 79 bony segments submitted to the elongation. Their classification as normotrophic, hypertrophic and hypotrophic type has been proposed. Every type requires different management during distraction in order to achieve elongation planned and avoid complications.


An integrated blood volume pulse biofeedback system for migraine treatment.
A blood volume pulse (BVP) biofeedback system is described that integrates BVP amplitude to provide a signal appropriate for auditory feedback. In comparison to binary BVP feedback methods, this integrated system offers the advantages of continuous feedback and increased scoring ease. The validity of this system was established by correlating the integrated BVP output with trough-to-peak measurements of the raw BVP signal during unassisted relaxation and temporal BVP biofeedback with eight migraine headache patients. Within-subject correlations of the integrated and raw BVP outputs ranged from .82 to .98 (means = .95). Although the integrated method admits unwanted BVP changes in rate, correlation analyses showed this confound factor to be small. Increments in biofeedback training effects were observed during the treatment course. Substantive migraine relief was achieved by the end of treatment and therapeutic gains were maintained at 1-year follow-up. In conclusion, it appears that this method successfully presents continuous auditory feedback from an integrated BVP signal resulting in therapeutic benefits to migraineurs.


Neonatal outcome among low birth weight infants delivered spontaneously or by low forceps.
In a population of 1065 singleton, low birth weight infants (1000 to 2500 g) delivered vaginally from vertex presentation, the neonatal mortality and morbidity of 394 delivered by low forceps were compared with those of 671 delivered spontaneously. There were no significant differences between the groups, either across the population as a whole or among any of the following birth weight subgroups: 1000 to 1500 g, 1501 to 2000 g, and 2001 to 2500 g. The data in the current study, as well as those from previous reports, argue against the routine use of prophylactic low forceps delivery and in favor of a more individualized approach to the vaginal delivery of infants in vertex presentation in this weight group.


Vortex-enhanced capture of airborne particulates.
The study reported here sought to exploit aeroelastically-generated vortices for enhanced capture of airborne particles by horizontal, flat plate collectors. Elastically-supported bluff bodies of different cross-sections were screened for suitable plunge (transverse) oscillation at air velocities ranging from about 1 to 10 m s(-1). Both "D" shapes and trapezoidal prisms proved to be particularly effective; the "D" provided an increase in particle capture of 64% relative to the undisturbed flow over a flat plate at a mean air speed of 1.5 m s(-1). At higher velocities, a "T" shaped cross-section (producing mainly torsional oscillation) was found to be extremely effective at increasing capture for airborne particles with a mean diameter of 8 microm. Dynamic pressure measurements made downstream from the oscillators revealed that the torsional oscillation of the "T" produced a flow with multiple periodicities, whereas the plunge oscillators produced a wake that was more sharply periodic. These results indicate that aeroelastically intensified vortices, generated at Reynolds numbers ranging from about 2300 to 5200, can significantly improve particle removal from air streams. Furthermore, the effect can be exploited in both internal (duct) and external (free) flows.


Alterations of the composition and size of the free fatty acid pool of Tetrahymena responding to low-temperature stress.
Cells of Tetrahymena mimbres (formerly T. pyriformis NT-1) in midlogarithmic growth under isothermal conditions (at 39 degrees C) contained a very small, compositionally discrete pool of free fatty acids, principally (60.6% of the total free fatty acid mass) palmitic and stearic acids. The composition, degree of unsaturation, and size of this free fatty acid pool were rapidly (15 min or less) altered in response to chilling. During the acclimation period following chilling to 15 degrees C, the size of the free fatty acid pool increased from a mean value of 15.5 nmol free fatty acid/mumol lipid phosphorus in 39 degrees C cells to 24.2 nmol free fatty acid/mumol lipid phosphorus. The degree of free fatty acid saturation rapidly increased over the initial hour following the onset of hypothermal conditions, but by 24 h the unsaturated free fatty acid/saturated free fatty acid ratio was 0.35 (equivalent to a 2.7-fold increase in unsaturation relative to 39 degrees C controls (unsaturated/saturated ratio = 0.13) and 4.4-fold greater than cells acclimated for 1 h (unsaturated/saturated ratio = 0.08)). By 24 h the percentage of palmitic and stearic acids had decreased to 45.6%. Similar, and in some instances more pronounced, changes were observed to occur in triacylglycerol-bound fatty acids. Modulation of steady-state free fatty acid composition could also be achieved by the addition of exogenous fatty acids to the growth medium. The ability to manipulate the level of intracellular free fatty acids should prove to be a valuable experimental tool in determining how specific fatty acids regulate various lipid-modifying enzymes.


Use of the EFI score in endometriosis-associated infertility: A cost-effectiveness study.
The management of endometriosis-related infertility is still under debate. The Endometriosis Fertility Index (EFI) score is performant to predict the occurrence of a spontaneous pregnancy following surgery, but was not evaluated in a cost-effectiveness perspective. Our objective was to quantify fertility outcomes, and costs of different care pathways for endometriosis-associated infertility after primary surgery, with a stratification on the EFI score. We conducted a cost-effectiveness analysis based on a decision-tree model in a Tertiary-care university hospital. Extracted form a prospectively maintained database, 608 patients with endometriosis-associated infertility, who underwent laparoscopic treatment with an evaluation of the EFI score, were discriminated between different strategies: natural conception, immediate IVF-ICSI, delayed IVF-ICSI. The pregnancy rate and the live birth rate were the effectiveness outcomes. We considered direct and indirect costs in each strategies. The analysis was stratified according to the EFI score. After surgery, 163 women with immediate IVF-ICSI (strategy I) were compared with 445 women who had natural conception attempts during a year (strategy II). After a year failure of natural conception attempts, 133 women continuing natural conception attempts (strategy III) were compared with 168 women who had delayed IVF-ICSI (strategy IV). The respective PR and LBR were 62.6 % and 52.1 % for strategy I, and 32.4 % and 23.8 % for strategy II. Compared to strategy II, strategy I was more costly and more effective (Incremental Cost Effectiveness Ratio (ICER): 31,469 €/pregnancy and 33,568 €/live birth)). No added benefit was observed for patients in strategy I with an EFI score [0-3] after two IVF-ICSI cycles. Strategy III was strongly dominant versus strategy IV for patients with an EFI score [9-10]. Compared to strategy III, strategy VI was more costly and more effective (ICER: 79,674 €/pregnancy, 53,188 €/pregnancy and 27,748 €/pregnancy respectively for patients with an EFI score [7-8], [4-6] and [0-3]). Immediate IVF-ICSI after surgery is effective but associated with substantial costs for the healthcare system. Taking into account healthcare costs, the EFI is a useful score for helping a couple decide between different care pathways -natural conception, immediate or delayed IVF-ICSI- after surgery for endometriosis-associated infertility.


Comparison of Skin Scraping and Standard Superficial Skin Biopsy in the Laboratory Diagnosis of Scabies
Scabies is diagnosed based on the presence of burrows on the skin, Sarcoptes scabiei adult, egg, or scybala in skin scrapings. The laboratory diagnosis of scabies poses various challenges. We aimed to compare the analytical performance of skin scraping and standard superficial skin biopsy (SSSB) and to investigate the correlation with false negative results in the laboratory diagnosis of scabies. Skin scraping and SSSB were applied from July 1 to December 31, 2018 on 42 patients whose burrows were marked using dermatoscopy, as obtained from the laboratory information system. The number of patients who tested positive for scabies with skin scraping was 18 (42.9%) and 24 (57.1%) with SSSB, and the difference was significant (p=0.003). Sensitivity was 42.9% for skin scraping and 57.1% for SSSB. The number of positive cases with both techniques was 15 (35.7%). The number of patients positive with only skin scraping was 3 (7.1%) and only SSSB was 9 (21.4%). To date, it has seemed impossible to diagnose scabies using a single clinical or laboratory test. According to our results, SSSB is an inexpensive and easy-to-apply method with high sensitivity for obtaining skin samples for scabies laboratory diagnosis.


