How do Trainers and Trainees use Formative Workplace-based Assessments of Operative Competence to Deliver and Receive Structured Feedback?
The aim of this study is to assess the quality of feedback provided to surgical trainees in the operating theatre, and to further investigate how trainees and trainers use workplace-based assessment in practice with regards to frequency and timing of assessments. A retrospective study of all submitted Supervised Structured Assessments of Operative Performance (SSAOPs) from April 25, 2016 to February 2, 2021 was conducted. Surgical trainees in the Republic of Ireland across all national surgical training sites submitted SSAOPs through an online platform. Assessments of operative competence (SSAOPs) from all Core Surgical Trainees (in their first two years of dedicated post-graduate surgical training) were included for analysis, regardless of surgical subspecialty. A total of 2294 assessments were submitted from April 25, 2016 to February 2, 2021 by 330 core surgical trainees and 379 surgeon assessors. Five hundred of these assessments were randomly selected and scored for quality of feedback using a modified "Task, Gap, Action (TGA)" framework. Of all 2294 submitted assessments, 1905 (83.04%) were submitted in the latter 3 months of each rotation, and 803 (35%) were submitted in the last month. Only 51 of 270 (18.89%) of trainees in their first year and 33 of 236 trainees in their second year (13.98%) submitted more than the minimum required number of assessments (6 per year). Of 500 randomly selected assessments, 362 (72.4%) had documented written feedback. The mean 'Gap' and 'Action' scores were low, at 0.44/3 and 0.53/3 respectively. Trainees do not submit more than the required number of operative workplace-based assessments. Assessments are submitted at the end of the trainee's rotation, limiting their formative value. The quality of written feedback is poor and could be improved significantly by encouraging a "Task," "Gap" and "Action" approach.


Role of CD19+ CD5+ CD1d+ Bregs in maintaining the Th17/Treg balance in mice with systemic lupus erythematosus complicated with atherosclerosis.
In this study, we aimed to investigate Bregs, their regulatory effects on Th17/Treg cell balance, and the release of downstream inflammatory factors in a mouse model of low-density lipoprotein receptor (LDLr)-/- + Pristane. After the establishment of the mouse model of systemic lupus erythematosus (SLE) complicated with atherosclerosis (AS), 8-week-old LDLr-/- + Pristane mice (n = 10) were included in the SLE + AS group. Furthermore, 8-week-old MRL/lpr and C57 mice were used as the SLE and normal control groups, respectively (n = 10 per group). After feeding the mice a high-fat diet for 14 weeks, peripheral blood and spleen of mice were collected, and Bregs, Th17, and Treg cells and related inflammatory factors were detected by flow cytometry, enzyme-linked immunosorbent assay, and reverse-transcription polymerase chain reaction. The number of Bregs and Tregs in spleen lymphocytes of SLE + AS mice significantly decreased compared with the C57 group (p < .05), whereas the number of Th17 cells significantly increased (p = .000). Furthermore, the proportion of Bregs showed a negative correlation with the Th17/Treg ratio (p = .03). Mice in the SLE + AS group showed higher serum interleukin (IL)-10, IL-17, and tumor necrosis factor-α levels than those in the SLE and C57 groups (p < .05). Furthermore, IL-35 and transforming growth factor (TGF)-β expression was reduced in the SLE + AS group compared with the C57 group (p < .05). The proportion of Breg decreases was negatively associated with increased Th17/Treg which was increased in SLE + AS mice, indicating that Bregs may regulate Th17/Treg cell homeostasis and cytokine release via IL-35 and TGF-β production.


Mechanism for bone disease found in inhabitants environmentally exposed to cadmium: decreased serum 1 alpha, 25-dihydroxyvitamin D level.
To investigate the mechanism for bone disease caused by exposure to cadmium serum samples were collected from 5 itai-itai disease patients, 36 Cd-exposed residents with renal tubular damage and 17 non-exposed individuals and analyzed for 1 alpha,25-dihydroxyvitamin D[1 alpha,25(OH)2D], parathyroid hormone, beta 2-microglobulin, calcium and inorganic phosphorus. Measurement of percentage tubular reabsorption of phosphate (%TRP) were performed only on the Cd-exposed subjects. Serum 1 alpha,25(OH)2D levels were lower in itai-itai disease patients and cadmium-exposed subjects with renal damage than in non-exposed subjects. Parathyroid hormone and beta 2-microglobulin concentrations in serum were higher in the Cd-exposed subjects. Decrease in serum 1 alpha,25(OH)2D levels were closely related to serum concentrations of parathyroid hormone, beta 2-microglobulin and %TRP. This study suggests that cadmium-induced bone effects were mainly due to a disturbance in vitamin D and parathyroid hormone metabolism, which was caused by the cadmium-induced kidney damage.


Sequential combination chemotherapy in advanced breast cancer.
The results of a prospective controlled study with alternating cycles of two effective non-cross resistant combinations in advanced breast cancer are reported. The two combinations consisted of adriamycin plus vincristine (AV) and cyclophosphamide, methotrexate and fluorouracil (CMF). The study was carried out with the main intent to obtain a higher incidence and a longer duration of response compared to that obtained with either combination alone. A total of 110 evaluable patients (55 for each treatment group) not previously treated with chemotherapy were randomly allocated to receive either Therapy A (2 AV followed by 2 CMF) or Therapy B (2 CMF followed by 2 AV). Complete plus partial response (53% vs 60%) as well as duration of remission (11 vs 12 months) were similar in both treatment groups. At the time of present analysis, 20 patients died from cancer (Therapy A: 9; Therapy B: 11) and in 9 of them death occurred during the first 12 months. The administration of sequential combinations was no more toxic than the administration of either combination alone.


Macroporous polyacrylamide monolithic gels with immobilized metal affinity ligands: the effect of porous structure and ligand coupling chemistry on protein binding.
Macroporous polyacrylamide gels (MPAAG) with iminodiacetic acid (IDA) functionality were prepared by (i) chemical modification of polyacrylamide gel, (ii) co-polymerization of acrylamide with allyl glycidyl ether (AGE) and N,N'metylene-bis(acrylamide) (MBAAm) followed by coupling IDA ligand or (iii) by copolymerization of acrylamide and MBAAm with functional monomer carrying IDA-functionality (1-(N,N-bis(carboxymethyl)amino-3-allylglycerol). Screening for optimized conditions for the production of the MPAAG with required porous properties was performed in a 96-well chromatographic format that allowed parallel production and analysis of the MPAAG prepared from reaction mixtures with different compositions. Scanning electron microscopy of the fabricated MPAAG revealed two different types of the porous structures: monomodal macroporous structure with large interconnected pores separated by dense non-porous pore walls in case of plain gels or gels produced via copolymerization with AGE. The other type of the MPAAG (gel produced via co-polymerization with functional monomer carrying IDA-functionality) had bimodal pore structure with large interconnected pores separated by the pore walls pierced through with micropores. The effect of different modifications of MPAAG monoliths and of porous structure of the MPAAG (monomodal and bimodal porous structure) on protein binding has been evaluated.


Value-based cognition and drug dependency.
Value-based decision-making is thought to play an important role in drug dependency. Achieving elevated levels of euphoria or ameliorating dysphoria/pain may motivate goal-directed drug consumption in both drug-naïve and long-time users. In other words, drugs become viewed as the preferred means of attaining a desired internal state. The bias towards choosing drugs may affect one's cognition. Observed biases in learning, attention and memory systems within the brain gradually focus one's cognitive functions towards drugs and related cues to the exclusion of other stimuli. In this narrative review, the effects of drug use on learning, attention and memory are discussed with a particular focus on changes across brain-wide functional networks and the subsequent impact on behaviour. These cognitive changes are then incorporated into the cycle of addiction, an established model outlining the transition from casual drug use to chronic dependency. If drug use results in the elevated salience of drugs and their cues, the studies highlighted in this review strongly suggest that this salience biases cognitive systems towards the motivated pursuit of addictive drugs. This bias is observed throughout the cycle of addiction, possibly contributing to the persistent hold that addictive drugs have over the dependent. Taken together, the excessive valuation of drugs as the preferred means of achieving a desired internal state affects more than just decision-making, but also learning, attentional and mnemonic systems. This eventually narrows the focus of one's thoughts towards the pursuit and consumption of addictive drugs.


Lipid lowering with PCSK9 inhibitors.
Statins are the most-effective therapy currently available for lowering the LDL-cholesterol (LDL-C) level and preventing cardiovascular events. Additional therapies are necessary for patients who cannot reach the target LDL-C level when taking the maximum-tolerated dose of a statin. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is an enzyme with an important role in lipoprotein metabolism. Rare gain-of-function mutations in PCSK9 lead to a high LDL-C level and premature coronary heart disease, whereas loss-of-function variants lead to a low LDL-C level and a reduced incidence of coronary heart disease. Furthermore, the PCSK9 level is increased with statin therapy through negative feedback, which promotes LDL-receptor degradation and decreases the efficacy of LDL-C lowering with statins. PCSK9 inhibition is, therefore, a rational therapeutic target, and several approaches are being pursued. In phase I, II, and III trials, inhibition of PCSK9 with monoclonal antibodies has produced an additional 50-60% decrease in the LDL-C level when used in combination with statin therapy, compared with statin monotherapy. In short-term trials, PCSK9 inhibitors were well tolerated and had a low incidence of adverse effects. Ongoing phase III trials will provide information about the long-term safety of these drugs, and their efficacy in preventing cardiovascular events.


Use of the Raman spectrometer in gemmological laboratories: review.
The current paper gives an overview of the development of Raman spectrometry in gemmological laboratories. While before 1990s, no commercial gemmological laboratory possessed such an instrument, all larger international labs have acquired these instruments by now. The Raman spectrometer is routinely used for the detection of emerald fillers, HPHT treatment of diamonds, analysis of the nature of a gemstone, analysis of gemstone inclusions and treatments, and the characterisation of natural or colour enhanced pearls and corals. Future developments in gemstone research lie in the closer analysis of the features of Raman and PL spectra and in the combination of several instruments.


