Unpacking capacity to utilize research: A tale of the Burkina Faso public health association.
One of the most important challenges in addressing global health is for institutions to monitor and use research in policy-making. In low- and middle-income countries (LMICs), civil society organizations such as health professional associations can be key contributors to effective national health systems. However, there is little empirical data on their capacity to use research. This case study was used to gain insight into the factors that affect the knowledge translation performance of health professional associations in LMICs by describing the organizational elements and processes constituting capacity to use research, and examining the potential determinants of this capacity. Case study methodology was chosen for its flexibility to capture the multiple and often tacit processes within organizational routines. The Burkina Faso Public Health Association (ABSP) was studied, using in-depth, semi-structured interviews and key documents review. Five key dimensions that affect the association's capacity to use research to influence health policy emerged: organizational motivation; catalysts; organizational capacity to acquire and organizational capacity to transform research findings; moderating organizational factors. Also examined were the dissemination strategies used by ABSP and its abilities to enhance its capacity through networking, to advocate for more relevant research and to develop its potential role as knowledge broker, as well as limitations due to scarce resources. We conclude that a better understanding of the organizational capacity to use research of health professional associations in LMICs is needed to assess, improve and reinforce such capacity. Increased knowledge translation potential may leverage research resources and promote knowledge-sharing.


Regulatory roles of ginseng on inflammatory caspases, executioners of inflammasome activation.
Inflammation is an immune response that protects against pathogens and cellular stress. The hallmark of inflammatory responses is inflammasome activation in response to various stimuli. This subsequently activates downstream effectors, that is, inflammatory caspases such as caspase-1, 4, 5, 11, and 12. Extensive efforts have been made on developing effective and safe anti-inflammatory therapeutics, and ginseng has long been traditionally used as efficacious and safe herbal medicine in treating various inflammatory and inflammation-mediated diseases. Many studies have successfully shown that ginseng plays an anti-inflammatory role by inhibiting inflammasomes and inflammasome-activated inflammatory caspases. This review discusses the regulatory roles of ginseng on inflammatory caspases in inflammatory responses and also suggests new research areas on the anti-inflammatory function of ginseng, which provides a novel insight into the development of ginseng as an effective and safe anti-inflammatory herbal medicine.


Hepatic arterial infusion chemotherapy for liver metastases from gastric cancer: an analysis in Western patients.
The advantage of administering chemotherapy by hepatic arterial infusion is the achievement of high drug concentrations in the liver. Oxaliplatin, irinotecan and 5-flourouracil are active agents in advanced gastric cancer. Therefore a retrospective analysis was performed to investigate the effects of these drugs administered by hepatic arterial infusion in heavily pretreated gastric cancer patients with predominant hepatic metastases. Very limited data about hepatic arterial infusion exist in western gastric cancer patients. Seven patients with advanced gastric cancer were included in the retrospective analysis. All patients had proven progressive disease prior to initiation of hepatic arterial infusion. All had an ECOG performance status of < or =2 and had received at least two previous systemic chemotherapy regimens, including the combination of cisplatin/5-fluorouracil. Patients were given chemotherapy by hepatic arterial infusion: 5-fluorouracil, 600 mg/m2, together with folinic acid, 300 mg/m2/2 h, followed by oxaliplatin, 85 mg/m2/2 h, every 2 weeks. Fifty-four cycles of hepatic arterial infusion (range, 2-21) with a median treatment duration of 6 cycles were administered in 7 patients. The treatment was feasible and safe, no grade 3-4 toxicity was observed. One patient showed stabilization of liver metastases over 7 months. In 6 of the 7 patients there was radiologically proven progressive disease after a median treatment time of 10 weeks. Chemotherapy by hepatic arterial infusion is modestly effective in heavily pretreated gastric cancer patients. Hepatic arterial infusion has a very favorable toxicity profile and can be safely administered even in elderly patients. It might be an additional therapeutic option and should be further investigated. The literature on hepatic arterial infusion in gastric cancer patients is reviewed.


The evolution of management of type B aortic dissection in a series of 100 consecutive cases in a tertiary center.
Management of aortic dissection is rapidly evolving. The present study aims to assess paradigm shifts in type B aortic dissection (TBAD) treatment modalities and their outcomes according to clinical presentation and type of treatment. We also aim to assess the impact of endovascular technology in TBAD management in order to define organizational strategies to provide an integrated cardiovascular approach. We performed a retrospective review with descriptive analysis of the last 100 consecutive patients with TBAD admitted to the Vascular Surgery Department of Centro Hospitalar Universitário Lisboa Norte over a 16-year period. Results were stratified according to treatment modality and stage of the disease. The study was further divided into two time periods, 2003-2010 and 2011-2019, respectively before and after the introduction of a dedicated endovascular program for aortic dissections. A total of 100 patients (83% male; mean age 60 years) were included, of whom 59 were admitted in the acute stage (50.8% with complicated dissections). The other 41 patients were admitted for chronic dissections, most of them for surgical treatment of aneurysmal degeneration. Temporal analysis demonstrated an increase in the number of patients operated for aortic dissection, mainly due to an increase in chronic patients (33.3% in 2003-2010 vs. 64.4% in 2011-2019) and a clear shift toward endovascular treatment from 2015 onward. Overall in-hospital mortality was 14% and was significantly higher in the chronic phase (acute 5.1% vs. chronic 26.8%; OR 5.30, 95% CI 1.71-16.39; p=0.003) and in patients with aneurysmal degeneration, regardless of the temporal phase. Only one death was recorded in the endovascular group. Management of TABD carried an overall mortality of 14% during a 16-year period, but the appropriate use of endovascular technology has substantially reduced in-hospital mortality.


Cerebral small vessel disease and perihematomal edema formation in spontaneous intracerebral hemorrhage.
Blood-brain barrier (BBB) dysfunction is implicated in the pathophysiology of cerebral small vessel disease (cSVD)-related intracerebral hemorrhage (ICH). The formation of perihematomal edema (PHE) is presumed to reflect acute BBB permeability following ICH. We aimed to assess the association between cSVD burden and PHE formation in patients with spontaneous ICH. We selected patients with spontaneous ICH who underwent 3T MRI imaging within 21 days after symptom onset from a prospective observational multicenter cohort study. We rated markers of cSVD (white matter hyperintensities, enlarged perivascular spaces, lacunes and cerebral microbleeds) and calculated the composite score as a measure of the total cSVD burden. Perihematomal edema formation was measured using the edema extension distance (EED). We assessed the association between the cSVD burden and the EED using a multivariable linear regression model adjusting for age, (log-transformed) ICH volume, ICH location (lobar vs. non-lobar), and interval between symptom onset and MRI. We included 85 patients (mean age 63.5 years, 75.3% male). Median interval between symptom onset and MRI imaging was 6 days (IQR 1-19). Median ICH volume was 17.0 mL (IQR 1.4-88.6), and mean EED was 0.54 cm (SD 0.17). We found no association between the total cSVD burden and EED (B = -0.003, 95% CI -0.003-0.03, p = 0.83), nor for any of the individual radiological cSVD markers. We found no association between the cSVD burden and PHE formation. This implies that mechanisms other than BBB dysfunction are involved in the pathophysiology of PHE.


Digital pressure-flow relationships in subjects with Raynaud's phenomenon.
In order to determine whether subjects with Raynaud's phenomenon have altered digital hemodynamics in the warm basal condition, we characterized the digital pressure-flow relationships in seven subjects with Raynaud's phenomenon and compared the results with age and sex matched control subjects. Digital pressure-flow relationships were measured by the use of a plethysmographic technique during passive elevation of the arm. Normal subjects demonstrated a positive finger systolic pressure at zero flow (48.3 mmHg), indicative of a critical closing pressure, however, the closing pressure was significantly higher in the subjects who had a history of Raynaud's phenomenon (64.7 mmHg, p less than .001). In contrast, there was no significant difference found in the conductance measured as the slope of the pressure-flow relationship. Subjects with Raynaud's phenomenon demonstrated a correlation between finger systolic pressure and critical closing pressure suggesting that these subjects may regulate arterial pressure through a critical closing pressure mechanism.


Needle EMG in certain uncommon clinical contexts.
It is the position of the AANEM that, based on the literature, there are no contraindications to needle electromyography (EMG) in patients with lymphedema or prosthetic joints. In patients with lymphedema, clinical judgment in each individual circumstance should be used in deciding whether the risk of complication is greater than the value of the information to be obtained from the needle electrode examination.


gammadeltaT cells are involved in liver transplant tolerance.
The role of nonconventional T cells in innate and adaptive immunity is just emerging; gammadeltaT cells play important roles in anti-tumor and anti-infectious diseases. The involvement of gammadeltaT cells in immunologic responses to hematopoietic cell transplantation remains controversial; divergent results have been reported depending on the murine strains and model systems. Whether gammadeltaT cells are involved in solid organ transplantation is understudied. We have characterized the gammadeltaT cells in mouse livers and spleens to evaluate their contributions to liver transplant tolerance posttransplantation using a murine allogeneic liver transplant model which induces spontaneous T regulatory cell (Treg)-dependent tolerance. Our studies revealed that gammadeltaT cells comprised about 20% of the population of liver nonparenchymal cells (NPCs). In naïve C3H mice they were CD4, CD8, and NK1.1 negative. The percentage of gammadeltaT cells decreased in spontaneously tolerated liver grafts posttransplantation from 20% in naïve C3H livers to <10% in allografts throughout the time course. In contrast, they increased in liver grafts with rejection induced by anti-CTLA4 plus anti-CD25 mAb administration. CD4 and CD8 expression on gammadeltaT cells dramatically increased in the tolerated but not rejected livers posttransplantation to >20% of CD4(+) and 30% of CD8(+). Our results suggested that gammadeltaT cells are involved in allogeneic immune responses. Whether gammadeltaT cells function as the causal or the effector cells in allograft tolerance rejection warrants further investigation.