Analyzing determinants from both compositional and contextual level impeding desired linear growth of children in Indian context.
Childhood stunting is recognized as significant public health concern in India. It is a form of malnutrition with impaired linear growth and creates a range of adversaries among children, including under-5 mortality, morbidity, and physical and cognitive growth. The purpose of the present study was to recognize the various leading determinants causing childhood stunting from both individual and contextual level in Indian context. Data were obtained from the India's Demography and Health Survey (DHS) conducted in 2019-2021. A total of 1, 46,521 children aged 0-59 months were included in this present study. The study applied a multilevel mixed-effect logistic regression model in which individual factors nested within community based contextual-level factors estimating the likelihood of childhood stunting phenomena among Indian children. The variance explained in full model accounted for about 35.8% of the odds of stunting across the communities. The present study elucidates that the recognized factors from individual level characteristics have really increased the odds of childhood stunting: gender of child, multiple births, low birth weight, low BMI among mothers, less educational attainment by mothers, maternal anemic status, breast feeding duration longer than usual, < 4 antenatal care (ANC) visits during gestation period. Similarly, contextual-level factors like rural places of residence, western Indian children, and communities with high poverty rates, lower literacy rates, improper sanitation, and unsafe drinking water were also found to have a significant positive association with childhood stunting. The study finally concludes that cross level interaction between individual and contextual-level factors are identified as significant determinants of linear growth retardation among child in India. In order to reduce this type of malnutrition among the child one should more concentrate on both individual and contextual-level factors as a notable reasons.


ARBRE: Computational resource to predict pathways towards industrially important aromatic compounds.
Synthetic biology and metabolic engineering rely on computational search tools for predictions of novel biosynthetic pathways to industrially important compounds, many of which are derived from aromatic amino acids. Pathway search tools vary in their scope of covered reactions and compounds, as well as in metrics for ranking and evaluation. In this work, we present a new computational resource called ARBRE: Aromatic compounds RetroBiosynthesis Repository and Explorer. It consists of a comprehensive biochemical reaction network centered around aromatic amino acid biosynthesis and a computational toolbox for navigating this network. ARBRE encompasses over 33'000 known and 390'000 novel reactions predicted with generalized enzymatic reactions rules and over 74'000 compounds, of which 19'000 are known to biochemical databases and 55'000 only to PubChem. Over 1'000 molecules that were solely part of the PubChem database before and were previously impossible to integrate into a biochemical network are included into the ARBRE reaction network by assigning enzymatic reactions. ARBRE can be applied for pathway search, enzyme annotation, pathway ranking, visualization, and network expansion around known biochemical pathways and products of lignin degradation to predict valuable compound derivations. In line with the standards of open science, we have made the toolbox freely available to the scientific community on git (https://github.com/EPFL-LCSB/ARBRE) and we provide the web-version at http://lcsb-databases.epfl.ch/arbre/. We envision that ARBRE will provide the community with a new computational resource and comprehensive search tool to predict and rank pathways towards industrially important aromatic compounds.


Clinical tools and biomarkers to predict preeclampsia.
Preeclampsia is pregnancy-specific, and significantly contributes to maternal, and perinatal morbidity and mortality worldwide. An effective predictive test for preeclampsia would facilitate early diagnosis, targeted surveillance and timely delivery; however limited options currently exist. A first-trimester screening algorithm has been developed and validated to predict preterm preeclampsia, with poor utility for term disease, where the greatest burden lies. Biomarkers such as sFlt-1 and placental growth factor are also now being used clinically in cases of suspected preterm preeclampsia; their high negative predictive value enables confident exclusion of disease in women with normal results, but sensitivity is modest. There has been a concerted effort to identify potential novel biomarkers that might improve prediction. These largely originate from organs involved in preeclampsia's pathogenesis, including placental, cardiovascular and urinary biomarkers. This review outlines the clinical imperative for an effective test and those already in use and summarises current preeclampsia biomarker research.


Trichothiodystrophy: an electron-histochemical study of the hair shaft.
We have used sensitive electron-histochemical methods to study the subtle ultrastructural variations of cystine incorporation into the hair shaft in trichothiodystrophy. We have shown a general reduction in the cystine (sulphur) content of both the cuticle and the cortex. Discontinuity, and in some cases, complete absence of the cuticular A-layer results in premature weathering of the cuticle and weakening of the hair shaft. The ultrastructural findings support the work of Gillespie & Marshall (1981) in demonstrating the absence or re-characterization of the high sulphur matrix proteins and show further evidence for the incorporation, and abnormal distribution and deposition of sulphur-rich proteins in the hair cortex and cuticle. We conclude that the similar yet different results obtained from each patient's hair sample are characteristic of trichothiodystrophy, a neuro-ectodermal symptom complex which may represent a final common pathway of more than one metabolic disturbance.


Multi-domain terpenoid cyclase architecture and prospects for proximity in bifunctional catalysis.
Crystal structures of terpenoid cyclases reveal assemblies of three basic domains designated α, β, and γ. While the biosynthesis of cyclic monoterpenes (C10) and sesquiterpenes (C15) most often involves enzymes with α or αβ domain architecture, the biosynthesis of cyclic diterpenes (C20), sesterterpenes (C25), and triterpenes (C30) can involve enzymes with α, αα, βγ, or αβγ domain architecture. Indeed, some enzymes of terpenoid biosynthesis are bifunctional, with distinct active sites that catalyze sequential reactions. Interestingly, some of these enzymes oligomerize to form dimers, tetramers, and hexamers. Not only can such assemblies enable enzyme regulation by allostery, but they can also provide a modest enhancement of terpenoid product flux through proximity channeling or cluster channeling. The mixing and matching of functional terpenoid cyclase domains through tertiary and/or quaternary structure may also comprise an evolutionary strategy for facile product diversification.


Effect and mechanisms of Gong-tone music on the immunological function in rats with Liver (Gan)-qi depression and Spleen (Pi)-qi deficiency syndrome in rats.
To investigate the effects and mechanisms of Gong-tone music on the immunological function in rats with the Chinese medicine syndrome of Liver (Gan)-qi stagnation and Spleen (Pi)-qi deficiency (LSSD). Twenty five male Wistar rats of SPF grade were randomly divided into 5 groups: normal group, model group, Xiaoyao Powder () group, Gong-tone group and combined group (the combination of Gong-tone and Xiaoyao Powder), with 5 rats in each group. The rat model for the Chinese medicine syndrome of LSSD was induced by chronic bandage and irregular diet. The course of treatment was 21 days. After the treatment, the levels of serum gastrin and IgG were detected by enzyme-linked immunoabsorbent assay (ELISA). Phagocytosis of macrophages was detected by the neutral red uptake assay and T cell proliferation was investigated by 3-(4,5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide (MTT) assay. The serum gastrin, macrophage phagocytosis, IgG level and proliferation ability of T cells in the model group were significantly decreased compared with those in the normal group (P <0.05). Compared with those in the model group, the serum levels of gastrin, macrophage phagocytosis, IgG level and proliferation ability of T cells in Gong-tone, Xiaoyao Powder, and combined groups were significantly increased (P <0.05). The combined group was superior to either Gong-tone group or Xiaoyao Powder group. Gong-tone music may upregulate the immunological function and play a role in adjuvant therapy in the Chinese syndrome of LSSD.


