Effect of aging on the shear bond strength of orthodontic brackets.
Bracket loss during the later stages of orthodontic treatment is a relatively frequent occurrence. The purpose of this study was to evaluate and isolate the effect of composite aging, one of many factors that can contribute to decreased bond strength during a normal 24-month orthodontic treatment period. Two orthodontic bonding adhesives--Transbond APC II (3M Unitek, Monrovia, Calif) and Quick Cure adhesive (Reliance Orthodontic Products, Itasca, Ill)--were used to bond brackets to 280 bovine incisors that were stored in distilled water at 37 degrees C for 30 minutes, 24 hours, and 1, 6, 12, 18, and 24 months before shear-peel testing. Bond strength increased over the first 24 hours and then tended to decrease over the next 24 months. The bond strengths (in MPa) for Transbond and Quick Cure, respectively, were as follows: 30 minutes, 14.99 +/- 0.75 and 21.02 +/- 1.79; 24 hours, 20.99 +/- 2.11 and 25.61 +/- 1.96; 1 month, 20.54 +/- 1.58 and 18.96 +/- 1.02; 6 months, 17.77 +/- 1.66 and 19.52 +/- 1.61; 12 months, 14.79 +/- 1.30 and 18.28 +/- 1.43; 18 months, 16.08 +/- 1.37 and 16.19 +/- 1.01; and 24 months, 12.44 +/- 1.06 and 8.62 +/- 1.03. Shear bond strength of orthodontic brackets increases from 30 minutes to 24 hours and then tends to decrease over the next 24 months. The decrease in bond strength due to the effects of composite aging in water appears to be a major factor in the decreased bond strength seen clinically.


Instabilities in the transient response of muscle.
We investigate the isometric transient response of muscle using a quantitative stochastic model of the actomyosin cycle based on the swinging lever-arm hypothesis. We first consider a single pair of filaments, and show that when values of parameters such as the lever-arm displacement and the cross-bridge elasticity are chosen to provide effective energy transduction, the T(2) curve (the tension recovered immediately after a step displacement) displays a region of negative slope. If filament compliance and the discrete nature of the binding sites are taken into account, the negative slope is diminished, but not eliminated. This implies that there is an instability in the dynamics of individual half sarcomeres. However, when the symmetric nature of whole sarcomeres is taken into account, filament rearrangement becomes important during the transient: as tension is recovered, some half sarcomeres lengthen whereas others shorten. This leads to a flat T(2) curve, as observed experimentally. In addition, we investigate the isotonic transient response and show that for a range of parameter values the model displays damped oscillations, as recently observed in experiments on single muscle fibers. We conclude that it is essential to consider the collective dynamics of many sarcomeres, rather than the dynamics of a single pair of filaments, when interpreting the transient response of muscle.


The Foundations of Autistic Flourishing.
All people-including Autistic people-deserve to live flourishing lives. But what does a flourishing life look like for Autistic people? We suggest that the hidden biases, methodological errors, and key assumptions of autism science have obscured answers to this question. Here, we seek to initiate a broader discussion about what the foundations for a good Autistic life might be and how this discussion might be framed. We identify five ways in which autism science can help us all to secure those foundations, including by (1) giving Autistic well-being prominence in research, (2) amplifying Autistic autonomy, (3) attending better to everyday experiences, (4) acknowledging context, and (5) working in partnership with Autistic people and their families and allies to ensure that they are at the heart of research decision-making. Such an approach would direct the focus of autism research to help shape good Autistic lives.


Comparative studies on a new concentrated fat emulsion: Intralipid 30% vs. 20%.
A concentrated fat emulsion (Intralipid 30%) was tested for clinical tolerance and metabolic effects in 2 studies comparing it with Intralipid 20%. 24 healthy subjects were given 100-g fat infusions of the two emulsions over a period of 6 h on two different days in random order. At 6 h of infusion, the mean increase in the plasma triglyceride (TG) concentration was similar for the two emulsions (3.3 +/- 0.5 (SD) and 3.9 +/- 2.9 mmol/l for the 30% and 20% emulsions, respectively; NS). A significantly lower increase in plasma phospholipid (PL) concentration was noted with Intralipid 30% (0.27 +/- 0.24 vs. 0.88 +/- 0.62 mmol/l; p < 0.05). The increases in cholesterol and free fatty acid (FFA) levels were similar for the two emulsions. In another study, 20 postoperative patients were randomized to receive 100 g fat per day during 5 days as either Intralipid 30% or Intralipid 20%. Modest increases (less than 1 mmol/l) in TG, PL, FFA and cholesterol levels were noted on day 3 and one day after the completion of TPN (day 6) and there were no significant differences between the 2 groups. It is concluded that, apart from a less pronounced increase in plasma PL levels after 6 h of infusion, the metabolic effects of Intralipid 30% were similar to those observed with the 20% emulsion. The new concentrated fat emulsion was found to be clinically safe and could be considered for use in patients requiring TPN.


Quantifying For-Profit Outcomes in GME: A Multispecialty Analysis of Board Certifying Examination Pass Rates in For-Profit Affiliated Residency Programs.
The number of for-profit hospitals has increased in the United States, but their role in and outcomes for graduate medical education (GME) are unclear. To describe for-profit involvement in internal medicine (IM), general surgery (GS), and pediatrics GME by quantifying change in for-profit affiliated residency programs and comparing for-profit and nonprofit affiliated program board certifying examination pass rates. We used Accreditation Council for Graduate Medical Education and Medicare data to quantify for-profit prevalence in IM, GS, and pediatrics GME from 2001 to 2021. We used public pass rate data from the American Board of Surgeons (2017-2019; n=242 programs; 6562 examinees), American Board of Internal Medicine (2018-2020; n=465 programs; 23 922 examinees), and American Board of Pediatrics (2018-2020; n=202 programs; 9819 examinees) to model the relationship between profit status and pass rate within each specialty and across specialties combined using linear regression. The proportion of for-profit affiliated residency programs increased 400.0% in IM, 334.4% in GS, and 23.2% in pediatrics from 2001 to 2021. Bivariate linear regression revealed significantly lower pass rate in for-profit affiliated programs in IM β =-7.73, P<.001), pediatrics (β =-14.6, P<.001), and the 3 specialties combined (β =-5.45, P<.001). Upon multiple regression with addition of program characteristic covariates, this relationship remained significant in pediatrics (β =-10.04, P=.006). The proportion of for-profit affiliated residency programs has increased in IM, GS, and pediatrics from 2001 to 2021. After controlling for covariates, for-profit affiliated programs were associated with lower board examination pass rates in pediatrics with no association in IM, GS, or the combined measure.


Surgery of pineal region lesions in childhood.
Personal experience with surgical exploration and total resection or evacuation of pineal and midbrain mass lesions in 20 pediatric patients from a total material of 52 cases demonstrate the efficacy of modern microsurgical techniques. Microtopography indicated the choice of the most suitable approach to these deep-seated lesions. The infratentorial supracerebellar approach proved to be the ideal exposure, except in one case of a lesion in the interpeduncular cistern, where a subtemporal approach was chosen. There was only one death as a consequence of the operation in a case of an extensive medulloblastoma; in all the other cases, no increase in morbidity occurred after surgery. Duration of post-operative observation with individual survival times will be demonstrated.


How nurse-led practices perceive implementation of the patient-centered medical home.
The Affordable Care Act (ACA) promotes the Patient-Centered Medical Home (PCMH) model as a way to improve healthcare quality, the patient experience, and has identified nurse-led primary care as a mechanism meeting the increasing demand for quality primary care. The purpose of this study was to investigate the implementation of a PCMH model in nurse-led primary care practices and to identify facilitators and barriers to the implementation of this model. Data were collected through in-depth interviews with providers and staff in nurse-led practices. These data suggest two categories of processes that facilitate the integration of PCMH in the nurse-led practice setting: patient-oriented facilitators and organizational facilitators. In addition, a number of barriers were identified to implementing the PCMH model. Overall, these practices creatively engaged in the transformation process by structuring themselves as a complex adaptive system and building upon the core principles of nurse-led care. Since the core principles of nurse-led care map onto many of the same principles of the PCMH model, this study discusses the possibility that nurse-led practices may experience fewer barriers when transitioning into PCMHs.


Impact of fresh olive leaves addition during the extraction of Arbequina virgin olive oils on the phenolic and volatile profiles.
Leaves incorporation during the extraction of olive oils can enhance their chemical-sensory quality. Thus, leaves from cvs. Arbequina or Santulhana were added (1%, w/w) during the extraction of Arbequina oils using an Abencor system, being discussed the impacts on the phenolics and volatiles formation enzymatic pathways. Leaves addition contributed to a significant decrease (P-value < 0.05) of the contents of secoiridoids (-11%), C6-aldehydes (-16%), and ester compounds (-22%). This could be tentatively related to a reduction of the enzymatic activity of secoiridoids biosynthesis and lipoxygenase pathways, promoted by the leaves' addition. Moreover, in the presence of leaves, the oils' total contents of phenolics and volatiles were significantly reduced (-7 and -17%, respectively). Contrary, the incorporation of leaves significantly increased (P-value < 0.05) the contents of C6-alcohols (+37%) and the intensities of the green fruity (+25%) and apple (+30%) sensations.


Influence of dissolved organic nitrogen on Ni bioavailability in Prorocentrum donghaiense and Skeletonema costatum.
Dissolved organic nitrogen (DON) is an important nutrient in the aquatic environment. This study examined the influence of DON addition on the adsorption, absorption, and distribution in macromolecular forms of environmentally deleterious trace metal (Ni) in Prorocentrum donghaiense and Skeletonema costatum over eight days. Ni adsorption and absorption of two species increased with the addition of urea, while Ni adsorption and absorption of two species in the presence of humic substances (HS) decreased. Meanwhile, Ni adsorption and absorption of P. donghaiense were higher than that of S. costatum. Furthermore, Ni contents in the protein fraction of the cells, both in P. donghaiense and S. costatum, were increased with both urea and HS addition. Thus, urea and HS input could impact Ni biogeochemistry and bioavailability, and then affect the biodynamics thereafter.


