DFT and molecular dynamics studies of astaxanthin-metal ions (Cu2+ and Zn2+) complex to prevent glycated human serum albumin from possible unfolding.
Glycated human serum albumin (gHSA) undergoes conformational changes of proteins caused by free radicals. The glycation process results in a reduced ability of albumin as an endogenous scavenger in diabetes mellitus type 2 (T2DM) patients. Astaxanthin (ASX) has been shown to prevent gHSA from experiencing unfolding events and improve protein stability of gHSA and HSA through molecular dynamics. In this study, astaxanthin is complexed with transition metal ions such as copper (Cu2+) and zinc (Zn2+) in two modes (M) and (2M). Complexing astaxanthin with Cu2+ and Zn2+ is expected to increase astaxanthin's ability as an endogenous scavenger than in native form. This research aims to characterize the antiradical property of ASX, ASX-Cu2+ and ASX-2Cu2+, ASX-Zn2+, and ASX-2Zn2+ with density functional theory (DFT) and to compare the capability to prevent conformational changes on glycated albumin through molecular dynamics simulation. DFT as implemented in Gaussian 09W, was used for all calculations. Analysis of data using GaussView 6.0. LANL2D2Z basis set and B3LYP density functional used for frequency analysis and optimization. The AutoDock Vina implemented in PyRx 0.8 is used to and receptor-ligand interactions analysis with the DS 2016 Client. YASARA for molecular dynamic simulation with 15,000 ps as running time. DFT analyzes such as energy gaps, HOMO, and LUMO patterns and electronic properties have shown that ASX-metal ions complex is better than ASX in native state as antioxidants. These results are also supported by the molecular dynamics simulation (RMSD backbone, RMSDr, RMSFr, and movie visualization), where the addition of ASX-metal ions complex on gHSA are better than ASX as a single compound in preventing gHSA from possible unfolding and maintaining protein molecule stability.


Complete mitochondrial genome of Micractinium singularis MM0003 (Chlorellaceae, Trebouxiophyceae).
The mitochondrial genome of Micractinium singularis MM0003 was completely sequenced. This mitogenome has 75,931 bp in length and consists of 62 genes including 32 protein-coding, 3 rRNA, and 27 tRNA genes. The overall GC content of the genome is 27.5%.


Intermolecular interactions between glycomodules of plant cell wall arabinogalactan-proteins and extensins.
Hydroxyproline-rich glycoproteins (HRGPs) are a unique component of plant cell walls, undergoing extensive posttranslational modification such as proline hydroxylation and hydroxyproline-O-glycosylation. Arabinogalactan proteins (AGPs) and extensins are major members of the HRGP superfamily. AGPs have repetitive AlaHyp, SerHyp, and ThrHyp peptides, the Hyp residues being glycosylated with large type II arabinogalactan polysaccharides, while extensins contain characteristic SerHyp4 and SerHyp2 motifs with arabinosylated (1-4 residues) Hyp. Although they are less than ten percent in all wall materials, AGPs and extensins play important roles in all aspects of plant growth and development. The detailed mechanisms of their functions are still under investigation. However, many of the functions may be attributed to their adhesive properties. Here, we used a forced unbinding technique to measure relative adhesive potential of the well characterized (AlaHyp)51 and (SerHyp4)18 glycomodules representing AGPs and extensins, respectively. In the presence of different wall ions such as protons, Ca2+, and boron, the glycomodules exhibited different adhesive patterns, suggesting that the wall ion-regulated intermolecular interactions/adhesions between AGPs and/or extensins may be involved in maintaining wall-plasma membrane integrity during wall loosening processes such as wall elongation or expansion. This research applies a biophysical approach to understand the biological function of plant cell wall glycoproteins.


Reconfigurable terahertz metamaterials: From fundamental principles to advanced 6G applications.
Terahertz (THz) electromagnetic spectrum ranging from 0.1THz to 10THz has become critical for sixth generation (6G) applications, such as high-speed communication, fingerprint chemical sensing, non-destructive biosensing, and bioimaging. However, the limited response of naturally existing materials THz waves has induced a gap in the electromagnetic spectrum, where a lack of THz functional devices using natural materials has occurred in this gap. Metamaterials, artificially composed structures that can engineer the electromagnetic properties to manipulate the waves, have enabled the development of many THz devices, known as "metadevices". Besides, the tunability of THz metadevices can be achieved by tunable structures using microelectromechanical system (MEMS) technologies, as well as tunable materials including phase change materials (PCMs), electro-optical materials (EOMs), and thermo-optical materials (TOMs). Leveraging various tuning mechanisms together with metamaterials, tremendous research works have demonstrated reconfigurable functional THz devices, playing an important role to fill the THz gap toward the 6G applications. This review introduces reconfigurable metadevices from fundamental principles of metamaterial resonant system to the design mechanisms of functional THz metamaterial devices and their related applications. Moreover, we provide perspectives on the future development of THz photonic devices for state-of-the-art applications.


Variation in immunophenotype of lactating mice.
Immunological factors have been shown to play a crucial role in mammary remodelling in rodent models of lactation, particularly at the stage of mammary involution. However, the relationship between immunological factors and the ability of normal mammary gland to produce milk, as well as the genetic components contributing to lactation performance remain largely unknown. In this study, we assessed the lactation and immunological phenotypes of 11 inbred mouse strains, namely 129X1/SvJ (129), A/J, AKR, C3H/HeJ (C3H), CBA/CaH (CBA), C57BL/6J (C57), DBA/1J, DBA/2J, FVB/N (FVB), QSi5 and SJL/J (SJL) to identify potential links. Leukocyte analyses showed no direct link between the fraction of splenic leukocytes and lactation performance. However, significant strain differences were discovered in the fraction of CD8+ T lymphocytes (P=0.016) and CD11b+Gr-1 mid-low monocytes (P<0.001). Cytokine profiles in plasma were examined and a subset of plasma cytokines, namely CCL2, CCL3, CCL5, CSF2, CSF3, IL10, IL15, IL1B, IL4, IL5, IL7 and TNF, were fitted to a linear regression model for prediction of lactation performance (R-sq=62%, S=0.309). Significant strain differences in the plasma cytokine levels were also discovered amongst these inbred strains. Analysis of immunological phenotypes showed strong correlations between splenic immune cell subsets and their regulating cytokine levels in plasma. The results demonstrate the extent of genetic variability in the immunological phenotypes of lactating mice, and provide a basis for understanding the role of cytokines in milk production, and identifying potential biomarkers of lactation performance.


Digital image processing of two dimensional echocardiograms: identification of the endocardium.
Digital computer image-processing techniques were applied to two dimensional echocardiograms to improve the accuracy of cardiac spatial measurements by enhancing endocardial recognition. Images were photographed from the two dimensional echocardiographic monitor and digitized using an optical densitometer. Image-processing algorithms were applied to the digitized images as follows: (1) Multiple images were averaged; (2) a gray level threshold was chosen to separate the image into tissue and cavity regions on the basis of amplitude (brightness) of the returning echoes; (3) endocardium was traced between the regions; (4) endocardial position was confirmed by matching this boundary with a contrast edge map of the original images; and (5) the endocardial boundaries were tested by comparison with simultaneous M mode echocardiograms. A linear correlation was found between M mode and computer-processed two dimensional echocardiographic measurements of ventricular septal thickness (r = 0.88); this was superior to the correlation between M mode and unprocessed two dimensional echocardiographic septal measurements (r = 0.55). The correlations between M mode and processed or unprocessed two dimensional echocardiographic measurements of left ventricular internal dimension were similar (r = 0.89 and 0.85, respectively), but the slope of the regression line for the processed data more closely approximated the line of identity (p less than 0.05). It is concluded that endocardial outlines derived with use of digital image-processing techniques lead to left ventricular measurements that correlate more closely with M mode measurements than do dimensions derived from unprocessed two dimensional echocardiography.


Estimation of concentration of radionuclides in skeletal muscle from blood, based on the data from abandoned animals in Fukushima.
The damage caused by the earthquake on 11 March, 2011 resulted in a serious nuclear accident in Japan. Due to the damage to the Fukushima Daiichi Nuclear Power Plant (FNPP), large amounts of radioactive substances were released into the environment. In particular, one of the largest safety concerns is radioactive cesium (134 Cs and 137 Cs). Due to the FNPP nuclear accident, a 20 km area was restricted from human activity, and various types of domestic animals were left in the zone. We collected the organs and tissues from sacrificed animals to obtain scientific data to evaluate the internal deposition of radioactive compounds. At first, we found there is a strong correlation between blood 137 Cs and organ 137 Cs with data from 44 cattle, indicating that skeletal muscle is the target organ of deposition of radioactive cesium. Second, we analyzed the relationship between blood 137 Cs and muscle 137 Cs within relatively lower radioactive concentration, suggesting that estimation of concentration of 137 Cs is possible from blood concentration of 137 Cs. Finally, we developed computer software to estimate the muscle 137 Cs concentration from blood samples. Our study contributes to the food safety of livestock products.


A neuroprotective effect of adenosine A1-receptor agonists on ischemia-induced decrease in 2-deoxyglucose uptake in rat hippocampal slices.
The effects of adenosine (A) receptor agonists on ischemia-induced impairment of 2-deoxyglucose (2-DG) uptake by rat hippocampal slices was evaluated. Hippocampal slices were exposed to 20-min hypoxia + hypoglycemia (ischemia) and then returned to oxygenated and glucose-containing Krebs-Ringer solution for 6 h. Ischemia reduced 2-DG uptake in the hippocampal slices. The ischemia-induced reduction in 2-DG uptake was attenuated by pretreatment with A1 receptor agonists but not with A2 receptor agonists. 8-Phenyltheophylline, an A1 receptor antagonist, exacerbated the ischemia-induced decrease. The A1 receptor agonist-induced neuroprotective effect was blocked by co-treatment with 8-phenyltheophylline. The present study suggests that the A1 receptor-mediated function has a protective role in ischemia-induced decreases in glucose metabolism in hippocampal slices.


Active school transport routines during school transitions: Socio-structural predictors of changes from childhood into early adulthood.
The purpose of this study is to investigate socio-structural predictors of active school transport (AST) change and to explore the stability and changes of transport modes during school transitions and into early adulthood in Germany. School transport mode, urbanicity level, socioeconomic status, and migration background were assessed in 624 children (8.9 ± 1.1 years, 51% female) and 444 adolescents (14.9 ± 1.7 years, 48% female) which were followed up longitudinally six years later. The results of multinomial logistic regressions and transition probability calculations indicated that residing outside of rural areas at baseline and follow-up predicts retaining or switching to AST in adolescence. Similarly, higher socioeconomic status at baseline predicted retaining or switching to AST in early adulthood. This research suggests that transition periods are crucial understanding AST behavior and may provide new opportunities for tailored AST promotion programs for different age groups.


