M.ALSHEIKH Technique: Modification to the Soft Tissue Reduction in the Baha® Attract Surgery.
To describe a modification to the Baha® Attract surgical technique that aims to enhance skin closure, create smooth skin across the surface of the wound, reduce surgery time, and improve cosmetics of the surgical site. Retrospective chart review. Patients were implanted between 2014 and 2016 at King Fahad General Hospital (KFGH) (Jeddah, Kingdom of Saudi Arabia). 20 adult patients (11 males, 9 females), all eligible for Baha® Attract system. One patient only had a previous Baha® surgery. The normal Baha® Attract surgical technique with modification to the soft tissue reduction stage is described. The mean surgical time was 35.25 min (range 25-55). Bleeding was present but not significant and easily controlled in four patients. All patients received the 4 mm implant. None of the patients experienced severe pain. The postoperative follow-up period was 6 months for 7 patients and 8 months for 13 patients. Patient feedback and monitoring indicates a good hearing performance and comfort in all patients. The modified Baha® Attract surgical method causes less postoperative complication, improve cosmetic effect, and provide shorter operative time compared to the conventional Attract procedure.


Spatial Variation in Contraceptive Practice Across the Districts of India, 1998-2016.
India is currently one of the most demographically diverse regions of the world. Fertility and mortality rates are known to show considerable variation at the level of regions, states and districts. Little is known however, about the spatial variations of the contraceptive usage-a critical variable that is relevant to fertility as well as health policy. This paper uses data from four national population-based household surveys conducted between 1998 and 2016 to explore district-level variations in the contraceptive prevalence rate. We find no clear evidence of convergence. The gap between the best and worst performing districts is more than 70 percent across the four rounds and does not diminish over time. We also find considerable evidence of spatial clustering across districts. Districts with high prevalence concentrate in Southern states and more recently, in the Northeast of the country. Our analysis suggests that female literacy and health care infrastructure are important correlates of spatial clusters. This suggests that investments in women's human capital and health-care infrastructure play a role in expanding women's opportunities to time their births.


Deferred Versus Performed Revascularization for Left Main Coronary Disease With Hemodynamic Significance.
The majority of randomized controlled trials of revascularization decision-making excludes left main coronary artery disease (LMD). Therefore, contemporary clinical outcomes of patients with stable coronary artery disease and LMD with proven ischemia remain poorly understood. The aim of this study was to assess the long-term clinical outcomes of physiologically significant LMD according to the treatment strategies of revascularization versus revascularization deferral. In this international multicenter registry of stable LMD interrogated with the instantaneous wave-free ratio, patients with physiologically significant ischemia (instantaneous wave-free ratio ≤0.89) were analyzed according to the coronary revascularization (n=151) versus revascularization deferral (n=74). Propensity score matching was performed to adjust for baseline clinical characteristics. The primary end point was a composite of death, nonfatal myocardial infarction, and ischemia-driven target lesion revascularization of left main stem. The secondary end points were as follows: cardiac death or spontaneous LMD-related myocardial infarction; and ischemia-driven target lesion revascularization of left main stem. At a median follow-up period of 2.8 years, the primary end point occurred in 11 patients (14.9%) in the revascularized group and 21 patients (28.4%) in the deferred group (hazard ratio, 0.42 [95% CI, 0.20-0.89]; P=0.023). For the secondary end points, cardiac death or LMD-related myocardial infarction occurred significantly less frequently in the revascularized group (0.0% versus 8.1%; P=0.004). The rate of ischemia-driven target lesion revascularization of left main stem was also significantly lower in the revascularized group (5.4% versus 17.6%; hazard ratio, 0.20 [95% CI, 0.056-0.70]; P=0.012). In patients who underwent revascularization for stable coronary artery disease and physiologically significant LMD determined by instantaneous wave-free ratio, the long-term clinical outcomes were significantly improved as compared with those in whom revascularization was deferred.


Survival of Minced Cartilage Grafts with Comparison Surgicel(®) Original and Fibrillar.
Cartilage grafts are commonly used in nasal surgery for structural and/or esthetic purposes. The viability of cartilage grafts has been investigated in many forms since the use of cartilage grafts in surgical procedures. The objective of this study was to investigate the viability of minced cartilage grafts and whether there is a difference between grafts wrapped in Surgicel(®) Original and Surgicel Fibrillar. A total of ten New Zealand rabbits were used for the study. Cartilage grafts were harvested from one side ear. Four groups were formed. Group 1: minced cartilage graft wrapped in Surgicel Fibrillar; Group 2: minced cartilage graft wrapped in Surgicel Original; Group 3: bare minced cartilage graft; and Group 4: bare diced cartilage graft. Four small subcutaneous pockets were made in the backs of the rabbits, and the grafts were placed in these pockets. All of the rabbits were sacrificed at the end of 3 months, and the samples were collected. The sections were stained with hematoxylin and eosin (H&E), toluidin blue, safranin-O, masson trichrome, and glial fibrillary acidic protein immunohistochemical. All specimens were assessed histopathologically under a light microscope. There was no statistically significant difference between the Surgicel Fibrillar and Surgicel Original groups with respect to any of the parameters. Bone formation, calcification, inflammation, fibrosis, and basophilia were similar in all groups, with no significant difference among them. In the Surgicel Fibrillar and Surgicel Original groups, a heavy chondrocyte nucleus loss accompanied by a minimal peripheral proliferation was observed. The viability of bare minced cartilage grafts was found to be similar to that of bare diced cartilage in this study. Minced cartilage grafts can be used in the correction of minor dorsal defects and irregularities in persons with thin nasal skins, especially in primary and revision rhinoplasty. Although there is no statistically significant difference between the Surgicel Fibrillary and Surgicel Original groups, we think that, if it is necessary to use oxidized regenerated cellulose, it should be in the fibrillar form. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors http://www.springer.com/00266 .


Palliative care and end-of-life planning in Parkinson's disease.
In Parkinson's disease (PD) typical "palliative care" type symptoms, such as pain, nausea, weight loss and breathlessness can occur throughout the condition, but become more prevalent in later disease stages. Pain may be specifically related to PD, e.g. dystonic pain with wearing off, but is more commonly due to other conditions. The cause can usually be elicited by a careful history and examination, and this guides intervention, both non-pharmaceutical, and pharmaceutical. For example, dystonic pain will respond best to appropriate changes to dopaminergic medication. In later disease stages people have increasing problems with swallowing, and also cognitive impairment. Impaired swallowing may lead to aspiration pneumonia, which is a common cause of hospital admission, and also death. Decisions about interventions towards the end of life, such as insertion of percutaneous endoscopic gastrostomy (PEG) tube for nutrition, can be very challenging, particularly if, as in most cases, the person with PD has not previously expressed their views upon this while they still maintained capacity to make decisions. Advance care planning (ACP) in PD should be encouraged in relation to interventions such as PEG tubes. It may also cover issues such as preferred place of death. Over recent years lower proportions of people have been dying at home, and this is especially true for PD, but home may well be where they would have preferred to die. However, there is little evidence to guide health professionals about how, when, and by whom, ACP should be approached.


Sex differences in preclinical models of hypertension.
Hypertension remains the primary contributor in the development of cardiovascular disease which is rapidly increasing worldwide. High blood pressure affects men and women differently and understanding these sex differences is the ultimate unmet need for researchers in this field. Due to the inherent differences in hypertension prevalence, control and outcomes between men and women, novel research needs to be carried out to tackle these disparities and improve targeted treatment. Animal models of hypertension have provided valuable insights into the sexual dimorphism of blood pressure mechanisms. The availability of genetic and non-genetic hypertensive strains allows the opportunity to study diverse environmental and genetic factors that affect blood pressure, therefore presenting a valuable tool for researchers. Sex differences are present before birth and throughout life, which presents a challenge for the study of disease development in humans, but these complexities can be resolved with the use of in vivo models that display similarities to human disease. The aim of the present review is to provide an overview of the different available animal models of hypertension that present sexual dimorphisms and to discuss their relevance to humans.


Choroidal Thickness in 3001 Chinese Children Aged 6 to 19 Years Using Swept-Source OCT.
The purpose of the cross-sectional study is to describe the values and distribution of choroidal thickness and to explore its related factors, especially age, in Chinese children. A total of 3001 Chinese school children aged 6 to 19 years underwent comprehensive ophthalmic examinations, including axial length and cycloplegic refraction. Choroidal thickness was measured by swept-source optical coherence tomography (SS-OCT). There was a greater difference in the more central regions between the myopes and emmetropes. Multiple regression analysis was performed to determine the associated factors of choroidal thickness. The results demonstrated that age was independently positively related to choroidal thickness for emmetropes (β = 3.859, p < 0.001), and mild myopes with spherical equivalent greater than -2.00 D (-1.25 D < spherical equivalent ≤ -0.50 D: β = 3.476, p = 0.006; -2.00 D < spherical equivalent ≤ -1.25 D: β = 3.232, p = 0.020). However, no significant relationship between age and choroidal thickness was found in children with spherical equivalent ≤ -2.00 D, suggesting that the protective effect of physiologic choroidal growth with age against rapid axial elongation disappeared while axial elongation becomes the dominant determinant of choroidal thickness among children with myopia worse than -2.00 D.


[3H]spiroperidol binding in crude membrane suspensions of gill tissue from the marine mussel, Mytilus californianus.
Saturable, high-affinity binding sites for [3H]spiroperidol can be demonstrated in crude suspensions of mussel gill tissue. This binding shows stereospecificity toward the d- and l-isomers of butaclamol. Competition studies show that both dopamine and serotonin can displace [3H]spiroperidol from binding sites at nanomolar concentrations. Evidence is presented that suggests that the [3H]spiroperidol-binding sites can be divided into two distinct groups: those with high affinity for dopamine and those with high affinity for serotonin.


Direct SERS detection of contaminants in a complex mixture: rapid, single step screening for melamine in liquid infant formula.
Melamine can be detected in infant formula without the need for additional sample preparation or purification using a simple galvanic displacement reaction to fabricate portable silver SERS substrates. The reaction is rapid, inexpensive, and robust enough to perform well on highly heterogeneous common metal objects such as tape and coins.


Minimally Invasive Adrenalectomy.
Minimally invasive adrenalectomy has become the gold standard for removal of benign adrenal tumors. The imaging characteristics, biochemical evaluation, and patient selection for laparoscopic transabdominal and posterior retroperitoneoscopic approaches are discussed with details of surgical technique for both procedures.