The right ventricle in sepsis.
Right ventricular dysfunction is common in sepsis and septic shock because of decreased myocardial contractility and elevated pulmonary vascular resistance despite a concomitant decrease in systemic vascular resistance. The mainstay of treatment for acute right heart failure includes treating the underlying cause of sepsis and reversing circulatory shock to maintain tissue perfusion and oxygen delivery. Decreasing pulmonary vascular resistance with selective pulmonary vasodilators is a reasonable approach to improving cardiac output in septic patients with right ventricular dysfunction. Treatment for right ventricular dysfunction in the setting of sepsis should concentrate on fluid repletion, monitoring for signs of RV overload, and correction of reversible causes of elevated pulmonary vascular resistance, such as hypoxia, acidosis, and lung hyperinflation.


Advances in Penetrating Multichannel Microelectrodes Based on the Utah Array Platform.
The Utah electrode array (UEA) and its many derivatives have become a gold standard for high-channel count bi-directional neural interfaces, in particular in human subject applications. The chapter provides a brief overview of leading electrode concepts and the context in which the UEA has to be understood. It goes on to discuss the key advances and developments of the UEA platform in the past 15 years, as well as novel wireless and system integration technologies that will merge into future generations of fully integrated devices. Aspects covered include novel device architectures that allow scaling of channel count and density of electrode contacts, material improvements to substrate, electrode contacts, and encapsulation. Further subjects are adaptations of the UEA platform to support IR and optogenetic simulation as well as an improved understanding of failure modes and methods to test and accelerate degradation in vitro such as to better predict device failure and lifetime in vivo.


Perspectives on Dual Targeting Delivery Systems for Brain Tumors.
Brain tumor remains one of the most serious threats to human beings. Different from peripheral tumors, drug delivery to brain tumor is largely restricted by the blood brain barrier (BBB). To fully conquer this barrier and specifically deliver drugs to brain tumor, dual targeting delivery systems were explored, which are functionalized with two active targeting ligands: one to the BBB and the other to the brain tumor. The development of dual targeting delivery system is still in its early stage, and attentions need to be paid to issues and concerns that remain unresolved in future studies.


Human error in strabismus surgery: quantification with a sensitivity analysis.
Reoperations are frequently necessary in strabismus surgery. The goal of this study was to analyze human-error related factors that introduce variability in the results of strabismus surgery in a systematic fashion. We identified the primary factors that influence the outcome of strabismus surgery. For each of the human-error related factors we quantified variation with clinical assessments: measurement of the angle of strabismus, surgical strategy and surgical accuracy. Firstly, six patients were examined by six orthoptists, and accuracy of prism cover tests was assessed. Secondly, a questionnaire with sample cases (10 degrees, 15 degrees and 20 degrees of infantile esotropia) was put to orthoptists, to determine variation in current surgical strategy. Finally, photographs made during surgery were analyzed to assess surgical accuracy. The influence of human-error related factors was related to the influence of inter-patient differences with a mechanical model. The relative contribution of all factors was assessed with a sensitivity analysis, and results were compared to clinical studies. The surgical trajectory of strabismus surgery could be modeled mathematically. Measurement of angle of strabismus, surgical technique, anatomy and physiology were considered. Variations in the human-error related factors were: (1) the latent angle at distant fixation was measured with a 90% confidence interval of 5 degrees , and comprised 20% of the total variance of the postoperative angle, (2) orthoptists decided for bilateral recessions of, respectively, 7.3 +/- 1.7 mm (total amount of two recessions), 9.1 +/- 1.2 mm and 10.3 +/- 1.3 mm, which comprised 15% of the total variance, and (3) surgical accuracy was estimated at +/-0.5 mm, which comprised 20% of the total variance. The human error in strabismus surgery could be quantified with a sensitivity analysis. Approximately half of the reoperations in strabismus surgery are caused by inaccuracy in the measurement of the angle of strabismus, variability in surgical strategy and imprecise surgery.


Eukaryotic release factor 3 is required for multiple turnovers of peptide release catalysis by eukaryotic release factor 1.
Eukaryotic peptide release factor 3 (eRF3) is a conserved, essential gene in eukaryotes implicated in translation termination. We have systematically measured the contribution of eRF3 to the rates of peptide release with both saturating and limiting levels of eukaryotic release factor 1 (eRF1). Although eRF3 modestly stimulates the absolute rate of peptide release (∼5-fold), it strongly increases the rate of peptide release when eRF1 is limiting (>20-fold). This effect was generalizable across all stop codons and in a variety of contexts. Further investigation revealed that eRF1 remains associated with ribosomal complexes after peptide release and subunit dissociation and that eRF3 promotes the dissociation of eRF1 from these post-termination complexes. These data are consistent with models where eRF3 principally affects binding interactions between eRF1 and the ribosome, either prior to or subsequent to peptide release. A role for eRF3 as an escort for eRF1 into its fully accommodated state is easily reconciled with its close sequence similarity to the translational GTPase EFTu.


Melatonin attenuates carbon tetrachloride-induced liver fibrosis via inhibition of necroptosis.
We investigated the protective mechanisms of melatonin (MLT) associated with necroptosis signaling and damage-associated molecular patterns, which are mediated by the activation of pattern recognition receptors in liver fibrosis. Rats were given an intraperitoneal injection of carbon tetrachloride (CCl4) dissolved in olive oil (1:3, vol/vol) twice a week (0.5 mL/kg) for 8 weeks. During this period, MLT was administered orally at 2.5, 5, and 10 mg/kg once a day. Chronic CCl4 administration increased hepatic hydroxyproline content and hepatocellular damage. MLT attenuated these increases. The expression levels of transforming growth factor β1 and α-smooth muscle actin that were increased by chronic CCl4 exposure were attenuated by MLT. CCl4 significantly increased receptor-interacting protein 1 (RIP1) expression, the formation of the RIP1 and RIP3 necrosome complex, and the level of mixed lineage kinase domain-like protein in liver tissue, which were attenuated by MLT. MLT also attenuated CCl4-induced increases in serum high-mobility group box 1 (HMGB1) and interleukin 1α, as well as the interaction between HMGB1 receptors for advanced glycation end products (RAGE). The increases in toll-like receptor 4 expression, p38, c-Jun N-terminal kinases phosphorylation, and nuclear factor κB translocation were suppressed by MLT. MLT attenuated the overexpression of RAGE, increased level of early growth response protein 1, and increased messenger RNA level of macrophage inflammatory protein 2. Our findings suggest MLT may prevent liver fibrosis by inhibiting necroptosis-associated inflammatory signaling.


Tetrathiafulvalene diindolylquinoxaline: a dual signaling anion receptor with phosphate selectivity.
Incorporation of tetrathiafulvalene into the backbone of a known neutral phosphate receptor, diindolylquinoxaline, yields a dual optical-electrochemical chemosensor for dihydrogen phosphate that functions in dichloromethane. This system shows selectivity for dihydrogen phosphate over other small anions and can be used to detect the presence of this analyte via fluorescence quenching or cyclic voltammetry.


Improving the cardiometabolic health of people with psychosis: A protocol for a randomised controlled trial of the Physical Health Nurse Consultant service.
Over 690,000 Australians experience psychosis annually, significantly impacting cardiometabolic illness and healthcare costs. Current models of care are fragmented and a critical implementation gap exists regarding the delivery of coordinated physical healthcare for Australians with psychosis. To describe a trial implementing a Physical Health Nurse Consultant (PHNC) role to coordinate physical health care in a community mental health setting. In this 24-month, 2-group randomised controlled trial, 160 adults with psychosis will be randomised to usual care, or to the PHNC in addition to usual care. Using the Positive Cardiometabolic Health treatment framework and working in collaborative partnerships with consumers (consumer-led co-design), the PHNC will provide care coordination including referral to appropriate programmes or services based on the treatment framework, with the consumer. Burden of Disease risk factors will be collected according to Australian Bureau of Statistics' National Health Survey guidelines. Consumer experience will be assessed using the 'Access', 'Acceptability' and 'Shared Decision Making' dimensions of the Patient Experiences in Primary Healthcare Survey. Cost-effectiveness will be modelled from Burden of Disease data using the Assessing Cost Effectiveness Prevention methodology. Data collection of two years duration will commence in late 2018. Preliminary findings are expected in December 2019. Primary outcomes will be the effect of the PHNC role on physical healthcare in community-based adults with psychosis. The PHNC is an innovative approach to physical health care for adults with psychosis which aims to meet the physical health needs of consumers by addressing barriers to physical health care.