Author Correction: Cell-type-dependent histone demethylase specificity promotes meiotic chromosome condensation in Arabidopsis.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Urinary Metals as a Marker of Exposure in Men and Women in the Welding and Electrical Trades: A Canadian Cohort Study.
Men and women working in the welding trades undergo the same apprenticeship training but it is unknown whether, once in the trade, their exposures differ. Comparison of urinary metal concentrations, having adjusted for estimated airborne exposure, may provide an answer. Men and women were recruited to a cohort study of workers in the welding and electrical trades (the Workers Health in Apprenticeship Trades-Metal working and Electrical [WHAT-ME study]). They completed a recruitment questionnaire and further questionnaires every 6 months for up to 5 years. At each follow-up, they gave details on employment and, if welding, answered trade-specific questionnaires. Urine samples were collected by mail. Welding exposure matrices were developed to estimate metal exposures from welding process, base metal, and consumables. Urinary metal concentrations, determined by ICP-MS, were compared by trade (welding or electrical). Within welding, the relation of urinary concentrations to estimated airborne exposure was examined, with adjustment for potential confounders including sex, use of respiratory protective equipment (RPE), and time spent outdoors. Natural logarithms were taken of exposure estimates and urinary concentrations, to reduce skew. All regression analyses included creatinine concentration. Urinary metal concentrations were analysed for 12 metals in 794 samples. Antimony, arsenic, lead, and mercury had a high proportion of samples with no metal detected and were not considered further. The urinary concentrations of aluminum, cadmium, chromium, cobalt, copper, manganese, nickel, and zinc were compared for welders (434 samples) and electrical workers (360). After adjustment for potential confounders, welders had higher urinary concentrations for aluminum (β = 0.13 95%CI 0.03-0.24) and chromium (β = 0.66 95%CI 0.55-0.77). Of 434 welder urines, 334 could be matched securely to detailed information about the most recent day welding. For these, an estimate of airborne exposure was made for aluminum, chromium, manganese, and nickel. Male welders were estimated to have higher airborne exposure to chromium and nickel than women welders. No difference was seen in the estimated exposures for aluminum or manganese (or total dust). Regression analyses of the relation of urinary metals to estimated exposure showed a good concordance for aluminum (β = 0.09 95%CI 0.04-0.15 (P < 0.001) and chromium (β = 0.11 95%CI 0.05-0.17 P < 0.001). The concordance for manganese and nickel was positive, but much weaker. Urinary concentrations of aluminum and nickel were somewhat lower with increasing time wearing RPE and, for chromium and nickel, with time working outdoors. Having adjusted for estimated exposure, creatinine and other confounders, male welders had lower urine concentrations of aluminum (β = -0.35 95%CI -0.51 to -0.19 P < 0.001) chromium (β = -0.38 95%CI -0.57 to -0.19 P < 0.001) and manganese (β = -0.36 95%CI -0.49 to -0.23 P < 0.001) than female welders. Welders had higher urinary concentrations of aluminum and chromium than electrical workers. Exposure estimates of aluminum and chromium for welders were a valid representation of the airborne exposures to these metals. Although male welders were estimated to have higher exposures of chrome and nickel than female welders, the higher urinary metal concentrations in women welders is of concern, particularly for women who may conceive while in the trade.


Assessing motor function in young children with transcranial magnetic stimulation.
Accurate noninvasive assessment of motor function using functional MRI (fMRI) and magnetoencephalography (MEG) is a challenge in patients who are very young or who are developmentally delayed. In such cases, passive mapping of the sensorimotor cortex is performed under sedation. We examined the feasibility of using transcranial magnetic stimulation (TMS) as a motor mapping tool in awake children younger than 3 years of age. Six children underwent motor mapping with TMS while awake as well as passive sensorimotor mapping under conscious sedation with MEG during tactile stimulation (n = 5) and fMRI during passive hand movements (n = 4). Stimulation of the motor cortex via TMS successfully elicited evoked responses in contralateral hand muscles in 5 patients. The location of primary motor cortex in the precentral gyrus identified by TMS corresponded with the postcentral location of the primary sensory cortex identified by MEG in 2 patients and to the sensorimotor cortex identified by fMRI in 3 children. In this cohort, we demonstrate that TMS can illuminate abnormalities in motor physiology including motor reorganization. We also demonstrate the feasibility of using TMS-derived contralateral silent periods to approximate the location of motor cortex in the absence of an evoked response. When compared to chronological age, performance functioning level appears to be better in predicting successful mapping outcome with TMS. Our findings indicate that awake TMS is a safe alternative to MEG and fMRI performed under sedation to localize the motor cortex and provides additional insight into the underlying pathophysiology and motor plasticity in toddlers.


Use of protease proteomics to discover granzyme B substrates.
A wide variety of proteases play important roles in immunity, including the destruction of microbes, induction of apoptosis, antigen processing, and regulation of the immune response. Characterization of these proteases requires not only an understanding of substrate specificity, but also the identification of specific protein substrates. Recent advances in proteomics technology have introduced new techniques for the study of protease function. Here, we highlight a proteomic approach used in our laboratory that employs two-dimensional gel electrophoresis coupled with mass spectrometry to identify native protease substrates. With this technique, we have successfully detected both known and novel granzyme B substrates, characterized cleavage products, and identified a granzyme B cleavage site. This approach may serve as an important discovery tool for other immunologic proteases.


[Microbial ecology of laboratory animals as a model in evaluation of the immunomodulating and antimicrobial agents].
Rats with altered microbial ecology and decreased colonization resistance due to neutropenia induced by cyclophosphamide were used as a model for estimating the effect of bacterial polysaccharides (lactulose and exopolysaccharide from Bacillus polymyxa) and fluoroquinolones (pefloxacin). Monotherapy with pefloxacin had a favourable effect both on normalization on the intestinal microflora in the rats and their hemopoiesis (decreased neutropenia). The highest correcting effect with respect to the lowered colonization resistance was observed when pefloxacin was used in combination with exopolysaccharide.


∗-fuzzy measure model for COVID-19 disease.
We introduce a mathematical model, namely, ∗-fuzzy measure model for COVID-19 disease and consider some properties of ∗-fuzzy measure such as Lebesque-Radon-Nikodym theorem.


Simultaneous determination of 12 steroids by isotope dilution liquid chromatography-photospray ionization tandem mass spectrometry.
Serum steroid assays play an important role in the clinical evaluation of a number of common endocrine disorders. Among various assays, tandem mass spectrometry (MS/MS) has being increasingly applied in clinical laboratories for its high sensitivity, specificity, and simultaneous multi-analyte quantitation capability. Our first generation isotope dilution steroid profile assay by HPLC-tandem MS/MS with a C-18 column allowed for the measurement of 9 steroids in 18 min employing a sample volume of 760 ul serum. We describe our second generation steroid profile assay which allows for the quantitation of 12 steroids simultaneously employing HPLC-MS/MS and isotope dilution tandem MS in 11 min. This method requires a sample volume of 200 microl. An API-5000 triple-quadrupole mass spectrometer (Sciex, Concord, Canada) coupled with the PhotoSpray source and Shimadzu HPLC system (Shimadzu Scientific Instruments, Columbia, MD) was used employing isotope dilution with deuterium labeled internal standard (IS) for each analyte. Two hundred microliters of serum were deproteinized by adding 300 microl of acetonitrile containing internal standards. After centrifugation, 450 microl of supernatant were diluted with 900 microl of water and 1000 microl aliquot were injected onto a C-8 column. After a 3 min wash the valve was activated to initiate the gradient elution program which eluted the steroids. Quantitation by MRM analysis was performed both in positive ion mode for 11 analytes and in negative ion mode for aldosterone. Within-day and between-day precision, reliability and accuracy of this method were assessed by correlation with other MS/MS and immunoassay methods and by recovery study. Within-day CVs were <11.5% for all analytes tested and between-day CVs ranged from 3.5% to 12.2%. The results of the comparison study yield r values ranging between 0.908 and 0.999. Recovery ranged from 90% to 110%. This method can simultaneously measure 12 steroids in serum within 11 min with minimal sample preparation. It can be routinely employed in a clinical environment and is attractive because of its simplicity in sample processing and high throughput.


Electron microscopic studies in dermatitis herpetiformis in relation to the pattern of immune deposits in the skin.
Electron microscopic studies were made in 12 cases of dermatitis herpetiformis: 6 of them with a continuous immunofluorescence line of IgA deposits at the dermo-epidermal junction, and the other 6 with granular IgA deposits in the dermal papillae. Six cases of bullous pemphigoid with a continuous immunofluorescence line of IgG deposits at the dermo-epidermal junction were examined similarly for comparison. In dermatitis herpetiformis with the continuous IgA line the ultrastructural characteristics both of dermatitis herpetiformis and bullous pemphigoid were present, even when the histological and clinical features as well as response to sulphapyridine and sulphones were typical of dermatitis herpetiformis. The ultrastructural pattern was essentially the same as in the cases with clinical and histological characteristics of the mixed dermatitis herpetiformis-bullous pemphigoid form, although in the latter there was some predominance of the characteristics of bullous pemphigoid.


Absence of horizontal transmission of herpesvirus saimiri between experimentally infected and noninfected owl monkeys.
We did not detect cell-free Herpesviurs saimiri (HVS) in the oropharyngeal secretions of owl monkeys with leukemia or lymphoma induced by this virus. These animals failed to transmit either virus or disease to their uninoculated cage-mates or room-mates. Comparison of oropharyngeal secretions of HVS from owl monkeys and squirrel monkeys may provide insight as to how human herpesviruses are maintained in the oropharynx.


Chlorophenols and other related derivatives of environmental concern: properties, distribution and microbial degradation processes.
Chlorophenols are chlorinated aromatic compound structures and are commonly found in pesticide preparations as well as industrial wastes. They are recalcitrant to biodegradation and consequently persistent in the environment. A variety of chlorophenols derivatives compounds are highly toxic, mutagenic and carcinogenic for living organisms. Biological transformation by microorganisms is one of the key remediation options that can be exploited to solve environmental pollution problems caused by these notorious compounds. The key enzymes in the microbial degradation of chlorophenols are the oxygenases and dioxygenases. These enzymes can be engineered for enhanced degradation of highly chlorinated aromatic compounds through directed evolution methods. This review underscores the mechanisms of chlorophenols biodegradation with the view to understanding how bioremediation processes can be optimized for cleaning up chloroaromatic contaminated environments.