New approaches in vaccine development for parasitic infections.
Vaccines have had a tremendous impact on the control of infectious diseases. Not only are vaccines potentially the least expensive mechanism to combat infectious diseases, under optimal conditions, widespread vaccination can result in disease eradication - as in the case of smallpox. Despite this great potential, vaccines have had little impact on human parasitic infections. The reasons for this are many - these eukaryotic pathogens are genetically and biologically complex organisms, some with elaborate life cycles and well-honed immune evasion mechanisms. Additionally, our understanding of the mechanisms of immune control of many parasitic infections -- of what constitutes an effective immune response and of how to induce high-quality immunological memory -- is not fully developed. This review attempts to highlight recent advances that could impact vaccine discovery and development in parasitic infections and proposes areas where future studies may lead to breakthroughs in vaccines for the agents of parasitic diseases. There are several other recent reviews highlighting the results of vaccine trials, specifically in the malaria field.


Upper airway obstruction by a fragmented tracheostomy tube: Case report and review of the literature.
Many objects were described in the literature as causes of upper airway obstruction including seeds, nuts and household particles but fragmented tracheostomy tube is a rarely reported cause of airway obstruction. We report a case of foreign body aspiration in the tracheobronchial tree due to a fragmented and migrated tracheostomy tube. We report a 4.5 year old female patient who had upper airway obstruction due to a fragmented and migrated tracheostomy tube. She was diagnosed by chest X-ray and the tube was removed by rigid bronchoscopy. Several factors contribute to fragmentation of the tracheostomy tube including repeated removal and reinsertion, cleaning, boiling or chemicals. Early breakage is most often due to manufacturing defects. The occurrence of a fractured tracheostomy tube in children is rare. Nevertheless, tracheobronchial foreign bodies in children can be life threatening and pose a dire emergency. Based on our experience, the doctors and other staff should check for any manufacturing defects before the first use of a tracheostomy tube, which should reduce the occurrence of this rare, but life threatening.


Zinc metabolism in endurance-trained volunteers during prolonged restriction of muscular activity and chronic hyperhydration.
The objective of this study was to evaluate the effects of hypokinesia (HK) and fluid- and salt supplementation (FSS) on zinc metabolism in endurance-trained volunteers (ETV) for a period of 364 d. Thirty long-distance runners aged 22-25 yr with a peak VO2 of 67 mL/min/kg with an average 13.8 km/d running distance were chosen as subjects. They were equally divided into three groups: 1. Controls; 2. HK subjects; and 3. HK + FSS subjects. Throughout the duration of the study, groups 2. and 3. were maintained under an average running distance of 2.7 km/d, whereas group 1. did not experience any modifications to their normal training routines and diets. Prior to and during the experimental period, plasma volume, hemoglobin, sodium, potassium, hematocrit, osmolality, and protein concentrations were determined along with the concentrations and urinary excretions of zinc, magnesium, calcium, and phosphorous. During the HK period, plasma concentrations of these minerals increased significantly when compared to the HK + FSS and control groups. The same was observed for the remaining parameters, which led us to conclude that during prolonged restriction of muscular activity, (PRMA) the body of the HK + FSS volunteers acquire an apparent tendency to retain zinc, whereas in the HK group the opposite is observed.


Method for distinguishing between drug action on impulse propagation versus impulse generation.
Systemic or regional application of local anaesthetics or tetrodotoxin eliminate repetitive impulse discharge, but do they do so by blocking impulse propagation or by suppressing impulse initiation? A method is described for making this distinction based on differences in the pattern of discharge change during the onset of the block. Suppression of conductances involved in downstream impulse propagation produces integer multiplication of the fundamental interspike interval (interspike interval (ISI) doubling, tripling, etc.) In contrast, progressive block of conductances responsible for either the creation of the generator potential, or for its encoding into a spike train, causes a smooth increase in the rhythmic ISI. These two patterns of block, predicted on the basis of fundamental principles and numerical simulations, were verified in in vivo single-axon recordings.


Kinetics of expression of genes involved in glucose metabolism after the last meal in overfed mule ducks.
In waterfowls, overfeeding leads to a hepatic steatosis, also called "foie gras." We decided to investigate the role of glucose metabolism in steatosis emergence. For this, we measured the expression of genes during the 12 h following the last meal of the overfeeding period. As expected, it showed that the expression of glucose transporter is more precocious in jejunal mucosa, especially for SGLT1, known to be the major transporter at the apical surface. In the liver, GLUT2 and HK1 are upregulated at the same time and seem to work together to import glucose. In peripherals tissues, such as muscle and subcutaneous adipose tissue (SAT), expression of genes of interest occurs later than the one in jejunum and liver. These results are in accordance with the evolution of glycemia. This study allows us to better understand the kinetic treatment of glucose after a meal in overfed ducks. It also will allow researchers to better target their sampling time knowing the optimal point of expression of each gene.


[Connection between the knowledge of the recommendations of the National Nutrition and Health Program and patterns of eating behaviour and physical activity].
Nutrition education is one of the main lines of the French nutrition policy that has been undertaken for several years. The underlying hypothesis of this approach is that knowledge improvement is one of the ways likely to contribute to health-enhancing diet and physical activity. The objective of this paper, based on the 2008 Health and nutrition Barometer, is to examine the associations observed between knowledge and behavior with regard to diet and physical activity. The 2008 Health and nutrition Barometer is a nationally representative telephone survey conducted on 4714 individuals aged 12-75 years. For six recommendations of the National Nutrition and Health Program (Programme national nutrition santé [PNNS]), multiple logistic models were used to identify associations between knowledge of these recommendations and behavior, among adults aged 18-75 years. For food consumed on the day before the interview, odds ratios were adjusted for sex, age, education level, agglomeration size and region. As bivariate analysis showed that income level was significant for recommended consumption of fish, this variable was introduced among adjustment variables. Similarly, the variable occupation was introduced for physical activity. A positive association between knowledge of recommendations and nutritional behavior on the day before interview was observed for fruit and vegetables (OR=1.7), dairy products (OR=1.6), and starchy food (OR=1.6). The same was observed for consumption of fish during the 15 days before the interview (OR=5.0) and for physical activity during a usual week (OR=1.5) but not for the "meat, seafood and eggs" food group. Eating habits and physical activity are positively associated with knowledge of nutritional recommendations, mainly acquired via nutritional information and educational actions. Nevertheless, the important differences observed for certain dietary groups between knowledge of recommendations and dietary intake emphasizes the need to further support individual-focused initiatives with health-enhancing environmental strategies.


Linked equilibria in regulation of transcription initiation.
Assembly of transcriptional regulatory complexes often involves multiple binding processes and these binding processes are frequently coupled to one another. Small molecule binding can promote or inhibit DNA-binding or protein-protein interactions. DNA binding may be coupled to protein association. Finally, proteins may bind cooperatively to multiple sites in a transcriptional regulatory region. The level of transcription initiation at a promoter reflects the assembly of regulatory complexes in a transcription control region. Quantitative mechanistic understanding of regulatory complex assembly requires dissection of the assembly process into its constituent interactions followed by measurements of linkage between the individual binding processes. Methods and approaches to achieving this quantitative understanding of transcription regulation are outlined in this chapter.


Geometric reconstruction methods for electron tomography.
Electron tomography is becoming an increasingly important tool in materials science for studying the three-dimensional morphologies and chemical compositions of nanostructures. The image quality obtained by many current algorithms is seriously affected by the problems of missing wedge artefacts and non-linear projection intensities due to diffraction effects. The former refers to the fact that data cannot be acquired over the full 180° tilt range; the latter implies that for some orientations, crystalline structures can show strong contrast changes. To overcome these problems we introduce and discuss several algorithms from the mathematical fields of geometric and discrete tomography. The algorithms incorporate geometric prior knowledge (mainly convexity and homogeneity), which also in principle considerably reduces the number of tilt angles required. Results are discussed for the reconstruction of an InAs nanowire.


Permeability of iodide in multilamellar liposomes modeled by two compartments and a reservoir.
A previously published rate law for the diffusion of iodide from multilamellar egg phosphatidylcholine liposomes (Schullery, S.E. (1975) Chem. Phys. Lipids 14, 49-58) is fitted to the relatively simple mathematical model of two compartments in series with a reservoir. All of the inner liposome compartments are assumed to behave as effectively one compartment in series with the liposome's outermost compartment. Based on this model, reasonable values are calculated for the fraction of the total solution trapped by liposomes which is in the outermost liposome compartment, 17%, and the permeability coefficient of iodide against isotonic, mixed iodide-chloride solution, 2-10(-9) cm/s.


History and Evolution of Modeling in Biotechnology: Modeling & Simulation, Application and Hardware Performance.
Biological systems are typically composed of highly interconnected subunits and possess an inherent complexity that make monitoring, control and optimization of a bioprocess a challenging task. Today a toolset of modeling techniques can provide guidance in understanding complexity and in meeting those challenges. Over the last four decades, computational performance increased exponentially. This increase in hardware capacity allowed ever more detailed and computationally intensive models approaching a "one-to-one" representation of the biological reality. Fueled by governmental guidelines like the PAT initiative of the FDA, novel soft sensors and techniques were developed in the past to ensure product quality and provide data in real time. The estimation of current process state and prediction of future process course eventually enabled dynamic process control. In this review, past, present and envisioned future of models in biotechnology are compared and discussed with regard to application in process monitoring, control and optimization. In addition, hardware requirements and availability to fit the needs of increasingly more complex models are summarized. The major techniques and diverse approaches of modeling in industrial biotechnology are compared, and current as well as future trends and perspectives are outlined.


Topically applied semaphorin 3A ointment inhibits scratching behavior and improves skin inflammation in NC/Nga mice with atopic dermatitis.
Epidermal hyperinnervation in atopic dermatitis (AD) is activated directly by various external stimuli, causing enhanced itching. Nerve density is regulated by the nerve repulsion factor semaphorin 3A (Sema3A), along with nerve elongation factors. To investigate the effects of Sema3A ointment in the NC/Nga mouse model of AD. An AD-like phenotype was induced by repeated application of Dermatophagoides farinae body (Dfb) ointment to the dorsal skin of NC/Nga mice. Vaseline, heparinoid, betamethasone, tacrolimus and recombinant Sema3A ointments were applied to the lesional skin once a day for 4 days. Transepidermal water loss (TEWL) was measured before and after each treatment. We also scored the degree of dermatitis and recorded videos to observe scratching behavior. Subsequently, we collected skin samples from these mice for histological analyses. Topical application of Sema3A, betamethasone and tacrolimus ointments significantly inhibited scratching behavior and improved dermatitis scores in Dfb-treated mice compared with control mice, whereas vaseline and heparinoid had no effects. A significant improvement of TEWL was observed only in Sema3A ointment-treated mice. Moreover, Sema3A ointment reduced the densities of PGP9.5- and substance P-immunoreactive nerve fibers in the epidermis and the numbers of inflammatory cells, such as CD4 immunoreactive T cells and eosinophils, and improved acanthosis in the Dfb-treated mice compared with controls. Sem3A ointment may have therapeutic efficacy in patients with pruritus and dermatitis of AD.