Simplification of glutathione-bicarbonate-Ringer solution: its effect on corneal thickness.
Glutathione and adenosine can safely be omitted from glutathione-bicarbonate-Ringer solution (GBR) which is used as an irrigating solution during vitrectomy, without significant reduction in the solution's efficacy or increase in corneal toxicity. Bicarbonate appears to be an essential ingredient and should not be omitted from the Ringer solution.


Household and Context Determinants of Child Labor in 221 Districts of 18 Developing Countries.
We develop a new theoretical framework that explains the engagement in child labor of children in developing countries. This framework distinguishes three levels (household, district and nation) and three groups of explanatory variables: Resources, Structure and Culture. Each of the three groups refers to another strand of the literature; economics, sociology and anthropology. The framework is tested by applying multilevel analysis on data for 239,120 children living in 221 districts of 18 developing countries. This approach allows us to simultaneously investigate effects of household and context factors. At the household level, we find that resources and structural characteristics influence child labor, whereas cultural characteristics have no effect. With regard to context factors, we find that children work more in rural areas, especially if there are more unskilled manual jobs, and in more traditional urban areas. In more developed regions, girls tend to work significantly less.


[Diagnosis of the active phase of periodontal disease. 2. Non-clinical parameters].
A review of the Literature shows that a lat of (non-clinical) umoral markers have been suggested as indicators of periodontal disease activity. The advantage of simultaneous evaluation of different markers to obtain a profile of local disease activity has been highlighted in this work as an approach that may provide an usefull picture of the local destructive disease.


Interactions between lipid source and vitamin A on broiler performance, blood parameters, fat and protein deposition rate, and bone development.
A total of 2622 male broilers were distributed in a 2 × 5 factorial design, using 2 lipid sources (soybean oil and palm fat), 5 levels of vitamin A supplementation (0, 3,000, 6,000, 12,000, and 24,000 IU kg-1), with 10 replicates, and also 1 control diet (CD) for each lipid source used (7 replicates), each experimental unit being composed of 23 birds. During the first 21 d (how were the birds fed) and from 22 to 42 d of age, a redistribution of the treatments was carried out in a 2 × 2 × 5 factorial design: half of the repetitions of each treatment received the diet of the initial treatment, and the others received the CD with its type of lipid source. In the phase from 1 to 21 d of age, the effect of lipid source on feed intake (FI) and feed conversion ratio (FCR), and the effect of vitamin supplementation on FI and weight gain (WG) were observed, with a quadratic response for both variables. At 42 d of age, the lipid source and vitamin A level influenced the FI, whereas the WG and FCR showed interactions between period and the level of vitamin A supplementation. Neither lipid source resulted in blood parameters out of the typical pattern for birds, and the same was observed in relation to dietary vitamin A supplementation. From 1 to 21 d of age, a vitamin A supplementation of 15,585 IU kg-1 was estimated, and at 42 d, 15,527 IU kg-1 and 15,148 IU kg -1 were estimated for the periods 1 to 21 d and 1 to 42 d, respectively.


Nuclear organization and chromatin dynamics in yeast: biophysical models or biologically driven interactions?
Over the past decade, tremendous progress has been made in understanding the spatial organization of genes and chromosomes. Nuclear organization can be thought of as information that is not encoded in DNA, but which nevertheless impacts gene expression. Nuclear organizational influences can be cell-specific and are potentially heritable. Thus, nuclear organization fulfills all the criteria necessary for it to be considered an authentic level of epigenetic information. Chromosomal nuclear organization is primarily dictated by the biophysical properties of chromatin. Diffusion models of polymers confined in the crowded nuclear space accurately recapitulate experimental observation. Diffusion is a Brownian process, which implies that the positions of chromosomes and genes are not defined deterministically but are likely to be dictated by the laws of probability. Despite the small size of their nuclei, budding yeast have been instrumental in discovering how epigenetic information is encoded in the spatial organization of the genome. The relatively simple organization of the yeast nucleus and the very high number of genetically identical cells that can be observed under fluorescent microscopy allow statistically robust definitions of the gene and chromosome positions in the nuclear space to be constructed. In this review, we will focus on how the spatial organization of the chromatin in the yeast nucleus might impact transcription. This article is part of a Special Issue entitled: Nuclear Transport and RNA Processing.


Current Concepts in the Diagnosis and Management of Pneumocystis Pneumonia in Solid Organ Transplantation.
Pneumocystis infection manifests predominantly as an interstitial pneumonia in immunocompromised patients. Diagnostic testing in the appropriate clinical context can be highly sensitive and specific and involves radiographic imaging, fungal biomarkers, nucleic acid amplification, histopathology, and lung fluid or tissue sampling. Trimethoprim-sulfamethoxazole remains the first-choice agent for treatment and prophylaxis. Investigation continues to promote a deeper understanding of the pathogen's ecology, epidemiology, host susceptibility, and optimal treatment and prevention strategies in solid organ transplant recipients.


Investigation of glycaemic traits in psychiatric disorders using Mendelian randomisation revealed a causal relationship with anorexia nervosa.
Data from observational studies have suggested an involvement of abnormal glycaemic regulation in the pathophysiology of psychiatric illness. This may be an attractive target for clinical intervention as glycaemia can be modulated by both lifestyle factors and pharmacological agents. However, observational studies are inherently confounded, and therefore, causal relationships cannot be reliably established. We employed genetic variants rigorously associated with three glycaemic traits (fasting glucose, fasting insulin, and glycated haemoglobin) as instrumental variables in a two-sample Mendelian randomisation analysis to investigate the causal effect of these measures on the risk for eight psychiatric disorders. A significant protective effect of a natural log transformed pmol/L increase in fasting insulin levels was observed for anorexia nervosa after the application of multiple testing correction (OR = 0.48 [95% CI: 0.33-0.71]-inverse-variance weighted estimate). There was no consistently strong evidence for a causal effect of glycaemic factors on the other seven psychiatric disorders considered. The relationship between fasting insulin and anorexia nervosa was supported by a suite of sensitivity analyses, with no statistical evidence of instrument heterogeneity or horizontal pleiotropy. Further investigation is required to explore the relationship between insulin levels and anorexia.


Oxidized LDL receptor LOX-1 is involved in neointimal hyperplasia after balloon arterial injury in a rat model.
LOX-1 is a multi-ligand receptor originally identified as the endothelial oxidized LDL receptor. LOX-1 expression is also induced in smooth muscle cells in response to proinflammatory and oxidative stimuli. Here, we report on the role of LOX-1 in intimal hyperplasia, in which proinflammatory and oxidative stimuli are increased. Left common carotid artery of rat was injured by a balloon catheter. The expression of LOX-1 was significantly increased within 24 h after the balloon injury and peaked at day 7. LOX-1 expression was observed predominantly in medial smooth muscle cells until day 3, and then shifted to predominantly intimal smooth muscle cells. At day 14, the expression was concentrated in the regenerated endothelial cells. To examine the contributory role of LOX-1 in the growth of intimal smooth muscle cells, rats were administered anti-LOX1 antibody intravenously every 3 days after balloon injury. Anti-LOX-1 antibody administration effectively suppressed intimal hyperplasia, oxidative stress, and leukocyte infiltration compared with control IgG. These findings suggest the importance of LOX-1 expression in the pathogenesis of neointimal formation in conjunction with oxidative stress and leukocyte infiltration. The LOX-1 expressed in smooth muscle cells is involved in intimal hyperplasia in a rat model of balloon injury. Manipulation of LOX-1 activity is a novel potential therapeutic target to prevent restenosis after angioplasty.