Life-threatening muscle complications of COL4A1-related disorder.
COL4A1-related disorder is recognized as a systemic disease because the alpha 1 chain of type IV collagen, encoded by COL4A1, is essential for basement membrane stability. However, muscular manifestations related to this disorder are rarely reported. We report the case of a 2-year-old boy with porencephaly, who harbored a de novo COL4A1 mutation of c.1853G > A, p. (Gly618Glu) and exhibited recurrent rhabdomyolysis with viral or bacterial infections. Moreover, he developed obstructive hypertrophic cardiomyopathy which required surgical intervention. Skeletal muscle biopsy revealed findings compatible with fiber-type disproportion. Ultrastructural study demonstrated the similar findings previously reported in mice with Col4a1 mutation including collagen disarray and reduction of electron density in the basement membrane of capillary endothelial cells and muscle fibers. Dilated endoplasmic reticulum in the capillary endothelial cells is also noted. This report adds another disease spectrum of COL4A1 mutation which include porencephaly, hypertrophic cardiomyopathy, rhabdomyolysis and fiber-type disproportion.


The effect of arch height on kinematic coupling during walking.
The purpose of the current study was to assess kinematic coupling within the foot in individuals across a range of arch heights. Seventeen subjects participated in this study. Weight-bearing lateral radiographs were used to measure the arch height, defined as angle between the 1st metatarsal and the calcaneus. A kinematic model including the 1st metatarsal, lateral forefoot, calcaneus and tibia was used to assess foot kinematics during walking. Four coupling ratios were calculated: calcaneus frontal to forefoot transverse plane motion (Calcaneal EV/Forefoot AB), calcaneus frontal to transverse plane motion (Calcaneus EV/AB), forefoot sagittal to transverse plane motion (Forefoot DF/AB), and 1st metatarsal sagittal to transverse plane motion (1st Metatarsal DF/AB). Pearson product moment correlations were used to assess the relationship between arch height and coupling ratios. Mean (SD) radiographic arch angles of 129.8 (12.1) degrees with a range from 114 to 153 were noted, underscoring the range of arch heights in this cohort. Arch height explained approximately 3%, 38%, 12% and 1% of the variance in Calcaneal EV/Forefoot AB, Calcaneus EV/AB, Forefoot DF/AB and 1st Metatarsal DF/AB respectively. Calcaneal EV/Forefoot AB, Calcaneus EV/AB, Forefoot DF/AB and 1st Metatarsal DF/AB coupling ratios of 1.84 ± 0.80, 0.56 ± 0.35, 0.96 ± 0.27 and 0.43 ± 0.21 were noted, consistent with the twisted foot plate model, windlass mechanism and midtarsal locking mechanisms. Arch height had a small and modest relationship with kinematic coupling ratios during walking.


Temperature acclimation in the Mongolian gerbil (Meriones unguiculatus): biochemical and organ weight changes.
1. Adult Mongolian gerbils (Meriones unguiculatus) were acclimated to 5 +/- 1, 24 +/- 1 and 34 +/- 1 degrees C for 6-8 weeks. 2. Body weights of temperature acclimated gerbils did not differ significantly from controls. Organ wt/body wt ratios of liver, kidney and heart increased in cold-acclimated and decreased in heat-acclimated gerbils. Adrenal wt/body wt ratio increased in the cold and was unchanged in the heat. Relative weights of brain, spleen, lungs, brown fat and ovaries + uterus did not change with temperature acclimation. 3. Cold acclimation produced significant increases in specific and total activity of brown fat alpha GPO and liver SO and AAO and in total activity of kidney SO; a significant decrease in liver mitochondrial ADP/O ratio with succinate as substrate; and no change in brown fat SO or liver alpha KGO. 4. Heat acclimation produced significant decreases in specific and total activity of liver and kidney SO, and in total activity of brown fat SO and alpha GPO, and liver AAO and alpha KGO. 5. The combined biochemical and organ wt changes seen in temperature-acclimated gerbils suggest that this species is capable of altering its metabolic thermogenic potential in response to a wide range of ambient temperatures.


Regional and temporal profiles of c-fos and nerve growth factor mRNA expression in rat brain after lateral cortical impact injury.
Lesion-induced increases in NGF mRNA are thought to be mediated by c-fos gene expression. Conversely, NGF induction of c-fos expression has been reported following administration of exogenous NGF. However, the relationship between c-fos and NGF gene expression after traumatic injury to the intact brain is not known. Thus, we applied in situ hybridization and semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) methods to determine temporal profiles of c-fos and NGF mRNA expression in rat brains after controlled impact to the exposed cortex. Using alternate sections from the same rat brains, in situ hybridization studies showed that in neocortex, c-fos mRNA transiently increased at 30 min, 1 hr, and 3 hr after injury, while there were no increases of NGF mRNA at these postinjury time points. In the hippocampus, in situ hybridization showed that c-fos mRNA increased at 30 min, 1 hr and 3 hr postinjury, while NGF mRNA increased at 1 hr, 3 hr but not at 30 min after injury. RT-PCR studies in hippocampus confirmed that c-fos mRNA increased as early as 5 min after injury, peaked at 30 min postinjury, and remained elevated 5 hr postinjury. Levels of hippocampal NGF mRNA expression increased by 1 hr after injury and plateaued until 3 and 5 hr postinjury. These data are consistent with the possible regulatory role of endogenous c-fos on NGF expression following traumatic brain injury.


Using social network analysis to examine collaborative relationships among PhD and DNP students and faculty in a research-intensive university school of nursing.
The nursing profession has seen a dramatic rise in the number of schools offering both DNP and PhD nursing programs. Information is limited on the impact of this parallel approach in doctoral education on the quality and scope of scholarly interactions or institutional culture.The authors studied collaboration characteristics across the DNP and PhD programs of a research-intensive university school of nursing, before and after programmatic enhancements. An IRB-approved online survey was delivered to faculty and students of both programs at baseline and one year after curricular changes. Response rates were 70% and 74%, respectively. The responses were analyzed by using social network analysis and descriptive statistics to characterize the number and strength of connections between and within student groups, and between students and faculty. At baseline, the flow of communication was centralized primarily through faculty. At Time 2, density of links between students increased and network centralization decreased, suggesting more distributed communication. This nonlinear quantitative approach may be a useful addition to the evaluation strategies for doctoral education initiatives.


COVID-19: concern about interrupting social isolation of healthcare workers and professionals. What should be done with the results of the available COVID-19 diagnostic tests?
Management of SARS-CoV-2 requires safe decision-making to minimize contamination. Healthcare workers and professionals in confined areas are affected by the risk of the activity and the environment. Isolation of contaminated workers and healthcare professionals requires clinical and diagnostic criteria. On the other hand, interrupting the isolation of healthcare employees and professionals is critical because diagnostic tests do not support clinical decisions. In addition to defining the best test in view of its accuracy, it is necessary to consider aspects such as the stage of the disease or cure, the viral load and the individual's own immunity. Uncertainty about natural and herd immunity to the disease leads to the development of appropriate antivirals, diagnostic tests and vaccines.


Characterization of crtRB1- and vte4-based biofortified sweet corn inbreds for seed vigour and physico-biochemical traits.
Sweet corn possessing recessive shrunken2 (sh2) gene is popular worldwide. Traditional sweet corn is poor in vitamin A and vitamin E. Plant breeders during the selection of sweet corn genotypes mainly emphasize on plant architecture and yield. Seed germination and seedling vigour play important role for early establishment in field, thereby increasing yield and income. Here, we analysed a set of 15 sh2-based biofortified sweet corn inbreds with crtRB1 (β-carotene hydroxylase1) and vte4 (γ-tocopherol methyltransferase) genes and three traditional sh2-based sweet corn inbreds for nutritional quality, seed vigour and various physico-biochemical traits. The newly developed inbreds possessed significantly higher provitamin A (proA: 15.60 µg/g) and vitamin E [α-tocopherol (α-T): 20.42 µg/g] than the traditional sweet corn inbreds (proA: 2.51 µg/g, α-T: 11.16 µg/g). The biofortified sweet corn inbreds showed wide variation for germination (80.67-87.33%), vigour index-I (2097.17-2925.28 cm), vigour index-II (134.27-216.19 mg) and electrical conductivity (10.19-13.21 μS cm-1 g-1). Wide variation was also observed for dehydrogenase (1.29-1.59 OD g-1 ml-1), super oxide dismutase (4.01-9.82 g-1), peroxidase (11.66-16.47 μM min-1 g-1), esterase (22.98-34.76 nM min-1 g-1) and α-amylase (5.91-8.15 OD g-1 ml-1). Enrichment of proA and vitamin E in sweet corn did not affect seed vigour and physico-biochemical traits. Correlation analysis revealed that electrical conductivity and α-amylase activity was the reliable indicator for assessing seed germination and vigour. The study identified superior biofortified sweet corn genotypes that would contribute to better vigour and establishment in field. This is the first report of analysis of biofortified sweet corn genotypes for seed vigour and physico-biochemical traits.


Posterior vitreous detachment following panretinal laser photocoagulation.
A total of 30 eyes of 19 patients with type I diabetes, varying severity of retinopathy, and no posterior vitreous detachment (PVD) were studied clinically, and vitreous examination was performed by preset lens biomicroscopy. Follow-up was 4.0-7.5 years. A total of 15 eyes underwent panretinal laser photocoagulation (PRP) and 15 eyes were left untreated. The incidence of PVD was 8 of 15 353%) after PRP and 1 of 15 (7%) in untreated eyes (P less than 0.02). Minimal vitreous hemorrhage occurred in 4 of 7 treated eyes (57%) that did not develop PVD and in only 2 of 8 (25%) that did. In treated eyes with no history of vitreous hemorrhage, the incidence of PVD was 6/9 (67%); in treated eyes with minimal vitreous hemorrhage at any time, it was 2/6 (33%). In treated eyes, the presence of Diabetic Retinopathy Study (DRS) high-risk characteristics was equally frequent in eyes that developed PVD as in those that did not. These data suggest that PVD occurs following PRP, independent of the severity of diabetic retinopathy or prior vitreous hemorrhage.