The precursor strategy: terminus methoxyoxalamido modifiers for single and multiple functionalization of oligodeoxyribonucleotides.
Synthesis of new terminus modifiers, bearing, along with a phosphoramidite moiety, one, two or four methoxyoxalamido (MOX) precursor groups, is described. These modifiers are introduced onto the 5'-end of a synthetic oligodeoxyribonucleotide as the last step of an automated synthesis to form the MOX precursor oligonucleotide. The MOX groups are then post-synthetically derivatized with an appropriate primary amine to construct a 5'-modified oligonucleotide. The efficiency and simplicity of the novel modifying strategy were demonstrated in the synthesis of a number of 5'-functionalized oligonucleotides.


Piroxicam serum levels in patients treated for rheumatic diseases.
Serum levels of piroxicam were observed for periods of one to 15 months in patients who had a variety of rheumatic diseases. At a dose of 20 mg per day, patients' serum levels ranged from undetectable (less than 0.5) to 24.8 micrograms/mL. Mean serum levels did not vary with age or body weight and remained relatively constant in individual subjects during the period of follow-up. Thus, there is no justification for altering the recommended dose of 20 mg based solely on patient age or weight. Concomitant administration of salicylate or acetaminophen was associated with decreased serum levels of piroxicam, but other drugs, such as diuretics, prednisone, and cimetidine, had no discernible effect on piroxicam levels. Gastrointestinal toxicity, requiring discontinuance of piroxicam therapy, occurred in only four patients, and there was no association between serum levels of piroxicam and gastrointestinal toxicity.


Synthesis and biological evaluation against Leishmania amazonensis of a series of alkyl-substituted benzophenones.
Nine O-alkyl and O-prenyl derivatives were synthesized from commercial 2,4-dihydroxybenzophenone, 4,e4,4'-dihydroxybenzophenone and were evaluated for their leishmanicidal activity against promastigote forms of Leishmania amazonensis, as well their toxicity in murine macrophages. All derivatives exhibited better biological activity than their hydroxylated benzophenones precursors, and new compound LFQM-123 (3c) was 250-fold more active than its precursor 4,4'-dihydroxybenzophenone (3). Moreover, some of the results were comparable to the standard drug Amphotericin B, suggesting that the increase in lipophilicity could facilitate protozoa membrane permeation. In this study we confirmed that benzophenone derivatives exhibit leishmanicidal properties, with relatively low toxicity, and thus could be exploited as promise prototypes for the design and development of new drug for the treatment of leishmaniasis.


A 70-Year-Old Woman With Long-Term Nonresolving Pneumonia.
A 70-year-old woman who had received a diagnosis of pneumonia in the right lower lobe was treated with antibiotics at a general practitioner's clinic 9 months earlier. Her pneumonia had improved, but the cough and lung infiltrates persisted for > 6 months, so the patient was referred to our hospital. She had undergone surgery for breast cancer 30 years earlier but had no other medical history. She was not taking any medications and had no history of smoking, including passive smoking.


Extrapleural thoracoscopic excision of a mediastinal bronchogenic cyst in a patient with dense pleural adhesions.
We report the case of a 70-year-old man with dense pleural adhesions who underwent an excision of a mediastinal bronchogenic cyst by video-assisted thoracoscopic surgery (VATS) through an extrapleural approach. The VATS approach for the diagnostic and therapeutic excision of a mediastinal tumor is easier and safer than an intrapleural approach if a patient has dense pleural adhesions.


Decreased lipid peroxidation in the rat kidney during gestation.
Renal malonaldehyde content and lipid peroxidation, induced by ascorbate, NADPH and cumene hydroperoxide, are significantly decreased during gestation in rats. Lipid peroxidation tends to reach normal levels in the kidney post partum. In the renal mitochondria lipid peroxidation without co-factors and that induced by cumene hydroperoxide, ascorbate and NADPH is decreased during pregnancy. However, in the microsomes, only lipid peroxidation induced by NADPH and cumene hydroperoxide is affected. The observed decrease in lipid peroxidation during gestation is reflected by low levels of total lipid and phospholipid. Endogenous inhibitors of lipid peroxidation also increase during pregnancy.


Validation of the 25 level modified shuttle test in children with cystic fibrosis.
To evaluate the validity and reliability of the modified shuttle 25-level test (MST-25) in children with cystic fibrosis (CF). A prospective single center study in clinically stable children with CF. Participants undertook two testing conditions on different days: (1) 2xMST-25 tests; (2) cardiopulmonary exercise test (CPET). Test order was randomized. Nadir oxygen saturation (SpO2 ), peak heart rate (HR), breathlessness (modified Borg), rate of perceived exertion (RPE), energy expenditure (EE) and metabolic equivalents (MET) from the MST-25 and CPET were compared to assess validity, while outcomes from 2xMST-25 tests were compared for reliability. CPET was performed using breath-by-breath analysis and EE from the MST-25 obtained using the SenseWear Armband. Strong correlations were found between MST-25 distance and peak oxygen uptake, peak work and minute ventilation on CPET (all r > 0.7, p < 0.01). Moderate correlations were found between MST-25 distance and CPET for METs (r = 0.5) and HR (r = 0.6). Weak associations between tests were evident for nadir SpO2 (r = 0.1), modified Borg (rs = 0.2) and RPE (rs = 0.2). Test-retest reliability was excellent for MST-25 distance (ICC 0.91), peak EE (ICC 0.99) and peak METs (ICC 0.90). Good reliability was achieved for HR (ICC 0.84) and modified Borg score (ICC 0.77), while moderate reliability for nadir SpO2 (ICC 0.64) and RPE (ICC 0.68) was observed. The MST-25 is a valid and reliable field test for the assessment of exercise capacity in children with CF. The MST-25 can be used to accurately monitor exercise capacity and prescribe exercise training, particularly when CPET is not available.


Prognostic relevance of circulating endothelial progenitor cells for severe traumatic brain injury.
Traumatic brain injury (TBI) promotes the recruitment of endothelial progenitor cells (EPCs) into the injured tissue where EPCs play an important role in repairing injured vasculature. However, the repair mechanism and prognostic significance of EPCs after TBI remain poorly understood. Blood samples were collected from 21 patients with severe TBI and 20 healthy subjects. EPCs were quantified by flow cytometry and serum VEGF and MMP-9 level measured by ELISA on days 1, 4, 7, 14 and 21 after TBI. EPCs in the patients decreased originally, then increased to the peak level at 7 days and was significantly correlated with GOS scores 6 months after TBI. VEGF and MMP-9 were significantly increased during the follow-up period after TBI. EPCs was also positively correlated with GCS score 1 day after TBI and with MMP-9 and VEGF 7 days and 14 days after TBI. The data demonstrate that TBI led to an increase of EPCs, VEGF and MMP-9, suggesting that increased VEGF and MMP-9 may mediate the recruitment of bone marrow-derived EPCs into the circulation. The association of EPCs with nerve functional recovery in patients provides evidence that EPCs may be a potential biomarker to monitor TBI angiogenesis and prognosis.


[Connective tissue diseases in childhood].
Connective tissue diseases are a heterogeneous group of chronic multisystem inflammatory disorders including systemic lupus erythematosus (SLE), progressive systemic sclerosis (PSS), dermato- (DM) and polymyositis (PM), mixed connective tissue disease (MCTD), and Sjögren's syndrome (SS). Patients can present with similar clinical features, particularly during the first onset of symptoms, which frequently makes the diagnosis of a specific disease difficult. The incidence of connective tissue diseases is much lower in children than adults; however, the clinical picture is more variable. Clinical signs, such as fatigue, fever, or weight loss, may precede any systemic organ involvement and in children, mucocutaneous manifestations develop most frequently during the varying disease course. This review summarizes recent information on epidemiology, clinical manifestations, diagnostic procedures, and treatment strategies of the different connective tissue diseases, concentrating on specific problems in childhood.


Lead-related superior vena cava syndrome: Management and outcomes.
Superior vena cava (SVC) syndrome includes the clinical sequalae of facial and bilateral upper extremity edema, dizziness, and occasional syncope. Historically, most cases have been associated with malignancy and treatment is palliative. However, cardiac device leads have been identified as important nonmalignant causes of this syndrome. There are little data on the effectiveness of venoplasty and lead extraction in the management of these patients. The objective of this study was to report the findings associated with the use of balloon angioplasty and lead extraction in the management of 17 patients with lead induced SVC syndrome. Data collected from January 2003 to July 2019 identified 17 cases of SVC syndrome at our tertiary center. Their outcomes were compared to a control group of patients without SVC syndrome. A P value of <.05 was considered statistically significant. Of the 17 patients, 13 (76%) underwent transvenous lead extraction and venoplasty. Three patients (18%) were treated with venoplasty alone, and 1 patient (6%) underwent surgical SVC reconstruction. In 10 patients (59%), transvenous reimplantation was necessary. Symptom resolution was achieved in all 17 patients and confirmed at both 6 and 12 months' follow-up. There was no significant difference in the rate of complications associated with transvenous lead extraction for SVC syndrome vs control. In patients with SVC syndrome, venoplasty and lead extraction are safe and effective for resolution of symptoms and maintaining SVC patency.


Is the early and aggressive administration of protein to very low birth weight infants safe and efficacious?
Most conventionally managed very low birth weight infants experience postnatal growth restriction. There is some evidence that this postnatal growth restriction may have long-lasting effects, and contribute to short stature and poor neurodevelopmental outcomes. There is also evidence suggesting that early protein intake may improve growth in these very low birth weight infants. Therefore, to optimize protein intake early in the infant's neonatal course seems a logical goal. Randomized controlled trials provide evidence of short-term safety and efficacy for starting amino acid infusion as soon as possible after birth at 2.5-3.0 g/kg/day in very low birth weight infants; however, there are no long-term data to support the safety or efficacy of this practice. There is some evidence from recent studies of improved growth by providing 4.0 g/kg/day of amino acid early in the neonatal period while keeping the nitrogen to energy ratio above 1:100 and continuing with this protein intake during the infants stay in the hospital. At the present time long-term safety of this strategy is also not known. Appropriately designed large-scale randomized controlled trials are needed to determine the long-term safety and efficacy of early and aggressive administration of protein to very low birth weight infants.