Endocrine disrupting potential of selected azole and organophosphorus pesticide products through suppressing the dimerization of human androgen receptor in genomic pathway.
Several pesticides widely used in agriculture have been considered to be endocrine disrupting chemicals through their binding affinities to estrogen or androgen receptors. This study was conducted to clarify the human androgen receptor (hAR)-mediated genomic endocrine disrupting mechanism of eight selected pesticide products by in vitro assay providing the Organization for Economic Co-operation and Development Test Guideline No. 458, 22Rv1/MMTV_GR-KO AR transcriptional activation assay and a homo-dimerization confirmation assay. None of the tested pesticide products showed an AR agonistic effect, whereas they were all determined to be AR antagonists at non-toxic concentrations. Also, the eight pesticide products were verified as true AR antagonists through a specificity control test. In the Bioluminescence Resonance Energy Transfer-based AR homo-dimerization confirmation assay, the eight pesticide products did not induce AR homo-dimerization. Additionally, western blotting revealed that none of the eight pesticide products induced AR translocation from the cytoplasm to the nucleus. In conclusion, we found for the first-time evidence to understand the AR-mediated endocrine disrupting mechanisms induced by selected azole and organophosphorus pesticide products.


Towards phase-coherent caloritronics in superconducting circuits.
The emerging field of phase-coherent caloritronics (from the Latin word calor, heat) is based on the possibility of controlling heat currents by using the phase difference of the superconducting order parameter. The goal is to design and implement thermal devices that can control energy transfer with a degree of accuracy approaching that reached for charge transport by contemporary electronic components. This can be done by making use of the macroscopic quantum coherence intrinsic to superconducting condensates, which manifests itself through the Josephson effect and the proximity effect. Here, we review recent experimental results obtained in the realization of heat interferometers and thermal rectifiers, and discuss a few proposals for exotic nonlinear phase-coherent caloritronic devices, such as thermal transistors, solid-state memories, phase-coherent heat splitters, microwave refrigerators, thermal engines and heat valves. Besides being attractive from the fundamental physics point of view, these systems are expected to have a vast impact on many cryogenic microcircuits requiring energy management, and possibly lay the first stone for the foundation of electronic thermal logic.


UK guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults 2016.
The overall objective of the guideline is to provide up-to-date, evidence-based recommendations for the diagnosis and management of the full spectrum of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and SJS-TEN overlap in adults during the acute phase of the disease. The document aims to.


Antibodies to infectious agents in individuals with recent onset schizophrenia.
We investigated the levels of antibodies to infectious agents in the serum and cerebral spinal fluids (CSFs) of individuals with recent onset schizophrenia and compared these levels to those of controls without psychiatric disease. We found that untreated individuals with recent onset schizophrenia had significantly increased levels of serum and CSF IgG antibody to cytomegalovirus and Toxoplasma gondii as compared to controls. The levels of serum IgM class antibodies to these agents were not increased. Untreated individuals with recent onset schizophrenia also had significantly lower levels of serum antibody to human herpesvirus type 6 and varicella zoster virus as compared to controls. Levels of antibodies to herpes simplex virus type 1, herpes simplex virus type 2, and Epstein Barr virus, and did not differ from cases and controls. We also found that treatment status had a major effect on the levels of antibodies in this population. Individuals who were receiving treatment had lower levels of antibodies to cytomegalovirus and Toxoplasma gondii, and higher levels of serum antibodies to human herpesvirus type 6 as compared to untreated individuals. The level of antibodies to Toxoplasma and human herpesvirus type 6 measured in treated individuals did not differ from the levels measured in controls. In the case of cytomegalovirus, the levels of CSF antibodies in treated individuals did not differ from those of controls, while the level of serum IgG antibodies to CMV remained slightly greater than controls in this population. Our studies indicate that untreated individuals with recent onset schizophrenia have altered levels of antibodies to cytomegalovirus, Toxoplasma gondii, and human herpesvirus type 6 while the levels of these antibodies in treated individuals with recent onset schizophrenia are similar to those of controls. These findings indicate that infectious agents may play a role in the etiopathogenesis of some cases of schizophrenia.


Safety of SARS-CoV-2 vaccination in patients with inflammatory bowel disease: A systematic review and meta-analysis.
Risk of adverse effects and flare of inflammatory bowel disease (IBD) are frequently cited reasons for COVID-19 vaccine hesitancy. Electronic databases were searched to identify studies reporting the use of COVID-19 vaccine in IBD. We selected studies reporting the incidence of various adverse effects (local or systemic) and flares of IBD after COVID-19 vaccination. The pooled incidence rates for various adverse effects, stratified for the dose and the type of vaccine (adenoviral or mRNA) were estimated. Nine studies (16 vaccination cohorts) were included. The pooled incidence rate of overall adverse events was 0.55 (95%CI, 0.45-0.64, I2= 95%). The pooled incidence rate of local adverse events was 0.64 (0.47-0.78, I2= 100%). The pooled incidence rates of fatigue, headache, myalgia, fever and chills were 0.30 (0.21-0.40, I2= 99%), 0.23 (0.17-0.30, I2= 99%), 0.18 (0.13-0.24, I2= 99%), 0.10 (0.06-0.17, I2= 98%) and 0.15 (0.06-0.3, I2= 86%), respectively. The pooled incidence rates of severe adverse events, adverse events requiring hospitalization and flares of IBD following COVID-19 vaccination were 0.02 (0.00-0.12, I2= 97%), 0.00 (0.00-0.01, I2= 27%) and 0.01 (0.01-0.03, I2= 45%), respectively. COVID-19 vaccination in patients with IBD appears to be safe with only mild adverse events. Flares of IBD and severe adverse events requiring hospitalization were infrequent.


Ultra-sensitive droplet digital PCR for detecting a low-prevalence somatic GNAQ mutation in Sturge-Weber syndrome.
Droplet digital PCR (ddPCR), a method for measuring target nucleic acid sequence quantity, is useful for determining somatic mutation rates using TaqMan probes. In this study, the detection limit of copy numbers of test DNA by ddPCR was determined based on Poisson distribution. Peptide nucleic acid (PNA), which strongly hybridises to target lesions, can inhibit target amplification by PCR. Therefore, by combination of PCR with PNA and ddPCR (PNA-ddPCR), the detection limit could be lowered. We reanalysed a somatic GNAQ mutation (c.548G > A) in patients with Sturge-Weber syndrome (SWS) using ddPCR and PNA-ddPCR. Importantly, among three patients previously found to be mutation negative by next-generation sequencing, two patients had the GNAQ mutation with a mutant allele frequency of less than 1%. Furthermore, we were able to find the same mutation in blood leukocyte or saliva DNA derived from four out of 40 SWS patients. Vascular anomalies and blood leukocytes originate from endothelial cells and haemangioblasts, respectively, which are both of mesodermal origin. Therefore, blood leukocytes may harbour the GNAQ mutation, depending on the time when the somatic mutation is acquired. These data suggest the possibility of diagnosis using blood DNA in some patients with SWS.


Serum thyrotropin concentration in children with isolated thyroid nodules.
To investigate the correlation between serum thyroid-stimulating hormone (TSH) concentration and nodule nature in pediatric patients with thyroid nodules, with the aim of identifying a marker able to differentiate benign and malignant nodules. This was a retrospective analysis of serum TSH concentrations in a multicentric case series of 125 pediatric patients with benign and malignant thyroid nodules. Of the 125 patients, 99 had benign thyroid nodules and 26 had differentiated thyroid cancer (24 papillary and 2 follicular). Final diagnosis was based on surgery in 57 cases and on a benign cytology plus clinical follow-up in 68 cases. Serum TSH concentration was significantly higher in patients with thyroid cancer compared with those with benign nodules (3.23 ± 1.59 mU/L vs 1.64 ± 0.99 mU/L; P < .001). Binary logistic regression analysis revealed that serum TSH was the sole predictor of malignancy (P < .001). Dividing the patient cohort into 5 groups based on serum TSH quintiles (TSH cutoffs 0.40, 1.00, 1.50, 1.80, and 2.80 mU/L), we observed that cancer prevalence increased in parallel with serum TSH (P < .001), with respective rates of 0%, 4%, 16%, 32%, and 52% in the 5 quintile groups. Because cases with malignant nodules are most likely seen in the upper normal serum TSH range (ie, >2.8 mU/L), serum TSH concentration can serve as a predictor of thyroid cancer in pediatric patients with thyroid nodules and can inform the decision of when to submit patients to further investigation by cytology.


Reducing anticoagulant medication adverse vents and avoidable patient harm.
The conventional standard of care for many patients at Saint Joseph HealthCare, a three-hospital system in Kentucky, includes the use of anticoagulant therapy. In view of the morbidity and mortality associated with anticoagulation-related complications, the prevention of bleeding and thrombotic adverse drug events was identified as a primary process improvement initiative. Following establishment of an interdisciplinary team, formal evaluations of anticoagulant-use practices and associated patient outcomes occurred via several mechanisms. A variety of process improvement activities were conducted, including the creation of a pharmacist-managed hospital anticoagulant therapy service. A pharmacist consult service for the medical staff provided initiation, management, and monitoring of anticoagulation, including bridge therapy and reversal if necessary. The rate of thrombotic events decreased from 4.6% in 2004 to 3.9% in 2006 and further decreased to 0.0% for patients managed by collaborative physician and pharmacist practice. Hospitalwide bleeding and thrombotic reactions decreased from a monthly average of 11.52 events per 1,000 anticoagulant doses dispensed in 2004 to 0.07 in 2006. A cost-benefit evaluation indicated an annual savings of up to $9.8 million in avoidable costs. In this interdisciplinary project, anticoagulant safety was integrated throughout the institution, and a variety of medication safety systems were successfully employed.


Oral Soft Tissue Grafting.
The presence of healthy soft tissue at the tooth and implant interface correlates to long-term success and stability in function and esthetics. Grafting procedures utilizing various techniques can be performed during any stage of the implant or restorative therapy. Materials of autogenous, allogeneic, and xenogeneic sources are available for oral soft tissue grafting. This article describes the classifications of soft tissue defects, treatment modalities, and materials used to enhance soft tissue quality and quantity and to achieve optimal esthetics and function around teeth and implants.