Bioethanol production from agricultural residues as lignocellulosic biomass feedstock's waste valorization approach: A comprehensive review.
Bioenergy is becoming very popular, drawing attention as a renewable energy source that may assist in managing growing energy costs, besides possibly affording revenue to underprivileged farmers and rural populations worldwide. Bioethanol made from agricultural residual-biomass provides irreplaceable environmental, socioeconomic, and strategic benefits and can be considered as a safe and cleaner liquid fuel alternative to traditional fossil fuels. There is a significant advancement made at the bench scale towards fuel ethanol production from agricultural lignocellulosic materials (ALCM). These process technologies include pretreatment of ALCM biomass employment of cellulolytic enzymes for depolymerizing carbohydrate polymers into fermentable sugars to effectively achieve it by applying healthy fermentative microbes for bioethanol generation. Amongst all the available process methods, weak acid hydrolysis followed by enzymatic hydrolysis process technique. Recovering higher proficient celluloses is more attractive in terms of economic benefits and long-term environmental effects. Besides, the state of ALCM biomass based bioethanol production methods is discussed in detail, which could make it easier for the scientific and industrial communities to utilize agricultural leftovers properly.


Is decreased activity of C-II activated lipoprotein lipase in type III hyperlipoproteinemia (broad-beta-disease) a cause or an effect of increased apolipoprotein E levels?
Apolipoprotein E (ApoE; "arginine-rich" polypeptide) strongly inhibited both C-I and C-II activated lipoprotein lipases but not the protamine insensitive triglyceride lipase. Inhibition of lipoprotein lipases by ApoE in contrast to inhibition by C-III was not reversed to any significant extent by either increased concentration of activator or triglyceride in the substrate. Our previous studies have shown that in a type III hyperlipoproteinemia (broad-beta-disease) a post-heparin plasma lipoprotein lipase activated by C-II polypeptide of lipoprotein C is decreased in enzyme activity and exhibits an impaired ability to hydrolyze triglycerides in very low density lipoproteins. Type III patients are characterized by elevated concentrations of ApoE in the serum. The data presented in this report suggest that the decreased C-II activated lipoprotein lipase may be further aggravated by increased ApoE levels. Since this enzyme is involved in the catabolism and removal of lipoproteins, decreased activity of C-II activativated lipoprotein lipase may presumably be responsible for increased ApoE.


Laboratory-confirmed transmission of vaccinia virus infection through sexual contact with a military vaccinee.
A laboratory-confirmed, inadvertent transmission of vaccinia virus from an unusual source highlights the importance of epidemiologic tracing, proper biosafety practices in the clinical diagnostic laboratories, and educating clinicians and laboratorians to potential bioterrorism-initiated outbreaks as well as look-alike disease discrimination.


EASL Clinical Practice Guidelines on non-invasive tests for evaluation of liver disease severity and prognosis - 2021 update.
Non-invasive tests are increasingly being used to improve the diagnosis and prognostication of chronic liver diseases across aetiologies. Herein, we provide the latest update to the EASL Clinical Practice Guidelines on the use of non-invasive tests for the evaluation of liver disease severity and prognosis, focusing on the topics for which relevant evidence has been published in the last 5 years.


Hydrogen peroxide induces apoptosis in HeLa cells through mitochondrial pathway.
Cervical cancer is the most common cancer amongst females in India and is associated with high risk HPVs, reactive oxygen species (ROS), and excessive inflammation in most cases. ROS in turn affects the expression of pro- and anti-apoptotic proteins. The objective of the present study was to elucidate the effect of hydrogen peroxide (H(2)O(2)) on apoptotic signaling molecules in vitro. HeLa cell line expresses the Human papilloma virus - 18, E6 oncoprotein which causes the ubiquitin mediated degradation of p53 protein and is thus p53 deficient. p53 is known to act as a cellular stress sensor and triggers apoptosis. p73, a member of the p53 family also induces apoptosis in response to DNA damaging agents but unlike p53, it is infrequently mutated in human tumors. We demonstrate here, that in HeLa cells, apoptosis is triggered by H(2)O(2) via the mitochondrial pathway involving upregulation of p73, and its downstream target Bax. This was accompanied by upregulation of ERK, JNK, c-Myc, Hsp-70 and down regulation of anti-apoptotic Bcl-XL, release of cytochrome c from mitochondria and activation of caspases-9 and -3.


Proteomic analysis of protein complexes in human SH-SY5Y neuroblastoma cells by using blue-native gel electrophoresis: an increase in lamin A/C associated with heat shock protein 90 in response to 6-hydroxydopamine-induced oxidative stress.
There is accumulating evidence that oxidative stress plays an important role in aging. Our previous phosphoproteomic study of the human neuroblastoma cell line SH-SY5Y revealed changes in the phosphorylation of several proteins such as lamin A/C during 6-hydroxydopamine-induced oxidative stress. The present study employed native proteomic analysis to clarify protein-protein interaction under physiological conditions. We examined oxidative stress-related changes in SH-SY5Y cellular proteins using blue-native polyacrylamide gel electrophoresis (BN-PAGE), a powerful tool for the separation of protein complexes. BN-PAGE gel images showed successful separation of several complexes. Components of these complexes, separated by 2-D BN-PAGE in combination with SDS-PAGE, were identified by peptide mass fingerprinting employing MALDI-TOF MS and an MS/MS ion search on LC-MS/MS. TCP-1 complex, ATP synthase, and the complex of heat shock protein 90 with its client proteins such as pyruvate kinase were detected. Two dimensional BN-PAGE and Western blot analysis revealed an increase of lamin A/C associated with heat shock protein 90 in response to 6-OHDA-induced oxidative stress.


Effects of some naturally occurring prostaglandins of the D-, E-, and I-type and synthetic analogues on adenylate cyclase of human fat cell ghosts.
The effects of various prostaglandins originating from arachidonic acid (prostaglandin E2, D2, I2) as well as of methylated analogues of prostaglandin E2 (16,16-dimethyl prostaglandin E2 and 15-S-methyl prostaglandin E2) on the human fat cell adenylate cyclase were studied. In addition, the stable breakdown product of prostaglandin I2, prostaglandin 6-keto-F1-alpha, was tested for activity. Prostaglandin E2 and its methylated analogues as well as prostaglandin D2 and I2 were active stimulators of the human fat cell enzyme. The stable breakdown product of prostaglandin I2 (prostaglandin 6-keto-F1-alpha) which is biologically inactive had no stimulatory effects, suggesting that stimulation of the human fat cell function. The stimulatory action of prostaglandin D2 is consistent with the elevation of cAMP-levels induced by this compound in intact fat cells. It is concluded that the stimulatory effects of prostaglandins on the human fat cell adenylate cyclase are related to their stimulatory effects upon lipolysis.


Calretinin-like immunoreactivity in the Ruffini endings, slowly adapting mechanoreceptors, of the periodontal ligament of the rat incisor.
The distribution and ultrastructural localization of calretinin (CR)-like immunoreactivity (-LI) were investigated in the lingual periodontal ligament of rat incisors. Some thick nerve fibers within the nerve bundle displayed CR-LI; these CR-like immunoreactive (-IR) nerve fibers entered the alveolar half of the lingual periodontal ligament of the incisor where dendritic terminal arborization was exhibited. Thin and beaded CR-IR nerve fibers were rarely observed in the periodontal ligament. Observations of adjacent sections immunostained with protein gene-product 9.5 (PGP 9.5) revealed that most, if not all, PGP 9.5-IR nerve terminals showing a dendritic arborization expressed CR-LI. Immunoelectron microscopic observations showed that electron-opaque immunoreaction products were localized in the axoplasm of the axon terminals, except for the mitochondria, which were surrounded by Schwann sheaths and multiple-layered basal lamina. Neither cell bodies, the cytoplasmic extension of terminal Schwann cells, nor other cellular elements such as periodontal fibroblasts exhibited CR-LI. The present findings suggest that Ruffini endings, an essential mechanoreceptor in the periodontal ligament and categorized as a slowly adapting mechanoreceptor, express CR-LI, and that CR may participate in the Ca2+ homeostasis against external stimuli in the periodontal Ruffini endings.


Functional Assessment of Coronary Artery Disease by Myocardial Flow Reserve Versus Pressure-wire Based Assessment: A Systematic Review.
Positron emission tomography (PET) permits the noninvasive quantification of myocardial blood flow (MBF). Myocardial flow reserve (MFR), calculated by dividing stress MBF by rest MBF is a reliable index for the functional information of coronary artery disease. A pressure-derived physiological index, such as fractional flow reserve (FFR) is also an important measurement. Both MFR and FFR values are used to evaluate coronary physiology; however, but they are not interchangeable because each test has certain discrepancies. In this systematic review, we provide an overview of coronary physiology with PET compared to pressure-derived physiological indices.


Dynamics of large-scale cortical interactions at high gamma frequencies during word production: event related causality (ERC) analysis of human electrocorticography (ECoG).
Intracranial EEG studies in humans have shown that functional brain activation in a variety of functional-anatomic domains of human cortex is associated with an increase in power at a broad range of high gamma (>60Hz) frequencies. Although these electrophysiological responses are highly specific for the location and timing of cortical processing and in animal recordings are highly correlated with increased population firing rates, there has been little direct empirical evidence for causal interactions between different recording sites at high gamma frequencies. Such causal interactions are hypothesized to occur during cognitive tasks that activate multiple brain regions. To determine whether such causal interactions occur at high gamma frequencies and to investigate their functional significance, we used event-related causality (ERC) analysis to estimate the dynamics, directionality, and magnitude of event-related causal interactions using subdural electrocorticography (ECoG) recorded during two word production tasks: picture naming and auditory word repetition. A clinical subject who had normal hearing but was skilled in American Signed Language (ASL) provided a unique opportunity to test our hypothesis with reference to a predictable pattern of causal interactions, i.e. that language cortex interacts with different areas of sensorimotor cortex during spoken vs. signed responses. Our ERC analyses confirmed this prediction. During word production with spoken responses, perisylvian language sites had prominent causal interactions with mouth/tongue areas of motor cortex, and when responses were gestured in sign language, the most prominent interactions involved hand and arm areas of motor cortex. Furthermore, we found that the sites from which the most numerous and prominent causal interactions originated, i.e. sites with a pattern of ERC "divergence", were also sites where high gamma power increases were most prominent and where electrocortical stimulation mapping interfered with word production. These findings suggest that the number, strength and directionality of event-related causal interactions may help identify network nodes that are not only activated by a task but are critical to its performance.


Interferon gamma and tumour necrosis factor alpha in relation to anaemia and prognosis in childhood cancer.
This study examined whether the initial plasma levels of tumour necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma) in 131 children with newly diagnosed cancer were associated with haematopoietic suppression, and whether plasma levels of TNFalpha or haemoglobin at diagnosis affects long-term prognosis in childhood acute lymphoblastic leukaemia (ALL). IFNgamma, and possibly also TNFalpha, were related to anaemia in children with solid tumours. Neither TNFalpha levels nor Hb levels were associated with increased risk of ALL relapse.