Quantitative analyses of the global proteome and phosphoproteome reveal the different impacts of propofol and dexmedetomidine on HT22 cells.
Propofol and dexmedetomidine are both commonly used anaesthetics. Although they employ two different mechanisms to induce anaesthesia, both compounds influence the hippocampus and the HT22 cell line. HT22 cells are broadly used in neurobiological research. In this study, we assessed the effects of propofol and dexmedetomidine on signalling in HT22 cells. Using the SILAC (stable isotope labelling with amino acids in cell culture) labelling technique, IMAC (immobilized metal affinity chromatography) enrichment and high-resolution LC-MS/MS (liquid chromatography tandem mass spectrometry) analysis, we investigated the quantitative proteome and phosphoproteome in HT22 cells treated with propofol or dexmedetomidine. In total, 4,527 proteins and 6,824 phosphosites were quantified in cells treated with these two anaesthetics. With the assistance of intensive bioinformatics, the propofol and dexmedetomidine treatments were shown to induce distinct proteome and phosphoproteome profiles in HT22 cells. Consistent with our bioinformatics analysis, dexmedetomidine had a smaller effect than propofol on cell survival. These findings deepen our understanding of drug-induced anaesthesia.


Aortic bifurcation: a cadaveric study of its relationship to the spine.
Vascular injuries are the main complication of the anterior approach to the lumbosacral spines. One of the key procedural steps is the identification and gentle manipulation of the aortic bifurcation to prevent the vascular injury and provide the adequate exposure during anterior lumbosacral operation. The present study was to determine the level of abdominal aortic bifurcation in Thai cadavers. The abdominal aortic bifurcation was studied on 187 cadavers (132 men, 55 women). The average ages of the cadavers were 67.3 +/- 0.8 years (range from 30 to 88 years). The accurate site of the abdominal aortic bifurcation was determined by the relationship of the bifurcation with the level of neighbor lumbosacral spine. The abdominal aorta descended and bifurcated into two common iliac arteries at the level of L4 vertebra in 131 cases (70.1%), at the fourth lumbar intervertebral disc in 23 cases (12.3%), and at the level of L5 vertebra in 33 cases (17.6%). The precise location of aortic bifurcation is useful for surgeons in the anterior approach of the lumbosacral spine to prevent harmful vascular injury.


Splicing Analysis of 16 PALB2 ClinVar Variants by Minigene Assays: Identification of Six Likely Pathogenic Variants.
PALB2 loss-of-function variants are associated with significant increased risk of breast cancer as well as other types of tumors. Likewise, splicing disruptions are a common mechanism of disease susceptibility. Indeed, we previously showed, by minigene assays, that 35 out of 42 PALB2 variants impaired splicing. Taking advantage of one of these constructs (mgPALB2_ex1-3), we proceeded to analyze other variants at exons 1 to 3 reported at the ClinVar database. Thirty-one variants were bioinformatically analyzed with MaxEntScan and SpliceAI. Then, 16 variants were selected for subsequent RNA assays. We identified a total of 12 spliceogenic variants, 11 of which did not produce any trace of the expected minigene full-length transcript. Interestingly, variant c.49-1G > A mimicked previous outcomes in patient RNA (transcript ∆(E2p6)), supporting the reproducibility of the minigene approach. A total of eight variant-induced transcripts were characterized, three of which (∆(E1q17), ∆(E3p11), and ∆(E3)) were predicted to introduce a premature termination codon and to undergo nonsense-mediated decay, and five (▼(E1q9), ∆(E2p6), ∆(E2), ▼(E3q48)-a, and ▼(E3q48)-b) maintained the reading frame. According to an ACMG/AMP (American College of Medical Genetics and Genomics/Association for Molecular Pathology)-based classification scheme, which integrates mgPALB2 data, six PALB2 variants were classified as pathogenic/likely pathogenic, five as VUS, and five as likely benign. Furthermore, five ±1,2 variants were catalogued as VUS because they produced significant proportions of in-frame transcripts of unknown impact on protein function.


Lack of association between GTF2H4 genetic variants and AERD development and FEV1 decline by aspirin provocation.
Aspirin-exacerbated respiratory disease (AERD) is prevalent in about 10% of asthma patients and is characterized by a severe decline in forced expiratory volume in 1-s (FEV(1) ), an important phenotype for total lung capacity, upon ingestion of aspirin. The general transcription factor IIH subunit 4 (GTF2H4) is positioned at 6p21.33, a part of the major histocompatibility complex (MHC) class II region that contains a number of genes that play an important role in the immune system. In addition, genetic variants in another general transcription factor IIH gene have revealed significant association with lung disease. To investigate whether GTF2H4 genetic variants could be a causative factor for AERD development and FEV(1) decline by aspirin provocation, five common single-nucleotide polymorphisms (SNPs) were genotyped in 93 patients with AERD and 96 aspirin-tolerant asthma (ATA) controls. As a result, when adjusted for age, gender, smoking status and atopy as covariates, the rs1264307 variant and two haplotypes showed nominal signals in the association with AERD (P = 0.02-0.04), but the significances disappeared after corrections for multiple testing (corrected P > 0.05). In further multiple regression analysis, no genetic variants of GTF2H4 showed significant associations with FEV(1) decline by aspirin provocation in asthmatics (P > 0.05). Despite the need for replications in larger cohorts, our preliminary findings suggest that GTF2H4 variants may not be associated with susceptibility to AERD and obstructive symptoms in asthmatics.


Applications of biomaterials in plastic surgery.
The expansion of the application of biomaterials in plastic surgery has led to the increased availability of commercial products in recent years. This overview discusses soft tissue fillers, bioengineered skins, acellular dermal matrices, biomaterials for craniofacial surgery, and peripheral nerve repair. We summarize indications, properties, uses, types, advantages and disadvantages of some of the currently available products from each category. Finally, the current state of development in drug delivery system is also briefly summarized.


Cloacal myiasis by Lucilia spp. (Diptera: Calliphoridae) in a rooster (Gallus gallus domesticus) and two Harris's hawks (Parabuteo unicinctus).
In this study, cloacal myiasis caused by dipterans of Lucilia genus was found in a rooster (Gallus gallus domesticus) and two Harris's hawks (Parabuteo unicinctus) from Peru. Larval dipteran were collected and preserved in ethanol. Morphological analysis indicated two species: Lucilia sericata in the rooster and in one Harris's hawk, and Lucilia cuprina in the other Harris's hawk. Molecular analysis confirmed the diagnosis by amplification of the nucleotide sequences of the cytochrome c oxidase subunit 1 gene and internal transcribed spacer 2 region. The sequences were compared with sequence references from a public sequence database, which showed a 100% matched identity. This study demonstrated for first time cloacal myiasis by L. sericata in a domestic bird from Peru and in Harris's hawk. Also, for the first time, L. cuprina was found in a bird of prey.


Task-specific measures of balance efficacy, anxiety, and stability and their relationship to clinical balance performance.
The main objective of this research was to investigate the effects of postural threat on performance of three clinical balance tests. Thirty-one healthy young adults performed quiet stance, maximal reach, and one-leg stance tasks at two levels of postural threat, which was modified through the use of a hydraulic lift. Increased postural threat significantly affected postural control measures for both simple and dynamic balance tests. Physiological and state anxiety increased as a result of increased postural threat whereas ratings of perceived stability and balance efficacy were reduced as a function of increased postural threat. Efforts to diagnose balance disorders based on balance performance may be confounded by the influence of psychological factors.


Pharmacokinetics of 17 alpha hydroxyprogesterone caproate in singleton pregnancy and its influence of maternal body size measures.
Reducing spontaneous preterm deliveries is a worldwide public health priority. Although many interventions have been studied, 1 of the most effective treatments to decrease recurrent preterm birth is the use of weekly 17 alpha hydroxy progesterone caproate. Previous studies on the influence of excessive adipose tissue and obesity on the use of 17 alpha hydroxyprogesterone caproate for the prevention of recurrent spontaneous preterm deliveries have shown conflicting findings. To estimate the pharmacokinetics of weekly17 alpha hydroxyprogesterone caproate in singleton and to evaluate the effect of maternal body size on the pharmacokinetics parameters. A prospective, open-label, longitudinal design was implemented for this population pharmacokinetic study. Plasma samples and clinical variables were collected in pregnant women between 16 and 36 weeks' gestational age, carrying a singleton pregnancy and receiving 17 alpha hydroxyprogesterone caproate, 250 mg intramuscularly weekly for the prevention of recurrent spontaneous preterm birth. Pharmacokinetics parameters and significant clinical covariates were estimated using mixed effect modeling. Four body size indicators were used in the model to predict pharmacokinetics parameters: lean body weight, total body weight, body mass index, and body surface area. A total of 56 pregnant women, aged 18-44 years with body mass index of 14.5-54.6 kg/m2, provided 114 17 alpha hydroxyprogesterone caproate plasma samples concentration for analysis. A 1-compartment model with first-order absorption satisfactorily described 17 alpha hydroxyprogesterone caproate pharmacokinetics. Compared to other body size indicators, lean body weight best explained intersubject variability. Age, race, and gestational age did not influence 17 alpha hydroxyprogesterone caproate pharmacokinetics. Lean body weight was the best descriptor for the influence of body size on 17 alpha hydroxyprogesterone caproate apparent clearance. Simulations showed that administration of a standard fixed dose of 250 mg intramuscularly produced substantially lower 17 alpha hydroxyprogesterone caproate plasma concentrations in pregnant women with body mass index >30 kg/m2 compared to those with body mass index <30 kg/m2. Conversely, adjustment of the standard dose for differences in total body weight among women resulted in markedly higher 17 alpha hydroxyprogesterone caproate concentrations in women with body mass index >30 kg/m2 compared to women with lower body mass index. Administration of doses adjusted for lean body weight produced nearly identical 117 alpha hydroxyprogesterone caproate plasma concentrations in both the low- and high-body mass index groups. Population pharmacokinetics analysis indicates the clearance significantly increases with increasing lean body mass. Higher 17 alpha hydroxyprogesterone caproate doses, adjusted by maternal lean body mass, may be required in patients with a body mass index >30 to achieve equivalent plasma concentrations in pregnant women with a body mass index <30. Adjustment of 17 alpha hydroxyprogesterone caproate doses for lean body weight produces equivalent systemic 17 alpha hydroxyprogesterone caproate exposure in pregnant women regardless of body size.