Occurrence of fungi with mycotoxic potential in grain of transylvania and potential hazardous effects in broiler chicken.
Investigations on the mycological quality of feeds from Transylvanian farms are presented. The investigations had two objectives: 1. survey for mycological contamination and related chemical composition; 2. the evaluation of effects ofFusarium graminearum Schw. infested wheat (8% in the diet) on productivity and digestibility of nutrients in broilers. More than 50% of the samples showed water contents exceeding 16%, due to inadequate harvesting and storage conditions. This correlated with high my-cological contamination, with dominant species of the genusFusarium, Aspergillus, Alternaria,Penicillium andRhizopus. Feeding trials with broilers showed that live weight gain and digestibility coefficients of protein and fat in animals givenFusarium infested grain were depressed. As well N-retention and feed conversion rate (kg feeding stuff/ kg weight gain) were impaired.


Antireflection Enhancement by Composite Nanoporous Zeolite 3A-Carbon Thin Film.
A straightforward and effective spin-coating technique at 120 °C was investigated for the deposition of a thin nanoporous layer with antireflection properties onto glass and indium tin oxide (ITO) coated glass. A mixture of zeolite 3A powder and high iodine value vegetable oil was deposited, creating a carbonic paste with embedded nanoporous grains. Experimental results evidenced excellent broadband antireflection over the visible-near-infrared wavelength range (450-850 nm), with a diffuse reflectance value of 1.67% and 1.79%. Structural and optical characteristics stabilized over time. The results are promising for the accessible and cost-effective fabrication of an antireflective surface for optoelectronic devices.


Comparison of effects of N-3 to N-6 fatty acids on serum level of lipoprotein(a) in patients with coronary artery disease.
The influence of dietary supplementation with n-3 versus n-6 fatty acids on plasma lipoprotein(a) (Lp[a]) levels was studied. Thirty-five male hospitalized patients with coronary artery disease were treated for 4 weeks with 12 g/day of fish oil (approximately 8.5 g of n-3 fatty acids) in combination with a 5,000 kilojoule, 30% fat diet and moderate exercise. Eighteen control patients given the same dietary and training program were treated with 12 g/day of rapeseed oil. Plasma Lp(a), in addition to several lipids and lipoproteins, blood clotting factors, and platelet reactivity, were measured before and at the end of therapy. Results can be summarized as follows: total cholesterol, low-density lipoprotein cholesterol, and apolipoprotein B levels decreased significantly in both the rapeseed oil (-14.4%, -20.3%, -15.2%, respectively) and fish oil (-12.2%, -16.0%, and -14.2%, respectively) groups. Triglycerides decreased (-20.3%) and high-density lipoprotein cholesterol increased (+8.3%) significantly only in patients treated with fish oil. Plasma Lp(a) levels were reduced by 14% in the fish oil group, but unaffected in the rapeseed oil group. Patients treated with fish oil could be categorized into 2 subgroups: "responders," with a reduction in Lp(a) by 24% and "nonresponders," with a small nonsignificant increase in serum Lp(a). Responders and nonresponders exhibited a marked reduction in cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and triglycerides, and an increase in high-density lipoprotein3 cholesterol. There was a large reduction in tissue plasminogen activator in the fish oil group, which correlated significantly with reduction in Lp(a).(ABSTRACT TRUNCATED AT 250 WORDS)


Psychometric Properties of the Hindi Version of the Fear-Avoidance Beliefs Questionnaire in Patients With Chronic Non-Specific Low Back Pain.
Prospective cohort study. To translate, adapt, and establish psychometric properties of the Fear-Avoidance Beliefs Questionnaire (FABQ) for Hindi-speaking patients with chronic non-specific low back pain. The FABQ is a patient-reported measure to assess beliefs regarding how physical activity and work are influenced based on fear related to low back pain. Standardized translation guidelines were implemented to confirm Hindi-version of the FABQ (FABQ-H). A cross-sectional study design was utilized. Construct validity analysis included factor analysis of the FABQ and use of Pearson correlation coefficients to report convergent and divergent validity. Reliability assessment included calculation of intraclass correlation coefficient (ICC) and Cronbach α for internal consistency. Outcome measures consisted of Numeric Rating Scale (NRS), Roland Morris Disability Questionnaire (RMDQ) Hindi, and Tampa Scale of Kinesiophobia (TSK). In total, 100 patients with chronic non-specific low back pain were recruited, with a mean age of 36.89 (±7.78). Factor analysis revealed a three-factor structure of the FABQ, which consisted of subscales FABQ Physical activity, FABQ Work, and FABQ Work prognosis. Convergent validity analysis demonstrated a moderate correlation between FABQ-H and TSK (r = 0.413). Divergent validity analysis displayed a moderate correlation between FABQ-H and NRS (r = 0.362) and RMDQ Hindi (r = 0.399). ICC value for the FABQ-H was observed as 0.938 indicating high significance for test-retest reliability. Cronbach α for the FABQ-H was recorded as 0.806 demonstrating high internal consistency. A successful translation and adaptation of the Hindi version of FABQ is reported in this study. The three-factored FABQ-H exhibited satisfactory construct validity, test-retest reliability, and internal consistency. Based on findings of this study, the FABQ-H can be implemented in Hindi-speaking patients with chronic non-specific low back pain (LBP). 3.


Synthesis, characterization and enhanced thermoelectric performance of structurally ordered cable-like novel polyaniline-bismuth telluride nanocomposite.
Bismuth telluride (Bi₂Te₃) nanorods and polyaniline (PANI) nanoparticles have been synthesized by employing solvothermal and chemical oxidative processes, respectively. Nanocomposites, comprising structurally ordered PANI preferentially grown along the surface of a Bi₂Te₃ nanorods template, are synthesized using in situ polymerization. X-ray powder diffraction, UV-vis and Raman spectral analysis confirm the highly ordered chain structure of PANI on Bi₂Te₃ nanorods, leading to a higher extent of doping, higher chain mobility and enhancement of the thermoelectric performance. Above 380 K, the PANI-Bi₂Te₃ nanocomposite with a core-shell/cable-like structure exhibits a higher thermoelectric power factor than either pure PANI or Bi₂Te₃. At room temperature the thermal conductivity of the composite is lower than that of its pure constituents, due to selective phonon scattering by the nanointerfaces designed in the PANI-Bi₂Te₃ nanocable structures. The figure of merit of the nanocomposite at room temperature is comparable to the values reported in the literature for bulk polymer-based composite thermoelectric materials.


Co-generation of microbial lipid and bio-butanol from corn cob bagasse in an environmentally friendly biorefinery process.
Biorefinery process of corn cob bagasse was investigated by integrating microbial lipid and ABE fermentation. The effects of NaOH concentration on the fermentations performance were evaluated. The black liquor after pretreatment was used as substrate for microbial lipid fermentation, while the enzymatic hydrolysates of the bagasse were used for ABE fermentation. The results demonstrated that under the optimized condition, the cellulose and hemicellulose in raw material could be effectively utilized. Approximate 87.7% of the polysaccharides were converted into valuable biobased products (∼175.7g/kg of ABE along with ∼36.6g/kg of lipid). At the same time, almost half of the initial COD (∼48.9%) in the black liquor could be degraded. The environmentally friendly biorefinery process showed promising in maximizing the utilization of biomass for future biofuels production.