[Lipoprotein (a) in children with end stage renal failure on maintenance hemodialysis and continuous ambulatory peritoneal dialysis].
The aim of this study was to evaluate serum lipid abnormalities, particularly lipoprotein (a) [Lp(a)] in children with end-stage renal failure undergoing chronic dialysis and to estimate the influence of treatment method on these disturbances. Studies were performed on 21 children aged +/- 14.8 years (10 girls, 11 boys) on maintenance hemodialysis and 10 children, aged 13.2 years (8 girls, 2 boys) on CAPD. Control group consisted of 27 healthy age-matched subjects. All children were tested for concentration of serum Lp(a), total cholesterol (TC), triglycerides (TG), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C). It was found a significantly increase in Lp(a), TG, TC, LDL-C and significantly decrease in HDL-C in all dialysed children compared to controls. CAPD patients had markedly elevated serum Lp(a) and TG compared to hemodialysed children. These results suggest that CAPD treatment may contribute to the pathogenesis of lipid abnormalities and increased risk of developing coronary heart disease.


Cyberchondria: a Growing Concern During the COVID-19 Pandemic and a Possible Addictive Disorder?
The main purpose of this narrative review is to provide a brief overview of the current empirical evidence regarding the conceptualization, assessment, and treatment of cyberchondria, with a focus on the potential classification of cyberchondria as a behavioral addiction. Although cyberchondria has been widely associated with anxiety, it has also been suggested that it may be linked to obsessive-compulsive features. A less explored proposal is the categorization of cyberchondria as a behavioral addiction. The present review explores the existing literature with respect to the possible classification of cyberchondria as a behavioral addiction by considering cyberchondria with respect to components of the interaction of person, affect, cognition and execution model. There is a lack of consensus regarding the definition and conceptualization of cyberchondria. The empirical evidence available to date suggests that cyberchondria is a multifactorial construct that operates transdiagnostically, particularly with respect to obsessive-compulsive-related disorders and health-related anxiety. The extent to which the condition may reflect a behavioral addiction as a form of problematic use of the internet also warrants consideration. Cyberchondria may have become more prevalent during the COVID-19 pandemic, with particular populations prone to health-related anxiety likely having greater vulnerability. Existing data in part support the potential classification of cyberchondria as a behavioral addiction, although many gaps in understanding currently exist. Cyberchondria appears to be a growing concern. However, there is not yet enough empirical evidence to determine whether this clinical condition has enough similarities with behavioral addictions to be considered as one. Likewise, psychometric instruments that exist to date have not been designed from the theoretical framework of behavioral addictions, so most of the factors that they evaluate may be preferentially related to anxiety. Finally, there is still no consensus on whether cyberchondria should be addressed in the context of health anxiety interventions, OCRD, or behavioral addictions; thus, more empirical evidence is needed.


Failure to block lymphocyte Fc receptor with anti-B lymphocyte sera (anti-DRW) in man.
Sera harvested from multiparous women or from allograft recipients who had rejected their kidneys and containing various anti-DRW specificities, were studied on peripheral blood or lymph-node lymphocytes bearing or lacking the relevant B-cell alloantigen, for their EA or EAC-rosette-inhibition activity. Inhibition of C3 or Fc-receptor occurred independently of their anti-B lymphocyte cytotoxicity pattern. The same conclusion was reached when lymphocytes were either macrophage depleted or B-lymphocyte enriched. These results do not suggest a relationship in man between B-lymphocyte (DRW) alloantigen and Fc or C3 receptor structure.


Designing dual inhibitors of Mdm2/MdmX: Unexpected coupling of water with gatekeeper Y100/99.
Mdm2 and MdmX share high structural similarity in their N-terminal domains, yet dual inhibitors are challenging to design due to differences in the conformations of the binding pockets, and notably of the proposed gatekeeper residue, Y100/99. Analysis of crystal structures and molecular dynamics (MD) simulations of complexes of Mdm2 and MdmX resulted in the identification of a water molecule with a long residence time that appears to be modulated by the conformation of Y100/99. These observations lead us to speculate that dual inhibitors either (i) stabilize both Mdm2 and MdmX with Y100/99 in the open conformation typically seen in complexes of Mdm2 with p53, or (ii) the dual inhibitors are agnostic to the conformation of Y100/99. The recently developed potent dual inhibitory stapled peptide Atsp7041 appears to be agnostic to the conformation of the gatekeeper residue. Proteins 2017; 85:1493-1506. © 2017 Wiley Periodicals, Inc.


Olaparib dose re-escalation in ovarian cancer patients who experienced severe and/or uncommon adverse events: A case series.
Few real-world studies have reported detailed management and dose adjustment strategies of adverse events (AEs) of ovarian cancer (OC) patients treated with the poly(adenosine diphosphate-ribose) polymerase inhibitor olaparib. This case series aimed to describe olaparib AEs in Chinese OC patients in real-life settings and to explore dose modification strategies. We conducted a detailed examination of the clinical records of OC patients who were treated with olaparib at the Gynecologic Oncology Unit in Hong Kong from September 2015 to December 2019, including baseline characteristics, treatment outcomes, AEs, and management strategies, particularly dose modifications. Nineteen patients were included, with a median olaparib treatment duration of 12 (range: 3-30) months. For recurrent platinum-sensitive cases (n = 16), the median progression-free survival was 16.0 months (95% confidence interval: 9.5-22.5). Eighteen (95%) patients experienced AE(s) of any grade, including four (21%) who experienced grade ≥3 AE(s). The most common AEs were as follows: nonhematologic fatigue (68%), nausea (42%), vomiting (26%), decreased appetite (26%), dyspepsia (21%), dizziness (21%), anemia (37%), neutropenia (26%), and thrombocytopenia (21%). Four specific cases involving anemia, lower limb lymphedema, myeloid neoplasm, and erythema nodosum are discussed separately. Eight patients required dose interruption or reduction due to AEs, of which five patients attempted and tolerated dose re-escalation. In this study, most AEs were mild, but rare AEs were observed. In OC patients, olaparib AE management with dose reductions followed by re-escalations was feasible, including for anemia.


Exploring the Pb1- x Srx HfO3 System and Potential for High Capacitive Energy Storage Density and Efficiency.
The hafnate perovskites PbHfO3 (antiferroelectric) and SrHfO3 ("potential" ferroelectric) are studied as epitaxial thin films on SrTiO3 (001) substrates with the added opportunity of observing a morphotropic phase boundary (MPB) in the Pb1- x Srx HfO3 system. The resulting (240)-oriented PbHfO3 (Pba2) films exhibited antiferroelectric switching with a saturation polarization ≈53 µC cm-2 at 1.6 MV cm-1 , weak-field dielectric constant ≈186 at 298 K, and an antiferroelectric-to-paraelectric phase transition at ≈518 K. (002)-oriented SrHfO3 films exhibited neither ferroelectric behavior nor evidence of a polar P4mm phase . Instead, the SrHfO3 films exhibited a weak-field dielectric constant ≈25 at 298 K and no signs of a structural transition to a polar phase as a function of temperature (77-623 K) and electric field (-3 to 3 MV cm-1 ). While the lack of ferroelectric order in SrHfO3 removes the potential for MPB, structural and property evolution of the Pb1- x Srx HfO3 (0 ≤ x < 1) system is explored. Strontium alloying increased the electric-breakdown strength (EB ) and decreased hysteresis loss, thus enhancing the capacitive energy storage density (Ur ) and efficiency (η). The composition, Pb0.5 Sr0.5 HfO3 produced the best combination of EB = 5.12 ± 0.5 MV cm-1 , Ur = 77 ± 5 J cm-3 , and η = 97 ± 2%, well out-performing PbHfO3 and other antiferroelectric oxides.


Implementation fidelity of a multifactorial in-hospital fall prevention program and its association with unit systems factors: a single center, cross-sectional study.
Falls are a common, costly global public health burden. In hospitals, multifactorial fall prevention programs have proved effective in reducing falls' incidence; however, translating those programs accurately into daily clinical practice remains challenging. This study's aim was to identify ward-level system factors associated with implementation fidelity to a multifactorial fall prevention program (StuPA) targeting hospitalized adult patients in an acute care setting. This retrospective cross-sectional study used administrative data on 11,827 patients admitted between July and December 2019 to 19 acute care wards at the University Hospital Basel, Switzerland, as well as data on the StuPA implementation evaluation survey conducted in April 2019. Data were analysed using descriptive statistics, Pearson's coefficients and linear regression modelling for variables of interest. The patient sample had an average age of 68 years and a median length of stay of 8.4 (IQR: 2.1) days. The mean care dependency score was 35.4 points (ePA-AC scale: from 10 points (totally dependent) to 40 points (totally independent)); the mean number of transfers per patient -(e.g., change of room, admission, discharge) was 2.6 (range: 2.4- 2.8). Overall, 336 patients (2.8%) experienced at least one fall, resulting in a rate of 5.1 falls per 1'000 patient days. The median inter-ward StuPA implementation fidelity was 80.6% (range: 63.9-91.7%). We found the mean number of inpatient transfers during hospitalisation and the mean ward-level patient care dependency to be statistically significant predictors of StuPA implementation fidelity. Wards with higher care dependency and patient transfer levels showed higher implementation fidelity to the fall prevention program. Therefore, we assume that patients with the highest fall prevention needs received greater exposure to the program. For the StuPA fall prevention program, our results suggest a need for implementation strategies contextually adapted to the specific characteristics of the target wards and patients.


Hydrotrifluoromethylthiolation of Unactivated Alkenes and Alkynes with Trifluoromethanesulfonic Anhydride through Deoxygenative Reduction and Photoredox Radical Processes.
An ongoing challenge in trifluoromethylthiolation reactions is the use of less expensive and easily available trifluoromethylthio sources. Herein, we disclose an unprecedented usage of trifluoromethanesulfonic anhydride (Tf2 O) as a radical trifluoromethylthiolating reagent. Hydrotrifluoromethylthiolation of unactivated alkenes and alkynes with Tf2 O in the presence of PMePh2 and H2 O under visible-light photoredox catalysis gave the addition products. The trifluoromethylthio radical (. SCF3 ) was first formed from Tf2 O through a photoredox radical processes and deoxygenative reduction of PMePh2 , and H2 O serves as the H-atom donor for the hydrotrifluoromethylthiolation reaction. This reaction provides a new strategy for radical trifluoromethylthiolation.