Vitamin D does not improve the metabolic health of patients with chronic kidney disease stage 3-4: a randomized controlled trial.
To assess the impact of vitamin D supplementation (cholecalciferol) on the insulin sensitivity and metabolic health of patients with chronic kidney disease (CKD). Twenty-eight adult patients with CKD stages 3-4 were recruited from the outpatient department of the Princess Alexandra Hospital (Brisbane, Australia) to a double-blind randomized trial of cholecalciferol (vitamin D3) 2000 IU/day or placebo for 6 months. Metabolic parameters at baseline were compared with 20 non-CKD adults. The primary outcome was an improvement in insulin resistance (glucose disposal rate, GDR) at 6 months (quantified by hyperinsulinaemic euglycaemic clamp). Carbohydrate and lipid oxidation rates were assessed by indirect calorimetry. At baseline, patients were significantly insulin-resistant compared with lean younger non-CKD individuals (n = 9; GDR 3.42 vs. 5.76 mg/kg per minute, P = 0.001), but comparable with their age-, gender- and weight-matched non-CKD counterparts (n = 11; 3.42 vs. 3.98 mg/kg per minute, P = 0.4). 25-Hydroxyvitamin D did not change in the placebo group, but rose from 95 ± 37 to 146 ± 25 nmol/L with treatment (P = 0.0001). Post treatment, there was no difference in GDR between groups (GDR 3.38 vs. 3.52 mg/kg per minute, ancova P = 0.4). There was a relative increase in hyperinsulinaemic oxidative disposal of glucose with treatment (within-group P = 0.03). Supplementation with cholecalciferol in CKD 3-4 results in appreciable increases in 25-hydroxyvitamin D concentrations, but does not increase insulin sensitivity. The insulin resistance observed was similar among age-, sex- and body mass index-matched individuals with and without CKD. Whether renal dysfunction per se has any influence on the insulin sensitivity of an individual should be the subject of future work.


Metabolite-Sensing Receptor Ffar2 Regulates Colonic Group 3 Innate Lymphoid Cells and Gut Immunity.
Group 3 innate lymphoid cells (ILC3s) sense environmental signals that are critical for gut homeostasis and host defense. However, the metabolite-sensing G-protein-coupled receptors that regulate colonic ILC3s remain poorly understood. We found that colonic ILC3s expressed Ffar2, a microbial metabolite-sensing receptor, and that Ffar2 agonism promoted ILC3 expansion and function. Deficiency of Ffar2 in ILC3s decreased their in situ proliferation and ILC3-derived interleukin-22 (IL-22) production. This led to impaired gut epithelial function characterized by altered mucus-associated proteins and antimicrobial peptides and increased susceptibility to colonic injury and bacterial infection. Ffar2 increased IL-22+ CCR6+ ILC3s and influenced ILC3 abundance in colonic lymphoid tissues. Ffar2 agonism differentially activated AKT or ERK signaling and increased ILC3-derived IL-22 via an AKT and STAT3 axis. Our findings suggest that Ffar2 regulates colonic ILC3 proliferation and function, and they identify an ILC3-receptor signaling pathway modulating gut homeostasis and pathogen defense.


Clinical features and outcomes in patients with cardiogenic shock complicating acute myocardial infarction: early vs recent experience with impella.
To compare clinical features and outcomes in patients with acute myocardial infarction complicated by cardiogenic shock (AMICS) treated in the early experience with Impella percutaneous ventricular assist device and patients treated recently. Since pre-market approval (PMA) of Impella device as treatment for AMICS, use of the device has grown considerably. We retrospectively analyzed 649 AMICS patients treated with perioperative Impella, with 291 patients treated from 2008 to 2014 comprising the early experience cohort and 358 patients treated from 2017 to 2019 comprising the recent experience cohort. The primary end point was risk adjusted in-hospital mortality. Mean age and gender distribution of patients was similar in the two cohorts. The recent cohort had more invasive hemodynamic monitoring (64% vs 46%; P < .001) and less use of an intra-aortic balloon pump prior to Impella (15% vs 41%; P < .001). Recently treated patients were significantly more likely to receive Impella support prior to PCI (58% vs 44%; P = .005). In-hospital mortality was lower in the recent cohort (48% vs 56%; P = .043). This difference was however no longer significant after risk adjustment (adjusted OR 0.89, 95% CI 0.59-1.34, P = .59). Rates of acute kidney injury, major bleeding, and vascular complications requiring surgery were also significantly lower in the recent cohort. Use of Impella for AMICS during recent years is associated with lower unadjusted in-hospital mortality, which may reflect better patient selection, earlier device implantation, and improved management algorithms. In-depth understanding of these factors may inform the development of future treatment protocols.


Performance assessment model for guideline-recommended pharmacotherapy in the secondary prevention of coronary artery disease and treatment of left ventricular dysfunction.
The Agency for Health Care Policy and Research, the National Heart Lung and Blood Institute of the National Institutes of Health, the American Heart Association, and the American College of Cardiology have all developed guidelines for improving the care of patients with cardiovascular disease. The guidelines include recommendations for intensive lipid-lowering therapy in patients with coronary artery disease (CAD) and angiotensin-converting enzyme (ACE) inhibitors in those patients with symptomatic heart failure and asymptomatic left ventricular dysfunction. Despite clinical trial evidence and consensus that these therapies improve survival in high-risk patients, data suggest that there is wide variation in the delivery of guideline-based care. To investigate whether evidence-based assessment of provider practice patterns can impact the delivery of quality cost-effective care, Merck and Company, in conjunction with leading cardiology group practices, the University of North Carolina at Chapel Hill, and Medical Review of North Carolina developed an ambulatory medical record abstraction study. This quality assurance initiative was conducted at practices beginning in the spring of 1996 and continues. Medical records and administrative claims of patients with ischemic heart disease or heart failure were abstracted by a healthcare consulting organization to maintain patient and physician confidentiality. As of mid-July 1997, 626 group practices had completed the medical record abstraction process, with > 1,136 practices participating at some stage of the project; >6,000 physicians participated in the project and >270,000 patients charts were abstracted. Analysis of these data will provide insight and benchmark patterns of care in the pharmacologic management of heart failure and CAD. This project represents a unique collaboration between a pharmaceutical company, an academic institution, a Peer Review Organization, and practicing physicians, to support evidence-based best medical practices.


Aqueous extract of Paeoniae Radix Rubra prevents deep vein thrombosis by ameliorating inflammation through inhibiting GSK3β activity.
Deep vein thrombosis (DVT) is a kind of blood stasis syndrome. Paeoniae Radix Rubra (PRR) has long been widely used for eliminating blood stasis in China, but its effect on DVT has not yet been reported. The present study aimed to assess the potential inhibitory effect of the aqueous extract of PRR (i.e.,PRR dispensing granule, PRRDG) on DVT and explore the underlying mechanism. The chemical profile of PRRDG was analyzed by high-performance liquid chromatography. Sprague-Dawley rats were intragastrically treated with PRRDG (0.625, 1.25 and 1.875 g crude drug/kg/d) once daily for 7 consecutive days. On the sixth day, a model of inferior vena cava (IVC) stenosis-induced DVT was established. All rats were sacrificed on the seventh day. Serum was collected for enzyme-linked immunosorbent assay. Thrombus-containing IVC was weighed and further processed for histopathologic examination, immunohistochemical analysis and western blotting. LiCl and LY294002 were adopted to block and increase the activity of glycogen synthase kinase 3β (GSK3β), respectively. The chemical profile analysis showed that paeoniflorin, benzoylpaeoniflorin, albiflorin, gallic acid and catechin were the main constituents of PRRDG. LiCl decreased thrombus weight, reduced the number of inflammatory cells in thrombus and vein wall, down-regulated phosphorylated NF-κB p65 (p-p65) protein expression. Similarly, PRRDG decreased thrombus weight and tissue factor (TF) protein expression. PRRDG reduced the protein expression levels of P-selectin, monocyte chemoattractant protein-1 (MCP-1), intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) in venous endothelium, serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β), and the number of inflammatory cells in thrombus and vein wall. Moreover, PRRDG down-regulated p-p65 protein expression and up-regulated phosphorylated GSK3β (p-GSK3β) protein expression. LY294002 abrogated the inhibitory effects of PRRDG on thrombus weight, TF protein expression, TNF-α and IL-1β serum levels, inflammatory cells influxes, and p-p65 protein expression. PRRDG prevents DVT by ameliorating inflammation through inhibiting GSK3β activity.


Adrenal medullary tissue transplants in the rat spinal cord reduce pain sensitivity.
Adrenal chromaffin cells contain and release several neuroactive substances which induce analgesia when injected directly into the spinal cord (e.g. opioid peptides and catecholamines). Furthermore, the release of these substances can be induced by nicotine. In order to determine whether adrenal medullary tissue transplanted to the spinal cord can produce alterations in pain sensitivity, pieces of dissected rat adrenal medulla were placed in the subarachnoid space of rat spinal cords. Stimulation by a low dose of nicotine induced potent analgesia in animals with adrenal medullary transplants, but not in animals with control transplants. Furthermore, this analgesia was reversed to pre-nicotine levels by the opiate antagonist naloxone. Thus adrenal medullary transplants in the spinal cord may provide a permanent and locally available source of opioid peptides for the relief of intractable pain.


The influence of climate on durum wheat quality in Tuscany, Central Italy.
Climate and meteorological conditions greatly affect agricultural activities, modifying plant responses and determining the quantity and the quality of production. In this respect, the aim of this research was to analyze the quality of winter durum wheat (Triticum turgidum L. var. durum), in terms of protein content through the use of meteorological information. Meteorological conditions were described utilizing both local weather station data (air temperature, cumulated precipitation) and large-scale information available freely on the internet, such as geopotential height (GPH), sea surface temperature (SST), and the North Atlantic Oscillation (NAO) index. The analysis was carried out for the period 1997-2009 in the Tuscany region, Central Italy. Grain protein was positively correlated with air temperature during the February to June period, and negatively with cumulative precipitation during the entire period from November to June. Protein content was also negatively correlated with 500 hPa GPH over Gibraltar and North-Western Africa during the March to June period and with the SST of the Atlantic Ocean south-west of the Canary Islands during the January to June period. Finally, with regard to the NAO, winter durum wheat quality was positively correlated with the specific index for several months, in particular during the winter period. These results demonstrate that precipitation and air temperature over the production area represent two crucial variables driving the vegeto-productive responses of winter durum wheat. On the other hand, the use of large-scale meteorological information showed great potential from the perspective of a local quality forecast system setup.