Screening for second malignancies in mycosis fungoides: non-Hodgkin lymphoma, Hodgkin lymphoma, lung cancer, bladder cancer and melanoma.
Patients with mycosis fungoides (MF) are at increased risk of developing non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), lung cancer, bladder cancer and melanoma. The characteristics of patients developing these malignancies have not been specifically delineated. In addition, there are no established guidelines for screening MF patients for second malignancies. We identified 742 patients with MF who developed second malignancies in the Surveillance Epidemiology and End Result-18 database. The majority of second malignancy patients were white and male, mean age 55-67 years at diagnosis of MF, and mean age 61-72 years at diagnosis of second malignancy. The majority of patients diagnosed with second malignancies had early stage MF. MF patients with NHL, lung cancer, and bladder cancer tended to be diagnosed at earlier stages of the second malignancy than patients without MF and demonstrated better 5-year overall survival. There was no improvement in stage at diagnosis or survival for MF patients who were diagnosed with melanoma compared to patients without MF. Improvements in survival in MF/NHL, MF/lung cancer and MF/bladder cancer patients may reflect differences in disease biology secondary to having MF or the importance of increased contact with the healthcare system. MF/melanoma data suggest that patients require regular pigmented-lesion-focused skin examinations. Tools for screening include regular lymph node examinations, pigmented-lesion-focused examinations and detailed review of systems questions. Smoking cessation counseling is key intervention in this population, as is ensuring that all age- and sex-specific cancer screenings are up-to-date (e.g. lung cancer screening, mammography, and colonoscopy). The utility of regular imaging for second malignancy screening and lab testing such as routine urinalysis requires additional study and expert consensus.


Quantitative structure-permeability relationships (QSPRs) for percutaneous absorption.
Quantitative structure-permeability relationships (QSPRs) have been derived by many researchers to model the passive, diffusion-controlled, percutaneous penetration of exogenous chemicals. Most of these relationships are based on experimental data from the published literature. They indicate that molecular size (as molecular weight) and hydrophobicity (as the logarithm of the octanol-water partition coefficient; log k(ow)) are the main determinants of transdermal penetration. This article reviews the current state of the art in QSPRs for absorption of chemicals through the skin, and where this technology can be exploited in future research. The main shortfalls in QSPR models result from inconsistency and error of the experimental values used to derive them. This is probably caused by the manner in which they employ data from a variety of sources and, in some cases, slightly different experimental protocols. Further, most current models are based on data generated from either aqueous or ethanolic solution, where each penetrant is present at its saturated solubility or a fraction of its saturated solubility. No models currently account for the influences of formulation upon percutaneous penetration. Current QSPR models provide a significant tool for assessing the percutaneous penetration of chemicals. They may be important in determining the bioavailability of a range of topically applied exogenous chemicals, and in issues of dermal toxicology and risk assessment. However, their current use may be limited by their lack of applicability across different formulation types. As a consequence, their true value may be to make predictions within specific formulation types, as opposed to a general model based on a range of formulation types. In addition, the endpoint of models may be inappropriate for specific applications other than the systemic delivery of topically applied chemicals.


Anterior hip dislocation with simultaneous anterior column and anterior wall acetabular fracture: A case report.
Isolated anterior column and anterior wall fractures are a relatively rare subgroup of acetabular fractures. They represent 6,3% of all acetabular fractures. Surgical treatment is indicated for fractures with displacement more than 5 mm and when incongruence of the articular surface and/or instability of the joint is evident, in order to allow early mobilization and prevent further complications, such as posttraumatic hip arthritis. Open reduction and internal fixation is the usual standard of care. Closed reduction and percutaneous fixation can be performed in minimally displaced fractures. In the herein article, we describe the unique combination of anterior hip dislocation along with anterior column and anterior wall fractures in a middle-aged patient, after a fall from small height. A 56-year-old female patient was brought to the emergency department after an accidental fall from height less than 2 m. Upon arrival her right hip was abducted, shortened and externally rotated. CT scan of the pelvis revealed anterior dislocation of the right hip, an impaction injury of the femoral head, and fractures of anterior column and anterior wall of the acetabulum. Closed reduction of the hip was performed. Open reduction and internal fixation of the fractures was carried out utilizing the extended Smith-Petersen approach in a scheduled manner 5 days after admission. At one-year follow-up after the injury the patient had returned to all of her pre-injury activities and she was able to walk exercising full weight bearing without residual pain. Anterior hip dislocation with simultaneous isolated anterior column and anterior wall fracture is an injury of rare incidence. Orthopaedic surgeons treating fractures should be aware of this entity and the herein article can serve as a reference regarding the management of such an uncommon injury.


Collapse-to-emergency medical service cardiopulmonary resuscitation interval and outcomes of out-of-hospital cardiopulmonary arrest: a nationwide observational study.
The relationship between collapse to emergency medical service (EMS) cardiopulmonary resuscitation (CPR) interval and outcome has been well documented. However, most studies have only analyzed cases of cardiac origin and Vf (ventricular fibrillation)/pulseless VT (ventricular tachycardia). We sought to examine all causes of cardiac arrest and analyze the relationship between collapse-to-EMS CPR interval and outcome in a nationwide sample using an out-of-hospital cardiac arrest (OHCA) registry. This was a retrospective observational study based on a nationwide OHCA patient registry in Japan between 2005 and 2008 (n = 431,968). We included cases where collapse was witnessed by a bystander and where collapse and intervention time were recorded (n = 109,350). Data were collected based on the Utstein template. One-month survival and neurologically favorable one-month survival were used as outcome measures. Logarithmic regression and logistic regression were used to examine the relation between outcomes and collapse-to-EMS CPR interval. Among collapse-to-EMS CPR intervals between 3 and 30 minutes, the logarithmic regression equation for the relationship with one-month survival was y = -0.059 ln(x) + 0.21, while that for the relationship with neurologically favorable one-month survival was y = -0.041 ln(x) + 0.13. After adjusting for potential confounders in the logistic regression analysis for all intervals, longer collapse-to-EMS CPR intervals were associated with lower rates of one-month survival (odds ratio (OR) 0.93, 95% confidence interval (CI): 0.93 to 0.93) and neurologically favorable one-month survival (OR 0.89, 95% CI 0.89 to 0.90). Improving the emergency medical system and CPR in cases of OHCA is important for improving the outcomes of OHCA.


Derivation and validation of the SEER-Medicare myelodysplastic syndromes risk score (SMMRS).
Accruing data since 2001, the SEER-Medicare dataset is an outstanding resource for MDS-related comparative effectiveness research; however, although several MDS prognostic models exist, complete data required to calculate them are not available therein. Using SEER-Medicare as a training and internal validation set (n=9820) and clinical data at our institution as an external validation set (n=307), we created a new MDS risk score (the SMMRS) for use with SEER-Medicare. Risk stratification by the SMMRS was comparable to the IPSS (net reclassification improvement index was 0.0), demonstrating that it is a useful research tool to stratify MDS patients in studies using SEER-Medicare.


Dopaminergic modulation of the septo-hippocampal cholinergic system activity under stress.
The effects of the dopaminergic agonist apomorphine or the antagonist sulpiride on high affinity choline uptake and newly synthesized acetylcholine release by hippocampal synaptosomal preparations, were examined in rats subjected to immobilization stress. Increased dopamine uptake by septal synaptosomal preparations was taken as evidence for increased mesoseptal dopaminergic activity in response to stress. While apomorphine treatment failed to alter choline uptake or acetylcholine release in unhandled rats, it did however prevent the stress-induced increase in these cholinergic parameters. In contrast, after treatment with sulpiride both choline uptake and acetylcholine release were increased in unhandled rats, as they were after acute stress. Acute stress of sulpiride treated rats however resulted in changes similar to those produced by administration of either sulpiride or stress separately. We conclude that the mesoseptal dopaminergic system plays an important role in modulating the activity of the septo-hippocampal cholinergic system under stress.


[Percutaneous transluminal angioplasty. An efficient alternative in the treatment of peripheral obstructive arteriopathy].
At the present, patients with obstructive vascular disease in the lower extremities can be treated with percutaneous procedures without surgery. By what is called Interventional Radiology. Three patients with iliac or femoral arterial obstructions were treated with Percutaneous Transluminal Angioplasty (PTA). For all of them, claudication was the principal symptom and was treated with PTA due the failure of regular treatment. The dilatation was performed with high pressure balloon. Both technical and clinical results showed success and there were no complications.


The heterogeneity in financial and time burden of caregiving to children with chronic conditions.
We examine the financial and time burdens associated with caring for children with chronic conditions, focusing on disparities across types of conditions. Using linked data from the 2003 to 2006 National Health Interview Survey and 2004-2008 Medical Expenditure Panel Survey, we created measures of financial burden (out-of-pocket healthcare costs, the ratio of out-of-pocket healthcare costs to family income, healthcare costs paid by insurance, and total healthcare costs) and time burden (missed school time due to illness or injury and the number of doctor visits) associated with 14 groups of children's chronic conditions. We used the two-part model to assess the effect of condition on financial burden and finite mixture/latent class model to analyze the time burden of caregiving. Controlling for the influences of other socio-demographic characteristics on caregiving burden, children with chronic conditions have higher financial and time burdens relative to caregiving burdens for healthy children. Levels of financial burden and burden sharing between families and insurance system also vary by type of condition. For example, children with pervasive developmental disorder or heart disease have a relatively low financial burden for families, while imposing a high cost on the insurance system. In contrast, vision difficulties are associated with a high financial burden for families relative to the costs borne by others. With respect to time burden, conditions such as cerebral palsy and heart disease impose a low time burden, while conditions such as pervasive developmental disorder are associated with a high time burden. This study demonstrates that differences exist in caregiving burden for children by type of chronic condition. Each condition has a unique profile of time and financial cost burden for families and the insurance system. These results have implications for policymakers and for families' savings and employment decisions.


Deletion of 11q24.2-qter in a male child with cleft lip and palate: an atypical feature of Jacobsen syndrome.
Jacobsen syndrome (JS) is caused by the terminal deletion at the long arm of chromosome 11. It is characterized by growth retardation, intellectual disability, facial dysmorphism, and other congenital abnormalities. The subband 11q24.1 has been confirmed to be the critical region for the typical features of JS. The patient in the current study is a 2-year-old male child with prominent craniofacial abnormalities and congenital heart disease. High-resolution single-nucleotide polymorphism arrays revealed breakage in chromosome 11q beginning at 11q24.2, with complete deletion of the distal portion. We collected all available reports describing patients with breakages at 11q24.1 or 11q24.2, and compared it with the typical features of JS. We found that the phenotype of cleft lip and palate (CLP) was present in both groups of patients with no overlap region in the deletion region (between 11q21-q23 and 11q24.2-qter), which indicated that other genes may be related to CLP in JS.