A qualitative study of substance use and sexual behavior among 18- to 29-year-old men while incarcerated in the United States.
The article describes men's perceptions of and experience with substance use and sexual behavior during incarceration. Grounded theory content analyses were performed on qualitative interviews conducted with 80 men, aged 18 to 29, in four U.S. states. Participants believed that drugs were easily available in prison. Half reported using substances, primarily marijuana or alcohol, while incarcerated. Key themes included the role of correctional personnel in the flow of substances in prison and the economic significance of substance trafficking. With regard to sexual behavior, most men acknowledged that it occurred but were hesitant to talk in-depth about it. There was a strong belief in "don't look, don't tell," and sex in prison was often associated with homosexual behavior or identity. Sex during incarceration was reported by 12 men, mostly with female partners. Participants were pessimistic about HIV/STD/hepatitis prevention efforts inside correctional facilities. These findings highlight the need for risk reduction programs for incarcerated men.


Cost-effectiveness of sacral neuromodulation compared to botulinum neurotoxin a or continued medical management in refractory overactive bladder.
This study assessed the cost-effectiveness and health-care budget impact of sacral neuromodulation (SNM) in refractory idiopathic OAB-wet patients in Spain. A 10-year Markov analytic model was developed to estimate quality-adjusted life-years (QALYs) gained and incontinence episode avoided associated with SNM therapy compared with botulinum neurotoxin A (BoNT-A) or continued optimized medical treatment (OMT). At 10 years, the cumulative costs of SNM, BoNT-A, and OMT were €29,166, €29,458, and €29,370, respectively, whereas the QALYs for SNM, BoNT-A, and OMT are 6.89, 6.38, and 5.12, respectively. Consequently, incremental cost-effectiveness ratios (ICERs) for SNM demonstrate that although the initial costs for SNM are higher than those for the other treatments, decreasing follow-up costs coupled with consistently greater effectiveness in the long term make SNM the economically dominant option at 10 years. Sensitivity analyses suggest that 99.7% and 99.9% (for SNM vs. BoNT-A and OMT, respectively) of the 1000 Monte Carlo iterations fall within the €30,000 cost-effectiveness threshold, considered to be acceptable in Spain. The 10-year incremental cost per incontinence episode avoided for SNM also makes this therapy the dominant option compared to BoNT-A or OMT. Additionally, the estimated budget impact of the gradually increased referral for SNM for the management of OAB patients in Spain is small. As a treatment option for refractory idiopathic OAB, at 10 years, SNM provides a considerable possibility of symptom and quality-of-life improvement and is cost-effective compared to BoNT-A or continued OMT.


Cell-based and biochemical screening approaches for the discovery of novel HIV-1 inhibitors.
The identification of novel HIV-1 inhibitors is facilitated by screening campaigns that combine the right screening strategy with a large diverse collection of drug-like compounds. Cell-based screening approaches offer some advantages in the quest for novel inhibitors because they can include multiple targets in a single screen and in some cases reveal targets and/or structures not captured in biochemical assays. However, follow-up activities for cell-based screens are often more complicated and resource intensive when compared to biochemical screens. Alternatively, biochemical screens usually offer the advantage of focusing on a single target with a well-defined set of follow-up assays. In this review we cover multiple cell-based and biochemical assay formats, many of which were designed to identify inhibitors that act through new mechanisms. Some of the assays discussed have been utilized in antiviral screens while others might be formatted for HTS or utilized as secondary assays in a screening campaign. As drug discovery efforts in the pharmaceutical industry shift away from traditional strategies, new approaches such as those presented here are likely to play a significant role in the identification of next generation HIV-1 inhibitors.


Optic atrophy 3 as a protein of the mitochondrial outer membrane induces mitochondrial fragmentation.
The optic atrophy 3 (OPA3) gene, which has no known homolog or biological function, is mutated in patients with hereditary optic neuropathies. Here, we identified OPA3 as an integral protein of the mitochondrial outer membrane (MOM), with a C-terminus exposed to the cytosol and an N-terminal mitochondrial targeting domain. By quantitative analysis, we demonstrated that overexpression of OPA3 significantly induced mitochondrial fragmentation, whereas OPA3 knockdown resulted in highly elongated mitochondria. Cells with mitochondria fragmented by OPA3 did not undergo spontaneous apoptotic cell death, but were significantly sensitized to staurosporine- and TRAIL-induced apoptosis. In contrast, overexpression of a familial OPA3 mutant (G93S) induced mitochondrial fragmentation and spontaneous apoptosis, suggesting that OPA3 mutations may cause optic atrophy via a gain-of-function mechanism. Together, these results indicate that OPA3, as an integral MOM protein, has a crucial role in mitochondrial fission, and provides a direct link between mitochondrial morphology and optic atrophy.


Mitochondrial enzymes responsible for oxidizing medium-chain fatty acids in developing rat skeletal muscle, heart, and liver.
Prior to weaning, medium-chain fatty acids constitute an important energy source in the developing rat. Fatty acid oxidation rates increase with age in most developing tissues, but the pattern of this increase may vary according to the role of the particular organ. In skeletal muscle, heart, and liver of developing rats, we measured mitochondrial activities of long- and short-chain enoyl-CoA hydratase, 3-hydroxyacyl-CoA dehydrogenase, and long- and short-chain acyl-CoA thiolase. In skeletal muscle, the pattern of development in fatty acid oxidation enzymes favored utilization of long-chain rather than medium-chain fatty acids. In liver, enzyme activities for medium-chain fatty acids were highest prior to weaning. Heart occupied a position intermediate between skeletal muscle and liver.


Transcatheter aortic valve replacement using the SAPIEN 3 valve versus surgical aortic valve replacement using the rapid deployment INTUITY valve: Midterm outcomes.
Little data have been published on the midterm effect of transapical/transfemoral-transcatheter aortic valve replacement (TA-/TF-TAVR) using the Edwards SAPIEN 3 valve (S3). We aimed to compare the outcomes after TA-/TF-TAVR utilizing the S3 (TA-/TF-S3) valve with those after surgical aortic valve replacement utilizing the rapid deployment Edwards INTUITY valve (RD-SAVR). Between March 2012 and April 2018, 122 patients with aortic stenosis underwent TA-S3, 77 patients underwent TF-S3 and 182 patients underwent RD-SAVR through partial sternotomy at our institution. We conducted clinical and echocardiographic midterm follow-ups. The primary outcomes of the study were the incidence of new pacemakers permanent pacemaker implantation (PPI), the occurrence of paravalvular leakage (PVL) and the hemodynamic performance of the valves. All study groups were at intermediate surgical risk. The 30-day all-cause mortality and stroke rates in the TA-S3, TF-S3, and RD-SAVR groups were 4.1% and 1.6%, 3.9% and 2.6%, and 3.8% and 2.2%, respectively. The RD-SAVR group had significantly smaller PVL and PPI rates than did the TA-/TF-S3 group (p < .0001). At the discharge, the one-year postprocedure mean gradients were 9 ± 5.1/10 ± 4.5 mmHg, 11 ± 4.1/12 ± 3.8 mmHg, and 10.1 ± 4.3/10.4 ± 2.6 mmHg in the TA-S3, TF-S3, and RD-SAVR groups, respectively. Midterm valve thrombosis, Re-TAVR/SVAR were low and similar among the study groups, whereas endocarditis was higher in the TAVR group. RD-SAVR was superior to TA-/TF-S3 in the PVL and PPI rates. We observed similar early outcomes and valve hemodynamics. The endocarditis was higher in the TAVR group.


Free radical generation during chemical depolymerization of heparin.
Low-molecular weight heparins (LMWHs), as compared with unfractionated heparin (UFH), present superior bioavailability, much longer plasma half-life, and lower incidence of side effects. For these reasons, over the past two decades LMWHs have become the drugs of choice for the treatment of deep venous thrombosis, pulmonary embolism, arterial thrombosis, and unstable angina. Furthermore, their use in acute ischemic stroke is currently under study. LMWHs are obtained by UFH depolymerization, which can be performed using various methods, including nitrous acid depolymerization, cleavage by beta-elimination of benzyl ester, enzymatic depolymerization, and peroxyl radical-dependent depolymerization. This article addresses the chemical depolymerization, obtained by free radical attack (mainly hydroxyl radical), of heparin. The electron spin resonance (ESR) spectroscopy, coupled to the spin trapping technique, was employed to study this reaction. Free radical-mediated heparin depolymerization was performed under different chemical conditions. The final products of the reactions were purified and classified on the basis of their molecular weight and other characteristics. The level of heparin fragmentation was different depending on the type of depolymerization reaction used. Moreover, the level of reproducibility and the resulting radical species were different for every type of reaction performed.


Crystallisation and preliminary structure determination of a NADH: quinone oxidoreductase from the extremophile Acidianus ambivalens.
NADH:quinone oxidoreductases (NDHs), constitute one of the electron entry points into membrane-bound respiratory chains, oxidising NADH and reducing quinones. Type-II NDHs (NDH-2) are functionally unable to translocate protons and are typically constituted by a single approximately 50 kDa subunit lacking iron-sulfur clusters and containing one flavin as the sole redox centre. No three dimensional crystal structure is yet available for NDHs. We describe the crystallisation and preliminary structure determination of a NDH-2 that contains a covalently bound FAD, isolated from the membrane fraction of Acidianus ambivalens, a hyperthermoacidophilic archaeon capable of growing at 80 degrees C and pH 2.0. NDH-2 was solubilised with the detergent n-dodecyl-beta-d-maltoside and crystallised using ammonium phosphate as precipitant. The structure was solved by MIRAS using Pt and I derivatives.


Oxytocin receptor variant rs53576 genotype is associated with dysphoric arousal symptoms of DSM-5 posttraumatic stress disorder in Chinese earthquake survivors.
Evidence suggests that the oxytocin receptor (OXTR) gene may be involved in the psychopathology of posttraumatic stress disorder (PTSD). This study aimed to investigate the effects of OXTR rs53576 genotype on PTSD symptoms introduced in the Diagnostic and Statistical Manual, Fifth Edition (DSM-5). This study was a cross-sectional study conducted among 1140 adults who had personally experienced the Wenchuan earthquake. PTSD symptoms were measured with the PTSD checklist for DSM-5. A custom-by-design 2 × 48-Plex SNPscanTM Kit were used to determine the OXTR rs53576. Multiple regression models were used to analyze the independent and interactive effects of OXTR rs53576 genotype and earthquake exposure on the severity of total PTSD symptoms and different dimensions of PTSD symptoms. The results revealed that the rs53576 genotype could significantly predict PTSD symptoms (β = 0.055, p = 0.045). Further analysis showed that the rs53576 genotype was only significantly associated with dysphoric arousal symptoms of PTSD (β = 0.080, p = 0.005). The rs53576 genotype × earthquake exposure interaction had no significant effect on different symptom clusters (p > 0.05). This study showed that the rs53576 genotype was only associated with the dysphoric arousal symptoms but not with other symptom clusters of PTSD. These findings support the role of the OXTR on the psychopathology of PTSD and help us to understand the genetic basis of PTSD.