An Automatic System to Monitor the Physical Distance and Face Mask Wearing of Construction Workers in COVID-19 Pandemic.
The COVID-19 pandemic has caused many shutdowns in different industries around the world. Sectors such as infrastructure construction and maintenance projects have not been suspended due to their significant effect on people's routine life. In such projects, workers work close together that makes a high risk of infection. The World Health Organization recommends wearing a face mask and practicing physical distancing to mitigate the virus's spread. In this paper, we developed a computer vision system to automatically detect the violation of face mask wearing and physical distancing among construction workers to assure their safety on infrastructure projects during the pandemic. For the face mask detection, we collected and annotated 1000 images, including different types of face mask wearing, and added them to a pre-existing face mask dataset to develop a dataset of 1853 images and increased the dataset to 3300 images by data augmentation. Then, we trained and tested multiple Tensorflow state-of-the-art object detection models on the face mask dataset and chose the Faster R-CNN Inception ResNet V2 network that yielded the accuracy of 99.8%. For physical distance detection, we employed the Faster R-CNN Inception V2 to detect people. A transformation matrix was used to eliminate the camera angle's effect on the object distances on the image. The Euclidian distance used the pixels of the transformed image to compute the actual distance between people. A threshold of six feet was considered to capture physical distance violation. We also used transfer learning for training the model. The final model was applied on four videos of road maintenance projects in Houston, TX, that effectively detected the face mask and physical distance. We recommend that construction owners use the proposed system to enhance construction workers' safety in the pandemic situation.


Color constancy.
A quarter of a century ago, the first systematic behavioral experiments were performed to clarify the nature of color constancy-the effect whereby the perceived color of a surface remains constant despite changes in the spectrum of the illumination. At about the same time, new models of color constancy appeared, along with physiological data on cortical mechanisms and photographic colorimetric measurements of natural scenes. Since then, as this review shows, there have been many advances. The theoretical requirements for constancy have been better delineated and the range of experimental techniques has been greatly expanded; novel invariant properties of images and a variety of neural mechanisms have been identified; and increasing recognition has been given to the relevance of natural surfaces and scenes as laboratory stimuli. Even so, there remain many theoretical and experimental challenges, not least to develop an account of color constancy that goes beyond deterministic and relatively simple laboratory stimuli and instead deals with the intrinsically variable nature of surfaces and illuminations present in the natural world.


A novel recessive hyperekplexia allele GLRA1 (S231R): genotyping by MALDI-TOF mass spectrometry and functional characterisation as a determinant of cellular glycine receptor trafficking.
Hyperekplexia or startle disease (stiff baby syndrome, STHE) is a hereditary neurological disorder characterised by an exaggerated startle response and infantile muscle hypertonia. Several autosomal dominant and recessive forms of the disorder have been associated with point mutations in GLRA1, the human gene encoding the alpha 1 subunit of the inhibitory glycine receptor. Here, we describe a recessive point mutation (C1073G) in exon 7 of GLRA1 leading to an amino acid exchange of serine 231 to arginine in transmembrane region TM1. The mutation was detectable by restriction digest analysis of genomic PCR amplimers by matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF-MS). Genotyping of family members was performed using an allele specific primer extension assay in combination with MALDI-TOF-MS and confirmed by conventional DNA sequencing. These studies demonstrate the broad applicability of MALDI-TOF-MS as a comparative screening tool applicable to the analysis of allelic gene variants. In comparison to the wild type alpha 1 subunit, biochemical, electrophysiological, and confocal microscopy data indicate a reduced integration of functional alpha 1(S231R) glycine receptors into the cell surface membrane upon recombinant expression. Apparently, the amino acid exchange S231R influences glycine receptor biogenesis and cellular trafficking by introducing a positive charge into transmembrane region TM1.


Hydrothermal carbonization of food waste after oil extraction pre-treatment: Study on hydrochar fuel characteristics, combustion behavior, and removal behavior of sodium and potassium.
This study aims to convert oil extracted food waste (OEFW) into hydrochar as potential solid fuel via hydrothermal carbonization (HTC) process. The effect of HTC temperature and residence time on the physicochemical characteristic, combustion behavior, and the removal behavior of sodium and potassium were evaluated. The raw OEFW material was successfully converted into energy densified hydrochar with higher high heating value (HHV) (21.13-24.07 MJ/kg) and higher fuel ratio (0.112-0.146). In addition, carbon content in hydrochar increased to 46.92-51.82% after HTC at various operating conditions. Compared with OEFW, the hydrochar had more stable and longer combustion process with the higher ignition temperature and burnout temperature. Besides, the HTC process showed high removal rates of sodium and potassium. It was found that the HTC temperature resulted in a significant reduction of sodium and potassium in hydrochar as compared to the residence time. The highest removal rate of sodium (70.98%) and potassium (84.05%) was obtained. Overall, the results show that the HTC is a promising alternative for conventional technologies (e.g., incineration and landfill) for treatment and energy conversion of OEFW.


The ubiquitin-proteasome system: focus on the heart.
Proteasomes are the main non-lysosomal multicatalytic protease complexes that are involved in the degradation of most intracellular proteins. The substrate proteins are marked by ubiquitin, which serves as a tag for their regulated proteasomal destruction. One major function of the ubiquitin-proteasome system (UPS) is to prevent accumulation of non-functional, potentially toxic proteins. Moreover, it has become clear that the UPS is involved in most aspects of eukaryotic biology, such as intracellular signaling, transcriptional control, or regulation of cell death. Recent studies demonstrated that the UPS regulates receptor internalization, hypertrophic response, apoptosis, and tolerance to ischemia and reperfusion in cardiomyocytes. Since structural remodeling of the myocardium, ischemia-reperfusion injury, and myocardial cell loss are important components in the genesis of progressive heart failure, these findings suggest a pathophysiological role of the UPS. This review briefly summarizes present knowledge about structure and function of the proteasome in the heart and discusses the relevance of the UPS for cardiac diseases.


Preliminary kinetic characterization of xylose reductase and xylitol dehydrogenase extracted from Candida guilliermondii FTI 20037 cultivated in sugarcane bagasse hydrolysate for xylitol production.
Candida guilliermondii FTI 20037 was cultured in sugarcane bagasse hydrolysate supplemented with 2.0 g/L of (NH4)2SO4, 0.1 g/L of CaCl2 x 2H2O, and 20.0 g/L of rice bran at 35 degrees C; pH 4.0; agitation of 300 rpm; and aeration of 0.4, 0.6, or 0.8 vvm. The high xylitol production (20.0 g/L) and xylose reductase (XR) activity (658.8 U/mg of protein) occurred at an aeration of 0.4 vvm. Under this condition, the xylitol dehydrogenase (XD) activity was low. The apparent K(M) for XR and XD against substrates and cofactors were as follows: for XR, 6.4 x 10(-2)M (xylose) and 9.5 x 10(-3) mM (NADPH); for XD, 1.6 x 10(-1)M (xylitol) and 9.9 x 10(-2) mM (NAD+). Because XR requires about 10-fold less xylose and cofactor than XD for the condition in which the reaction rate is half of the Vmax, some interference on the overall xylitol production by the yeast could be expected.


Efficacy and safety of surgical treatment of cluster headache.
Cluster headache (CR) is the most severe human headache and is chronic in 10%-20% of patients, and 10% can become refractory to all effective drugs. In this scenario, surgical procedures are indicated: radiofrequencies of the sphenopalatine ganglion ipsilateral to pain (RF-SPG), bilateral stimulation of the occipital nerves (NOM-S) and deep brain stimulation (DBS) of the ipsilateral posterior hypothalamus. The efficacy and safety of each of these procedures has been specifically analyzed, but the progress of a series of patients following this surgical route in order of aggressiveness has not been described. Patients with chronic and refractory CR according to the criteria of the European Headache Federation. The patients underwent RF-SPG, NOM-S sequentially if the previous procedure had been ineffective, and DBS if the previous procedure had been ineffective. We prospectively included 44 patients between November 2003 and June 2018 with an average age of 38.3 years; 70% were men. The mean follow-up was 87.4 months. Nineteen patients responded to 74 procedures of RF-SPG (33.3%). Of the remaining 25 patients, a NOM-S device was implanted in 22, showing an efficacy of 50%. Finally, 9 patients underwent ECP of the ipsilateral lower-posterior hypothalamus with an efficacy of 88.8%. No serious complications were found following any of these 3 procedures. The sequential application of these three surgical procedures succeeded in reversing the serious situation of chronic CR refractory to an episodic CR in 93% of patients with acceptable surgical morbidity.


Identification of a novel linear B-cell epitope using a monoclonal antibody against the carboxy terminus of the canine distemper virus nucleoprotein and sequence analysis of the identified epitope in different CDV isolates.
The Nucleoprotein (NP) is the most abundant and highly immunogenic protein in canine distemper virus (CDV), playing an important role in CDV viral replication and assembly. In this study, a specific monoclonal antibody, named C8, was produced against the NP protein C terminal (amino acids 401-523). A linear N protein epitope was identified by subjecting a series of partially overlapping synthesized peptides to enzyme-linked immunosorbent assay (ELISA) analysis.The results indicated that 444GDKYPIHFNDER455 was the minimal linear epitope that could be recognized by mAb C8. Sequence alignments demonstrated that this linear epitope is less conserved among three CDV genotypes. We next analyzed the level of conservation of the defined epitope in19 Chinese CDV clinical isolates, and it has one site variation in amino acid among these CDV isolations. 2 isolates have the amino acid mutations F451L, while one has P448Ssubstitution.Phylogenetic analysis showed the two isolates with F451Lsubstitution had a closer relationship in a virulent strain ZJ-7, so the epitope may be a significant tag associated with virus virulence. This collection of mAb along with defined linear epitope may provide useful reagents for investigations of NP protein function and the development of CDV specific diagnostics.


Nanomedicine of synergistic drug combinations for cancer therapy - Strategies and perspectives.
Nanomedicine of synergistic drug combinations has shown increasing significance in cancer therapy due to its promise in providing superior therapeutic benefits to the current drug combination therapy used in clinical practice. In this article, we will examine the rationale, principles, and advantages of applying nanocarriers to improve anticancer drug combination therapy, review the use of nanocarriers for delivery of a variety of combinations of different classes of anticancer agents including small molecule drugs and biologics, and discuss the challenges and future perspectives of the nanocarrier-based combination therapy. The goal of this review is to provide better understanding of this increasingly important new paradigm of cancer treatment and key considerations for rational design of nanomedicine of synergistic drug combinations for cancer therapy.


A new system to measure and compare hepatitis C virus replication capacity using full-length, replication competent viruses.
Measuring the in vitro replication capacity of viruses is an important tool for assessing the effects of selective pressure of immune responses and drug therapy. Measuring hepatitis C virus (HCV) replication capacity utilizing primarily sub-genomic reporter constructs is limited. To overcome some of these limitations a quantitative reverse transcriptase PCR (RT-qPCR) was designed to measure simultaneously the growth rate of 2 whole genome HCV variants under identical culture conditions. The assay demonstrates 100% specificity of detection of each variant and a linear detection range from 200 to 2×10(8) copies. The system was validated using a panel of HCV mutants, including the NS3 protease inhibitor drug resistance mutants R155K and T54A. The creation of a unique sequence tag results in highly sensitive and specific discrimination of parental JFH-FNX and modified clones using distinct probes in a RT-qPCR allowing for comparison of the effect of drug resistance or immune escape mutations on HCV replication. This system has advantages over existing methods both by permitting direct comparison of the replication capacity of fully replication-competent HCV mutants under identical culture conditions and by measuring effects on replication capacity due to mutations affecting all stages of the viral life cycle including entry and egress.