Concurrent and Predictive Validity of AND-ASPEN Malnutrition Consensus Is Satisfactory in Hospitalized Patients: A Longitudinal Study.
Subjective Global Assessment (SGA) is the reference method to identify hospital malnutrition. The Academy of Nutrition and Dietetics and American Society for Parenteral and Enteral Nutrition (AND-ASPEN) proposed a more objective consensus, but studies regarding its validity are still scarce. This study aimed to evaluate the concurrent and predictive validity of the AND-ASPEN Consensus. Prospective cohort conducted with hospitalized adult and elderly patients. At admission, general data were collected and patients were evaluated by SGA and AND-ASPEN with and without handgrip strength (HGS) for nutrition diagnoses. Patients were followed up for collection of outcomes-length of hospital stay (LOS), in-hospital death, readmission, and mortality within 6 months after being discharged. Concurrent and predictive validity were tested. Six hundred patients (55.7 ± 14.8 years, 51.3% males) were evaluated. The median of LOS was 10.0 (5.018.0) days and in-hospital mortality was 2.7%. SGA identified 34.0% and AND-ASPEN 34.6% of patients as malnourished. AND-ASPEN had substantial agreement with SGA (κ = 0.690) and satisfactory accuracy (AUC = 0.85; 95% CI, 0.810.88). Malnutrition defined by AND-ASPEN predicted about 1.4 times higher risk of prolonged LOS (95% CI, 1.2-1.6) and hospital readmission (95% CI, 1.2-1.8), besides 5.0 times higher risk of hospital death (95% CI, 1.3-18.8) and 6 months' death (95% CI, 2.6-9.9), in an adjusted analysis. The validity of AND-ASPEN without HGS was also satisfactory. AND-ASPEN can be used for malnutrition diagnoses, even without HGS because it has satisfactory concurrent and predictive validity.


Identification of novel mutation in RANKL by whole-exome sequencing in a Thai family with osteopetrosis; a case report and review of RANKL osteopetrosis.
Osteopetrosis is a rare form of skeletal dysplasia characterized by increased bone density that leads to bone marrow failure, compressive neuropathy, and skeletal dysmorphism. Molecular diagnosis is essential as it guides treatment and prognosis. We report Thai siblings with an ultra-rare form of osteopetrosis. The older brother and the younger sister presented with chronic mandibular osteomyelitis in their 20s. Since childhood, they had visual impairment, pathological fracture, and skeletal dysmorphism. Quadruplet whole-exome sequencing was performed and confirmed with Sanger sequencing. Novel mutation in TNFSF11 (RANKL) c.842T>G, p.Phe281Cys was identified in a homozygous state in both siblings. Surgical debridement, antibiotic, and hyperbaric oxygen therapy were used and discontinued over a 6-month period with normalization of C-reactive protein. Hematopoietic stem cell transplantation candidacy was excluded by molecular diagnosis. We report a novel mutation in an ultra-rare form of osteopetrosis. Our siblings manifested with a milder phenotype in comparison with nine cases previously published.


Head-repositioning does not reduce the reproducibility of fMRI activation in a block-design motor task.
It is hypothesized that, based upon partial volume effects and spatial non-uniformities of the scanning environment, repositioning a subject's head inside the head coil between separate functional MRI scans will reduce the reproducibility of fMRI activation compared to a series of functional runs where the subject's head remains in the same position. Nine subjects underwent fMRI scanning where they performed a sequential, oppositional finger-tapping task. The first five runs were conducted with the subject's head remaining stable inside the head coil. Following this, four more runs were collected after the subject removed and replaced his/her head inside the head coil before each run. The coefficient of variation was calculated for four metrics: the distance from the anterior commisure to the center of mass of sensorimotor activation, maximum t-statistic, activation volume, and average percent signal change. These values were compared for five head-stabilization runs and five head-repositioning runs. Voxelwise intraclass correlation coefficients were also calculated to assess the spatial distribution of sources of variance. Interestingly, head repositioning was not seen to significantly affect the reproducibility of fMRI activation (p<0.05). In addition, the threshold level affected the reproducibility of activation volume and percent signal change.


Application of lambda Red recombination system to Vibrio cholerae genetics: simple methods for inactivation and modification of chromosomal genes.
The lambda Red-based recombination system is very useful for genetic manipulation of some Gram-negative bacteria. Here we report simple procedures for the inactivation and modification of genes of interest on Vibrio cholerae chromosome using this recombination technique. For this purpose, a polymerase chain reaction (PCR) fragment carrying an antibiotic resistance cassette flanked by regions homologous to the target locus was electroporated into recipient V. cholerae strains expressing a highly proficient lambda Red recombination system. Two PCR procedures were tested to generate an amplification product carrying an antibiotic resistance cassette flanked by short (50 or 100 nt) or long (1000 nt) homologous extensions, which allowed successful disruption of four chromosomal loci (ctxB, toxT, lacZ, and recA). Our results suggest that 100-nt homology between the PCR product and the target gene is sufficient to stimulate the lambda Red-dependent recombination. To increase recombination efficiency, however, the PCR procedure should be used to generate a product with 1000-nt homologous extensions. Furthermore, we applied this gene replacement method to create lacZ reporter fusion to the target gene. Transcriptional fusion to the V. cholerae ctxA gene was constructed using a PCR product that contains the 100-nt homologous extension to ctxA on each side of the lacZ::cat cassette, and was shown to respond appropriately to a null mutation in the regulatory gene, toxT. Use of the techniques presented here should prompt rapid and efficient mutagenesis/modification of V. cholerae chromosomal genes.


Prevention of human cancer by modulation of chronic inflammatory processes.
Chronic inflammation induced by biological, chemical and physical factors has been associated with increased risk of human cancer at various sites. Inflammation facilitates the initiation of normal cells and their growth and progression to malignancy through production of pro-inflammatory cytokines and diverse reactive oxygen and nitrogen species. These also activate signaling molecules involved in inflammation and carcinogenesis such as nuclear transcription factor (NF-kappaB), inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Several chemopreventive agents act through inhibition of signaling pathways (e.g. NF-kappaB), inhibition of oxidant-generating enzymes (e.g. iNOS) and mediators of inflammation (e.g. COX-2), scavenging reactive oxygen and nitrogen species, and modulation of xenobiotic-metabolizing enzymes (especially phase II enzyme induction). Some anti-inflammatory drugs have been tested in clinical trials to prevent human cancer at several sites. Better understanding of the molecular mechanisms by which chronic inflammation increases cancer risk will lead to further development of new strategies for cancer prevention at many sites.


Cholesterol content of serum lipoprotein fractions in children maintained on chronic hemodialysis.
Lipoprotein analyses were performed on serum samples from nine hemodialyzed children, 8 to 18 years old, and from nine pair-matched control children. Cholesterol was measured by gas-liquid chromatography in lipoprotein fractions separated by polyacrylamide gel electrophoresis. Total serum triglycerides and cholesterol levels were higher in the hemodialyzed group. Very low density lipoprotein cholesterol concentration was higher. The increase of low density lipoprotein cholesterol concentration and the decrease of high density lipoprotein cholesterol concentration were not significant, but the ratio of the low density lipoprotein cholesterol to the high density lipoprotein cholesterol was increased. These results outline the potential risk of premature atherosclerosis in uremic children on maintenance hemodialysis. In addition, lipoprotein cholesterol reference values are presented from a group of 113 healthy children.


Targeted dendrimer chemotherapy in an animal model for head and neck squamous cell carcinoma.
Nanoparticle drug delivery offers a potential solution in the treatment of cancer. Using a heterotopic tumor model for head and neck squamous cell carcinoma (HNSCC), tumors of variable folate binding protein-alpha (FBP-α) have been treated to delineate receptor necessity as well as efficacy and toxicity of folate targeted chemotherapy. University of Michigan Squamous Cell Carcinoma (UM-SCC) and American Type Culture Collection (ATCC) cell lines were screened using quantitative real-time polymerase chain reaction for FBP-α expression. Acetylated generation 5 dendrimers conjugated to the targeting moiety folic acid and the therapeutic moiety methotrexate were fabricated and administered to severe combined immunodeficiency (SCID) CB-17 mice inoculated with UM-SCC-1, UM-SCC-17B, and UM-SCC-22B cancer cells. Mice were injected with targeted therapy, free methotrexate, or saline control and monitored for drug efficacy and toxicity. Targeted therapy was effective relative to receptor level expression. Targeted therapy could be delivered in molar doses 3 times that of free drug. The treatment of a high folate expression tumor cell population was noted to have increased efficacy over saline (P < .01) and free methotrexate (P = .03) as well as decreased systemic toxicity. This report represents the first translation of dendrimer-based chemotherapy to HNSCC and underscores its effectiveness as an antitumor agent in human cancer cell lines with lower levels of FBP-α than the in vitro and in vivo models previously reported.


Primary prophylaxis in haemophilia care: Guideline update 2016.
This paper reviews the current status on recommendations or guidelines for primary prophylaxis based on recent published papers from organizations or group of experts as well as some original key papers. A rather uniform view exists that prophylaxis should be initiated at an early age before or after no more than a single joint bleed and, if possible, preferably be continued for life. The dose and dose frequency of prophylaxis is dependent on the goal of treatment, bleeding phenotype, compliance, venous access and economic resources in the health care system and should be tailored individually based on clinical outcome and pharmacokinetics. For children, the effectiveness of prophylaxis is more dependent on maintaining minimum trough levels than in adults. Novel extended half-life products are being introduced, which should not affect the decision on when to start prophylaxis nor the initial dose, but which may be helpful for patients with difficult venous access and which may enable higher trough levels of factor VIII.


Lipoprotein-Like Nanoparticle Carrying Small Interfering RNA Against Spalt-Like Transcription Factor 4 Effectively Targets Hepatocellular Carcinoma Cells and Decreases Tumor Burden.
Patients with advanced hepatocellular carcinoma (HCC) are often unable to tolerate chemotherapy due to liver dysfunction in the setting of cirrhosis. We investigate high-density lipoprotein (HDL)-mimicking peptide phospholipid scaffold (HPPS), which are nanoparticles that capitalize on normal lipoprotein metabolism and transport, as a solution for directed delivery of small interfering RNA (siRNA) cargo into HCC cells. Spalt-like transcription factor 4 (SALL4), a fetal oncoprotein expressed in aggressive HCCs, is specifically targeted as a case study to evaluate the efficacy of HPPS carrying siRNA cargo. HPPS containing different formulations of siRNA therapy against SALL4 were generated specifically for HCC cells. These were investigated both in vitro and in vivo using fluorescence imaging. HPPS-SALL4 effectively bound to scavenger receptor, class B type 1 (SR-BI) and delivered the siRNA cargo into HCC cells, as seen in vitro. HPPS-SALL4 effectively inhibited HCC tumor growth (P < 0.05) and induced a 3-fold increase in apoptosis of the cancer cells in vivo compared to HPPS-scramble. Additionally, there was no immunogenicity associated with HPPS-SALL4 as measured by cytokine production. Conclusion: We have developed unique HDL-like nanoparticles that directly deliver RNA interference (RNAi) therapy against SALL4 into the cytosol of HCC cells, effectively inhibiting HCC tumor growth without any systemic immunogenicity. This therapeutic modality avoids the need for hepatic metabolism in this cancer, which develops in the setting of cirrhosis and liver dysfunction. These natural lipoprotein-like nanoparticles with RNAi therapy are a promising therapeutic strategy for HCC.