The influence of multiple scorers on cytogenetics study results.
Cytogenetics data resulting from one laboratory in a multiple-laboratory study were analyzed to determine if 5 well-trained scorers produced significantly different results using metaphase scoring procedures. Although the scorers reached the same general conclusion, results show that scorer differences exists (p less than 0.01). Consequently, all participating scorers in a laboratory should be used equally in all treatment groups and the results should be analyzed accordingly to account for scorer variations. This is easily accomplished in controlled prospective experiments; however, it is often difficult in retrospective studies using data which exists. In such studies, every effort should be made to analyze and interpret the data so that scorer differences are taken into account. For severely damaged cells not only were there scorer differences but the difference were greater at higher doses. This phenomenon may be related to the operational definition of a severely damaged cell, since scorers who identify more damage than other scorers would logically tend to classify more cells as severely damaged both overall and at lower doses.


Forensic child sexual abuse evaluations: assessing subjectivity and bias in professional judgements.
Evaluators examining the same evidence often arrive at substantially different conclusions in forensic assessments of child sexual abuse (CSA). This study attempts to identify and quantify subjective factors that contribute to such disagreements so that interventions can be devised to improve the reliability of case decisions. Participants included 1106 professionals in the field of child maltreatment representing a range of professional positions or job titles and years of experience. Each completed the Child Forensic Attitude Scale (CFAS), a 28-item survey assessing 3 forensic attitudes believed to influence professional judgments about CSA allegations: emphasis-on-sensitivity (i.e., a focus on minimizing false negatives or errors of undercalling abuse); emphasis-on-specificity (i.e., a focus on minimizing false positives or errors of overcalling abuse); and skepticism toward child and adolescent reports of CSA. A subset of 605 professionals also participated in 1 of 3 diverse decision exercises to assess the influence of the 3 forensic attitudes on ratings of case credibility. Exploratory factor analysis identified 4 factors or attitude subscales that corresponded closely with the original CFAS scales: 2 subscales for emphasis-on-sensitivity and 1 each for emphasis-on-specificity and skepticism. Attitude subscale scores differed significantly by sample source (in-state trainings vs. national conferences), gender, years of experience, and professional position, with Child Protective Service workers unexpectedly more concerned about overcalling abuse and more skeptical of child disclosures than other professionals-a pattern of scores associated with an increased probability of disbelieving CSA allegations. The 3 decision exercises offered validation of the attitude subscales as predictors of professional ratings of case credibility, with adjusted R(2)s for the three exercises ranging from .06 to .24, suggesting highly variable effect sizes. Evaluator disagreements about CSA allegations can be explained, in part, by individual differences in 3 attitudes related to forensic decision-making: emphasis-on-sensitivity, emphasis-on-specificity, and skepticism toward child reports of abuse. These attitudes operate as predispositions or biases toward viewing CSA allegations as likely true or likely false. Several strategies for curbing the influence of subjective factors are highlighted including self-awareness of personal biases and team approaches to assessment.


Measurement of Scaphoid Bone Microarchitecture: A Computed Tomography Imaging Study and Implications for Screw Placement.
High bone density and quality is associated with improved screw fixation in fracture fixation. The objective of this study was to assess bone density and quality in the proximal and distal scaphoid to determine optimum sites for placement of 2 screws in scaphoid fracture fixation. Twenty-nine cadaveric human scaphoid specimens were harvested and scanned using micro-computed tomography. Bone density (bone volume fraction) and bone quality (relative bone surface area, trabecular number, and trabecular thickness) were evaluated in 4 quadrants within each of the proximal and distal scaphoid. The proximal radial quadrant of the scaphoid had significantly greater bone volume than the distal ulnar (mean difference, 33.2%) and distal volar quadrants (mean difference, 32.3%). There was a significantly greater trabecular number in the proximal radial quadrant than in the distal ulnar (mean difference, 16.7%) and in the distal volar quadrants (mean difference, 15.9%) and between the proximal ulnar and the distal ulnar quadrants (mean difference, 12%). There was a significantly greater bone surface area in the proximal radial and distal radial quadrants than in the distal ulnar and distal volar quadrants. There were no significant differences in trabecular thickness between the 8 analyzed quadrants CONCLUSIONS: Although there are differences in bone volume, trabecular number, and bone surface area between the proximal pole of the scaphoid and that of the distal pole, there were no significant differences in the bone quality (trabecular thickness, trabecular number, and relative bone surface area) and density (bone volume fraction) between the 4 quadrants of the proximal or distal pole of the cadaveric scaphoids studied. Insertion of 2 headless compression screws can be determined by ease of surgical access and ease of screw positioning and not by differences in bone quality or density of the proximal or distal scaphoid.


Liver transplantation versus liver resection for hepatocellular carcinoma in intention to treat: An attempt to perform an ideal meta-analysis.
This meta-analysis compared the effects of liver transplantation (LT) and liver resection (LR) on overall survival (OS) and disease-free survival (DFS) in patients with hepatocellular carcinoma (HCC) small transplantable HCC or within Milan criteria. Articles comparing LR with LT for HCC, based on Milan criteria or small size, published up to June 2015 were selected, and a meta-analysis was performed. No randomized controlled trial has been published to date comparing survival outcomes in patients with HCC who underwent LR and LT. Nine studies were identified, including 570 patients who underwent LR and 861 who underwent LT. For HCC within the Milan criteria, the 1-year OS rates following LR and LT were 84.5% (473/560) and 84.4% (710/841), respectively (odds ratio [OR], 0.98; 95% confidence interval [CI], 0.71-1.33; P = 0.8), and the 5-year OS rates were 47.9% (273/570) and 59.3% (509/858), respectively (OR, 0.60; 95% CI, 0.35-1.02; P = 0.06). One-year DFS rates were similar (OR, 1.00; 95% CI, 0.39-2.61; P = 1.00), whereas the 3-year DFS rate was significantly lower in the LR group (54.4%, 210/386) than in the LT group (74.2%, 317/427; OR, 0.24; 95% CI, 0.07-0.80; P = 0.02), and the 5-year DFS rate was significantly lower for LR than LT (OR, 0.18; 95% CI, 0.06-0.53; P < 0.01). For small HCCs, the 5-year OS rate was significantly lower for patients who underwent LR than LT (OR, 0.30; 95% CI, 0.19-0.48; P < 0.001). In conclusion, relative to LR, LT in patients with HCC meeting the Milan criteria had no benefits before 10 years for OS. For DFS, the benefit is obtained after 3 years. Liver Transplantation 23 836-844 2017 AASLD.


Evolving multidisciplinary treatment of squamous cell carcinoma of the head and neck in India✰.
In this article, we highlight the evolution of a multimodal approach in the overall management of squamous cell carcinoma of the head and neck (SCCHN) in India; present advances in technology (newer surgical techniques), novel medical and radiotherapy (RT) approaches; review their roles for an integrated approach for treating SCCHN and discuss the current role of immunotherapy in SCCHN. For locally advanced (LA) SCCHN, the multidisciplinary approach includes surgery followed by RT, with or without chemotherapy (CT) or concurrent chemoradiotherapy. Improved surgical techniques of reconstruction and voice-preservation are being implemented. Advanced forms of high-precision conformal techniques like intensity-modulated radiotherapy are used to deliver highly conformal doses to tumors, sparing the surrounding normal tissue. Compared with RT alone, novel CT regimens and targeted therapeutic agents have the potential to improve locoregional control and survival and reduce treatment-induced toxicities. Several clinical trials have demonstrated efficacy, safety, and quality of life benefits of adding cetuximab to RT regimens in LASCCHN. Studies have also suggested a cetuximab-related laryngeal preservation benefit. At progression, platinum-based CT combined with cetuximab (a monoclonal anti-epidermal growth factor receptor antibody) is the only validated option available as the first-line therapy. Thus, an integrated multidisciplinary approach plays a key role in maximizing patient outcomes, reduction in treatment related morbidities that consequently impact quality of life of survivors.


Environmental effects on luminescence of meso-tetra-2-chlorophenylporphyrin.
Effects of solvent polarity on the photophysical behaviour of meso-tetra-2-chlorophenylporphyrin have been studied by means of steady-state absorption and fluorescence, as well as time-resolved fluorescence techniques. A non-mirror symmetric absorption and emission spectra due to vibronic borrowing were obtained. Time-resolved fluorescence study indicated the bi-exponential decay kinetics for both the emission bands, observed in steady-state emission spectra. Such findings implied that there exists two emitting species on the photoinduced conformational excursions of the excited-state equilibrium and also that their relative contributions to emission change with solvent polarity. Monte Carlo conformational search based on force-field molecular mechanics was performed to locate equilibrium conformers in the ground state which enable evaluation of the ground-state barrier energies. This was followed by CIS and ZINDO calculations to explore the excited-state barriers.


Neurology in the People's Republic of China--an update.
The present note provides an overview of the historical development of neurology and its current status in the People's Republic of China, against the backdrop of the current massive transformation of Chinese society. We trace the origins of neurology in China to missionary medicine during the Republican period (1911-1949), and describe how the discipline grows with difficulty throughout the subsequent decades (1950-1976). We then introduce an influential legacy of the post-revolutionary period, the ideal of integrating traditional Chinese medicine (TCM) and Western medicine, and briefly describe recent efforts to modernize medical education and training. Finally, we provide a brief overview of topics in neurology and neuropsychiatry that have a 'Chinese face', last but not least the successful integration of TCM and Western medicine in the treatment of hepatolenticular degeneration/Wilson's disease.


Group A Streptococcus, Acute Rheumatic Fever and Rheumatic Heart Disease: Epidemiology and Clinical Considerations.
Early recognition of group A streptococcal pharyngitis and appropriate management with benzathine penicillin using local clinical prediction rules together with validated rapi-strep testing when available should be incorporated in primary health care. A directed approach to the differential diagnosis of acute rheumatic fever now includes the concept of low-risk versus medium-to-high risk populations. Initiation of secondary prophylaxis and the establishment of early medium to long-term care plans is a key aspect of the management of ARF. It is a requirement to identify high-risk individuals with RHD such as those with heart failure, pregnant women, and those with severe disease and multiple valve involvement. As penicillin is the mainstay of primary and secondary prevention, further research into penicillin supply chains, alternate preparations and modes of delivery is required.