Psychiatric "survivors" and testimonies of self-harm.
UK "Psychiatric Survivors"-a variety of activist groups comprising individuals who have been on the "receiving end" of psychiatric treatment-have, since the mid-1980s, mounted a challenge to the psychiatric system. "Survivors" have formulated their own knowledge-base concerning a range of human problems hitherto regarded as the province of "official" psychiatry only. "Official" knowledge stresses scientific classification, professional expertise, and statistical evidence: "Survivor" knowledge, by contrast, emphasises individual experience, the traumas of the life-course, and the personal testimony of the survivor as itself expert data. This paper focuses upon the truth-claims enacted by the "testimony of the survivor" and the relation of "testimony" to political practice. Specifically, I analyse a key text containing the testimonies of female survivors whose behaviour has been officially labelled as "deliberate self-harm"; that is, women who harm themselves, through self-poisoning or self-laceration, and subsequently receive medical/psychiatric treatment. The main focus is upon the political functions of testimony in theory and practice-the ways in which "survivors" challenge the power of psychiatry.


Serum paraoxonase undergoes inhibition and proteolysis during experimental acute pancreatitis.
Oxidative stress has a primary role in the pathogenesis of severe acute pancreatitis. Then, the antioxidant capacity is a critical factor in the progression of this disease. Serum paraoxonase-1 (PON1) is an esterase associated with high-density lipoprotein, which clinical interest resides in its ability to prevent or limit the lipid oxidation. The aim of this study was to investigate changes in PON1 activity in the early stages of acute pancreatitis and to find out if its alteration is related with the severity of the disease. To this purpose, we used an experimental model of taurocholate-induced mild and severe acute pancreatitis. Our results showed that serum activity and PON1 concentration decreased 18 h after the induction of a severe acute pancreatitis. In vitro analysis revealed that incubation with oxidized lipids obtained from pancreatitis samples results in the inactivation of the enzyme in a concentration-dependent manner. In addition to oxidative inactivation, we observed by Western blot, an immunoreactive band suggestive of proteolytic degradation of the enzyme, altogether indicating that during severe acute pancreatitis, there is a significant decrease in serum PON1 activity. This decrease is related with inactivation of the enzyme by oxidized lipids, probably followed by proteolytic degradation of the enzyme.


Effects of NPY and the specific Y1 receptor agonist [D-His(26)]-NPY on the deficit in brain reward function and somatic signs associated with nicotine withdrawal in rats.
Tobacco addiction is a chronic disorder that is characterized by dysphoria upon smoking cessation and relapse after periods of abstinence. Previous research suggests that Neuropeptide Y (NPY) and Y1 receptor agonists attenuate negative affective states and somatic withdrawal signs. The aim of the present experiments was to investigate the effects of NPY and the specific Y1 receptor agonist [D-His(26)]-NPY on the deficit in brain reward function and somatic signs associated with nicotine withdrawal in rats. The intracranial self-stimulation procedure was used to assess the effects of nicotine withdrawal on brain reward function as this procedure can provide a quantitative measure of emotional states in rodents. Elevations in brain reward thresholds are indicative of a deficit in brain reward function. In the first experiment, NPY did not prevent the elevations in brain reward thresholds associated with precipitated nicotine withdrawal and elevated the brain reward thresholds of the saline-treated control rats. Similar to NPY, [D-His(26)]-NPY did not prevent the elevations in brain reward thresholds associated with precipitated nicotine withdrawal and elevated the brain reward thresholds of the saline-treated control rats. Neither NPY nor [D-His(26)]-NPY affected the response latencies. In a separate experiment, it was demonstrated that the specific Y1 receptor antagonist BIBP-3226 prevented the NPY-induced elevations in brain reward thresholds. NPY attenuated the overall somatic signs associated with precipitated nicotine withdrawal. [D-His(26)]-NPY did not affect the overall somatic signs associated with precipitated nicotine withdrawal, but decreased the number of abdominal constrictions. Both NPY and [D-His(26)]-NPY attenuated the overall somatic signs associated with spontaneous nicotine withdrawal. These findings indicate that NPY and [D-His(26)]-NPY attenuate somatic nicotine withdrawal signs, but do not prevent the deficit in brain reward function associated with precipitated nicotine withdrawal. In addition, NPY decreases the sensitivity to rewarding electrical stimuli via an Y1 dependent mechanism.


Refractory juvenile myoclonic epilepsy: a meta-analysis of prevalence and risk factors.
Juvenile myoclonic epilepsy (JME) is a common epilepsy syndrome for which treatment response is generally assumed to be good. We aimed to determine the prevalence and prognostic risk factors for refractoriness of JME. We systematically searched PubMed and EMBASE and included 43 eligible studies, reporting seizure outcome after antiepileptic drug (AED) treatment in JME cohorts. We defined refractory JME as persistence of any seizure despite AED treatment and performed a random-effects meta-analysis to assess the prevalence of refractory JME and of seizure recurrence after AED withdrawal in individuals with well-controlled seizures. Studies reporting potential prognostic risk factors in relation to seizure outcome were included for subsequent meta-analysis of risk factors for refractoriness. Overall, 35% (95% confidence interval, 29-41%) of individuals (n = 3311) were refractory. There was marked heterogeneity between studies. Seizures recurred in 78% (95% confidence interval, 52-94%) of individuals who attempted to withdraw from treatment after a period of seizure freedom (n = 246). Seizure outcome by publication year suggested that prognosis did not improve over time. Meta-analysis suggested six variables as prognostic factors for refractoriness, i.e. having three seizure types, absence seizures, psychiatric comorbidities, earlier age at seizure onset, history of childhood absence epilepsy and praxis-induced seizures. One-third of people with JME were refractory, which is a higher prevalence than expected. Risk factors were identified and can be used to guide treatment and counselling of people with JME.


National Practice Patterns in Malignant Peritoneal Mesothelioma: Updates in Management and Survival.
Malignant peritoneal mesothelioma (MPM) is a rare malignancy with a historically poor prognosis. Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as an effective therapy for patients with peritoneal malignancies. A contemporary analysis of trends in management of and survival from MPM is warranted. Patients with MPM were identified from the National Cancer Database (2004-2018). Patients were categorized by treatment (CRS-HIPEC, CRS-chemotherapy, CRS only, chemotherapy only, no treatment), and joinpoint regression was employed to compute the annual percent change (APC) in treatment over time. Multivariable Cox proportional hazards models were used to analyze factors associated with survival. Of 2683 patients with MPM, 19.1% underwent CRS-HIPEC, and 21.1% received no treatment. Joinpoint regression revealed a statistically significant increase in the proportion of patients undergoing CRS-HIPEC over time (APC 3.21, p = 0.01), and a concurrent decrease in the proportion of patients who underwent no treatment (APC - 2.21, p = 0.02). Median overall survival was 19.5 months. Factors independently associated with survival included CRS-HIPEC, CRS, histology, sex, age, race, Charlson Comorbidity Index, insurance, and hospital type. Although there was a strong association between year of diagnosis and survival on univariate analysis (2016-2018 HR 0.67, p < 0.001), this association was attenuated after adjustment for treatment. CRS-HIPEC is increasingly employed as a treatment for MPM. In parallel, there has been a decrease in patients receiving no treatment with an increase in overall survival. These findings suggest that patients with MPM may be receiving more appropriate therapy; however, a substantial proportion of patients may remain undertreated.


Australian health care providers' views on opt-out HIV testing.
Opt-out HIV testing is a novel concept in Australia. In the opt-out approach, health care providers (HCPs) routinely test patients for HIV unless they explicitly decline or defer. Opt-out HIV testing is only performed with the patients' consent, but pre-test counselling is abbreviated. Australian national testing guidelines do not currently recommend opt-out HIV testing for the general population. Non-traditional approaches to HIV testing (such as opt-out) could identify HIV infections and facilitate earlier treatment, which is particularly important now that HIV is a chronic, manageable disease. Our aim was to explore HCPs' attitudes toward opt-out HIV testing in an Australian context, to further understanding of its acceptability and feasibility. In this qualitative study, we used purposeful sampling to recruit HCPs who were likely to have experience with HIV testing in Western Australia. We interviewed them using a semi-structured guide and used content analysis as per Graneheim to code the data. Codes were then merged into subcategories and finally themes that unified the underlying concepts. We refined these themes through discussion among the research team. Twenty four HCPs participated. Eleven participants had a questioning attitude toward opt-out HIV testing, while eleven favoured the approach. The remaining two participants had more nuanced perspectives that incorporated some characteristics of the questioning and favouring attitudes. Participants' views about opt-out HIV testing largely fell into two contrasting themes: normalisation and routinisation versus exceptionalism; and a need for proof versus openness to new approaches. Most HCPs in this study had dichotomous attitudes toward opt-out HIV testing, reflecting contrasting analytical styles. While some HCPs viewed it favourably, with the perceived benefits outweighing the perceived costs, others preferred to have evidence of efficacy and cost-effectiveness.


Advanced stage of breast cancer hoist alkaline phosphatase activity: risk factor for females in India.
Breast cancer is the most common neoplasm affecting women in the western world with an average frequency of 1 in 11, developing the malignancy and it is second most common cancer in India. Variations in serum levels of biochemical parameters especially alkaline phosphatase (ALP) changes may be of great help in diagnosis of breast carcinoma. Serum ALP activity was assayed in 388 histopathologically proven breast cancer patients using spectrophotometric methods and monitored association with cancer stages. Breast cancer is a female-biased disease and our study was conducted in a group of female patients with mean age of 48.67 ± 8.32 years. A significant increase in levels of ALP (809.65 ± 145.97 IU/L) was observed in stage IV of the disease. The logistic regression study gave a significant result (P < 0.001) when we compared the group of ALP level (>500 IU/L) with metastatic presentation. The present study besides being cost effective suggested the usefulness of ALP in differentiating breast cancer stages and metastasis.