Predicting masticatory jaw movements from chin movements using multivariate linear methods.
Previously, we have used bivariate correlations of maximum and minimum displacement, velocity and acceleration variables to compare masticatory chin and jaw movements (J. Prosthet. Dent. 81 (1999) 179). This previous study represented a first step in exploring the hypothesis that the chin contained useful information regarding jaw kinematics. The current study extends our understanding of the relationship between masticatory chin and jaw movements by: (1) reconstructing and evaluating a more continuous trajectory of chin and jaw movements, and (2) performing multivariate correlations comparing chin and jaw movements at discrete points along the trajectory in order to gain insight into the coupling of chin and jaw movements during a chewing cycle. Results indicated that chin and jaw movement trajectories were visually similar in the lateral, vertical, and anteroposterior axes. The adjusted R(2) results in the lateral, vertical, and anteroposterior dimensions averaged 0.74, 0.78, and 0.89, respectively. Within chewing cycles, the lowest correlations between chin and jaw movements in the lateral and vertical dimensions occurred when the jaw was relatively closed, whereas the lowest correlations between chin and jaw movements in the anteroposterior dimension occurred while the jaw was opening from a closed position. The results indicated that jaw and chin movements were qualitatively similar and that at least 74% of the variation in jaw movements could be accounted for by multivariate linear models of chin movement.


Cosmogenic 10Be and equilibrium-line altitude dataset of Holocene glacier advances in the Himalayan-Tibetan orogen.
A comprehensive analysis of the variable temporal and spatial responses of tropical-subtropical high-altitude glaciers to climate change is critical for successful model predictions and environmental risk assessment in the Himalayan-Tibetan orogen. High-frequency Holocene glacier chronostratigraphies are therefore reconstructed in 79 glaciated valleys across the orogen using 519 published and 16 new terrestrial cosmogenic 10Be exposure age dataset. Published 10Be ages are compiled only for moraine boulders (excluding bedrock ages). These ages are recalculated using the latest ICE-D production rate calibration database and the scaling scheme models. Outliers for the individual moraine are detected using the Chauvenet's criterion. In addition, past equilibrium-line altitudes (ELAs) are determined using the area-altitude (AA), area accumulation ratio (AAR), and toe-headwall accumulation ratio (THAR) methods for each glacier advance. The modern maximum elevations of lateral moraines (MELM) are also used to estimate modern ELAs and as an independent check on mean ELAs derived using the above three methods. These data may serve as an essential archive for future studies focusing on the cryospheric and environmental changes in the Himalayan-Tibetan orogen. A more comprehensive analysis of the published and new 10Be ages and ELA results and a list of references are presented in Saha et al. (2019, High-frequency Holocene glacier fluctuations in the Himalayan-Tibetan orogen. Quaternary Science Reviews, 220, 372-400).


Computationally-guided exchange of substrate selectivity motifs in a modular polyketide synthase acyltransferase.
Polyketides, one of the largest classes of natural products, are often clinically relevant. The ability to engineer polyketide biosynthesis to produce analogs is critically important. Acyltransferases (ATs) of modular polyketide synthases (PKSs) catalyze the installation of malonyl-CoA extenders into polyketide scaffolds. ATs have been targeted extensively to site-selectively introduce various extenders into polyketides. Yet, a complete inventory of AT residues responsible for substrate selection has not been established, limiting the scope of AT engineering. Here, molecular dynamics simulations are used to prioritize ~50 mutations within the active site of EryAT6 from erythromycin biosynthesis, leading to identification of two previously unexplored structural motifs. Exchanging both motifs with those from ATs with alternative extender specificities provides chimeric PKS modules with expanded and inverted substrate specificity. Our enhanced understanding of AT substrate selectivity and application of this motif-swapping strategy are expected to advance our ability to engineer PKSs towards designer polyketides.


Principal component analysis of lipid and protein oxidation products and their impact on color stability in bison longissimus lumborum and psoas major muscles.
The study aims were to compare lipid (malondialdehyde [MDA], 4-hydroxy-2-nonenal [HNE]) and protein (carbonyl content [CAR]) oxidation products between two bison muscles (longissimus lumborum [LL] and psoas major [PM]) at different aging and retail display time and determine their influence on muscle color stability. Regardless of the aging and retail display time, LL showed greater redness (a* value; P = 0.04) and lower surface discoloration (P < 0.01) than PM as well as LL exhibited lower MDA, HNE, and CAR content compared to PM (P < 0.05). In both muscles, MDA showed the highest correlation to a* (r = -0.78; P < 0.01) and discoloration (rs = 0.82; P < 0.01) scores, particularly in PM muscle compared to LL muscle. In conclusion, the principal component analysis revealed 4 distinct color deterioration clusters within steaks displayed at d 4 according to the muscle and aging time, and MDA critically influences color deterioration patterns in bison muscles.


Disrupting Sc-uORFs of a transcription factor bZIP1 using CRISPR/Cas9 enhances sugar and amino acid contents in tomato (Solanum lycopersicum).
Induced mutations in the SC-uORF of the tomato transcription factor gene SlbZIP1 by the CRISPR/Cas9 system led to the high accumulation of sugar and amino acid contents in tomato fruits. Tomato (Solanum lycopersicum) is one of the most popular and consumed vegetable crops in the world. Among important traits for tomato improvement such as yield, biotic and abiotic resistances, appearance, post-harvest shelf life and fruit quality, the last one seems to face more challenges because of its genetic and biochemical complexities. In this study, a dual-gRNAs CRISPR/Cas9 system was developed to induce targeted mutations in uORF regions of the SlbZIP1, a gene involved in the sucrose-induced repression of translation (SIRT) mechanism. Different induced mutations in the SlbZIP1-uORF region were identified at the T0 generation, stably transferred to the offspring, and no mutation was found at potential off-target sites. The induced mutations in the SlbZIP1-uORF region affected the transcription of SlbZIP1 and related genes in sugar and amino acid biosynthesis. Fruit component analysis showed significant increases in soluble solid, sugar and total amino acid contents in all SlbZIP1-uORF mutant lines. The accumulation of sour-tasting amino acids, including aspartic and glutamic acids, raised from 77 to 144%, while the accumulation of sweet-tasting amino acids such as alanine, glycine, proline, serine, and threonine increased from 14 to 107% in the mutant plants. Importantly, the potential SlbZIP1-uORF mutant lines with desirable fruit traits and no impaired effect on plant phenotype, growth and development were identified under the growth chamber condition. Our result indicates the potential utility of the CRISPR/Cas9 system for fruit quality improvement in tomato and other important crops.


Mutational definition of binding requirements of an hnRNP-like protein in Arabidopsis using fluorescence correlation spectroscopy.
Arabidopsis thaliana glycine-rich RNA binding protein 7 (AtGRP7) is part of a negative feedback loop through which it regulates alternative splicing and steady-state abundance of its pre-mRNA. Here we use fluorescence correlation spectroscopy to investigate the requirements for AtGRP7 binding to its intron using fluorescently-labelled synthetic oligonucleotides. By systematically introducing point mutations we identify three nucleotides that lead to an increased Kd value when mutated and thus are critical for AtGRP7 binding. Simultaneous mutation of all three residues abrogates binding. The paralogue AtGRP8 binds to an overlapping motif but with a different sequence preference, in line with overlapping but not identical functions of this protein pair. Truncation of the glycine-rich domain reduces the binding affinity of AtGRP7, showing for the first time that the glycine-rich stretch of a plant hnRNP-like protein contributes to binding. Mutation of the conserved R(49) that is crucial for AtGRP7 function in pathogen defence and splicing abolishes binding.


Erythrocyte dehydration in pathophysiology and treatment of sickle cell disease.
A prominent feature of sickle cell disease is the presence of cells with markedly increased sickle cell hemoglobin concentration, as a consequence of the loss of potassium, chloride, and water from the erythrocyte. Because of the extreme dependency of the kinetic of polymerization on sickle cell hemoglobin concentration, these dehydrated erythrocytes have an increased tendency to polymerize and sickle. Thus blockade of the loss of potassium from the erythrocyte should prevent the increase in sickle cell hemoglobin concentration and reduce sickling. The availability of this potential therapeutic option is based on a detailed knowledge of the mechanisms leading to cell dehydration. Two ion transport pathways, the K-Cl cotransport and the Ca(2+)-activated K+ channel, play a prominent role in the dehydration of sickle erythrocytes. Possible therapeutic strategies include inhibition of K-Cl cotransport by increasing erythrocyte Mg2+ content and inhibition of the Ca(2+)-activated K channel by oral administration of clotrimazole.


[Elbow dislocation].
Elbow dislocation is the most frequent dislocation in the upper limb after shoulder dislocation. Closed reduction is feasible in outpatient care when there is no associated fracture. A review is presented of the different reduction procedures.


Studies on the interaction between benzophenone and bovine serum albumin by spectroscopic methods.
The interaction between benzophenone (BP) and bovine serum albumin (BSA) was investigated by the methods of fluorescence spectroscopy combined with UV-Vis absorption and circular dichroism (CD) measurements under simulative physiological conditions. The experiment results showed that the fluorescence quenching of BSA by BP was resulted from the formation of a BP-BSA complex and the corresponding association constants (Ka) between BP and BSA at four different temperatures had been determined using the modified Stern-Volmer equation. The enthalpy change (ΔH) and entropy change (ΔS) were calculated to be -43.73 kJ mol(-1) and -53.05 J mol(-1) K(-1), respectively, which suggested that hydrogen bond and van der Waals force played major roles in stabilizing the BP-BSA complex. Site marker competitive experiments indicated that the binding of BP to BSA primarily took place in site I (sub-domain IIA). The conformational investigation showed that the presence of BP decreased the α-helical content of BSA and induced the slight unfolding of the polypeptides of protein, which confirmed some micro-environmental and conformational changes of BSA molecules.


Genetic features of cerebrospinal fluid-derived subtype B HIV-1 tat.
Since HIV-1 Tat has been associated with neurocognitive dysfunction, we investigated 60 HIV-1 subtype B-infected individuals who were characterized for neurocognitive functioning and had paired CSF and blood plasma samples available. To avoid issues with repeated sampling, we generated population-based HIV-1 tat sequences from each compartment and evaluated these data using a battery of phylogenetic, statistical, and machine learning tools. These analyses identified position HXB2 5905 within the cysteine-rich domain of tat as a signature of CSF-derived HIV-1, and a higher number of mixed bases in CSF, as measure of diversity, was associated with HIV-associated neurocognitive disorder. Since identified mutations were synonymous, we evaluated the predicted secondary RNA structures, which showed that this mutation altered secondary structure. As a measure of divergence, the genetic distance between the blood and CSF-derived tat was inversely correlated with current and nadir CD4+ T cell counts. These data suggest that specific HIV-1 features of tat influence neurotropism and neurocognitive impairment.