Portomesenteric vein thrombosis following sleeve gastrectomy: Case report focusing on the role of pathogenetic factors.
Sleeve gastrectomy has currently become the most commonly performed bariatric. procedure worldwide according to the last IFSO survey, overtaking gastric bypass with. a share of more than 50% of all primary bariatric-metabolic surgery. Gastric leak, intraluminal bleeding, bleeding from the staple-line and strictures are the most common complications. Portomesenteric vein thrombosis (PMVT)after sleeve gastrectomy is. another complication that has been increasingly reported in case-series in recent.years, although it remains uncommon. In this case report is described an extended portomesenteric vein thrombosis after. sleeve gastrectomy interesting splenic vein too with a favorable course and an. uneventful follow-up. We try to search in this case for pathogenetic factors involved in. this complication. A 42-year old man, with a body mass index (BMI) of 45 kg/m2, with a medical history of Obstructive Sleep Apnea Sindrome (OSAS) underwent laparoscopic sleeve gastrectomy. Early postoperative course was uneventful. Six days after discharge he complained abdominal pain and was admitted at the Emergency Department. A CT scan with intravenous contrast showed an occlusion of the portal vein, of the intrahepatic major branches and an extension to the superior mesenteric vein and the splenic vein. The patient received heparin and oral anticoagulation together with intravenous hydration and proton pump inhibitors. Considering the favourable course the patient was discharged after six days with long-term oral anticoagulation therapy. Anticoagulation with acenocumarol was continued for six months after a CT scan showed resolution of the PMVT without cavernoma. He had no recurrence of symptoms. Porto-mesenteric thrombosis after sleeve gastrectomy is a rare complication but it has been increasingly reported over the last 10 years along with the extensive use of sleeve gastrectomy. Because PMVT is closely associated with sleeve gastrectomy in comparison with other bariatric procedures, we need to investigate what pathogenetic factors are involved in sleeve gastrectomy. Thrombophylic state, prolonged duration of surgery, high levels of pneumoperitoneum, thermal injury of the gastroepiploic vessels during greater curvature dissection, high intragastric pressure, inadequate antithrombotic prophylaxis and delayed mobilization of the patient after surgery have been reported as pathogenetic factors of portmesenteric vein thrombosis. Most of the cases presented in the literature such as our clinical case resolve with medical therapy, although portal vein thrombus extends into the superior mesenteric vein and the splenic vein. Portomesenteric venous thrombosis is a rare but serious complication of bariatric surgery, especially associated with sleeve gastrectomy. Diagnosis is based on CT examination with intravenous contrast, and initial therapy is anticoagulation. Etiologic factors reported in the literature include a long duration of surgery, a high degree of pneumoperitoneum, high intragastric pressure after sleeve gastrectomy and thermal injury to the short gastric vessels and gastroepiploic arcade. Limited operative time, controlled values of pneumoperitoneum, careful dissection with energy device of gastric greater curvature, appropriate prophylaxis with low molecular weight heparin may be useful tools to prevent and limit this complication. Nonetheless we have to search which factors may condition the evolution of an extended PMVT as that described in this case towards resolution or to a further worsening clinical state. Early diagnosis? Correct treatment? Undiscovered patientrelated factors?


Higher expression of androgen receptor is a significant predictor for better endocrine-responsiveness in estrogen receptor-positive breast cancers.
The aim was to investigate the implications of androgen receptor (AR) expression levels on outcomes for estrogen receptor (ER)-positive tumors. Immunohistochemically AR levels were determined from tissue microarrays of 614 ER-positive patients who received adjuvant endocrine with or without chemotherapy between November 1999 and August 2005. Characteristics and survival were analyzed using a Chi-square test, Kaplan-Meier methods, and Cox's models. AR levels were categorized into 3 subgroups as follows: low, AR < 10%; intermediate, 10% ≤ AR < 50%; high, AR ≥ 50%. Low, intermediate, and high AR levels were observed in 29.0, 44.0, and 27.0% of patients, respectively. High AR was associated with smaller size, nodal uninvolvement, grade I/II tumor, higher progesterone receptor expression, and lower proliferation index. With a median follow-up of 70.9 months, the high AR subgroup showed better survival, and these associations were maintained in 119 patients who received endocrine therapy alone [hazard ratio (HR), 0.111; 95% CI, 0.013-0.961 for disease-free survival (DFS); HR, 0.135; 95% CI, 0.015-1.208 for overall survival (OS)]. No significant benefits from chemotherapy were demonstrated in the high AR subgroup; however, the benefit from chemotherapy was significant among 448 AR-intermediate or -low patients (HR, 2.679; 95% CI, 1.452-4.944 for DFS; HR, 3.371; 95% CI, 1.611-7.052 for OS). High AR is an independent prognostic factor and a significant predictor for better endocrine-responsiveness in ER-positive tumors. AR-low or -intermediate levels could give an additional indication for use of chemotherapy in ER-positive tumors.


Therapeutical potential of autologous peripheral blood mononuclear cell transplantation in patients with type 2 diabetic critical limb ischemia.
The aim was to evaluate the therapeutic effectiveness of granulocyte colony-stimulating factor (G-CSF) mobilized peripheral blood mononuclear cells (PBMNCs) in critical limb ischemia (CLI) of type 2 diabetic patients. Forty diabetic patients with CLI were enrolled and randomized to treatment and control groups. In the treatment group, the patients received subcutaneous injections of recombinant human G-CSF (30 MU/day) for 5 days to mobilize stem cells. PBMNCs were collected and transplanted by multiple intramuscular injections of 1 ml in 1-1.5-cm depth into ischemic limbs. At the end of 12 weeks of follow-up, the baseline and end point results in transplant group were as follows: Fontaine score improved from 3.8±03 to 3±0.5 (P=.0001), ankle brachial pressure index increased from 0.68±0.24 to 0.87±024 (P=.001), transcutaneous oxygen increased from 33±14 mmHg to 44±10 mmHg (P=.0001), and 6-min walking distance improved from 280±82 m to 338±98 m (P=.0001). Pain score decreased from 8.2±1.3 to 5.63±1.6 (P=.001), and the number of patients with limb ulcers was reduced from 9/20 (45%) to 3/20 (15%) (P=.031). In the control group, Fontaine score, 6-min walking distance, and pain score were improved; ankle brachial pressure index and transcutaneous oxygen pressure were not improved. The number of patients with limb ulcers did not change in the control group. There are improvement in amputation rates, collateral vessel development, and number of limb ulcers healed. These results indicate that the autologous transplantation of G-CSF that mobilized PBMNCs in CLI diabetic patients is safe and effective in patient compliant reduction and improved perfusion.


Anticoagulation strategies in patients with extracorporeal membrane oxygenation: A network meta-analysis and systematic review.
Extracorporeal membrane oxygenation (ECMO) plays an important role in providing temporary life support for patients with severe cardiac or pulmonary failure, but requires strict anticoagulation and monitoring. This network meta-analysis systematically explored the most effective anticoagulation and monitoring strategies for patients receiving ECMO. MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched up to January 31, 2023, for studies comparing unfractionated heparin (UFH), argatroban (Arg), bivalirudin (Biv), and/or nafamostat mesylate (NM) in patients receiving ECMO. The primary outcomes included device-related thrombosis, patient-related thrombosis, and major bleeding events. The secondary outcomes included ECMO survival, ECMO duration, and in-hospital mortality. A total of 2522 patients from 23 trials were included in the study. Biv was associated with a decreased risk of device-related thrombosis (odd ratio [OR] 0.51, 95% confidence interval [CI]: 0.33-0.84) compared with UFH, whereas NM (OR 2.2, 95% CI: 0.24-65.0) and Arg (OR 0.92, 95% CI: 0.43-2.0) did not reduce the risk of device-related thrombosis compared with UFH. Biv was superior to Arg in decreasing the risk of device-related thrombosis (OR 0.14, 95% CI: 0.03-0.51). Biv reduced the risk of patient-related thrombosis compared with UFH (OR 0.44, 95% CI: 0.18-0.85); NM (OR 0.65, 95% CI: 0.14-3.3) and Arg (OR 3.1, 95% CI: 0.94-12.0) did not decrease risk of patient-related thrombosis compared with UFH. No significant difference was observed in the risk of major bleeding between three alternatives and UFH: Biv (OR 0.54, 95% CI: 0.23-1.3), Arg (OR 1.3, 95% CI: 0.34-5.8), and NM (OR 0.60, 95% CI: 0.13-2.6). NM showed a reduced risk of in-hospital mortality compared with UFH (OR 0.27, 95% CI: 0.091-0.77), whereas Arg (OR 0.43, 95% CI: 0.15-1.2) and Biv (OR 0.75, 95% CI: 0.52-1.1) did not decrease risk of in-hospital mortality. Compared with UFH and Arg, Biv reduces the risk of thrombosis and appears to be a better choice for patients requiring ECMO. NM was associated with a reduced risk of in-hospital mortality.


The neuromuscular junctions of the slow and the fast excitatory axon in the closer of the crab Eriphia spinifrons are endowed with different Ca2+ channel types and allow neuron-specific modulation of transmitter release by two neuropeptides.
Most crustacean muscle fibers receive double excitatory innervation by functionally different motor neurons termed slow and fast. By using specific omega-toxins we show that the terminals of the slow closer excitor (SCE) and the fast closer excitor (FCE) at a crab muscle are endowed with different sets of presynaptic Ca(2+) channel types. omega-Agatoxin, a blocker of vertebrate P/Q-type channels, reduced the amplitude of EPSCs by decreasing the mean quantal content of transmitter release in both neurons by 70-85%, depending on the concentration. We provide the first evidence that omega-conotoxin-sensitive channels also participate in transmission at crustacean neuromuscular terminals and are colocalized with omega-agatoxin-sensitive channels in an axon-type-specific distribution. omega-Conotoxin, a blocker of vertebrate N-type channels, inhibited release by 20-25% only at FCE, not at SCE endings. Low concentrations of Ni(2+), which block vertebrate R-type channels, inhibited release in endings of the SCE by up to 35%, but had little effects in FCE endings. We found that two neuropeptides, the FMRFamide-like DF(2) and proctolin, which occur in many crustaceans, potentiated evoked transmitter release differentially. Proctolin increased release at SCE and FCE endings, and DF(2) increased release only at FCE endings. Selective blocking of Ca(2+) channels by different omega-toxins in the presence of peptides revealed that the target of proctolin-mediated modulation is the omega-agatoxin-sensitive channel (P/Q-like), that of DF(2) the omega-conotoxin-sensitive channel (N-like). The differential effects of these two peptides allows fine tuning of transmitter release at two functionally different motor neurons innervating the same muscle.