Association of peripheral total and differential leukocyte counts with metabolic syndrome and risk of ischemic cardiovascular diseases in patients with type 2 diabetes mellitus.
There is increasing evidence that leukocytes play a central role in obesity, glucose intolerance, type 2 diabetes mellitus (T2DM), and cardiovascular diseases, but the role of differential leukocytes in metabolic syndrome (MetS) and atherosclerosis is largely unknown. The aim of this study was to examine the relationship between the component features of MetS and peripheral leukocyte counts and to explore whether leukocyte counts are associated with clustering of MetS and macrovascular diseases in patients with T2DM. 1872 subjects with T2DM who enrolled in a diabetes disease management program were studied. The definition of MetS was modified from that outlined by the criteria of NCEP-ATP III. Areas under the receiver-operating characteristic curve and odds ratios at various intervals of the WBC counts were computed. The peripheral total leukocyte, monocyte, and neutrophil cell counts are increased parallel to the clustering of components of MetS. When white cell counts were analyzed per quartile and as continuous variables after adjustment for age, sex, and other known risk factors with multiple regression analysis, peripheral total leukocyte, monocyte, neutrophils, and lymphocyte counts were independently and significantly associated with specific features of clustering of MetS and prevalence of ischemic cardiovascular diseases. Leukocyte counts, especially neutrophil/lymphocyte ratio, in addition with MetS is associated with the risk of ischemic cardiovascular diseases. Our results indicate that differential leukocyte counts are associated with MetS and that peripheral leukocytes may play a role in the pathogenesis of macrovascular complications in patients with T2DM.


A novel purgative protocol for capsule endoscopy of the small bowel produces better quality of visibility than 2 l of PEG: Timing is of the essence.
The ideal way of preparing patients for small-bowel capsule endoscopy has been controversial. Previous studies have shown that ingestion of 2 l of polyethylenglycol (PEG) 12 hours prior to capsule ingestion leads to improved visibility in comparison to no preparation at all. We speculated that using a post-ingestion (PI), booster-based cleansing protocol might provide an alternative to the PEG cleansing protocol. This randomized, blinded, prospective study enrolled 45 individuals. Patients were allocated to either of two groups. The PEG group ingested 2 l PEG 12 hours prior to the exam (n = 22) and the PI group ingested one sachet of Picolax® dissolved in 250 ml of water one hour after swallowing the capsule with 500 ml of water (n = 18). Primary endpoints were overall small bowel and distal third of small bowel cleansing levels. Secondary endpoints were average gastric and small-bowel transit time. Forty-five patients participated in this study. Five individuals were excluded because of incomplete study. Percentage of patients with adequate visibility in the distal third of the small bowel in the PEG group was 9% vs 72% in the PI group (p < 0.0001). Average gastric time and total transit time were shorter in the PI group vs the PEG group (p = 0.0065). Timing of ingestion of the Picolax® purgative 60 minutes after swallowing the capsule endoscopy delivers better visibility in the distal third of the small bowel than the accepted cleansing protocol of ingesting 2 l PEG 12 hours prior to the capsule endoscopy procedure.


Effect of different patterns of low-frequency stimulation on piriform cortex kindled seizures.
Low-frequency stimulation (LFS) is an antiepileptic and antiepileptogenic electrical stimulation. In this study the effect of changes in some LFS (1Hz, monophasic square wave) parameters (intensity, pulse duration and train duration) on piriform cortex kindled seizures was investigated both in fully kindled rats and during kindling acquisition. In fully kindled animals, application of different patterns of LFS immediately before kindling stimulation had no significant effect on seizure parameters. However, daily (15 min) application of LFS (0.1 ms pulse duration at intensity equal to after-discharge threshold (ADT) and 1 ms pulse duration at intensity equal to 1/4 ADT) during inter-seizure interval of 7 days significantly reduced the stage 5 duration of the next kindled seizure. Application of the same two LFS protocols for 3 days and 2 weeks had no effect on seizure parameters. The effect of LFS was also tested using different paradigms during kindling acquisition. When LFS (0.1 and 1 ms pulse duration, intensity equal to ADT and 1/4 ADT) was delivered daily after each kindling stimulation, it could significantly decrease after-discharge duration in various days during kindling development. In this experiment, only LFS with 0.1 ms pulse duration and intensity equal to ADT significantly delayed the appearance of seizure stages 1 and 2. According to obtained results, it may be concluded that in fully kindled rats application of different patterns of LFS before kindling stimulation has no anticonvulsant effect, but it can exert an inhibitory effect when applied during an inter-seizure interval of 7 days. In addition, LFS has antiepileptogenic effect during kindling acquisition. These effects depend on the applied LFS parameters (e.g. intensity, pulse duration and train duration).


Daphnia populations are similar but not identical in tolerance to different protease inhibitors.
Cyanobacterial blooms often produce different classes and chemical variants of toxins such as dietary protease inhibitors (PIs) that affect the keystone grazer Daphnia. However, it has been shown that Daphnia populations are able to locally adapt to frequently occurring dietary PIs by modulating their digestive proteases. Up until now, local adaptation has exclusively been tested by making use of single cyanobacterial strains and by measuring average population tolerance. In contrast, we measured juvenile somatic growth rates and egg numbers of several individual clones per each of three different D. magna populations that have previously been found to be either tolerant or sensitive to the Microcystis strain BM25. Clones from the three D. magna populations were either treated with BM25 that produces three different protease inhibitor variants of the class of Ahp-cyclodepsipeptides or another Microcystis strain that produces two other Ahp-cyclodepsipeptide variants. Subsequently, the population growth was calculated as mean of the single-clone growth rates. Both tolerant populations (which originate from ponds with a cyanobacterial history) proved to be similarly tolerant to both Microcystis strains. However, single genotypes of the populations differed in their response to the different strains. Both the tolerant and the sensitive populations contained both sensitive and tolerant genotypes but in different proportions. Furthermore, the genotypes from the sensitive population showed a higher variance in response to one or both strains. Trade-offs between somatic growth rate and clutch size were found in one of the tolerant populations that originated from a pond where cyanobacteria were frequent in the past but completely absent since the pond's restoration. Because of those intra-population difference, we conclude that the tolerant populations were putatively selected by different Ahp-cyclodepsipeptide variants in the past and that all populations still possess the potential to adapt to other environmental conditions by genotype frequency shifts.


Controlling low rates of cell differentiation through noise and ultrahigh feedback.
Mammalian tissue size is maintained by slow replacement of de-differentiating and dying cells. For adipocytes, key regulators of glucose and lipid metabolism, the renewal rate is only 10% per year. We used computational modeling, quantitative mass spectrometry, and single-cell microscopy to show that cell-to-cell variability, or noise, in protein abundance acts within a network of more than six positive feedbacks to permit pre-adipocytes to differentiate at very low rates. This reconciles two fundamental opposing requirements: High cell-to-cell signal variability is needed to generate very low differentiation rates, whereas low signal variability is needed to prevent differentiated cells from de-differentiating. Higher eukaryotes can thus control low rates of near irreversible cell fate decisions through a balancing act between noise and ultrahigh feedback connectivity.


Definition and validation of SNOMED CT subsets using the expression constraint language.
SNOMED CT Expression Constraint Language (ECL) is a declarative language developed by SNOMED International for the definition of SNOMED CT Expression Constraints (ECs). ECs are executable expressions that define intensional subsets of clinical meanings by stating constraints over the logic definition of concepts. The execution of an EC on some SNOMED CT substrate yields the intended subset, and it requires an execution engine able to receive an EC as input, execute it, and return the matching concepts. An important issue regarding subsets of clinical concepts is their use in terminology binding between clinical information models and terminologies for defining the set of valid values of codified data. To define and implement methods for the simplification, semantic validation and execution of ECs over a graph-oriented SNOMED CT database, and to provide a method for the visual representation of subsets in order to explore, understand and validate its content, as well as to develop an EC execution platform, called SNQuery, which makes use of these methods. Since SNOMED CT is a directed and acyclic graph, we have used a graph-oriented database to represent the content of SNOMED CT, where the schema and instances are represented as graphs and the data manipulation is expressed by graph-oriented operations. For the execution of ECs over the graph database, it is performed a translation process in which ECs are translated into a set of Cypher Query Language queries. We have defined some EC simplification methods that leverage the logic structure underlying SNOMED CT. The purpose of these methods is to reduce the complexity of ECs and, in turn, its execution time, as well as to validate them from a SNOMED CT Concept Model and logical definition points of view. We also have developed a graphic representation based on the circle packing geometrical concept, which allows validating subsets, as well as pre-defined refsets and the terminology itself. We have developed SNQuery, a platform for the definition of intensional subsets of SNOMED CT concepts by means of the execution of ECs over a graph-oriented SNOMED CT database. Additionally, we have incorporated methods for the simplification and semantic validation of ECs, as well as for the visualization of subsets as a mechanism to understand and validate them. SNQuery has been evaluated in terms of EC execution times. In this paper, we provide methods to simplify, semantically validate and execute ECs over a graph-oriented database. We also offer a method to visualize the intensional subsets obtained by executing ECs to explore, understand and validate them, as well as refsets and the terminology itself. The definition of intensional subsets is useful to bind content between clinical information models and clinical terminologies, which is a necessary step to achieve semantic interoperability between EHR systems.


Bedbugs (Cimicidae infestation): the worldwide renaissance of an old partner of human kind.
Bedbugs have been known as a human parasite for thousands of years, but scientific studies about this insect are recent and limited. Cimex lectularius, the common bedbug, was a well-known parasite in human dwellings until the end of the Second World War. Nowadays, bedbugs are considered uncommon in the industrialized world. Anecdotal reports suggest that bedbugs are getting more common in the United States, Canada, and United Kingdom. In Brazil, there are few reports about bedbug infestations in the literature. The aim of this article was to alert physicians, especially in Brazil, about this ectoparasitosis, including aspects of the bedbug biology, their parasitism in human host, treatment and prophylaxis.