Bio-fabricated green silver nano-architecture for degradation of methylene blue water contaminant: A mini-review.
The advent of global industrialization advancements has proven to be both a blessing and a curse for humanity, with significant detrimental consequences on marine bodies, and methylene blue is one of the common offenders through textile industry runoffs. These dye runoffs are complex, neurotoxic, and carcinogenic and prevent sunlight from penetrating the water to hinder photosynthesis and increase the biological/biochemical oxygen demand (BOD), hence hampering the ontogenesis of photoautotrophic organisms and thus threatening marine life and causing an increase in unavailability and inaccessibility to healthy water for eco-fundamental networking. Traditional methods came into the limelight, but they are costly and inefficient. Amazingly, due to exceptional surface features, eco-friendliness, cost-effectiveness, catalytic efficiency, and antibacterial capabilities, biosynthesized nanoparticles emerged as a potential solution to these drawbacks encounter by the traditional approach. This review was based on a comprehensive review of publicly available literature (majorly 2019-2021 original research reports) using major scientific databases such as SciFinder, Scopus, PubMed, Google Scholar, and Science Direct. The keywords that were utilized to scoop up the scientific journals were as follows: dye degradation and decolorization, biosynthesis, methylene blue, silver nanoparticles, wastewater, and dye runoffs. Thus, this review highlights the green sources used for the bio-fabrication of silver nanoparticles, the current level of knowledge of biosynthesis mechanism, mechanism of degradation, and methylene blue dye degradation efficiency. PRACTITIONER POINTS: Bio-fabrication mechanism of green silver nano-architecture from plant, bacteria, fungi, and algae extract has been discussed. Various biological capping/reducing agents have been reported. Degradation efficiency of methylene blue dyes using silver nanoparticles has been discussed. Mechanism of degradation of methylene blue by green silver nanoparticles has been reported.


Many-body exchange-repulsion in polarizable molecular mechanics. I. Orbital-based approximations and applications to hydrated metal cation complexes.
We have quantified the extent of the nonadditivity of the short-range exchange-repulsion energy, E(exch-rep), in several polycoordinated complexes of alkali, alkaline-earth, transition, and metal cations. This was done by performing ab initio energy decomposition analyses of interaction energies in these complexes. The magnitude of E(exch-rep(n-body, n > 2)) was found to be strongly cation-dependent, ranging from close to zero for some alkali metal complexes to about 6 kcal/mol for the hexahydrated Zn(2+) complex. In all cases, the cation-water molecules, E(exch-rep(three-body)), has been found to be the dominant contribution to many-body exchange-repulsion effects, higher order terms being negligible. As the physical basis of this effect is discussed, a three-center exponential term was introduced in the SIBFA (Sum of Interactions Between Fragments Ab initio computed) polarizable molecular mechanics procedure to model such effects. The three-body correction is added to the two-center (two-body) overlap-like formulation of the short-range repulsion contribution, E(rep), which is grounded on simplified integrals obtained from localized molecular orbital theory. The present term is computed on using mostly precomputed two-body terms and, therefore, does not increase significantly the computational cost of the method. It was shown to match closely E(three-body) in a series of test cases bearing on the complexes of Ca(2+), Zn(2+), and Hg(2+). For example, its introduction enabled to restore the correct tetrahedral versus square planar preference found from quantum chemistry calculations on the tetrahydrate of Hg(2+) and [Hg(H(2)O)(4)](2+).


Using intravital microscopy to observe bevacizumab-mediated anti-angiogenesis in human head and neck squamous cell carcinoma xenografts.
The study showed the value of using intravital microscopy (IVM) analysis for the study of neoangiogenesis. It demonstrated that the model and the analytical methodology could be used to evaluate in detail the effects of treatment strategies for solid tumours. Neoangiogenesis is a key component of tumour progression, invasion and metastasis. In clinical trials monoclonal antibodies specific for vascular endothelial growth factor - VEGF (bevacizumab) - have been shown to significantly affect tumour progression when given in combination with standard chemotherapy, and also to improve the overall survival of patients. For squamous cell carcinoma of the head and neck (HNSCC), we still await definitive evidence of the effect of such treatment. The present study was designed to investigate the anti-angiogenesis effect of beviacizumab in green fluorescent protein (GFP)-labelled HNSCC xenografts using IVM technology. We performed IVM and used image analysis for quantification of angiogenesis and of effects of bevacizumab on cell viability, combined with histochemical and immunohistochemical analysis to standardize the digital analysis of changes in tumour vascularization and cell viability. We found significant effects of bevacizumab on angiogenesis and cancer cell survival in HNSCC. Repeated injections of bevacizumab were found to provide the greatest effects.


Bond assessment of resin modified glass ionomer cement to dentin conditioned with photosensitizers, laser and conventional regimes.
To assess different conditioning regimes on shear bond strength (SBS) of resin modified glass ionomer cement (RMGIC) bonded to dentin MATERIAL AND METHODS: Fifty non carious intact maxillary molars were cleaned, isolated and randomly divided into five groups (n = 10). Before randomization, dentin surface was exposed and finished. Samples in group 1 were conditioned with methylene blue photosensitizer (MBP) 50 mg/l and activated by photodynamic therapy (PDT), Group 2: surface treated with Er,Cr:YSGG (ECL), Group 3: surface conditioned with polyacrylic acid (PAA) (control), Group 4: surface conditioned with 17 % Ethylenediaminetetraacetic acid (EDTA), Group 5: surface conditioned with total etch (Optibond solo Plus). For SBS testing the samples were placed in universal testing machine. Fracture analysis of debonded surfaces were evaluated using stereomicroscope at 40x magnification. Means and standard deviations were calculated using analysis of variance (ANOVA) and Tukey's post hoc test at a significance level of (p < 0.05). The maximum bond strength was found in group 5 conditioned with Optibond solo plus total etch (23.15 ± 3.21 MPa). Whereas, the lowest bond values were observed in group 1 treated with MBP (15.25 ± 1.54 MPa). Moreover, samples in group 2, group 3 and group 4 resulted in comparable bond strength (p > 0.05). MBP at 50 mg/l is not recommended to condition dentin prior to RMGIC application. Moreover, ECL has a potential to be suggested for dentin conditioning compared to PAA.


An optogenetic application of proton pump ArchT to C. elegans cells.
Application of novel light-driven ion channel/pumps would benefit optogenetic studies of Caenorhabditis elegans. A recent study showed that ArchT, a novel light-driven outward proton pump, is >3 times more light-sensitive than the Arch proton pump. Here we report the silencing effect of ArchT in C. elegans cells. ArchT expressed by using a body-wall muscle or pan-neuronal-promoters caused a quick and reliable locomotion paralysis when worms were illuminated by green light. Unlike the report on mouse neurons, however, light sensitivity of ArchT is similar to that of Arch in C. elegans. ArchT-mediated acute silencing of serotonergic neurons quickly triggered backward locomotion. This response was abolished in the presence of exogenously added serotonin, suggesting that, in a normal situation, serotonin is secreted in a constitutive fashion to repress backward movement.


Microsomic and macrosomic body structure in children and adolescents affected by syndromes or diseases associated with neurodysfunction.
In Poland the issue of microsomic body structure (micro-SBS) and macrosomic body structure (macro-SBS) has so far been overlooked. Up until now only a small amount of data have been published, most often as an overview of the problem. The current study was designed to investigate the co-occurrence of microsomic/macrosomic body structure (micro/macro-SBS) and congenital nervous system disorders or neurological syndromes with symptoms visible from infancy, based on essential data acquired during admission procedures at a neurological rehabilitation ward for children and adolescents. The study applied a retrospective analysis of data collected during hospitalization of 327 children and adolescents, aged 4-18 years who had been affected since infancy by congenital disorders of the nervous system and/or neurological syndromes associated with a minimum of one neurodysfunction. To identify subjects with microsomic or macrosomic body structure in the group of children and adolescents, the adopted criteria took into account z-score values for body height (z-score Ht), body weight (z-score Wt), head circumference (z-score HC), BMI (z-score BMI) and head circumference index (z-score HCI). The rates of micro/macro-SBS in the study group amounted to 7.3% and 0.6%, respectively. The findings show a more frequent co-occurrence of, as well as statistically significant correlations between, micro/macro-SBS and type of spasticity (cerebral palsy) (p = 0.024) as well as hydrocephalus not treated surgically (p < 0.001). Macro-SBS was found to more frequently co-occur with hemiplegia and hydrocephalus not treated surgically.


Robustness of Quantitative Diffusion Metrics from Four Models: A Prospective Study on the Influence of Scan-Rescans, Voxel Size, Coils, and Observers.
Quantitative diffusion metrics provide additional microstructural information of diseases. The robustness of quantitative diffusion metrics should be established before clinical application. To evaluate the variability and reproducibility of quantitative diffusion MRI metrics. Prospective. 14 volunteers (7 men; median age, range, 28, 26-59 years). 3.0-T/Diffusion spectrum imaging. Brain MRI studies were performed four times per subject: involving different combinations of coil types and voxel sizes. Regions of interest of 13 brain anatomical sites were drawn by one observer twice and another observer once to allow interobserver and intraobserver reproducibility assessment. Twenty-five quantitative metrics were calculated using four diffusion models. The variability was evaluated with coefficients of variation (CV), and quartile coefficient of dispersion (QCD). The reproducibility was assessed with intraclass correlation coefficient (ICC), and concordance correlation coefficient (CCC). Wilcoxon signed rank test was used to compare the influence of factors on robustness of quantitative diffusion metrics. A two-tailed P < 0.05 was considered statistically significant. The variability of quantitative diffusion metrics showed CV of 2.4%-68.2%, and QCD of 0.6%-48.2%, respectively. The reproducibility of scans using 20-channel coils with voxels of 2 × 2 × 2 mm3 and 3 × 3 × 3 mm3 , respectively (ICC 0.03-0.84, CCC 0.03-0.84) was significantly worse than that of repeated scans using a 20-channel coil with a voxel size of 2 × 2 × 2 mm3 (ICC of 0.74-0.97, CCC 0.74-0.97) and that of scans using 20- and 64-channel coils, respectively, with a voxel size of 2 × 2 × 2 mm3 (ICC 0.59-0.95, CCC 0.59-0.95). The intraobserver reproducibility (ICC 0.49-0.94, CCC 0.49-0.94) was significantly better than the interobserver reproducibility (ICC 0.28-0.91, CCC 0.28-0.91). Our study indicated that the voxel size has a greater influence on the reproducibility of quantitative diffusion metrics than scan-rescans and coils. The reproducibility within one observer was higher than that between two observers. 2 TECHNICAL EFFICACY: Stage 1.