Automatic localization and segmentation of focal cortical dysplasia in FLAIR-negative patients using a convolutional neural network.
Focal cortical dysplasia (FCD) is a common cause of epilepsy; the only treatment is surgery. Therefore, detecting FCD using noninvasive imaging technology can help doctors determine whether surgical intervention is required. Since FCD lesions are small and not obvious, diagnosing FCD through visual evaluations of magnetic resonance imaging (MRI) scans is difficult. The purpose of this study is to detect and segment histologically confirmed FCD lesions in images of normal fluid-attenuated inversion recovery (FLAIR)-negative lesions using convolutional neural network (CNN) technology. The technique involves training a six-layer CNN named Net-Pos, which consists of two convolutional layers (CLs); two pooling layers (PLs); and two fully connected (FC) layers, including 60 943 learning parameters. We employed activation maximization (AM) to optimize a series of pattern image blocks (PIBs) that were most similar to a lesion image block by using the trained Net-Pos. We developed an AM and convolutional localization (AMCL) algorithm that employs the mean PIBs combined with convolution to locate and segment FCD lesions in FLAIR-negative patients. Five evaluation indices, namely, recall, specificity, accuracy, precision, and the Dice coefficient, were applied to evaluate the localization and segmentation performance of the algorithm. The PIBs most similar to an FCD lesion image block were identified by the trained Net-Pos as image blocks with brighter central areas and darker surrounding image blocks. The technique was evaluated using 18 FLAIR-negative lesion images from 12 patients. The subject-wise recall of the AMCL algorithm was 83.33% (15/18). The Dice coefficient for the segmentation performance was 52.68. We developed a novel algorithm referred to as the AMCL algorithm with mean PIBs to effectively and automatically detect and segment FLAIR-negative FCD lesions. This work is the first study to apply a CNN-based model to detect and segment FCD lesions in images of FLAIR-negative lesions.


Interactions between the class II transactivator and CREB binding protein increase transcription of major histocompatibility complex class II genes.
Class II major histocompatibility (class II) genes are regulated in a B-cell-specific and gamma interferon-inducible fashion. The master switch for the expression of these genes is the class II transactivator (CIITA). In this report, we demonstrate that one of the functions of CIITA is to recruit the CREB binding protein (CBP) to class II promoters. Not only functional but also specific binding interactions between CIITA and CBP were demonstrated. Moreover, a dominant negative form of CBP decreased the activity of class II promoters and levels of class II determinants on the surface of cells. Finally, the inhibition of class II gene expression by the glucocorticoid hormone could be attributed to the squelching of CBP by the glucocorticoid receptor. We conclude that CBP, a histone acetyltransferase, plays an important role in the transcription of class II genes.


Circ_0004712 Silencing Suppresses the Aggressive Changes of Rheumatoid Arthritis Fibroblast-Like Synoviocytes by Targeting miR-633/TRAF6 Axis.
Circular RNA_0004712 (circ_0004712) is reported to be up-regulated in rheumatoid arthritis (RA) patients. Nevertheless, its role and mechanism in RA pathology remain to be clarified. RNA and protein expression was determined by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot assay. Cell viability, proliferation, apoptosis, migration, and inflammation were assessed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, 5-ethynyl-20-deoxyuridine assay, flow cytometry, scratch test, and enzyme-linked immunosorbent assay. The target correlation between microRNA-633 (miR-633) and circ_0004712 or TNF receptor associated factor 6 (TRAF6) was verified by dual-luciferase reporter assay and RNA immunoprecipitation assay. Circ_0004712 was up-regulated in RA synovial tissues and RA fibroblast-like synoviocytes (RA-FLSs). Circ_0004712 silencing suppressed the viability, proliferation, migration and inflammatory response and facilitated the apoptosis of RA-FLSs. miR-633 was confirmed to be a direct target of circ_0004712, and miR-633 knockdown reversed circ_0004712 silencing-mediated protective effects on the dysfunction and inflammation of RA-FLSs. TRAF6 was a direct target of miR-633, and miR-633 overexpression suppressed the aggressive changes of RA-FLSs by down-regulating TRAF6. Circ_0004712 could up-regulate TRAF6 expression by sponging miR-633 in RA-FLSs. Circ_0004712 interference inactivated nuclear factor (NF)-κB signaling by targeting miR-633/TRAF6 axis. Circ_0004712 silencing inhibited the aggressive changes of RA-FLSs by targeting miR-633/TRAF6 axis and NF-κB signaling, which provided new targets for RA therapy.


The risk of noise-induced hearing loss performing knee replacement surgery.
Powered surgical instruments use to cut bones and fashion them for joint implant produce noise. Prior studies have not analyzed direct in vivo measurements of multiple procedures and exposure time. This study evaluates actual surgical noise levels exposure to the surgeon and this cumulative exposure that can result in noise-induced hearing loss (NIHL). Prior studies evaluated short duration noise exposure to surgical equipment in vitro, or in an operating room environment. This study evaluated in vivo cumulative measurements over an entire operating day and the associated risks. Noise exposure to operating room personnel was measured during multiple knee replacement surgeries over three days. Measurements were compared to occupational exposure limits set by the National Institute for Occupational Safety and Health (NIOSH) and the Occupational Safety and Health Administration (OSHA). Surgeons' noise exposures exceed noise occupational exposure limits. Recorded levels of 104 dBA did occur with levels of 85dBA found from 10-18% of the time. Surgeons performing multiple total knee replacements per day are at risk of NIHL due to noise exposures that exceed National Institute for Occupational Safety and Health recommendations. Surgeons should be included in a hearing loss prevention program. Therapeutic Level 1.


A clinical model to predict the progression of knee osteoarthritis: data from Dryad.
Knee osteoarthritis (KOA) is a multifactorial, slow-progressing, non-inflammatory degenerative disease primarily affecting synovial joints. It is usually induced by advanced age and/or trauma and eventually leads to irreversible destruction of articular cartilage and other tissues of the joint. Current research on KOA progression has limited clinical application significance. In this study, we constructed a prediction model for KOA progression based on multiple clinically relevant factors to provide clinicians with an effective tool to intervene in KOA progression. This study utilized the data set from the Dryad database which included patients with Kellgren-Lawrence (KL) grades 2 and 3. The KL grades was determined as the dependent variable, while 15 potential predictors were identified as independent variables. Patients were randomized into training set and validation set. The training set underwent LASSO analysis, model creation, visualization, decision curve analysis and internal validation using R language. The validation set is externally validated and F1-score, precision, and recall are computed. A total of 101 patients with KL2 and 94 patients with KL3 were selected. We randomly split the data set into a training set and a validation set by 8:2. We filtered "BMI", "TC", "Hypertension treatment", and "JBS3 (%)" to build the prediction model for progression of KOA. Nomogram used to visualize the model in R language. Area under ROC curve was 0.896 (95% CI 0.847-0.945), indicating high discrimination. Mean absolute error (MAE) of calibration curve = 0.041, showing high calibration. MAE of internal validation error was 0.043, indicating high model calibration. Decision curve analysis showed high net benefit. External validation of the metabolic syndrome column-line graph prediction model was performed by the validation set. The area under the ROC curve was 0.876 (95% CI 0.767-0.984), indicating that the model had a high degree of discrimination. Meanwhile, the calibration curve Mean absolute error was 0.113, indicating that the model had a high degree of calibration. The F1 score is 0.690, the precision is 0.667, and the recall is 0.714. The above metrics represent a good performance of the model. We found that KOA progression was associated with four variable predictors and constructed a predictive model for KOA progression based on the predictors. The clinician can intervene based on the nomogram of our prediction model. This study is a clinical predictive model of KOA progression. KOA progression prediction model has good credibility and clinical value in the prevention of KOA progression.


The burned ear; possibilities and challenges in framework reconstruction and coverage.
Ear reconstruction remains a challenging procedure, especially in burn victims. The ear is particularly vulnerable to thermal injury because of its location and the thin integument. The thermal injury could subsequently include skin and the deeper located auricular cartilage framework. This type of injury could have long lasting mutilating effect not only because the ear's morphology is mainly related to this framework but also because it will not recover or regenerate once injured. Grafts of costal cartilage or synthetic materials might replace missing cartilage. However, the poor quality of the adjacent skin and subcutaneous tissues makes the reconstruction of a burned ear an even more daunting procedure than congenital or many oncologic indications. As such, regeneration of the skin will be the next step in reconstruction of the burned ear. There is still much development and research to be done, but encouraging results have been shown in tissue engineering of skin and cartilage. Furthermore, 3D (bio)printing of cartilage to facilitate reproduction of the ear's complex shape certainly has potential and might find an interesting role in ear reconstruction. In this review, different clinical challenges and options for ear reconstruction in burn patients are described. Subsequently, although still far from large scale clinical application, state of the art developments in the field of tissue engineering and 3D (bio)printing are also discussed.


Septochoanal polyp with osseous metaplasia: a case report.
Polyps originating from the posterior septum with choanal extension, also known as "septochoanal polyps," are uncommon, and septochoanal polyps with central calcification are extremely rare. We report the second case of septochoanal polyps with central calcification in the English literature. A 55-year-old Thai woman presented with a progressive left-side nasal obstruction. An examination of her nose revealed an irregular lobulated mass, yellow in color, with a smooth surface that arose from her posterior nasal septum and extended down to her nasopharynx. Computed tomography revealed a large choanal mass with a central ossified structure. A punch biopsy was performed and microscopic examination showed an inflammatory polyp. The mass was removed using an endoscopic surgery technique, and the histology of this lesion confirmed a typical presentation of choanal polyps. Although septochoanal polyps with osseous metaplasia are known to be very rare, physicians should be aware of them and include them in the differential diagnosis of choanal mass with central calcification lesions.