Sustainable synthesis of ordered mesoporous materials without additional solvents.
Micelles with well-defined nanostructures were generally formed in the presence of a suitable solvent. We report herein the accelerated construction of micelles with ordered nanostructures without assistance of additional solvents. The micelles were employed for ultrafast fabrication of ordered mesoporous silicas (OMS) using tetramethyl orthosilicate (TMOS) as silica source. When γ-aminopropyl triethoxysilane precursor was introduced, we obtained amine group (-NH2) decorated ordered mesoporous silicas (OMS-NH2-x, where x stands for the molar ratio of γ-aminopropyl triethoxysilane to TMOS). The resulted materials are large in BET surface area and tunable in content of -NH2 site, which are highly efficient for catalytic elimination of gaseous carbonyl sulfide and hydrogen sulfide. Using this strategy, other functionalized groups such as thiol and benzene can be also introduced into OMS. Furthermore, the introducing of phenolic precursor into the system leads to multiphase co-assembly for the formation of ordered mesoporous silica-polymer nanocomposites. It is demonstrated that the solvent-free ultrafast assembly offers a sustainable route for preparation of ordered mesoporous functional materials.


Purification to homogeneity of camel pituitary pro-opiocortin, the common precursor of opioid peptides and corticotropin.
Pro-opiocortin was purified from camel pituitaries by procedures including high-performance liquid chromatography. The precursor relationship of the pure protein to the opioid peptides and to corticotropin was confirmed. Partial chemical analysis consisting of amino acid analysis and tryptic peptide mapping was carried out with the aid of sensitive fluorescence detection.


Catabolite inactivation of the high-affinity hexose transporters Hxt6 and Hxt7 of Saccharomyces cerevisiae occurs in the vacuole after internalization by endocytosis.
After addition of high concentrations of glucose, rates of high-affinity glucose uptake in Saccharomyces cerevisiae decrease rapidly. We found that the high-affinity hexose transporters Hxt6 and Hxt7 are subject to glucose-induced proteolytic degradation (catabolite inactivation). Degradation occurs in the vacuole, as Hxt6/7 were stabilized in proteinase A-deficient mutant cells. Degradation was independent of the proteasome. The half-life of Hxt6 and Hxt7 strongly increased in end4, ren1 and act1 mutant strains, indicating that the proteins are delivered to the vacuole by endocytosis. Moreover, both proteins were also stabilized in mutants defective in ubiquitination. However, the initial signal that triggers catabolite inactivation is not relayed via the glucose sensors Snf3 and Rgt2.


Heart rate changes with exercise and voluntary heart rate acceleration.
The present study examined the relationship between heart rate (HR) changes accompanying isometric and isotonic exercises and HR changes during attempted voluntary HR acceleration. Substantial cardiac accelerations accompanied both types of exertion, with the isotonic exercise attracting the larger magnitude HR changes. Significant HR increases were also observed during attempted voluntary HR acceleration both with and without feedback; however, feedback prompted larger HR increases than instructions alone. The HR changes accompanying both types of exercise reliably predicted the extent of voluntary HR increase but only for the condition in which feedback was available. This occurred in spite of the absence of observable EMG changes during attempted HR acceleration. Changes in respiration rate during voluntary HR increase were highly correlated with changes in HR. A similar co-variation occurred with the isotonic exercise but was absent with the isometric exercise. The results are discussed in terms of the possible mediational mechanisms underlying voluntary HR acceleration.


Antibacterial Potential of Jatropha sp. Latex against Multidrug-Resistant Bacteria.
This study was aimed to evaluate the antibacterial activity of the latex of three species members of Jatropha (J. curcas, J. gossypilofia Linn., and J. multifida) against methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase- (ESBL-) producing Escherichia coli and ESBL-producing Klebsiella pneumonia, carbapenemase-resistant Enterobacteriaceae (CRE)-E. coli, K. pneumoniae-carbapenemase (KPC), and carbapenemase-resistant Pseudomonas aeruginosa (CRPA). The antibacterial activities were calculated based on the inhibition zones using the Mueller-Hinton agar diffusion method, minimum inhibitory concentration (MIC) using Mueller-Hinton broth in a microdilution method, and minimum bactericidal concentration (MBC) using blood agar plate. The latex of Jatropha showed antibacterial activities against the MRSA and CRPA. All latex of Jatropha appeared to have the antibacterial activities against MRSA and CRPA in the diffusion method (20.4-23.7 mm and 12-15 mm), MIC (0.19-6.25%, and 25%), and MBC (0.39-12.5% and 50%). Phytochemical screening of latex indicated the presence of flavonoids. The latex of J. curcas, J. gossypilofia Linn., and J. multifida has the potential to be developed as antibacterial agents, especially against MRSA and CRPA strain, but further in vivo research and discovery of the mode of its action are required to shed the light on the effects.


Role of Gemcitabine and Pemetrexed as Maintenance Therapy in Advanced NSCLC: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.
Gemcitabine and pemetrexed have been used as maintenance therapy. However, few systematic reviews and meta-analyses have assessed their effects in the newest studies. This systematic review and meta-analysis were conducted to assess the role of gemcitabine and pemetrexed in the maintenance treatment of non-small-cell lung carcinoma (NSCLC). We performed a literature search using PubMed, EMBASE and Cochrane library databases from their inceptions to September 16, 2015. We also searched the American Society of Clinical Oncology (ASCO), European Society for Medical Oncology (ESMO), and National Comprehensive Cancer Network (NCCN) databases from 2008 to 2015. Two authors independently extracted the data. The Cochrane Collaboration's risk of bias graph was used to assess the risk of bias. The GRADE system was used to assess the grading of evidence, and a meta-analysis was conducted using Stata 11.0 software. Eleven randomized controlled trial (RCT) studies were collected. Ten studies were included in the meta-analysis and divided into the following 4 groups: gemcitabine vs. best supportive care (BSC)/observation, pemetrexed vs. BSC/placebo, pemetrexed + bevacizumab vs. bevacizumab and pemetrexed vs. bevacizumab. Gemcitabine exhibited significantly improved progression-free survival (PFS) compared with BSC (hazard ratio (HR) = 0.62, p = 0.000). Pemetrexed exhibited significantly improved PFS (HR = 0.54, p = 0.000) and OS (HR = 0.75, p = 0.000) compared with BSC. Pemetrexed + bevacizumab almost exhibited significantly improved PFS (HR = 0.71, p = 0.051) compared with bevacizumab. Pemetrexed exhibited no improvement in PFS or overall survival (OS) compared with bevacizumab. Regarding the grade, the GRADE system indicated that the gemcitabine group was "MODERATE", the pemetrexed group was "HIGH", and both the pemetrexed + bevacizumab vs. bevacizumab groups and pemetrexed vs. B groups were "LOW". Gemcitabine or pemetrexed compared with BSC/observation/placebo significantly improved PFS or OS. Whether pemetrexed + bevacizumab compared with bevacizumab alone significantly improves PFS requires further investigation.


SENet: A deep learning framework for discriminating super- and typical enhancers by sequence information.
Super-enhancers are large domains on the genome where multiple short typical enhancers within a specific genomic distance are stitched together. Typically, they are cell type-specific and responsible for defining cell identity and regulating gene transcription. Numerous studies have demonstrated that super-enhancers are enriched for trait-associated variants, and mutations in super-enhancers are possibly related to known diseases. Recently, several machine learning-based methods have been used to distinguish super-enhancers from typical enhancers by using high-throughput data from various experimental methods. The acquisition of such experimental data is usually costly and time-consuming. In this paper, we innovatively proposed SENet, a groundbreaking method based on a deep neural network model, for discriminating between the two categories solely utilizing sequence information. SENet employs dna2vec feature embedding, convolution for local feature extraction, attention pooling for refined feature retention, and Transformer for contextual information extraction. Experiments demonstrate that SENet outperforms all current state-of-the-art computational methods and shows satisfactory performance in cross-species validation. Our method pioneers the distinction between super-enhancers and typical ones using only sequence information. The source code and datasets are stored in https://github.com/lhy0322/SENet.


Purification, characterization and thermodynamic analysis of cellulases produced from Thermomyces dupontii and its industrial applications.
Cellulases involved in the hydrolysis of cellulose and plays a vital role in different industries like textile, detergent paper and Feed industry. Cellulases have been a prospective target for research by both the academic and industrial sectors because of the intricacy of the enzyme system and the enormous industrial potential. In the present work Thermomyces dupontii, which had previously been isolated and recorded as a promising cellulase producer were used. Both endoglucanases and betaglucosidases were purified to its homogeneity by ammonium sulfate followed by anion exchange and gel filtration chromatography. The recovery and purification fold for endoglucanases and betaglucosidases were 13.7, 10.7 % and 5.9, 2.7, respectively. The molecular weight of endoglucanases and betaglucosidases were estimated as 37 and 66 kDa on SDS-PAGE. Upon kinetic analysis the purified endoglucanases and betaglucosidases showed Km 0.63; 28.56 mg/ml and Vmax 82; 80 U/ml/min, respectively. Characterization revealed that enzyme was found to be acidophilic cellulase having optimal pH of 5.5 and 70 ⁰C. Furthermore, cellulases were accelerated in the presence of Ca2+ and EDTA. The cellulases had activation energy (Ea) of -44.55; -50.02 kJ/mol for carboxy-methyl-cellulose hydrolysis and Enthalpy (ΔH) 42.20; 47.70 kJ/mol and entropy ΔS -5.1 and -5.7 kJ/mol for EG and BGL, respectively. In addition to this the enzyme had a secondary structure of protein as represented by FTIR spectrum The current study suggested that purified cellulases can be used as a detergent additive to improve washing. Furthermore, it shows the biostoning ability when applied on jean fabric.


Spatial regulation of inflammation by human aortic endothelial cells in a linear gradient of shear stress.
Atherosclerosis is a focal disease that develops at sites of low and oscillatory shear stress in arteries. This study aimed to understand how endothelial cells sense a gradient of fluid shear stress and transduce signals that regulate membrane expression of cell adhesion molecules and monocyte recruitment. Human aortic endothelial cells were stimulated with TNF-alpha and simultaneously exposed to a linear gradient of shear stress that increased from 0 to 16 dyne/cm2. Cell adhesion molecule expression and activation of NFkappa B were quantified by immunofluorescence microscopy with resolution at the level of a single endothelial cell. Monocyte recruitment was imaged using custom microfluidic flow chambers. VCAM-1 and E-selectin upregulation was greatest between 2-4 dyne/cm2 (6 and 4-fold, respectively) and above 8 dyne/cm2 expression was suppressed below that of untreated endothelial cells. In contrast, ICAM-1 expression and NFkappa B nuclear translocation increased with shear stress up to a maximum at 9 dyne/cm2. Monocyte recruitment was most efficient in regions where E-selectin and VCAM-1 expression was greatest. We found that the endothelium can sense a change in shear stress on the order of 0.25 dyne/cm2 over a length of approximately 10 cells, regulating the level of protein transcription, cellular adhesion molecule expression, and leukocyte recruitment during inflammation.