Minimizing injuries and enhancing performance in golf through training programs.
Golf is a popular sport, particularly in older populations. Regardless of age and skill level, golfers risk injury to the back, shoulder, wrist and hand, elbow, and knee. Because of the unique compressive, shear, rotational, and lateral bending forces created in the lumbar region during the golf swing, the primary sport-related malady experienced by amateurs and professionals is low back pain. Extrinsic and intrinsic injury risk factors have been reported in the literature. A growing body of evidence supports the prescription of strength training routines to enhance performance and reduce the risk of injury. Relevant studies were reviewed on golf injuries, swing mechanics, training routines, and general training program design. The following electronic databases were used to identify research relevant to this report: MEDLINE (from 1950-November 2009), CINAHL (1982-November 2009), and SPORTDiscus (1830-November 2009). Injuries may be associated with lack of warm-up, poor trunk flexibility and strength, faulty swing technique, and overuse. Implementing a training program that includes flexibility, strength, and power training with correction of faulty swing mechanics will help the golfer reduce the likelihood of injury and improve overall performance.


Taurine enhances the metabolism and detoxification of ethanol and prevents hepatic fibrosis in rats treated with iron and alcohol.
The study examines the effects of taurine on the metabolism and detoxification of ethanol in liver fibrosis induced by simultaneous administration of iron carbonyl (0.5%, w/w) and ethanol (6g/(kgday)). Ethanol and iron administration caused liver damage and fibrosis as evidenced by liver histology and biochemical profile in plasma. Over accumulation of iron and a loss in taurine in hepatic tissue was observed in fibrotic animals. The activities of alcohol dehydrogenase and aldehyde dehydrogenase were significantly reduced in these rats compared to control. Adaptive induction of activities of Cytochrome P4502E1 (CYP2E1) and aniline hydroxylase accompanied by the reduction in glutathione-S-transferase, DT-diaphorase and glyoxalases I and II was observed. Taurine administration (2% in drinking water) ameliorated the effects of ethanol and iron. Hepatic damage and fibrosis were reduced in taurine-supplemented rats. Thus taurine has the potential for the treatment of alcoholic liver fibrosis.


Emerging role for NK cells in the pathogenesis of inflammatory arthropathies.
Natural killer (NK) cells are large, granular lymphocytes devoted to the defense against microbial agents and cancer cells, traditionally recognized as an important arm of the innate immunity, even if more recent data underpin a role also in the responses of acquired immunity. Several studies have led to ascertain that NK cells are involved in the pathogenesis of many immune-mediated diseases, where they may exert both protective and pathogenic roles. In particular, the CD56(bright) NK cell subset, showing immunoregulatory properties, has been found to accumulate in tissue sites of inflammation, such as the skin lesions in psoriatic patients and the synovial membrane in rheumatoid arthritis (RA) patients. In this latter disease, while data on the number of NK cells are still controversial among the different studies, more consensuses exist on the impaired activity of these cells. In another group of inflammatory arthritides, the spondyloarthropathies (SpA), the presence of peculiar allotypes of the killer cell immunoglobulin-like receptors (KIR) superfamily, coding for molecules expressed on NK cells, seems to modulate the susceptibility to this group of diseases, especially ankylosing spondylitis and psoriatic arthritis. Interestingly, in vitro studies showed that NK cells of patients with inflammatory arthropathies might produce pro-inflammatory Th1 cytokines; furthermore, they are involved in bone damage, interact and activate different cell types such as monocytes, dendritic cells and resident fibroblast-like synoviocites cells, thus creating and/or maintaining the inflammatory response. Certainly, these features encourage more research on the role of NK cells in the pathogenesis of inflammatory arthropathies, which could be essential to define potential new therapeutic strategies.


Special regulatory T-cell review: Suppressors regulated but unsuppressed.
The rise-and-fall and reincarnation of suppressor T cells is reviewed from the perspective of a participant in the field.


Co-cultures of Macrophages with Muscle Stem Cells with Fibroadipogenic Precursor Cells from Regenerating Skeletal Muscle.
Adult muscle stem cells rebuild myofibers after damage. Although they are highly powerful to implement the adult myogenic program, they need environmental cues provided by surrounding cells for efficient and complete regeneration. Muscle stem cell environment includes fibroadipogenic precursors, vascular cells, and macrophages. A way to decipher the complexity of the interactions muscle stem cells establish with their neighborhood is to co-culture cells freshly isolated from the muscle and assess the impact of one cell type on the behavior/fate of the other cell type. Here, we present a protocol allowing the isolation of primary muscle stem cells, macrophages, and fibroadipogenic precursors by Fluorescence Activated Cell Sorting (FACS) or Magnetic Cell Separation (MACS), together with co-culture methods using a specific setup for a short time window to keep as much as possible the in vivo properties of the isolated cells.


SPME determination of volatile aldehydes for evaluation of in-vitro antioxidant activity.
The in-vitro antioxidant activity of natural (essential oils, vitamin E) or synthetic substances ( tert-butyl hydroxy anisole (BHA), Trolox) has been evaluated by monitoring volatile carbonyl compounds released in model lipid systems subjected to peroxidation. The procedure employed methodology previously developed for the determination of carbonyl compounds as their pentafluorophenylhydrazine derivatives which were quantified, with high sensitivity, by means of capillary gas chromatography with electron-capture detection. Linoleic acid and sunflower oil were used as model lipid systems. Lipid peroxidation was induced in linoleic acid by the Fe2+ ion (1 mmol L-1, 37 degrees C, 12 h) and in sunflower oil by heating in the presence of O2 (220 degrees C, 2 h). The change in hexanal (the main lipoxidation product) concentration found in the lipid matrix subjected to oxidation with and without the substance being tested was used to calculate the antioxidant protection effect. These procedures were employed to evaluate the antioxidant activity of the essential oils of cilantro ( Coriander sativum L.), fennel ( Foeniculum vulgare Mill.), rosemary ( Rosmarinus officinalis L.), "salvia negra" ( Lepechinia schiedeana), and oregano ( Origanum vulgare L.), and the well-known antioxidants BHA, vitamin E, and Trolox, its water-soluble analog. In the sunflower oil system, the essential oils had a stronger protective effect against lipid peroxidation than BHA, vitamin E, and Trolox within the range of concentrations examined (1-20 g L-1). The highest protecting effect, corresponding to a 90% drop in hexanal release, was observed for cilantro oil at 10 g L-1.


Human exposure to chemical mixtures: Challenges for the integration of toxicology with epidemiology data in risk assessment.
Little is known about the potential adverse effects from longterm exposure to complex mixtures at low doses, close to health-based reference values. Traditional chemical-specific risk assessment based on animal testing may be insufficient and the lack of toxicological studies on chemical mixtures remains a major regulatory challenge. Hence, new methodologies on cumulative risk assessment are being developed but still present major limitations. Evaluation of chemical mixture effects requires an integrated and systematic approach and close collaboration across different scientific fields, particularly toxicology, epidemiology, exposure science, risk assessment and statistics for a proper integration of data from all these disciplines. Well designed and conducted epidemiological studies can take advantage of this new paradigm and can provide insight to support the correlation between humans low-dose exposures and diseases, thus avoiding the uncertainty associated with extrapolation across species. In this regard, human epidemiology studies may play a significant role in the new vision of toxicity testing. However, this type of information has not been fully considered in risk assessment, mainly due to the inherent limitations of epidemiologic studies. An integrated approach of in vivo, in vitro and in silico data, together with systematic reviews or meta-analysis of high quality epidemiological studies will improve the robustness of risk assessment of chemical mixtures and will provide a stronger basis for regulatory decisions. The ultimate goal is that experimental and mechanistic data can lend support and biological plausibility to the human epidemiological observations.


Operando visualisation of battery chemistry in a sodium-ion battery by 23Na magnetic resonance imaging.
Sodium-ion batteries are a promising battery technology for their cost and sustainability. This has led to increasing interest in the development of new sodium-ion batteries and new analytical methods to non-invasively, directly visualise battery chemistry. Here we report operando 1H and 23Na nuclear magnetic resonance spectroscopy and imaging experiments to observe the speciation and distribution of sodium in the electrode and electrolyte during sodiation and desodiation of hard carbon in a sodium metal cell and a sodium-ion full-cell configuration. The evolution of the hard carbon sodiation and subsequent formation and evolution of sodium dendrites, upon over-sodiation of the hard carbon, are observed and mapped by 23Na nuclear magnetic resonance spectroscopy and imaging, and their three-dimensional microstructure visualised by 1H magnetic resonance imaging. We also observe, for the first time, the formation of metallic sodium species on hard carbon upon first charge (formation) in a full-cell configuration.


The expression of cyclin G in nasopharyngeal carcinoma and its significance.
To investigate the expression of cyclin G1, cyclin G2 in nasopharyngeal carcinoma (NPC) cell lines and its significance. The protein expression of cyclin G1, cyclin G2 in NPC cell lines of different differentiation degree (HNE2, CNE1) was detected by indirect immunofluorescence. The mRNA expression of cyclin G1, cyclin G2 in HNE2 and CNE1 was measured with RT-PCR. The cyclin G1 expression in HNE2 and CNE1 was weak, and cyclin G2 expression in the cytoplasm near cell membrane was strong, continuous, and homogeneous. The expression level of cyclin G1-mRNA in HNE2 was 2.097 ± 0.262, which was significantly higher than CNE1 (0.997 ± 0.286, P < 0.05); the expression level of cyclin G2-mRNA in HNE2 was 0.708 ± 0.107, which was significantly lower than CNE1 (1.216 ± 0.037, P < 0.05). Abnormal expression of cyclin G was closely related to tumor differentiation, the origin, and progression of NPC.


Analysis of factors associated with brittle response in patients with Parkinson's disease.
The brittle response (BR) in patients with Parkinson's disease (PD) refers to a special type of levodopa-induced dyskinesia (LID). This study aimed to describe the clinical characteristics of BR patients and to analyze the associated risk factors. A retrospective study was conducted to analyze the data of 97 patients with PD. Patients were divided into a BR group and a non-brittle response (NBR) group. Demographic and clinical data, motor symptoms, and non-motor symptoms of the two groups were assessed. Among 97 PD patients, 11 were in the BR group and 86 were in the NBR group. The proportion of female patients was 72.7% and 38.3%, respectively, in the BR and NBR groups (P < 0.05). Compared to NBR patients, BR patients had relatively low body weight, low BMI, long disease duration, high levodopa equivalent daily dosage (LEDD), and high levodopa dose per weight (P < 0.05). The BR group had significantly higher scores of UPDRS (II, III, and IV) (P < 0.05). But no difference was found in the UPDRS I, emotional state, cognitive status, and accompanied by REM sleep behavior disorder (RBD) (P> 0.05). Multivariate logistic regression analysis showed that BR patients had lower body weight and higher levodopa dose per weight. BR is associated with being female, low body weight, low BMI, long disease duration, high LEDD, and high levodopa dose per weight. Body weight and levodopa dose per body weight are independent risk factors for BR.