Human homologs of two testes-expressed loci on mouse chromosome 17 map to opposite arms of chromosome 6.
Our laboratory has recently cloned and characterized two testes-expressed loci--the Tcp-10 gene family cluster and the D17Si11 gene--that map to the proximal portion of mouse chromosome 17. Human homologs of both loci have been identified and cloned. Somatic cell hybrid lines have been used to map the human homolog of D17Si11 to the short arm of chromosome 6 (p11-p21.1) along with homologs of other genes from the (Pim-1)-(Pgk-2) region of the mouse chromosome. The human TCP 10 locus maps to the long arm of chromosome 6 (q21-qter) along with homologs of other genes from the mouse chromosome 17 region between the centromere and Pim-1. The mapping of large portions of the mouse t haplotype to unlinked regions on human chromosome 6 rules out the possibility that a t-haplotype-like chromosome could exist in humans.


Early prediction of normocalcemia after thyroid surgery.
Hypocalcemia is the principal factor that determines length of hospital stay after thyroid surgery. Seventy-nine patients who underwent thyroidectomy were prospectively evaluated in order to define risk factors for postoperative hypocalcemia. Serum samples were taken postoperatively at 8, 14, 24, and 48 hours to measure total calcium levels. The slope of change in serum calcium level between each sample time was calculated. Patients were also examined for age, gender, surgical indications, type and extension of surgery, thyroid function, presence of substernal extension, initial operation versus reoperation, and application of parathyroid autotransplantation. All comparisons were made between hypocalcemic and normocalcemic groups. Hypocalcemia occurred in 15 (19%) patients. In univariate analysis, type and extent of thyroidectomy, serum calcium levels at each time point, as well as the slope of change in serum total calcium levels between 8 and 14 hours were found to be significantly predictive of normocalcemia. All patients who underwent hemithyroidectomy and who had a positive or neutral slope of calcium change after surgery remained normocalcemic. By multivariate logistic regression analysis, only the slope of change in calcium levels within the first 14 postoperative hours independently predicted calcium status after thyroidectomy. All patients who undergo unilateral thyroid surgery who have a positive/neutral slope of change in serum total calcium levels within the first 14 hours after surgery can be safely discharged early if they have no other risks.


Metabolite profiling of traditional Chinese medicine XIAOPI formula: An integrated strategy based on UPLC-Q-Orbitrap MS combined with network pharmacology analysis.
XIAOPI formula has been approved for mammary hyperplasia treatment by National Medical Products Administration in China. However, the absorbed substances of XIAOPI formula and their influences on metabolic pathways are largely remained unknown. Liquid chromatography coupled with mass spectrometry was used to identify the substances existing in the serum. Network pharmacology was utilized to explore the underlying metabolic targets and pathways involved in. Western blotting and immunofluorescence assays were carried out for target validation. The exogenous results demonstrated 196 compounds were filtered as absorbed substances, among which 63 constituents or metabolites were tentatively identified in rat serum, and the metabolites of tanshinone II and tanshinone I were found to act as the major metabolic pathways. Subsequently, the endogenous results revealed that XIAOPI formula could significantly regulate serum biochemical indices and the bile acid secretion signaling ranks as top1 among all the involved pathways. The levels of intermediates including cholic acid, glycocholic acid, taurochenodeoxycholic acid and taurocholic acid were significantly upregulated following XIAOPI treatment, accompanied by increased expression of key enzyme CYP7A1, indicating that XIAOPI formula could accelerate the bile acid metabolism pathway. Our study presented a comprehensive metabolic profile of XIAOPI formula in vivo for the first time, and bile acid synthesis pathway might be one of the key mechanisms contributing to the pharmacological function of the formula.


Associations of serum folate and vitamin C levels with metabolic dysfunction-associated fatty liver disease in US adults: A nationwide cross-sectional study.
Clinical research results on the relationship between folate and non-alcoholic fatty liver disease are contradictory. Metabolic dysfunction-associated fatty liver disease (MAFLD) is a recently proposed concept. Evidence about the relationship between serum folate and MAFLD, especially considering the status of serum vitamin C, is scarce. This study was aimed to investigate the association of serum folate levels with the prevalence of MAFLD, and further to analyze the potential impact of serum vitamin C status on their association. Totally 2,797 participants from National Health and Nutrition Examination Survey (NHANES) 2017-2018 were included. Vibration-controlled transient elastography was used to detect liver steatosis and fibrosis. Participants were divided in groups based on the tertiles of serum folate or vitamin C, and the serum folate or vitamin C level in T1 was low. Logistic regression analysis in the complex sample module was performed to illustrate the association of serum folate levels with the prevalence of MAFLD. Stratification analysis by serum vitamin C status was performed as well. Compared with the serum folate levels of T1 group, participants in the T3 group had 47.9% lower risk of MAFLD [OR = 0.521 (95% CI: 0.401-0.677)]. However, when participants were stratified by serum vitamin C levels, there was no association between the serum folate levels and MAFLD in the T1 or T2 group. Among participants in the T3 group of vitamin C status, participants in the T3 group of serum folate had a 63.6% lower risk of MAFLD compared with the T1 group [OR = 0.364 (95% CI: 0.147-0.903)]. High serum folate level is associated with lower prevalence of MAFLD, especially in participants with sufficient vitamin C.


Publisher Correction: A stabilized glycomimetic conjugate vaccine inducing protective antibodies against Neisseria meningitidis serogroup A.
A Correction to this paper has been published: https://doi.org/10.1038/s41467-020-20120-4.


New aniline derivatives from the volva of Phallus rubrovolvatus and their anti-inflammatory activity.
Phallus rubrovolvatus is an important commercially cultivated mushroom species in China. However, the volva of P. rubrovolvatus usually discarded as a by-product due to the unpleasant flavor and difficulty in processing. In this study, we investigated the chemical constituents and bioactivities of the volva of P. rubrovolvatus. As a result, fifteen rare aniline derivatives, including twelve new compounds (1-11, 14) and three new natural products (12, 13, 15) were isolated from the volva. Their structures were determined using 1D and 2D NMR data and HR-ESI-MS data, while the relative and absolute configurations were confirmed by NOESY correlations and comparison between experimental and calculated ECD spectra. In addition, compounds 1-15 were tested for anti-inflammatory activity against lipopolysaccharide (LPS)-induced NO production in RAW264.7 macrophages. Compounds 4, 9 and 10 exhibited anti-inflammatory activity with IC50 values ranging from 12.5 to 15.6 μM.


Interleukin-1 beta induced corticosterone elevation and hypothalamic NE depletion is vagally mediated.
Processes occurring within the immune system can alter neural function. Cytokines released by cells of the immune system during illness are key messengers in immune-to-brain communication. Interleukin-1 beta (IL-1 beta) is particularly important in this regard and is known to stimulate a myriad of illness-related outcomes such as fever, sickness behavior, aphagia, adipsia, hypothalamic-pituitary-adrenal activation, and changes in pain reactivity. Thus peripherally released IL-1 beta has potent neural effects and is a critical mediator of the impact of immune processes on brain. There is, however, uncertainty concerning the communication pathways involved. We provide evidence that a primary route of peripheral cytokine signalling is through stimulation of peripheral vagal afferents rather than or in addition to direct cytokine access to brain. Subdiaphragmatic, but not hepatic vagotomy, blocked rhIL-1 beta-induced hypothalamic norepinephrine depletion and attenuated rhIL-1 beta-induced increases in serum corticosterone. These data suggest that rhIL-1 beta activates the hypothalamic-pituitary-adrenal axis via stimulation of peripheral vagal afferents and further support the hypothesis that peripheral cytokine signalling to the CNS is mediated primarily by stimulation of peripheral afferents.