A fatal case of gram negative bacterial sepsis associated with disseminated strongyloidiasis in an immunocompromised patient.
We report a fatal case of disseminated strongyloidiasis in a patient with multiple myeloma receiving chemrotherapy. A fifty-seven years old man presented with severe diarrhoea and vomiting, fever, weight loss and dysphagia,due to mouth ulcers. Despite broad-spectrum intravenous antibiotics, albendazole (anti protozoal) and supportive treatment, the patient died of Gram-negative sepsis.


Skin Thermal Management for Subcutaneous Photoelectric Conversion Reaching 500 mW.
Despite possessing higher tissue transmittance and maximum permissible exposure power density for skin relative to other electromagnetic waves, second near-infrared light (1000-1350 nm) is scarcely applicable to subcutaneous photoelectric conversion, owing to the companion photothermal effect. Here, skin thermal management is conceived to utmostly utilize the photothermal effect of a photovoltaic cell, which not only improves the photoelectric conversion efficiency but also eliminates skin hyperthermia. In vivo, the output power can be higher than 500 mW with a photoelectric conversion efficiency of 9.4%. This output power is promising to recharge all the clinically applied implantable devices via wireless power transmission, that is, clinical pacemakers (6-200 µW), drug pumps (0.5-2 mW), cochlear (5-40 mW), and wireless endo-photo cameras (≈100 mW).


Level and contributing factors of health data quality and information use in two districts in Northwest Ethiopia: social-ecological perspective.
The health management information system has been implemented at all levels of healthcare delivery to ensure quality data production and information use in Ethiopia. Including the capacity-building activities and provision of infrastructure, various efforts have been made to improve the production and use of quality health data though the result is still unsatisfactory. This study aimed to examine the quality of health data and use in Wogera and Tach-Armacheho districts and understand its barriers and facilitators. The study utilized a mixed-method; for the quantitative approach, institution-based cross-sectional study was conducted to determine the quality of health data and use by 95 departments in the two districts. The qualitative approach involved 16 in-depth interviewees from Wogera district. A descriptive Phenomenological design was used to explore factors influencing the quality and use of health data. The quantitative data were expressed descriptively with tables, graphs, and percent whereas the qualitative data were analyzed with content analysis guided by the social-ecological model framework. The average levels of information use for Wogera and Tach-Armacheho districts were estimated at 29 and 35.9, respectively. The overall average level of accuracy of reports for six different health services in the HCs of Wogera and Tach Armacheho districts were 0.95 and 0.86, respectively. The qualitatively identified factors that influence the production and use of quality health data include valuing data, getting staff training, being a patriotic staff, and getting supportive supervision, were identified from individual-level characteristics; similarly, coaching, supportive supervision, and peer-to-peer learning from relational/interpersonal level characteristics, and organizational culture, incentive, infrastructure establishing accountability, and staff turnover, were identified from organizational level characteristics. The quality of data and routine information utilization was low and were influenced by a number of actors presented in and around the health system including individual, interpersonal, and organizational characteristics. Incentive affects data quality and information use directly or indirectly after modifying factors at all levels of the social-ecological model. Therefore, interventions should gear towards addressing multiple social-ecological factors of the health system concomitantly or intervene on incentive which has a multifaceted effect on the outcome.


Improving mental health through integration with primary care in rural Karnataka: study protocol of a cluster randomized control trial.
People who are diagnosed with both mental and chronic medical illness present unique challenges for the health care system. In resource-limited settings, such as rural India, people with depression and anxiety are often under-served, due to both stigma and lack of trained providers and resources. These challenges can lead to complications in the management of chronic disease as well as increased suffering for patients, families and communities. In this study, we evaluate the effects of integrating mental health and chronic disease treatment of patients in primary health care (PHC) settings using a collaborative care model to improve the screening, diagnosis and treatment of depression in rural India. This study is a multi-level randomized controlled trial among patients with depression or anxiety and co-morbid diabetes, or cardiovascular disease. Aim 1 examines whether patients screened at community health-fairs are more likely to be diagnosed and treated for these co-morbid conditions than patients screened after presenting at PHCs. Aim 2 evaluates the impact of collaborative care compared to usual care in a cluster RCT, randomizing at the level of the PHCs. Intervention arm PHC staff are trained in mental health diagnoses, treatment, and the collaborative care model. The intervention also involves community-based "Healthy Living groups" co-led by Ashas, using cognitive-behavioral strategies to promote healthy behaviors. The primary outcome is severity of common mental disorders, with secondary outcomes being diabetes and cardiovascular risk, staff knowledge and patient perceptions. If effective, our results will contribute to the field in five ways: 1) expand on implementation research in low resource settings by examining how multiple chronic diseases can be treated using integrated low-cost, evidence-based strategies, 2) build the capacity of PHC staff to diagnose and treat mental illness within their existing clinic structure and strengthen referral linkages; 3) link community members to primary care through community-based health fairs and healthy living groups; 4) increase mental health awareness in the community and reduce mental health stigma; 5) demonstrate the potential for intervention scale-up and sustainability. http://Clinicaltrials.gov : NCT02310932 registered December 8, 2014 URL: https://clinicaltrials.gov/ct2/show/record/NCT02310932 ; Clinical Trials Registry India: CTRI/2018/04/013001 retrospectively registered on April 4, 2018.


Novel mechanism by which hemoglobin induces constriction of cerebral arteries.
Since oxyhemoglobin (OxyHb) is implicated in the pathogenesis of cerebral vasospasm, we have investigated the role of protein tyrosine phosphorylation in OxyHb-mediated signalling in canine cerebral arteries and cultured canine cerebrovascular smooth muscle cells. OxyHb produced a contraction of basilar artery preparations, which was reversed by genistein, an inhibitor of tyrosine kinases, and PD098059, an inhibitor of mitogen-activated protein kinase. In cerebrovascular smooth muscle cells, OxyHb induced tyrosine phosphorylation of 42, 46, 54-60 and 80-100 kDa proteins with a time-course which paralleled the contractile action of OxyHb, suggesting that these events might be functionally linked. The 42 and 60 kDa proteins were immunologically related to the mitogen-activated protein kinase, extracellular signal regulated protein kinase (ERK2), and to p60c-Src (c-Src), respectively. The increase in protein tyrosine phosphorylation was attenuated by genistein, and the phosphorylation of the 42 kDa protein (ERK2) was inhibited by PD098059. These results suggest that OxyHb-mediated signalling utilizes a protein tyrosine kinase-based mechanism.


A comparison of the treatment of trochanteric fractures of the femur by internal fixation with a nail plate and the Ender technique.
In our experience, trochanteric fractures fixed with Ender nails achieved a degree of success similar to those treated by nail plating, but the risk of wound infection was much less with the former method. The results of 78 trochanteric fractures of the femur internally fixed with Ender nails have been analysed and compared with the results in 100 similar patients treated by nail plate fixation. The Ender method has advantages over existing operative methods, in that in our series the infection rate was zero and we found that the operation produced less shock. We consider that this method, although technically more difficult, can be used for most intertrochanteric fractures and merits further trial.


Immuno-isotachophoretic determination of monoclonal immunoglobulin light chains produced by neoplastic B-cells: use in diagnosis, monitoring and detection of residual disease.
We suggest that countercurrent isotachophoresis performed on cellulose acetate membranes (ITP-CAM) should be used for detecting trace amounts of Bence-Jones protein (BJP) in urine of patients with chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL) and related diseases. ITP-CAM allows simultaneous concentration and electrophoretic separation of proteins present in highly diluted solutions, as well as easy immunological detection of separated substances. BJP was found in 24 out of 42 patients with CLL, 33 of 56 with NHL and 3 of 3 with Waldenström macroglobulinemia. Twenty-three patients were followed during the course of chemo- or radiotherapy. In 19 cases the BJP findings correlated well with clinical status. In no case of partial or complete clinical response did BJP completely disappear from the urine.


Seasonal dynamics of digestion in relation to diet quality and intake in European roe deer (Capreolus capreolus).
Three tame, hand-reared adult roe deer (Capreolus capreolus) were fed a low-quality diet (blueberry stems) or high-quality concentrate either restricted or ad libitum in summer and winter. Total mean retention time (TMRT) and rumen retention time (RRT) were significantly longer, indigestible fill was significantly higher and apparent digestibility and intake were significantly lower when fed blueberry stems compared to concentrate. The feeding regimes of concentrate did not affect the digesta kinetic estimates, except that total fill and apprent digestibility were significantly higher when deer were fed ad libitum than when they were fed a restricted ration. TMRT was significantly longer when they were fed a restricted ration of blueberry stems than for ad libitum intake, whereas all other estimates were equal. Intake was significantly higher and TMRT and RRT were significantly shorter in summer compared to winter when they were fed concentrate. These findings support the theory that roe deer, as small-bodied concentrate selectors, are adapted to high intake, rapid turnover, and rapid digestion when fed high-quality concentrate. When fed a low-quality diet the roe deer may be limited by rumen bulk. A strategy based on increased rumen retention accompanied by increased cell-wall digestion has therefore severe limitations in roe deer. This indicates that roe deer are dependent on a selective feeding strategy to enhance winter survival.


Effects of homeodomain-interacting protein kinase 2 on renal tubular epithelial cells.
To research the role of homeodomain-interacting protein kinase 2 (HIPK2) on the oxidative stress (OS) and apoptosis induced by hypoxia/reoxygenation (H/R) of normal rat kidney-52E (NRK-52E) cells, through the JAK2/STAT3 signaling pathway MATERIALS AND METHODS: First, we transfected the NRK-52E cells with small interfering RNA (siRNA) of HIPK2 by LipofectamineTM 2000, Real Time-Polymerase Chain Reaction (RT-PCR) and Western blot (WB) were used to test the efficiency of transfection after 48 h. After cells were treated with H/R, we tested cell apoptosis by Cell Counting Kit-8 (CCK-8) assay, flow cytometry, TUNEL staining, PCR, and Western blot. After NRK-52E cells were transfected with siRNA-HIPK2, the protein expression of HIPK2 was remarkably decreased. Cell apoptosis and OS in the H/R group were significantly increased. However, in the HIPK2-siRNA + H/R group, apoptosis and OS were markedly decreased compared with the H/R group. Inhibition of HIPK2 expression can promote H/R-induced proliferation of NRK-52E cells through the JAK2/STAT3 signaling pathway, relieve the OS response, and reduce apoptosis.