Idiopathic early ovarian aging: is there a relation with premenopausal accelerated biological aging in young women with diminished response to ART?
To evaluate whether young women with idiopathic early ovarian aging, as defined by producing fewer oocytes than expected for a given age over multiple in vitro fertilization (IVF) cycles, have changes in telomere length and epigenetic age indicating accelerated biological aging (i.e., increased risk of morbidity and mortality). A prospective cohort study was conducted at two Danish public fertility clinics. A total of 55 young women (≤ 37 years) with at least two IVF cycles with ≤ 5 harvested oocytes despite sufficient stimulation with follicle-stimulating hormone (FSH) were included in the early ovarian aging group. As controls, 52 young women (≤ 37 years) with normal ovarian function, defined by at least eight harvested oocytes, were included. Relative telomere length (rTL) and epigenetic age acceleration (AgeAccel) were measured in white blood cells as markers of premenopausal accelerated biological aging. rTL was comparable with a mean of 0.46 (± SD 0.12) in the early ovarian aging group and 0.47 (0.14) in the normal ovarian aging group. The AgeAccel of the early ovarian aging group was, insignificantly, 0.5 years older, but this difference disappeared when adjusting for chronological age. Sub-analysis using Anti-Müllerian hormone (AMH) as selection criterion for the two groups did not change the results. We did not find any indications of accelerated aging in whole blood from young women with idiopathic early ovarian aging. Further investigations in a similar cohort of premenopausal women or other tissues are needed to fully elucidate the potential relationship between premenopausal accelerated biological aging and early ovarian aging.


"In vitro" and in animal model studies on a double virus-inactivated factor VIII concentrate.
To improve the safety of plasma derived factor VIII (FVIII) concentrate, we introduced a final super heat treatment (100 degrees C for 30 min) as additional virus inactivation step applied to a lyophilized, highly purified FVIII concentrate (100 IU/mg of proteins) already virus inactivated using the solvent/detergent (S/D) method during the manufacturing process. The efficiency of the super heat treatment was demonstrated in inactivating two non-lipid enveloped viruses (Hepatitis A virus and Poliovirus 1). The loss of FVIII procoagulant activity during the super heat treatment was of about 15%, estimated both by clotting and chromogenic assays. No substantial changes were observed in physical, biochemical and immunological characteristics of the heat treated FVIII concentrate in comparison with those of the FVIII before heat treatment.


Corrigendum to "Evaluation of algorithmic, textual and pictorial forms of representation of standard operating procedures for error reduction in complex systems" [Heliyon 6 (2) (2020) e03291].
[This corrects the article DOI: 10.1016/j.heliyon.2020.e03291.].


Current status of hepatic resection for hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is one of the most common tumors worldwide. For this disease, a variety of therapeutic measures have been applied, including hepatic resections, total hepatectomy followed by allografting, transarterial chemoembolization, and percutaneous tumor ablative therapy by ethanol, microwave coagulation, and radiofrequency ablation. This article focuses on the current status of hepatic resections for HCC.


Computed tomography findings of paranasal sinuses in patients with eosinophilic granulomatosis with polyangiitis: Comparison with other eosinophilic sinus diseases and clinical relevance of their severity.
Although paranasal sinuses are one of the most representative organs affected by eosinophilic granulomatosis with polyangiitis (EGPA), they have not been studied sufficiently. The aim of this study was to compare computed tomography (CT) findings in paranasal sinuses of EGPA with those of other eosinophilic sinus diseases and elucidate the clinical relevance of their severity. CT findings of paranasal sinuses in EGPA patients prior to therapeutic intervention (n = 30) were evaluated using the Lund-Mackay staging (LMS) system and compared with those of three control diseases [(NSAID-exacerbated respiratory disease (N-ERD), aspirin-tolerant asthma, and eosinophilic chronic rhinosinusitis without asthma (ECRS)]. We divided EGPA patients into three groups based on their LMS scores and examined their association with disease manifestation. Total scores of the LMS system in EGPA were significantly lower than those of N-ERD and ECRS without asthma. There was a large variation in total LMS scores in EGPA, suggesting considerable heterogeneity of their sinus lesions. Although EGPA with low LMS system scores showed only minor findings in maxillary and anterior ethmoid regions, those with high LMS system scores were characterized by high scores in the ostiomeatal complex. However, the frequencies of patients with a Five-Factor Score ≥2 and with cardiac involvement were significantly higher for EGPA with low LMS system scores. Although paranasal sinus lesions in EGPA were less severe than those of other eosinophilic sinus diseases, their milder CT findings may be associated with a higher frequency of extra-respiratory organ involvement.


Symptomatic severe hypophosphatemia after intravenous ferric carboxymaltose.
Intravenous iron is commonly prescribed for treatment of iron deficiency, with modern formulations demonstrating an acceptable safety profile in the majority of patients. We report the case of a patient who was hospitalised with muscle pain, deteriorating mobility and multiple fractures following repeated ferric carboxymaltose infusions. Investigations revealed severe hypophosphatemia with serum phosphate of 0.27 mmol/L, 25-hydroxyvitamin D (25OHD) level of 32 nmol/L and insufficiency fractures of the sacrum and L5 transverse process. The patient's hypophosphatemia was corrected with several infusions of intravenous phosphate, as well as oral phosphate and calcitriol, with subsequent resolution of her muscle aches, back pain and immobility. The risk of persistent hypophosphatemia and osteomalacia may be higher with iron carboxymaltose than other iron formulations and a transient increase in intact fibroblast growth factor-23 with reduced renal tubular phosphate absorption has been postulated as the key mechanism. This risk appears increased by repeated iron infusions, underlying malnutrition, hypophosphatemia at baseline, vitamin D deficiency, hyperparathyroidism or anti-resorptive medication use. The true risk and incidence of hypophosphatemia need to be clarified so that appropriate monitoring, prevention and treatment strategies can be developed.


Proteomic profiling for detection of early-stage heart failure in the community.
Biomarkers may provide insights into molecular mechanisms underlying heart remodelling and dysfunction. Using a targeted proteomic approach, we aimed to identify circulating biomarkers associated with early stages of heart failure. A total of 575 community-based participants (mean age, 57 years; 51.7% women) underwent echocardiography and proteomic profiling (CVD II panel, Olink Proteomics). We applied partial least squares-discriminant analysis (PLS-DA) and a machine learning algorithm [eXtreme Gradient Boosting (XGBoost)] to identify key proteins associated with echocardiographic abnormalities. We used Gaussian mixture modelling for unbiased clustering to construct phenogroups based on influential proteins in PLS-DA and XGBoost. Of 87 proteins, 13 were important in PLS-DA and XGBoost modelling for detection of left ventricular remodelling, left ventricular diastolic dysfunction, and/or left atrial reservoir dysfunction: placental growth factor, kidney injury molecule-1, prostasin, angiotensin-converting enzyme-2, galectin-9, cathepsin L1, matrix metalloproteinase-7, tumour necrosis factor receptor superfamily members 10A, 10B, and 11A, interleukins 6 and 16, and α1-microglobulin/bikunin precursor. Based on these proteins, the clustering algorithm divided the cohort into two distinct phenogroups, with each cluster grouping individuals with a similar protein profile. Participants belonging to the second cluster (n = 118) were characterized by an unfavourable cardiovascular risk profile and adverse cardiac structure and function. The adjusted risk of presenting echocardiographic abnormalities was higher in this phenogroup than in the other (P < 0.0001). We identified proteins related to renal function, extracellular matrix remodelling, angiogenesis, and inflammation to be associated with echocardiographic signs of early-stage heart failure. Proteomic phenomapping discriminated individuals at high risk for cardiac remodelling and dysfunction.


Pharmacokinetics of loratadine and pseudoephedrine following single and multiple doses of once- versus twice-daily combination tablet formulations in healthy adult males.
The pharmacokinetic profiles of single and multiple doses of loratadine, descarboethoxyloratadine (DCL) (the major active metabolite of loratadine), and pseudoephedrine were determined in a randomized, open-label, two-way crossover study in 24 healthy men. Subjects received a single dose (day 1) and multiple doses (days 3 to 10) of a once-daily (QD) formulation of loratadine 10 mg in an immediate-release coating and pseudoephedrine sulfate 240 mg in an extended-release core (CLAR-ITIN-D 24 HOUR tablets), and a twice-daily (BID) formulation of loratadine 5 mg in an immediate-release coating and pseudoephedrine sulfate 120 mg, with 60 mg in an immediate-release coating and 60 mg in the barrier-protected core (CLARITIN-D 12 HOUR tablets) in study sessions, each separated by a 10-day washout period. Both regimens were safe and well tolerated. On day 1, plasma loratadine, DCL, and pseudoephedrine concentrations were higher following the QD formulation than following the BID formulation, as expected. On day 10, loratadine and DCL maximum plasma concentration (Cmax) values were, on average, 87% and 35% higher, respectively, for the QD formulation than for the BID formulation; however, the values of the area under the plasma concentration-time curve from 0 to 24 hours (AUC0-24) for loratadine and DCL were equivalent (90% confidence interval [CI]: 83% to 110% for loratadine; 90% to 107% for DCL). On day 10, pseudoephedrine Cmax and AUC0-24 values were equivalent (90% CI for Cmax: 94% to 109%; for AUC: 91% to 106%) for the two formulations, and lower pseudoephedrine concentrations were observed from 16 to 24 hours with the QD formulation. Both loratadine/pseudoephedrine formulations produced equivalent loratadine and DCL AUC0-24 values and equivalent pseudoephedrine Cmax and AUC0-24 values following multiple dosing. The lower pseudoephedrine concentrations in the evening with the QD formulation may minimize the potential for insomnia in patients when compared with the BID formulation.


Adaptation of the repellency response to DEET in Rhodnius prolixus.
For many years it has been accepted that DEET interferes with the detection of odours from the host instead of having a repellent effect. However, recent work showed that DEET acts as an odorant molecule and elicits a behavioural response in the absence of other stimuli. Therefore, DEET must promote some phenomenon connected with the stimuli-sensory system interaction, such as a sensory adaptation, where the sensory system regulates its sensitivity to different stimuli intensities during continuous or repetitive exposure. In this work, we studied different aspects of the insect-DEET interaction through behavioural observations. Previous exposure of fifth instar Rhodnius prolixus nymphs to DEET decreased the behavioural response to this repellent. We observed a decrease in repellence after different times of continuous stimulation with DEET in a time-dependent manner. The response to DEET was recovered 10 min after exposure, when insects were continuously stimulated during 5 or 10 min; maximum repellence was recovered 20 min after exposure when insects were stimulated for 20 min. DEET produced a repellent effect when nymphs were exposed only to its vapours. These results suggest that exposure to DEET produces adaptation in R. prolixus nymphs, and that the behavioural response elicited by DEET occurs via olfaction when no other stimuli are present.