Trends in ventricular fibrillation/flutter mortality in US population, 1999 to 2019.
The Ventricular fibrillation and flutter (VF/VFL)-related mortality trends in the United States (US) population have not yet been investigated. We aimed to assess the trends of VT/VFL-related mortality from 1999 to 2019 among subjects aged more than 15 years old in the US. Data derived from the Centers for Disease Control and Prevention's (CDC) WONDER were analyzed between 1999 and 2019 for VF/VFL-related mortality in subjects aged more than 15 years of age. Adjusted mortality rates (AAMRs) per 100,000 people by year, sex, race and urban-rural status with relative confidence intervals (CIs) were determined. Both the average annual percent change (AAPC) and the annual percent change (APC) with 95% Cis were calculated. Between 1999 and 2019, 242,125 VT/VFL-related deaths occurred in the US. The overall AAMR steadily declined [AAPC -4.4% (95% CI: -4.7 to -4.0, p < .0001)]. Women showed a more pronounced AAMRs decline [AAPC: -4.8% (95% CI: -5.3 to -4.3, p < .0001). AAMR steadily declined in white subjects and in those of other races [AAPC: -4.5 (95% CI: -4.7 to -4.2, p < .0001) and AAPC: -4.3 (95% CI: -5.1 to -3.5, p < .001), respectively]. Conversely, African Americans showed a steadily AMMR decline between 1999 and 2007 [APC: -8.3 (95% CI: -9.2 to -7.3, p < .0001)], followed by a period of stability from 2007 to 2019 (p = .73). A similar decline was observed for the AAMR among subjects living in urban and rural areas. VT/VFL-related mortality steadily decreased between 1999 and 2019 in US. Despite the encouraging results, further efforts are needed to prevent VF/VFL-related mortality in US subjects.


COVID-19 and schools. Guidelines of the French Pediatric Society.
The educational and social benefits provided by school far outweigh the risks of a possible COVID-19 contamination of children in school environments or in daycare centers. Following summer break, the back-to-school period in France is taking place in the context of an increasing viral spread and requires strict adherence to health measures to limit the risk of outbreaks in communities. Based on a critical update of the role of children in the transmission of the infection, and of children's susceptibility to infection, the French Pediatric Society published practical guidelines for school re-entry and the management of COVID-19 infections in schools.


Statistical inference for the additive hazards model under outcome-dependent sampling.
Cost-effective study design and proper inference procedures for data from such designs are always of particular interests to study investigators. In this article, we propose a biased sampling scheme, an outcome-dependent sampling (ODS) design for survival data with right censoring under the additive hazards model. We develop a weighted pseudo-score estimator for the regression parameters for the proposed design and derive the asymptotic properties of the proposed estimator. We also provide some suggestions for using the proposed method by evaluating the relative efficiency of the proposed method against simple random sampling design and derive the optimal allocation of the subsamples for the proposed design. Simulation studies show that the proposed ODS design is more powerful than other existing designs and the proposed estimator is more efficient than other estimators. We apply our method to analyze a cancer study conducted at NIEHS, the Cancer Incidence and Mortality of Uranium Miners Study, to study the risk of radon exposure to cancer.


Synthesis and evaluation of 2-amido-3-carboxamide thiophene CB₂ receptor agonists for pain management.
SAR studies on a series of thiophene amide derivatives provided CB(2) receptor agonists. The activity of the compounds was characterized by radioligand binding determination, multiple functional assays, ADME, and pharmacokinetic studies. A representative compound with selectivity for CB(2) over CB(1) effectively produced analgesia in behavioral models of neuropathic, inflammatory, and postsurgical pain. Control experiments using a CB(2) antagonist demonstrated the efficacy in the pain models resulted from CB(2) agonism.


Bayesian tracking of intracranial pressure signal morphology.
The waveform morphology of intracranial pressure (ICP) pulses holds essential informations about intracranial and cerebrovascular pathophysiological variations. Most of current ICP pulse analysis frameworks process each pulse independently and therefore do not exploit the temporal dependency existing between successive pulses. We propose a probabilistic framework that exploits this temporal dependency to track ICP waveform morphology in terms of its three peaks. ICP and electrocardiogram (ECG) signals were recorded from a total of 128 patients treated for various intracranial pressure related conditions. The tracking is posed as inference in a graphical model that associates a random variable to the position of each peak. A key contribution is to exploit a nonparametric Bayesian inference algorithm that offers robustness and real time performance. A simple, yet effective learning procedure estimates the statistical, nonlinear, dependencies between the peaks in a nonparametric way using evidence collected from manually annotated pulses. Experiments demonstrate the effectiveness of the tracking framework on real ICP pulses and its robustness to occlusion and missing peaks. On artificialy distorted ICP sequences, the average error in latency in comparision with MOCAIP detector was reduced as follows: 11.88-8.09 ms, 11.80-6.90 ms, and 11.76-7.46 ms for the first, second, and third peak, respectively. The proposed tracking algorithm sucessfuly increases the temporal resolution of detecting ICP pulse morphological changes from the minute-level to the beat-level.


Phosphate excretion is decreased in older cardiac patients with normal kidney function: an emerging dietary risk factor?
Serum phosphate independently predicts cardiovascular events and mortality. Sixteen healthy adults and 9 adults with cardiovascular disease (CVD) ingested 500 mg of sodium phosphate after an over-night fast. In control subjects, the urine phosphate/creatinine ratio was significantly higher at 2 h (3.12 ± 1.02) than at baseline (1.98 ± 0.58, p < 0.001) but no change was observed in CVD patients. Decreased postprandial urinary excretion of phosphate could accelerate vascular calcification and may be an under-recognized risk factor for CVD.


One-pot fusion polymerase chain reaction for combinatorial synthesis of DNA from several cassettes.
The fusion of DNA fragments is becoming increasingly more important. The ability to work without being constrained by restriction sites enables DNA fusion to be applied to a much broader range of fragments. Therefore, we describe a simplified polymerase chain reaction (PCR)-based method for fusion of DNA fragments in one step. In a single PCR, two templates, an overlapping primer, and template-specific forward and reverse primers are used. After a few cycles, the fusion DNA is assembled and is amplified. The ratio of overlapping primer to forward/reverse primers and template DNA is essential for the success of the reaction.


Proximal perimeter encoding in the rat rostral thalamus.
Perimeters are an important part of the environment, delimiting its geometry. Here, we investigated how perimeters (vertical walls; vertical drops) affect neuronal responses in the rostral thalamus (the anteromedial and parataenial nuclei in particular). We found neurons whose firing patterns reflected the presence of walls and drops, irrespective of arena shape. Their firing patterns were stable across multiple sleep-wake cycles and were independent of ambient lighting conditions. Thus, rostral thalamic nuclei may participate in spatial representation by encoding the perimeters of environments.


Histopathological baseline levels and confounding factors in common sole (Solea solea) for marine environmental risk assessment.
Liver and gonad histopathology, biometric parameters and hepatic metal bioaccumulation were assessed monthly over a one-year period in common soles from the Basque continental shelf, in order to determine baseline levels and confounding factors within biomonitoring studies. Biometric parameters and hepatic metal bioaccumulation varied according to season and gender. Accordingly, hepatic histopathological traits presented seasonal variations related to the reproductive cycle. However, the hepatic histopathological index showed that seasonality and gender were not significant confounding factors. Conversely, the gonad histopathological index was modulated by season and gender. As for organ comparison, the liver endured more severe histopathological damage than the gonad. In brief, the sampling period and gender may not affect the estimation of hepatic histopathological indices for biomonitoring purposes. Nonetheless, due to different sensitivities to environmental 'noise' variables, the sampling period and gender differentiation should be thoroughly considered for the assessment of gonad histopathology, biometrics and metal bioaccumulation.