Morphological and morphometric changes in revascularised bowel grafts reconstructing the cervical oesophagus.
Revascularised grafts of jejunum and colon have been used to reconstruct the cervical oesophagus in dogs. The grafts were examined at 2 months to assess their morphological and morphometric behaviour in their new position in the oesophagus. The colonic grafts appeared to adapt completely, while the jejunal ones manifest persisting mucosal changes attributable to their new environment.


Fluoride concentration in saliva and biofilm fluid following the application of three fluoride varnishes.
Most of the commercially available fluoride varnishes (FV) have not been evaluated for their cariostatic properties. Consequently, the aim of this in vivo study was to investigate intra-oral fluoride retention and clearance patterns from three different FV. Eighteen subjects (7-11 years) participated in a laboratory analyst-blinded, randomized, crossover study comparing the ability of 5% sodium fluoride varnishes (CavityShield-CS, Enamel Pro-EP, Vanish-V) to enhance fluoride concentrations in biofilm fluid, centrifuged and whole saliva over a period of 48h after a single FV application. Similar fluoride concentration×time patterns were noted for all investigated FV and studied variables, with the highest fluoride concentrations observed for the first biological sample collected after FV application (30min). Mean±SE (area under fluoride clearance curve) values were (μg F/g or ml×min): biofilm fluid - CS (472±191), EP (423±75),V (1264±279); centrifuged saliva - CS (42±7), EP (19±3),V (41±8); whole saliva - CS (68±11), EP (64±10),V (60±7).V delivered more fluoride to biofilm fluid than CS (p=0.0116) and EP (p=0.0065), which did not differ (p=0.27). For centrifuged saliva, CS and V were not significantly different (p=0.86), but resulted in higher fluoride retention than EP (p<0.0008). No significant differences among FV were observed for whole saliva (p=0.79). The present study has shown that FV vary in their ability to deliver fluoride intra-orally potentially related to formulation differences. To what extent the present findings relate to clinical efficacy remains, however, to be determined. Clinical research that investigates fluoride release patterns into saliva and biofilm fluid from different FV products is insufficient. More research is needed to investigate different FV formulations for their efficacy in order to help clinicians make better evidence based treatment choices.


Denver ED Trauma Organ Failure Score predicts healthcare resource utilization in adult trauma patients.
Early identification of trauma patients who need specialized healthcare resources may facilitate goal-directed resuscitation and effective secondary triage. To estimate associations between Denver Emergency Department (ED) Trauma Organ Failure (TOF) Score and healthcare resource utilization. Retrospective study of adult trauma patients at Denver Health Medical Center. The outcome was resource utilization including: intensive care unit (ICU) length of stay (LOS), hospital LOS, procedures, and costs. Multivariable regression analyses were used to estimate associations between moderate- or high-risk patients, as determined by the Denver ED TOF Score, and healthcare resource utilization. We included 3000 patients with a median age of 42 (IQR 27-56) years, 71% male, median injury severity score 9 (IQR 5-16), and 83% blunt mechanism. Among the cohort, 1379 patients (46%) were admitted to the ICU and 122 (4%) died. The adjusted relative risk for high- and moderate-risk as compared to low risk for number of procedures performed was 2.31 (95% CI 2.07-2.57) and 1.80 (95% CI 1.59-2.03) respectively; ICU LOS was 2.87 (95% CI 2.70-3.05) and 1.71 (95% CI 1.60-1.83) respectively; hospital LOS was 3.33 (95% CI 3.21-3.45) and 1.97 (95% CI 1.90-2.05) respectively. The adjusted geometric mean for high-, moderate-, and low-risk for costs was $48,881 (95% CI $43,799-$54,552), $27,890 (95% CI $25,460-$30,551), and $12,983 (95% CI $12,493-$13,492), respectively. The Denver ED TOF Score predicts healthcare resource utilization, and is a useful bedside tool to identify patients early after injury that are likely to require significant healthcare resources and specialized trauma care.


Targeted next-generation sequencing reveals activating CTNNB1 mutations in SMARCA4/BRG1-deficient sinonasal carcinomas: a report of two new cases and a brief review of the literature with an emphasis on histogenesis.
SMARCA4/BRG1 is a catalytic subunit of the SWItch/sucrose non-fermentable (SWI/SNF) complex and its inactivation is known to drive a variety of cancers across different organs. SMARCA4/BRG1-deficient carcinoma is a relatively new entity in the sinonasal region, and a comprehensive molecular investigation of the underlying genetic abnormalities is largely lacking. In this study, we report two new cases of SMARCA4/BRG1-deficient sinonasal carcinoma with targeted next-generation sequencing analysis, both of which revealed activating mutation of CTNNB1 in addition to somatic loss-of-function mutation of SMARCA4, providing further insights into its tumorigenesis and theoretical basis for the potential future targeted therapy. Activating CTNNB1 mutations in our cases may provide further evidence that SMARCA4-deficient sinonasal carcinoma, sinonasal teratocarcinosarcoma, and olfactory carcinoma are genetically closely related lesions, as recently proposed in the literature.


Three-year outcomes of macular buckling for macular holes and foveoschisis in highly myopic eyes.
To assess the functional and structural outcomes of macular buckling using a silicone sponge-titanium exoplant for the treatment of foveoschisis (FS) and full-thickness macular holes (FTMHs) in highly myopic eyes. Forty-nine consecutive patients with high myopia who underwent macular buckling for the treatment of FS and FTMHs were included. The outcomes measured included the anatomical success rate with FS resolution, retinal reattachment, MH closure, best corrected visual acuity (BCVA), axial length (AL) and complications of surgery. Moreover, the correlations between the BCVA at year three and series of factors, including age, duration of symptoms, baseline BCVA, AL, surgical type, preoperative macular status and severity of myopic maculopathy, were analysed. This study involved 28 patients (28 eyes) with FS and 21 patients (21 eyes) with FTMHs with macular detachment. Retinal reattachment was achieved in 100% of cases, while MH closure was achieved in 76.19% of cases. The BCVA significantly improved one year after macular buckling in the FS cases and two years after macular buckling in the FTMH cases, and it remained stable throughout the rest of the follow-up period. The mean AL decreased by 2.09 mm postoperatively. No major perioperative complications were observed, although one patient needed to explant the buckling device due to intolerable diplopia. Macular buckling with a silicone sponge-titanium exoplant may represent a safe and effective surgical option for the treatment of FS and FTMH in highly myopic eyes. Macular buckling showed a high closure rate and virtually no tendency to recur.


Enhancement of production and activity of alkaline zinc metalloprotease from Salinivibrio proteolyticus using low intensity direct electric current and zinc nanoparticles.
To improve the production and activity of an alkaline zinc metalloprotease from Salinivibrio proteolyticus in response to ZnSO4 (ionic and nanoparticle forms) and low intensity direct electric current (LIDC). A DC of 50 µA for 10 min increased enzyme production from 35 to 53 U ml(-1) when applied to the stationary phase bacterial cells. Zn(2+) improved enzyme production better than zinc nanoparticles (52 vs. 43.5 U ml(-1)). Zinc nanoparticles (0.5 mM) added to an enzyme reaction mixture containing casein (0.65 %) and 20 mM Tris/HCl buffer (pH 8) improved enzyme activity more than Zn(2+) (42 vs. 36 U ml(-1)). LIDC exposure (50 µA, 10 min) to the stationary phase bacterial cells increases metalloprotease production in Salinivibrio. A low concentration of zinc nanoparticles (0.5 mM) increases maximum enzyme activity.


An attempt to assess the effects of monocular deprivation and strabismus on synaptic efficiency in the kitten's visual cortex.
The relative effectiveness of the two eyes in exciting cells in the visual cortex was assessed, using both natural stimulation and electrical stimulation of the optic discs. It is is argued that supramaximal electrical stimulation of the optic nerve could possibly reveal 'subliminal' synaptic inputs even after monocular deprivation or artificial strabismus has caused a loss of natural input from that eye, if such 'silent' synaptic input still survives. However, in kittens monocularly deprived for various periods of time or made artificially strabismic, there was usually excellent agreement between the relative visual excitability in the two eyes and their relative electrical excitability. In one animal, monocularly deprived continuously until 23 weeks of age, we examined the effect of reversibly turning off signals from the normal eye by pressure blinding. There was no evidence of a very rapid return of sensitivity to either electrical or natural stimulation of the deprived eye.


Putative Clinical Potential of ERBB2 Amplification Assessment by ddPCR in FFPE-DNA and cfDNA of Gastroesophageal Adenocarcinoma Patients.
Anti-HER2 monoclonal antibody trastuzumab improves the survival of those patients with advanced gastroesophageal adenocarcinoma (GEA) exhibiting HER2/ERBB2 overexpression/amplification. The current gold standard methods used to diagnose the HER2 status in GEA are immunohistochemistry (IHC) and silver or fluorescence in situ hybridization (SISH or FISH). However, they do not permit spatial and temporal tumor monitoring, nor do they overcome intra-cancer heterogeneity. Droplet digital PCR (ddPCR) was used to implement the assessment of HER2 status in formalin-fixed paraffin-embedded (FFPE) tumor DNA from a retrospective cohort (86 patients) and in cell-free DNA (cfDNA) samples from a prospective cohort (28 patients). In comparison to IHC/SISH, ddPCR assay revealed ERBB2 amplification in a larger patient fraction, including HER2 2+ and 0-1+ of the retrospective cohort (45.3% vs. 15.1%). In addition, a considerable number of HER2 2+ and 0-1+ prospective patients who were negative in FFPE by both IHC/SISH and ddPCR, showed ERBB2 amplification in the cfDNA collected just before surgery. cfDNA analysis in a few longitudinal cases revealed an increasing ERBB2 trend at progression. In conclusion, ddPCR in liquid biopsy may improve the detection rate of HER2 positive patients, preventing those patients who could benefit from targeted therapy from being incorrectly excluded.


Dinoflagellate vertical migration fuels an intense red tide.
Harmful algal blooms (HABs) are increasing globally, causing economic, human health, and ecosystem harm. In spite of the frequent occurrence of HABs, the mechanisms responsible for their exceptionally high biomass remain imperfectly understood. A 50-y-old hypothesis posits that some dense blooms derive from dinoflagellate motility: organisms swim upward during the day to photosynthesize and downward at night to access deep nutrients. This allows dinoflagellates to outgrow their nonmotile competitors. We tested this hypothesis with in situ data from an autonomous, ocean-wave-powered vertical profiling system. We showed that the dinoflagellate Lingulodinium polyedra's vertical migration led to depletion of deep nitrate during a 2020 red tide HAB event. Downward migration began at dusk, with the maximum migration depth determined by local nitrate concentrations. Losses of nitrate at depth were balanced by proportional increases in phytoplankton chlorophyll concentrations and suspended particle load, conclusively linking vertical migration to the access and assimilation of deep nitrate in the ocean environment. Vertical migration during the red tide created anomalous biogeochemical conditions compared to 70 y of climatological data, demonstrating the capacity of these events to temporarily reshape the coastal ocean's ecosystem and biogeochemistry. Advances in the understanding of the physiological, behavioral, and metabolic dynamics of HAB-forming organisms from cutting-edge observational techniques will improve our ability to forecast HABs and mitigate their consequences in the future.