Initiating or switching to biphasic insulin aspart 30 in type 2 diabetes patients from Algeria: a sub-analysis of the A₁chieve study.
To determine the safety and effectiveness of biphasic insulin aspart 30 (BIAsp 30) in Algerian patients with type 2 diabetes initiating insulin or switching from prior insulin therapy. Insulin-naive and insulin-experienced patients, including prior basal insulin users, starting BIAsp 30 were evaluated in this sub-analysis of the 24-week, open-label, non-interventional A₁chieve study. Clinical safety and effectiveness was evaluated as a part of routine clinical care. A total of 134 insulin-naive patients initiating BIAsp 30 at a mean dose of 0.44 ± 0.23 U/kg and 283 insulin-experienced patients, including 129 prior basal insulin users, switching from a mean pre-study insulin dose of 0.51 ± 0.23 U/kg to BIAsp 30 (0.54 ± 0.20 U/kg) were evaluated. At Week 24, the average BIAsp 30 dose was 0.60 ± 0.25 U/kg and 0.66 ± 0.24 U/kg in insulin-naive and insulin-experienced patients, respectively. No serious adverse drug reactions were reported. From baseline to Week 24, the proportion of patients experiencing overall hypoglycaemia increased in the insulin-naive group (p = 0.0067) and no significant changes were reported in the insulin-experienced group including prior basal insulin users. Glucose control improved significantly in the insulin-experienced group (p < 0.001) and appeared to improve in the insulin-naive patients and prior basal insulin users as well. Body weight increased significantly in all patients (p < 0.001). Quality of life was positively impacted after 24 weeks of BIAsp 30 therapy. Initiating or switching to BIAsp 30 therapy in this Algerian cohort was well-tolerated and significantly improved glucose control.


Bone marrow-derived T lymphocytes responsible for allograft rejection.
Lethally irradiated mice reconstituted with syngeneic bone marrow cells were grafted with allogeneic skin grafts 6-7 weeks after irradiation and reconstitution. Mice with intact thymuses rejected the grafts whereas the mice thymectomized before irradiation and reconstitution did not. Thymectomized irradiated mice (TIR mice) reconstituted with bone marrow cells from donors immune to the allografts rejected the grafts. Bone marrow cells from immunized donors, pretreated with Thy 1.2 antibody and C', did not confer immunity to TIR recipients. To determine the number of T lymphocytes necessary for the transfer of immunity by bone marrow cells from immunized donors, thymectomized irradiated mice were reconstituted with nonimmune bone marrow cells treated with Thy 1.2 antibody and C' and with various numbers of splenic T lymphocytes from nonimmune and immune donors. Allogeneic skin graft rejection was obtained with 10(6) nonimmune or 10(4) immune T cells. The effect of immune T cells was specific: i.e., immune T cells accelerated only rejection of the relevant skin grafts whereas against a third-party skin grafts acted as normal T lymphocytes.


Cross your heart: Some historical comments about fibrinous pericarditis.
This article briefly describes the origin of one of the more common (food-related) pathologic terms--"bread and butter pericarditis." The eminent French physician, Laennec, the inventor of the stethoscope amongst several other important medical contributions, can be credited for having coined the term that is still in common usage amongst pathologists.


Enterococcal meningitis: combined vancomycin and rifampin therapy.
Intrathecal vancomycin and oral rifampin have been used together to successfully treat a patient with enterococcal meningitis who was allergic to penicillin and who had failed a course of treatment with chloramphenicol. This therapy was tolerated very well and represents an alternate mode of therapy which should be considered in penicillin allergic patients with enterococcal meningitis.


Behavioral problems of Mandarin-speaking late-talking toddlers and preschool aged children: A prospective case-control study in Taiwan.
This study aimed to examine whether Mandarin-speaking late-talking (LT) toddlers have a higher incidence of behavioral problems than typical language developing (TLD) children in toddlerhood and at preschool age from a community sample in Taiwan.This prospective case-control study comprised 32 LT and 32 TLD toddlers. Participants' parents provided reports about their children at 2 and 4 years using the Child Behaviors Checklist, a component of the Achenbach System of Empirically Based Assessment.The results indicated that compared to the TLD group, a higher percentage of the LT group was at risk of behavioral problems at both two and four years. Similarly, the chance of internalizing problems was higher in the LT group than the TLD group at both ages.The findings indicated that LT toddlers are at risk for behavioral problems not only in toddlerhood, but also at preschool age. Thus, it is crucial to identify LT toddlers with behavioral problems and enroll them in early developmental evaluation programs in their communities and also include them in early intervention programs if necessary. In addition, the underlying mechanism of the association between language delay and behavioral problems in children needs to be longitudinally explored from a young age.


DNA sequence-dependent formation of heterochromatin nanodomains.
The mammalian epigenome contains thousands of heterochromatin nanodomains (HNDs) marked by di- and trimethylation of histone H3 at lysine 9 (H3K9me2/3), which have a typical size of 3-10 nucleosomes. However, what governs HND location and extension is only partly understood. Here, we address this issue by introducing the chromatin hierarchical lattice framework (ChromHL) that predicts chromatin state patterns with single-nucleotide resolution. ChromHL is applied to analyse four HND types in mouse embryonic stem cells that are defined by histone methylases SUV39H1/2 or GLP, transcription factor ADNP or chromatin remodeller ATRX. We find that HND patterns can be computed from PAX3/9, ADNP and LINE1 sequence motifs as nucleation sites and boundaries that are determined by DNA sequence (e.g. CTCF binding sites), cooperative interactions between nucleosomes as well as nucleosome-HP1 interactions. Thus, ChromHL rationalizes how patterns of H3K9me2/3 are established and changed via the activity of protein factors in processes like cell differentiation.


Activation of adenylate cyclase by forskolin prolongs calcium action potential duration in lamprey sensory neurons.
Calcium-dependent action potentials of primary sensory neurons in the isolated spinal cord of the lamprey were greatly prolonged in duration by forskolin, an activator of adenylate cyclase in other systems. This effect was dose-dependent over the tested range of 25-400 microM with an EC50 of 55 microM. Experiments were performed to establish a role for adenylate cyclase and adenosine 3',5'-cyclic monophosphate (cAMP) as mediators of the forskolin effect. The prolonging action of forskolin on the Ca action potential was significantly reduced in the presence of the adenylate cyclase inhibitor 2',5'-dideoxyadenosine. The inactive forskolin analogue 1,9-dideoxyforskolin did not prolong the duration of the Ca action potential, while forskolin treatment of the same cells produced a large and rapid increase in action potential duration. In addition, the prolonging action of forskolin was potentiated by the phosphodiesterase inhibitor, theophylline. It is concluded that forskolin acts in lamprey sensory neurons to activate adenylate cyclase and raise intracellular cAMP levels which in turn mediate the increase in Ca action potential duration.


Leukocyte telomere length in patients with schizophrenia and related disorders: a meta-analysis of case-control studies.
Telomere length may serve as a biomarker of cellular aging. The literature assessing telomere length in schizophrenia contains conflicting results. To assess differences in leukocyte telomere length (LTL) in peripheral blood in patients with schizophrenia and related disorders and healthy controls and to explore the effect of potential confounding variables. A search of Ovid MEDLINE, and Proquest databases was conducted to identify appropriate studies published from database inception through December 2020. The review protocol was registered with PROSPERO-ID: CRD42021233280. The initial literature search yielded 192 studies. After study selection in 3 phases, we included 29 samples from 22 studies in the meta-analysis database. We used random effects and meta-regression models to derive Cohen d values with pooled 95% confidence intervals (CI) as estimates of effect size (ES) and to test effects of potential moderators. The overall meta-analysis included 4145 patients with schizophrenia and related disorders and 4184 healthy controls and showed that LTL was significantly shorter in patients, with a small to medium effect size (ES, -0.388; 95% CI, -0.492 to -0.283; p < 0.001). Subgroup meta-analyses did not find a significant effect of age or illness duration on differences in LTL in patients with psychosis relative to controls. Meta-regression analyses showed that none of the putative moderators had a significant effect on effect size estimates. This meta-analysis find further support for the hypothesis of accelerated cellular aging in schizophrenia and related disorders and highlights the need for large longitudinal studies with repeated LTL measurements over time and appropriate assessments of associated factors.


Regressing atypical histiocytosis: a case report of control following low dose radiation therapy.
A case of regressing atypical histiocytosis with a 10-year local course is reported. Long term control of a large fungating mass was achieved with low dose electron beam irradiation to 1500 cGy. Whereas spontaneous resolution of regressing atypical histiocytosis has been noted in the literature, this case demonstrates that certain lesions may be more aggressive than commonly assumed. In these particularly destructive lesions radiation therapy may have a role.


Effects of recurrent urinary tract infections on graft and patient outcomes after kidney transplantation.
Urinary tract infections (UTIs) are common following kidney transplantation (KT); however, the influence of recurrent post-KT UTI (R-UTI) is not well-characterized. We compared graft outcomes, patient outcomes and multidrug-resistance rates between patients with no UTI, nonrecurrent UTI (NR-UTI) (urine sample containing >105 bacterial colony-forming units/mL) and R-UTI (≥2 UTIs in any 6-month period or ≥3 UTIs in any 12-month period) post-KT in a retrospective cohort study (1999-2014) at Barnes-Jewish Hospital (St Louis, MO). All adult KT recipients were included and those experiencing mortality within 30 days of KT were excluded. Of 2469 recipients included, 1835 (74.3%) had no UTI, 465 (18.8%) had NR-UTI and 169 (6.8%) had R-UTI. R-UTI was associated with poorer graft survival compared with NR-UTI [hazard ratio (HR) 1.45; 95% confidence interval (CI) 1.23-1.83; P < 0.001) and no UTI (HR 2.11; 95% CI 2.02-3.80; P < 0.001). This relationship persisted after adjusting for confounding factors in Cox regression (HR 2.01; 95% CI 1.53-2.66; P < 0.001). There was no difference in patient survival between no UTI and NR-UTI (HR 1.21; 95% CI 0.91-1.63; P = 0.181); however, R-UTI was associated with poorer patient survival compared with nonrecurrent cases (HR 1.87; 95% CI 1.21-2.89; P = 0.005). R-UTI were more likely to be caused by multidrug-resistant Gram-negative organisms (risk ratio 1.49; 95% CI 1.31-1.70; P < 0.001). R-UTIs were associated with poorer graft and patient outcomes, as well as increased multidrug-resistance compared with nonrecurrent cases.