[Experiences with a cardiorecorder system for continuous 24-hour registration of heart rate].
Studies regarding to the continuous registration of the heart frequency by a transportable instrument, which can store the data of the heart frequency per minute up to 24h, are presented. It is a tape recorder the speed of which is geared down. Thus a normal tape cassette C 60 is sufficient for a registration of the heart frequency during 2 X 24h. The R-wave of the ECG is registered on the first channel of the tape as a biological signal. Moreover every minute an impulse of a clock is recorded on the second channel of the tape. With help of a second instrument the play back procedure for the 24-h-recording can be performed in about 15 min. The signals of both channels of the tape are transformed in digital rectangle impulses by an installed impulse-converter. The serial impulses are counted per minute with help of the time-mark by an interface in a counter. These data are at disposal in BCD-code. They can be passed on the following peripherals: digital printer, computer, pen-recorder and so on. A parallel standardized recording of the physical activity observed by the subject or by an experimenter allows a statistical evaluation and comparison of the physical activity with the corresponding heart frequency data. Some examples of the aread of occupational health, epidemiology and exercise physiology are discussed.


How subgroup analyses can miss the trees for the forest plots: A simulation study.
Subgroup analyses of clinical trial data can be an important tool for understanding when treatment effects differ across populations. That said, even effect estimates from prespecified subgroups in well-conducted trials may not apply to corresponding subgroups in the source population. While this divergence may simply reflect statistical imprecision, there has been less discussion of systematic or structural sources of misleading subgroup estimates. We use directed acyclic graphs to show how selection bias caused by associations between effect measure modifiers and trial selection, whether explicit (e.g., eligibility criteria) or implicit (e.g., self-selection based on race), can result in subgroup estimates that do not correspond to subgroup effects in the source population. To demonstrate this point, we provide a hypothetical example illustrating the sorts of erroneous conclusions that can result, as well as their potential consequences. We also provide a tool for readers to explore additional cases. Treating subgroups within a trial essentially as random samples of the corresponding subgroups in the wider population can be misleading, even when analyses are conducted rigorously and all findings are internally valid. Researchers should carefully examine associations between (and consider adjusting for) variables when attempting to identify heterogeneous treatment effects.


Core level ionization or excitation and Auger relaxation induce clustered DNA damage.
Ionizing radiation causes various types of DNA damage, such as single- (SSBs) and double-strand breaks (DSBs), nucleobase lesions, abasic sites (AP sites), and cross-linking between complementary strands of DNA or DNA and proteins. DSBs are among the most harmful type of DNA damage, inducing serious genetic effects such as cell lethality and mutation. Nucleobase lesions and AP sites, on the other hand, may be less deleterious and are promptly repaired by base excision repair (BER) pathways. Recently, biochemical approaches to quantify nucleobase lesions and AP sites have revealed certain types of non-strand break lesions as harmful DNA damage, called clustered DNA damage. Such clusters can retard nucleobase excision repair enzymes, and can sometimes be converted to DSBs by BER catalysis. This unique character of clustered DNA damage strongly depends on the spatial density of ionization or excitation events occurring at the track end of initial radiation or low energy secondary electrons. In particular, the photoelectric effect of elements comprising biological molecules, followed by emission of Auger electrons, are key factors in determining the future fate of each clustered damage site. This chapter describes biological studies of clustered nucleobase lesions with SSBs or AP sites, and mechanistical studies on core level excitation and Auger relaxation giving rise to clustered DNA damage.


A novel land use approach for assessment of human health: The relationship between urban structure types and cardiorespiratory disease risk.
Extensive evidence shows that in addition to lifestyle factors, environmental aspects are an important risk factor for human health. Numerous approaches have been used to estimate the relationship between environment and health. For example, the urban characteristics, especially the types of land use, are considered a potential proxy indicator to evaluate risk of disease. Although several studies have used land use variables to assess human health, none of them has used the concept of Urban Morphology by Urban Structure Types (USTs) as indicators of land use. The aim of this study was to assess the relationship between USTs and cardiorespiratory disease risks in the Federal District, Brazil. Toward this end, we used a quantile regression model to estimate risk. We used 21 types of UST. Income and population density were used as covariates in our sensitivity analysis. Our analysis showed an association between cardiorespiratory diseases risk and 10 UST variables (1 related to rural area, 6 related to residential area, 1 recreational area, 1 public area and 1 commercial area). Our findings suggest that the conventional land use method may be missing important information about the effect of land use on human health. The use of USTs can be an approach to complement the conventional method. This should be of interest to policy makers in order to enhance public health policies and to create future strategies in terms of urban planning, land use and environmental health.


Effect of sodium citrate/polyethylene glycol on plasticization and retrogradation of maize starch.
Maize starch was plasticized by mixtures of sodium citrate and polyethylene glycol 200 (PEG200) at varied weight ratios (citric acid/PEG200, 25/0, 20/5, 15/10, 10/15, 5/20 and 0/25). The structure and pasting, aging, moisture absorption and thermal properties of the plasticized starches were studied by means of Fourier transformed infrared, X-ray diffraction, rapid viscosity analysis, tension test and thermogravimetric analysis. Comparing with single plasticizer, co-plasticizers with appropriate proportions are more effective in hindering the retrogradation of starch paste and film. The results also showed that the mechanical property and humidity sensitivity of the starch film worsen after the introduction of PEG200 compared with sodium citrate plasticized starch, but the thermal stability and anti-aging property increase. This is consistent with the association ability of plasticizers with starch observed from FTIR. In addition to the simple additive effect of components on some properties, special formulations also show some synergistic effects, such as the co-plasticizer of 20% citric acid and 5% PEG200 has a better comprehensive property for plasticizing the maize starch bulk than sodium citrate or PEG200 alone. The mixture of sodium citrate and PEG200 can be used as a candidate plasticizer for preparing thermoplastic starch for food and packaging industries.


Single-step fabrication of patterned gold film array by an engineered multi-functional peptide.
This study constitutes a demonstration of the biological route to controlled nano-fabrication via modular multi-functional inorganic-binding peptides. Specifically, we use gold- and silica-binding peptide sequences, fused into a single molecule via a structural peptide spacer, to assemble pre-synthesized gold nanoparticles on silica surface, as well as to synthesize nanometallic particles in situ on the peptide-patterned regions. The resulting film-like gold nanoparticle arrays with controlled spatial organization are characterized by various microscopy and spectroscopy techniques. The described bio-enabled, single-step synthetic process offers many advantages over conventional approaches for surface modifications, self-assembly and device fabrication due to the peptides' modularity, inherent biocompatibility, material specificity and catalytic activity in aqueous environments. Our results showcase the potential of artificially-derived peptides to play a key role in simplifying the assembly and synthesis of multi-material nano-systems in environmentally benign processes.


From bench to bedside: stealth of enteroinvasive pathogens.
Bacterial enteric infections are often associated with diarrhoea or vomiting, which are clinical presentations commonly referred to as gastroenteritis. However, some enteric pathogens, including typhoidal Salmonella serotypes, Brucella species and enteropathogenic Yersinia species are associated with a clinical syndrome that is characterized by abdominal pain and/or fever and is distinct from acute gastroenteritis. Recent insights into molecular mechanisms of the host-pathogen interaction show that these enteric pathogens share important characteristics that explain why the initial host responses associated with these agents more closely resemble host responses to viral or parasitic infections. Host responses contribute to the clinical presentation of disease and improved understanding of these responses in the laboratory is beginning to bridge the gap between bench and bedside.