Altered distribution of synaptic densities at aberrant synapses in the chick cochlear nucleus.
The role of axon-target cell interactions in shaping the prevalence and distribution of synaptic densities was studied in an experimentally-induced aberrant functional projection from the chick cochlear nucleus (nuc. magnocellularis, NM) to the contralateral NM. Contact with an abnormal target appears to induce in the aberrant axons a pattern of presynaptic densities resembling that in normal cochlear nerve endings in NM. NM axon terminals induced similar numbers of postsynaptic densities (PSDs) per unit length of membrane apposition in both their normal and abnormal targets but the longer membrane apposition in the highly invaginated aberrant terminal in NM results in a significantly greater amount of postsynaptic density per ending. These auditory neurons thus appear able to adjust a variety of features to permit assembly and maintenance of a novel functional synapse.


DNA vaccines against enteric infections.
The first DNA vaccines for prevention of infectious diseases were described in 1993 and have since been shown to generate protective humoral and cellular immune responses to numerous infectious agents. For enteric infections, protective immunity has been obtained with DNA vaccines against several enteric viral, bacterial, and parasitic agents. Inoculation of DNA vaccines has generally been by intramuscular injection or by gene gun delivery of vaccine DNA-coated gold microparticles into the skin. Administration of DNA vaccines by the oral route would target the vaccines to enteric mucosal tissues, as well as providing a convenient means for vaccine delivery. Orally administered plasmid DNAs encapsulated in polymeric microparticles or inserted in live bacterial vectors have been effective in animal models for rotavirus DNA vaccines and Listeria monocytogenes DNA vaccines, respectively. Human trials of enteric DNA vaccines have not been initiated, but trials of veterinary vaccines have shown promise.


[Obturator dislocation of the hip joint].
Luxatio obturatoria may occur in the case of a trauma affecting the hip joint when the latter is in a position of flexion, abduction and external rotation. The femoral head dislocates anteriorly and caudally towards the foramen obturatum. A recent case will be presented with a discussion of the general aspects of this injury, with special emphasis on concomitant injuries and their significance of the long-term prognosis.


Does micropuncture technique really help reduce vascular complications?
Micropuncture technique (MPT) is being adapted nationally to reduce vascular complications (VC). We initiated a quality improvement project in our cath lab to reduce VCs utilizing MPT. We utilized MPT on all of our non-STEMI femoral artery (FA) access cases starting September 2016. As a comparator group, we collected data from April to August 2016. Anatomic localization of FA and fluoroscopic marking of femoral head was utilized in all cases. VCs were defined by BARC definitions for bleeding/hematomas, retroperitoneal bleed, pseudoaneurysm, AV fistula, arterial thrombosis, distal embolism, dissection, and transient limb ischemia. A total of 647 patients (Male 357, Female 290; MPT 333) were included in the analysis. MPT as compared to regular 18-gauge needle access did not demonstrate a reduction in VCs (2.4% vs. 2.2%; p = 1.0). MPT utilization did not affect the risk of VCs on univariate (OR 1.08; 95% CI 0.38-3.01; p = 0.88) or multivariate analysis (OR 0.91, 95% CI 0.28-2.93; p + 0.87). Vascular closure device (VCD) utilization as compared to manual/fem-stop hemostasis was the only factor that demonstrated a statistically significant and lower VC rate on both univariate (OR 0.28; 95% CI: 0.08-0.89; p = 0.03), and multivariate (OR 0.24; 95% CI 0.06-0.93; p = 0.039) analysis. Utilization of MPT in conjunction with fluoroscopic marking of the femoral head and without ultrasound guidance did not contribute to statistically significant reduction in the VC rate. The only factor found to be beneficial is utilization of VCDs. Further large randomized studies are required to demonstrate benefit of routinely utilizing MPT.


Visual feedback in treatment of residual phonological disorders.
The use of visual biofeedback in the treatment of individuals who have Residual Phonological Errors is discussed. This type of treatment was used with clients who had not improved through traditional auditory/production based treatments. Biofeedback is conceptualized as a cognitive treatment that requires the client's analysis of visual information. The information is used in developing correct productions of Residual Phonological Errors. The reported results indicate that visual feedback is a viable alternative treatment for those who have been unable to develop correct sound production through traditional methods.


Mechanisms underlying the effects of leukocyte apheresis with a fiber filter in a rat model of dextran sulfate sodium-induced colitis.
While several clinical trials have suggested that leukocytapheresis (LCAP) by filtration can benefit patients with active ulcerative colitis, the mechanisms underlying these benefits are largely unknown. The aim of this study was to address the mechanisms that may underlie the therapeutic effects of LCAP using a dextran sulfate sodium-induced colitis model in rats. Treatment with the active column, but not the sham column, improved disease severity by down-regulating pro-inflammatory events, including the cell-proliferative responses and inflammatory cytokine and reactive oxygen production, as well as by up-regulating protective events, including hepatocyte growth factor production, bone marrow-derived endothelial progenitor cell induction, and colonic blood flow levels, which were mediated predominantly by calcitonin gene-related peptide. The improvement was also associated with the increase of Ki-67 labeling in the colonic epithelium. In conclusion, the LCAP procedure was used in a dextran sulfate sodium-induced colitis model in rats under extracorporeal circulation conditions. This approach down-regulated pro-inflammatory events and up-regulated protective events in association with disease improvement. These data suggest that LCAP is feasible in animals and should shed light on the mechanisms of LCAP in clinical settings.


Attitudes of the elderly living independently towards the use of robots to assist with activities of daily living.
Robots are gaining attention as a potential solution to aging. The purpose of this study is to explore the attitude of robot assistance in Activities of Daily Living (ADLs) among elderly people living independently. The one-on-one interview, buddy robot video and questionnaire survey were used to analyze mean, median, range, and the test results of non-parametric statistical methods such as Wilcoxon sign-rank test statistic and one-sample Wilcoxon sign-rank test statistic, so as to explore the attitude of the elderly living independently towards robot-assisted ADLs and the acceptance of the use of robots in 32 ADLs. The results showed that there were significant differences in the attitudes, usability and ease of use of elderly people towards robot assistance before and after watching the Buddy Robot video and they had a more positive attitude after watching the video. According to the results, the elderly was more receptive to the use of robots in activities such as "reminding to carry objects" and "reminding to take medicine", while they were less receptive to the use of robots in the group or private activities such as "playing mahjong" and "taking a bath". The results showed that the elderly had a positive attitude towards the use of robot-assisted ADLs, and there were differences in the acceptance of robot-assisted ADLs. The results are helpful to understand the assistance needs and attitudes of the elderly, and provide a reference for the design of assistive robots that meet user needs, and ultimately improve the ability of the elderly to live independently at home.


An inventory of plants commonly used in the treatment of some disease conditions in Ogbomoso, South West, Nigeria.
This study was designed to take an inventory of medicinal plants, recipes and methods commonly used traditionally to treat some cardiovascular and inflammatory diseases in five local government areas in Ogbomoso, Oyo State, Nigeria. First-hand field survey through semi-structured questionnaire was employed in the 5 months study. A total of 101 plant species (medicinal plants (80.90%), spices (17.5%) and vegetables (1.53%)) belonging to 51 different families were mentioned for the treatment of various types of cardiovascular and inflammatory diseases. The survey revealed that 51.5% of the plants mentioned are used for the management of inflammatory diseases, 34.7% for the treatment of cardiovascular diseases and 11.9% of the plants are used for the treatment of both diseases. Euphorbiaceae (7.9%) are the most frequently used families of plants for the treatment of the various types of diseases mentioned, followed by Caesalpiaceae, (4.9%), Apocynoceae (4.9%) and Poaceae (4.9%). Fifty-nine recipes are usually prepared for the treatment of the six types of inflammatory diseases while twenty-three recipes are reportedly used for the treatment of the four types of cardiovascular diseases mentioned in this study. The recipes covered in the survey were mostly prepared from leaves (37.6%) and roots (23.8%) decoction or infusions. Medications are mostly administered orally with few numbers of the recipes showing side effect. The study has documented indigenous plants in Ogbomoso as a potential source for the development of new drugs for the treatment of cardiovascular and inflammatory diseases.


Chromosome 11 aberrations in small colony L5178Y TK-/- mutants early in their clonal history.
We have developed a cytogenetic technique that allows observation of chromosome rearrangements associated with TK-/- mutagenesis of the L5178Y/TK+/-3.7.2C cell line early in mutant clonal history. For a series of mutagenic treatments we show that the major proportion (93%) of small-colony (sigma) mutants studied have chromosome 11 rearrangements (the chromosome containing the thymidine kinase gene) while large-colony (lambda) mutants do not have detectable chromosome rearrangements. In addition, we find among the chromosome abnormalities in sigma mutants a significant proportion (34%) with dicentric chromosomes involving chromosome 11. These potentially unstable chromosome rearrangements may help to explain the karyotypic instability and heterogeneity among chromosome 11 aberrations previously noted in sigma mutants when they are analyzed later in their clonal history.


Stress fracture of the pelvis and lower limbs including atypical femoral fractures-a review.
Stress fractures, that is fatigue and insufficiency fractures, of the pelvis and lower limb come in many guises. Most doctors are familiar with typical sacral, tibial or metatarsal stress fractures. However, even common and typical presentations can pose diagnostic difficulties especially early after the onset of clinical symptoms. This article reviews the aetiology and pathophysiology of stress fractures and their reflection in the imaging appearances. The role of varying imaging modalities is laid out and typical findings are demonstrated. Emphasis is given to sometimes less well-appreciated fractures, which might be missed and can have devastating consequences for longer term patient outcomes. In particular, atypical femoral shaft fractures and their relationship to bisphosphonates are discussed. Migrating bone marrow oedema syndrome, transient osteoporosis and spontaneous osteonecrosis are reviewed as manifestations of stress fractures. Radiotherapy-related stress fractures are examined in more detail. An overview of typical sites of stress fractures in the pelvis and lower limbs and their particular clinical relevance concludes this review. Teaching Points • Stress fractures indicate bone fatigue or insufficiency or a combination of these. • Radiographic visibility of stress fractures is delayed by 2 to 3 weeks. • MRI is the most sensitive and specific modality for stress fractures. • Stress fractures are often multiple; the underlying cause should be evaluated. • Infratrochanteric lateral femoral fractures suggest an atypical femoral fracture (AFF); endocrinologist referral is advisable.