The underutilization of EUS-guided FNA in the lymph-node staging of non-small-cell lung cancer: perceptions of chest physicians in Wisconsin.
Recently, the American College of Chest Physicians (ACCP) published evidence-based guidelines for the invasive staging of non-small-cell lung cancer (NSCLC), which shows the potential value of transesophageal sampling by EUS-guided FNA (EUS-FNA). The objective of the study was to determine the perceptions and the clinical practice of chest physicians regarding EUS-FNA as a staging modality for NSCLC. We mailed a questionnaire to all members of the ACCP in Wisconsin. Seventy-one of 173 members (41%) responded. Chest physicians were more likely to perceive positron emission tomography, transbronchial needle aspiration, transthoracic needle aspiration, and mediastinoscopy to be able to make a difference in managing patients with NSCLC instead of EUS-FNA (p=0.01). Of the 40 chest physicians who believed that EUS-FNA can change the management of NSCLC, only 8 (20%) have sent a patient for EUS-FNA in the past year. Our findings may not necessarily reflect the opinions of chest physicians in other areas of the United States. Many of the chest physicians surveyed do not believe EUS-FNA impacts the management of NSCLC. This limited awareness may represent a barrier to successful utilization of EUS-FNA in lung-cancer staging.


Automatic Identification of Papillary Projections in Indeterminate Biliary Strictures Using Digital Single-Operator Cholangioscopy.
Characterization of biliary strictures is challenging. Papillary projections (PP) are often reported in biliary strictures with high malignancy potential during digital single-operator cholangioscopy. In recent years, the development of artificial intelligence (AI) algorithms for application to endoscopic practice has been intensely studied. We aimed to develop an AI algorithm for automatic detection of PP in digital single-operator cholangioscopy images. A convolutional neural network (CNN) was developed. Each frame was evaluated for the presence of PP. The CNN's performance was measured by the area under the curve, sensitivity, specificity, and positive and negative predictive values. A total of 3,920 images from 85 patients were included. Our model had a sensitivity and specificity 99.7% and 97.1%, respectively. The area under the curve was 1.00. Our CNN was able to detect PP with high accuracy. Future development of AI tools may optimize the macroscopic characterization of biliary strictures.


[Primary round-cell liposarcoma of the bladder].
To report a rare case of primary round cell liposarcoma of the urinary bladder. A case of primary round cell liposarcoma of the urinary bladder in an 80-year-old female with hematuria is presented. The patient had a large, solid, non-circumscribed bladder tumor of 6.5 cms. The radiological, histological and immunohistochemical findings are discussed. The neoplasm was composed of isolated lipoblasts among numerous small round cells that were positive for S-100 and vimentin, and a high proliferation rate was demonstrated by Ki-67. The patient died 10 months after the histologic diagnosis. Primary liposarcoma of the urinary bladder is a very rare tumor with a poor prognosis that usually presents as a large tumor mass.


Effects of a hypoproteic diet on myosin-V immunostained myenteric neurons and the proximal colon wall of aging rats.
The objective of this work was to analyze the morphoquantitative behavior of neurons of the myenteric plexus, as well as the morphometry of elements of the proximal colon wall of Wistar rats (Rattus norvegicus) fed a normoproteic (22%) and a hypoproteic (8%) diet, and sacrificed at 360 days of age. To perform the neuronal evaluation, we used whole-mount preparations of the proximal colon immunostained with the antibody anti-myosin-V. The neurons were quantified in 80 microscopic fields (16.98 mm(2)/animal). The neuronal cell body morphometry was performed in 100 neurons/animal. Samples of the proximal colon were weighed and measured, and then submitted to routine histological processing. They were later stained using the hematoxylin--eosin method in order to carry out morphometric analysis on the mucosa and external muscular layers. The number of neurons and the neuronal cell body morphometry did not present significant differences between the studied groups. A significant reduction in the weight and length of the proximal colon and in mucosa layer thickness was observed in the animals fed with the hypoproteic diet. We concluded that the neuronal and non-neuronal components of the proximal colon adapted to the imposed nutritional condition, which guaranteed the maintenance of their functions.


Reflexology in the management of low back pain: a pilot randomised controlled trial.
The current study was designed as a pilot study for a randomised controlled trial to investigate the effectiveness of reflexology in the management of low back pain (LBP). Participants suffering non-specific LBP were recruited and randomised into either a reflexology or a sham group. Patients and outcome assessor were blinded to group allocation. Each patient received either a 40 min reflexology treatment or sham treatment (according to group allocation) once per week for six consecutive weeks. The primary outcome measure was pain (visual analogue scale), secondary outcome measures were the McGill pain questionnaire, Roland-Morris disability questionnaire, and SF-36 health survey. Outcome measures were performed at baseline, week 6, week 12 and week 18. VAS scores for pain reduced in the treatment group by a median value of 2.5 cm, with minimal change in the sham group (0.2 cm). Secondary outcome measures produced an improvement in both groups (McGill pain questionnaire: 18 points in the reflexology group and 11.5 points in the sham group). Results indicate that reflexology may have a positive effect on LBP. Reflexology appears to offer promise as a treatment in the management of LBP; however, an adequately powered trial is required before any more definitive pronouncements are possible.


Predictive Value of Mean Platelet Volume for Aneurysm Recurrence in Patients with Aneurysmal Subarachnoid Hemorrhage After Endovascular Treatment.
The purpose of this study was to explore the relationship between mean platelet volume (MPV) and aneurysm recurrence in aneurysmal subarachnoid hemorrhage (aSAH) patients who received endovascular treatment for intracranial aneurysms. Data were collected and analyzed from 204 aneurysms in 187 aSAH patients who received endovascular treatment at our institution between January 2014 and January 2019. All aneurysms were divided into 2 groups based on aneurysm recurrence. Univariate and multivariable analyses were performed to investigate whether MPV was an independent predictor of aneurysm recurrence. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were determined. A total of 42 (20.6%) aneurysms recurred. Recurrent aneurysms had a lower rate of complete obliteration (P = 0.002) and lower MPV values on admission (P < 0.001) than nonrecurrent aneurysms. The multivariable analysis showed that the Raymond-Roy classification (odds ratio [OR]: 3.217, 95% confidence interval [CI]: 1.308-7.913, P = 0.011) and MPV (OR: 0.247, 95% CI: 0.151-0.402, P < 0.001) was significantly associated with aneurysm recurrence. The ROC curve analysis determined that MPV could predict aneurysm recurrence with an AUC of 0.846 (95% CI: 0.788-0.892, P < 0.001). An MPV ≤9.9 fL could predict aneurysm recurrence with a sensitivity of 80.95% and a specificity of 79.63%. A low perioperative MPV may be associated with aneurysm recurrence in aSAH patients who receive endovascular treatment for intracranial aneurysms. Therefore, MPV can be used in clinical settings to screen for patients at high risk for aneurysm recurrence.


Long-term impact of salinity on the performance and microbial population of an aerobic granular reactor treating a high-strength aromatic wastewater.
The effect of salinity over granular biomass treating a mixture of aromatic compounds (phenol, o-cresol and p-nitrophenol) was evaluated in a continuous airlift reactor. To mimic an industrial wastewater, increasing concentrations (from 2.0 to 29.0 g salts L(-1)) of a mixture of salts (MgSO4, NaCl, KCl, CaCl2 and NaHCO3) were introduced in the influent. The gradual salinity increase led to a good acclimation of the biomass obtaining complete biodegradation of the aromatic compounds and no accumulation of metabolic intermediates. However, a deterioration of the morphology of aerobic granules with a complete loss of granulation after 125 days was produced at 29.0 g salts L(-1). At that moment, anaerobic granules were added to promote granulation and after 50 days new aerobic granules were formed. These new aerobic granules remained stable for more than 100 days at the highest salinity condition with 100% removal of the mixture of aromatic compounds.


Vertebroplasty in the treatment of symptomatic vertebral haemangiomas without neurological deficit.
To evaluate the effectiveness of vertebroplasty in symptomatic vertebral haemangiomas (VHs) with no neurological deficit, with or without features of aggressiveness in imaging studies. A retrospective study was conducted to review 31 consecutive patients with symptomatic VHs that underwent vertebroplasty procedures (13 males, 18 females; mean age, 57.5 years), for a total of 33 affected vertebral levels (range, T4-L5 levels). Pre procedure radiological examinations were reviewed. The presence of predominant soft tissue stroma on CT, low signals on T1W of MRI, epidural tissue, and cortical erosion are considered features of aggressiveness. The clinical effects were evaluated using the visual analogue scale (VAS) and modified Roland-Morris Disability Questionnaire (RDQ) at the pre and each postoperative follow-up time point (mean follow-up of 15.8 months). Symptomatic VHs with no signs of aggressiveness were observed in 26 lesions and those with signs of aggressiveness in 7 lesions. Vertebroplasty was successfully performed under fluoroscopic guidance with a unipedicular approach in 16 levels, a bipedicular approach in 17 levels. VAS scores and RDQ scores were significantly improved after vertebroplasty (P < 0.001). Extraosseous cement leakage was observed in 4 patients without clinical complications. Vertebroplasty is an optional treatment for symptomatic VHs with no neurological deficit. • Vertebral haemangiomas with or without aggressive signs may cause pain. • Radiological signs of aggressiveness include evidence of lesions that contain less fat predominance, evidence of epidural soft tissue and evidence of cortical erosion. • Vertebroplasty provides effective treatment for symptomatic vertebral haemangiomas causing no neurological deficit.


Surgical enhancement of fracture healing - operative vs. nonoperative treatment.
Although the success story of surgical fracture treatment led to a tremendous improvement of treatment outcome for certain fractures such as femur or tibia shaft fractures, the overall benefit of surgical versus conservative treatment remains controversial for several types of fractures. For this sake, we carried out a narrative review of high-level of evidence studies comparing treatment outcomes in fractures with controversial debates on the value of surgical therapy in clavicle, proximal humerus, olecranon, ankle, calcaneus and Jones fractures. We identified eight studies (Level-I and -2) with functional and quality of life outcomes in these fractures. Only in Jones fractures of the fifth metatarsal bone, bone healing and functional outcomes were significantly better after surgical compared to conservative treatment. In terms of patient-related quality of life, surgical treatment was not found to be superior compared to conservative treatment in all the above-mentioned fractures. In many trials, lower nonunion rates after surgical treatment were offset by complications due to the surgical procedure. Nonunion after conservative treatment often seemed to have only limited impact on functional results. However, the comparability of studies was limited due to age-differences between patients. Therefore, we emphasize the need for further investigations to determine which patient-related factors favor a conservative treatment approach and for whom surgery is the best option.