Overview of Head Muscles with Special Emphasis on Extraocular Muscle Development.
The head is often considered the most complex part of the vertebrate body as many different cell types contribute to a huge variation of structures in a very limited space. Most of these cell types also interact with each other to ensure the proper development of skull, brain, muscles, nerves, connective tissue, and blood vessels. While there are general mechanisms that are true for muscle development all over the body, the head and postcranial muscle development differ from each other. In the head, specific gene regulatory networks underlie the differentiation in subgroups, which include extraocular muscles, muscles of mastication, muscles of facial expression, laryngeal and pharyngeal muscles, as well as cranial nerve innervated neck muscles. Here, I provide an overview of the difference between head and trunk muscle development. This is followed by a short excursion to the cardiopharyngeal field which gives rise to heart and head musculature and a summary of pharyngeal arch muscle development, including interactions between neural crest cells, mesodermal cells, and endodermal signals. Lastly, a more detailed description of the eye development, tissue interactions, and involved genes is provided.


Determining the optimal pulse number for theta burst induced change in cortical excitability.
Theta-burst stimulation (TBS) is a form of non-invasive neuromodulation which is delivered in an intermittent (iTBS) or continuous (cTBS) manner. Although 600 pulses is the most common dose, the goal of these experiments was to evaluate the effect of higher per-dose pulse numbers on cortical excitability. Sixty individuals were recruited for 2 experiments. In Experiment 1, participants received 600, 1200, 1800, or sham (600) iTBS (4 visits, counterbalanced, left motor cortex, 80% active threshold). In Experiment 2, participants received 600, 1200, 1800, 3600, or sham (600) cTBS (5 visits, counterbalanced). Motor evoked potentials (MEP) were measured in 10-min increments for 60 min. For iTBS, there was a significant interaction between dose and time (F = 3.8296, p = 0.01), driven by iTBS (1200) which decreased excitability for up to 50 min (t = 3.1267, p = 0.001). For cTBS, there was no overall interaction between dose and time (F = 1.1513, p = 0.33). Relative to sham, cTBS (3600) increased excitability for up to 60 min (t = 2.0880, p = 0.04). There were no other significant effects of dose relative to sham in either experiment. Secondary analyses revealed high within and between subject variability. These results suggest that iTBS (1200) and cTBS (3600) are, respectively, the most effective doses for decreasing and increasing cortical excitability.


Hepatitis C virus infection facilitates gallstone formation.
Bile duct damage and hepatic steatosis are two characteristic histological findings in hepatitis C virus infection; and high prevalence of hepatitis C antibody is noted in patients with cholangiocarcinoma. The purpose of the present study was to examine the relationship between biliary diseases and hepatitis C virus infection. Persons who received a general checkup in Chang Gung Memorial Hospital between 2000 and 2002 were included. All of them had hemogram, serum biochemistry, hepatitis B surface antigen, hepatitis C antibody and ultrasonography studies. The prevalence of gallbladder stone, bile duct stone and gallbladder polyp/cholesterolosis were compared in different viral infection groups. Of the 28 486 persons, 22 967 were negative for both hepatitis B surface antigen and hepatitis C antibody (group NBNC), 4152 were hepatitis B surface antigen carriers (broup B), 1195 were positive for hepatitis C antibody (group C), and 172 were positive for both markers. The 379 persons (1.3%) having had cholecystectomy were considered to have gallbladder stone at the time when cholecystectomy was done. Gallbladder stone was found in 6.0% persons of group NBNC, 5.4% in group B and 11.7% in group C. The prevalence of gallbladder stone in group C was found especially high for age groups 31-40 years and 61-70 years. The prevalence of bile duct stone was higher in group C (0.4%) than in group NBNC or B (both 0.1%). Stepwise logistic regression analysis showed that age, liver cirrhosis, body mass index, hepatitis C virus infection and gender were independent factors associated with gallbladder stone. Hepatitis C virus infection facilitates gallstone formation.


Regulation of the renal Na-HCO3 cotransporter: VII. Mechanism of the cholinergic stimulation.
Cholinergic agents regulate proximal tubule acidification but the mechanism responsible for this effect is unclear. We examined the effect of the cholinergic agent carbachol on the activity of the Na-HCO3 cotransporter in primary cultures of the proximal tubule of the rabbit. The activity of the cotransporter was assayed either as HCO3-dependent 22Na uptake or as the recovery of intracellular pH in cells perfused continuously with Cl-free physiologic solution containing amiloride to block the Na-H antiporter. Carbachol caused a dose-dependent stimulation of the cotransporter activity with a maximum increase of 90% above control values at 10(-5) M and half maximal stimulation at 10(-7) M. The stimulation was blocked by atropine and pirenzepine indicating an effect through the M1 muscarinic receptor. Carbachol increased intracellular calcium fourfold and the rise in cytosolic calcium was prevented by the intracellular calcium chelator, BAPTA. BAPTA also blocked the effect of carbachol on the cotransporter. Because carbachol activates phospholipase C and protein kinase C, we examined the effect of carbachol in the presence of the phospholipase C inhibitor, U73122, or the PKC inhibitor, calphostin C, or PKC depletion. The phospholipase C inhibitor prevented both the effect of carbachol on the cotransporter and on the intracellular Ca. Calphostin C and PKC depletion also prevented the stimulation of the cotransporter. Carbachol increased PKC activity and caused translocation of the PKC to the particulate fraction. We also examined the effect of the phosphatase inhibitor, calyculin A or the calmodulin kinase inhibitor, W-13 on carbachol stimulation. Calyculin A and W13 likewise prevented the carbachol-induced stimulation of the cotransporter. These results demonstrate that cholinergic stimulation modulated the activity of the cotransporter through multiple pathways including phospholipase C/PKC and phosphatase systems.


Effects of antiestrogen versus antiprogestin on transformed and nontransformed steroid receptors.
In order to determine if different physicochemical properties exist among antihormone-receptor complexes, we have compared the interaction of the antiprogestin RU486 with progesterone receptor (PR) versus the triphenylethylene antiestrogen H1285 (4-(N,N-diethyl-aminoethoxy)-4'-methoxy-alpha-(p-hydroxyphenyl-alp ha'- ethylstilbene] with estrogen receptor (ER) from rabbit uterine tissue. Contrary to other reports, we observed no difference in the sedimentation properties of transformed PR (4S) when bound by the antagonist RU486 versus the progesterone agonist R5020 in either cytosol or DEAE partially-purified receptor preparations analyzed on sucrose gradients containing 0.3 M KCl. In addition, we found no difference in the sedimentation properties of these receptor preparations in the presence of 10 mM sodium molybdate: the nontransformed RU486-PR and nontransformed R5020-PR both sedimented as a 6S species. These same results were obtained when the receptor preparation and gradient analysis were performed in the absence of monothioglycerol. Likewise, there was no change in the sedimentation properties of the transformed PR when the receptor, partially purified in the absence of molybdate, was analyzed on sucrose gradients containing 10 mM sodium molybdate to prevent receptor alteration during centrifugation. From DNA-cellulose assays performed with partially purified PR in the absence of molybdate we determined that the 4S form of R5020-PR and RU486-PR is transformed receptor; whereas in the presence of molybdate, the 6S species is nontransformed. In contrast, we found a different pattern of sedimentation when comparing transformed antiestrogen-receptor complexes with transformed estrogen-receptor complexes. In this case, transformed H1285-ER sedimented as 6S and estradiol-ER sedimented as 4S. We conclude from these experiments that these two antihormones, RU486 and H1285, may have different mechanisms of action in their antagonism of steroid hormone action. Antiestrogen stabilizes the salt-transformed ER as a dimer while antiprogestin appears to permit dissociation of the oligomeric form of the receptor to the monomeric form.


Comparison of inductively coupled mass spectrometry and ultra low-level gamma-ray spectroscopy for ultra low background material selection.
The main target of this study is the development and the validation of an internal procedure to measure the pg g(-1) levels, of naturally occurring radioisotopes to select ultra low background detector materials. As there are no ultra low-level certified reference materials commercially available, the performance of ICP-MS was compared with the well established ultra low-level gamma-spectroscopy. This work shows also the reliability of very quick ICP-MS semi-quantitative analyses of an environmental matrix such as a geological sample treated according to conventional protocols.


A randomized clinical trial of PTFE versus human umbilical vein for femoropopliteal bypass surgery. Preliminary results.
PTFE (Goretex) and modified human umbilical vein (Biograft) vascular grafts were compared in femorodistal popliteal artery bypass surgery in a randomized clinical multicentre trial. During 18 months 104 patients (104 limbs) entered the trial. Twenty-five patients suffered from claudication, 54 suffered rest pain and 25 patients had ulceration or gangrene. The median preoperative ankle-arm blood pressure index was 0 . 34. Twenty-three limbs had 3 patent tibial arteries, 45 limbs had 2 tibial arteries, 31 limbs had 1 tibial artery while 5 limbs had an isolated popliteal segment. Thirty-six of the operations were redo-operations. Fifty-four patients were allocated to PTFE and 50 to umbilical vein. During follow-up (maximum 650 days) 24 PTFE grafts occluded against 12 umbilical veins. The 1-year patency rate was 40 per cent in the PTFE group against 75 per cent in the umbilical vein group (P = 0 . 014, Gehans test). During the first year the PTFE failure rate was on average 3 . 1 times higher than that of the umbilical vein.


Are intra-operative gastric drainage procedures necessary in esophagectomy: a systematic review and meta-analysis.
Surgical pyloroplasty or pyloromyotomy are often performed during esophagectomy with a view of improving gastric conduit drainage. However, the clinical importance of this is not clear, and some centers opt to omit this step. The aim of this meta-analysis is to compare the rates of pulmonary complications, anastomotic leak, mortality, delayed gastric emptying, and the need for further pyloric intervention, in patients undergoing esophagectomy with and without a drainage procedure. A database search of Medline, EMBASE, and Cochrane Library was performed to identify randomized control trials and cohort studies published between 2000 and 2020 which compared outcomes of esophagectomy with and without drainage procedures. A random-effects meta-analysis model was used to compare the rates of pulmonary complications, anastomotic leak, mortality, delayed gastric emptying, and the need for further pyloric intervention. Three randomized and 12 non-randomized publications were identified, comprising a total of 2339 patients. No significant differences were found between the two groups with regard to pulmonary complications (RR 1.02 [95% CI, 0.78-1.33], p = 0.91), anastomotic leak (RR 1.14 [95% CI, 0.80-1.62], p = 0.48), mortality (RR 0.53 [95% CI, 0.23-1.26], p = 0.15), delayed gastric emptying (RR 0.98 [95% CI, 0.59-1.62], p = 0.93), and the need for further pyloric intervention (RR 1.99 [95% CI, 0.56-7.08], p = 0.29). Where post-operative pyloric treatment is available on demand, surgical pyloric drainage procedures may not have any significant clinical impact on patient outcomes for patients undergoing esophagectomy, though further good-quality randomized controlled trials are needed to confirm this.