Integrated and finger-actuated microfluidic chip for point-of-care testing of multiple pathogens.
The integration of gel-based loop-mediated isothermal amplification (gLAMP) and finger-actuated microfluidic chip (μFAchip) was developed for the simultaneous detection of various different types of bacterial pathogens. The developed μFAchip consisted of three PDMS layers attached together by two adhesive tapes. Multiple chambers in the top PDMS layer were used for sample preparation, and the corresponding chambers in the bottom PDMS layer was used for long-term storage of LAMP reagents without DNA templates. The thin PDMS layer in the middle contained cross-shaped cuts as finger-actuated valves for fluid control. To reduce operation steps on the chip, such as pipetting and manipulation of samples, Whatman CloneSaver card was pre-embedded in the top chambers for on-chip DNA extraction and purification. Upon a simple press on the top layer, the finger-actuated valve was opened up, allowing DNA samples on the top layer flow into the bottom reaction chambers for gLAMP reaction. For POCT applications, on-chip LAMP reaction and imaging were conducted on a miniaturized peltier heater and a portable fluorescence imaging system respectively. Under the optimized condition, multiple pathogens were detected simultaneously with high selectivity and sensitivity (as low as 1.6 cells). The developed μFAchip provided a rapid and easy-to-operate platform for gLAMP-based pathogen detection, with the potential for in-field detection, especially in areas with limited resources.


Metaphyseal Stem Tip Location is a Risk Factor for Aseptic Loosening of Cemented Distal Femoral Replacements.
The objective of this study was to describe the incidence of aseptic loosening (AL) of cemented stem distal femoral replacements (DFR) and to identify modifiable risk factors for its development. A retrospective review was performed of 245 consecutive primary, cemented stem DFRs implanted at a single institution over a 40-year period. The primary outcome was revision surgery for AL. A multivariate analysis was performed to identify risk factors for AL. Radiographs were reviewed to identify stem tip location, which was defined as diaphyseal or metaphyseal. Implant survival to AL was compared using Kaplan-Meier analysis. AL and structural failure were the most common causes of implant failure (incidence 11.8%, 29/245). Younger age (P = .002), male sex (P = .01), longer resection length (P = .04), and nonmodular implants (P = .002) were all significantly associated with AL. After 1:1 matching, stem tip location in metaphyseal bone was independently associated with AL (P = .04). 36% (9/25) of implants that loosened had a stem tip located in the metaphysis vs only 8% (2/25) of implants that did not fail. 30-year survival to AL was lower for implants with a metaphyseal stem tip than implants with a diaphyseal stem tip (22.7% vs 47.6%; P = .11). A stem tip location in metaphyseal bone is associated with diminished survival to AL. When templating before DFR, stem tip location can assist in identifying high-risk reconstructions that may benefit from alternative or supplemental fixation techniques to prevent the development of AL.


Fabrication, characterization, and application of ternary magnetic recyclable Bi2WO6/BiOI@Fe3O4 composite for photodegradation of tetracycline in aqueous solutions.
We aim at fabricating a ternary magnetic recyclable Bi2WO6/BiOI@Fe3O4 composite that could be applied for photodegradation of tetracycline (TC) from synthetic wastewater. To identify any changes with respect to the composite's morphology and crystal structure properties, ΧRD, FTIR, FESEM-EDS, PL and VSM analyses are carried out. The effects of Fe3O4 loading ratio on the Bi2WO6/BiOI for TC photodegradation are evaluated, while operational parameters such as pH, reaction time, TC concentration, and photocatalyst's dose are optimized. Removal mechanisms of the TC by the composite and its photodegradation pathways are elaborated. With respect to its performance, under the same optimized conditions (1 g/L of dose; 5 mg/L of TC; pH 7; 3 h of reaction time), the Bi2WO6/BiOI@5%Fe3O4 composite has the highest TC removal (97%), as compared to the Bi2WO6 (63%). After being saturated, the spent photocatalyst could be magnetically separated from solution for subsequent use. In spite of three consecutive cycles with 71% of efficiency, the spent composite still has reasonable photocatalytic activities for reuse. Overall, this suggests that the composite is a promising photocatalyst for TC removal from aqueous solutions.


The transseptal approach to lesions of the pituitary and parasellar regions.
In a series of 505 consecutive procedures, the transseptal-transsphenoidal pituitary operation has proved safe and effective. The overall mortality in this series is 1.39%. A wide variety of sphenoid and sellar lesions and nearly every pituitary adenoma have been found suitable for the exposure provided through the sublabial-transseptal approach. This statement rests on the premise that both the rhinologist's and the neurosurgeon's skills are optimally applied to each case. The role of the otorhinolaryngologist is defined in this paper, and the benefits of the team approach are explored. An interpretive history of the transsphenoidal approach is presented, and the evolution of the transseptal technique developed at the Mayo Clinic from 1972 to 1978 is reviewed. Emphasizing the rhinologic aspects, all details of the surgical technique are described and illustrated. Our experience with the special endocrine syndromes is also reviewed to spotlight clinical features that require individual consideration by the rhinologic surgeon.


Balancing the customization and standardization: exploration and layout surrounding the regulation of the growing field of 3D-printed medical devices in China.
Medical devices are instruments and other tools that act on the human body to aid clinical diagnosis and disease treatment, playing an indispensable role in modern medicine. Nowadays, the increasing demand for personalized medical devices poses a significant challenge to traditional manufacturing methods. The emerging manufacturing technology of three-dimensional (3D) printing as an alternative has shown exciting applications in the medical field and is an ideal method for manufacturing such personalized medical devices with complex structures. However, the application of this new technology has also brought new risks to medical devices, making 3D-printed devices face severe challenges due to insufficient regulation and the lack of standards to provide guidance to the industry. This review aims to summarize the current regulatory landscape and existing research on the standardization of 3D-printed medical devices in China, and provide ideas to address these challenges. We focus on the aspects concerned by the regulatory authorities in 3D-printed medical devices, highlighting the quality system of such devices, and discuss the guidelines that manufacturers should follow, as well as the current limitations and the feasible path of regulation and standardization work based on this perspective. The key points of the whole process quality control, performance evaluation methods and the concept of whole life cycle management of 3D-printed medical devices are emphasized. Furthermore, the significance of regulation and standardization is pointed out. Finally, aspects worthy of attention and future perspectives in this field are discussed.


Molecular imaging in patients with mood disorders: a review of PET findings.
Mood disorders are chronic, recurrent psychiatric disorders with high morbidity rates that cause severe disability. Researchers have used molecular imaging extensively in studies of mood disorders. In this article, we concisely and selectively review the major findings of positron emission tomography studies of patients with mood disorders. Specifically, we describe findings from cerebral blood flow, cerebral glucose/oxygen metabolism, and radioligand studies in both cross-sectional and longitudinal investigations. Patients with mood disorders have mood-correlated regional metabolism changes and molecular abnormalities in several neurotransmitter systems. Although the findings of these studies are not completely consistent and confounding factors, including drug effects and specific methodology, should be strictly controlled, these results reveal the pathophysiology of mood disorders and aid the development of novel treatment approaches for mood disorders. Future positron emission tomography research will benefit greatly from the development of better radioligands to simultaneously identify multiple neurotransmitter systems in the specific brain region and the integration of more detecting methods in specifying the neurobiological predictors of treatment response in patients with mood disorders. Understanding the molecular mechanisms in underlying mood disorders will result in aetiological diagnosis and individualization of treatment of these disorders.


Integrating miRNA and mRNA Profiling to Assess the Potential miRNA-mRNA Modules Linked With Testicular Immune Homeostasis in Sheep.
Beyond its well-known role in spermatogenesis and androgen production, mammalian testes are increasingly recognized as an immune-privileged organ for protecting autoantigenic germ cells, especially meiotic and postmeiotic germ cells, from systemic immune responses. Despite its importance, the molecular mechanisms underlying this regulation in mammals, including sheep, are far from known. In this study, we searched for the genes associated with testicular immune privilege and assessed their possible modulating mechanisms by analyzing systematic profiling of mRNAs and miRNAs on testicular tissues derived from prepubertal and postpubertal Tibetan sheep acquired by RNA sequencing. We identified 1,118 differentially expressed (DE) mRNAs associated with immunity (245 increased mRNAs and 873 decreased mRNAs) and 715 DE miRNAs (561 increased miRNAs and 154 decreased miRNAs) in postpubertal testes compared with prepuberty. qPCR validations for 20 DE mRNAs and 16 miRNAs showed that the RNA-seq results are reliable. By using Western blot, the postpubertal testes exhibited decreased protein abundance of CD19 and TGFBR2 (two proteins encoded by DE mRNAs) when compared with prepuberty, consistent with mRNA levels. The subsequent immunofluorescent staining showed that the positive signals for the CD19 protein were observed mainly in Sertoli cells and the basement membrane of pre- and postpubertal testes, as well as the prepubertal testicular vascular endothelium. The TGFBR2 protein was found mostly in interstitial cells and germ cells of pre- and postpubertal testes. Functional enrichment analysis indicated that DE mRNAs were mainly enriched in biological processes or pathways strongly associated with the blood-testis barrier (BTB) function. Many decreased mRNAs with low expression abundance were significantly enriched in pathways related to immune response. Also, multiple key miRNA-target negative correlation regulatory networks were subsequently established. Furthermore, we verified the target associations between either oar-miR-29b or oar-miR-1185-3p and ITGB1 by dual-luciferase reporter assay. Finally, a putative schematic model of the miRNA-mRNA-pathway network mediated by immune homeostasis-related genes was proposed to show their potential regulatory roles in sheep testicular privilege. Taken together, we conclude that many immune-related genes identified in this study are negatively regulated by potential miRNAs to participate in the homeostatic regulation of testicular immune privilege of sheep by sustaining BTB function and inhibiting immune responses under normal physiological conditions. This work offers the first global view of the expression profiles of miRNAs/mRNAs involved in sheep testicular immune privilege and how the genes potentially contribute to immune-homeostatic maintenance.