Activation of low Km hexokinases in purified hepatocytes by binding to mitochondria.
Hepatocytes were purified on a Percoll gradient. The cell membrane of these hepatocytes was disrupted by digitonin in the presence of albumin, glucose and physiological concentrations of monovalent and divalent cations. This treatment led to a separation between free and loosely structure-bound cytosolic enzymes which is not achieved by conventional subfractionation techniques. According to kinetic and immunological analyses, the free extractable cytosolic fraction contained high Km, hexokinase (glucokinase) and less than 10% of low Km hexokinases, while the hexokinase activity bound to the cell structures represented exclusively low Km isozymes. The total activity of the bound hexokinases was comparable to that observed in the supernate (approx. 1.0 U per g fresh weight). This activity decreased more than 10-fold upon desorption at higher digitonin concentrations. Such activation by binding, as well as inactivation by desorption, could also be demonstrated in intact hepatocytes correlated to different metabolic states, and also in vitro with isolated mitochondria and purified isozyme I. The binding of low Km hexokinases in hepatocytes was restricted to the mitochondrial fraction and there it was observed in the contact sites between the two mitochondrial boundary membranes. In view of these findings it appears that the binding-dissociation equilibrium of low Km hexokinases plays an important role in metabolic regulation of glucose uptake and glycogen synthesis in the liver and presumably in muscle.


Developing of an environmental cell TEM holder for dynamic in situ observation.
This paper deals with the subject of "in situ" development of environmental-transmission electron microscope (E-TEM) holder assemblies. In E-TEM, the sample is continuously subjected to gases as opposed to conventional TEM where the sample is under high vacuum. E-TEM offers the possibility of achieving a new level of material analysis. E-TEM allows obtaining information about chemical information during the reaction at atomic level. Rarefied gas dynamics analysis is used to assess the proposed design. The analysis is focused on determining the molecular distribution inside the vacuum chamber and calculating the impingement rate on the target surface of the specimen. Simulations are performed to predict the molecular interaction with the specimen at given pressures to determine the proper position of a specimen within a vacuum chamber to optimize and predict reaction characteristics. Results of direct simulation Monte Carlo show that the two sides of the sample operate at different temperatures due to the gas flow and experience different molecular distributions.


COVID-19 and HIV among children and adolescents: Current inequalities.
The HIV epidemic enters its fifth decade amid a global pandemic. The increasing poverty, mental health problems, and abuse are raising the risk of infection for children, adolescents, and women. The inequalities driving the HIV epidemic, which are now exacerbated by COVID-19, demonstrate the social and clinical inequalities of more children infected with HIV and more children losing their fight against AIDS. In this context, current evidence highlights that, alarmingly, two out of five children living with HIV worldwide are unaware of their status, and just over half of children with HIV are receiving antiretroviral treatment. Discrimination and gender inequalities permeate significant situations in HIV services due to COVID-19 in early 2020 and throughout 2021. It was observed in recent studies substantial reductions in births in health facilities, maternal HIV testing, and initiation of antiretroviral treatment for HIV. An AIDS-free generation should be possible, but we are not there yet. HIV remains a burden.


Three-body-wear resistance of the experimental composites containing filler treated with hydrophobic silane coupling agents.
This paper evaluated the wear resistance of resin composite materials with fillers which were modified with a novel hydrophobic silane coupling agent. The novel silane coupling agent containing hydrophobic phenyl group 3-(3-methoxy-4-methacryloyloxyphenyl)propyltrimethoxysilane (p-MBS) was synthesized. The experimental light-cure hybrid composites containing 85wt% of filler modified with this silane were formulated. Twelve specimens were prepared for the three-body-wear test with the ACTA machine and the collected data were analyzed statistically using a one-way ANOVA and Tukey's multiple comparison test as the post hoc test. The wear of the composites containing fillers treated with p-MBS was significantly lower compared with the composite materials containing fillers pretreated with 3-methacryloyloxypropyltrimethoxysilane or the commercially composites (AP-X and ELS extra low shrinkage) after a wear test for 200,000 cycles (p<0.05). It is suggested that the resin composites containing fillers modified with the novel hydrophobic silane has high wear resistant, because of the coupling layers treated with this silane had an excellent affinity with the base resin and formed a highly hydrophobic layer on the filler surface.


Knowledge, attitudes and practices concerning breast cancer, cervical cancer and screening among healthcare professionals and students in Mogadishu, Somalia: a cross-sectional study.
Somali women face exceptionally high mortality and incidence rates from both breast cancer (BC) and cervical cancer (CC). They experience the highest age-standardised BC mortality rate in Africa and an age-standardised BC incidence rate of 41.7 per 100,000 women. Somalia's second-highest cancer-related mortality and incidence rates are due to CC, both behind BC. It is critical to identify the underlying factors that may influence healthcare workers' management of both cancers. At present, there is a lack of evidence regarding providers' knowledge of these two cancers and their screening in Somalia. A cross-sectional questionnaire was administered with a purposive sampling strategy to 469 healthcare professionals and students and was completed by 405 (86%). Healthcare workers were recruited from Mogadishu-based hospitals. One hundred and ninety-seven healthcare professionals and 207 students completed the survey and were included in the analysis. 89% and 73% of respondents demonstrated good knowledge of BC and CC, respectively. Only 46% knew that a vaccine could prevent CC, and 89% of healthcare professionals disagreed that human papillomavirus (HPV) vaccines were available to their patients. Attitudes towards cancer screening, in addition to breast self-examination (BSE), were overwhelmingly positive. For both BC and CC, 24% reported having treated a patient and 30% reported having conducted a screen for either disease. Overall, while knowledge of both diseases and screening was good, there remain areas for clear educational targeting such as HPV vaccine availability and BC preventability. Attitudes to screening for both diseases were exceedingly positive but, with the exception of BSE, failed to translate into practice due to inadequate resources and patient refusal. Future investments into Somalia's chronic care management should prioritise technology necessary to conduct screenings for both diseases, expanding HPV vaccine access and understanding patients' potential motivations for refusing screening.


Zinc oxide nanoparticles synthesized from Fraxinus rhynchophylla extract by green route method attenuates the chemical and heat induced neurogenic and inflammatory pain models in mice.
Fraxinus rhynchophylla belongs to the family of Oleaceae and also called as Chinese ash wood possesses various pharmacological properties such as neuroprotective, antimicrobial, anti-inflammatory, etc. Therefore we synthesized ZnO nanoparticles using Fraxinus rhynchophylla wood extract as reducing and capping agent. The synthesized nanoparticles were characterized with the aid of UV-Spec, DLS, FT-IR and TEM analysis. Green synthesized ZnO nanoparticles were then assessed for anti-nociceptive property by using various nociception models such as thermal stress-induced, acetic acid, glutamate, capsaicin, and formalin-induced nociception. The sedative effect of synthesized ZnO nanoparticles was evaluated with an open field test. UV-Spectroscopic analysis confirms the formation of ZnO nanoparticles and the characterization studies DLS, FT-IR, and TEM analysis prove it has ideal nanoparticle can be used as a nano-drug. Results of both thermal stress-induced methods hot plate and tail immersion nociception test verified the synthesized ZnO nanoparticles are a potent antinociceptive drug. ZnO nanoparticles effectively reduced the abdominal writhes in acetic acid-induced nociception and it also significantly decreased the nociception activity in another glutamate, capsaicin, and formalin-induced nociception models. Open field experiment proved that synthesized ZnO nanoparticles are less sedative compared to the standard antinociceptive drug morphine. Overall our findings authentically confirm ZnO nanoparticles synthesized from Fraxinus rhynchophylla wood extract is a novel drug that persuasively reduces nociception in different nociceptive induced mice models and can be the best alternative for allopathic drugs which renders severe side effects.


Factors associated with use of dental services among HIV-infected and high-risk uninfected women.
The authors explored the frequency of dental care utilization and identified the main barriers to access to dental care among U.S. women with HIV infection and uninfected women at high risk of becoming infected. The authors' prospective study included HIV-infected and uninfected women enrolled in the northern California and Chicago sites of the Women's Interagency HIV Study. A trained interviewer administered a standardized questionnaire to participants by phone. The authors explored subjects' utilization of dental care in relation to predisposing, enabling and need variables using both univariate and multivariate analyses. The 363 participants were predominantly black and unemployed and had a history of using injected drugs. Not using dental care was most prevalent among HIV-negative women, particularly in Chicago. Multivariate analyses revealed that the strongest predictors of nonuse of dental care included being of a race other than white, fear of dentists and perception of poor or fair oral health. Women not infected with HIV but at high risk of developing the infection appear to have even greater unmet dental needs than do HIV-positive women. Being of a race other than white and fear of dentists are strong predictors of not using dental care. The Ryan White Comprehensive AIDS Resources Emergency Act facilitates dental care access for people who are HIV-positive, and is the likely explanation for the higher prevalence of dental care use in this group compared with uninfected women at high risk of becoming infected. This underscores the need for Medicaid to include dental coverage for low-income populations in all states.


Mechanical Thrombectomy with Intravenous Thrombolysis versus Thrombolysis Alone for the Treatment of Stroke: A Systematic Review of Economic Evaluations.
Mechanical thrombectomy has revolutionized the management of stroke by improving the recanalization rates and reducing deleterious consequences. It is now the standard of care despite the high financial cost. A considerable number of studies have evaluated its cost effectiveness. Therefore, this study aimed to identify economic evaluations of mechanical thrombectomy with thrombolysis compared with thrombolysis alone to provide an update of existing evidence, focusing on the period after proof of effectiveness of mechanical thrombectomy. Twenty-one studies were included in the review: 18 were model-based economic evaluations to simulate long-term outcomes and costs, and 19 were conducted in high-income countries. Incremental cost-effectiveness ratios ranged from -$5,670 to $74,216 per quality-adjusted life year. Mechanical thrombectomy is cost-effective in high-income countries and in the populations selected for clinical trials. However, most of the studies used the same data. There is a lack of real-world and long-term data to analyze the cost effectiveness of mechanical thrombectomy in treating the global burden of stroke.