Automated Detection of Vulnerable Plaque for Intravascular Optical Coherence Tomography Images.
Vulnerable plaque detection is important to acute coronary syndrome (ACS) diagnosis. In recent years, intravascular optical coherence tomography (IVOCT) imaging has been used for vulnerable plaque detection. Current automated detection methods adopt the traditional image classification and object detection algorithms, such as the logistic regression model, SVM, and Haar-Adaboost, to detect vulnerable plaques. The detection quality of these methods is relatively low. The aim of this study is to improve the detection quality of vulnerable plaque. We propose an automatic detection system of vulnerable plaque for IVOCT images based on deep convolutional neural network (DCNN). The system is mainly composed of four modules: pre-processing, deep convolutional neural networks (DCNNs), post-processing, and ensemble. The IVOCT images input to DCNNs are firstly pre-processed by using the methods of de-noising and data augmentation. Then multiple DCNNs are used to detect the vulnerable plaques in the IVOCT images; the vulnerable plaque regions and their corresponding labels and scores are output. Next, the output results of each network are processed by the post-processing module. We propose three algorithms, union of intersecting regions, duplicated region processing, and small gaps removal for post-processing. Finally, the output detection results of multiple networks are combined using a proposed combining method in ensemble module. We evaluated the proposed method in a dataset of 300 IVOCT images. Experimental results show that our system can achieve a precision rate of 88.84%, a recall rate of 95.02%, and an overlap rate of 85.09%; the detection quality score is 88.46%. The proposed algorithms can detect vulnerable plaques with superior performance; our system can be used as an auxiliary diagnostic tool for vulnerable plaque detection in IVOCT images.


[A clinical study on changes of EGF in serum before and after endoscopic surgery in patients with chronic sinusitis disease].
To evaluate the changes of epidermal growth factor (EGF) in serum before and after endoscopic surgery in patients with chronic sinusitis, and then to explore its clinical significance. Serum was collected before and after operation and EGF concentrations were measured by the radioimmunoassay at different times. EGF levels in patients with chronic sinusitis (1.24 +/- 0.41) microg/L were higher than that in control group (0.92 +/- 0.23) microg/L, but there were no significantly difference between them (P > 0.05). The concentrations of EGF were reduced after surgery, and the lowest were evaluated after 4 weeks. Significant difference of EGF concentrations were found between before and 4 weeks after operation (P < 0.01). The concentration of EGF were raised 6 weeks after surgery, and returned to normal after 8 weeks. The changes of EGF in serum before and after endoscopic surgery may relate with the epithelization process of sinus mucosa after endoscopic surgery.


Relationship between objectively measured physical activity on neuropathology and cognitive outcomes in older adults: Resistance versus resilience?
Physical activity (PA) is associated with better cognitive and brain health. However, it remains unclear whether PA relates to accumulation of disease pathology ("resistance") or indirectly moderates adverse effects of pathology on cognition ("cognitive resilience"). Five hundred thirteen Rush Memory and Aging Project (MAP) decedents completed longitudinal actigraphy monitoring, cognitive testing, and neuropathological examination. Cross-sectional models tested the relationship between average PA and pathology, and the moderating effect of baseline PA on the association between pathology and cognition. Longitudinal models examined whether changes in PA moderated associations between pathology and cognition. PA was negatively associated with Lewy body disease (LBD), but positively associated with Alzheimer's disease (AD) burdens. Baseline PA attenuated the association between cerebrovascular pathology and cognition, whereas longitudinal change in PA attenuated associations between AD, cerebral amyloid angiopathy, TAR DNA-binding protein 43, and atherosclerosis on cognitive decline. Whereas PA relates to "cognitive resilience" against cerebrovascular disease, AD, and other neuropathologies, "resistance" effects were limited.


Correlation between choline signal intensity and acetylcholine level in different brain regions of rat.
Acetylcholine is an important excitatory neurotransmitter, which plays a crucial role in synaptic transmission. The level of acetylcholine is decreased in the early stages of Alzheimer disease (AD), the most common neurodegenerative disease. Therefore, measurement of acetylcholine in the brain may help the clinical diagnosis of AD. However, the methods used till now to detect the brain acetylcholine level are invasive, which are neither recommended nor acceptable in the clinic. Acetylcholine is synthesized from choline-containing compounds (Cho), the latter can be estimated by noninvasive proton magnetic resonance spectroscopy ((1)H MRS). To explore whether the Cho signal intensity could be used to represent the acetylcholine level in the brain, we employed (1)H MRS to detect the Cho signal, and simultaneously, we also used microdialysis and high-performance liquid chromatography (HPLC) to measure the level of acetylcholine in hippocampus, striatum, frontal cortex, and somatosensory barrel field (S1BF cortex) of rats, respectively. The results showed that the correlations between Cho signal intensity and acetylcholine level in hippocampus, striatum, frontal cortex, and S1BF cortex were, respectively, 0.823 (p = 0.044), 0.851 (p = 0.032), 0.817 (p = 0.047), and 0.822 (p = 0.045). The F-values of the regression model were, respectively, 8.404 (p = 0.044), 10.47 (p = 0.032), 8.000 (p = 0.047), and 8.326 (p = 0.045). And the derived regression equations were y = 0.67x + 1.363 (hippocampus), y = 5.398x + 6.684 (striatum), y = 0.656x + 0.564 (frontal cortex), and y = 0.394x + 1.127 (S1BF cortex), respectively (y means acetylcholine, and x means Cho). These data suggest that the Cho signal intensity observed by (1)H MRS may be used as an indicator of acetylcholine level in different brain regions of the rats.


Hippocampal Oxidative Stress Induced by Radiofrequency Electromagnetic Radiation and the Neuroprotective Effects of Aerobic Exercise in Rats: A Randomized Control Trial.
The present study determined whether 4 weeks of moderate aerobic exercise improves antioxidant capacity on the brain of rats against oxidative stress caused by radiofrequency electromagnetic radiation emitted from cell phones. Responses of malondialdehyde, catalase, glutathione peroxidase, and superoxide dismutase, as well as the number of hippocampal dead cells, were examined. Male Wistar rats (10-12 wk old) were randomly assigned to 1 of 4 groups (N = 8): (1) moderate aerobic exercise (EXE) (2 × 15-30 min at 1215 m/min speed with 5 min of active recovery between sets), (2) exposure to 900/1800 MHz radiofrequency electromagnetic waves 3 hours per day (RAD), (3) EXE + RAD, and (4) exposure to an experimental phone without battery. Following the exposure, the number of the hippocampal dead cells was significantly higher in group RAD compared with groups EXE, EXE + RAD, and control group. Malondialdehyde concentration in group RAD was significantly higher than that of groups EXE, EXE + RAD, and control group. Also, the activity of catalase, glutathione peroxidase, and superoxide dismutase in groups EXE, EXE + RAD, and control group was significantly higher compared with those of the exposure group. This study demonstrated that moderate aerobic exercise enhances hippocampal antioxidant capacity against oxidative challenge in the form of radiofrequency electromagnetic waves.


Ebstein cardiac anomaly, functional pulmonary atresia and isovaleric acidemia: A case report.
In this report, we present a rare association between Ebstein anomaly (EA) and isovaleric acidemia (IVA) in a newborn who was admitted to our cardiac center. He underwent for PDA stenting to maintain adequate pulmonary blood flow, later he developed recurrent metabolic acidosis, prominent sweaty feet odor, neutropenia and thrombocytopenia. His organic acids profile in the urine confirmed the diagnosis of IVA. To the best of our knowledge, there is no association between these two rare diseases. We are presenting this case report to highlight this rare association.


One new flavonoid from Solanum rostratum.
One new flavonoid, 5,7,8,4'-tetrahydroxy-3-methoxyflavone-8-O-β-d-xylopyranoside (2), along with other four known flavones (1, 3-5) were isolated from the aerial parts of Solanum rostratum. 8-hydroxyflavonoid was isolated from series Androceras for the first time. The structure of the new compound 2 was determined on the basis of spectroscopic techniques, including IR, NMR and HRESI-MS. The chemotaxonomic significance of these compounds was summarised.


Influence of vehicle and pavement characteristics on dust resuspension from soil pavement of open-pit mine.
It is essential to explore the distribution characteristics of dust concentration distribution near the surface of soil pavement in open-pit mines to develop effective dust control measures. Therefore, in this study, the dust resuspension process of soil pavement was analyzed by building the dust resuspension experimental system of open-pit mine, and the change rules of dust concentration under different factors were investigated. The results showed that under the action of wheel rolling, the dust moved around the wheel along the vertical direction, and the diffusion trajectory in the horizontal direction was approximately parabolic. After re-suspension of the open-pit mine soil pavement, the area of high dust concentration behind the wheel is roughly triangular. The relationship between the average dust concentration (Total dust, Respirable dust and PM2.5) and the vehicle speed and weight were fit to a power function, while the relationship with silt content and water content were quadratic. Vehicle speed and water content had significant effect on the total dust, respirable dust (RESP) and PM2.5 average concentration, while vehicle weight and silt content had little effect on the respirable dust and PM2.5 average concentration. When the water content of mine soil pavement reached 3 %, the average dust concentration could be reduced to <10 mg/m3, and the vehicle speed should be reduced as much as possible under the mine production permitting conditions.


Draft Genomic Analysis of Pseudomonas sp. Strain OA3, a Potential Plant Growth-Promoting Rhizospheric Bacterium.
The genome analysis of the plant growth-promoting rhizospheric Pseudomonas sp. strain OA3, isolated from maize in North West Province, South Africa, is reported in this study. Pseudomonas sp. strain OA3 exhibits plant growth-promoting ability by enhancing maize and soybean growth.


Social work roles in health care: an educational framework.
Changes in demography, technology, and values have created new health problems and increased the number of people whose needs for service are extensive and complex. The authors describe an educational design intended to prepare social work students for the complicated new roles evolving for workers in health care.


How Swedish nurses are tackling nurse prescribing.
The prescription of a limited range of products by nurses in the UK is now into its second year of evaluation. This paper describes a visit made to study nurse prescribing in Sweden. The Swedish scheme is analysed and compared with the system being developed in the UK. One scheme involves prescribing with a protocol, while the other involves diagnosis and treatment.