Subacute sclerosing panencephalitis with atypical features.
The incidence of subacute sclerosing panencephalitis may be rising. This report describes three patients identified in New York City with atypical features including age of onset, prolonged prodrome, and lack of specific electroencephalographic changes. The diagnosis was confirmed with the identification of measles antibodies in the cerebrospinal fluid. Awareness of the possibility that the clinical presentation of subacute sclerosing panencephalitis may be changing may increase its timely diagnosis.


High-dose steroids for perioperative management of patients with myasthenia gravis undergoing thymectomy. A preliminary report.
To eliminate the morbidity associated with thymectomy, we used high-dose corticosteroids perioperatively in 32 patients who had Class II and III myasthenia gravis. All patients were extubated within 2 hours after the operation, and none required respiratory support postoperatively. The average stay in the intensive care unit was 20 hours and the average hospital stay, 6 days. Addition of high-dose corticosteroids to the perioperative managment of patients with myasthenia gravis undergoing thymectomy improved the immediate operative results and eliminated the morbidity associated with this procedure.


Determination of atorvastatin in human serum by reversed-phase high-performance liquid chromatography with UV detection.
A rapid and sensitive high-performance liquid chromatographic method was validated and described for determination of atorvastatin in human serum. Following liquid-liquid extraction of the drug and an internal standard (sodium diclofenac), chromatographic separation was accomplished using C18 analytical column with a mobile phase consisting of sodium phosphate buffer (0.05 M, pH 4.0) and methanol (33:67, v/v). Atorvastatin and the internal standard were detected by ultraviolet absorbance at 247 nm. The average recoveries of the drug and internal standard were 95 and 80%, respectively. The lower limits of detection and quantification were 1 and 4 ng/ml, respectively, and the calibration curves were linear over a concentration range of 4-256 ng/ml of atorvastatin in human serum. The analysis performance was studied and the method was applied in a randomized cross-over bioequivalence study of two different atorvastatin preparations in 12 healthy volunteers.


Investigating macromolecular complexes using top-down mass spectrometry.
MS has emerged as an important tool to investigate noncovalent interactions between proteins and various ligands (e.g. other proteins, small molecules, or drugs). In particular, ESI under so-called "native conditions" (a.k.a. "native MS") has considerably expanded the scope of such investigations. For instance, ESI quadrupole time of flight (Q-TOF) instruments have been used to probe the precise stoichiometry of protein assemblies, the interactions between subunits and the position of subunits within the complex (i.e. defining core and peripheral subunits). This review highlights several illustrative native Q-TOF-based investigations and recent seminal contributions of top-down MS (i.e. Fourier transform (FT) MS) to the characterization of noncovalent complexes. Combined top-down and native MS, recently demonstrated in "high-mass modified" orbitrap mass spectrometers, and further improvements needed for the enhanced investigation of biologically significant noncovalent interactions by MS will be discussed.


Morphometric Evaluation of Soft Palate in OSMF Patients Using Cephalometrics.
Oral submucous fibrosis (OSF) is a chronic disease and a well-recognized potentially malignant condition of the oral cavity characterized by inflammation and a progressive fibrosis of the lamina propria and deeper connective tissues. To study the morphology of soft palate in different stages of OSF on digital lateral cephalogram. To compare the changes in morphology of soft palate in OSF patients with control. The study was conducted from 2017 to 2018 on 217 patients with their age ranging from 17 to 60 years. All patients detailed clinical examination and history was taken and cephalometric evaluation was done. Type I (51.14%) was found to be the most common in OSF group followed by type II (21.86%) and type VI (13.64%). The present study highlighted the variable radiographic appearances of the soft palate on lateral cephalograms with type I as most common morphology. Cephalometric analysis is one of the most commonly accepted techniques for evaluating the soft palate in both normal individuals and in those with cleft lip and palate.


pH regulation of calcium efflux by turtle liver mitochondria.
1. Turtle liver mitochondria are capable of taking up calcium in a pattern similar to that described from rat liver mitochondria. 2. Turtle liver mitochondria also possess a system for calcium efflux which is extremely sensitive to changes in extramitochondrial pH. A decrease in extramitochondrial pH by addition of HCl or by gassing with CO2 caused a rapid release of calcium. 3. The profound changes in pH and pCO2 during deep diving likely affects Ca efflux from mitochondria in the turtle liver.


[Methodological approaches to studying substances influencing blood rheology].
Optimum design of preclinical research for pharmacological agents influencing the rheological properties of blood is presented. Models of hyperviscosity syndrome and approaches to studying the hemorheological activity mechanisms are described.


The spinal basis of opioid tolerance and physical dependence: Involvement of calcitonin gene-related peptide, substance P, and arachidonic acid-derived metabolites.
Chronic opioid use in the management of pain is limited by development of analgesic tolerance and physical dependence. The mechanisms underlying tolerance-dependence are not entirely clear, however, recent evidence suggests that spinal adaptations leading to increased activity of sensory neuropeptides (calcitonin gene-related peptide (CGRP), substance P) and their downstream signaling messengers derived from metabolism of arachidonic acid: prostaglandins (PG), lipoxygenase (LOX) metabolites, and endocannabinoids, plays an important role in this phenomenon. In this communication we review the evidence implicating these factors in the induction and expression of opioid tolerance and physical dependence at the spinal level.


Chemopreventive effects of anthocyanins on colorectal and breast cancer: A review.
The present review has analyzed the scientific literature, available in the PubMed and Scopus databases, in order to summarize the current state of diet anthocyanin research in breast cancer (BC) and colorectal cancer (CRC) animal models but also for up-to-date human studies. For CRC, 28 preclinical and 9 clinical studies were selected in line with our search query in science databases. In relation to BC, 14 preclinical and 5 clinical studies were selected. Remarkably, all the preclinical studies, to a greater or lesser degree, suggested a chemoprevention effect of anthocyanin in BC/CRC rodent models. These encouraging results from animal models are not extrapolated to the same degree to human studies where, from the similar theoretical daily doses of anthocyanins in these studies, the opposite results were reported. Nevertheless, it is worth mentioning that the anthocyanin doses in the human studies carried out recently are low if we consider the estimated exposure to anthocyanins issued by the European Food Safety Agency (EFSA) or extremely low if we consider with caution the human equivalent dose based on body surface area from the preclinical dosage regimes used. Therefore, although some clinical data has demonstrated an inverse relation between anthocyanin consumption and BC/CRC, this could, in fact, be more relevant if we increase the daily human anthocyanin dose (as observed in animal model dose-effect studies) while new toxicological data for this flavonoid subtype are brought to light.


[Screening and identification of glycoproteins from Campylobacter jejuni NCTC 11168 based on specific affinity between lectins and glycoproteins].
To screen glycoproteins from Campylobacter jejuni NCTC 11168. We introduced a screening strategy based on specific affinity between lectins and glycoproteins. First, the specific affinity between Soybean Agglutinin (SBA) and glycoproteins in C. jejuni was confirmed by western blotting. Then, magnetic beads coating with Soybean Agglutinin (SBA) were used to capture the putative glycoproteins. Putative glycoproteins were competitively eluted by N-acetylgalactosamine and separated by two-dimensional gel electrophoresis. Spots in gels were further analyzed by mass spectrometry. A total of 22 proteins were identified by mass spectrometric analysis, of which 5 have ever been identified to be glycoproteins. Others including Cj0633 have not been proved to be glycosylated so far. The method could be used to screen glycoproteins in bacteria.


Specific decreasing of Na+ channel expression on the lateral membrane of cardiomyocytes causes fatal arrhythmias in Brugada syndrome.
Reduced cardiac sodium (Na+) channel current (INa) resulting from the loss-of-function of Na+ channel is a major cause of lethal arrhythmias in Brugada syndrome (BrS). Inspired by previous experimental studies which showed that in heart diseases INa was reduced along with expression changes in Na+ channel within myocytes, we hypothesized that the local decrease in INa caused by the alteration in Na+ channel expression in myocytes leads to the occurrence of phase-2 reentry, the major triggering mechanism of lethal arrhythmias in BrS. We constructed in silico human ventricular myocardial strand and ring models, and examined whether the Na+ channel expression changes in each myocyte cause the phase-2 reentry in BrS. Reducing Na+ channel expression in the lateral membrane of each myocyte caused not only the notch-and-dome but also loss-of-dome type action potentials and slowed conduction, both of which are typically observed in BrS patients. Furthermore, the selective reduction in Na+ channels on the lateral membrane of each myocyte together with spatial tissue heterogeneity of Na+ channel expression caused the phase-2 reentry and phase-2 reentry-mediated reentrant arrhythmias. Our data suggest that the BrS phenotype is strongly influenced by expression abnormalities as well as genetic abnormalities of Na+ channels.


Relationships between the effects of insect herbivory and sheep grazing on seasonal changes in an early successional plant community.
The effects of spring grazing by sheep and of natural levels of insect herbivory were studied in 1985 on a limestone field abandoned from arable land for four years. A split-plot design was adopted in which paddocks, arranged in Latin squares, were either left ungrazed or heavily grazed by sheep for ten days in April. Within each paddock plots were either sprayed regularly with Malathion-60 or untreated.Natural levels of insect herbivory, compared to the reduced levels in insecticide-treated plots, had effects of similar magnitude to those from the short burst of spring grazing. Many attributes of the grazed/insecticide-treated sward were either increased or decreased by a factor of two within a season. Both types of herbivore caused changes in the direction of plant succession as well as in its rate. Effects on early successional species were large and similar when caused by either type of herbivore. Effects on later successional species were often smaller, but also showed differences in the action of the two herbivore types, as did effects on sward height, species richness and total cover. The effects of sheep and insect herbivory were not always additive or in the same direction.The results suggest that manipulations of both mammal and insect herbivores may be powerful tools for directing changes in plant community composition.