Bizarre stromal cells in ischemic bowel disease.
The presence of bizarre stromal cells has been reported in gastrointestinal and extraintestinal lesions. We describe, for the first time, the presence of bizarre stromal cells with a cytomegalovirus (CMV)-like appearance or ganglion-like cells in 3 cases of ischemic colitis. The 3 patients were males ranging in age from 62 to 78 years, showed varying degrees of cardiovascular insufficiency, and were diagnosed with ischemic colitis. Colonic biopsies showed changes of ischemic colitis of variable severity. Common to all 3 cases, within the granulation tissue, stromal cells showed a broad spectrum of morphologic alterations, ranging from just nuclear enlargement to striking atypical features, large pleomorphic, hyperchromic nuclei, and eccentric prominent nucleoli. Occasionally, these cells displayed an eosinophilic oval nuclear inclusion, surrounded by a clear halo, resembling CMV inclusions. In conclusion, the etiopathogenesis of these cells can be partially explained by hypoxia, inflammation, regeneration/repair, and cell turnover alone or, more probably, in combination in the granulation tissue response to injury. The morphologic spectrum of bizarre stromal cells and ganglion-like cells suggests an obvious differential diagnosis, which includes carcinoma and sarcoma. The finding of enlarged cells with eccentric intranuclear eosinophilic inclusions requires the exclusion of CMV. However, immunohistochemistry, together with an awareness of those atypical stromal cells, can occur in the setting of ulceration and/or polypoid lesions, preventing an incorrect diagnosis.


Sodium tanshinone IIA sulfonate protects ARPE-19 cells against oxidative stress by inhibiting autophagy and apoptosis.
Oxidative stress in retinal pigment epithelium (RPE) is considered to be a major contributor to the development and progression of age-related macular degeneration (AMD). Previous investigations have shown that sodium tanshinone IIA sulfonate (STS) can alleviate oxidative stress in haemorrhagic shock-induced organ damage and cigarette smoke-induced chronic obstructive pulmonary disease in mice. However, whether STS has a protective effect in ARPE-19 cells under oxidative stress and its exact mechanisms have not yet been fully elucidated. In the present study, we utilized H2O2 to establish an oxidative stress environment. Our findings show that STS activated the PI3K/AKT/mTOR pathway to inhibit autophagy and diminished the expression of the autophagic proteins Beclin 1, ATG3, ATG7 and ATG9 in ARPE-19 cells under oxidative stress. Detection of the intrinsic apoptosis-related factors BAX, mitochondrial membrane potential (MMP), caspase-9, caspase-3 and BCL-2, as well as the extrinsic apoptosis-related factors c-FLIP, v-FLIP and caspase-8, confirmed that STS inhibited the intrinsic and extrinsic apoptotic pathways, and attenuated apoptosis in ARPE-19 cells under oxidative stress conditions. These findings shed new light on the protective effects of STS in ARPE-19 cells and its mechanisms under oxidative stress to provide novel and promising therapeutic strategies for AMD.


Role of functional activity of phagocytic mononuclear system in the formation of autoprostheses for angioplasty.
The possibility of formation of connective-tissue vascular prostheses on subcutaneously implanted polychlorovynil base was demonstrated in experiments on rats. Suppression of the function of phagocytic cell with carrageenan decelerates, while its stimulation with tamerit accelerates the formation of connective-tissue autoprostheses.


Antiprotozoal QSAR modelling for trypanosomiasis (Chagas disease) based on thiosemicarbazone and thiazole derivatives.
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, remains a neglected endemic infection that affects around 8 million people worldwide and causes 12,000 premature deaths per year. Traditional chemotherapy is limited to the nitro-antiparasitic drugs Benznidazole and Nifurtimox, which present serious side effects and low long-term efficacy. Several research efforts have been made over the last decade to find new chemical structures with better effectiveness and tolerance than standard anti-Chagas drugs. Among these, new sets of thiosemicarbazone and thiazole derivatives have exhibited potent in vitro activity against T. cruzi, especially for its extracellular forms (epimastigote and trypomastigote). In this work, we have developed three antiprotozoal quantitative structure-relationship (QSAR) models for Chagas disease based on the in vitro activity data reported as IC50 (μM) and CC50 (μM) over the last decade, particularly by Lima-Leite's group in Brazil. The models were developed using the replacement method (RM), a technique based on Multivariable Linear Regression (MLR), and external and internal validation methodologies, like the use of a test set, Leave-one-Out (LOO) cross-validation and Y-Randomization. Two of these QSAR models were developed for trypomastigotes form of the parasite Trypanosoma cruzi, one based on IC50 and the other on CC50 data; while the third QSAR model was developed for its epimastigotes form based on CC50 activity. Our models presented sound statistical parameters that endorses their prediction capability. Such capability was tested for a set of 13 hitherto-unknown structurally related aromatic cyclohexanone derivatives.


Risk analysis in persistent cervical lymphadenopathies: Malignant or benign?
The objective of the study was to determine the parameters that can be used to predict malignancy in persistent cervical lymphadenopathies. We retrospectively reviewed the files of 162 patients diagnosed with persistent cervical lymphadenopathy who underwent an excisional biopsy in our department between January 2011 and October 2019. Patient demographics and the size, side, duration, and localization of lymphadenopathy were recorded, and their relationship with histopathological results was investigated. Multiple regression analysis was used to determine the relationship between clinical parameters and malignancy. Of the 162 patients, 91 (56.2%) were male and 71 (43.8%) were female, and the mean age was 45.40±20.41 (2-84) years. Male gender (OR=3.099; p=0.003), increasing age (OR=1.029; p=0.002), short duration of lymphadenopathy (OR=0.989; p=0.048), and neck level V (OR=2.604; p=0.031) patients had a statistically significantly higher risk of malignancy. There was no statistically significant relationship between the side and size of the lymph node and the risk of malignancy (p>0.05). In our study, male gender was determined to be the most predictive risk factor for malignancy in patients with cervical lymphadenopathy, followed by lymph node neck level, increased age, and duration of the disease.


Attitudes associated with alcohol and marijuana referral actions by resident assistants.
This exploratory study examined associations between resident assistant (RA) attitudes and referral actions to identify training strategies for strengthening the ability of these paraprofessionals to recognize and refer college students in their living units who misuse alcohol and marijuana. The study's hypotheses were that (1) referral self-efficacy and perceived referral norms would be positively associated with RA referral actions and (2) perceived referral barriers and referral anticipatory anxiety would be negatively associated with RAs' referral actions. A total of 317 RAs at eight residential campuses in different regions of the U.S. took part in the study. All participating RAs had at least one semester of work experience. Just prior to the Fall semester of 2012, RA's responded to an online survey that assessed their alcohol and marijuana referral attitudes and referral actions. Overall, RAs reported considerable anxiety about approaching and referring students who may have an alcohol and/or marijuana problem. Perceived referral norms among RAs indicated substantial variability in perceptions about others' expectations of them for referring students who may have alcohol and marijuana problems. Results from two multivariable logistic regression analyses showed that referral self-efficacy distinguished RAs who took alcohol referral actions and marijuana referral actions from those who did not do so. Neither length of RA service nor time spent on campus was associated with referral actions. RA training programs could give attention to strengthening referral self-efficacy through a series of increasingly difficult skill-building activities during pre- and in-service training. In addition, senior residence life and housing professional staff may consider assessing the extent to which RAs under their supervision follow established protocols for assisting students with possible alcohol and marijuana problems. The development of evidence-based RA training programs will require additional research.


Specialty career preferences among final year medical students at Makerere University College of health sciences, Uganda: a mixed methods study.
Uganda has an imbalanced distribution of the health workforce, which may be influenced by the specialty career preferences of medical students. In spite of this, there is inadequate literature concerning the factors influencing specialty career preferences. We aimed to determine the specialty career preferences and the factors influencing the preferences among fifth year medical students in the School of Medicine, Makerere University College of Health Sciences (MakCHS). A sequential explanatory mixed methods study design with a descriptive cross-sectional study followed by a qualitative study was used. A total of 135 final year medical students in MakCHS were recruited using consecutive sampling. Self-administered questionnaires and three focus group discussions were conducted. Quantitative data was analysed in STATA version 13 (StataCorp, College Station, Tx, USA) using descriptive statistics, chi-square tests and logistic regression. Qualitative data was analysed in NVIVO version 12 (QRS International, Cambridge, MA) using content analysis. Of 135 students 91 (67.4%) were male and their median age was 24 years (IQR: 24, 26). As a first choice, the most preferred specialty career was obstetrics and gynecology (34/135, 25.2%), followed by surgery (27/135, 20.0%), pediatrics (18/135, 13.3%) and internal medicine (17/135, 12.6%). Non-established specialties such as anesthesia and Ear Nose and Throat (ENT) were not selected as a first choice by any student. Female students had 63% less odds of selecting surgical related specialties compared to males (aOR = 0.37, 95%CI: 0.17-0.84). The focus group discussions highlighted controlled lifestyle, assurance of a good life through better financial remuneration and inspirational specialists as facilitators for specialty preference. Bad experience during the clinical rotations, lack of career guidance plus perceived poor and miserable specialists were highlighted as barriers to specialty preference. Obstetrics and Gynecology, Surgery, Pediatrics and Internal Medicine are well-established disciplines, which were dominantly preferred. Females were less likely to select surgical disciplines as a career choice. Therefore, there is a need to implement or establish career guidance and mentorship programs to attract students to the neglected disciplines.


Parental mental illness and eating disorders in offspring.
To investigate which parental mental illnesses are associated with eating disorders in their offspring. We used data from a record-linkage cohort study of 158,679 children aged 12-24 years at the end of follow-up, resident in Stockholm County from 2001 to 2007, to investigate whether different parental mental illnesses are risk factors for eating disorders in their offspring. The outcome measure was diagnosis of any eating disorder, either from an ICD or DSM-IV code, or inferred from an appointment at a specialist eating disorder clinic. Mental illness in parents is a risk factor for eating disorders in female offspring (Adjusted Hazard Ratio (AHR) 1.57 (95% CI 1.42, 1.92), p < 0.0001). Risk of eating disorders is increased if there is a parental diagnosis of bipolar affective disorder (AHR 2.28 (95% CI 1.39, 3.72), p = 0.004), personality disorder (AHR 1.57 (95% CI 1.01, 2.44), p = 0.043) or anxiety/depression (AHR 1.57 (95% CI 1.32, 1.86), p < 0.0001). There is a lack of statistical evidence for an association with parental schizophrenia (AHR 1.41 (95% CI 0.96, 2.07), p = 0.08), and somatoform disorder (AHR 1.25 (95% CI 0.74, 2.13), p = 0.40). There is no support for a relationship between parental substance misuse and eating disorders in children (AHR 1.08 (95% CI 0.82, 1.43), p = 0.57). Parental mental illness, specifically parental anxiety, depression, bipolar affective disorder, and personality disorders, are risk factors for eating disorders in their offspring.