[Quantitative cytochemical study of the RNA in tumor cells. II. The characteristics of the cell populatoins].
The quantity of DNA and RNA in tymocytes of AKR mice has been determined by Methylen blue staining. Cell populations of normal and tumor animals were divided into two groups with equal content of DNA to measure RNA content in either of them. The tumor cells had up to 380% RNA, if the normal content be taken for 100%. Dynamics of RNA modifications in cells of normal tymocytes corresponded to the increasing DNA quantity. The RNA quantity in tumor cells increased in the beginning of S-phase.


"The Stay at Home Order is Causing Things to Get Heated Up": Family Conflict Dynamics During COVID-19 From The Perspectives of Youth Calling a National Child Abuse Hotline.
The purpose of this study was to identify changes in family conflict and abuse dynamics during COVID-19 stay-at-home orders from the perspectives of youth calling a national child abuse hotline. We analyzed text and chat transcripts from Childhelp's National Child Abuse Hotline from May-June 2020 that were flagged as coming from a child with a COVID-19-related concern (N = 105). Thematic analysis was used to identify COVID-19 related influences of family conflict as well as how COVID-19 constraints influenced coping and survival for youth reporting distress or maltreatment to the hotline. Family conflict most commonly disclosed stemmed from parental or child mental health concerns, often manifesting in escalated child risk taking behaviors, parental substance use, and violence in the home. Conflict was also mentioned surrounding caregiver issues with child productivity while sheltering-in-place, commonly related to school or chores. Youth often voiced feeling unable to find relief from family conflict, exacerbated from physical distance from alternative social supports, technological isolation, and limited contact with typical safe places or supportive adults. To cope and survive, youth and crisis counselors found creative home-based coping skills and alternative reporting mechanisms. Understanding the unique impact of COVID-19 on youth in homes with family conflict and abuse can point to areas for intervention to ensure we are protecting the most vulnerable as many continue to shelter-in-place. In particular, this study revealed the importance of online hotlines and reporting mechanisms to allow more youth to seek out the help and professional support they need.


Natriuretic peptides, but not nitric oxide donors, elevate levels of cytosolic guanosine 3',5'-cyclic monophosphate in ependymal cells ex vivo.
Atrial natriuretic peptide-(1-28) (ANP), brain natriuretic peptide-(1-32) (BNP) and C-Type natriuretic polypeptide (CNP) occur in the brain, are concentrated in the anteroventral area of the third cerebral ventricle and participate in the regulation of body fluid homeostasis. The ventricles of the mammalian brain are lined by a continuous monolayered epithelium of polyciliated ependymal cells. In the adult rat, the ependymocytes continue to express the intermediate filament vimentin, but do not contain glial fibrillary acidic protein. Ependymal functions are poorly understood, but may extend to osmoregulation and volume sensing. Ependymal cells possess receptors for the natriuretic peptides, and in cell culture respond to them with an increase in their cyclic GMP content. In this study, a cyclic GMP-specific antibody was employed together with an ex vivo brain slice system to assess the ependymal response to ANP, BNP and CNP under close to life-like conditions. While ANP in concentrations of 0.1 nM and 1 nM had no effect, at concentrations of 10nM and 100 nM it increased ependymal cyclic GMP levels in a concentration-dependent manner. The other natriuretic peptides BNP, and CNP, also increased the cyclic GMP content of ependymocytes, while nitric oxide (NO) donors had no effect. However, in contrast to the natriuretic peptides, the NO donors elevated the level of cyclic GMP in the brain parenchyma below the ependymal layer.


Superoxide dismutase (SOD) as a selection criterion for triticale grain yield under drought stress: a comprehensive study on genomics and expression profiling, bioinformatics, heritability, and phenotypic variability.
The main objectives of this study were to find the possible structural association between the activity of enzymatic antioxidants and the grain yield of triticale plants as well as identifying the genotypic variability which might be effective on this association. Accordingly, expression levels of superoxide dismutase (SOD) isozymes (Mn-SOD, Cu/Zn-SOD, and Fe-SOD) were appraised to distinguish any possible relationship between SOD expression and drought resistance of triticale. A novel analytical method for distinguishing elite genotypes based on measured features was proposed. Additionally, a new programing based on SAS-language (IML) was introduced to estimate the genetic parameters rooted from combined ANOVA model (linear mixed model), which is capable of being used in any field study other than the current one. Thirty genotypes of triticale were studied under normal and drought stress conditions during 6 years (three different locations). Accordingly, based on the results of genetic variability, heatmap analysis, biplot graph, and clustering technique, two genotypes with the highest genetic distance were selected to appraise the differential expression profiling of three SOD isozyme in shoot and root organs. Field experiments and bioinformatics results showed that superoxide dismutase (SOD) was the most influential antioxidant in resistance of triticale to drought stress; therefore, it could be used as an indirect selection index in early stages to distinguish resistant genotypes to drought stress. Additionally, Mn-SOD and Fe-SOD showed roughly similar expression levels for both genotypes under drought stress. However, Cu/Zn-SOD expression level was higher in root and shoot of the tolerant genotype than the susceptible genotype. Heatmap analysis that is applied for the first time to screen suitable genotypes, showed to be highly capable of distinguishing elite genotypes and pointing out the proper features for selection criteria. Bioinformatics results indicated that SOD is more important than other enzymatic antioxidant for being considered as selection criteria or candidate gene for transgenic purposes. Based on expressional results, Mn-SOD announced as a general isozyme that is probably highly expressed in most of the species, while, Cu/Zn-SOD was introduced as a genotype specific isozyme that is likely more expressed in tolerant genotypes.


Automated assessment of mitral regurgitant volume and regurgitant fraction by a newly developed digital color Doppler velocity profile integration method.
Recent development of the automated cardiac flow measurement (ACFM) method has provided automated measurement of stroke volume and cardiac output by spatial and temporal integration of digital Doppler velocity profile data. The purpose of this study was to evaluate the clinical usefulness of the ACFM method using digital color Doppler velocity profile integration in the assessment of mitral regurgitant volume and regurgitant fraction from measurements of both aortic outflow and mitral inflow volumes. We calculated both aortic outflow and mitral inflow volumes from the apical approach with the ACFM and pulsed Doppler (PD) methods in 20 patients with isolated mitral regurgitation. Mitral regurgitant volume and regurgitant fraction were calculated by the following equation: mitral regurgitant volume = (mitral inflow volume) - (aortic outflow volume), % regurgitant fraction = (mitral regurgitant volume)/(mitral inflow volume) x 100. Mitral regurgitant volume and regurgitant fraction were compared with that determined by the PD method. Mitral regurgitant volume measurement by the ACFM method showed a good correlation with that measured by the PD method (r = 0.90, y = 0.77x + 11.6, SEE = 9.0 ml); the mean differences between PD and ACFM measurements was -1.7 +/- 12.5 ml. Regurgitant fraction estimated by the ACFM method correlated well with that of the PD method (r = 0.92, y = 0.98x + 2.1, SEE = 8.8%). The mean difference for the measurement of regurgitant fraction between the PD and ACFM methods was 0.8 +/- 6.6%. Total time required for mitral regurgitant volume calculation in 1 cardiac cycle by the ACFM method was significantly shorter than that of the PD method (126 +/- 15 seconds vs 228 +/- 36 seconds, p <0.01). In conclusion, the newly developed ACFM method is simple, quick, and accurate in the automated assessment of mitral regurgitant volume and regurgitant fraction.


A systematic review comparing the macrophage inflammatory response to hydrophobic and hydrophilic sandblasted large grit, acid-etched titanium or titanium-zirconium surfaces during in vitro studies.
Macrophages are among the first cells to interact with the dental implant surface and are critical regulators for controlling the immune response toward biomaterials. Macrophages can polarize between two main phenotypes: proinflammatory M1 macrophages and anti-inflammatory M2 macrophages. This systematic review aims to determine if a differing macrophage inflammatory response exists on hydrophilic sandblasted large grit, acid-etched (SLActive) surfaces compared to sandblasted large grit, acid-etched (SLA) titanium or titanium-zirconium surfaces during in vitro studies. MATERIAL AND METHODS: A systematic search of three electronic databases, Medline, DOSS (Dentistry and Oral Sciences Source), and WoS (Web of Science), was performed. Only in vitro studies were included in this systematic review. The electronic search was supplemented with a search of the references. Genetic expression and production of proinflammatory and anti-inflammatory proteins were assessed. The synthesis of quantitative data was completed by narrative synthesis. A total of 906 studies were found with the systematic search. Eight studies remained after the application of inclusion and exclusion criteria. Six studies used murine macrophages, while two used human macrophages. Discs were used in six studies, while dental implants were used in the remaining two studies. Genetic expression and cytokine production of proinflammatory cytokines on SLActive surfaces were reduced compared to SLA. Anti-inflammatory genetic expression and cytokine production was increased on SLActive surfaces. The overall quality of the included studies was low to moderate. SLActive surfaces modulate macrophages to reduce proinflammatory and increase anti-inflammatory gene expression and cytokine production compared to SLA surfaces. The in vitro nature of the included studies does not replicate the in vivo healing cascade. Further in vivo studies are required to assess the macrophage response toward SLActive implant surfaces compared to SLA surfaces.


Negative regulation of cadmium tolerance in Arabidopsis by MMDH2.
MMDH2 gene negatively regulates Cd tolerance by modulating reactive oxygen species (ROS) levels and the ROS-mediated signaling, thus, affecting the expression of PDR8. The molecular mechanism by which plants respond to stress caused by cadmium (Cd), one of the most toxic heavy metals to plants, is not well understood. Here, we show that MMDH2, a gene encoding mitochondrial malate dehydrogenase, is involved in Cd stress tolerance in Arabidopsis. The expression of MMDH2 was repressed by Cd stress. The mmdh2 knockdown mutants showed enhanced Cd tolerance, while the MMDH2-overexpressing lines were sensitive to Cd. Under normal and Cd stress conditions, lower H2O2 levels were detected in mmdh2 mutant plants than in wild-type plants. In contrast, higher H2O2 levels were found in MMDH2-overexpressing lines, and they were negatively correlated with malondialdehyde levels. In addition, the expression of the PDR8, a gene encoding a Cd efflux pump, increased and decreased in the mmdh2 mutant and MMDH2-overexpressing lines, in association with lower and higher Cd concentrations, respectively. These results suggest that the MMDH2 gene negatively regulates Cd tolerance by modulating reactive oxygen species (ROS) levels and the ROS-mediated signaling, thus, affecting the expression of PDR8.